Effects of polyphenols on cardio-metabolic risk factors and risk of type 2 diabetes. A joint position statement of the Diabetes and Nutrition Study Group of the Italian Society of Diabetology (SID), the Italian Association of Dietetics and Clinical Nutrition (ADI) and the Italian Association of Medical Diabetologists (AMD)

Highlights

• Observational evidence supports the beneficial effects of polyphenol-rich diets in the prevention of type 2 diabetes risk.

• Clinical trials did not support specific phenolic compounds/polyphenol-rich foods to improve cardio-metabolic risk factors.

• Polyphenol-based supplements to reduce type 2 diabetes and cardiovascular disease risk are not recommended.

• Daily consumption of naturally polyphenol-rich foods and beverages might be recommended.

Abstract

Aim

A large body of evidence supports a role of polyphenols in the prevention of chronic diseases, i.e. type 2 diabetes (DMT2), cardiovascular diseases and some types of cancer. In the present manuscript, the effect of polyphenol/phenolic compounds on the main cardio-metabolic risk factors (body weight, blood pressure, blood glucose concentrations, plasma lipids, inflammation and oxidative stress) in humans will be discussed.

Data synthesis

Epidemiological evidence supports the beneficial effects of polyphenol-rich diets in the prevention of T2D risk. However, the available evidence from randomized controlled clinical trials did not allow the identification of specific phenolic compounds or polyphenol-rich foods that effectively improve cardio-metabolic risk factors. The most promising results in terms of the management of cardio-metabolic risk factors derive from RCTs based on a long-term intake of polyphenol-rich foods and beverages. Therefore, future studies should focus on a diet containing different classes of polyphenols rather than a specific food or phenolic compound. The hypothesis is that a polyphenol-rich diet may have a pleiotropic effect on cardiometabolic risk factors thanks to the specific action of different polyphenol subclasses.

Conclusion

The lack of conclusive evidence on the effectiveness of polyphenols in the management of cardio-metabolic risk factors does not allow recommendation of their use as supplements to reduce T2D and CVD risk. However, the daily consumption of naturally polyphenol-rich foods and beverages might be advised according to the current nutritional dietary recommendation.

Introduction

Polyphenols account for a huge family of plant-derived compounds that have at least one aromatic ring with one or more hydroxyl groups attached. Based on their chemical structure they are classified into flavonoids-which include several subclasses as flavones, flavonols, flavan-3-ols, flavanones, isoflavones and anthocyanins, and phenolic acids, stilbenes, lignans and other polyphenols (Fig. 1).

Flavonoids are the most representative class of polyphenol of the human diet. The main dietary sources are fruits (in particular berries and citrus fruits) and vegetables, but a large amount can be found also in dark chocolate, extra-virgin olive oil, and some beverages (tea, coffee and wine) [1].

In recent decades, mounting evidence indicated that higher intake of polyphenol-rich foodstuff is closely related to a reduction of chronic-degenerative diseases, i.e. type 2 diabetes (T2D), cardiovascular diseases (CVD) and some type of cancer [[2], [3], [4]]. As a consequence, consumers from developed countries increased their awareness of the role of polyphenols in promoting health [5].

The average dietary intake of polyphenols in Western populations range from 500 to 1000 mg/day [4,6] while more plant-based diets provide greater amount of polyphenol as demonstrated by plasma concentration of phenolic metabolites in vegan and vegetarian individuals [7]. However, since low adherence to plant-based food recommendations has been reported in several populations [8,9], polyphenol intake may be scant. As a consequence, due to the growing interest for their effects on health, polyphenol-based supplements consumption has dramatically increased worldwide. Although health benefits may arise from the use of different polyphenol-based supplements, their consumption might be also associated with possible risks. Indeed, some studies reported pro-oxidant effects induced by polyphenols (generally known for their antioxidant effects) and/or inhibiting activity on enzymes involved in drug metabolism, thus having an important impact on the pharmacokinetic data and toxicity of these drugs [5].

Moreover, the independent buying and use of supplements might encourage patients under pharmacological treatment to reduce or discontinue their medications without a prior consultation with doctors. Finally, the large and uncontrolled availability of supplements (i.e. e-commerce, pharmacies and drugstores) and the possibility that their use may be suggested by health-care professionals (physicians, nutritionists, dietitians, nurses) but also friends, relatives, or self-decided might predispose to the risk of incorrect consumption of these preparations and to potential side effects.

Therefore, the purpose of this position paper is to: 1) critically evaluate whether polyphenol intake is effective for T2D prevention and the management of cardio-metabolic risk factors; 2) point out if the increase of polyphenol intake should be recommended trough dietary changes and/or supplements. For this purpose we reviewed evidence coming from observational studies, randomized clinical trials (RCTs) and meta-analyses in humans.

A literature search was conducted using PubMed databases for epidemiological studies and randomized controlled clinical trials and meta-analyses on adults published in the English language. We used as keywords “dietary polyphenols” or “polyphenols” and separate search terms for each of the cardiovascular risk factors. The search yielded 123 epidemiological studies for “polyphenols” OR “polyphenols AND “diabetes mellitus, type 2″, 141 articles for “polyphenols and body weight ”, 163 articles for “polyphenols and blood glucose”, 123 articles for “polyphenols and plasma lipids”, 132 articles for “polyphenols and blood pressure”, 140 studies for “polyphenols and inflammation”.

This document includes: (1) the meta-analyses of randomized clinical trials; 2) clinical trials not available in the meta-analyses that added significant information to the current knowledge on the effects of polyphenols on health.