Polyphenols for radiation sickness; a chemistry lesson; Election results, a questionable math lesson, via ZeroHedge.

Math is hard ... when you are bad at fudging the numbers.

Good morning everyone! Math is hard - a graph of the US Presidential Election Popular Vote: Democrat vs Republican (in millions), by ZeroHedge, includes results from 2012, 2016, 2020, and 2024. The Get-Out-To-Vote by Democrats for the 2020 results must have been sensational (or sin-sensational, pardon the pun). … When faking data, try to look at the routine range and remain within that routine range…this is not a recommendation.

ZeroHedge would like to talk about this bar graph... (ZeroHedge)

Chemistry is also hard, so let’s talk about polyphenols some more.

In a continuation of the recent post on cytoplasm, radiation and cancer risk, and as an intro to the second topic brought up in the comment sections of other recent posts; (spoiler, this post on kudzu for benzodiazepine withdrawal was being recommended by The Mentalist - thanks!).

Polyphenols are a large category containing many healing phytonutrients. The many names and subgroups get confusing. This post is a breakdown of subcategories of the larger group “polyphenols”, food sources and biological activity are included in varying amounts … and pomegranate phytonutrient chemistry is excerpted from my pomegranate paper.

• Polyphenols are a broad class of compounds, including (1) flavonoids, (2) stilbenes, (3) lignans, and (4) phenolic acids. (Pandey and Rizvi, 2009) *(#)’s are in the order they are discussed below.

“Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases.”

‘Plant polyphenols as dietary antioxidants in human health and disease.’ (Pandey and Rizvi, 2009)

Polyphenolic compounds can influence plant hormone signaling, affecting growth patterns, flower and fruit development, and stress tolerance - and the same phytonutrients can affect our hormone signaling.

• Polyphenolic compounds can interact with hormone receptors, influencing hormone-mediated signaling pathways and potentially affecting metabolism, inflammation, and disease susceptibility.

• They also may interact with bitter taste receptors serving functional roles in organs and tissue types that are not the tongue.

• Polyphenols may interact with leptin receptors and TRP or calcium ion channels. Polyphenols may act as a receptor agonist, antagonist, co-regulator, or simply electrically stabilize a receptor in a way that promotes activity without acting directly as an agonist.

Polyphenols may be reducing inflammation by regulating microRNA in a way that inhibits inflammatory proteins from being produced or promotes anti-inflammatory ones; or by interacting with receptors or other membrane ion channels. Polyphenols can promote or inhibit activity of the receptor or ion channel without being the agonist. They may be stabilizing the shape of the receptor structure - or maybe they help to support structured ‘EZ’ layering of the cytoplasm fluid.

• Phenolic acids can bind to and inhibit enzymes involved in plant defense, such as polyphenol oxidases, to regulate the production of reactive oxygen species (ROS), and they can perform a similar function for us. Phenolic acids can bind to and inhibit human enzymes, such as cyclooxygenases and lipoxygenases, to regulate eicosanoid production and reduce inflammation.

• Polyphenolic compounds can bind to and modify the activity of other flavonoids, and bioactive molecules like carotenoids, influencing their biological effects.

• Polyphenolic compounds can modulate the gut microbiome, affecting the metabolism and bioavailability of other nutrients and bioactive compounds.

  • Pomegranate peel supports butyrate producing species which also can make the postbiotic urolithin A from ellagitannins.

  • See: The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut–Brain Axis, (Banc, et al., 2023)

A very large subcategory of polyphenols is the group of flavonoids, which is divided into further subcategories. Except for resveratrol, the majority of the phytonutrients that we hear about like quercetin, EGCG, or luteolin are flavonoids.

*The chemistry structure minutia is not my strong suit.

One carboxylic acid group (-COOH) is included in polyphenols (Kumar and Goel, 2019) and they may have one or more phenol groups, a six-carbon ring. A polyphenol has more than one carbon ring. Benzene is the simplest aromatic six carbon ring made with 6 atoms of carbon and 6 of hydrogen (C6H6).

