L-carnitine is a nutrient that the body needs in order to keep it functioning properly.
In recent years, this amino acid has been promoted as an effective weight loss aid because of its ability to turn fat into energy and lower our levels of insulin – which can make you feel more comfortable about continuing with your fitness routine.
We’ll discuss what Acetyl L Carnitines (ALC) do for us here alongside why they’re important when looking at brain health over time; but first, let’s take care of the basics.
Where To Buy ALCAR
Acetyl L-Carnitine (ALCAR)
Improve cognitive function
Protect the brain from damage
Boost energy levels
Enhance athletic performance
Acetyl L-Carnitine (ALCAR) is a supplement that has many potential benefits. It is most commonly known for its nootropic effects, which means that it can help to improve cognitive function.
ALCAR is thought to work by increasing levels of acetylcholine, a neurotransmitter that is essential for memory and learning.
ALCAR has been shown to protect the brain from damage caused by free radicals, and it may even help to reverse some of the cognitive declines that occurs with age.
In addition to its nootropic effects, ALCAR has also been shown to boost energy levels and athletic performance. This is thought to be due to its ability to increase levels of carnitine, an amino acid that helps the body to burn fat for fuel.
Additionally, ALCAR has been shown to improve heart health by reducing oxidative stress and improving blood flow.
Overall, ALCAR is a safe and effective supplement that offers many potential benefits.
What Is L-Carnitine
We can refer to carnitine as the umbrella term that includes other amino acid forms that include L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine.
L-carnitine comes from red meat and dairy, and if a person eats enough of these food items, the body can make enough L-carnitine it needs to.
The kidneys, liver, and brain are the main organs where carnitine is synthesized from a balanced diet that includes animal protein, especially red meat, and dairy products like milk and cheese.
Trace amounts can also be found in some non-animal foods like whole-wheat bread and asparagus1Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201. 2017
Who Needs ALCAR?
Since carnitine is mostly found in animal foods, it should be supplemented by vegetarians and vegans to reach the recommended daily allowance.2Institute of Medicine; Food and Nutrition Board; Panel on Macronutrients; Panel on the Definition of Dietary Fiber; Subcommittee on Upper Reference Levels of Nutrients; Subcommittee on Interpretation and Uses of Dietary Reference Intakes; Standing Committee on the Scientific Evaluation of Dietary Reference IntakesDietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids Institute of Medicine. 2005.3 U.S. Department of Health and Human Services and U.S. Department of AgricultureDietary Guidelines for Americans, Eighth Edition, 2015-2020, Appendix 7. Nutritional Goals for Age-Sex Groups Based on Dietary Reference Intakes and Dietary Guidelines RecommendationsU.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. 2015.
Premature infants, the elderly, persons with diabetes, and genetic conditions also need to supplement the body with adequate L-carnitine levels for the proper development and functioning of the brain.4Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201. 2017
It has also been found that the administration of ALCAR can improve memory, which explains its potential as a means to improve the brain performance of persons with Alzheimer’s Disease.5Carlo Ori, Ulderico Freo, Gilberto Pizzolato, Mauro Dam Effects of acetyl-l-carnitine on regional cerebral glucose metabolism in awake rats Department of Anesthesiology, University of Padova, Padova, Italy; Department of Neurology, University of Padova, Padova, Italy. 2002
Difference Between ALCAR, L-Carnitine, and Free Carnitine
The main difference between Acetyl-L-carnitine and L-carnitine is an acetyl unit that increases the central nervous system (brain and spinal cord).
