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vitamin D

Recommended daily allowance (RDA): 1) 400 IU (10 ug) infants [40] - older recommendation of 200 IU (5 ug)/day (infants)* [2] 2) 600 IU (15 ug) (children & adults) Institute of Medicine [40] 3) 1600 IU (40 ug) (elderly) [68] - 600 IU (15 ug) appears to be adequate for elderly white women [49] 4) 800-2000 (20-50 ug) IU (adults) [11,40] 5) 600 IU daily age 18-70 years, then 800 IU daily after age 70 years [149] *Breast milk does NOT contain sufficient vitamin D; supplementation recommended [2]; use children's multivitamin Indications: - vitamin D deficiency* - hypocalcemia - hypocalcemic tetany [63] - hypophosphatemia [63] - hypoparathyroidism - osteomalacia - prevention of preterm delivery [62] - prevention & treatment of osteoporosis - in combination with Ca+2 supplementation - diminishes risk of vertebral & hip fractures at dose of 800 IU (20 ug)/day [4,44] - 30% reduction in risk of hip fracture at a dose of 800-2000 IU (20-50 ug)/day [50] - chronic renal failure [63] - renal osteodystrophy - end-stage renal disease - chronic heart failure - may improve LV ejection fraction & LV end diastolic volume - no benefit for 6 minute walk [87] - psoriasis [63] - may reduce risk of cutaneous melanoma [137] - fall prevention in the elderly ? [2,14,59,68] - all healthy adults without year-round regular sun exposure - controversial, but bulk of evidence seems to suggest not (see contraindications) - benefit may be restricted to vitamin D deficient elderly women also supplemented with calcium [43] - doses of > 800 IU (20 ug) /day may be needed for benefit [43] - 800 IU-1000 IU/day reduces falls in the elderly - lower or higher doses do not [147] - benefit may be via increased muscle strength - seems controversial (see contraindications) - also increases muscle strength in adolescent girls - increases muscle strength & balance in older adults [58] - improves handgrip strength in postmenopausal women with or without calcium [134] - in combination with calcium, may reduce risk of vertebral fracture [67] - vitamin D supplementation may reduce LDL cholesterol in postmenopausal women [70] - risk reduction of multiple sclerosis [7] - may reduce risk of respiratory tract infections [91] - vitamin D supplementation during pregnancy is associated with improved neonatal outcomes [99] - may reduce risk for recurrent wheeze among black preterm infants [98] - may reduce progression of mild cognitive impairment [102] - vitamin D supplementation reduces risk of dementia (40%) [140] - may reduce all-cause mortality in the elderly [68] - may reduce risk of cancer-related mortality but not all-cause mortality [109] - supplementation with vitamin D 1000 IU/day in adults > 50 years may reduce cancer deaths by 13% [120] - data neither support nor refute recommendations for calcium & higher dose vitamin D supplementation to reduce mortality [146] - high-dose vitamin D may reduce toxic erythema of chemotherapy [136] - may reduce risk of diabetes mellitus type 2 at dose of > 1000 IU/day if BMI < 30 (RR=0.88) or if severe insulin resistance [112] - may reduce Covid-19 ICU admission/mortality (RR=0.32-0.41) when administered after diagnosis (dose, duration, & mode of administration unknown) [122,145] - may reduce risk of Covid-19 infection (RR=0.40-0.59) [145] - vitamin D supplementation may reduce 5 year risk of autoimmune disease (RR=0.78) - coadministration of omega-3 fatty acids may further reduce risk (RR=0.69) [125] - vitamin D supplementation improves quality of life in patients with irritable bowel syndrome [133] - Endocrine Society recommends vitamin D supplementation for all children & adolescents [149] - 1000 IU vitamin D supplement is reasonable [149] * for most adults, diet does not provide adequate amounts of vitamin D [68] * unless exposed to adequate sunlight (10-30 minutes of midday sunlight several times/week), adults should take supplemental vitamin D [68] * studies on vitamin D, calcium, or both & health outcomes are inconsistent [30,31,71] Contraindications: 1) does not diminish risk of hypertension [10,75] or lower blood pressure [79, 116] 2) does not improve diffuse musculoskeletal pain [26] 3) no effect on wintertime respiratory tract infections [38,95] 4) no clear evidence that vitamin D supplementation prevents cardiovascular disease [44,75,78,107,143] - cardiovascular risk reduction ? [23,24,28,129] - does not improve lipid panel, blood pressure, or serum C-reactive protein [54] - supplementation with vitamin D of no benefit for reducing risk for major cardiovascular events in adults > 60 years of age [143] - monthly vitamin D (100,000 IU) does not reduce risk of cardiovascular events [93] - 2000 IU/day of vitamin D3 does not reduce cardiovascular risk [103] - 1600 or 3200 IU/day of vitamin D3 does not reduce cardiovascular risk [129] - does not prevent stroke [131] 5) conflicting findings on whether vitamin D might decrease (or even increase) the risk for cancer [44] a) lymphoma, prostate cancer?, lung cancer, skin cancer colon cancer (& colorectal adenomatous polyps) [8] b) breast cancer [25] - may lower risk of in-situ breast cancer