Description
Carnitine is the generic term for several compounds including L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine. It is a substance occurring naturally in humans, where it is synthesized endogenously in the liver, kidneys, and brain from the aminoacids lysine and methionine. The name carnitine comes from the Latin word for meat ('caro', genitive 'carnis'), as it was first discovered in muscle tissue.
Carnitine is naturally present in many foods and most of the daily requirements of L-carnitine is provided through the diet. It is also available as a dietary supplement.
In the context of cancer, L-carnitine has been mainly investigated for alleviating adverse effects of chemo- or radiotherapy treatment.
Efficacy
Nine randomized controlled trials (RCTs) and one systematic (SR) investigated the efficacy of L-carnitine in the supportive care of cancer: Four for the prevention and one for the treatment of chemotherapy-induced peripheral neuropathy, one systematic review of three RCTs for the treatment of cancer-related fatigue, two RCTs for protection against cardiotoxicity, one for the treatment of sexual dysfunction after chemotherapy and one for tumour cachexia.
Prevention of chemotherapy-induced neuropathy (CIPN): Two RCTs investigating taxane-based chemotherapies (n=437, n=160) and one RCT examining non-taxane-based chemotherapies (sagopilone, n=150) demonstrated that acetyl-L-carnitine had no prophylactic effect on CIPN. The largest of these RCTs reported that prophylactic therapy with ALE even increased the risk of CIPN and its persistence.
Treatment of CIPN: The results of one RCT (n=240) suggest that acetyl-L-carnitine may be effective in the treatment of CIPN induced by paclitaxel, cisplatin or vinblastine (low certainty of results).
Fatigue: A systematic review (n=3 RCTs) concluded that results do not support the use of carnitine supplementation for cancer-related fatigue.
Cardiotoxicity: Two small RCTs reported conflicting results. One RCT (n=40) found no significant differences in the echocardiographic parameters recorded while the other (n=30) reported a significant reduction in cardiac events requiring treatment.
Sexual disfunction : In one RCT (n=96), patients in the L-carnitine group reported significantly less erectile dysfunction.
Cancer cachexia : One RCT (n=72) reported a significant increase in body mass index and a significant improvement in nutritional status.
Safety
The available clinical data suggest that L-carnitine is generally well tolerated and has been safely used in clinical trials at doses from 250mg to 6g per day for up to six months. Interactions with thyroid medications have been reported.
Description and background
L-carnitine (LC) is a naturally occurring chemical compound found in humans, most animal species, numerous microorganisms and plants. LC is a major component of carnitine stored in the human body. It is both absorbed from food and synthesised from the two amino acids lysine and methionine. Most of the body’s carnitine is located within skeletal muscles, where it is crucial for the supply of energy by the beta-oxidation of fatty acids. It also plays an important role in the stress response by modulating inflammatory and oxidative processes.
Sources of L-carnitine are animal products, particularly red meat but also poultry, fish and dairy products. (ODS 2023, NatMed 2024) For supplementation or pharmacological purposes, LC is available in capsule, tablet or powder form for oral use and as a solution for intravenous administration.
The name carnitine comes from the Latin word for meat (‘caro, carnis’), as it was first discovered in muscle tissue. (Bremer 1983) Other names include: Levocarnitine, Carnitor, Carnitene, Carnitine and Vitamin BT (obsolete term).
Ingredients and quality issues
Most carnitine supplements in Europe contain LC, but preparations containing the esterified forms acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) are also available over the counter. ALC is best absorbed by the intestine. As L-carnitine is not considered an essential nutrient, no recommended daily allowance or other dietary reference values have been established. (ODS 2023)
Alleged indications
Supplemental LC is mainly used to treat L-carnitine deficiency caused by certain genetic diseases or other disorders. Its role is also being investigated for Alzheimer’s disease and dementia, cardiovascular and peripheral artery disease, insulin resistance and diabetes, infertility, osteoarthritis, athletic performance enhancement, and weight loss. (ODS 2023)
In the context of cancer, supplementation with LC has been claimed to protect organs from chemo- and radiotherapy-related toxicities, to alleviate cancer-related fatigue and cancer anorexia-cachexia syndrome. However, current guidelines do not recommend L-carnitine for cancer-related fatigue (Bower 2024, S3-Leitlinie) and advise against its use for preventing chemotherapy-induced peripheral neuropathy (Loprinzi 2020, Lyman 2018).
Application and dosage
For supplementation or pharmacological purposes, LC is available in capsule, tablet or powder form for oral use and as a solution for intravenous administration. The usual dosages used in clinical studies range from 250 mg to 6 g per day (NatMed 2024).
