Vitamin D

Vitamin D3 (Cholecalciferol). Source: Wikimedia Commons

Vitamin D is a fat-soluble vitamin that is found in food, and can also be made in the body after exposure to ultraviolet (UV) rays from the sun. It exists in several forms, each with a different level of activity. Calciferol (vitamin D3) is the most active form of vitamin D. Other forms are relatively inactive in the body. Active vitamin D functions as a hormone because it sends a message to the intestines to increase the absorption of calcium and phosphorus.

How Vitamin D Works

Vitamin D obtained from sun exposure, food, and supplements is biologically inert (inactive) and must undergo two chemical changes called hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol.

Sources

Few foods in nature provide vitamin D. The flesh of fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these foods is primarily in the form of vitamin D3 (cholecalciferol) and its metabolite 25(OH)D3. Some mushrooms provide vitamin D2 (ergocalciferol) in variable amounts.

Selected food sources of vitamin D

*DV = Daily Value. DVs are reference numbers developed by the Food and Drug Administration (FDA) to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for vitamin D is 400 IU (10 μg) for adults. Most food labels do not list vitamin D content unless a food has been fortified with this nutrient. The percent DV (%DV) listed on the table above is the percent of the DV provided in one serving. A food providing 5% of the DV or less is a low source while a food that provides 10-19% of the DV is a good source and a food that provides 20% or more of the DV is high in that nutrient. It is important to remember that foods that provide lower percentages of the DV also contribute to a healthful diet. For foods not listed in this table, refer to the U.S. Department of Agriculture's Nutrient Database Web site.

Sunlight

Sunlight is a significant source of vitamin D because UV rays from sunlight trigger vitamin D synthesis in the skin. The sun is perhaps the most important source of vitamin D, as exposure to sunlight provides most humans with their vitamin D requirement. Season, geographic latitude, time of day, cloud cover, smog, and sunscreen affect UV ray exposure and vitamin D synthesis. For example, sunlight exposure from November through February in Boston is insufficient to produce significant vitamin D synthesis in the skin. Complete cloud cover halves the energy of UV rays, and shade reduces it by 60%. Industrial pollution, which increases shade, also decreases sun exposure and may contribute to the development of rickets in people with insufficient dietary intake of vitamin D. Sunscreens with a sun protection factor (SPF) of 8 or greater will block UV rays that produce vitamin D, but it is still important to routinely use sunscreen to help prevent skin cancer and other negative consequences of excessive sun exposure. An initial exposure to sunlight (10-15 minutes) allows adequate time for vitamin D synthesis and should be followed by application of a sunscreen with an SPF of at least 15 to protect the skin. Ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen is usually sufficient to provide adequate vitamin D. It is very important for individuals with limited sun exposure to include good sources of vitamin D in their diet.

UV-B rays are responsible for vitamin D synthesis. These rays also cause sunburn, increase the production of melanin (which protects again sunburn), and stimulate the production of melanocyte-stimulating hormone. UV-B rays are greatest during midday hours and the vitamin D produced on the skin is absorbed into the body after it is made. For this reason, showering or swimming right after sun exposure may prevent the body from making vitamin D.^[1]

Fortified foods

Fortified foods are common sources of vitamin D. In the 1930s, rickets was a major public health problem in the United States. Rickets is caused by low blood calcium or vitamin D, and produces bones that are deformed and break easily. A milk fortification program was implemented to combat rickets, and it nearly eliminated this disorder in the U.S. About 98% to 99% of the milk supply in the U.S. is fortified with 10 micrograms (μg) (equal to 400 International Units or IU) of vitamin D per quart. One cup of vitamin D-fortified milk supplies one-half of the recommended daily intake for adults between the ages of 19 and 50, one-fourth of the recommended daily intake for adults between the ages of 51 and 70, and approximately 15% of the recommended daily intake for adults age 71 and over.

Although milk is fortified with vitamin D, dairy products made from milk, such as cheese and ice creams, are generally not fortified with vitamin D and contain only small amounts. Some ready-to-eat breakfast cereals may be fortified with vitamin D, often at a level of 10% to 15% of the Daily Value.

