Effect of Vitamin D and calcium supplementation on cancer incidence in older women: A randomized clinical trial

Joan M. Lappe, Patrice Watson, Dianne Travers-Gustafson, Robert R. Recker, Cedric Garland, Edward Gorham, Keith Baggerly, Sharon L. McDonnell

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE Evidence suggests that low vitamin D status may increase the risk of cancer. OBJECTIVE To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women. DESIGN, SETTING, AND PARTICIPANTS A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015 - the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years. INTERVENTIONS The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500mg/d of calcium; the placebo group received identical placebos. MAIN OUTCOMES AND MEASURES The primary outcomewas the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95%CI, -0.06%to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95%CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95%CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95%CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group). CONCLUSIONS AND RELEVANCE Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.

Original languageEnglish (US)
Pages (from-to)1234-1243
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume317
Issue number12
DOIs
StatePublished - Mar 28 2017

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Cholecalciferol
Vitamin D
Randomized Controlled Trials
Placebos
Calcium
Incidence
Neoplasms
Serum
Kidney Calculi
Kaplan-Meier Estimate
Skin Neoplasms
Survival Analysis
Dietary Supplements
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Effect of Vitamin D and calcium supplementation on cancer incidence in older women : A randomized clinical trial. / Lappe, Joan M.; Watson, Patrice; Travers-Gustafson, Dianne; Recker, Robert R.; Garland, Cedric; Gorham, Edward; Baggerly, Keith; McDonnell, Sharon L.

In: JAMA - Journal of the American Medical Association, Vol. 317, No. 12, 28.03.2017, p. 1234-1243.

Research output: Contribution to journalArticle

Lappe, Joan M. ; Watson, Patrice ; Travers-Gustafson, Dianne ; Recker, Robert R. ; Garland, Cedric ; Gorham, Edward ; Baggerly, Keith ; McDonnell, Sharon L. / Effect of Vitamin D and calcium supplementation on cancer incidence in older women : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 317, No. 12. pp. 1234-1243.
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abstract = "IMPORTANCE Evidence suggests that low vitamin D status may increase the risk of cancer. OBJECTIVE To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women. DESIGN, SETTING, AND PARTICIPANTS A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015 - the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years. INTERVENTIONS The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500mg/d of calcium; the placebo group received identical placebos. MAIN OUTCOMES AND MEASURES The primary outcomewas the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90{\%}) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89{\%}) in the vitamin D3 + calcium group and 64 (5.58{\%}) in the placebo group (difference, 1.69{\%} [95{\%}CI, -0.06{\%}to 3.46{\%}]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95{\%}CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95{\%}CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95{\%}CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group). CONCLUSIONS AND RELEVANCE Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.",
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T1 - Effect of Vitamin D and calcium supplementation on cancer incidence in older women

T2 - A randomized clinical trial

AU - Lappe, Joan M.

AU - Watson, Patrice

AU - Travers-Gustafson, Dianne

AU - Recker, Robert R.

AU - Garland, Cedric

AU - Gorham, Edward

AU - Baggerly, Keith

AU - McDonnell, Sharon L.

PY - 2017/3/28

Y1 - 2017/3/28

N2 - IMPORTANCE Evidence suggests that low vitamin D status may increase the risk of cancer. OBJECTIVE To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women. DESIGN, SETTING, AND PARTICIPANTS A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015 - the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years. INTERVENTIONS The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500mg/d of calcium; the placebo group received identical placebos. MAIN OUTCOMES AND MEASURES The primary outcomewas the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95%CI, -0.06%to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95%CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95%CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95%CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group). CONCLUSIONS AND RELEVANCE Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.

AB - IMPORTANCE Evidence suggests that low vitamin D status may increase the risk of cancer. OBJECTIVE To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women. DESIGN, SETTING, AND PARTICIPANTS A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015 - the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years. INTERVENTIONS The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500mg/d of calcium; the placebo group received identical placebos. MAIN OUTCOMES AND MEASURES The primary outcomewas the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling. RESULTS Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95%CI, -0.06%to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95%CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95%CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95%CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group). CONCLUSIONS AND RELEVANCE Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.

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