Flavonoids bring clear benefits, but direct antioxidant effects may not be the primary reason 01/02/2019
Some surprising conclusions about the ways in which food-borne antioxidants benefit the human body—and don't—come to us from a surprising source.
Researchers from Oregon State University's Linus Pauling Institute often focus on antioxidants, as you'd expect from an organization inspired by the late Nobel-winning chemist, who was an insistent — but sadly mistaken — advocate for vitamin C and other antioxidants.
Flavonoids are potent polyphenol-type antioxidants found in fruit, vegetables, coffee, tea and chocolate.
A large, fast-growing body of research in cells, animals, and human populations indicates that flavonoids possess anti-cancer potential and also improve cardiovascular health.
It's been assumed that most of the health benefits associated with flavonoids stem directly from the potent antioxidant power these polyphenols demonstrate in test tubes.
Chemists can measure the “antioxidant capacity” of fruits and vegetables, which explains these foods' ability to neutralize the unstable, cell- and DNA-damaging, pro-aging oxygen molecules called free radicals.
But they can only measure antioxidant capacity in test tubes, and doubts have lingered concerning the accuracy of these measures with regard to food-borne antioxidants' actions in the body.
Barriers to direct antioxidant benefit
An evidence analysis by the Oregon State team — led by Balz Frei, P.D., former director of the Linus Pauling Institute — affirmed the idea that flavonoids exert very little direct antioxidant effect in the body.
Dr. Frei's report noted three facts that preclude the probability that flavonoids exert direct antioxidant effects in human blood or other bodily fluids:
- Only about five percent — often much less —of dietary flavonoids are absorbed into the blood stream.
Most of this small proportion is metabolized and excreted rapidly.
The chemical structures of flavonoids get altered when they are metabolized by the body, and these changes reduce their ability to act as antioxidants, directly.
- Flavonoids produce measurable impacts on levels of free radicals and inflammation in human and animal blood and tissues.
- Flavonoids produce anti-inflammatory, anti-cancer, heart-health, anti-Alzheimer's and related effects in cell, animal, clinical, and epidemiological studies.
The Oregon team addressed the disconnect, and identified likely ways in which fruits and vegetables may produce these benefits, despite poor absorption and retention of their flavonoids.
In addition to the indirect "nutrigenomic" effects described below,Dr. Frie pointed to four ways in which flavonoids could benefit the body despite a dearth of direct antioxidant impact:
- Fructose and similar compounds in flavonoid-rich foods increase blood levels of uric acid, which is an important antioxidant in the human body (Glantzounis GK et al 2005). However, this hypothesis is controversial, since high blood levels of uric acid are associated with cardiovascular disease, and are common in people with hypertension, metabolic syndrome, or kidney disease (Heinig M, Johnson RJ 2006).
- Flavonoids may accumulate in tissues over time, and exert localized antioxidant effects.
- Flavonoids may inhibit cancers in very small amounts, via non-antioxidant mechanisms (e.g., they're known to modulate cell-signaling and regulate genes).
- The body sees flavonoids as unwanted compounds and triggers its Phase II enzymes, which help eliminate toxins and carcinogens. In other words, flavonoids may stimulate the body's normal “house-cleaning” processes.
Flavonoid antioxidants probably exert indirect health effects
The polyphenol and carotenoid compounds in whole plant foods are commonly called “antioxidants” because they behave that way in test tube experiments.
But in general, these health allies do not exert direct antioxidant effects in the body … at least not to a very substantial extent.
Instead, polyphenols appear to exert strong indirect effects on oxidation and inflammation via so-called nutrigenomic effects on gene switches (e.g., transcription factors) in our cells.
These nutrigenomic effects tend to moderate inflammation and stimulate the body's own antioxidant network … which includes enzymes, lipoic acid, CoQ10, melatonin, and vitamins C and E.
The richest known food source of polyphenols are raw (non-alkalized / non-“Dutched”) cocoa, berries, plums, prunes, tea, coffee, extra virgin olive oil, beans, and whole grains.
(Highly beneficial procyanidin-type polyphenols abound in cocoa, dark-hued berries – e.g., blackberries, blueberries açaí berries – grapes, red wine, and tea. Comparably beneficial anthocyanin-type polyphenols abound in cherries and most berries.)
Extra virgin olive oil is uniquely rich in hydroxytyrosol, oleuropein, oleocanthal, and other tyrosol esters … a particularly potent class of polyphenols with clinically documented vascular and brain benefits.
Does this mean that we should ignore research-generated charts that rank foods by their antioxidant power in the test tube?
The answer, almost certainly, is “no”, since the antioxidant effects that flavonoid-rich foods exert in human blood correlate well with their rankings on the test-tube-derived antioxidant scales, while human studies validate the bountiful benefits of foods high in the most potent antioxidants.
But the new report does reveal that we have a lot to learn about how antioxidant-rich foods work their health-promoting wonders.
- Lotito SB, Frei B. Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radic Biol Med. 2006 Dec 15;41(12):1727-46. Epub 2006 Jun 3.
- Heinig M, Johnson RJ. Role of uric acid in hypertension, renal disease, and metabolic syndrome. Cleve Clin J Med. 2006 Dec;73(12):1059-64. Review.
- Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Curr Pharm Des. 2005;11(32):4145-51. Review.
- Finaud J, Lac G, Filaire E. Oxidative stress : relationship with exercise and training. Sports Med. 2006;36(4):327-58. Review.