overview of vitamin d

Official reprint from UpToDatewww.uptodate.com ©2015 UpToDate

AuthorsSassan Pazirandeh, MDDavid L Burns, MD

Section EditorsKathleen J Motil, MD, PhDMarc K Drezner, MD

Deputy EditorJean E Mulder, MD

Overview of vitamin D

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Feb 2015. | This topic last updated: May 08, 2014.

INTRODUCTION — Vitamin D is a fat-soluble vitamin. Very few foods naturally contain vitamin D (fatty fishlivers are the exception), so dermal synthesis is the major natural source of the vitamin. Vitamin D from thediet or dermal synthesis is biologically inactive and requires enzymatic conversion to active metabolites(figure 1). Vitamin D is converted enzymatically in the liver to 25-hydroxyvitamin D (25[OH]D), the majorcirculating form of vitamin D, and then in the kidney to 1,25-dihydroxyvitamin D, the active form of vitamin D.

Vitamin D and its metabolites have a significant clinical role because of their interrelationship with calciumhomeostasis and bone metabolism. Rickets (children) and osteomalacia (children and adults) due to severevitamin D deficiency are now uncommon except in populations with unusually low sun exposure, lack ofvitamin D in fortified foods, and malabsorptive syndromes. Subclinical vitamin D deficiency, as measured bylow serum 25(OH)D, is very common. In the National Health and Nutrition Examination Survey (NHANES)2005 to 2006, 41.6 percent of adult participants (≥20 years) had 25(OH)D levels below 20 ng/mL (50 nmol/L)[1]. This degree of vitamin D deficiency may contribute to the development of osteoporosis and an increasedrisk of fractures and falls in the elderly. Vitamin D may also regulate many other cellular functions.

This topic review provides an overview of vitamin D. Other reviews discuss specific issues related to vitaminD:

CHEMISTRY — Vitamin D, or calciferol, is a generic term and refers to a group of lipid soluble compoundswith a four-ringed cholesterol backbone. 25-hydroxyvitamin D (25[OH]D) is the major circulating form ofvitamin D. It has a half-life of two to three weeks, compared with 24 hours for parent vitamin D [2]. It hasactivity at bone and intestine, but is less than 1 percent as potent as 1,25-dihydroxyvitamin D, the mostactive form of vitamin D. The half-life of 1,25-dihydroxyvitamin D is approximately four to six hours.1,25-dihydroxyvitamin D binds to intracellular receptors in target tissues and regulates gene transcription [3].It appears to function through a single vitamin D receptor (VDR), which is nearly universally expressed innucleated cells. The receptor is a member of the class II steroid hormone receptor, and is closely related to

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(See "Causes of vitamin D deficiency and resistance".)●

(See "Overview of rickets in children" and "Etiology and treatment of calcipenic rickets in children".)●

(See "Epidemiology and etiology of osteomalacia" and "Clinical manifestations, diagnosis, andtreatment of osteomalacia".)

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(See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Vitamin Dinsufficiency and deficiency in children and adolescents".)

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(See "Vitamin D and extraskeletal health".)●

(See "Calcium and vitamin D supplementation in osteoporosis".)●

Overview of vitamin D http://www.uptodate.com/contents/overview-of-vitamin-d?topi...

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the retinoic acid and thyroid hormone receptors [4]. Its most important biological action is to promoteenterocyte differentiation and the intestinal absorption of calcium. Other effects include a lesser stimulationof intestinal phosphate absorption, direct suppression of parathyroid hormone (PTH) release from theparathyroid gland, regulation of osteoblast function, and permissively allowing PTH-induced osteoclastactivation and bone resorption (figure 1).

