Polymorphisms at Cytokine Genes May Determine the Effect of Vitamin E on Cytokine Production in the Elderly , ,

Abstract

Vitamin E has been shown to affect cytokine production. However, individual response to vitamin E supplementation varies. Previous studies indicate that cytokine production is heritable and common single nucleotide polymorphisms (SNP) may explain differences in cytokine production between individuals. We hypothesize that the differential response to the immunomodulatory actions of vitamin E reflects genetic differences among individuals, including SNP at cytokine genes that modulate cytokine production. We used data from a double-blind, placebo-controlled 1-y vitamin E (182 mg d,l-alpha-tocopherol) intervention study in elderly men and women (mean age 83 y) to test this hypothesis (vitamin E, n = 47; placebo, n = 63). We found that the effect of vitamin E on tumor necrosis factor (TNF)-alpha production in whole blood stimulated for 24 h with lipopolysaccharide (1.0 mg/L) is dependent on TNFalpha -308G > A. Participants with the A/A and A/G genotypes at TNFalpha -308G > A who were treated with vitamin E had lower TNFalpha production than those with the A allele treated with placebo. These observations suggest that individual immune responses to vitamin E supplementation are in part mediated by genetic factors. Because the A allele at TNFalpha has been previously associated with higher TNFalpha levels in whole blood and isolated immune cells, our observations suggest that the antiinflammatory effect of vitamin E is specific to those genetically predisposed to higher inflammation. Further studies are needed to determine the biological mechanism driving the interaction between vitamin E treatment and TNFalpha -308G > A and its implications for disease resistance.

Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress

“…For example, SNPs in the TNF-α gene (eg, −308 G>A) affected the inflammatory response of elderly individuals to supplementation with 273 IU/day of α tocopherol for 1 year 165. When carriers of the A allele received vitamin E, they had lower TNF-α synthesis upon exposure to lipopolysaccharides compared to their nonsupplemented counterparts.…”

Vitamin E supplementation and mammalian lifespan

“…For example, middle-aged, type-II diabetic patients carrying a haptoglobin 2-2 polymorphism were protected against cardiovascular disease following vitamin E supplementation relative to individuals carrying different polymorphisms [35]. In addition, individual differences in the inflammatory response following vitamin E supplementation in humans appear to be partly mediated by polymorphisms in genes that modulate cytokine production [36]. Systematic reviews of the effects of vitamin E on all cause mortality in humans suggest that the overall impact of high levels of vitamin E supplementation is negative, with a 4% increase in mortality risk relative to placebo [37,38].…”

Serum cytokines and muscle strength after anterior cruciate ligament surgery are not modulated by high-doses of vitamins E (α- and γ-tocopherol’s) and C

“…Future research investigating the influence of vitamin E and C supplementation on the systemic cytokine response to surgery is encouraged to include perioperative assessments. Finally, polymorphisms at cytokine genes influence the capacity of vitamin E to modulate cytokine production [54], and unfortunately, were not examined in this investigation.…”