L-Carnitine

• Mitochondrial function
• Energy metabolism
• Cardiovascular health

• Exercise performance
• Cognitive function
• Fatty acid metabolism
• Insulin sensitivity
• Antioxidant protection

L-Carnitine is a quaternary ammonium compound that plays a crucial role in energy metabolism, particularly in the transport of long-chain fatty acids into the mitochondria for beta-oxidation and energy production. The primary mechanisms of action include: 1) Fatty Acid Transport: L-Carnitine facilitates the transport of activated long-chain fatty acids from the cytosol across the inner mitochondrial membrane via the carnitine palmitoyltransferase (CPT) system. This process is essential for beta-oxidation of fatty acids, which generates acetyl-CoA for the tricarboxylic acid (TCA) cycle and subsequent ATP production. 2) Regulation of Acyl-CoA/CoA Ratio: L-Carnitine helps maintain the balance between acyl-CoA and free CoA in the mitochondria, which is crucial for optimal energy metabolism.

By converting excess acyl-CoA to acylcarnitine and exporting it from the mitochondria, L-Carnitine prevents the accumulation of potentially toxic acyl-CoA compounds and ensures sufficient free CoA for metabolic processes. 3) Mitochondrial Function: Beyond its role in fatty acid transport, L-Carnitine enhances mitochondrial function by stabilizing mitochondrial membranes, improving electron transport chain efficiency, and reducing oxidative stress. It helps maintain mitochondrial membrane potential and supports overall mitochondrial bioenergetics. 4) Antioxidant Properties: L-Carnitine and its derivatives (particularly Acetyl-L-Carnitine) exhibit antioxidant properties by scavenging free radicals, chelating metal ions, and enhancing the activity of endogenous antioxidant enzymes such as superoxide dismutase and glutathione peroxidase.

5) Neurotransmitter Modulation: Acetyl-L-Carnitine, a derivative of L-Carnitine, can donate acetyl groups for the synthesis of acetylcholine, a neurotransmitter important for cognitive function. It also modulates other neurotransmitter systems, including dopamine and serotonin, potentially contributing to its neuroprotective and cognitive-enhancing effects. 6) Gene Expression Regulation: L-Carnitine influences the expression of genes involved in lipid metabolism, mitochondrial function, and inflammation. It activates peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes involved in fatty acid oxidation and glucose metabolism.

7) Insulin Sensitivity: L-Carnitine may improve insulin sensitivity by enhancing glucose utilization, reducing intracellular accumulation of toxic lipid metabolites, and modulating inflammatory pathways that contribute to insulin resistance. 8) Cardiovascular Protection: L-Carnitine supports cardiovascular health through multiple mechanisms, including improved energy metabolism in cardiac tissue, reduced oxidative stress, enhanced nitric oxide production (improving endothelial function), and modulation of inflammatory pathways. 9) Exercise Performance: During exercise, L-Carnitine may enhance performance by increasing fatty acid oxidation (sparing glycogen), reducing lactic acid accumulation, improving oxygen delivery to muscles, and accelerating recovery through reduced muscle damage and inflammation. 10) Ammonia Detoxification: L-Carnitine participates in ammonia detoxification by forming acylcarnitines, which can be excreted in urine, potentially reducing ammonia levels in the blood and tissues.

The typical dosage range for L-Carnitine supplementation is 500-2,000 mg per day, with most research supporting efficacy within this range. The body naturally produces approximately 0.3-1.9 μmol/kg/hour of L-Carnitine, and dietary intake from omnivorous diets provides roughly 100-300 mg per day. Vegetarians and vegans may benefit more from supplementation due to lower dietary intake.

L-Carnitine has relatively low oral bioavailability, ranging from 5-18% depending on the form and dosage. When consumed in smaller doses (≤1 gram), bioavailability tends to be higher (14-18%), while larger doses (≥2 grams) show reduced bioavailability (5-10%) due to saturation of intestinal transporters. Absorption occurs primarily in the small intestine via active transport mechanisms, specifically the organic cation transporter OCTN2. After absorption, L-Carnitine is distributed throughout the body, with highest concentrations found in tissues with high energy demands such as cardiac and skeletal muscle.

