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Research ArticleClinical Review

Not enough vitamin D

Health consequences for Canadians

Gerry Schwalfenberg
Canadian Family Physician May 2007; 53 (5) 841-854;
Gerry Schwalfenberg
Clinical lecturer in the Department of Family Medicine at the University of Alberta in Edmonton
MD CCFP
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  • For correspondence: schwalfe@ualberta.ca
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    Figure 1

    Physiologic actions and potential benefits of vitamin D: References are listed in Tables 1,3, and 7.

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    Table 1

    Articles reviewed, number of subjects, design, outcomes, and comments

    STUDYNDESIGNOUTCOMECOMMENTS
    Krejs et al110Intestinal perfusion study before and after administration of VTDCalcium and magnesium absorption increased 2%– 300% from baselineNone
    Zittermann et al268: 34 controls, 34 patients with congestive heart failureCase-control studyWith lower VTD levels (P < .001), PTH levels (P < .001) and inflammatory markers (P < .001) were raisedLower VTD levels were seen in patients with more severe congestive heart failure
    Latham et al32496Systematic reviewNS reduction in falls among patients receiving VTDNone
    Chui et al4126Univariate and multivariate regression analysisPositive 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 al5116Open-label treatment groups: 1000 IU VTD3, 10 000 IU VTD3, 50 000 IU VTD3Raised 25(OH)D levels by 29 nmol/L, 146 nmol/L, and 643 nmol/L, respectively8 weeks before steady state achieved
    Chapuy et al61569Population prevalence study (cross-sectional study) of VTD and PTH levelsParathyroid secretion initiated when serum 25(OH)D falls below 78 nmol/L14% of the population had wintertime levels <30 nmol/L
    Moussavi et al7318Population prevalence study (cross-sectional study) of VTD deficiency in Iran46.2% had levels <50 nmol/L (72.1% of women and 18.3% of men)95% of women had levels <80 nmol/L
    Rucker et al8188Population prevalence study (cross-sectional study) of VTD and PTH levels in western Canada97% of subjects had levels <80 nmol/L at some time during the year; levels were lower during fall, winter, and spring than during summer34% had levels <40 nmol/L sometime during the year; levels were taken 4 times yearly
    Pasco et al93280Cross-sectional study of seasonal periodicity of serum VTD, PTH, and fractures in AustraliaIn 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 al10160Cross-sectional study in Manitoba43% of children and 76% of mothers had levels <25 nmol/L70% of mothers drank no milk; 24% were intolerant of milk
    Waiters et al11121: 22 whites, 51 Inuit, 37 Native Canadians*Cross-sectional study of mothers and newborns in InuvikAverage 25(OH)D levels at time of delivery were 50.1 nmol/L in Natives and 59.8 nmol/L in non-NativesPlasma levels of 25(OH)D in newborns averaged only 67% of levels in mothers
    Vieth et al12796Cross-sectional study in Toronto, Ont, of women aged 18–35 y21% 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 monthsRecommended intake is too low to prevent VTD insufficiency and deficiency; deficiency could be determined only by laboratory tests, not by dietary history
    Roth et al1390Cross-sectional study in children presenting to a emergency department in Edmonton, Alta34% of patients had VTD levels <40 nmol/L, 6% had levels <25 nmol/L (deficiency)Levels taken at end of winter
    Thomas et al14290Cross-sectional study in consecutive medical inpatients57% 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 al15205: 106 inpatients, 99 outpatientsCross-sectional study in consecutive medical inpatients and outpatients70% 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/LInpatients were more deficient in VTD than outpatients
    Hochwald et al16296Cross-sectional study of consecutive medical inpatients in Israel26.27% of inpatients had levels <37.5 nmol/LEven in a sunny country, >25% of patients were deficient in VTD
    Lee et al1753Analysis of dietary intake in Canadian long-term care70% of nursing-home patients consumed inadequate amounts of VTD through diet aloneSupplementation is necessary in these settings
    Liu et al18155Cross-sectional study in Toronto; prevalence and seasonal variation in long-term care9% 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 al1935Cross-sectional study in internal medicine residents74% had VTD levels <50 nmol/L in spring compared with 26% in fall69% of residents took in <400 IU/d of VTD
    Holick et al201536Cross-sectional study of postmenopausal women in North AmericaSerum 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 al2111 023Systematic review of VTD status in postmenopausal women with osteoporosis50%–70% of women with a fracture had VTD levels <37.5 nmol/LHigh prevalence of low VTD levels in women with a history of fractures
    Matsuoka et al2240Randomized controlled trialVTD 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 al2314: 7 healthy, 7 with fat malabsorptionControlled trial. Intestinal absorption study before and after VTD radiolabeledAbsorption reduced from 60% in normal subjects to <18% (pancreatitis) in study subjects, 0% in those with bilary obstruction, and <50% in those with celiac diseaseVarious conditions involving malabsorption result in VTD insufficiency or deficiency
    Jones et al24209Double-blind, placebo-controlled study19% reduction in absorption of VTD in treated groupUnlikely to have substantial reduction with cutaneous production of VTD
    Binet and Kooh2517Case review in TorontoNative people* and immigrants at risk of VTD deficiencyRickets is still a public health issue
    Bischoff-Ferrari et al2619 114: 9294 in hip and other fracture trial, 9820 in non- vertebral fracture trialsMeta-analysis of randomized controlled trials of fracture preventionRR 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 al27389Randomized, double-blind, placebo-controlled studyPrevalence 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 al28583Multicentre, randomized, double- masked, placebo-controlled confirmatory studyPrevalence 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 al293314Randomized controlled trial of primary preventionNo evidence that calcium and VTD reduced fractures in community-dwelling older womenOnly 63% of subjects were taking the supplements at 12 mo (poor compliance); no baseline or follow-up VTD levels taken
    Grant et al305292Randomized, placebo-controlled trial of secondary fracture preventionNo 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 groupOnly 60% had compliance rates of >80% of tablets taken; only 60 patients had baseline and follow-up 25(OH)D levels taken
    Dhesi et al31139Randomized, double-blind, placebo-controlled studyWith 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 al321237, 5 trials reviewedMeta-analysis of double-blind, randomized controlled trialsVTD reduced risk of falling by 22%Number needed to treat was 15 to prevent 1 fall
    Bischoff-Ferrari et al334100Cross-sectional, population-based survey2.5-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 levelsIn ambulatory patients, active or inactive concentrations of 40–94 nmol/L of 25(OH)D resulted in better lower- extremity musculoskeletal function
    Sato et al3496Randomized placebo-controlled trial1000 IU of VTD2 resulted in 59% reduction in falls (P = .049) in patients with long-standing strokeVTD levels were deficient with 25(OH)D levels <25 nmol/L
    Al Faraj and Al Mutairi35341Cross-sectional interventional study299 (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 normalIn 299 patients, VTD levels were clearly deficient; very high doses were used for repletion therapy with no side effects
    Al-Allaf et al3687Case-control study25(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 Quigley37150Cross-sectional population study93% of patients with persistent nonspecific musculoskeletal pain had 25(OH)D levels <30 nmol/LOsteomalacia is a known cause of nonspecific musculoskeletal pain
    Hyppönen et al3810 821Study of children given 2000 IU of VTD supplementsRegular supplementation resulted in a 78% reduction in risk of developing type 1 diabetes later in lifeA subset receiving supplementation with >2000 IU of VTD had an 86% RR39
    Pfiefer et al40148Randomized placebo-controlled trial of blood-pressure therapy supplementing with VTD800 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 al41124Randomized controlled trial; comparison of 200 and 500 IU of VTDC-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 al42216 313Summary of 3 large prospective cohort studiesHigher VTD intake was not associated with lower risk of incident hypertensionPatients followed up for 8 years
    Garland et al43UnstatedSummary of 63 epidemiologic studies: 30 of colon cancer, 13 of breast cancer, 26 of prostate cancer, and 7 of ovarian cancer25(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/LNo studies showed an increase in cancer rates with VTD, but some showed no effect
    Munger et al44187 563Summary of 2 prospective cohort studiesSupplementation with =400 IU of VTD resulted in a 41% decrease in incidence of multiple sclerosisDietary intake of VTD resulted in a lower reduction of 33%
    Merlino et al4529 368Prospective cohort studySupplementation with =400 IU of VTD resulted in a 36% decrease in incidence of rheumatoid arthritisDietary intake resulted in a slightly lower reduction of 28%
    Berwick et al46528Population-based study of cutaneous melanomaIntermittent sun exposure was associated with increased survival in melanoma patientsAntiproliferative effect of VTD
    Kennedy et al47966Cohort case-control studyPainful sunburn early in life increased melanoma, squamous cell carcinoma, and especially actinic keratosisLifelong moderate sun exposure decreased risk of melanoma
    Linday et al4894Case-control studySupplement 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 al49150Case-control studyLow 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 al50145Randomized controlled trial using calcium and VTD supplements13% of patients taking supplements lost teeth compared with 27% of patients not taking supplementsVTD was not independently related to risk of losing teeth
    Vieth et al5164Randomized 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 mood6-mo trials
    Vieth et al5261Randomized comparison control study; 1000 vs 4000 IU of VTD supplementation for 3 moAverage 25(OH)D levels were 68.7 nmol/L and 96.4 nmol/L, respectively, after 3 moNS changes in serum calcium and urinary calcium excretion in patients taking high doses
    Aloia et al53208Randomized controlled trial in 50- to 70-year-old African- American womenOnly 60% of women treated with 2000 IU of VTD daily achieved normal 25(OH)D levels after a year87% 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.

