- Vitamin D
- Sunshine vitamin
For Patients & Caregivers
How It Works
Adequate vitamin D intake is needed for bone health and other important biologic functions. There are links between increased vitamin D intake and reduced risk of breast and colorectal cancers, but protection against other cancers remains unclear.
Vitamin D is an essential vitamin that is found in certain foods such as fortified milk and cereals, egg yolks, and fish. It is also produced in skin that is exposed to sunlight. Its primary function is to maintain adequate blood calcium and phosphorus levels by increasing absorption of these minerals from the diet through the small intestine. When dietary calcium intake is too low, vitamin D helps move calcium stores from the bones into the blood.
Vitamin D is also involved in many other biologic functions such as immune and hormone regulation, and has anti-cancer properties. Intake of vitamin D through diet may protect against breast or colorectal cancers or improve markers of prostate cancer. However, effects against other cancers remain unclear.
The Institute of Medicine recommends a higher Dietary Allowance of vitamin D at 600 IU/day with the Upper level Intake at 4,000 IU/day for bone health. Scientists know that it is helpful to take vitamin D supplements when patients are deficient in this vitamin, and certain populations including cancer patients can be especially prone to this deficiency. However, there is some debate about what level of supplementation is appropriate. Patients should consult with their physicians if more vitamin D is needed for health maintenance or to treat deficiency.
- To prevent or treat cancer
Intake of vitamin D through diet may protect against breast or colorectal cancers or affect markers for prostate cancer. However, vitamin D by itself does not prevent or treat cancer. Other large studies show that high vitamin D levels do not reduce the risk of many other cancers, and may increase risk for pancreatic or aggressive prostate cancer. More studies are needed to evaluate vitamin D in different populations.
- For immune regulation
Vitamin D contributes to hormone regulation and other processes involving immune function. In addition, a deficiency in this vitamin can be prevalent in certain populations, including those with cancer or autoimmune disorders. However, studies on effects of vitamin D supplementation on immune regulation are lacking.
- To prevent osteoporosis
Several clinical trials and population studies show that adequate levels of vitamin D intake are needed to prevent osteoporosis and bone fractures. In postmenopausal women and elderly populations, vitamin D supplementation may improve bone mineral density and help to prevent fractures.
- To prevent multiple sclerosis (MS)
A recent study involving a large number of women suggests that correcting vitamin D deficiency may reduce future risk of MS.
- To treat seasonal affective disorder (SAD)
Vitamin D supplementation does not appear to improve SAD.
Do Not Take If
- You take aluminum hydroxide: Vitamin D supplementation may increase the absorption and blood level of aluminum.
- You take atorvastatin: Vitamin D reduces blood levels of atorvastatin, but it also helps to lower cholesterol concentrations.
- You take thiazide diuretics: Vitamin D supplementation may increase serum calcium levels.
- Although rare, too much vitamin D can cause abnormally high levels of calcium in the blood or urine, or kidney stones.
- Patients with kidney stones, kidney disease, high blood calcium levels, gastrointestinal disease, heart disease, liver disease or other diseases associated with disorders of calcium metabolism should seek medical advice before taking supplemental vitamin D.
For Healthcare Professionals
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 improved 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). In another study, high-dose vitamin D had no benefit on lower extremity function, and was associated with increased risk of falls (64).
Results from studies evaluating its effect on cardiovascular (CV) risk factors have varied across populations and regimens: in a Women’s Health Initiative sub-study, calcium+vitamin D and hormone therapy had a greater effect than either intervention alone or placebo (67); but daily vitamin D did not appear to improve CV risk factors or physical function in a large long-term trial of older adults (68). Yet in another placebo-controlled trial, vitamin D supplementation benefitted diabetic patients with coronary artery disease who were vitamin D-deficient (69). In addition, a single large dose of vitamin D2 improved endothelial function in type-2 diabetic patients (11). In non-dialysis patients with chronic kidney disease, D3 was more effective than D2 in raising serum D levels (70).
Vitamin D supplementation did not decrease incidence or severity of upper respiratory tract infections (URTIs) in healthy adults (16) or prevent viral upper respiratory tract infections in children (71). It also did not reduce infections or antibiotic use in an elderly population (17), or improve seasonal affective disorder (SAD) (18) (19). Other studies suggest that D3 supplementation can reduce relapse risk in patients with Crohn’s disease (12), and that D3+calcium may reduce weight gain in postmenopausal women (10). A single oral high-dose of D3 significantly improved fatigue in healthy persons who were vitamin D-deficient (72).
