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'''Carnitine''' (also known as '''L-carnitine''', or as the acylated form '''Acetyl-L-Carnitine''') is a naturally occurring amino acid nutrient in the body that is important for turning fat into energy. It is a derivative of the amino acid, [[lysine]]. Its function in [[:Category:Fatty acids |fatty acid]] metabolism is to transport long-chain acyl groups from fatty acids into the [[mitochondrial matrix]] so that they can be broken down through [[Beta-oxidation|β-oxidation]] to [[acetyl CoA]] to generate energy in the [[citric acid cycle]]. Carnitine plays an especially important role in heart, brain, and muscle function, as these energy-intensive organs rely on energy from fatty acids. == In human disease == Low serum carnitine is found in [[systemic primary carnitine deficiency]], a genetic disease, and causes chronic [[muscle weakness]], cardiomyopathy, hypoglycemia and liver dysfunction. Secondary primary carnitine deficiency can develop secondary to other genetic mitochondrial disorders, in chronic kidney failure, and as a side effect of some medications.{{Citation needed}} == ME/CFS == [[Chronic fatigue syndrome]] (CFS) patients have been found to have statistically significantly lower serum total carnitine, free carnitine, and acylcarnitine levels.<ref name=":0">{{Citation| issn = 1058-4838| volume = 18| pages = 62-67| last1 = Kuratsune | first1 = H. | last2 = Yamaguti | first2 = K. | last3 = Takahashi | first3 = M. | last4 = Misaki | first4 = H. | last5 = Tagawa | first5 = S. | last6 = Kitani | first6 = T.| title = Acylcarnitine deficiency in chronic fatigue syndrome| journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America | date = January 1994 | pmid = 8148455|url= | author-link = | issue = Supp 1|chapter=|edition=|isbn=}}</ref><ref name=":1">{{Citation| doi = 10.1111/j.1468-1331.1995.tb00151.x| issn = 1351-5101| volume = 2 | issue = 5| pages = 425–428| last1 = Majeed | first1 = T. | last2 = de Simone | first2 = C. | last3 = Famularo | first3 = G. | last4 = Marcellini | first4 = S. | last5 = Behan | first5 = P.O. | title = Abnormalities of carnitine metabolism in chronic fatigue syndrome| journal = European Journal of Neurology | date = November 1995 | pmid = 24283722}}</ref><ref name="plioplys1995">{{Citation| issn = 0302-282X| volume = 32 | issue = 3| pages = 132–138| last1 = Plioplys | first1 = A.V. | last2 = Plioplys | first2 = S.| title = Serum levels of carnitine in chronic fatigue syndrome: clinical correlates| journal = Neuropsychobiology | date = 1995 | pmid = 8544970}}</ref> These serum levels were also found to correlate with clinical symptoms, where higher serum carnitine levels correlated with better functional capacity. Serum carnitine levels appeared to return to normal during remission. As carnitine is needed by the mitochondria, these findings may imply mitochondrial dysfunction. In a study in 1997, both L-carnitine and Amantadine were tested on 30 [[chronic fatigue syndrome|CFS]] patients. Amantadine was not well tolerated, but the L-carnitine was found to be very safe and to improve the clinical status of CFS patients.<ref name="plioplys1997">{{Citation| issn = 0302-282X| volume = 35 | issue = 1| pages = 16–23| last1 = Plioplys | first1 = A.V. | last2 = Plioplys | first2 = S.| title = Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome| journal = Neuropsychobiology | date = 1997 | pmid = 9018019}}</ref> [[Sarah Myhill]] checks acetyl-L-carnitine levels as part of her Mitochondrial Function tests.<ref>{{Cite web | url = https://drmyhill.co.uk/wiki/L_-_Carnitine | title = L - Carnitine | last = Myhill | first = Sarah | author-link = Sarah Myhill | date = | website = DoctorMyhill| archive-url = | archive-date = |url-status = | access-date=2021-03-21}}</ref> In a study of the levels of serum acylcarnitine in Japanese patients with various kinds of diseases, a significant decrease was only found in patients with CFS and chronic hepatitis type C, indicating that this might be a characteristic abnormality in only certain types of diseases.<ref name="kuratsune1998">{{Citation| issn = 1107-3756| volume = 2 | issue = 1| pages = 51–56| last1 = Kuratsune | first1 = H. | last2 = Yamaguti | first2 = K. | last3 = Lindh | first3 = G. | last4 = Evengard | first4 = B. | last5 = Takahashi | first5 = M. | last6 = Machii | first6 = T. | last7 = Matsumura | first7 = K. | last8 = Takaishi | first8 = J. | last9 = Kawata | first9 = S. | last10 = Långström | first10 = B. | last11 = Kanakura | first11 = Y. | last12 = Kitani | first12 = T. | last13 = Watanabe | first13 = Y.| title = Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases| journal = International Journal of Molecular Medicine | date = July 1998 | pmid = 9854142 | url = https://pubmed.ncbi.nlm.nih.gov/9854142 | author-link = |chapter=|edition=|isbn=}}</ref> A study of 25 patients and 25 controls in 2000 could not reproduce the finding of CFS patients having lower carnitine levels than control subjects. The authors concluded that "the present study demonstrates that serum carnitine deficiency does not contribute to or cause the symptoms in many CFS patients".<ref name="patricia2000">{{Citation| doi = 10.1016/S0300-2977(00)00030-9| issn = 0300-2977| volume = 57 | issue = 1| pages = 20–24| last1 = Soetekouw | first1 = Patricia M.M. B| last2 = Wevers | first2 = Ron A| last3 = Vreken | first3 = Peter | last4 = Elving | first4 = Lammy D| last5 = Janssen | first5 = Antoon J. M| last6 = van der Veen | first6 = Yvette | last7 = Bleijenberg | first7 = Gijs | last8 = van der Meer | first8 = Jos W. M| title = Normal carnitine levels in patients with chronic fatigue syndrome| journal = The Netherlands Journal of Medicine| access-date = 2016-11-09| date = July 2000| url = http://www.sciencedirect.com/science/article/pii/S0300297700000309}}</ref> While this conclusion refers to 'many' patients, the small study size may temper this conclusion. In 2004 acetyl-L-carnitine, propionyl-L-carnitine, and their combination were compared in 3 groups of 30 CFS patients during 24 weeks. Acetyl-L-carnitine significantly improved mental fatigue and propionyl-L-carnitine improved general fatigue.<ref name="vermeulen2004">{{Citation| issn = 1534-7796| volume = 66 | issue = 2| pages = 276–282| last1 = Vermeulen | first1 = Ruud C.W. | last2 = Scholte | first2 = Hans R.| title = Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome| journal = Psychosomatic Medicine | date = April 2004 | pmid = 15039515 | url = https://pubmed.ncbi.nlm.nih.gov/15039515 | author-link = |chapter=|edition=|isbn=}}</ref> In 2011 another study on 44 CFS patients and 49 healthy controls found that patients with chronic fatigue syndrome exhibited significantly altered concentrations of acylcarnitines. Significant correlations between acylcarnitine concentrations and clinical symptomatology were also demonstrated. The authors proposed that this disturbance in carnitine homeostasis could possibly be a result of the accumulation of [[omega 6 fatty acid]]s previously observed in this patient population. They hypothesized that the administration of [[omega 3 fatty acid]]s, in combination with carnitine, would increase CPT-1 activity and improve [[chronic fatigue syndrome]] symptoms.<ref name="reuter2011">{{Citation| doi = 10.1111/j.1365-2796.2010.02341.x| issn = 1365-2796| volume = 270 | issue = 1| pages = 76–84| last1 = Reuter | first1 = S.E. | last2 = Evans | first2 = A.M.| title = Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity| journal = Journal of Internal Medicine| access-date = 2016-11-09| date = 2011-07-01| url = http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02341.x/abstract}}</ref> == Testing == Serum carnitine can be tested via the following blood tests: total carnitine, free carnitine, and carnitine esters.