recommended levels of this key vitamin in a completely vegetarian form. Vitamin D is normally obtained from the diet or produced by the skin from the ultraviolet energy of the sun. However, it is not abundant in food. As more people avoid sun exposure, Vitamin D supplementation becomes even more necessary to ensure that your body receives an adequate supply.
Vitamin D2 (as Ergocalciferol) 1,000 IU

Sun exposure
Most people meet their vitamin D needs through exposure to sunlight [5,31]. Ultraviolet (UV) B radiation with a wavelength of 290-315 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3 [9,32,33]. Season, geographic latitude, time of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis [33]. The UV energy above 42 degrees north latitude (a line approximately between the northern border of California and Boston) is insufficient for cutaneous vitamin D synthesis from November through February [5]; in far northern latitudes, this reduced intensity lasts for up to 6 months. In the United States, latitudes below 34 degrees north (a line between Los Angeles and Columbia, South Carolina) allow for cutaneous production of vitamin D throughout the year [27].

Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60% [34]. UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D [35]. Sunscreens with a sun protection factor of 8 or more appear to block vitamin D-producing UV rays, although in practice people generally do not apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly [36]. Skin likely synthesizes some vitamin D even when it is protected by sunscreen as typically applied.

The factors that affect UV radiation exposure and research to date on the amount of sun exposure needed to maintain adequate vitamin D levels make it difficult to provide general guidelines. It has been suggested by some vitamin D researchers, for example, that approximately 5-30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen usually lead to sufficient vitamin D synthesis and that the moderate use of commercial tanning beds that emit 2%-6% UVB radiation is also effective [10,33]. Individuals with limited sun exposure need to include good sources of vitamin D in their diet or take a supplement.

Despite the importance of the sun to vitamin D synthesis, it is prudent to limit exposure of skin to sunlight [36] and UV radiation from tanning beds [37]. UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000 deaths due to metastatic melanoma that occur annually in the United States [36]. Lifetime cumulative UV damage to skin is also largely responsible for some age-associated dryness and other cosmetic changes. It is not known whether a desirable level of regular sun exposure exists that imposes no (or minimal) risk of skin cancer over time. The American Academy of Dermatology advises that photoprotective measures be taken, including the use of sunscreen, whenever one is exposed to the sun [38].

Dietary 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 [10]. 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 [5,39,40]. 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 [40]. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH)D levels [5].
Vitamin D Intakes and Status
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) [41]. 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 provides 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) [42].

In NHANES 2000-2004, age-adjusted mean serum 25(OH)D concentrations were 2-8 ng/mL (5-20 nmol/L) lower compared to NHANES III [43]. However, after adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 2.0-3.6 ng/mL (5-9 nmol/L)) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of assay differences changed mean serum 25(OH)D concentrations by ~4 ng/mL (~10 nmol/L), and adjustment for changes in the factors likely related to real changes in vitamin D status (such as body mass index (BMI), milk intake, and sun protection) changed mean serum 25(OH)D concentrations by 0.4-0.64 ng/mL (1.0-1.6 nmol/L).

Subsequent to this report, another investigator [44] evaluated vitamin D levels measured in NHANES 2001-2004 compared to NHANES III and reported a marked decline, leading some to suggest that the majority of children and adults in the United States (and almost all African Americans and Mexican Americans) are vitamin D insufficient. However, this analysis exaggerates the temporal and demographic trends in vitamin D status because it uses a higher than usual cutoff to characterize vitamin D insufficiency, does not separate the independent effects of season and latitude in data and, most seriously, fails to compensate for a change in the 25(OH)D measurement assay used between both sets of NHANES surveys [45]. Over time, mean serum 25(OH)D concentrations in the United States have declined, but only modestly, when compensating for the assay change [43]. The real decline (~2.0-3.6 ng/mL (~5-9 nmol/L)) is likely due to simultaneous increases in BMI, reduced milk intake, and greater use of sun protection in the U.S. population.

According to NHANES data from 2005-2006, only 29% of adult men and 17% of adult women (ages 19 and older) had intakes of vitamin D from food alone that exceeded their AIs. Overall in the U.S. population, only about one-third of individuals 1 year of age and older had vitamin D intakes from food exceeding their respective AIs [46]. However, dietary supplements as well as foods contribute vitamin D, so both sources must be included to obtain a true picture of total intakes. In 2005-2006, 37% of people in the United States reported the use of a dietary supplement containing vitamin D. Total intake estimates of vitamin D from both food and supplements are currently being tabulated by the Office of Dietary Supplements.
Vitamin D Deficiency
Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is limited, the kidneys cannot convert vitamin D to its active form, or absorption of vitamin D from the digestive tract is inadequate. Vitamin D-deficient diets are associated with milk allergy, lactose intolerance, and strict vegetarianism [47].

