Cited by 613Metabolism and Genetic DisordersClinical Nutrition and GastroenterologyMuscle metabolism and nutrition

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Role of carnitine in disease

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Flanagan, Judith L, Simmons, Peter A, Vehige, Joseph, Willcox, Mark DP, Garrett, Qian·2010·Nutrition & Metabolism

DOI 10.1186/1743-7075-7-30PMC PMC2861661

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Abstract

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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Figure 1 Carnitine biosynthesis and metabolism.CC BY · PubMed Central

Figure 2 Carnitine is actively transported via OCTN2 into the cytosol to participate in the shuttling of activated long chain fatty acids into the mitochondria where β-oxidation takes place. Carnitine also regulates the Coenzyme A (CoA)/acylCoA ratio within the mitochondria, modulation of which reduces accumulation of toxic acyl-CoA compounds and maintains energy production.CC BY · PubMed Central

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Tanaka, K., Nakamura, S., & Narimatsu, H. (2022) · Nutrients · doi:10.3390/nu14020345 · Cited by 32
Characterization of Exosomal SLC22A5 (OCTN2) carnitine transporter
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Lysine: biosynthesis, catabolism and roles
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The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders
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The Relationship between Body Composition, Fatty Acid Metabolism and Diet in Spinal Muscular Atrophy
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“Whereas longer chained fatty acids will undergo carnitine esterification at high concentrations and shorter chained fatty acids are able to diffuse into cells, C12 chain length is such that it will not readily do either and so remains in the serum [47].”
Background
Effect of L-Carnitine Supplementation on Circulating C-Reactive Protein Levels: A Systematic Review and Meta-Analysis / Uticaj Suplementacije L-Karnitinom Na Nivoe C-Reaktivnog Proteina U Cirkulaciji: Sistematski Pregled I Metaanaliza
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Human macrophage differentiation induces OCTN2–mediated L-carnitine transport through stimulation of mTOR–STAT3 axis
Ingoglia, F., Visigalli, R., Rotoli, B. M., Barilli, A., Riccardi, B., Puccini, P., Milioli, M., Lascia, M. D., Bernuzzi, G., & Dall’Asta, V. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.1a0616-254r · Cited by 31
“evidence demonstrates that nutritional or pharmacologic supplementation with the amino acid may be beneficial for a number of human disorders [47, 48].”
Background
Effects of L-carnitine supplementation on biomarkers of oxidative stress, antioxidant capacity and lipid profile, in patients with pemphigus vulgaris: a randomized, double-blind, placebo-controlled trial
Mohammadi, H., Djalali, M., Daneshpazhooh, M., Honarvar, N. M., Chams‐Davatchi, C., Sepandar, F., Fakhri, Z., Yaghubi, E., Zarei, M., & Javanbakht, M. H. (2017) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2017.131 · Cited by 30
Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high‐fat and high‐fructose diets
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“Furthermore, associations between L-carnitine deficiency and cardiomyopathy, cardiac arrhythmia, and heart failure have been reported previously.(27) Another study indicated that creatine supplements improve heart muscle strength in patients with congestive heart failure.”
Background
Urinary metabolite markers characterizing tuberculosis treatment failure
Luies, L., Mienie, L. J., Motshwane, C., Ronacher, K., Walzl, G., & Loots, D. T. (2017) · Metabolomics · doi:10.1007/s11306-017-1261-4 · Cited by 30
“also associated with these carnitine transporters (Flanagan et al. 2010).”
High l -Carnitine Ingestion Impairs Liver Function by Disordering Gut Bacteria Composition in Mice
Wu, Q., Zhang, X., Zhao, Y., & Yang, X. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b08313 · Cited by 29
Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study
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Deregulation of Lipid Homeostasis: A Fa(c)t in the Development of Metabolic Diseases
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Integrating metabolomics and network pharmacology to explore Rhizoma Coptidis extracts against sepsis-associated acute kidney injury
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Longitudinal metabolic imaging of hepatocellular carcinoma in transgenic mouse models identifies acylcarnitine as a potential biomarker for early detection
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The Effect of Different l‐Carnitine Administration Routes on the Development of Atherosclerosis in ApoE Knockout Mice
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Short-Term Activation of Peroxisome Proliferator-Activated Receptors α and γ Induces Tissue-Specific Effects on Lipid Metabolism and Fatty Acid Composition in Male Wistar Rats