SOURCES — Very few foods naturally contain vitamin D (fatty fish livers are the exception); dermalsynthesis is the major natural source of the vitamin. Previtamin D3 is synthesized nonenzymatically in skinfrom 7-dehydrocholesterol during exposure to the ultraviolet (UV) rays in sunlight. Previtamin D3 undergoesa temperature-dependent rearrangement to form vitamin D3 (cholecalciferol) (figure 1). This system isexceedingly efficient, and it is estimated that brief casual exposure of the arms and face is equivalent toingestion of 200 international units per day [5]. However, the length of daily exposure required to obtain thesunlight equivalent of oral vitamin D supplementation is difficult to predict on an individual basis and varieswith the skin type, latitude, season, and time of day [6,7]. Prolonged exposure of the skin to sunlight doesnot produce toxic amounts of vitamin D3 because of photoconversion of previtamin D3 and vitamin D3 toinactive metabolites (lumisterol, tachysterol, 5,6-transvitamin D, and suprasterol 1 and 2) [8,9]. In addition,sunlight induces production of melanin, which reduces production of vitamin D3 in the skin.

Infants, disabled persons, and older adults may have inadequate sun exposure, while the skin of those olderthan 70 years of age also does not convert vitamin D effectively. In addition, at northern latitudes, there isnot enough radiation to convert vitamin D, particularly during the winter. For these reasons, in the UnitedStates, milk, infant formula, breakfast cereals, and some other foods are fortified with synthetic vitamin D2(ergocalciferol), which is derived from radiation of ergosterol found in plants, the mold ergot, and plankton, orwith vitamin D3. In other parts of the world, cereals and bread products are often fortified with vitamin D.

ABSORPTION — Dietary vitamin D is incorporated into micelles, absorbed by enterocytes, and thenpackaged into chylomicrons. Disorders associated with fat malabsorption, such as celiac disease, Crohndisease, pancreatic insufficiency, cystic fibrosis, short gut syndrome, and cholestatic liver disease, areassociated with low serum 25-hydroxyvitamin D (25[OH]D) levels. (See "Causes of vitamin D deficiency andresistance", section on 'Gastrointestinal disease'.)

METABOLISM — Vitamin D from the diet or dermal synthesis is biologically inactive and requires enzymaticconversion in the liver and kidney to active metabolites.

Hepatic — Dietary vitamin D travels to the liver, bound to vitamin D–binding protein and in continuedassociation with chylomicrons and lipoproteins, where it and endogenously-synthesized vitamin D3 aremetabolized [10,11]. The hepatic enzyme 25–hydroxylase places a hydroxyl group in the 25 position of thevitamin D molecule, resulting in the formation of 25-hydroxyvitamin D (25[OH]D, calcidiol) (figure 1).25-hydroxyvitamin D2 has a lower affinity than 25-hydroxyvitamin D3 for vitamin D-binding protein. Thus,25-hydroxyvitamin D2 has a shorter half-life than 25-hydroxyvitamin D3, and treatment with vitamin D2 maynot increase serum total 25(OH)D levels as efficiently as vitamin D3. The treatment of vitamin D deficiency isdiscussed in detail elsewhere. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, andtreatment", section on 'Preparations'.)

Renal — 25-hydroxyvitamin D2 and D3 produced by the liver enter the circulation and travel to the kidney,again bound to vitamin D-binding protein. This protein has a single binding site, which binds vitamin D andall of its metabolites. Only 3 to 5 percent of the total circulating binding sites are normally occupied; as aresult, this protein is not rate-limiting in vitamin D metabolism unless large amounts are lost in the urine, asin the nephrotic syndrome [12]. In the renal tubule, entry of the filtered 25(OH)D-vitamin D-binding protein


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complex into the cells is facilitated by receptor-mediated endocytosis [13]. At least two proteins working intandem are involved in this process: cubilin and megalin [13,14]. Cubilin and megalin, expressed in the renalproximal tubule, are multiligand receptors that facilitate uptake of extracellular ligands. Deficiency of either ofthese proteins results in increased 25(OH)D excretion in the urine and, at least in experimental models,1,25-dihydroxyvitamin D deficiency and bone disease [13-15].

