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Vitamin A

Red Arrow  Facts Red Arrow  Functions
Red Arrow  Requirements & Recommendations Red Arrow  Deficiency Signs and Symptoms
Red Arrow  Toxicity Red Arrow  Dietary Sources
Red Arrow  Populations w/ Special Needs Red Arrow  Drug-Vitamin Interaction
Red Arrow  Research Summary

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Vitamin A facts
  • Vitamin A is a fat-soluble vitamin.
  • Vitamin A is a nutritional term that describes a family of essential compounds that are structurally related. The vitamin A family includes retinol, retinal or retinaldehyde, retinyl esters, retinoic acid, and provitamin carotenoids such as beta-carotene.
  • Vitamin A is essential for growth and life, taking part not only in vision but also in developmental processes that begin early in embryogenesis. Vitamin A continues to be necessary to maintain normal cellular differentiation throughout life and is essential for immune function, vision, reproduction, and cellular communication.1
  • Preformed vitamin A (retinol and retinyl esters) comes from animal sources, such as liver and egg yolk, while the provitamin beta-carotene is found only in foods of plant origin, particularly carrots and dark leafy vegetables.
  • Vitamin A requires some fat present in the digestive system for absorption and is better absorbed than the carotenoids. Protein enhances the conversion of carotenoids to retinol.
  • The human body stores only limited amounts of vitamin A, mostly in the liver, making dietary intake essential. The liver stores 50 to 80% of whole body vitamin A. Small amounts are also found in lungs, body fat and kidneys. Unlike most vitamins, vitamin A concentrations tend to increase with age. Plasma vitamin A concentrations are tightly regulated and do not vary much until liver stores are dangerously low.1
  • Excess or deficiency of vitamin A in the mother's diet during pregnancy has been shown to cause birth defects.
Beta-Carotene facts
  • Beta-carotene is one of almost 600 carotenoids. Fifty of these compounds have vitamin A activity. Beta-carotene may provide as much as two-thirds of the vitamin A in the human diet. Carotenoids are deposited more widely throughout the body than retinoids and are found in adipose tissues, adrenals and liver.2
  • Carotenoids are brightly colored red, yellow, and orange compounds produced by plants.
  • Six carotenoids found in the highest concentrations in human serum are beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin.
  • Certain carotenoids, such as beta-carotene, alpha-carotene and beta-cryptoxanthin, are dietary precursors of vitamin A, called provitamin A.
  • Beta-carotene is found only in foods of plant origin, particularly carrots and dark leafy vegetables.
  • Beta-carotene becomes an essential nutrient when dietary intake of retinol is inadequate.

  • Functions

    Vitamin A functions
    • Vitamin A is essential for night vision, due to its involvement in photochemical reactions in the retina as a component of rhodopsin.
    • Growth and maintenance of epithelial tissue depends on vitamin A including the cornea, all mucous membranes of gastrointestinal tract, lungs, vagina, urinary tract, bladder and skin.
    • Reproductive function in humans requires vitamin A.
    • Vitamin A is required for nerve formation and function.
    • Epithelial cell proliferation and epidermal differentiation are effected by vitamin A.  Natural and synthetic retinoids have been used increasingly as systemic or topical agents in the treatment of hyperkeratotic disorders, acne, and certain skin cancers.
    • Both cell-mediated and antibody-mediated immune response require sufficient vitamin A.
    • Vitamin A is involved in signal transduction via retinoic acid's hormonal action.
    Beta-carotene functions
    • Beta-carotene functions as an antioxidant, regulator of cell communication and growth, and has shown immunomodulatory activities thought to be independent of its role as a pro-vitamin A compound.
    • As an antioxidant, beta-carotene may quench certain free radicals and inhibit lipid peroxidation.
    • Beta-carotene may exert anti-carcinogenic activity.