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“It is also interesting to reveal PPAR effects on carnitine metabolites, which are potential biomarkers in human disease [49].”
Background
Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype
Niska-Blakie, J., Gopinathan, L., Low, K. N., Kien, Y. L., Goh, C. M. F., Caldez, M. J., Pfeiffenberger, E., Jones, O. S., Ong, C. B., Kurochkin, I. V., et al. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03359-z · Cited by 28
Decrease in hyperosmotic stress-induced corneal epithelial cell apoptosis by L-carnitine.
Khandekar, N., Willcox, M. D. P., Shih, S. M.-H., Simmons, P. A., Vehige, J. G., & Garrett, Q. (2013) · Europe PMC (PubMed Central) · Cited by 28
Self-citation
Proximate Composition, and L-Carnitine and Betaine Contents in Meat from Korean Indigenous Chicken
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A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes
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Cats with IRIS stage 1 and 2 chronic kidney disease maintain body weight and lean muscle mass when fed food having increased caloric density, and enhanced concentrations of carnitine and essential amino acids
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Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID
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Side Effects and Behavioral Outcomes Following High-Dose Carnitine Supplementation Among Young Males With Autism Spectrum Disorder: A Pilot Study
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Maternal obesity results in decreased syncytiotrophoblast synthesis of palmitoleic acid, a fatty acid with anti‐inflammatory and insulin‐sensitizing properties
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“The transport of FAs across the mitochondrial membrane is mediatedbyCPT1andCPT2 (46, 47),which represents the rate-limiting step in mitochondrial b-oxidation of longchain FAs.”
Background
Plasma Metabolites Link Dietary Patterns to Stroke Risk
Bhave, V. M., Ament, Z., Patki, A., Gao, Y. L., Kijpaisalratana, N., Guo, B., Chaudhary, N. S., Guarniz, A. G., Gerszten, R. E., Correa, A., et al. (2022) · Annals of Neurology · doi:10.1002/ana.26552 · Cited by 27
“Carnitines—including C7 carnitine—are also known to have numerous functions in metabolic and cardiovascular health.(48) This study has several strengths, including a large number of incident stroke cases and controls ascertained in a prospective and biracial cohort.”
Background
Determination of carnitine and acylcarnitines in human urine by means of microextraction in packed sorbent and hydrophilic interaction chromatography–ultra-high-performance liquid chromatography–tandem mass spectrometry
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Trimethylamine- N -oxide formation, the bacterial taxa involved and intervention strategies to reduce its concentration in the human body
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“Another TMA precursor is L-carnitine, also a conditionally essential nutrient that is primarily obtained through diet from red meat; however, it can also be synthesized endogenously in various tissues from methionine and lysine [18].”
Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine
Mahmoud, Y. K., Ali, A. A., Abdelrazek, H. M. A., Aldayel, T. S., Abdel‐Daim, M. M., & Menyawi, M. A. I. E. (2021) · Biology · doi:10.3390/biology10070682 · Cited by 27
Acquired resistance to PI3K/mTOR inhibition is associated with mitochondrial DNA mutation and glycolysis
Koh, K. X., Tan, G. H., Low, S. H. H., Omar, M. F. M., Han, M. J., Iacopetta, B. J., Soo, R. A., Beloueche‐Babari, M., Bhattacharya, B., & Soong, R. (2017) · Oncotarget · doi:10.18632/oncotarget.22655 · Cited by 25
“Since lactate is the end product of glycolysis [18], and carnitine is involved in mitochondrial lipid transport [19] and acetyl-CoA equilibrium [20], the observed increase in expression of MCT2 and MCT9 prompted us to investigate the metabolic activity of the cells.”
Modulation of tissue fatty acids by l -carnitine attenuates metabolic syndrome in diet-induced obese rats
Panchal, S. K., Poudyal, H., Ward, L. C., Waanders, J., & Brown, L. (2015) · Food & Function · doi:10.1039/c5fo00480b · Cited by 25
Binding of Per- and Polyfluoroalkyl Substances (PFAS) to the PPARγ/RXRα–DNA Complex
Almeida, N. M. S., Bali, S. K., James, D., Wang, C., & Wilson, A. K. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01384 · Cited by 25
Longitudinal characterization of the metabolome of dairy cows transitioning from one lactation to the next: Investigations in blood serum
Ghaffari, M. H., Daniel, J., Sadri, H., Schuchardt, S., Martín‐Tereso, J., & Sauerwein, H. (2023) · Journal of Dairy Science · doi:10.3168/jds.2023-23841 · Cited by 24
“Incomplete oxidation of long-chain FA caused by impaired activity of carnitine palmitoyltransferase or depletion of intermediates of the tricarboxylic acid cycle can increase concentrations of long-chain acylCN (Flanagan et al., 2010; Murphy et al., 2012; Ramos-Roman et al., 2012).”
Background
Conductive Paper with Antibody-Like Film for Electrical Readings of Biomolecules