Supplements

In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol). Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol. The two forms have traditionally been regarded as equivalent based on their ability to cure rickets, but evidence has been offered that they are metabolized differently. Vitamin D3 could be more than three times as effective as vitamin D2 in raising serum 25(OH)D concentrations and maintaining those levels for a longer time, and its metabolites have superior affinity for vitamin D-binding proteins in plasma. Because metabolite receptor affinity is not a functional assessment, as the earlier results for the healing of rickets were, further research is needed on the comparative physiological effects of both forms. Many supplements are being reformulated to contain vitamin D3 instead of vitamin D2. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH)D levels.

Benefits

The major biologic function of vitamin D is to maintain normal blood levels of calcium and phosphorus. Vitamin D is essential for promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevent tetany (continuous muscle contraction) caused by low calcium. Vitamin D is also needed for bone growth and bone remodeling. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults. Together with calcium, vitamin D also helps protect older adults from osteoporosis.

Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D. Many laboratory-cultured human cells have vitamin D receptors and some convert 25(OH)D to 1,25(OH)2D. It remains to be determined whether cells with vitamin D receptors in the intact human carry out this conversion.

Recommended Daily Intake

Recommendations for vitamin D are provided in the Dietary Reference Intakes (DRIs) developed by the Institute of Medicine (IOM) of the National Academy of Sciences.

The IOM determined there was insufficient scientific information to establish an RDA for vitamin D. Instead, the recommended intake is listed as an Adequate Intake (AI), which represents the daily vitamin D intake that should maintain bone health and normal calcium metabolism in healthy people.

AIs for vitamin D may be listed on food and dietary supplement labels as either micrograms (μg) or International Units (IU). The biological activity of 1 μg vitamin D is equal to 40 IUs.

Adequate intake for vitamin D for infants, children, and adults

Vitamin D deficiency

According to the IOM's report on the Dietary Reference Intakes for vitamin D, median intakes of vitamin D for both younger and older women are below current recommendations. Median intake refers to a statistical mid-point. Half of the population surveyed consumed more than the median intake while half consumed less. In this case, data suggest that more than 50% of younger and older women are not consuming recommended amounts of vitamin D.

Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and utilization, increased requirement, or increased excretion (loss). A deficiency of vitamin D can occur:

• When usual intake is below recommended levels
• Where is limited exposure to sunlight
• When the kidney cannot convert vitamin D to its active hormone form
• When someone cannot adequately absorb vitamin D from the digestive tract

Vitamin D-deficient diets are more common in people with milk allergy, lactose intolerance, and strict vegetarianism.

Child with rickets. Source: Wikimedia Commons

The classic vitamin D deficiency diseases are rickets and osteomalacia. In children, vitamin D deficiency causes rickets. Rickets is a bone disease characterized by a failure to properly mineralize bone tissue. Rickets results in soft bones and skeletal deformities. Rickets was first described in the mid-17th century by British researchers. In the late 19th and early 20th century, German physicians noted that consuming 1 to 3 teaspoons (3 teaspoons is equal to 1 tablespoon) of cod liver oil per day could reverse rickets. The most common causes of rickets are vitamin D deficiency from a vitamin D-deficient diet, lack of sunlight, or both. The recommendation to fortify milk with vitamin D made rickets a rare disease in the U.S. for many years. However, rickets has recently reemerged in the US as well as Europe, in particular among dark-skinned infants and children. It is also on the rise around the world.^[2]

Prolonged exclusive breastfeeding without vitamin D supplementation, particularly in dark-skinned infants breastfed by mothers who are vitamin D deficient, can cause rickets. Additional causes include extensive use of sunscreens and increased use of day-care, resulting in decreased outdoor activity and sun exposure among children.

Rickets is more prevalent among immigrants from Asia, Africa, and Middle Eastern countries for a variety of reasons. Among immigrants, vitamin D deficiency has been associated with iron deficiency, leading researchers to question whether or not iron deficiency may impair vitamin D metabolism. Immigrants from these regions are also more likely to follow dress codes that limit sun exposure. In addition, darker skin converts UV rays to vitamin D less efficiently than lighter skin.

In adults, vitamin D deficiency can lead to osteomalacia, which results in muscular weakness in addition to weak bones. Symptoms of bone pain and muscle weakness may indicate vitamin D deficiency, but symptoms may be subtle and go undetected in the initial stages.

