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HomeA FocusVitamin D and Omega-3 supplementation reduced autoimmune disease – VITAL trial

Vitamin D and Omega-3 supplementation reduced autoimmune disease – VITAL trial

Vitamin D supplementation for five years reduced autoimmune disease by 22%, while taking both vitamin D and omega-3 fatty acid supplements decreased autoimmune disease by about 30%, found the Harvard-led VITAL randomised trial, published in BMJ. It showed no benefits from the extra supplementation in preventing either cardiovascular disease or cancer.

“It is exciting to have these new and positive results for non-toxic vitamins and supplements preventing potentially highly morbid diseases,” said lead author Dr Karen Costenbader, a professor of medicine at Harvard Medical School in the division of Rheumatology, Inflammation and Immunity, and the director of the lupus program at Brigham and Women’s Hospital in Boston.

“This is the first direct evidence we have that daily supplementation may reduce AD incidence, and what looks like more pronounced effect after two years of supplementation for vitamin D. We look forward to honing and expanding our findings and encourage professional societies to consider these results and emerging data when developing future guidelines for the prevention of autoimmune diseases in midlife and older adults.”

“Now, when my patients, colleagues, or friends ask me which vitamins or supplements I’d recommend they take to reduce risk of autoimmune disease, I have new evidence-based recommendations for women age 55 years and older and men 50 years and older,” said Costenbader. “I suggest vitamin D 2000 IU a day and marine omega-3 fatty acids (fish oil), 1000 mg a day — the doses used in VITAL.”

That vitamin D dosage is two to three times the recommended daily dose of vitamin D for adults, which is 600 IU for people up to 69 years old and 800 IU for those age 70 and up, according to the National Institutes of Health.
 Once people had been taking vitamin D for at least two years, the prevention rate from autoimmune disorders, like rheumatoid arthritis, psoriasis, thyroid diseases and polymyalgia rheumatica, rose to 39%, according to the study

The study also found a possible link between taking 1,000 milligrams of omega-3 fatty acid (fish oil) and a reduction in autoimmune disorders, but the association was not statistically significant until possible cases of autoimmune disease, not just confirmed cases, were factored into the analysis.

However, the study did find that taking both vitamin D and omega-3 fatty acid supplements, versus the placebo alone, decreased autoimmune disease by about 30%.

People should not just run out and start popping vitamin D pills to boost their chances of avoiding autoimmune disease, Costenbader warned, as there are significant consequences to taking too much of the supplement. Unlike water-soluble vitamins, which the body can easily eliminate, vitamin D is stored in the fat cells and can build up to toxic levels, leading to bone pain and kidney damage.

Because the body makes vitamin D when the skin is exposed to sunshine, and milk and other foods like cereals are often fortified with vitamin D, many experts say healthy, younger people are not likely to require vitamin D supplements, especially in amounts over the recommended level of 600 IU/day.

Levels do drop in older age, but “I would say everybody should talk to their doctor first before taking 2,000 international units of vitamin D on top of whatever else you’re taking”, Costenbader said. “And there are certain health problems such as kidney stones and hyperparathyroidism (a rise in calcium levels), where you really shouldn’t take extra vitamin D.”

Costenbader and colleagues conducted a two-by-two factorial designed, nationwide, randomized, double-blind, placebo-controlled study of 12,786 men aged 50 years or older and 13,085 women aged 55 years or older in the US. Participants were randomly assigned to receive one of four treatment groups: vitamin D (2,000 IU/day) with Omacor omega-3 fatty acid (1,000 mg/day) supplementation, vitamin D with a placebo, omega-3 fatty acid with a placebo or placebo only. The researchers reviewed medical records to assess the incidence of autoimmune diseases from baseline to a median follow up of 5.3 years.

Among the participants, 71.3% were non-Hispanic white and 20.2% were Black. The mean age was 67.1 years. The trial did not intentionally seek a population that was vitamin D deficient, Costenbader and colleagues noted.

Because prior research has shown both vitamin D and omega-3 fatty acids derived from seafood can have a positive effect on inflammation and immunity in autoimmune disorders, Costenbader decided to use the same trial to investigate whether the supplements might prevent such diseases.

Autoimmune disease occurs when the body’s natural defence system suddenly sees normal cells as invaders and begins destroying those cells by mistake. In rheumatoid arthritis, for example, the immune system attacks the lining of joints, creating inflammation, swelling and pain.

With psoriasis, overactive T-cells, which are among the body’s best defenders, cause inflammation that creates raised, scaly patches on the skin.
In Type 1 diabetes, the body’s defenders destroy the insulin-producing cells of the pancreas. There’s even some evidence to show that inflammation throughout the body might be part of the progression of Type 2 diabetes.

Autoimmune disorders can develop at any stage of life but do appear more among older adults, particularly women, Costenbader said. To date, no large randomised clinical trials (considered the gold standard of research) had investigated whether fish oil and vitamin D could actually prevent the development of autoimmune diseases.

“This is the first direct evidence in older adults that taking vitamin D or omega-3 fatty acids, or a combination, for five years reduces autoimmune disease incidence, with more pronounced effect after two years of supplementation,” Costenbader said.

At five years into the research, the study could not tease apart which of the 80 or more autoimmune diseases might benefit most from vitamin D and fish oil supplements, Costenbader said, but research is continuing. The study is now in its seventh year, she said. and more data should be released in the future.

Study details

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

Jill Hahn, Nancy R Cook, Erik K Alexander, Sonia Friedman, Joseph Walter, Vadim Bubes, Gregory Kotler, I-Min Lee, JoAnn E Manson, Karen H Costenbader.

Published in The BMJ on 26 January 2022


To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.

Vitamin D and omega 3 trial (VITAL), a nationwide, randomised, double blind, placebo controlled trial with a two-by-two factorial design.

25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.

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.

A total of 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.

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).


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


See more from MedicalBrief archives:


Vitamin D may help prevent onset of inflammatory diseases


Mixed results from trials on cardiovascular benefits of fish oil


Fish oil may reduce pain in osteoarthritis – UK meta-analysis


Sub-optimal vitamin D levels in the elderly


Little benefit from vitamin D supplements for over 70s



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