Vitamin D (Calciferols)
Vitamin D is the name given to a group of hormones known as secosteroids. Their primary function in the body is optimizing intestinal absorption of the essential minerals calcium, magnesium, and phosphate, but they play key roles in many other physiological actions as well. The dietary D-vitamins basic to human health are vitamin D2 (known as ergocalciferol) and vitamin D3 (cholecalciferol), with D3 being the most studied in medical research because it is converted more abundantly to the active form 1,25-dihydroxycholecalciferol (also known as calcitriol)1.
Vitamin D is known to modulate the functions of immune cells, and it has been shown in cell studies to enhance immune function2-6. In certain immune cells, vitamin D facilitates their conversion to healthy regulatory types, increases production of anti‐inflammatory cytokines, and decreases pro‐inflammatory7-12. The anti‐inflammatory effect of vitamin D supplementation is believed to be responsible for the observed increase in Treg proportions13,14.
Just as in animal studies, observational studies in humans have suggested a link between increased risk of MS and low vitamin D status as measured by blood levels of 25-hydroxycholecalciferol (25OHD, the tested form)15-17. Further, a genetic study comparing 14,802 MS patients with 26,703 controls from around the world18 found that lower genetic risk of vitamin D deficiency risk was associated with lower risk of MS. This effect applied to both adult-onset and childhood-onset MS19.
In an observational study in patients with CIS (most already receiving DMT), low vitamin D status was found to be a greater risk factor for disease progression and cognitive decline than smoking and Epstein-Barr virus infection over a period of 11 years. The results suggest that adequate vitamin D levels could contribute to long-term neuroprotection in individuals at risk for full-blown MS, independent of DMT20.
Interventional studies, including randomized controlled clinical trials, have investigated immunological improvements following vitamin D supplementation in MS patients21-24. Additionally, regular use of vitamin D supplements was associated with improved MRI outcomes compared to occasional or no use25-27.
In a randomized, controlled clinical study, patients with RRMS receiving interferon beta-1a (Rebif®) were also given a daily vitamin D3 dose of approximately 14,000 IU (350 mcg) or placebo. Though no difference was observed between groups in disease activity (defined as no relapses, disability progression, or combined unique active lesions), vitamin D3 treatment was associated with reduced development of new lesions and lesion growth27. Interestingly, in a similarly designed study in vitamin D-deficient RRMS patients receiving Rebif®, a lower overall vitamin D dose of 100,000 IU (2,500 mg) every two weeks was associated with a significant reduction in relapse rate, fewer new lesions, and less progression of disability25. The combination of vitamin D3 with interferon beta-1b (Betaseron®/Betaferon®, Extavia®) was also associated with both significant decreases in new lesions and trends toward reduced disability accumulation and improved walking28.
Vitamin D supplementation has also been evaluated for general well-being in MS. In one study, RRMS patients receiving interferon-beta were given either 50,000 IU vitamin D3 or placebo every five days for three months, with the treatment group showing significantly improved mental quality of life compared to controls29. In another study, cognitive changes were compared between RRMS and CIS patients either deficient in vitamin D and receiving an oral daily vitamin D3 dose of 10,000 IU (250 mg), or sufficient in vitamin D. Vitamin D3 supplementation improved the MS patients’ cognitive performance, with sufficient serum 25OHD level predicting better results both pre- and post-treatment30. Alfacalcidiol (a vitamin D metabolite) at a dose of 1 mcg/day was found to decrease fatigue and number of relapses in MS patients compared to placebo31.
To assess the impact of high-dose vitamin D3 supplementation on RRMS patients positive for the Epstein-Barr virus – an increasingly accepted risk factor for MS – biomarkers were compared between participants given daily vitamin D3 7,000-14,000 IU (175-350 mcg) and controls given placebo. The vitamin D3-treated patients showed significantly reduced Epstein-Barr virus antigens compared to pre-treatment and to controls32,33.
Overall, an excellent safety profile has been observed at all vitamin D dosages in MS studies conducted thus far, even with greater than 10,000 IU daily11,21,22,25,27,28,33,34.
The DRI recommendation for vitamin D intake in pregnant women is 600 IU (15 mcg) per day35, with up to 60,000 IU (1500 mcg) per day observed to be safe in this group36.
The most natural source of vitamin D is conversion from 7-dehydrocholesterol in the skin through exposure to ultraviolet-B radiation from sunlight. However, many people do not get enough sun to synthesize sufficient vitamin D, and so are dependent upon dietary sources and supplements to meet even just the basic daily recommendation of 400 IU (10 mcg). Foods high in vitamin D2 include sun-exposed mushrooms and D2-fortified plant-based milk alternatives; those high in vitamin D3 include fatty fish (e.g., herring, mackerel, salmon, sardines), cod liver oil, beef liver, egg yolks, and vitamin D3-fortified foods (e.g., dairy and orange juice)1.
Of note, when vitamin D3 is supplemented, there was observed to be more of a beneficial effect in females, likely due to an interaction with estrogen hormones37-40.
References
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