Polyphenols are micronutrients found in numerous foods. Fruits and other plants are rich sources of polyphenols where they act as defensive weapons. Deep within these plants, polyphenols function to protect the plant from UV light and pathogens.

Over 8,000 polyphenols have been determined in plants. A small handful of these have long been researched for their health benefit. In numerous epidemiological studies, these compounds have been found to offer protection from many common conditions such as diabetes, cancer, heart disease, and neurodegenerative disease. These studies show that daily consumption of foods/beverages high in polyphenols can reduce the incidences of dementia by 50%, and possibly delay the onset of Alzheimer's disease, and reduce the occurrences of Parkinson's disease. BUT do remember, these conclusions come from epidemiological studies which can only show correlations.

8,000 Polyphenols

Polyphenols come in various classes. Many. The most common of which are the flavonoids. There are also the phenolic acids like caffeic acid (coffee), gallic acid (tea). Then there’s the lignans like cinnamic acid (cinnamon). And the class of stilbenes—plant antifungals—most notably red wine extract, resveratrol. Below is how some of these are classified.

Foods High in Polyphenols

Of the fruits, grapes, apples, pears, cherries and berries contains up to 200-300 mg of polyphenols per 100 grams fresh weight. Beans, dark leafy greens, and dark chocolate also contribute a considerable portion of polyphenols. And don’t forget the beverages! A glass of red wine or a cup of tea or coffee contains about 100 mg polyphenols. Polyphenols are also present in herbs, spices, and stems. Yes, use the stems of your herbs. As a general principle, foods that have bitter of astringent qualities are highest in polyphenols.

It is without question that regular intake of foods high in polyphenols has its benefits. However, one must also consider that these micronutrients are delicate and succumb to damage when stored, processed, or cooking. For example, onions and tomatoes lose 75-80% of their polyphenol content after boiling 15 min, 65% after microwaving, and 30% after frying. Polyphenols are sensitive to not only temperature but also light. Storing polyphenol rich foods/beverages in dark, cool places can prevent micronutrient degradation to some degree.

How the Body Handles Polyphenols

Once ingested, polyphenols embark on an extensive tour of the digestive system and the liver before exerting effects in the blood. First, polyphenols must be made water-soluble (hydrolyzed) either by gut enzymes or bacteria. They are further modified by the enzymes lactase—yes, the one associated with mild digestion. They then are able to pass through the intestinal cells and undergo further chemical modification at the liver—methylation being one such example.

Different classes of polyphenols require differing handling and processing by the gut. Some can even enter the cell easily through glucose transporters. Because of the varied and extensive handing of polyphenols, it is difficult (if not impossible) to study precisely the effects of specific polyphenols. However studies taking indirect measures have shown that once absorbed through the gut barrier, there is an increase in the antioxidant capacity of the plasma after the consumption of polyphenol-rich foods. It is not clear however if these effects are due to the single, free-form polyphenol itself OR due to the processed (bound) form of that micronutrient OR if the effect is due to some microbiome effect.

It stands to reason that the absorption and potential effectiveness of any polyphenol is dependent on the microbiome. Those with clear gut dysfunction be it inflammatory bowel disease or a lack of bacterial diversity may lead to sensitivity to polyphenol-rich foods. However, studies in inflammatory bowel disease show that polyphenol-rich diets reduce symptoms in the gut. They reduce gut inflammation and repair the gut lining.

Polyphenols are Essential Nutrition for Chronic Fatigue Syndrome, Fibromyalgia, & Long COVID

Dietary polyphenols are vital for managing conditions like chronic fatigue syndrome and fibromyalgia. They function to protect the cell against oxidative damage and thus reduce the oxidative burden that perpetuates these two conditions. But to shelve polyphenols simply as antioxidants does them a great disservice. Their function is far, far more complex. They do stabilize various free radicals (oxidative stress) by quenching them but they also inhibit the enzymes that generate them.

Also, a vital function of polyphenols is their ability to bind metals which helps to reduce free radical production. Quercetin, for example, chelates iron and stabilizes iron from producing free radicals. Quercetin is an essential nutrient for those with iron overload—a genetic condition called hereditary hemochromatosis. This is also a condition with mimicking symptoms of ME/CFS and Fibro.

Polyphenols are effective at reducing general inflammation by blocking the key inflammatory mediator, NF-κB. Not only do they function to stop the cascade of inflammation where it starts, but they also activate nrf2. Nrf2 is the major player in oxidative stress protection, where it turns on our body’s own antioxidant and protective genes.

Polyphenols block key enzymes involved in pain, COX and LOX. COX and LOX are two key enzymes involved in pain and are drug targets of pain-relieving drugs such as NSAIDs. Polyphenols block the release of arachidonic acid from cells which is the stimulus for COX and LOX activity. NSAIDs can’t do that.

Foods that Reduce Pain

Polyphenols have been shown to reduce various types of pain including neuropathic pain, nociceptive pain (acute), and inflammatory pain. In a small (n=38) trial of women with fibromyalgia, intake of foods rich in polyphenols was associated with lower numbers of tender points and better quality of life.

Arthroben is a medical food containing polyphenols. The main ingredient of Arthroben is flavocoxid which is a natural blend of the flavonoids baicalin (ginger) and catechin (tea). It is as effective as the NSAID Naproxen in managing knee osteoarthritis and produced improvement in 87% of patients. It’s also the most popular product offered in the FullScript store.

Polyphenols Exert their Effects in the Brain

Polyphenols can cross the blood-brain barrier in physiologically relevant concentrations. The effects these micronutrients have on the brain are two-fold. They may exert indirect effects such as increasing blood flow to the brain. This is a very desirable outcome since low blood flow to the brain has long been associated with the ME/CFS condition.

They also have direct effects including acting on factors related to nerve growth, repair, survival, and the cross-talk that occurs among other specialized cells in the brain. Perhaps most amazing, a 2017 paper from Nature showed that once polyphenols cross into the brain, cells (endothelial cells) are able to metabolize these compounds into novel components opening the possibility of an array of brain-available metabolites never previously studied.

Polyphenols Reduce Neuroinflammation

Since ME/CFS and Fibromyalgia are known to have related neuroinflammatory aspects, any treatment to lower that inflammation is desired to improve symptoms. Polyphenols have been shown to interact with and modulate the toll-like receptor4, TLR-4. You may recall that TLR4 is an important receptor on microglia cells of the central nervous system—the nervous system’s specialized immune cells. Dysregulation of the receptor and these microglia cells results in neuroinflammation. For example, low-dose naltrexone (LDN) is known also to interact with the TLR4 and exert anti-inflammatory neuroeffects. Other options studied to reduce TLR4 expression are curcumin, tea extract, resveratrol, and quercetin.

Polyphenols Exert Profound Effects on the Gut Microbiota

Foods containing probiotics like fermented foods, or prebiotics like garlic, are well-known ways to influence the gut microbiome through diet. Dietary polyphenols are just as big a player. In a tit-for-tat manner, the microbiota improves the bioavailability of dietary polyphenols, while the polyphenols themselves modulate the microbiota community to avoid the growth of pathogens. Some studies have shown that polyphenols can increase beneficial strains like Bifidobacteria Lactobacilli, and reduce pathogenic bacteria like C. perfringens and C. histolyticum. The polyphenols found in green and black tea, have been shown to inhibit the growth of Helicobacter pylori, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, Listeria monocytogenes, and Pseudomonas aeruginosa, as well as hepatitis C virus, influenza, HIV, and Candida.

In addition to helping shape the microbiome environment, polyphenols can exert indirect health effects with the aid of the microbiota. The gut microbiome can synthesize neurotransmitters which then traverse to the brain via the vagus nerve, or exert effects on the local intestinal cells. For example, Streptococcus, Escherichia, and Enterococcus are producers of serotonin. Studies using polyphenols in animals and humans have supported the notion that these dietary micronutrients can alter levels of neurotransmitters.

Polyphenols collectively with the microbiota also exert anti-inflammatory effects which can affect the immune cells of the gut. Together they produce short-chain fatty acids which are an energy source for intestinal cells and act as potent signaling molecules for innate immune cells. This too can have brain effects via the vagus nerve, and gut-brain axis.

These factors combined highlight the high degree of diversity associated with polyphenol intake. Since no two microbiomes are the same, it follows that dietary polyphenols will be processed by each microbiome differently and shift bacterial populations uniquely. It makes for an exquisitely complex web of food-microbiome-immune system interaction. Better understanding through research will also be exquisitely difficult. Increasing dietary polyphenols is generally good nutrition advice. Learn how to do just that in the next post. But, because of the close relationship between dietary polyphenols and the gut, some individuals will likely be sensitive to certain polyphenol-rich foods demanding a bit of cautious trial and error.  

References

Vauzour, D. (2012) Dietary Polyphenols as Modulators of Brain Functions: Biological Actions and Molecular Mechanisms Underpinning Their Beneficial Effects. Oxid Med Cell Longev. 2012; 2012: 914273.

Hussain, T. et al (2016) Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev. 2016: 7432797.

Figueira, I., Garcia, G., Pimpão, R.C. et al. (2017) Polyphenols journey through blood-brain barrier towards neuronal protection. Sci Rep 7, 11456.

Rahimifard, M., Maqbool, F., Moeini-Nodeh, S., Niaz, K., Abdollahi, M., Braidy, N., … Nabavi, S. F. (2017). Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation. Ageing Research Reviews, 36, 11–19.

Fraga, CG. Et al (2019) The effects of polyphenols and other bioactives on human health. Food Funct. 10(2):514-528.

Costa de Miranda R. et al. (2017) Polyphenol-Rich Foods Alleviate Pain and Ameliorate Quality of Life in Fibromyalgic Women. Int J Vitam Nutr Res. 87(1-2):66-74.

Pandey, KB & Rizvi, SI (2009) Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2(5): 270–278.

Filosa, S. et al (2018) Polyphenols-gut microbiota interplay and brain neuromodulation. Neural Regen Res. 13(12): 2055–2059.