Acetyl L-Carnitine (ALCAR) is an endogenous short-chain acetyl ester of free carnitine that crosses the blood-brain barrier6J W Pettegrew, J Levine & R J McClure Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer’s disease and geriatric depression Department of Psychiatry, Neurophysics Laboratory, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Beersheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel. 2000 resulting in the improvement of major depressive disorders and Alzheimer’s Disease.7J W Pettegrew, J Levine & R J McClure Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer’s disease and geriatric depression Department of Psychiatry, Neurophysics Laboratory, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Beersheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel. 2000
ALCAR is believed to have a positive effect on cerebral energy metabolism. One study showed that it regulates glucose metabolism and stimulates glycogen production in rats.8Susanna Scafidi, Gary Fiskum, Steven L. Lindauer, Penelope Bamford, Da Shi, Irene Hopkins, and Mary C. McKennaMetabolism of acetyl-L-carnitine for energy and neurotransmitter synthesis in the immature rat brain Department of Pediatrics, University of Maryland, Baltimore, MD 21201, USA; Department of Anesthesiology, University of Maryland, Baltimore, MD 21201, USA; Center for Shock Trauma and Anesthesiology Research, University of Maryland, Baltimore, MD 21201, USA; Corresponding Author: Mary C. McKenna, Ph.D., Department of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore St., R 13-019, Baltimore, MD 21201, Phone: (410) 706-1990, Fax: (410) 706-0020. 2010
However, carnitine and ALCAR work together to improve the motility of spermatozoa in boars and man.9Jeulin C, Soufir JC, Marson J, Paquignon M, Dacheux JL Acetylcarnitine and spermatozoa: relationship with epididymal maturation and motility in the boar and man. Reproduction, Nutrition, Developpement. 1988
By increasing the energy efficiency of the sperm, it can maintain its motility, resulting in better reproductive capacity,10Steven P.Brinsko, Terry L.Blanchard, Dickson D.Varner, JamesSchumacher, Charles C.Love, KatrinHinrichs, David L.HartmanExamination of the Stallion for Breeding Soundness College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas; Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee; Hartman Equine Reproduction Center, Whitesboro, Texas. 2011 though this observation may not be true to all species.
L-Carnitine For Depression
Acetyl L-Carnitine has been shown to promote rapid antidepressant responses in rodent models.11Nadia M Tsankova, Olivier Berton, William Renthal, Arvind Kumar, Rachel L Neve, Eric J NestlerSustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nature neuroscience. 2006
Evidence points to those suffering from MDD (major depressive disorder) are significantly deficient in ALCAR compared to healthy controls.12Carla Nasca, Benedetta Bigio, Francis S. Lee, Sarah P. Young, Marin M. Kautz, Ashly Albright, James Beasley, David S. Millington, Aleksander A. Mathé, James H. Kocsis, James W. Murrough, Bruce S. McEwen, and Natalie RasgonAcetyl-l-carnitine deficiency in patients with major depressive disorder Proceedings of the National Academy of Sciences of the United States of America. 2018
It was also found out that the low level of L-carnitine in the blood is strongly linked with depression. In the same study, the administration of L-carnitine has improved the symptoms of depression in just a few days.13Natalie RasgonStudy links depression to low blood levels of acetyl-L-carnitine Stanford Neurosciences Institute. 2018
LAC exerts rapid antidepressant actions by acetylating histones to regulate key genes’ expression important for synaptic plasticity, including BDNF,14T. Lau, B. Bigio, D. Zelli, BS. McEwen, and C. NascaStress-induced structural plasticity of medial amygdala stellate neurons and rapid prevention by a candidate antidepressant Laboratory of Neuroendocrinology, The Rockefeller University, New York; 10065, USA.; The Rockefeller University, Center for Clinical & Translational Science, New York, USA. 2017 while also regulating the release of glutamate.15Carla Nasca, Dionysios Xenos, Ylenia Barone, Alessandra Caruso, Sergio Scaccianoce, Francesco Matrisciano, Giuseppe Battaglia, Aleksander A. Mathé, Anna Pittaluga, Luana Lionetto, Maurizio Simmaco, and Ferdinando NicolettiL-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors Proceedings of the National Academy of Sciences of the United States. 2013
In many studies on animals, LAC supplementation has shown improvement in glutamatergic neurons’ function and the associated decrease in the neurons’ size in the hippocampus and medial amygdala.16Sheng-Min Wang, Changsu Han, Soo-Jung Lee, Ashwin A Patkar, Prakash S Masand, Chi-Un Pae. A review of current evidence for acetyl-l-carnitine in the treatment of depression Journal of Psychiatric Research. 2014
Cases of MDD tied to early childhood trauma also show ALCAR deficiency, especially in women.17Myriam Garcia, Itziar Montalvo, Marta Creus, Ángel Cabezas, Montse Solé, Maria José Algora, Irene Moreno, Alfonso Gutiérrez-Zotes, Javier LabadSex differences in the effect of childhood trauma on the clinical expression of early psychosis Comprehensive Psychiatry. 2016
Childhood trauma can be evaluated through the Childhood Trauma Questionnaire.
ALCAR and Anxiety
L-Carnitine has demonstrated anxiolytic effects in animal studies.