Mechanism of action
The vital metabolic functions of LC are the channelling of fatty acids (acyl groups) as acylcarnitines across the mitochondrial membrane for β-oxidation, the maintenance of sufficient levels of free coenzyme A in the mitochondria and the buffering of excess acetyl coenzyme A (Bremer 1990). Other functions include regulation of apoptosis and inflammation, protection against free radicals and modulation of proteins, cellular stress response and gene expression. (Famularo 2004; Calabrese 2006; Chapela 2009; Jones 2010; NatMed 2024).
Legal issues
In the EU, LC and PLC are approved for use in so-called "foods intended for particular nutritional uses" (Anton 2003). In the USA, LC is approved by the US Food and Drug Administration (FDA) for the treatment of carnitine deficiency, and LC and ALC are approved as dietary supplements. (Drugs 2024)
Nine randomized controlled trials (RCTs) and one systematic review (SR) investigated the efficacy of L-carnitine in the supportive care of cancer: Four for the prevention (Mondal 2014; Campone 2013; Hershman 2013; Hershman 2018) and one for the treatment of chemotherapy-induced peripheral neuropathy (CIPN, Sun 2016), one systematic review of three RCTs for the treatment of cancer-related fatigue (Marx 2017), two for protection against cardiotoxicity (Lissoni 1993, Waldner 2006), one for the treatment of sexual dysfunction after chemotherapy (Cavallini 2005) and one for tumour cachexia (Kraft 2012). Details of the RCTs can be found in Table 1.
Description of included studies
Prevention of chemotherapy-induced peripheral neuropathy
Mondal investigated the efficacy of acetyl-L-carnitine for the prophylaxis of CIPN in a 4-arm, non-blinded RCT (Mondal 2014). A total of 160 patients with lung, breast or ovarian cancer received either carboplatin or doxorubicin and cyclophosphamide as first- or second-line chemotherapy in addition to paclitaxel. The 4 intervention groups received either vitamin E, glutamine, vitamin B12 or acetyl-L-carnitine (250mg day 1-7 of each chemotherapy cycle) in addition to chemotherapy. In the patients who had received vitamin B12 or vitamin E, the doctors rated the change in CIPN symptoms in terms of changes in pain, sensory and motor function categorised according to CTCAE 4.02 (Common Terminology of Adverse Events) as significantly lower than in those who had taken L-carnitine or glutamine (low certainty of results).
Campone investigated the efficacy of acetyl-L-carnitine for the prevention of sagopilone-induced CIPN in patients with ovarian or prostate cancer in a double-blind, placebo-controlled RCT (n=150). (Campone 2013) The verum group received acetyl-L-carnitine 1g 3 times daily during chemotherapy with sagopilone (16mg/m2). The primary outcome measure of the study was the incidence of CIPN during the first 6 cycles of chemotherapy. The authors found no significant difference in the incidence of CIPN in the two groups, but a significantly lower severity of CIPN in the verum group, although only in patients with ovarian cancer and not in patients with prostate cancer (low certainty of results).
In a double-blind, placebo-controlled RCT (n=409), investigated the efficacy of acetyl-L-carnitine for the prevention of CIPN in women with breast cancer (stages I-III) who were receiving taxane-based chemotherapy. (Hershman 2013) The serum group received acetyl-L-carnitine 3g/day for 24 weeks from the start of chemotherapy. The primary endpoint ‘CIPN at week 12’ was assessed using a self-assessment questionnaire (FACT-NTX) and showed no significant difference between the two groups. After a further 12 weeks, there was a significant increase in self-assessed symptoms (FACT-NTX) and a significantly higher estimated severity of CIPN (CTCAE version 3.0) in the L-carnitine group (high certainty of results).
In the two-year follow-up of this study (Hershman 2018), the authors found that there was no recovery of CIPN after discontinuation of L-carnitine. In both groups, CIPN (measured by the drop in FACT-NTX >10%) continued to increase over time in the two-year follow-up. The difference between the two groups did not change significantly (high certainty of results).
Based on the reported aggravation of CIPN reported in these trials, current guidelines recommend against the use of LC in CIPN (Loprinzi 2020, Lyman 2018).
Treatment of chemotherapy-induced peripheral neuropathy
Sun 2016 investigated the efficacy of acetyl-L-carnitine for the treatment of CIPN in 240 patients with various tumours in a double-blind, placebo-controlled RCT. Inclusion criteria included physician-assessed polyneuropathy grade ≥ 2 or 3 (NCI-CTC version 3.0) that occurred during chemotherapy with paclitaxel, cisplatin or vinblastine and persisted for at least one month after therapy. The verum group received 3x1g acetyl-L-carnitine per day for 8 weeks, the placebo group a corresponding placebo. The authors found a significant improvement in CIPN defined as an improvement ≥1 grade (NCI-CTC version 3.0). There was a better regeneration of nerve conduction velocities in the L-carnitine group (low certainty of results).