A deficiency is accurately diagnosed by measuring the concentration of a specific form of vitamin D in blood, 25-hydroxyvitamin D [25(OH)D]. Some experts (see New England Journal of Medicine letters to the editor, Volume 357:1980-1982, November 8, 2007) recommend screening of adults with routine measurement of this level at least once, but certainly it is called for with anyone in the high-risk groups for deficiency.

Diagnosing vitamin D deficiency

Serum concentration of 25-hydroxyvitamin D [25(OH)D] is the best indicator of vitamin D status. It reflects both vitamin D produced from the skin and that obtained from food and supplements and has a fairly long circulating half-life (15 days). However, serum 25(OH)D levels do not indicate the amount of vitamin D stored in other body tissues. Circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe.

There is considerable discussion of the serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and optimal overall health. A concentration of <20 nanograms per milliliter (ng/mL) (or <50 nanomoles per liter [nmol/L]) is generally considered inadequate.

Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health*

* Serum concentrations of 25(OH)D are reported in both nanograms per milliliter (ng/mL) and nanomoles per liter (nmol/L). ** 1 ng/mL = 2.5 nmol/L

Groups at risk

It can be difficult to obtain enough vitamin D from natural food sources. For many people, consuming vitamin D-fortified foods and adequate sunlight exposure are essential for maintaining a healthy vitamin D status. In some groups, dietary supplements may be needed to meet the daily need for vitamin D.

Infants

In infants, vitamin D requirements cannot be met by human (breast) milk alone, which usually provides approximately 25 IU vitamin D per liter. Sunlight is a potential source of vitamin D for infants, but the American Academy of Pediatrics (AAP) advises that infants be kept out of direct sunlight and wear protective clothing and sunscreen when exposed to sunlight. The American Academy of Pediatrics (AAP) recommends a daily supplement of 200 IU vitamin D for breastfed infants beginning within the first 2 months of life unless they are weaned to receive at least 500 ml (about 2 cups) per day of vitamin D-fortified formula. Children and adolescents who are not routinely exposed to sunlight and do not consume at least two 8-fluid ounce servings of vitamin D-fortified milk per day are also at higher risk of vitamin D deficiency and may need a dietary supplement containing 200 IU vitamin D.

Formula-fed infants usually consume recommended amounts of vitamin D because the 1980 Infant Formula Act requires that infant formulas be fortified with vitamin D. The minimal level of fortification required is 40 IU vitamin D per 100 calories of formula. The maximum level of vitamin D fortification allowed is 100 IU per 100 calories of formula. This range of fortification produces a standard 20 calorie per ounce formula providing between 265 and 660 IU vitamin D per liter.

Older adults

Americans age 50 and older are believed to be at increased risk of developing vitamin D deficiency. As people age, skin cannot synthesize vitamin D as efficiently and the kidney is less able to convert vitamin D to its active hormone form. It is estimated that as many as 30%–40% of older adults with hip fractures are vitamin D-insufficient. Therefore, older adults may benefit from supplemental vitamin D.

Persons with limited sun exposure

Homebound individuals, people living in northern latitudes such as in New England and Alaska, women who wear robes and head coverings for religious reasons, and individuals working in occupations that prevent sun exposure are unlikely to obtain much vitamin D from sunlight. It is important for people with limited sun exposure to consume recommended amounts of vitamin D in their diets or consider vitamin D supplementation.

Persons with greater skin melanin content

Melanin is the pigment that gives skin its color. Greater amounts of melanin result in darker skin. The high melanin content in darker skin reduces the skin's ability to produce vitamin D from sunlight. It is very important for African Americans and other populations with dark-pigmented skin to consume recommended amounts of vitamin D. Some studies suggest that older adults, especially women, in these groups are at even higher risk of vitamin D deficiency. Individuals with darkly pigmented skin who are unable to get adequate sun exposure and/or consume recommended amounts of vitamin D may benefit from a vitamin D supplement.

