Polyphenols: Definition, Natural Sources, Benefits, Risks, Side Effects, Mechanisms and Extracts

They represent a complex group of phytochemicals.

These provide one of the main methods plants use to fight to defend themselves from microbial invasion.

They are also nutrients that can activate gene transcription factors, thereby changing gene expression.

Polyphenols cannot be synthesized by the human body and therefore must be provided by the daily diet.

They are now known to be powerful activators of human genes involved in the synthesis of antioxidant enzymes, the modulation of anti-inflammatory pathways, and the activation of anti-aging genes, as well as critical factors in maintaining a healthy gut microbiota.

Polyphenols are micronutrients that we obtain through certain foods of plant origin.

They are packed with antioxidants and potential health benefits.

Polyphenols are believed to improve or help treat digestion problems, weight control difficulties, diabetes, neurodegenerative diseases, and cardiovascular disease.

You can get polyphenols by eating foods that contain them, you can also take supplements, which come in powder and capsule form.

However, polyphenols can have several unwanted side effects.

These are more common when taking polyphenol supplements rather than getting them naturally through food.

The most common side effect with the strongest scientific evidence is the possibility that polyphenols may interfere with or limit iron absorption.

Factors that influence the activity of polyphenols in the body include metabolism, intestinal absorption, and the bioavailability of the polyphenol.

Although some foods may have higher polyphenol levels than others, this does not necessarily mean that they are absorbed and used at higher rates.

There are approximately 8,000 known polyphenols, and probably twice that number that have not been structurally analyzed.

Little was known about the biological activities of polyphenols before 1995.

There is a large body of epidemiological data indicating that increased food intake of polyphenol-rich components (vegetables, fruits, and whole grains) is associated with lower rates of chronic disease and mortality.

Furthermore, elevated levels of polyphenols in the urine (indicating absorption) are strongly associated with reduced mortality and frailty in older populations.

Polyphenols can be classified into the following groups:

  • Flavonoids.
  • Phenolic acids.
  • Stilbenes.
  • Lignans

Foods rich in polyphenols

Plant-based foods, such as vegetables and fruits, are usually high in polyphenols. Within these we have:


Oranges, apples, grapes, peaches, grapefruit juice, cherries, blueberries, pomegranate juice, raspberries, blueberries, blackberries, black currants, plums, blackberries, strawberries, apricots.


Spinach, onions, shallots, potatoes, black and green olives, artichokes, broccoli, asparagus, carrots.

Whole grains

Whole wheat flour, rye and oats.

Nuts, seeds and legumes

Roasted Soybeans, Black Beans, White Beans, Chestnuts, Hazelnuts, Pecans, Almonds, Walnuts, Flaxseed.


Coffee, tea, red wine.


Dark chocolate, virgin olive oil, sesame seed oil.

Spices and condiments

Cocoa powder, capers, saffron, dried oregano, dried rosemary, soy sauce, cloves, dried mint, star anise, celery seeds, dried sage, dried mint, dried thyme, dried basil, curry powder, dried ginger, cumin , cinnamon.

The number of polyphenols in a food can vary depending on where the food is grown, how it is grown and transported, how ripe it is, and how it is cooked or prepared.


Type 2 diabetes

Some researchers have reported that polyphenols can reduce the risk of type 2 diabetes.

Polyphenols can increase insulin sensitivity, as well as reduce the rate at which the body digests and absorbs sugar.

According to one review, a type of flavonoid called flavan-3-ols may be especially beneficial in lowering insulin resistance.

The same review also found that flavonoids appear to be the type of polyphenol most often associated with a lower risk of type 2 diabetes.

An analysis of studies on flavonoid intake and type 2 diabetes concluded that people who consumed the most flavonoids had a lower risk of developing type 2 diabetes than those who consumed the least.

Increasing your intake of flavonoids also appears to be a way to significantly reduce your risk of disease.

Raw cocoa is a rich source of flavonoids. One review found that cocoa consumption significantly decreased a marker of insulin resistance.

It is worth noting that raw cocoa is very different from the chocolate in chocolate bars or traditional desserts. Raw cacao comes directly from the cacao plant with no added sugar.


An animal study looked at the effect of green tea polyphenols on inflammation measures after exercise.

Lignans are a class of polyphenols that occur at their highest levels in virgin olive oil, flaxseed, and whole grain rye flour. One way to study lignan consumption is to look at the levels of lignans in the urine.

In a study of adults, higher levels of lignans in the urine were found to be associated with lower levels of measures of inflammation.

This could be important as long-term inflammation has been associated with certain diseases, such as heart disease and cancer.

Heart disease

A review of the studies examined the impact of cocoa polyphenols on risk factors for heart disease.

The scientists found that consuming cocoa for at least two weeks led to a significant decrease in blood pressure.

He also found that cocoa significantly lowered LDL cholesterol and increased HDL.


Polyphenol intake may also play a role in regulating body weight.

One study compared intake of flavonoids, a class of polyphenols, with body mass index and waist circumference.

The researchers found that higher flavonoid intake was associated with lower body mass index and waist circumference.

These results are significant because  obesity  is associated with an increased risk of many chronic diseases.

