Interleukin-1 genotype-selective inhibition of inflammatory mediators by a botanical: a nutrigenetics proof of concept.
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-1beta (IL-1beta) 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-1beta 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-1beta 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.


CONCLUSIONS
This study represents one of a few prospective clinical trials in which genetic variations were shown to differentially influence nutrient effects on outcomes.
Kornman
Kenneth
K
Interleukin Genetics, Waltham, Massachusetts, USA. kkornman@ilgenetics.com
Rogus
John
J
Roh-Schmidt
Haeri
H
Krempin
David
D
Davies
Audra J
AJ
Grann
Kerry
K
Randolph
R Keith
RK
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000032:analysis*; D002478:Cells, Cultured; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D054647:Nutrigenomics; D010936:Plant Extracts / Q000494:pharmacology*; D011446:Prospective Studies; D027826:Rosa / Q000737:chemistry
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D010936:Plant Extracts; D002097:C-Reactive Protein