However, the effect seems to mimic a U-shaped curve, meaning moderate doses showed significantly lower anxiety, and a high dose led to more anxiety.18Joseph Levine, Zeev Kaplan, Jay W Pettegrew, Richard J McClure, Samuel Gershon, Igor Buriakovsky, Hagit CohenEffect of intraperitoneal acetyl-L-carnitine (ALCAR) on anxiety-like behaviors in rats The International Journal of Neuropharmacology. 2004
There is a lot of evidence that demonstrates L-carnitine can lower anxiety by lowering oxidative stress and inflammation.19Majid S. Koozehchian, Amin Daneshfar, Ebrahim Fallah, Hamid Agha-Alinejad, Mohammad Samadi, Mojtaba Kaviani, Maryam Kaveh B, Y. Peter Jung, Mozhgan Hassanzadeh Sablouei, Najmeh Moradi, Conrad P. Earnest, T. Jeff Chandler, and Richard B. KreiderEffects of nine weeks L-Carnitine supplementation on exercise performance, anaerobic power, and exercise-induced oxidative stress in resistance-trained males Department of Kinesiology, Jacksonville State University, Alabama, USA; School of Health Science, University of Canterbury, Christchurch, New Zealand; Kinesiology, Tarbiat Modares University, Tehran, Iran; Exercise Physiology Research Center, Baqiyatallah University of Medical Science, Tehran, Iran; School of Nutrition and Dietetics, Acadia University, Wolfville, Canada; Department of Physical Education and Sport Sciences, Kharazmi University, Tehran, Iran; Department of Pharmacy Practice, Karnataka College of Pharmacy, Bangalore, India; Exercise & Sport Nutrition Lab, Texas A&M University, Texas, USA; Department of Kinesiology, Azad University, Tehran, Iran; Kinesiology, Azad University, Isfahan, Iran. 201820Chieh-Hsin Lee and Fabrizio GiulianiThe Role of Inflammation in Depression and Fatigue Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada; Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada. 2019
Typically anxiety and depression come together, so it’s reasonable to think that if ALCAR lowers depression, it should do the same with anxiety.21Shixun Wang, Jingtao Xu, Jiahui Zheng, Xincai Zhang, Jingbo Shao, Luyan Zhao, and Junqiang HaoAnti-Inflammatory and Antioxidant Effects of Acetyl-L-Carnitine on Atherosclerotic Rats Second Department of Cardiology, Weifang People’s Hospital, Weifang, Shandong, P.R. China. 2020
ALCAR and Memory
ALCAR can help memory and learning capabilities through its ability to boost acetylcholine synthesis.22Helen L. White, Philip W. Scates Acetyl-L-carnitine as a precursor of acetylcholine Neurochemical Research. 1990
In a study conducted on aging rats, ALCAR improved their learning capacity, suggesting the strong link between long-term administration of ALCAR and improved cognitive function.23S. Ando, T. Tadenuma, Y. Tanaka, F. Fukui, S. Kobayashi, Y. Ohashi, T. Kawabata Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats Journal of Neuroscience Research. 2001
When the brain’s cholinergic pathways located in the thalamus and the hippocampus are impaired or have degenerated due to aging or trauma, the memory and the cognitive processes are affected.24Sara V. Maurer and Christina L. Williams The Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells Frontiers in Immunology. 2017
The damage also results in the inflammation of the neurons, which is linked to Alzheimer’s disease. Attention span and learning capabilities are also affected.25Sara V. Maurer and Christina L. WilliamsThe Cholinergic System Modulates Memory and Hippocampal Plasticity via Its Interactions with Non-Neuronal Cells Frontiers in Immunology. 2017
Essentially, if the cholinergic pathways are healthy in part due to the antioxidative protection from a steady administration of ALCAR, the brain’s learning and memory performance significantly increase.26Fumihiko Yasui, Seiichi Matsugo, Masaru Ishibashi, Takahiro Kajita, Yoshiharu Ezashi, Yutaka Oomura, Shosuke Kojod, Kazuo SasakiEffects of chronic acetyl-L-carnitine treatment on brain lipid hydroperoxide level and passive avoidance learning in senescence-accelerated mice Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Yamanashi University, Yamanashi 400-8511, Japan; Division of Bio-Information Engineering, Faculty of Engineering, Toyama University, 3190 Gofuku Toyama 930-8555, Japan; Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan; Department of Food Science and Nutrition, Nara Women’s University, Nara 630-8506, Japan. 2002
Another important factor in enhancing memory and cognitive learning that is strongly linked to ALCAR is dopamine. We know dopamine as a stress hormone, but it actually serves as a neurotransmitter and is associated with learning, long-term memory formation, and working memory.27J K Seamans, S B Floresco, A G PhillipsD1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat The Journal of Neuroscience. 1998
Studies conducted in senescent rats showed improved levels of dopamine in the cortex and hippocampus after carnitine administration.28JPackiasamy A. R. Juliet, Deepak Balasubramaniam, Naveen Balasubramaniam, and Chinnakannu Panneerselvam Carnitine: A Neuromodulator in Aged Rats Journal of Gerontology: Biological Sciences. 2003
ALCAR and ADHD
The overall benefits of ALCAR for ADHD are largely mixed.
