When is carnitine supplementation recommended and what is the typical dose?

Carnitine Supplementation: Indications and Dosing

Carnitine supplementation is not routinely recommended except in specific deficiency states, with dosing typically ranging from 0.5-1 g/day for prevention and 2-5 mg/kg/day for proven deficiency, while pharmacologic doses of 50-100 mg/kg/day (approximately 3 g/day in adults) are reserved for specific clinical scenarios. 1

Indications for Carnitine Supplementation

Primary Indications (Proven Deficiency States)

• Primary carnitine deficiency (genetic disorder of carnitine transport) 2
• Secondary carnitine deficiencies:
  • Patients on prolonged parenteral nutrition (PN) 1
  • Patients on prolonged continuous renal replacement therapy 1
  • Hemodialysis patients with specific symptoms unresponsive to standard treatments 3
  • Patients with certain inborn errors of metabolism 4
  • Valproate-induced hepatotoxicity (IV administration) 5
  • Valproate overdose (IV administration) 5

Clinical Presentations Suggesting Deficiency

• Unexpected loss of lean body mass with hypertriglyceridemia and hyperlactatemia 1
• Symptoms in dialysis patients: fatigue, muscle cramps, exercise intolerance 3
• In children: hypoketotic hypoglycemia, hepatomegaly, elevated transaminases 2
• Cardiomyopathy, skeletal myopathy, elevated creatine kinase 2

Dosing Recommendations

Prevention in At-Risk Patients

• Systematic supplementation of 0.5-1 g/day for patients at risk 1

Treatment of Proven Deficiency

• 2-5 mg/kg/day until carnitine levels and acyl-to-free ratio normalize 1
• For dialysis patients: 1g before and after dialysis or up to 2g/day in divided doses 3

Pharmacologic Dosing (Special Situations)

• 50-100 mg/kg/day (adults often receive 3 g/day) for:
  • Antiretroviral drug toxicity 1
  • Removal of toxic compounds from the body 6
  • Inborn errors of metabolism 4

Monitoring and Assessment

Diagnostic Testing

• Simultaneous measurement of:
  • Total carnitine, free carnitine, carnitine esters and precursors 1
  • Calculation of acyl-to-free carnitine ratio (normal ≤0.25, deficiency >0.4) 1
  • Blood triglycerides, liver function tests, glucose, lactate, ammonium, urine ketones 1

Treatment Monitoring

• Regular plasma carnitine levels
• For dialysis patients: assess symptom improvement at 1,2, and 3 months 3
• Trial duration typically 3-4 months for dialysis patients 3
• Annual echocardiogram and electrocardiogram in primary deficiency 2

Side Effects and Precautions

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

• Nausea, vomiting, abdominal cramps, diarrhea
• "Fishy" body odor 1, 3

Rare Side Effects

• Muscle weakness in uremic patients
• Seizures in those with seizure disorders 1, 3

Drug Interactions

• L-carnitine and levothyroxine should be taken at different times of day 3
• Monitor thyroid function tests 6-8 weeks after starting carnitine in patients on levothyroxine 3

Clinical Pearls

• Carnitine is not considered an essential nutrient for most people 1
• Bioavailability of oral L-carnitine is low (5-18%) compared to dietary carnitine (up to 75%) 7
• Intravenous administration may be necessary in acute deficiency states 4
• The number of antiepileptic drugs used is a risk factor for carnitine deficiency 5
• Infants and young children (especially <2 years) on valproate should be considered for supplementation 5

Carnitine supplementation should be targeted to specific populations with proven deficiency or high risk, as there is insufficient evidence to support its routine use in enteral or parenteral nutrition for the general population 1.