The Dynamic Coenzyme Network of B Vitamins in Nutritional Neuropathy and Neuropsychiatric Vulnerability: A Mechanistic Narrative Review

Yonghyun Yoon, Jihyo Hwang, Rowook Park, Jaehyun Shim, King Hei Stanley Lam, Jeimylo C. de Castro, Teinny Suryadi, Anwar Suhaimi and Chan-Mo Yang

Nutrients 2026, 18(14), 2306

Abstract

Nutritional peripheral neuropathy is a clinically important condition associated with inadequate intake, malabsorption, bariatric surgery, aging, metabolic disease, and chronic medication exposure. B vitamins serve as essential coenzymes in mitochondrial energy metabolism, one-carbon metabolism, neurotransmitter synthesis, redox regulation, and myelin maintenance. This narrative review synthesizes mechanistic and clinical evidence linking B vitamin-dependent coenzyme systems to nutritional neuropathy and selected neuropsychiatric manifestations. Particular emphasis is placed on the tricarboxylic acid cycle, electron transport chain, urea cycle, folate–methionine cycle, and MTHFR-dependent one-carbon metabolism. The proposed “dynamic coenzyme network” is intended as an integrative mechanistic framework rather than a stand-alone therapeutic recommendation. Although biochemical interdependence among B vitamins supports evaluation for combined or functional deficiencies in selected patients, mechanistic plausibility should not be equated with clinical efficacy. Clinical consideration of B vitamin repletion should be guided by documented deficiency, dietary and gastrointestinal risk factors, medication exposure, neurological phenotype, and functional biomarkers such as homocysteine and methylmalonic acid. Adjunctive nutrients, including alpha-lipoic acid and acetyl-L-carnitine, may have context-specific relevance, particularly in metabolic neuropathies, but evidence for fixed multi-nutrient combinations remains heterogeneous. Further well-designed clinical studies are needed to determine whether this mechanistic framework translates into meaningful neurological or neuropsychiatric benefit beyond established deficiency states.

Keywords: B vitamins; nutritional neuropathy; mitochondrial metabolism; coenzyme network; functional deficiency; one-carbon metabolism; homocysteine; cobalamin; folate; medication-associated deficiency; neuropsychiatric vulnerability; narrative review

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