A randomized clinical trial to evaluate the efficacy of L-carnitine L-tartrate to modulate the effects of SARS-CoV-2 infection.

Introduction: L-carnitine (LC) has been associated with inflammatory mediator reduction and with downregulating the angiotensin-converting enzyme-2 (ACE2) receptor, which is the target of SARS-CoV-2 attachment. Methods: This pilot phase 2 randomized, double-blind placebo-controlled trial contained two cohorts. Cohort 1 comprised 101 individuals with negative RT-PCR SARS-CoV-2 test results who cohabitated with an individual diagnosed with SARS-CoV-2 infection. Cohort 2 comprised 122 individuals with positive SARS-CoV-2 RT-PCR test results who were asymptomatic or had mild COVID-19 pneumonia symptoms. Participants in each cohort were randomized 1:1 to receive either 2 g elemental oral LC supplementation or placebo daily for 21 days. Primary endpoints included adverse events, SARS-CoV-2 infection incidence in Cohort 1, and disease progressions in Cohort 2. Secondary endpoints included between-group laboratory profile comparisons and Cohort 2 ACE1/ACE2 plasma levels. Disease progression was compared between the Cohort 2 groups using chest computed tomography. Results: In Cohort 1, two SARS-CoV-2 infections occurred in each group. The common adverse events included headache, dyspnea, and tiredness. In Cohort 2, platelet counts were elevated, and fibrinogen levels reduced in the LC group compared with those of the placebo group. Conclusion: Our study showed that LC was well-tolerated and suggests it modulates coagulation pathways. Furthermore, chest computed tomography images of the Cohort 2 LC group showed significant lung lesion improvement, suggesting that LC may slow COVID-19 progression.

L-Carnitine Tartrate Supplementation for 5 Weeks Improves Exercise Recovery in Men and Women: A Randomized, Double-Blind, Placebo-Controlled Trial.

L-carnitine tartrate has been shown to improve relatively short-term recovery among athletes. However, there is a lack of research on the longer-term effects in the general population. OBJECTIVE: The primary objectives of this randomized double-blind, placebo-controlled trial were to evaluate the effects of daily L-carnitine tartrate supplementation for 5 weeks on recovery and fatigue. METHOD: In this study, eighty participants, 21- to 65-years-old, were recruited. Participants were split into two groups of forty participants each, a placebo, and a L-carnitine Tartrate group. Seventy-three participants completed a maintenance exercise training program that culminated in a high-volume exercise challenge. RESULTS: Compared to placebo, L-carnitine tartrate supplementation was able to improve perceived recovery and soreness (p = 0.021), and lower serum creatine kinase (p = 0.016). In addition, L-carnitine tartrate supplementation was able to blunt declines in strength and power compared to placebo following an exercise challenge. Two sub-analyses indicated that these results were independent of gender and age. Interestingly, serum superoxide dismutase levels increased significantly among those supplementing with L-carnitine tartrate. CONCLUSIONS: These findings agree with previous observations among healthy adult subjects and demonstrate that L-carnitine tartrate supplementation beyond 35 days is beneficial for improving recovery and reducing fatigue following exercise across gender and age.

Effect of arabinogalactan on the gut microbiome: A randomized, double-blind, placebo-controlled, crossover trial in healthy adults.

OBJECTIVE: Promising evidence suggests beneficial health effects of arabinogalactan, but little is known about the effect of this non-digestible carbohydrate on the gut microbiota, a crucial mediator of human health. The objective of this study was to investigate the effect of an arabinogalactan product (ResistAid) on the fecal microbiome and short-chain fatty acids and gastrointestinal tolerance in healthy adults in a randomized, double-blind, crossover trial. METHODS: Thirty adults were randomly assigned to consume 15 g/d maltodextrin (control) or ResistAid for 6 wk. RESULTS: At week 6, compared to placebo, ResistAid supplementation led to a significant decrease in the ratio of fecal Firmicutes to Bacteroidetes, driven by an increase in Bacteroidetes and a decrease in Firmicutes. Moreover, the relative abundance of Bifidobacterium tended to increase with ResistAid supplementation. Additionally, ResistAid significantly decreased the α-diversity of the fecal microbiome. Predicted functional abundances based on 16S rRNA sequences showed that ResistAid supplementation increased the gene abundance of the gut microbiome for α-l-rhamnosidase, ß-fructosidase, and levanase, as well as tricarboxylic acid and vitamin B6 biosynthesis pathways. Fecal isovaleric, valeric, and hexanoic acids were significantly lower after ResistAid consumption. There were no statistically significant changes in bowel habit, stool consistency, gastrointestinal tolerance symptoms, chemistry profile, metabolic panel, or vitals, suggesting that consumption of 15 g daily ResistAid over 6 wk is safe. CONCLUSION: These results demonstrate that the gut microbiome composition and predicted functions can be modulated by ResistAid consumption, perhaps suggesting a mechanistic explanation on its reported benefits in metabolic parameters and the immune system.