  • Requirements & Recommendations

    Vitamin A: Dietary Reference Intake: Institute of Medicine.3
    (RAE=retinol activity
    Tolerable Upper Intake Levels
    (UL, mcg/day)
    0 to 6 months
    7 to 12 months
    1-3 years
    4-8 years
    9-13 years
    14-18 years
    19+ years
    14-18 years
    19+ years
    <14-18 years
    19 to 50 years
    <14-18 years
    19 to 50 years
    • * as RAE.
    • Vitamin A dietary reference intakes (DRIs) are expressed in IU (international units), RAE (retinol activity equivalents) or mcg (micrograms). One RAE is 1 mcg of retinol, also equivalent to 3.33 IU of vitamin A activity from retinol. One RAE is also equivalent to 2 mcg all-trans-beta-carotene as a supplement or 12 mcg all-trans-beta-carotene in food. Additionally, 24 mcg of other provitamin A carotenoids in food are equivalent to 1 RAE.
    • A generally recognized safe upper limit of intake for vitamin A is 8,000 to 10,000 IU/day (2,400 mcg to 3,000 mcg/day). There is no established recommended daily allowance (RDA) for beta-carotene.
    • Studies of beta-carotene indicate that 6 mg/day (10,000 IU) should be adequate. One mg of beta-carotene is equivalent to 1,667 IU of beta-carotene.

  • Deficiency Signs and Symptoms

    • Symptoms of vitamin A deficiency are due to its participation in skin, bone, dental health and immune function. The earliest symptom of vitamin A deficiency is inability to see in dim light, called night blindness or nyctalopia. Other symptoms soon appear including rough, scaly skin (called follicular hyperkeratosis), sinus infection, chronic sore throat and abscesses in mouth and ears.
    • In children, deficiency of vitamin A results in growth retardation, and impaired bone and tooth formation.
    • Both deficiency and excess vitamin A cause fetal malformations.
    • Vitamin A deficiency interferes with fertility by causing spermatogenesis cessation.

  • Toxicity

    Vitamin A toxicity
    • Symptoms of vitamin A toxicity include loss of appetite, headache, blurred vision, irritability, hair loss, drying and flaking of the skin, swelling in the extremities, drowsiness, diarrhea, nausea, and enlargement of the spleen and liver.
    • Since vitamin A stores increase with age, the elderly are at particular risk for toxicity.
    • Vitamin A excess during the first trimester of pregnancy can result in severe craniofacial and oral clefts and limb defects of the fetus.
    • High doses of vitamin A (retinol and retinyl esters) during pregnancy have been associated with birth defects. It is recommended that women who are pregnant or may become pregnant do not exceed the tolerable Upper Limits.
    Beta-Carotene toxicity
    • Chronic doses of 30 mg/day or higher of beta-carotene may cause carotenodermia. Carotenodermia is characterized by yellowish discoloration of the skin and is considered harmless and reversible with the discontinuation of beta-carotene supplementation.
    • Supplementation of 20 mg/day or greater of beta-carotene has been linked to increased lung cancer incidence in smokers. Smokers should avoid 15 mg/day beta-carotene supplementation pending further research.

  • Dietary Sources

    • Rich sources of vitamin A are liver and cod liver oil. The major source of vitamin A in the diet is from beta-carotene. Sources of beta-carotene include yellow and green leafy vegetables such as carrots, spinach, sweet potatoes, squash, and yellow fruits such as peaches and cantaloupe.

  • Populations w/ Special Needs

    • A synthetic derivative of vitamin A, Accutane®, has been proven to be teratogenic in animals and humans. Therefore, it is recommended that women who could become pregnant not take this drug.
    • Vitamin A absorption is impaired by intestinal disorders that alter absorption of fats. Retinyl palmitate is a form of vitamin A that is absorbed even without dietary fat and is useful in management of long-term intestinal diseases, such as sprue, cystic fibrosis, or celiac disease.
    • Vegetarians, people who do not consume enough calories, and those with disorders that cause fat malabsorption, are also at risk for vitamin A deficiency.