Food sensitivities to this whole group of phytonutrients may occur when a person has gene alleles affecting their ability to detoxify benzene rings. (Skypala, et al., 2015)

The polyphenols seem to help support each other in health benefits - there is synergy in eating the whole food rather than taking a “quercetin” or “EGCG” supplement.

We may hear less about phenolic acids and lignans, but they can synergistically combine and enhance antioxidant protection against oxidative stress or pathogens.

Research with whole fruit pomegranate peel extract or juice compared to isolated phytonutrients from the fruit, extract or the postbiotic urolithin A, have consistently shown that there is synergistic benefits from use of the whole fruit extract/juice. The individual phytonutrients do show benefits, but use of the whole fruit extract shows greater health benefits. The pectin fiber itself has health benefits against the inflammatory effects of galectin-3, suggesting that eating a little of the inner pith with the seeds is a healthy functional food rather than something to sell as a concentrated extract in a tiny capsule.

In general, flavonoids exhibit a range of biological activities, including:

• Antioxidant and anti-inflammatory effects

• Antimicrobial and antiviral activities

• Anti-cancer and anti-diabetic properties

• Cardiovascular protective effects

• Neuroprotective effects

• Bone health benefits

The chemistry of flavonoids and subcategories:

• Flavonoids are characterized by their heterocyclic ring structure, which can include a pyran ring (flavones and flavonols) or a chromane ring (flavanones and isoflavones).

• Flavanols and proanthocyanidins are subcategories of flavonoids which contain a saturated or partially saturated six-membered ring.

• Anthocyanidins are a subclass of flavonoids that are responsible for the red, purple, and blue colors of fruits and flowers. Delphinidin is distinctive because it changes colors based on acidity - red when more acidic and it may be blue when more alkaline. Color changes to brown or yellow may also occur in an alkaline solution compared to it turning more pink or red in a more acidic solution. Add pomegranate peel to a pale-colored bean soup and the broth changes to humic acid brown because of the gallocatechins are tannins - like oak leaves turning river water more brown.

• Polyphenolic compounds can be linked to each other through ester, ether, or glycosidic bonds, forming more complex structures like proanthocyanidins and tannins. The gallocatechins are tannins can form large complexes similar to humic acid and turn a soup broth brown, like old leaves turn water brown in a swamp.

Tahquamenon Falls, located in Michigan’s Upper Peninsula, is known for having very brown water — from all the leaf tannins. (solotravellerapp.com)

Polyphenol Categories:

(1) Flavonoids: A subclass of polyphenols, flavonoids can be further divided into subcategories - a few examples are included but many others may exist. The flavonol called “Quercetin” is really a group of many variations ~ 500. A supplement of quercetin may have listed on the label QE ~ quercetin equivalents - and that is more accurate than saying it contains specifically “quercetin”. (QE - a journal graphic)

• See page Phytonutrients (jenniferdepew.com) for more info and food sources for many of these phytonutrients.

• Flavones: Chrysin (*found in raw honey, has anti-cancer benefits), Luteolin, Apigenin, Tangeritin; (luteolin and apigenin are in many vegetables and fruits and tangeritin is a citrus peel phytonutrient).

  • Chrysin - Cancer,: Adjuvant Therapies - a long-alphabetized list, useful. (lifeextension.com) Raw honey is traditionally used medicinally in combination with Nigella Sativa seeds (black cumin seeds) (see post) or with a spoonful of apple cider vinegar or herb steeped vinegar in a glass of water in a traditional drink called Oxymel. (see other post)

  • Benefits of luteolin and apigenin, and also the flavonols quercetin and kaempferol, - these flavonoids can help calm a niacin flush*: (Rajman, Chwalek, Sinclair, 2018). (*See Niacin post)

• Flavonols: Quercetin, Myricetin, Kaempferol, Rutin; (*found in many vegetables and fruits; myricetin may have sleepy effects).