Rickets and osteomalacia are the classical vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, a disease characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities [34]. Rickets was first described in the mid-17th century by British researchers [34,48]. In the late 19th and early 20th centuries, German physicians noted that consuming 1-3 teaspoons of cod liver oil per day could reverse rickets [48]. In the 1920s and prior to identification of the structure of vitamin D and its metabolites, biochemist Harry Steenbock patented a process to impart antirachitic activity to foods [27]. The process involved the addition of what turned out to be precursor forms of vitamin D followed by exposure to UV radiation. The fortification of milk with vitamin D has made rickets a rare disease in the United States. However, rickets is still reported periodically, particularly among African American infants and children [34,48]. A 2003 report from Memphis, for example, described 21 cases of rickets among infants, 20 of whom were African American [48].

Prolonged exclusive breastfeeding without the AAP-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete [6]. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure [34,48]. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure [34].

In adults, vitamin D deficiency can lead to osteomalacia, resulting in weak muscles and bones [6,7,11]. Symptoms of bone pain and muscle weakness can indicate inadequate vitamin D levels, but such symptoms can be subtle and go undetected in the initial stages.
Groups at Risk of Vitamin D Inadequacy
Obtaining sufficient vitamin D from natural food sources alone can be difficult. For many people, consuming vitamin D-fortified foods and being exposed to sunlight are essential for maintaining a healthy vitamin D status. In some groups, dietary supplements might be required to meet the daily need for vitamin D.

Breastfed infants
Vitamin D requirements cannot be met by human milk alone [4,49], which provides only about 25 IU/L [50]. A recent review of reports of nutritional rickets found that a majority of cases occurred among young, breastfed African Americans [51]. The sun is a potential source of vitamin D, but AAP advises keeping infants out of direct sunlight and having them wear protective clothing and sunscreen [52]. As noted earlier, AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of vitamin D per day [20].

Older adults
Americans aged 50 and older are at increased risk of developing vitamin D insufficiency [33]. 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 [4,53]. As many as half of older adults in the United States with hip fractures could have serum 25(OH)D levels <12 ng/mL (<30 nmol/L) [5].

People with limited sun exposure
Homebound individuals, people living in northern latitudes (such as New England and Alaska), women who wear long robes and head coverings for religious reasons, and people with occupations that prevent sun exposure are unlikely to obtain adequate vitamin D from sunlight [54,55].

People with dark skin
Greater amounts of the pigment melanin result in darker skin and reduce the skin's ability to produce vitamin D from exposure to sunlight. Some studies suggest that older adults, especially women, with darker skin are at high risk of developing vitamin D insufficiency [41,56]. However, one group with dark skin, African Americans, generally has lower levels of 25(OH)D yet develops fewer osteoporotic fractures than Caucasians (see section below on osteoporosis).

People with fat malabsorption
As a fat-soluble vitamin, vitamin D requires some dietary fat in the gut for absorption. Individuals who have a reduced ability to absorb dietary fat might require vitamin D supplements [57]. Fat malabsorption is associated with a variety of medical conditions including some forms of liver disease, cystic fibrosis, and Crohn's disease [27].

People who are obese or who have undergone gastric bypass surgery
Individuals with a BMI =30 typically have a low plasma concentration of 25(OH)D [58]; this level decreases as obesity and body fat increase [59]. Obesity does not affect skin's capacity to synthesize vitamin D, but greater amounts of subcutaneous fat sequester more of the vitamin and alter its release into the circulation. Even with orally administered vitamin D, BMI is inversely correlated with peak serum concentrations, probably because some vitamin D is sequestered in the larger pools of body fat [58]. Obese individuals who have undergone gastric bypass surgery may become vitamin D deficient without a sufficient intake of this nutrient from food or supplements, since part of the upper small intestine where vitamin D is absorbed is bypassed [60,61].
Vitamin D and Health
Optimal serum concentrations of 25(OH)D for bone and general health throughout life have not been established [5,10] 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.

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) [12]. 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).

Osteoporosis
More than 25 million adults in the United States have or are at risk of developing osteoporosis, a disease characterized by fragile bones that significantly increases the risk of bone fractures [62]. Osteoporosis is most often associated with inadequate calcium intakes (generally <1,000-1,200 mg/day), but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption [63]. Although rickets and osteomalacia are extreme examples of the effects of vitamin D deficiency, osteoporosis is an example of a long-term effect of calcium and vitamin D insufficiency [64]. Adequate storage levels of vitamin D maintain bone strength and might help prevent osteoporosis in older adults, nonambulatory individuals who have difficulty exercising, postmenopausal women, and individuals on chronic steroid therapy [65].

