Carnitine

Carnitine (also known as L-carnitine, or as the acylated form Acetyl-L-Carnitine) is a naturally occurring amino acid nutrient in the body that is important for turning fat into energy. It is a derivative of the amino acid, lysine. Its function in fatty acid metabolism is to transport long-chain acyl groups from fatty acids into the mitochondrial matrix so that they can be broken down through β-oxidation to acetyl CoA to generate energy in the citric acid cycle. Carnitine plays an especially important role in heart, brain, and muscle function, as these energy-intensive organs rely on energy from fatty acids.

In human disease
Low serum carnitine is found in systemic primary carnitine deficiency, a genetic disease, and causes chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. Secondary primary carnitine deficiency can develop secondary to other genetic mitochondrial disorders, in chronic kidney failure, and as a side effect of some medications.

ME/CFS
Chronic fatigue syndrome (CFS) patients have been found to have statistically significantly lower serum total carnitine, free carnitine, and acylcarnitine levels. These serum levels were also found to correlate with clinical symptoms, where higher serum carnitine levels correlated with better functional capacity. Serum carnitine levels appeared to return to normal during remission. As carnitine is needed by the mitochondria, these findings may imply mitochondrial dysfunction.

In a study in 1997, both L-carnitine and Amantadine were tested on 30 CFS patients. Amantadine was not well tolerated, but the L-carnitine was found to be very safe and to improve the clinical status of CFS patients. Sarah Myhill checks acetyl-L-carnitine levels as part of her Mitochondrial Function tests.

In a study of the levels of serum acylcarnitine in Japanese patients with various kinds of diseases, a significant decrease was only found in patients with CFS and chronic hepatitis type C, indicating that this might be a characteristic abnormality in only certain types of diseases.

A study of 25 patients and 25 controls in 2000 could not reproduce the finding of CFS patients having lower carnitine levels than control subjects. The authors concluded that "the present study demonstrates that serum carnitine deficiency does not contribute to or cause the symptoms in many CFS patients". While this conclusion refers to 'many' patients, the small study size may temper this conclusion.

In 2004 acetyl-L-carnitine, propionyl-L-carnitine, and their combination were compared in 3 groups of 30 CFS patients during 24 weeks. Acetyl-L-carnitine significantly improved mental fatigue and propionyl-L-carnitine improved general fatigue.

In 2011 another study on 44 CFS patients and 49 healthy controls found that patients with chronic fatigue syndrome exhibited significantly altered concentrations of acylcarnitines. Significant correlations between acylcarnitine concentrations and clinical symptomatology were also demonstrated. The authors proposed that this disturbance in carnitine homeostasis could possibly be a result of the accumulation of omega 6 fatty acids previously observed in this patient population. They hypothesized that the administration of omega 3 fatty acids, in combination with carnitine, would increase CPT-1 activity and improve chronic fatigue syndrome symptoms.

Testing
Serum carnitine can be tested via the following blood tests: total carnitine, free carnitine, and carnitine esters.

Treatments
The standard treatment of low serum carnitine is Levocarnitine, a prescription form of carnitine. Acetyl-L-carnitine is popular supplement.

Studies

 * 1994, "Acylcarnitine deficiency in chronic fatigue syndrome" (Abstract)
 * 1995, "Abnormalities of carnitine metabolism in chronic fatigue syndrome" (Abstract)
 * 1995, "Serum levels of carnitine in chronic fatigue syndrome: clinical correlates" (Full text)
 * 1997, "Amantadine and L-Carnitine: Treatment of Chronic Fatigue Syndrome" (Full text)
 * 1998, "Low levels of serum acylcarnitine in chronic fatigue syndrome and chronic hepatitis type C, but not seen in other diseases" (Abstract)
 * 2000, "Normal carnitine levels in patients with chronic fatigue syndrome" (Abstract)
 * 2004, "Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome" (Full text)
 * 2011, "Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome. Potential involvement of altered carnitine palmitoyltransferase-I activity" (Abstract)
 * 2018, "Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics" (Full text)
 * 2019, "Carnitine conjugation profiling in a selected cohort of patients with chronic fatigue syndrome" (Full text)