Article Figures & Data
Figures
- Figure 1
Physiologic actions and potential benefits of vitamin D: References are listed in Tables 1,3, and 7.
Tables
STUDY N DESIGN OUTCOME COMMENTS Krejs et al1 10 Intestinal perfusion study before and after administration of VTD Calcium and magnesium absorption increased 2%– 300% from baseline None Zittermann et al2 68: 34 controls, 34 patients with congestive heart failure Case-control study With lower VTD levels (P < .001), PTH levels (P < .001) and inflammatory markers (P < .001) were raised Lower VTD levels were seen in patients with more severe congestive heart failure Latham et al3 2496 Systematic review NS reduction in falls among patients receiving VTD None Chui et al4 126 Univariate and multivariate regression analysis Positive correlation of VTD levels with insulin sensitivity (P < .0001); negative effect on beta cell function (P < .0045) Subjects with VTD deficiency are at higher risk of insulin resistance Barger-Lux et al5 116 Open-label treatment groups: 1000 IU VTD3, 10 000 IU VTD3, 50 000 IU VTD3 Raised 25(OH)D levels by 29 nmol/L, 146 nmol/L, and 643 nmol/L, respectively 8 weeks before steady state achieved Chapuy et al6 1569 Population prevalence study (cross-sectional study) of VTD and PTH levels Parathyroid secretion initiated when serum 25(OH)D falls below 78 nmol/L 14% of the population had wintertime levels <30 nmol/L Moussavi et al7 318 Population prevalence study (cross-sectional study) of VTD deficiency in Iran 46.2% had levels <50 nmol/L (72.1% of women and 18.3% of men) 95% of women had levels <80 nmol/L Rucker et al8 188 Population prevalence study (cross-sectional study) of VTD and PTH levels in western Canada 97% of subjects had levels <80 nmol/L at some time during the year; levels were lower during fall, winter, and spring than during summer 34% had levels <40 nmol/L sometime during the year; levels were taken 4 times yearly Pasco et al9 3280 Cross-sectional study of seasonal periodicity of serum VTD, PTH, and fractures in Australia In winter, VTD levels were lower (P < .001) and falls were more likely to result in fractures (P < .001) VTD levels of <28 nmol/L were found in 14% of subjects in winter Lebrun et al10 160 Cross-sectional study in Manitoba 43% of children and 76% of mothers had levels <25 nmol/L 70% of mothers drank no milk; 24% were intolerant of milk Waiters et al11 121: 22 whites, 51 Inuit, 37 Native Canadians* Cross-sectional study of mothers and newborns in Inuvik Average 25(OH)D levels at time of delivery were 50.1 nmol/L in Natives and 59.8 nmol/L in non-Natives Plasma levels of 25(OH)D in newborns averaged only 67% of levels in mothers Vieth et al12 796 Cross-sectional study in Toronto, Ont, of women aged 18–35 y 21% of women reporting no consumption of VTD, 26% of women reporting <200 IU, and 20% reporting >200 IU of VTD were deficient (<40 nmol/L) during winter months Recommended intake is too low to prevent VTD insufficiency and deficiency; deficiency could be determined only by laboratory tests, not by dietary history Roth et al13 90 Cross-sectional study in children presenting to a emergency department in Edmonton, Alta 34% of patients had VTD levels <40 nmol/L, 6% had levels <25 nmol/L (deficiency) Levels taken at end of winter Thomas et al14 290 Cross-sectional study in consecutive medical inpatients 57% considered deficient in VTD (<37.5 nmol/L); 22% severely deficient (<20 nmol/L) 37% of patients who consumed more than the recommended intake of VTD were deficient Kauppinen- Makelin et al15 205: 106 inpatients, 99 outpatients Cross-sectional study in consecutive medical inpatients and outpatients 70% of female and 61% of male inpatients had levels <37.5 nmol/L, and 44% of female and 37% of male outpatients had levels <37.5 nmol/L Inpatients were more deficient in VTD than outpatients Hochwald et al16 296 Cross-sectional study of consecutive medical inpatients in Israel 26.27% of inpatients had levels <37.5 nmol/L Even in a sunny country, >25% of patients were deficient in VTD Lee et al17 53 Analysis of dietary intake in Canadian long-term care 70% of nursing-home patients consumed inadequate amounts of VTD through diet alone Supplementation is necessary in these settings Liu et al18 155 Cross-sectional study in Toronto; prevalence and seasonal variation in long-term care 9% of subjects had VTD levels <25 nmol/L in September; 18% had similar levels after the winter <25 