L-carnitine

L-carnitine is a nutrient belonging to the non-essential amino acid class.

L-carnitine is also known as Acetyl-L-carnitine, ALC, ALCAR, Bicarnesine, Carnitor, L-carnitine, LC, Levocarnitine, Propionyl-L-carnitine and Vitamin BT.

L-carnitine is necessary for producing energy in the mitochondria of every cell and is involved in many metabolic processes.

A deficiency of L-carnitine causes harmful fatty acid and acyl-CoA accumulation, interfering with energy synthesis. A few of the symptoms are fatigue, myasthenia, and hypoglycemia. Carnitine's function in the metabolism of fatty acids may lead to increased triglycerides.

L-carnitine is most abundant in the diet. The body may absorb L-carnitine far more readily through meals than supplements. Ice cream, cheese, avocado, tempeh, whole milk, red meat, chicken breasts, and codfish are the best food sources of L-carnitine.

The small intestine absorbs levocarnitine, which is then transported throughout tissues like the heart and muscles. It facilitates mitochondrial fatty acid degradation. It is excreted through the urine and is affected by dietary factors, physical conditions, and medicine.

The common side effects of L-carnitine include GI disturbances, hypoglycemia and allergic reactions.

L-carnitine is available in tablets, capsules, oral and injectable solutions.

Biochemical action of L-carnitine

L-carnitine belonging to the supplement class acts in several physiological processes. It works via fatty acid transport and oxidation pathway.

Levocarnitine plays an essential role in the metabolic structure of the body. Its primary responsibility is to make it easier for fatty acids to pass cell membranes, which is a necessary step in energy production. L-carnitine directs long-chain fatty acids into the beta-oxidation pathway within mitochondria, producing essential ATP energy. This energy is required for muscular contractions and different metabolic processes. L-carnitine has significant benefits for the heart and skeletal muscles, both of which depend on fatty acids for energy. Additionally, this substance helps maintain healthy levels of acyl-CoA, a coenzyme essential for adequate energy generation and control of fatty acid metabolism.

Cellular energy production: The transport of fat across muscle cell membranes is facilitated by Carnitine, which is essential for energy production. The skeletal muscle and heart both depend on it for proper operation. Exercise does not appear to enhance fat metabolism or exercise performance significantly, nor does l-carnitine supplementation.

Improved blood sugar control: L-carnitine supplementation enhances tissue insulin sensitivity and peripheral glucose utilisation while decreasing insulin secretion.

Cellular function and integrity: The effects of Carnitine include preserving membrane components, maintaining a healthy CoA-sulfate hydrate/acetyl-CoA ratio, and decreasing lactate production.

Antioxidant: Carnitine acts as an antioxidant in the cell membrane, preventing protein oxidation and pyruvate and lactate oxidative damage.

Bioavailability: 10-20%

Distribution half-life: 0.585 hr

Half-life elimination: 17.4 hr

Peak plasma time: (PO) 3.3 hr

Peak plasma concentration: (PO) 80 umol/L

Total Body Clearance: 4 L/hr

L-carnitine can be used as a supplement when the amount of L-carnitine taken from the diet is insufficient.

Taking L-carnitine supplements orally may effectively treat L-carnitine deficiency caused by specific genetic diseases or other disorders.

L-carnitine supplements help in fat metabolism and support weight loss efforts.

When used as a supplement, L-carnitine may help enhance insulin sensitivity and glucose utilization in individuals with diabetes.

L-carnitine supplements may support brain health and cognitive function.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

L-carnitine can be used as a supplement when the amount of L-carnitine taken from the diet is insufficient.

Taking L-carnitine supplements orally may effectively treat L-carnitine deficiency caused by specific genetic diseases or other disorders.

L-carnitine supplements help in fat metabolism and support weight loss efforts.

When used as a supplement, L-carnitine may help enhance insulin sensitivity and glucose utilization in individuals with diabetes.

