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TABLE 1 Dietary Reference Intakes for Riboflavin by Life Stage Group DRI values (mg/day) EARa RDAb AIc ULd males females males females Life stage group 0 through 6 mo 0.3 7 through 12 mo 0.4 1 through 3 y 0.4 0.4 0.5 0.5 4 through 8 y 0.5 0.5 0.6 0.6 9 through 13 y 0.8 0.8 0.9 0.9 14 through 18 y 1.1 0.9 1.3 1.0 19 through 30 y 1.1 0.9 1.3 1.1 31 through 50 y 1.1 0.9 1.3 1.1 51 through 70 y 1.1 0.9 1.3 1.1 > 70 y 1.1 0.9 1.3 1.1 Pregnancy £ 18 y 1.2 1.4 19 through 50 y 1.2 1.4 Lactation £ 18 y 1.3 1.6 19 through 50 y 1.3 1.6 a EAR = Estimated Average Requirement. b RDA = Recommended Dietary Allowance. c AI = Adequate Intake. d UL = Tolerable Upper Intake Level. Data were insufficient to set a UL. In the absence of a UL, extra caution may be warranted in consuming levels above the recommended intake.

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PART III: RIBOFLAVIN 275 RIBOFLAVIN R iboflavin (vitamin B2) functions as a coenzyme for numerous oxidation– reduction reactions in several metabolic pathways and in energy pro- duction. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. The requirements for riboflavin are based on intake in relation to a combi- nation of indicators, including the excretion of riboflavin and its metabolites, blood values for riboflavin, and the erythrocyte glutathione reductase activity coefficient. Data were insufficient to set a Tolerable Upper Intake Level (UL). DRI values are listed by life stage group in Table 1. Major food sources of riboflavin for the U.S. adult population include milk and milk drinks, bread products, and fortified cereals. Riboflavin deficiency (ariboflavinosis) is most often accompanied by other nutrient deficiencies, and it may lead to deficiencies of vitamin B6 and niacin, in particular. Diseases such as cancer, cardiac disease, and diabetes mellitus are known to precipitate or exacerbate riboflavin deficiency. There is no evidence of adverse effects from excess riboflavin intake. Its apparent nontoxic nature may be due its limited absorption in the gut and its rapid excretion in the urine. RIBOFLAVIN AND THE BODY Function Riboflavin functions as a coenzyme for numerous oxidation–reduction reac- tions in several metabolic pathways and in energy production. The primary form of the vitamin is as an integral component of the coenzymes flavin mono- nucleotide and flavin-adenine dinucleotide. It is in these bound coenzymes that riboflavin functions as a catalyst for redox reactions. Absorption, Metabolism, Storage, and Excretion Primary absorption of riboflavin occurs in the small intestine via a rapid, satu- rable transport system. A small amount is absorbed in the large intestine. The rate of absorption is proportional to intake, and it increases when riboflavin is ingested along with other foods and in the presence of bile salts. At low intake levels, most absorption of riboflavin occurs via an active or facilitated trans-

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 276 port system. At higher levels of intake, riboflavin can be absorbed by passive diffusion. In the plasma, a large portion of riboflavin associates with other proteins, mainly immunoglobulins, for transport. Pregnancy increases the level of carrier proteins available for riboflavin, which results in a higher rate of riboflavin uptake at the maternal surface of the placenta. The metabolism of riboflavin is a tightly controlled process that depends on a person’s riboflavin status. Riboflavin is converted to coenzymes within most tissues, but primarily in the small intestine, liver, heart, and kidneys. When riboflavin is absorbed in excess, very little is stored in the body. The excess is excreted primarily in the urine. Urinary excretion of riboflavin varies with intake, metabolic events, and age. In healthy adults who consume well- balanced diets, riboflavin accounts for 60–70 percent of the excreted urinary flavins. In newborns, urinary excretion is slow; however, the cumulative amount excreted is similar to the amount excreted by older infants. DETERMINING DRIS Determining Requirements The requirements for riboflavin are based on intake in relation to a combina- tion of indicators, including the excretion of riboflavin and its metabolites, blood values for riboflavin, and the erythrocyte glutathione reductase activity coefficient. Special Considerations Individuals with increased needs: People undergoing hemodialysis or perito- neal dialysis and those with severe malabsorption are likely to require extra riboflavin. Women who are carrying more than one fetus or breastfeeding more than one infant are also likely to require more riboflavin. It is possible that individuals who are ordinarily extremely physically active may also have in- creased needs for riboflavin. Criteria for Determining Riboflavin Requirements, by Life Stage Group Life stage group Criterion 0 through 6 mo Human milk content 7 through 12 mo Extrapolation from younger infants and from adults 1 through 18 y Extrapolation from adults

