Chapter 071. Vitamin and Trace Mineral Deficiency and Excess (Part 8)

FlavonoidsFlavonoids constitute a large family of polyphenols that contribute to the aroma, taste, and color of fruits and vegetables. Major groups of dietary flavonoids include anthocyanidins in berries; catechins in green tea and chocolate; flavonols (e.g., quercitin) in broccoli, kale, leeks, onion, and the skins of grapes and apples; and isoflavones (e.g., genistein) in legumes. Isoflavones have a low bioavailability and are partially metabolized by the intestinal flora. The dietary intake of flavonoids is estimated to be between 10 and 100 mg/d, although this is almost certainly an underestimate due to the lack of knowledge of their concentrations in...
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Chapter 071. Vitamin and Trace Mineral Deficiency and Excess (Part 8) Chapter 071. Vitamin and Trace Mineral Deficiency and Excess (Part 8) Flavonoids Flavonoids constitute a large family of polyphenols that contribute to thearoma, taste, and color of fruits and vegetables. Major groups of dietary flavonoidsinclude anthocyanidins in berries; catechins in green tea and chocolate; flavonols(e.g., quercitin) in broccoli, kale, leeks, onion, and the skins of grapes and apples;and isoflavones (e.g., genistein) in legumes. Isoflavones have a low bioavailabilityand are partially metabolized by the intestinal flora. The dietary intake offlavonoids is estimated to be between 10 and 100 mg/d, although this is almostcertainly an underestimate due to the lack of knowledge of their concentrations inmany foods. Several flavonoids have been shown to have antioxidant activity andto affect cell signaling. From observational epidemiologic studies and from limitedclinical human and animal studies, flavonoids have been postulated to play a rolein the prevention of several chronic diseases, including neurodegenerative disease,diabetes, and osteoporosis. The ultimate importance and usefulness of theircompounds against human disease have yet to be demonstrated. Vitamin A Vitamin A, in the strictest sense, refers to retinol. However, the oxidizedmetabolites, retinaldehyde and retinoic acid, are also biologically activecompounds. The term retinoids includes all molecules (including synthetic molecules)that are chemically related to retinol. Retinaldehyde (11-cis) is the essential formof vitamin A that is required for normal vision, whereas retinoic acid is necessaryfor normal morphogenesis, growth, and cell differentiation. Retinoic acid does not function in vision and, in contrast to retinol, is notinvolved in reproduction. Vitamin A also plays a role in iron utilization, humoralimmunity, T cell–mediated immunity, natural killer cell activity, andphagocytosis. Vitamin A is commercially available in esterified forms (e.g.,acetate, palmitate) since it is more stable as an ester. There are more than 600 carotenoids in nature, and approximately 50 ofthese can be metabolized to vitamin A. β-Carotene is the most prevalentcarotenoid in the food supply that has provitamin A activity. In humans, significant fractions of carotenoids are absorbed intact and arestored in liver and fat. It is now estimated that 12 µg or greater of dietary β-carotene is equivalent to 1 µg of retinol, whereas 24 µg or greater of other dietaryprovitamin A carotenoids (e.g., cryptoxanthin, α-carotene) is equivalent to 1 µg ofretinol. Metabolism The liver contains approximately 90% of the vitamin A reserves andsecretes vitamin A in the form of retinol, which is bound to retinol-bindingprotein. Once this has occurred, the retinol-binding protein complex interacts witha second protein, transthyretin. This trimolecular complex functions to prevent vitamin A from beingfiltered by the kidney glomerulus, to protect the body against the toxicity of retinoland to allow retinol to be taken up by specific cell-surface receptors that recognizeretinol-binding protein. A certain amount of vitamin A enters peripheral cells even if it is not boundto retinol-binding protein. After retinol is internalized by the cell, it becomesbound to a series of cellular retinol-binding proteins, which function assequestering and transporting agents as well as co-ligands for enzymatic reactions.Certain cells also contain retinoic acid–binding proteins, which have sequesteringfunctions but also shuttle retinoic acid to the nucleus and enable its metabolism. Retinoic acid is a ligand for certain nuclear receptors that act astranscription factors. Two families of receptors (RAR and RXR receptors) areactive in retinoid-mediated gene transcription. Retinoid receptors regulate transcription by binding as dimeric complexesto specific DNA sites, the retinoic acid response elements, in target genes (Chap.332). The receptors can either stimulate or repress gene expression in response totheir ligands. RAR binds all-trans retinoic acid and 9-cis retinoic acid, whereasRXR binds only 9-cis retinoic acid. The retinoid receptors play an important role in controlling cellproliferation and differentiation. Retinoic acid is useful in the treatment ofpromyelocytic leukemia (Chap. 104) and is also used in the treatment of cysticacne because it inhibits keratinization, decreases sebum secretion, and possiblyalters the inflammatory reaction (Chap. 53). RXRs dimerize with other nuclear receptors to function as coregulators ofgenes responsive to retinoids, thyroid hormon ...