Tavares, A. P. M., Ferreira, N., Truta, L. A. A. N. A., & Sales, M. G. F. (2016) · Scientific Reports · doi:10.1038/srep26132 · Cited by 24
L-Carnitine Improves Skeletal Muscle Fat Oxidation in Primary Carnitine Deficiency
Madsen, K. L., Preisler, N. R., Rasmussen, J., Hedermann, G., Olesen, J. H., Lund, A. M., & Vissing, J. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00953 · Cited by 28
The effects of L-carnitine supplementation on lipid concentrations inpatients with type 2 diabetes: A systematic review and meta-analysis of randomized clinical trials
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Alterations of the acylcarnitine profiles in blood serum and in muscle from periparturient cows with normal or elevated body condition
Ghaffari, M. H., Sadri, H., Schuh, K., Dusel, G., Prehn, C. P., Adamski, J., Koch, C., & Sauerwein, H. (2020) · Journal of Dairy Science · doi:10.3168/jds.2019-17713 · Cited by 23
Dietary methionine requirement of the pre-adult gibel carp (Carassius auratus gibeilo) at a constant dietary cystine level
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Carnitine and Cardiac Dysfunction in Childhood Cancer Survivors Treated with Anthracyclines
Armenian, S. H., Gelehrter, S. K., Vase, T., Venkatramani, R., Landier, W., Wilson, K. D., Herrera, C., Reichman, L., Menteer, J., Mascarenhas, L., et al. (2014) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-13-1384 · Cited by 23
“Carnitine homeostasis is maintained through endogenous biosynthesis of L-carnitine, absorption of carnitine from dietary sources, and elimination and reabsorption by the kidneys (17).”
Background
Role of L-carnitine and Coenzyme Q10 as Adjuvant Therapy in Patients with Type 2 Diabetes Mellitus
Mohammed-Jawad, N. K., & Al-Sabbagh, M. S. (2014) · American journal of pharmacological sciences · doi:10.12691/ajps-2-5-2 · Cited by 24
l ‐Carnitine and Long‐Chain Acylcarnitines are Positively Correlated with Ambulatory Blood Pressure in Humans: The SABPA Study
Mels, C. M. C., Schutte, A. E., Erasmus, E., Huisman, H. W., Schutte, R., Fourie, C. M. T., Kruger, R., van Rooyen, J. M., Smith, W. T., Malan, N. T., et al. (2012) · Lipids · doi:10.1007/s11745-012-3732-8 · Cited by 24
Associations of serum trimethylamine N‐oxide and its precursors with colorectal cancer risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort
Byrd, D. A., Zouiouich, S., Karwa, S., Li, X. S., Wang, Z., Sampson, J. N., Loftfield, E., Huang, W., Hazen, S. L., & Sinha, R. R. (2024) · Cancer · doi:10.1002/cncr.35219 · Cited by 23
“4 Choline, L ‐ alpha glycerylphosphorylcholine, phosphatidylcholine, L ‐ carnitine, and betaine are diet ‐ and endogenously derived 5,6 and contain trimethylamine substrates that are cleaved by gut bacteria to form trimethylamine, which is absorbed, travels via portal circulation to the liver, and…”
Background
Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity
Latham, L. E., Wang, C., Patterson, T. A., Slikker, W., & Liu, F. (2021) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00479 · Cited by 25
Metabolomics of Arterial Stiffness
Paapstel, K., & Kals, J. (2022) · Metabolites · doi:10.3390/metabo12050370 · Cited by 23
Experimental treatments for mitochondrial dysfunction in sepsis: A narrative review.
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Anti-adipogenic and antiviral effects of l -carnitine on hepatitis C virus infection
Tsukuda, Y., Suda, G., Tsunematsu, S., Ito, J., Sato, F., Terashita, K., Nakai, M., Sho, T., Maehara, O., Shimazaki, T., et al. (2016) · Journal of Medical Virology · doi:10.1002/jmv.24692 · Cited by 22
“Secondary carnitine deficiency can be caused by the increased renal tubular loss of carnitine (Fanconi syndrome), hemodialysis, a poor diet [Flanagan et al., 2010], administration of pharmacological agents such as valproic acid [Verrotti et al., 2002], and liver cirrhosis [Rudman et al., 1977].”
BackgroundInfluential
Emerging Biomarkers of Illness Severity: Urinary Metabolites Associated with Sepsis and Necrotizing Methicillin‐Resistant Staphylococcus aureus Pneumonia
Ambroggio, L., Florin, T. A., Shah, S. S., Ruddy, R. M., Yeomans, L., Trexel, J., & Stringer, K. A. (2017) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1973 · Cited by 22
Metabolome profiling in skeletal muscle to characterize metabolic alterations in over-conditioned cows during the periparturient period
Sadri, H., Ghaffari, M. H., Schuh, K., Dusel, G., Koch, C., Prehn, C. P., Adamski, J., & Sauerwein, H. (2020) · Journal of Dairy Science · doi:10.3168/jds.2019-17566 · Cited by 23
Nutritional Support During Long COVID: A Systematic Scoping Review
Bradbury, J., Wilkinson, S., & Schloss, J. M. (2023) · Journal of Integrative and Complementary Medicine · doi:10.1089/jicm.2022.0821 · Cited by 21
“46 Reduced adenosine triphosphate and increased oxidative stress have been associated with the development of mitochondrial damage, and it has been associated with premature aging 47 and neurodegenerative diseases.”
Role of Supplementary L -Carnitine in Exercise and Exercise Recovery
Huang, A., & Owen, K. Q. (2012) · Medicine and sport science/Medicine and sport · doi:10.1159/000341934 · Cited by 21