L-carnitine supplements may support brain health and cognitive function.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

L-carnitine can help to support as a supplement for the following health benefits:

• Treatment of deficiency: Traditional methods for treating or preventing deficiency include l-carnitine supplementation. It is suggested in inherited metabolic disorders or hemodialyses. Within 10 days, plasma carnitine levels have been normalised using l-carnitine 50–200 mg/kg/day.
• Alzheimer's disease and dementia: Carnitine supplementation studies in dementia patients with Alzheimer's disease or other types of dementia have yielded conflicting findings. Carnitine may benefit those who have mild dementia or Alzheimer's disease, according to a few studies. Other studies have only found transient benefits or no impact at all. For an understanding of how carnitine supplements affect dementia and Alzheimer's disease, additional research is required.
• Heart disease and peripheral artery disease: There are conflicting results from studies on carnitine supplementation for heart disease. Some studies indicate possible advantages, such as lowering the risk of angina and arrhythmia, but not heart failure or an attack. On the other hand, continued usage may increase the risk of heart disease. There is conflicting evidence about how Carnitine affects leg discomfort brought on by peripheral vascular disease. More additional research is needed.
• Insulin resistance and diabetes: Insulin's ability to regulate blood sugar is impaired by insulin resistance. Supplemental Carnitine may improve insulin action, resulting in lower A1C and blood glucose levels and a decreased risk of developing diabetes. Carnitine may lower cholesterol but not triglycerides in diabetics, according to limited research. To prove carnitine function in reducing the risk of insulin resistance and diabetes, a further comprehensive study is required.
• Infertility: Despite showing potential in improving male sperm health for infertility, carnitine supplements do not increase couples chances of becoming pregnant. Higher ovulation and conception rates are shown with Carnitine combined with infertility medicine usage, according to studies on female infertility caused by PCOS. Ovulation, pregnancy, and menstrual irregularity increased, but the risk of miscarriage remained unaltered. Carnitine effect on pregnancy rates and infertility due to PCOS has to be studied further.
• Osteoarthritis: Research on carnitine supplementation for osteoarthritis has shown conflicting findings. According to small research, Carnitine helped middle-aged women with osteoarthritis feel less discomfort in their knees. Carnitine did not reduce pain, stiffness, or ease of movement in another small research on obese people with knee arthritis. To determine if carnitine supplements reduce osteoarthritis symptoms, more significant research in more varied populations is required.
• Athletic performance: Muscles contain the majority of the Carnitine in your body. Researchers are looking into whether carnitine supplements improve muscular efficiency and athletic performance. There are contradictory results: while some small studies demonstrate ease in endurance tests, others only have a tiny influence. In vegetarians, Carnitine enhanced muscle storage, but in trained athletes, it varied. Understanding Carnitine's effects on athletic performance requires further research.
• Weight loss: Researchers investigated the possibility of weight loss by researching the function of Carnitine in converting food into energy. Studies on people with type 2 diabetes produced contradictory findings. Another study reported people using orlistat with Carnitine decreased 4 pounds more yearly, despite a 6-month trial demonstrating no benefit on weight reduction. While some research suggests, Carnitine may have a slight weight reduction advantage, more significant problems are required for a more comprehensive analysis.

L-carnitine supplementation may be administered orally and parenterally.

• Orally: L-carnitine supplements are available as tablets and capsules that can be taken orally. It is best taken with a meal or food.

Consume oral solution slowly combined with liquids if desired, and distribute dosages evenly throughout the day (every 3 to 4 hours), ideally before or after meals (may lessen GI distress).

• Parenterally: Administer IV bolus slowly over at least 2-3 min.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 250mg, 330mg, 500 mg
• Capsule: 250mg, 500 mg
• Oral solution: 1g/10mL
• Injectable solution: 200mg/mL

Dosage Adjustment for Adult Patients

Carnitine Deficiency

Tablet: 990 mg oral every 8 to 12hr, up to 3 g/day

Oral solution: 1000 mg/day orally initially divided

50 mg/kg IV bolus, followed by 50 mg/kg over the next 24 hr (divided every 3 to 6hr)

Valproic Acid Overdose (Orphan)

For the treatment or prevention of secondary carnitine deficiency in valproic acid toxicity

100 mg/kg intravenously but not to exceed 6 g/dose once

May give an additional dose of 15 mg/kg IV every 4hr infused over 30 min

Recommendations vary; some sources advocate limiting the total dose to 3 g/day.

