What conditions is Levocarnitine (L-carnitine) used to treat?

Levocarnitine Clinical Indications

Levocarnitine is FDA-approved for treating primary systemic carnitine deficiency and secondary carnitine deficiencies resulting from inborn errors of metabolism, with additional evidence-based uses in hemodialysis patients and specific high-risk clinical scenarios. 1

FDA-Approved Indications

Primary Systemic Carnitine Deficiency

• Levocarnitine is definitively indicated for primary carnitine deficiency, a genetic disorder of the cellular carnitine-transporter system that typically manifests by age 5 years. 1, 2
• Clinical presentation includes:
  • Recurrent Reye-like encephalopathy 1
  • Hypoketotic hypoglycemia 1, 2
  • Cardiomyopathy 1, 2
  • Skeletal muscle weakness 1, 2
  • Hypotonia and failure to thrive 1
• Diagnosis requires documented low serum, red cell, and/or tissue carnitine levels with exclusion of primary defects in fatty acid or organic acid oxidation. 1

Secondary Carnitine Deficiency

• Levocarnitine is FDA-approved for acute and chronic treatment of secondary carnitine deficiency from inborn errors of metabolism. 1
• This includes organic acidurias where carnitine supplementation improves hypotonia, muscle weakness, motor skills, and wasting. 3, 4

Evidence-Based Clinical Uses

Hemodialysis Patients

• The 2022 ESPEN guidelines recommend systematic supplementation of 0.5-1 g/day for patients on prolonged hemodialysis to prevent deficiency. 2, 5
• L-carnitine supplementation in hemodialysis patients significantly reduces inflammatory markers (CRP) compared to controls, particularly with treatment duration exceeding 12 weeks. 2
• The 2000 K/DOQI guidelines note insufficient evidence for routine use but support consideration in selected dialysis patients with: 2
  • Erythropoietin-resistant anemia (most promising indication) 2, 6
  • Intradialytic hypotension and cramps 2
  • Post-dialytic malaise or asthenia 2, 6
  • General weakness or fatigue 2, 6
  • Decreased exercise capacity 2, 6

Important caveat: These symptoms must have failed standard therapies before considering L-carnitine. 2

Prolonged Parenteral Nutrition

• Patients on prolonged PN should receive systematic supplementation of 0.5-1 g/day to prevent carnitine deficiency. 2, 5
• Consider deficiency when unexplained loss of lean body mass occurs with concomitant hypertriglyceridemia and hyperlactatemia. 2, 5

Continuous Renal Replacement Therapy

• Systematic supplementation of 0.5-1 g/day should be considered in patients on prolonged CRRT. 2, 5

Clinical Scenarios Requiring Evaluation

When to Suspect Deficiency

The 2022 ESPEN guidelines recommend carnitine evaluation in critically ill patients with: 2

• Unexpected loss of lean body mass 2, 5
• Hypertriglyceridemia with hyperlactatemia 2, 5
• Prolonged parenteral nutrition 2, 5
• Prolonged continuous renal replacement therapy 2, 5

Diagnostic Workup

When deficiency is suspected, obtain simultaneously: 2, 5

• Total and free carnitine levels (acyl-to-free ratio >0.4 indicates deficiency; normal ≤0.25) 2
• Blood triglycerides 2
• Liver function tests (AST, ALT) 2
• Glucose, lactate, ammonium 2
• Urine ketones 2

Dosing Algorithm

Nutritional Supplementation (Prevention)

• 0.5-1 g/day for at-risk patients (prolonged PN, hemodialysis, CRRT) 2, 5, 6

Treatment of Confirmed Deficiency

• 2-5 mg/kg/day until normalization of carnitine levels and acyl/carnitine ratio 5

Pharmacologic Doses

• 50-100 mg/kg/day (approximately 3 g/day in adults) for medication toxicity or elimination of toxic compounds 2, 5

Conditions with Emerging Evidence

Cardiovascular Applications

• Small RCTs show L-carnitine (1 g) attenuates inflammation in coronary artery disease patients. 2
• Evidence suggests potential benefit in cardiomyopathy with reduced ejection fraction, though more trials are needed. 2, 6

Perioperative Use

• In gastric or colorectal cancer surgery, L-carnitine supplementation significantly decreased CRP between postoperative days 3-7 compared to placebo (P=0.011). 2

Other Proposed Uses

• Hyperlipidemia (particularly hypertriglyceridemia): mixed evidence, not routinely recommended 2, 6, 4
• Valproic acid-induced toxicity prevention 3, 4
• Anthracycline-induced toxicity prevention 3

Critical note: These applications require more robust evidence before routine clinical adoption. 3, 7

Safety Considerations

Common Side Effects (at ~3 g/day doses)

• Nausea, vomiting, abdominal cramps, diarrhea 2, 5
• "Fishy" body odor 2, 5, 6

Rare but Serious Side Effects

• Muscle weakness in uremic patients 2, 5, 6
• Seizures in patients with pre-existing seizure disorders 2, 5, 6

Metabolic Effects

• Acute high-dose infusion (100 mg over 4 hours) may increase protein oxidation and reduce fat oxidation. 2

Clinical Pitfalls to Avoid

• Do not use L-carnitine routinely in all dialysis patients—reserve for those with specific symptoms unresponsive to standard therapy. 2, 6
• Always exclude other causes of anemia (iron, B12, folate deficiency, chronic infection, inflammation) before attributing symptoms to carnitine deficiency. 6
• Biologic effects of low carnitine may not be clinically significant until levels reach <10-20% of normal, so mild reductions may not warrant treatment. 2
• Carnitine deficiency does not cause inflammation—rather, carnitine acts as an anti-inflammatory agent. 2