Vitamin D refers to several forms of fat-soluble vitamins found in fortified milk and cereals, egg yolks, and fish. The two forms utilized in humans are ergocalciferol (D2) and cholecalciferol (D3). Sunlight can promote the synthesis of D3 in the skin.
Vitamin D maintains serum calcium and phosphorus levels by regulating their absorption and excretion, and is important for bone formation. Other biologic functions include its role as an antiproliferative agent (1), and as a pro-differentiation hormone (2) with anti-inflammatory and immunoregulatory effects (3).
Vitamin D was shown to improve bone mineral density and fracture prevention in the elderly (4) (5) and in postmenopausal women (6). However, there are conflicting data for primary fracture prevention in men or women when combined with calcium supplements (7) (8) (9).
Data show that calcium and vitamin D supplementation may reduce weight gain in postmenopausal women (10). In type 2 diabetic patients, a single large dose of vitamin D2 improved endothelial function (11). Vitamin D3 supplementation reduced relapse risk in patients with Crohn's disease (12). Low vitamin D levels are associated with a greater risk of mortality (13) and may affect cardiovascular health (14). Another large study found no association between low vitamin D levels and cognitive function (15). Vitamin D supplementation did not decrease incidence or severity of upper respiratory tract infections (URTIs) in healthy adults (16) or reduce infections or antibiotic use in an elderly population (17). It also does not appear to improve seasonal affective disorder (SAD) (18) (19).
Vitamin D has been examined for its benefits as a preventative agent and as a treatment for many types of cancer. In animal models, dietary vitamin D3 demonstrates chemopreventive effects against breast cancer equivalent to those elicited by calcitriol without causing hypercalcemia (20).
In humans, vitamin D from sunlight exposure and dietary intake may have protective effects against breast cancer (21) (22), and correlates with observations in many breast cancer survivors who were vitamin D-deficient (23). In postmenopausal women who do not use estrogen therapy, vitamin D and calcium supplementation may reduce the incidence of colorectal cancer (24) (25). In men, vitamin D improved pain and muscle strength in patients with advanced hormone-refractory prostate cancer (26), and slowed the rate of rise of prostate specific antigen (13). In older patients with diffuse large B-cell lymphoma, vitamin D supplementation normalized deficient levels and enhanced rituximab efficacy (27). Active vitamin D compounds may also decrease the incidence of post-transplant malignancy among kidney transplant recipients (28).
Despite associations between increased vitamin D intake and reduced cancer risk (29) (30) (31), data from a large prospective study showed that with the exception of colorectal cancer (32), vitamin D may not protect against other cancers (33) (34). Similarly, data from the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) epidemiological studies do not support associations between high circulating vitamin D levels and reduced risk of non-Hodgkin lymphoma (35), ovarian (36), kidney (37), endometrial (38), or esophageal and gastric (39) cancers, but were associated with a significant increase in pancreatic cancer risk (40). Other data reveal no associations between vitamin D levels and skin cancer incidence (41) or survival for advanced pancreatic cancer patients (42). Another study found higher D levels correlated with greater risk of aggressive prostate cancer (43).
The most recent meta-analyses evaluating vitamin D supplementation for cancer prevention in adults indicates that although it decreased cancer mortality and all-cause mortality, these findings are at risk of error due to the small numbers of participants across studies and attrition bias (44). More studies are needed to evaluate its effects in different populations, such as patients with low vitamin D status, men, and younger adults, using longer treatment durations and higher dosages.
Vitamin D deficiency can cause rickets or other bone disorders, and may also be a risk factor for extraskeletal diseases (45). Deficiencies can also be prevalent in certain demographics including time of year or living in northern climates (9), non-Caucasian race (46), or obese individuals (47); with chronic use of steroids or anticonvulsants; or with diseases such as autoimmune disorders (3), cystic fibrosis (48), kidney disease, and cancer (46) (48) (49).
The Institute of Medicine generally recommends a Daily Dietary Allowance of vitamin D at 600 IU/day with the Upper Level Intake at 4,000 IU/day for bone health (50), but food sources are limited. Oral supplementation has been shown to be the safest way to increase vitamin D levels (51), although considerable debate continues on how this may translate in optimizing vitamin D status (45). Therefore, patients should consult with their physicians if a deficiency is suspected to assess whether more vitamin D is needed for health maintenance and to avoid side effects such as kidney stones or high levels of calcium in blood or urine.