{{Citation needed}} == Treatments == The standard treatment of low serum carnitine is Levocarnitine, a prescription form of carnitine. Carnitine can be supplemented in different forms, eg. l-carnitine, l-carnitine l-tartrate, L-carnitine Fumarate, etc. The different forms are believed to have slightly different areas of use. It is advised to avoid D-carnitine and DL-carnitine. These forms of carnitine might block the effects of L-carnitine and cause symptoms that resemble L-carnitine deficiency. Acetyl-L-carnitine (ALCAR) is popular supplement, but is considered to have a slightly different effect than other forms of l-carnitine, because of its ability to cross the blood-brain-barrier. ALCAR is sometimes called the "neurological l-carnitine". There are some people who should be extra careful with carnitine-supplementation. These include patients with thyroid disease, patients taking medication for thyroid disease, patients on blood thinning medications and in those with a history of seizures. ==Studies== * 1994, "Acylcarnitine deficiency in chronic fatigue syndrome"<ref name=":0" /> ([[pubmed:8148455|Abstract]]) * 1995, "Abnormalities of carnitine metabolism in chronic fatigue syndrome"<ref name=":1" /> ([[pubmed:24283722|Abstract]]) * 1995, "Serum levels of carnitine in chronic fatigue syndrome: clinical correlates"<ref name="plioplys1995" /> ([http://plioplys.com/wp-content/uploads/2016/05/10_serum_1995.pdf Full text]) * 1997, "Amantadine and L-Carnitine: Treatment of Chronic Fatigue Syndrome"<ref name="plioplys1997" /> ([https://drmyhill.co.uk/drmyhill/images/b/b6/Amantadine_and_L-carnitine_treatment_of_Chronic_Fatigue_Syndrome.pdf Full text]) * 1998, "Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases"<ref name="kuratsune1998" /> ([[pubmed:9854142|Abstract]]) * 2000, "Normal carnitine levels in patients with chronic fatigue syndrome"<ref name="patricia2000" /> ([[pubmed:10862998|Abstract]]) * 2004, "Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome"<ref name="vermeulen2004" /> ([http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.502.994&rep=rep1&type=pdf Full text]) * 2011, "Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity"<ref name="reuter2011" /> ([[pubmed:21205027|Abstract]]) * 2018, "Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics"<ref>{{Cite journal | title = Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics | date = 2018-07-03 | url = https://www.nature.com/articles/s41598-018-28477-9 | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 10056 | last = Nagy-Szakal | first = Dorottya | last2 = Barupal | first2 = Dinesh K. | last3 = Lee | first3 = Bohyun | last4 = Che | first4 = Xiaoyu | last5 = Williams | first5 = Brent L. | last6 = Kahn | first6 = Ellie J.R. | last7 = Ukaigwe | first7 = Joy E. | last8 = Bateman | first8 = Lucinda | last9 = Klimas | first9 = Nancy G. | last10 = Komaroff | first10 = Anthony L. | last11 = Levine | first11 = Susan|language=en|doi=10.1038/s41598-018-28477-9|issn=2045-2322}}</ref> ([https://www.nature.com/articles/s41598-018-28477-9 Full text]) * 2019, "Carnitine conjugation profiling in a selected cohort of patients with chronic fatigue syndrome"<ref>{{Cite book | title = Carnitine conjugation profiling in a selected cohort of patients with chronic fatigue syndrome | pages = |isbn=|edition= | volume = |language=| title-link = | url = http://worldcat.org/oclc/1129437146|access-date= | date = Jul 2019| publisher = North-West University, South Africa | last = Du Plessis | first = Liana | author-link = |veditors=|others=|doi=|oclc=1129437146|quote=|archive-url=|archive-date=|location=}}</ref> [https://repository.nwu.ac.za/bitstream/handle/10394/34126/Du%20Plessis%20L%20%2021648859.pdf?sequence=1&isAllowed=y (Full text]) ==Learn more== * ==See also== *[[Omega 3 fatty acid]] *[[Mitochondrion]] ==References== {{Reflist}} [[Category:Supplements]] [[Category:Potential treatments]] [[Category:Nutrients]] [[Category:Biochemistry and cell biology]] [[Category:Amino acids]]
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