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By Mike Murray, RDN, CSCS, CISSN

 

Riboflavin (Vitamin B2)

 

The riboflavin molecule consists of an isoalloxazine ring bound to a ribitol side chain. It is an integral part of the coenzymes flavin mono-nucleotide (FMN) and flavin adenine dinucleotide (FAD). 

Riboflavin is converted to FAD and FMN in the cellular cytoplasm of most tissues, and it is in these coenzyme forms that riboflavin functions as a catalyst for oxidation-reduction reactions (i.e., a reaction in which electrons are transferred from one atom to another). 

Riboflavin also acts as an antioxidant and plays a role in red blood cell production and the transportation of oxygen to cells.

The main antioxidant activity of riboflavin is related to the conversion of glutathione –- an endogenously synthesized tripeptide known as the “master antioxidant”. Glutathione can exist intracellularly either in the oxidized or reduced state. The oxidized form is potentially toxic to cells and the reduced form detoxifies reactive oxygen species. Glutathione reductase converts oxidized glutathione to the reduced form and requires FAD to do so. 

Dietary sources contain free riboflavin, but mainly FMN and FAD bound to a food protein that need to be hydrolyzed to riboflavin before they can be absorbed. In the stomach, the acidic environment releases the coenzymes FMN and FAD from the protein. The coenzymes are then hydrolyzed to riboflavin by nonspecific pyrophosphatases and phosphatases in the brush border membranes of enterocytes. 

The primary absorption of riboflavin occurs in the proximal small intestine via a rapid, saturable transport system, and a small amount is absorbed in the large intestine. The rate of absorption is proportional to intake, and it increases when ingested along with other foods and in the presence of bile salts. At low intakes, most absorption is via an active or facilitated transport system. At higher levels of intake, riboflavin can be absorbed by passive diffusion. 

The RDA for riboflavin is 1.3 mg/day and 1.1 mg/day for adult men and women. The EAR is 1.1 mg/day and 0.9 mg/day for men and women. 

Riboflavin is found in fortified grains and cereals, milk and milk products, beef, and green vegetables. The following foods are some of the most efficient to meet the daily value for riboflavin. 

Oats, instant, fortified, cooked with water 1.1 mg per serving (1 cup)
Greek yogurt 0.57 mg per serving (1 cup)
Eggs 0.63 mg per serving (3 eggs)
Milk, 2% fat 0.5 mg per serving (1 cup)
Beef, tenderloin steak, boneless, trimmed of fat, grilled 0.35 mg per serving (3 oz)

Clinical signs of deficiency, such as sore throat, angular stomatitis (i.e., cracks or sores at the corners of the mouth), glossitis (i.e., magenta tongue), seborrheic dermatitis (i.e., moist, scaly skin), weakness, and normochromic normocytic anemia, have been shown to appear at intakes less than 0.5–0.6 mg/day. 

Notably, riboflavin is typically associated with deficiency of other B vitamins including pyridoxine (vitamin B6), niacin (vitamin B3), and folate (vitamin B9), due to the role of flavin coenzyme activity in their metabolism: 

 

  • The conversion of vitamin B6 to its coenzyme form, pyridoxal 5’-phosphate, requires the FMN-dependent enzyme, pyridoxine 5’-phosphate oxidase.
  • The synthesis of niacin-containing coenzymes, NAD and NADP, from the amino acid tryptophan, requires the FAD-dependent enzyme, kynurenine 3-monooxygenase.
  • Methylenetetrahydrofolate reductase is a key enzyme in the metabolism of folate and uses FAD as a cofactor. 

 

Riboflavin also alters iron metabolism, and deficiency may impair iron mobilization and globin production and reduce intestinal absorptive capacity; indeed, correcting riboflavin deficiency has been shown to improve the response to iron supplementation.

The risk of riboflavin deficiency may be increased in the following populations: very physically active people, women who are pregnant or lactating, vegetarians/vegans, dialysis patients, and alcoholics

Due to insufficient data, a UL has not been established for riboflavin; there are no demonstrated functional or structural adverse effects documented in humans or animals after excess consumption. One study reported no short-term side effects in 49 patients treated with 400 mg/day as a single oral dose for at least 3 months. 

The apparent lack of harm from high oral doses of riboflavin may be due to its limited capacity for absorption and its rapid excretion in the urine. The maximal amount of riboflavin that can be absorbed from a single oral dose has been shown to be about 27 mg. In healthy adults who consume well-balanced diets, riboflavin accounts for 60–70% of excreted urinary flavins.  

Riboflavin can be measured through the erythrocyte glutathione reductase activation coefficient assay (EGRAC), erythrocyte flavin, and urinary flavin. EGRAC is the most common method to determine riboflavin status. 

In this assay, erythrocyte glutathione reductase activity is measured in vitro before and after exposure to FAD. A low value indicates little to no stimulation by FAD due to adequate riboflavin status, and a higher activity coefficient reflects a larger amount of unsaturated glutathione reductase apoenzyme resulting from a lack of FAD (i.e., inadequate riboflavin status). 

EGRAC Riboflavin status
< 1.2 Adequate
1.2–1.4 Low
> 1.4 Deficient