Introduction

Polyphenols comprise a group of antioxidant compounds found in a variety of plants consumed as foods and beverages. Polyphenols are one of the most common classes of bioactive compounds found in plants, along with alkaloids (e.g., berberine), organosulfur compounds (e.g., sulforaphane), and terpenoids (e.g., beta carotene). A growing body of evidence suggests that polyphenols have disease-fighting properties, although the evidence to support these claims varies in quality.

Research has demonstrated some degree of efficacy of polyphenol consumption for:

  • reducing intestinal hyperpermeability (i.e., leaky gut syndrome)[1]
  • increasing antioxidant defenses[2]
  • reducing cardiovascular disease risk[3]
  • ameliorating metabolic syndrome[4]
  • improving memory[5], cognitive function[6], and mood[7]
  • promoting good quality sleep[8]

Chemically, polyphenols comprise a group of organic compounds containing two or more phenol rings. These six-carbon rings contain three double bonds that are capable of donating an electron to oxidative compounds such as superoxide, hydrogen peroxide, and peroxyl radicals. Electron donation neutralizes free radicals, giving polyphenols powerful antioxidant properties. Their unique electron structure also contributes to the vibrant colors produced by many polyphenol pigments, such as yellow flavonoids in lemons or blue anthocyanins in blueberries.

The main classes of polyphenols include phenolic acids, flavonoids, stilbenes, and lignans;[9] however, due to the limited selection of plant foods in the standard American diet, not all polyphenols are commonly-consumed. The most common classes of polyphenolic compounds found in a standard diet include:[10]

  • Flavanols (e.g., epigallocatechin gallate and other catechins and tannins from tea)
  • Flavanones (mostly hesperidin from citrus)
  • Flavonols (e.g., quercetin from tea, apples, and onions)
  • Hydroxycinnamic acids (e.g., chlorogenic acids, abundant in coffee and many fruits and vegetables)
  • Anthocyanins (blue/purple pigments found in fruits such blueberries and chokeberries).

To see the extensive list of bioactive compounds found in the polyphenol family, visit Phenol-explorer, a database compiled by researchers.

Polyphenols are dual-mechanism antioxidants.

Polyphenolic compounds act as direct antioxidants, scavenging reactive oxygen and nitrogen species generated during normal metabolism or from exogenous sources such as pollution or radiation. When antioxidant capacity is low, oxygen and nitrogen radicals accumulate in the body and promote oxidative damage to DNA, proteins, and lipids. Polyphenols increase antioxidant capacity and protect cells from damage.

Polyphenols also act as indirect antioxidants, binding to short sequences of DNA called response elements, which activate the production of endogenous antioxidant enzymes. For example, polyphenols in green tea activate the transcription factor Nrf2 (i.e., nuclear factor (erythroid-derived 2)-like 2), which binds to a portion of DNA called the antioxidant response element. Upon binding, Nrf2 activates the transcription of genes that produce enzymes such as glutathione, a potent antioxidant.[11]

Summaries of current research

Below is a selection of summaries from current research investigating the effects of polyphenols on health.

Polyphenols from common foods prevent leaky gut syndrome.

Polyphenols

Intestinal hyper-permeability, often referred to as “leaky gut,” is a condition in which the gaps between the cells that line the gut expand. These expanded gaps allow bacteria and endotoxins (i.e., lipopolysaccharides, major components of the cell membrane of gram-negative bacteria) to leak through the intestinal wall and pass directly into the bloodstream. Leaky gut is common among older adults,[12] putting them at risk for many acute and chronic diseases.

Investigators conducted a randomized, controlled, crossover trial with 51 adults (60 years and older) who were living in a residential care facility and had elevated zonulin, a biomarker of impaired gut barrier function. Half of the participants followed their typical diet, but they substituted some items with polyphenol-rich foods while maintaining the same caloric and nutrient intake for eight weeks. The other half consumed their normal diet with no substitutions. After eight weeks, the two groups switched to the opposite diet.

The polyphenol-rich foods included berries, blood oranges (and their juice), pomegranate juice, green tea, apples, and dark chocolate. The study investigators noted that participants on the polyphenol-rich diet had higher levels of beneficial gut bacteria than those on the typical diet.[13] They also noted that metabolites from cocoa and green tea polyphenols were associated with having higher levels of butyrate (a short-chain fatty acid that benefits gut health) and lower levels of zonulin. These changes improved overall gut health in the study participants, but the participants' age, baseline zonulin levels, and numbers of beneficial gut bacteria, especially those of the Porphyromonadaceae family, influenced the extent of benefit.