nmol/L is considered high risk for osteomalacia Haney et al19 35 Cross-sectional study in internal medicine residents 74% had VTD levels <50 nmol/L in spring compared with 26% in fall 69% of residents took in <400 IU/d of VTD Holick et al20 1536 Cross-sectional study of postmenopausal women in North America Serum VTD was <50 nmol/L in 18%, <62.5 nmol/L in 36%, and <75 nmol/L in 52% of women >50% of women taking osteoporosis therapy had inadequate VTD levels Gaugris et al21 11 023 Systematic review of VTD status in postmenopausal women with osteoporosis 50%–70% of women with a fracture had VTD levels <37.5 nmol/L High prevalence of low VTD levels in women with a history of fractures Matsuoka et al22 40 Randomized controlled trial VTD levels lower in sunscreen users (40.2 nmol/L) than controls (91.3 nmol/L) (P <.001) Lower 25(OH)D levels suggest lower VTD stores Lo et al23 14: 7 healthy, 7 with fat malabsorption Controlled trial. Intestinal absorption study before and after VTD radiolabeled Absorption reduced from 60% in normal subjects to <18% (pancreatitis) in study subjects, 0% in those with bilary obstruction, and <50% in those with celiac disease Various conditions involving malabsorption result in VTD insufficiency or deficiency Jones et al24 209 Double-blind, placebo-controlled study 19% reduction in absorption of VTD in treated group Unlikely to have substantial reduction with cutaneous production of VTD Binet and Kooh25 17 Case review in Toronto Native people* and immigrants at risk of VTD deficiency Rickets is still a public health issue Bischoff-Ferrari et al26 19 114: 9294 in hip and other fracture trial, 9820 in non- vertebral fracture trials Meta-analysis of randomized controlled trials of fracture prevention RR 0.74 (95% CI 0.61–0.88); reduced hip fracture by 26%; RR 0.77 (95% CI 0.68–0.89); reduced nonvertebral fracture by 23% 700–800 IU/d of VTD reduces risk of hip and nonvertebral fractures; 400 IU/d does not Dawson-Hughes et al27 389 Randomized, double-blind, placebo-controlled study Prevalence of fractures in placebo group was 10% compared with 4% in treatment group (P = .02) 500 mg of calcium and 700 IU of VTD reduced incidence of nonvertebral fractures Chapuy et al28 583 Multicentre, randomized, double- masked, placebo-controlled confirmatory study Prevalence of fractures in placebo group was 11.1% compared with 6.9% in treatment group ( P = .07, NS) 1200 mg of calcium and 800 IU of VTD reduced incidence of nonvertebral fractures Porthouse et al29 3314 Randomized controlled trial of primary prevention No evidence that calcium and VTD reduced fractures in community-dwelling older women Only 63% of subjects were taking the supplements at 12 mo (poor compliance); no baseline or follow-up VTD levels taken Grant et al30 5292 Randomized, placebo-controlled trial of secondary fracture prevention No evidence for secondary prevention of fractures with use of VTD or combined VTD and calcium; baseline 25(OH)D level rose from 38 to 62.25 nmol/L in treatment group Only 60% had compliance rates of >80% of tablets taken; only 60 patients had baseline and follow-up 25(OH)D levels taken Dhesi et al31 139 Randomized, double-blind, placebo-controlled study With treatment, significant change in choice reaction time (P < .01), postural sway ( P < .02), and aggregate functional performance time (P < .05) NS difference in falls; small trial Bischoff-Ferrari et al32 1237, 5 trials reviewed Meta-analysis of double-blind, randomized controlled trials VTD reduced risk of falling by 22% Number needed to treat was 15 to prevent 1 fall Bischoff-Ferrari et al33 4100 Cross-sectional, population-based survey 2.5-m walk test (P = .001 for trend) and sit-to-stand test (P = .017 for trend); comparison of highest to lowest quartile 25(OH)D levels In ambulatory patients, active or inactive concentrations of 40–94 nmol/L of 25(OH)D resulted in better lower- extremity musculoskeletal function Sato et al34 96 Randomized placebo-controlled trial 1000 IU of VTD2 resulted in 59% reduction in falls (P = .049) in patients with long-standing stroke VTD levels were deficient with 25(OH)D levels <25 nmol/L Al Faraj and Al Mutairi35 341 Cross-sectional interventional study 299 (83% of total) with 25(OH)D levels <22.5 nmol/L and idiopathic back pain had a 100% improvement in symptoms when treated with 5000–10 000 IU of VTD until 25(OH)D levels were normal In 299 patients, VTD levels were clearly