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    Table 2

    Canadian recommendations for adequate intake of vitamin D: 1975 to 2007.

    AGE1975–1983 IU1990 IU1997 IU1997–2007 IU
    0–12 mo100200200400*
    1–50 y100200200200
    51–70 y100200400800†
    =71 y100200600800†
    • Data derived from Committee for the Revision of Dietary Standards in Canada,54,55 Scientific Review Committee,56 and Institute of Medicine.57

    • ↵* Recommended by the Canadian Paediatric Society.

    • ↵† Recommended by the Canadian Osteoporosis Society for patients at risk of osteoporosis.

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    Table 3

    Studies of functions of vitamin D

    ORGAN OR SYSTEMEFFECT OF SUFFICIENT VITAMIN DEFFECT OF INSUFFICIENT OR DEFICIENT LEVELS OF VITAMIN DOPTIMAL VITAMIN D INTAKE FOR HEALTH
    Jejunum and ileumIncreases absorption of calcium and magnesium to 30%1Absorption 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
    BoneMaintains calcium and phosphate homeostasis and is required for proper mineralization59Rickets or osteomalacia;62 short- latency diseaseRickets and osteomalacia are prevented when VTD levels are >25 nmol/L67
    ParathyroidRegulates calcium and phosphate levels, controls conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D59Parathyroid hormone excretion increases as levels of VTD decrease resulting in secondary hyperparathyroidism, which in turn results in resorption of calcium from bone and exacerbates osteoporosisParathyroid 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 VDRInhibition 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 system68Might contribute to congestive heart failure2,69; deficiency results in loss of calciotropic effect in long- latency diseaseCurrently unknown, but 2000–4000 IU of vitamin D3 are being suggested70
    Muscle via VDRModulates calcium transport, protein synthesis, and kinetics of muscle contraction71Muscle weakness, limb pain, and impaired physical function72; loss of calciotropic effectMaximum neuromuscular performance achieved with VTD levels of 125 nmol/L33
    Skin via VDRProduction of calcitrol that regulates cellular function in keratocytesAntiproliferative, immunosuppressive, and prodifferentiating effectsVTD analogues are used for psoriasis73
    Islet cells via VDRImprovement in insulin sensitivity4Negative effect on beta cell function with reduced insulin secretion; loss of immune modulatory effectRaising VTD levels from 25 to 75 nmol/L improves sensitivity by 60%; optimal level has not been determined
    Certain cancer cell types mediated via VDRSuppressed growth and increased apoptosis74,75; stabilized chromosomal structure and prevented DNA breakdown76Loss of antiproliferative effectOptimal level undetermined
    Immune system modulatorStimulated expression of potent anti- microbial peptides, increased “oxidative burst” potential of macrophages77Increased susceptibility to influenza77 and tuberculosis78Optimal level undetermined; summer levels of 125 nmol/L likely required77
    Innate immune functionIncreased production of cathelicidins effective against Escherichia coli, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and CandidaDecreased wound barrier functionOptimal dose undetermined79–82
    • VTD—vitamin D, VDR—vitamin D receptor.

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    Table 4

    Assessment of vitamin D levels

    ASSAYMEASUREMENTCOMMENTS
    RadioimmunoassayUses antibodies that recognize both 25(OH)D3 and 25(OH)D2Most 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 assayReagent separates VTD from binding proteinsOften 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.

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    Table 5

    Risk factors for low serum vitamin D levels

    RISK FACTORSREASON
    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 skinFor various religious or cultural reasons
    Inadequate dietary intakeLimited 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
    ObesityIrreversible sequestration of VTD in the fat pool, especially if body mass index is >30 and person does little outdoor activity94
    Exclusive breastfeedingBreast milk is low in VTD10,95; supplementing with 4000 IU of VTD has been shown to achieve adequate levels in both mother and child96
    PregnancyAdequate 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 conditionsMalabsorption 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 VTDSome 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.