Leaky gut reduces the beneficial effects of dietary polyphenol compounds.

Bacteria in the human gut break down polyphenols into smaller compounds to increase their bioavailability. As humans age, the quality of the gut microbiota decreases, leading to poor gut barrier integrity and causing contents of the gut to leak into the bloodstream (i.e., leaky gut syndrome). This leaking of toxins, dietary antigens, viruses, and bacteria is associated with increased inflammation and disease risk.[14] In addition to causing a leaky gut, poor microbiota quality may decrease the beneficial effects of polyphenol-rich plant foods.

One group of investigators tested the effects of a polyphenol-rich diet in 51 adults (greater than 60 years of age) residing in an assisted living setting. Participants consumed either the normal menu prepared by their facility for eight weeks or a menu that included three servings of polyphenol-rich fruits, teas, and cocoa for eight weeks and then switched to the opposite diet. The researchers collected blood samples to measure serum zonulin, a marker of gut barrier integrity, and urine samples to analyze polyphenol metabolite content before and after each diet period.

Overall, serum zonulin decreased following eight weeks of a polyphenol-rich diet, meaning that gut barrier integrity improved.[15] Participants who started the trial with better gut barrier integrity had a significantly greater increase in blood levels of polyphenol metabolites compared to participants with leakier guts. The metabolites found in the group with greater gut barrier integrity were microbial-derived, suggesting these participants had a more health-promoting gut microbiota. Based on these results, the authors hypothesized that changes in the gut microbiota damage the gut barrier and cause a subsequent reduction in the absorption of dietary polyphenol compounds. They concluded that personalized diet plans could be effective for managing leaky gut in older adults.

Extra virgin olive oil improves antioxidant status.

Antioxidant compounds such as the polyphenols found in olive oil may reduce cardiovascular disease risk by resolving oxidative stress and inflammation.[16] Oxidative compounds damage the cells that line blood vessels, called endothelial cells. Increased concentrations of proinflammatory cytokines, such as interleukin-6 and C-reactive protein, and oxidized low-density lipoprotein (LDL) cholesterol contribute to endothelial dysfunction and the generation of atherosclerotic plaques. Increased concentrations of antioxidant enzymes in the blood decrease oxidative damage and reduce the risk of chronic diseases such as cardiovascular disease.[17]

Authors of a 2021 study recruited 50 participants (between ages 18 and 75 years) who were not consuming dietary supplements or large quantities of olive oil (greater than one tablespoon per day). They assigned participants to consume about four tablespoons per day of either high-polyphenol or low-polyphenol olive oil for three weeks. After a two-week wash-out period, participants consumed the opposite treatment for three weeks. The researchers measured total antioxidant capacity and plasma concentrations of oxidized LDL cholesterol and C-reactive protein (a marker of inflammation) before and after each treatment.

High-polyphenol olive oil consumption significantly reduced oxidized LDL cholesterol and increased total antioxidant capacity.[18] These changes were greatest in participants who were at high risk for cardiometabolic disease due to their high waist circumference.

Blueberry anthocyanins improve cardiovascular health.

Anthocyanins

Flow-mediated dilation refers to the capacity of an artery to expand in response to increased blood flow. It is a widely accepted measure of vascular endothelial function, and poor flow-mediated dilation is a recognized feature of cardiovascular disease. Previous research has demonstrated a relationship between higher blueberry and strawberry intake and decreased risk of heart attack;[19] however, the mechanisms that drive this relationship are under-investigated.

Authors of one comprehensive report analyzed data from four studies measuring the effects of blueberry anthocyanins involving a total of 60 participants. They conducted a follow-up experiment in mice. They found that isolated anthocyanins improved endothelial function as measured by flow-mediated dilation in a dose-dependent manner, meaning that the effects were more robust as dose increased.[20] The effects of these isolated anthocyanins were similar to those of wild blueberries. However, a sham beverages containing fiber, minerals, or vitamins and minerals had no significant effect on flow-mediated dilation. Twice daily wild blueberry consumption for one month also increased long-term flow-mediated dilation. Finally, injection of metabolites derived from the phenolic compounds found in blueberries improved flow-mediated dilation in mice. These results demonstrate the beneficial effects of blueberries on cardiovascular health and elucidates the function of anthocyanin compounds as major mediators of vascular function in mice and humans.

Colorful compounds in berries promote brain and heart health.