  • Drug-Vitamin Interaction

    • Warfarin (Coumadin®), an anticoagulant, increases the risk of abnormal bleeding when taken with high-dose supplements of fat-soluble vitamins, including vitamin A. It is recommended to avoid combining vitamin A with warfarin unless supervised by a physician or pharmacist.
    • Bile acid sequestrants such as cholestyramine (Questran) and colestipol(Colestid) are used to lower cholesterol concentrations by preventing reabsorption of bile acids from the digestive system and by preventing micelle formation in gastrointestinal (GI) lumen. Since fat-soluble vitamin A requires the presence of bile for absorption, deficiency may occur if these drugs are used for a long period of time. During long-term administration of these medications, it is recommended to take a daily supplement that is a water-miscible preparation of vitamin A.
    • Oral antibiotics such as neomycin (Mycifradin) decrease absorption of many nutrients including vitamin A. People taking antibiotics for longer than 10 days should take multivitamin supplements.
    • Chronic use of laxatives that contain mineral oil can lead to malabsorption of fat-soluble vitamins, including vitamin A. It is recommended to take the vitamin two hours before or after mineral oil is used.
    • Retinoid drugs, such as tretinoin (Retin-A and others), isotretinoin (Accutane), and 13-cis as well as all-trans-retinoic acids, are structurally similar to vitamin A. They are used topically and systemically for the reduction of acne and the appearance of wrinkles. Tretinoin, marketed as Vesanoid, is also used to treat acute promyelocytic leukemia. People using these compounds should avoid vitamin A-containing supplements due to a possible toxicity.
    • Orlistat (Xenical), a weight loss gastrointestinal (GI) agent, may decrease GI absorption of fat-soluble vitamins. In clinical studies, vitamin concentrations during drug therapy remained within normal range for most patients. Vitamin supplementation was only occasionally needed. Orlistat and vitamin A supplementation should be at least 2 hours from each other; fat-soluble vitamins may be taken conveniently at bedtime. 
    Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature.  In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship. 7 8 9

  • Research Summary

    Topic: Lung Cancer

    The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements.
    The Beta-Carotene and Retinol Efficacy Trial (CARET) investigated the effects of beta-carotene and retinyl palmitate supplements on lung cancer incidence. The trial was terminated early because initial analysis indicated a 28% increase in lung cancer and a 17% increase in death in addition to an increased rate of cardiovascular disease mortality in the supplemented group. The trial included 18,314 people with elevated risk for lung cancer due to smoking or asbestos exposure. Participants continue to be followed; this report included data from 1996 through 2001. For the supplemented group, relative risk of lung cancer was 1.12 (95% CI 0.97 to 1.31) compared to placebo. Relative risk for all-cause mortality was 1.08 (95% CI 0.99 to 1.17) for the supplemented group compared to the placebo group. Relative risks for lung cancer and all-cause mortality remained above 1.0 for the follow-up period; risk for cardiovascular disease mortality rapidly decreased to 1.0 after the intervention stopped. Risks were stratified by sex during the post-intervention period: lung cancer mortality (1.33 for female vs 1.14 for male, P=0.36), cardiovascular disease mortality (1.44 for female vs 0.93 for male, P=0.03), and all-cause mortality (1.37 for female vs 0.98 for male, P=0.001). The results of this analysis suggest that increased risks associated with the beta-carotene and retinyl palmitate supplements used in this trial have persisted after the intervention was stopped.7
    Red Arrow Read Abstract
    Topic: Breast Cancer