Results from clinical studies are not conclusive because much of the research was done with L-carnitine paired with ADHD drugs.
Without looking at ALCAR in isolation, it is hard to determine it’s effectiveness for ADHD.
However, some studies show the benefits of improved ADHD symptoms with ALCAR supplementation.
Children with ADHD given ALCAR and methylphenidate showed improvement in their social skills and reported less frequent headaches and irritability as a side effect of medication.29Seyed-Hesameddin Abbasi, Shahram Heidari, Mohammad-Reza Mohammadi, Mina Tabrizi, Ali Ghaleiha, Shahin AkhondzadehAcetyl-L-carnitine as an adjunctive therapy in the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a placebo-controlled trial Child Psychology and Human Development. 2011
In another study of children with Fragile X syndrome, administration of methylphenidate and LAC (20-50 mg/kg/day) resulted in better social interaction and more attention to their activities than children given the placebo.
Attention deficit hyperactivity disorder (ADHD) is one of the manifestations of a child with Fragile X syndrome.30M Giulia Torrioli, Silvia Vernacotola, Laura Peruzzi, Elisabetta Tabolacci, Montserrat Mila, Roberto Militerni, Sebastiano Musumeci, Feliciano J Ramos, Marìa Frontera, Giovanni Sorge, Elisabetta Marzullo, Giusi Romeo, Louis Vallee, Edvige Veneselli, Elena Cocchi, Eleonora Garbarino, Umberto Moscato, Pietro Chiurazzi, Stefania D’Iddio, Menotti Calvani, Giovanni NeriA double-blind, parallel, multicenter comparison of L-acetylcarnitine with placebo on the attention deficit hyperactivity disorder in fragile X syndrome boys American Journal of Modern Genetics. 2008
One systematic review shows ALCAR positively affects the inattentive type of ADHD over behavioral issues tied to ADHD.31Kirstie DominiqueIs Acetyl-L-Carnitine Effective and Safe in Treating Children with ADHD? Philadelphia College of Osteopathic Medicine. 2019
There is also evidence of carnitine’s ability to reduce headaches, irritability, and improve the inattention and social skills commonly experienced by children with ADHD.32Kirstie DominiqueIs Acetyl-L-Carnitine Effective and Safe in Treating Children with ADHD? Philadelphia College of Osteopathic Medicine. 2019
While it cannot be considered a primary treatment for ADHD, acetyl L-Carnitine can be effective as part of a more comprehensive plan.
ALCAR is Neuroprotective
L-Carnitine has demonstrated an ability to be neuroprotective and neuroregenerative by preventing decay and accelerating neurons’ ability to regenerate both in vitro and in vivo studies.33A Manfridi, G L Forloni, E Arrigoni-Martelli, M ManciaCulture of dorsal root ganglion neurons from aged rats: effects of acetyl-L-carnitine and NGF International Journal of Developmental Neuroscience. 1992
One example of hyperammonemia is characterized by seizures caused by overly high ammonia levels in the bloodstream that may be primary or secondary.34Cecilia Maldonado, Natalia Guevara, Alicia Silveira, Pietro Fagiolino, Marta VázquezL-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report The Journal of International Medical Research. 2017
Patients with epilepsy, severe migraine headaches, and mood conditions due to hyperammonemia may be prescribed valproic acid to manage these conditions. However, the side effects may also be life-threatening after long-term use.
