Vitamin D supplementation for prevention of cancer in adults
Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Krstic G, Wetterslev J, Gluud C
The Cochrane database of systematic reviews · 117 citas
Etiquetas de revisión
Financiación no declaradaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2014-06-23 · Cochrane Database Syst Rev · vol. 2014 · número 6 · pág. CD007469
- Editorial
- Elsevier BV
- Citado
- 212 citas · más que el 100% de estudios similares · 17.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 282 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Vitamin D Research Studies · Nutritional Studies and Diet · Nutrition and Health Studies
- Palabras clave
- vitamin D supplementation, cancer prevention, vitamin D3, vitamin D2, 1,25-dihydroxyvitamin D3, alfacalcidol, cancer incidence, risk of bias, trial sequential analysis, futility, adverse effects, vitamin D deficiency, healthy adults, older women
- MeSH
- humans, neoplasms, cholecalciferol, hydroxycholecalciferols, calcitriol, vitamins, vitamin d, dietary supplements, aged, middle aged, female, male, randomized controlled trials as topic
7 autores
- Goran Bjelaković🇷🇸🇩🇰🇨🇦University of Nis; Copenhagen University Hospital; Rigshospitalet; Cochrane; Cochrane
- Lise Lotte Gluud🇩🇰Hvidovre Hospital; Copenhagen University Hospital
- Dimitrinka Nikolova🇩🇰🇨🇦Copenhagen University Hospital; Rigshospitalet; Cochrane; Cochrane
- Kate Whitfield🇩🇰Copenhagen University Hospital; Rigshospitalet
- Goran Krstic🇨🇦Fraser Health
- Jørn Wetterslev🇩🇰Copenhagen University Hospital; Rigshospitalet
- Christian Nyfeldt Gluud🇩🇰🇨🇦Copenhagen University Hospital; Rigshospitalet; Cochrane; Cochrane
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory.
Objectives
To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded, and the Conference Proceedings Citation Index-Science to February 2014. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials.
Selection criteria
We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population, or diagnosed with a specific disease. Vitamin D could have been administered as supplemental vitamin D (vitamin D₃ (cholecalciferol) or vitamin D₂ (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), or 1,25-dihydroxyvitamin D (calcitriol)).
Data collection and analysis
Two review authors extracted data independently. We conducted random-effects and fixed-effect model meta-analyses. For dichotomous outcomes, we calculated the risk ratios (RRs). We considered risk of bias in order to assess the risk of systematic errors. We conducted trial sequential analyses to assess the risk of random errors.
Main results
Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the GRADE instrument). Trial sequential analysis (TSA) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias; of trials assessing primary prevention compared to trials assessing secondary prevention; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry; or of trials using concomitant calcium supplementation compared to trials without calcium. Vitamin D decreased all-cause mortality (1854/24,846 (7.5%) versus 2007/25,020 (8.0%); RR 0.93 (95% CI 0.88 to 0.98); P = 0.009; I² = 0%; 15 trials; 49,866 participants; moderate quality evidence), but TSA indicates that this finding could be due to random errors. Cancer occurrence was observed in 1918/24,908 (7.7%) recipients of vitamin D₃ versus 1933/24,983 (7.7%) in recipients of control interventions (RR 1.00 (95% CI 0.94 to 1.06); P = 0.88; I² = 0%; 14 trials; 49,891 participants; moderate quality evidence). TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. Vitamin D₃ decreased cancer mortality (558/22,286 (2.5%) versus 634/22,206 (2.8%); RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I² = 0%; 4 trials; 44,492 participants; low quality evidence), but TSA indicates that this finding could be due to random errors. Vitamin D₃ combined with calcium increased nephrolithiasis (RR 1.17 (95% CI 1.03 to 1.34); P = 0.02; I² = 0%; 3 trials; 42,753 participants; moderate quality evidence). TSA, however, indicates that this finding could be due to random errors. We did not find any data on health-related quality of life or health economics in the randomised trials included in this review.
Authors' conclusions
There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality, but these estimates are at risk of type I errors due to the fact that too few participants were examined, and to risks of attrition bias originating from substantial dropout of participants. Combined vitamin D₃ and calcium supplements increased nephrolithiasis, whereas it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. We need more trials on vitamin D supplementation, assessing the benefits and harms among younger participants, men, and people with low vitamin D status, and assessing longer duration of treatments as well as higher dosages of vitamin D. Follow-up of all participants is necessary to reduce attrition bias.
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