  • Quercetin is found in many plant foods in small amounts, and rich in some foods like capers (Alcaparras) and cilantro. It is also found in citrus and pomegranate peel along with rutin.

  • "The researchers note that pickling promotes conversion of rutin (flavonoid compound also called rutoside in capers) to quercetin, the ingredient that they found to be an efficacious KCNQ channel activator. This makes pickled capers as the richest known “natural” source of quercetin, with a maximum reported concentration of 520 mg/100 g for canned capers, compared to a maximum of 323 mg/100 g quercetin for raw capers." (todayspractioner)

• Flavanones: Hesperatin, Hesperidin, Naringenin, Naringin Eriodictyol; (*citrus peel phytonutrients).

  • Biological activities: Antioxidant, anti-inflammatory, and anti-viral/antimicrobial with antibiofilm properties; protects against cancer, diabetes, cardiovascular disease and neurocognitive conditions and supports bone health in medical disorders or with use of bioengineered bone tissue.

  • Benefits of hesperidin in central nervous system disorders: a review, (Kim, et al., 2019)

• Isoflavones: Daidzein (*an isoflavone with estrogen-like effects similar to genistein, found in soy or mung beans, Singh, et al, 2023), Genistein (*phytoestrogen in soy), Curcumin, (*in turmeric root).

  • Biological activities of isoflavones: Antioxidant, anti-inflammatory, and may support menopausal health; protects against cancer, diabetes, cardiovascular and kidney disease and supports bone health or bioengineered bone tissue constructs. Isoflavones can have estrogen-like effects or may have anti-estrogenic effects due to interaction with the estrogen receptor.

• Flavanols: Catechin, Epicatechin, Gallocathechin, Proanthocyanidins; <«« <«« 400/600 mg per day intake of this type of flavonoid is the new dietary recommendation by the Academy of Nutrition and Dietetics (Crowe-White, et al, 2022).

  • the most well known in this category is EGCG - (-)-Epigallocatechin gallate.

  • Food sources of flavanol gallocatechins/gallates: (de Pascual-Teresa, et al, 2000) — catechin tannins are part of the nature healing found in pomegranate peel, goji berries, edible Sumac, red raspberries, and green or black tea. Three cups of green tea provides about 200 mg of EGCG.

  • Hydrolysable Tannins in pomegranate include gallotannins and ellagitannins and make up 92% of the antioxidant capacity. Ellagitannins, including punicalin and punicalagin, are found more in the inner and outer peel, seeds, and flowers and gallotannins are more present in the leaves. (Uzuner, 2020) Viewable excerpt: (Hydrolysable Tannin)

  • Biological activities of flavanols: Antioxidant, anti-inflammatory, and antimicrobial properties; protects against cancer, diabetes, cardiovascular disease and neurocognitive conditions and supports bone health.

• Anthocyanidins: Cyanidin, Malvidin, Delphinidin, Pelargonidin;

  • Anthocyanidins are Condensed tannins. (Uzuner, 2020)

  • Food Sources: blue, black or reddish-purple varieties of produce have anthocyanidins. Blue lotus flower, chicory flowers and blue butterfly flowers are edible sources of delphinidin. Brilliant blue delphinium flowers are a non-edible source and namesake of the phytonutrient. Pomegranate is a good source of delphinidin, an anthocyanidin which contains four atoms of magnesium. (Noda, et al, 2002)  

  • Biological activities of anthocyanidins: Antioxidant, anti-inflammatory, and antimicrobial properties; protects against cancer, diabetes, cardiovascular disease and neurocognitive conditions.

(2) Stilbenes: Resveratrol and other related compounds. Resveratrol is found in the peels of grapes and is found in wine and grape juice. It has estrogen receptor agonist functions and may support healthy skin and reduce effects of aging. Resveratrol is also antioxidant, anti-inflammatory, etc, etc, and a Nrf2 promoter.