Carnitine supplementation was shown to potentially reverse hyperammonemia.35Cecilia Maldonado, Natalia Guevara, Alicia Silveira, Pietro Fagiolino, Marta VázquezL-Carnitine supplementation to reverse hyperammonemia in a patient undergoing chronic valproic acid treatment: A case report The Journal of International Medical Research. 2017
Interest in further research on L-carnitine’s therapeutic potential and acetyl-L-carnitine (ALCAR) for neuroprotection was sparked in the last decade after finding out that the positive effects of ALCAR in treating chronic degenerative diseases.36Lauren L Jones, David A McDonald, Peggy R BorumAcylcarnitines: role in brain Progress in Lipid Research. 2009
While there are no lipids in the brain itself, the improved metabolism of lipids in the other parts of the body feeds the brain, and adequate L-carnitine and ALCAR levels result in improved cerebral bioenergetics and cholinergic neurotransmission. This shows the importance of L-carnitine and ALCAR in proper brain function and protection.37Masato Inazu 1, Teruhiko MatsumiyaPhysiological functions of carnitine and carnitine transporters in the central nervous system Japanese Journal of Psychopharmacology. 2008
Brain Injuries
ALCAR was also found to specifically protect cells from death and damage during hypoxic-ischemic encephalopathy, oxygen deprivation, and other brain injuries.38Thomas F. Rau, Qing Lu, Shruti Sharma, Xutong Sun, Gregory Leary, Matthew L. Beckman, Yali Hou, Mark S. Wainwright, Michael Kavanaugh, David J. Poulsen, and Stephen M. Black, Valentin Ceña, EditorOxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana, United States of America; Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, United States of America; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, Illinois, United States of America, Universidad de Castilla-La Mancha, Spain. 2012
Not only that, but it also promotes neurogenesis (formation of new neurons) in the adult brain by balancing cell survival and cell death in patients with Parkinson’s Disease.39Sonu Singh, Akanksha Mishra, Sandeep Kumar Mishra, Shubha ShuklaALCAR promote adult hippocampal neurogenesis by regulating cell-survival and cell death-related signals in rat model of Parkinson’s disease like-phenotypes Neurochemistry International. 2017
Anti-Inflammatory
ALCAR has anti-inflammatory properties as it lowers oxidative stress markers in both brain tissue and cerebrospinal fluid resulting in delayed cell death.40Santina A Zanelli 1, Nina J Solenski, Robert E Rosenthal, Gary FiskumMechanisms of ischemic neuroprotection by acetyl-L-carnitine Annals of the New York Academy of Sciences. 2005
There is compelling evidence that the administration of ALCAR after injury in the developing brain can attenuate injury and improve long-term functional outcomes.41Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201. 2017
This is achieved by improving the brain’s energy status, decreasing the oxidative stress, and preventing cell death from brain injury.42Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201. 2017
Also, L-carnitine significantly reverses NMDA antagonists’ negative results that cause both acute and delayed cell death. NMDA antagonists are used as anesthetics in animals and are often used as a hallucinatory recreational drug.
Alzheimer’s and Multiple Sclerosis
ALCAR supplementation shows promise in treating Alzheimer’s and Multiple Sclerosis.43Gustavo C Ferreira, Mary C McKennaL-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain Neurochemical Research. 2017
In multiple sclerosis, ALCAR used with dexamethasone as a treatment was found to improve cell lifespan as signaled by the change in the indicator numbers and the improvement of immunosuppressive effect as exhibited by the decrease in CD4+ T cells.44Amr Zidan, Sabeha E.Hedya, Dina M. Elfeky, Amany A. AbdinThe possible anti-apoptotic and antioxidant effects of acetyl l-carnitine as add-on therapy on a relapsing-remitting model of experimental autoimmune encephalomyelitis in rats Department of pharmacology, Faculty of Medicine, Tanta University, Egypt. 2018
ALCAR treatment has shown decreased inflammatory markers such as Reactive Oxygen Species, peroxide hydroxyl radical, superoxide radical, iNOS expression, nitrite content, and lipid peroxidation and increased the glutathione content in the hippocampus and PFC regions.
ALCAR demonstrates the ability to enhance nerve growth factors that improve overall cognitive function and ameliorate age-related cognitive decline.45Sonu Singh 1, Akanksha Mishra, Neha Srivastava, Rakesh Shukla, Shubha ShuklaAcetyl-L-Carnitine via Upregulating Dopamine D1 Receptor and Attenuating Microglial Activation Prevents Neuronal Loss and Improves Memory Functions in Parkinsonian Rats Molecular Neurobiology. 201846L Angelucci, M T Ramacci, G Taglialatela, C Hulsebosch, B Morgan, K Werrbach-Perez, R Perez-PoloNerve growth factor binding in aged rat central nervous system: effect of acetyl-L-carnitine Journal of Neuroscience Research. 1988
ALCAR is also helpful in slowing the age-related degradation of mice’s central nervous system by improving the rats’ cognitive performance.
