Derin AAgirdir B L-carnitine and immune system, Derin NDinç IjmuneOral cancer KOzcaglar H immunr, Kilinçarslan S Clin Otolaryngol Allied L-crnitine29 L-carnitine and immune system01 Jun Cited by: 12 articles PMID: The authors suggest that the amount of Acetyl-CoA in the mitochondrion available for esterification of free carnitine was reduced in fasted or energy-restricted animals leading to increased tissue carnitine concentrations while acetylcarnitine levels were reduced [ ]. Brief content visible, double tap to read full content.

Video

Acetyl L-Carnitine Benefits [Supplements, Side Effects \u0026 What it?]

L-carnitine and immune system -

The MR-PRESSO analysis detected no potential instrumental outlier at the nominal significance level of 0. The leave-one-out results suggest that the causal effect was not driven by single instrumental variable Supplementary Figures 1 , 2. Recent studies have proposed the potential role of carnitine as therapy options for COVID, but whether there is any correlation between them has not been explored yet.

Meanwhile, unmeasured confounding factors in clinical studies can potentially bias the association evidence, as is a common criticism inherent to observational studies.

Here, based on results from comprehensive two-sample MR analyses, we demonstrated that higher carnitine level was causally associated with decreased susceptibility and severity of COVID Carnitine occurs in two forms known as D-carnitine and L-carnitine, and only L-carnitine is biologically active in the body L-carnitine is an essential carrier for long-chain fatty acids from the cytosol through the inner mitochondrial membrane into the matrix, where β-oxidation takes place Although no studies have investigated the correlation between carnitine and COVID, previous research on carnitine might provide some insights from molecular aspects of why L-carnitine might protect against COVID L-carnitine plays an important role in fatty acid metabolism and could act as an adjuvant agent in the improvement of dyslipidemia L-carnitine was previously found to increase high-density lipoprotein and lower triglyceride, total cholesterol and low-density cholesterol 23 , while dyslipidemia has been shown to be associated with the risk and severity of COVID repeatedly 7 , In addition, as an effective antioxidant, L-carnitine was involved in modulating the mechanisms of the immune system and the nervous system 8 , and could inhibit the expression of inflammatory factors 25 , Antioxidants supplementation has been recommended in therapeutic strategies against COVID 27 , since antioxidant therapy could improve oxygenation rates, glutathione levels and strengthen the immune response Meanwhile, anti-inflammatory drugs were suggested to potentially inhibit a key enzyme in the replication and transcription of SARS-CoV-2 29 , and anti-inflammatory agents have also been proposed as potential therapies for COVID due to their prevention of cardiovascular events.

Furthermore, L-carnitine plays a critical role in energy production, as it transports long-chain fatty acids into the mitochondria so they can be oxidized to produce energy More energy for the immune system means more immune cells can be produced to protect against infection from virus.

Lastly, current evidence showed that severely ill patients with COVID tend to have a high concentration of pro-inflammatory cytokines, such as IL-6, compared to those who are moderately ill, and the high level of cytokines also indicates a poor prognosis in COVID L-carnitine could suppress the production of pro-inflammatory cytokines by preventing the hyperosmolarity-induced oxidative stress 32 , and thus might help prevent patients with COVID from cytokine storm.

Taken together, so many biological functions make L-carnitine a potential therapeutic option to protect against COVID Unfortunately, no clinical or epidemiological studies have investigated the correlation between them. Here, using the MR approach, we clarified the protective role of carnitine on COVID susceptibility and severity from a genetic perspective.

Future clinical or functional studies could put importance to this, and further explore the role of carnitine in protecting against COVID Based on the Mendelian randomization results obtained from large-scale GWAS summary data, we demonstrated that carnitine might have a protective role on COVID, and carnitine might be a therapy which is worth further exploration in clinical trials.

These results help better understand the role of carnitine on COVID, and will facilitate therapeutic drugs in future clinical trials. The strength of our work is the Mendelian randomization method which could avoid confounding factors. And comprehensive sensitivity analyses guaranteed the reliability of the association.

Meanwhile, current results have very important clinical implications. Up till now, global efforts were still invested in finding effective drugs for COVID Our findings provided some guidance and new direction for future clinical trials.

