International Journal of Molecular Sciences Review Riboflavin Deficiency—Implications for General Human Health and Inborn Errors of Metabolism 1, 1,2, 1 1 1 Signe Mosegaard y, Graziana Dipace y , Peter Bross , Jasper Carlsen , Niels Gregersen and Rikke Katrine Jentoft Olsen 1,* 1 Research Unit for Molecular Medicine, Department for Clinical Medicine, Aarhus University and Aarhus University Hospital, 8200 Aarhus N, Denmark;
[email protected] (S.M.);
[email protected] (G.D.);
[email protected] (P.B.);
[email protected] (J.C.);
[email protected] (N.G.) 2 Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari ‘Aldo Moro’, 70121 Bari, Italy * Correspondence:
[email protected]; Tel.: +45-78455412 These authors contributed equally to this work. y Received: 30 April 2020; Accepted: 26 May 2020; Published: 28 May 2020 Abstract: As an essential vitamin, the role of riboflavin in human diet and health is increasingly being highlighted. Insufficient dietary intake of riboflavin is often reported in nutritional surveys and population studies, even in non-developing countries with abundant sources of riboflavin-rich dietary products. A latent subclinical riboflavin deficiency can result in a significant clinical phenotype when combined with inborn genetic disturbances or environmental and physiological factors like infections, exercise, diet, aging and pregnancy. Riboflavin, and more importantly its derivatives, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), play a crucial role in essential cellular processes including mitochondrial energy metabolism, stress responses, vitamin and cofactor biogenesis, where they function as cofactors to ensure the catalytic activity and folding/stability of flavoenzymes. Numerous inborn errors of flavin metabolism and flavoenzyme function have been described, and supplementation with riboflavin has in many cases been shown to be lifesaving or to mitigate symptoms.