Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight‐obese individuals consuming pomegranate: A randomized clinical trial

Abstract

Scope The pomegranate lipid‐lowering properties remain controversial, probably due to the interindividual variability in polyphenol (ellagitannins) metabolism. Objective We aimed at investigating whether the microbially derived ellagitannin‐metabolizing phenotypes, i.e. urolithin metabotypes A, (UM‐A), B (UM‐B), and 0 (UM‐0), influence the effects of pomegranate extract (PE) consumption on 18 cardiovascular risk biomarkers in healthy overweight‐obese individuals. Methods and results A double‐blind, crossover, dose–response, randomized, placebo‐controlled trial was conducted. The study ( POMEcardio ) consisted of two test phases (dose‐1 and dose‐2, lasting 3 weeks each) and a 3‐week washout period between each phase. Forty‐nine participants (BMI > 27 kg/m 2 ) daily consumed one (dose‐1, 160 mg phenolics/day) or four (dose‐2, 640 mg phenolics/day) PE or placebo capsules. Notably, UM‐B individuals showed the highest baseline cardiovascular risk. After dose‐2, total cholesterol (–15.5 ± 3.7%), LDL‐cholesterol (–14.9 ± 2.1%), small LDL‐cholesterol (–47 ± 7%), non‐HDL‐cholesterol (–11.3 ± 2.5%), apolipoprotein‐B (–12 ± 2.2%), and oxidized LDL‐cholesterol –24 ± 2.5%) dose dependently decreased ( P < 0.05) but only in UM‐B subjects. These effects were partially correlated with urolithin production and the increase in Gordonibacter levels. Three (50%) nonproducers (UM‐0) became producers following PE consumption. Conclusions UM clustering suggests a personalized effect of ellagitannin‐containing foods and could explain the controversial pomegranate benefits. Research on the specific role of urolithins and the microbiota associated with each UM is warranted.