Homocysteine & glyphosate; more on methylation cycles, microbiome and how pomegranate helps promote PPAR alpha and gamma receptors (which is a good thing).
Post too long for email and it is moving to the Pomegranate section.
Into another new book - a good companion for the Seneff book “Toxic Legacy” (discussed in this post) - “Glyphosate Free; An essay on functional nutrition and the homeopathic clearing of glyphosate toxicity.” - by Kate Birch, RHom(NA), CCH. (a review of the book, homeopathy.ac.nz/product/glyphosate-free/, *and brand new price - you can find this book for resale for less money.)
A brief word about homeopathy for anyone immediately dismissive - when the remedies are properly made with many repetitions of diluting and shaking the initial toxic compound, nanoparticles of the substance are created leaving a tiny amount of the negative substance which seems to act on our stem cell production within our Acupuncture Prime meridian/Primovascular nodes. If you say What Primovascular nodes? I couldn’t blame you - there is another whole system of the body that Western medicine has been ignoring since the 1950/6s when it was discovered by a North Korean scientist. Hopefully more people/readers are ready to believe that Western medicine needs to get out of the way of ‘healthcare.’ {Because they really aren’t very good at anything more than emergency type issues like resetting a broken leg.}
This post also follows up the homocysteine topic in the last post about a book on cancer by Dr. Thomas Cowan.
Folate and methyl/hydroxy cobalamin are needed for breakdown of homocysteine.
Kate Birch’s book is somewhat list oriented - a reference work to organize the body of research available about glyphosate and its affects on health with a little more explainer about background concepts than is included in the more biochemically detailed book by Stephanie Seneff. The microbiome chapter of Kate’s book has an extensive list of research findings about the negative effects of glyphosate on our microbiome.
Species that make folate and methyl B12 are harmed while negative species that can survive glyphosate flourish instead. Bifidobacteria are killed off and they are needed to help us convert the bile acids that we produce into bile salts; and they make methionine for us. (vi. p 78) The loss of Bifidobacteria species allows overgrowth by Clostridium difficile which is a known cause of diarrhea issues, and non-beneficial E. coli species, Salmonella, and Pseudomonas; and Candida yeast may flourish. (iv., p 78) Too much overgrowth of Candida can lead to alcohol production in the gut which can reach levels causing symptoms of ‘drunkenness’ in the person. (vii, 78-79)
Excerpt from the microbiome chapter:
“xiv. (p 80) Deficiency in folate (B9) and cobalamin (B12) leads to hyperhomocysteinemia due to the need for B9 and B12 to convert homocysteine to cystine in the methionine methylation pathway. Increased homocysteine levels increase the risk of cardiovascular disease, Alzheimer’s dementia, declining memory, poor concentration and judgement, and lowered mood. Women with high homocysteine levels find it harder to conceive and are at risk from repeated early miscarriage. Hyperhomocysteinemia has also been linked to migraines, diabetes, and osteoporosis.” (Birch, 2019)
Vitamin B6 and P5P are also needed to breakdown homocysteine.
Vitamin B6 is also important for preventing hyperhomocysteine and some people have a genetic need for a high dose supplement of B6 and zinc because of pyroluria and others need a supplement of the bioactive form of B6 (P5P) because of a gene allele that makes them unable to activate the B6. A supplement of B6 would make the second person feel worse possibly and improve mental health and physical symptoms for the first person. I am in the pyroluria category - I waste B6 and zinc in urinary excretion because I can’t recycle them after the breakdown of hemoglobin. Symptoms of chronic B6 deficiency include a lack of dreaming. When I have consistently taken my high dose B6 and P5P - I use one in the morning and one in the evening, I start having dreams again. Not always a plus if they are anxious dreams, but still interesting versus no dreaming.
Resistant starch and Short-Chain Fatty Acids - too much of a good thing becomes a bad thing….
In the last post I briefly mentioned the question of ‘endotoxin production from resistant starches’ brought up by Dr. Mercola and Georgi Dinke - we learn in point ix, (p 79) that Clostridia, Bacteriodetes, and Desulfovibrio species overproduce propionic acid (PPA) and other related short-chain fatty acids (SCFAs). Butyrate is not mentioned by name. The PPA is also a signaling chemical for the body but instead of being anti-inflammatory and helpful like butyrate, it (and related SCFAs ?) can cause “abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions,” (Birch, 2019), < that all sounds a lot like being on the ‘autism spectrum’.
Blogging tips include picking a ‘niche’ - perseveration of a repetitive interest - my niche is pomegranate products and why pomegranate are a royal fruit that is revered in ancient religious texts. It has become known that the ratio of Firmicutes/Bacteriodetes species is important for health. (Magne, et al., 2020) Both types are butyrate/short chain fatty acid producing. Pomegranate products in the diet tends to promote the healthier balance of more Firmicutes and less Bacteriodetes. The information about PPA may be the underlying issue - does Firmicutes species make butyrate more preferentially than PPA? I don’t know, but it is my guess.
