Abstract
Vitamin D has immunomodulatory properties with potential etiologic implications for autoimmune diseases. The relevant exposure time during which vitamin D may influence disease risk is unknown. Our objective was to examine the relationship between reported vitamin D intake during adolescence and adult-onset rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) incidence in prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII). Food frequency questionnaires concerning high school diet completed by 73,629 NHS (1986) and 45,544 NHSII (1998) participants were used to calculate nutrient intakes during adolescence. Incident RA and SLE cases prior to 2006 (NHS) and 2007 (NHSII) were confirmed by medical record review. Cox proportional hazards models calculated relative risks and 95% confidence intervals of incident RA and SLE according to quintile cutoffs of vitamin D intake. Age- and calorie-adjusted and multivariable-adjusted (including sun exposure factors) analyses were completed. Random-effects models were used to meta-analyze estimates of association from the 2 cohorts. Incident RA was confirmed in 652 NHS and 148 NHSII participants and SLE was confirmed in 122 NHS and 54 NHSII participants over a mean followup time of 351 months (NHS) and 209 months (NHSII). Age- and calorie-adjusted and multivariable-adjusted models did not show significant associations between adolescent vitamin D intake and risk of adult-onset RA or SLE. We did not find associations between adolescent dietary vitamin D intake and adult RA or SLE risk among NHS and NHSII women, suggesting that other time periods during the life course should be studied.
Highlights
Vitamin D has been implicated as a potential etiologic factor in several related autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)(1–6)
The cohort consisted of 73,629 nurses in Nurses’ Health Study (NHS) followed through June 2006, and 45,544 nurses in Nurses’ Health Study II (NHSII) followed through June 2007, after excluding 1382 NHS participants for reporting caloric intakes 5000 kcal per day consumption
In the multivariable models for RA or SLE we did not observe any association for sun exposure, sunscreen use or physical activity during adolescence, which could be proxys for sun exposure
Summary
Vitamin D has been implicated as a potential etiologic factor in several related autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)(1–6). The large, prospective Iowa’s Women’s Study of women aged 55–69 years observed an inverse association between both dietary and supplemental vitamin D intake and RA risk[7], yet prospective study of vitamin D intake and RA risk among women in the NHS found no association[8]. There is mounting evidence for the immunomodulatory effects of vitamin D(1, 4). The hormonally active form of vitamin D mediates immunological effects by binding to nuclear vitamin D receptors (VDR) which are present in most immune cell types involved in innate and adaptive immunity. Activation of VDR has potent antiproliferative, pro-differentiative, and immunomodulatory functions which are both immuneenhancing and immunosuppressive[9]
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