With age, the carnitine concentration in the brain decreases, resulting in the degradation of memory capacity, but this can be mitigated with carnitine administration in the diet.47M Castorina, L FerrarisAcetyl-L-carnitine affects aged brain receptorial system in rodents Life Sciences. 1994
Alzheimer’s Patients diagnosed with Alzheimer’s Disease who were unresponsive to acetylcholinesterase inhibitors were given oral ALCAR (2g/daily for three months) along with donepezil or rivastigmine showed positive results.
Though the study was not conclusive, it does show promise that ALCAR can improve the cognitive processes, functional status, and behavior of persons with mild AD.48A Bianchetti, R Rozzini, M TrabucchiEffects of acetyl-L-carnitine in Alzheimer’s disease patients unresponsive to acetylcholinesterase inhibitors Current Medical Research and Opinion. 2003
L-Carnitine and Insulin Resistance
L-Carnitine helps lower insulin resistance, which has been tied to depression.49Benedetta Bigio, Aleksander A Mathé, Vasco C Sousa, Danielle Zelli, Per Svenningsson, Bruce S McEwen, Carla Nasca Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance Proceedings of the National Academy of Sciences of the United States of America. 2016
A study shows that the brain synapses’ ability to adapt to their activity can be the root of depression.
Known as synaptic plasticity, it is regulated by insulin actions in the brain.
Suppose the brain response is too rigid, and it suddenly goes through a stressful situation. In that case, the brain insulin resistance can affect the brain’s reward system, resulting in depressive symptoms.50Natalia de M. Lyra e Silva, Minh P. Lam, Claudio N. Soares, Douglas P. Munoz, Roumen Milev, and Fernanda G. De FeliceInsulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes Centre for Neuroscience Studies, Queen’s University, Kingston, ON, Canada; Department of Psychiatry, Queen’s University, Kingston, ON, Canada; Institute of Medical Biochemistry Leopoldo De Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 2019
LAC controls glutamate toxicity, which rapidly reduces depression.
It is also seen as a potential treatment for insulin resistance in people diagnosed with depression.51Benedetta Bigio, Aleksander A Mathé, Vasco C Sousa, Danielle Zelli, Per Svenningsson, Bruce S McEwen, Carla Nasca Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance Proceedings of the National Academy of Sciences of the United States of America. 2016
It has been found that oral L-carnitine supplementation has varied effects on healthy and diabetic patients.
Still, there is also evidence that L-carnitine supplementation on glucose metabolism can positively affect parameters for lipid and oxidative stress.52Judit Bene, Kinga Hadzsiev & Bela Melegh Role of carnitine and its derivatives in the development and management of type 2 diabetes Nutrition and Diabetes. 2018
L-Carnitine For Aging and Resilience
In humans, while frailty is associated with aging, there is also a strong indication that carnitine levels in the body can cause weakness.53Nicholas J. W. Rattray, Drupad K. Trivedi, Yun Xu, Tarani Chandola, Caroline H. Johnson, Alan D. Marshall, Krisztina Mekli, Zahra Rattray, Gindo Tampubolon, Bram Vanhoutte, Iain R. White, Frederick C. W. Wu, Neil Pendleton, James Nazroo & Royston GoodacreMetabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty Nature Communications. 2019
This state includes the body’s weakness, a decline of cognitive function, high risk of falls and fractures, impairment of vision and hearing, and even increased depression levels, not to mention chronic diseases that come with age.54Nicholas J. W. Rattray, Drupad K. Trivedi, Yun Xu, Tarani Chandola, Caroline H. Johnson, Alan D. Marshall, Krisztina Mekli, Zahra Rattray, Gindo Tampubolon, Bram Vanhoutte, Iain R. White, Frederick C. W. Wu, Neil Pendleton, James Nazroo & Royston GoodacreMetabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty Nature Communications. 2019
This is achieved by maintaining a healthy level of ALCAR in the body, which serves as a precursor for acetylcholine, increasing cholinergic transmission.55Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201 2017
L-Carnitine and Alcoholism
L-carnitine has exhibited positive effects of neurodegeneration after prolonged alcohol intake.