Authors: Flanagan, J. L., Simmons, P. A., Vehige, J., Willcox, M. D., & Garrett, Q.
Affiliations: Brien Holden Vision Institute (AU)
Allergan (United States) (US)
Corresponding author: Flanagan, Judith L
ORCID: Flanagan, Judith L
Willcox, Mark DP
Garrett, Qian
Venue: Nutrition & Metabolism
Publisher: Springer Science and Business Media LLC
Published: 2010
Volume: 7
Issue: 1
Pages: 30
ISSN: 1743-7075 (ISSN-L)
DOI: 10.1186/1743-7075-7-30
PMC: PMC2861661
OpenAlex: W2084023408
Cited by: 611
References: 176
Citations by year: 2026: 27 · 2025: 50 · 2024: 46 · 2023: 43 · 2022: 62 · 2021: 64 · 2020: 61 · 2019: 40 · 2018: 45 · 2017: 30 · 2016: 30 · 2015: 31 · 2014: 36 · 2013: 19 · 2012: 18
FWCI: 9.03
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Nutrition & Metabolism (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Allergan
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords: L-carnitine, carnitine deficiency, carnitine transporter, fatty acid metabolism, energy production, carnitine supplementation, primary carnitine deficiency, diabetes mellitus, sepsis, cardiomyopathy, malnutrition, liver cirrhosis, aging, uremia, neuropathic pain, Alzheimer's disease, hepatic encephalopathy, dry eye, obesity, impaired glucose tolerance, cardiovascular disease

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