Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial

The BMJ

Jan 2022

DOI: 10.1136/bmj-2021-066452

Citations:298

Influential Citations:10

Interventional (Human) Studies

Enhanced Details

Methods

Randomized, double-blind, placebo-controlled trial conducted in the United States; 25,871 participants (men ≥50 years and women ≥55 years) with mean age 67.1 years; 18% reported autoimmune disease at baseline; eligible participants excluded renal failure or dialysis, cirrhosis, hypercalcemia, cancer (except non-melanoma), cardiovascular disease, or other serious illness; follow-up median 5.3 years.

Intervention

Vitamin D 2000 IU/day; Omega-3 fatty acids 1000 mg/day; duration five years; daily oral capsules.

Results

Vitamin D 2000 IU/day for ~5 years reduced confirmed autoimmune disease incidence by about 22% vs placebo (HR 0.78; 95% CI 0.61–0.99; P=0.05). Omega-3 fatty acids 1000 mg/day did not significantly reduce incidence (HR 0.85; 95% CI 0.67–1.08; P=0.19). In four-arm comparisons, vitamin D with omega-3 (HR 0.69), vitamin D alone (HR 0.68), and omega-3 alone (HR 0.74) all showed lower incidence than placebo; combining both vitamins reduced risk by about 30% vs placebo. Overall, daily vitamin D supplementation reduces autoimmune disease incidence in older adults; omega-3 alone shows no clear preventive effect; findings support vitamin D as a potential preventive measure with ongoing follow-up to assess durability.

Limitations

Limited power to detect effects on individual autoimmune diseases due to small event counts; only one dose and formulation tested; results may not generalize to younger populations; some diagnoses (e.g., autoimmune thyroid disease) were challenging to confirm from medical records; sensitivity analyses including probable autoimmune disease suggest potential misclassification concerns.

Abstract

Abstract Objective To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk. Design Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design. Setting Nationwide in the United States. Participants 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment. Interventions Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence. Main outcome measures The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others. Results 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease. Conclusions Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo). Study registration ClinicalTrials.gov NCT01351805 and NCT01169259 show less