Is there controversy with treating Medium-Chain Acyl-CoA Dehydrogenase (MCAD) deficiency with L-carnitine?

From the Guidelines

There is controversy surrounding the use of carnitine for treating Medium-Chain Acyl-CoA Dehydrogenase (MCAD) deficiency, and its use should be individualized based on the patient's clinical presentation and laboratory values, with a recommended dose of 2-5 mg/kg/day in cases of proven deficiency, as suggested by the most recent guideline 1. The controversy stems from the fact that unlike other fatty acid oxidation disorders, MCAD deficiency typically doesn't cause significant carnitine depletion in most patients. Some key points to consider when deciding on carnitine supplementation for MCAD patients include:

• The patient's carnitine levels in blood tests or during metabolic crises
• The potential benefits of carnitine in removing toxic metabolites and supporting energy metabolism during times of stress
• The potential risks of excessive carnitine supplementation, including increased production of medium-chain acylcarnitines
• The individualized approach to treatment, taking into account the patient's specific clinical presentation and laboratory values According to the most recent guideline, carnitine supplementation is recommended in cases of proven deficiency, with a dose of 2-5 mg/kg/day 1. In other cases, such as antiretroviral drug toxicity, pharmacologic doses of 50-100 mg/kg/day may be administered 1. However, it's essential to note that the availability of suitable supplements may be limited, and the decision to use carnitine should be made in consultation with a metabolic specialist. Additionally, other studies suggest that intravenous L-carnitine may be used in specific situations, such as hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy, with a loading dose of 50 mg/kg and a daily dose of 100-300 mg/kg 1. But the most recent and highest quality study should be prioritized, which is the espen micronutrient guideline 1.

From the Research

Controversy with Treating MCAD with Carnitine

• The use of L-carnitine supplementation in the treatment of Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is controversial, as evidenced by studies such as 2 and 3.
• Some studies suggest that L-carnitine supplementation may promote clearance of accumulating acylcarnitines during moderate-intensity exercise, but no apparent beneficial effect on clinical and biochemical parameters was observed in MCAD patients 2.
• Other studies have found that L-carnitine treatment can improve exercise tolerance in MCAD-deficient patients, with significant improvements in peak oxygen uptake and other exercise-related parameters 4.
• However, a large retrospective observational study found no real-world evidence in favor of routine carnitine analysis and carnitine supplementation in the follow-up of persons with MCAD, with no difference in frequency and duration of acute unscheduled preventive hospital visits between persons with and without secondary carnitine deficiency 3.
• Additionally, a study found that patients with MCAD have impaired oxidation of fat during exercise, but L-carnitine supplementation had no effect on fuel utilization during exercise 5.
• The time course of serum free carnitine concentration during acute attacks of Reye-like illness in patients with MCAD deficiency may provide insight into carnitine depletion in MCAD deficiency, with low serum free carnitine concentrations continually decreasing for up to 8-13 days after an attack 6.