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Dietary Supplement Fact Sheet: Vitamin D Office of Dietary Supplements • National Institutes of Health
Office of Dietary Supplements • National Institutes of Health
Table of Contents
Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis [1-3]. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two 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 .
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 hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [4-6]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults [3,7,8]. 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 [4,6,9,10]. 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.
Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements  and has a fairly long circulating half-life of 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 [6,11].
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 (Table 1). A concentration of <20 nanograms per milliliter (ng/mL) (or <50 nanomoles per liter [nmol/L]) is generally considered inadequate.
Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health*
|<11||<27.5||Associated with vitamin D deficiency and rickets in infants and young children .|
|<10-15||<25-37.5||Generally considered inadequate for bone and overall health in healthy individuals [5,13].|
|≥30||≥75||Proposed by some as desirable for overall health and disease prevention, although a recent government-sponsored expert panel concluded that insufficient data are available to support these higher levels [13,14].|
|Consistently >200||Consistently >500||Considered potentially toxic, leading to hypercalcemia and hyperphosphatemia, although human data are limited. In an animal model, concentrations ≤400 ng/mL (≤1,000 nmol/L) demonstrated no toxicity [15,16].|
Intake reference values for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) . DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender , include:
The FNB established an AI for vitamin D that represents a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. AIs for vitamin D are listed in both micrograms (mcg) and International Units (IUs); the biological activity of 1 mcg is equal to 40 IU (Table 2). The AIs for vitamin D are based on the assumption that the vitamin is not synthesized by exposure to sunlight .
Table 2: Adequate Intakes (AIs) for Vitamin D 
|Birth to 13 years||5 mcg
|14-18 years||5 mcg
|19-50 years||5 mcg
|51-70 years||10 mcg
|71+ years||15 mcg
In 2008, the American Academy of Pediatrics (AAP) issued recommended intakes for vitamin D that exceed those of FNB . The AAP recommendations are based on evidence from more recent clinical trials and the history of safe use of 400 IU/day of vitamin D in pediatric and adolescent populations. AAP recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume ≥1,000 mL/day of vitamin D-fortified formula or whole milk . (All formulas sold in the United States provide ≥400 IU vitamin D3 per liter, and the majority of vitamin D-only and multivitamin liquid supplements provide 400 IU per serving.) Similarly, all non-breastfed infants ingesting <1,000 mL/day of vitamin D-fortified formula or milk should receive a vitamin D supplement of 400 IU/day. AAP also recommends that older children and adolescents who do not obtain 400 IU/day through vitamin D-fortified milk and foods should take a 400 IU vitamin D supplement daily .
Sources of Vitamin D
Very few foods in nature contain 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 [20-22].
Fortified foods provide most of the vitamin D in the American diet [5,22]. For example, almost all of the U.S. milk supply is fortified with 100 IU/cup of vitamin D (25% of the Daily Value or 50% of the AI level for ages 14-50 years). In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem. This program virtually eliminated the disorder at that time [5,14]. Other dairy products made from milk, such as cheese and ice cream, are generally not fortified. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, and margarine. In the United States, foods allowed to be fortified with vitamin D include cereal flours and related products, milk and products made from milk, and calcium-fortified fruit juices and drinks . Maximum levels of added vitamin D are specified by law.
Several food sources of vitamin D are listed in Table 3.
Table 3: Selected Food Sources of Vitamin D [23-25]
|Food||IUs per serving*||Percent DV**|
|Cod liver oil, 1 tablespoon||1,360||340|
|Salmon, cooked, 3.5 ounces||360||90|
|Mackerel, cooked, 3.5 ounces||345||90|
|Tuna fish, canned in oil, 3 ounces||200||50|
|Sardines, canned in oil, drained, 1.75 ounces||250||70|
|Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup||98||25|
|Margarine, fortified, 1 tablespoon||60||15|
|Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75-1 cup (more heavily fortified cereals might provide more of the DV)||40||10|
|Egg, 1 whole (vitamin D is found in yolk)||20||6|
|Liver, beef, cooked, 3.5 ounces||15||4|
|Cheese, Swiss, 1 ounce||12||4|
*IUs = International Units.
**DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents of products within the context of a total diet. The DV for vitamin D is 400 IU for adults and children age 4 and older. Food labels, however, are not required to list vitamin D content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.
The U.S. Department of Agriculture's Nutrient Database Web site, http://www.nal.usda.gov/fnic/foodcomp/search/ , lists the nutrient content of many foods; relatively few have been analyzed for vitamin D content.
Most people meet their vitamin D needs through exposure to sunlight [6,27]. 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 [11,27-28]. 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 . 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 ; in far northern latitudes, this reduced intensity lasts for up to 6 months. Latitudes below 34 degrees north (a line between Los Angeles and Columbia, South Carolina) allow for cutaneous production of vitamin D throughout the year 
Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60% . UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D . 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 . 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 [11,28]. 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 . 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 . 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 .
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 [6,32,33]. 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 .
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