Who is at risk for RAGE related neurocognitive conditions?

Potentially anyone who got the CoV injections is at this increased risk for amyloidosis and neurocognitive degenerative conditions. Also anyone who did get sick with something that had real symptoms rather than just having a ‘positive PCR test’. And that sickness might have been during 2020 ‘CoV’ outbreak, but it also may have occurred later, due to passive exposure illness to CoV injections that other people got, even if you hadn’t gotten the injection yourself. Exosomes from injected people can spread it. The worse risk for passive exposure spread, seems to be the first couple weeks to a couple months, occasionally lasting longer, 15 months has been seen and one person has been found still making chimeric spike 36 months - 3 years later.

Spoiler - what to do about it?

Eat pomegranate or citrus peel, or rosemary, or maybe try camphor essential oil topically or as an aerosol. Or drink green or black tea, or pomegranate rind tea, (or skullcap tea), and rosemary also can be made into a medicinal strength, long steeped tea.

Artemisia species would likely all help, one species is mentioned later that was shown beneficial against RAGE activity and the group of Artemisia and Mugwort species tend to all be similarly medicinal. Look for Sweet Wormwood tea or extracts, as ‘Wormwood’ would be the type used to make Absinthe, and it contains thujone which has stimulating effects, but also may be habit forming and an excess can cause seizures.

Other edible tea pine needles would likely also be effective, long or short needle pine varieties, or spruce, and Arbor vitae shrubs, or cedar trees, but avoid using Yew needles as those are poisonous. Steep a couple tablespoons of needles for 20 minutes at least, in water that was brought to a boil - but remove from the heat.

Similar functional foods to tea and pomegranate peel, include Goji berries (sold by Young Living, as their medicinal beverage mix, or whole, but it isn’t a great price), and powdered Sumac. Sumac is an invasive plant throughout many areas of the US - the red berries are the edible type and Native Americans made a citrusy beverage with it. Sumac is used in the Middle Eastern spice mix called zaatar and is available for sale at Middle Eastern groceries (Arabic more than Indian) as plain Sumac powder or Zaatar. Both products tend to be sold in shaker jars, for use at the dinner table. People can add to their own taste preferences, like salt or pepper, and not overheating the spice during cooking preserves the medicinal value.

RAGE, SARS-CoV-2 and amyloidosis

Thread by Daniel Brittain Dugger, (x.com/dbdugger) about amyloidosis and SARS-coV-2 chimeric spike, (the Thread continues after this initial conversation):

“If folks would put HIV as a hashtag, we would not been in the shape we are. Amyloid deposition has been known since 2022.” - Daniel Brittain Dugger, (x.com/dbdugger),

*See: About amyloidosis and SARS-COV-2: Amyloidogenesis of SARS-CoV-2 Spike Protein, (Nyström and Hammarström, 2022) and (Milton, 2023) excerpted below.

Who was reposting:

“#SARSCoV2 amyloid, is #COVID19-exacerbated dementia an #amyloid disorder in the making? #PASC #LongCovid #MECFS #HIV” - Gary Anderson, @G_A_grandsong

Who was reposting:

“SARS-CoV-2 AMYLOID, is COVID-19-EXACERBATED DEMENTIA an amyloid disorder in the making?

An interesting article [(Milton, 2023)]

and are promoted by the CoV chimeric spike.” - Emmanuel, (x.com/ejustin46)

“Figure 1. SARS-CoV-2 amyloid formation and interactions. Extracellular SARS-CoV-2 virus enters cells via an interaction of the spike protein (S) with the cellular angiotensin-converting enzyme 2 (ACE2) receptor. Once inside cells, the mRNA is translated into a range of viral proteins including the structural spike (S), envelope (E), membrane (M) and nucleocapsid (N) proteins plus the accessory proteins ORF6 and ORF10, all of which can form amyloid fibrils that are likely to be generated intracellularly. The spike (S) protein can also bind Amyloid-ß and this is likely to occur where the Amyloid-ß fibrils are deposited extracellularly.” (Milton, 2023)

Other links that were shared in the Thread by Daniel Brittain Dugger, (x.com/dbdugger):

1. About amyloidosis and SARS-COV-2: Amyloidogenesis of SARS-CoV-2 Spike Protein, (Nyström and Hammarström, 2022)

2. “Unsurprising as RAGE is involved [in the amyloidosis risks] and Protein E operates mechanistically as HIV’s Tat.” (x.com/dbdugger) and link shared for:

   About RAGE: Journey to a Receptor for Advanced Glycation End Products [RAGE] Connection in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: With Stops Along the Way in the Lung, Heart, Blood Vessels, and Adipose Tissue. (Roy, et al., 2021)

What is RAGE? ;-)

“The receptor for advanced glycation end products (RAGE) is a multiligand protein belonging to the immunoglobulin superfamily that can bind with a broad range of ligands such as:

• advanced glycation end products (AGEs),

• amyloid β (Aβ),

• high mobility group box 1 (HMGB1), and

• S100/calgranulin (Schmidt et al., 2001; Ding and Keller, 2005).

Ligation [activation by one of the ligands listed above] of RAGE triggers a series of cellular signaling events, including the activation of transcription factor nuclear factor-κB (NF-κB), leading to the production of pro-inflammatory cytokines, and causing inflammation. The stimulation of RAGE is able to activate the mitogen-activated protein kinase (MAPK) signaling cascades, which thereby release and activate NF-κB in the downstream (Tobon-Velasco et al., 2014).

Indeed, RAGE involvement has been demonstrated in the pathogenesis of a number of inflammation-associated conditions including diabetes, atherosclerosis, arthritis, and Alzheimer’s disease (AD) (Chuah et al., 2013). Evidence shows that RAGE were highly expressed in Parkinson’s disease (PD) patients when compared to age-matched controls and RAGE gene polymorphisms were associated with sporadic PD in Asians (Guerrero et al., 2013; Gao et al., 2014), suggesting that RAGE might play a crucial role in the pathogenesis of PD.” (Wang, et al., 2020) *Formatting changes were added by me, for emphasis or ease of reading.

Solution 1. Inhibit inflammation and RAGE with Pomegranate peel extract and other polyphenols.

Pomegranate peel would help inhibit NFkB and kinases (MAPK and others) and reduce activation of RAGE receptors.

- search result:

Pomegranate peel extract has been shown to inhibit the activity of Receptor for Advanced Glycation End-products (RAGE), a key player in the development of various inflammatory and oxidative stress-related diseases.

Mechanisms of Inhibition

Studies have demonstrated that pomegranate peel extract's polyphenolic compounds, particularly punicalagin and ellagic acid, can:

1. Bind to RAGE, thereby pr… (search.brave.com/search?q=inhibition+of+RAGE+by+pomegranate+peel+extract)

The postbiotic formed from pomegranate phytonutrients called urolithin A inhibited RAGE. Polyphenols from Gingko biloba, Artemisia herbalba, and from tea, green or black tea probably, also inhibited RAGE activity. AGEs are protein that have a sugar attached, it changes function usually towards inflammatory. They can be made internally, and are increased by oxidative stress, or they can be consumed in our diet, from crispy things like Barbecued meats, charred food in general, crispy baked goods, or deep fried or high temperature extruded cereal or snack foods. This article has a good overview of the varied sources of AGEs. - RAGE Inhibitors in Neurodegenerative Diseases, (Reddy, et al., 2023)

“Among other neuroprotective polyphenol antioxidants and polyphenolic metabolites, urolithin A was shown to attenuate the oxidative stress, downregulate inflammatory cytokines and inhibit NF-κβ activation, and was thus proposed as a potential therapeutic candidate, for treating inflammatory diseases, including neurodegenerative diseases [61,62,63,64]. Some of the chemically synthesized analogs of urolithins inhibit the binding of the bovine-serum albumin derived AGEs to the soluble RAGEs (AGE2-BSA/sRAGE) and their RAGE antagonist characteristics are comparable to that of the RAGE antagonists Azeliragon and FPS-ZM1, which are at various phases of clinical trials [65,66].

Plant extracts derived from Artemisia herbalba were demonstrated to attenuate the production of pro-inflammatory cytokines, such as TNF-α and interleukin-6 (IL-6), which are formed through AGE–RAGE signaling pathways [67]. Polyphenols from tea also regulate the RAGE expression and thereby attenuate the MAPK and TGF-β signaling pathways [68]. Polyphenols act as effective antioxidants by scavenging reactive oxygen species (ROS), and thereby attenuate the oxidative stress. The exacerbated oxidative stress would lead to the overproduction of AGEs and thereby increased AGE–RAGE interactions and the concomitant signal transduction pathways and the activation of the pro-inflammatory cytokines. Polyphenols regulate the microbiota–gut–brain axis and attenuate AGE–RAGE interactions and thereby the onset of neurodegenerative diseases and other pathological effects, as described above [29]. Ginkgolide-B, a constituent of Ginkgo biloba plants, also helps to decrease the levels of RAGE and thereby attenuate the oxidative stress and thereby neurological damage (Figure 4) [69].” (Reddy, et al., 2023)

Solution 2 is the same as Solution 1. Inhibit inflammation and RAGE activity with polyphenols from a variety of herbals and foods or beverages.

Citrus peel - nobiletin, or curcumin-turmeric, the herb Rosemary, green or black tea, Gingko biloba, Artemesia (varied species probably) and other polyphenols, inhibit RAGE receptors; (Brave AI summary) and excerpts.

Phytonutrients, chemical compounds produced by plants to defend against pathogens and environmental threats, have been shown to inhibit the receptor for advanced glycation end products (RAGE). RAGE is a key player in chronic inflammatory processes, including neurodegenerative diseases.

Mechanisms of Inhibition

1. Antioxidant Properties: Phytonutrients, such as polyphenols, exhibit antioxidant pro…

…

• Nobiletin: A citrus flavonoid that has been demonstrated to attenuate methylglyoxal-induced toxicity and reduce RAGE expression in AD models. *** Citrus peel would be a good source.

• ss-Caryophyllene: A polyphenolic compound found in camphor and caraway seeds, which has shown anti-inflammatory and neuroprotective effects by inhibiting RAGE. ***Camphor essential oil is great for clearing congestion.

• Carnosic acid: A phenolic acid found in rosemary, which has been shown to exhibit anti-inflammatory and antioxidant properties, potentially inhibiting RAGE activity.

search.brave.com/search?q=inhibition+of+RAGE+by+phytonutrient

*I didn’t find the specific link for all of those phenols, but they are similar phytonutrients as the references that I did find. Catechins were mentioned in the Pomegranate section between the pomegranate and the green or black tea, so Sumac powdered spice and goji berries would provide similar benefits.

via (x.com/deNutrients)

Hispidin from Phellinus linteus is also an inhibitor of RAGE and the NF-kB pathway.

“Hispidin is a polyphenol compound derived from Phellinus linteus and it has several biological activities such as antioxidant [148] and anticancer [149]. Hispidin could be a new gemcitabine chemosensitizer and potentially a synergistic agent to increase the gemcitabine therapeutic index to treat pancreatic cancer [150]. In addition, hispidin significantly induced apoptosis in colon cancer cells by generation of reactive oxygen species (ROS) [149]. Rat pheochromocytoma (PC12) cells were pre-incubated with 2μM of ergothioneine, thiol molecule synthesized by some fungi and bacteria, hispidin, or a combination of them. The results revealed a significant attenuation of AGEs’ formation, RAGE expression, and NF-κB pathway activation through antioxidant activities [44]. Both the antioxidant compounds ergothioneine and hispidin counteracted the AGEs-RAGE axis-related induction of carcinogenesis (Figure 3).” (El-Far, et al., 2020)

Semi related- sales of alcohol have dropped post CoV era. (forbes.com)

- it is likely due to an increase in MCAS and histamine sensitivity.

Pomegranate peel or niacin would help inhibit mast cell degranulation and reduce inflammation

Lara Crowther suggests the drop in alcohol sales maybe related to LongCovid causing intolerance.

The Post-Covid Decline of Wines and Spirits Sales Is Accelerating, (forbes.com)

“I was wondering when this would get said. How many of us can’t tolerate alcohol with Long Covid?” - Lara Crowther, (x.com/fillthewhole)

Alcohol could cause negative symptoms if MCAS had become a new and lingering problem. It requires major diet and lifestyle changes to manage and reduce the symptoms.

Anything fermented is a histamine trigger food or beverage. Pomegranate peel inhibits mast cell degranulation, so it helps improve or prevent MCAS symptoms. Avoiding fermented products might remain a need though, once there are overactive or an excess number of mast cells present. Histamine excess or increased inflammation for any reason could then increase AGE (glycated proteins) which leads to more RAGE receptor activity. (Example of AGEs - the crispy coating on barbecue or cookies or deep fried food.)

A reply to the above post and article link:

“Great point!! I had already experienced this intolerance when diagnosed with MS. I have had a lot of friends lately saying they can’t tolerate alcohol but they chalked it up to getting older. I never thought of the C19 connection.” - Sonia Kir, (x.com/gazoo32) *image above.

And a repost by the original account:

“How many others aren’t connecting covid to not being able to tolerate alcohol? It’s not just age!” - Lara Crowther, (x.com/fillthewhole) *image above.

Additional Tip from my own experience with undiagnosed histamine excess and/or MCAS - also avoid strobe light type action movies or night driving. The flickering also triggers mast cells and can lead to symptoms like migraine. Wearing dark sunglasses 🕶 to action movies, helps block the flickering effect, or night driving - 🚗 🤔. Learned that the hard way and then I found the research showing why. See page MCAS/Histamine on www.jenniferdepew.com.

• The Post-Covid Decline of Wines and Spirits Sales Is Accelerating, by

  Joseph V Micallef, 10/10/2024, (forbes.com) via:

HIV-1 Tat protein also increases RAGE.

Copied again: “Unsurprising as RAGE is involved [in the amyloidosis risks] and Protein E operates mechanistically as HIV’s Tat.” (x.com/dbdugger) The link: ‘About RAGE: Journey to a Receptor for Advanced Glycation End Products [RAGE] Connection in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: With Stops Along the Way in the Lung, Heart, Blood Vessels, and Adipose Tissue.’ (Roy, et al., 2021)

HIV TAT is a viral protein essential for HIV transcription, binding to TAR RNA and recruiting p-TEFb for phosphorylation of RNA polymerase II. (Brave AI summary)

• ‘hiv tat RAGE’ search on Google, (x.com/dbdugger)

HIV Tat Functionality - on Brave, (AI summary)

The HIV-1 Tat protein has been shown to regulate the expression of RAGE (Receptor for Advanced Glycation End-products) in brain endothelial cells. RAGE is a multiligand receptor involved in the pathogenesis of various diseases, including neurodegeneration and inflammation. [* “multiligand” = the receptor can be activated by many agonists - many chemicals can trigger the RAGE receptors.]

According to the search results, exposure to HIV-1 Tat resulted in:

• Markedly higher levels of RAGE protein and mRNA

• Stronger immunoreactivity compared to the untreated group

This upregulation of RAGE was mediated by the RhoA/ROCK signaling pathway, highlighting the complex interplay between HIV Tat and RAGE. HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway - PubMed

Implications

1. Neuroinflammation: Elevated RAGE expression can contribute to neuroinflammation, a hallmark of HIV-associated neurocognitive disorders (HAND).

2. Cellular toxicity: RAGE activation can lead to cytotoxicity, potentially exacerbating HIV-associated comorbidities, such as HAND, cardiovascular impairment, and accelerated aging.

3. Therapeutic targets: Understanding the HIV Tat-RAGE axis may identify novel therapeutic strategies for mitigating these comorbidities, potentially by targeting RAGE or modulating the RhoA/ROCK signaling pathway.

In summary, the HIV-1 Tat protein regulates RAGE expression in brain endothelial cells through the RhoA/ROCK signaling pathway, with potential implications for neuroinflammation, cellular toxicity, and therapeutic targets.

Follow up

• What are the specific RAGE ligands involved in HIV Tat-mediated RAGE upregulation?

• How does HIV Tat-induced RAGE expression contribute to blood-brain barrier disruption?

• Do other HIV proteins, besides Tat, regulate RAGE expression and contribute to HIV-associated neurocognitive disorders?

1. pubmed.ncbi.nlm.nih.gov, HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway - PubMed

2. ncbi.nlm.nih.gov, The HIV-1 Tat Protein Has a Versatile Role in Activating Viral Transcription - PMC

3. ncbi.nlm.nih.gov, Tat is a multifunctional viral protein that modulates cellular gene expression and functions - PMC

4. frontiersin.org, Frontiers | HIV-1 Tat

Also linked in the Thread by Daniel Brittain Dugger, (x.com/dbdugger) about RAGE and amyloidosis - Protein E is involved in ribosome biogenesis:

“Protein E and Ribosome Biogenesis: Protein E, also known as RimE, is a ribosome biogenesis factor in Escherichia coli (E. coli). Ribosome biogenesis is the process by which ribosomes are assembled and matured in the cell. Protein E plays a crucial role in this process, specifically in the maturation of the 30S ribosomal subunit. […]

Disease Relevance

Dysregulation of ribosome biogenesis, including the function of protein E, has been implicated in various diseases, including:

1. Cancer: Altered ribosome biogenesis and protein synthesis can contribute to cancer development and progression.

2. Neurodegenerative disorders: Defects in ribosome biogenesis and protein synthesis have been linked to neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). (Brave AI summary)

Ribosomal biogenesis can be targeted by SARS-CoV-2 or some other pathogens

• HIV TAT is a viral protein essential for HIV transcription, binding to TAR RNA and recruiting p-TEFb for phosphorylation of RNA polymerase II. NSP1 is a cellular protein involved in RNA processing and translation regulation, with no direct connection to HIV TAT. (a different search, Brave AI summary, I had missed the Protein E mention earlier.)

“Notably, various viruses target host ribosome biogenesis.⁴⁸ The coronavirus mouse hepatitis virus can induce the cleavage of 28S rRNA,⁴⁹ while the Nsp1 protein of influenza A silences the rRNA gene promoter.⁵⁰ Hendra and Nipah virus matrix proteins interact with rRNA gene regulators and activate nucleolar DNA damage responses.⁵¹ Poliovirus inhibits RNA Pol I by inactivating its transcription factors,⁵² and herpes simplex virus 1 interferes with pre-rRNA processing.⁵³ Finally, the Tat protein of human immunodeficiency virus interacts with FBL and U3 snoRNA, impairing pre-rRNA processing and depleting mature ribosomes.⁵⁴ On a related note, the 123–130 region of SARS-CoV-2 Nsp1 is well conserved among bat coronavirus strains, and studies monitoring Nsp1’s evolution only detected an R124C mutation within this region,^6,16,55,56 implying its crucial role.

In conclusion, we report that Nsp1 targets ribosome biogenesis and mature ribosomes, revising our understanding of how SARS-CoV-2 impacts human protein synthesis. Considering the crucial role of Nsp1 during SARS-CoV-2 infection, work is underway to identify inhibitors of this virulence factor.⁵⁷ Testing whether such candidate drugs effectively block Nsp1’s diverse functions, including the herein-uncovered inhibition of ribosome biogenesis, will be critical. We expect our findings to help guide efforts to combat SARS-CoV-2 and its related viruses.”

3. SARS-CoV-2 targets ribosomal RNA biogenesis, (Yerlici, et al., 2024)

»» Ignoring the What did all that mean? question - lets jump ahead to the solutions, which is what I think of as the important part - Do polyphenols help support ribosome biogenesis? The answer is a resounding yes.

Polyphenols and Ribosome Biogenesis - Brave AI

Polyphenols, a class of plant-derived compounds, have been shown to modulate ribosome biogenesis, a crucial process in cellular protein synthesis. Ribosome biogenesis is tightly regulated to ensure proper protein synthesis and cellular homeostasis. Dysregulation of ribosome biogenesis has been implicated in various diseases, including cancer.

Mechanisms of Polyphenol-Induced Ribosome Biogenesis Modulation

1. SIRT1 activation: Polyphenols, such as resveratrol and quercetin, activate SIRT1 (silent information regulator 1), a NAD±dependent deacetylase. SIRT1 regulates ribosome biogenesis by deacetylating and activating key transcription factors, including PGC-1α (peroxisome proliferator-activated receptor γ coactivator 1α) and NRF-1 (nuclear respiratory factor 1).

2. PGC-1α/NRF-1 pathway: Activated SIRT1 promotes the expression of PGC-1α and NRF-1, which in turn regulate the transcription of ribosomal protein genes and rRNA genes. This leads to increased ribosome biogenesis and protein synthesis.

3. Inhibition of mTOR: Polyphenols, such as epigallocatechin gallate (EGCG), have been shown to inhibit the mechanistic target of rapamycin (mTOR) pathway, which regulates cell growth and protein synthesis. Inhibition of mTOR reduces ribosome biogenesis and protein synthesis.

4. Modulation of ribosomal protein synthesis: Polyphenols can directly regulate the synthesis of specific ribosomal proteins, such as RPL10 and RPS20, which are involved in ribosome biogenesis.

Cancer-Related Implications

1. Anti-tumor effects: Polyphenols’ ability to modulate ribosome biogenesis may contribute to their anti-tumor effects by reducing protein synthesis and inhibiting cancer cell growth.

2. Therapeutic resistance: Dysregulation of ribosome biogenesis can lead to therapeutic resistance in cancer cells. Polyphenols may help overcome resistance by modulating ribosome biogenesis and protein synthesis.

3. Targeting onco-ribosomes: Polyphenols may target aberrant ribosomes found in cancer cells, which are characterized by altered ribosomal protein composition and function.

Examples of Polyphenols and Ribosome Biogenesis

1. Resveratrol: Increases ribosome biogenesis and protein synthesis in human fibroblasts and endothelial cells.

2. Quercetin: Activates SIRT1 and increases PGC-1α expression, leading to enhanced ribosome biogenesis in mouse liver and skeletal muscle.

3. Epigallocatechin gallate (EGCG): Inhibits mTOR and reduces ribosome biogenesis in human breast cancer cells.

4. Hydroxytyrosol: Activates SIRT1 and increases PGC-1α expression, leading to enhanced ribosome biogenesis in rat retinal pigment epithelial cells.

In summary, polyphenols modulate ribosome biogenesis through various mechanisms, including SIRT1 activation, PGC-1α/NRF-1 pathway regulation, mTOR inhibition, and direct regulation of ribosomal protein synthesis. These effects may contribute to their anti-tumor and anti-cancer properties, as well as their potential to overcome therapeutic resistance and target aberrant onco-ribosomes. (Brave AI summary)

In conclusion,

I rest my case - to protect against SARS-CoV-2 related RAGE neurodegenerative risks, eat pomegranate peel!

…or other sources of catechins like green or black tea (oxalate load caution), Sumac or Zaatar, or Goji berries. Or try other polyphenol foods like citrus peel (MCAS/histamine risk!), turmeric/curcumin (Vit D receptor agonist), rosemary or other pine needle tea. The Artemesia or Mugwort herbals would likely all help - look for ‘Sweet Wormwood’, not ‘Wormwood’.

Camphor essential oil may help, but it is not edible, use it diluted topically or diffused - I use this everyday, it helps reduce or prevent congestion for me.

Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

Reference List

(El-Far, et al., 2020) El-Far AH, Sroga G, Jaouni SKA, Mousa SA. Role and Mechanisms of RAGE-Ligand Complexes and RAGE-Inhibitors in Cancer Progression. Int J Mol Sci. 2020 May 20;21(10):3613. doi: 10.3390/ijms21103613. PMID: 32443845; PMCID: PMC7279268. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279268/

(Milton, 2023) Milton Nathaniel G. N., SARS-CoV-2 amyloid, is COVID-19-exacerbated dementia an amyloid disorder in the making?, Frontiers in Dementia, VOL 2, 2023, DOI=10.3389/frdem.2023.1233340, ISSN=2813-3919, https://www.frontiersin.org/journals/dementia/articles/10.3389/frdem.2023.1233340

(Nyström and Hammarström, 2022) Nyström, Sofie, Hammarström, Per, Amyloidogenesis of SARS-CoV-2 Spike Protein, 2022/05/25, Journal of the American Chemical Society, pp Vol 144, Issue 20, 8945-8950, doi: 10.1021/jacs.2c03925, https://doi.org/10.1021/jacs.2c03925, https://pubs.acs.org/doi/10.1021/jacs.2c03925

(Reddy, et al., 2023) Reddy VP, Aryal P, Soni P. RAGE Inhibitors in Neurodegenerative Diseases. Biomedicines. 2023 Apr 9;11(4):1131. doi: 10.3390/biomedicines11041131. PMID: 37189749; PMCID: PMC10136230. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136230/

(Roy, et al., 2021) Roy D, Ramasamy R, Schmidt AM. Journey to a Receptor for Advanced Glycation End Products Connection in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: With Stops Along the Way in the Lung, Heart, Blood Vessels, and Adipose Tissue. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):614-627. doi: 10.1161/ATVBAHA.120.315527. Epub 2020 Dec 17. PMID: 33327744; PMCID: PMC7837689. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837689/

(Wang, et al., 2020) Wang X, Sun X, Niu M, Zhang X, Wang J, Zhou C, Xie A. RAGE Silencing Ameliorates Neuroinflammation by Inhibition of p38-NF-κB Signaling Pathway in Mouse Model of Parkinson's Disease. Front Neurosci. 2020 Apr 29;14:353. doi: 10.3389/fnins.2020.00353. PMID: 32410941; PMCID: PMC7201072. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201072/

(Yerlici, et al., 2024) Yerlici VT, Astori A, Kejiou NS, Jordan CA, Khosraviani N, Chan JNY, Hakem R, Raught B, Palazzo AF, Mekhail K. SARS-CoV-2 targets ribosomal RNA biogenesis. Cell Rep. 2024 Mar 26;43(3):113891. doi: 10.1016/j.celrep.2024.113891. Epub 2024 Feb 29. PMID: 38427561. https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00219-5 Pdf: https://www.dropbox.com/scl/fi/biyks8xie5q4bvcqwxhbp/PIIS2211124724002195.pdf?rlkey=chnlif9axlokf4s6kc43ub704&dl=0

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“For example, mycorrhizal fungi are symbiotes that colonize the root systems of plants and help to increase water and nutrient uptake while they benefit from the carbohydrates produced by the plant.” (study.com)

*This quote was in a previous post that gets into more detail about soil and our gut microbiome, which I discuss more later; “We are symbionts…” (post).

The bad news, the bright lights and harsh sounds of hospitals are a bad Terrain environment. They promote species of our normal microbes to grow out of control into a bad “infection”. The “infection” was the bad light and sounds though.

What to do? Get out in early morning light with some skin exposure, more is better. Midriff baring tops in traditional cultures may have been serving a health purpose in climates warm enough for light clothing.

In northern climates, use of fires for warmth and light would have been helping the microbiome. Light is sensed through our skin and eyes, so sleeping with the TV on is not healthy, but smoldering red coals from a campfire, has been found to not interfere with our circadian health.

I am currently lucky with my parent's home choice. I live in a postcard:

Clip from a longer interview, focused on the light and sound research that can negatively or positively impact our microbiome, interview of Mary Ruddick, ‘Ancestral Nutritionist’, International Keynote Speaker, Writer, & Film Scout, (maryruddick.com), interview by Jesse Chappus, *video shared by Solo in a comment, thanks!

Early morning sunlight is enough if you are sun sensitive and firelight is also healing, so traditional cultures in colder areas had live fires for warmth.

In the full video interview, (see later in post), the opening moments share that Akkarmansia species of the gut microbiome help promote the GLP-1 appetite regulating hormone which the trendy medication Ozempic promotes - with some side effect risks and weight returning when the medication is stopped. Skip the Ozempic cost and risks and take the now-available Akkarmansia supplement by Pendulum. I’ve tried it, tastes like vanilla (by product design). Pomegranate also promotes the Akkarmansia species and other beneficial butyrate producing species.

Not mentioned in the video - that is also a species associated with people who are over 100 years old. They were more likely to have Akkarmansia sp. than people in younger Senior Citizen age groups. The Centurions may have had the beneficial species all along, and it helped them reach that age. (Brave AI summary has the research links)

See (post) *It is an overview on symbionts, our mitochondria and gut microbes, and includes a list of topic ideas, a content plan, which I didn’t complete, sorry.

Excerpt from the post on zinc needs of our microbiome:

Zinc - Our microbes eat a lot.

1. Zinc supplementation or a zinc rich diet is also benefiting our intestinal microbiome. Beneficial bacterial species need zinc in their diet too. When low zinc is available less beneficial species that don't need zinc thrive instead. (Tako, IECN2020) (jenniferdepew.com/zinc) *as much as 30% of the zinc in our diet.

2. More zinc may be needed than the current nutrition guidelines for optimal health, particularly as we age. The thymus gland needs zinc to help make antibodies and mature T-cells. Extra zinc supplementation has been found to improve age related loss of thymus gland function in animal based research. (Haase et al 2009) (jenniferdepew.com/zinc) *Senior Citizens likely need at least double the current recommendation of ~ 18 mg/day zinc. Use 2-3 mg of copper if supplementing with higher dose zinc to maintain trace mineral balance.

Addition - Resistant starch is the other essential food that the good butyrate and Akkarmansia species need besides zinc for them to thrive. Negative species can survive on the modern ultra processed food diet, but the helpful species need quite a bit of zinc and a bulky amount of resistant starch in our diet, not just a capsule or spoonful. See two pages on jenniferdepew.com - Resistant Starch/Butyrate and How much RS/Butyrate?.

The Bare Foot Healer reiterated in a comment the importance of good light habits for having a healthy microbiome and that the Carnivore Diet and plant-based diets can fail due to not addressing our need for sunshine and reduced brightness in the evening and black-out darkness during sleep. I suggested that an experimental design could control the light/dark - provide healthy light to a group of Carnivore dieters and plant-based dieters and see if both improve, or if both still have microbiome issues. The Carnivore Diet would provide a good amount of zinc on average but might be low or quite low in resistant starch, while a plant-based diet would likely provide a lot of resistant starch but likely could be low in zinc content and any zinc present might be more likely to be bound up to plant chemicals reducing bioavailability.

• Summary point: Based on my review of research on microbiome health - light, zinc, and resistant starch matter, and movement also seems to be quite important to our microbiome and mitochondria.

My guess regarding movement, is that as a symbiotic organism, when we are moving regularly, daily, then we are telling our symbionts that collectively, we all are still functional and we all need to keep functioning in balance with each other. But lack of movement, bed rest, may suggest to our symbionts that the collective organism is no longer viable, and so the microbes should just grow, unchecked. Signaling to stay within balance seem to be reduced with lack of our physical movement.

The Bare Foot Healer may also be pointing out that, if there is too much bright light at the wrong hours of the sleep/wake cycle, then even a great diet might not be able to counteract the overgrowth effect caused by the stimulation of the bright lights or wrong type of sounds on our gut microbes. The extra EMF or light energy can stimulate a growth burst in microbes. Pomegranate peel or other phytonutrients in the diet can be protective by acting as an antimicrobial agent - killing off negative species, or reducing an overgrowth problem of something like Candida yeast. But unlike antibiotics, pomegranate peel also promotes the growth of the beneficial butyrate producing species.

Note that I am not trying to sell you expensive capsule products - I am encouraging you to buy pomegranate at your grocery market and just start trying the peel in various ways in your foods. The inner pith can be minced like garlic and added fresh to salads or soups. Add at the end of heating, roughly only heat at a gentle simmer for 10 minutes or so. The outer rind is more potent, and I use it in teas or extracts and discard after steeping for ~ 10-20 minutes or making sun tea. See: Pomegranate Peel Prep Tips (Substack).

Pomegranate helps health of us and our microbiome

Pomegranate is a traditional food of many cultures. It stores well at room temperatures, so it would have been part of early trade route commerce.

Pomegranate are mentioned with reverence in the Bible and other ancient texts.

These ancient bottles have a pomegranate shape with the crown on top.

The pomegranate shaped bottles may have been closed with something like a cork.

Full Interview - Ancestral Nutritionist: How to Optimize Your Microbiome, Lose Fat & Prevent Disease | Mary Ruddick; interview by Jesse Chappus:

Health tips from the interview or with additions from me (and Brave AI on blue light filters for the computer screen).

• Modern life tip: use red or dim light bulbs in evening hours or blue light blocking glasses for the last three hours before bedtime.

• LED lights are particularly bad for us, fluorescent lights are not good, incandescent lights are better for our health and the government has made it difficult to find them in the US. LED lights are being sold now.

• Screen blue light filter aps can be found online, a fee/subscription service maybe, or a physical filter that you put over your computer screen.

  • Iris Software: A popular blue light filter app for PC, which can be used to eliminate blue light from multiple computers. An info page: (iristech.co/blue-light-filter-app-for-pc/).

  • Iris mini: A free blue light filter app for Windows, Mac, and Linux, designed to reduce blue light emission while using your computer.

  • f.lux: A free app that adjusts the color of your computer screen to match the time of day, shifting to a reddish amber tone in the evening to reduce blue light exposure. (justgetflux.com)

  • PC SunScreen: A powerful software app for Windows 7 or later, which automatically adjusts screen color to mimic natural daylight, gradually increasing blue content during the day and reducing it before bedtime.

  • 9 Free Blue Light Filters For Desktop Windows PC, Apple Mac And Chrome Browser, (geckoandfly.com).

  These apps can help reduce eye strain, promote better sleep, and improve overall computer use experience. (Brave AI summary)

• Modern life tip: don't wear sunglasses, use a hat with a visor in brighter lighting, it cuts a glare and really does make a different. 😀 Baseball hat wearers are onto something.