Normal bone is constantly being remodeled. During menopause, the balance between these processes changes, resulting in more bone being resorbed than rebuilt. Hormone therapy with estrogen and progesterone might be able to delay the onset of osteoporosis. However, some medical groups and professional societies recommend that postmenopausal women consider using other agents to slow or stop bone resorption because of the potential adverse health effects of hormone therapy [66-68].

Most supplementation trials of the effects of vitamin D on bone health also include calcium, so it is difficult to isolate the effects of each nutrient. The authors of an evidence-based review of research concluded that supplements of both vitamin D3 (at 700-800 IU/day) and calcium (500-1,200 mg/day) decreased the risk of falls, fractures, and bone loss in elderly individuals aged 62-85 years [5]. The decreased risk of fractures occurred primarily in elderly women aged 85 years, on average, and living in a nursing home. A subsequent review confirms that vitamin D supplementation is effective in reducing falls among elderly people [69]. Women should consult their healthcare providers about their needs for vitamin D (and calcium) as part of an overall plan to prevent or treat osteoporosis.

African Americans have lower levels of 25(OH)D than Caucasians, yet they develop fewer osteoporotic fractures. This suggests that factors other than vitamin D provide protection [70]. African Americans have an advantage in bone density from early childhood, a function of their more efficient calcium economy, and have a lower risk of fracture even when they have the same bone density as Caucasians. They also have a higher prevalence of obesity, and the resulting higher estrogen levels in obese women might protect them from bone loss [70]. Further reducing the risk of osteoporosis in African Americans are their lower levels of bone-turnover markers, shorter hip-axis length, and superior renal calcium conservation. However, despite this advantage in bone density, osteoporosis is a significant health problem among African Americans as they age [70].

Cancer
Laboratory and animal evidence as well as epidemiologic data suggest that vitamin D status could affect cancer risk. Strong biological and mechanistic bases indicate that vitamin D plays a role in the prevention of colon, prostate, and breast cancers. Emerging epidemiologic data suggest that vitamin D has a protective effect against colon cancer, but the data are not as strong for a protective effect against prostate and breast cancer, and are variable for cancers at other sites [71,72]. Studies do not consistently show a protective effect or no effect, however. One study of Finnish smokers, for example, found that subjects in the highest quintile of baseline vitamin D status have a three-fold higher risk of developing pancreatic cancer [73].

Vitamin D emerged as a protective factor in a prospective, cross-sectional study of 3,121 adults aged =50 years (96% men) who underwent a colonoscopy. The study found that 10% had at least one advanced cancerous lesion. Those with the highest vitamin D intakes (>645 IU/day) had a significantly lower risk of these lesions [74]. However, the Women's Health Initiative, in which 36,282 postmenopausal women of various races and ethnicities were randomly assigned to receive 400 IU vitamin D plus 1,000 mg calcium daily or a placebo, found no significant differences between the groups in the incidence of colorectal cancers over 7 years [75]. More recently, a clinical trial focused on bone health in 1,179 postmenopausal women residing in rural Nebraska found that subjects supplemented daily with calcium (1,400-1,500 mg) and vitamin D3 (1,100 IU) had a significantly lower incidence of cancer over 4 years compared to women taking a placebo [64]. The small number of cancers reported (50) precludes generalizing about a protective effect from either or both nutrients or for cancers at different sites. This caution is supported by an analysis of 16,618 participants in NHANES III, where total cancer mortality was found to be unrelated to baseline vitamin D status [77]. However, colorectal cancer mortality was inversely related to serum 25(OH)D concentrations. A large observational study with participants from 10 western European countries also found a strong inverse association between prediagnostic 25(OH)D concentrations and risk of colorectal cancer [78].

Further research is needed to determine whether vitamin D inadequacy in particular increases cancer risk, whether greater exposure to the nutrient is protective, and whether some individuals could be at increased risk of cancer because of vitamin D exposure [71,79].

Other conditions
A growing body of research suggests that vitamin D might play some role in the prevention and treatment of type 1 [80] and type 2 diabetes [81], hypertension [82], glucose intolerance [83], multiple sclerosis [84], and other medical conditions [85,86]. However, most evidence for these roles comes from in vitro, animal, and epidemiological studies, not the randomized clinical trials considered to be more definitive. Until such trials are conducted, the implications of the available evidence for public health and patient care will be debated. A systematic review of health outcomes related to vitamin D and calcium intakes, both alone and in combination, was published in August 2009 [87].