Plasma levels typically peak within 3-4 hours after oral administration, with a half-life of approximately 15 hours.

Taking with carbohydrates: Consuming L-Carnitine with carbohydrates increases insulin levels, which enhances OCTN2 transporter activity and improves L-Carnitine uptake into tissues, particularly muscle., Using more bioavailable forms: Acetyl-L-Carnitine (ALCAR) has better bioavailability than free L-Carnitine and crosses the blood-brain barrier more effectively, making it superior for cognitive applications., Propionyl-L-Carnitine (PLCAR) has enhanced bioavailability for vascular tissues and may be preferred for cardiovascular applications., L-Carnitine L-Tartrate (LCLT) appears to be more rapidly absorbed and may have better uptake into muscle tissue, making it potentially superior for exercise performance., Liposomal delivery systems can significantly improve bioavailability by protecting L-Carnitine from degradation in the digestive tract and enhancing cellular uptake., Dividing larger doses throughout the day rather than taking a single large dose can improve overall absorption by preventing saturation of intestinal transporters.

For general health purposes, L-Carnitine can be taken once or twice daily with meals containing carbohydrates to enhance absorption. For exercise performance, taking L-Carnitine approximately 90 minutes before exercise with a carbohydrate-containing meal or beverage may optimize tissue uptake and utilization during physical activity. Alternatively, taking it immediately after exercise with post-workout carbohydrates may enhance recovery and muscle carnitine retention. For cognitive benefits, Acetyl-L-Carnitine may be taken in the morning to support mental energy and focus throughout the day.

For individuals using L-Carnitine to support fat metabolism or weight management, taking it before meals may theoretically enhance fatty acid oxidation during the post-prandial period, although evidence for timing-specific effects on weight management is limited. Long-term supplementation (several weeks to months) is typically required to significantly increase muscle carnitine stores and observe maximum benefits, particularly for exercise performance and metabolic health.

• Gastrointestinal discomfort (nausea, vomiting, abdominal cramps, diarrhea) – most common, particularly at higher doses
• Fishy body odor (due to bacterial metabolism of carnitine to trimethylamine in the gut)
• Mild headaches
• Restlessness or insomnia (particularly with Acetyl-L-Carnitine taken later in the day)
• Increased seizure frequency in individuals with seizure disorders (rare)
• Muscle weakness in individuals with uremia (rare)

• Individuals with seizure disorders (L-Carnitine may lower seizure threshold in some cases)
• Individuals with hypothyroidism (may interfere with thyroid hormone action)
• Individuals on anticoagulant therapy (theoretical interaction with warfarin)
• Individuals with kidney disease (may affect carnitine clearance)
• Pregnant or breastfeeding women (insufficient safety data)
• Individuals with trimethylaminuria (fish odor syndrome)

• Anticonvulsants: May affect seizure threshold and potentially reduce the effectiveness of anticonvulsant medications
• Thyroid medications: May reduce the effectiveness of thyroid hormone replacement therapy
• Anticoagulants: Theoretical interaction with warfarin, potentially affecting INR values
• Valproic acid: L-Carnitine may reduce valproic acid-induced hepatotoxicity and hyperammonemia
• Isotretinoin: Concurrent use may increase risk of isotretinoin-induced hepatotoxicity
• AZT (zidovudine): L-Carnitine may reduce AZT-associated myopathy
• Certain antibiotics: May affect intestinal microbiota and potentially alter carnitine metabolism

No established upper limit by major regulatory bodies. Clinical trials have used doses up to 6 grams per day with acceptable safety profiles. However, doses above 3 grams per day are more likely to cause gastrointestinal side effects and are generally unnecessary for most applications. For most individuals, staying within the 500-2,000 mg per day range minimizes the risk of side effects while providing potential benefits.

In the United States, L-Carnitine has dual status. As L-Carnitine (levocarnitine), it is approved as a prescription drug (Carnitor®) for the treatment of primary systemic carnitine deficiency and for acute and chronic treatment of patients with inborn errors of metabolism that result in secondary carnitine deficiency. Simultaneously, L-Carnitine is available as a dietary supplement under the Dietary Supplement Health and Education Act (DSHEA) of 1994. As a supplement, manufacturers cannot make specific disease claims without FDA approval, but can make general structure/function claims.