Within the tubular cell, 25(OH)D is released from the binding protein. The renal tubular cells contain twoenzymes, 1-alpha-hydroxylase (CYP27B1) and 24-alpha-hydroxylase (CYP24), that can further hydroxylate25(OH)D, producing 1,25-dihydroxyvitamin D, the most active form of vitamin D, or 24,25-dihydroxyvitaminD, an inactive metabolite (figure 1) [16-18]. Both enzymes are members of the P-450 system [19]. Studies invitamin D-deficient animals suggest that the proximal tubule is the important site of synthesis. In contrast,studies in the normal human kidney indicate that the distal nephron is the predominant site of 1-alpha-hydroxylase expression under conditions of vitamin D sufficiency [18].

The 1-alpha-hydroxylase enzyme is also expressed in extrarenal sites, including the gastrointestinal tract,skin, vasculature, mammary epithelial cells, osteoblasts, and osteoclasts [20,21]. The most widelyrecognized manifestation of extrarenal synthesis of 1,25-dihydroxyvitamin D is hypercalcemia andhypercalciuria in patients with granulomatous diseases, such as sarcoid. In this setting, parathyroid hormone(PTH)-independent extrarenal production of 1,25-dihydroxyvitamin D from 25(OH)D by activatedmacrophages occurs in the lung and lymph nodes. (See "Hypercalcemia in granulomatous diseases",section on 'Sarcoidosis'.)

The plasma 1,25-dihydroxyvitamin D concentration is a function both of the availability of 25(OH)D and ofthe activities of the renal enzymes 1-alpha-hydroxylase and 24-alpha-hydroxylase. The renal 1-alpha-hydroxylase enzyme is primarily regulated by the following factors [11,19]:

Increased PTH secretion (most often due to a fall in the plasma calcium concentration) andhypophosphatemia stimulate the enzyme and enhance 1,25 dihydroxyvitamin D production [22].1,25-dihydroxyvitamin D, in turn, inhibits the synthesis and secretion of PTH, providing negative feedbackregulation of 1,25-diydroxyvitamin D production. 1,25-dihydroxyvitamin D synthesis may also be modulatedby vitamin D receptors (VDRs) on the cell surface; downregulation of these receptors may play an importantrole in regulating vitamin D activation [23].

FGF23 inhibits renal production of 1,25-dihydroxyvitamin D by limiting 1-alpha-hydroxylase activity in therenal proximal tubule and by simultaneously increasing expression of 24-alpha-hydroxylase and productionof 24,25-dihydroxyvitamin D (an inactive metabolite) [24]. 1,25-dihydroxyvitamin D stimulates FGF23, aphosphaturic hormone, creating a feedback loop. Experimental data suggest that FGF23 decreases renalreabsorption of phosphate, and thereby counteracts the increased gastrointestinal phosphate reabsorptioninduced by 1,25-dihydroxyvitamin D, maintaining phosphate homeostasis [25].

Both 1,25-dihydroxyvitamin D and 25(OH)D are degraded in part by hydroxylation by a 24-hydroxylase[11,17]. The activity of the 24-hydroxylase gene is increased by 1,25-dihydroxyvitamin D, which thereforepromotes its own inactivation, and decreased by PTH, thereby allowing more active hormone to be formed[17].

PTH●

Serum calcium and phosphate concentrations●

Fibroblast growth factor 23 (FGF23)●


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REQUIREMENTS

Adequate intake — In 2010, the Institute of Medicine (IOM) released a report on dietary intakerequirements for calcium and vitamin D (table 1) [26]. Its Recommended Dietary Allowance (RDA) of vitaminD for children 1 to 18 years and adults through age 70 years is 600 international units (15 mcg) daily. ItsRDA is 800 international units (20 mcg) daily after age 71 years [26]. For pregnant and lactating mothers, itrecommends 600 international units (15 mcg) per day. The intake can be provided in the diet or as a vitaminD supplement. Vitamin D intake is often low in older adults, who also do not have regular effective sunexposure. Thus, for older adults, we suggest supplementation with 600 to 800 international units of vitamin Ddaily. Older persons confined indoors and other high risk groups may have low serum 25-hydroxyvitamin D(25[OH]D) concentrations at this intake level and may require higher intakes (See "Vitamin D deficiency inadults: Definition, clinical manifestations, and treatment", section on 'Groups at high risk for suboptimalintake'.)

