Vitamin D With or Without Calcium Supplementation for Prevention of Cancer and Fractures: An Updated Meta-analysis for the U.S. Preventive Services Task Force

Chung, Mei; Lee, Jounghee; Terasawa, Teruhiko; Lau, Joseph; Trikalinos, Thomas A

doi:10.7326/0003-4819-155-12-201112200-00005

Cited by 366 publications

(255 citation statements)

References 95 publications

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“…25,27,28 When vitamin D was combined with calcium, the RR reductions were significant for total or nonvertebral fracture [25][26][27][28][29] and hip fractures, 25,28 with two results non-significant for hip fractures. 26,29 Two of the systematic reviews 26,29 found that higher doses of vitamin D (>400 IU or a median dose of 800 IU) resulted in better and statistically significant RR reductions for nonvertebral and hip fractures.…”

Section: Systematic Reviews/meta-analysesmentioning

confidence: 99%

Vitamin D: A Narrative Review Examining the Evidence for Ten Beliefs

Allan

Cranston²,

Lindblad

et al. 2016

J GEN INTERN MED

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Over the past decade, a large body of observational evidence has suggested an association between lower vitamin D status (25-hydroxyvitamin D) and multiple acute and chronic disorders, including cancer, multiple sclerosis, depression and respiratory tract infections. This evidence has fostered the hypothesis that increasing vitamin D intake may treat and prevent such disorders. Our objective was to perform a critical analysis of the highestlevel evidence for ten common beliefs regarding vitamin D for the prevention of falls, fractures and respiratory tract infections, the reduction of cancer incidence/mortality and overall mortality, and the prevention or treatment of depression/mental well-being, rheumatoid arthritis and multiple sclerosis, as well as maximum dosing and regular testing. We searched the Cochrane Database of Systematic Reviews and PubMed (up to August 2014) for randomized controlled trials and systematic reviews/ meta-analyses based on those studies. All searches were performed, all evidence reviewed and each section written by at least two authors. The evidence shows that vitamin D supplementation provides some benefit in fracture prevention (likely ∼10-15 % relative reduction), particularly at a dose ≥800 IU and with calcium; a likely benefit in the rate of falls, though it is less clear whether the number of fallers changes; and a possible small (∼5 %) relative reduction in mortality. Evidence does not support the use of vitamin D supplementation for the prevention of cancer, respiratory infections or rheumatoid arthritis. Similarly, evidence does not support vitamin D supplementation for the treatment of multiple sclerosis and rheumatoid arthritis or for improving depression/mental well-being. Regular testing of 25-hydroxyvitamin D is generally not required, and mega-doses (≥300,000 IU) appear to increase harms. Much of the evidence is at high risk of bias, with multiple flaws, including analyses of secondary endpoints, small and underpowered studies, inconsistent results and numerous other issues. Therefore, enthusiasm for a vitamin D panacea should be tempered.

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Section: Systematic Reviews/meta-analysesmentioning

confidence: 99%

Vitamin D: A Narrative Review Examining the Evidence for Ten Beliefs

Allan

Cranston²,

Lindblad

et al. 2016

J GEN INTERN MED

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“…In other cohort studies (Cawthon et al, 2010;Eaton et al, 2011;Hutchinson et al, 2010;Melamed et al, 2008), either no association or an inverse association between 25(OH)D concentration and risk for mortality from cancer was reported. A meta-analysis of observational studies published up to July 2011 showed no association between 25(OH)D concentration and breast cancer (five studies) or prostate cancer (11 studies), and an inverse association with colorectal cancer (nine studies) (Chung et al, 2011). In RCTs using vitamin D doses between 10 and 27.5 µg/day and lasting four to seven years in which cancer of the breast or colon were secondary outcomes, there was no evidence of an increased cancer risk in subjects receiving vitamin D (Chlebowski et al, 2008;Lappe et al, 2007;Wactawski-Wende et al, 2006).…”

Section: Vitamin D Intake or Status And Long-term Health Outcomes In mentioning

confidence: 99%

Untitled

2012

EFSA Journal

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Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to re-evaluate the safety in use of vitamin D and to provide, if necessary, revised Tolerable Upper Intake Levels (ULs) of vitamin D for all relevant population groups. The ULs for adults including pregnant and lactating women, children and adolescents were revised. For adults, hypercalcaemia was selected as the indicator of toxicity. In two studies in men, intakes between 234 and 275 µg/day were not associated with hypercalcaemia, and a no observed adverse effect level (NOAEL) of 250 µg/day was established. Taking into account uncertainties associated with these studies, the UL for adults including pregnant and lactating women was set at 100 µg/day. Despite a continuing paucity of data for high vitamin D intakes in children and adolescents, the UL was adapted to 100 µg/day for ages 11-17 years, considering that owing to phases of rapid bone formation and growth this age group is unlikely to have a lower tolerance for vitamin D compared to adults. The same applies also to children aged 1-10 years, but taking into account their smaller body size, a UL of 50 µg/day is proposed. For infants, the UL of 25 µg/day based on previously available data relating high vitamin D intakes to impaired growth and hypercalcaemia was retained as limited additional evidence has emerged since the previous risk assessment. Data Hypercalciuria can be associated with hypercalcaemia, but it can also occur without.For the derivation of the UL, the occurrence of hypercalcaemia and hypercalciuria has been assessed in studies using daily or weekly supplementation of vitamin D for several weeks to months. The shorter-term studies were generally performed in seasons of low sun exposure. Study populations were not generally vitamin D-deficient, and two studies were conducted in subjects with a high vitamin D status at baseline. Study populations included whites, African Americans, young men, preand postmenopausal women, elderly nursing home residents, and overweight and obese adults. It was concluded that vitamin D at doses up to 275 µg/day does not lead to persisting hypercalcaemia or hypercalciuria in adults.Long-term health outcomes (all-cause mortality, cardiovascular disease, cancer, fractures and kidney stones) were also considered, but no studies reported an association between vitamin D intake and increased risk for adverse long-term health outcomes. Studies reporting on an association between 25(OH)D concentration and all-cause mortality or cancer were inconsistent. When 25(OH)D concentrations were associated with an increased risk for adverse long-term health outcomes in some studies, there was a wide variation in 25(OH)D concentrations associated with the adverse effect. It was considered that 25(OH)D concentrations cannot be used to characterise the risk for adverse long-term health outcomes.In adults, a daily vitamin D dose of 250 µg/day (range 234-275 µg/day) was considered to reflect a no observed adverse...

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“…Observational data suggest that inadequate vitamin D status is associated with an increased risk of fracture, cancer, and other chronic diseases (1)(2)(3)(4). Although the definition of an adequate serum concentration remains controversial (12 ng/mL) (5,6), it has been argued that one-quarter of Americans have inadequate serum concentrations of 25- (12)(13)(14)(15)(16)(17)(18)(19)(20) ng/mL), and 8% are deficient (<12 ng/mL) (7,8).…”

Section: Introductionmentioning

confidence: 99%