Based on this observation, L-carnitine has a potential to help an alcoholic having withdrawal symptoms.56P M Abdul Muneer, Saleena Alikunju, Adam M Szlachetka, James Haorah Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: preventive role of acetyl-L: -carnitine Psychopharmacology. 201157Tempesta E, Troncon R, Janiri L, Colusso L, Riscica P, Saraceni G, Gesmundo E, Calvani M, Benedetti N, Pola P Role of acetyl-L-carnitine in the treatment of cognitive deficit in chronic alcoholism Department of Psychiatry and Pharmacology, Catholic University of Rome, Italy.1990
Aside from the brain, the liver is also one of the organs most damaged after long-term alcohol intoxication.
L-carnitine can be an effective way to treat the diseased liver after prolonged alcohol exposure.58Kępka A, Szajda SD, Waszkiewicz N, Płudowski P, Chojnowska S, Rudy M, Szulc A, Ladny JR, Zwierz K Carnitine: function, metabolism and value in hepatic failure during chronic alcohol intoxication Zakład Biochemii i Medycyny Doświadczalnej, Instytut Pomnik-Centrum Zdrowia Dziecka w Warszawie. 2011
However, it should be noted that studies also show an elevated amount of carnitine in acylcarnitine in the plasma of alcoholic persons and persons with alcoholic liver disease.59Richard K. Fuller MD Charles L. Hoppel MD Plasma Carnitine in AlcoholismAlcoholism Clinical and Experimental Research. 1988
This means that carnitine supplementation has little effect in stopping neurodegeneration since it will only be eliminated from the body.
L-Carnitine Stacking Options
L-carnitine has been proven to work well with Alpha Lipoic Acid (ALA), a polyunsaturated fatty acid, in neuroprotection.60Gregory E Bigford, Gianluca Del RossiSupplemental substances derived from foods as adjunctive therapeutic agents for treatment of neurodegenerative diseases and disorders Advances in Nutrition. 2014
From a naturopathic standpoint, L-carnitine supplementation also works well with flavonoids like curcuminoids (turmeric), rosmarinic acid (chiefly from rosemary), and resveratrol (from grapes).61Gregory E Bigford, Gianluca Del RossiSupplemental substances derived from foods as adjunctive therapeutic agents for treatment of neurodegenerative diseases and disorders Advances in Nutrition. 2014
Choline has also been found to decrease oxidative stress in women if used with carnitine.
It acts in promoting the conservation of retinol and alpha-tocopherol in women, both of which are known as good antioxidants.62Dileep S. SachanDecreasing Oxidative Stress with Choline and Carnitine in Women Journal of the American College of Nutrition. 2005
It has also been proven that carnitine and choline enhance acetylcholine synthesis.63A Wawrzeńczyk, K A Nałecz, M J NałeczSynergistic effect of choline and carnitine on acetylcholine synthesis in neuroblastoma NB-2a cells Biochemical and Biophysical Research Communications. 1994
Caffeine has also been proven to increase the fat oxidation process leading to better performance in athletes administered with the combination.64Y S Cha, S K Choi, H Suh, S N Lee, D Cho, K LiEffects of carnitine coingested caffeine on carnitine metabolism and endurance capacity in athletes Journal of Nutritional Science and Vitaminology. 2001
How L-Carnitine Works In The Brain
Carnitine is an important factor for fat metabolism and energy production for essential body processes.65Carla Nasca, Benedetta Bigio, Francis S. Lee, Sarah P. Young, Marin M. Kautz, Ashly Albright, James Beasley, David S. Millington, Aleksander A. Mathé, James H. Kocsis, James W. Murrough, Bruce S. McEwen, and Natalie Rasgon Acetyl-l-carnitine deficiency in patients with major depressive disorder Proceedings of the National Academy of Sciences of the United States of America. 2018
The mitochondria are considered the powerhouse of the body’s cells.
To function properly, it should be adequately fed with long-chain fatty acids, which is the function of carnitine.
The oxidation of these long-chain fatty acids, in turn, supplies the necessary energy needed to sustain the brain’s metabolism and the rest of the body.66Bruce S. McEwen, Nicole P. Bowles, Jason D. Gray, Matthew N. Hill, Richard G. Hunter, Ilia N. Karatsoreos, and Carla NascaMechanisms of stress in the brain Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065; Hotchkiss Brain Institute, University of Calgary, Calgary AB, Canada T2N4N1; Department of Psychology, University of Massachusetts Boston, Boston, USA; Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, 99164. 201567SP Chapela, N. Kriguer, EH Fernandez, CA Stella Involvement of L-carnitine in cellular metabolism: beyond Acyl-CoA transport Mini Reviews in Medical Chemistry. 2009
The Carnitine Shuttle
The carnitine shuttle plays an important role in the accumulation of long-chain fatty acids in the cells.
