Bottom Line: Adequate vitamin D intake is needed for prevention of osteoporosis. It should not be used to treat cancer.
Vitamin D is an essential vitamin that is found in foods such as fortified milk, cereals, egg yolks, and fish. It is also produced in the skin when the skin is exposed to sunlight. Its primary function in humans is to maintain adequate blood calcium and phosphorus levels by increasing the absorption of these minerals from the diet through the small intestine. When the intake of calcium from the diet is too low, vitamin D helps move calcium stores from the bones into the blood. Although scientists know that it is helpful to take vitamin D supplements when patients are deficient in this vitamin, it is not clear that taking extra vitamin D will provide any extra benefit. Because vitamin D facilitates the absorption of calcium from the intestine, women taking calcium supplements to prevent osteoporosis should get enough vitamin D in their diet.
To prevent cancer Very few clinical trials have tested this use. One population-based cohort study found that people with a lower vitamin D intake had a higher risk of colorectal cancer, while one pilot study found that vitamin D could slow the rising of PSA levels in men with recurrent prostate cancer. No other clinical trials have tested this use.
To prevent osteoporosis and bone fractures Several clinical trials and population studies show that adequate levels of vitamin D intake are needed to prevent osteoporosis and bone fractures.
To treat psoriasis This use is supported by clinical trials.
To treat scleroderma No scientific evidence supports this use.
To treat seasonal affective disorder (SAD) Clinical trial results are inconsistent regarding this use.
Prevention of osteoporosis and hip fractures: The ability of vitamin D intake in the diet to prevent hip fractures was studied in a population-cased cohort study. For 18 years, 72,337 postmenopausal women were asked about their diets and supplement use and they were followed to monitor falling and hip fractures. It was found that women who had a high vitamin D intake (>12.5 micrograms per day) were 37% less likely to have a hip fracture than women with low vitamin D intake (<3.5 micrograms per day). This is a very large study and its results are most likely valid.
Bone pain and muscle strength in prostate cancer: Vitamin D deficiency develops in a large percent of patients with advanced prostate cancer that has not responded to hormone therapy. A small clinical trial tested whether vitamin D supplements could reduce bone pain from metastases and increase muscle strength in 16 men with advanced prostate cancer. After three months, four men reported less pain (although they didn't reduce their usage of pain medications) and six men had improved muscle strength. These results are not very strong, although it may be that vitamin D supplements may only be helpful in prostate cancer patients who have a vitamin D deficiency.
Prostate cancer: In the body, vitamin D is processed to its active form, 1,25-dihydroxy vitamin D, also known as calcitriol. A small pilot study examined the ability of calcitriol to prevent progression of recurrent prostate cancer. Seven men were studied for 6 to 15 months, in which time they were given anywhere from 0.5 to 2.5 micrograms of calcitriol daily. (Maximum dose was limited by high levels of calcium in the blood and urine.) After treatment with calcitriol, six of the men had significantly reduced rate of rise of prostate specific antigen (PSA), which is an indicator of prostate cancer growth. These results are promising, but because this is only a pilot study, they need to be confirmed with a randomized controlled trial.
This product is regulated by the F.D.A. as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
Toxicity associated with long-term and high-dose use of vitamin D includes: excessive thirst, depression, headache, drowsiness, weakness, calcium and bone loss, hypercalcemia (abnormally high blood calcium levels) and calcification of the soft tissues in the kidney, heart, blood vessels, and lung.
Vitamin D refers to several forms of fat-soluble vitamins found naturally in plants, fish, and dairy products. The two forms utilized in humans are ergocalciferol (D2) and the more potent 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. It also important for bone formation and deficiency can cause rickets and other bone disorders. Other biologic functions include its role as a potent antiproliferative agent and as a pro-differentiation hormone (1)(2).