(3) Lignans: Lignans are a phenolic dimer - a polyphenol with 2 carbon rings. Lignans are structural parts of cell walls and are rich in the bran of rye. Gut microbiome species can change plant lignans into mammalian forms that we use. (ScienceDirect/Lignans) Enterolactone may help prevent heart attacks. Lignans also show anti-cancer benefits. (enterolactone)

Lignans

Lignans are phenolic dimers possessing a 2,3-dibenzylbutane structure. Such compounds are known to exist as minor constituents of many plants, where they form the building blocks for the formation of lignin in the plant cell wall. The compounds occur mainly in the glycosidic form. In rye, lignans are predominantly present in the bran fraction (Table 2). The glycosides are converted by fermentation in the proximal colon to mammalian lignans. The two major mammalian lignans, enterodiol and enterolactone, are the products of colonic bacterial metabolism of the plant lignans secoisolariciresinol and matairesinol. (ScienceDirect/Lignans)

(4) Phenolic Acids - a type of polyphenol but in the form of acids rather than flavonoids.

• Hydroxybenzoic acids are derived from benzoic acid; p-hydroxybenzoic, protocatechuic, vanillic, and syringic acids.

• Hydroxycinnamic acids are derived from cinnamic acid; “Chlorogenic acid is the most abundant and ferulic, caffeic, p-coumaric, and sinapic acids are common.” (Kumar, Goel, 2019)

  • This sub-group is more likely to be found in red fruits, onions, and purple/black varietals and may be present as an ester with glucose or quinic acid. (Kumar, Goel, 2019)

• Gallic, caffeic, and chlorogenic acids are the most prevalent phenols in pomegranate peel. (Mahmoud, Ibrahim, 2013)

• Pomegranate molasses, mineral and phenolic content analysis:

  Minerals: Calcium (280 mg/kg), magnesium (28 mg/kg), phosphorus (16 mg/kg), potassium (20 mg/kg), iron (16 mg/kg), and zinc (7 mg/kg).

  Total phenolic content: ~52 mg gallic acid equivalent/g. (Yilmaz, et al, 2007)

• Biologic activity: antioxidant, anti-inflammatory, etc, etc, (Kumar, et al, 2019) AND - activation of bitter taste receptors may also affect leptin receptor function and promote satiety and easier weight loss or maintenance. Caffeic acid (Frank, et al, 2007) and many other pomegranate phytonutrients are bitter tasting. These bitter tasting phenolic acids may help promote weight loss possibly by reducing leptin resistance.

• Ethanol extract of phenols seems to promote weight loss more than the aqueous extract; pomegranate juice or ellagic acid also observed to lower leptin levels.

Caffeic acid and ρ-Cumaric acid phenols may help with weight loss.

The ethanol extract of pomegranate peel promoted weight loss, while the aqueous solution, did not, in an animal-based study. (Rabiee, et al., 2015) The main difference seen by (Cruz-Valenzuela, et al, 2022) between alcohol and aqueous extracts in phenol concentration was more Caffeic acid and ρ-Cumaric acid in the ethanolic extract and Gallic acid, Chlorogenic acid and Catechin predominated in both types of extracts.

• Various 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)

• When the bioavailability and bioactivity of free ellagic acid and pomegranate juice were compared, a decrease in leptin levels was noted. (Long, et al, 2019)

• Background info: Elevated leptin levels and leptin resistance are associated with obesity. (Ahima, 2008)

Leptin receptors seem to be coregulated by a bitter taste receptor. See my pomegranate paper, or this post for a version focused just on this topic. Tooting my own horn - this is an independent research theory that I developed as I learned more about my pomegranate topic - yours for free here, or a paid subscription - thanks! The medical world is confused by leptin resistance, and I think the reason is they aren’t looking at bitter taste receptors or why pomegranate extract is so helpful for weight control.

Leptin, POMC, Iodine and Pomegranate

The GLP-1 receptor may involve a bitter taste receptor too, as bitter tasting hops is a promoter of the receptor.

