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