The estimated adequate intake for infants up to 12 months is 400 international units (10 mcg) daily (table 2).Vitamin D supplementation should be given to infants who are exclusively breast fed, because the vitamin Dcontent of human milk is low. The Lawson Wilkins Pediatric Endocrine Society also recommendssupplementation with 400 international units daily of vitamin D beginning within days of birth for infants whoare exclusively breast-fed [27]. Most infant formulas contain at least 400 units/L of vitamin D, so formula-fedinfants will also require supplementation to meet this goal, unless they consume at least 1000 mL daily offormula. Vitamin D intake of at least 400 units/day is also recommended for children who do not consume atleast one liter of vitamin D-fortified milk daily [27]. (See "Vitamin D insufficiency and deficiency in childrenand adolescents", section on 'Prevention'.)

The recommendations for dietary vitamin D intake were based upon the beneficial effects of calcium andvitamin D on skeletal health (see "Calcium and vitamin D supplementation in osteoporosis", section on'Efficacy'). The evidence supporting a benefit of vitamin D on extraskeletal outcomes was inconsistent,inconclusive as to causality, and insufficient, and therefore was not used as a basis for dietary referenceintake development [28]. (See "Vitamin D and extraskeletal health".)

Estimates of vitamin D requirements vary and depend in part upon sun exposure and the standards used todefine a deficient state. The IOM committee assumed minimal sun exposure when establishing the dietaryreference intakes for vitamin D. Casual exposure to sunlight provides amounts of vitamin D that areadequate to prevent rickets in many people, but is influenced by geographic location, season, use of sunblock lotion, and skin pigmentation [29]. (See "Vitamin D insufficiency and deficiency in children andadolescents", section on 'Decreased synthesis'.)

Vitamin D requirements also may depend on disease states and concomitant medications. As an example,patients undergoing long-term treatment with glucocorticoids may benefit from higher levels ofsupplementation of vitamin D and calcium. (See "Prevention and treatment of glucocorticoid-inducedosteoporosis", section on 'Calcium and vitamin D'.)

Optimal serum 25-hydroxyvitamin D — The best laboratory indicator of vitamin D adequacy is the serum25(OH)D concentration [30]. The lower limit of normal for 25(OH)D levels varies depending on thegeographic location and sunlight exposure of the reference population (range 8 to 15 ng/mL). However,there is no consensus on the optimal 25(OH)D concentration for skeletal or extraskeletal health. The IOMconcluded that a serum 25(OH)D concentration of 20 ng/mL (50 nmol/L) is sufficient for most individuals [2],but other experts (Endocrine Society, National Osteoporosis Foundation [NOF], International OsteoporosisFoundation [IOF], American Geriatrics Society [AGS]) suggest that a minimum level of 30 ng/mL (75 nmol/L)


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is necessary in older adults to minimize the risk of falls and fracture [31-35]. The serum parathyroid hormone(PTH) level typically is inversely related to 25(OH)D levels in adults, and may be a useful secondaryindicator of vitamin D insufficiency. In general, this relationship is weak for children. Controversiessurrounding the optimal serum 25(OH)D concentration are reviewed separately. (See "Vitamin D deficiencyin adults: Definition, clinical manifestations, and treatment", section on 'Defining vitamin D sufficiency'.)

DEFICIENCY AND RESISTANCE — Vitamin D deficiency or resistance is caused by one of fourmechanisms (see "Causes of vitamin D deficiency and resistance"):

Several studies have shown suboptimal serum levels of 25(OH)D and vitamin D intake in the United Statesand other countries [27,36-40]. (See 'Requirements' above and "Vitamin D insufficiency and deficiency inchildren and adolescents" and "Vitamin D deficiency in adults: Definition, clinical manifestations, andtreatment".)