And the answer is yes:
“On the other hand, the increased Firmicutes/Bacteroidetes ratio did not correlate with the production of SCFAs observed in obese individuals. Indeed, MacFarlane et al. reported that Bacteroidetes mainly produce acetate and propionate, whereas Firmicutes produce more butyrate [36]. (Magne, et al., 2020)
Before leaving this section, more about Proprionic acid (PPA) from the glyphosate book by Kate Birch:
“ix. Propionic acid induces neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. PPA has a bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, tight junction gating, immune function, and alteration of gene expression. xcvii” (p 79) (Birch, 2019)
“These [observations listed above, from an animal-based study] directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with [Autism Spectrum Disorders] ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut.” xcvii: ‘Short-chain fatty acid fermentation product of the gut microbiome: implications in autism spectrum disorders.’ (MacFabe, 2012)
More on butyrate and the Firmicutes/Bacteriodetes ratio
Butyrate is considered a health-promoting molecule due to its capacity to [37] increase insulin sensitivity [38], exert anti-inflammatory activities [39], regulate energy metabolism, and increase leptin gene expression [40]. Propionate, in the colon, stimulates GLP-1 and PYY release by L-entero-endocrine cells, resulting in the inhibition of appetite [41]. It may also reach the portal circulation, being mainly captured by the liver where it participates in hepatic gluconeogenesis and reduces the expression of enzymes involved in the de novo synthesis of fatty acids and cholesterol [42]. Acetate is also absorbed and reaches the systemic circulation and peripheral organs including adipose tissue, muscle, and brain. In the liver, contrary to propionate, it stimulates the hepatic synthesis of lipids [43], contributing to dyslipidemia. In the brain, it activates the parasympathetic nervous system, promoting the secretion of insulin and ghrelin, by the pancreas and the gastric mucosa, respectively [44]. These events result in increased fat storage and appetite that contribute to obesity. Based on these results, acetate is generally considered as more obesogenic. The increased Firmicutes/Bacteroidetes ratio in obese individuals would mean a higher butyrate and lower propionate and acetate production in these subjects, a finding that is partially contradictory with the respective anti-obesogenic and obesogenic effects of these SCFAs. An explanation is that the butyrate-producing bacteria decrease in the obese individuals and are progressively replaced by other bacteria belonging to the same phylum, resulting in lower production of butyrate in the colonic lumen.” (Magne, et al., 2020)
Excerpt from my pomegranate paper on its effects on butyrate producing species and Urolithin A and B production:
Benefits of pomegranate against SARS-CoV-2 and the chimeric spike protein are numerous.
This post includes a shorter, older version of my list: (Substack)
11. Improves gut and microbiome health, promotes butyrate species which helps kidney health, membrane and cardiovascular health, and reduces neuroinflammation.
Pomegranate peel extract improves gut health, (Zhang, et al, 2017) membrane health, and cardiovascular health. (Wang, D., et al, 2018; Sadeghipour, et al, 2014; Salwe, et al, 2015; Yang, J., et al, 2018; Asgary, et al, 2017). PPE improved endothelial function in the placenta for a diabetic pregnancy animal model. (El-Sayyad, El-Ghawet, El-Sayed, 2019) Protecting the gut protects the brain via the vagal nerve, as seen in Parkinson’s disease. PPE improved experimental autoimmune encephalomyelitis by modulation of gut species. (Lu, X.Y., et al, 2020)
Pomegranate promotes the microbiome, which may be a negative if overgrowth in sepsis is the issue, (Tavasoli, et al, 2014), and improved the balance between Firmicutes and Bacteroidetes species, butyrate producing microbial species in the gut, to be less obesogenic. (George, et al, 2019) Butyrate is anti-inflammatory and has regulatory control of TRPC channels in the kidney against excess calcium levels. (Felizardo, et al, 2019)
Firmicutes are the main butyrate producing species, Ruminococcaceae also produce it, and Akkermansia muciniphlia produce other short-chain fatty acids. They are anaerobes fermenting undigested starches within the colon and the short chain fatty acids help feed the colon cells and butyrate is immune supporting and anti-inflammatory. (Parada Venegas, et al, 2019)
With a butyrate producing microbiome, postbiotic metabolites urolithin A and B can cross the blood brain barrier and reduce neuroinflammation. (Kujawska, et al, 2020) Urolithin A may be helpful against aging, metabolic dysfunction, IBD, and neurodegenerative disorders by promoting mitophagy and removal of defective mitochondria leading to healthier mitochondria. (Tan, et al, 2019)
Species that help produce urolithin A and B from ellagitannins may include Firmicutes, Clostridiales and Ruminococcaceae family and Akkermansia muciniphlia. Having more Bacteroides in ratio to Firmicutes was associated with non-production of urolithin A in response to 8 oz of pomegranate juice. A 500 mg supplement product, MitoPure TM, led to much greater increases in plasma levels of urolithin than the juice, in a crossover self-controlled clinical study. (Singh, et al, 2022)
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)
PPAR agonist may be a Pomegranate mechanism of action
There are a few types of PPAR receptors which can do opposite things. This paper has a lengthy section on the types that pomegranate promotes which have an anti-inflammatory and anti-obesity effect, (Viladomiu, Hontecillas, Bassaganya-Riera, 2013), rather than the increased risk that may be caused by 9-cis-Retinoic Acid or a diet with more than 10% of calories from saturated fats causing inhibition of aerobic glycolysis with the Citric Acid Cycle and 36 ATP generated per glucose.