If not enough carnitine is present in the body, the transport of these fatty acids to the mitochondria is delayed.
The fatty acids accumulate in the cells68Gustavo C. Ferreira and Mary C. McKennaL-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain 1Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201. 2017 leading to impaired homeostasis and mitochondrial dysfunction, therefore starving the cells.69Thomas F Rau, Qing Lu, Shruti Sharma, Xutong Sun, Gregory Leary, Matthew L Beckman, Yali Hou, Mark S Wainwright, Michael Kavanaugh, David J Poulsen, Stephen M BlackOxygen glucose deprivation in rat hippocampal slice cultures results in alterations in carnitine homeostasis and mitochondrial dysfunction National Library of Medicine; National Center of Biotechnology Information. 2012
Synthesis of fatty acids in the adult brain is preferred to be through the carbons from the acetyl moiety.70K A Nałecz , M J NałeczCarnitine–a known compound, a novel function in neural cells Acta Neurobiologiae Experimentalis. 1996
In the developing brain, the acetyl moiety may be oxidized for energy and incorporated into neurotransmitters and lipids71Susanna Scafidi, Gary Fiskum, Steven L Lindauer, Penelope Bamford, Da Shi, Irene Hopkins, Mary C McKennaMetabolism of acetyl-L-carnitine for energy and neurotransmitter synthesis in the immature rat brain Journal of Neurochemistry. 2010
Carnitine has also been found to be important in the synthesis of acetylcholine, a neurotransmitter that controls the smooth muscles, blood vessels, bodily secretions, and heart rate.72Helen L. White & Philip W. Scates Acetyl-L-carnitine as a precursor of acetylcholine Neurochemical Research. 1990
Carnitine also stimulates the release of acetylcholine by mimicking its functions to control the muscles mentioned above and organs.73A Imperato , M T Ramacci, L AngelucciAcetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats Neuroscience Letters. 1989
It also increases dopamine, glycine, serine, threonine, alanine, and glutamine in selected brain regions.
By stimulating these amino acids to perform their necessary functions, the brain benefits largely from it.74E Toth, L G Harsing Jr, H Sershen, M T Ramacci, A LajthaEffect of acetyl-L-carnitine on extracellular amino acid levels in vivo in rat brain regions Neurochemical Research. 1993
ALCAR was also proven to reduce glutamate oxidation, which can result in neurotoxicity leading to cell death.75V Felipo, M D Miñana, H Cabedo, S GrisolíaL-carnitine increases the affinity of glutamate for quisqualate receptors and prevents glutamate neurotoxicity Neurochemical Research. 1994
L-carnitine is important in energy metabolism. In mammals, the carnitine level is maintained by producing adequate liver, kidneys, and brain levels.
It can also be absorbed from the diet or reabsorbed from the kidneys.76Frédéric M Vaz, Ronald J A WandersCarnitine biosynthesis in mammals The Biochemical Journal. 2002
Carnitine Deficiency Deficiency in the OCTN2 carnitine transporter is a rare inherited disease that leads to systemic primary carnitine deficiency77Nicola LongoPrimary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle Annals of Nutrition and Metabolism. 2016 which can result in autism and improper brain development.78Caroline Demarquoy and Jean DemarquoyAutism and carnitine: A possible link World Journal of Biological Chemistry. 2019
L-Carnitine Safety
ALCAR is considered safe with no serious adverse reactions but always should be taken with medical supervision.79RxListACETYL-L-CARNITINE RxList
However, stay away from ALCAR if you are pregnant or are breastfeeding since there is no adequate information to its effect on these situations.80RxListACETYL-L-CARNITINE RxList
It should not also be used when diagnosed with hyperthyroidism or when having nerve pains following chemotherapy.81RxListACETYL-L-CARNITINE RxList
If you have seizures or have experienced one in the past, do not take ALCAR, unless under medical supervision.82RxListACETYL-L-CARNITINE RxList
Drug Interactions Acenocoumarol (Sintrom) – Possible blood clotting issues Warfarin (Coumadin)- Possible Blood clotting issues.83RxListACETYL-L-CARNITINE RxList
Suggested Dose
A daily dose of 1500-2000mg for most cognitive enhancement issues for 3-12 months is recommended with close medical supervision.84RxList ACETYL-L-CARNITINE RxList