Vitamin A Intake and Hip Fractures Among Postmenopausal Women

Feskanich, Diane; Singh, Vir; Willett, Walter C.; Colditz, Graham A.

doi:10.1001/jama.287.1.47

Cited by 397 publications

(310 citation statements)

References 43 publications

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“…Other case -control studies did not find an association between plasma (Stryker et al, 1990;Knekt et al, 1991) or dietary (Stryker et al, 1990;Kirkpatrick et al, 1994) levels of retinol and risk of melanoma. It is possible that our observed inverse association for total retinol intake among the low-risk women is a chance finding, but even if real, we would not recommend high retinol intakes for women at such low risk of melanoma since higher intakes have been associated with increased risk of hip fracture among postmenopausal women (Feskanich et al, 2002). An unexpected finding was the increased risk of melanoma with higher intakes of vitamin C from food, and more frequent consumption of fruits and vegetables high in vitamin C, particularly orange juice.…”

Section: Discussionmentioning

confidence: 86%

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women

et al. 2003

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Within the two Nurses' Health Study cohorts of US women, we examined whether higher intakes of vitamin C, vitamin E, retinol, or individual tocopherols or carotenoids are associated with a lower risk of melanoma. We confirmed 414 cases of invasive melanoma among over 162 000 Caucasian women aged 25 -77 years during more than 1.6 million person-years of follow-up. Diet was measured every 4 years with a food frequency questionnaire and supplement use was reported every 2 years. Several measures of sun sensitivity were assessed and included in proportional hazards models. We found that vitamins A, C, E and their individual components were not associated with a lower risk of melanoma. Only retinol intake from foods plus supplements appeared protective within a subgroup of women who were otherwise at low risk based on nondietary factors (relative risk (RR) ¼ 0.39, 95% confidence interval (CI) 0.22 -0.71 for X1800 vs o400 mg day À1 , P for linear trend ¼ 0.01). Contrary to expectation, we observed higher risks of melanoma with greater intakes of vitamin C from food only (RR ¼ 1.43, 95% CI 1.01 -2.00 for X175 vs o90 mg day À1 , P for linear trend ¼ 0.05) and a significant positive dose -response with frequency of orange juice consumption (P ¼ 0.008). Further research is needed to determine whether another component in foods such as orange juice may contribute to an increase in risk.

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Section: Discussionmentioning

confidence: 86%

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women

et al. 2003

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“…Addition of 9cRA to 1,25D treatment completely prevented the weight loss and kidney calcification seen with 1,25D treatment alone, without decreasing the effectiveness of 1,25D treatment against lung tumor incidence and multiplicity. An effect of retinoids on calcium homeostasis has been shown more clearly in studies investigating the association between vitamin A and fracture risk, [45][46][47][48] and the influence of retinoids on vitamin D regulation of serum calcium and bone mineral homeostasis. 35,49,50 Unfortunately, we were unable to obtain sufficient data to report serum or urine calcium levels in our study.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Mernitz

