Vitamin D is fat-soluble and the only vitamin whose active form (calcitrol) is a hormone. Its most important role is to maintain serum calcium and phosphorus levels within an acceptable range, which is critical for many body functions, including the normal development of bones and teeth, normal cell growth, and regulation of the immune and nervous systems. Low levels of vitamin D lead to osteomalacia, a mineralization deficit of the bones, associated with osteoporosis, osteoarthritis, rheumatoid arthritis, multiple sclerosis, diabetes, heart disease, and an overactive parathyroid.

The elderly, particularly those in northern climates and those who are housebound, are at significant risk for vitamin D deficiency. A 1998 study in the New England Journal of Medicine found vitamin D deficiency in 57% of a random group of 290 hospitalized patients over age 65. Studies support vitamin D supplementation for the prevention and treatment of osteoporosis in postmenopausal women. In a 1997 study by Tufts University, supplementation with calcium (500 mg) and vitamin D (700 IU/day) was provided to 176 men and 213 women over age 65. The results were a significant increase in bone mass and a 50% reduction in fracture rate after three years.

Vitamin D is involved in cell growth and maturation and has shown anticancer properties. In vitro studies have suggested that vitamin D inhibits growth of breast and prostate cancer cells. The Physicians' Health Study, published in 1996, found links between dietary vitamin D and a slightly decreased risk of prostate cancer. A 1996 epidemiological study in Sweden and the 1996 Harvard Nurses' Health Study found that dietary vitamin D decreased the risk of colorectal cancer.

Vitamin D is involved in regulating the immune system and is being considered as a therapy for autoimmune disorders and to suppress rejection of transplanted organs. Vitamin D analogs have successfully been used to treat the skin disorder psoriasis.

• Cod liver oil
• Salmon
• Tuna
• Fortified milk
• Oysters
• Mushrooms
• Fortified cereals
• Egg yolk

Few foods are natural sources. The primary source for humans has traditionally been sunlight. A fair-skinned person can receive adequate vitamin D through the skin with 20 to 30 cumulative minutes of daily sun exposure. A dark-skinned person may require three hours for a similar dose. Clouds, smog, clothing, sunscreen, and window glass all filter the ultraviolet light necessary for vitamin D3 to be synthesized by provitamin D in the skin. Latitude, time of day, and season of the year also impact synthesis.

There are three forms of vitamin D.

• D1: calciferol, found in some foods
• D2: ergocalciferol, the form most widely found in food and most commonly added to food and nutritional supplements
• D3: cholecalciferol, originates in the skin

All these forms of vitamin D are converted into calcitriol, the active form of the vitamin, in the liver and kidney

• Supplemental vitamin D is available in natural and synthetic forms.
• Fish liver oil is the common natural source and provides vitamin D2.
• Over-the counter preparations of vitamin D2 are available in 50 IU, 100 IU, 400 IU, 500 IU, 600 IU, and 1,000 IU dosage as soft gel capsules, tablets, and liquid.
• Prescription preparations of vitamins D2 and D3 are available in tablets from 400 IU to 50,000 IU.
• Synthetic dihydrotachysterol is a reduction product of a close isomer to vitamin D2, available by prescription.

• Protects against rickets, osteomalacia, osteoporosis, and osteopenia
• Protects against bone fractures in the elderly
• Recommended in the treatment of osteoporosis in postmenopausal women
• Recommended during fall and winter months for the elderly in northern climates and for those who do not receive daily exposure to direct sunlight
• Indicated for those with fat malabsorption disorders, including celiac disease, tropical sprue, cystic fibrosis, pancreatic disease, and short bowel syndrome
• Indicated for those on anticonvulsant drug therapy or glucocorticoid therapy
• Recommended for those on strict vegan diets
• Helps prevent some cancers by inhibiting the growth of human leukemia, colon cancer, skin cancer, and breast cancer cells
• Involved in the regulation of the immune system; may be indicated to treat autoimmune disorders and to suppress rejection of transplanted organs
• Plays a role in the secretion of insulin, thus aiding regulation of blood sugar
• Suppresses action of parathyroid hormone and may play a role in the treatment of an overactive parathyroid
• May reduce cartilage damage in osteoarthritis
• May decrease disease activity for rheumatoid arthritis
• May protect against multiple sclerosis
• May prevent diabetes mellitus
• May decrease the risk of arteriosclerosis
• May help prevent inflammatory bowel disease, tuberculosis, stroke, and high blood pressure

Adequate Daily Intake (AI)* is as follows.

• Infants and children: 5 mcg (200 IU)
• Adults up to age 50: 5 mcg (200 IU)
• Adults ages 51 to 70: 10 mcg (400 IU)
• Adults over age 70: 15 mcg (600 IU)

*AI reflects a level at which normal values and functional indicators of nutrition are maintained.

RDA:

• Infants up to 6 months: 7.5 mcg (300 IU)
• Children: 10 mcg (400 IU)
• Adults up to age 25: 10 mcg (400 IU)
• Adults age 25 and older: 5 mcg (200 IU)

High daily doses (more than 1,000 IU) of vitamin D can be toxic. The range between therapeutic and toxic doses is narrow. The major effect of toxicity is hypercalcemia, with symptoms of excessive thirst, metallic taste, bone pain, fatigue, sore eyes, itching skin, vomiting, diarrhea, urinary urgency, impaired muscle function, and cardiovascular and renal failure. Prolonged exposure to sunlight does not result in vitamin D toxicity.

Vitamin D should not be given to those with high blood calcium levels or high blood phosphorus levels. Vitamin D should be given with caution to those suffering from cardiac or kidney diseases.

Antacids that bind phosphate may alter the levels, metabolism, and availability of vitamin D. There is a case report of osteomalacia in a patient that consumed large amounts of antacids (Godsall et al. 1984). Aluminum-containing antacids may also increase the risk of fractures from osteomalacia resistant to the administration of vitamin D; this is of particular concern for people at risk for aluminum toxicity including newborns, elderly, and people with kidney or liver disease (Henning 1989).

The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), interacted synergistically with doxorubicin by increasing the cytotoxic activity of the drug against breast cancer cells in vitro (Ravid et al. 1999).

In one study, both total and free 1,25-(OH)2D concentrations increased in women within 5 years of menopause who were being treated with unopposed estrogen for three cycles (Bikle et al. 1992). With the addition of progestin, the levels of vitamin D returned toward baseline. Progestin may antagonize some of the beneficial effects of estrogen on calcium balance and bone metabolism; it is not clear if vitamin D supplementation will overcome this effect.

Thiazide diuretics enhance the biological activity of vitamin D and increase the risk of hypercalcemia (Hines Burnham et al 2000).

Verapamil may induce parathyroid hormone (PTH) resistance accompanied by a decrease in 1,25(OH)D3 levels (Fox 1988). Studies in rats have demonstrated that the negative correlation between PTH and vitamin D levels is significant. However, this interaction does not appear to have long-term effects on calcium homeostasis because of a dose-dependent increase in duodenal absorption of calcium.

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