Persons with fat malabsorption

As a fat soluble vitamin, vitamin D requires some dietary fat for absorption. Individuals who have a reduced ability to absorb dietary fat may require vitamin D supplements. Symptoms of fat malabsorption include diarrhea and oily stools. Fat malabsorption is associated with a variety of medical conditions:

• Pancreatic enzyme deficiency: Pancreatic enzymes are essential for fat absorption, and a deficiency of these enzymes can result in fat malabsorption.
• Crohn disease is an inflammatory bowel disease that affects the small intestines. People with Crohn disease often experience diarrhea and fat malabsorption.
• Cystic fibrosis (CF) is a hereditary disorder that causes the body to secrete a thick, sticky mucus. This mucus clogs the pancreas and lungs. People with CF often experience fat malabsorption.
• Celiac disease is a genetic disorder. People with celiac disease are intolerant to a protein called gluten. In celiac disease, gluten can trigger damage to the small intestines, where most nutrient absorption occurs. People with celiac disease often experience fat malabsorption. They need to follow a gluten free diet to avoid malabsorption and other symptoms of celiac disease.
• Liver disease includes a wide variety of disorders that impair liver function. Some people with liver disease experience fat malabsorption.
• Surgical removal of part or all of the stomach or intestines can impair digestion and absorption of many nutrients. Fat malabsorption can occur after this type of surgery.

Too much vitamin D

Vitamin D toxicity can cause nausea, vomiting, poor appetite, constipation, weakness, and weight loss. It can also raise blood levels of calcium, causing mental status changes such as confusion. High blood levels of calcium also can cause heart rhythm abnormalities. Calcinosis, the deposition of calcium and phosphate in the body's soft tissues such as the kidney, can also be caused by vitamin D toxicity.

Sun exposure alone can not result in vitamin D toxicity as a steady state is reached between synthesis and destruction of Vitamin D. Dietary intake alone is unlikely to cause vitamin D toxicity, unless large amounts of cod liver oil are consumed. Vitamin D toxicity is much more likely to occur from high intakes of vitamin D in supplements. The Food and Nutrition Board of the Institute of Medicine has set the tolerable upper intake level (UL) for vitamin D at 25 μg (1,000 IU) for infants up to 12 months of age and 50 μg (2,000 IU) for children, adults, pregnant, and lactating women. Long term intakes above the UL increase the risk of adverse health effects.

Tolerable upper intake levels for vitamin D for infants, children, and adults

Several nutrition scientists recently challenged these ULs, first published in 1997. They pointed to newer clinical trials conducted in healthy adults that found no evidence of vitamin D toxicity at doses of less than 10,000 IU/day. Although vitamin D supplements above recommended levels given in clinical trials have not shown harm, most trials were not adequately designed to assess harm. Evidence is not sufficient to determine the potential risks of excess vitamin D in infants, children, and women of reproductive age.

Risks

Interactions

Vitamin D supplements have the potential to interact with several types of medications.

Steroids

Corticosteroid medications such as prednisone, often prescribed to reduce inflammation, can reduce calcium absorption and impair vitamin D metabolism. These effects can further contribute to the loss of bone and the development of osteoporosis associated with their long-term use.

Other medications

Both the weight-loss drug orlistat (Xenical and alli) and the cholesterol-lowering drug cholestyramine (Questran, LoCholest, and Prevalite) can reduce the absorption of vitamin D and other fat-soluble vitamins. Both phenobarbital and phenytoin (Dilantin), used to prevent and control epileptic seizures, increase the liver's breakdown of vitamin D to inactive compounds and reduce calcium absorption.

Research

In 1988-1994, as part of the third National Health and Nutrition Examination Survey (NHANES III), the frequency of use of some vitamin D-containing foods and supplements was examined in 1,546 non-Hispanic African American women and 1,426 non-Hispanic white women of reproductive age (15-49 years). In both groups, 25(OH)D levels were higher in the fall (after a summer of sun exposure) and when milk or fortified cereals were consumed more than three times per week. The prevalence of serum concentrations of 25(OH)D ≤15 ng/mL (≤37.5 nmol/L) was 10 times greater for the African American women (42.2%) than for the white women (4.2%).

The 2000-2004 NHANES provided the most recent data on the vitamin D nutritional status of the U.S. population. Generally, younger people had higher serum 25(OH)D levels than older people; males had higher levels than females; and non-Hispanic whites had higher levels than Mexican Americans, who in turn had higher levels than non-Hispanic blacks. Depending on the population group, 1%-9% had serum 25(OH)D levels <11 ng/mL (<27.5 nmol/L), 8%-36% had levels <20 ng/mL (<50 nmol/L), and the majority (50%-78%) had levels <30 ng/mL (<75 nmol/L). Among adults in the United Kingdom, nationally representative data collected between 1992 and 2001 found show that 5%-20% in most age groups on average had serum 25(OH)D levels <10 ng/ml (<25 nmol/L); the prevalence of deficiency was greater (range 20%-40%) for older people >65 years of age in residential care homes and among women >85 years. Among all adults, 20-60% had levels ≤20 ng/ml (≤50 nmol/L) and 90% had levels ≤32 ng/ml (≤80 nmol/L).

