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Lack of acetyl-L-carnitine linked to treatment-resistant depression

A deficiency of acetyl-L-carnitine could result in resistance to certain antidepressants, new research has found.

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Researchers at Stanford University, in collaboration with Rockefeller University, have found that low blood levels of the substance acetyl-L-carnitine may be linked to severe depression, or major depressive disorder.

The study, which analyzed collective data from rodents, is the first known indication acetyl-L-carnitine might also treat symptoms in humans. Additionally, it gives researchers insight into the potential creation of new antidepressants, with a faster onset of action.

Natalie Rasgon, a professor of psychiatry at Stanford and an author of the study, called the findings “an exciting addition to our understanding of the mechanisms of depressive illness.”

In previous studies by Rockefeller University, Dr. Nasca concluded that a deficiency of acetyl-L-carnitine was associated with depressive-type behavior in rodents, with their behavior restoring to normal within two to four weeks following oral or intravenous administration of the substance.

Researchers believe acetyl-L-carnitine may also play a crucial role in the brain, affecting regions like the hippocampus and frontal cortex, based on the findings from rodents.

New research on humans

In the new study, researchers examined patients diagnosed with depression, aged 20 to 70, both men and women, admitted for treatment. Blood samples and medical histories were taken from the participants. They were also given a detailed questionnaire to fill out.

When accessed clinically, researchers noted that 28 of the participants suffered from moderate depression, while 43 had severe depression.

Upon analysis, researchers compared the blood samples of patients with a sample of 45 demographically-matched healthy participants. They found those who were depressed exhibited lower blood levels of acetyl-L-carnitine, demonstrated in both genders.

Furthermore, the findings also showed that the lowest blood levels of the substance triggered the most severe symptoms. These participants exhibited resistance to treatments and onset of their mood disorder began earlier in life. Lower levels were also correlated with a history of abuse, poverty, and exposure to violence.

More clinical tests needed

Although the findings shine a spotlight on the possibility of more efficient treatment in patients resistant to pharmacological intervention, researchers caution about the use of acetyl-L-carnitine for alleviating depression in humans.

“We have many previous examples of how nutritional supplements widely available over the counter and unregulated by the Food and Drug Administration – for example, omega-3 fatty acids or various herbal substances – are touted as panaceas for you-name-it, and then don’t pan out,” researchers say.

Researchers still need more answers as to the mechanism of action, including dose, frequency, and duration, before the substance can be considered therapeutic for depressive symptoms.

“We’ve identified an important new biomarker of major depressive disorder. We didn’t test whether supplementing with that substance could actually improve patients’ symptoms. What’s the appropriate dose, frequency, duration? We need to answer many questions before proceeding with recommendations, yet. This is the first step toward developing that knowledge, which will require large-scale, carefully controlled clinical trials.”

The findings were published in the Proceedings of the National Academy of Sciences and funded by the Hope for Depression Research Foundation, the Pritzker Neuropsychiatric Disorders Research Consortium, and the Robertson Foundation.

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