L-carnitine is available in tablets, capsules, oral and injectable solutions.

L-carnitine should be used as a supplement that helps in several physiological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Limit foods and drinks with high L-carnitine content, like energy drinks, saturated fat, and sodium.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

The RDA of L-carnitine is not established.

Upper Tolerable Intake (UTL):

L-carnitine has no upper therapeutic limit (UTL), as it is widely regarded as safe, and there is little proof of adverse effects from food consumption or supplementation.

L-carnitine supplementation may be contraindicated in the following conditions:

• Hypersensitivity; sensitive to L-carnitine.
• Chronic liver disease — may impair metabolism or increase biosynthesis of l-carnitine
• Epilepsy or seizures
• Underactive thyroid (hypothyroidism)
• Dialysis
• Kidney disease.

Breastfeeding is generally considered to be safe for use.

Pregnancy is generally considered to be safe for use.

Limit the consumption of foods and beverages higher in added sugars, saturated fat, and energy drinks, as these substances could hinder L-carnitine absorption.

The adverse reactions related to L-carnitine can be categorized as-

• Common: GI disturbances like stomach upset, nausea, or diarrhoea, especially with high doses.
• Less Common: Muscle weakness, increased appetite, rashes or skin irritation.
• Rare: Allergic reactions, hypoglycemia, seizures or convulsions.

The clinically relevant drug interactions of L-carnitine are briefly summarized here:

• Warfarin (Coumadin): Warfarin is used to prevent blood clots. Warfarin's effects and the likelihood of bleeding and bruising might be exacerbated by l-carnitine- dosage adjustment may be required.
• Anticonvulsants (including valproate, phenobarbitone, phenytoin, and carbamazepine): The toxicity of valproate and the signs and symptoms of fatigue are known to be worsened or caused by l-carnitine deficiency, respectively. No adverse effects were reported in a study using l-carnitine to treat acute valproate poisoning. Long-term treatment might require increased carnitine intake—a potentially beneficial interaction managed by a medical professional.
• Pivalate-conjugated antibiotics: Antibiotics that are pivalate-conjugated and used to treat urinary tract infections, including pivampicillin, interact with Carnitine. Depletion of Carnitine may result from using these antibiotics on a long-term basis. There haven't been any reported cases of sickness caused by a carnitine shortage in this population, despite the possibility that tissue carnitine levels in those who take these antibiotics may get low enough to restrict fatty acid oxidation.
• Adriamycin (doxorubicin): Increased carnitine intake may be required with long-term therapy — potentially beneficial interaction, only under professional supervision.
• Carboplatin: The suppression of carnitine reabsorption in the kidney after carboplatin treatment appears to cause significant urine losses of l-carnitine and acetyl-L-Carnitine.
• Cisplatin: L-carnitine 4 g/day for 7 days was found to reduce tiredness after receiving cisplatin in studies; this positive interaction is feasible under qualified supervision.
• HIV drugs (zidovudine): L-carnitine supplementation may help reduce muscle damage caused by depletion, according to in vitro studies. Patients with HIV on antiretroviral treatment may see an increase in CD4 cells, a decrease in apoptosis, and a better quality of life. Professional monitoring is necessary for the potential advantages of Carnitine, especially with prolonged usage.
• HMG CoA-reductase inhibitors (statins): Human studies have shown that simvastatin medication combined with l-carnitine (2 g/day) reduces lipoprotein-a serum levels in people with type 2 diabetes mellitus. Positive interaction potential.

The common side of L-carnitine includes the following:

• Nausea
• Diarrhoea
• Headaches
• Abdominal pain.
• Vomiting
• Heartburn
• Nausea
• Abdominal cramps
• Muscle weakness
• Foul body odour: A fishy odour due to carnitine breakdown.
• Seizures
• Rashes or skin irritation.
• Increased appetite.
• Muscle weakness.

L-carnitine should be prudent in the following group of special populations.

