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Vitamin D and Multiple Sclerosis

Garrett Heinrich
Tags: Neuroscience

Summary:

  • Vitamin D can come from plants, skin's reactions to UV radiation, or animal food sources
  • Vitamin D3 from sunlight or animal sources is more effective than plants in raising active Vitamin D metabolites in circulation
  • Vitamin D deficiency is associated with the autoimmune disease Multiple Sclerosis



Introduction

"Hot enough for you?"
As summertime draws near in the northern hemisphere, that is a common refrain you may hear from your friends and neighbors. Summertime brings warmth, drawing people outside, and the summer solstice brings the year's longest days. Those long days provide ample sunshine to drive photosynthesis in plants, and sunlight benefits humans as well (when taken in moderation, of course). One of these benefits is the production of Vitamin D. Vitamin D helps with calcium absorption, so not surprisingly, deficiency of Vitamin D results in bone problems, including reduced density, osteoporosis, and increased risk of breakage. In children, Vitamin D deficiency can cause rickets, a disease where the bones become soft and distorted, commonly resulting in bowed legs. As with most things, an excess of Vitamin D is also bad for your health. Too much Vitamin D is toxic, resulting in high blood calcium levels, nausea, and kidney damage, among other issues. But do not worry too much about getting Vitamin D toxicity from the sun, as the amount produced by this route is not enough to be toxic. There are more significant threats from sun overexposure to worry about than Vitamin D production (e.g., melanoma). Usually, these excessive levels of Vitamin D are achieved by taking too many dietary supplements. Vitamin D is being actively investigated for connections to diabetes, hypertension, cancer, and immune function.


Sources of Vitamin D

Vitamin D comes in two main forms, and each of these forms has different sources (Table 1). Vitamin D2 (a.k.a. ergocalciferol) is from plants exposed to sunlight, such as mushrooms, foods you can purchase that are fortified with plant-derived Vitamin D2, or dietary supplements. Plants contain a compound called ergosterol in their oils, which gets converted to Vitamin D2 when exposed to the ultraviolet B radiation from the sun. Vitamin D3 (a.k.a. cholecalciferol) comes from either animal products or can be produced directly in your skin. The skin contains a compound called 7-dehydrocholesterol, which forms Vitamin D3 when exposed to UVB radiation, similar to the plants.

Sources of Vitamin D

Vitamin D2
Mushrooms Plants
Fortified Foods
Dietary Supplements (Plant-based)

Vitamin D3
UV Sunlight Fish Oil
Eggs
Butter, Dairy (Animal-based)


Table 1. Sources of Vitamin D.

Vitamin D2 and D3 are absorbed into the bloodstream and metabolized in the liver via hydroxylation into the circulating form of Vitamin D, called calcifediol. This circulating calcifediol is actually the collective name of the two metabolized products of Vitamin D2 and Vitamin D3, 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively, and is also known as 25-hydroxycaolecalciferol, or 25(OH) Vitamin D. The main difference is that Vitamin D2 produces less calcifediol than Vitamin D3, so the animal- and sunlight-based sources of Vitamin D3 are better for circulating calcifediol than the plant- or supplement-based Vitamin D2. After hydroxylation in the liver, 25(OH) Vitamin D travels to the kidney, where it is converted to the active form of Vitamin D, also known as 1,25(OH)2Vitamin D or calcitriol (Figure 1). The active form has a shorter half-life than 25(OH) Vitamin D and is not used to measure Vitamin D levels in circulation. Enzo Life Sciences offers the 25(OH) Vitamin D ELISA kit to determine these levels in human plasma or serum.


Figure 1: Metabolism of Vitamin D2 and Vitamin D3 to an active form of Vitamin D.



Vitamin D and Disease

Several researchers have investigated whether Vitamin D levels are associated with disease states. Nayak and Ramnanansingh used the 25(OH) Vitamin D ELISA kit to determine if there are links between systolic blood pressure and type 2 diabetes mellitus (T2DM), and circulating Vitamin D1. They studied 76 subjects (24 males and 52 females) in Trinidad and measured Vitamin D in their plasma after an 8-10 hour fast. While they did not find any correlation between T2DM and Vitamin D levels in this particular population, they did find an unexpected association of higher Vitamin D levels with systolic blood pressure above 130mmHg.

Other diseases are also being investigated for associations with Vitamin D in attempts to determine a possible pathway to prevention or treatment. Multiple sclerosis is one of these diseases. Multiple sclerosis is a disease in which the body's own immune system targets the protective coating surrounding nerves in the brain and spinal cord. This protective coating is known as myelin; if the myelin coating is damaged, the rate at which the nerves fire and send signals is diminished. No cure currently exists for MS. Some symptoms of MS include vision problems, muscle weakness, impaired coordination, and cognitive impairments, with some more severe symptoms possible, including pain and paralysis. Many believe MS is an autoimmune disease, and researchers are investigating the role of Vitamin D due to its effects on the immune system and correlations between Vitamin D deficiency and MS.

Vitamin D affects different immune cell types, including monocytes, macrophages, dendritic cells, T cells, and B cells. In the monocytes, Vitamin D upregulates the expression of the Vitamin D receptor and cytochrome P450 proteins. Cytochrome P450 proteins are enzymes that enhance immune response and are important in chemical reactions such as hydroxylation, which is involved in the metabolism of Vitamin D to its active form. Single nucleotide polymorphisms of some cytochrome p450 genes, specifically CYP27B1 and CYP24A1, are associated with an increased risk of MS. In macrophages, which digest and remove foreign pathogens, Vitamin D induces proliferation and also increases Vitamin D receptor and CYP27B1. Vitamin D inhibits cell maturation and reduces expression of major histocompatibility complex (MHC) class II molecules that present antigen to T cells in dendritic cells, which are essential for the adaptive immune response. This inhibition of dendritic maturation is accompanied by stimulation of IL-10 and inhibition of pro-inflammatory cytokines such as TNF-alpha, IFN-gamma, and IL-12. In T cells, Vitamin D reduces IFN-gamma, which is vital in both innate and adaptive immune responses. Vitamin D also reduces the proliferation and cytotoxicity of CD4+ and CD8+ T cells. In the antibody-producing B cells, Vitamin D reduces cell proliferation and CYP24A1 expression. One hypothesis for MS's autoimmune cause is that T cells proliferate with Vitamin D deficiency. Eventually, T cells with receptors recognizing myelin enter the brain, causing inflammation that attacks central nervous system cells.

Like other autoimmune diseases like lupus, arthritis, Crohn's disease, and ulcerative colitis, the body would attack itself. Why the autoimmune response is localized to a particular type of cell or tissue remains unclear. Vitamin D levels seem to play only a part in the risk for MS, and other Vitamin D-dependent and -independent pathways and causes for MS are yet to be discovered. Until then, try to get some sun when you can (but not too much).


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References:

  1. Nayak Shivananda B. and Ramnanansingh TG. Evaluation of vitamin D relationship with type 2 diabetes and systolic blood pressure. BMJ Open Diabetes Res Care. 2016; 4(1); e000285.

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