The role of vitamin D in autoimmunity and mood

Vitamin D is known as the “sunshine vitamin” because it is generated within the skin upon exposure to ultraviolet B (UVB) rays, the rays responsible for suntans.[1] Vitamin D is essential for strong bones, immunity, and many other bodily functions.[2],[3],[4] In the absence of sun exposure, however, it is necessary to obtain vitamin D solely from the diet and supplementation.

Many variables affect sun exposure and therefore influence vitamin D levels in the body: the latitude at which one resides, the season (winter vs. summer), time of day, cloud cover, air pollution (which filters out UVB), skin melanin content (which absorbs UVB), age, and sunscreen use (which blocks UVB).[1],[5],[6],[7] Public health organizations recommend the use of sunscreen, because prolonged sun exposure damages the skin and increases the risk for skin cancer. Unfortunately, the use of sunscreen also inhibits vitamin D synthesis.[3]

Diet is considered a relatively unreliable source of vitamin D because vitamin D is found naturally in only a few foods, namely dairy products, eggs, fish, and cod liver oil. Some foods (milk, various brands of cereal, yogurt, and orange juice) are fortified with vitamin D, but the levels are not enough to prevent deficiency.[8],[9],[10],[11],[12]

Insufficient vitamin D causes a decrease in bone mineral density as we age, which increases the risk of osteoporosis, falling, and bone fractures in the elderly.[13] Vitamin D insufficiency is also associated with diabetes, heart disease, respiratory infections, and some cancers.[11],[14],[15],[16] Compelling evidence suggests that vitamin D insufficiency also plays a role in mood disturbances and autoimmune diseases, as discussed below.

How does vitamin D influence mood?

Vitamin D’s reputation as the sunshine vitamin is well deserved for another reason: vitamin D influences mood.[17],[18],[19],[20] The well-known phenomenon of seasonal depression may be due in part to lower vitamin D levels in winter, especially in Northern climates.[21],[22]

“Effective detection and treatment of inadequate vitamin D levels in persons with depression and other mental disorders may be an easy and cost-effective therapy which could improve patients’ long-term health outcomes as well as their quality of life.”

In placebo-controlled clinical trials, supplementation with vitamin D significantly improved mood in various groups: overweight and obese individuals,[18] women with type 2 diabetes,[23] older adults,[24] individuals with osteoarthritis,[25] and adolescents experiencing depression.[26] Scientists studying the connection between vitamin D and mood discovered that the vitamin helps regulate dopamine transport in the so-called “reward center” of the brain, a region closely linked to our ability to feel pleasure.[27]

One research group states: “Effective detection and treatment of inadequate vitamin D levels in persons with depression and other mental disorders may be an easy and cost-effective therapy which could improve patients’ long-term health outcomes as well as their quality of life.”[23]

How does vitamin D influence autoimmunity?

More than 100 human diseases are classified as autoimmune conditions, in which the immune system attacks the body’s own healthy cells and tissues.[28] Autoimmune diseases are caused by genetic, environmental, and hormonal factors, and vitamin D is thought to be the environmental factor that most strongly influences autoimmune disease development.[29],[30],[31] Supplementation to correct low vitamin D levels may significantly benefit individuals with autoimmune conditions.  For example:

Multiple Sclerosis. In multiple sclerosis (MS), the immune system attacks the protective myelin sheath that coats nerve fibers, causing inflammation that disrupts communication between the brain and the rest of the body. Low levels of vitamin D are associated with disease progression and disability.[32],[33]

“Given the prominent reduction in the quarterly relapse rate in late winter/early spring, our data indicate a beneficial effect of supplementing MS patients with vitamin D.”

One key study showed that supplementation with vitamin D (18,950 IU per week, equivalent to about 2700 IU per day) eliminated seasonal variation in vitamin D levels, and cut the relapse rate in half.[34] The authors wrote, “Given the prominent reduction in the quarterly relapse rate in late winter/early spring, our data indicate a beneficial effect of supplementing MS patients with vitamin D, especially during this period of the year.”[34]

Rheumatoid Arthritis. Up to 80% of all patients with rheumatoid arthritis (RA) have insufficient vitamin D levels,[35],[36],[37] and a meta-analysis of studies involving 215,757 participants suggests that low vitamin D intake is associated with an elevated risk of RA development.[38] Furthermore, individuals with the highest total vitamin D intakes had a less severe disease course than those with lower intakes.[38],[39],[40],[41] The authors of a 2018 study conclude: “Vitamin D deficiency is associated with the clinical activity of the disease. The quantification of serum 25 (OH) D levels and, consequently, vitamin D supplementation, should be considered in the management of patients with RA.”[41]

“The quantification of serum 25 (OH) D levels and, consequently, vitamin D supplementation, should be considered in the management of patients with RA.”