A recent meta-analysis found that use of vitamin D supplements was associated with a reduction in overall mortality from any cause by a statistically significant 7% [88,89]. The subjects in these trials were primarily healthy, middle aged or elderly, and at high risk of fractures; they took 300-2,000 IU/day of vitamin D supplements.
Health Risks from Excessive Vitamin D
Vitamin D toxicity can cause nonspecific symptoms such as nausea, vomiting, poor appetite, constipation, weakness, and weight loss [90]. More seriously, it can also raise blood levels of calcium, causing mental status changes such as confusion and heart rhythm abnormalities [7]. The use of supplements of both calcium (1,000 mg/day) and vitamin D (400 IU/day) by postmenopausal women was associated with a 17% increase in the risk of kidney stones over 7 years in the Women's Health Initiative [91]. Deposition of calcium and phosphate in the kidneys and other soft tissues can also be caused by excessive vitamin D levels [47]. A serum 25(OH)D concentration consistently >200 ng/mL (>500 nmol/L) is considered to be potentially toxic [11]. In an animal model, concentrations =400 ng/mL (=1,000 nmol/L) were not associated with harm [14].

Excessive sun exposure does not result in vitamin D toxicity because the sustained heat on the skin is thought to photodegrade previtamin D3 and vitamin D3 as it is formed [10,35]. High intakes of dietary vitamin D are very unlikely to result in toxicity unless large amounts of cod liver oil are consumed; toxicity is more likely to occur from high intakes of supplements.

Long-term intakes above the UL increase the risk of adverse health effects [4] (Table 4). Substantially larger doses administered for a short time or periodically (e.g., 50,000 IU/week for 8 weeks) do not cause toxicity. Rather, the excess is stored and used as needed to maintain normal serum 25(OH)D concentrations when vitamin D intakes or sun exposure are limited [11,92].

Table 4: Tolerable Upper Intake Levels (ULs) for Vitamin D [4]
Age Children Men Women Pregnancy Lactation
Birth to 12 months 25 mcg
(1,000 IU)
1-13 years 50 mcg
(2,000 IU)
14+ years 50 mcg
(2,000 IU) 50 mcg
(2,000 IU) 50 mcg
(2,000 IU) 50 mcg
(2,000 IU)

Several nutrition scientists recently challenged these ULs, first published in 1997 [92]. They point to newer clinical trials conducted in healthy adults and conclude that the data support a UL as high as 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 [5]. Evidence is not sufficient to determine the potential risks of excess vitamin D in infants, children, and women of reproductive age.

As noted earlier, the FNB is currently reviewing data to determine whether updates to the DRIs (including the ULs) for vitamin D are appropriate [4].
Interactions with Medications
Vitamin D supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these medications on a regular basis should discuss vitamin D intakes with their healthcare providers.

Steroids
Corticosteroid medications such as prednisone, often prescribed to reduce inflammation, can reduce calcium absorption [93-95] 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 [94,95].

Other medications
Both the weight-loss drug orlistat (brand names Xenical® and alli™) and the cholesterol-lowering drug cholestyramine (brand names Questran®, LoCholest®, and Prevalite®) can reduce the absorption of vitamin D and other fat-soluble vitamins [96,97]. Both phenobarbital and phenytoin (brand name Dilantin®), used to prevent and control epileptic seizures, increase the hepatic metabolism of vitamin D to inactive compounds and reduce calcium absorption [98].
Vitamin D and Healthful Diets
According to the 2005 Dietary Guidelines for Americans, "nutrient needs should be met primarily through consuming foods. Foods provide an array of nutrients and other compounds that may have beneficial effects on health. In certain cases, fortified foods and dietary supplements may be useful sources of one or more nutrients that otherwise might be consumed in less than recommended amounts. However, dietary supplements, while recommended in some cases, cannot replace a healthful diet."

The Dietary Guidelines for Americans describes a healthy diet as one that

* Emphasizes a variety of fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products.

Milk is fortified with vitamin D, as are many ready-to-eat cereals and a few brands of yogurt and orange juice. Cheese naturally contains small amounts of vitamin D.

* Includes lean meats, poultry, fish, beans, eggs, and nuts.

Fish such as salmon, tuna, and mackerel are very good sources of vitamin D. Small amounts of vitamin D are also found in beef liver and egg yolks.

* Is low in saturated fats, trans fats, cholesterol, salt (sodium), and added sugars.

Vitamin D is added to some margarines.

* Stays within your daily calorie needs.

For more information about building a healthful diet, refer to the Dietary Guidelines for Americans (http://www.health.gov/dietaryguidelines/dga2005/document/default.htm) and the U.S. Department of Agriculture's food guidance system, My Pyramid (http://www.mypyramid.gov).

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Updated: 11/13/2009