Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.
Level 2 - randomized trial
Individual randomized, double-blinded, placebo-controlled phase II trial.
PubMed 39816194 · doi:10.1093/braincomms/fcae478
What was done
Parkinson's disease patients were enrolled in an 84-day randomized, double-blind, placebo-controlled phase II trial (NCT04044131). Patients received either placebo or a combined metabolic activator (CMA) formulation containing L-serine (12.35 g), N-acetyl-L-cysteine (2.55 g), nicotinamide riboside (1 g), and L-carnitine tartrate (3.73 g) once daily for the first 28 days, then twice daily for 56 days. The primary objective was evaluating motor function using the Unified Parkinson's Disease Rating Scale (UPDRS) along with safety and tolerability. Secondary objectives included cognitive assessment via the Montreal Cognitive Assessment (MoCA), brain activity via functional MRI, and plasma metabolomics and proteomics analysis.
What was found
No improvement in UPDRS motor function was observed. Cognitive function significantly improved in the CMA group over 84 days (P < 0.0000), while no change was seen in the placebo group (P > 0.05). The abstract also notes a significant reduction (P = 0.001) in MoCA scores in the CMA group versus no decline (P > 0.05) in placebo among severe Parkinson's disease patients with lower baseline MoCA scores. Cognitive improvement correlated with altered functional MRI brain network connectivity in cognitive regions and multi-omic biomarker shifts.
Why it matters
Supplementation with metabolic precursors targeting mitochondrial energy and redox pathways may support cognitive function in Parkinson's disease, even when primary motor symptoms remain unchanged.
Limits
The abstract does not disclose the sample size, patient baseline demographics, or specific adverse event rates. Cognitive improvement was a secondary endpoint whereas the primary motor endpoint was negative. The reported decline in MoCA scores among patients with lower baseline scores is noted but not fully contextualized in the abstract. Duration was limited to 84 days.
Cited by
- partial Evidence shows that supporting mitochondria with cofactors including vitamin B2, vitamin B3, and magnesium is beneficial in Parkinson's disease.