Table 1

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

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.