Risks and side effects

Foods rich in polyphenols, such as grapefruit and grapefruit juice, can interact with medications.

Including foods rich in polyphenols as part of a healthy diet is safe for most people.

However, people with food allergies or certain medical conditions may need to avoid certain foods rich in polyphenols.

While polyphenols occur naturally in many plant foods, they can be added to some foods or extracted and used to make supplements.

Although polyphenols appear to offer many benefits, excessive amounts can have adverse effects. Some supplements contain polyphenols in higher amounts than would be consumed in a healthy diet.

A publication on the safety of polyphenols reported that a high dose of a polyphenol can cause kidney damage, lead to the development of tumors, and disrupt the production of thyroid hormones.

Some foods rich in polyphenols can also affect the absorption of certain nutrients, such as tea and iron from plant foods.

Grapefruit juice is known to interact with multiple medications, and part of this interaction may be related to a type of polyphenol found in grapefruit juice.

Mechanisms of polyphenols in health

The complexity of the health benefits of polyphenols must be understood in two distinct areas. These are its effect on human cells and its effect on the gut microbiota.

The most intriguing mechanism for polyphenol actions in human cells is its ability to activate key genes, particularly those involved in the production of antioxidant enzymes, the reduction of inflammatory responses, and the activation of genes associated with a reduced rate of aging.

Although polyphenols have antioxidant actions per se, they have a much greater impact on the activation of antioxidant genes such as Nrf2 (a regulatory protein of genes involved in the production of numerous antioxidant enzymes).

Once these genes are activated, they generate increased expression of antioxidant enzymes such as glutathione peroxidase, superoxide dismutase, and catalase.

Unlike typical dietary antioxidants, these antioxidant enzymes can reduce free radicals a thousand times more.

The reduction of excess free radicals and their associated decrease in oxidative stress are generally associated with a decrease in mortality.

The anti-inflammatory actions of polyphenols are associated with their stimulation of the gamma receptor activated by the peroxisome-proliferator-activated receptor gamma, which controls lipid uptake and fat cell synthesis.

Increased expression of this gene transcription factor also inhibits the activation of nuclear factor kappaB (NF-κB), which is the main switch for activating the innate inflammatory response.

Finally, polyphenols activate the anti-aging gene (SIRT-1) that expresses the increase in protein kinase activated by AMP, which controls general metabolism and initiates autophagy.

The activation of all these human genes depends on the levels of polyphenols in the blood and since polyphenols generally have poor bioavailability (2 to 20%), activating these genes generally requires consuming large amounts of polyphenols in the diet.

The role of polyphenols in gut health is even more complex. Unlike the human body, where oxygen is required for life, the colon that houses the gut microbiota does not have oxygen.

Polyphenols can cause the absence of oxygen to act like classic antioxidants, since they can reach the colon without being absorbed in the small intestine.

It is only when the environment in the colon is totally oxygen-free that many pathogens have a difficult time establishing themselves.

The second important purpose for polyphenols in the gut is their ability to be a primary defense against pathological microbial invaders as they do for plants.

Polyphenols enhance the production of unique strains of bacteria (such as Akkermansia muciniphila) in the gut microbiota.

Polyphenols that seem to act as a master switch to control the gut microbiota especially to improve the integrity of the mucosal barrier and the tight junctions of the mucosa, cells to prevent the penetration of bacterial fragments such as a lipopolysaccharide into the blood.

As lipopolysaccharide levels increase in the blood, they can interact with toll-like receptors to generate chronic low-level inflammation leading to metabolic endotoxemia with a corresponding increase in obesity and diabetes.

Although the low availability of polyphenols limits the speed of their actions on the activation of gene transcription factors in human cells, their inability to be absorbed by the small intestine allows a delivery directed to the colon and the microbiota in that region for a maximum impact.

Within the colon, a large number of metabolic modifications of polyphenols can take place, yet many of the details of that metabolism remain unknown.

It is estimated that 40% of the metabolites in the blood come from the metabolism of polyphenols.

Because the shelf life of these polyphenol metabolites is relatively short, often measured with a half-life of a few hours, a constant supply of polyphenols is required to maintain optimal levels in the gut and their metabolites in the blood.

Polyphenol extracts

Regardless of the potential of polyphenols for gene activation and improving gut health, their levels in food are very low.

As an example, polyphenol levels in vegetables are generally around 0.1% by weight and only slightly higher (0.2% by weight) in fruits.

Therefore, it requires a constant consumption of adequate levels of fruits and vegetables to maintain an adequate intake of polyphenols for optimal health.

However, plant sources can be processed to produce polyphenol extracts containing up to 40% polyphenols by weight.

Such extracts make it possible to consume adequate levels of polyphenols to generate consistent therapeutic benefits.

The extraction methodology for polyphenol extracts begins with dehydration of the food source to obtain a dry powder.

This dehydration step generally doubles the polyphenol concentration.

The dry powder can be further extracted with alcohol to increase the polyphenol content.

This is because polyphenols have higher solubility in alcohol compared to other components of the plant.

This explains the use of wine as a classic way of ingesting higher levels of polyphenols.

However, alcoholic extracts can be further purified by chromatography to generate refined polyphenol extracts that approximate 40 to 50% polyphenols by dry weight.