Vitamin D was shown to have a beneficial effect on bone mineral density and the prevention of bone fractures in the elderly (3)(4). However, conflicting data from the Women's Health Initiative studies found no such effects (5). Recent data show that calcium and vitamin D supplementation may reduce weight gain (6), but does not affect cardiovascular events (7), or reduce risk of invasive breast cancer (37) in postmenopausal women. In type 2 diabetic patients, a single, large dose of vitamin D2 improved endothelial function (8); however, vitamin D supplementation did not reduce infections or antibiotic use in an elderly population (9). Vitamin D is effective in treating psoriasis (10), but data are inconsistent regarding its role in seasonal affective disorder (SAD) (11)(12). Low levels of Vitamin D have been associated with greater risk of mortality (18).
Vitamin D has been examined for its benefits as a preventative agent and as a treatment for many types of cancer. Vitamin D from sunlight exposure and from dietary intake may have protective effect against breast cancer (13)(14). This correlates with observations in many breast cancer survivors who were vitamin D deficient (15).
In prostate cancer patients, higher serum levels of vitamin D were correlated with greater risk of aggressive cancer (16). Vitamin D improved pain and muscle strength in patients with advanced hormone-refractory prostate cancer (17), and slowed the rate of rise of prostate specific antigen (18). There are studies on using vitamin D and its analogs singly or with chemotherapy in prostate cancer patients (19)(20). Preliminary results suggest vitamin D did not increase toxicity of docetaxel (21)(22) and may offer other treatment benefits (23).
Although reduced risk of cancer has been associated with increased vitamin D intake (24)(25)(26), data from a large, prospective study showed that with the exception of colorectal cancer, vitamin D may not protect against other cancers (27). In postmenopausal women, vitamin D and calcium supplementation may reduce the incidence of colorectal cancer, but only in women who did not use estrogen therapy concurrently (28)(29). Oral vitamin D intake is generally safe but high doses can cause hypercalcemia (30).
Vitamin D's primary function in humans is to maintain serum calcium and phosphorus concentrations within normal limits by enhancing the efficiency of the small intestine to absorb these minerals from the diet. 1,25-dihydroxyvitamin D enhances the efficiency of calcium and phosphorus absorption along the entire small intestine, but primarily in the duodenum and jejunum (4). When the intake of calcium from the diet is insufficient, 1,25(OH)²D 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 (31). Vitamin D is thought to have physiological effects in other parts of the body as receptors are also found in the cells of other organs, like the intestine, kidney, stomach, brain, prostate, breast, and white blood cells (32)(2). The anticancer effect of vitamin D is thought to be due to the induction of cell differentiation (1)(33)and antiproliferation (34).
Absorption: Dietary vitamin D is well absorbed from the small intestine. Absorption occurs principally in the duodenum and jejunum, and bile salts are required for peak efficiency (4). Vitamin D is fat soluble and, once ingested, incorporated into the chylomicron fraction and absorbed via the lymph system. It has been estimated that approximately 80 percent of dietary vitamin D enters the body by this pathway. Distribution: Vitamin D enters the circulation from the skin or from the lymph system via the thoracic duct. It accumulates in the liver where it undergoes hydroxylation at the 25-carbon position and thereafter reappears in the circulation as 25-hydroxyvitamin D (25(OH)D). Its half-life in the circulation is approximately 10 days to 3 weeks. To become biologically active at physiological concentrations, 25(OH)D must be hydroxylated in the kidneys on the 1-carbon position to form 1,25-dihydroxyvitamin D (1,25(OH)D²), which has been described as a biologically active hormone and the form of vitamin D responsible for most, if not all, of its biological functions. 1,25(OH)²D has a relatively short serum half-life of approximately 4-6 hours. Due to the kidney's tight regulation of its production, and its short half-life, it is not a useful marker of vitamin D deficiency, adequacy, or excess. Metabolism/Excretion: Vitamin D is excreted primarily in the bile, but a small amount is reabsorbed in the small intestine (31).
High dose of vitamin D can cause hypercalcemia (30).
Rare: Dry mouth, metallic taste, nausea/vomiting, constipation, diarrhea. Toxicity associated with long-term and high-dose use includes: polydipsia, depression, headache, drowsiness, weakness, calcium and bone loss, hypercalcemia, and metastatic calcification of soft tissues in kidney, heart, blood vessels, and lung (35).
Pittas AG, Harris SS, Stark PC, et al. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes Care 2007 Apr;30(4):980-6. Epub 2007 Feb 2. Because studies have shown an inverse association between type 2 diabetes and high calcium and vitamin D intake, a double-blind, randomized, placebo-controlled trial was initiated to determine the effects of calcium (500 mg daily) and vitamin D (700 IU daily) supplementation in nondiabetic adults (65 years). After 3 years, fasting blood glucose, insulin sensitivity (as assessed by HOMA-IR), C-reactive protein, and IL-6 levels were determined in 314 participants. In adults with impaired fasting blood glucose, calcium and vitamin D reduced increases in plasma glucose and insulin resistance whereas no differences were detected in adults with normal fasting blood glucose levels. Further studies are required to determine if these effects are due to either supplement alone or the combination.
Caan B, Neuhoser M, Aragaki A, et al. Calcium plus vitamin D supplementation and the risk of postmenopausal weight gain. Arch Int Med 2007 May 14;167(9):893-902. In order to determine if calcium and vitamin D supplementation affected weight gain in postmenopausal women, the Women's Health Initiative recruited 36,282 women for this randomized, double-blind, placebo-controlled trial. Participants received calcium (1000 mg/day) and vitamin D (400 IU/day) or placebo and were followed for an average of 7 years. A modest reduction in weight gain was reported in participants receiving calcium and vitamin D supplementation, especially in those women who reported low initial calcium intake. Further studies are required to determine if these effects are due to calcium alone or its combination with vitamin D.
Jackson, RD, et al. Calcium plus Vitamin D supplementation and the risk of fractures. N Engl J Med 2006; 354(7): 669-83. Data obtained from the Women's Health Initiative study was analyzed to determine the efficacy of calcium and vitamin D supplementation for reducing hip fractures. The study involved 36,282 postmenopausal women who were randomized to receive 1000mg of calcium as calcium carbonate with 400 IU vitamin D3 daily or placebo for seven years. There was no significant reduction in hip fractures. But there was a small but significant improvement in hip bone density and an increased risk of kidney stones.
Wactawski-Wende J, et al. Calcium plus Vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 2006; 354(7):684-96. Data obtained from the Women's Health Initiative study was analyzed to determine the association of calcium and vitamin D supplementation with reduced risk of colorectal cancer. The study invovled 36,282 postmenopausal women who were randomly assigned to receive 500 mg calcium as calcium carbonate with 200 IU of vitamin D3 twice daily or a matching placebo for seven years. Results showed no effect of supplementation on the incidence of colorectal cancer.
These data conflict those of several earlier studies that associate increased calcium and vitamin D supplementation with reduced risk of cancer. Researchers point to the drawbacks of earlier studies since most were observational in nature and prone to bias. They also indicate the limitations of the present study that may have contributed to these findings. These include the timing of supplementation and the short follow-up period as colorectal cancer can be latent for 10-20 years. In addition, participants in the study were taking calcium and vitamin D supplements prior to enrollment. So the higher intake of supplements during the study period may have also affected the rates of colorectal cancer.
Feskanich D, et al. Calcium, vitamin D, milk consumption, and hip fractures: a prospective study among postmenopausal women. Am J Clin Nutr 2003;77:504-11. An eighteen year prospective analysis of 72,337 postmenopausal women. Dietary intake and nutritional supplement use were assessed at baseline and updated several times during follow-up. 603 hip fractures resulting from low or moderate trauma were identified. A 37% lower risk was associated with women consuming more than 12.5 micrograms per day of vitamin D versus those consuming less than 3.5 micrograms per day. Calcium levels did not correlate with any trend, nor did milk consumption. Given the large number of people in this study, a significant effect of vitamin D is shown therein.
