Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
Altay et al.
, Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19
, Advanced Science, doi:10.1002/advs.202101222
RCT 304 low-risk outpatients, 229 treated with N-acetylcysteine, l-carnitine tartrate, nicotinamide riboside chloride, and serine, showing significantly faster recovery with treatment. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism were significantly improved in treated patients.
risk of hospitalization, 80.1% lower, RR 0.20, p = 0.25, treatment 0 of 229 (0.0%), control 1 of 76 (1.3%), NNT 76, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of no recovery, 82.7% lower, RR 0.17, p < 0.001, treatment 229, control 75, inverted to make RR<1 favor treatment, multivariate Cox regression.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Altay et al., 28 Jun 2021, Double Blind Randomized Controlled Trial, placebo-controlled, Turkey, peer-reviewed, 18 authors, this trial uses multiple treatments in the treatment arm (combined with l-carnitine tartrate, nicotinamide riboside chloride, serine) - results of individual treatments may vary.
Abstract: RESEARCH ARTICLE
Combined Metabolic Activators Accelerates Recovery in
Ozlem Altay, Muhammad Arif, Xiangyu Li, Hong Yang, Mehtap Aydın, Gizem Alkurt,
Woonghee Kim, Dogukan Akyol, Cheng Zhang, Gizem Dinler-Doganay, Hasan Turkez,
Saeed Shoaie, Jens Nielsen, Jan Borén, Oktay Olmuscelik, Levent Doganay,
Mathias Uhlén, and Adil Mardinoglu*
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
Dr. O. Altay, M. Arif, Dr. X. Li, H. Yang, Dr. W. Kim, Dr. C. Zhang,
Dr. S. Shoaie, Prof. M. Uhlén, Prof. A. Mardinoglu
Science for Life Laboratory
KTH—Royal Institute of Technology
Stockholm, SE-100 44, Sweden
Dr. O. Altay
Department of Clinical Microbiology
Dr Sami Ulus Training and Research Hospital
University of Health Sciences
Ankara 06080, Turkey
The ORCID identiﬁcation number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/advs.202101222
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
This is an open access article under the terms of the Creative Commons
Attribution License, which permits use, distribution and reproduction in
any medium, provided the original work is properly cited.
Adv. Sci. 2021, 8, 2101222
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