A recent study provides evidence of increased risk for development of multiple sclerosis in women with vitamin D deficiency (74).
Vitamin D has been examined for its benefits as a preventive 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); and in women with grade 1 cervical intraepithelial neoplasia, long-term vitamin D supplementation resulted in regression and in improved metabolic status (66). However, in a large trial of healthy postmenopausal women with mean vitamin D levels above those of the US population, taking vitamin D3+calcium did not lower cancer risk after 4 years of supplementation (73). 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).
Increased vitamin D intake reduces the risk of colorectal cancer (29) (30) (31) (32) (33), but has no effect on colorectal adenomas (65). High circulating vitamin D levels may also not reduce the risk of non-Hodgkin lymphoma (34), ovarian (35), kidney (36), endometrial (37), skin (38), or esophageal and gastric (39) cancers, and may significantly increase risk of pancreatic (40) or aggressive prostate cancer (41). Other data reveal vitamin D deficiency was highly prevalent in advanced pancreatic cancer (42) and colorectal cancer patients (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.
Low vitamin D levels are associated with a greater risk of mortality (13) and may affect cardiovascular health (14), but a large study found no association between low vitamin D levels and cognitive function (15). However, vitamin D deficiency during pregnancy may affect the neurocognitive development of newborns (75). A vitamin D deficiency can also cause rickets or other bone disorders, and may be a risk factor for extraskeletal diseases (45). Deficiencies can be particularly prevalent with certain demographics including time of year or living in northern climates (9); in 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.
Mechanism of Action
The most biologically active metabolite of vitamin D is calcitriol, which regulates calcium and phosphate homeostasis (52).
In humans, the primary function of vitamin D is to maintain normal levels of serum calcium and phosphorus concentrations by enhancing small intestine dietary absorption efficiency of these minerals. 25-hydroxyvitamin D [25(OH)D] enhances the efficiency of calcium and phosphorus absorption along the entire small intestine, but primarily in the duodenum and jejunum (5). When dietary calcium intake is insufficient, 25(OH)D and parathyroid hormone (PTH) mobilize monocytic stem cells in the bone marrow to become mature osteoclasts. These osteoclasts mobilize calcium from the bones, thereby maintaining blood calcium levels (50). Vitamin D is thought to have physiological effects in other parts of the body as vitamin D receptors (VDRs) are also found in the cells of other organs, like the intestine, kidney, stomach, brain, prostate, breast, and white blood cells (2) (53).
The anticancer effect of vitamin D is thought to be due to induction of cell differentiation (1) (54) and antiproliferation (55). In lymphoma cells, interventional 25(OH)D3 to normalize levels (>30 ng/mL) resulted in significantly stronger antibody-dependent cell-mediated cytotoxicity, suggesting benefit in D-deficient individuals receiving chemotherapies such as rituximab that utilize this mechanism (27). In xenograft models of breast cancer, dietary D3 elevated circulating D levels and increased CYP27B1 expression in both tumor and intestines, suggesting it stimulates local calcitriol synthesis in the tumor microenvironment and promotes ensuing paracrine/autocrine actions that contribute to its anticancer activity (20). The upregulation of CYP27B1 expression by tumors was unique to D3 versus calcitriol in the same tissue (20). In other animal models, a positive feedback signaling loop between the serine-protein kinase ATM (ataxia telangiectasia mutated) and the VDR was identified as critical for cancer chemoprevention by vitamin D (56).
Calcitriol, the hormonally active form of vitamin D3, targets the vitamin D degrading enzyme CYP24A1, which is most abundant in the kidney, but also expressed in several other tissues (57). CYP24A1 overexpression in colon, ovary, breast, lung, and esophageal malignancies, likely leads to degradation of the locally available D3, impairing its antitumorigenic action in the tumor tissue (57).
Individuals with kidney stones, kidney disease, high blood calcium levels, gastrointestinal disease, heart disease, liver disease or other diseases associated with disorders of calcium metabolism should seek medical advice before taking supplemental vitamin D (9).
Life-threatening hypercalcemia: In two women resulting from intake of over-the-counter vitamin-D concentrated supplements that were 100 — 1,000 times higher than stated on the label (58). Hypercalcemic crisis: A 5-day history of worsening abdominal pain, nausea, and vomiting in a 30-year old woman who had been taking large quantities of vitamin D for an unknown period of time (59). Acute renal failure and hypervitaminosis A: In a 51-year old woman after consuming an over-the-counter vitamin D supplement, which also caused Vitamin A toxicity possibly caused by renal failure related to the hypercalcemia induced by vitamin D toxicity (60).