There were also some limitations to the current study. Though we identified a protective role of carnitine against COVID, the biological mechanism of this protection was still unclear. Further clinical and functional studies were necessary to clarify the effect of carnitine on COVID php ID: M Code or algorithm used to generate results in this study are available from the corresponding authors on reasonable request.

CL and HS conceived the study. CL performed the statistical analyses and prepared the drafted manuscript. RO, QW, and HS contributed to writing and editing of the manuscript.

All authors reviewed and approved the final manuscript. This study was supported by the funding of the National Natural Science Foundation of China and , the China Postdoctoral Science Foundation M , the 1.

Z , and the Science Foundation of Chengdu Science and Technology Bureau YFSN. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

COVID, coronavirus disease ; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; MR, Mendelian randomization; GWAS, genome-wide association study; SNP, single nucleotide polymorphism; LD, linkage disequilibrium; SD, standard deviation; IVW, inverse variance weighted.

Li H, Liu SM, Yu XH, Tang SL, Tang CK. Coronavirus disease COVID : current status and future perspectives. Int J Antimicrob Agents. doi: PubMed Abstract CrossRef Full Text Google Scholar. Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, et al. Drug treatments for covid living systematic review and network meta-analysis.

Liu Y, Van Der Leij FR. Long-term effects of neonatal treatment with dexamethasone, L-carnitine, and combinations thereof in rats. Pediatr Res. Tsukuda Y, Suda G, Tsunematsu S, Ito J, Sato F, Terashita K, et al. Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection.

J Med Virol. Moretti S, Alesse E, Di Marzio L, Zazzeroni F, Ruggeri B, Marcellini S, et al. Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Vasiljevski ER, Summers MA, Little DG, Schindeler A.

Lipid storage myopathies: Current treatments and future directions. Prog Lipid Res. Sorokin AV, Karathanasis SK, Yang ZH, Freeman L, Kotani K, Remaley AT. COVIDAssociated dyslipidemia: implications for mechanism of impaired resolution and novel therapeutic approaches.

FASEB J. Budhwar S, Sethi K, Chakraborty M. A rapid advice guideline for the prevention of novel coronavirus through nutritional intervention. Curr Nutr Rep. Fakhrolmobasheri M, Khanahmad H, Kahlani MJ, Shiravi AA, Shahrokh SG, Zeinalian M.

L-Carnitine Can Extinguish the COVID19 Fire: A Review on Molecular Aspects. Zenodo Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. Bandres-Ciga S, Noyce AJ, Traynor BJ.

Mendelian randomization—a journey from obscurity to center stage with a few potholes along the way. JAMA Neurol. Shin SY, Fauman EB, Petersen AK, Krumsiek J, Santos R, Huang J, et al.

An atlas of genetic influences on human blood metabolites. Nat Genet. Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics Nucleic Acids Res.

COVID Host Genetics Initiative. The COVID Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet. Verbanck M, Chen CY, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.

Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. Burgess S, Davies NM, Thompson SG.

Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. Hemani G, Tilling K, Davey Smith G. Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet. Brion MJ, Shakhbazov K, Visscher PM. Calculating statistical power in Mendelian randomization studies.

Int J Epidemiol. Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome.

Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann NY Acad Sci. Hoppel C. The role of carnitine in normal and altered fatty acid metabolism.

Am J Kidney Dis. Taken together, these findings demonstrate that L-carnitine tartrate treatment significantly decreases the susceptibility of Calu-3 cells to SARS-CoV-2 infection.

These effects are probably mediated through a decrease in the expression of the host factors required by the virus to attach to and enter the cell Figure 4. Figure 4. L-carnitine and lung-cell infection.

L-carnitine reduces levels of ACE2, TMPRSS2 and furin in exercise-induced inflammation models in rats and humans, thereby decreasing susceptibility to SARS-CoV-2 infection.

Oxidative stress induced by acute viral infection helps to stimulate an increased inflammatory response. With the current pandemic, COVID is a primary research target, and scientists and physicians are investigating a wide array of intervention strategies including the use of methods for blunting the inflammatory states that are characteristic of the virus.

Medical presentations of COVID include fever, dry cough and respiratory complications. These symptoms can escalate to life-threatening difficulties for individuals with comorbidities such as type II diabetes, frailty, heart disease and general aging.