Cancer-related fatigue
A systematic review with meta-analysis included three studies (Hershman 2013, Cruciani 2012 and Kraft 2012) and came to the following conclusion: ‘Results from studies with lower risk of bias do not support the use of carnitine supplementation for cancer-related fatigue.’ (Marx 2017)
Cardiotoxicity
A double-blind RCT (n=40) investigated the efficacy of L-carnitine for the prophylaxis of anthracycline-induced cardiotoxicity in patients with non-Hodgkin's lymphoma. (Waldner 2006) Patients received either placebo or L-carnitine 3g before each chemotherapy cycle followed by 1g per day for 21 days over 6 cycles of chemotherapy. The authors found no significant difference in the echocardiographic parameters recorded (low certainty of results).
The efficacy of L-carnitine for the prophylaxis of cardiotoxicity under high-dose interleukin-2 therapy was investigated in a double-blind RCT (n=30) in patients with different metastatic cancers. (Lissoni 1993) The patients received L-carnitine 1g per day or no additional therapy. The authors found a significant reduction in cardiac events requiring treatment such as arrhythmias (including atrial fibrillation, ventricular tachycardia) and acute heart failure in the L-carnitine group (low certainty of results).
Sexual disfunction
A three-arm, placebo-controlled RCT (n=96) investigated the efficacy of L-carnitine for the treatment of sexual dysfunction in patients with erectile dysfunction following bilateral, nerve-sparing prostatectomy. (Cavalini 2005) The patients received sildenafil 100mg per day if required and additionally either propionyl-L-carnitine 2g per day or placebo. Patients in the L-carnitine group reported significantly less erectile dysfunction in the IIEF self-assessment questionnaire (moderate certainty of results).
Tumour cachexia
The efficacy of L-carnitine in the treatment of tumour cachexia was assessed in a placebo-controlled RCT (n=72) in patients with advanced pancreatic cancer. (Kraft 2012) The patients received L-carnitine 4g per day for 12 weeks. The authors found a significant increase in body mass index and a significant improvement in nutritional status (moderate certainty of results).
Adverse effects
LC is generally well-tolerated and only mild and transient adverse effects mainly affecting the gastrointestinal tract have been reported. It has been safely used orally in children for up to 6 months (NatMed 2024).
Contraindications
People with low or borderline low thyroid levels should not supplement with LC as it may interfere with the action of thyroid hormones. (Benvenga 2005)
Interactions
Theoretically, L-carnitine might increase the anticoagulant effects of anticoagulants acenocoumarol and warfarin, and decrease the effectiveness of thyroid hormone replacement. (Benvenga 2005; NatMed 2024)
Warnings
Not enough information about its safety during pregnancy is available (NatMed 2024).
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Campone, M., et al. (2013). "A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy." Oncologist 18(11): 1190-1191.
Cavallini, G., et al. (2005). "Acetyl-L-carnitine plus propionyl-L-carnitine improve efficacy of sildenafil in treatment of erectile dysfunction after bilateral nerve-sparing radical retropubic prostatectomy." Urology 66(5): 1080-1085.
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Marx, W. (2017). "Efficacy and Effectiveness of Carnitine Supplementation for Cancer-Related Fatigue: A Systematic Literature Review and Meta-Analysis." Nutrients 9(11).
Mondal, S., et al. (2014). "Comparative study among glutamine, acetyl-L-carnitine, vitamin E and methylcobalamine for treatment of paclitaxel-induced peripheral neuropathy." Clin Cancer Investig J 3(3): 213-219.
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S3-Leitlinie Komplementärmedizin in der Behandlung von onkologischen PatientInnen Langversion Mai 2024, AWMF-Registernummer: 032/055OL
Sun, Y., et al. (2016). "A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy." Exp Ther Med 12(6): 4017-4024.
Waldner, R., et al. (2006). "Effects of doxorubicin-containing chemotherapy and a combination with L-carnitine on oxidative metabolism in patients with non-Hodgkin lymphoma." J Cancer Res Clin Oncol 132(2): 121-128.
Citation
CAM Cancer Collaboration. L-Carnitine, December 2024.
Document history
Assessed as up to date in November 2024 by Tessy Boedt. Updated in July 2023 by Ali Behzad. Assessed as up to date in January 2015 by Barbara Wider. Summary updated in July 2014 by Peter Renner and Markus Horneber. Summary first published in September 2012, authored by Peter Renner and Markus Horneber.
