Combined Metabolic Activators accelerates recovery in mild-to-moderate COVID-19

Abstract

BACKGROUND The characteristics of COVID-19 outbreak and high fatality rate of COVID-19 infection have attracted the attention of scientists due to the strong interactions between components of metabolic syndrome, metabolic abnormalities, and viral pathobiology of COVID-19. Combined metabolic cofactors supplementation (CMCS) consisting of L-serine, N-acetyl-L-cysteine (NAC), nicotinamide riboside (NR), and L-carnitine tartrate is being studied for the treatment of patients with COVID-19. METHODS We conducted a placebo-controlled, phase-2 clinical trial involving ambulatory COVID-19 patients. A total of 100 patients were randomly assigned on a 3:1 basis to hydroxychloroquine plus CMCS or hydroxychloroquine plus placebo. The total treatment period for the hydroxychloroquine was 5 days, and for the CMCS/placebo was 14 days. Clinical status was evaluated daily by phone, using a binomial scale for subject reported presence or absence for multiple COVID-19 related symptoms. Plasma samples for clinical chemistry analyses were collected on day 0 and day 14. RESULTS A total of 93 patients completed the trial. The combination of CMCS and hydroxychloroquine significantly reduced the average complete recovery time compared with hydroxychloroquine and placebo (6.6 days vs 9.3 days, respectively). Moreover, there was a significant reduction in ALT, AST and LDH levels on day 14 compared to day 0 in the hydroxychloroquine plus CMCS group. The adverse effects were uncommon and self-limiting. CONCLUSIONS In patients with mild-to-moderate COVID-19, CMCS resulted in a significant reduction in recovery time and liver enzymes associated with hepatic function compared to placebo. We observed that CMSC is associated with a low incidence of adverse events.

Clinical trials in COVID-19 management & prevention: A meta-epidemiological study examining methodological quality

“…The 91 included trials enrolled a total of 46,802 patients between January 18 (first recruitment) and October 4 (last recruitment). Included trials evaluated one or more drugs (n = 76, [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , ...…”

Biological and Clinical Factors contributing to the Metabolic Heterogeneity of Hospitalized Patients with and without COVID-19

“…Interestingly, declines in tryptophan-derived de novo nicotinamide synthesis is associated with aging and in ammation, 70 suggesting that nutritionally replenishing NAD reservoirs (e.g., nicotinamide riboside) may be therapeutic in facilitating recovery from severe COVID-19. 71 Depleting tryptophan to promote kynurenine synthesis may also lead to serotonin depletion, a key component of platelet dense granules with a role in platelet activation. 72 This is relevant given the importance of coagulopathy in COVID-19, with increased plasma levels of FVIII, D-dimers, and VWF (i.e., increased VWF:collagen binding activity, increased VWF:ADAMTS-13 activity ratio), which are among the top correlates of mortality in our cohort.…”

N-Acetylcysteine as Adjuvant Therapy for COVID-19 – A Perspective on the Current State of the Evidence

“…Only two patients in the intervention group (2.8%) reported a similar adverse event of mild rash on the upper part of the body. 72 A case report of a 54-year-old male patient with preexisting hypertension, hyperlipidemia, and obesity who was tested positive for COVID-19 11 days prior to admission to Holy Family Hospital in Massachusetts showed that combination therapy of hydroxychloroquine and N-acetylcysteine led to a progressive clinical improvement and a decrease in inflammatory markers for inflammation, for instance, C-reactive protein and lactic acid. The patient was mechanically ventilated for only 3 days, was then transferred from the ICU to the general ward on Day 7, and was finally discharged from the hospital on Day 12 with stable vital signs and normalized laboratory results.…”

“…In non-G6PD deficient patients, significant overall reductions in inflammatory markers (C-reactive protein and ferritin) were observed with the use of N-acetylcysteine. Altay et al (2020), Turkey 72 Single center, double-blind, randomized, open-label, placebo-controlled trial, Phase 2 Adults aged 18 years or older with confirmed COVID-19 within 24 hours and had a stable clinical course 100 Hydroxychloroquine of an initial dose of 2×400 mg orally, followed by 400 mg/day (2x200 mg) for 5 days. Subsequently, a combined metabolic cofactors supplementation (CMCS) comprising L-carnitine tartrate 7.46 g/day, N-acetylcysteine 5.1 g/day, Nicotinamide riboside 2 g/day plus Serine 24.7 g/day was given orally twice a day for 14 days (n=71).…”

“…Only two patients in the intervention group (2.8%) reported a similar adverse event of mild rash on the upper part of the body. 72 …”