    Serum levels of micronutrients, antioxidants and total antioxidant status predict risk of breast cancer in a case control study.
    A case-control study investigated the relationships between certain micronutrients and antioxidants on breast cancer risk. One-hundred-fifty-three newly diagnosed breast cancer patients (who had not yet been treated) and 151 age and location matched women without breast cancer participated in the study. Included participants ranged in age from 30 to 84 years. Blood serum samples were collected from all participants and were evaluated for retinol, alpha-tocopherol, lycopene, alpha- and beta-carotene, total antioxidant status (by the Trolox-equivalent antioxidant assay), albumin, bilirubin, and uric acid. Adjustments were made for factors known to influence breast cancer risk: age at menarche, parity, dietary fat, and alcohol intake. Breast cancer risk was reduced with increasing serum beta-carotene concentration (odds ratio for highest compared to lowest quintile 0.47; 95% CI 0.24 to 0.91; P for trend=0.016) and serum retinol concentration (0.53; CI 0.28 to 1.01; P for trend=0.040). Bilirubin (0.50; CI 0.26 to 0.97; P for trend=0.050) and total antioxidant status (0.47; CI 0.24 to 0.94; P for trend=0.030) also reduce risk with increasing concentrations (also highest quintile compared to lowest quintile for each). The authors concluded that increased serum levels of beta-carotene, retinol, bilirubin, and total antioxidant status were associated with reduced risk for breast cancer. Studies to determine the clinical relevance of these results are needed.8
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    Carotenoids, alpha-tocpherols, and retinol in plasma and breast cancer risk in northern Sweden.
    A nested case-referent design study investigated associations between plasma carotenoids, alpha-tocopherol, and retinol and breast cancer risk. Participants were selected from population-based cohorts in Sweden and included 201 cases and 290 referents. Blood samples were collected at enrollment and stored at -80 °C. Plasma carotenoid concentrations were positively intercorrelated but were not significantly correlated to breast cancer risk. Plasma alpha-tocopherol and retinol were also not significantly correlated with breast cancer risk. Lycopene was significantly associated with a decreased risk of breast cancer for a group of postmenopausal women from a mammography cohort. Lutein was positively associated with a reduced risk of breast cancer from a combination of population-based cohorts. No statistically significant associations with breast cancer risk were found in analysis of the combined cohorts for plasma carotenoids, alpha-tocopherol, or retinol. Lycopene and lutein may reduce risk for breast cancer for certain populations.9
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    Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression.
    A meta-analysis and meta-regression were completed to investigate the associations between retinol, vitamin A, vitamin C, and vitamin E and breast cancer risk. Fifty-one studies were included in the analysis. Total vitamin A intake was found to reduce risk of breast cancer by 17% (highest vs. lowest intake, pooled odds ratio=0.83, 95% CI 0.78 to 0.88); subgroup analysis did not change the result. Dietary vitamin A, dietary vitamin E, and total vitamin E intake significantly reduced breast cancer risk; when data from cohort studies were pooled, the reduction was nonsignificant. The significant association between total retinol intake and breast cancer in all studies became nonsignificant in case-control studies but remain significant in cohort studies. No significant dose-response relationship was observed. The results of this meta-analysis and meta-regression suggest that total intake of vitamin A and retinol could reduce risk for breast cancer.10
    Red Arrow Read Abstract
    Topic: Prostate Cancer

    Serum retinol and risk of prostate cancer.
    A prospective study evaluated associations between serum retinol concentrations and prostate cancer incidence in an analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study participants. At baseline, 29,104 men were assessed and at three year follow-up, 22,843 men were reassessed. After three years, 2,041 cases of prostate cancer were identified; 461 cases were identified as aggressive in nature. Serum retinol quintiles at baseline, at three years, and change in serum retinol were evaluated for association with prostate cancer risk and aggressiveness. The hazard ratio for prostate cancer was 1.19 comparing the highest to lowest quintiles at baseline (95% CI: 1.03 to 1.36, P for trend=0.009); a dose-risk association was evident. Aggressive prostate cancer risk was found to be similar to total prostate cancer risk: hazard ratio comparing highest to lowest quintile at baseline 1.22 (95% CI: 0.92 to 1.63, P for trend=0.05). Men who were in the highest quintile of serum retinol at baseline and at three year follow-up had the highest risk for prostate cancer (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio=1.31, 95% CI: 1.08 to 1.59). In this study of retinol and prostate cancer, high serum retinol was found to be associated with increased risk of prostate cancer.11
    Red Arrow Read Abstract

    Dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial.
    Prostate cancer risk was assessed as a secondary outcome in the Carotene and Retinol Efficacy Trial (CARET). CARET examined the efficacy of beta-carotene (30 mg) and retinyl palmitate (25,000 IU) supplements to prevent lung cancer in a RDBPC trial. Participants in the trial included current or former male and female smokers aged 50 to 69 years with a history of at least 20 pack-years of cigarette smoking (n=14,254, 55.9% of whom were male) and men aged 45 to 69 years with occupational exposure to asbestos (n=4,060; also current or former smokers). For the secondary outcome measure of prostate cancer, 5,803 men in the placebo group and 6,197 men from the active vitamins group were included. During an average 11 year follow-up period, 890 prostate cancer cases were identified. For total prostate cancer risk, neither CARET supplements nor other supplements were found to be associated with risk. However, use of the CARET supplements and additional supplements increased relative risk for aggressive prostate cancer: RR 1.52, 95% CI 1.03 to 2.24 (P<0.05, relative to all others). The association disappeared after the intervention stopped (RR 0.75; 95% CI 0.51 to 1.09). Since only smokers were included in this trial, the results may not be relevant to nonsmokers. The results of this analysis suggest that use of the specific supplements studied plus additional dietary supplements may increase risk of aggressive prostate cancer for smokers and former smokers.12
    Red Arrow Read Abstract

    Associations between alpha-tocopherol, beta-carotene, and retinol and prostate cancer survival.
    Serum alpha-tocopherol, serum beta-carotene, serum retinol, or use of the supplements during the Alpha-Tocopherol, Beta-Carotene trial (ATBC) were evaluated for associations with prostate cancer survival. The ATBC investigated the effects of alpha-tocopherol, beta-carotene, or both supplements on risk of cancer. Participants (n=29,133 male smokers aged 50 to 69 years in Finland) were randomly assigned to one of four groups: (a) alpha-tocopherol (dl-alpha-tocopherol acetate, 50 mg/d), (b) beta-carotene (20 mg/d), (c) both supplements, or (d) placebo capsules for 5 to 8 y until death or trial closure (1993). Between 1985 and 2005, 1,891 prostate cancer cases were identified; 395 men died from prostate cancer. Serum alpha-tocopherol was associated with improved prostate cancer survival: higher serum concentration at baseline (HR 0.67, 95% CI 0.45 to 1.00); highest quintile at baseline and alpha-tocopherol supplements during the trial (HR 0.51, 95% CI 0.20 to 0.90); and higher serum concentration at three year follow-up (HR 0.26, 95% CI 0.09 to 0.71). In contrast, serum beta-carotene, supplemental beta-carotene, and serum retinal were not associated with prostate cancer survival. The results of this analysis suggest that higher alpha-tocopherol may improve prostate cancer survival for smokers.13
    Red Arrow Read Abstract
    Topic: Non-Hodgkin's Lymphoma

    Intake of antioxidant nutrients and risk of non-Hodgkin's Lymphoma in the Women's Health Initiative.
    The possible associations between antioxidant nutrient intake and risk for non-Hodgkin’s lymphoma were assessed in the Women’s Health Initiative. The Women’s Health Initiative included 154,363 postmenopausal women; 1,104 cases of non-Hodgkin’s lymphoma were identified in eleven years of follow-up. Total vitamin A intake was inversely associated with risk for non-Hodgkin’s lymphoma (multivariate adjusted HR for highest vs. lowest quartile 0.83, 95% CI 0.69 to 0.99). No other nutrients included in the study were associated with risk for non-Hodgkin’s lymphoma. Vitamin C intake was inversely associated with risk for diffuse large B-cell lymphoma (HR for highest vs. lowest quartile 0.69, 95% CI 0.49-0.98). This study indicates that vitamin A intake from food and supplements may reduce risk for non-Hodgkin’s lymphoma and vitamin C intake from food and supplements may reduce risk for diffuse large B-cell lymphoma.14
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    Topic: Cervical Cancer