Lack of vitamin D activity leads to reduced intestinal absorption of calcium and phosphorus. Early in vitaminD deficiency, hypophosphatemia is more marked than hypocalcemia. With persistent vitamin D deficiency,hypocalcemia occurs and causes secondary hyperparathyroidism, which leads to phosphaturia,demineralization of bones, and, when prolonged and severe, to osteomalacia in adults and rickets andosteomalacia in children. (See "Epidemiology and etiology of osteomalacia" and "Etiology and treatment ofcalcipenic rickets in children", section on 'Nutritional rickets'.)

Overt vitamin D deficiency resulting in rickets and osteomalacia in children and osteomalacia in adults isnow uncommon in most developed countries. However, subclinical vitamin D deficiency occurs even indeveloped countries and is associated with osteoporosis, increased risk of falls, and possibly fractures. (See"Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Clinicalmanifestations'.)

Glucocorticoids, when used chronically in high doses, inhibit intestinal vitamin D-dependent calciumabsorption, which is one of the mechanisms whereby chronic glucocorticoid excess leads to osteoporosisand fractures. (See "Pathogenesis, clinical features, and evaluation of glucocorticoid-induced osteoporosis".)

Vitamin D stores decline with age, especially in the winter. Controlled trials have demonstrated that vitaminD and calcium supplementation can reduce the risk of falls and fractures in the elderly. (See "Calcium andvitamin D supplementation in osteoporosis" and "Vitamin D deficiency in adults: Definition, clinicalmanifestations, and treatment", section on 'Benefits of vitamin D repletion'.)

EXCESS — The intake at which the dose of vitamin D becomes toxic is not clear. The Institute of Medicine(IOM) has defined the "tolerable upper intake level" (UL) for vitamin D as 100 micrograms (4000international units) daily for healthy adults and children 9 to 18 years [26]. This is also the UL for pregnantand lactating women. The UL for infants and children up to nine years old is lower (table 2). For patients withmalabsorption (eg, celiac disease, gastrectomy, inflammatory bowel disease), oral dosing of vitamin D

Impaired availability of vitamin D, secondary to inadequate dietary vitamin D, fat malabsorptivedisorders, and/or lack of sunlight (photoisomerization)

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Impaired hydroxylation by the liver to produce 25-hydroxyvitamin D (25[OH]D)●

Impaired hydroxylation by the kidneys to produce 1,25-dihydroxyvitamin D (vitamin D-dependentrickets type 1, chronic renal insufficiency)

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End organ insensitivity to vitamin D metabolites (hereditary vitamin D-resistant rickets [HVDRR, vitaminD-dependent rickets type 2])

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depends upon the absorptive capacity of the individual patient. High doses of vitamin D of 10,000 to 50,000units daily may be necessary to replete vitamin D in some patients. Such patients require careful monitoringto avoid toxicity. Indications for high dose vitamin D supplementation and the UL for vitamin Dsupplementation are discussed in more detail separately. (See "Vitamin D deficiency in adults: Definition,clinical manifestations, and treatment", section on 'Dosing'.)

Vitamin D intoxication generally occurs after inappropriate use of vitamin D preparations. It may occur in faddieters who consume "megadoses" of supplements or in patients who take vitamin D replacement therapyfor malabsorption, renal osteodystrophy, osteoporosis, or psoriasis. Vitamin D intoxication has beendocumented in adults taking more than 60,000 international units per day [41]. Case reports have describedhypervitaminosis D due to errors in manufacturing, formulation or prescription, including milk that wasinadvertently excessively fortified with vitamin D [42,43]. Prolonged exposure of the skin to sunlight does notproduce toxic amounts of vitamin D3 (cholecalciferol) because of photoconversion of previtamin D3 andvitamin D3 to inactive metabolites [8,9]. Multiple studies reveal that prolonged exposure of the skin tosunlight results in a maximum serum 25-hydroxyvitamin D (25[OH]D) level of <80 ng/ml (200 nmol/L)[7,44,45].

