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      Carnitine in Human Muscle Bioenergetics: Can Carnitine Supplementation Improve Physical Exercise?

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          Abstract

          l-Carnitine is an amino acid derivative widely known for its involvement in the transport of long-chain fatty acids into the mitochondrial matrix, where fatty acid oxidation occurs. Moreover, l-Carnitine protects the cell from acyl-CoA accretion through the generation of acylcarnitines. Circulating carnitine is mainly supplied by animal-based food products and to a lesser extent by endogenous biosynthesis in the liver and kidney. Human muscle contains high amounts of carnitine but it depends on the uptake of this compound from the bloodstream, due to muscle inability to synthesize carnitine. Mitochondrial fatty acid oxidation represents an important energy source for muscle metabolism particularly during physical exercise. However, especially during high-intensity exercise, this process seems to be limited by the mitochondrial availability of free l-carnitine. Hence, fatty acid oxidation rapidly declines, increasing exercise intensity from moderate to high. Considering the important role of fatty acids in muscle bioenergetics, and the limiting effect of free carnitine in fatty acid oxidation during endurance exercise, l-carnitine supplementation has been hypothesized to improve exercise performance. So far, the question of the role of l-carnitine supplementation on muscle performance has not definitively been clarified. Differences in exercise intensity, training or conditioning of the subjects, amount of l-carnitine administered, route and timing of administration relative to the exercise led to different experimental results. In this review, we will describe the role of l-carnitine in muscle energetics and the main causes that led to conflicting data on the use of l-carnitine as a supplement.

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          Role of carnitine in disease

          Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.
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            Muscle fatigue: general understanding and treatment

            Muscle fatigue is a common complaint in clinical practice. In humans, muscle fatigue can be defined as exercise-induced decrease in the ability to produce force. Here, to provide a general understanding and describe potential therapies for muscle fatigue, we summarize studies on muscle fatigue, including topics such as the sequence of events observed during force production, in vivo fatigue-site evaluation techniques, diagnostic markers and non-specific but effective treatments.
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              l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans

              l-Carnitine, an abundant nutrient in red meat, accelerates atherosclerosis in mice via gut microbiota-dependent formation of trimethylamine (TMA) and trimethylamine N-oxide (TMAO) via a multistep pathway involving an atherogenic intermediate, γ-butyrobetaine (γBB). The contribution of γBB in gut microbiota-dependent l-carnitine metabolism in humans is unknown.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                01 January 2020
                January 2020
                : 25
                : 1
                : 182
                Affiliations
                [1 ]Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, Italy; antonio.gnoni@ 123456uniba.it
                [2 ]Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; serena.longo@ 123456unisalento.it (S.L.); gabriele.gnoni@ 123456unisalento.it (G.V.G.)
                Author notes
                Author information
                https://orcid.org/0000-0002-9204-040X
                Article
                molecules-25-00182
                10.3390/molecules25010182
                6982879
                31906370
                8f8894e5-8fc2-4594-9559-5e4638573a52
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 November 2019
                : 31 December 2019
                Categories
                Review

                l-carnitine,fatty acid oxidation,muscle energetics,physical exercise

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