From Houston We Have a Problem post: “The excess Retinoic Acid problem may directly cause the mitochondrial dysfunction by activating PPAR beta/delta receptors. (1, 2)” …which inhibits the PDK enzyme and blocks acetyl CoA production needed for the Citric acid cycle to work - it switches the mitochondria to fermentation type of glycolysis or fat oxidation.
“PPARs are ligand-induced transcription factors that belong to the nuclear hormone receptor superfamily with 48 members identified in the human genome. They regulate gene expression by binding with Retinoid X Receptor (RXR) as a heterodimeric partner to specific DNA sequence elements named Peroxisome Proliferator Response Element (PPRE) [46]. PPARs are the main modulators of lipid and carbohydrate metabolism [47]. Functionally, PPARs regulate inflammation, immunity, and metabolism [48]. There are three known PPAR isoforms: α, β or δ, and γ, which differ in their tissue distribution and functional activity [49]. PPARα is important in the clearance of circulating or cellular lipids via the regulation of gene expression involved in lipid metabolism in liver and skeletal muscle [50]. PPAR β/δ is involved in lipid oxidation and cell proliferation [51], whereas PPARγ promotes adipocyte differentiation to enhance blood glucose uptake [50].” (Viladomiu, Hontecillas, Bassaganya-Riera, 2013)
Pomegranate helps activate the alpha and gamma PPARs via the increase in production of short chain fatty acids by promoting beneficial microbiome species.
“Commensal bacteria provide the host with colonization resistance against pathogens, stimulate the host immune system, prevent food allergies and tumors, produce vitamins, metabolize cholesterol and other lipids, and increase mineral bioavailability [37, 38]. However, the overgrowth of these normally beneficial bacteria can cause acute and chronic intestinal diseases and has also been associated with cancer, aging, and obesity [39]. Ellagitannins contained in pomegranate interact with the gut microflora. Pomegranate byproducts and punicalagins inhibit the growth of certain pathogenic Clostridia species, Staphylococcus aureus, and Pseudomonas aeruginosa but increase the growth of Bifidobacterium breve and Bifidobacterium infantis as well as the production of short chain fatty acids [37, 40], which have been shown to elicit beneficial effects through the activation of peroxisome proliferator-activated receptors (PPARs).” […]
“Pomegranate seed oil activates PPARγ in mice, thus resulting in an alteration of adiposity, lower leptin levels, and increased adiponectin when fed a high-fat diet (HFD) [62]. PPAR reporter activity data demonstrated a dose-dependent increase in the ability of punicic acid to activate PPAR α and γ in 3T3-L1 cells [62]. Furthermore, the similar patterns of PPAR α and γ activation by punicic acid and pomegranate seed oil suggested that the effects of pomegranate seed oil on PPAR α and γ reporter activities were mediated by punicic acid. Punicic acid robustly bound and activated PPAR α and γ, thus upregulating PPAR α and its responsive genes (Stearoyl-CoA desaturase-1, SCD1; Carnitine palmitoyltransferase 1, Cpt-1; and acyl-coenzyme A dehydrogenase) as well as PPAR γ-responsive genes expression (CD36 and Fatty Acid Binding Protein4, FABP4) in intra-abdominal white adipose tissue while suppressing expression of the inflammatory cytokine tumor necrosis factor α (TNF-α) and NF-κB activation. Moreover, these changes in gene expression correlated with improved fasting glucose concentrations and glucose-normalizing abilities in mice treated with punicic acid.” (Viladomiu, Hontecillas, Bassaganya-Riera, 2013)
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
(Magne, et al., 2020) Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, Balamurugan R. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients. 2020 May 19;12(5):1474. doi: 10.3390/nu12051474. PMID: 32438689; PMCID: PMC7285218. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285218/
(Viladomiu, Hontecillas, Bassaganya-Riera, 2013) Viladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J. Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evid Based Complement Alternat Med. 2013;2013:789764. doi: 10.1155/2013/789764. Epub 2013 Apr 30. PMID: 23737845; PMCID: PMC3657449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657449/
Also, I’ve studied under Stephanie Senoff several times and I love that book ..
Jennifer , do you have any posts on Paxlovid ? Or any information ? I’m asking you bc I think you are brilliant !