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Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors.
Kim, H, Lipsyc-Sharf, M, Zong, X, Wang, X, Hur, J, Song, M, Wang, M, Smith-Warner, SA, Fuchs, C, Ogino, S, et al
Gastroenterology. 2021;(4):1208-1217.e9
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Abstract
BACKGROUND & AIMS Vitamin D has been implicated in colorectal cancer (CRC) pathogenesis, but it remains unknown whether total vitamin D intake is associated with early-onset CRC and precursors diagnosed before age 50. METHODS We prospectively examined the association between total vitamin D intake and risks of early-onset CRC and precursors among women enrolled in the Nurses' Health Study II. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for early-onset CRC were estimated with Cox proportional hazards model. Multivariable-adjusted odds ratios (ORs) and 95% CIs for early-onset conventional adenoma and serrated polyp were estimated with logistic regression model. RESULTS We documented 111 incident cases of early-onset CRC during 1,250,560 person-years of follow-up (1991 to 2015). Higher total vitamin D intake was significantly associated with a reduced risk of early-onset CRC (HR for ≥450 IU/day vs <300 IU/day, 0.49; 95% CI, 0.26-0.93; P for trend = .01). The HR per 400 IU/day increase was 0.46 (95% CI, 0.26-0.83). The inverse association was significant and appeared more evident for dietary sources of vitamin D (HR per 400 IU/day increase, 0.34; 95% CI, 0.15-0.79) than supplemental vitamin D (HR per 400 IU/day increase, 0.77; 95% CI, 0.37-1.62). For CRC precursors, the ORs per 400 IU/day increase were 0.76 (95% CI, 0.65-0.88) for conventional adenoma (n = 1,439) and 0.85 (95% CI, 0.75-0.97) for serrated polyp (n = 1,878). CONCLUSIONS In a cohort of younger women, higher total vitamin D intake was associated with decreased risks of early-onset CRC and precursors.
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Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial.
Chandler, PD, Chen, WY, Ajala, ON, Hazra, A, Cook, N, Bubes, V, Lee, IM, Giovannucci, EL, Willett, W, Buring, JE, et al
JAMA network open. 2020;(11):e2025850
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Abstract
IMPORTANCE Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways. OBJECTIVE To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index. DESIGN, SETTING, AND PARTICIPANTS VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017. INTERVENTIONS Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements. MAIN OUTCOMES AND MEASURES For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations. RESULTS Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01169259.
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Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.
McCullough, ML, Zoltick, ES, Weinstein, SJ, Fedirko, V, Wang, M, Cook, NR, Eliassen, AH, Zeleniuch-Jacquotte, A, Agnoli, C, Albanes, D, et al
Journal of the National Cancer Institute. 2019;(2):158-169
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BACKGROUND Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. CONCLUSIONS Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.
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Supplemental Vitamins and Minerals for CVD Prevention and Treatment.
Jenkins, DJA, Spence, JD, Giovannucci, EL, Kim, YI, Josse, R, Vieth, R, Blanco Mejia, S, Viguiliouk, E, Nishi, S, Sahye-Pudaruth, S, et al
Journal of the American College of Cardiology. 2018;(22):2570-2584
Abstract
The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.
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Effect of multivitamin supplementation on measles vaccine response among HIV-exposed uninfected Tanzanian infants.
Sudfeld, CR, Duggan, C, Histed, A, Manji, KP, Meydani, SN, Aboud, S, Wang, M, Giovannucci, EL, Fawzi, WW
Clinical and vaccine immunology : CVI. 2013;(8):1123-32
Abstract
Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/μl than for infants whose mothers had a CD4 T-cell count of >350 cells/μl (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/μl were associated with decreased avidity compared to counts of >350 cells/μl (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.).