• Do get out into nature often. Japanese culture tend to get into the forest for forest bathing at least weekly. Laying on a natural materials blanket on the ground or sitting with your back against a tree can increase the energy benefits from negative ions found in nature.

Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

It was a foggy dawn today. Glare on the image is making additional fog spots in the foreground- that is reflected light on the digital image.

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What is Bullous pemphigoid? The Monkeypox like skin rash condition that is autoimmune based and more common in the CoV injected than the control group in the Korean based study.

“Bullous pemphigoid (a type of pemphigoid) is an autoimmune pruritic skin disease that typically occurs in people aged over 60, that may involve the formation of blisters (bullae) in the space between the epidermal and dermal skin layers.” Wikipedia.

~~ The rest of the post is about ‘My labs the continued story’ - a follow up to aprior post - Ginger, my autoimmune Kryptonite. This post gets into pecans, almonds, pistachios, Brazil and hazelnuts…my other Kryptonite I guess. They are also plant sources of albumin like proteins. However, pomegranate peel is still my Underdog Secret Energy Pill - microRNA became a part of this post, in a dipping the toes in way. It is a huge topic and I let Mother Nature handle most of the details for me. I just need to prep the pomegranate instead of over-eating pecans and not cooking healthy meals. We do tend to know which habits are helping and which aren’t.

My autoimmune disease is no longer invisible though, a win? I could tell that I hadn't removed all the causal factors because the hair follicles hurt with the swelling and itched. Rubbing too much, like dry seasonal allergy eyes but it was the eyebrows and eyelash area specifically. Since stopping all ginger, they feel better but my eyelids still look a little swollen. Scary photo later in the post.

My digging around in microRNA minutia could be a long time, so I am posting this - it has been in draft mode for a few days.

This post follows one that has my thyroid lab results, except for Reverse T3 which still isn’t available. (Substack)

Excerpt from that post: The autoimmune thyroid panel is not looking good however.

• TSH - 14.43 High (Normal range: 0.40-4.50 mIU/L)

• T4 free is low normal at 0.8, range 0.8-1.8 ng/dL

• T3 free is also low normal at 2.5, range 2.3-4.2 pg/mL

• T3 Reverse is Pending

• Thyroglobulin antibodies - 61 High, anything equal to or over 1 is high.

• Thyroid Peroxidase antibodies - 836 High, over 9 IU/mL is high

I didn't heed my own advice to not mess with autoimmune disease. I knew I should avoid ginger but didn't avoid it consistently and then binged when I did buy it - addict style use.

Plant albumin may also be in almonds, so a nut allergy might be involved in my autoimmune thyroiditis and the hair loss. Pru du 2S is an albumin like protein and may cause food allergy IgE binding but might not cause typical allergy symptoms in all patients.

Do pecans have it too? Yes.

• Cloning and characterization of 2S albumin, Car i 1, a major allergen in pecan (Sharma, et al., 2011)

I knew my Squirrelly diet had some problems, in theory or reality. (previous post) I knew that I was eating too many nuts for a balanced diet or life, at the time, because I wasn’t cooking often enough. And I had cut out tofu for a while to see if that was a problem. However, the ginger definitely was linked to flair ups in pain or itchiness of the hair follicles of my eyebrows and eyelids. 🤔 I will cut out or reduce the nuts too and see if that helps. Six months clear of a molecular mimicry autoimmune protein and the body’s level of autoimmune antibodies can drop back down.

Cutting out the ginger has improved the occasional painful feeling in the eyebrows. The eyelids are still a little swollen - inflamed with too many white blood cells ‘fighting’ the hair follicles it seems like.

What role does albumin have in thyroid follicles or hair follicles?

Well, albumin and prealbumin - transthyretin, plays a big role in thyroid hormone availability throughout the body, as it is a carrier protein. “Circulating T4 is almost entirely (99%) bound to plasma proteins: approximately 70% bound to TBG, 20% to transthyretin (prealbumin), and 10% to albumin....” (ScienceDirect/Thyroid Follicle)

“Outside the hypothalamic-pituitary-thyroid axis, the major regulator of thyroid hormone production is the concentration of thyroid hormone globulin (TBG). Circulating T₄ is almost entirely (99%) bound to plasma proteins: approximately 70% bound to TBG, 20% to transthyretin (prealbumin), and 10% to albumin.”

Endocrine Disturbances Affecting Reproduction, Alice Y. Chang, Richard J Auchus, in Yen & Jaffe's Reproductive Endocrinology (Sixth Edition), 2009, viewable at (ScienceDirect/Thyroid Follicle)

My “Thyroglobulin antibodies” were elevated - so I may be autoimmune attacking the TBG too.

Transthyretin (TRR or prealbumin) is also involved with the transport of retinol to the liver for activation into Retinoic Acid or other retinoids. (Brave AI Summary) Loss of TRR in knockout mice causes rapid loss of Retinol Binding Protein (RBP) in the urine - which would likely mean the mice/patient would have insufficient vitamin A or activated retinoids for optimal health. (Newcomer and Ong, 2000-2013)

“Whether vitamin A is to be ultimately utilized as retinoic acid, 11-cis-retinal or another retinoid, [retinol binding protein] RBP delivers only all-trans-retinol, and only retinol can trigger secretion of RBP.⁴ In the plasma, RBP binds to the larger protein, transthyretin (TTR, previously referred to as thyroxine binding prealbumin). The binding of RBP to TTR was suggested to prevent extensive loss of the low molecular weight RBP through glomerular filtration.³ This hypothesis was supported by the much later experiments of Blaner and colleagues with TTR “knockout” mice that demonstrate that RBP is rapidly clearly from the plasma in TTR deficient mice.^11” (Newcomer and Ong, 2000-2013)

Autoimmune antibodies against transthyretin (prealbumin) may be involved in Rheumatoid arthritis (Sharma, et al, 2014, retracted for a data image questions) and Juvenile Rh. arthritis. (Clement, et al., 2016) Rh. arthritis is considered an autoimmune disease but may also have an intracellular pathogen as a causal factor. (Lida Mattman/Stealth Pathogen) I am having early symptoms of Rh. arthritis in my thumbs and toes but I haven’t seen the doctor about it.

Albumin - egg white, can also be an autoimmune antibody concern. Antibodies against human or bovine albumin have been associated with presence and severity of SLE, an autoimmune disease also known as Lupus. (Nehring, et al., 2018) Auto-antibodies against albumin has also been observed in chronic liver disease and was associated with severity of chronic hepatitis. (Lenkai, et al., 1981) Treatment with interferon is linked to formation of auto-antibodies in chronic hepatitis and greater oxidative stress is likely causal in more auto-antibody formation in liver disease. They are common in liver disease even when it is not called autoimmune liver disease. (Himoto and Nishioka, 2013)

Brave AI really flubbed on that question - It said albumin didn’t appear to have a causal role in multiple autoimmune conditions based on the search results, which included those in previous paragraph. (summary) And the subpoints it shared are not unexpected. A higher albumin level would likely support a better immune response (Jang, et al., 2018) as it is also an indicator of the person being a healthier/less frail patient. the other subpoint - low albumin level is associated with more severe myasthenia gravis (MG) - also not unusual - sicker/frailer people tend to have lower albumin levels. (Weng, et al., 2016)

The symptoms of Lupus are vague enough that I do fit within them and hair loss is one of them. Sun sensitivity skin rashes or reddening of the face is common - a ‘butterfly rash’ over the cheeks and nose - I don’t have that but my sun-exposed neckline is reddened and rashy and has a few tiny shingles; and Raynaud’s - cold/blue fingertip symptoms. I have tingling LongCovid or B12 deficiency type finger symptoms, mild, not a severe pain level - which I had when off of medical marijuana for a while in 2020 when traveling. (SLE symptoms, Brave AI)

I napped today (Thursday). I have been generally fatigued this summer and overdid it once or twice trying to get things done in my old style. A moderate pace is not my style but that is what is needed to reduce the risk of inflammatory myokine excess. Myokines are like cytokines except they are produced by muscles during exercise. Some are good, but an excess would be like oxidative stress - a problem the body has to cope with or it leads to worse inflammation.

Autoimmune disease is a puzzle. My goal - Six months of strict avoidance of a triggering protein can reduce the antibody flair up. Continue to avoid it after that though, no little tastes or binges later. The memory B cells would remain active, ready to make more antibodies if the protein was present again.

Knowledge is power, but it has to be put in action - practiced in daily routine.

Uh, oh, no eyebrows. Or eyelashes. And allergy/adrenal fatigue dark rings under my eyes. Need a suntan? Not really, I have been burning too easily and currently have a bit of sunburn pox on my neck.

Yes, it is weird to not have eyelashes and eyebrows. I use eyebrow makeup sometimes but adding anything artificial to my sore eyelids is not in my plans.

I shared the thyroid labs in a previous post. (Ginger…Substack) Excerpt - The autoimmune thyroid panel is not looking good, however.

• TSH - 14.43 High (Normal range: 0.40-4.50 mIU/L)

• T4 free is low normal at 0.8, range 0.8-1.8 ng/dL

• T3 free is also low normal at 2.5, range 2.3-4.2 pg/mL

• T3 Reverse is Pending

• Thyroglobulin antibodies - 61 High, anything equal to or over 1 is high.

• Thyroid Peroxidase antibodies - 836 High, over 9 IU/mL is high

Thyroid follicular cells are the main cell type in the thyroid and they make the enzyme thyroperoxidase and thyroglobulin which is involved in thyroid hormone production (Brave AI summary, excerpt below) but thyroglobulin is different from the thyroid binding protein, also called the thyroxine binding globulin, (TBG) or thyroid hormone globulin, (TBG), which is made in the liver. (different question, Brave AI Summary) So my immune system is making antibodies against the proteins being made by the thyroid follicular cells - the thyroglobulin and thyroid peroxidase - but the T3 and T4 levels were in the low normal range - a little more towards hypothyroid - which I had been feeling and had added seaweed back to my diet and then high dose iodine again (Iodoral, 12.5 mg). My blood albumin level was tested with the CBC panel and it was okay.

Thyroid Follicular Cells’ Interaction with Albumin

• Thyroid follicular cells take up iodide and amino acids from the blood circulation on their basolateral side.

• They synthesize thyroglobulin and thyroperoxidase, which are then secreted into the follicular lumen along with iodide.

• The follicular cells subsequently take up iodinated thyroglobulin by endocytosis, extract thyroid hormones from it, and release them into the bloodstream.

• Albumin is involved in the transport of thyroid hormones produced by the follicular cells, carrying them away from the thyroid gland and delivering them to target tissues. (Brave AI summary)

What does all that have to do with hair follicles? …. plenty. Thyroid stimulating hormone can affect hair follicle stem cell growth and T3 thyroid hormone has regulatory function over hair growth - lack of T3 is going to lead to a lack of hair growth. (excerpt below, Brave AI summary)

Thyroid Hormone Regulation of Hair Follicle Stem Cell Dynamics

Based on the provided search results, thyroid hormones (T3) regulate hair follicle biology and stem cell function through several mechanisms:

1. Epigenetic alterations: T3 deficiency leads to epigenetic changes in bulge stem cells, including aberrant activation of Smad signaling and reduced nuclear activity (Contreras-Jurado et al., 2015).

2. BMP-Smad signaling: Excessive BMP-Smad signaling, triggered by T3 deficiency, contributes to reduced stem cell proliferation (Contreras-Jurado et al., 2015).

3. Wnt/β-catenin signaling: T3 regulates Wnt/β-catenin signaling, which is essential for stem cell maintenance and hair follicle homeostasis (Ruiz-Llorente et al., 2018).

4. Nuclear thyroid hormone receptors (TRs): TRs directly regulate the expression of microRNAs with key roles in skin homeostasis, including those involved in hair follicle development and maintenance (Ruiz-Llorente et al., 2018).

5. Cellular quiescence: T3 regulates the balance between stem cell quiescence and activation, with excessive signaling leading to exhaustion of the stem cell reservoir (Contreras-Jurado et al., 2015).

6. Epigenetic profile: Quiescent stem cells in the hair follicle bulge are enriched in H3K9me3, which is regulated by T3 (Frye et al., 2007).

7. Thyroid hormone receptor-mediated transcriptional regulation: TRs regulate the expression of genes involved in hair follicle development, maintenance, and cycling, including those involved in stem cell self-renewal and differentiation (Takeda et al., 2013). (Brave AI summary)

A microRNA, miR-218-5p, has been identified that promotes hair follicle growth:

Based on the provided search results, the following microRNAs are associated with hair follicle development and maintenance:

1. miR-218-5p: Regulated by T3, miR-218-5p plays a crucial role in promoting hair follicle growth and regeneration. It enhances the molecular pathway responsible for promoting hair follicle growth and could be a candidate for future drug development (North Carolina State University research*). *MicroRNA shows promise for hair regrowth, July 27, 2020, (sciencedaily.com)

   1. The same microRNA, miR-218-5p, may be aberrant in atherosclerosis and arthritis. Upregulation of it occurs during chronic stress (study on rats). (Yoshino, et al., 2022)

2. miR-214: This microRNA modulates the activity of the Wnt pathway, controlling skin and hair follicle development (Ahmed et al., 2014). Although not directly regulated by T3, its involvement in hair follicle development and maintenance is mentioned. (Brave AI Summary)

Also from that search:

• Downregulation of microRNA 31 is related to hair loss with aging, (Zhang and Yi, 2021), and stress can cause upregulation of it and is associated with skin aging. (Yu, et al., 2021)

• ‘Thyroid hormone action in epidermal development and homeostasis and its implications in the pathophysiology of the skin’, Open access, (Mancino, et al., 2021) Alopecia, hair loss and skin conditions of eczema or vitiligo (melanin loss - albino white skin patches) are associated with autoimmune thyroid conditions.

• ‘Thyroid hormones directly alter human hair follicle functions: anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation’. (van Beek, et al., 2008)

“The skin of hyperthyroid patients is dry and thinner than the skin of euthyroid subjects, as well as patients frequently experience flushing of the face, erythema of the palms and hyperhidrosis of the palms and soles (Tables 1 and 2) [46]. The skin in hypothyroid subjects, caused by Hashimoto’s thyroiditis or congenital hypothyroidism in pediatric population, appears thicker, colder and has classical myxoedema respect a euthyroid subjects (Tables 1 and 2).” (Mancino, et al., 2021)

*Myxoedema: “non-pitting edema caused by increased deposition of mucopolysaccharides in the skin” - Wikipedia

The term “myxedema” can mean severely advanced hypothyroidism. But it’s also used to describe skin changes in someone with severely advanced hypothyroidism. The classic skin changes are:

• swelling of your face, which can include your lips, eyelids, and tongue

• swelling and thickening of skin anywhere on your body, especially in your lower legs. (Healthline)

“The most widely accepted hypothesis explaining the wide variety of cases in which skin diseases are associated with chronic autoimmune thyroiditis is the autoimmune hypothesis, which argues that thyroid antibodies as thyroglobulin (TgAb) and thyroperoxidase (TPOAb), are among the serum autoantibodies that react with and destroy melanocytes [48]. A fascinating hypothesis by Li et al., [52] proposes that, autoantibodies such as TgAb and TPOAb can induce a sustained oxidative stress, which in turn can result in enhanced apoptosis and senescence of melanocytes [52].” (Mancino, et al., 2021)

Plant polyphenols or other phytonutrients can be a solution to varied health issues

The nice thing about plant polyphenols or other phytonutrients and microRNA modulation is that they tend to up or down regulate as needed - when present in therapeutic amounts, too much can be an irritant or may ecom Plants intuitively are designed to react very quickly to changes in the weather, to prevent cell damage from extremes of temperature or sun, and changes in microRNA can rapidly lead to big changes in what the cells are doing. Oxidative stress is the negative signaling ~ “too hot”, “too cold”, “too sunny”, “too dark”, and the plant responds somehow to reduce the negative inputs from the environment. Flowers or leaves may open or close or turn in response to the sun or temperature changes. How does the plant “know”? Chemicals react or they don’t react based on environmental inputs of temperature or solar UV radiation.

“Using transgenic and conditional knockout mouse models plus a lineage-tracing technique, we show that miR-31 acts as a key driver of HFSC aging by directly targeting Clock, a core circadian clock gene whose deregulation activates a MAPK/ERK cascade to induce HFSC depletion via transepidermal elimination.” (Yu, et al., 2021)

From my pomegranate paper, I know that pomegranate/peel would be helpful for inhibiting a MAPK cascade:

Mitogen-activated protein kinase (MAPK) is inhibited by phytonutrients in pomegranate peel extract (PPE) by the regulation of Fox03, which would decrease unwanted phosphorylation of proteins, observed in an animal-based study in which PPE reduced ototoxicity caused by amikacin (AMK). (Liu, et al, 2017) Ototoxicity, damage to Hair cells within the inner ear, is associated with certain medications like amikacin and also seems to be caused by CoV/chimeric spike subunit S1 disrupting ankyrin binding domains of TRP channels in the Hair cells. (Liviero, et al, 2021)

• ‘Pomegranate Products for the Pain of Histamine Excess.’ copyright Jennifer Depew, RD (Pom pdf in my sync file)

Other microRNA involved in the MAPK pathway

MAPK signaling is aberrant in myeloid leukemia, a review article looked at the microRNA that are involved in the MAPK pathway. (Chakraborty, et al., 2016)

“Several miRNAs play regulatory role in MAPK1 expression, of which, miR-17 and miR-19a can directly regulate the MAPK1.” […] “Several miRNAs play significant role in the MAPK signaling pathway and among them, the following miR-203, miR-196b, miR-29b, miR-30a, miR-138, miR-155, miR-19a, miR-17, miR-126, miR-128, miR-221, miR-15a, miR-188-5p and miR-181a are well studied (Table ​(Table1,1, ​,2)2) [39].” (Chakraborty, et al., 2016)

»> Daily reminder that pomegranate peel/extract is VERY effective against cancer, and against cancer metastasis in particular. It is also helpful for autoimmune conditions, is a broad spectrum antimicrobial while also promoting beneficial species (eat the inner pith for the benefit of pectin, rather than only using an extract is my synergistic tip) and it helps in many, many other health conditions as well as being effective as a mouthwash/tooth brushing substitute, (seriously, and isn’t that cool?)

I think pomegranate and its peel has a variety of phytonutrients that can modulate microRNA as needed to reduce oxidative stress and restore normal cell functions - as needed situationally. That is the magic of nature - let the phytonutrients modulate as needed to adjust to the environment they find themselves in. That makes our job to be eating the plants or extracts, so the nature magic can happen for us. Pomegranate will be in season in the US growing areas soon!

MicroRNA and hair follicles: (Brave AI summary) *I think this is linked earlier too, but I will leave it here.

Switching lab sections - do I have VAIDS? or Micro-clotting? - it seems not too bad yet.

My D-Dimer level is slightly elevated at 0.55, range below 0.50. That was an additional lab I ordered as a stand alone. It may be an early indication of microclotting within my blood vessels ~ potentially related to chimeric spike issues.

The T cell and B cell panel included Absolute CD19+ - 238, range 110-660 cells/uL; % CD19 (B cells) - 14, range 6-29%; Absolute CD3+ - 1275, range 840-3060 cells/uL; % CD3 (Mature…) - 74, range 57-85%.

I don’t know enough about the T and B cell counts. Is being towards the lower end of the range a bad thing? - lower immune function? Or would be being towards the higher end of the range be a bad thing — indicating an infection is being fought? Regarding diagnosis of VAIDS, not having enough of the cells is the concern, so my being towards the low end of the range is maybe not a great thing. My sunshine, less stress - but not too much sunshine either, I’m a little sun sensitive lately.

Platitude: Today is a present to open with glee. Moving forward is the goal. I also have a baseline lab value now for my immune cells.

The lymphocyte panel looks normal, no infection or outrageous autoimmune excess of white blood cells.

My liver labs and uric acid levels were improved but kidney function had an improvement in my elevated creatinine, 262 dropped to 182, range 29-143. That can be a sign of muscle breakdown or tissue damage - or thyroid dysfunction, more on that is next.

Elevated creatinine and reduced kidney filtration is seen with low thyroid function

…in Hashimoto’s thyroiditis (hypothyroid typically but can fluctuate between high or low levels of thyroid hormone) or increased filtration and low creatinine was seen in Grave’s disease (a hyperthyroid condition).

The findings in the excerpt below, would suggest that I am functionally more hypothyroid currently than hyperthyroid, as my creatinine is elevated and my filtration reduced. I have had active Grave’s disease in the past ~ 2012/2013. More recently I had been feeling hypothyroid and increased my use of iodine rich foods and then added a high dose iodine supplement (Iodoral - 12.5 mg/day) and it seems to have helped. Trying a month of a loading dose (50 mg) might be worth trying to clear fluoride and bromide.

Case study: “Our patients demonstrate a remarkable effect of thyroid function on glomerular filtration rate.

• The creatinine clearance of the patient with hyperthyroidism was doubled,

• while the creatinine clearance of the hypothyroid patient was halved.

Both patients were treated, the hyperthyroid patient with β blockade and methimazole, and the hypothyroid patient with thyroid hormone. After several months, the creatinine clearance of both patients had returned to normal.” (Claus, et al., 2005) *Reformatting emphasis added by me.

My creatinine level might also be more elevated because I have been supplementing with creatine now, about 5 mg once or twice a day. Creatine is used in the muscles and creatinine is the breakdown product which is excreted by the kidneys. (Brave AI summary)

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

Reference List

(Chakraborty, et al., 2016) Chakraborty C, Sharma AR, Patra BC, Bhattacharya M, Sharma G, Lee SS. MicroRNAs mediated regulation of MAPK signaling pathways in chronic myeloid leukemia. Oncotarget. 2016 Jul 5;7(27):42683-42697. doi: 10.18632/oncotarget.7977. PMID: 26967056; PMCID: PMC5173166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173166/

(Claus, et al., 2005) Theresa Claus, Saban Elitok, Roland Schmitt, Friedrich C. Luft, Ralph Kettritz, Thyroid function and glomerular filtration—a potential for Grave errors, Nephrology Dialysis Transplantation, Volume 20, Issue 5, May 2005, Pages 1002–1003, https://doi.org/10.1093/ndt/gfh708 https://academic.oup.com/ndt/article/20/5/1002/1852139

(Clement, et al., 2016) Clement CC, Moncrieffe H, Lele A, Janow G, Becerra A, Bauli F, Saad FA, Perino G, Montagna C, Cobelli N, Hardin J, Stern LJ, Ilowite N, Porcelli SA, Santambrogio L. Autoimmune response to transthyretin in juvenile idiopathic arthritis. JCI Insight. 2016 Feb;1(2):e85633. doi: 10.1172/jci.insight.85633. Epub 2016 Feb 25. PMID: 26973882; PMCID: PMC4784708. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784708/

(Dreskin, et al., 2020) Dreskin SC, Koppelman SJ, Andorf S, Nadeau KC, Kalra A, Braun W, Negi SS, Chen X, Schein CH. The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds. J Allergy Clin Immunol. 2021 Apr;147(4):1154-1163. doi: 10.1016/j.jaci.2020.11.004. Epub 2020 Nov 18. PMID: 33217410; PMCID: PMC8035160. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035160/

(Himoto and Nishioka, 2013) Himoto T, Nishioka M. Autoantibodies in liver disease: important clues for the diagnosis, disease activity and prognosis. Auto Immun Highlights. 2013 Feb 22;4(2):39-53. doi: 10.1007/s13317-013-0046-7. PMID: 26000142; PMCID: PMC4389052. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389052/

(Jang, et al., 2018) Jang, Y., Lee, ST., Kim, TJ. et al. High albumin level is a predictor of favorable response to immunotherapy in autoimmune encephalitis. Sci Rep 8, 1012 (2018). https://doi.org/10.1038/s41598-018-19490-z https://www.nature.com/articles/s41598-018-19490-z

(Jung, et al., 2024) Jung, SW., Jeon, J.J., Kim, Y.H. et al. Long-term risk of autoimmune diseases after mRNA-based SARS-CoV2 vaccination in a Korean, nationwide, population-based cohort study. Nat Commun 15, 6181 (2024). https://doi.org/10.1038/s41467-024-50656-8 https://www.nature.com/articles/s41467-024-50656-8

(Lenkai, et al., 1981) Lenkei R, Buligescu L, Belascu I, Pospai D, Dobre I. Anti-albumin antibodies in chronic liver diseases: diagnostic significance of these antibodies in patients with conventional or immunosuppressive therapy. Clin Exp Immunol. 1981 Feb;43(2):381-9. PMID: 6974071; PMCID: PMC1537282. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1537282/

(Liu, et al, 2017) Liu, S., Zhang, X., Sun, M., Xu, T., Wang, A., (2017). ‘FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity’. Int J Mol Med. Jul;40(1):175-181. doi: 10.3892/ijmm.2017.3003. Epub 2017 May 26. PMID: 28560451; PMCID: PMC5466397. Available at: https://www.spandidos-publications.com/10.3892/ijmm.2017.3003 (Accessed: 26 October 2022)

(Liviero, et al, 2021) Liviero, F., Campisi, M., Mason, P., Pavanello, S., (2021). ‘Transient Receptor Potential Vanilloid Subtype 1: Potential Role in Infection, Susceptibility, Symptoms and Treatment of COVID-19’. Front Med (Lausanne). Nov 4;8:753819. doi: 10.3389/fmed.2021.753819. PMID: 34805220; PMCID: PMC8599155. Available at:  https://www.frontiersin.org/articles/10.3389/fmed.2021.753819/full (Accessed: 27 October 2022)

(Mancino, et al., 2021) Mancino, G., Miro, C., Di Cicco, E. et al. Thyroid hormone action in epidermal development and homeostasis and its implications in the pathophysiology of the skin. J Endocrinol Invest 44, 1571–1579 (2021). https://doi.org/10.1007/s40618-020-01492-2 https://link.springer.com/article/10.1007/s40618-020-01492-2

(Mandalari, et al., 2018) Mandalari G, Mackie AR. Almond Allergy: An Overview on Prevalence, Thresholds, Regulations and Allergen Detection. Nutrients. 2018 Nov 8;10(11):1706. doi: 10.3390/nu10111706. PMID: 30412996; PMCID: PMC6266711. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266711/

(Milenkovic, et al., 2021) Milenkovic D, Ruskovska T, Rodriguez-Mateos A, Heiss C. Polyphenols Could Prevent SARS-CoV-2 Infection by Modulating the Expression of miRNAs in the Host Cells. Aging Dis. 2021 Aug 1;12(5):1169-1182. doi: 10.14336/AD.2021.0223. PMID: 34341700; PMCID: PMC8279534. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279534/

(Nehring, et al., 2018) Nehring, J., Schirmbeck, L.A., Friebus-Kardash, J., Dubler, D., Huynh-Do, U., Chizzolini, C., Ribi, C., Trendelenburg, M., Autoantibodies Against Albumin in Patients With Systemic Lupus Erythematosus, Frontiers in Immunology, Vol 9, 2018, DOI=10.3389/fimmu.2018.02090 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02090

(Newcomer and Ong, 2000-2013) Newcomer ME, Ong DE. Retinol Binding Protein and Its Interaction with Transthyretin. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6223/

(Sharma, et al., 2011) Sharma GM, Irsigler A, Dhanarajan P, Ayuso R, Bardina L, Sampson HA, Roux KH, Sathe SK. Cloning and characterization of 2S albumin, Car i 1, a major allergen in pecan. J Agric Food Chem. 2011 Apr 27;59(8):4130-9. doi: 10.1021/jf104319d. Epub 2011 Mar 11. PMID: 21395309. https://pubmed.ncbi.nlm.nih.gov/21395309/

(Sharma, et al, 2014, retracted for a data image questions) Sharma S, Ghosh S, Singh LK, Sarkar A, Malhotra R, Garg OP, Singh Y, Sharma RS, Bhakuni DS, Das TK, Biswas S. Identification of autoantibodies against transthyretin for the screening and diagnosis of rheumatoid arthritis. PLoS One. 2014 Apr 8;9(4):e93905. doi: 10.1371/journal.pone.0093905. Retraction in: PLoS One. 2018 Oct 11;13(10):e0205914. doi: 10.1371/journal.pone.0205914. PMID: 24714506; PMCID: PMC3979706. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093905

(van Beek, et al., 2008) van Beek N, Bodó E, Kromminga A, Gáspár E, Meyer K, Zmijewski MA, Slominski A, Wenzel BE, Paus R. Thyroid hormones directly alter human hair follicle functions: anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation. J Clin Endocrinol Metab. 2008 Nov;93(11):4381-8. doi: 10.1210/jc.2008-0283. Epub 2008 Aug 26. PMID: 18728176. https://pubmed.ncbi.nlm.nih.gov/18728176/

(Weng, et al., 2016) Weng YY, Yang DH, Qian MZ, Wei MM, Yin F, Li J, Li X, Chen Y, Ding ZN, He YB, Zhang X. Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis. Medicine (Baltimore). 2016 Sep;95(39):e5000. doi: 10.1097/MD.0000000000005000. PMID: 27684858; PMCID: PMC5265951. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265951/

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Series on BDNF: (Part 1 niacin, butyrate, EGCG and BDNF) (Part 2 exercise & butyrate producing microbes) (Part 3 kynurenine pathway, tryptophan, butyrate producing microbes and peaceful thinking) (This post, Pomegranate peel, ALCAR & BDNF, Part 4)

This post doesn’t get into boron and magnesium in detail - but a list is included at the end.

A reply had suggested I look up ALCAR, boron and magnesium and the ALCAR link set me off on a pomegranate peel tangent. At the very end of this post is a link to a nice blog article which lists 31 research-based things that promote BDNF and magnesium is included in that article. I list the items at the end of this post and I added a reference with some dosing guidance regarding boron and ALCAR.

No speculation is needed about the use of pomegranate peel for increasing BDNF.

Levels of BDNF increased in a study on Alzheimer’s dementia risk. The experimental group of mice were given “PPE, 800 mg/kg/day,” as the experimental treatment against amyloid beta infusion. The PPE treated group and the control group of mice were able to find their way out of an escape box, while the amyloid beta treated mice that didn’t receive Pomegranate peel extract didn’t find their way out. (Morzelle, et al., 2016)

How much pomegranate peel extract to use per day?

~ 1 1/2 teaspoons to 1 or 2 tablespoons in divided doses possibly - drink extra water and have it earlier in the day rather than at bedtime (it’s a diuretic).

Later in this post I do the math for an approximate human dosing equivalent and the results ~ about 2 tablespoons might provide 800 mg/70kg average human/day. I also discuss the edibility and cautions and link to some How-to prepare pages.

“To this end, here we demonstrate the effects of pomegranate (Punica granatum) peel extract (PPE) regarding spatial memory, biomarkers of neuroplasticity, oxidative stress and inflammation in a mouse model of neurodegeneration. Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1–42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.– βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group. The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE.” (Morzelle, et al., 2016)

What is neurotrophin BDNF and what are its functions?

- brain cell support & it activates tyrosine receptor kinase B.

“The second discovered neurotrophin in CNS, brain-derived neurotrophic factor (BDNF) is highly expressed and widely distributed in the brain [17], [18]. It provides trophic support to neurons and plays a crucial role in various neurodevelopmental processes, such as development, maintenance and survival of the nervous system, synaptic plasticity and cognitive function [17], [18], [19], [20], [21]. (Kazak and Yarim, 2017)

What pathways are activated by TRKb? - MAPK, PLC gamma, and PI3K.

Brain-derived neurotrophic factor demonstrates these functions by binding its receptor (tyrosine receptor kinase B), [(TrkB)],

• and activating the mitogen-activated protein kinase, [(MAPK)],

• the phospholipase C gamma, [(PLC gamma)].

• and the phosphatidylinositol 3-kinase pathways [(PI3K)] (19).

Based on these functions, researchers have proposed that dysregulation of BDNF signaling leads to the onset of neurodegenerative diseases and neuropsychiatric disorders [22], [23], [24], [25].” (Kazak and Yarim, 2017)

Pomegranate peel extract also helps those pathways. In the following animal model of atherosclerosis, TNF alpha levels were reduced and IL-10 increased in the PPE treated group.

Pomegranate peel extract (200 mg/kg dose) studied in an atherosclerosis animal-based model was found to decrease levels of TNF-alpha (G in the Figure below) and increase levels of cytokine IL-10 quite a bit [*IL-10 is beneficial for T-cell immunity and is generally anti-inflammatory (Gorby, et al., 2020)] (the H is missing in the graphic excerpted below). Blood lipid levels improved (D and E) and body weight decreased in the graphic below (F), click through to see the other lab values that were measured. (FIGURE 1, Manickam, et al., 2022)

Inhibition of NMDA receptors has also been found to improve BDNF levels in the brain, (Tanqueiro, et al., 2018), which adds further support to my pomegranate, niacin/butyrate graphic - inhibiting NFkB (and TNF alpha) helps prevent degranulation of mast cells, prevent over activation of NMDA receptors and prevent the gradual destruction of the hippocampus.

Pomegranate peel extract Dosing math

For dietary equivalents, let’s do the math from that second mouse study: 200 mg/kg body weight of pomegranate peel extract (Manickam, et al., 2022) would be 0.2 grams times ~ 70 Kg human = 14 grams of pomegranate peel extract per day (about 3 teaspoons) - to greatly improve atherosclerosis risk, blood lipids and reduce weight (in rodents). That would be approximately three teaspoons, which divided over the day would not be an unreasonable amount to take, BUT it would be at a diuretic level. So, have it earlier in the day and drink some extra non-caffeinated beverage too (like water or herbal tea - non-calorie is generally a better beverage choice).