The FDA has not established a recommended daily allowance (RDA) or tolerable upper intake level (UL) for L-Carnitine.

The European Food Safety Authority (EFSA) has evaluated several health claims for L-Carnitine but has not approved any specific health claims due to insufficient evidence. L-Carnitine is regulated as a food supplement under Directive 2002/46/EC. In some European countries, L-Carnitine is also available as a prescription medication for specific carnitine deficiency conditions.

Health Canada permits L-Carnitine as a Natural Health Product (NHP) ingredient. It is listed in the Natural Health Products Ingredients Database (NHPID) with both medicinal and non-medicinal roles. Health Canada has approved certain claims related to L-Carnitine’s role in fat metabolism, energy production, and exercise recovery when specific conditions are met.

The Therapeutic Goods Administration (TGA) of Australia regulates L-Carnitine both as a prescription medicine for carnitine deficiency and as a listed complementary medicine (supplement). As a listed medicine, it can be used with certain limited claims related to energy metabolism and exercise recovery.

Regulations regarding L-Carnitine supplementation vary significantly by country. In Japan, L-Carnitine is recognized under the Foods for Specified Health Uses (FOSHU) system for certain applications. In Russia and several Eastern European countries, L-Carnitine is often classified as a metabolic medication rather than a supplement. Some countries have established maximum daily doses for supplement use, typically ranging from 1,000-2,000 mg per day.

The regulatory status of different forms of L-Carnitine (such as Acetyl-L-Carnitine or Propionyl-L-Carnitine) may vary from the base form in some jurisdictions.

Prescription-grade L-Carnitine (levocarnitine) is required for the treatment of primary and certain secondary carnitine deficiencies in most countries. The prescription form is typically available as oral solution, tablets, or injectable formulations. Non-prescription L-Carnitine supplements are widely available over-the-counter in most countries, though maximum dosages and approved claims vary by jurisdiction. In some countries, higher-dose formulations (typically >2 grams per day) may require a prescription or pharmacist supervision.

L-Carnitine supplements typically range from $0.10 to $0.50 per gram, depending on the form, brand, and quality. Acetyl-L-Carnitine tends to be more expensive, ranging from $0.30 to $0.80 per gram. Prescription-grade L-Carnitine (levocarnitine) is significantly more expensive, often costing $1.00 to $3.00 per gram. For a typical monthly supply at a dosage of 2 grams per day, consumers can expect to pay approximately $15-$30 for basic L-Carnitine supplements, $20-$50 for Acetyl-L-Carnitine, and $60-$180 for prescription formulations.

When compared to other energy-enhancing and mitochondrial support supplements, L-Carnitine offers good value, particularly in its basic form.

It is generally less expensive per effective dose than Coenzyme Q10, PQQ, or NMN, but more expensive than basic B vitamins or creatine. For cardiovascular applications, L-Carnitine may offer cost-effective benefits compared to some prescription medications, though

it should not be used as a replacement without medical supervision. For cognitive enhancement, Acetyl-L-Carnitine is moderately priced compared to other nootropics, offering better value than many patented cognitive enhancers but costing more than basic supplements like B vitamins or omega-3 fatty acids.

Purchasing L-Carnitine powder in bulk (250g-1kg) can significantly reduce costs, often bringing the price down to $0.05-$0.15 per gram. This approach is most economical for those requiring higher doses or long-term supplementation. However, proper measurement tools (such as a milligram scale) and storage containers are necessary when purchasing bulk powder. Bulk purchasing of Acetyl-L-Carnitine can reduce costs to $0.20-$0.40 per gram.

Prescription L-Carnitine (levocarnitine) is often covered by health insurance when prescribed for diagnosed carnitine deficiency or other approved medical conditions. Coverage varies by insurance provider and specific plan. Over-the-counter L-Carnitine supplements are typically not covered by conventional health insurance. Some Health Savings Accounts (HSAs) or Flexible Spending Accounts (FSAs) may cover L-Carnitine supplements with a physician’s recommendation, though policies vary.

