The characteristics of the women participating in the NHS and NHS2 in 1990 and 1991 respectively are shown in according to quintiles of Vitamin D intake. Women with higher vitamin D intake had other markers of a healthy lifestyle. Fewer were current smokers and more were past smokers, they had more physical activity, lower intake of caffeine, higher intake of calcium, protein and vitamin A, and a higher proportion had breastfeed their infants for a year or more. Only 3-4% of participants were postmenopausal in NHSII in 1991. In NHS, more postmenopausal women, and more taking postmenopausal hormones, had high vitamin D intake. There were no differences in race, susceptibility to sunburn, natural hair color, BMI, husband's educational status, geographic area at age 15, age at menarche, or parity according to vitamin D intake. There were also no important differences in the characteristics (listed in ) of women who responded to our additional mailings compared to those who did not respond (data not shown).
Age-adjusted characteristics of the cohort participants
Characteristics at diagnosis of the SLE and RA cases included in these analyses in each of the cohorts are shown in . Almost all cases of SLE had antinuclear antibodies at diagnosis and 57% of RA cases were rheumatoid factor positive at diagnosis. Most cases in both cohorts were diagnosed by a physician who was an ACR member.
Results of age-adjusted and multivariable Cox proportional hazards models investigating the relative risks of developing SLE or RA according to quintile of cumulative intake of vitamin D from food and supplements combined, and supplements alone, are shown in and . The final multivariable models for SLE included age at menarche, oral contraceptive use, menopausal status, postmenopausal hormone use, cigarette smoking, latitude of residence at age 15 (North, Middle or South U.S.), physical activity in metabolic equivalent hours per week, BMI in kg/m2
, and race. Final multivariable models for RA included the same covariates plus parity and total duration of breastfeeding as we have found these to be related to risk of RA in our prior analyses.[22
] Additional adjustments for BMI at age 18, alcohol intake, husband's educational level, menstrual regularity, skin type, hair color, UV index in state of residence at birth, and ages 15 and 30, did not affect the relative risks in any of the multivariable models in either cohort and so these variables were not included in the final models. There was no evidence of statistical heterogeneity between the cohorts (p heterogeneity > 0.05) for all analyses.
Vitamin D intake and risk of SLE among women in the Nurses' Health Study 1980-2002 and the Nurses' Health Study II 1991-2003
Vitamin D intake and risk of RA among women in the Nurses' Health Study 1980-2002 and the Nurses' Health Study II 1991-2003
We observed no associations between cumulative average vitamin D intake, defined in different models as vitamin D from food sources only, from food and supplements, and divided into quintiles, into quartiles, in multiple or dichotomous categories of daily intake, or as a continuous measure, and the risks of SLE or RA. The only significant association we observed was for > 400 IU/day of supplemental vitamin D with increased risk of RA among women in the NHSII younger cohort (p trend =0.04). () This association was not seen in the NHS cohort or in the combined analyses. The point estimates for the relative risk of RA among women in the higher categories of supplemental vitamin D intake in the NHSII cohort did increase after adjustment in our multivariable models. We did not find that any single covariate in the multivariable models was responsible for confounding however. The pooled relative risk for incident SLE in the highest category of vitamin D intake was 1.4 (95%CI 0.8, 2.3) and the pooled relative risk for RA was 1.0 (95%CI 0.8, 1.3). In a sensitivity analysis excluding women who reported cancer at baseline or during follow-up, results in both cohorts and for both outcomes were unchanged. No relationship between vitamin D intake and the risk of rheumatoid factor-positive RA was observed in either cohort. Analyses of vitamin D from the baseline questionnaire only or updated vitamin D intake reflecting more recent intake were similarly null for both diseases.