Controversy

Evidence that humans may be relatively deficient in vitamin D, that increased vitamin D levels may prevent or treat a wide variety of diseases, and that sunlight should not be studiously avoided runs counter to the public-health message to avoid sunlight that has been espoused for several decades by the dermatology community. Dermatologists hold that even small amounts of sunlight can raise the risk of the deadly skin cancer melanoma, but vitamin D advocates argue that this public-health message has been disastrous, and that the evidence that this action prevents melanoma is lacking.

The debate has led to the firing of at least one prominent researcher, Michael Holick, MD, PhD, from the Department of Dermatology at Boston University (he is still a professor of endocrinology there), after he wrote a book arguing that people should get 10 to 15 minutes of sunlight^[3] daily before applying sunscreen. Holick has suggested that many dermatology departments are biased because they receive funding from sunscreen companies.^[4]

Optimum concentrations

Optimal serum concentrations of 25(OH)D for bone and general health throughout life have not been established and are likely to vary at each stage of life, depending on the physiological measures selected. The three-fold range of cut points that have been proposed by various experts, from 16 to 48 ng/mL (40 to 120 nmol/L), reflect differences in the functional endpoints chosen (e.g., serum concentrations of parathyroid hormone or bone fractures), as well as differences in the analytical methods used. The numerous assays for 25(OH)D provide differing results. One reason for these issues of precision and variability is that no standard reference preparations or calibrating materials are available commercially to help reduce the variability of results between methods and laboratories. Efforts are underway to standardize the quantification of 25(OH)D to measure vitamin D status.

In March 2007, a group of vitamin D and nutrition researchers published a controversial and provocative editorial contending that the desirable concentration of 25(OH)D is ≥30 ng/mL (≥75 nmol/L). They noted that supplemental intakes of 400 IU/day of vitamin D increase 25(OH)D concentrations by only 2.8-4.8 ng/mL (7-12 nmol/L) and that daily intakes of approximately 1,700 IU are needed to raise these concentrations from 20 to 32 ng/mL (50 to 80 nmol/L).

Vitamin D and osteoporosis

It is estimated that over 25 million adults in the United States have, or are at risk of developing, osteoporosis. Osteoporosis is a disease characterized by fragile bones, and it significantly increases the risk of bone fractures. Osteoporosis is most often associated with inadequate calcium intake. However, a deficiency of vitamin D also contributes to osteoporosis by reducing calcium absorption. While rickets and osteomalacia are extreme examples of vitamin D deficiency, osteopororsis is an example of a long-term effect of vitamin D insufficiency. Adequate storage levels of vitamin D help keep bones strong and may help prevent osteoporosis in older adults, in non-ambulatory individuals (those who have difficulty walking and exercising), in post-menopausal women, and in individuals on chronic steroid therapy.

Researchers know that normal bone is constantly being remodeled, a process that describes the breakdown and rebuilding of bone. During menopause, the balance between these two systems changes, resulting in more bone being broken down or resorbed than rebuilt. Hormone therapy with sex hormones such as estrogen and progesterone may delay the onset of osteoporosis. However, some medical groups and professional societies such as the American College of Obstetricians and Gynecologists, The North American Menopause Society, and The American Society for Bone and Mineral Research recommend that postmenopausal women consider using other agents to slow or stop bone-resorption because of the potential adverse health effects of hormone therapy.

Vitamin D deficiency, which is often seen in post-menopausal women and older Americans, has been associated with greater incidence of hip fractures. In a review of women with osteoporosis hospitalized for hip fractures, 50 percent were found to have signs of vitamin D deficiency. Daily supplementation with 20 μg (800 IU) of vitamin D may reduce the risk of osteoporotic fractures in elderly populations with low blood levels of vitamin D. The Decalyos II study examined the effect of combined calcium and vitamin D supplementation in a group of elderly women who were able to walk indoors with a cane or walker. The women were studied for two years, and results suggested that such supplementation could reduce the risk of hip fractures in this population.

Vitamin D and cancer

Laboratory, animal, and epidemiologic evidence suggests that vitamin D may be protective against some cancers. Epidemiologic studies suggest that a higher dietary intake of calcium and vitamin D, and/or sunlight-induced vitamin D synthesis, correlates with lower incidence of cancer. In fact, for over 60 years researchers have observed an inverse association between sun exposure and cancer mortality. The inverse relationship between higher vitamin D levels in blood and lower cancer risk in humans is best documented for colon and colorectal cancers. Vitamin D emerged as a protective factor in a study of over 3,000 adults (96% of whom were men) who underwent a colonoscopy between 1994 and 1997 to look for polyps or lesions in the colon. About 10% of the group was found to have at least one advanced neoplastic (cancerous) lesion in the colon. There was a significantly lower risk of advanced cancerous lesions among those with the highest vitamin D intake.

Additional well-designed clinical trials need to be conducted to determine whether vitamin D deficiency increases cancer risk, or if an increased intake of vitamin D is protective against some cancers. Until such trials are conducted, it is premature to advise anyone to take vitamin D supplements for cancer prevention.

In 2007 in the American Journal of Clinical Nutrition, Lappe and coworkers published the first population-based, double-blind, randomised, placebo-controlled, interventional trial of cholecalciferol (vitamin D₃) taking internal cancer prevention as their principal secondary end point — breast, colon, lung, lymph, leukemia, myeloma, uterus, others — with fractures as their primary end point.^[5] They reported that 1100 IU of vitamin D (cholecalciferol) combined with 1500 mg of calcium per day administered for four years greatly reduced the risk for new cancers compared with placebo controls (p < 0.005). They also noted that the concentrations of serum 25-hydroxy-vitamin D (25[OH]D) levels, both pre-treatment and during treatment, independently predicted cancer risk. The treatment group achieved mean concentrations of serum 25-hydroxy-vitamin D (25[OH]D) of 96 nmol/L (38 ng/ml). Natural levels for people who live and work in the sun: ~125-175 nmol/L (~50-70 ng/ml).^[6]

Vitamin D and steroids

Corticosteroid medications such as prednisone are often prescribed to reduce inflammation from a variety of medical problems. These medicines may be essential for medical treatment, but they have potential side effects, including decreased calcium absorption. There is some evidence that steroids may also impair vitamin D metabolism, further contributing to the loss of bone and development of osteoporosis associated with long term use of steroid medications. One study demonstrated that patients who received 0.25 μg of active vitamin D and 1000 mg calcium per day in addition to corticosteroid therapy after a kidney transplant avoided rapid bone loss commonly associated with post-transplant therapy. For these reasons, individuals on chronic steroid therapy should consult with a qualified health care professional about the need to increase vitamin D intake through diet and/or dietary supplements.

Vitamin D and Alzheimer's disease

Alzheimer's disease is associated with an increased risk of hip fractures. This may be because many Alzheimer's patients are homebound, frequently sunlight deprived, and older. With aging, less vitamin D is converted to its active form. One study of women with Alzheimer's disease found that decreased bone mineral density was associated with a low intake of vitamin D and inadequate sunlight exposure. Physicians should evaluate the need for vitamin D supplementation as part of an overall treatment plan for adults with Alzheimer's disease.

Vitamin D and caffeine

High caffeine intake may accelerate bone loss. Caffeine may inhibit vitamin D receptors, thus limiting absorption of vitamin D and decreasing bone mineral density. A study found that elderly postmenopausal women who consumed more than 300 milligrams per day of caffeine (which is equivalent to approximately 18 oz of caffeinated coffee) lost more bone in the spine than women who consumed less than 300 milligrams per day. However, there is also evidence that increasing calcium intake (by, for example, adding milk to coffee) can counteract any potential adverse effect that caffeine may have on bone. More evidence is needed before health professionals can confidently advise adults to decrease caffeine intake as a means of preventing osteoporosis.

Vitamin D and heart disease

A 2008 Framingham Heart study published in Circulation reports a connection between vitamin D deficiency and cardiac disease. Further studies are needed to determine if correcting Vitamin D deficiency will prevent heart disease. ^[7]

History

Rickets was first described in the mid-17th century by British researchers. In the 1800s, both sunbathing and cod liver oil were reported as cures for rickets.

Experts

• Bess Dawson‑Hughes, MD: Tufts University

• Cedric F. Garland, DrPH: Moores Cancer Center, University of California, San Diego

• Edward Giovannucci MD, ScD: Harvard School of Public Health

• William B. Grant PhD: Former Senior Research Scientist, Atmospheric Sciences SRI International Jet Propulsion Laboratory NASA Langley Research Center Elected Fellow, Optical Society of America; Director, Sunlight, Nutrition, and Health Research Center

• Robert P. Heaney, MD: Creighton University Medical Center

• Michael Holick, MD, PhD: Boston University School of Medicine

• Bruce W. Hollis, PhD: Professor, Pediatrics Professor, Biochemistry and Molecular Biology Director, Pediatric Nutritional Sciences, Medical University of South Carolina

• Christel Lamberg‑Allardt, PhD: University of Helsinki, Finland

• Anthony W. Norman PhD: University of California Riverside

• Reinhold Vieth, PhD: University of Toronto

How vitamin D was discovered

Researcher Elmer McCollum, who also discovered vitamin A, conducted studies on cod liver oil to determine what other active substances it contained. He found that when the vitamin A component was destroyed, cod liver oil no longer cured night blindness, but still cured rickets. He published this finding in 1922.

Researchers later found that irradiation (or sunlight exposure) led to the production of vitamin D in animals.^[8]

References

1. ↑ Sullivan K. The Weston A. Price Foundation: Basic Nutrition: The Miracle of Vitamin D.
2. ↑ Pettifor JM. Vitamin D &/or calcium deficiency rickets in infants & children: a global perspective. Indian J Med Res. 2008 Mar;127(3):245-9. Abstract | PDF
3. ↑ Dreifus C. A conversation with Michael Holick: Shining a light on the health benefits of vitamin D. New York Times. January 28, 2003.
4. ↑ O'Neill B. 'They have vilified the sun - and me.' spiked-online.com. July 23, 2004.
5. ↑ Lappe,J.M.; Travers-Gustafson,D.; Davies,K.M.; Recker,R.R.; Heaney,R.P. (2007) Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J. Clin Nutr. 85(6):1586-1591. Full Text

   • Abstract: BACKGROUND: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking. OBJECTIVE: The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types. DESIGN: This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged >55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were randomly assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo. RESULTS: When analyzed by intention to treat, cancer incidence was lower in the Ca + D women than in the placebo control subjects (P < 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca + D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk. CONCLUSIONS: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00352170.

6. ↑ Vieth R. (2006) What is the optimal vitamin D status for health? Prog. Biophys. Mol. Biol. 92(1):26-32. Full Text

   • Abstract: The most objectively substantiated health-related reason for tanning is that it improves vitamin D status. The serum 25-hydroxyvitamin D concentration (25(OH)D) is the measure of vitamin D nutrition status. Human biology was probably optimized through natural selection for a sun-rich environment that maintained serum 25(OH)D higher than 100 nmol/L. These levels are now only prevalent in people who spend an above-average amount of time outdoors, with the sun high in the sky. The best-characterized criteria for vitamin D adequacy are based on randomized clinical trials that show fracture prevention and preservation of bone mineral density. Based upon these studies, 25(OH)D concentrations should exceed 75 nmol/L. This concentration is near the upper end of the 25(OH)D reference ("normal") range for populations living in temperate climates, or for people who practice sun-avoidance, or who wear head coverings. Officially mandated nutrition guidelines restrict vitamin D intake from fortified food and supplements to less than 25 mcg/day, a dose objectively shown to raise serum 25(OH)D in adults by about 25 nmol/L. The combined effect of current nutrition guidelines and current sun-avoidance advice is to ensure that adults who follow these recommendations will have 25(OH)D concentrations lower than 75 nmol/L. Therefore, advice to avoid UVB light should be accompanied by encouragement to supplement with vitamin D in an amount that will correct for the nutrient deficit that sun-avoidance will cause.

7. ↑ Wang T, Pencina M, Booth S, Jaques P, Ingelsson E, Lanier K. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008 Jan 29;117(4):503-11. Epub 2008 Jan 7. Abstract | PDF
8. ↑ National Academy of Sciences Web site. Unraveling the Enigma of Vitamin D.

External Links

USDA: National Nutrient Database for Standard Reference

National Institute of Health Office of Dietary Supplements: Dietary Supplement Fact Sheet: Vitamin D