A unifying theme connecting these comorbidities is chronic inflammation and low endogenous L-carnitine levels. Lonza has shown that this nutritional ingredient can blunt systemic exercise-induced inflammation and oxidative stress in both humans and rodents.

Supplementation reduced serum and tissue levels of ACE2, furin and TMPRSS2, which are considered host factors for SARS-CoV-2 entry into human cells. Reduction in expression levels of host factors was correlated with reduced virus infectivity of human epithelial lung cells in a cell-culture model.

Lonza has established the safety and tolerability profile of L-carnitine tartrate in humans at a daily dose of up to 3 g equivalent to 2 g elemental L-carnitine. Future investigations of the effects of L-carnitine tartrate in preventing SARS-CoV-2 infection and complications in human clinical trials are now warranted.

Shane E. Durkee 1 , Zainulabedin M. Saiyed 2 and Aouatef Bellamine 3. Thangasamy, T. et al. Biogerontology 10 , — Article PubMed Google Scholar. Acta , 19—24 World Health Organization. Bruls, Y.

EBioMedicine 49 , — Bellamine, A. Nutrients 13 , Abd-Allah, A. Mast, J. Adeva-Andany, M. IUBMB Life 69 , — Flanagan, J. Article Google Scholar. Bestle, D. Life Sci. Alliance 3 , 1—14 Sriram, K. Phillips, T.

Sports Exerc. Gomes-Santos, I. PLoS One 9, e Emilsson, V. Sahin, K. Nutrients 12 , Fathizadeh, H. Diabetes Metab. Suzuki, K. Antioxidants Basel 9 , Förster, L.

Pinto, B. Download references. Skip to main content Thank you for visiting nature. L-carnitine tartrate supplementation in the fight against infectious disease.

Download PDF. Produced by. L-carnitine in immune function Inflammation is an essential part of the immune response to injury and infection 1 , 2. Inflammation-centric COVID COVID is caused by the severe acute respiratory syndrome coronavirus 2 SARS-CoV L-carnitine as an immunomodulator through anti-inflammatory effects Lonza hypothesized that L-carnitine tartrate supplementation may impact ACE2 expression and, consequently, its attachment to the SARS-CoV-2 spike protein through lowering inflammation.

Effects of L-carnitine on host-dependency factors and inflammatory markers during exercise-induced inflammation Our initial study explored the dose-dependent response of L-carnitine tartrate at the tissue level, to determine whether it altered protein and mRNA levels of the host-dependency factors of SARS-CoV-2 infection, ACE1, ACE2, TMPRSS2 and furin, and the inflammatory markers serum CRP and interleukin-6 IL L-carnitine tartrate decreases SARS-CoV-2 infection of Calu-3 cells by downregulating ACE2 receptor expression Immune responses, clinical presentations and severity of outcomes vary notably among patients infected by COVID, and include muscle weakness, fever and respiratory complications.

Conclusions Oxidative stress induced by acute viral infection helps to stimulate an increased inflammatory response. AUTHORS Shane E. Saiyed 2 and Aouatef Bellamine 3 ADDRESS Lonza Consumer Health Inc.

References Thangasamy, T. Article PubMed Google Scholar Thangasamy, T. Article PubMed Google Scholar World Health Organization. Article PubMed Google Scholar Bellamine, A. Article PubMed Google Scholar Abd-Allah, A.

Article PubMed Google Scholar Mast, J. Article PubMed Google Scholar Adeva-Andany, M. Article PubMed Google Scholar Flanagan, J. Article Google Scholar Bestle, D. Article Google Scholar Sriram, K. Article PubMed Google Scholar Phillips, T. Article PubMed Google Scholar Gomes-Santos, I.

Article PubMed Google Scholar Emilsson, V. Article Google Scholar Fathizadeh, H. Article PubMed Google Scholar Suzuki, K. Article Google Scholar Förster, L. Article PubMed Google Scholar Pinto, B. Article PubMed Google Scholar Download references.

Search Search articles by subject, keyword or author. Show results from All journals.

Thank Kiwi fruit ripening process for visiting nature. You are Syxtem a L-carnitine and immune system version with limited support for CSS. L-carnitin obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Inflammation is an essential part of the immune response to injury and infection 12.