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PART III: RIBOFLAVIN 277 19 through 70 y Excretion of riboflavin and its metabolites, blood values for riboflavin, and the erythrocyte glutathione reductase activity coefficient > 70 y Extrapolation from younger adults Pregnancy £ 18 y through 50 y Age-specific requirement + increased energy utilization and growth needs during pregnancy Lactation £ 18 y through 50 y Age-specific requirement + energy expenditure of human milk production The UL The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse effects for almost all people. Due to insufficient data on adverse effects of excess riboflavin consumption, a UL for riboflavin could not be determined. Although no adverse effects have been as- sociated with excess riboflavin intake, this does not mean that there is no po- tential for adverse effects to occur with high intakes. Because data on adverse effects are limited, caution may be warranted. DIETARY SOURCES Foods Most plant and animal tissues contain at least small amounts of riboflavin. Data from the Continuing Survey of Food Intakes by Individuals (CSFII, 1994–1996) indicate that the greatest contribution to the riboflavin intake by the U.S. adult population came from milk and milk beverages, followed by bread products and fortified cereals. Organ meats are also good sources of riboflavin. (It should be noted that the riboflavin content of milk is decreased if the milk is exposed to light.) Dietary Supplements Approximately 26 percent of all adults reported taking a supplement contain- ing riboflavin, according to the 1986 National Health Interview Survey (NHIS). For adults who took supplements and participated in the Boston Nutritional Status Survey (1981–1984), median supplemental riboflavin intakes were 1.9 mg/day for men and 2.9 mg/day for women.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 278 Bioavailability Approximately 95 percent of food flavin is bioavailable, up to a maximum of about 27 mg absorbed per single meal or dose. More than 90 percent of ribofla- vin is estimated to be in the form of readily digestible flavocoenzymes. Dietary Interactions Riboflavin interrelates with other B vitamins: notably niacin, which requires riboflavin for its formation from tryptophan, and vitamin B6, which also re- quires riboflavin for a conversion to a coenzyme form. These interrelationships are not known to affect the requirement for riboflavin. INADEQUATE INTAKE AND DEFICIENCY Riboflavin deficiency (ariboflavinosis) has been documented in industrialized and developing nations and across various demographic groups. Riboflavin deficiency is most often accompanied by other nutrient deficiencies, and it may lead to deficiencies of vitamin B6 and niacin, in particular. The signs and symp- toms of riboflavin deficiency include the following: • Sore throat • Hyperemia and edema of the pharyngeal and oral mucous membranes • Cheilosis • Angular stomatitis • Glossitis (magenta tongue) • Seborrheic dermatitis (dandruff) • Normocytic anemia associated with pure erythrocyte cytoplasia of the bone marrow Special Considerations Conditions that increase deficiency risk: Diseases such as cancer, cardiac dis- ease, and diabetes mellitus are known to precipitate or exacerbate riboflavin deficiency. EXCESS INTAKE No adverse effects associated with excess riboflavin consumption from food or supplements have been reported. However, studies involving large doses of riboflavin have not been designed to systematically evaluate adverse effects. The apparent lack of harm resulting from high oral doses of riboflavin may be due to its limited solubility and limited capacity for absorption in the human gastrointestinal tract and its rapid excretion in the urine.

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PART III: RIBOFLAVIN 279 KEY POINTS FOR RIBOFLAVIN Riboflavin (vitamin B2) functions as a coenzyme in numerous 3 oxidation–reduction reactions in several metabolic pathways and in energy production. The metabolism of riboflavin is a tightly controlled process that 3 depends on a person’s riboflavin status. The requirements for riboflavin are based on intake in relation 3 to a combination of indicators, including the excretion of riboflavin and its metabolites, blood values for riboflavin, and the erythrocyte glutathione reductase activity coefficient Data were insufficient to set a UL. 3 Certain individuals may have an increased need for riboflavin, 3 including those undergoing dialysis, those with severe malabsorption, and women who are carrying more than one fetus or breastfeeding more than one infant. Major food sources of riboflavin for the U.S. adult population 3 include milk and milk beverages, bread products, and fortified cereals. Riboflavin deficiency is most often accompanied by other 3 nutrient deficiencies, and it may lead to deficiencies of vitamin B6 and niacin, in particular. The signs and symptoms of riboflavin deficiency include sore 3 throat, hyperemia and edema of the pharyngeal and oral mucous membranes, cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, and normocytic anemia associated with pure erythrocyte cytoplasia of the bone marrow. Diseases such as cancer, cardiac disease, and diabetes 3 mellitus are known to precipitate or exacerbate riboflavin deficiency. There is no evidence of adverse effects from excess riboflavin 3 intake. Its apparent nontoxic nature may be due to its limited absorption in the gut and rapid excretion in the urine.