Lynette S. Leka

VITAMIN E STATUS AND IMMUNE FUNCTION

Evidence from animal and human studies indicates that vitamin E plays an important role in the maintenance of the immune system. Even a marginal vitamin E deficiency impairs the immune response, while supplementation with higher than recommended dietary levels of vitamin E enhances humoral and cell-mediated immunity. The current RDA level of vitamin E prevents clinical deficiency syndrome but in some situations, especially in older subjects or in a disease state, fails to maintain optimal host defense. The immunological parameters reviewed are all sensitive to changes in the availability of vitamin E and, therefore, may reflect the vitamin E status of a given individual more accurately than conventional methods.

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

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.

IL-2 and IL-10 gene polymorphisms are associated with respiratory tract infection and may modulate the effect of vitamin E on lower respiratory tract infections in elderly nursing home residents

BACKGROUND Vitamin E supplementation may be a potential strategy to prevent respiratory tract infections (RIs) in the elderly. The efficacy of vitamin E supplementation may depend on individual factors including specific single nucleotide polymorphisms (SNPs) at immunoregulatory genes. OBJECTIVE We examined whether the effect of vitamin E on RIs in the elderly was dependent on genetic backgrounds as indicated by SNPs at cytokine genes. DESIGN We used data and DNA from a previous vitamin E intervention study (200 IU vitamin E or a placebo daily for 1 y) in elderly nursing home residents to examine vitamin E-gene interactions for incidence of RI. We determined the genotypes of common SNPs at IL-1beta, IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma in 500 participants. We used negative binomial regression to analyze the association between genotype and incidence of infection. RESULTS The effect of vitamin E on lower RI depended on sex and the SNP at IL-10 -819G-->A (P = 0.03 for interaction for lower RI). Furthermore, we observed that subjects with the least prevalent genotypes at IL-2 -330A-->C (P = 0.02 for upper RI), IL-10 -819G-->A (P = 0.08 for upper RI), and IL-10 -1082C-->T (P < 0.001 for lower RI in men) had a lower incidence of RI independent of vitamin E supplementation. CONCLUSIONS Studies that evaluate the effect of vitamin E on RIs should consider both genetic factors and sex because our results suggest that both may have a significant bearing on the efficacy of vitamin E. Furthermore, common SNPs at cytokine genes may contribute to the individual risk of RIs in the elderly. This trial was registered at clinicaltrials.gov as NCT00758914.

Immunological Effects of Low-Fat Diets with and without Weight Loss

Objective: The immunologic effects of isocaloric reduced- and low-fat diets and a voluntary calorie-restricted low-fat diet resulting in weight loss were compared to the immunologic effects of an average American diet in hyperlipidemic individuals. Methods: Ten hyperlipidemic subjects were studied during three six-week weight maintenance phases: baseline (BL) [35% fat {14% saturated fat (SFA), 13% monounsaturated fat (MUFA), 8% polyunsaturated fat (PUFA)} and 147 mg cholesterol (C)/1000 kcal], reduced-fat (RF) [26% fat (4% SFA, 11% MUFA, 11% PUFA) and 45 mg C/1000 kcal], and low-fat (LF) [15% fat (5% SFA, 5% MUFA, 3% PUFA) and 35 mg C/1000 kcal] diets followed by 12-week, low-fat calorie reduced phase (LFCR). Results: During the last phase, the subjects’ weight significantly decreased (p = 0.005). Cholesterol levels were significantly reduced during all phases, compared to BL diet (p < 0.05). Delayed-type hypersensitivity (DTH) was assessed using Multi-test CMI. Maximum induration diameters were 22.7, 25.4, 30.5, 34.5 mm for BL, RF, LF and LFCR diets, respectively. Subjects on the LFCR diets had significantly higher DTH compared to the BL diet (p = 0.005). No significant effect of diet was observed on lymphocyte proliferation or interleukin (IL)-1, IL-2 and prostaglandin (PG) E2 production. Conclusions: These data suggest that low-fat diets (15% energy), under conditions which result in weight loss, do not compromise and may enhance the immune response of middle-aged and elderly hyperlipidemic subjects. The results of this study provide support for the hypothesis that moderate caloric restriction in humans may have a beneficial effect on cell-mediated immunity such as those reported in calorie-restricted rodents.

Metabolic aging and predicted longevity: Results of a cross-sectional study in post-menopausal women

Background and aims: The extent to which general characteristics of metabolic aging contribute to differences in life span among individuals remains uncertain. The objective of this study was to examine the association of age-related physiological and metabolic variables with predicted longevity in post-menopausal women. Methods: Subjects were 33 healthy women aged 55–65 years. Total and resting energy expenditure, body temperature, immune function as assessed by a delayed-type hypersensitivity skin test (DTH), lipid profile, and reported dietary intake were measured. Results: There were no significant associations between longevity, energy expenditure, body temperature, lipid profile, or dietary intake. However, there was a significant association of predicted longevity with DTH (partial r=0.44, p=0.023). Conclusions: These results suggest that immune function may predict familial differences in longevity, while energy expenditure, body temperature, lipid profile, and dietary intake are unrelated. Although the small sample size may have limited the ability to detect metabolic effects on longevity in this study, the general approach may be broadly applicable to examinations of metabolic aging in humans.