deficient; very high doses were used for repletion therapy with no side effects Al-Allaf et al36 87 Case-control study 25(HO)D levels <20 nmol/L were more common in fibromyalgia patients than in controls (P = .015) Unclear whether low VTD levels are causative in fibromyalgia or result from the disease Plotnikoff and Quigley37 150 Cross-sectional population study 93% of patients with persistent nonspecific musculoskeletal pain had 25(OH)D levels <30 nmol/L Osteomalacia is a known cause of nonspecific musculoskeletal pain Hyppönen et al38 10 821 Study of children given 2000 IU of VTD supplements Regular supplementation resulted in a 78% reduction in risk of developing type 1 diabetes later in life A subset receiving supplementation with >2000 IU of VTD had an 86% RR39 Pfiefer et al40 148 Randomized placebo-controlled trial of blood-pressure therapy supplementing with VTD 800 IU of VTD supplementation decreased systolic hypertension by 9.3% (P < .01) Short-term study (8 weeks). No statistical benefit on diastolic blood pressure Van den Berghe et al41 124 Randomized controlled trial; comparison of 200 and 500 IU of VTD C-reactive protein levels fell significantly in the group taking the higher dose (P <.05) 25(HO)D levels were deficient and did not normalize with 200 IU of VTD Forman et al42 216 313 Summary of 3 large prospective cohort studies Higher VTD intake was not associated with lower risk of incident hypertension Patients followed up for 8 years Garland et al43 Unstated Summary of 63 epidemiologic studies: 30 of colon cancer, 13 of breast cancer, 26 of prostate cancer, and 7 of ovarian cancer 25(OH)D levels <75 nmol/L double the risk of those with levels >75 nmol/L; women in lowest quartile of VTD intake had 5 times the risk of developing breast cancer than those in highest quartile. In a study on prostate cancer (19 000 men), incidence was 70% higher among those with 25(OH)D levels <40 nmol/L than among those with levels >40 nmol/L No studies showed an increase in cancer rates with VTD, but some showed no effect Munger et al44 187 563 Summary of 2 prospective cohort studies Supplementation with =400 IU of VTD resulted in a 41% decrease in incidence of multiple sclerosis Dietary intake of VTD resulted in a lower reduction of 33% Merlino et al45 29 368 Prospective cohort study Supplementation with =400 IU of VTD resulted in a 36% decrease in incidence of rheumatoid arthritis Dietary intake resulted in a slightly lower reduction of 28% Berwick et al46 528 Population-based study of cutaneous melanoma Intermittent sun exposure was associated with increased survival in melanoma patients Antiproliferative effect of VTD Kennedy et al47 966 Cohort case-control study Painful sunburn early in life increased melanoma, squamous cell carcinoma, and especially actinic keratosis Lifelong moderate sun exposure decreased risk of melanoma Linday et al48 94 Case-control study Supplement with ~700 IU of VTD significantly decreased upper respiratory tract infections over time (P < .042) Decreased need for antibiotics in control group; compliance was only 70% Wayse et al49 150 Case-control study Low VTD levels were associated with increased risk of severe acute lower respiratory infection: 25(OH)D <22.5 nmol/L (P < .001) Despite abundant sunlight, 25(OH)D levels were deficient Krall et al50 145 Randomized controlled trial using calcium and VTD supplements 13% of patients taking supplements lost teeth compared with 27% of patients not taking supplements VTD was not independently related to risk of losing teeth Vieth et al51 64 Randomized comparison control study; 4000 IU of VTD compared with 600 IU (current recommended intake); based on 1-tail Mann-Whitney well-being score, (P = .034) No side effects of high dose of VTD other than improved mood 6-mo trials Vieth et al52 61 Randomized comparison control study; 1000 vs 4000 IU of VTD supplementation for 3 mo Average 25(OH)D levels were 68.7 nmol/L and 96.4 nmol/L, respectively, after 3 mo NS changes in serum calcium and urinary calcium excretion in patients taking high doses Aloia et al53 208 Randomized controlled trial in 50- to 70-year-old African- American women Only 60% of women treated with 2000 IU of VTD daily achieved normal 25(OH)D levels after a year 87% compliance for 1 y 25(OH)D—25-hydroxyvitamin D, CI—confidence interval, IU—international units, NS—nonsignificant, PTH—parathyroid hormone, RR—risk reduction, VTD—vitamin D.