c) relative risk 43% in post-menopausal women with 1100 IU (27.5 ug)/day vitamin D3 [15] d) neither vitamin D nor calcium supplements affect cancer incidence or mortality or overall mortality [45,78,103] e) no effect on colon cancer [67] f) vitamin D & calcium supplementation does not help prevent cancer in healthy elderly women [92] g) high-dose oral vitamin D 100,000 IU monthly does not prevent cancer (3.3 year trial) [100] 6) no therapeutic benefit patients with colorectal cancer 7) does not prevent common cold [52] or other upper respiratory tract infections [64,86] 8) does not reduce risk of childhood pneumonia [53] 9) not useful for treatment of asthma [74] - not useful for prevention of severe asthma exacerbations [114] - high-dose vitamin D during pregnancy does not lower risk for asthmma in offspring [111] 10) in combination with calcium, does not improve muscle strength in young women with low serum 25-OH vitamin D [56] - supplementation does not improve any measure of physical conditioning in elderly black women [105] 11) of no benefit for osteoarthritis of the knee [57] 12) although low serum 25-OH vitamin D is associated with an increase in all cause mortality, a mortality benefit with supplementation has not been proven [23] 13) does not reduce risk of falls in the elderly or risk of fracture [68,101,130] - vitamin D + calcium supplementation associated with a small but statistically significant absolute reduction in hip fractures or any fractures [127] - reduction not observed when analyses limited to community-dwelling elders [127] - supplementation with vitamin D alone not associated with reductions in hip fractures or any fractures in any population [127] - insufficient data to recommend calcium plus vitamin D supplementation for primary prevention of bone fractures (USPSTF) [78] - USPSTF recommends against vitamin D supplementation to prevent falls in community-dwelling adults >= 65 years (GRS11) [68,96] - vitamin D supplementation does not reduce the risk of falls in older adults (GRS11) [68,72] - vitamin D supplementation reduces risk of falls in care facilities [110] - does not reduce risk of hip fracture [67] - calcium supplements &/or vitamin D does not reduce fracture risk in community-dwelling older adults [97,130,141] - supplementation does not improve bone mineral density in the absence of vitamin D deficiency [62] - 2000 IU of vitamin D3 daily did not lower incidence of falls in community-dwelling adults - vitamin D3 supplementation at doses of 1000-4000 IU/day does not prevent falls compared with doses of 200 IU/day in elderly with elevated fall risk & low serum 25-OH vitamin D levels (10-29 ng/mL) [117] - vitamin D3 doses of 2000 IU & 4000 IU/day associated with increased fall risk vs 200 IU or 1000 IU/day [117] - neither 800 IU vit D QD nor 50,000 IU twice monthly increases bone mineral density or reduces falls in elderly with serum 25-OH vitamin D of 14-27 ng/mL [82] - high-dose vitamin D3 (60,000 IU monthly or 24,000 IU + 300 ug of calcifediol) does not improve functional ability in community living elderly & actually increases fall risk [83] - vitamin D 1000-4000 IU/day might increase risk of fall with fracture [123] - vitamin D supplementation does not reduce risk of fractures in healthy elderly [148] - may increase rosl of hip fractures in healthy elderly women [146] 14) unlikely to reduce risk of type 2 diabetes [76] - does not prevent progression of prediabetes to diabetes [88,106] - combining results of 3 randomized trials that found no benefit, vitamin D supplementation conferred a 3% absolute risk reduction for progression of prediabetes to diabetes over 3 years [139] 15) supplementation of little if any benefit for pregnant women - marginal if any benefit as prenatal supplement in preventing childhood asthma [84] - high-dose supplementation (2400 IU)/day) does improve neurodevelopmental outcomes in offsprimng [118] 16) supplementation does not reduce risk for depression in the elderly [113] 17) vitamin D (2000 IU/day) does not prevent cognitive impairment in healthy adults > 70 years of age [116] - vitamin D supplementation has no benefit or harm for cognitive function in elderly > 60 years [142] 18) vitamin D3 of no benefit for hospitalized patients with COVID-19 [119] 19) vitamin D (2000 IU/day) &/or fish oil (840 mg of omega-3 fatty acids EPA/DHA) of no benefit in preventing atrial fibrillation [121] 20) 60,000 IU of vit D3 oral monthly for 5 years of no benefit for mortalilty in adults [124] 21) of no benefit in preventing statin myopathy [132] 22) vitamin D therapy does not reduce the risk of all-cause death in people with chronic kidney disease [144]. Benefit/risk: - community-dwelling elderly [80] - no benefit in preventing fractures - vitamin D3 2000 IU daily did not reduce risk of falls [115] - institutionalized elderly [81] - number needed to treat (NNT) - 36 patients for an undisclosed period of time to prevent 1 hip fracture - number need to harm - 36 patients for an undisclosed period of time to induce 1 case of kidney disease, kidney stone or other [81] Dosage: 1) recommended daily allowance - infants: 400 IU/day adequate [61] - children & adults <= 70 years of age: 600 IU/day [40,68] - elderly > 70 years of age: 800 IU/day - higher levels not associated with increased bone density - 1800 IU/day associated with increased risk of hypercalcemia* 2) hypocalcemia: a) requires weeks to achieve full effect b) 50,000 IU (1250 ug) PO QD (initially) c) 50,000-100,000 (1250-2500 ug) IU PO QD (maintenance) d) dose may be increased at 4-6 week intervals 3) osteoporosis, fracture & fall prevention: a) 800 IU (20 ug) QD [2,3,4] b) 2000 IU (50 ug) QD for prevention of hospital re-admission after hip fracture in women with vitamin D deficiency [41] c) 500,000 IU (12.5 mg) PO given to women annually paradoxically increases risk of fracture [33] 4) vitamin D deficiency: - 50,000 IU (1.25 mg) weekly for 6-12 weeks [36] 5) toxic erythema of chemotherapy: 50,000-200,000 single dose [136] * ~ 1/5 of adults take >= 1000 IU/day, 3% take >= 4000 IU/day [94] * increases in total serum 25-OH vitamin D with vitamin D supplementation is lower at higher in persons with higher BMI [138] Adverse effects: 1) toxicity a) risk begins at doses above 4000 IU/day b) doses > 10,000 IU (250 ug)/day associated with kidney damage [40] c) may occur at doses of 50,000 (1.25 mg) IU/day for several months in adults [36] d) bone mineral density loss at the radius at doses > 4000 IU/day [108] 2) hypercalcemia & hypocalciuria [33] a) hypercalciuria at higher doses b) may take over 2 months to resolve c) symptomatic hypercalcemia due to vitamin D should be treated with prednisone 3) serum PTH is suppressed [33] 3) corneal opacification Drug interactions: - inducers of CYP3A4 - carbamazepine - statins, except rosuvastatin Laboratory: - serum 25-OH vitamin D provides best indicator of total body vitamin D status - 30-100 ng/mL is target [50] - not necessary prior to initiation of vitamin D supplementation in elderly without regular sun exposure [68]* - neither 800 IU vit D QD nor 50,000 IU twice monthly increases bone mineral density or reduces falls in elderly with serum 25-OH vitamin D of 14-27 ng/mL [82] * GRS11 recommmends repeat DEXA scan every 5 years in women starting at age 65 years rather than initiation of vitamin D supplementation or measuring serum 25-OH vitamin D (seems that vitamin D supplementation is correct according to accompanying explanation) [68] Mechanism of action: 1) precursor to calcitriol, thus role in absorption of Ca+2 & phosphate from the intestines (primary role) [33] a) supplemental vitamin D enhances Ca+2 absorption very little in women with mild vitamin D insufficiency [55] b) only 6% difference in Ca+2 absorption in women with serum 25-OH vitamin D levels of 60 ng/mL vs 20 ng/mL (58% vs 52%) [55] 2) reduces production of renin [6] 3) stimulates production of insulin [6] 4) vitamin D2 & vitamin D3 equally effective in raising serum levels of 25-OH vitamin D [16] a) vitamin D3 more effective than vitamin D2 [66] b) vitamin D2 decreases plasma 25-hydroxyvitamin D3 [66] 5) upregulates genes to induce Toll-like receptor-2 (TLR-2) on keratinocytes & increases expression of antimicrobial peptides such as cathelicidin; effects may be mediated through activation of SRC3 [27] 6) high-dose vitamin D 50,000-200,000 single dose has a dose-dependent anti-inflammatory response, reducing redness & swelling within 24-48 hours without significant increase in serum vitamin D or serum calcium [136] Notes: 1) vitamin D production from exposure to sunlight varies by age, Fitzpatrick skin type, geographic location, season & time of day [35] a) fair-skin persons produce more vitamin D than dark-skin persons b) exposure to 1 hour of bright sunlight can generate production of 20,000 IU (500 ug) of vitamin D in a fair-skin person at southern lattitudes &/or summer months c) north of the sun-belt, it is difficult to obtain sufficient sunlight exposure during the winter to produce the RDA of vitamin D [35] 2) vitamin D should be obtained through foods, beverages, & supplements, not through unprotected exposure to sunlight [18] - plant-based milk (almond milk, soy milk) & goat's milk may contain inadequate amounts of vitamin D for children in Canada [77] 3) most Americans get enough vitamin D [40] 4) medications that adversely affect vitamin D status include phenobarbital, phenytoin, carbamazepine, rifampicin, & antiretroviral 5) activated macrophages in granulomatous diseases in the setting of renal failure can cause extrarenal metabolism of vitamin D, resulting in hypercalcemia 6) higher serum 25-hydroxyvitamin D levels associated with better cognitive function in adults a) this does not seem to be apparent in adolescents [47] b) low serum 25-hydroxyvitamin D is associated with cognitive decline [37] c) low serum 25-hydroxyvitamin D is associated increased risk of Parkinson's disease [48] 7) higher brain 25-OH vit D3 associated with better cognitive function prior to death, but not associated with any neuropathology or biomarker outcome [135] 8) no causal association between vitamin D status & health [65] 9) response of serum 25-hydroxyvitamin D levels to vitamin D supplementation is 30% lower in obese persons (on average) but individual responses vary widely [69]

