Combined Metabolic Activators (CMAs) Improve Cognitive Functions without Altering Motor Scores in Parkinson's Disease

A new study assessing whether administration of a mixture of Combined Metabolic Activators (CMAs), including NAD+ precursor nicotinamide riboside (NR), could treat Parkinson’s disease patients, is now available on the open access preprint publication server medRxiv.org.

Why This Matters

Parkinson’s Disease (PD) is a neurodegenerative disease largely characterized by impairments in motor functions, including tremors, stiffness, slow movement, or difficulty in maintaining balance, as well as in non-motor functions, such as cognitive impairment [1]. Those who suffer from PD may also experience mental and behavioral changes, memory difficulties, and depression. There’s currently no cure for PD, only medication, surgical treatment, and therapies to treat some symptoms [2]. The authors of this study set out to explore potential treatments for patients with PD by supplementing mild-to-moderate PD patients with combined metabolic activators (CMAs) consisting of L-carnitine tartrate, NAD+ precursor nicotinamide riboside (NR), serine, and N-acetyl-L-cysteine (NAC) [3].

Results Demonstrated Improved Cognitive Function and Markers of Liver Health in Patients with Parkinson’s Disease

The study was a randomized, double-blinded, placebo-controlled phase II clinical study of mild-to-moderate PD patients who were between 41-84 years of age. Majority of the patients were male. Each dose consisted of 3.73g L-carnitine tartrate, 1g NR, 12.35g serine, and 2.55g (NAC). All patients received one dose of CMA twice per day [3]. 

Researchers found that CMA supplementation significantly improved cognitive function by 21% in patients with PD, compared to 11% in the placebo group after 84 days. The improvement in cognitive function was more dramatic in more severe PD patients. Although an improvement in cognitive function was observed, CMA supplementation did not alter the patients’ motor scores [3]. 

CMAs also significantly improved levels of serum aspartate aminotransferase (AST, a marker of liver damage), total bilirubin, high-density lipoprotein (HDL, or “good” cholesterol), and triglycerides [3].

Built Upon Previously Successful Studies

The use of this CMA was based on previously successful clinical trials demonstrating CMA supplementation improved liver health in patients with nonalcoholic fatty liver disease (NAFLD) [4,5], recovery time of patients with COVID-19 [6], and cognitive function in Alzheimer’s disease (AD) patients [7]. In all four trials, the success of the CMA was partly attributed to its beneficial effect on mitochondrial health and function.

The Significance of This Study

This study is the first to investigate the effects of CMA supplementation on PD patients. The positive outcome of this study contributes to the growing body of evidence suggesting that CMAs may provide a therapeutic benefit in a variety of conditions by targeting mitochondrial health and function. More research is needed to investigate the use of this metabolic cocktail as a therapeutic strategy for PD.

Relevant Studies That Also Used CMAs

Footnote

The study used nicotinamide riboside (NR) from ChromaDex.

References

  1. Kouli, A., K.M. Torsney, and W.L. Kuan, Parkinson's Disease: Etiology, Neuropathology, and Pathogenesis, in Parkinson's Disease: Pathogenesis and Clinical Aspects, T.B. Stoker and J.C. Greenland, Editors. 2018: Brisbane (AU). https://pubmed.ncbi.nlm.nih.gov/30702842/

  2. Parkinson’s Disease. (2017). NIH. Retrieved August 5, 2021, from https://www.nia.nih.gov/health/parkinsons-disease

  3. Yulug, B., et al., Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson's Disease. medRxiv, 2021. DOI: https://doi.org/10.1101/2021.07.28.21261293

  4. Zhang, C., et al., The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease. Mol Syst Biol, 2020. 16(4): p. e9495. https://pubmed.ncbi.nlm.nih.gov/32337855/

  5. Zeybel, M., et al., Combined Metabolic Cofactor Supplementation Reduces Liver Fat in Nonalcoholic Fatty Liver Disease Patients. Cell Press Sneak Peek, 2021. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3778301

  6. Altay, O., et al., Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19. Adv Sci (Weinh), 2021: p. E2101222. https://pubmed.ncbi.nlm.nih.gov/34180141/

  7. Yulug, B., et al., Combined Metabolic Activators Improves Cognitive Functions in Alzheimer’s Disease. medRxiv, 2021: p. 2021.07.14.21260511. https://www.medrxiv.org/content/10.1101/2021.07.14.21260511v2

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