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      Mammalian Metabolism of β-Carotene: Gaps in Knowledge

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          Abstract

          β-carotene is the most abundant provitamin A carotenoid in human diet and tissues. It exerts a number of beneficial functions in mammals, including humans, owing to its ability to generate vitamin A as well as to emerging crucial signaling functions of its metabolites. Even though β-carotene is generally considered a safer form of vitamin A due to its highly regulated intestinal absorption, detrimental effects have also been ascribed to its intake, at least under specific circumstances. A better understanding of the metabolism of β-carotene is still needed to unequivocally discriminate the conditions under which it may exert beneficial or detrimental effects on human health and thus to enable the formulation of dietary recommendations adequate for different groups of individuals and populations worldwide. Here we provide a general overview of the metabolism of this vitamin A precursor in mammals with the aim of identifying the gaps in knowledge that call for immediate attention. We highlight the main questions that remain to be answered in regards to the cleavage, uptake, extracellular and intracellular transport of β-carotene as well as the interactions between the metabolism of β-carotene and that of other macronutrients such as lipids.

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          Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

          Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
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            Antioxidants in human health and disease.

            Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so diet-derived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.
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              Dietary (n-3) fatty acids and brain development.

              The (n-3) fatty acids are essential dietary nutrients, and one of their important roles is providing docosahexaenoic acid [22:6(n-3)] (DHA) for growth and function of nervous tissue. Reduced DHA is associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that DHA functions in neurogenesis, neurotransmission, and protection against oxidative stress. These functions relate to the roles of DHA within the hydrophobic core of neural membranes and effects of unesterified DHA. Reviewed here are some of the recent studies that have begun to elucidate the role of DHA in brain development and function. A better understanding of development and age-specific changes in DHA transfer and function in the developing brain may provide important insight into the role of DHA in developmental disorders in infants and children, as well as at other stages of the lifespan.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                27 November 2013
                December 2013
                : 5
                : 12
                : 4849-4868
                Affiliations
                Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA; E-Mail: varsha.shete@ 123456gmail.com
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: quadro@ 123456aesop.rutgers.edu ; Tel.: +1-848-932-5491; Fax: +1-732-932-6776.
                Article
                nutrients-05-04849
                10.3390/nu5124849
                3875911
                24288025
                1c68cc84-94aa-473f-93a8-03af476e23b2
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 14 October 2013
                : 14 November 2013
                : 15 November 2013
                Categories
                Review

                Nutrition & Dietetics
                β-carotene-15,15′-oxygenase,carotenoids,β-carotene,β-carotene-9′,10′-oxygenase,β-apocarotenoids,vitamin a,retinoids

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