    Vitamin A and risk of cervical cancer: a meta-analysis.
    Meta-analysis of eleven articles on dietary vitamin A and cervical cancer and four articles on blood vitamin A and cervical cancer was completed to evaluate associations between vitamin A and cervical cancer risk. The trials included a total of 12,136 participants. For the eleven trials of vitamin A intake, the pooled odds ratio for cervical cancer was 0.59 (95% CI 0.49 to 0.72). For the four trials of blood vitamin A levels, the pooled odds ratio for cervical cancer was 0.60 (95% CI 0.41 to 0.89). The combined odds ratios of cervical cancer were 0.80 (95% CI 0.64 to 1.00) for retinol, 0.51 (95% CI, 0.35-0.73) for carotene, and 0.60 (95% CI, 0.43-0.84) for other carotenoid intake, and 1.14 (95% CI, 0.83-1.56) for blood retinol and 0.48 (95% CI, 0.30-0.77) for blood carotene. This meta-analysis found vitamin A intake and blood levels were inversely associated with the risk for cervical cancer.15
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    Topic: Asthma

    Association between antioxidant vitamins and asthma outcome measures: systematic review and meta-analysis.
    A meta-analysis of studies investigating serum concentrations or intake of vitamins A, C and E and asthma, wheeze, or airway responsiveness was completed. A total of 40 studies were identified and included. Vitamin A intake was found to be lower for people with asthma than those without: mean difference -82 mcg/day (95% CI -288 to -75 mcg/day; data from 3 studies). People with severe asthma were found to have significantly lower dietary vitamin A intake than people with mild asthma: mean difference -344 mcg/day (data from 2 studies). For vitamin c, lower quintile intake was associated with increased risk for asthma (OR 1.12, 95% CI 1.04 to 1.21; data from 9 studies); lower serum levels of vitamin C were also associated with increased risk for asthma. Vitamin E intake was not associated with asthma. However, vitamin E intake was significantly lower for people with severe asthma than mild asthma (mean difference -1.20 mcg/day, 95% CI -2.3 to -0.1; data from 2 studies). The results of this meta-analysis suggest that insufficient vitamin A, vitamin C, and possibly vitamin E intake may increase risk for asthma or for more severe asthma symptoms. Further studies should investigate the utility of supplements or dietary intervention for improving asthma symptoms.16
    Red Arrow Read Abstract

    Nutrients and foods for the primary prevention of asthma and allergy: systematic review and meta-analysis.
    A meta-analysis including 62 studies evaluated the hypothesis that diet influences development of asthma and allergy in children. Serum vitamin A was lower in children with asthma compared to controls (OR, 0.25; 95% CI, 0.10 to 0.40). High maternal intake of vitamins D and E during pregnancy were found to protect against development of various wheezing outcomes (OR, 0.56, 95% CI, 0.42-0.73; and OR, 0.68, 95% CI, 0.52-0.88, respectively). A Mediterranean diet was protective for persistent wheeze (OR, 0.22; 95% CI, 0.08-0.58) and atopy (OR, 0.55; 95% CI, 0.31-0.97). Vitamin C and selenium were not found to protect against allergy or asthma in this analysis. The results of this trial support the idea that higher vitamin A intake is protective against asthma although the design of included trials is not optimal. These results are in agreement with other trials. Further studies are needed to verify these results.17
    Red Arrow Read Abstract
    Topic: Bone Health