Symptoms of acute intoxication are due to hypercalcemia and include confusion, polyuria, polydipsia,anorexia, vomiting, and muscle weakness. Chronic intoxication may cause nephrocalcinosis, bonedemineralization and pain. The diagnosis and treatment of vitamin D toxicity are reviewed separately. (See"Diagnostic approach to hypercalcemia" and "Treatment of hypercalcemia".)

There is some feedback regulation of the hepatic 25-hydroxylase, and the liver has the capacity tometabolize 25(OH)D to inactive metabolites. This is accomplished by the P-450 system and is enhanced byalcohol, barbiturates, and phenytoin. However, it is insufficient to prevent vitamin D intoxication following theingestion of large amounts of vitamin D. The liver is the usual storage system for vitamin D. When largeamounts of vitamin D are ingested, much of the excess vitamin D is stored in adipose tissue [46]. As thesesites become saturated, the vitamin D remains in serum and is converted to toxic levels of 25(OH)D [4]. (See"Etiology of hypercalcemia", section on 'Hypervitaminosis D'.)

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Beyond the Basics topics (see "Patient information: Vitamin D deficiency (Beyond the Basics)" and"Patient information: Calcium and vitamin D for bone health (Beyond the Basics)")

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Very few foods naturally contain vitamin D; fatty fish and eggs are the exceptions. Dermal synthesisand foods fortified with vitamin D are the major sources of the vitamin. (See 'Sources' above.)

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Vitamin D3 (cholecalciferol) is synthesized nonenzymatically in skin from 7-dehydrocholesterol duringexposure to the ultraviolet (UV) rays in sunlight. Vitamin D3 from the skin or diet must be25-hydroxylated in the liver, then 1-hydroxylated in the kidneys to the active form,1,25-dihydroxycholecalciferol (calcitriol) (figure 1). (See 'Metabolism' above.)

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The Recommended Dietary Allowance (RDA) for vitamin D is 600 international units (units) daily foradults through age 70 years and for children 1 to 18 years of age (table 2). For adults 71 years andolder, 800 units (20 micrograms) daily is recommended for the prevention and treatment ofosteoporosis. Vitamin D intake and effective sun exposure are often inadequate in older adults. In olderadults, particularly those at increased risk of falls and fracture, we suggest supplementation withvitamin D (Grade 2B). We administer 600 to 800 international units daily. (See 'Requirements' aboveand "Calcium and vitamin D supplementation in osteoporosis".)

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Vitamin D deficiency can be caused by unusually low sun exposure combined with lack of vitaminD-fortified foods or malabsorption. Alternatively, impaired hydroxylation of vitamin D in liver or kidneycan prevent metabolism into the physiologically active form. Rarely, genetic defects may cause the endorgans to be unresponsive to vitamin D, as in hereditary vitamin D-resistant rickets (HVDRR). (See'Deficiency and resistance' above and "Causes of vitamin D deficiency and resistance".)

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Vitamin D intoxication generally occurs after inappropriate use of vitamin D preparations. Prolongedexposure of the skin to sunlight does not produce toxic amounts of vitamin D3 because ofphotoconversion of previtamin D3 and vitamin D3 to inactive metabolites. Symptoms of acuteintoxication are due to hypercalcemia and include confusion, polyuria, polydipsia, anorexia, vomiting,and muscle weakness. Long-term intoxication can cause bone demineralization and pain. In children,the hypercalcemia can cause brain injury. (See 'Excess' above and "Diagnostic approach tohypercalcemia" and "Treatment of hypercalcemia".)

