The results of the Vitamin D and omega 3 trial (VITAL), originally published in BMJ in 2022, found that vitamin D supplementation at 2000 IU D3 per day significantly reduced the risk of autoimmune disease incidence by 22% when taken over a 5-year period. This was a large nationwide randomized and controlled trial (2x2 factorial design) that included nearly 26,000 participants, finding benefit with vitamin D with or without omega-3 fatty acids compared to placebo, and a non-significant reduction in risk with omega-3 supplementation. It’s worth noting that the effect of vitamin D was even stronger if the first two years of the trial were excluded, i.e., only the final three years were included in the analysis. In this case, rather than a 22% decrease in risk, there was a 39% decrease (with a p-value of 0.005 vs. 0.05 as well).
The journal Arthritis & Rheumatology published a follow-up analysis two years after the completion of Vital, which found that seven years after the trial began, there was no significant reduction in autoimmune risk with vitamin D supplementation. In contrast, there was now a 17% lower incidence of autoimmune disease among people who had received omega-3 fatty acids. It’s important to keep in mind that the trial officially ended at five years; in other words, participants may or may not have continued taking supplements after the trial’s completion. One possible takeaway is that vitamin D may require maintenance dosing to provide benefit, i.e., once it is discontinued, the benefit may fade. Vitamin D3 is thought to have a ½ life of approximately 15 days (modified by vitamin D binding protein levels and genotype), so it’s plausible that within months of discontinuing supplementation, levels return to baseline.
Overall, it’s tempting to say that vitamin D supplementation has a benefit in reducing autoimmune incidence that builds over time, something important to keep in mind when conducting clinical trials. Two years was sufficient to detect a reduction, but this effect increased over time, and it’s not clear what trial length is needed to observe the benefit. In one recent study, published in the Journal of Pediatric Endocrinology & Metabolism, high-dose vitamin D supplementation (60,000 IU vitamin D every fortnight) given to children with type 1 diabetes seemed to preserve residual β-cell function (RBCF) and prolong partial remission (PR) rates when given over six months. A previous trial by this same group, conducted among youth with new-onset type 1 diabetes, found reductions in TNF-α concentration at 3, 6, and 9 months compared to placebo, but they were only significant at 12 months (with significant benefits to HbA1c and Insulin Dose–adjusted A1c as well). Allowing enough time to observe benefit is critical in these trials, as well as the possibility that a maintenance dose of vitamin D is necessary to sustain the benefits.