Vitamin B2: Function

Oxidation-reduction (redox) reactions

Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes involving the transfer of electrons. Flavin coenzymes participate in redox reactions in numerous metabolic pathways. Flavins are critical for the metabolism of carbohydrates, fats, and proteins. FAD is part of the electron transport (respiratory) chain, which is central to energy production. In conjunction with cytochrome P-450, flavins also participate in the metabolism of drugs and toxins.

Antioxidant functions

Glutathione reductase is an FAD-dependent enzyme that participates in the redox cycle of glutathione. The glutathione redox cycle plays a major role in protecting organisms from reactive oxygen species, such as hydroperoxides.

Glutathione peroxidase, a selenium-containing enzyme, requires two molecules of reduced glutathione to break down hydroperoxides (see diagram).

Glutathione reductase requires FAD to regenerate two molecules of reduced glutathione from oxidized glutathione. Riboflavin deficiency has been associated with increased oxidative stress. Measurement of glutathione reductase activity in red blood cells is commonly used to assess riboflavin nutritional status .

Xanthine oxidase, another FAD-dependent enzyme, catalyzes the oxidation of hypoxanthine and xanthine to uric acid. Uric acid is one of the most effective water-soluble antioxidants in the blood. Riboflavin deficiency can result in decreased xanthine oxidase activity, reducing blood uric acid levels .

Nutrient Interactions

B-complex vitamins: Because flavoproteins are involved in the metabolism of several other vitamins (vitamin B6, niacin, and folic acid), severe riboflavin deficiency may impact many enzyme systems. Conversion of most naturally available vitamin B6 to its coenzyme form, pyridoxal 5'-phosphate (PLP), requires the FMN-dependent enzyme, pyridoxine 5'-phosphate oxidase (PPO). At least two studies in the elderly have documented significant interactions between indicators of vitamin B6 and riboflavin nutritional status. The synthesis of the niacin-containing coenzymes, NAD and NADP, from the amino acid, tryptophan, requires the FAD-dependent enzyme, kynurenine mono-oxygenase. Severe riboflavin deficiency can decrease the conversion of tryptophan to NAD and NADP, increasing the risk of niacin deficiency. Methylene tetrahydrofolate reductase (MTHFR) is an FAD-dependent enzyme, which plays an important role in maintaining the specific folate coenzyme required to form methionine from homocysteine (see diagram). Along with other B-vitamins, increased riboflavin intake has been associated with decreased plasma homocysteine levels. Recently, increased plasma riboflavin levels were associated with decreased plasma homocysteine levels mainly in those individuals who were homozygous for the C677T polymorphism of the MTHFR gene and whose folate intake was low. Such results illustrate the potential for complex interactions between genetic and dietary factors on chronic disease risk.

Iron: Riboflavin deficiency alters iron metabolism. Although the mechanism is not clear, research in animals suggests that riboflavin deficiency may impair iron absorption, increase intestinal loss of iron, and/or impair iron utilization for the synthesis of hemoglobin. In humans, improving riboflavin nutritional status has been found to increase circulating hemoglobin levels. Correction of riboflavin deficiency in individuals who are both riboflavin deficient and iron deficient improves the response of iron-deficiency anemia to iron therapy.