Causes and Clinical Sequelae of Riboflavin Deficiency

Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant potential and metabolic interactions with other micronutrients, including iron, vitamin B6 and folate. Severe riboflavin deficiency, largely confined to low-income countries, clinically manifests as cheilosis, angular stomatitis, glossitis, seborrheic dermatitis and severe anemia with erythroid hypoplasia. Sub-clinical deficiency may be much more widespread, including in high-income countries, but typically goes undetected because riboflavin biomarkers are rarely measured in human studies. There are adverse health consequences of low and deficient riboflavin status throughout the lifecycle, including anemia and hypertension, that could contribute substantially to the global burden of disease. This review will consider the available evidence on causes, detection and consequences of riboflavin deficiency, ranging from clinical deficiency signs to manifestations associated with less severe deficiency, and the related research, public health and policy priorities.