Definition: Riboflavin is a water-soluble B vitamin, also known as vitamin B2.

• Riboflavin is the precursor of the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). FAD and FMN act as electron carriers in a number of oxidation-reduction (redox) reactions involved in energy production, cellular antioxidant function, and numerous metabolic pathways.
• Riboflavin (as FAD or FMN) is required for the metabolism of iron and vitamin B6 and in the synthesis of niacin from tryptophan. It also plays an essential role in folate and related one-carbon metabolism, where FAD is required as a cofactor for methylenetetrahydrofolate reductase (MTHFR), a key folate-metabolizing enzyme.
• Clinical signs of riboflavin deficiency include skin disorders, angular stomatitis, cheilosis, glossitis, and corneal vascularization. Riboflavin deficiency occurs commonly in low- and middle-income countries.
• Subclinical deficiency (low status) of riboflavin without clinical signs may be widespread, including in high-income countries, but it usually goes undetected because riboflavin biomarkers are very rarely measured in human studies.
• Low riboflavin status is associated with preeclampsia in pregnant women, a condition that may progress to eclampsia and cause severe bleeding and death. It is also linked with cataracts in older individuals.
• Deficient/low status of riboflavin interferes with the metabolism of folate, particularly in individuals with the variant 677TT genotype in MTHFR. There is some evidence that these individuals exhibit a higher risk of cancer.
• Case reports have shown that patients with autosomal recessive disorders of riboflavin metabolism may benefit from riboflavin supplementation.
• The MTHFR C677T polymorphism is associated with an increased risk of hypertension. Intervention studies have shown that supplementation with riboflavin (the MTHFR cofactor) effectively lowers blood pressure, specifically in individuals with the variant MTHFR 677TT genotype.
• Riboflavin supplementation has been evaluated as a prophylactic agent for migraine headaches, but the results are conflicting.
• Riboflavin supplementation has been studied as a potential adjunct therapy in cancer, certain eye disorders, and multiple sclerosis.

Drug interactions

• Anticonvulsants: Urinary riboflavin excretion was significantly lower in children receiving anticonvulsants than in healthy controls. In a case report, a patient developed phenytoin-induced erythroid aplasia, which was reversed by administration of riboflavin.
• Chlorpromazine: The administration of chlorpromazine (which is structurally similar to riboflavin) may cause riboflavin deficiency in malnourished patients by increasing urinary riboflavin excretion and by interfering with riboflavin metabolism. Riboflavin deficiency may cause psychiatric symptoms that could be confused with the symptoms for which chlorpromazine is being prescribed.
• Contraceptives, oral: The use of oral contraceptives may lead to suboptimal riboflavin status.
• Doxorubicin (Adriamycin): In animal studies, riboflavin supplementation prevented doxorubicin-induced cardiotoxicity.
• Nucleoside reverse transcriptase inhibitors: In patients with HIV infection who were taking nucleoside reverse transcriptase inhibitors, riboflavin appeared to be effective in the treatment of lactic acidosis and hepatic steatosis, which are potentially fatal complications associated with the use of these drugs.

Nutrient interaction

• Calcium salts form a chelate with riboflavin. Riboflavin absorption was decreased in women by concurrent ingestion of calcium.

Food sources

Good food sources of riboflavin include dairy products, eggs, legumes, meat, fish, poultry, green leafy vegetables, fruits, and grains. Since riboflavin is water-soluble, some may be lost in discarded cooking water.

Preparations

Riboflavin is the most frequently used vitamin B2 supplement. Riboflavin 5′-phosphate is also commercially available. Although riboflavin 5′-phosphate is one of the biologically active forms of vitamin B2, it is largely converted to riboflavin in the intestine before being absorbed. Moreover, clinical trials of oral vitamin B2 therapy have generally used riboflavin. Therefore, there does not appear to be any compelling reason to use riboflavin 5′-phosphate as an alternative to riboflavin.

Dosage and administration

The dosage of riboflavin used most often to treat various conditions has ranged from 15–50 mg/day. Inborn errors of metabolism have been treated with 100–200 mg/day. In some studies, 400 mg of riboflavin was given as a single daily dose for migraine prophylaxis. However, evidence from uncontrolled trials suggests that dosages much lower than 400 mg/day are effective for migraine prophylaxis. Patients with Parkinson’s disease were treated in one study with 30 mg of riboflavin 3 times per day. Since the maximum amount of riboflavin that can be absorbed at one time is around 25–30 mg, amounts larger than that should be taken in 2 or more divided doses per day.