Levodopa Metabolism, Folate Deficiency, and Cardiovascular Risk in Lewy Body Dementia

BackgroundL-DOPA remains the cornerstone of Parkinsons disease (PD) therapy, yet its long-term metabolic consequences are poorly understood. Folate deficiency appears disproportionately frequent in patients with dementia with Lewy bodies (DLB), a synucleinopathy closely related to PD. We hypothesized that folate deficiency is more prevalent in DLB than in Alzheimers disease (AD) or cognitively normal controls (NC), possibly due to excessive folate consumption during L-DOPA metabolism, which may elevate homocysteine levels and increase vascular risk. MethodsWe conducted a retrospective cross-sectional study comparing serum folate levels among DLB (n = 15), AD (n = 73), and NC (n = 7). Deficiency rates for folate, vitamin B12 (B12), and vitamin B1 (B1) were compared using Fishers exact test. Within DLB, associations) between folate/B12 deficiency and L-DOPA usage were assessed. Scatter plots visualized relationships between daily L-DOPA dosage and serum folate or B12 levels. Macrocytosis (MCV >100 fL) was evaluated as a potential indicator of vitamin depletion. ResultsFolate deficiency was significantly more prevalent in DLB than in AD or NC (p = 0.0021). Within DLB, folate deficiency was more frequent among L-DOPA users (p = 0.0406), while B12 deficiency showed no significant association. B12 levels varied widely, with some patients showing elevated concentrations. In contrast, folate levels tended to fall below the reference limit in all but one L-DOPA user. MCV was not a reliable indicator of deficiency. ConclusionL-DOPA-treated DLB patients may require individualized monitoring and tailored supplementation to mitigate vascular risk.