Smith

Wood

et al. 2007

Intl Journal of Cancer

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9-cis-Retinoic acid (9cRA) and 1a, 25-dihydroxyvitamin D 3 (1,25D) show promise as potential chemopreventive agents. We examined 9cRA and 1,25D, alone and in combination, for their potential to inhibit carcinogen (NNK)-induced lung carcinogenesis in A/J mice. A/J mice (n 5 14/group) were treated with 9cRA (7.5, 15, or 30 mg/kg diet), 1,25D (2.5 or 5.0 lg/kg diet), or a combination of 9cRA (15 mg/kg diet) plus 1,25D (2.5 lg/kg diet) for 3 weeks before and 17 weeks after carcinogen injection. Lung tumor incidence, tumor multiplicity, plasma 1,25D levels and kidney expression of vitamin D 24-hydroxylase (CYP24) were determined. Compared to carcinogen-injected controls, mice receiving 9cRA supplementation had significantly lower tumor multiplicity at all doses (decreased 68-85%), with body weight loss at the higher doses of 9cRA. Mice receiving 1,25D supplementation had significantly lower tumor incidence (decreased 36 and 82%) and tumor multiplicity (decreased 85 and 98%), but experienced significant body weight loss, kidney calcium deposition, elevated kidney CYP24 expression and decreased fasting plasma 1,25D levels. Although, there was no apparent influence on chemopreventive efficacy, addition of 9cRA to 1,25D treatment effectively prevented the weight loss and kidney calcification associated with 1,25D treatment alone. These data demonstrate that 9cRA and 1,25D, alone or combined, can inhibit lung tumor promotion in the A/J mouse model. Combining 1,25D with 9cRA has the potential to mitigate the toxicity of 1,25D, while preserving the significant effect of 1,25D treatment against lung carcinogenesis. The underlying mechanism behind this effect does not appear to be related to retinoid modulation of vitamin D catabolism. ' 2006 Wiley-Liss, Inc.Key words: lung cancer; 9-cis retinoic acid; 1a,25-dihydroxyvitamin D 3Chemoprevention by diet or drug intervention may offer a realistic and practical means of modifying the risk of lung cancer, the leading cause of cancer deaths in both men and women in the United States. 1 Two classes of chemopreventive compounds that have been considered are the retinoids and the active form of vitamin D, 1a,25-dihydroxyvitamin D 3 (1,25D, also calcitriol).Retinoids are required for proper differentiation of lung and upper airway epithelium, 2 and both 9-cis retinoic acid (9cRA, also 9-cis tretinoin) and all-trans retinoic acid have been shown to inhibit cell growth and proliferation in lung cancer cell lines. 3 Studies in animal models of lung cancer suggest that retinoids may be effective in cancer chemoprevention in vivo, but results have varied with species, dose and timing of treatment in relation to induction of carcinogenesis. [4][5][6] In human lung cancer, epidemiological evidence supports a role for vitamin A-rich foods and supplements in protection against the development of lung cancer in smokers and nonsmokers alike 7 ; however, clinical trials assessing the efficacy of retinoid supplementation against lung cancer have yielded inconsistent and inconclusive results. [8][...

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“…Several groups of investigators have shown that a high dietary intake of vitamin A or high serum concentration of retinol may increase the risk of fracture in both men and women (1)(2)(3)(4). Studies have also reported an association between high intake of vitamin A and reduced bone mineral density (BMD) (2,5,6).…”

Section: Introductionmentioning

confidence: 99%

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

Högström

Nordström

2008

European Journal of Endocrinology

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Context: The association between retinol and bone mineral density (BMD) in males after puberty has not been fully investigated previously. Objective: To investigate the association between retinol, retinol-binding protein-4 (RBP-4), BMD (g/cm 2 ), abdominal fat mass, and markers of bone metabolism in young men. Design: Longitudinal study. Participants: Seventy-eight healthy males with a mean age of 22.6G0.7 years at baseline. A follow-up was conducted in 73 of the participants 2.0G0.4 years later. Main outcome measures: Associations between serum concentrations of retinol and RBP-4, and BMD of the total body, lumbar spine, and hip, serum concentrations of osteocalcin, and carboxy terminal telopeptide of type 1 collagen (CTX), were investigated. Results: Both retinol and RBP-4 showed an inverse relationship with that of osteocalcin (rZK0.23 to K0.25, P!0.05). Levels of RBP-4 (rZ0.26, PZ0.02) and osteocalcin (rZK0.23, PZ0.04) were also related to abdominal fat mass, and the relationship between RBP-4, retinol, and osteocalcin disappeared after adjusting for this influence of abdominal fat mass. Neither retinol nor RBP-4 concentrations were associated with BMD at any site, CTX as baseline, or changes in BMD during the 2-year follow-up period. Levels of RBP-4 showed a strong association with levels of retinol (rZ0.61, P!0.001). Conclusion: We found a negative association between the bone formation marker osteocalcin with retinol and RBP-4. The association disappeared when adjusting for the influence of abdominal fat mass. Neither retinol nor RBP-4 were associated with peak BMD in young men. 158 765-770 European Journal of Endocrinology

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Vitamin A Intake and Hip Fractures Among Postmenopausal Women

Abstract: Long-term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women. The amounts of retinol in fortified foods and vitamin supplements may need to be reassessed.

Cited by 397 publications

References 43 publications

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

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Vitamin A Intake and Hip Fractures Among Postmenopausal Women

Abstract: Long-term intake of a diet high in retinol may promote the development of osteoporotic hip fractures in women. The amounts of retinol in fortified foods and vitamin supplements may need to be reassessed.

Cited by 397 publications

References 43 publications

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women

Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women

Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity

Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: the Northern Osteoporosis and Obesity (NO2) Study

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Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D₃ and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity