Polyphenols - Antioxidant, anti-inflammatory, anti-cancer effects

Polyphenols provide most of our dietary antioxidants

Polyphenols recognized for their value in restoring health

Polyphenols have the potential for having antioxidant, anti-inflammatory, antineoplastic (anti-tumor), antiaging, cardioprotective / anti-hypertensive,  and antimicrobial properties/effects.  There are over 4,000 polyphenol compounds, some having a potent effect on disease and health issues with sufficient dosages. 

Polyphenols contain multiple phenols.   A phenol (C₆O₅OH) has 6 carbon atoms bonded into a hexagonal ring, 5 of which are bonded to hydrogen atoms and 1 is bonded to a hydroxyl group (OH);

The original hypothesis that polyphenols are direct antioxidants has been disproven.     i.e. they don't directly fight against inflammation and free radicals. Instead, they act by stimulating and upregulating the body's natural antioxidant / anti-inflammatory defense systems,  involving such as:

• Cell signaling and inflammation.  (Shimizu, 2017)
• Oxidative stress (Hussain et al, 2016)
• INSULIN signaling and INSULIN resistance (www.hindawi.com/journals/omcl/2016/7432797/)
• Adipose tissue modeling (Domínguez Avila et al, 2017)

Polyphenols (aka phenolics) add astringency to the taste of food or drinks

In plants, polyphenols defend against attack by insects and provide color to plants 

Examples:  Resveratrol in red wine, and polypenols in the culinary spices capsaicin in chilli and paprika, thymol in thyme, cinnamic acid in cinnamon, rosmarinic acid in rosemary, thyme, oregano, sage and peppermint.

Best foods for polyphenols:

Top foods having >1 mg polyphenols in a serving size

• Spices: Cloves, star anise, capers, curry powder, ginger, cumin, cinnamon, nutmeg, chili peppers (red and orange habeneros, cayenne);
• Dried herbs: Peppermint, oregano, sage, rosemary, thyme, basil, lemon verbena, parsley, marjoram;
• Beverages: red wine, cocoa, green tea, black tea;
• Dark berries: Black chokeberry, black elderberry, low bush blueberry, plum, cherry, blackcurrant, blackberry, strawberry, raspberry, prune, black grapes.
• Other fruit: Apples, apple juice, pomegranate juice, peach, blood orange juice, lemon juice, apricot, quince.
• Seeds: Flaxseed, celery seeds, fennel, chili pepper seeds (red and orange habenero seeds, cayenne)
• Nuts: Chestnuts, hazelnuts, pecans, almonds, walnuts;
• Olives: black and green olives;
• Vegetables: globe artichokes, red chicory, green chicory, red onion, spinach, broccoli, curly endive;
• Oils: Extra-virgin olive oil, rapeseed (canola) oil;

Some of the better known polyphenols

Anthocyanin

High content in cherries

• Tart cherries (e.g. Montmorency) contain roughly twice as many phenolic compounds than sweet cherries (E.g. Bing), but sweet cherries contain roughly twice as many anthocyanins. Cherries are also rich in carotenoids, quercetin, melatonin, and vitamins E and C.
• High anthocyanin content in cherries thought to provide an anti-inflammatory effect.    A Review of the Health Benefits of Cherries
• Consuming cherries, or juice or extract effective against GOUT (a form of arthritis marked by sudden attacks of joint pain /inflammation) - eating at least 10 cherries (type not specified)/day is associated with a 50% reduction of recurrent gout flares over a 48hr period  - study by Boston univ Med. Center, published 2012 in J. Arthritis & Rheumatism.
• 2010 study at Robert Wood Johnson Medical School in New Brunswick, N.J., involving 24 gout patients, achieved similar results when taking 1 Tbsp. cherry extract (equiv. ~45-60 cherries) twice daily for 4 months.  Study reference?
• Drinking an 8oz bottle of tart cherry juice ( juice of ~45 cherries) twice daily for 6 weeks relieved OSTEOARTHRITIS.    So found a 2013 study by Philadelphia VA medical center.  Participants showed significant decrease in the standard inflammation marker, C-reactive protein (CRP).
• Selective COX-2 inhibitor better than both COX-1 and COX-2 inhibitors.   NSAID (or coxib) drugs such as ibuprofen® and naproxen®, reduce pain and inflammation by suppressing the COX-2 enzyme. Unfortunately, they also suppress the COX-1 enzyme, which is a primary protector of the stomach lining, and extended use of these coxibs can cause GI discomfort and stomach ulcers leading to internal bleeding, with the risk of dying after only 2 months of NSAID use increasing to 1 in 1200. (To put this in perspective: this is 1000 times more perilous than taking a single flight) Number Needed To Kill Individual Drug Risk with NSAIDs

NSAIDS /coxibs warning

• Comparing data published from pre-1997 to that from 1997-2008, mortality in patients suffering from an upper gastrointestinal bleed or perforation has fallen from 1 in 9 to 1 in 13 overall, but has actually increased from about 1 in 7 to 1 in 5 in those exposed to NSAID or aspirin! S.Straube et al, Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. 2009 Jun 5;BMC Gastroenterol. 9:41.
• Obscenely expensive Vioxx® was an attempt at suppressing COX-2, whilst preserving COX-1 - it failed.    Causing tens of thousands of deaths due to heart attack or stroke. HOWEVER :) it turns out that cherries are a natural selective COX-2 inhibitor.

