Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical: a nutrigenetics proof of concept

Abstract

Objective Although observational studies have shown that genotype may influence nutritional effects on target outcomes, there are few reported studies that stratified subjects by genotype before a nutritional intervention. This proof-of-concept trial determined whether specifically formulated botanical mixtures reduced inflammation in individuals with genetic variations that predispose to overexpression of interleukin-1β (IL-1β) and early heart disease. Methods Healthy adults with elevated C-reactive protein (CRP) were stratified into genetic groups based on being positive (IL1 Pos) or negative (IL1 Neg) for the at-risk IL-1 gene variations. IL1 Pos ( n = 39) and IL1 Neg ( n = 40) subjects were then randomized to the candidate botanical formulation or placebo. The botanical formulation included rose hips, a blueberry and blackberry mixture, and a grapevine extract. Results At 12 wk of dosing with the botanical formulation, IL-1β gene expression by stimulated peripheral blood mononuclear cells was significantly lower than at baseline and significantly lower than placebo in IL1 Pos and IL1 Neg subjects. Mean IL-1β gene expression treatment effect over the 12-wk period was greater in IL1 Pos than in IL1 Neg subjects. At 12 wk of dosing the botanical mixture produced no mean change in serum CRP levels. However, in IL1 Pos subjects, significantly more subjects achieved a reduction in CRP with the botanical mixture than with placebo. No CRP effect was observed in the IL1 Neg subjects. Conclusion This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes.