Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
Journal article, 2021

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.



combined metabolic activators

omics data



Ozlem Altay

University of Health Sciences

Royal Institute of Technology (KTH)

Muhammad Arif

Royal Institute of Technology (KTH)

Xiangyu Li

Royal Institute of Technology (KTH)

Hong Yang

Royal Institute of Technology (KTH)

Mehtap Aydın

University of Health Sciences

Gizem Alkurt

University of Health Sciences

Woonghee Kim

Royal Institute of Technology (KTH)

Dogukan Akyol

University of Health Sciences

C. Zhang

Zhengzhou University

Royal Institute of Technology (KTH)

Gizem Dinler-Doganay

Istanbul Technical University (ITÜ)

Hasan Turkez

Atatürk University

Saeed Shoaie

Royal Institute of Technology (KTH)

King's College London

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Jan Borén

Sahlgrenska University Hospital

Oktay Olmuscelik

Istanbul Medipol Universitesi

Levent Doganay

University of Health Sciences

Mathias Uhlen

Royal Institute of Technology (KTH)

Adil Mardinoglu

King's College London

Royal Institute of Technology (KTH)

Advanced Science

2198-3844 (ISSN) 21983844 (eISSN)

Vol. 8 17 2101222

Subject Categories


Gastroenterology and Hepatology

Cardiac and Cardiovascular Systems





More information

Latest update

4/5/2022 5