Pure L-Carnitine powder typically has a shelf life of 2-3 years when stored properly. L-Carnitine in capsule or tablet form generally has a shelf life of 2-3 years, depending on the formulation and presence of other ingredients. Liquid L-Carnitine formulations typically have a shorter shelf life of 1-2 years, and may require refrigeration after opening.

Store in a cool, dry place away from direct sunlight, Optimal temperature range: 15-25°C (59-77°F), Keep container tightly closed to protect from moisture, Refrigeration is not necessary for powder, tablet, or capsule forms but may extend shelf life, Liquid formulations may require refrigeration after opening, Avoid exposure to heat sources or temperature fluctuations

Exposure to high humidity (can cause clumping and degradation of powder forms), Prolonged exposure to high temperatures (>30°C/86°F), Direct sunlight or UV radiation, Oxidation (particularly in liquid formulations), Microbial contamination if exposed to moisture, Extreme pH conditions (highly acidic or alkaline environments)

L-Carnitine is generally stable in aqueous solution at neutral pH for short periods (1-2 weeks) when refrigerated. Stability decreases in acidic or alkaline conditions. For maximum stability in solution, a pH range of 6.5-7.5 is optimal. Solutions should be stored in the refrigerator (2-8°C) in a tightly sealed, opaque container.

Acetyl-L-Carnitine is less stable in solution than free L-Carnitine and should be used within 1 week of preparation. Adding preservatives such as sodium benzoate (0.1-0.2%) can extend the shelf life of liquid formulations. Antioxidants such as vitamin E or BHT may help prevent oxidative degradation in liquid formulations.

Natural Sources

Synthetic Production Methods

Quality Indicators

Sustainability Considerations

Unlike many other nutritional compounds, L-Carnitine does not have a significant history of traditional medicinal use as an isolated compound. However, foods rich in L-Carnitine, particularly red meat, have been valued in various cultures for their strength-giving and energizing properties. Traditional diets high in animal products naturally provided significant amounts of L-Carnitine, though it was not recognized as a specific beneficial compound until the 20th century.

L-Carnitine was first isolated from meat extracts in 1905 by Russian scientists Gulewitsch and Krimberg, and its chemical structure was established in 1927. However, its biological importance remained unclear until the 1950s and 1960s, when its role in fatty acid metabolism was discovered by Fritz and Bremer. In 1973, the first case of human carnitine deficiency was described, highlighting its essential role in human metabolism. The 1980s saw the beginning of L-Carnitine supplementation for various clinical conditions, particularly carnitine deficiency syndromes, liver disease, and cardiovascular disorders.

By the 1990s, research expanded to explore L-Carnitine’s potential benefits for exercise performance, weight management, and cognitive function.

Initially, L-Carnitine was primarily used in clinical settings to treat diagnosed carnitine deficiency, which can be either primary (genetic) or secondary (resulting from certain medications, medical conditions, or dietary factors). In the 1980s and 1990s, L-Carnitine supplementation expanded to include treatment for cardiovascular conditions, particularly angina, heart failure, and recovery from myocardial infarction. The late 1990s and early 2000s saw increased interest in L-Carnitine for sports performance, with athletes using it to enhance fat metabolism, improve endurance, and accelerate recovery. Acetyl-L-Carnitine emerged as a popular supplement for cognitive enhancement and neuroprotection, particularly for age-related cognitive decline and neurodegenerative conditions.

More recently, research has explored L-Carnitine’s potential benefits for metabolic health, including glucose metabolism, insulin sensitivity, and non-alcoholic fatty liver disease. Current applications span from clinical use in specific medical conditions to general wellness supplementation for energy production, exercise support, and healthy aging. The evolution of L-Carnitine usage reflects the growing understanding of its diverse roles in human physiology and potential therapeutic applications beyond its fundamental role in fatty acid metabolism.

Effects of L-Carnitine supplementation on cognitive function in patients with mild cognitive impairment (ClinicalTrials.gov Identifier: NCT04823143), L-Carnitine for the prevention of chemotherapy-induced peripheral neuropathy (ClinicalTrials.gov Identifier: NCT03040375), L-Carnitine supplementation for fatigue in multiple sclerosis patients (ClinicalTrials.gov Identifier: NCT03266497)