Vitamin D and prevention of autoimmune diseases
It has always been argued that low vitamin D levels are a consequence of autoimmune disease rather than a risk factor for developing autoimmunity. Have we made a mistake?
Chicken or egg? It has always been argued that low vitamin D (vD) levels are a consequence of autoimmune diseases (AIDs) and/or inflammation and are not a cause or risk factor for developing AIDs. This is the so-called reverse causation theory.
I attended a National MS Society Vitamin D MS Prevention Task Force meeting in 2011 when we the MS community made a commitment to do a vD MS prevention study. We in fact designed three trials to take forward. Sadly nothing happened.
Why the lament? The study below, albeit in older adults, suggests that a relatively modest dose of vD of only 2,000 IU/day reduced the risk of getting rheumatoid arthritis, polymyalgia rheumatic, autoimmune thyroid disease, psoriasis, and other AIDs by about 20%. Imagine if this study’s finding applies to MS? We could have potentially prevented 10,000’s of young people from getting MS. Sadly without data, we can’t extrapolate this study’s findings to MS.
However, I personally think low vD levels or lack of sun exposure are causally linked to MS. This is based on a large body of epidemiological evidence and the fact the whole genome associations studies and Mendelian Randomisation studies show genetic determinants of low vD levels are linked to an increased MS risk. This is why I have been recommending to all my patients to make sure their family members, in particular, their children and siblings are vD replete.
If you have MS being vD replete is good for your bone health. I am doubtful vitamin D makes much difference to MS outcomes, but stand to be corrected if larger well-designed studies show a robust disease-modifying effect of vD.
Please note the current recommended daily allowance of vD as promoted by public health experts is too low and is based historically on rickets and osteoporosis prevention. However, for the immunological effects of vD, you probably need an order of magnitude higher level of vD supplementation.
My current recommendations for what dose of vD supplements to take are the following:
0-2 years of age 600 IU/day
2-10 years of age 2,000 IU/day
>10 years of age 4,000 IU/day
These recommendations are based on the now-defunct vD Council and EFSA (European Food Safety Authority) recommendations on safe doses of vD.
In reality, we should probably supplement vD to target a blood level of between 100 and 250 nmol/L or between 40 and 100 ng/mL. This target is not based on population studies, but evolutionary medicine principles, i.e. what levels of vD did our ancestors have and what levels do populations of people who work outdoors in sunny environments maintain spontaneously without vD supplementation.
Hahn et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ . 2022 Jan 26;376:e066452. doi: 10.1136/bmj-2021-066452.
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).
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.