Interactions

drug interactions

Related

25-hydroxyvitamin D3 (calcifediol) in serum calcifediol; 25-OH cholcalciferol; 25-OH vitamin D3 (Calderol) calcitriol; 1,25-dihydroxycholcalciferol; 1,25-dihydroxyvitamin D3 hypervitaminosis D vitamin D binding protein, Gc globulin; group-specific component vitamin D deficiency

Specific

calcipotriene; calcipotriol (Dovonex, Dovobet) cholecalciferol; vitamin D3 dihydrotachysterol; DHT, (Hytakerol, Dichystrolum, Antitanil) doxercalciferol (Hectorol) ergocalciferol (vitamin D2, Drisdol)

General

endocrine agent sterol vitamin

Properties

References

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  20. Prescriber's Letter 16(5): 2009 Vitamin D Dosing Detail-Document#: 250508 (subscription needed) http://www.prescribersletter.com
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Component-of

alpha tocopheryl acetate/ascorbate/calcium carbonate/cobalamin/copper sulfate/ferrous fumarate/folic acid/magnesium oxide/nicotinamide/potassium iodide/pyridoxine/retinol/riboflavin/thiamine/vitamin d/zinc sulfate ascorbate/cobalamin/folic acid/nicotinic acid/pyridoxine/riboflavin/sodium fluoride/thiamine/vitamin a/vitamin d/vitamin e ascorbate/cobalamin/nicotinic acid/pyridoxine/riboflavin/thiamine/vitamin a/vitamin d/vitamin e ascorbate/ferrous sulfate/nicotinic acid/pyridoxine/riboflavin/thiamine/vitamin a/vitamin d/vitamin e ascorbate/ferrous sulfate/vitamin A/vitamin D ascorbate/vitamin a/vitamin d ca+2/vitamin d calcium carbonate/calcium gluconate/vitamin d calcium carbonate/vitamin D calcium carbonate/vitamin d/vitamin k calcium citrate/magnesium oxide/vitamin D calcium citrate/vitamin D calcium phosphate/vitamin D calcium/magnesium/vitamin D calcium/magnesium/vitamin D/zinc vitamin a/vitamin d