Potential Vitamin B6 Depletion During Carbidopa/Levodopa Therapy in Parkinson's Disease: A Scoping Review of Direct Evidence.

Vitamin B6 depletion during carbidopa/levodopa therapy has been linked to polyneuropathy, seizures, and anemia, but the direct evidence is heterogeneous, and causality remains uncertain. We conducted a focused scoping review of direct empirical evidence on vitamin B6 biology during carbidopa/levodopa exposure and on vitamin B6-related clinical consequences supported by biochemical assessment. We also included studies of biomarker-guided monitoring, supplementation, and direct carbidopa-vitamin B6 chemistry. PubMed, Scopus, and Web of Science were searched without date or language limits on July 21, 2026. Of 656 database records, 448 unique records were screened, 161 reports were assessed in full, and 36 reports met the focused criteria. These comprised 34 reports involving human participants, including 18 group-level studies and 16 case reports or series, and two nonclinical experimental reports. Direct chemistry supports stable carbidopa-pyridoxal 5'-phosphate binding, and high-dose carbidopa exposure in dogs produced a preventable deficiency phenotype. Human studies reported lower vitamin B6 biomarkers most consistently with high or rapidly increased exposure, but findings were not uniform, and dose, route, advanced disease, nutrition, supplementation, and overlapping cohorts could not be separated. Severe deficiency accompanied axonal neuropathy, refractory seizures, and microcytic or sideroblastic-pattern anemia in individual case reports. No study established population-level incidence of vitamin B6 depletion or attributable clinical outcomes, a causal exposure threshold, an optimal testing interval, or a prophylactic dose. Direct vitamin B6 testing, interpreted with laboratory-specific reference intervals and complementary nutritional, hematologic, and neurologic assessment, is better supported by the available evidence than reliance on homocysteine alone. Prospective exposure-resolved studies are required before route-specific risk or universal supplementation can be recommended.