Proanthocyanidins

High content in grape skins and juice, but highly concentrated in grape seed extract (up to 70-90% proanthocyandins). Also contain many other polyphenols. Main active ingredient is the polyphenol flavonoid oligomeric proanthocyanidin (OPC) - OPCs are major free-radical scavengers / antioxidants

Catechins (flavonols)

High content in: 

• Green tea, green tea extract (Epigallocatechin gallate (EGCG));  Lipton Green teabag contains 71mg EGCG;
• Unprocessed cocoa component of dark chocolate (epicatechin)

Dark chocolate -"Anti-inflammatory / Antidepressant"

Both their caffeine and polyphenol content increase energy levels - promote activity of the neurotransmitter NOREPINEPHRINE to increase metabolic rate, which burns/oxidizes fat.

Curcuminoids

High content in turmeric

• Curcumin is the main curcuminoid found in the rhyzome of turmeric (Curcuma longa) - a popular Indian spice and a member of the ginger family (Zingiberaceae); curcuminoids are natural phenols responsible for turmeric's yellow color; turmeric root extract is ~4% curcumin.
• Curcumin shown to have an anti-inflammatory effect - but its mechanism is as yet unknown; has shown beneficial in IBS, Crohn's disease and osteoarthritis; 4-month, 160 patient, double-blind study demonstrating anti- inflammatory effect in osteoarthritis of the knee;  In vitro study shows curcumin's effect on certain inflammatory makers in IBD
• Supports cognitive function / memory - breaks down build-up of plaque (protein-clumps) on brain tissue which interrupts cell signalling. Also aids brain cell growth.
• Curcuminoids inhibit enzymes which participate in the synthesis of inflammatory prostaglandins and leukotrienes (locally operating communication messengers derived from polyunsaturated fats) - the anti-inflammatory effect of curcumnoids has been found comparable to steroidal drugs, and such nonsteroidal drugs as indomethacin and phenylbutazone, but without the negative side-effects;
• Heating curcumin destroys many of its beneficial properties
• Curcumin must be in bioavailable form.    Typically used  as 95% standardized extract, but when refined curcumin extract is combined with a water-soluble substance called PVP and fat soluble forms of vitamins A and C, it is made 136 times more bioavailable than standardized form.  Preferable to use 100% organic form. (Jager et al, 2014)
• Turmeric seen to kill H. Pylori.    Suspected of being the microbe responsible for hijacking cells and turning them cancerous;

Cinnamic acid

High content in cinnamon:

• Active ingredient methylhydroxychalcone polymer (MHCP) -  identified as the substance lowering the probability of getting type 2 diabetes in those eating apple pies. (Dr. Richard Anderson)
•  Having similar effects as INSULIN, MHCP stimulates glucose uptake and aids glycogen (storage form of glucose) synthesis - both helpful in blood sugar metabolism:

Ellagic Acid

High content in:  Raspberries, strawberries, blackberries, grapes, pomegranates, walnuts, pecans;

Lignans

Lignan precursors high in a wide variety of plant-based foods - including seeds (superlatively high amounts are found in flaxseeds, but not their oil), whole grains, legumes, fruit, and vegetables.

• Lignans enterodiol and enterolactone have weak estrogenic activity - may have a role in hormone-related cancers  (breast, uterine, ovarian, and prostate), heart disease and osteoporosis (estrogen improves bone density); (Oregon state article)

Resveratrol

High amounts in: grapes (in skins and seeds - including red wine, which is fermented with skins), peanuts, pistachios, strawberries, blueberries, raspberries, mulberries, dark chocolate;

A stilbene:

• Supports cardiovascular and cognitive health - also associated with increased blood flow to the brain;
• Pairs with body's major in-house-produced antioxidant glutathione -  to prevent oxidative damage to cell

Quercetin

High amounts of this flavonol in:  fruits, vegetables (especially red onions), leaves and grains;

Ginger

Inhibits  both COX-1 and COX-2 enzymes as well as other pro-inflammatory chemicals

Bromelain

Family of proteolytic enzymes commonly used for treating soft tissue injuries and treating inflammation

• Reduces swelling / pain;

• Increases fibrinolysis (promotes plasminogen conversion to plasmin) (Taussig & Batkin, 1988)

Recommended Dose: 500 -2000 mg/day (with enzymatic activity of at least 2,000 mcu/g)

Polyphenol-rich foods

Manuka Honey

• Polyphenols found in plant nectar.   Bees convert nectar into honey.
• Polyphenol antioxidant content of honey counters oxidant activity.   The polyphenols account for its anti-inflammatory activity and are able to prevent the feedback amplification of inflammation via hydrogen peroxide.

Boswellia Serrata Frankincense)

References

Dr. Richard A. Anderson, at the HumanNutritionResearchCenter (USDA)

Domínguez Avila JA, Rodrigo García J, González Aguilar GA, de la Rosa LA (2017 May 30) The Antidiabetic Mechanisms of Polyphenols Related to Increased Glucagon-Like Peptide-1 (GLP1) and Insulin Signaling. Molecules; 22(6) Link

Hussain, Tarique et al (2016) Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxidative Medicine and Cellular Longevity. Volume 2016, Article ID 7432797, 9 pages Link

Jager R. et al (2014) Comparative absorption of curcumin formulations,  Nutr.J; 13:11 PubMed

Oregon State Article  https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/lignans#food-sources

Shimizu, Makoto (Jan 2017), Multifunctions of dietary polyphenols in the regulation of intestinal inflammation. J. of Food and Drug Analysis Volume 25, Issue 1:93-99.  LInk

Taussig SJ, Batkin S. (1988) Bromelain, the enzymecomplex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 22:191-203.