• Pregnancy:

There is no sufficient scientific evidence traceable regarding the use and safety of L-carnitine for use in special populations.

• Paediatrics:

Foods often include the amino acid L-carnitine. It may be safe when given orally to children as medicine for up to 12 weeks.

Dosage Adjustment for Paediatric Patients

Carnitine Deficiency

50 mg/kg/day orally divided every 8 to 12hr initially

May increase to 100 mg/kg/day orally divided every 8 to 12hr but not to exceed 3 g/day

IV: 50 mg/kg IV bolus which may repeat 50 mg/kg IV daily if indicated but not to exceed 300 mg/kg

End-Stage Renal Disease

Indicated for ESRD in patients on hemodialysis

Initial dose: 10 to 20 mg/kg intravenously bolus infused over 2 to 3 minutes; administer into venous return line after a dialysis session

Adjust doses by predialysis levocarnitine concentrations

Downward dose titration may begin within 3 to 4 weeks after initiating.

Valproic Acid Overdose (Orphan)

For the treatment or prevention of secondary carnitine deficiency in valproic acid toxicity

Overdose or hyperammonemia: 150 to 500 mg/kg/day IV but not to exceed 3 g/day or until clinical improvement observed

100 mg/kg/day PO; not to exceed 2 g/day in divided doses.

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of L-carnitine for use in special populations.

• Lactating mothers:

There is no sufficient scientific evidence traceable regarding the use and safety of L-carnitine for use in special populations

Dosage Adjustment in Kidney Impairment

End-Stage Renal Disease

Indicated for ESRD in patients on hemodialysis

Initial dose: 10-20 mg/kg IV bolus infused over 2-3 minutes; administer into venous return line after dialysis session

Adjust doses by predialysis levocarnitine concentrations

Downward dose titration may begin within 3-4 weeks after initiating

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of L-carnitine. Overconsumption of L-carnitine may lead to health concerns such as gastrointestinal distress, hypoglycaemia and allergic reactions.

There is no specific antidote or treatment for excessive intake of supplemental Carnitine. L-carnitine supplements should be terminated immediately when an overdose is suspected or experience any unusual symptoms after L-carnitine supplement use or dietary intake. Induce vomit, gastric lavage, or activated charcoal may also be used if ingestion is recent but only under the supervision of a medical professional. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Biochemistry profile of L-carnitine

A hydrophilic quaternary amine, Carnitine (-hydroxy-trimethylammonium butyrate), plays a vital role in energy metabolism. Carnitine may be produced by the human body from lysine and methionine. The chief function of carnitine is to transport long-chain fatty acids to the mitochondria for oxidation afterwards. As a scavenger, carnitine also binds acyl residues from the intermediate metabolism of amino acids and aids in their removal. Because it facilitates the movement of long-chain fatty acids through the innermost membrane of the mitochondria, carnitine is essential for the oxidation of these acids. It promotes enhanced CoA availability through the intramitochondrial reaction of acetyl-CoA with Carnitine. This mechanism appears highly significant when pathogenic short-chain fatty acids accumulate inside the mitochondrial matrix.

This process is crucial for maintaining enough levels of free coenzyme A inside the mitochondrion to enable energy metabolism and removing too many short- and medium-chain fatty acids from the mitochondrion, which might be harmful.

Kinetic profile:

• Absorption: The small intestine is where levocarnitine is absorbed. Active transport systems are used to transport it into cells.
• Distribution: Levocarnitine is found in several bodily tissues, including the heart and muscles. Also, the liver and kidneys contain it.
• Metabolism: Levocarnitine is essential in transporting fatty acids into the mitochondria, where they are converted to trimethylamine-N-oxide and gamma-butyrobetaine for energy production. It contributes to the fatty acids' breakdown by participating in beta-oxidation.
• Elimination: Levocarnitine is mostly eliminated in urine through the kidneys. Sweating and other body fluids can contribute to the elimination of some levocarnitine.

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2. https://ods.od.nih.gov/factsheets/carnitine -consumer/
3. https://ods.od.nih.gov/factsheets/Carnitine-HealthProfessional/#h8
4. https://www.drugs.com/npp/l-carnitine.html