This dosing info supports my premise that we should view pomegranate peel as a functional food, rather than as a 200 mg capsule product.

The dosing math as a percent of total daily food intake:

Two hundred milligrams per kilogram for a mouse sized mammal… is more of a macro-food dose, rather than a trace nutrient. An average lab mouse weighs ~ 30 grams, one ounce. (Kinaneh, et al., 2018) 200/1000 = x/30 200 = 1000x/30 200*30/1000 = x x = 6 mg, the amount the mice received. Lab mice tend to eat about 23 grams of food per day, or almost double that during early rapid growth weeks. (Kinaneh, et al., 2018) That means they were given 0.26% of their daily intake as pomegranate peel extract.

Humans vary in the nutrient density of their food choices - celery provides bulk without calories compared to dried nuts or a marbled cut of beef. Salad with low calorie salad dressing would add bulk without calories. But … we might average an intake of 3-6 pounds of food per day (Brave AI Summary) - multiplied by 0.26% we arrive at 7 grams of pomegranate peel extract as a potentially comparable dose - about two teaspoons per day.

The first mouse study on Alzheimer’s dementia risk used four times as much - 800 mg/kg, which would be 4 times ~ 7-14 grams, or 28-56 grams, and that is a lot - 1 to 2 ounces, which I probably have used - one or two tablespoons a couple times a day would provide that amount. But I think we need some human trials for tolerance in addition to measuring lab values.

*And/or plan on a dietary and nursing care plan for dehydration prevention or treatment. Drinking extra fluids and having adequate potassium and salt and magnesium is important with a diuretic. It can help with detox and lymphatic flow. Detox benefits for smog and lung health too: later in the post there is a section on nanoparticles and the benefits of pomegranate for clearing particulate matter smaller than 10 micromoles (PM10).

Bonus: Pomegranate peel extract also tends to reduce appetite and improve leptin and insulin resistance.

Why I recommend buying pomegranate and processing your own peel - cost and ability to separate the outer and inner peel.

People ask me about good ‘supplement products’ to buy and I hesitate to support any versus buying the whole fruit in season (but I have mentioned that Dr. Mercola has one that I have heard is helpful).

Any capsule product is likely going to be a minimal dose, or a dose to use several times a day if you are actively trying to treat something rather than just for preventive health goals. And taking several capsules per day of a product that can easily cost $1 per capsule is going to add up fast compared to buying pomegranate in season and freezing or drying the peel. I strongly encourage that method as you can separate the outer and inner peel to use in different ways. The outer rind is too high in tannins to use as a functional food as the diuretic potential and bitter taste are so great. The inner pith is higher in pectin which provides additional health benefits and the tannin concentration is lower.

Several house mice and I agree - the inner pith of pomegranate is edible, the outer rind is an insect proof barrier to the good stuff within. House mice will also choose pomegranate over other available fruit (but they eat most anything ;-).

Inner pith dosing - about 1/4 to 1/2 teaspoon fresh, minced is what I have come to consider a single serving, and I might have that 1-3 times a day or slightly more, but too much more is a negative. I have learned that cookies are not a good choice for a functional food ingredient - too likely to overeat compared to bean soup. I use about 2 tablespoons minced inner pith in a two-to-three-quart batch of soup or 24 muffin batch of quick bread. See effectivecare.info for a few recipes on page G13. Pomegranate and G10. Nrf2 Promoting Foods. (*Which are basically the same foods and spices as SIRT1 promoting foods which had become part of a trendy “SIRT food” weight loss diet, a few years back - Brave AI gives it a not well-researched and may be low protein and other nutrients - I would agree based on a knockoff diet book I saw. Also high oxalate would be likely.)

Tangent into benefits of Pomegranate peel extract (PPE) for nanoparticulates in air.

Use of pomegranate peel extract helps monocytes to clean up the nanoparticles, otherwise nanoparticles are ignored due to being too small. Pomegranate phytonutrients helps clump nano-sized things (PM10 < 10 micrometers) into a larger cluster including heavy metals and other toxins found in smog or smoke.

*TNF alpha was also reduced - leading to my finding the search result.

In the image below, compare the dots on black images - the first is the Control, second is exposure to PM10 particulate matter, third is the same PM10 particulate exposure but with Pomegranate peel extract too. It visibly helped a lot - but it was still better to not be exposed to the equivalent of smog though (control image). (Park, et al., 2016)

PM10 = particulate matter smaller than 10 micrometers

“Particulate matter is known to cause airway epithelium injury and endothelial dysfunction [4, 5]. Larger particles can be filtered in the nose and throat via cilia and mucus, but particulate matter smaller than 10 micrometers (PM10) can enter the deepest parts of the lungs, such as the bronchioles and alveoli [6]. PM10 may cause severe effects on human health due to the broad range of miscellaneous toxic compounds present in this particulate matter fraction, such as transition metals, endotoxins, and ultrafine components. The mechanism of action of PM10 may include the induction of oxidative stress and activation of nuclear factor kappa B (NF-κB) pathway, leading to inflammation [7]. PM10 increases the production of reactive oxygen species (ROS) and cytokines in human and rat alveolar macrophages [8]. In addition, PM10-induced inflammation is attenuated by antioxidants from plant sources [9–11].” (Park, et al., 2016)

Pomegranate peel is a censored topic because it is not bannable, inexpensive, and quite effective with minimal risk. Cautions: salicylate/phenols, oxalate, and the diuretic tannins may lead to side effect symptoms if pomegranate peel/extract is used in excess or by people with increased sensitivity. As someone with genetically poor clearance of phenols, I can use too much if I am not watching portion sizes but the 1/4-1/2 teaspoon dose once or a few times a day generally is not too much for me.

Skullcap, a source of baicalin, has become a tea herb that I use regularly. It also increases BDNF levels. (Li, et al., 2021)

Nutshell: basically, my entire list of Nrf2 promoting phytonutrients/foods, is also a list of substances that help increase BDNF and they would also help tryptophan to be made into serotonin instead of it being directed down the kynurenine pathway. I’m late to the BDNF party, but I had been in the neighborhood with my work on the inhibitors of NFkB and TNF alpha being the same things that promote Nrf2 - and BDNF.

See this helpful article for more herbs and nutrients that help increase levels of brain cell supporting BDNF, and yes, exercise is mentioned too:

• 31 Proven Ways to Increase BDNF, Your Brain's Growth Hormone,

  February 4, 2024, Jordan Fallis, (optimallivingdynamics.com) *Click through for his free downloadable grocery shopping guide.

1. Coffee fruit extract

2. Curcumin

3. Green Tea [and pomegranate peel/extract, powdered Sumac, or goji berries]

4. Omega 3 fatty acids

5. Resveratrol

6. Prebiotics and Resistant Starch

7. Magnesium

8. Lithium orotate [5 mg is a low dose used for health support rather than the higher dosing used in psychiatric care.]

9. Dark chocolate

10. N-acetyl-cysteine [600 mg is recommended as a preventive health dose - an excess may inhibit methylation cycles. If actively sick, take more frequent dosing to add more to the daily intake. It is plentiful in animal and plant protein foods, so getting adequate protein generally leads to having a good intake of cysteine too.]

11. Theanine

12. Adaptogenic herbs “Rhodiola, bacopa and ginseng are the three main herbs I have used to increase BDNF and support my brain function.

    But there are several other herbs that have been shown to increase BDNF, including baicalin (Skullcap), ashwagandha, gotu kola, and magnolia officinalis (81-84).”

13. Zinc

14. Blueberries

15. Progesterone

16. Dehydroepiandrosterone (DHEA) - [*Men can use a higher dose than females (25-75 mg maybe), females should stick to a lower dose (5-25 mg, or use 7-keto DHEA) as it can be turned into testosterone.]

17. Quercetin

18. Coffee and caffeine

19. Niacin [*The flush type is the one that helps the most. Niacinamide is a less bioactive form but is the standard form in mixed supplements now.]

20. Extra virgin olive oil

21. Taurine

22. Saffron

23. Exercise “Lift heavy weights 1-4 times per week
    •    High-intensity interval sprinting 1-2 times per week
    •    Walk as much as you can (ideally 30-60 minutes every day)”

24. Sunlight [Dawn or early morning light helps get our circadian cycle switched to day mode and then more sunshine later in the day helps us make vitamin D and other nutrients related to sunshine (sulfur compounds and vitamin A have sunshine related metabolism).]

25. Intermittent Fasting

26. Avoid Processed Food and Refined Sugar

27. Lose fat

28. Socialize

29. Deep sleep

30. Neurofeedback/meditation/reduce stress;

31. Ketogenic Diet/or occasional ketosis from intermittent fasting

    1. List by: Jordan Fallis, (optimallivingdynamics.com)

32. Boron - 160 mg/L helped ostrich chick brain development but 640 mg/L was too much and caused worse development. (Tang, et al., 2016) Boron has a narrow safety range. I have exceeded it with ~ 3 tbs of Borox in my bath weekly for one month. An excess causes hand cramping that just does not stop - disabling muscle cramping - you can’t move your hand normally. I switched to a trace mineral supplement with 3 mg/day which is the recommended intake goal.

33. ALCAR / N-acetyl-carnitine - 100 mg/kg/day was more helpful than a higher 300 mg/kg/day dose (animal based study); Abstract below. (Kazak and Yarim, 2017)

34. Butyrate

Abstract:

Neuroinflammation is the inflammation of nervous tissue that can lead to neurodegeneration. Brain-derived neurotrophic factor (BDNF) is a neurotrophin which affects growth, function and survival of neurons, enhances the stabilization of synapses, regulates synaptic function and branching of dendrites and axons. Brain-derived neurotrophic factor is believed to be involved in the pathophysiology of central nervous system (CNS) diseases associated with neuroinflamation.

The aim of this study was to investigate new protective and therapeutic effect of acetyl-l-carnitine (ALCAR) in neuroinflammation. Acetyl-l-carnitine was administered into Swiss Albino mice as 100mg/kg/day and 300mg/kg/day for 5days. Neuroinflammation was induced by lipopolysaccharide (LPS). Histopathological findings associated with ALCAR administration on neuroinflammation in the brain were determined. Moreover, the effects of ALCAR on BDNF concentration in the brain tissue was evaluated. The LPS administration showed higher microglial activation in the brain of LPS, 100A+LPS and 300A+LPS groups compared to that in the control (p<0.05). In the 100A+LPS group, microglial activation was lower and BDNF concentration was higher than in the 300A+LPS group (p>0.05).

The findings suggest that the dose of ALCAR at 100mg/kg/day i.p. may have a beneficial effect on LPS-induced neuroinflammation in mice. As a conclusion, ALCAR may be used as an optional neuroprotective and therapeutic agent to attenuate inflammatory damage in the CNS regarding BDNF, in a dose dependent manner. (Kazak and Yarim, 2017)

BDNF series links

1. (Part 1 niacin, butyrate, EGCG and BDNF)

2. (Part 2 exercise & butyrate producing microbes)

3. (Part 3 kynurenine pathway, tryptophan, butyrate producing microbes and peaceful thinking)

Disclaimer: This information is being shared for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

Reference List

(Gorby, et al., 2020) Claire Gorby et al., Engineered IL-10 variants elicit potent immunomodulatory effects at low ligand doses. Sci. Signal. 13, eabc0653(2020). DOI:10.1126/scisignal.abc0653 https://www.science.org/doi/10.1126/scisignal.abc0653

(Kazak and Yarim, 2017) Filiz Kazak, Gul Fatma Yarim, Neuroprotective effects of acetyl-l-carnitine on lipopolysaccharide-induced neuroinflammation in mice: Involvement of brain-derived neurotrophic factor, Neuroscience Letters, Vol 658, 2017, pp 32-36, ISSN 0304-3940, https://doi.org/10.1016/j.neulet.2017.07.059. https://www.sciencedirect.com/science/article/pii/S0304394017306353.

(Kinaneh, et al., 2018) Kinaneh S, Agbaria M, Abu-Saleh N, Hamoud S. Dataset on mice body weights and food intake following treatment with PG545. Data Brief. 2018 Sep 6;20:1305-1308. doi: 10.1016/j.dib.2018.08.179. PMID: 30238043; PMCID: PMC6143748. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143748/

(Li, et al., 2021) Li C, Sui C, Wang W, Yan J, Deng N, Du X, Cheng F, Ma X, Wang X, Wang Q. Baicalin Attenuates Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron-Astrocyte Cocultures. Front Pharmacol. 2021 Jun 21;12:599543. doi: 10.3389/fphar.2021.599543. PMID: 34234667; PMCID: PMC8255628. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255628/

(Manickam, et al., 2022) Manickam V, Dhawan UK, Singh D, Gupta M, Subramanian M. Pomegranate Peel Extract Decreases Plaque Necrosis and Advanced Atherosclerosis Progression in Apoe^-/- Mice. Front Pharmacol. 2022 Jun 1;13:888300. doi: 10.3389/fphar.2022.888300. PMID: 35721222; PMCID: PMC9198482. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198482/

(Morzelle, et al., 2016) Morzelle MC, Salgado JM, Telles M, Mourelle D, Bachiega P, Buck HS, Viel TA. Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice. PLoS One. 2016 Nov 9;11(11):e0166123. doi: 10.1371/journal.pone.0166123. PMID: 27829013; PMCID: PMC5102433. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102433/

(Park, et al., 2016) Park S, Seok JK, Kwak JY, Suh HJ, Kim YM, Boo YC. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evid Based Complement Alternat Med. 2016;2016:6836080. doi: 10.1155/2016/6836080. Epub 2016 May 10. PMID: 27247608; PMCID: PMC4877489. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877489/

(Tang, et al., 2016) Tang J, Zheng XT, Xiao K, Wang KL, Wang J, Wang YX, Wang K, Wang W, Lu S, Yang KL, Sun PP, Khaliq H, Zhong J, Peng KM. Effect of Boric Acid Supplementation on the Expression of BDNF in African Ostrich Chick Brain. Biol Trace Elem Res. 2016 Mar;170(1):208-15. doi: 10.1007/s12011-015-0428-y. Epub 2015 Jul 31. PMID: 26226831. https://link.springer.com/article/10.1007/s12011-015-0428-y

(Tanqueiro, et al., 2018) Tanqueiro SR, Ramalho RM, Rodrigues TM, Lopes LV, Sebastião AM, Diógenes MJ. Inhibition of NMDA Receptors Prevents the Loss of BDNF Function Induced by Amyloid β. Front Pharmacol. 2018 Apr 11;9:237. doi: 10.3389/fphar.2018.00237. PMID: 29695962; PMCID: PMC5904251. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904251/

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My rating system was not 0-10 with 10 being most severe. It was more descriptive of what I felt. My scalp has a specific pain location and MRI imaging found that blood vessels in the area were “tortuous” (Brave AI summary) - an appropriate word I thought. It means the vessels in the area are twisted or convoluted. Injury can be a cause and I was a forceps baby. There has been a bald spot on my head in that area as long as I can remember.

• Is my migraine a pounding needle like spot? - Mild.

• Or a pounding icepick? - Worse.

• Or a pounding steak knife? - Really not good.

• Or was it the pounding railroad spike? - I just don’t want my head anymore.

The conversation on social media was about my having said I was shocked when I learned that people go to the ER for migraines. And I said ~ they just need to be coped with. The ensuing conversation revealed that while I might have gotten more immediate pain relief by going to an ER, that my experience with migraine had gone better. While vomiting excessively can be part of it, dehydration for me never became severe enough to make it a medical emergency. While a ‘pounding railroad spike’ migraine might seem like an emergency to the body, migraines are really not ‘life threatening’ in the way that dehydration can be.

When you see the medical system as a route to health, then you might end up a decade later on ten medications and still have severe daily pain - that is where the person considering MAID suicide is at currently.

For the government to make suicide an easy out, to save on health care costs, seems like a bad thing to me. It took me a while, but I have mostly gotten to no-migraine months. If I had taken the suicide route, it would have ended my life ~ the early 2000s. Adding iodine in 2005, and then following the Marshall Protocol for a year and a half ~ 2006-8, is what helped to curb the severity of my migraines and the number of triggers, but I didn’t get into that in this post. Mold is still a trigger for me and lack of nutrients that I discuss below can be a trigger, or excess of excitotoxins or other environmental toxins like smoking too much can be a cause.

The problem is that government funded health care is not going to help the person in Canada to achieve no-migraine months. Most of my strategies, discussed below, or the Marshall Protocol and high dose iodine, are not funded or even screened for consistently by Western medical practitioners.

Migraines are a big topic, this is a long post, but it is not everything there is to know about migraines.

Discussed in the post: an overview of pain and migraines; acid/alkaline balance; electrolyte balance/hyponatremia - low salt; inflammatory signaling - deserves more info on topical magnesium; methylation cycle dysfunction and how riboflavin might help; pyroluria and low B6 and zinc; excitotoxins - glutamate, aspartic acid and other amino acids; too much or too little glycine; and poor detox of phenols and amines - salicylate excess.

Related posts:

Migraines are very disabling because it is in-the-brain-pain and you can’t really think, or move, or digest well.

Pain is variable I have noticed. Internal pain from headaches or in the gut can be more disabling, harder to ignore and get on with life, than pain from a surface wound.

I had a scalp biopsy at one point during my migraine years to assess for eczema in the area of the bald spot and the external wound was practically no big deal compared to migraine pain. My recent broken toe/bruised foot made me realize that I do have a high pain tolerance and almost kind of enjoy a low-level throbbing - as if it is an awareness of my existence. I am a little messed up though from childhood stuff. I am not suggesting that is a good thing. Pain was not unpresent at random times from family members ‘playing’ or showing affection. Dissociating was an escape for me at times.

Dissociation can be associated with self-injury during the dissociation, which might lead to an endorphin rush, but later leads to some pain and healing. Dissociation or self-injury is kind of an escapist behavior that can become habitual or addictive. Eating the wrong things, once I had a firm association that they likely would cause a migraine the next day, was somewhat of a self-injurious pattern that I had to work on stopping. Recognizing that one little taste generally does not work helped me to stop risking a little taste or a few blue M&Ms.

Migraines can become a frequent problem as painkillers that are used may provide some immediate relief but they can cause ‘rebound headaches’, so use of them is really just putting yourself on a Merry-Go-Round of recurring headaches.

Migraines are unlike other headaches in that it seems to be a vascular constriction or expansion issue leading to poor blood flow in a certain region and that means low oxygen levels are reaching that area and that hurts - the body signals pain.

TRP channel overactivation seemed to have been a causal trigger for my headaches, but poor sleep and dehydration were also triggers. My salicylate sensitivity has been with me longer than my awareness of it as a causal problem. Major triggers for my migraines, early, were red food dye #40 and #27. Then yellow food dye became one too. I was left eating Blue M & M’s for a while, until chocolate became a migraine trigger food too. I could use blue gel Ibuprofen capsules but not red pseudoephedrine tablets. Mint lozenges were a favorite until I realized they were a migraine trigger too. I had thought it was mint as a TRP channel activator but mint as a salicylate could be reason too.

For about fifteen years I lived with weekly migraines that might last 3 days. Laying in bed was needed with lights out and a cool compress over my eyes and forehead, (a freezable sore-ankle gel pack wrapped in cloth).

Speeding forward to the Why's? Why do migraines occur?

Inflammatory signaling is involved and that can mean poor detox and poor methylation is involved and lack of glutathione. Lack of nutrients from poor diet or metabolic differences might be causing the dysfunctional detox and methylation pathways. Vitamins B2 and B6, zinc, magnesium and sodium might be low or extra high doses might be needed due to genetic differences. Electrolyte imbalance and/or lack of dietary salt or excess sweating might be causal of low sodium - hyponatremia. Electrolyte imbalance for other reasons might be a causal factor and low potassium or calcium levels might be seen.

Elevated histamine might be a factor leading to headaches the next day and strobe lights or driving at night or watching an action movie can be a cause of mast cell degranulation and elevated histamine.

Migraines are associated with obesity and elevated leptin; and also with autoimmune disease and elevated CRP, Substance P, inflammatory cytokines, IL-6, IL-1β and TNF-α. (Demartini, et al., 2023)

Environmental or dietary toxins are also causal by adding to the inflammatory signaling. Emotional stress can be causal as it causes us to make formaldehyde internally and that can be a TRP channel activator and migraine trigger. Formaldehyde is also in smog or first, second or thirdhand smoke, and it can be a dietary risk in older bottles of juice, aging causes creation of it within the bottled juice. Off-gassing of volatile chemicals from ‘new car’ or ‘new carpet’ or new vinyl shower curtain can be causal.

Acid/alkaline balance matters

When the body is overly acidic, that can also increase problems with excreting salicylates and symptoms might worsen until the body is more alkaline again.

We tend to get overly acidic when the body is inflamed for any reason or when methylation cycles are dysfunctional and the body is burning energy anaerobically.

Inflammatory cytokines IL-6 and IL-1β IL-6 and TNF-α tend to be elevated in migraines (variable in the research somewhat, so not suggested as a biomarker), and migraines are associated with autoimmune diagnosis which tends to have elevated cytokines. While Substance P does tend to be elevated consistently in migraines, making it a potential biomarker, trials of inhibitors of Substance P for migraine treatment didn’t provide relief. (Demartini, et al., 2023) That suggests that we need to figure out what is causing the elevated Substance P and stop that - modify diet and lifestyle to reduce the inflammatory signaling.

Anything elevating IL-6, IL-1β and TNF-α likely could be causing the increase in Substance P also, so identifying anything inflammatory in the diet and lifestyle and removing it would be the therapeutic strategy. Adding pomegranate peel, niacin, butyrate or other Nrf2 promoters would also likely be helpful.

Cyclooxygenase 2 (COX-2) tends to be elevated in migraine and it promotes the prostaglandin PGE2. Pomegranate peel might be helpful as a preventative as it inhibits COX-2. Migraines are more likely during the week prior to menstruation because of increase in some prostaglandins like PGE2, along with a drop in estrogen levels. (Demartini, et al., 2023)

“Among the members of the prostaglandin family, the most studied in migraine mechanisms is prostaglandin-E2 (PGE2). Serum levels of PGE2 are lower in EM patients than in HC [155], but no difference has been reported between EM and HC in PGE2 saliva levels [156]. During a migraine attack, plasma and saliva PGE2 levels increase compared with a pain-free period [48,152,157]. Notably, during migraine attacks, the serum levels of cyclooxygenase 2 (COX-2), an enzyme implicated in the production of PGE2 [158], were higher in migraine patients than in HC [159]. PGE2 serum levels positively correlated with headache frequency in migraine patients [155].” (Demartini, et al., 2023)

Excitotoxin amino acids include glutamate and aspartic acid and seem to be correlated with migraine or migraine with aura.

Many studies have found a correlation between elevated glutamate/glutamic acid and migraine or migraine with aura. It may be useful as a biomarker to test for migraine and assess type. Episodic migraine is considered to be migraine presence less than 15 days per month and chronic migraine is considered to be more than 15 days per month for three months or longer. (Demartini, et al., 2023)

Increased levels of the excitotoxins glutamate and aspartic acid were seen in patients with migraine or migraine with aura (seeing stars/sparkles or other vision changes I think). Glycine was also measured but I didn’t buy access to learn more details about what form was being measured. (D’Andrea, et al., 1991)

“Platelet levels of glutamic and aspartic acid and glycine were measured in patients with migraine with aura, migraine without aura, tension headache and cluster headache. High levels of these amino acids were found in patients with migraine with aura compared to normal subjects and other headache groups. During headache, glutamate levels further increased in migraine with aura patients. These findings may have relevance to the neurological symptoms of migraine with aura.” (D’Andrea, et al., 1991) *Paywall, this is the Abstract.

Glutamic acid, glycine, serine, arginine and tyrosine were found to be elevated in the saliva of people with migraine or migraine with aura. Glycine and serine have calming roles. Glutamic acid can be an excitotoxin - glutamate. Tyrosine is known to cause headaches and is in aged cheeses or red wine.

“In this study, free amino acid concentrations were measured by RP-HPLC in the saliva of 23 migraineurs without aura, 14 migraineurs with aura, and 20 healthy subjects. Significantly higher concentrations of glutamic acid, serine, glycine, arginine, and tyrosine were found in the saliva samples of both groups of migraineurs relative to the control group. It is suggested that amino acids causing hyperexcitability in the central nervous system may be linked to the pathogenesis of migraine.”

Elevated glycine might indicate a back-up is occurring in methylation cycles. Yes, lack of methylated folate could be a cause of elevated glycine which is then a dangerous thing.

“GCS catalyzes the interconversion of glycine into serine and it requires N5-N10-methylene tetrahydrofolate or tetrahydrofolate [31, 32]. The physiological importance of the GCS in degradation of glycine is characterized by its defect in humans which results in glycine encephalopathy and very high levels of plasma glycine.” (Razak, et al., 2022)

Lack of Dimethylglycine (DMG) or Betaine (TMG) can also be a cause of brain over-excitement or methylation cycle dysfunction (and other problems, (Razak, et al., 2022)).

Dimethylglycine is a calming signaling chemical within the brain. It helps cool the brain before sleep. (Razak, et al., 2022) I have tried 1/2 teaspoon in a glass of water before bed, mix with a little sodium or potassium bicarbonate if it seems too acidic for your taste preference or stomach. We all may be getting too little glycine now, compared to glyphosate from the GMO crops and use of RoundUp as a desiccant on many crops.

Trimethylglycine has a critical role within the methylation cycles. It can donate a methyl group leaving Dimethylglycine. The DMG might then go on to be used for making a molecule of our main endogenously created antioxidant, glutathione, or it might be remethylated back to TMG for reuse in the methylation cycles.

My genetic differences leave me low in glycine, and the entire US population is likely lower than they used to be because of the increased use of glyphosate in our food. It competes with glycine but would make a protein ineffective if it was made with glyphosate instead of glycine which has been shown to be possible in work by Seneff & Samsel. Glycine is also available in the form TMG or betaine. I have a gene allele that slows down conversion of TMG to DMG and the two have different roles in health. Really rich sources of TMG like quinoa kind of leave me feeling queasy after eating a standard serving - so I don’t I stopped eating quinoa.

Lack of glycine also increases the salicylate sensitivity as glycine is needed to excrete salicylates.

Poor detox of phenols and amines

Poor detox of phenols and amines can be genetic and would add to headache risks - the red and yellow dyes are phenols. Other medications and the ibuprofen could also add to a phenol/salicylate excess problem . . . and cause headaches. Avoiding free glutamate, aspartic acid, and tyramine can help prevent headaches in people who are prone to headaches and who may also be poor detoxer’s of phenols and amines. Red wine was the first or an early thing I noticed that was a migraine cause. It made me laugh and have fun - I liked it until the next day. Red wine is rich in free amino acids.

I managed my migraine problem by watching for patterns and stopping use of anything that seemed causal - or tried to stop use. Binge/emotional overeating is a problem for me and I would have slip ups, but severe pain is a motivator to not have slip ups and I got better at skipping little tastes of binge prone foods. One blue M&M can just set off a sweet tooth desire for more.

As I restricted more and more things to try to have more migraine free days than migraine days, my internal motto would be “as long as I can still have chocolate”, but then I became sensitized to chocolate too. Life was kind of depressing and the grocery store had become a trauma triggering place with what seemed like “nothing for me to eat”. There really isn’t much to eat there for me besides some whole foods. I do mostly cook my own foods now.

Chocolate is a phenol food, so is coffee and many herbs and spices.

Pyroluria - vitamin B6 and zinc matter

A genetic issue with breakdown of hemoglobin for reuse of the parts can cause chronic excretion of vitamin B6 and zinc when normally it would be reused again. People with pyroluria need a high dose vitamin B6 and zinc supplement most days, for their entire life.

Low vitamin B6 and zinc can be a cause of migraines and other mood and physical symptoms.

People with congenital (birth) gene differences like Down’s Syndrome are more likely to also have pyroluria than the average person. It might be 40% of Down’s syndrome patients - BUT - the Western medical system doesn’t really believe in the problem or screen for it typically or treat it. Lack of zinc and B6 will disrupt the methylation cycles and many other functions within the body and can cause migraines.

Forgetfulness can be a problem. I REALLY need those two supplements most days of the week in order to not get a little weird/more ADHD → scattered thinking, racy thoughts, hard to stay focused or complete things. Salicylate excess seems to be part of ADHD symptoms as it causes similar changes in thinking and mood. Doing things too fast and too recklessly can occur when salicylate is in excess. Losing my cell phone in my own purse (twice - different purses though) and freaking out about a lost phone, searching everywhere for it but never thoroughly enough to find it in the purse . . . is an example of what salicylate excess can look like.

Taking ibuprofen or Excedrin or aspirin for a headache would all make a salicylate excess worse. Caffeine is also a polyphenol too. Mint is a salicylate, so my mint lozenges were also adding to salicylate excess.

Methylation cycles, MTHFR, and riboflavin

If your methylation cycles aren’t functioning well, then sulfate metabolism and glutathione production would be thrown off, which means breakdown of the phenols and salicylates wouldn’t work well and other drugs might also accumulate instead of being broken down. Gene differences in MTHFR were focused on as THE problem in methylation, and giving methyl folate was/is the standard solution. But it turns out that high dose riboflavin might be safer for the C677 allele as the dysfunction is in keeping a cofactor of B2 attached to the enzyme. Having plenty of B2 all day long, helps keep resupplying the MTHFR enzyme with the cofactor it needs.

Taking high dose folate is more problematic because it can inhibit methylation cycles as a negative feedback control. Excess cysteine as a supplement also can act as a negative feedback control and put the brakes on the methylation cycles. This means, random high dose supplements CAN make things worse. Over methylation or under methylation can both cause negative mood and physical symptoms.

The high dose riboflavin doesn’t seem to have any negative feedback controls. Taking 100 mg several times per day is a recommendation by Bethany Briggs. Her tip is to keep the urine the bright yellow of a highlighter marker and that indicates that the body had plenty of B2 for methylation purposes - yes, it is being dumped in ‘expensive’ urine but what price is not having migraines worth to you? Bright yellow urine is not a high cost to pay.

• A product example, MigreLief by Akeso, puts in two tablets - 400 mg of riboflavin (B2) with 360 mg of Magnesium (citrate and oxide) and 100 mg of Feverfew, an herb known to help with migraines. They do seem to be recommending taking this product as a daily preventative - twice a day. (store.migrelief.com)

This product does contain titanium dioxide in the fine print, I notice now, and I try to avoid that. It is a heavy metal nanoparticle which the body has a hard time excreting. It is added to supplements and foods as a whitening agent. Riboflavin is bright yellow and yet these tablets are whitish/caramel colored. The fine print lists the titanium dioxide and caramel color. What was wrong with pretty yellow?

Pomegranate peel can help with excretion of heavy metal nanoparticles though, but I would rather avoid the ingredient. Feverfew is also available as an herbal supplement, and I take that instead. (Feverfew for migraine/Brave AI summary)

I have found this product helpful during a migraine, but I don’t take it daily. I use a 100 mg riboflavin instead, about 2-3 times per day now.

Low sodium - lack of salt can be a headache cause

With the salicylate sensitivity, salt retention became a problem and so I greatly restricted that to try to reduce leg swelling. I ended up over-restricting it and found that low level headaches were a result. I try to use some but not loads of salt now.

In research by Pogodo, et al., published in the Headache journal, severe headache or migraine history was found to be inversely correlated with sodium intake - in other words the people who ate the least sodium, (per total calories), were the most likely to also have a history of headache, (in the NHANES 1999-2004 study/database). (Pogodo, et al., 2016)

“Results from both crude and covariate‐adjusted analyses of the relationship between dietary sodium and migraine status are shown in Table 2. Compared to respondents with the lowest dietary sodium residuals, there was a significant trend of decreasing odds of migraine history with increasing levels of dietary sodium residuals (OR = 0.93, 95% CI = 0.87, 1.00, P = .0455);” (Pogodo, et al., 2016)

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

Reference List

(D’Andrea, et al., 1991) D'Andrea G, Cananzi AR, Joseph R, Morra M, Zamberlan F, Ferro Milone F, Grunfeld S, Welch KM. Platelet glycine, glutamate and aspartate in primary headache. Cephalalgia. 1991 Sep;11(4):197-200. doi: 10.1046/j.1468-2982.1991.1104197.x. PMID: 1683816. https://pubmed.ncbi.nlm.nih.gov/1683816/ *paywall

(Demartini, et al., 2023) Demartini C, Francavilla M, Zanaboni AM, Facchetti S, De Icco R, Martinelli D, Allena M, Greco R, Tassorelli C. Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings. Int J Mol Sci. 2023 Mar 10;24(6):5334. doi: 10.3390/ijms24065334. PMID: 36982428; PMCID: PMC10049673. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049673/

(Pogodo, et al., 2016) Pogoda JM, Gross NB, Arakaki X, Fonteh AN, Cowan RP, Harrington MG. Severe Headache or Migraine History is Inversely Correlated With Dietary Sodium Intake: NHANES 1999-2004. Headache. 2016 Apr;56(4):688-98. doi: 10.1111/head.12792. Epub 2016 Mar 26. PMID: 27016121; PMCID: PMC4836999. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836999/

(Rajda, et al., 1999) Rajda C, Tajti J, Komoróczy R, Seres E, Klivényi P, Vécsei L. Amino acids in the saliva of patients with migraine. Headache. 1999 Oct;39(9):644-9. doi: 10.1046/j.1526-4610.1999.3909644.x. PMID: 11279959. https://pubmed.ncbi.nlm.nih.gov/11279959/

(Razak, et al., 2022) Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi: 10.1155/2017/1716701. Epub 2017 Mar 1. Erratum in: Oxid Med Cell Longev. 2022 Feb 23;2022:9857645. doi: 10.1155/2022/9857645. PMID: 28337245; PMCID: PMC5350494. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350494/

(Rothrock, et al., 1995) Rothrock JF, Mar KR, Yaksh TL, Golbeck A, Moore AC. Cerebrospinal fluid analyses in migraine patients and controls. Cephalalgia. 1995 Dec;15(6):489-93. doi: 10.1046/j.1468-2982.1995.1506489.x. PMID: 8706112.

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• Leptin is part of the discussion in a video shared by Timothy Winey. The video is a talk by Dr. Jack Kruse being interviewed by, or meeting with Andrew Huberman and the guest Rick Rubin was invited by Dr. Kruse, in part as a health success story of Dr. Kruse’s health recommendations, (~4 hours), and there was mention of a second part to be filmed some other time. https://podcastnotes.org/tetragrammaton-rick-rubin/dr-jack-kruse-and-andrew-huberman-ph-d-tetragrammaton-with-rick-rubin/

I will have to have a part two to this post, the leptin story I already had discovered, as I look into what Dr. Kruse is discussing regarding POMC and leptin and our internal light producing capabilities - iodine is involved - and sunshine helps, and melanin is involved. But not our skin’s tan, but internal melanin.

POMC and leptin are involved in appetite and weight, which is what much of my lengthy post is about. Dr. Kruse is discussing a role in energy production through UV light I think. I need a couple more listens yet and some time with a search engine.

• This research dissertation seems to be related to the topic described by Jack Kruse. (Melanopsin-and-Leptin-Dissertation)

Dr. Kruse and I both wouldn’t have learned about leptin in college because it was discovered in 1994 he mentioned. It is involved in appetite and research has been focused on weight and obesity more than leptin’s roles in immune function. It has signaling power similar to inflammatory cytokines and it can degranulate allergy mast cells.

What I had learned about leptin while writing my pomegranate paper…. and forgot much of - good thing I can reread it…a few summary points:

1. Pomegranate peel decreased leptin levels, improved bone density, and improved biomarkers for kidney and liver damage and for oxidative stress in overweight rats. (Soliman, et al, 2022)

2. Leptin and thymus function need zinc, and leptin metabolism seems to need bitter phytonutrients for normal function.

3. Elevated leptin levels may be due to a high fat diet that lacks bitter phytonutrients; negative effects on the microbiome from lack of zinc and bitter phytonutrients may be an additive factor.

4. My impression: Bitter taste receptors may have some co-regulatory function with leptin receptors.

5. Leptin is produced in so many tissue types that it may be an underlying link to the kidney, liver, and brain damage that is often seen with histamine and Retinoid excess as leptin degranulates mast cells.

Microbiome health can be worsened towards an obesogenic profile by high fat diet and there is cross talk between the lungs and gut, a gut-lung axis in addition to the gut-brain axis. (Bruno, et al, 2021) The gut microbes promote leptin expression in a normal fat diet (10% of total calories, mice) by epigenetic methylation of the leptin promoter gene. The increased leptin expression stops with a high fat diet (60% of total calories) and increased weight followed and seemed to promote gut dysbiosis and reduced sensitivity to leptin, (animal based study). Leptin output increases with increasing adipose tissue. (Yao, et al, 2020)

Pomegranate/peel decreases leptin

Leptin can degranulate mast cells and increase inflammation; zinc may be needed and a moderate to low fat diet.

Elevated leptin levels are seen in sepsis and respiratory infections. Elevated leptin may be involved in COVID19 severity. (Bruno, et al, 2021) Pomegranate peel decreased leptin levels, improved bone density, and improved biomarkers for kidney and liver damage and for oxidative stress in overweight rats. (Soliman, et al, 2022)

Leptin is a pleiotropic adipocytokine, cytokine-like but released by white adipose tissue in its endocrine gland capacity, (Tilg, Moschen, 2006), and it is produced by lymphoid tissues, bone marrow, brain, gastric mucosa, intestine, skeletal muscle, mammary gland and the placenta. “(Wolsk et al., 2012; Vernooy et al., 2013; Li et al., 2017; Pan et al., 2017; Pérez-Pérez et al., 2018).” (CC-BY Bruno, et al, 2021) Pomegranate has been found beneficial in all of those tissue types – including improved endothelial function in the placenta, (El-Sayyad, El-Ghawet, El-Sayed, 2019), anti-microbial for bovine mastitis of the mammary gland, (Raheema, 2016), and Table 3. Pom Health has other studies.

• Leptin caused degranulation of rat mast cells, release of histamine, and increased intracellular calcium. (Żelechowska, et al, 2018) Which suggests that leptin adds to the hyperinflammation positive feedback loop shown in Figure 1. Graphical Abstract. Niacin treatment reduced leptin levels in a hypercholesterolemia animal model by promoting PPAR gamma. (Yang, J. et al, 2008)

• Leptin activates the Sympathetic Autonomic Nervous System and can increase cardiovascular disease risks and it can also be affected by ANS activity. (Rahmouni, 2010) Leptin also has pro-inflammatory immune roles promoting Th1 cellular immunity and upregulates inflammatory cytokines TNF-α, IL-6, and IL-12, (Iikuni, et al, 2008), which may play a role in the increased mortality risk of COVID19 for obese patients. (Maurya, et al, 2021)

• Leptin regulates appetite and helps maintain weight, but elevated levels and leptin resistance are associated with obesity along with too few leptin receptors. (Iikuni, et al, 2008)

• Leptin activates TRPV1 channels which blocks Leptin-CCK regulation, (Table 1, Kumar, Goswami, Goswami, 2013) which could increase appetite, as leptin and cholecystokinin (CCK) interact to produce satiety in lean mice. (Barrachina, et al, 1997). Antagonists of the CCK receptor led to an increase in plasma leptin and seemed to increase uptake to the cerebrospinal fluid. (Cano, et l, 2003)

• Leptin activates TRPC1, 4-7 channels (Table 1, Kumar, Goswami, Goswami, 2013) which generate an action potential in T-type calcium channels which causes calcium influx and activation of Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. (Perissinotti, Martínez-Hernández, Piedras-Rentería, 2021) In normal health POMC neurons are activated during energy abundance leading to satiety signals and weight loss and are inhibited by lack of food energy. Reduced POMC activity is associated with increased appetite and obesity. (Rau, Hentges, 2019) POMC neurons may be regulated by signaling from leptin, insulin, and glucose. (Pinto et al., 2004; Parton et al., 2007; Belgardt et al., 2009; Dodd et al., 2018, as cited by Rau, Hentges, 2019)

  • The T-type calcium channels can be inhibited by 6-phenylnaringenin, from hops, and it reduced visceral and neuropathic pain in mice, but naringenin was not an inhibitor. (Sekiguchi, et al, 2018)

  • Naringenin is a bitter tasting bioflavonoid found in tangerine peel with anti-cancer (El-Kersh, et al, 2021) and weight control benefits. (Ke, et al, 2015) It may promote conversion of white adipose tissue to brown adipose which releases energy as heat. (Rebello, et al, 2019)

  • Inhibiting the POMC neurons, as 6-phenylnaringenin might, would lead to increased appetite and weight gain. (Rau, Hentges, 2019)

  • In the TRPC4 and -5 section we learn that TRPC4 and TRPC5 channels also require PLC for activation. TRPC4 required coincident activation by a G coupled receptor and PLC. (Thakur, et al, 2016) Taste receptors are G-coupled protein receptors. (Sanematsu, et al, 2014)

Flavonoids, like those found in pomegranate/peel are ROS scavengers … and removal of Reactive oxidative stress chemicals might help to inhibit TRPC channels from being activated by the ROS chemicals and prevent calcium from entering a cell.

Pomegranate or other ROS scavengers might not help against mechanical stress - pressure change activation of TRPC channels though.

Mechanical stress and oxidative stress are activators of TRPC channels and activation by mechanical stress persisted even in the presence of PLC and G protein coupled receptor inhibitors. (Hall, Wang, Spurney, 2020)

TRPC channels are activated by oxidative stress (ROS) - hydrogen peroxide is an example.

“A third mechanism of TRPC activation is oxidative stress, which is reported to activate TRPC5 and TRPC6 [38,39,40]. In podocytes, TRPC6 activation by angiotensin II and cell permeable DAG analogs is inhibited by both scavengers of reactive oxygen species (ROS) and by pharmacologic inhibition of NADPH oxidase 2 (NOX2) [41,42]. Similarly, ROS quenchers inhibit TRPC6 activation by ATP [43]. In addition, TRPC6 coimmunoprecipitates with the catalytic subunit of NOX2, and the TRPC6–NOX2 interaction appears to require podocin because knockdown of the scaffolding protein podocin eliminates the TRPC6–NOX2 protein–protein interaction [42]. Taken together, these data suggest that localized production of ROS plays a key role in GPCR-induced TRPC6 activation.” (CC BY Hall, Wang, Spurney, 2020)

TRPC channels and phospholipase C (PLC):

“All TRPC ion channels are calcium permeable, but the channels are poorly selective, with permeability ratios (PCa/PNa) that vary significantly between family members [26]. The calcium influx is stimulated following receptor-induced phospholipase C (PLC) activation in response to both tyrosine kinase receptors (TKRs) and G protein coupled receptors (GPCRs) [27]. PLC catalyzes hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and generates the second messengers diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (IP3) [28] that differentially affect TRPC activation, as reviewed elsewhere [27].” (CC BY Hall, Wang, Spurney, 2020)

Our endogenous antioxidants such as superoxide dismutase (SOD), peroxidase, glutathione (GSH) and nutrients like vitamin C and E or minerals like selenium can help reduce oxidative chemicals - neutralizing risk of damage to other tissues. Oxidative chemicals are a similar risk to the rust on our iron garden gate.

Glutathione production is promoted by Nrf2 and that anti-inflammatory protein is promoted by pomegranate and other functional foods. Oxidative chemicals, can cause damage by taking electrons from healthy cells, and that can damage them. Over-acidity accumulation would be an added risk.

Adding Nrf2 promoting phytonutrients or foods like pomegranate can help prevent degranulation of mast cells and reduce inflammation that may lead to degranulation because Nrf2 inhibits NF-κB. Produce rich diets can help and other nutrients like magnesium. Magnesium supplementation increased Nrf2 in a HIV-1 animal-based study. (ElZohary, et al, 2019)

Having adequate antioxidants from dietary sources or our own internal production of glutathione, promoted by Nrf2, helps reduce the oxidative damage that can result from normal or over-active metabolism and lead to neurodegenerative conditions. (Paladino, et al, 2018) Small molecules found to inhibit NF-κB includes phytonutrients (Gupta, et al, 2010) that also have been found to promote Nrf2 - the two pathways are linked. It makes sense that the same chemical would inhibit one and promote the other.

Flavonoids including luteolin, quercetin and apigenin, help prevent breakdown of NAD+ and help reduce symptoms of histamine excess. (Rajman, Chwalek, Sinclair, 2018) They are also Nrf2 promoting phytonutrients. Olives or olive oil are also Nrf2 promoting and contain phenols, hydroxytyrosol and oleuropein, found to inhibit mast cells. (Persia, et al, 2014)

Histamine excess causes symptoms of seasonal allergies, but can also cause severe mental symptoms including paranoia, mania, and self harm or violent urges. Leptin degranulates mast cells so an excess of leptin seen with obesity, might also be causing symptoms of histamine excess.

Mitochondrial melatonin is also an antioxidant

Healthy Circadian Cycle, good sleep and light/dark habits also promote Nrf2 and mitochondrial health.

NF-κB inhibiting phytonutrients are also Nrf2 promoting phytonutrients as the two pathways share a circadian cycle Clock protein. Restoring a healthy circadian cycle with sleep/wake, dark/full spectrum light strategies is also a need as Nrf2 activity reduces inflammation and pain and is involved in DNA damage repair. Reducing inflammation is needed to reduce breakdown of endocannabinoids as that leads to activation of TRP channels, increased calcium entry into cells, edematous changes, and increased expression of TRP channels on cell surfaces may result – which would lead to increased sensitivity to TRP activators into the future.

Our mitochondria also have periodic activity and may need us to have a daily blackout/full spectrum light cycle in order for their optimal health and melatonin production.

Mitochondria have been found to produce melatonin in quantity and to actively maintain a high concentration. Their oscillatory cycles are periodic like the circadian cycle. Melatonin within mitochondria acts as an antioxidant against ROS, promotes mitochondrial fission instead of fusion, inhibits the mitochondrial permeability transition pore (MPTP), and can activate Uncoupling Proteins. These functions help preserve the mitochondrial membrane potential at optimal levels. (Tan, Manchester, Qin, Reiter, 2016)

“In addition, melatonin acts on the mitochondrial specific proteins such as uncoupling proteins (UCPs) to dissipate the proton gradient across the inner membrane of the mitochondria to moderately reduce the inner membrane potential [57,58,59,60]. The relative lowering of the inner membrane potential significantly increases the activities of complex I and III, and accelerates electron transport through the ETC. These changes decrease electron leak from the ETC and reduce free radical formation. This is referred to as the free radical avoidance reaction of melatonin [61].” (CC-BY the authors: Tan, Manchester, Qin, Reiter, 2016)

What is a high fat diet? In humans 20-30% calories from fat are typical, with a goal of 10% or less to be from saturated fats and zero from trans fats. Above 35-50% of the total calories from fats is considered high fat for human meal planning. Saturated fats in particular trigger PPAR inhibition of CoA production for Citric Acid Cycle use by mitochondria – they are switched to fermentation of fats instead – meant to be temporary for survival, becomes mitochondrial dysfunction with many modern diets.

Lack of nutrients and cofactors needed in the Citric Acid Cycle can be involved and a high saturated fat diet may be adding to the shift in mitochondrial energy production to fermentation instead of using the more productive and less waste producing Citric Acid Cycle (pyruvate is a waste product of fermentation).

The curve ball is that Retinoid Toxicity may also be a undiagnosed cause of chronic inhibition of PDK by PPAR activation by the activate form of vitamin A that is called 9-cis-Retinoic Acid - leading to mitochondrial dysfunction with an ongoing use of fermentation instead of the Citric Acid Cycle.

Diet with moderate to low saturated fats. Added complexity, a high saturated fat diet is the normal cause for the PPAR beta/delta inhibition of PDK and the Citric Acid Cycle by limiting CoA production . . . which blocks the Citric Acid Cycle from functioning, and the mitochondria switch to using fat for energy. (Tyagi, et al, 2011) (Zhang S, et al, 2014, Fig. 2)

This PDK switch is a standard part of metabolism and would be lifesaving when food was scarce - a rapid switch to using whatever type of energy was most available at the time. In modern life saturated fats can be a significant part of the diet. Using fermentation for energy production is more inefficient for energy needs though, and produces more waste and lactate build up from the accumulating pyruvate. Elevated pyruvate levels are seen in ME/CFS. (Anderson and Maes, 2020)

Zinc is needed to promote Leptin which has roles in immunity & growth of T-cells in the thymus gland

Leptin is structurally similar to interleukins IL-2 and IL-6. Deficiency has negative impacts on immune function and thymus T-cell growth. It promoted thymus function, CD+4 and Th1 cells and inhibited Th2 cells. » Lack of zinc led to less leptin and supplementation increased leptin levels and TNF-alpha and IL-2 in a review of research, but the reason why zinc seems to have a regulatory role over leptin is not known. Zinc’s role in gene transcription was briefly considered in the review by Baltaci and Mogulkoc, 2012.

Zinc may be needed for Gene expression of leptin:

The link between zinc deficiency and leptin levels may be connected to a need for zinc finger proteins for the expression of leptin or leptin receptors, as they are involved in gene transcription and adipocyte growth for white and brown adipose tissue. (Wei, et al, 2013)

Zinc may promote gut species that promote production of leptin:

An indirect effect may be changes in microbiome species with zinc deficiency. Lack of zinc negatively effects microbiome health and beneficial gut species epigenetically promote leptin expression when there is a normal fat diet. (Yao, et al, 2020) When low zinc is available less beneficial species that don't need zinc thrive instead of beneficial butyrate producing species. (Tako, Koren, 2020) 

Pomegranate and other bitter phytonutrient foods might help by promoting beneficial microbiome species:

Pomegranate promotes balanced growth of species that produce butyrate and other short chain fatty acids (SCFA), improving the ratio of Bacteroidetes to Firmicutes. Rosaburia and Blauta were increased and also are SCFA producing species. (George, et al, 2019) Pomegranate does not provide zinc however, unless in a combined supplement or food that was considering the advantages of prebiotic nutrients that work together synergistically.

Bitter taste receptors do need Zinc finger protein for gene expression:

Lack of bitter taste receptors due to zinc deficiency might be a factor in the benefits of zinc and pomegranate on leptin levels as bitter taste receptors need zinc finger proteins for transcription, (Sekine, et al, 2012), and pomegranate could be helping leptin by way of the bitter taste receptor function in a possible co-regulatory function.

Bitter taste receptors may be coregulators of the leptin receptor:

Example: The leptin receptor is co-regulated by a G protein coupled receptor in the pedunculopontine nucleus (PPN) of the reticular activating system (RAS) of the brain which regulates waking and rapid eye movement (REM) sleep. Leptin also promoted NMDA receptor-mediated responses in the PPN and single neurons, (Beck, et al, 2013), which may add to Alzheimer’s risk with chronic leptin elevation.

Processed foods have little bitter tasting phytonutrients:

Lack of bitter tasting phytonutrients in processed foods may be a factor if bitter taste receptors have regulatory control. Processed foods tend to have had the bitter tasting phytonutrients removed to increase consumer acceptance.

Bitter tasting polyphenols and phospholipids (precursors for endocannabinoids) are found in the pomegranate peel, arils or seeds.

Leptin and thymus function need zinc, and leptin metabolism seems to need bitter phytonutrients for normal function.

It might be a combination - bitter taste receptors as coregulators of the leptin receptor would create a need for both adequate zinc for gene transcription of bitter taste receptors and adequate bitter phytonutrients in the diet

Zinc

• Zinc is needed for gene transcription of taste and odor receptors.

• The recommended intake guidelines may be significantly low for elderly people.

• Zinc is needed by butyrate producing and other beneficial microbiome species.

Zinc deficiency effects gene transcription of taste receptors and other genes. Zinc deficiency would cause a lack of bitter taste receptors as Zinc finger proteins are needed for gene transcription of odor and taste receptors, (Sekine, et al, 2012), and many other proteins including genes transcribed by other nuclear transcription factors. (Mackeh, et al, 2018) Zinc deficiency can impact gene transcription by retinoid X receptors (RXR) and 27 other types of gene transcription factors, so deficiency of zinc can negatively impact stem cell differentiation in neonatal or adult neurogenesis. (Morris and Levenson, 2013) The elderly and chronically ill may have zinc deficiency as an underlying causal factor, as bitter taste receptors on immune cells and within the kidney and elsewhere in the body affect health. Supplementation at higher than standard recommendation may be needed for at least three months to see improvement in taste and odor sensation, (Kodama, et al, 2020), and other chronic symptoms may improve also due to the functional nature of bitter taste receptors.

Beneficial species of the microbiome need adequate zinc, up to 30% of our daily intake may be used by beneficial species. Unhealthy species can survive without.

Leptin and weight

• Healthy weight and microbiome need good zinc levels and bitter tasting phytonutrients.

• Bitter taste receptors in the gut promote satiety and better blood sugar regulation and improve weight and dyslipidemia.

• Processed foods tend to lack bitter phytonutrients.

• Leptin helps regulate weight and satiety in normal function but is elevated in obesity and the receptors are unresponsive.

• Coregulation by bitter taste receptors or modulation by bitter phytonutrients may be involved. « My theory.

Maintaining a healthy weight – pomegranate and zinc can help. Bitter tasting phenolic compounds have been found to have weight loss/anti-obesity benefits including: resveratrol, caffeic acid, naringenin, proanthocyanidins, catechins, and cyanidin. (Sharma, S.P., et al., 2016) Proanthocyanidins, and catechins are present in pomegranate and chlorogenic and caffeic acid, both gallic acids.(Mahmoud, Ibrahim, 2013) Caffeic acid (Frank, et al, 2007)  and many other pomegranate phytonutrients are bitter tasting. Bitter taste receptors in the gut promote satiety and stable blood sugar. Pomegranate juice was more effective compared to an extract for improving glycemic response with a high-glycemic index food. (Kerimi, et al, 2017) There is synergy in the whole fruit products.

Taste 2 receptors, TAS2Rs, are a type of bitter taste receptor in the gut which stimulate Nrf2 mediated immune responses. (Liszt, et al, 2021) Bitter taste receptors (Tas2rs) increase glucose tolerance, improve weight and dyslipidemia, and decrease insulin resistance, in part by stimulating production of the hormone glucagon-like peptide 1 (GLP-1); animal-based study on hops isohumulones. (Kok, et al, date) GLP-1 promotes satiety through interaction with ghrelin and leptin, resulting in inhibition of glucagon and increased insulin secretion. (Ronveaux, et al, 2015)

Bitter taste receptors seem to be co-regulatory with weight and appetite. Processed foods tend to have had the bitter tasting phytonutrients removed to increase consumer acceptance.

Leptin regulates appetite and helps maintain weight, but elevated levels and leptin resistance are associated with obesity along with too few leptin receptors. (Iikuni, et al, 2008) Leptin also stimulates GLP-1, and GLP-1 is low in obesity, leptin resistance is suggested to be a factor. (Anini, et al, 2003) Leptin levels fall during fasting or weight loss, and the decrease signals to eat, and then regain may occur. Maintaining leptin levels helped weight (animal study). (Ahima, 2008)

»Hyperleptinemia itself leads to leptin resistance as opposed to a high fat diet with inhibited leptin levels, (animal study). (Knight, et al, 2010)

Pomegranate peel decreased leptin levels, improved bone density, and improved biomarkers for kidney and liver damage and for oxidative stress in overweight rats. (Soliman, et al, 2022)

Adequate zinc is needed for transcription of taste and odor receptors (Sekine, et al, 2012) and adipocyte growth. (Wei, et al, 2013) Zinc also is needed for butyrate producing microbiome species to thrive. (Tako, Koren, 2020)

Microbiome health can be worsened towards an obesogenic profile by high fat diet and there is cross talk between the lungs and gut, a gut-lung axis in addition to the gut-brain axis. (Bruno, et al, 2021) The gut microbes promote leptin expression in a normal fat diet (10% of total calories, mice) by epigenetic methylation of the leptin promoter gene. The protective effect is lost with a high fat diet (60% of total calories) and increased weight leading to obesity seems to promote gut dysbiosis and reduced sensitivity to leptin. Leptin output increases with increasing adipose tissue. (Yao, et al, 2020)

Reduce weight and inflammation to reduce leptin. It can activate TRPV1 and TRPC1, 4-7 channels.

Leptin activates TRPV1 channels which blocks Leptin-CCK regulation, (Table 1, (Kumar, Goswami, Goswami, 2013) which could increase appetite, as leptin and cholecystokinin (CCK) interact to produce satiety in lean mice. (Barrachina, et al, 1997). Antagonists of the CCK receptor led to an increase in plasma leptin and seemed to increase uptake to the cerebrospinal fluid. (Cano, et l, 2003)

Leptin activates TRPC1, 4-7 channels (Table 1, (Kumar, Goswami, Goswami, 2013) which generate an action potential in T-type calcium channels which causes calcium influx and activation of Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. (Perissinotti, Martínez-Hernández, Piedras-Rentería, 2021)

In normal health POMC neurons are activated during energy abundance leading to satiety signals and weight loss and are inhibited by lack of food energy. Reduced POMC activity is associated with increased appetite and obesity. (Rau, Hengtes, 2019) POMC neurons may be regulated by signaling from leptin, insulin, and glucose. (Pinto et al., 2004; Parton et al., 2007; Belgardt et al., 2009; Dodd et al., 2018, as cited by (Rau, Hengtes, 2019)

The T-type calcium channels can be inhibited by 6-phenylnaringenin, from hops, and it reduced visceral and neuropathic pain in mice, but naringenin was not an inhibitor. (Sekiguchi, et al, 2018)

Bitter citrus bioflavonoids like naringenin found in tangerine peel have anti-cancer (El-Kersh, et al, 2021) and weight control benefits. (Ke, et al, 2015) It may promote conversion of white adipose tissue to brown adipose which releases energy as heat instead of storing it as more fat. (Rebello, et al, 2019) Inhibiting the POMC neurons, as 6-phenylnaringenin might, would lead to increased appetite and weight gain. (Rau, Henges, 2019)

Leptin summary points.

• A high fat diet and lack of bitter phytonutrients may be involved in elevated leptin levels;

• Negative effects on the microbiome from lack of zinc and bitter phytonutrients may be an additive factor.

• Mast cell degranulation by elevated levels of leptin, and leptin is produced in so many tissue types that it may be an underlying factor to the risk for kidney, liver, and brain damage that is seen with both histamine excess and Retinoid excess.

A high fat diet can cause inflammatory problems by disrupting microbiome support of leptin production and high saturated fats can cause mitochondria to switch to fermentation instead of using the Citric Acid Cycle. Leptin resistance in obesity involves the elevated leptin levels but may also involve a lack of zinc and bitter tasting phytonutrients in the diet. Elevated leptin can increase appetite by activating TRPV1 channels that block CCK co-regulation with leptin of satiety - that satisfied feeling after eating a normal meal.

Inflammation would increase leptin production in non-adipose tissues which impact many areas of the body: lymphoid tissues, bone marrow, brain, gastric mucosa, intestine, skeletal muscle, mammary gland and the placenta. “(Wolsk et al., 2012; Vernooy et al., 2013; Li et al., 2017; Pan et al., 2017; Pérez-Pérez et al., 2018).” (CC-BY the authors Bruno, et al, 2021)

Over exertion may increase myokines and the leptin; bowel troubles may include excess leptin output; bone marrow affects blood cell production and lymphoid tissue also affects cardiovascular health; the brain affects everything; and leptin is elevated in early breast milk suggesting an essential role for it in early life. (Ilcol, Hizli, Ozkan, 2006) It would provide immune support to an infant with an underdeveloped system. Leptin excess may be key to the kidney, liver and brain risks seen with histamine and Retinoid Toxicity as leptin degranulates mast cells.

Lactation factoid: More leptin is in the early colostrum and declining levels as the baby is older. Weight of the woman and other hormone levels affect the leptin concentration - insulin and thyroxin for mature milk and insulin and cortisol for the first milk, colostrum. Breast fed infant’s leptin levels are correlated with their mother’s leptin level. (Ilcol, Hizli, Ozkan, 2006)

Disclaimer: Like much of my work, this is incomplete to my level of curiosity and perfectionism, but it is interesting and is being provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual health care guidance, however, pomegranate is pretty awesome.

References - see: ‘Pomegranate Products for the Pain of Histamine Excess.’ copyright Jennifer Depew, RD (Pom pdf in my sync file)

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Hashimoto's, I learned, is very confusing to live through as it can fluctuate between low and high levels of thyroid hormone based on the phase of tissue breakdown.

When the thyroid tissue is being attacked by our own immune cells, then damaged cells may leak excess thyroid hormone into circulation causing hyperthyroid symptoms. At other times too little thyroid hormone may be prosent because the body removes the excess of thyroid hormone.

Gluten is also likely part of the confusion. It is a chemical similarly shaped to the thyroid gland so molecular mimicry antibodies can be set up against it due to dietary gluten that leaked through an unhealthy gut lining.

Soy and dairy are also common sensitivities seen in Hashimoto’s according to a free ebook by Izabella Wentz, PharmD, ‘Supplements for Subduing Hashimoto's Symptoms’. (pdf in my Sync file) Supplements she recommends include stomach acid supporting Betaine HCl & Pepsin, probiotics, methyl forms of folate and B12, thiamine B12, magnesium glycinate, vitamin D3. *Addition, astonishingly, I don’t think she recommends iodine (?) I should reread it though. ….No, I didn’t miss it:

From the Table of Contents: #1: NALTREXONE, #2: PROBIOTICS, #3: SELENIUM, #4: BETAINE WITH PEPSIN, #5: SYSTEMIC ENZYMES, #6: MODUCARE, #7: THIAMINE (B1), #8: B12, #9: VITAMIN D, #10: MAGNESIUM, #11: FERRITIN

From the text: “The following nutrients are often going to be deficient even with a nutrient dense diet: selenium, vitamin D, the B vitamins (especially thiamine and B12), ferritin, zinc, and magnesium.”

“Most people with hypothyroidism, intestinal permeability, toxins, and adrenal stress have numerous nutrient depletions.” Izabella Wentz, PharmD, (pdf in my Sync file)

** A different blog post on the topic of iodine and thyroid, (shared by Nattering Naybob, thanks!), provides more specific recommendations and her article goes into detail about the substitution that can occur with an excess of fluoride, bromide or chloride present in the body instead of adequate iodine.

“I also recommend taking a comprehensive multivitamin that contains iodine. While writing my book, I custom formulated a multivitamin that is specially designed for patients with Hashimoto’s and Graves. It contains 300 mcg of iodine, in addition to selenium, zinc, and other key nutrients for thyroid health.

However, as I mentioned, too much iodine can have a negative impact. That’s why I recommend keeping dietary and supplemental iodine intake between 150 and 450mcg daily.” - Amy Myers, MD, The Iodine & Thyroid Connection (amymyersmd.com)

Addition regarding how iodine likely would be needed and helpful during autoimmune thyroid conditions -

Picture a jigsaw puzzle where you have not many of the correct shape and a whole bunch of a close match, fits, but doesn't look right. The picture does not work even though the space was filled. Dr. Brownstein's method, (which I used, minus the selenium - my mistake), his method is to flood the body with excess iodine for one month, and then to continue providing it with plenty, equal to the amount in the Japanese diet.

The recommendation by Amy Myers of 150-400 mcg is more conservative, the RDA or slightly more. Her 300 mcg one-a-day is a better amount than typical but wouldn't be enough to counter balance the jigsaw puzzle box full of wrong pieces, all competing for the space.

The higher dose may be needed more in our goitrogenic environment with its overload of wrong shaped puzzle pieces.

The fluoride and bromide are also likely toxic to the body so flushing them out may help other problems too. My fibrocystic breast pain went away and only returned somewhat more recently when I was feeling like I was going hypothyroid again.

Keep in mind regarding decision making that the mental effects of hypothyroidism is a challenge too. Fight the molasses of brain fog or apathy or depression and try some new things. Whatever you have been doing all along hasn't been working, therefore, change of some sort is needed would be the logical conclusion. Then you have to consider choices and decide. ...and take action. Plan the steps, commit to it with a friend, ....sometimes it might take a little momentum to get on with trying something new

Our mitochondria need iodine to function correctly and it protects them as an antioxidant.

Naltrexone vs Pomegranate Peel Extract

She also recommends a medication, low doses of Naltrexone has been found to help reduce Th17 T-cells which are more prevalent in autoimmune disease. Pomegranate peel extract would do that for you too, without a prescription. (Čolić, et al., 2022)

“Twelve cytokines associated with the function of T-cell subsets were analyzed in PHA-stimulated PBMC cultures in different concentrations of PoPEx (Figure 8). The level of TNF-α was significantly decreased at the concentrations of PoPEx from 12.5–200 µg/mL, dose-dependently, whereas IL-6 was downregulated only at higher concentrations (100 µg/mL and 200 µg/mL). Both T helper (Th)1 cytokine (Interferon-γ) (IFN-γ) and Th17 (IL-17A and IL-17F) cytokines were significantly downregulated at all concentrations applied, dose-dependently.” […]

“The level of IL-10, a key Treg cytokine, was increased at lower concentrations of PoPEx (12.5 µg/mL) and significantly decreased at 50–200 µg/mL of PoPEx.” (Čolić, et al., 2022)

From my pomegranate paper, Table 3.

Immunomodulatory on T-cells, varying effects by dose and type of T-cell.

The effects of pomegranate peel extract (PoPEx) on the adaptive immune system was investigated by Čolić, et al, 2022 with a range of concentrations (range 6.25–400 µg/mL) used for treatment of human peripheral blood mononuclear cells (PBMC). Complex immunomodulatory effects on T-cells were observed. T-cell effects varied with dose and type of T-cells. Doses starting at 12.5 µg/mL of PoPEx suppressed Th1 (IFN-γ), Th17 (IL-17A, IL-17F, and IL-22), and Th9 (IL-9), and pro-inflammatory TNF- α and IL-6. Responses by Th2 (IL-5 and IL-13) and Treg (IL-10) cells and frequency of CD4+CD25hiFoxp3+ cells was upregulated by lower concentrations while higher concentrations increased the frequency of T-cells producing IL-10 and TGF- β.

