Vitamin D and fish oil supplements and risk of autoimmune disease (January 2022)

Link to full paper: https://www.bmj.com/content/376/bmj-2021-066452.full

Link to opinion piece by the authors: https://www.bmj.com/content/376/bmj.o243

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In this huge US study, 12786 men ≥50 years and 13 085 women ≥55 years were studied over a period of 5 years. During this period, they received either:

1. 1) vitamin D and omega-3 fish oils;
2. 2) vitamin D and omega-3 placebo;
3. 3) vitamin D placebo and omega-3 fish oils; or
4. 4) vitamin D placebo and omega-3 placebo.

The vitamin D (2000 International Units/day) and omega-3 fish oil (1gram/day, of which 460mg EPA and 380mg DHA) contained similar doses to supplements that can typically be bought in shops. Vitamin D status was measured one year in, as the level of plasma 25(OH)D₃ (storage form of vitamin D, which can be turned into active form 1,25-(OH)₂D₃ in liver). Vitamin D increased on average by 40% in people who received vitamin D supplements. Omega-3 status was also measured at one year, as the omega-3 index (concentration of EPA and DHA relative to total fats). Omega-3 levels increased by 55% after one year in those receiving omega-3 fish oil supplements.

Each year, participants completed a questionnaire about newly diagnosed autoimmune disease such as rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis and inflammatory bowel disease, they could also write in any others. The study does not mention alopecia areata directly, but as AA is believed to be an autoimmune condition too, the results of this study may still be useful to those with AA. Because it can be hard to reach a confirmed diagnosis for many of these autoimmune conditions, the researchers classified participants into two groups: confirmed disease (with sufficient evidence and documentation) or probable disease (insufficient documentation).

In those receiving vitamin D supplements, 123 developed new onset confirmed autoimmune disease, compared to 155 in the placebo group. So, the risk (or ‘Hazard Ratio’) of developing new confirmed autoimmune disease was 0.78 in those receiving vitamin D compared to placebo, meaning there was a 22% lower chance of developing new onset autoimmune disease for those taking vitamin D supplements. When those with probable disease were also included, the evidence was not as strong and no beneficial effect was observed. 

Of people receiving omega-3, 130 in the treatment and 148 in the placebo group had new onset confirmed autoimmune disease. Statistically, the evidence was not strong enough to say there was an effect of omega-3. But, when those with probable autoimmune disease were included, 208 in the omega-3 and 249 in the placebo group had new onset autoimmune disease. This represented an 18% lower risk overall. They also showed that the difference between omega-3 and placebo was more evident during the last 2 years of the study (years 3-5).

Interestingly, the reduction in risk with vitamin D supplementation was higher in those with a lower body mass index (BMI = weight ÷ height²). For omega-3, the beneficial effect was greater in those with a family history of autoimmune disease compared to those with no family history. Vitamin D is mostly known for its roles in calcium uptake and bone health. But it is also known to affect immune cells, which are able to bind vitamin D on their surface through specific vitamin D receptors. When the active form of vitamin D binds to an immune cell, the cell changes its function and which types of molecules it spits out to control the environment around it (called cytokines).

Omega-3 fats can also affect the local environment in and around cells, as EPA and DHA can react with oxygen to turn into active signalling molecules called eicosanoids. This process may improve the way the immune system works, as the environment becomes less stressful (lower inflammation) when omega-3s are present.

It should be noted that this study was done in adults over the age of 50, so it is unclear if similar effects would be seen in younger people, and autoimmune diseases with a low age of onset. The authors also note that autoimmune disease in the US is on the rise in general and this may reflect the aging population and the underlying issues with diet and lifestyle (lack of exercise and weight status).

Conclusion:

2000 IU/d vitamin D, 1g/d high EPA + DHA omega-3 fish oil, or a combination of vitamin D and omega-3 supplements, reduced the risk of new onset autoimmune disease in a US population over the age of 50, with more pronounced effects after 2 years of supplementation.

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Disclaimer: This is an interpretation of the results by the Research Manager, and does not reflect official Alopecia UK policy, nor does it constitute medical advice. Supplements can have negative health effects. For advice on nutrition talk to your doctor or a registered dietitian.