    Vitamin A intake and hip fractures among postmenopausal women.
    Vit A intake & hip fracture was assessed in the Nurses's Health Study, a study with 18 yrs follow-up. The Nurses's Health Study included 72,337 nurses in 11 states, from 34-77 yrs of age. Dietary questions were used to assess intake of specific nutrients at baseline & updated periodically during follow-up. The study includes data related to vit A & hip fractures from 1980-1998. Compared to the lowest quintile of vit A intake (<1,250 mcg/day retinol equivalents), women with high vit A intake had higher risk of hip fracture (highest quintile was >3,000 mcg/day retinol equivalents; RR 1.48, 95% CI 1.05-2.07, P for trend=0.003). The increased risk was primarily due to retinol intake (RR 1.89, 95% CI 1.33-2.68, P for trend<0.001 comparing >2,000 mcg/day vs <500 mcg/day). Intake of postmenopausal estrogen therapy attenuated the association of high retinol intake with hip fracture. Beta-carotene was not associated with risk for hip fracture (RR 1.22, 95% CI 0.90-1.66, P for trend=0.10 comparing >6300 mcg/day vs <2,550 mcg/day). For those taking vit A supplements, there was a 40% increase in risk for hip fracture (compared to those not taking a supplement; RR 1.40, 95% CI, 0.99-1.99). Retinol from food was associated with fracture risk for those not taking supplements (RR 1.69, 95% CI 1.05-2.74, P for trend=0.05 comparing (>1,000 mcg/day vs <400 mcg/day). The results suggest that high intake of vit A from food or supplements may increase risk for hip fracture.18
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    High serum retinyl esters are not associated with reduced bone mineral density in the Third National Health and Nutrition Examination Survey, 1988-1994.
    Serum retinyl esters and bone mineral density were examined in the Third National Health and Nutrition Examination Survey (NHANES III). Bone mineral density at the femoral neck, trochanter, intertrochanter, and total hip were evaluated for all nonpregnant participants (aged 20 years or older) and complete data including fasting serum retinyl esters and covariates including age, body mass index (BMI), smoking, alcohol consumption, dietary supplement use, diabetes, physical activity, and, among women, parity, menopausal status, and the use of oral contraceptives or estrogen-replacement therapy were collected for 5,790 participants. Non-Hispanic white, non-Hispanic black, and Mexican American men and women were included in the analysis. No significant associations were found between fasting serum retinyl esters and bone mineral density at any site. Osteopenia and osteoporosis were also not found to be associated with serum retinyl ester concentrations. Interestingly, high fasting serum retinyl esters and low bone mineral density were both found to be prevalent in this population but no associations were found between the parameters studied.19
    Red Arrow Read Abstract

    Serum retinol levels and the risk of fracture.
    A population-based, longitudinal cohort study investigated the relationship between serum retinol and fracture risk in men over the age of forty-nine. At enrollment, serum retinol and beta-carotene levels were assessed in 2,322 men between the ages of 49 and 51 years. During 30 years of follow-up, 266 men with fractures were identified. Risk for any fracture in the highest quintile of serum retinol was 1.64 compared to the middle quintile (>75.62 mcg/dL vs 62.16 to 67.60 mcg/dL; 95% CI 1.12 to 2.41). For the highest quintile compared to the middle quintile of serum retinol, the risk for hip fracture was 2.47 (95% CI 1.15 to 5.28). Men with the highest retinol levels (99th percentile) had the highest risk of fracture (univariate rate ratio, 6.85 [95% CI 3.38 to 13.90]; multivariate rate ratio, 7.14 [95% CI 3.43 to 14.86]; P<0.001). Serum beta-carotene was not associated with the risk of fracture. The results of this study suggest that the highest serum levels of vitamin A may increase risk for fractures in men over the age of 49.20
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    Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study.
    The associations between retinol intake & markers of bone health were assessed among community-dwelling older people in the United State. In 958 participants aged 55-92 yrs, baseline bone mineral density (BMD) was determined for total hip, femoral neck, & lumbar spine between 1988-1992 with follow-ups between 1992-1996. Regression analysis found an inverse U-shaped association between & baseline BMD. A similar inverse U-shaped association was found for retinol & BMD 4 years later, as well as the change in BMD. Supplemental retinol use was an effect modifier in women; the associations of log retinol with BMD and BMD change were negative for supplement users and positive for nonusers at the hip, femoral neck, and spine. For retinol supplement users, every unit increase in log retinol intake resulted in 0.02 g/cm2 lower BMD at the femoral neck (p=0.02) and greater annual bone loss (0.23%, p=0.05). Nonusers had 0.02 g/cm2 higher bone mineral density (p=0.04) and 0.22% greater bone retention (p=0.19). Among supplement users, retinol from dietary & supplement sources had similar associations with BMD suggesting that total intake is more important than the source. Increasing retinol intake was negatively associated with bone health at intakes not much greater than the recommended daily allowance. This study suggests that bone health is supported by vitamin A but that it is important to find a balance between too little and too much.21
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