Cytotoxicity occurred at concentrations of 100 µg/mL and higher. It increased apoptosis and oxidative stress, and reduced autophagy. Non-cytotoxic doses had the opposite effect, increasing autophagy and reducing apoptosis and oxidative stress. Non-cytotoxic doses also inhibited PHA-induced PBMC proliferation and led to a decrease in CD4 expression. (Čolić, et al, 2022)

“A new finding in our study was related to the effect of PoPEx on Tregs. We observed an increase in the proportion of CD4⁺CD25^hiFoxp3⁺ cells in PBMC cultures treated with lower concentrations of PoPEx which correlated with increased production of IL-10. Our findings are similar to the results of Lu et al., 2020 [90], who showed that the treatment of mice with EAE with PoPEx was followed by an increased proportion of CD4⁺Foxp3⁺ and CD4⁺IL-10⁺ in the spleens and brain infiltrates. Tregs are phenotypically and functionally heterogeneous cell populations. Human Tregs produce IL-10 and TGF-β, two main pleiotropic immunosuppressive cytokines which play key roles in protecting the host from infection-associated immunopathology, autoimmunity, and allergy [102,103].” (Čolić, et al, 2022)

Molecular Mimicry, Thyroid tissue and Gluten

Once you have an autoimmune condition, the activated antibodies will attach to any matching proteins and trigger a white blood cell to come and kill and engulf that thing - which if it is a thyroid gland cell, that is self-destruction. Whether to take iodine or not, is a secondary point. The primary need with an autoimmune condition is to remove any of the offending substance if that is possible and in this case it is - stop, TOTALLY STOP using gluten containing foods extremely strictly for best results, and also totally stop using corn products. It doesn’t contain gluten but it does contain a substance that adds to leaky gut membranes. We need to heal the gut lining and stop dietary proteins from entering the blood stream where it can then add to the risk of more antibodies being formed against it.

Normally we want the body to identify and remove foreign proteins from the body, but in this case, the look-alike gluten set up antibodies that are now also leading to an attack on the thyroid gland. There may be other reasons that autoimmune antibodies form against the thyroid gland, but an unknown reason can’t be managed as well as a known suspect. It is worth trying the strict gluten free diet as it can lead to rapid improvement in symptoms and long term resolution or remission.

Aside: Rutin is found in pomegranate peel.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854619/#:~:text=Rutin%20(RU)%20is%20a%20polyphenol,such%20as%20cancer%20%5B96%5D.

Reducing bromide and fluoride in the diet and water and medications can help support normal thyroid hormone production and it might help mitigate autoimmune causal factors. The metals are not good for health and are hard for the body to excrete.

In follow-up to the last post Are You Iodine Deficient?, (Substack), I found some evidence in an ebook about Hashimoto’s written by a Pharmacist who developed Hashimoto’s herself.

“Levothyroxine (generic for Synthroid) which contains the T4 hormone, is the most commonly prescribed medication. Believe it or not, it was the number one drug in the United States in 2013 and 2014.”

- Izabella Wentz, PharmD, “Supplements to Subdue Hashimoto’s Symptoms”.

*Visit her site for a free download - thyroidpharmacist.com **I couldn't refund the same offer, she has another better sign up offer, so I am sharing the one I have screenshots from.

I believe it. Harvard University researchers have tried to tell us that the reason the average person’s core metabolic temperature is now about a degree lower than it used to be is because we are ‘less inflamed’ due to the ease of modern life. Uh no, modern life is more inflammatory and when the core body temperature drops that low the sensible person thinks about hypothyroidism and iodine deficiency.

“The Root Cause of Hashimoto’s

Hashimoto’s is an autoimmune condition where the immune system begins to attack the thyroid gland, in a case of mistaken identity, as though the thyroid gland was a foreign invader. When we think about Hashimoto’s, we know that there are triggers, or root causes, that lead to the immune system attacking the thyroid. This results in a destruction of the thyroid gland as it can no longer produce the thyroid hormone. Root causes include

• food sensitivities, [like gluten],

• nutrient depletions, [like iodine & selenium],

• infections, [EBV is mentioned],

• toxins, [like glyphosate, (Oliveira, et al., 2023)]

• and an impaired stress response.” [That might include lack of magnesium, zinc, and B vitamins - includes myo-inositol, omega 3 fatty acids, and/or lack of a balanced amount of vitamin A and D. The thyroid hormone and activated hormone D and Retinoic Acid all interact in various ways and problems with one can cause problems with the others’ immune and gene transcription functions. EBV likely affects vitamin A and glyphosate negatively effects CYP enzymes needed for vitamin D metabolism.]

From: “Supplements to Subdue Thyroid Symptoms”, by Izabella Wentz, PharmD, (pdf in my Sync file)

Current treatment tends to be to provide Synthroid as it gives the overworked or attacked thyroid gland a break. Antibodies are not worried about apparently. Izabella Wentz, PharmD, disagrees with that, increased thyroid antibody levels are associated with anxiety OCD, and other mental symptoms. Misdiagnosis may occur.

“Selenium and myo-inositol are two supplements that have been shown to lower thyroid antibodies, and I often recommend them for those with Hashimoto’s, as research has shown that they also happen to reduce obsessive-compulsive symptoms. ^[9] Taken together, they are especially effective!”

[…]

“As mentioned in the study regarding blood sugar, Hashimoto’s patients with antibodies over 1,000 IU/mL were found to have lower serum HDL levels. ^[15] Researchers are still working to understand the full extent of how thyroid antibodies impact cholesterol levels.” [*All blood lipid levels are affected and it isn’t understood apparently.]

- Izabella Wentz, PharmD, Why Thyroid Antibodies Matter. (thyroidpharmacist/blog)

The article opens by informing us that self-tolerance is lost in autoimmune disease and that is the ultimate cause of autoimmune thyroid problems. I think, cool, yes, agree, and read on……………………… the article never mentioned vitamin D or Tolerance cells. #facepalm This pharmacist is a young and very attractive female whose website is fancy and she has many major media logos on it suggesting media appearances in many venues. She is the author of four books and appears to be a major presence in autoimmune thyroid care - and had the condition herself - yet, doesn’t seem to know about vitamin D and autoimmunity. I would kindly think she just wasn’t writing about solutions in the article, yet she included the combined use of selenium and myo-inositol for reducing thyroid antibodies.

…So I read her free ebook on supplements which the article pop-up had offered, and indeed vitamin D is a recommendation but its role with regulation of Tolerance cells is still not discussed. I will discuss it later.

Vitamin D and magnesium are teammates - vitamin D needs magnesium to function properly.

Double Brownie points for the magnesium coverage, 5-6 pages on the topic, one of the largest sections.

She does have a supplement line now too, called Rootcology - she likes to get at the root of the problem. Low stomach acid was a precursor for her case of Hashimoto's … and that leads to gut dysbiosis … and that leads to leaky membranes and protein in the blood and if vitamin D is low, … then autoimmune intolerance may be created with molecular mimicry antibodies being created against a food particle that looks like a human protein. … The antibodies cause immune attack on the thyroid gland … and that causes bad health and odd thinking or brain fog.

Later is here - funny story, I went to my site looking for my info on vitamin D and Tolerance regulatory T cells, and looked through my page on G5. Preeclampsia & TRP Channels …. a few times …. there was only a little bit on vitamin D….????…..oh, wrong page. I was looking for page G4. Autoimmune Disease & Vit. D which opens with:

1. Vitamin D helps immune cells to be "tolerant," and not over-allergic.

"What does stress have to do with autoimmune disease? or vitamin D?

You want me to take a bath? [with Epsom salt or magnesium chloride flakes]

Are you kidding me?"

Answer: "No."

The body needs vitamin D and magnesium in order to protect against allergic sensitivity within the immune system. Some types of immune cells can be made to be more or less “tolerant” of foreign protein - such as the DNA of an expectant infant, which is “foreign” to its mother’s DNA. The baby has half the DNA from the father too.    

[The placenta is very rich in vitamin D compared to the rest of the body - as if nature had a plan…that we shouldn’t muck up with glyphosate….]

…

5. Vitamin D helps mom know that baby is a friend instead of a foe.

This information about vitamin D is not part of standard education about the nutrient - yet. The area of immunology during pregnancy and early implantation is advancing.

    The fetus plays a role in decreasing the activity of the maternal immune T cells. A decrease in the internal level of tryptophan within the maternal T cells seems to be involved. A diet containing large amounts of tryptophan was associated with more fetal loss than a standard diet in animal research. For ethical reasons this field of research takes place with lab animals or murine animals. (G.19)

• "And third, fetal survival depends on tolerogenic mechanisms
  that block maternal T cell responses." (G.19)

The estrogen level of the mother may affect the ability of the fetus to inhibit her immune T cells:

• "Estrogen treatment and pregnancy both induced FoxP3 protein expression to a similar degree both in vitro and in vivo, suggesting that high estrogen levels during pregnancy may help maintain fetal tolerance by promoting regulation (G.20.65). Trophoblast-derived chemokines have also been implicated (G.21.63)." (G.22)

It had previously been known that estrogen has protective effects against autoimmune disease. Symptoms for some types can improve for a woman during her pregnancy and then flair back up after delivery.

• "Estrogen has been shown to protect against the development of autoimmune disease, yet the mechanism is not known." (G.20.65)

The study found that estrogen treatment led to an increase in the FoxP3 protein in CD4+CD25− T cells. These are a type of regulatory T cell of the immune system which are essential for protecting against self intolerance - ie autoimmunity:

• "Recently, in a TCR-transgenic mouse model where full protection against spontaneous experimental autoimmune encephalomyelitis could be achieved by the transfer of wild-type CD4+CD25− T cells, Furtado et al. (G.23.47) showed that responsiveness to IL-2 was required for the suppressive function."  (G.24)

     Having walked this around a block or two, I'll get to the point, cholecalciferol, vitamin D3, helps the body make adequate supplies of Treg immune cells, and it is better at it than calcitriol. (G.25) Calcitriol is a synthetic form of vitamin D3 called "Rocaltrol", (G.26), I'm not sure of the exact difference chemically - but they both can help our body tell us who is friend and who is foe.

6. Pair bonds may be better for the chance that baby is conceived too.

There seems to be a very, very strong biological urge in men to be the "only one" and it may be to help assure that his sperm will be the ones that succeed at impregnation and research does suggest that familiarity by the woman's body may help her ovum to recognize sperm with the familiar DNA and reject/kill off by apoptosis any sperm that try to enter the ovum with unfamiliar DNA. Natural fertilization is safest for the baby because in test tube fertilization the sperm is made to enter the cell by the technology instead of letting the ovum do whatever it would normally do  - which allows sperm DNA to enter but not sperm mitochondrial DNA, while the test tube fertilization allows the sperm mitochondrial DNA to enter the ovum making the babies genetically different than most other humans who only have maternal mitochondrial DNA. (G.27)

*I added section 6 as a bonus. See: G4. Autoimmune Disease & Vit. D, for the rest and a link to pdf with the reference list. Aside - rereading my old work shows me that I have improved in organization and should really rewrite those pages.

ZINC

Also critical - don’t forget the zinc if you want to produce plenty of T-cells - good Tolerant ones or any at all - the thymus gland needs to have plenty of zinc. Healthy microbiome species also need plenty of zinc.

**I should probably rewrite this too, but it is late.

The question/comment: Dizzy, Apr 19, Liked by Jennifer Depew, R.D.

I have Hashimotos and I’ve been told to NOT take iodine but I believe Dr Brownstein says I should take it. I’m so confused.

My reply: Jennifer Depew, R.D., Apr 19, Author

The standard medical industry messaging about iodine is largely false/wrong or even deliberately wrong - but the health people are educated with the wrong information so they believe it.

See this post: https://open.substack.com/pub/denutrients/p/iodine-and-an-old-lie-still-being?r=os7nw&utm_campaign=post&utm_medium=web

I would want to read a bit more about Hashimoto's but I think it is an autoimmune issue - totally restricting gluten might be an important strategy. Also the bromide and fluoride in our lives would likely be adding to autoimmune reactions. High dose iodine plus selenium could be the needed treatment to help the body clear out stored bromide and fluoride that is making your thyroid hormone not functional.

This type of issue - controversy between the medical industry and alternative recommendations is a personal hurdle to investigate and consider trying or not trying on your own - or hire a naturopath who knows the real story - not all functional practitioners know about iodine though is what I noticed eventually.

Consider that Dr Brownstein is hassled by the FDA and suppressed by the current system - which has been shown to be a dangerous and not safe or effective system....

But, it is something that you as an adult will have to consider for yourself.

I had to choose to be a "non-compliant patient" as I found the doctor recommendations weren't helping me. But I did listen and modify some of my own strategies occasionally based on what the doctor was saying.

We are in a dangerous situation is the honest way to look at "for-profit healthcare". It is not a good idea to ask for help from people who either are wrong and don't realize that, or who know they are wrong and don't care because curing illness is not their real goal.

Here is a post I wrote in 2015 about being a compliant patient https://open.substack.com/pub/denutrients/p/whether-to-be-compliant-or-to-be-healthy-seems-like-an-easy-question-to-answer?r=os7nw&utm_campaign=post&utm_medium=web

*It is IMPORTANT to NOT get "non-compliant patient" written in your medical chart if you have psychiatric symptoms because the for-profit system will get a judge to force treatment on you and force commitment against your will. Especially if female it seemed to me - females are just crazy bipolar patients who need lots of psych drugs.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

Reference List

(Čolić, et al., 2022) Čolić M, Bekić M, Tomić S, Đokić J, Radojević D, Šavikin K, Miljuš N, Marković M, Škrbić R. Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture. Pharmaceutics. 2022 May 27;14(6):1140. doi: 10.3390/pharmaceutics14061140. PMID: 35745713; PMCID: PMC9228601. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228601/

(Oliveira, et al., 2023) Oliveira JM, Zenzeluk J, Bargi-Souza P, Szawka RE, Romano MA, Romano RM. The effects of glyphosate-based herbicide on the hypothalamic-pituitary thyroid axis are tissue-specific and dependent on age exposure. Environ Pollut. 2023 Oct 1;334:122216. doi: 10.1016/j.envpol.2023.122216. Epub 2023 Jul 19. PMID: 37479171. https://pubmed.ncbi.nlm.nih.gov/37479171/

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That might explain mixed results in some types of studies - some pomegranate might not have much of mannose, xylose or arabinose and those monosaccharides have medicinal and microbiome benefits. But it also gives us information about other supplements that might help if pomegranate isn't available. It also gives us a clue about synergy - why is whole pomegranate better? Why does it seem like isolated phytonutrients from pomegranate can’t do everything singly that they can perform in the whole fruit extract?

Maybe because of the pectin and monosaccharide starches? Pomegranate peel provides us macronutrients, not just micro nutrients?

• This post is a continuation of the biofilm topic started here: Biofilm, polyphenols, microRNA, MMPs, metastasis, and cancer, (Substack); and continued in Pomegranate Paper relaunch, Mannose, and Herbs for Vitality, (Substack).

To combine the mannose info into this post: Mannose is found in cranberries and other produce in small amounts. Mannose does seem to be helpful against cancer because it is providing nutrients to the person but it starves the cancer cells which need glucose and anaerobic glycolysis for energy. (Luo, et al., 2022) Link via Nattering Naybob.

We likely get a little mannose from a variety of foods. Cranberries are best known for mannose as it has been linked to prevention of UTI bladder infections.

“Mannose can be found in fruits (peaches, apples, oranges, blueberries, black currants, cranberries), legumes (green beans, kidney beans, lima beans, soybeans), vegetables (cabbage, turnip, tomatoes), ivory nuts, Aloe vera and baker’s yeast ^{[2,3,10,11,12]}. The amount of mannose that can be absorbed from these foods in not known ^[3,4].” (nutrientsreview.com)

Aloe vera has wound healing benefits when used topically and the mannose content may aid in that function. (Davis, et al., 1994)

Ketone diets try to starve the cancer from carbohydrates too, but too high fat of a diet would be shifting methylation cycles to the anaerobic pathways too. A moderate carbohydrate diet with 50% or less of calories from fat and no more than 10% of those from saturated fat should help keep methylation cycles chugging along aerobically as long as the many nutrients and cofactors were available.

How much mannose to eat?

I still didn’t find a number but one of the animal studies was providing the mannose supplement as sweetened mannose water. A diet plan that was attempting to be higher than standard in mannose content would need to have less total carbohydrate foods and some refined mannose supplement because no single food is that high in mannose. Some of the pomegranate peel samples had up to 18.1% but no one is going to want to eat just pomegranate peel.

Glucomannan is a fibrous starch from the konjac root and it is a combination of glucose and mannose ~ 50 % mannose. It is quite viscous when hydrated - a thick gooey liquid. It is used as a thickening agent as a food additive or to increase fiber content in a food. It is considered a beneficial oligosaccharide. (Tripetch, et al., 2023) You would want to count it as carbohydrate calories within a diet plan - i.e. swap it for carbohydrate grams being used for bread, starchy veg, milk, fruit, or beans. Too large of a intake could overfeed the gut microbiome and lead to uncomfortable gassiness. Also drink plenty of water when increasing fiber rich foods in the diet.

Only one gram of glucomannan taken three times a day is the recommendation for weight loss purposes.

Mannose may be helping weight in part due to shifts in microbiome species towards less inflammatory species or a more beneficial ratio of Firmicutes to Bacteroidetes species. More on that topic will be discussed later.

~~

*Liver health… farther along in the post, is where this post started initially at the end of a different post, and I worked through the mannose information to the realization that pomegranate peel helps oral and gut microbiome due to the peel’s arabinose, xylose and mannose content. The special monosaccharide sugars help promote beneficial bacteria which can eat the special sugars and signaling aspects of the chemicals can help break up the biofilm of negative species (Zhang, et al., 2023) which allows our white blood cells to remove them more easily. The way arabinose helps decrease biofilm is by gene regulation - less biofilm will be produced due to signaling by the monosaccharide causing less biofilm to be produced (Zhang, et al., 2023) - that is handy. Thanks Mother Nature.

That also explains why medical research has consistently shown synergistic benefits from use of whole fruit extracts compared to isolated polyphenols or other single isolates or the postbiotic urolithin-A which does have potent benefits. But none of the potent isolates seemed to have all the benefits that whole pomegranate extract showed.

Monosaccharides are macronutrients - a functional food used for energy purposes, not just cofactor or vitamin like roles. That is how I have described the inner pith of pomegranate peel, as a food to eat in tiny teaspoon amounts, rather than being a trace nutrient to have in microscopic capsule amounts. Too much fiber can overfeed our microbiome and then we can regret our hastily eating too much raw fruit or veg or pasta salad. Pectin is also a beneficial fiber found in pomegranate peel.

Plants make more antioxidant and signaling chemicals in harsher climates.

More beneficial phytonutrients are produced in plants that are experiencing harsher growing conditions. That is part of the reason that ‘organic’ produce has more nutrients than found in commercially grown, artificial fertilizer crops.

A microbiome coincidence?

In exploring the topic of mannose I learned that it effects microbiome species (Zhang, et al., 2021) in the same way that pomegranate does, (Singh, et al, 2022), improves the ratio between Firmicutes and Bacteroidetes species. Having too much of the Firmicutes is associated with obesity. Both are beneficial short chain fatty acid producing species though. This seemed coincidental.

Applying the Gibbs rule #39, “There are no coincidences",” led me to the fact that pomegranate peel can contain mannose and also xylose and arabinose and those monosaccharides have similar microbiome effects. They promote a beneficial balance between species and more of the short chain fatty acid producing species. Short chain fatty acids then feed our colon cells and the butyrate can also activate the immune supporting GP109 receptor.

Biofilm may be used as a protective cloak around cavity causing species.

Biofilm enters the story in that the acid producing cavity promoting bacterial species are also biofilm producing - they make a thicker slime goo coating which is difficult for our white blood cells to penetrate. Somehow the special monosaccharides help modify that biofilm in a way that allows proper immune defense. Arabinose helps against dental pathogens. (An, et al., 2022) Oral cavity causing bacteria may help each other - one species forms more of a protective biofilm layer (S. mutans) and another makes extra lactic acid (Veillonella sp.) which both species like and promotes their growth - but which causes cavities in our teeth. (Luo, et al., 2024)

Cavity causing oral bacteria are team players: “The cariogenic bacteria within the oral microbiota do not exist as isolated entities but rather interact and influence each other. To a certain extent, S. mutans creates a lactic acid-rich environment in carious lesions that facilitates the proliferation of Veillonella species¹², which have been shown to promote the growth of S. mutans in biofilm studies²⁴.” (Luo, et al., 2024)

The yeast Candida (oral thrush) also is acid producing & cavity promoting. - Pomegranate is antimicrobial against it too.

Lactic acid producing Candida yeast in the mouth also can be cavity promoting, (Luo, et al., 2024) , and pomegranate is particularly effective against Candida infections in addition to helping against cariogenic bacterial species. Ellagic acid, an anti-fungal phenol, inhibits an aspartic protease enzyme secreted by Candida albicans. (Polya, 2003, viewable at Corilagin)

Pomegranate products are antimicrobial against dental pathogens.

• Oral mouthwash made with pomegranate extract was tested and found effective against: Pseudomonas aeruginosa and Candida albicans, but not against Enterococcus faecalis. (Oliveira Leite, et al, 2014) *I made myself some pom peel extract and froze it in ice cube trays to use a little at a time as a mouthwash alternative and it really feels effective. See this post for the How-To recipe with photos, Essential oils are FAST… (Substack)

• Pomegranate peel extract was compared to chlorhexidine in an oral mouth rinse clinical trial and the PPE reduced all pathogens that were analyzed but was not as effective against S. mutans as the chlorhexidine. (Jacob, B., et al., 2021)

• Use of 30 ml unsweetened pomegranate juice reduced dental plaque in a small clinical trial. Participants were asked to not brush their teeth for 24 hours prior to the study when a sample was taken before and after the juice. (Kote, Kote, Nagesh, 2011)

~~

Liver health - reduce anger, and reduce fructose and glucose.

And maybe increase use of mannose rich pomegranate peel…

or cranberries (except those are a histamine trigger food).

If I want a healthier liver and body I may need to cut down on angry thinking and on foods with glucose and fructose. Dried fruit may be healthy in moderation but it is concentrated sugar when eaten in excess and that hits the liver and is turned into fats.

Sugar intake, mainly glucose and fructose, within generic diets has increased dramatically during the past century. Hexose, especially glucose, is the most important energy source in living organisms. However, it has been well documented that consuming too much sugar can raise the incidence of many health problems, including diabetes and obesity. Recently, more studies have demonstrated the harmful effects of sugar. For example, one study reported that glucose-fructose syrup (HFCS) enhances intestinal tumor growth in mice via activation of glycolysis and increased synthesis of fatty acids in tumor cells that support tumor growth (1); Another study found that high fructose intake is associated with increased hepatic fatty acid synthesis and marked insulin resistance (2), and a final study showed that dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate (3). More than that, one clinical study among US adults found that consumption of sugar-sweetened beverages (SSBs) is positively associated with total mortality (4).

In addition, high glucose intake and high fructose intake have also been proven to have pro-inflammatory roles for inflammatory diseases. Zhang et al. revealed that high glucose intake exacerbates autoimmunity in mouse models of colitis and experimental autoimmune encephalomyelitis (EAE) by promoting T helper-17 (Th17) cell differentiation (5). Jones et al. found that fructose reprograms glutamine-dependent oxidative metabolism in mononuclear phagocytes to support LPS-induced inflammation (6). Another study found that high-fructose diet (HFrD) elicited endotoxemia, could activate toll-like receptor (TLR) signaling in liver macrophages, and induce liver inflammation (7). Another two studies also reported that dietary simple sugars alter microbial ecology in the gut and promote colitis and EAE in mice (8, 9).” (Zhang, et al., 2021)

Mannose is a similar monosaccharide that has anti-inflammatory properties instead of inflammatory ones.

“We conclude that treatment with mannose can suppress inflammation by inducing regulatory T cells, suppressing effector T cells and inflammatory macrophages, and increasing anti-inflammatory gut microbiome. By summarizing all the important findings, we highlight that mannose treatment is a safe and promising novel strategy to suppress inflammatory diseases, including autoimmune disease and allergic disease.” (Zhang, et al., 2021)

Mannose helps the gut microbiome in similar ways as pomegranate juice - improving the ratio of Bacteriodetes to Firmacutes which may have anti-obesity benefits.

Mannose “May Increase Anti-Inflammatory Gut Microbiome”

“Within the past decade, the gut microbiome has been proven to have critical functions in immune homeostasis and inflammation (35, 36). Sharma et al. showed that mannose treatment by drinking-water supplementation prevented weight gain, lowered adiposity, reduced liver steatosis, and improved glucose tolerance during the induction of obesity in high-fat diet (HFD) mice (20). Interestingly, these beneficial effects of mannose were observed only when initiated early in life, but not when provided later. These changes in HFD mice with different ages, coupled with the fact that continuous mannose supplementation is required, made authors postulate that mannose treatment might change gut microbiome in HFD mice. Indeed, they proved that mannose treatment initiated early in life increased the Bacteroidetes to Firmicutes ratio in the gut microbiota of HFD mice, showing an association between gut microbiota composition and the timing of mannose introduction (20). The decrease of the Bacteroidetes to Firmicutes ratio in the gut microbiota has been shown to cause obesity in both mice and human, and the increase of the ratio is positively associated with weight loss (37–39). These findings show that mannose suppressed obesity by increasing the Bacteroidetes to Firmicutes ratio in the gut microbiota.

Importantly, Bacteroides are the most abundant members of Bacteroidetes in the intestinal tract of mammals, and the immunomodulatory activities of Bacteroides have been identified (40–43). Lower levels of Bacteroides in the gut microbiota have been shown to be associated with Inflammatory Bowel Disease (IBD) (40),…” (Zhang, et al., 2021)

That factoid suggests pomegranate may have mannose content. Xylose content found in some peel samples could help explain why pomegranate is so helpful for dental health and microbiome balance. Beneficial species can eat xylose and bad ones can’t.

“Many studies examined the sugars in the pomegranate fruit, mainly in the juice, revealing glucose, and fructose as the main component of the juice sugars (Figure 1). Sugars found in the fruit peel were in some controversy among studies from different countries. It should be noted that those studies were done for different purposes and therefore followed different procedures of extraction and detection that might explain this disagreement. Some of the studies indicated glucose and fructose as the main sugars while others found that xylose and arabinose are the main sugars (Hasnaoui et al., 2014).” (Bar-Ya’akov, et al., 2019)

Where your pomegranate are grown seems to matter - varieties have differing monosaccharide content in the peels. Tunisian and Iranian species had xylose and arabinose predominating as 60% of the sugar content and had 3.4-18.1% mannose. Species from Israel had glucose and fructose as the major sugars.

“Notably, the major sugars that were detected in the peels differed between the varieties grown in Tunisia, Iran and Israel. In the 12 Tunisian varieties, xylose and arabinose represented more than 60% of the total content, followed by galactose (14%), glucose (∼10%), mannose (∼5%), rhamnose (∼4%), and fucose (∼1.5%) (Hasnaoui et al., 2014). Peels from one Iranian variety showed that the main sugar is glucose (44.9–68.1%), followed by galactose (14.6–19.4%), mannose (3.4–18.1%), arabinose (3.1–18.1%), and rhamnose (3.5–6.0%) (Ahmadi Gavlighi et al., 2018). However, in the 29 worldwide varieties grown in Israel, the major sugars were glucose and fructose.” (Bar-Ya’akov, et al., 2019)

A hotter growing climate leads to lower glucose and fructose ratios:

“The varieties grown in Mediterranean climate showed significantly higher levels of glucose and fructose in the juice than those grown in a hotter habitat (Schwartz et al., 2009)” (Bar-Ya’akov, et al., 2019)

Better quality pomegranate juice is whole fruit pressed in a way that includes peel nutrients in the juice without adding so much that the juice is too bitter to enjoy.

Checking the dental pomegranate juice theory - ‘arabinose and dental cariogenic pathogens pubmed’

» Why is drinking pomegranate juice as effective as brushing your teeth? It is sweet…that doesn’t make sense….unless some of the sugar is xylose, arabinose, and mannose.

Arabinose does have an inhibitory effect on the biofilm created by oral bacteria on titanium discs used for oral implants. (An, et al., 2022) Current dental methods wipe out all of the oral microbiome. Strategies using certain sugars can help adjust the mouth species towards beneficial and away from more cariogenic species that form biofilm and produce excess acid (examples include: S. mutans and Streptococcus sobrinus). Protective species seen during early childhood include Rothia, Neisseria, and Haemophilus, while children with dental caries were more likely to have Prevotella spp., S. mutans, and Human herpesvirus 4 (EB virus). Dental cavities seem to involve the overall microbiome balance rather than being specific to one species. (Luo, et al., 2024)

Incidentally, or causally, Prevotella species may be more prevalent in patients with Alzheimer’s dementia. (Taati Moghadam, et al., 2022)

I seem to have dropped the ball on Tibetan Medicine, Ho’oponopono, and self-compassion. *Referring to the other post, which is not finished yet.

Or maybe I picked up the ball on the interconnectedness of life.

Some sugars cause obesity and over-acidity in us and in bacterial species (glucose and fructose) and other sugars promote health in us and in our bacterial species (mannose, xylose, and arabinose).

Galactose is a sugar that can be used in aerobic methylation cycles and therefore is ‘inflammatory’ in that metabolic waste is created from glucose, however it has not been found to be cavity promoting in the way that glucose and fructose have. Galactose has to be converted into glucose first, so it is slower to affect blood sugar levels or insulin than other carbohydrate foods. (intelligentsugar.info/sugars/galactose/)

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

References

(An, et al., 2022) An SJ, Namkung JU, Ha KW, Jun HK, Kim HY, Choi BK. Inhibitory effect of d-arabinose on oral bacteria biofilm formation on titanium discs. Anaerobe. 2022 Jun;75:102533. doi: 10.1016/j.anaerobe.2022.102533. Epub 2022 Feb 7. PMID: 35143955. https://pubmed.ncbi.nlm.nih.gov/35143955/

(Bar-Ya’akov, et al., 2019) Bar-Ya'akov I, Tian L, Amir R, Holland D. Primary Metabolites, Anthocyanins, and Hydrolyzable Tannins in the Pomegranate Fruit. Front Plant Sci. 2019 May 17;10:620. doi: 10.3389/fpls.2019.00620. PMID: 31164897; PMCID: PMC6534183. https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2019.00620/full

(Braga-Silva and Santos, 2011) Braga-Silva, Lys & Santos, André. (2011). Aspartic Protease Inhibitors as Potential Anti-Candida albicans Drugs: Impacts on Fungal Biology, Virulence and Pathogenesis. Current Medicinal Chemistry. 18. 2401-19. 10.2174/092986711795843182. https://www.researchgate.net/publication/51123515_Aspartic_Protease_Inhibitors_as_Potential_Anti-Candida_albicans_Drugs_Impacts_on_Fungal_Biology_Virulence_and_Pathogenesis

(Davis, et al., 1994) Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc. 1994 Feb;84(2):77-81. doi: 10.7547/87507315-84-2-77. PMID: 8169808.

(Luo, et al., 2022) Luo H, Wang X, Wang Y, Dan Q, Ge H. Mannose enhances the radio-sensitivity of esophageal squamous cell carcinoma with low MPI expression by suppressing glycolysis. Discov Oncol. 2022 Jan 3;13(1):1. doi: 10.1007/s12672-021-00447-0. PMID: 35201482; PMCID: PMC8777573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777573/

(Luo, et al., 2024) Luo, SC., Wei, SM., Luo, XT. et al. How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: an oral microbiota perspective. npj Biofilms Microbiomes 10, 14 (2024). https://doi.org/10.1038/s41522-024-00488-7 https://www.nature.com/articles/s41522-024-00488-7

(Taati Moghadam, et al., 2022) Taati Moghadam M, Amirmozafari N, Mojtahedi A, Bakhshayesh B, Shariati A, Masjedian Jazi F. Association of perturbation of oral bacterial with incident of Alzheimer's disease: A pilot study. J Clin Lab Anal. 2022; 36:e24483. doi:10.1002/jcla.24483 https://onlinelibrary.wiley.com/doi/full/10.1002/jcla.24483

(Tripetch, et al., 2023) Tripetch P, Lekhavat S, Devahastin S, Chiewchan N, Borompichaichartkul C. Antioxidant Activities of Konjac Glucomannan Hydrolysates of Different Molecular Weights at Different Values of pH. Foods. 2023; 12(18):3406. https://doi.org/10.3390/foods12183406 https://www.mdpi.com/2304-8158/12/18/3406

(Zhang, et al., 2023) Zhang M, Luo X, Li X, Zhang T, Wu F, Li M, Lu R, Zhang Y. L-arabinose affects the growth, biofilm formation, motility, c-di-GMP metabolism, and global gene expression of Vibrio parahaemolyticus. J Bacteriol. 2023 Sep 26;205(9):e0010023. doi: 10.1128/jb.00100-23. Epub 2023 Sep 1. PMID: 37655915; PMCID: PMC10521368. https://pubmed.ncbi.nlm.nih.gov/37655915/

(Zhang, et al., 2021) Zhang W, Cheng H, Gui Y, Zhan Q, Li S, Qiao W, Tong A. Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation. Front Immunol. 2021 Sep 27;12:756920. doi: 10.3389/fimmu.2021.756920. PMID: 34646279; PMCID: PMC8502929. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502929/

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The goal was 12,000 word article, so anything extra got put in a Table, I have a dozen or more. There is a lengthy Table of Health Benefits and one on Phytonutrient content of pomegranate which list many research studies with a brief blurb about the study’s findings. Those are handy as a quick reference guide. What was I trying to remember? Oh, there it is.

Pomegranate peel is consistently safe and effective, no joke, no fraud. Revered by ancient kings because it simply is that great for our overall health and mental clarity.

• ‘Pomegranate Products for the Pain of Histamine Excess.’ copyright Jennifer Depew, RD (Pom pdf in my sync file)

Mannose - found in cranberries and other produce in small amounts.

Mannose does seem to be helpful against cancer because it is providing nutrients to the person but it starves the cancer cells which need glucose and anaerobic glycolysis for energy. (Luo, et al., 2022) Link via Nattering Naybob.

We likely get a little mannose from a variety of foods. Cranberries are best known for mannose as it has been linked to prevention of UTI bladder infections.

“Mannose can be found in fruits (peaches, apples, oranges, blueberries, black currants, cranberries), legumes (green beans, kidney beans, lima beans, soybeans), vegetables (cabbage, turnip, tomatoes), ivory nuts, Aloe vera and baker’s yeast ^{[2,3,10,11,12]}. The amount of mannose that can be absorbed from these foods in not known ^[3,4].” (nutrientsreview.com)

Aloe vera has wound healing benefits when used topically and the mannose content may aid in that function. (Davis, et al., 1994)

Ketone diets try to starve the cancer from carbohydrates too, but too high fat of a diet would be shifting methylation cycles to the anaerobic pathways too. A moderate carbohydrate diet with 50% or less of calories from fat and no more than 10% of those from saturated fat should help keep methylation cycles chugging along aerobically as long as the many nutrients and cofactors were available.

Herbs for Vitality - free webinar series, temporary availability.

Really great Herbal webinar on herbs for stress individualized to whether symptoms are more anxious or angry or grieving and other variations. Part one of three parts by different educators, limited time free viewing. Herbs for Vitality Free Series by the Herbal Academy, (theherbalacademy.com/hfv-pt1/). Part one focuses on the stress response and the educator, Lindsey Feldpaush, RH (AHG), is so peaceful. It feels healing just to listen to her.

Oat milky seed is an early stage of oats growing season. The oat seeds are milky when small and the entire greenish top.is used in herbal preparations. It and Blue vervain may be helpful when feeling overwhelmed is dominating. Variations in feelings can indicate more specifically which herb may suit a particular need best.

Skullcap fresh is preferred for making a tincture but dried works too.

Hawthorn is nutritive, rose as in powdered rose hips and tulsi is a basil - herbs that may help during grieving.

Passionflower, hops and lavender are in a tea blend for easing worry.

Chamomile or ashwagandha when feelings of frustration are excessive.

Herbal tea gummies, yum. Ease anger with a gut microbiome treat made with skullcap, lemon balm and chamomile.

The educator for Part 1 is so soothing you might feel better just from listening to Lindsey's discussion of herbs and strategies for improving negative feelings that can occur with the fear/stress response. Some of us may tend towards anxiety more while others may have anger bubbling under their surface.

Meme for today - you can't see your reflection in a pot of boiling water. Only in still waters can you look within.

Overwhelmed by my pomegranate paper 's reference list …. I went ahead with the rest of the paper and decided not to worry about the reference list’s beauty or excess links right now. It is useful in its current form.

And it is needed.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

References

(Davis, et al., 1994) Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc. 1994 Feb;84(2):77-81. doi: 10.7547/87507315-84-2-77. PMID: 8169808.

(Luo, et al., 2022) Luo H, Wang X, Wang Y, Dan Q, Ge H. Mannose enhances the radio-sensitivity of esophageal squamous cell carcinoma with low MPI expression by suppressing glycolysis. Discov Oncol. 2022 Jan 3;13(1):1. doi: 10.1007/s12672-021-00447-0. PMID: 35201482; PMCID: PMC8777573. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777573/

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Biofilm is a complex topic – a Goldilocks topic. We need biofilm in just the right amount. This post got long and I made it into a document, pdf in my sync file.

• The Glycocalyx – Our Jelly Lining. One of my very first posts has additional video of living tissue showing our extracellular matrix in action and other reference links at the end which I added later. Fiber rich foods to make our jelly lining was the initial focus of the post. *And it was my very first photo shoot for a blog graphic. (substack)

I’m not sure if the jelly coated jar makes my visual point – our intestines are lined with a gooy gelatin-like layer.

Biofilm is just the same thing basically as our extracellular matrix except it is a thicker area of the Jello-like layer that surrounds cells and organs. We need this thicker goo layer along our intestinal cells to protect them. White blood cells will travel in that area looking for stuff to clean up and it helps them not be swept away with the flow of food/chyme in the intestine.

Eating a diet rich in fiber helps us have a good goo layer because it is made of fibrous starches holding onto water molecules by electrical attraction. Polyphenols and other plant chemicals also stabilize the gelatin structure of a cell.

The electricity of an acidic solution or if EMF can disrupt the goo layer like pouring lemonade on a chilled Jello mold would melt it.

<visual image, the Wicked Witch of the West being melted by Dorothy's bucket of water>.

Bacteria or cancer cells make a goo layer. Healthy cells make a goo layer. What we eat makes a difference in the goo and its ability to help white blood cells and out health or to harm it by being absent, too thin, allowing stuff in that shouldn't. And white blood cells can't travel in that, but they also would have trouble with thick sticky congestion. Some cancer cell types make thicker goo layer, or glycocalyx, and disrupting that can allow white blood cells to recognize the cells as something to remove. (Piplani, et al., 2024)

---- Biofilm is nose mucus or what we cough up from our lungs - except that would be unhealthy biofilm.

<Visual and smell image - bronchitis mucus turns greenish yellow and smells foul and that is when antibiotics are needed.>

Bitter tasting phytonutrients

Grapefruit or any other citrus peel is extremely effective at thinning over-thick mucus, and the bitter tasting phytonutrients also cause the airways to open more and cilia to move the thinned mucus up and out.

microRNA

Pomegranate and other functional foods have many phytonutrients that can help up or down regulate protein production in whichever direction is needed to reduce oxidative stress and restore balance. They do it via microRNA and that would correct epigenetic dysfunction causing production of too much if the wrong/inflammatory proteins. "Biofilm" is an important topic due to methylation cycle function in cell cytoplasm impacting whether there will be proper epigenetic control of cell nuclear DNA. No cytoplasm and mitochondrial methylation cycles and then no methylation in the nucleus and no epigenetic brakes in regarding cell growth. Like a developing baby - full forward growth but with no proper controls to guide it into baby shape.

Eating better helps make healthy cell fluid and glycocalyx/biofilm/jelly lining that will be protective and functional instead of watery or sticky and thick. "Cancer biofilm" is likely sticky and thick because cancer tends to occur in more acidic bodies and having a more acidic body is like pouring lemonade on your Jello it will mess it up. Or like adding too much vinegar to pickled eggs - the protein will condense into a tough rubbery texture instead of being like a tender hard boiled egg. Being overly acidic is also a sign that methylation cycles aren't working properly. There's lots more to correcting the dysfunction in methylation cycles but I need to go do other stuff. Healthy cell cytoplasm and jelly goo is a critical need and probably 'cancer cell biofilm' is thick sticky not healthy fluid balance in the body. Specific biofilm disrupted are not what I would focus on as much as how to get the entire body less acidic and more flowing properly.

Polyphenols from pomegranate and other superfoods are amazing because they can stabilize proteins or receptors in a beneficial shape, help stabilize the structured water - organized Jello-like aspect of our cell fluid, and turn off inflammatory protein production. So even if cells have genes saying "make this inflammatory stuff" and are producing messenger mRNA which would encode the inflammatory stuff, a plant polyphenol wants to reduce oxidative stress for the plant and it can cause microRNA to be made that will break down mRNA encoding inflammatory things.

Microbiome tangent

Pomegranate has several or more phytonutrients that help in varied ways. Whole fruit extract generally shows most benefit over isolated chemicals from it. However our healthy microbiome is part of that - of isolates, the post-biotic urolithin -A is very potent and can enter the brain. BUT only people with butyrate producing gut species will have it being made from ellagic acid from the pomegranate/ Sumac / goji berries / green tea. Those species are preferentially killed by spike. They need a lot of zinc, 30% of our intake goes to our gut microbiome. They also need resistant starch which includes the pectin/inner pith or tapioca, arrowroot or cold pasta or potatoes salad, or polenta. Corn is bad for our gut in other ways, skip the corn starch and polenta. Amaranth is polenta like after cooking and chilling.

microRNA and polyphenols:

Why do we care about microRNA? It affects gene transcription by breaking down mRNA - and polyphenols can help with the regulatory function by affecting the expression of microRNAs (miRNA).

“However, recent findings revealed that polyphenols could interact with cellular signaling cascades regulating the activity of transcription factors and consequently affecting the expression of genes. Together with this classical regulatory pathway, polyphenols have been shown to affect the expression of microRNAs (miRNA). miRNAs are small, noncoding RNAs implicated in the regulation of gene expression that control both physiological and pathological processes such as development and cancer. Furthermore, expression of miRNAs can be affected by different external stimuli including nutrients such as vitamins, lipids, and phytochemicals. In this paper, we review studies assessing modulation of miRNAs expression by dietary polyphenols that could constitute a new pathway by which these compounds may exert their health effects. Over 100miRNAs, involved in the control of different cellular processes such as inflammation or apoptosis, were identified as modulated by polyphenols.” (Milenkovic, Jude, Morand, 2013)

Solutions exist in nature.

Polyphenols including catechins can help epigenetics via modulatory effects on microRNA or non-coding RNA (ncRNA). (Shirazi-Tehrani, et al., 2022) Extensive detail about five microRNA promoted by nine different phytonutrients and the genes and pathways that they promote is available in a study by Milenkovic, et al., 2012 with apo-e -/- mice compared to wild type mice. The phytonutrient effects mitigated changes seen in the knockout mice compared to the wild type mice in addition to promoting anti-inflammatory and cell signaling effects.

The cancer industry will not listen though. Speaking to people directly is needed because good methods exist....in Mexico. Doctors have been run out of the US when they successfully treat cancer. The medical industry treats cancer as an enemy to kill and pay no attention to the fact that the body is also being killed. Then the cancer reoccurs - because the underlying issues were never addressed - AND because the cancer ‘treatments’ tend to make the underlying issues even worse (*disrupted methylation cycles, unhealthy cytoplasm and mitochondrial dysfunction).

Some people make positive changes in the effort to heal and sticking with those changes may keep them in remission, while others may still have the underlying factors going on and cancer reoccurs because something is causing methylation cycle dysfunction. That can include genetic metabolic differences, so a "healthy" diet and lifestyle might never be adequate because a high dose targeted/specific nutrient is needed or the methylation cycles slow down to acid producing rates and fatigue levels of speed.

The approach of disrupting the biofilm around a tumor to let a cancer killing agent get in better is focusing on the kill-the-enemy approach. Terrain rebuilding approach would look at making the cytoplasm healthier and promote immune function. And provide polyphenol type things that literally stop inflammatory protein production and literally stabilize our cytoplasm’s jello-like structure. Healthier cytoplasm supports aerobic methylation cycles which produce less acidic waste than anaerobic methods.

“One of the aberrations observed in cancer cells is increased glycosylation of the cell surface macromolecules [31] that collectively constitute the glycocalyx. Studies have shown that the cancer cell glycocalyx is lengthier and more heterogenous compared to normal cells [32] which leads to greater cell proliferation and invasion as a consequence of hyper-active PI3K-Akt signalling [33,34]. The glycocalyx also plays a pivotal role in modulating cell-ECM adhesions by channelling integrins at distinct sites of the cell membrane that have minimal glycosylation [33], and cell shape by altering the surface morphology [35]; both of which impact the metastatic potential. Interestingly, in breast cancer cell lines which exhibit considerable phenotypic heterogeneity, cancer stem cells (CSCs) expressing higher levels of CD44 glycoprotein were found to form the leading front during spheroid invasion [36]; similarly, overexpression of the carbohydrate binding protein - galectin-9 increased collective migration through the ECM via FAK mediated signalling [37].” […]

“Strikingly, enzymatic deglycosylation-mediated glycocalyx disruption not only reduced translocation efficiency but led to dramatic increase in the extent of nuclear damage. Collectively, these results illustrate the direct impact of the surface glycocalyx in conferring a pro-survival advantage to cancer cells by physically shielding migration-associated stresses.” (Piplani, et al., 2024)

The thicker glycocalyx protects cancer cells during migration so they are more able to metastasize without damage to the nucleus than cancer cells that had the glycocalyx broken down by deglycosylation (removal of surface sugars). (Piplani, et al., 2024)

Phytonutrients in pomegranate peel work synergistically – isolates don’t perform the same singly as a combination can perform together. (Teniente, et al., 2023) Some may affect the cancer cell glycocalyx and others affect a change that leads to apoptosis of the cancer cell.

“Similar results were obtained by Pandey et al. in SiHa cells treated with RU (40–200 µM) for 24 h, in which cell death was induced in a dose-dependent manner. This apoptotic effect was associated with the upregulation of bax and caspases 3 and 9 and the downregulation of bcl-2 expression. Moreover, the authors demonstrated that RU downregulated the expression of the jab1 oncogene, which plays a role in cancer progression by inactivating p53 and p27 tumor suppressors, leading to cell cycle arrest [99].” (Teniente, et al., 2023)

Others may affect a cancer cell’s overuse of MMP enzymes which help a metastasizing cell to ‘eat’ its way through the jello-like extracellular matrix. (Aytanski and Poretsky, 2018) Pomegranate peel extract has been observed to inhibit at least one type of MMP. (Aslam, Lansky, Varani, 2005)

“Migratory cancer cells show elevated expression MMPs, which are Calcium-dependent Zinc-containing endopeptidases capable of degrading extracellular matrix (ECM) proteins (Verma & Hansch 2007). There is a strong correlation between the MMP expression and cancer invasion and metastasis (Kanadaswami et al. 2005). MMPs participate in all stages of carcinogenesis and are particularly important for tumor invasion (McCawley & Matrisian 2000). Generally, overexpression of MMPs is linked to higher metastasis capacity in many tumors (Kanayama 2001; Saito et al. 2007; Castellano et al. 2008; Lee et al. 2008). Expression of MMPs is induced by growth factors (like epithelial growth factors [EGFs]) and receptor tyrosine kinase (RTKs) (such as EGF receptor [EGFR]) involving PI3K (phosphatidylinositol-3-kinase) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling cascades (Sen & Chatterjee 2011).” (Aytanski and Poretsky, 2018)

Aside: Eating seaweed provides fucose, a monosaccharide that helps make necessary surface glycoproteins. Monosaccharides form a more complex language than amino acids within protein can. White blood cells recognize the branching surface sugar markers as ‘self’ or ‘foreign’. Cancer cells may form such a thick goo layer that white blood cells can’t identify what is on the cell’s surface. The modern diet is deficient in the range of monosaccharides that we need in addition to glucose to provide the complex ‘language’ that is possible with the shrubby or tree like surface glycoproteins.

We don’t need fructose, the main fruit sugar, but mannose found in cherries is one of the beneficial special monosaccharides. Glucose and fructose are the two monosaccharides that form the disaccharide, sucrose, Table sugar. Galactose and glucose are monosaccharides in lactose, the milk sugar disaccharide which some people have difficulty digesting due to lacking the enzyme lactase.

Fucose was found on 7.2% of 3299 surface glycoproteins that were examined in a study. Negatively charged sialic acid is the only more common sugar in surface proteins. We can make fucose from mannose but we would still need to eat the mannose. Ninety percent of our fucose may be formed internally from mannose. Mutations in the enzyme needed to convert mannose to fucose,  GDP-mannose-4,6-dehydratase (GMDS), has been observed in colon cancer cells. Too much or too little fucosylation may be seen in cancer cell types. (Miyoshi, et al., 2012)

“Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation.” (Miyoshi, et al., 2012)

There are thirteen known enzymes, fucosyltransferases, that can add fucose to a glycoprotein and three of them are critical for life. Genetically disabling those three causes death to knockout mice. Fucosylation can be involved in cancer and immunity. Differences in fucose are part of the difference between blood type O and types, A, B, and AB. H-antigen is secreted by people with A, B, or AB blood types and it may be protective by promoting more beneficial Lactobacillus and Bifidobacterium species in the gut, while non-secretors (about 20% of the population) may have more negative Prevotella species. The non-secretor gut microbiome profile is associated with Crohn’s disease, an inflammatory bowel condition. (Schneider, et al., 2017)

“Cancer metastasis

As a byproduct of their role in promoting selectin-mediated rolling and adhesion, Sialyl Lewis antigens play an important role in promoting cancer migration and metastasis (Kannagi 1997). These antigens are upregulated in a variety of cancer types including lung (Zenita et al. 1988), breast (Jeschke et al. 2005) and colorectal (Kudo et al. 1998; Zipin et al. 2004) cancers and serve as prognostic factors for increased risk of metastasis (Itai et al. 1991). Studies have shown that elimination of terminal fucose from these antigens with an α-l-fucosidase can impair their ability to roll within endothelial tissue and decrease cancer cell invasion (Yuan et al. 2008). Additionally, one study demonstrated that preventing terminal fucosylation by knocking down FUT1 and FUT4 inhibits tumor growth (Zhang et al. 2008). Similarly, endogenous fucosidases have been shown to play a role in preventing cancer cell proliferation. Decreased expression of α-l-fucosidase 1 (FUCA1) has been identified in a number of different cancer types including colorectal (Otero-Estévez et al. 2013; Ezawa et al. 2016), gastric (Liu et al. 2009) and breast (Cheng et al. 2015) cancers.

Altered fucosylation has also been implicated in affecting TNF-related apoptosis inducing ligand activity in colon cancer, a ligand important for promoting destruction of transformed cells. Although the precise role for fucose in the regulation of this signaling pathway remains unclear (Haltiwanger 2009), defects in the de novo synthesis of GDP-fucose cause increased tumor growth and metastasis of colon cancer in mice (Moriwaki et al. 2009).” (Schneider, et al., 2017)

How do polyphenols help against cancer metastasis? By inhibiting NFkB is the short answer. Pomegranate peel extract has also been seen to inhibit VEGF which is involved in excess blood vessel growth in a tumor.

“NF-κB is a main player in the metastatic process because it is crucial regulator of cell proliferation and survival. NF-κB levels may predict the potential of the tumor cells to metastasize (Jin et al. 2014). In resting cells NF-κB exists in inactive form, located in the cytoplasm, bound to a family of inhibitory proteins referred as IκB (inhibitors of κB). Members of IκB family include IκB-α, IκB-β, IκB-γ, IκB-ε, IκB-ζ, p105, p100, and bcl3, as IκB-α (also known as nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha [NFKBIA]) is the most abundant among them. The control of NF-κB activity is carried out by IκB kinase (IKK) kinases which include mitogen-activated protein kinase kinase (MAPKK) family comprising of NF-κB-inducing kinase (NIK) and MAPK/ERK kinase kinase (MEKK) 1, 2, and 3. When activated, NF-κB translocates to the nucleus where it serves as transcription factor regulating genes controlling cell cycle, apoptosis, transformation, and other processes. Constitutively active NF-κB is characteristic for many cancers. It protects the activation of apoptotic signal by inhibiting p53 activity thus promoting the survival and neoplastic transformation of the cancer cells. The NF-κB signaling induces the expression of a number of target genes involved in angio- and lymphangiogenesis among them the vascular endothelial growth factor (VEGF). NF-κB directly induces the expression of urokinase-type plasminogen activator (uPA) (Sliva et al. 2002), MMP-9, and chemokine receptor CXCR4 (Helbig et al. 2003), which in turn results in promotion of ECM degradation and metastasis. The regulation of tumor metastasis by NF-κB is exerted by reciprocal regulation of prometastatic (heparanase, etc.) and antimetastatic (MMP-1, MMP-2, plasminogen activator inhibitor [PAI]-2, etc.) factors. Thus NF-κB is considered as an attractive candidate for metastasis treatment.”  (Avtanski and Poretsky, 2018

Fucoidan, found in brown seaweed helps against cancer by affecting two microRNAs. (Wu, et al., 2016) Species of seaweed with fucoidan include: Fucus vesiculosus (wracks), Cladosiphon okamuranus, Laminaria japonica (kombu, sugar kelp) and Undaria pinnatifida (wakame). (Wikipedia)

“In this study, we observed that brown seaweed fucoidan inhibited human breast cancer progression by upregulating microRNA (miR)-29c and downregulating miR-17-5p, thereby suppressing their target genes, a disintegrin and metalloproteinase 12 (ADAM12) and phosphatase and tensin homolog (PTEN), respectively.” (Wu, et al., 2016)

If breast cancer cell dysfunction can be controlled by microRNA affected by eating wakame and kombu, or pomegranate peel, or turmeric, then why are toxic chemotherapy and radiation still being used? If microRNA can prevent metalloproteinase overactivity, then a cancer cell would be unable to migrate as well, because it could no longer ‘eat’ its way through our Jello-like extracellular fluid.

Sialic Acid

Other background info: Sialic acid in surface proteins adds a negative charge which helps keep the sides of the intestinal wall open by constantly repelling each other. Red blood cells in health are covered with negatively charged sialic acid rich glycoproteins. Chimeric spike can disrupt sialic acid and red blood cell rouleaux/coin-stacking is seen in the blood.

We cannot eat sialic acid to get more, we have to make it or maybe swap – put extra sialic acid from one place onto another place. Eating foods with nucleotides can save some steps in the assembly process. That might include sardines and a variety of other animal products and for vegans, two teaspoons of Nutritional Yeast Flakes per day can help provide some nucleotides.

