Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19

The study “Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19” aimed to investigate whether a mixture of combined metabolic activators (CMAs), consisting of precursors for glutathione and nicotinamide adenine dinucleotide (NAD+), could improve metabolic function and expedite recovery in COVID-19 patients.

Here’s a detailed summary:

Study Overview and Hypothesis

  • Objective: To assess if CMAs could restore metabolic function and aid recovery in COVID-19 patients, especially targeting mitochondrial dysfunction and metabolic abnormalities.
  • Background: Previous research indicated CMAs, including l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, improved plasma levels of metabolites associated with antioxidant metabolism and inflammatory proteins.
  • Hypothesis: Administering CMAs would improve conditions associated with COVID-19, increase NAD+ and glutathione levels, activate mitochondrial metabolism, and potentially accelerate recovery or reduce severity​​.


  • Phase 2 Study: Involved 100 adults with confirmed COVID-19; 93 completed the study (71 in the CMA group, 22 in the placebo group). Patients also received standard care therapy with hydroxychloroquine.
  • Phase 3 Study: Included 309 adult patients; 304 completed the study (229 in CMA group, 75 in placebo group). Standard therapy with hydroxychloroquine and Favipiravir was also administered.
  • Primary Endpoint: Time to symptom-free recovery.
  • Additional Analysis: Involved measuring clinical variables, analyzing plasma metabolome and proteome to understand the molecular mechanisms of the disease and CMA administration​​.

Key Findings

  1. Recovery Time: In both phases, the CMA group had significantly shorter recovery times compared to placebo (6.6 vs. 9.3 days in phase 2; 5.7 vs. 9.2 days in phase 3).
  2. Clinical Variables: Serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatinine levels improved significantly in the CMA group. Increases in plasma glucose levels were observed only in the placebo group.
  3. Metabolomics Data: Analysis revealed significant differences in plasma metabolite levels between the CMA and placebo groups, suggesting metabolic changes due to CMA administration.
  4. Cytokine Levels: Plasma levels of several cytokines, including IL6, IL10, and TNF, were significantly downregulated in the CMA group, indicating an improvement in inflammation-related markers. This effect was more pronounced in the CMA group compared to the placebo group​​.


  • Effectiveness of CMAs: The study suggests that CMAs can potentially accelerate symptom-free recovery in COVID-19 patients, with improved clinical parameters and reduced inflammatory markers.
  • Implications for COVID-19 Treatment: The findings advocate for considering CMAs as a complementary approach in treating mild-to-moderate COVID-19 cases, particularly focusing on metabolic and inflammatory aspects of the disease.

The study provides significant insights into the potential role of metabolic activators in the management of COVID-19, emphasizing the importance of targeting metabolic dysfunctions and inflammation in treatment strategies.

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