An excerpt from a GLP-1 post:

This finding suggests that more natural GLP-1 agonist would also be protective . . . but maybe safer for the gallbladder. If bitter tasting phytonutrients are GLP-1 promoters, then the simple solution here is to have more bitter tasting foods and herbs/spices with your meals and snacks.

• Brave AI sees no direct research link (yet) between bitter taste receptors, GLP-1 agonists, and Alzheimer’s dementia prevention/treatment. (Brave AI summary/GLP-1 Phytonutrients and Alzheimer's) <- did include a lot of research links regarding GLP-1 medications and Alz.

• There is research showing that berberine, a bitter tasting phytonutrient, stimulates GLP-1 production. (Brave AI summary/Bitter Taste Receptors and GLP-1)

The logic follows that if bitter taste receptors promote GLP-1, and if GLP-1 agonist medications seem to be protective against Alzheimer’s dementia, then bitter tasting phytonutrients would also be protective against Alzheimer’s dementia - and that research does exist, but has looked at other mechanisms of action.

• See this thorough review article: Phytochemicals: A Promising Alternative for the Prevention of Alzheimer’s Disease. (Koul, et al., 2023) An excerpt from the paper on RAGEs and Alzheimer’s is included later in this post.

This post:

A Tale of Two GLP-1 Agonist Webinars - pharma vs hops; for Type 2 diabetes or weight loss & found helpful for Alzheimer's dementia prevention.

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

Some of the text is based on this Brave AI summary. https://search.brave.com/search?q=chemical+name+categories+and+connections+for+polyphenols%2C+flavonoids%2C+flavanols&source=desktop&summary=1&conversation=ade844ea47209e5acc3fd5&summary_og=2bbaa9a39234369e2a08b6

Some text is based on this follow up question to that summary: What are the specific biological activities and health benefits associated with each subclass of flavonoids?

Two other follow up questions:

• What are the key factors influencing the biosynthesis and accumulation of flavonoids and flavanols in plant tissues?

• How do polyphenolic compounds interact with other bioactive molecules, such as phenolic acids and lignans, in plants and humans?

• What Are Polyphenols? Types, Benefits, and Food Sources, (healthline.com).

• Polyphenols - an overview, (sciencedirect.com),

• Polyphenol (en.wikipedia.org)

(Banq, et al., 2023) Banc R, Rusu ME, Filip L, Popa DS. The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut-Brain Axis. Foods. 2023 Jan 6;12(2):270. doi: 10.3390/foods12020270. PMID: 36673365; PMCID: PMC9858309. https://pmc.ncbi.nlm.nih.gov/articles/PMC9858309/

(Kumar and Goel, 2019) Naresh Kumar, Nidhi Goel, Phenolic acids: Natural versatile molecules with promising therapeutic applications, Biotechnology Reports, Vol 24, 2019, e00370, ISSN 2215-017X, https://doi.org/10.1016/j.btre.2019.e00370. https://www.sciencedirect.com/science/article/pii/S2215017X19302383

(Pandey and Rizvi, 2009) Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009 Nov-Dec;2(5):270-8. doi: 10.4161/oxim.2.5.9498. PMID: 20716914; PMCID: PMC2835915. https://pmc.ncbi.nlm.nih.gov/articles/PMC2835915/

(Skypala, et al., 2015) Skypala, I.J., Williams, M., Reeves, L., Meyer, R. and Venter, C. (2015), Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence. Clin Transl Allergy, 5: 34. https://doi.org/10.1186/s13601-015-0078-3 https://onlinelibrary.wiley.com/doi/10.1186/s13601-015-0078-3?msockid=23469011574e61491cd983cf569d60b4

(Tsao, 2010) Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010 Dec;2(12):1231-46. doi: 10.3390/nu2121231. Epub 2010 Dec 10. PMID: 22254006; PMCID: PMC3257627. https://pmc.ncbi.nlm.nih.gov/articles/PMC3257627/