Riboflavin Requirements and Reference Intakes

Glutathione reductase is especially sensitive to riboflavin depletion. In deficient cinimtds, the activity of glutathione reductase responds etulier tuid more meu kedly them any other index of riboflavin status apart from liver concentrations of flavin coenzymes emd the activity of hepatic flavokintise (Prentice tmd Bates, 1981a, 1981b). The activity of the enzyme in erythrocytes ctm therefore be used as an index of riboflavin status. 

Interpretation of the results cem be complicated by anemia, emd it is more usucd to use the activation of EGR by FAD added in vitro. An activation coefficient of 1.0 to 1.3 reflects adequate nutritiontd status 1.7 indicates deficiency. EGR activation coefficient between 1.3 to 1.7 represents ameuginal status, with no cliniccd signs of deficiency. 

Like glutathione reductase, pyridoxine oxidase is sensitive to riboflavin depletion. In normal subjects and in experimental animals, the EGR and pyridoxine oxidase activation coefficients eu e correlated, emd both reflect riboflavin nutritional status. In subjects with glucose 6-phosphate dehydrogenase deficiency, there is an apparent protection of EGR, so that even in riboflavin deficiency it does not lose its cofactor, and the EGR activation coefficient remains within the normal range. The mechanism of this protection is unknown. In such subjects, the erythrocyte pyridoxine oxidase activation coefficient gives a response that mirrors riboflavin nutritional status (Clements and Anderson, 1980). 

On the basis of depletion/repletion studies, the minimum adult requirement for riboflavin is 0.5 to 0.8 mg per day. In population studies, vtdues of the EGR activation coefficient 1.3 are seen in subjects whose habitual intake of riboflavin is 1.2 to 1.5 mg per day. At intakes between 1.1 to 1.6 mg per day, urinetry excretion rises shtuply, suggesting that tissue reserves tue saturated. On the basis of such studies, reference inttikes (see Table 7.6) tue in the remge of 1.2 to 1.6 mg per day (Bates, 1987a, 1987b). 

Because of the central role of flavin coenzymes in energy-yielding metabolism, reference inttikes tue sometimes calculated on the basis of energy inteike 0.6 to 0.8 mg per 1,000 kcal (0.14 to 0.19 mg per MJ). However, in view of the wide remge of riboflavin-dependent reactions, in addition to energy-yielding metabolism, it is difficult to justify this basis for the cedculation of requirements. 

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A more generous estimate of requirements, and the basis of reference intakes, is the intake at which there is normalization of the activity of the red cell enzyme glutathione reductase, a flavoprotein whose activity is especially sensitive to riboflavin nutritional status. Normal values of the activation coefficient (section 11.7.4.1) are seen in subjects whose habitual intake of riboflavin is between 1.2 and 1.5 mg/day. 

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