↵* Native is used to refer to the indigenous and aboriginal inhabitants of Canada and their descendants.
ORGAN OR SYSTEM EFFECT OF SUFFICIENT VITAMIN D EFFECT OF INSUFFICIENT OR DEFICIENT LEVELS OF VITAMIN D OPTIMAL VITAMIN D INTAKE FOR HEALTH Jejunum and ileum Increases absorption of calcium and magnesium to 30%1 Absorption of calcium and magnesium reduced to 10% 85 nmol/L allows maximum absorption64,65; with adequate VTD levels, >800 mg of calcium might be unnecessary66 Bone Maintains calcium and phosphate homeostasis and is required for proper mineralization59 Rickets or osteomalacia;62 short- latency disease Rickets and osteomalacia are prevented when VTD levels are >25 nmol/L67 Parathyroid Regulates calcium and phosphate levels, controls conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D59 Parathyroid hormone excretion increases as levels of VTD decrease resulting in secondary hyperparathyroidism, which in turn results in resorption of calcium from bone and exacerbates osteoporosis Parathyroid hormone levels are dramatically suppressed when VTD levels are maintained at >50 nmol/L67; levels begin to rise when 25-hydroxyvitamin D levels fall <78 nmol/L Cardiovascular system via VDR Inhibition of vascular smooth-muscle proliferation; suppression of vascular calcification; down-regulation of pro- inflammatory cytokines; up-regulation of anti-inflammatory cytokines. VTD acts as a negative endocrine regulator of the renin-angiotensin system68 Might contribute to congestive heart failure2,69; deficiency results in loss of calciotropic effect in long- latency disease Currently unknown, but 2000–4000 IU of vitamin D3 are being suggested70 Muscle via VDR Modulates calcium transport, protein synthesis, and kinetics of muscle contraction71 Muscle weakness, limb pain, and impaired physical function72; loss of calciotropic effect Maximum neuromuscular performance achieved with VTD levels of 125 nmol/L33 Skin via VDR Production of calcitrol that regulates cellular function in keratocytes Antiproliferative, immunosuppressive, and prodifferentiating effects VTD analogues are used for psoriasis73 Islet cells via VDR Improvement in insulin sensitivity4 Negative effect on beta cell function with reduced insulin secretion; loss of immune modulatory effect Raising VTD levels from 25 to 75 nmol/L improves sensitivity by 60%; optimal level has not been determined Certain cancer cell types mediated via VDR Suppressed growth and increased apoptosis74,75; stabilized chromosomal structure and prevented DNA breakdown76 Loss of antiproliferative effect Optimal level undetermined Immune system modulator Stimulated expression of potent anti- microbial peptides, increased “oxidative burst” potential of macrophages77 Increased susceptibility to influenza77 and tuberculosis78 Optimal level undetermined; summer levels of 125 nmol/L likely required77 Innate immune function Increased production of cathelicidins effective against Escherichia coli, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Candida Decreased wound barrier function Optimal dose undetermined79–82 VTD—vitamin D, VDR—vitamin D receptor.
ASSAY MEASUREMENT COMMENTS Radioimmunoassay Uses antibodies that recognize both 25(OH)D3 and 25(OH)D2 Most commonly used assay; coefficient of variability in assay is 12%–18% in normal range of VTD (85–147.5 nmol/L) and 10%-25% in lower range of VTD (20–62.5 nmol/L)86 Competitive binding protein assay Reagent separates VTD from binding proteins Often yields values about 30% higher (nonspecific) but might not detect 25(OH)D287 25(OH)D3—25-hydroxyvitamin D3, 25(OH)D2—25-hydroxyvitamin D2, VTD—vitamin D.
