Introduction
Vitamin D (also referred to as “calciferol”) is a fat-soluble vitamin that is naturally present in a few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet (UV) rays from sunlight strike the skin and trigger vitamin D synthesis.
Vitamin D obtained from sun exposure, foods, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first hydroxylation, which occurs in the liver, converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as “calcidiol.” The second hydroxylation occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as “calcitriol” [1].
Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal bone mineralization and to prevent hypocalcemic tetany (involuntary contraction of muscles, leading to cramps and spasms). It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [1-3]. 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 reduction of inflammation as well as modulation of such processes as cell growth, neuromuscular and immune function, and glucose metabolism [1-3]. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D. Many tissues have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D.
In foods and dietary supplements, vitamin D has two main forms, D2 (ergocalciferol) and D3 (cholecalciferol), that differ chemically only in their side-chain structures. Both forms are well absorbed in the small intestine. Absorption occurs by simple passive diffusion and by a mechanism that involves intestinal membrane carrier proteins [4]. The concurrent presence of fat in the gut enhances vitamin D absorption, but some vitamin D is absorbed even without dietary fat. Neither aging nor obesity alters vitamin D absorption from the gut [4].
Serum concentration of 25(OH)D is currently the main indicator of vitamin D status. It reflects vitamin D produced endogenously and that obtained from foods and supplements [1]. In serum, 25(OH)D has a fairly long circulating half-life of 15 days [1]. Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL). One nmol/L is equal to 0.4 ng/mL, and 1 ng/mL is equal to 2.5 nmol/L.
Assessing vitamin D status by measuring serum 25(OH)D concentrations is complicated by the considerable variability of the available assays (the two most common ones involve antibodies or chromatography) used by laboratories that conduct the analyses [5,6]. As a result, a finding can be falsely low or falsely high, depending on the assay used and the laboratory. The international Vitamin D Standardization Program has developed procedures for standardizing the laboratory measurement of 25(OH)D to improve clinical and public health practice [5,7-10].
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 measured in hours, and serum levels are tightly regulated by parathyroid hormone, calcium, and phosphate [1]. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe [2].
Serum concentrations of 25(OH)D and health
Although 25(OH)D functions as a biomarker of exposure, the extent to which 25(OH)D levels also serve as a biomarker of effect on the body (i.e., relating to health status or outcomes) is not clear [1,3].
Researchers have not definitively identified serum concentrations of 25((OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and overall health. After reviewing data on vitamin D needs, an expert committee of the Food and Nutrition Board (FNB) at the National Academies of Sciences, Engineering, and Medicine (NASEM) concluded that people are at risk of vitamin D deficiency at serum 25(OH)D concentrations less than 30 nmol/L (12 ng/mL; see Table 1 for definitions of “deficiency” and “inadequacy”) [1]. Some people are potentially at risk of inadequacy at 30 to 50 nmol/L (12–20 ng/mL). Levels of 50 nmol/L (20 ng/mL) or more are sufficient for most people. In contrast, the Endocrine Society stated that, for clinical practice, a serum 25(OH)D concentration of more than 75 nmol/L (30 ng/mL) is necessary to maximize the effect of vitamin D on calcium, bone, and muscle metabolism [11,12]. The FNB committee also noted that serum concentrations greater than 125 nmol/L (50 ng/mL) can be associated with adverse effects [1] (Table 1).
Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health [1]nmol/L*ng/mL*Health status<30<12Associated with vitamin D deficiency, which can lead to rickets in infants and children and osteomalacia in adults30 to <5012 to <20Generally considered inadequate for bone and overall health in healthy individuals≥50≥20Generally considered adequate for bone and overall health in healthy individuals>125>50Linked to potential adverse effects, particularly at >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). One nmol/L = 0.4 ng/mL, and 1 ng/mL = 2.5 nmol/L.
Optimal serum concentrations of 25(OH)D for bone and general health have not been established because they are likely to vary by stage of life, by race and ethnicity, and with each physiological measure used [1,13,14]. In addition, although 25(OH)D levels rise in response to increased vitamin D intake, the relationship is nonlinear [1]. The amount of increase varies, for example, by baseline serum levels and duration of supplementation.
Recommended Intakes
Intake recommendations for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by expert committees of NASEM [1]. DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include:
Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.
An FNB committee established RDAs for vitamin D to indicate daily intakes sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both micrograms (mcg) and international units (IU); 1 mcg vitamin D is equal to 40 IU (Table 2). Even though sunlight is a major source of vitamin D for some people, the FNB based the vitamin D RDAs on the assumption that people receive minimal sun exposure [1]. For infants, the FNB committee developed AIs based on the amount of vitamin D that maintains serum 25(OH)D levels above 20 ng/mL (50 nmol/L) and supports bone development.
Table 2: Recommended Dietary Allowances (RDAs) for Vitamin D [1]Age,Male,Female,Pregnancy, Lactation
0-12 months*10 mcg
(400 IU)10 mcg
(400 IU)
1–13 years15 mcg
(600 IU)15 mcg
(600 IU)
14–18 years15 mcg
(600 IU)15 mcg
(600 IU)15 mcg
19–50 years15 mcg
(600 IU)15 mcg
(600 IU)15 mcg
(600 IU)15 mcg
(600 IU)
51–70 years15 mcg
(600 IU)15 mcg
(600 IU)
>70 years20 mcg
(800 IU)20 mcg
(800 IU)
*Adequate Intake (AI)
Many other countries around the world and some professional societies have somewhat different guidelines for vitamin D intakes [15]. These differences are a result of an incomplete understanding of the biology and clinical implications of vitamin D, different purposes for the guidelines (e.g., for public health in a healthy population or for clinical practice), and/or the use in some guidelines of observational studies in addition to randomized clinical trials to establish recommendations [9,15]. The Endocrine Society states, for example, that to maintain serum 25(OH)D levels above 75 nmol/L (30 ng/mL), adults might need at least 37.5 to 50 mcg (1,500–2,000 IU)/day of supplemental vitamin D, and children and adolescents might need at least 25 mcg (1,000 IU)/day [11]. In contrast, the United Kingdom government recommends intakes of 10 mcg (400 IU)/day for its citizens aged 4 years and older [16].
Sources of Vitamin D
Food
Few foods naturally contain vitamin D. The flesh of fatty fish (such as trout, salmon, tuna, and mackerel) and fish liver oils are among the best sources [17,1]. An animal’s diet affects the amount of vitamin D in its tissues. Beef liver, egg yolks, and cheese have small amounts of vitamin D, primarily in the form of vitamin D3 and its metabolite 25(OH)D3. Mushrooms provide variable amounts of vitamin D2 [17]. Some mushrooms available on the market have been treated with UV light to increase their levels of vitamin D2. In addition, the Food and Drug Administration (FDA) has approved UV-treated mushroom powder as a food additive for use as a source of vitamin D2 in food products [18]. Very limited evidence suggests no substantial differences in the bioavailability of vitamin D from various foods [19].
Animal-based foods typically provide some vitamin D in the form of 25(OH)D in addition to vitamin D3. The impact of this form on vitamin D status is an emerging area of research. Studies show that 25(OH)D appears to be approximately five times more potent than the parent vitamin for raising serum 25(OH)D concentrations [17,20,21]. One study found that when the 25(OH)D content of beef, pork, chicken, turkey, and eggs is taken into account, the total amount of vitamin D in the food is 2 to 18 times higher than the amount in the parent vitamin alone, depending on the food [20].
Fortified foods provide most of the vitamin D in American diets [1,22]. For example, almost all of the U.S. milk supply is voluntarily fortified with about 3 mcg/cup (120 IU), usually in the form of vitamin D3 [23]. In Canada, milk must be fortified with 0.88–1.0 mcg/100 mL (35–40 IU), and the required amount for margarine is at least 13.25 mcg/100 g (530 IU). Other dairy products made from milk, such as cheese and ice cream, are not usually fortified in the United States or Canada. Plant milk alternatives (such as beverages made from soy, almond, or oats) are often fortified with similar amounts of vitamin D to those in fortified cow’s milk (about 3 mcg [120 IU]/cup); the Nutrition Facts label lists the actual amount [24]. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, margarine, and other food products.
The United States mandates the fortification of infant formula with 1–2.5 mcg/100 kcal (40–100 IU) vitamin D; 1–2 mcg/100 kcal (40–80 IU) is the required amount in Canada [1].
A variety of foods and their vitamin D levels per serving are listed in Table 3.
Table 3: Vitamin D Content of Selected Foods [25]FoodMicrograms
(mcg) per
serving
International Units (IU)
per serving
Percent DV*
Cod liver oil, 1 tablespoon
34.01,360170
Trout (rainbow), farmed, cooked, 3 ounces16.264581
Salmon (sockeye), cooked, 3 ounces14.257071
Mushrooms, white, raw, sliced, exposed to UV light, ½ cup9.236646
Milk, 2% milkfat, vitamin D fortified, 1 cup
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