Updated Information of the Effects of (Poly)phenols against Type-2 Diabetes Mellitus in Humans: Reinforcing the Recommendations for Future Research

Abstract

(Poly)phenols have anti-diabetic properties that are mediated through the regulation of the main biomarkers associated with type 2 diabetes mellitus (T2DM) (fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (IR)), as well as the modulation of other metabolic, inflammatory and oxidative stress pathways. A wide range of human and pre-clinical studies supports these effects for different plant products containing mixed (poly)phenols (e.g., berries, cocoa, tea) and for some single compounds (e.g., resveratrol). We went through some of the latest human intervention trials and pre-clinical studies looking at (poly)phenols against T2DM to update the current evidence and to examine the progress in this field to achieve consistent proof of the anti-diabetic benefits of these compounds. Overall, the reported effects remain small and highly variable, and the accumulated data are still limited and contradictory, as shown by recent meta-analyses. We found newly published studies with better experimental strategies, but there were also examples of studies that still need to be improved. Herein, we highlight some of the main aspects that still need to be considered in future studies and reinforce the messages that need to be taken on board to achieve consistent evidence of the anti-diabetic effects of (poly)phenols.

The role of dietary polyphenols in the control of chronic noncommunicable diseases

“…A wide range of human intervention trials and preclinical studies have also shown the possible antidiabetic properties of polyphenols, but evidence is still limited and inconsistent (Menezes et al, 2022).…”

“…For instance, prospective analysis in the context of the PREDIMED-Plus trial conducted by Menezes et al (2022) showed that a diet with higher polyphenols lowered the levels of glucose and HbA1c after 1 year in a senior population with T2DM or are at high risk of developing T2DM. In another study carried out by Grabež et al (2022), they observed that polyphenols extracted from pomegranate peel decreased oxidative stress biomarkers such as O −2 , NO −2 , TBARS, inflammatory factors (IL-6, TNF-α, hsCRP), and homocysteine in overweight patients with T2DM.…”

The (Poly)phenol-Carbohydrate Combination for Diabetes: Where Do We Stand?

“…Resveratrol, curcumin, genistein, quercetin, phloretin, caffeic acid, and epigallocatechin gallate—just to name a few—are remarkably popular natural compounds that, together with their glycosides, make up some of the most vastly studied sets of molecules for diabetes. In spite of the high amount of in vitro cell-based assays claiming promising (poly)phenol-induced antidiabetic effects, those results translate very poorly into successful outcomes in clinical studies [ 9 ]. Indeed, the antidiabetic effects of natural (poly)phenols in human subjects are often small or non-significant, with high variability between studies [ 9 ].…”

“…In spite of the high amount of in vitro cell-based assays claiming promising (poly)phenol-induced antidiabetic effects, those results translate very poorly into successful outcomes in clinical studies [ 9 ]. Indeed, the antidiabetic effects of natural (poly)phenols in human subjects are often small or non-significant, with high variability between studies [ 9 ]. Overall, the existing data has been found to be rather limited and even contradictory, highly contrasting with lab bench research.…”

“…Study design quality, population heterogeneity, interindividual variability, low compound bioavailability, and administration of multi-component mixtures (e.g., plant extracts) are some of the reasons frequently pointed out to explain these contradictions. Moreover, even when statistically significant antidiabetic effects are found, studies often fail to prove that these are sustainable in time with no relevant toxic effects [ 9 ]. All of these complex issues call for internationally harmonized natural product research recommendations.…”