Featured article | October 2026
Riboflavin as a Regulator of Cellular Metabolism: From the Classic Vitamin B2 to a Key Redox Factor
Kaźmierczak-Barańska, J., et al. (2026). Nutrients, 18(19), 3223.
This narrative review examines riboflavin (vitamin B2) as a regulator of mitochondrial energy production, antioxidant defenses and cellular metabolism. The review also addresses its biochemical mechanisms, the consequences of deficiency and emerging evidence for its involvement in neurological disorders, diabetes and other conditions associated with oxidative stress.
Discussed in the article:
Riboflavin is essential for mitochondrial energy production
- Riboflavin is converted into flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), coenzymes required by numerous metabolic enzymes.
- FMN functions in mitochondrial respiratory complex I, while FAD supports complex II and fatty acid β-oxidation.
- Riboflavin deficiency can impair electron transport, reduce ATP production and increase mitochondrial oxidative stress.
Riboflavin supports antioxidant defenses
- FAD is required by glutathione reductase to regenerate reduced glutathione (GSH) from oxidized glutathione (GSSG).
- The enzyme FAD-dependent thioredoxin reductase helps maintain cellular redox balance and protect against oxidative damage.
- Riboflavin may help the body produce more mitochondria and strengthen its antioxidant defenses through signaling pathways involving AMPK, PGC-1α, and heme oxygenase-1.
Riboflavin can also act as a pro-oxidant
- Although riboflavin primarily supports antioxidant defenses, exposure to blue or ultraviolet light can activate it to generate reactive oxygen species that may damage lipids, proteins and DNA.
- Outside the scope of this review, this light-sensitive chemistry has practical relevance to food preservation (such as light-exposed milk) and medical applications, including corneal cross-linking and blood-product pathogen reduction.
Riboflavin deficiency can affect neurological function
- Neurons are particularly dependent on mitochondrial ATP production and antioxidant protection.
- Inherited riboflavin transporter deficiencies can cause severe neurological dysfunction, including motor neuron damage.
- Experimental studies suggest that riboflavin may protect neuronal mitochondria against oxidative injury. In a model of riboflavin transporter deficiency, combined treatment with riboflavin and N-acetylcysteine improved mitochondrial morphology.
Riboflavin may improve metabolic dysfunction associated with diabetes
- In diabetic mice, riboflavin supplementation increased glutathione reductase activity by 34% in the liver, 35% in the kidneys and 52% in the pancreas.
- Riboflavin treatment also restored GLUT4 expression in skeletal muscle and adipose tissue, potentially supporting glucose uptake.
Why it matters
The findings highlight how inadequate riboflavin availability may contribute to cellular dysfunction and suggest that riboflavin status deserves greater consideration when evaluating neurological and metabolic health.
“[…] a survey in Ireland found more than 50% of older adults to have low or deficient riboflavin status (i.e., EGRAC > 1.3), and approximately 20% to have an inadequate intake of riboflavin.”
