Homocysteine, vitamin B metabolites, dopamine-substituting compounds, and symptomatology in Parkinson's disease: clinical and therapeutic considerations

Emerging studies suggest a correlation between elevated plasma homocysteine (hcy) levels and the risk of atherosclerosis, vascular disorders, and neurodegenerative diseases, including Parkinson's disease (PD). This narrative review delves into the intricate relationships between Hcy, vitamin B metabolites, dopamine-substituting compounds, and various symptoms of PD. Patients undergoing a long-term L-dopa/dopa-decarboxylase inhibitor (DDI) regimen, especially without a concurrent catechol-O-methyl transferase (COMT) inhibitor or methyl group-donating vitamin supplementation, such as vitamins B6 and B12, exhibit an elevation in Hcy and a decline in vitamin B metabolites. These altered concentrations appear to be associated with heightened risks of developing non-motor symptoms, including peripheral neuropathy and cognitive disturbances. The review underscores the impact of levodopa metabolism via COMT on homocysteine levels. In light of these findings, we advocate for the supplementation of methyl group-donating vitamins, notably B6 and B12, in patients undergoing a high-dose L-dopa/DDI regimen, particularly those treated with L-dopa/carbidopa intestinal gel (LCIG) infusion.

Automated summary

Emerging studies show a correlation between elevated plasma homocysteine levels and the risk of atherosclerosis, vascular disorders, and neurodegenerative diseases. This review explores the intricate relationships between homocysteine, vitamin B metabolites, dopamine-substituting compounds, and various symptoms of Parkinson's disease (PD). Patients on a long-term L-dopa/dopa-decarboxylase inhibitor regimen without concurrent catechol-O-methyl transferase (COMT) inhibitor or methyl group-donating vitamin supplementation exhibit higher homocysteine levels and decreased vitamin B metabolites, which are associated with an increased risk of non-motor symptoms including peripheral neuropathy and cognitive disturbances. The review highlights the impact of levodopa metabolism via COMT on homocysteine levels and suggests methyl group-donating vitamin supplementation, particularly with vitamins B6 and B12, for patients on a high-dose L-dopa/DDI regimen, especially those treated with L-dopa/carbidopa intestinal gel infusion.