ABSTRACT
BACKGROUND: Vitamin A deficiency (VAD) impairs T-cell-mediated immunity. In regions where VAD is prevalent, vitamin A supplementation (VAS) reduces child mortality, perhaps by improving immune function. OBJECTIVE: Our objective was to determine if neonatal VAS would improve thymic function in Bangladeshi infants, and to determine if such effects differed by sex or nutritional status (i.e., birth weight above/below the median). METHODS: Three hundred and six infants were randomly assigned to 50,000 IU vitamin A (VA) or placebo (PL) within 48 h of birth. Primary outcomes were measured at multiple ages and included 1) thymic index (TI) at 1, 6, 10, and 15 wk; 2) T-cell receptor excision circles (TREC), an index of thymic output of naïve T cells; and 3) total/naïve T cells in peripheral blood at 6 wk, 15 wk, and 2 y. A mixed linear model for repeated measures was used to assess group differences at each age and identify interactions with sex and birth weight. RESULTS: VAS did not significantly (P = 0.21) affect TI overall (i.e., at all ages) but decreased TI by 7.8% (P = 0.029) at 6 wk: adjusted TI means for the PL and VA groups at 1, 6, 10, and 15 wk were 4.09 compared with 3.80 cm2, 7.78 compared with 7.18 cm2, 8.11 compared with 7.84 cm2, and 7.91 compared with 7.97 cm2, respectively. VAS did not significantly (P = 0.25) affect TREC overall but decreased TREC by 19% (P = 0.029) at 15 wk: adjusted TREC means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 13.6 compared with 16.1 copies/pg DNA, 19.4 compared with 15.7 copies/pg DNA, and 11.8 compared with 10.0 copies/pg DNA, respectively. VAS did not significantly affect overall total (P = 0.10) or naïve (P = 0.092) T cells: adjusted naïve T-cell means for the PL and VA groups at 6 wk, 15 wk, and 2 y were 3259 compared with 3109 cells/µL, 3771 compared with 3487 cells/µL, and 1976 compared with 1898 cells/µL, respectively. CONCLUSION: In contrast to our hypothesis, VAS decreased thymic function early in infancy but health effects are presumably negligible owing to the transience and small magnitude of this effect. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.
Subject(s)
Thymus Gland/drug effects , Vitamin A Deficiency/drug therapy , Vitamin A/administration & dosage , Dietary Supplements , Female , Humans , Infant, Newborn , Male , Nutritional Status , T-Lymphocytes/physiologyABSTRACT
BACKGROUND: Metabolic imbalance is a key determinant of risk of chronic diseases. Metabolic health cannot be assessed solely by body mass calculations or by static, fasted state biochemical readouts. Although previous studies have described temporal responses to dietary challenges, these studies fail to assess the environmental factors associated with certain metabolic phenotypes and therefore, provide little scientific rationale for potentially effective intervention strategies. METHODS/DESIGN: In this phenotyping study of healthy US adults, we are evaluating lifestyle, biological and environmental factors in addition to metabolic parameters to determine the factors associated with variations in metabolic health. A series of practical fitness, dietary, and emotional challenges are introduced and temporal responses in various areas of specialization, including immunology, metabolomics, and endocrinology, are monitored. We expect that this study will identify key factors related to healthy or unhealthy metabolic phenotypes (metabotypes) that may be modifiable targets for the prevention of chronic diseases in an individual. DISCUSSION: This study will provide novel insights into metabolic variability among healthy adults in balanced strata defined by sex, age and body mass index. Usual dietary intake and physical activity will be evaluated across these strata to determine how diet is associated with health status defined using many indicators including immune function, metabolism, body composition, physiology, response to exercise andmeal challenges and neuroendocrine assessment. A principal study goal is to identify dietary and other personal factors that will differentiate different levels of "health" among study participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02367287.
ABSTRACT
BACKGROUND: Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions in mothers and infants. Vitamin D supplementation in pregnancy may support the maintenance of pregnancy by its effects on innate and adaptive immunity. OBJECTIVE: We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status and markers of immune function associated with adverse pregnancy outcomes. METHODS: We conducted a randomized, controlled, double-blind intervention of 2 doses of cholecalciferol (400 and 2000 IU/d) from <20 wk to delivery in 57 pregnant women. Vitamin D status, regulatory and inflammatory T cells, markers of innate immunity and systemic inflammation, and clinical outcomes including maternal blood pressure and birth weight were assessed at 26 and 36 wk of pregnancy. RESULTS: Supplementation with 2000 IU/d vitamin D had a greater effect on the change in vitamin D status over pregnancy (P < 0.0001) and the final value at 36 wk (P < 0.0001) than 400 IU/d, increasing serum 25-hydroxyvitamin D from 81.1 nmol/L at baseline to 116 nmol/L at 36 wk and from 69.6 nmol/L at baseline to 85.6 nmol/L at 36 wk, respectively. The 2000-IU/d group had 36% more interleukin-10+ regulatory CD4+ T cells at 36 wk than did the 400-IU/d group (P < 0.007). The daily intake of 2000 compared with 400 IU/d tended to dampen the pregnancy-related increase in diastolic blood pressure by 1.3-fold (P = 0.06) and increase birth weight by 8.6% (P = 0.06), but these differences were not statistically significant. CONCLUSIONS: Supplementation with 2000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory T cell immunity that may prevent adverse outcomes caused by excess inflammation. This trial was registered at clinicaltrials.gov as NCT01417351.