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    Table 6

    Sources of vitamin D

    SOURCERISKS AND BENEFITS
    SunExposure has never been known to cause toxicity; however, risk of skin cancer increases with exposure47
    Oily fish or fish oilsHigh 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 juiceLactose intolerance limits consumption of milk for some people; celiac disease limits consumption of cereal for some people
    Shittake mushrooms (sun-dried)91Beneficial for those on a strict vegan diet
    SupplementsInexpensive (<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
    • View popup
    Table 7

    Benefits of vitamin D for various diseases, dosages, and comments

    DISEASEDOSE OF VITAMIN D USED OR CHANGE IN LEVEL OF VITAMIN DRISK REDUCTION OR IMPROVEMENTCOMMENTS
    Rickets111Requires repletion therapy when diagnosed; usually prevented with VTD levels >25 nmol/LComplete resolution of symptoms and signs (except in cases of vitamin D resistance132)Adequate intake of calcium also needed
    Osteomalacia112800 IU required; patients might need up to 2200 IU for up to a yearResolution of symptoms, including bone pain, especially in pelvis, lumbar spine, and ribs
    PsoriasisTopical VTD creamsPlaque thickness and redness markedly improved by UVB and VTD analoguesFirst-line therapy worldwide73
    Multiple sclerosis44400 IU/d40% risk reduction
    Rheumatoid arthritis45400 IU/d40% risk reduction
    Type 1 diabetes382000 IU/d80% risk reduction
    Type 2 diabetes4VTD level raised from 25 to 75 nmol/L63% improvement in insulin sensitivity
    Gestational diabetes and hypertension during pregnancy98Individualized dosing to restore levels to >80 nmol/LMarked improvement in insulin sensitivity and insulin production
    Birth weight133For each IU/d of VTD intake, birth weight increasedBirth weight increased by 11 g/IU of VTD
    Osteogenesis imperfecta6–8 IU/kg dailyCorrection of deficiency statusRecommendation of the Kennedy Krieger Osteogenesis Imperfecta Clinic
    Polycystic ovary disease13450 000 IU of VTD weekly or biweeklyNormalized menstrual cycles in >50% of patientsVery small study
    Premenstrual syndrome135700 IU/d40% reduction in risk of having symptomsIncreased dietary calcium is known to decrease symptoms135
    Colon cancer136–138To achieve levels of 65-100 nmol/L40%–80% risk reduction with supplement; rectal cancer reduced by 48%; exposure to sunlight reduced risk by 38%137Increased dietary calcium is known to decrease risk, but benefit for >700 mg/d is minimal139
    Cancer of the prostate140Serum level of 25(OH)D =40– <60 nmol/L50% risk reduction1251 study suggests >80 nmol/L might increase risk141
    Cancer of the pancreas142300–450 IU/d compared with 150 IU/d43% risk reduction 22% risk reductionHigher doses gave no further protection142
    Cancer of the breast>50 nmol/L compared with 50 nmol/L50%–70% risk reduction143Sun exposure reduces mortality144
    Cancer of the ovary144,145Exposure to sunlight16% risk reduction; risk is 5 times higher among those living farther north in the United StatesDespite these studies, more information is needed
    Upper respiratory tract infections48600–700 IU given as cod-liver oil50% risk reductionAlso given selenium and omega-3 fatty acids
    Lower respiratory tract infections49Children with levels <25 nmol/L11 times more likely to be infected
    Seasonal influenza77Levels as high as 125 nmol/L have been suggestedImmune function improved in various immune cellsClinical trials needed
    Mycobacterium tuberculosis78To restore levels to normal physiologic levels, >100 nmol/L are suggestedIncreased production of macrophages’ antimicrobial peptide cathelicidin kills Mycobacterium tuberculosisClinical trials needed
    Idiopathic back pain35Restoring levels from <25–>80 nmol/L100% of deficient patients had pain resolve using 5000 IU/d of VTD340 patients (85%) had deficient levels of 25(OH)D
    Nonspecific chronic musculoskeletal pain117Restoring levels from 21 nmol/L to normal levels67% of patients had complete resolution of symptomsDiagnosis prior to VTD deficiency was somatization
    Reduced tooth loss in the elderly400–600 IU of VTD and 1000 mg of calcium50% improvement in tooth retention over 2 yEffect of VTD not assessed independently50
    • 25(OH)D—25-hydroxyergocalciferol, IU—international units, UVB—ultraviolet B, VTD—vitamin D.

    • View popup
    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 TOXICITYCOMMENTS
    Maximum sun exposureNo known vitamin D toxicity, but too much exposure to UVB (burns) results in increased risk of skin cancer10 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 cancerDark 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 effectsFailed to achieve a level of 80 nmol/L in 40% of patients53
    Use of 4000 IU for 6 moImproved mood the only side effect notedAverage 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 moNo notable side effects52
    Use of vitamin D2 (synthetic analogue)Several metabolites with unknown side effectsToxicity reported using higher levels152,153
    • UVB—ultraviolet B.

    • ↵* Vitamin D3 unless specified.

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Canadian Family Physician: 53 (5)
Canadian Family Physician
Vol. 53, Issue 5
1 May 2007
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Canadian Family Physician May 2007, 53 (5) 841-854;

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    • 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
  • PDF

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