RISK FACTORS REASON Inadequate exposure to the sun • Skin type - Dark skin requires up to 5 times the length of exposure because of melanin content • Season, latitude, angle of the sun - People living at latitudes higher than the 37th parallel cannot get adequate amounts of UVB from the sun during winter months • Use of sunscreen22,90 - Continuous use of sunscreen with greater than factor 8 UVB protection22; controversial because of risk of skin cancer, but UVB decreases risk of internal cancer • Time of day - Ultraviolet B is at its maximum from 10:00 AM to 2:00 PM91; exposure to 1 minimal erythemal dose* in a swimsuit can provide the equivalent of 10 000 IU of VTD92 • Covering the skin For various religious or cultural reasons Inadequate dietary intake Limited intake of foods rich in VTD, such as oily fish and fish-liver oil, low intake of fortified foods or no use of supplements; strict vegans and non-milk drinkers are at higher risk93 Obesity Irreversible sequestration of VTD in the fat pool, especially if body mass index is >30 and person does little outdoor activity94 Exclusive breastfeeding Breast milk is low in VTD10,95; supplementing with 4000 IU of VTD has been shown to achieve adequate levels in both mother and child96 Pregnancy Adequate maternal VTD levels are required to ensure fetal bone health and general health of mother and child97–100 Age • Decreased production of VTD through the skin - A 70-year-old person’s skin can synthesize only 25% as much VTD as a young person’s101–102; conversion of 7-dehydrocholesterol in aging skin is considerably lessened103 • Age-related lactose intolerance - Reduced intake of fortified milk • Immobility - More time housebound or in hospital; many are institutionalized • Aging kidneys - Decreased renal conversion of VTD Comorbid conditions Malabsorption syndromes, such as Crohn disease, Whipple disease, cystic fibrosis, and sprue, as well as severe liver disease23 Drug interactions • Drugs that impair VTD activation or increase its clearance - Phenytoin, carbamazepine, rifampin, cimetidine, thiazides104–106; lithium raises parathyroid hormone levels and lowers levels of the active hormone 1,25-dihydroxyvitamin D107 • Drugs that impair VTD absorption - Mineral oil laxatives or fat substitutes, such as Olestra24; obesity management medications, such as orlistat108; or bile-acid sequestrants, such as cholestyramine and colestipol109 Variations in metabolism of VTD Some Indo-Asians have increased 24-hydroxylase activity that results in low serum levels of 25-hydroxyvitamin D110 IU—international units, UVB—ultraviolet B, VTD—vitamin D.
↵* The amount of sunlight to which a person can be exposed before the skin begins to turn slightly red. Minimal erythemal dose varies from person to person depending on skin type.
SOURCE RISKS AND BENEFITS Sun Exposure has never been known to cause toxicity; however, risk of skin cancer increases with exposure47 Oily fish or fish oils High levels of vitamin A in fish oils (cod, halibut); sometimes high levels of mercury and other toxins (dioxins) are found in fish130,131 Fortified foods, such as milk, soya milk, or rice milk (in some countries); cereal; orange juice Lactose intolerance limits consumption of milk for some people; celiac disease limits consumption of cereal for some people Shittake mushrooms (sun-dried)91 Beneficial for those on a strict vegan diet Supplements Inexpensive (<5¢/d for 2000 international units of vitamin D3); vitamin D2 is ergocalciferol; vitamin D3 is cholecal-ciferol, which is 1.7 times as potent as ergocalciferol DISEASE DOSE OF VITAMIN D USED OR CHANGE IN LEVEL OF VITAMIN D RISK REDUCTION OR IMPROVEMENT COMMENTS Rickets111 Requires repletion therapy when diagnosed; usually prevented with VTD levels >25 nmol/L Complete resolution of symptoms and signs (except in cases of vitamin D resistance132) Adequate intake of calcium also needed Osteomalacia112 800 IU required; patients might need up to 2200 IU for up to a year Resolution of symptoms, including bone pain, especially in pelvis, lumbar spine, and ribs Psoriasis Topical VTD creams Plaque thickness and redness markedly improved by UVB and VTD analogues First-line therapy worldwide73 Multiple sclerosis44 400 IU/d 40% risk reduction Rheumatoid arthritis45 400 IU/d 40% risk reduction Type 1 diabetes38 2000 IU/d 80% risk reduction Type 2 diabetes4 VTD level raised from 25 to 75 nmol/L 63% improvement in insulin sensitivity Gestational diabetes and hypertension during pregnancy98 Individualized dosing to restore levels to >80 nmol/L Marked improvement in insulin sensitivity and insulin production Birth weight133 For each IU/d of VTD intake, birth weight increased Birth weight increased by 11 g/IU of VTD Osteogenesis imperfecta 