Cognitive performance refers to a set of mental skills such as attention, memory, psychomotor speed, and executive function that develop through early adulthood and then decline in old age. Impaired vascular function, a factor that contributes to poor brain health and cognitive performance with age, may be modifiable with diet and lifestyle changes, such as increased polyphenol consumption.

The authors of one systematic review searched for studies investigating the six most anthocyanin-rich fruits (i.e., blackcurrant, black raspberry, blueberry, bilberry, chokeberry, and elderberry). They selected all randomized, placebo-controlled intervention studies in humans that investigated at least one cardiometabolic or cognitive performance parameter for inclusion in their analysis. Although methods of data collection used among the studies widely varied, the authors extracted data from their selected studies and combined it into clusters for comparison.

In young and middle-aged adults, multiple studies found improvements in attention and psychomotor speed with anthocyanin supplementation.[21] The research revealed that short-term berry supplementation was sufficient to produce benefits on attention and psychomotor speed, but long-term supplementation was best for memory. All studies that measured flow-mediated dilation, the most accurate measure of vascular function, found an improvement following anthocyanin supplementation except for one study in smokers. Long-term berry supplementation also lowered blood pressure in adults at high risk for cardiometabolic disease, but not healthy adults, indicating that individual characteristics alter a person's response to anthocyanin supplementation.

Wild blueberry extract improves metabolic function and cognitive performance.

Metabolic function and cognitive performance begin to decline as early as the middle-age years – between the ages of 40 and 65 years. Dietary modifications, such as consuming more polyphenol-rich berries, might be a useful strategy for improving or even reversing these declines. In one randomized controlled cross-over trial, 35 middle-aged participants consumed a beverage containing 25 grams of freeze-dried blueberries (roughly equivalent to 1 cup of fresh berries) or no blueberries. The participants completed the opposite treatment on a separate day.

The authors of the study assessed the participants for changes in their episodic memory and executive function as well as plasma levels of glucose, insulin, and triglycerides. They found that the participants who drank the blueberry beverage performed better on the cognitive tests than those who drank the placebo.[22] They also noted that the blueberry beverage drinkers had lower insulin and glucose levels than those who drank the placebo. These findings suggest that blueberry consumption improves metabolic markers and cognitive performance in middle-aged adults and underscore the importance of regular consumption of flavonoid-rich fruits and vegetables.

Compounds in herbs and tea improve sleep and daytime functioning.

Rosmarinic acid and EGCG

Rosmarinic acid is found in many culinary herbs, including rosemary, oregano, sage, thyme, and peppermint. Evidence suggests it influences sleep by regulating neurotransmitters in the brain such as GABA[23] and acetylcholine.[24] Epigallocatechin gallate (EGCG) is found in tea. It exerts potent antioxidant, anti-cancer, and anti-proliferative properties.[25] EGCG suppresses neuroendocrine pathways involved in alertness, thus providing anti-anxiety and hypnotic effects.[26] Evidence from a recent study suggests that rosmarinic acid and EGCG improve sleep and daytime function in people with poor sleep.

The intervention study involved 89 healthy adults (average age, 31 years) who reported having poor sleep. Half of the participants took a blend of rosmarinic acid and EGCG (providing at least 65 milligrams of the two combined) in capsule form every night before bed for 30 days, while the other half took a placebo. The investigators found that participants who took the rosmarinic and EGCG blend experienced better sleep quality and less severe insomnia than those who took the placebo.[27] In addition, those who took the blend did not exhibit any cognitive impairments, but they did demonstrate improvements in daytime attention, working memory, and risk assessment.

Frequently Asked Questions

  • Q: Do quercetin and fisetin reverse senescence?

  • A: Research using animal models has found evidence for the senolytic power of fisetin and quercetin; however, there is no experimental evidence in human participants yet.

  • Q: Does green tea promote autophagy?

  • A: Check out this clip of the FoundMyFitness podcast with Dr. Guido Kroemer reviewing the effects of another polyphenol-rich beverage, coffee, on autophagy.

  • Q: Do polyphenols suppress the benefits of exercise?

  • A: Some direct antioxidants (such as vitamins C and E) can reduce physiological adaptations to exercise when taken in large doses close to time of exercise. Indirect antioxidants (such as resveratrol) work by activating genetic pathways for the production of endogenous antioxidants and are not a concern for reducing exercise adaptations. Still, it may be best to wait to take any antioxidant supplements until a few hours following exercise.

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