Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial
BMJ 2022; 376 doi: https://doi.org/10.1136/bmj-2021-066452 (Published 26 January 2022) Cite this as: BMJ 2022;376:e066452Linked Opinion
Vitamin D and fish oil supplements and risk of autoimmune disease
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Dear Editor
The VITAL randomised controlled trial has demonstrated that vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced the occurrence of new-onset autoimmune disease by 22%, as compared with placebo.
This result is surprising, as the study population included people who were replete with vitamin D at baseline. Indeed, the mean 25(OH)D levels were 30.7 ng/ml, which is normal, and only 13.3% were deficient (i.e. 20 ng/mL). Previously, a systematic review and meta-analysis failed to show a significant effect of vitamin D supplementation on fractures risk and falls (1). However, one major caveat of such studies was that they mainly included people with normal vitamin D levels.
The VITAL study reported by Hahn et al. informs that 2000 IU daily, taken for five years, could be sufficient (and safe) in patients with normal vitamin D to counteract the progression of inflammation and acquired and innate immune responses leading to autoimmune processes. However, this study did not tell us whether correcting vitamin D deficiency in people at risk of autoimmune diseases could have even a more significant effect size. Hence, people with vitamin D deficiency or insufficiency may or may not need higher doses to achieve the same biological effects.
Another critical point is that prespecified subgroup analyses for confirmed autoimmune disease suggested that people with lower body mass index (BMI<25) seem to benefit more from vitamin D treatment than overweight or obese people. We also previously showed that vitamin D supplementation is essential for musculoskeletal health in people with very low body weight and 25(OH)D deficiency (2). Obesity is common among people with established autoimmune diseases, explaining why the benefit of vitamin D supplements might have been challenging to ascertain in prior observational studies.
References:
1) Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018 Nov;6(11):847-858
2) Giollo A, Idolazzi L, Caimmi C, Fassio A, Bertoldo F, Dalle Grave R, et al. Int J Eat Disord. 2017 Sep;50(9):1041-1049.
Competing interests: No competing interests
Vitamin D and marine omega 3 fatty acid supplementation prevents autoimmune disease? Not so fast.
Dear Editor
According to its website, the VITAL study included at least 16 "ancillary studies." The main study results for cardiovascular disease were all negative. Thus there have been about 20 statistical tests performed on the VITAL data, one of which should produce a p value less than 0.05 by chance. An unstated limitation of the analysis by Hahn and her co-workers is the failure to adjust for multiple comparisons. Accordingly, these results should be considered exploratory. Further research would be needed to test the hypothesis that supplementation with vitamin D and omega 3 fatty acids can reduce incident autoimmune disease.
Competing interests: No competing interests