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.

Studies in ME/CFS patients

Measured Carnitine Levels

Chronic fatigue syndrome (CFS) patients have been (inconsistently) 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In a 1994 study of the levels of serum acylcarnitine in Japanese patients (diagnosed with the outdated Holmes criteria). However, free L-carnitine was not significantly different between patients and controls. The study also identified a correlation between acylcarnitine levels and improvement in symptoms. A follow-up study by the same author in Swedish and Japanese patients with various ilnesses, a significant decrease of both acylcarnitine and free carnitine 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 1995 study of 35 patients found that total carnitine levels, free carnitine levels and acylcarnitine levels were statistically significantly lower on average for CFS patients than healthy persons. Caution is warranted for this study as it used the outdated Holmes criteria (which do not require patients to have post-exertional malaise), has a small sample size and did not have a proper control group. The authors did not measure carnitine levels in a control group - they relied on normative data from the Mayo Clinic and control data from a prior study that used a different methodology. Although the average carnitine levels were higher in the patient group, there was considerable overlap between carnitine levels in the healthy and patient groups. Most patients had carnitine levels within normal range. The authors identified a correlation between free carnitine levels and symptom severity as measured by the CFS Impairment Index and the Fatigue Severity Scale (p<0.05) and between total carnitine levels and the Fatigue Severity Scale (p<0.02). By implication, no significant correlation was identified between total carnitine levels and the CFS Impairment Index. No significant correlation was identified between acylcarnitine levels and symptom severity.

A separate 1995 study found serum levels of total, free and short chain carnitine did not significantly differ between patients and controls, however levels of all three in peripheral blood lymphocytes were significantly lower in CFS patients.

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 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.

Carnitine Supplementation

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.

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.

Testing

Serum carnitine can be tested via the following blood tests: total carnitine, free carnitine, and carnitine esters. Sarah Myhill checks acetyl-L-carnitine levels as part of her Mitochondrial Function tests.

Treatments

The standard treatment of low serum carnitine is Levocarnitine, a prescription form of carnitine. Carnitine can be supplemented in different forms, eg. l-carnitine, l-carnitine l-tartrate, L-carnitine Fumarate, etc. The different forms are believed to have slightly different areas of use.

It is advised to avoid D-carnitine and DL-carnitine. These forms of carnitine might block the effects of L-carnitine and cause symptoms that resemble L-carnitine deficiency.

Acetyl-L-carnitine (ALCAR) is popular supplement, but is considered to have a slightly different effect than other forms of l-carnitine, because of its ability to cross the blood-brain-barrier. ALCAR is sometimes called the "neurological l-carnitine".

There are some people who should be extra careful with carnitine-supplementation. These include patients with thyroid disease, patients taking medication for thyroid disease, patients on blood thinning medications and in those with a history of seizures.

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)

See also

• Omega 3 fatty acid
• Mitochondrion