Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol

Gina L Ambrosini, Helman Alfonso, Alison Reid, Dorothy Mackerras, Alexandra Bremner, John Beilby, Nola Olsen, Arthur Musk, Nicholas de Klerk

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007.

Methods:
Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5mg RE/d) or beta-carotene (30mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models.

Results:
Over a median follow-up of 7.8y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86?mol/L; 95% confidence interval [CI], 0.65-1.14) or osteoporotic fracture (HR, 0.97?mol/L; 95% CI, 0.66-1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85?mol/L; 95% CI, 0.71-1.01).

Conclusions: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation. � 2014 Elsevier Inc.
Original languageEnglish
Pages (from-to)551-556
Number of pages6
JournalNutrition
Volume30
Issue number5
DOIs
Publication statusPublished - May 2014

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Carotenoids
Vitamin A
Osteoporotic Fractures
beta Carotene
Confidence Intervals
Observational Studies
Ambulatory Care
Proportional Hazards Models
Self Report
Life Style

Cite this

Ambrosini, G. L., Alfonso, H., Reid, A., Mackerras, D., Bremner, A., Beilby, J., ... de Klerk, N. (2014). Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol. Nutrition, 30(5), 551-556. https://doi.org/10.1016/j.nut.2013.10.007
Ambrosini, Gina L ; Alfonso, Helman ; Reid, Alison ; Mackerras, Dorothy ; Bremner, Alexandra ; Beilby, John ; Olsen, Nola ; Musk, Arthur ; de Klerk, Nicholas. / Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol. In: Nutrition. 2014 ; Vol. 30, No. 5. pp. 551-556.
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abstract = "Objective: Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. Methods: Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5mg RE/d) or beta-carotene (30mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models. Results: Over a median follow-up of 7.8y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86?mol/L; 95{\%} confidence interval [CI], 0.65-1.14) or osteoporotic fracture (HR, 0.97?mol/L; 95{\%} CI, 0.66-1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85?mol/L; 95{\%} CI, 0.71-1.01). Conclusions: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation. � 2014 Elsevier Inc.",
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Ambrosini, GL, Alfonso, H, Reid, A, Mackerras, D, Bremner, A, Beilby, J, Olsen, N, Musk, A & de Klerk, N 2014, 'Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol', Nutrition, vol. 30, no. 5, pp. 551-556. https://doi.org/10.1016/j.nut.2013.10.007

Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol. / Ambrosini, Gina L; Alfonso, Helman; Reid, Alison; Mackerras, Dorothy; Bremner, Alexandra; Beilby, John; Olsen, Nola; Musk, Arthur; de Klerk, Nicholas.

In: Nutrition, Vol. 30, No. 5, 05.2014, p. 551-556.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol

AU - Ambrosini, Gina L

AU - Alfonso, Helman

AU - Reid, Alison

AU - Mackerras, Dorothy

AU - Bremner, Alexandra

AU - Beilby, John

AU - Olsen, Nola

AU - Musk, Arthur

AU - de Klerk, Nicholas

PY - 2014/5

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N2 - Objective: Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. Methods: Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5mg RE/d) or beta-carotene (30mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models. Results: Over a median follow-up of 7.8y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86?mol/L; 95% confidence interval [CI], 0.65-1.14) or osteoporotic fracture (HR, 0.97?mol/L; 95% CI, 0.66-1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85?mol/L; 95% CI, 0.71-1.01). Conclusions: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation. � 2014 Elsevier Inc.

AB - Objective: Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. Methods: Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5mg RE/d) or beta-carotene (30mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models. Results: Over a median follow-up of 7.8y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86?mol/L; 95% confidence interval [CI], 0.65-1.14) or osteoporotic fracture (HR, 0.97?mol/L; 95% CI, 0.66-1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85?mol/L; 95% CI, 0.71-1.01). Conclusions: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation. � 2014 Elsevier Inc.

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