Many people are aware of the importance of healthy vitamin D levels with regards to bone health. But vitamin D has many other important functions. In fact, just about every tissue and cell in your body has vitamin D receptors. Unfortunately, many people are deficient in vitamin D. Others fall within the recommended lab reference range, but while most of the research still suggests that optimal levels should be above 30 ng/mL, some sources, including the vitamin D Council, suggest for these levels to be greater than 50 ng/mL.
I’d like to start out by discussing the mechanism of action of vitamin D. This can get pretty complex, and so I’m just going to cover the basics. Although vitamin D is referred to as a vitamin, the active form is actually a prohormone, and this is produced in the skin through the ultraviolet irradiation of 7-dehydrocholesterol, which is a cholesterol precursor. So 7-dehydrocholesterol is converted into vitamin D3 (also known as cholecalciferol) in the skin. However, vitamin D3 is biologically inert, and it needs to be metabolized to 25-hydroxy vitamin D3 in the liver, and then it gets metabolized to 1, 25 hydroxy vitamin D3 (also known as calcitriol) in the kidneys by the enzyme CYP27B1, although other tissues have this enzyme as well.
More Facts About Vitamin D
Vitamin D and its metabolites are carried in the blood mostly bound to vitamin D binding protein (DBP) (1). So what happens is that after cholecalciferol (vitamin D3) is manufactured or taken as a supplement, it binds to DBP, and after it gets converted into calcitriol, this also is carried through the blood by DBP before binding to the vitamin D receptor.
Vitamin D increases the intestinal absorption of calcium and phosphorus, which in turn promotes bone mineralization and remodeling, and it is also involved in regulating serum calcium and phosphorus levels. This is the main reason why most medical doctors test for Vitamin D, as they are concerned about low levels affecting bone mineral density. However, vitamin D has numerous other functions, as it also plays a role in neuromuscular function and influences cellular growth and differentiation. It also plays a big role in immunity, which of course is important for those with autoimmune thyroid conditions such as Graves’ Disease and Hashimoto’s Thyroiditis. I’ll talk more about this later.
What’s The Difference Between Vitamin D2 and D3?
Supplemental vitamin D comes in two primary forms. When someone purchases vitamin D in a health food store they are usually getting cholecalciferol, which is also known as vitamin D3. On the other hand, when a medical doctor writes a prescription it is for ergocalciferol, which is known as vitamin D2. Even though some sources claim that these two are equivalent, vitamin D3 has been proven to be the more potent form of vitamin D in all primate species, including humans (2). In addition to vitamin D3 being more effective than vitamin D3, there is diminished binding of vitamin D2 metabolites to vitamin D binding protein in the plasma, a nonphysiologic metabolism, and a shorter shelf life of vitamin D2 (2).
Vitamin D and The Research
What I’d like to do now is discuss some of the research involving vitamin D, including numerous conditions which are affected by a vitamin D deficiency.
Vitamin D in dementia and cognition. A few studies show that a vitamin D deficiency can increase one’s risk of dementia, and even Alzheimer’s disease (3) (4) (5). Vitamin D receptors are abundant in the tissues of the brain, and the active form of vitamin D has neuroprotective effects which include the clearance of amyloid plaques, which is a hallmark of Alzheimer’s disease (6).
Inflammation/autoimmunity. There are also numerous studies which show that vitamin D plays an important role in modulating the immune system and inflammation (7) (8) (9). It appears to do this by decreasing pro-inflammatory cytokines, and is also associated with higher regulatory T cells (10) (11), which help to suppress autoimmunity. However, some sources question whether a vitamin D deficiency is a cause of inflammation, or if it is a consequence of the inflammatory process (12) (13).
High Blood Pressure/Cardiovascular disease. Numerous studies show that vitamin D might have antihypertensive effects in those people with essential hypertension, which in turn can help to prevent the development of a stroke (14) (15). There is also evidence that a vitamin D deficiency can be a risk for the development of peripheral arterial disease (16) (17). Although there is some evidence linking a vitamin D deficiency to atherosclerosis (18), other studies suggest that more research is needed in this area (19).
Osteoporosis. One of the main functions of the active form of vitamin D is to enhance the intestinal absorption of calcium. And this is why healthy vitamin D levels are important for healthy bone mineral density (20) (21).
Gut microbiota/Intestinal mucosal barrier. There is evidence that vitamin D may play an important role in gut homeostasis and in the signaling between the microbiota and the host (22). In addition, the vitamin D receptor appears to play a critical role in homeostasis of the intestinal mucosal barrier by preserving the integrity of the junction complexes (23).
Cancer. Since vitamin D is important for optimal immune system health then it shouldn’t be surprising that some studies show that intake or synthesis of vitamin D leads to the reduced incidence and death rates of colon, breast, prostate, and ovarian cancers (24) (25) (26) (27).
Thyroid Health. Numerous studies show a correlation between vitamin D deficiency and autoimmune thyroid disease. A few studies have shown that low levels of vitamin D is associated with the presence of antithyroid antibodies and abnormal thyroid function (28) (29). Both people with Hashimoto’s Thyroiditis and Graves’ Disease commonly have low levels of vitamin D (30) (31) (32). This doesn’t mean that a vitamin D deficiency is the cause of these conditions, although having such a deficiency might make someone more susceptible to developing thyroid autoimmunity.
Autism. There is evidence that healthy levels of vitamin D might reduce the risk of autism (33). In addition, supplementation of vitamin D (in those who are deficient) may significantly improve the outcome of some children with Autism Spectrum Disorder through its anti-inflammatory actions, antiautoimmune effects, increasing regulatory T cells, protecting the mitochondria, and upregulating glutathione (33) (34) (35).
Infections. Since healthy vitamin D levels are necessary for a healthy immune system, it makes sense that a vitamin D deficiency can increase one’s risk of developing infections. There is some evidence that it can reduce the incidence of influenza (the flu), and one study suggests keeping the levels around 50 ng/mL to prevent infection (36) (37) (38).
In the next blog post I will start out by talking about why many people are deficient in vitamin D. I will also talk about how to test the vitamin D levels, as while most healthcare professionals test for 25-OH vitamin D, since 1,25-OH vitamin D is the active form, I’m sure that some people reading this are wondering if this should be tested. I will also discuss three ways to increase vitamin D levels.