Position PaperEffects 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)
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.
Section snippets
Type 2 diabetes risk
In the last decades, a role of polyphenols in type 2 diabetes (T2D) risk reduction has been argued thanks to their effects on fasting and postprandial blood glucose concentrations [[10], [11], [12]].
Several epidemiological studies indicate that polyphenols-rich diets, including whole grains, vegetables, fruit, extra-virgin olive oil, coffee, tea, or chocolate, are tightly associated with a reduction in T2D, CVD and some type of cancer risk [3,[13], [14], [15]]. In addition, evidence from
Cardio-metabolic risk factors
Undoubtedly, polyphenols are known for their antioxidant activity which will not be discussed in this position statement. However, they have been shown to influence also the main cardio-metabolic risk factors, such as body weight, blood glucose, lipid profile, blood pressure and inflammation.
Body weight
In recent years, polyphenols have been pointed out as potentials modulators of energy metabolism and, therefore, of body weight control. Indeed, several in vitro and animal models have shown that polyphenols can inhibit adipocyte differentiation, increase fatty acids oxidation, increase thermogenesis and energy expenditure, and inhibit the digestive enzyme activity [[37], [38], [39]]. However, to date, few human studies evaluated the effect of polyphenols on body weight regulation. Furthermore,
Blood glucose
Several studies have evaluated the effects of polyphenols on glucose and insulin metabolism in healthy subjects, as well as individuals with metabolic syndrome (MS) or with type 2 diabetes.
Firstly, in individual at high cardio-metabolic risk, a medium-term polyphenol-rich diet (3 g/day) has shown to significantly improve glucose response to an OGTT-challenge, likely through an improved insulin sensitivity and early insulin secretion as compared to a control diet (~300 mg/day of total
Plasma lipids
Growing evidence suggest that the beneficial role of polyphenols in cardiovascular risk reduction is linked to their ability to reduce LDL-cholesterol while increase HDL-cholesterol. In fact, the results of in vitro and animal studies have shown that polyphenols may reduce Apo B-containing lipoproteins and increase HDL cholesterol concentrations [67].
A naturally polyphenol-rich diet (3 g/day) significantly reduced fasting and postprandial triglycerides in individuals at high cardiometabolic
Blood pressure
Blood pressure (BP) control reduces the incidence of cardiovascular complications. Recently, observational studies have suggested a possible favorable effect of polyphenols on systolic (SBP) and diastolic (DBP) BP. In particular, an inverse relationship between the intake of polyphenols and BP has been detected in a large cohort of individuals with T2D [33]. Moreover, a cross-sectional study showed that the highest consumption of tea or 4-O-methylgallic acid (a biomarker of tea intake) is
Inflammation
Scientific evidence indicates that low-grade chronic inflammation, named subclinical inflammation, is strictly related to the development of chronic-degenerative diseases, primarily T2D and CVD.
So far, meagre evidence is available from RCTS evaluating polyphenols effects on inflammatory markers.
As an example, only three studies were carried out with green tea. The results showed no significant changes of inflammatory status after short- and medium-term consumption of green tea in adult smokers [
Conclusions
Epidemiological evidence supports the beneficial effects of polyphenol-rich diets in the prevention of T2D risk.
So far, the results provided by RCTs did not allow the identification of specific phenolic compounds or polyphenol-rich foods that effectively improve cardio-metabolic risk factors. The major flaws related to the studies are: poor-quality of study planning, inadequate sample size, and huge variability of polyphenol amount.
The most promising results in terms of the management of
Conflicts of interest
None declared.
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Cardiometabolic risk, biomarkers of low-grade subclinical inflammation and flavonoid intake: A cross-sectional study in Argentina
2022, PharmaNutritionCitation Excerpt :Although previous reports have addressed these relationships, to the best of our knowledge this is the first time, in Argentina, that these variables are evaluated from an approach that considers the cardiometabolic risk and the entire intake of source foods and not the isolated bioactive compounds. It has been reported that increased intake of flavonoids may help to reduce the risk of CMD through anti-inflammatory and anti-oxidative mechanisms [29,30]. The mechanism of action is thought to be related to the ability of polyphenols to modulate oxidative and inflammation processes and thus regulating cell signaling related to insulin, glucose, and lipid metabolism amongst others [11,31,32].
Recent advances and possibilities for the use of plant phenolic compounds to manage ageing-related diseases
2020, Journal of Functional FoodsCitation Excerpt :In contradiction, a study pointed out that the most data available on the effects of phenolic compounds on cardiometabolic risk factors refer to randomized controlled clinical based on long-term consumption of phenolic-rich foods and beverages. As well, such results are limited and did not allow to identify target phenolic compounds or food sources rich in phenolic compounds that can effectively to improve cardiometabolic risk factors since the most of flaws are related to poor-quality of study design, inadequate sample size, heterogeneity of the clinical features of the sample group and huge variability of phenolic compounds amount (Giacco et al., 2020). Additionally, a randomized double-blind placebo-controlled 4-arm crossover trial, including 42 participants (male and female aged ≥50 years old), corroborated that epicatechin-rich and procyanidin-rich apple extracts do not affect blood pressure and cardiometabolic biomarkers in individuals with moderately elevated blood pressure (Hollands et al., 2018).
(Poly)phenols and cardiovascular diseases: Looking in to move forward
2020, Journal of Functional FoodsCitation Excerpt :Otherwise, less conclusive evidence is available on inflammation, body weight regulation and lipid metabolism. Furthermore, very few data are available on the effects of (poly)phenols on postprandial lipid response, an independent CVD risk factor (Giacco et al., 2019). Overall, the major flaws are related to poor-quality of study design, inadequate sample size, heterogeneity of the clinical characteristics of the participants and huge variability of (poly)phenol amount (Giacco et al., 2019).