Riboflavin deficiency and apoptosis: a review.

Abstract

Riboflavin, commonly known as vitamin B₂, is an essential micronutrient critical for the function of flavoproteins, which utilize flavin mononucleotide and flavin adenine dinucleotide as cofactors in energy metabolism, lipid metabolism, redox regulation, and protein folding. Nutritional riboflavin deficiency has previously been observed in humans and animals, leading to adverse outcomes such as growth retardation, increased mortality, and liver damage, which may be attributed to apoptosis. While such deficiencies are now uncommon due to improved living standards, certain high-risk groups (e.g., those with chronic diseases, the elderly, and pregnant) have increased riboflavin demands, making them vulnerable to physiological riboflavin deficiency associated with apoptosis. Understanding the pathways through which riboflavin deficiency induces apoptosis, including mitochondrial dysfunction, endoplasmic reticulum stress, and reactive oxygen species, is essential for grasping its broader health impacts. Additionally, this deficiency disrupts fatty acid metabolism, potentially resulting in lipotoxic apoptosis. Despite its significance, riboflavin deficiency-induced apoptosis remains underexplored in the literature. Therefore, this review will discuss the roles of redox imbalance, mitochondrial dysfunction, endoplasmic reticulum stress, and lipotoxicity in apoptosis regulation due to riboflavin deficiency, aiming to highlight its importance for improving riboflavin nutrition and overall health.