L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.

Phytoplankton Supplementation Lowers Muscle Damage and Sustains Performance across Repeated Exercise Bouts in Humans and Improves Antioxidant Capacity in a Mechanistic Animal.

The purpose of this study was to investigate the impact of antioxidant-rich marine phytoplankton supplementation (Oceanix, OCX) on performance and muscle damage following a cross-training event in endurance-trained subjects. Additionally, an animal model was carried out to assess the effects of varying dosages of OCX, with exercise, on intramuscular antioxidant capacity. METHODS: In the human trial, endurance-trained subjects (average running distance = 29.5 ± 2.6 miles × week-1) were randomly divided into placebo (PLA) and OCX (25 mg) conditions for 14 days. The subjects were pre-tested on a one-mile uphill run, maximal isometric strength, countermovement jump (CMJ) and squat jump (SJ) power, and for muscle damage (creatine kinase (CK)). On Day 12, the subjects underwent a strenuous cross-training event. Measures were reassessed on Day 13 and 14 (24 h and 48 h Post event). In the animal model, Wistar rats were divided into four groups (n = 7): (i) Control (no exercise and placebo (CON)), (ii) Exercise (E), (iii) Exercise + OCX 1 (Oceanix, 2.55 mg/day, (iv) Exercise + OCX 2 (5.1 mg/day). The rats performed treadmill exercise five days a week for 6 weeks. Intramuscular antioxidant capacity (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)) and muscle damage (CK and myoglobin (MYOB) were collected. The data were analyzed using repeated measures ANOVA and t-test for select variables. The alpha value was set at p < 0.05. RESULTS: For the human trial, SJ power lowered in PLA relative to OCX at 24 h Post (-15%, p < 0.05). Decrements in isometric strength from Pre to 48 h Post were greater in the PLA group (-12%, p < 0.05) than in the OCX. Serum CK levels were greater in the PLA compared to the OCX (+14%, p < 0.05). For the animal trial, the intramuscular antioxidant capacity was increased in a general dose-dependent manner (E + Oc2 > E + Oc1 > E > CON). Additionally, CK and MYOB were lower in supplemented compared to E alone. CONCLUSIONS: Phytoplankton supplementation (Oceanix) sustains performance and lowers muscle damage across repeated exercise bouts. The ingredient appears to operate through an elevating oxidative capacity in skeletal muscle.

A Dose-Dependent Effect of Carnipure® Tartrate Supplementation on Endurance Capacity, Recovery, and Body Composition in an Exercise Rat Model.

The objective of this work is to investigate the effects of Carnipure® Tartrate (CT) supplementation with or without exercise on endurance capacity, recovery, and fatigue by assessing time to exhaustion as well as body weight and composition in rats. In addition, antioxidant capacity has been evaluated by measuring malondialdehyde (MDA) levels and antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathioneperoxidase; GSHPx) activities. Fifty-six male Wistar rats were divided into eight groups including seven rats each. A control group did not receive CT nor exercise. Another control group received 200 mg/kg CT without exercise. The other six groups of rats went through an exercise regimen consisting of a 5-day training period with incremental exercise capacity, which was followed by 6 weeks of the run at 25 m/min for 45 min every day. CT was supplemented at 0, 25, 50, 100, 200, and 400 mg/kg per day during the 6 weeks. Rats submitted to exercise and supplemented with CT had a significant and dose-dependent increase in time to exhaustion and this effect seems to be independent of exercise (p < 0.05). Additionally, recovery and fatigue were improved, as shown by a significant and dose-dependent decrease in myoglobin and lactic acid plasma levels, which are two markers of muscle recovery. CT supplementation led to a dose-response decrease in body weight and visceral fat. These effects become significant at 200 and 400 mg/kg doses (p < 0.05). Additionally, the antioxidant capacity was improved, as shown by a significant and dose-dependent increase in SOD, CAT, and GSHPx. Serum MDA concentrations decreased in exercising rats with CT supplementation. CT supplementation led to a decrease in serum glucose, triglycerides, and total cholesterol concentrations with the lowest levels observed at 400 mg/kg dose (p < 0.05). These effects correlated with a significant dose-dependent increase in serum total L-carnitine, free L-carnitine, and acetyl-carnitine, which linked the observed efficacy to CT supplementation. These results demonstrate that CT supplementation during exercise provides benefits on exercise performance, recovery, and fatigue as well as improved the lipid profile and antioxidant capacity. The lowest dose leads to some of these effects seen in rats where 25 mg/kg corresponds to 250 mg/day as a human equivalent.