We have to make nucleotides or eat them in order to be able to make RNA and DNA. It takes 14 enzymatic steps to make one nucleotide. A strand of mRNA may have 100s of nucleotides. Eating some in our diet can save us energy and time. A fragile, malnourished, or elderly person may not be making a lot of chemicals as well as they used to, even if the genes to do so are not dysfunctional alleles - even if the person had been able to make the chemicals fine for the majority of their lives. Now they aren’t able to very well so eating more nutritious foods becomes more essential for basic function and overall health.

~~~

I’m not sure if I made my point - polyphenols and other phytonutrients can help the body stop making bad proteins even if a cell’s epigenetic control is lost. They can up or downregulate microRNA expression which can then stop mRNA from being made into a protein by a cell, or promote other types of mRNA. Plant nutrients figure out what is needed to restore balance and reduce inflammation based on the inflammatory environment that is present. Is it a drought or a flood? Is it cloudy and cold or super hot noonday sun? The plant chemicals respond to environmental cues without a cancer doctor being anywhere near.

Breaking up a biofilm layer on a pathogenic cell or thinning overly concentrated ‘mucus,’ extracellular fluid, is also part of what plant polyphenols are used to doing when necessary. Life is more like the ocean, and it is up to a cell or plant or animal to keep its fluid and mineral balance in the desirable ocean like ratio instead of becoming too watery or too thick and gooey. Breaking up the thick biofilm around cancer cells or a pathogenic microbe takes away its protective layer that can help a cancer cell to metastasize and protect the cancer or pathogenic microbe from being detected and removed by white blood cells.

While the underlying dysfunction in the cytoplasm that prevents methylation cycles from occurring aerobically needs to be corrected to prevent more cancer from occurring, eating the plant nutrients that can regulate microRNA can help mitigate for the bad epigenetics of cancer cells that are growing without epigenetic “off” switches. Why don’t all plants get nonstop growth? Because they have only certain functions turned on at any one time.

The cancer industry may not like being second fiddle to a not patentable seaweed or fruit peel, but that’s the facts Jack. (Bill Murray, Stripes)

Addition - my reply to a question about what seaweed to eat and how much.

Kombu is high in salicylate and is generally added to soup broth or a batch of beans, a one inch piece. It reduces gassiness of beans and makes the broth creamier.

Wakame is the lettuce like seaweed used to make a cold vegetable salad in Thai or Vietnamese cuisine.

This post, Meals for Trace Minerals and Iodine, has a menu handout by a different dietitian to which I added a section on types of seaweeds. Eating a serving (one tablespoon dried roughly) daily or 5 times a week would be a good dietary goal or any versus none. (substack) How much specific to breast cancer? that is harder to know but I would suggest just be sensible and try some, see how you feel. Bucket loads would be too much.

Hijiki is a seaweed that has been found to have some contaminants occasionally and Arame is similar and doesn't have that concern.

I have used this Emerald Cove brand of Arame and Wakame. vitacost.com/emerald-cove-pacific-arame Eden Foods is a reputable brand too. Japanese brands may be fine too, but I can’t read the Japanese label.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

References

(Aslam, Lansky, Varani, 2005) Aslam MN, Lansky EP, Varani J. Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells. J Ethnopharmacol. 2006 Feb 20;103(3):311-8. doi: 10.1016/j.jep.2005.07.027. Epub 2005 Oct 10. PMID: 16221534. https://pubmed.ncbi.nlm.nih.gov/16221534/

(Avtanski and Poretsky, 2018) Avtanski D, Poretsky L. Phyto-polyphenols as potential inhibitors of breast cancer metastasis. Mol Med. 2018 Jun 5;24(1):29. doi: 10.1186/s10020-018-0032-7. PMID: 30134816; PMCID: PMC6016885. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016885/

Milenkovic, D., Jude, B., Morand, C., (2013). ‘miRNA as molecular target ofpolyphenols underlying their biological effects’. Free Radic Biol Med.Sep;64:40-51. doi: 10.1016/j.freeradbiomed.2013.05.046. Epub 2013 Jun 7. PMID:23751562. Available at: https://www.sciencedirect.com/science/article/abs/pii/S0891584913002748?via%3Dihub  (Accessed 24 Nov 2022)

Milenkovic, D., Deval, C., Gouranton, E., Landrier,J.F., Scalbert, A., Morand, C., Mazur, A., (2012). ‘Modulation of miRNA expression by dietary polyphenols in apoE deficient mice: a new mechanism of the action of polyphenols’. PLoS One. 7(1):e29837. doi:10.1371/journal.pone.0029837. Epub 2012 Jan 10. PMID: 22253797; PMCID:PMC3254631. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029837 (Accessed: 27 Nov 2022)

(Miyoshi, et al., 2012) Miyoshi E, Moriwaki K, Terao N, Tan C-C, Terao M, Nakagawa T, Matsumoto H, Shinzaki S, Kamada Y. Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy. Biomolecules. 2012; 2(1):34-45. https://doi.org/10.3390/biom2010034 https://www.mdpi.com/2218-273X/2/1/34

(Piplani, et al., 2024) Niyati Piplani, Tanusri Roy, Neha Saxena, Shamik Sen, Bulky glycocalyx shields cancer cells from invasion-associated stresses, Translational Oncology, Volume 39, 2024, 101822, ISSN 1936-5233, https://doi.org/10.1016/j.tranon.2023.101822. https://www.sciencedirect.com/science/article/pii/S1936523323002085

(Schneider, et al., 2017) Schneider M, Al-Shareffi E, Haltiwanger RS. Biological functions of fucose in mammals. Glycobiology. 2017 Jul 1;27(7):601-618. doi: 10.1093/glycob/cwx034. PMID: 28430973; PMCID: PMC5458543. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458543/

Shirazi-Tehrani, E., Chamasemani, A., Firouzabadi, N., Mousaei, M., (2022). ‘‘ncRNAs and polyphenols: new therapeutic strategies for hypertension, RNA Biology, 19:1, 575-587, DOI: 10.1080/15476286.2022.2066335Available at: https://www.tandfonline.com/doi/full/10.1080/15476286.2022.2066335  (Accessed 24 Nov 2022)

(Teniente, et al., 2023) Teniente SL, Flores-Gallegos AC, Esparza-González SC, Campos-Múzquiz LG, Nery-Flores SD, Rodríguez-Herrera R. Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer. Antioxidants. 2023; 12(1):127. https://doi.org/10.3390/antiox12010127 https://www.mdpi.com/2076-3921/12/1/127

(Wu, et al., 2016) Wu SY, Wu AT, Yuan KS, Liu SH. Brown Seaweed Fucoidan Inhibits Cancer Progression by Dual Regulation of mir-29c/ADAM12 and miR-17-5p/PTEN Axes in Human Breast Cancer Cells. J Cancer. 2016 Dec 9;7(15):2408-2419. doi: 10.7150/jca.15703. PMID: 27994679; PMCID: PMC5166552. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166552/

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A documentarian, Justin Smith, was part of an FLCCC webinar along with Dr Paul Marik and Dr. Joe Varon. Justin Smith has a new documentary called In the Shadow of Flexner. (official trailer video) The interview was moderated by Betsy Ashton, creative director at Frontline Covid19 Critical Care Alliance.

“Dr. Paul Marik and Dr. Joe Varon were joined by Independent filmmaker and author Justin Smith to discuss the Flexner Report and his new documentary - In The Shadow Flexner.” - Flexner Report and Rise of Big Pharma, FLCCC Weekly Update, March 28, 2024, (odysee.com)

The discussion is about the history of traditional health care and the modern takeover by Rockefeller which was helped by the Flexner Report and what the doctors have experienced or seen happen to other doctors who treat with nutrition instead of pushing the suggested medications. Doctors in the UK can face legal charges if they don't prescribe the standard care and provide holistic care instead. Some are giving up their medical license to just treat holistically because the harassment from medical circles was so bad. (odysee.com)

The gist was that any physician who didn’t fully support the petroleum based pharmaceutical market that was growing larger at the time should be labeled “a quack” and should not be allowed to train others in their methods that did not use petroleum-based medications. In the Shadow of Flexner. (official trailer video)

The Carnegie Flexner Report, ‘Medical Education in the United States and Canada, by Abraham Flexner, was written by a non-physician, an educator was chosen to try to prevent suggestions of bias. It was a major turning point in health care in the US and Canada. The report is 364 pages long and viewable on the funding site of the Carnegie Institute. (pdf) The two page chapter on ‘Negros’ as physicians or patients is extremely racist in tone and may have led to the closing of medical schools that trained people of color as physicians. (review article, pdf)

“Flexner carefully placed words such as pretense and ignorance within the context of shoddy medical schools to warn against blacks in possession of medical degrees. However, this statement revealed the understanding among white academicians that blacks could not attain the intellectual skills to pursue all aspects of the practice of medicine.7

The issue of black inferiority stood out when more sophisticated medical practice was considered. Flexner implied that blacks were not to be trusted in surgery or in research by virtue of their ignorance. Even so, blacks pushed for greater access to adequate preparation in these areas. As a result, overt hostile and skeptical attitudes grew to enormous proportions and effectively limited black participation in medicine throughout this century.5

"Make-believe in the matter of negro medical schools is therefore intolerable." The term makebelieve was used by Flexner to justify recommendations to close five ineffective black medical schools (Flint, Leonard, Knoxville, Louisville, and Memphis). Unfortunately, "make-believe" alluded to more than those five schools.”

THE FLEXNER REPORT AND BLACK ACADEMIC MEDICINE: AN ASSIGNMENT OF PLACE, by Susan Hunt, EdD, (review article, pdf)

Other schools of complimentary or alternative care and psychiatric care were also closed after the 1910 report.

“America experienced a genuinely vast development of biomedical science in the early decades of the twentieth century, which in turn impacted the community of academic psychiatry and changed the way in which clinical and basic research approaches in psychiatry were conceptualized. This development was largely based on the restructuring of research universities in both of the USA and Canada following the influential report of Johns Hopkins-trained science administrator and politician Abraham Flexner (1866-1959). Flexner's report written in commission for the Carnegie Foundation for the Advancement of Teaching in Washington, DC, also had a major influence on complementary and alternative medicine (CAM) in psychiatry throughout the 20th century. This paper explores the lasting impact of Flexner's research published on modern medicine and particularly on what he interpreted as the various forms of health care and psychiatric treatment that appeared to compete with the paradigm of biomedicine. We will particularly draw attention to the serious effects of the closing of so many CAM-oriented hospitals, colleges, and medical teaching programs following to the publication of the Flexner Report in 1910.” (Stahnisch and Verhoef, 2012) (pdf in my sync file)

“Fact-based expression” is the new little black dress of censorship via the Poynter Institute - more info here: Poynter’s Creepy “Fact-based expression”, by Thomas Buckley, April 5, 2024. (brownstone.org)

Poynter is a company that has grown a lot in the CoV era and is used by Google, Meta (Facebook) and TikTok to limit reach of posts that don’t support the current administration’s definition of “truth”. It also runs Politifact, a fact checking site and they were hired by the American Medical Association to make a training webinar for local health care workers regarding the CoV injections - the goal was to increase acceptance of the jab, and the second jab. The webinar roll-out included both topics as of Dec. 4, 2020 - before many people had got the first dose.

• “(And you can watch a rerun of the webinar here.)” (brownstone.org)

• The Poynter Institute report with the new speech-is-not-free phrase can be viewed here: “read the institute’s annual and recently released “Impact Report,”.” (brownstone.org)

Was the Flexner report “fact-based expression”? - probably it would be deemed such in today’s era of even worse ‘pharma’ products.

This is a cute video, Why Smart People Believe Stupid Things. In it we learn that smart people are more likely to fool themselves into believing wrong information, possibly because we believe our own belief in it. The solution is try to retain a sense of humility - “I can be wrong,” and a sense of curiosity to encourage seeking more information to further evaluate whether you might be right, wrong or lacking complete info.

Ehden commented in his private Telegram chat group: "While unintelligent people are more easily misled by other people, intelligent people are more easily misled by themselves. They are better at convincing themselves at things they want to believe than things which are actually true". [Quote from the video.] Or, as Saul Bellow has stated, "a great deal of intelligence can be invested in ignorance when the need for illusion is deep". The only solution to it is... humility and curiosity.” (Telegram group, you would have to ask to join)

The video suggested humility and curiosity as our tools to combat the tendency to believe what we believe because we trust our own beliefs.

The video includes an odd assumption about why intelligence evolved - he totally missed the problem solving point of intelligence. How did monkeys learn to poke a long stick into an ant hill? From watching an anteater stick its long tongue in for a meal of insects. How did the monkeys learn to wash their sweet potatoes? by watching other monkeys do that. Intelligence is about problem solving and is shared through imitation.

Our today trending “Disease X” on X.com (Twitter) is H5N1 - Avian flu, which has led to killing millions of chickens in factory farming settings (the big risk for quasiswarm mutations of RNA virus) and the new variant seems to be able to infect cows, cats, and humans. We’ll see it this is fear-mongering or another way to reduce the food supply and add to hardship and desperation. Test Confirms Avian Flu - New Mexico Dairy Farm Probe Finds Cats Positive, (cidrap.umn.edu) via (x.com/catladyactivist).

And dead penguins are suspected of having died of avian flu (x.com/spectatorindex) however, mass animal population deaths have been occurring for unknown reasons for a while. Geological upset of Earth’s crust can cause methane leaks that poison animals in a narrow region where the leak was. Inhaling too much methane gas can cause respiratory distress and hypoxia and requires immediate medical help. (Jo, et al., 2013)

Fact based expression of truth about the efficacy of pomegranate peel extract against flu strains:

“This study demonstrated that the antiviral effect of PPE on influenza virus is most probably associated with inhibition of viral adsorption and viral RNA transcription.” (Malviya, et al., 2014)

“Results: The crude pomegranate peel extract and its n-butanol and ethyl acetate fractions had the highest inhibitory effect against influenza A virus with IC₅₀ value of 6.45, 6.07 and 5.6 μg/ml in MDCK cells, respectively. Our results also showed that, the production of virus was significantly reduced upon treatment with crude extract, n-butanol and ethyl acetate fractions in a dose-dependent manner (p<0.05).” (Moradi, et al., 2019)

“Because of the alarming emergence of resistance to anti-influenza drugs, there is a need to identify new naturally occurring antiviral molecules. We tested the hypothesis that pomegranate polyphenol extract (PPE) has anti-influenza properties. Using real time PCR, plaque assay, and TCID 50% hemagglutination assay, we have shown that PPE suppresses replication of influenza A virus in MDCK cells. PPE inhibits agglutination of chicken red blood cells (cRBC) by influenza virus and is virucidal. The single-cycle growth conditions indicated that independent of the virucidal effect PPE also inhibits viral RNA replication. PPE did not alter virus ribonucleoprotein (RNP) entry into nucleus or translocation of virus RNP from nucleus to cytoplasm in MDCK cells. We evaluated four major Polyphenols in PPE (ellagic acid, caffeic acid, luteolin, and punicalagin) and demonstrated that punicalagin is the effective, anti-influenza component of PPE. Punicalagin blocked replication of the virus RNA, inhibited agglutination of chicken RBC's by the virus and had virucidal effects. Furthermore, the combination of PPE and oseltamivir synergistically increased the anti-influenza effect of oseltamivir. In conclusion, PPE inhibited the replication of human influenza A/Hong Kong (H3N2) in vitro. Pomegranate extracts should be further studied for therapeutic and prophylactic potential especially for influenza epidemics and pandemics.” (Haidari, et al., 2009)

A combination of cranberry and pomegranate juice was also found effective against virus. (Howell and D’Souza, 2013)

“Pomegranate extracts have also shown antiviral effects against influenza virus, HIV-1 and poxviruses [52, 53, 76].

»> Influenza virus continues to be a major cause of morbidity and mortality each year with 31,000 deaths reported yearly in the US, despite access to vaccines [52].” (Howell and D’Souza, 2013)

The facts suggest that vaccines are not really that effective at preventing illness while pomegranate and cranberry juice and pomegranate peel extracts all seem fairly effective at preventing viral entry into cells. (Haidari, et al., 2009; Howell and D’Souza, 2013; Malviya, et al., 2014) And it helps in a dose-dependent manner - more is more potent. (Moradi, et al., 2019) Punicalagin (Haidari, et al., 2009) may be the polyphenol that prevents cleavage of the gp-120 protein which allows fusion to a cell membrane and entry of viral genes into the cell. (Neurath, et al, 2004)

“Sundararajan et al. [78] also showed that the acidity of pomegranate juice and concentrated liquid pomegranate extract (POMxl) solutions contributed to rapid anti-influenza activity, whereas pomegranate polyphenol (PP) powder (POMxp) did not. A 5-minute treatment at room temperature with 800 μg/mL PP was shown to result in at least a 3 log titer reduction of influenza viruses PR8 (H1N1), X31 (H3N2), and a reassortant H5N1 virus derived from a human isolate. Loss of hemagglutinating activity was reported to accompany the loss of influenza infectivity, with decreased antibody binding to viral surface molecules after treatments with PP. Viral structural damage was also reported using electron microscopic analysis of PP-treated viral particles. However, they found that the antiviral activity was less against avian isolates of one coronavirus and reassortant H5N1 influenza viruses. Kotwal [54] suggested that pomegranate juice can neutralize the infectivity of diverse enveloped viruses and a number of subtypes of a given enveloped virus, indicating potential for development as a treatment option that can be broadly effective against pandemic viruses like HIV, potentially pandemic viruses like influenza, and some carcinogenic viruses.

»>It was shown that influenza A/HK/x31(H3N2), influenza A/Vietnam/1203/04 (H5N1), and a reassortant x31 containing the NS gene segment of an H5N1 isolate were inactivated when treated for 5 minutes at 37°C with pomegranate juice [54].” (Howell and D’Souza, 2013)

If five minutes in pomegranate juice can kill H5N1 virus, then why are we supposed to be super afraid and kill off millions of chickens?

Please explain these facts to me Poynter Institute.

Pomegranate peel extract is also potent against SARS-CoV-2 and protects bifidobacterium, needed for butyrate production & urolithin-A.

Not coincidentally, pomegranate peel extract has also been found to be protective against ‘SARS-CoV-2 novel virus’. It prevents entry at that humanized mouse ACE2 receptor. Urolithin-A was found to be involved in the antiviral activity of pomegranate extract on SARS-CoV-2. (Suručić, et al., 2021; Tito, et al., 2021) That means that it would be important to also have protected your gut bifidobacterium from spike effects in the gut, as they are a species type that might be able to form urolithin-A as a postbiotic from ellagitannins/ellagic acid/gallocatechins.

“Bifidobacterium pseudocatenulatum INIA P815 was the only strain able to produce urolithins A and B from ellagic acid.” (Gaya, et al., 2018)

Adequate resistant starch and generous zinc in the diet help give bifidobacterium the food that need. Pomegranate products also support growth of the butyrate producing species and improves the Firmicutes/Bacteroides ratio by reducing Firmicutes species. (George, et al, 2019) Only about 40% of us may have the microbiome species that are needed to form urolithin-A. And only 12% of study participants had urolithin-A present at baseline - meaning they had both the necessary species and a source of ellagitannins/gallocatechins in their diet. (Singh, et al, 2022) Green tea is a source. Epigallocatechin gallate (EGCG) is an example of a gallocatechin.

A dietary recommendation has been made by an advisory panel of the Academy for Nutrition and Dietetics for flavanols from foods of 400/600 mg/day for cardiometabolic health. Tea, apples, berries are mentioned as sources. (Crowe-White, et al, 2022)  Pomegranate is a source of flavanols, and was a better source of gallocatechins than other Spanish foods tested. (de Pascual-Teresa, et al, 2000)

Colon Cancer rates are increasing (along with other turbo-cancers) - please note the fact that our colon cells need butyrate producing microbiome species for their food supply and immune support.

Incidentally, I have also heard there has been a dramatic increase in colon cancer rates these days - our butyrate producing species are also feeding our colon cells and butyrate activates immune functions which would help against cancer or other inflammatory problems for the colon cells.

Those butyrate producing species need about a third of our dietary zinc - so we need plenty of zinc and many of us may not get enough - particularly older adults (>65) who need about double the current official recommendation. It is the same recommendation for all ages of adults and fact-based research has found that to not support thymus gland function in older adults.

Zinc for Senior Citizens

Senior citizens may need twice as much zinc for thymus function as younger adults, yet the official recommendations do not reflect that. Lack of zinc and reduced or lack of thymus function is common among the elderly and higher dose supplementation can help (~50 mg/day). (Kodama, et al, 2020) Extra zinc supplementation has been found to improve age related loss of thymus gland function in animal-based research. (Haase, Rink, 2009) Zinc supplementation may help increase T-cell type of immune reaction and reduce NF-kappa B inflammatory activity. (McCarty et al, 2021)

Additional comment from TwXtter:

Reminder that #H1N1 affords decent cross-immunity against #H5N1. Also, L-lysine prophylaxis blocks the hospitality of L-arginine to viruses. ‘Cross-immunity and age patterns of influenza A(H5N1) infection’, (Kucharski and Edmunds, 2015) via @MiriWood.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

References

(Gaya, et al., 2018) Pilar Gaya, Ángela Peirotén, Margarita Medina, Inmaculada Álvarez, José M. Landete, Bifidobacterium pseudocatenulatum INIA P815: The first bacterium able to produce urolithins A and B from ellagic acid, Journal of Functional Foods, Volume 45, 2018, Pages 95-99, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2018.03.040. https://www.sciencedirect.com/science/article/pii/S1756464618301324

(Haidari, et al., 2009) Mehran Haidari, Muzammil Ali, Samuel Ward Casscells, Mohammad Madjid, Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir, Phytomedicine, Volume 16, Issue 12, 2009, Pages 1127-1136, ISSN 0944-7113, https://doi.org/10.1016/j.phymed.2009.06.002. https://www.sciencedirect.com/science/article/pii/S0944711309001652

(Howell and D’Souza, 2013) Amy B. Howell, Doris H. D'Souza, "The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health", Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 606212, 11 pages, 2013. https://doi.org/10.1155/2013/606212

(Jo, et al., 2013) Jo JY, Kwon YS, Lee JW, Park JS, Rho BH, Choi WI. Acute respiratory distress due to methane inhalation. Tuberc Respir Dis (Seoul). 2013 Mar;74(3):120-3. doi: 10.4046/trd.2013.74.3.120. Epub 2013 Mar 29. PMID: 23579434; PMCID: PMC3617131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617131/

(Kucharski and Edmunds, 2015) Kucharski AJ, Edmunds WJ. Cross-immunity and age patterns of influenza A(H5N1) infection. Epidemiol Infect. 2015 Apr;143(6):1119-24. doi: 10.1017/S0950268814001976. Epub 2014 Aug 13. PMID: 25115493; PMCID: PMC4411649. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411649/

(Malviya, et al., 2014) Malviya S, Arvind, Jha A, Hettiarachchy N. Antioxidant and antibacterial potential of pomegranate peel extracts. J Food Sci Technol. 2014 Dec;51(12):4132-7. doi: 10.1007/s13197-013-0956-4. Epub 2013 Feb 22. PMID: 25477693; PMCID: PMC4252460. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252460/

(Moradi, et al., 2019) Moradi MT, Karimi A, Shahrani M, Hashemi L, Ghaffari-Goosheh MS. Anti-Influenza Virus Activity and Phenolic Content of Pomegranate (Punica granatum L.) Peel Extract and Fractions. Avicenna J Med Biotechnol. 2019 Oct-Dec;11(4):285-291. PMID: 31908736; PMCID: PMC6925405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925405/

(Stahnisch and Verhoef, 2012) Stahnisch, Frank & Verhoef, Marja. (2012). The Flexner Report of 1910 and Its Impact on Complementary and Alternative Medicine and Psychiatry in North America in the 20th Century. Evidence-based Complementary and Alternative Medicine. 2012. 647896. 10.1155/2012/647896. https://www.researchgate.net/publication/235368754_The_Flexner_Report_of_1910_and_Its_Impact_on_Complementary_and_Alternative_Medicine_and_Psychiatry_in_North_America_in_the_20th_Century (pdf in my sync file)

(Suručić, et al., 2021) Relja Suručić, Maja Travar, Miroslav Petković, Biljana Tubić, Miloš P. Stojiljković, Milkica Grabež, Katarina Šavikin, Gordana Zdunić, Ranko Škrbić, Pomegranate peel extract polyphenols attenuate the SARS-CoV-2 S-glycoprotein binding ability to ACE2 Receptor: In silico and in vitro studies, Bioorganic Chemistry, Volume 114, 2021, 105145, ISSN 0045-2068, https://doi.org/10.1016/j.bioorg.2021.105145. https://www.sciencedirect.com/science/article/pii/S0045206821005228

(Tito, et al., 2021) Tito A, Colantuono A, Pirone L, Pedone E, Intartaglia D, Giamundo G, Conte I, Vitaglione P, Apone F. Pomegranate Peel Extract as an Inhibitor of SARS-CoV-2 Spike Binding to Human ACE2 Receptor (in vitro): A Promising Source of Novel Antiviral Drugs. Front Chem. 2021 Apr 28;9:638187. doi: 10.3389/fchem.2021.638187. PMID: 33996744; PMCID: PMC8114579. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114579/

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Posted on: Thursday, January 18th 2024 at 1:45 pm

Written By: GreenMedInfo Research Group

This article is copyrighted by GreenMedInfo LLC, 2024, Visit our Re-post guidelines

Before you head to a clinic, check your kitchen - what you need to fight COVID-19 symptoms may already be in your pantry

A recent clinical trial published in Mediators of Inflammation explored using pomegranate juice and sumac spice to help relieve COVID-19 symptoms. The randomized controlled study on 182 outpatients found the supplemental foods reduced issues like fever, cough, nausea, and more versus standard care alone. This highlights the potential for certain natural agents to help confront viruses when used alongside conventional approaches.

Summary of Clinical Trial Methods and Outcomes

The trial took place at an Iranian health center during the country's first pandemic wave. Eligible adult outpatients who tested positive for COVID-19 without requiring hospitalization were recruited and randomly split into two groups.

The treatment group consumed 200 mL pomegranate juice three times per day and 1.5 grams sumac spice twice daily on top of standard symptomatic medications like acetaminophen as needed. The control group received only standard medical care. After the roughly one-month intervention period, COVID-19 symptoms were reassessed.  

Multiple respiratory, pain, gastrointestinal, and constitutional symptoms improved more in the phytonutrient-supplemented group. For example, the pomegranate/sumac cohort saw bigger decreases in rates of fever (75% to 0% in men), cough (97% to 27%), muscle pain (100% to 2%), diarrhea (84% to 2%), and weakness (85% to 12%) than controls. The supplementary foods were well tolerated without adverse effects.^[1]

Mechanisms of Botanical Agents Against Viruses

Pomegranates contain compounds like punicalagin and anthocyanins that exhibit antiviral, antioxidant and anti-inflammatory properties based on previous research.^[2] Ellagitannins may inhibit viral binding, entry, replication and activity through direct virion damage and host cell effects.^[3]

Similarly, sumac is rich in gallic acid, flavonoids and anthocyanins. Past studies reveal antiviral effects against influenza, herpesviruses and HIV. Proposed mechanisms include inhibition of neuraminidase enzymes in flu viruses preventing cell penetration and tannins deactivating herpesvirus particles before infection occurs.^[4]

While clinical signs improved, this study did not measure actual viral levels. But the symptom control, especially combined with conventional care, highlights natural products' therapeutic potential for viruses through multimodal actions.

Implications for Integrative COVID-19 Therapy  

This trial focused on outpatients with relatively mild disease not needing hospital admission. Yet the implications span the full COVID-19 severity spectrum.

The anti-inflammatory characteristics of phytochemicals may help counter the excessive cytokine production behind pneumonia and acute respiratory distress syndrome in severe cases, for example.^[5] Additionally, properties like improving antioxidant status could protect organ tissues from damage attributed to virus infection.^[6]

While vaccines, antivirals and monoclonal antibodies dominate the standard of care as primary medical therapies, this study and past research suggest certain supplemental foods like pomegranate and sumac carry benefits too.^[7]

This promising new study indicates the diverse phytochemicals in plants offer much therapeutic promise against viruses like SARS-CoV-2. Intelligently incorporating select natural products alongside standard treatments appears an evidence-based adjunctive approach. More rigorous trials are warranted, but this clinical study reveals pomegranate and sumac's anti-COVID-19 symptom utility.

Visit the GreenMedInfo databases on Pomegranate, Sumac, and Coronavirus Disease to learn more about each of these subjects.

IMPORTANT NOTE ON 'GERM THEORY' AND COVID-19: Discussion of COVID-19 and infectious disease often comes with a wide range of unexamined assumptions, including the presumed lethality of viral particles, or even that viruses per se exist as classically defined by virologists. This is not something that should go without discussion and debate, as the topic deserves a much deeper exploration than is presently being conducted by the mainstream media and conventional medical authorities. In order to rectify this conspicuous lacunae, Sayer Ji has presented an alternative perspective which calls into question conventional models of infectious disease and contagion attributed to viruses, replacing it with what he calls the Xenogen Hypothesis. Learn more by watching his two presentations on the topic. 1) Covid-19: is it really about a virus? And 2) A New Biophysical Paradigm: Viruses, Exosomes, & Infection with Sayer Ji. 

References

1. Forouzanfar F, et al. The Effect of Pomegranate Juice and Sumac Consumption in the Treatment of Outpatients with COVID-19. Mediators Inflamm. 2022 Nov 30;2022:6850342.

2. Conidi C, et al. Perspective of membrane technology in pomegranate juice processing: A review. Foods. 2020 Jul 9;9(7):889.

3. Stefanou V, et al. Pomegranate as an Anti-Viral Agent and Immune System Stimulant. Int J Adv Res Microbiol Immunol. 2021;3(1):1-12.

4. Korkmaz H. Could Sumac Be Effective on COVID-19 Treatment? J Med Food. 2021 Jun 1;24(6):563-568.

5. Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol. 2020 May;20(5):269-270.

6. Messarah M, et al. Prophylactic effects of pomegranate (Punica granatum) juice on sodium fluoride induced oxidative damage in liver and erythrocytes of rats. Can J Physiol Pharmacol. 2016 Jul;94(7):709-18.

7. Benarba B, Pandiella A. Medicinal plants as sources of active molecules against COVID-19. Front Pharmacol. 2020;11:1189.

8. Butler MJ, Barrientos RM. The impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun. 2020 Aug;87:53-54.

The GMI Research Group (GMIRG) is dedicated to investigating the most important health and environmental issues of the day.  Special emphasis will be placed on environmental health.  Our focused and deep research will explore the many ways in which the present condition of the human body directly reflects the true state of the ambient environment.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

Sumac posts:

• Sumac tea was a lemony drink used by Native Americans, (Substack)

• For those who can't grow pomegranates, consider sumac instead, (Substack). Sumac is an invasive shrub that we see along the highway in farming areas.

• Pistachio Sumac Pilaf - recipe, (Substack)

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance. *I have a professional membership with GreenMedInfo which includes the right to repost articles as long as I don’t change them.

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I am sorry that happened. Kidney stones can be extremely painful. and I failed to write that in my [*insensitive] reply:

That doesn't seem like it was just the pomegranate juice [*alone]. I am oxalate sensitive and I don't react to pomegranate juice, but I also don't drink much juice, about 2 ounces diluted. I really haven't noticed oxalate from the tea made with rind either though. Google search shows that pomegranate is considered high oxalate with 121 mg per 100 grams. However research with animals has found pomegranate juice to protect against oxalate damage.

"Crystal depositions were evident on day 7, and mild and severe crystallization were observed on day 15 and 45 in EG group, respectively. There was limited or no crystal formation in rats in both middle- and high-dose PJ groups when compared to low-dose PJ group. Crystal depositions, iNOS, p38-MAPK and p65-NF-kB activity, and oxidative stress markers were found to be decreased by middle- and high-dose PJ treatment. PJ was found to have inhibitory effects on renal tubular cell injury and oxidative stress caused by oxalate crystals by reducing ROS, iNOS, p38-MAPK, and NF-kB expression."

https://www.tandfonline.com/doi/full/10.1080/08860220902963871

Prickly pear cactus fruit are very in oxalate and I did use too much of that in some experiments with it. 152 mg in the fruit and 250 from the leaf. I only had problems when I used the peel like I was using pomegranate peel. https://ohf.org/fruit-oxalate/ Whoa, rhubarb, raw 1060 mg/100 gr. This reference says pomegranate seeds/juice have 78 mg/100 gr which would put it in the moderately high group instead of the High group. Rhubarb and prickly pear leaf (Nopal) would be in the Very High group. Star fruit is also Very High and cooking Rhubarb brings it down a little but is still quite high compared to the other fruits.

Having adequate calcium is important to help the body not make the sharp crystals instead of breaking it down but Vonu makes the excellent point that that won't work without vitamin K2. Supplements of vit K2 are ridiculously low. I get a higher dose supplement from Life Extension. Also being overly acidic is a controllable risk factor. Taking Mucinex daily was part of my risk as it is changed into uric acid before excretion. My high dose niacin was also adding to that. Gut microbiome can also be part of sensitivity as some species add to the oxalate load.

Vonu’s comment, 2 hrs ago:

“Calcium oxalate is a calcium salt of oxalic acid and calcium builds up in the body when someone has a deficiency of vitamin K2, which is explained in Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life by Kate Rheaume-Bleue.”

Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life, by Kate Rheaume-Bleue:

“The secret to avoiding calcium-related osteoporosis and atherosclerosis

While millions of people take calcium and Vitamin D supplements thinking they're helping their bones, the truth is, without the addition of Vitamin K2 , such a health regimen could prove dangerous. Without Vitamin K2, the body cannot direct calcium to the bones where it's needed; instead, the calcium resides in soft tissue (like the arteries)—leading to a combination of osteoporosis and atherosclerosis, or the dreaded "calcium paradox."

This is the first book to reveal how universal a Vitamin K2 deficiency is, and the risk (in the form of cancer and diabetes, among other ailments) the absence of Vitamin K2 poses. Written by Dr. Kate Rheaume-Bleue, a popular health expert on Canadian television and radio, Vitamin K2 and the Calcium Paradox sounds a warning about the popularity of the calcium and Vitamin D craze, while illustrating the enormous health benefits of Vitamin K2 in making the body less susceptible to dental cavities, heart disease, prostate cancer, liver cancer, diabetes, wrinkles, obesity, varicose veins, and other ailments. An essential book for anyone interested in bone health, or maintaining their overall health, Vitamin K2 and the Calcium Paradox is the guide to taking the right combination of supplements—and adding Vitamin K2 to a daily regimen. (*GoodReads)

Life Extension is having a sale on their ‘Mega’ K2. Standard supplement dosage seems like a psy op on learning more about it. A low dose of 45 mcg is a 1000 times less than the ‘Mega Vitamin K2’ dose of 45 mg.

(**Both products are on sale right now, I just got a flyer in the snail mail. Sale ends May 20, 2024. lifeextension.com the 40% off would be a better discount than you get through my Fullscript account (20% or 25% if it is a monthly autoship order). Fullscript has added a great new future where you can enter whatever supplements you take and it totals them all up into what you are getting overall for the day. Sign up link, Fill in your own supplements link - and then I could give feedback if you wanted me to look at it too. Free shipping on orders over $50 and it is very fast. Orthomolecular brand requires me to set up a plan for you but just ask, the system sends me a notice to set up a plan.)

In a study with rabbits (Happy Easter! but poor bunnies…) and atherosclerosis risk, the doses of vitamin K2 (menatetrenone) used were in the milligrams, not micrograms; and they were per kg of body weight. The human equivalent would then be much higher than the amount a lightweight rabbit would get. A high cholesterol diet was used as a risk factor to promote arterial plaque. (Kawashima, et al., 1997)

“Vitamin K2 in daily doses of 1, 10 and 100 mg/kg was given with a 0.5% cholesterol diet for 10 weeks to 8 rabbits each.” (Kawashima, et al., 1997)

If a rabbit weighs about the same as a cat, then ten to 12 pounds would be about 5 kilograms and a daily dose of 5 mg or 50 mg or 500 mg of vitamin K2 would have been given. The 1 and 10 mg doses were effective at reducing lipid imbalance on the high cholesterol diet. The high doses were not a problem and even the 100 mg dose did not cause adverse effects. (Kawashima, et al., 1997)

“The plasma levels of total cholesterol in the vitamin K₂-treated groups were clearly lower than that of the hypercholesterolemic control group. The excessive dose of vitamin K₂, even at the high dose of 100 mg/kg/day for 10 weeks, did not accelerate the progression of atherosclerosis and did not promote the coagulative tendency in the rabbits. In contrast, the vitamin K₂ treatment (1 to 10 mg/kg/day) suppressed the progression of atherosclerotic plaques, intima-thickening and pulmonary atherosclerosis, the increase of ester-cholesterol deposition in the aorta, and both the elevation in plasma factor X level and increase in Hepaplastin ® test value in the rabbits. These results indicate that the pharmacological dose of vitamin K₂ prevents both the progression of atherosclerosis and the coagulative tendency by reducing the total-cholesterol, lipid peroxidation and factor X activity in plasma, and the ester-cholesterol deposition in the aorta in hypercholesterolemic rabbits.” (Kawashima, et al., 1997)

A human equivalent dose would be for a 70 Kg person ~ 150 pounds, either 70 mg or 700 mg to achieve the 1 mg/Kg or 10 mg/Kg dose. A 100 mg/Kg dose would be 7000 mg = 7 grams - so yes, that was a super duper mega dose. Yet for human supplement purchases, I can’t find a dose higher than Life Extension’s Mega Vitamin K2 product with 45 mg per capsule. Taking it twice a day would reach the 1 mg/Kg range but you would need to take 14 capsules to get near 700 mg/day. (LE sale price is $17.10 for a bottle of 30 capsule for the Mega K2 product.)

Developing a taste for the Japanese fermented soybean dish called Natto would net you both vitamin K2 and the biofilm disrupting nattokinase enzyme. Three ounces might provide 880 mg of vitamin K2. Which suggests that humans are safe to take that amount. It is fat soluble so having a larger amount occasionally may cover the body ‘s needs for a while. (Fact check needed)

https://www.vinatura.store/blogs/articles/nattokinase-and-vitamin-k2 Natto news to use via a comment by Nattering Naybob.

Vitamin K2 helps prevent excessive clotting rather than causing clotting to occur. It is used in clotting factors which other signals would induce.

Caution is used with vitamin K supplements when clotting is a risk and blood thinning medication is being used. “As Vitamin K interferes with the effect of anticoagulant drugs (like Coumadin), the concurrent use of these agents should be avoided.” - A liquid Thorne brand product that is recommending the 45 mg/day amount in 3 divided doses of 15 drops each. (That would be highly annoying to count out every day.) A NOW brand product suggests to us that 200 mcg is a high dose. I found a 600 mcg product (0.6 mg) and a 5 mg product by other brands.

…why did the rabbits do fine with the equivalent of 700 mg per day? and tolerated 7000 mg? Why aren’t humans being treated with even 70 mg per day instead of 15 mg x 3 or 45 mg/day? I don’t know. I haven’t seen the studies suggesting that be the recommended limit.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

Reference List

(Kawashima, et al., 1997) Kawashima H, Nakajima Y, Matubara Y, Nakanowatari J, Fukuta T, Mizuno S, Takahashi S, Tajima T, Nakamura T. Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Jpn J Pharmacol. 1997 Oct;75(2):135-43. doi: 10.1254/jjp.75.135. PMID: 9414028. https://www.jstage.jst.go.jp/article/jphs1951/75/2/75_2_135/_article

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Posted on: Wednesday, March 13th 2024 at 4:00 am

Written By: GreenMedInfo Research Group

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Could a simple fruit hold the key to reversing heart disease? A groundbreaking study from 2004 suggests that pomegranate juice may possess unparalleled potential in the fight against atherosclerosis, yet this natural solution has been largely ignored by the medical establishment

In the face of an epidemic of heart disease, the search for effective preventive solutions has never been more urgent. While pharmaceutical therapies dominate the landscape of cardiology, a groundbreaking study from 2004 suggests that a natural approach--drinking pomegranate juice--may hold the key to combating atherosclerosis, the buildup of plaque in the arteries that underlies many forms of cardiovascular disease.

The study, led by Dr. Michael Aviram and published in the journal Clinical Nutrition, followed 19 patients with severe carotid artery stenosis, a narrowing of the arteries that supply blood to the brain.¹ Ten of these patients consumed 50mL of pomegranate juice daily, while the other nine served as a control group. The results were nothing short of remarkable: after one year, the pomegranate group experienced a significant reduction in the thickness of their carotid artery walls, a key measure of atherosclerosis progression.¹

