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. 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 promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and to prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [1,2]. 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 the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation [1,3,4]. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D . Many cells have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D.
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 . 25(OH)D functions as a biomarker of exposure, but it is not clear to what extent 25(OH)D levels also serve as a biomarker of effect (i.e., relating to health status or outcomes) . Serum 25(OH)D levels do not indicate the amount of vitamin D stored in body tissues.
In contrast to 25(OH)D, 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 [2,6].
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, and cut points have not been developed by a scientific consensus process. Based on its review of data of vitamin D needs, a committee of the Institute of Medicine concluded that persons are at risk of vitamin D deficiency at serum 25(OH)D concentrations <30 nmol/L (<12 ng/mL). Some are potentially at risk for inadequacy at levels ranging from 30–50 nmol/L (12–20 ng/mL). Practically all people are sufficient at levels ≥50 nmol/L (≥20 ng/mL); the committee stated that 50 nmol/L is the serum 25(OH)D level that covers the needs of 97.5% of the population. Serum concentrations >125 nmol/L (>50 ng/mL) are associated with potential adverse effects  (Table 1).
|Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health* |
|<30||<12||Associated with vitamin D deficiency, leading to rickets|
in infants and children and osteomalacia in adults
|30 to <50||12 to <20||Generally considered inadequate for bone and overall health|
in healthy individuals
|≥50||≥20||Generally considered adequate for bone and overall health|
in healthy individuals
|>125||>50||Emerging evidence links potential adverse effects to such|
high levels, particularly >150 nmol/L (>60 ng/mL)
* Serum concentrations of 25(OH)D are reported in both nanomoles
per liter (nmol/L) and nanograms per milliliter (ng/mL).
** 1 nmol/L = 0.4 ng/mL
An additional complication in assessing vitamin D status is in the actual measurement of serum 25(OH)D concentrations. Considerable variability exists among the various assays available (the two most common methods being antibody based and liquid chromatography based) and among laboratories that conduct the analyses [1,7,8]. This means that compared with the actual concentration of 25(OH)D in a sample of blood serum, a falsely low or falsely high value may be obtained depending on the assay or laboratory used . A standard reference material for 25(OH)D became available in July 2009 that permits standardization of values across laboratories and may improve method-related variability [1,10].
Sources of Vitamin D
Very few foods in nature contain vitamin D. The flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources [1,11]. 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 and its metabolite 25(OH)D3 . Some mushrooms provide vitamin D2 in variable amounts [13,14]. Mushrooms with enhanced levels of vitamin D2 from being exposed to ultraviolet light under controlled conditions are also available.
Fortified foods provide most of the vitamin D in the American diet [1,14]. For example, almost all of the U.S. milk supply is voluntarily fortified with 100 IU/cup . (In Canada, milk is fortified by law with 35–40 IU/100 mL, as is margarine at ≥530 IU/100 g.) In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem . 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, margarine and other food products.
Both the United States and Canada mandate the fortification of infant formula with vitamin D: 40–100 IU/100 kcal in the United States and 40–80 IU/100 kcal in Canada .
Several food sources of vitamin D are listed in Table 3.
|Table 3: Selected Food Sources of Vitamin D |
|Food||IUs per serving*||Percent DV**|
|Cod liver oil, 1 tablespoon||1,360||340|
|Swordfish, cooked, 3 ounces||566||142|
|Salmon (sockeye), cooked, 3 ounces||447||112|
|Tuna fish, canned in water, drained, 3 ounces||154||39|
|Orange juice fortified with vitamin D, 1 cup (check product labels, as amount of added vitamin D varies)||137||34|
|Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup||115-124||29-31|
|Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide more of the DV)||80||20|
|Margarine, fortified, 1 tablespoon||60||15|
|Sardines, canned in oil, drained, 2 sardines||46||12|
|Liver, beef, cooked, 3 ounces||42||11|
|Egg, 1 large (vitamin D is found in yolk)||41||10|
|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|
|Cheese, Swiss, 1 ounce||6||2|
* IUs = International Units.
** DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents among products within the context of a total daily diet. The DV for vitamin D is currently set at 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, but foods providing lower percentages of the DV also contribute to a healthful diet.
The U.S. Department of Agriculture’s (USDA’s) Nutrient Database Web site lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin D arranged by nutrient content and by food name. A growing number of foods are being analyzed for vitamin D content. Simpler and faster methods to measure vitamin D in foods are needed, as are food standard reference materials with certified values for vitamin D to ensure accurate measurements .
Animal-based foods can provide some vitamin D in the form of 25(OH)D, which appears to be approximately five times more potent than the parent vitamin in raising serum 25(OH)D concentrations . One study finds that taking into account the serum 25(OH)D content of beef, pork, chicken, turkey, and eggs can increase the estimated levels of vitamin D in the food from two to 18 times, depending upon the food . At the present time, the USDA’s Nutrient Database does not include 25(OH)D when reporting the vitamin D content of foods. Actual vitamin D intakes in the U.S. population may be underestimated for this reason.
Most people meet at least some of their vitamin D needs through exposure to sunlight [1,2]. Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3 . Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis . Perhaps surprisingly, geographic latitude does not consistently predict average serum 25(OH)D levels in a population. Ample opportunities exist to form vitamin D (and store it in the liver and fat) from exposure to sunlight during the spring, summer, and fall months even in the far north latitudes .
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 (SPF) 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 [1,19]. Therefore, 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 [6,20]. Individuals with limited sun exposure need to include good sources of vitamin D in their diet or take a supplement to achieve recommended levels of intake.
Despite the importance of the sun for vitamin D synthesis, it is prudent to limit exposure of skin to sunlight  and UV radiation from tanning beds . 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. The American Academy of Dermatology advises that photoprotective measures be taken, including the use of sunscreen, whenever one is exposed to the sun . Assessment of vitamin D requirements cannot address the level of sun exposure because of these public health concerns about skin cancer, and there are no studies to determine whether UVB-induced synthesis of vitamin D can occur without increased risk of skin cancer .