Diabetes.The incidence of diabetes mellitus (type 1 diabetes, or T1D) peaks in the winter and spring, coinciding with low seasonal levels of vitamin D.[42] In Finland, which has one of the highest rates of T1D in the world, supplementation with vitamin D during the first year of life is associated with a lower risk of T1D.[3],[43] The benefits of vitamin D are most apparent if supplementation is initiated in the earliest phases of the disease, rather than at later stages.[31],[44]

“Advising patients with higher HbA1c to test their vitamin D level and correct any deficiency will result in better blood glucose control and benefit the patient’s overall health.”

Type 2 diabetes (T2D) is characterized by insulin resistance and an inadequate compensatory insulin secretion. Vitamin D supplementation was shown to reduce blood levels of hemoglobin A1c (HbA1c), a marker of diabetes, in vitamin D-deficient patients with T2D and/or prediabetes.[45],[46],[47],[48] The authors of a recent meta-analysis of controlled clinical trials, representing more than 3,800 participants, concluded: “Advising patients with higher HbA1c to test their vitamin D level and correct any deficiency will result in better blood glucose control and benefit the patient’s overall health.”[47]

New research also suggests that supplementation with vitamin D prior to pregnancy may help lower the risk of gestational diabetes mellitus (GDM) in pregnant women.[49] The authors concluded, “Pre-pregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.”[49]

How much vitamin D do we need?

The only way to assure you are getting enough vitamin D is to have your blood tested for the 25-hydroxy form of the vitamin, or 25(OH)D. One frequently asked question is, “What 25(OH)D level should I have?” There is considerable controversy on the subject, briefly summarized here:

  • The Institute of Medicine (IOM) guidelines, used by many laboratories for analyzing test results, classify blood 25(OH)D levels as follows: < 30 nmol/L as “deficient”; 30–50 nmol/L as “insufficient”; and 50–75 nmol/L as “sufficient.”[50]
  • However, many experts believe the IOM recommendations for 25(OH)D are too low. They argue that the level indicating sufficiency should be 75 nmol/L (30 ng/mL) or higher.[6],[9],[51],[52],[53],[54],[55]
  • The average 25(OH)D concentration in the Maasai people, who live a pastoral lifestyle in East Africa, is about 115 nmol/L (46 ng/mL).[56] This may be the “natural” 25(OH)D level experienced by our Paleolithic ancestors, who lived near the equator and wore minimal clothing.

Individuals with limited sun exposure will likely need to take a vitamin D supplement to meet their needs.[57] The recommended dietary allowance (RDA) is 600 IU of vitamin D per day for adults up to age 70, and 800 IU daily thereafter.[54] However, 800 IU per day is not sufficient to correct pre-existing vitamin D deficiencies.[58],[59],[60]

To reach a 25(OH)D blood level of at least 75 nmol/L (30 ng/mL) – the level advised by many experts, as discussed above – requires at least 1,000–2,000 IU per day of supplemental vitamin D, or even more in some individuals.[61],[62],[63],[64],[65],[66],[67] Supplemental vitamin D doses up to 4,000 IU per day are considered safe for adults.[54]

The form of vitamin D is also important: the studies cited herein mainly utilized vitamin D3 (cholecalciferol), which is superior to vitamin D2 (ergocalciferol). Cholecalciferol raises blood levels more effectively and is more active biologically than ergocalciferol.[68]

In sum, supplementation to correct vitamin D deficiency can help reduce age-related bone loss, prevent seasonal mood fluctuations, and support better health in individuals with autoimmune conditions. So for optimal health, consider having your blood tested for vitamin D, and grab a little sunshine – whether from the sun or from a bottle!

 

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