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The Institute of Medicine (IOM) has defined the "tolerable upper intake level" (UL) for vitamin D as 100micrograms (4000 units) daily for healthy adults and children 9 to 18 years (table 2). The UL for infantsand children up to nine years old is lower. (See 'Excess' above.)

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Vogiatzi MG, Jacobson-Dickman E, DeBoer MD, Drugs, and Therapeutics Committee of The PediatricEndocrine Society. Vitamin D supplementation and risk of toxicity in pediatrics: a review of currentliterature. J Clin Endocrinol Metab 2014; 99:1132.

43.

Nair-Shalliker V, Clements M, Fenech M, Armstrong BK. Personal sun exposure and serum25-hydroxy vitamin D concentrations. Photochem Photobiol 2013; 89:208.

44.

Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab 2002; 87:4952.

45.

Wortsman J, Matsuoka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J ClinNutr 2000; 72:690.

46.


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Topic 2033 Version 17.0


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GRAPHICS

Pathways of vitamin D synthesis

Metabolic activation of vitamin D to calcitriol and its effects on calciumand phosphate homeostasis. The result is an increase in the serumcalcium and phosphate concentrations.

UV: ultraviolet.

Graphic 65360 Version 4.0


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Institute of Medicine Dietary Reference Intakes for calcium andvitamin D

Life stagegroup

Calcium Vitamin D

Estimatedaverage

requirement(mg/day)

Recommendeddietary

allowance(mg/day)

Upperlevel

intake(mg/day)

Estimatedaverage

requirement(IU/day)

Recommendeddietary

allowance(IU/day)

Infants 0 to 6months

* * 1000 • •

Infants 6 to 12months

* * 1500 • •

1 to 3 years old 500 700 2500 400 600

4 to 8 years old 800 1000 2500 400 600

9 to 13 years old 1100 1300 3000 400 600

14 to 18 years old 1100 1300 3000 400 600

19 to 30 years old 800 1000 2500 400 600

31 to 50 years old 800 1000 2500 400 600

51 to 70 year oldmales

800 1000 2000 400 600

51 to 70 year oldfemales

1000 1200 2000 400 600

>70 years old 1000 1200 2000 400 800

14 to 18 yearsold,pregnant/lactating

1100 1300 3000 400 600

19 to 50 yearsold,pregnant/lactating

800 1000 2500 400 600

* For infants, adequate intake is 200 mg/day for 0 to 6 months of age and 260 mg/day for 6 to 12months of age.• For infants, adequate intake is 400 IU/day for 0 to 6 months of age and 400 IU/day for 6 to 12months of age.

Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Otten JJ, Hellwig JP,Meyers LD (Eds), The National Academies Press, Washington, DC 2006. pp.530-541. Modified withpermission from the National Academies Press, Copyright © 2006, National Academy of Sciences.Sources: Dietary reference intakes for Thiamin, Riboflavin, Niacin, Vitamin B , Folate, Vitamin B ,Panthothenic acid, Biotin, and Choline (1998); Dietary reference intakes for Vitamin C, Vitamin E,Selenium, and Carotenoids (2000); Dietary Reference Intake reports of the Food and NutritionBoard, Institute of Medicine (2010). These reports may be accessed via www.nap.edu.

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Dietary reference intakes for fat-soluble vitamins

Nutrient Age group RDA*/AI ULAdverse

effects ofexcess

Vitamin A

1 mcg retinolactivityeqivalent =3.3 unitvitamin A

Micrograms

dailyMicrograms

dailyAtaxia, alopecia,hyperlipidemia,hepatotoxicity,bone andmuscle pain;teratogenic

Infants

0 to 6 months 400 600

7 to 12 months 500 600

Children

1 to 3 years 300 600

4 to 8 years 400 900

Males

9 to 13 years 600 1700

14 to 18 years 900 2800

≥19 years 900 3000

Females

9 to 13 years 600 1700

14 to 18 years 700 2800

≥19 years 700 3000

Pregnancy

<18 years 750 2800

≥19 years 770 3000

Lactation

<18 years 1200 2800

≥19 years 1300 3000

Vitamin D

(calciferol)

