Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a substudy of the PREDIMED trial

Br J Clin Pharmacol. 2017 Jan;83(1):114-128. doi: 10.1111/bcp.12986. Epub 2016 May 19.


High dietary polyphenol intake is associated with reduced all-cause mortality and a lower incidence of cardiovascular events. However, the mechanisms involved are not fully understood. The aim of the present substudy of the PREvención con DIetaMEDiterránea (Prevention with Mediterranean diet; PREDIMED) trial was to analyse the relationship between polyphenol intake measured by total urinary polyphenol excretion (TPE), and circulating inflammatory biomarkers and cardiovascular risk factors in elderly individuals. A substudy of 1139 high-risk participants was carried out within the PREDIMED trial. The subjects were randomly assigned to a low-fat control diet or to two Mediterranean diets, supplemented with either extra-virgin olive oil or nuts. Dietary intake, anthropometric data, clinical and laboratory assessments, including inflammatory biomarkers, and urinary TPE were measured at baseline and after the one-year intervention. Participants in the highest tertile of changes in urinary TPE (T3) showed significantly lower plasma levels of inflammatory biomarkers [vascular cell adhesion molecule 1 (VCAM-1) (-9.47 ng ml-1 ), intercellular adhesion molecule 1 (-14.71 ng ml-1 ), interleukin 6 (-1.21 pg ml-1 ), tumour necrosis factor alpha (-7.05 pg ml-1 ) and monocyte chemotactic protein 1 (-3.36 pg ml-1 )] than those inthe lowest tertile (T1, P < 0.02; all). A significant inverse correlation existed between urinary TPE and the plasma concentration of\VCAM-1 (r = -0.301; P < 0.001). In addition, systolic and diastolic blood pressure (BP) decreased and plasma high-density lipoprotein cholesterol increased in parallel with increasing urinary TPE (T3 vs. T1) (P < 0.005 and P = 0.004, respectively). Increases in polyphenol intake measured as urinary TPE are associated with decreased inflammatory biomarkers, suggesting a dose-dependent anti-inflammatory effect of polyphenols. In addition, high polyphenol intake improves cardiovascular risk factors- mainly BP and the lipid profile.

Keywords: Folin-Ciocalteu; Mediterranean diet; blood pressure; hypertension; inflammatory biomarkers; urinary polyphenol biomarker.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / immunology
  • Atherosclerosis / prevention & control*
  • Atherosclerosis / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Diet, Mediterranean*
  • Humans
  • Polyphenols / administration & dosage*
  • Polyphenols / blood
  • Polyphenols / urine
  • Randomized Controlled Trials as Topic


  • Biomarkers
  • Polyphenols