6–8 IU/kg daily Correction of deficiency status Recommendation of the Kennedy Krieger Osteogenesis Imperfecta Clinic Polycystic ovary disease134 50 000 IU of VTD weekly or biweekly Normalized menstrual cycles in >50% of patients Very small study Premenstrual syndrome135 700 IU/d 40% reduction in risk of having symptoms Increased dietary calcium is known to decrease symptoms135 Colon cancer136–138 To achieve levels of 65-100 nmol/L 40%–80% risk reduction with supplement; rectal cancer reduced by 48%; exposure to sunlight reduced risk by 38%137 Increased dietary calcium is known to decrease risk, but benefit for >700 mg/d is minimal139 Cancer of the prostate140 Serum level of 25(OH)D =40– <60 nmol/L 50% risk reduction125 1 study suggests >80 nmol/L might increase risk141 Cancer of the pancreas142 300–450 IU/d compared with 150 IU/d 43% risk reduction 22% risk reduction Higher doses gave no further protection142 Cancer of the breast >50 nmol/L compared with 50 nmol/L 50%–70% risk reduction143 Sun exposure reduces mortality144 Cancer of the ovary144,145 Exposure to sunlight 16% risk reduction; risk is 5 times higher among those living farther north in the United States Despite these studies, more information is needed Upper respiratory tract infections48 600–700 IU given as cod-liver oil 50% risk reduction Also given selenium and omega-3 fatty acids Lower respiratory tract infections49 Children with levels <25 nmol/L 11 times more likely to be infected Seasonal influenza77 Levels as high as 125 nmol/L have been suggested Immune function improved in various immune cells Clinical trials needed Mycobacterium tuberculosis78 To restore levels to normal physiologic levels, >100 nmol/L are suggested Increased production of macrophages’ antimicrobial peptide cathelicidin kills Mycobacterium tuberculosis Clinical trials needed Idiopathic back pain35 Restoring levels from <25–>80 nmol/L 100% of deficient patients had pain resolve using 5000 IU/d of VTD 340 patients (85%) had deficient levels of 25(OH)D Nonspecific chronic musculoskeletal pain117 Restoring levels from 21 nmol/L to normal levels 67% of patients had complete resolution of symptoms Diagnosis prior to VTD deficiency was somatization Reduced tooth loss in the elderly 400–600 IU of VTD and 1000 mg of calcium 50% improvement in tooth retention over 2 y Effect of VTD not assessed independently50 25(OH)D—25-hydroxyergocalciferol, IU—international units, UVB—ultraviolet B, VTD—vitamin D.
- Table 8 Source and dose of vitamin D, side effects, and potential toxicity:
Reported side effects of vitamin D include nausea, vomiting, headache, metallic taste, vascular or nephrocalcinosis, and pancreatitis. Reported contraindications to vitamin D include hypercalcemia in sarcoidosis; metastatic bone disease148; other granulomatous diseases, such as tuberculosis and Crohn disease (active phase) that have disordered vitamin D metabolism in activated macrophages149; and Williams syndrome150 (infantile hypercalcemia).
SOURCE AND DOSE OF VITAMIN D* SIDE EFFECT OR TOXICITY COMMENTS Maximum sun exposure No known vitamin D toxicity, but too much exposure to UVB (burns) results in increased risk of skin cancer 10 000 IU (oral equivalent easily achieved with full-body exposure and results in levels of 148–163 nmol/L); in lifeguards exposed to the sun, kidney stones are more common151 About 10 to 15 min of sun exposure of hands and arms midday when sun is overhead needed to achieve daily requirement (about 400 IU) No known side effects; too much exposure to UVB (burns) results in increased risk of skin cancer Dark skin requires 4 times as much sun exposure to get the same dose Use of 2000 IU in African Americans (after 1 y) No known side effects Failed to achieve a level of 80 nmol/L in 40% of patients53 Use of 4000 IU for 6 mo Improved mood the only side effect noted Average level of 25-hydroxyvitamin D was 110 nmol/L,51 a level seen with adequate sun exposure; no increase in serum calcium noted 4000 IU for 3 mo No notable side effects52 Use of vitamin D2 (synthetic analogue) Several metabolites with unknown side effects Toxicity reported using higher levels152,153 UVB—ultraviolet B.
↵* Vitamin D3 unless specified.
In this issue
Jump to section
- Article
- Abstract
- Quality of evidence
- Background
- Assessing VTD status
- Prevalence of VTD insufficiency or deficiency
- Etiology of VTD deficiency and insufficiency
- Classic effects of VTD insufficiency or deficiency on disease
- Effects of insufficiency or deficiency on other disease states
- Sources of VTD
- Treatment of VTD insufficiency and deficiency
- Conclusion
- Notes
- Footnotes
- References
- Figures & Data
- eLetters
- Info & Metrics
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