1 mcgcalciferol =40 int. unit

Micrograms

dailyMicrograms

dailyHypercalcemia,hypercalciuria,polydipsia,polyuria,confusion,anorexia,vomiting, bonedemineralization

Infants

0 to 12 months 10 (400 int. unit) 0 to 6 months: 25(1000 int. unit)

6 to 12 months:37.5 (1500 int.unit)

• Δ


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Children and adolescents

1 to 18 years 15 (600 int. unit) 1 to 3 years: 62.5(2500 int. unit)

4 to 8 years: 75(3000 int. unit)

9 to 18 years: 100(4000 int. unit)

Males and females (including pregnancy and lactation)

19 to 50 years 15 (600 int. unit) 100 (4000 int.unit)

50 to 70 years 15 100

>70 years 20 (800 int. unit) 100

Vitamin E

(alpha-tocopherol)

1 mg = 1.47int. unit"naturalsource"vitamin E, or2.2 int. unitsyntheticvitamin E

Milligrams daily Milligrams daily Increased risk ofbleeding;possiblyincreased risk ofnecrotizingenterocolitis ininfants

Infants

0 to 6 months 4 ND

7 to 12 months 5 ND

Children

1 to 3 years 6 200

4 to 8 years 7 300

Males and females (including pregnancy)

9 to 13 years 11 600

14 to 18 years 15 800

>18 years 15 1000

Lactation

≤18 years 19 800

>19 years 19 1000

Vitamin K

Microgramsdaily

Microgramsdaily

No adverseeffectsassociated withvitamin Kconsumptionfrom food orsupplementshave beenreported,however data

Infants

0 to 6 months 2 ND

7 to 12 months 2.5 ND

Children

1 to 3 years 30 ND

4 to 8 years 55 ND


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are limitedMales

9 to 13 years 60 ND

14 to 18 years 75 ND

>19 years 120 ND

Females (including pregnancy and lactation)

9 to 13 years 60 ND

14 to 18 years 75 ND

>19 years 90 ND

Vitamin A doses given as retinol activity equivalents (RAE). 1 RAE = 1 mcg retinol, 12 mcgbeta-carotene, 14 mcg alpha-carotene, or 24 mcg beta-cryptoxanthin.

RDA: recommended dietary allowance; AI: adequate intake; UL: upper tolerable level.* The RDA is the level of dietary intake that is sufficient to meet the daily nutrient requirements of97 percent of the individuals in a specific life stage group.• The AI represents an approximation of the average nutrient intake that sustains a definednutritional state, based on observed or experimentally determined values in a defined population.Δ The UL is the maximum level of daily nutrient intake that is likely to pose no risk of adversehealth effects in almost all individuals in the specified life-stage or gender group.

Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Otten JJ, Hellwig JP,Meyers LD (Eds), The National Academies Press, Washington, DC 2006. pp.530-541. Modified withpermission from the National Academies Press, Copyright © 2006, National Academy of Sciences.Sources: Dietary reference intakes for Thiamin, Riboflavin, Niacin, Vitamin B , Folate, Vitamin B ,Panthothenic acid, Biotin, and Choline (1998); Dietary reference intakes for Vitamin C, Vitamin E,Selenium, and Carotenoids (2000); Dietary Reference Intake reports of the Food and NutritionBoard, Institute of Medicine (2010). These reports may be accessed via www.nap.edu.


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Disclosures: Sassan Pazirandeh, MD Nothing to disclose. David L Burns, MD Nothing to disclose. Kathleen J Motil, MD, PhDConsultant/Advisory Boards: NPS Pharmaceuticals [Short gut syndrome (Teduglutide)]. Marc K Drezner, MD Nothing to disclose.Jean E Mulder, MD Employee of UpToDate, Inc.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vettingthrough a multi-level review process, and through requirements for references to be provided to support the content. Appropriatelyreferenced content is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures


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