Even more strikingly, five patients continued drinking pomegranate juice for a total of three years, and the benefits only increased with time. Carotid intima-media thickness (IMT), a measure of arterial wall thickening, decreased by 35% after one year and remained reduced for the duration of the study.¹ In contrast, IMT increased by 9% in the control group over the same period.¹

So how does this unassuming fruit wield such power against a formidable disease? The answer lies in its unrivaled antioxidant content. Pomegranates are rich in polyphenols, tannins, and anthocyanins, all of which scavenge the free radicals that contribute to oxidative stress and inflammation in the body.² This is critical because oxidized low-density lipoprotein (LDL) cholesterol is a key player in the development of atherosclerosis.³

Indeed, the study found that pomegranate juice consumption reduced oxidative stress markers and increased antioxidant capacity in the participants' blood. Serum levels of antibodies against oxidized LDL decreased by 19%, while total antioxidant status increased by 130% after one year of daily pomegranate intake.¹ The juice also boosted the activity of paraoxonase, an enzyme that protects against LDL oxidation, by up to 83%.¹

But the benefits didn't stop there. Pomegranate juice appeared to reduce blood pressure as well, with systolic blood pressure decreasing by 21% after one year.¹ This is likely due to the juice's ability to improve endothelial function and reduce oxidative stress in the blood vessels.⁴

Perhaps most intriguing of all, the study examined carotid artery plaque specimens from two patients who had consumed pomegranate juice before undergoing surgery. Compared to plaques from control patients, these specimens showed significantly lower levels of oxidized lipids and higher antioxidant content, suggesting that pomegranate juice may directly impact the atherosclerotic lesions themselves.¹

The implications of these findings are profound. While current medical therapies focus primarily on risk factor management, such as surrogate measures like lowering cholesterol and blood pressure, pomegranate juice appears to target the root cause of atherosclerosis by reducing oxidative stress and inflammation, and healing the underlying damage to the endothelium and arteries. And unlike many pharmaceutical drugs, it is a safe and well-tolerated food, and accessible to virtually everyone.

Yet despite the extraordinary results of this study, pomegranate juice has not been widely embraced as a therapeutic option by the medical community. This raises questions about a potential bias against natural remedies, even when they are supported by rigorous scientific evidence. If a drug showed similar effects on atherosclerosis, it would undoubtedly be hailed as a major breakthrough and rapidly incorporated into standard treatment protocols.

The time has come for a paradigm shift in our approach to heart disease prevention and treatment. While pharmaceuticals certainly have their place, we cannot afford to overlook the immense potential of natural therapies like pomegranate juice. With millions of lives at stake, it is imperative that we prioritize further research into this remarkable fruit and its cardiovascular benefits.

In the meantime, the message to patients is clear: incorporating pomegranate juice into a heart-healthy lifestyle may offer a safe, effective, and delicious way to protect against atherosclerosis and its devastating consequences. As we continue to unravel the mysteries of this ancient fruit, one thing is certain--the humble pomegranate may just hold the key to a brighter, healthier future for us all.

Learn more about the health benefits of pomegranate here.

Learn more about natural approaches to addressing atherosclerosis plaque here.

References

1. Aviram, Michael, Mira Rosenblat, Diana Gaitini, Samy Nitecki, Aaron Hoffman, Leslie Dornfeld, Nina Volkova, et al. "Pomegranate Juice Consumption for 3 Years by Patients with Carotid Artery Stenosis Reduces Common Carotid Intima-Media Thickness, Blood Pressure and LDL Oxidation." Clinical Nutrition 23, no. 3 (June 2004): 423-33. https://doi.org/10.1016/j.clnu.2003.10.002.

2. Gil, M. I., F. A. Tomás-Barberán, B. Hess-Pierce, D. M. Holcroft, and A. A. Kader. "Antioxidant Activity of Pomegranate Juice and Its Relationship with Phenolic Composition and Processing." Journal of Agricultural and Food Chemistry 48, no. 10 (October 2000): 4581-89. https://doi.org/10.1021/jf000404a.

3. Aviram, Michael. "Review of Human Studies on Oxidative Damage and Antioxidant Protection Related to Cardiovascular Diseases." Free Radical Research 33 Suppl (2000): S85-97. https://pubmed.ncbi.nlm.nih.gov/11191279/. 

4. Aviram, M., and L. Dornfeld. "Pomegranate Juice Consumption Inhibits Serum Angiotensin Converting Enzyme Activity and Reduces Systolic Blood Pressure." Atherosclerosis 158, no. 1 (September 2001): 195-98. https://doi.org/10.1016/s0021-9150(01)00412-9.

The GMI Research Group (GMIRG) is dedicated to investigating the most important health and environmental issues of the day.  Special emphasis will be placed on environmental health.  Our focused and deep research will explore the many ways in which the present condition of the human body directly reflects the true state of the ambient environment.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance. *I have a professional membership with GreenMedInfo which includes the right to repost articles as long as I don’t change them.

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Written By: GreenMedInfo Research Group

This article is copyrighted by GreenMedInfo LLC, 2024, Visit our Re-post guidelines

For aging men watching their vitality slowly drain away each year, a proprietary botanical blend represents newfound hope of restoring lost vigor and masculinity

A new double-blind, placebo-controlled trial published in the International Journal of Medical Sciences evaluated a proprietary blend of pomegranate and cocoa extracts (LN18178) for relieving symptoms associated with aging in men, known as aging males' symptoms (AMS).¹ AMS encompasses declining physical, psychological, and sexual function that often accompany age-related testosterone decline.²

Background

Testosterone levels in men begin decreasing around age 30, falling 1-2% annually.³ By age 50, many men start experiencing symptoms like fatigue, mood issues, and reduced muscle mass.⁴ TermED "late-onset hypogonadism" reflects this age-related testosterone deficiency and its effects on men's health.

Testosterone replacement can alleviate symptoms, but has risks like prostate issues.⁵ Also, when you replace the hormone through exogenous sources, you can activate a negative feedback loop within the endocrine system encouraging even lowered hormone production and gland atrophy. Plant compounds provide a safer alternative for supporting healthy testosterone levels with aging. Previous studies found herbal extracts helped mitigate AMS while boosting testosterone.^6,7 LN18178 combines standardized pomegranate fruit rind and cocoa seed extracts with antioxidant and anti-inflammatory effects.⁸ Early research showed muscle and testosterone benefits in young men.⁹

Study Results 

This study examined LN18178 in 120 men aged 36-55 with mild to moderate AMS. The LN18178 groups showed significant 15-19% decreases in total AMS scores, including psychological, somatic, and sexual domains compared to only 4.5% improvement for placebo. They also exhibited 39-48% increases in serum free and total testosterone versus baseline and placebo. Muscular strength improved 18-25% and perceived stress scores reduced 15-23% with LN18178.safety analysis was favorable.

Implications

These results have important ramifications for menopausal health and longevity. Maintaining testosterone levels with aging via safe supplementation like LN18178 could help mitigate concerns like loss of strength and sexual function. Supportive care is increasingly vital amidst rising life expectancy and years spent in later-life stages like menopause and andropause. LN18178 may help enhance quality of life and independence for maturing men. Further research on long-term efficacy and optimal dosing will illuminate its potential against aging's multifaceted declines.  

For more information on natural substances that promote longevity visit here.

Learn more about the health benefits of pomegranate here. 

Learn more about the health benefits of cocoa here. 

Learn more about how to address low testosterone here. 

Learn more about low libido here. 

Learn more about how to regenerate your hormones with vitamin C here. 

References

1. Pandit, S.L., Yaligar, D., Halemane, M. et al. A proprietary blend of standardized Punica granatum fruit rind and Theobroma cocoa seed extracts mitigates aging males' symptoms: a randomized, double-blind, placebo-controlled study. Int J Med Sci 19, 1290-1299 (2022). https://doi.org/10.7150/ijms.73645

2. Yeap BB. Testosterone and ill-health in aging men. Nat Clin Pract Endocrinol Metab. 2009;5(2):113-121. doi:10.1038/ncpendmet1027

3. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab. 2001 Oct;86(10):724-31. doi: 10.1210/jcem.86.2.7219. PMID: 11549674.

4. Liu CC, Wu WJ, Lee YC, et al. The prevalence of and risk factors for androgen deficiency in aging Taiwanese men. J Sex Med. 2009;6(4):936-946. doi:10.1111/j.1743-6109.2008.01137.x

5. Santella C, Renoux C, Yin H, Yu OHY, Azoulay L. Testosterone Replacement Therapy and the Risk of Prostate Cancer in Men With Late-Onset Hypogonadism. Am J Epidemiol. 2019 Nov 1;188(9):1666-1673. doi: 10.1093/aje/kwz138. PMID: 31155515.

6. Rao A, Steels E, Inder WJ, Abraham S, Vitetta L. Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study. Aging Male. 2016;19(2):134-142. doi:10.3109/13685538.2015.1135323

7. Lopresti AL, Drummond PD, Smith SJ. A randomized, double-blind, placebo-controlled, crossover study examining the hormonal and vitality effects of ashwagandha (Withania somnifera) in aging, overweight males. Am J Mens Health. 2019;13(2):155798831983598. Published 2019 Mar 26. doi:10.1177/1557988319835985

8. Ricci D, Giamperi L, Bucchini A, Fraternale D. Antioxidant activity of Punica granatum fruits. Fitoterapia. 2006;77(4):310-312. doi:10.1016/j.fitote.2006.01.008

9. Sreeramaneni PGA, Yalamanchi A, Konda MR, et al. A proprietary herbal blend containing extracts of Punica granatum fruit rind and Theobroma cocoa seeds increases serum testosterone level in healthy young males: A randomized, double-blind placebo-controlled study. J Diet Suppl. 2022;1-17. doi:10.1080/19390211.2022.2035037

The GMI Research Group (GMIRG) is dedicated to investigating the most important health and environmental issues of the day.  Special emphasis will be placed on environmental health.  Our focused and deep research will explore the many ways in which the present condition of the human body directly reflects the true state of the ambient environment.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

While chocolate covered pomegranate peel doesn’t sound very good compared to chocolate covered citrus peel, dehydrated and powdered inner pith of pomegranate can be used in jams or baked goods.

• Citrus and Fig Marmalade Jam - and a bunch of other variations including pomegranate peel jams and a chocolate ganache/fudge sauce made with the jams. (Substack)

• Dark Chocolate Orange Peel Cookies (Substack)

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance. *I have a professional membership with GreenMedInfo which includes the right to repost articles as long as I don’t change them.

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The take home point is that pomegranate products would help along with niacin and other Nrf2 promoters.

• Autism Health Summit - Functional Genomics and Autism, Tree of Life Health, (vimeo.com)

In the graphic above we see that EMF energy from our cellphone, laptop, or 5G cell tower, can activate the Calcium channels that allow calcium to enter and lead to over-activity of the cell - whether it is a human cell or a microbial cell within us. EMF is causing increased activity. NMDA receptors also allow calcium entry and can activate the channels if activated by glutamate or aspartic acid. Magnesium would be protective by providing the energy needed to keep the calcium channel closed, like a lock on the door. With magnesium deficiency, there can be much more calcium over-activity. Chronic pain, headaches, muscle cramps, and other symptoms like tinnitus may occur with excess calcium channel activity.

Arachidonic acid is produced from membrane breakdown that the calcium triggered. Endocannabinoids are released by an increase in calcium concentration within the cell and initially they are anti-inflammatory, but the endocannabinoid breaks down into the inflammatory arachidonic acid. Arachidonic acid causes other inflammatory pathways to progress leading to more mast cell activation and more inflammation and NMDA receptor stimulation - hyperinflammation positive feedback loop.

Butyrate or niacin or polyphenols from pomegranate peel or other superfoods can help prevent the mast cell degranulation. My graphic is about this same process and Alzheimer’s dementia or more severe autism spectrum disorder seem to be related risks.

Ferroptosis – anemia of chronic infection/inflammation – severe fatigue.

The body will shift iron out of hemoglobin to protect it from suspected pathogens. In severe CoV, the normal response is overactive and can continue in LongCovid. Too little hemoglobin means too little oxygen, and extreme fatigue. Too much iron elsewhere can lead to cell damage from oxidative stress – ‘rust’ caused by electrically active iron. Thread about ferroptosis, with ref and ref and images.

Eating too much, carbohydrates and glutamate seasonings, can greatly increase the risk of ferroptosis – excess free iron and oxidative stress, and lead to increased blood sugar and insulin resistance.

“It is now accepted that nutrient abundance in the blood, especially glucose, leads to the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response from antioxidant mechanisms, the cell, or indeed the tissue, becomes overwhelmed by oxidative stress, leading to the activation of intracellular stress-associated pathways. Activation of the same or similar pathways also appears to play a role in mediating insulin resistance, impaired insulin secretion, and late diabetic complications. The ability of antioxidants to protect against the oxidative stress induced by hyperglycemia and elevated free fatty acid (FFA) levels in vitro suggests a causative role of oxidative stress in mediating the latter clinical conditions. “ (Newsholme, et al, 2019) (ref)

The graphic by Newsholme, et al, 2019, below, (ref), shows the Krebs cycle, also called the Citric Acid Cycle, in the top left:

The Islets of Langerhans are cell clusters in the pancreas (on the left side of the image above) involved with producing insulin as needed, (on the right side of image).

More and more sugar, glucose or carbohydrates including fruit (fruit has fructose and glucose), leads to more and more insulin production. Not shown in this image is the effect on fat cells – once overloaded they can become insulin resistant and no longer respond to insulin by taking up the excess glucose in the blood stream – the glucose and the insulin become elevated, excessive.

The point in sharing the image is not to suggest you need to understand it all – but to see the complexity – and the basic point – more glucose/sugar leads to more insulin. If that continues over many years the pancreas cells can become damaged from too much “ROS” = Reactive Oxidative Stress (circle in the very center of the image.

An iNOS inhibitor would be helpful. See the lower left corner showing Pro-inflammatory cytokines: TNF-alpha, IL-6, IL-1beta, Adipkines, IFN-gamma. The inflammatory cytokines lead to increased activity of the NADPH oxidase system (NOX) which promotes iNOS, which makes Nitric oxide (NO), which helps increase the ROS – reactive oxidative stress when in excess. Nitric oxide can be helpful for health in the correct amounts.

Chalcones are the basic unit of flavonoids that provide a yellow pigment in many flowers. Types of chalcones are found in many plant foods and they have anti-microbial and anti-inflammatory effects. (Muraleedharan KM, et al., 2007) (ref) Chalcone flavonoids may help by inhibiting iNOS, (Young Hoon Kim, et al, 2007) (ref), so less Nitric oxide (NO) is made. In very severe oxidative stress excess nitric oxide may crystallize into a solid mass, disrupting function of cell function.

Chalcones:

“Indeed, chalcones constitute an important group of natural compounds that are especially abundant in fruits (e.g., citruses, apples), vegetables (e.g., tomatoes, shallots, bean sprouts, potatoes) and various plants and spices (e.g., licorice),—many of which have been used for centuries in traditional herbal medicine [29]. ” (Orlikova, 2011) (ref)

Whole licorice root, not the deglycyrrhised form, is a traditional medicinal herb used in Chinese medicine and has been used elsewhere as a herbal remedy. Citrus peel is a very good source of the chalcone called naringenin. Pomegranate peel is also a very good source of chalcones, (ref), and cinnamon is too. (ref)

Anemia of Chronic Inflammation can be a result of excessive ferroptosis.

• See the later half of this post for more info about anemia of chronic inflammation: Artemisinin, arteannuin-b, sgp130Fc, and Covid-19.

• The post also has a link to my unfinished book: Tipping the Clock Towards Health, which is available for sale, updates would be emailed to purchasers. (LeanPub/Tipping the Clock) *Which I have added to but it is still incomplete as of this page update on Feb. 6, 2024.

In researching anti-inflammatory phytonutrients I learned that the same foods that increase the anti-inflammatory Nrf2 pathway also inhibit the inflammatory Nf-Kb pathways. Many foods and nutrients can do both – promote anti-inflammatory Nrf2 and inhibit Nf-Kb. We hear a lot about sulforaphane and broccoli sprouts – research has shown it to be a rich source of Nrf2 promoting power – but there are oodles of other tasty choices:

That led to my learning that circadian chemistry uses the same proteins for the two pathways – so it has to be an either/or choice between the chemical pathways. It is a night/day ‘choice’ of modern life. In more ancient times people didn’t have bright light in the evening or at night. The glow of a campfire doesn’t disrupt circadian chemistry the way bright blue containing light can.

Aim for doing the opposite of the following list:

Vitamin C and iron chelators are needed, and it would also help to avoid iron rich foods in quantity. Some is reasonable, snacking on fortified breakfast cereal or liver and onions would likely be adding to the body’s inflammatory load. Methyl B complex would also be helpful to restore normal red blood cell growth within the bone marrow. Growing more healthy red blood cells is the goal so adequate protein intake is also needed.

Iron chelators:

Quercetin is in citrus peel, EGCG in pomegranate peel or 3 cups green tea per day, Resveratrol, Artemisinin or wormwood as tea, 10 gr/day goal is used to prevent malaria, Hydroxychloroquine, HCQ, or Cinchona bark tea/extract (source of quinine), Lactoferrin, fisetin, or cloves/clove essential oil. (cloves, ref, ref)

More info about this is in the Health Aids for Special Times document:

Health Aids for Special Times – document with link to Spanish translation.

• Health Aids for Special Times – phytonutrients, foods, other aids that may help with removing cellular debris such as a chimeric spike protein, and reduce inflammation. (document)

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to Provide individual health care guidance.

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Both Macro- and Micro-nutrients are needed in balance for us to have health within our gut microbiome and in our overall body.

Both essential oils and herbal extracts can provide a more concentrated dose of phytonutrients than eating the functional food would provide. Both provide the synergistic balance of phytonutrients which are found within the whole plant — minus either the water soluble or fat soluble chemicals. Health benefits are likely going to be different for an essential oil versus a water or alcohol based extract and the phytonutrient specialist needs to be aware of which type of extract is needed for a health treatment goal.

Dental Health Update

Essential oils and pomegranate extract have helped my gum infection which had led to my lower jaw hurting too. Now it doesn't hurt and the sore area is no longer inflamed looking.

Oil pulling - coconut or sesame oil

Coconut oil pulling simply means gently swishing a spoonful of coconut oil in your mouth for about 20 minutes and then discarding the oil somewhere other than a sink drain (oil is clogging). Oil binds with the oils in bacteria membranes and swishing gets the fluid between the teeth and gums. Spit it out at the end to discard the bacteria.

Activated Charcoal - to swish, whiten and polish

Activated charcoal binds with some types of toxins and can help whiten teeth and leave them smoother, polished. Caution with brushing with a charcoal toothpaste as that may add too much force and cause scratching of the tooth enamel.

Tea Tree, Clove, Myrrh and Cedarwood essential oils can help gum and tooth issues.

My sore gums are much better after just a few days using of Tea Tree oil with coconut oil pulling after meals; occasionally swishing with activated charcoal; and use of clove essential oil topically on the sore gum.

Clove oil is an irritant oil, dilution with carrier oil is recommended, and stings a little but then numbs the pain. Making a fractionated coconut oil blend with Tea Tree oil and clove would be a time saving step.

Myrrh essential oil and cedarwood are also supposed to be helpful topically on gum tissue. I have found my structured water hot beverage with Myrrh soothing for my gums but now am waiting on another bottle to arrive.

Taken internally, Myrrh may help with neuroinflammation and Alzheimer's dementia.

Pomegranate extract or juice is antimicrobial for the mouth while also supporting good species.

I just made a batch of pomegranate rind extract to try making mouthwash with. There was a recipe in a recent post from an article by Dr. Mercola, (Substack), and I suggested using pomegranate extract instead of water in the recipe - but on thinking it through, I made pomegranate extract and use that first as a mouth wash. I follow-up with an alkaline rinse (potassium bicarbonate in water as I am using that anyway to reduce my over-acidity from the high dose niacin protocol). It is a little like battery acid but leaves the mouth feeling really clean.

The phytonutrients in pomegranate extract are more stable in an acidic solution. Children might enjoy the magical color change effect. Due to the pH sensitive pigments, the pomegranate extract goes in the mouth pink, and comes out yellow after swishing for a minute or so. It only keeps about two weeks in the fridge so I made ice cubes with the extract. That way I can have a fresh batch of mouthwash every few days. It only takes a spoonful of slightly diluted extract.

I used the outer rind of one large pomegranate with three cups of water. The inner pith I have been mincing, mixing with the powder from a 1000 mg vitamin C capsules, and freezing. I then add a little of that to soup or salad or baked goods ~ 1/4 to 1/2 teaspoon per serving

Simmered for 20 minutes and strained. Yield was 2 1/2 cups of concentrated extract.

The pomegranate extract is acidic and bitter, I diluted it with one or two parts water before using a tablespoon for swishing. Saliva in the mouth then thins it down further.

The pomegranate extract is quite acidic for tooth mineralization - it would be bad for teeth, so I follow that with an alkaline rinse with potassium bicarbonate (1/4 teaspoon in a few ounces of water).

Essential oils are speedy support for the body. Essential oils can be extremely fast at changing a person’s mood or symptoms.

Essential oils have an advantage of being extremely fast at providing symptom relief or a change of mood because they are so potent and readily absorbed into the brain when inhaled deeply with the nose. Taken internally, the symptom relief would be slightly slower and more similar to using a water or alcohol extract - the phytonutrients have to pass through the digestive system rather than being inhaled straight into the mood regulating areas of the brain or being absorbed quickly through the skin into blood or lymphatic vessels.

Salicylate overdose again, Ylang Ylang to the rescue again, ~ 20 minutes to calm the racing heart when combined with trying to breath slowly and relax.

An example of the speed of symptom change with essential oils occurred this morning for me. After a nice relaxing magnesium chloride bath. I applied quite a bit of rosemary oil (antimicrobial), cypress (good for veins), and fennel (decongestant) on my legs and body along with aloe vera gel and a massage oil blend that contains some black seed oil (which is a salicylate source). I use castor oil too but have been trying to do zone treatment - castor oil on upper thighs where I have an old leg wound/bruise and poor circulation, and the essential oils that likely contain salicylates on my lower legs and upper body. I also used a little Birch oil on a sore neck/shoulder area. Birch oil is higher in salicylate and quickly pain relieving - it even smells like wintergreen. I should probably not use it, or not at the same time as all the others.

Castor oil in the morning and essential oils before bed, or every other day - the zones need to be wider apart I think - in time, not just in body regions.

Shortly later, my heart was racing, I felt a little nauseous but managed to not throw up, and my thinking was getting more disoriented . . . what had I done again? Dosed myself with too much salicylates. So I then dosed myself with Ylang Ylang and got my heart to slow down again. A couple hours later I felt okay and I did okay after eating a late breakfast. Yet another reminder that essential oils are extremely potent, and extremely fast acting.

As a medicinal product that kind of speediness at slowing a ‘panicky’ heart rate is astoundingly helpful. Leading me to ask:

The answer of course is that essential oils aren’t patentable and enormous piggy profits cannot be made from ‘medical’ use of essential oils, or TCM herbs and ancient wisdom.

Dental and liver health and Traditional Chinese Medicine

A practitioner of TCM would have known I had a liver condition by looking at which of my teeth had more problems, a pattern of three vertical wrinkles between my eyebrows, and a look at my bone spur feet would be extra clarification.

Fortunately my teeth seem to be improving and that might suggest my liver is too (the labs were improving when last checked.) Two were turning a little grayish black and I was thinking, “What? I am not a meth-head.” However I was using marijuana and mint nicotine lozenges and the mint was adding to salicylate excess and the sweetness was adding to plaque bacteria. Bad habits aren’t called good habits for a reason.

The darkened teeth are looking more like the others (a little grungy) now. In TCM, gray/black teeth are associated with a liver condition.

• Your Body Never Lies - The Complete Book of Oriental Diagnosis, Michio Kushi, 2006. (Amazon)

To help with calcium absorption and reduce phytic acid, I have also been doing the presoaking of all nuts, seeds, and grains (except white rice - the hull is removed, how can it still have growth inhibiting chemicals?) I have also doubled my calcium supplements and have been more consistent with vitamin K2 and the rest of my supplements.

Reducing the infection/inflammation load using oil pulling, Tea Tree, clove and myrrh essential oils, and activated charcoal, also seemed to help with the discolored teeth.

Pomegranate extract may sanitize well, and be healthy in various ways, but it is not a whitener to teeth or anything else. The tannins tend to darken or stain skin and can leave darkened lines on your palm - easy for palm readers to see.

Amazingly, the reason chewing is associated with cognitive health may be that it is increasing aether energy for use throughout the body.

Our teeth generate energy for us and each pair of teeth are linked energetically to other regions of the body via vessels of the Primo vascular system. The Primo vascular system is formed during embryology first, ‘Primo’, prior to the formation of blood and lymphatic vessels. The Primo vascular system pathways and nodes were initially discovered as the Prime Meridian channels which are used for acupuncture and acupressure. The physical structures were discovered in the 1960s by a North Korean scientist whose work was eventually dismissed or censored.

The full body diagram of the main Meridian channels can be viewed or purchased here: (abposters.com).

Even as a baby I didn’t like baby food. I like crunchy or chewy food.

Meridian Tooth Charts, (DrRoze.com), (BiologicalDentistsofNJ.com) (MillDental.com)

More on the way about my Medicine cabinet makeover - doing things differently can lead to better health but there may be some trial and error along the way.

Disclaimer This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

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https://www.dovepress.com/pomegranate-seeds-and-peel-ethanolic-extracts-anticancer-potentials-an-peer-reviewed-fulltext-article-JEP

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175583/

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health guidance.

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Benefits mitochondria perform for us in addition to energy production:

• Calcium homeostasis - Modulate intracellular Ca2+ levels important for muscle contraction, neuron excitability.

• Stem cell regulation - Influence success of stem cell transplants through DNA and protein modification. [This suggests that mitochondria naturally would be helping our own Primo Vascular System make our own stem cells as needed - We weren’t born with medical system stem cell transplants as part of nature’s plan for us.]

• Apoptosis - Release proteins that activate proteases to dismantle cells.

• Circadian rhythms - Regulate circadian clock through NAD+ production and SIRT1 and SIRT3 activation.

• Immune health - Pivotal role in cytokine response related to inflammation and immune signaling.

• Metabolic health - Produce 95% of a cell’s ATP to drive metabolic pathways and cellular metabolism.

• ROS balance - Unhealthy mitochondria lead to excessive ROS production, while healthy mitochondria keep ROS balanced.

• Detoxification - Helps detoxify ammonia from hepatocytes.

• Regulate aging - Toxic burden can damage mtDNA that causes fast cell turn over and accelerated aging.

• Epigenetic modulation - mtDNA can influence nuclear DNA coding through HDAC and methylation.

• Microbiome health - Influence microbiome composition, barrier function, and enterochromaffin cell function.

I took notes worth transferring from my handwriting

Threats to Mitochondria

• Heavy metals, lead, arsenic

• Pesticides; Chlorpyrifos (CPF), DDT, Paraquat (PQ)

• Cyanide (including cyanocobalamin)

• Carbon monoxide

• Statin drugs

• NSAIDs

• Anti-diabetic drugs

• Oxidative stress

• Insomnia

• Mycotoxins

• Gut Dysbiosis

There is a Gut-Mitochondrial Axis.

Secondary bile acids activate TGR5 signaling which helps promote GLP-1, promotes conversion of T4 to T3, and helps prevent leaky gut membranes via Farensoid X Receptor (FXR) signaling. More information: (Larabi, et al., 2023; Ridlon, et al., 2014)

GLP-1 is a hot trend in weight loss medications currently with the medication Ozempic which can have some bad side effects. We can promote our own GLP-1 naturally instead of needing a bottled product with adverse risks.

Too high fat a diet causes too much bile acid and too much leads to gut dysbiosis and mitochondrial death. Some gut microbe species love to eat bile and will grow in excess then Bilophila Wadsworthia is a bile loving pathogen.

While avoiding a too high fat diet balance that leads to the bile eating pathogen overgrowth, we can enhance GLP-1 signaling naturally by promoting species that make bile acids for us. That would help with the beneficial TGR5 signaling, conversion of thyroid hormone in peripheral tissues and reduce leaky membrane risk in the gut. Those species include:

• Rumminococcaceae families and Lactinospiraceae families

• Parabacteroides merdae

• Parabacteroides goldsteinii

• Clostridium scindens [and other Clostridium species, (Ridlon, et al., 2014)]

Urolithin A production helps which means that eating pomegranate fruit and peel would help provide the precurser ellagitannins. And adequate zinc and other resistant starches besides the inner pith of pomegranates would be needed to help support the butyrate producing species which also can make urolithin A and B from the pomegranate ellagitannins. Other resistant starch foods include: artichokes, leeks, onions, cold pasta or rice or potato salad, polenta, tapioca or arrowroot starch, taro root, yucca root, celeriac (celery root), burdock root (Japanese gobo). Pomegranate peel products also can promote AmpK (Park, et al., 2014) which would help promote mitochondrial fusion. A fermented pomegranate vinegar or wine would have the double benefit of likely containing urolithin A from the fermentation process.

Corn starch and polenta might count as resistant starches, but corn contains a chemical (zonulin) that can cause intestinal cell tight junctions to open. (Fasano, 2020) This is a similar issue as gluten, either can add to leaky gut risks of allergy or autoimmune conditions developing by affecting tight junctions and intestinal wall permeability. Undigested proteins normally would be too large to squeeze between cells lining our intestines because gooey tight junctions fill the crack, like mortar between bricks.

Urolithin Producing Microbiome Species

• Bifodobacterium pseudoeatenulatum NIA P815

• Eggerthellaceae family

  • Godonibacter and Ellagibacter genera

• Lachnopiraeceae family

  • Enterocloster spp

• Clostridiales

• Ruminococcaceae

• Akkermansia mucinophilia

• plus having higher alpha diversity and Shannon’s Index

Vitamin K2 is also important for mitochondrial function as it is used in Complexs I, II and III for the Carbolic Acid Cycle/Kreb’s Cycle. Green veggies give us vitamin K1 and organ meats or natto fermented soybeans are a dietary source of vitamin K2.

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide invidual health care guidance.

Reference List

(Fasano, 2020) Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020 Jan 31;9:F1000 Faculty Rev-69. doi: 10.12688/f1000research.20510.1. PMID: 32051759; PMCID: PMC6996528. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996528/

(Larabi, et al., 2023) Larabi AB, Masson HLP, Bäumler AJ. Bile acids as modulators of gut microbiota composition and function. Gut Microbes. 2023 Jan-Dec;15(1):2172671. doi: 10.1080/19490976.2023.2172671. PMID: 36740850; PMCID: PMC9904317. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904317/

(Park, et al., 2014) Park, J.E., Kim, J.Y., Kim, J., Kim, Y.J., Kim, M.J., Kwon, S.W., Kwon, O., Pomegranate vinegar beverage reduces visceral fat accumulation in association with AMPK activation in overweight women: A double-blind, randomized, and placebo-controlled trial, J of Functional Foods, 2014, 8;274-281, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2014.03.028. https://www.sciencedirect.com/science/article/pii/S1756464614001273

(Ridlon, et al., 2014) Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014 May;30(3):332-8. doi: 10.1097/MOG.0000000000000057. PMID: 24625896; PMCID: PMC4215539. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215539/

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A daily plan for how much of different types of foods might be given too - diet exchanges for the diabetic diet. Those food group serving equivalents can also be handy for weight loss purposes or just to become more familiar with the nutrients found in common foods.

To break through any negative mindsets around ‘diets’ or ‘meal planning’ it might be helpful to think about your larger health goals. What motivates? More energy, easier movement, easier to fit in clothes? Greater strength or immune resilience? Better mood? Less tension or bottled up anger?

What we eat and do each day does affect us throughout the day and into the next. Meal planning can help with time and money management as well as working on nutrient or calorie content of a daily or weekly menu. Feast days aren’t everyday because it is too much work for the cook and dishwasher - if you are the kitchen staff. Having money to buy convenience foods saves time but it is losing quality and might run into feast levels of excess.

Any overly large meal is putting a larger strain on the liver and causing the body to focus on storing extra calories instead of other growth, repair or clean-up jobs like removing amyloid protein tangles from the brain before dementia damage occurs. Alzheimer’s seems to be an excess of glucose in the brain with poor utilization of it for energy needs.

Learning about the micro and macronutrients that make up typical servings of foods can help with choosing mixed meals and snacks that don’t raise blood sugar levels as much as foods that are high in refined starches and sugar. Having protein, fat, or fiber with carbohydrates helps slow down digestion and the rate that sugar reaches the blood stream. A slow trickle of nutrients gives us energy without causing a hyperactive high followed by low blood sugar crash.

Some people read cookbooks for ideas or just to learn about other cultures. Recipes can be tinkered with if basic methods and ratios are known. Baked goods and sauces are a little more particular in needing exact ratios and therefore fairly exact measurements or a familiarity with the consistency of the desired batter or dough. Soups, stews, stir-fry’s and salads are more forgiving in the mix of ingredients that can be used.

This menu plan (Dropbox) is for a New Year 21 Day Meal-Prep Challenge, by The Clean Life, it has 3 weeks of menus with shopping lists and simple recipes to follow - sometimes very simple. The goal may be to help people ease into using whole foods for meals instead of using processed or take-out foods. Weight loss is not specified as the goal but the portions listed are fairly small. I would want more food.

Time is saved writing the menu and recipes, and for preparing the meals, by having the same thing four days in a row. That can get boring. Creative menu planning has you cook base items that then might be seasoned or used in different ways so the exact same meal isn’t being served four days in a row. The plan might have some helpful ideas for people who pack a lunch regularly, as boxed meals are used in a few ways - prepping several meals at once that are easy to grab and go later.

Sprinkling on different spices or adding different veggies could be a way to vary the Cook once, eat four times meal. If weight loss or better blood sugar control is desired, adding citrus peel as a seasoning would help as long as histamine excess isn’t a problem. The chicken, broccoli and carrot dish in the menu plan would be good with citrus peel as an accent, about one to two teaspoons of the zest layer minced, add at the end of cooking or at the table as we see in Middle Eastern cuisine.

The New Year 21 Day Meal Prep Challenge is written for one person. If cooking for two or four people, you would need to double or quadruple, and then there would be too many little boxes in the fridge. Cooking and meal planning has to be flexible for a person’s needs and tastes and family size.

Probably not a coincidence, but I am a person who likes to read cookbooks just for ideas or cultural or historical interest.

If weight gain is a New Year goal, then the Farmer’s Almanac suggests starting on January 13, 14, 22, 23, or 24. If weight loss is a goal but just not today, then Farmer’s Almanac has you covered - your auspicious dates are to start on January 7, 8, 25, 26, 27, 28, or 29 - okay? Plenty of choices…Ready, set, go! The last post had a week of menus with a focus on increasing trace mineral intake: (Substack) And this recent post had a useful handout about organizing your kitchen pantry for healthy meals: (Substack)

Food Group Equivalents or Exchanges - seen in Diabetic meal planning.

Here is one more tool to help with learning typical food group serving equivalents - one slice of bread is roughly similar in protein, carbohydrates and fat grams as one third cup of rice or oatmeal or a half an English muffin or half of a not-giant bagel or six Saltines/low fat crackers. The Better Nutrition Plan (my Dropbox) stresses balance in protein, fat and carbohydrates within meals and snacks and that is what helps with better blood sugar control and feeling satisfied after a meal.

Balance in macronutrients in meals and snacks helps keep blood sugar levels stable.

Meals and snacks that are too high in carbohydrates tend to leave us wanting more food and likely more carbohydrates. Protein and fat within a meal or snack helps tell the brain ‘We had enough, stop eating now.’ A range of total servings per day is provided but if you were being seen individually by a Registered Dietitian, then I would also be providing you with a more specific number of servings to use per day or per meal or snack - along with the general guide about food group equivalents. The number of servings of each food group would be based on your weight loss/gain/maintenance goals and other health needs or personal preferences. Planning can work around food dislikes or intolerances by trying to swap in acceptable foods that have similar nutrients, or a targeted supplement could be used.

I have been considering setting up a virtual clinic for seeing individual clients or doing groups. Let me know in the comments or an email if you would be interested in that possibility. I am not sure if time allows, but not starting takes so much longer. Email: jen@effectivecare.info

Adequate protein also is likely helping the body prevent Alzheimer’s damage. We need protein to make the proteins that make other proteins that help do the growth and repair and detox, and build new cells or DNA and everything else that we produce for ourselves. Pomegranate can help with brain protection too.

• This post has more information on both topics and links to pomegranate prep posts or webpages: Protein inadequacy likely a risk factor for dementia; Garlic mustard; Pomegranate Ellagitannins video. Building a better brain is a daily task, throughout life, not just something for a pregnant person to think about. Protein, other nutrients & polyphenols helps. (Substack) *Garlic mustard is a salicylate source, but also is fairly cold hardy making it a green veggie that you might be able to forage during winter thaws or early spring.

Citrus or pomegranate peel can be very helpful for weight and blood sugar goals.

Hesperidin as a supplement or from citrus peel may help with weight loss and improve metabolism. Pomegranate peel is also beneficial for weight maintenance or weight loss purposes and also helps with blood sugar control. The high dose niacin protocol and other mitochondrial support nutrients also can help with weight loss or weight maintenance.

Weight gain a need? Endocannabinoid deficiency can be an underlying cause.

If weight gain is a chronic problem, throughout youth and body build seems kind of skeletal, lanky, with little muscle mass, then a genetic need for cannabinoids may be present. Or in a breastfed baby, the mother may need more cannabinoids in her diet. Adequate cannabinoids help stimulate the baby to suckle and helps prevent failure to thrive. Chocolate is a source but not a very rich one compared to medical marijuana products. Cardamom is also a source.

• More about food sources of cannabinoids and symptoms of clinical endocannabinoid deficiency is in this post: Clinical Endocannabinoid Deficiency, (CED), and phospholipids. (Substack).

• Hypersensitivity to noise, even when you know the noise will be happening again, can be a symptom. See this post: Endocannabinoid deficiency and the neuropathic pain of noise hyper-sensitivity. Ototoxicity vs CNS over-activity. Also: Post-Translational modification (PTM) of proteins. Pomegranate, CoQ10, mitochondrial support nutrients and cannabinoids may help. (Substack).

Disclaimer: This information is being provided for educational purposes within the guidelines of Fair Use and is not intended to provide individual health care guidance.

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