Depression Linked to Low Levels of Naturally Occurring Substance in the Body

Depression could be influenced by a naturally occurring substance in the body called acetyl-L-carnitine, says study.

Highlights:

Depressed individuals have low levels of acetyl-L-carnitine (ALC) in their blood
ALC is a naturally-produced substance that is also available as a nutritional supplement
People with severe or treatment-resistant depression have low blood levels of the substance ALC

Depressed people have decreased blood levels of a substance called acetyl-L-carnitine that is naturally produced and involved in many important reactions in the body, according to a Stanford University School of Medicine scientist and her collaborators in a multicenter study.

Acetyl-L-carnitine (ALC) is also available as a nutritional supplement in pharmacies, supermarkets, and health food catalogs.

The findings were published online in the Proceedings of the National Academy of Sciences.

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‘Depression is now associated with low blood levels of a compound produced in the body called acetyl-L-carnitine; the lower the levels of acetyl-L-carnitine, the more severe the depression.’

Link between Depression and ALC: Previous Studies

An earlier review lists clinical studies that have been conducted with ALC in animal and cellular models and show that the effects of ALC on the neuroplasticity (brain plasticity - the ability of the brain to change throughout an individual's life) could be the basis of it being a potentially effective and tolerable next treatment option for patients with depression.

The review also says that this must be backed up with more data from advanced clinical trials to determine whether ALC could work alone or has to be given with another pill to be clinically beneficial for depression.

Although the current study has been done with animals, the authors mark that the link between acetyl-L-carnitine levels and depression may apply to people, too. They say this could lead the way to a new class of antidepressants devoid of side effects and faster-acting than current medications, and that may help patients for whom existing treatments do not work or have stopped working.

Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences at Stanford, described the findings as "an exciting addition to our understanding of the mechanisms of depressive illness. As a clinical psychiatrist, I have treated many people with this disorder in my practice. It's the No. 1 reason for absenteeism at work, and one of the leading causes of suicide," Rasgon said. "Worse, current pharmacological treatments are effective for only about 50 percent of the people for whom they're prescribed. And they have numerous side effects, often decreasing long term compliance."

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Acetyl-L-carnitine’s Connection with the Brain: Current Study

Dr. Carla Nasca PhD, a postdoctoral scholar, had earlier conducted experiments on rodents where he had shown that a deficiency of acetyl-L-carnitine was associated with depression-like behavior and when the animals were given acetyl-L-carnitine orally or as an injection the symptoms reversed and they restored their normal behavior.

The response time to acetyl-L-carnitine supplementation was within a few days. In contrast, current antidepressants typically take two to four weeks to start working in experiments with animals and among patients.

The animal studies indicated that ALC (much needed in fat metabolism and energy production throughout the body) might play a special role in the brain.

In the current study, Nasca recruited 20- to 70-year-old men and women with a diagnosis of depression and who had been admitted for treatment to either Weill Cornell Medicine or Mount Sinai School of Medicine (New York) during episodes of acute depression.

The scientists then screened the participants using a detailed questionnaire, assessed them clinically, and took their blood samples and medical histories. They diagnosed twenty-eight of them to have moderate depression, and 43 to have severe depression.

The research team compared the blood samples of the test participants with 45 demographically matched healthy people.

The results clearly indicated that acetyl-L-carnitine levels in the blood of the depressed patients were substantially lower compared to the control individuals. These findings were seen in both men and women, regardless of age.
The lowest levels of ALC were found in those whose symptoms were most severe (because they were resistant to previous treatments, or the disorder had set in much earlier early in life).
Patients reporting a childhood history of abuse, neglect, poverty or exposure to violence also had low ALC levels.

Rasgon performed the bulk of the advanced data analysis for the study and concluded that the patients in the study, who collectively accounted for 25-30 percent of all people with major depression disorder, are precisely the ones who need effective medications. However, she said it does not mean rushing to the store to pick up the next available bottle of acetyl-L-carnitine and self-medicating for depression.

"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," she said.

Rasgon has plans for future studies like would patients’ symptoms improve if the newly identified biomarker of the major depressive disorder is used as a supplement and if so, what would be its appropriate dose, frequency, and duration.

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Depression

Depression is also known as a major depressive disorder or clinical depression. It is the most prevalent mood disorder in the world, affecting 8-10 percent of the general population at any given time – the reason being it is a condition by itself and co-occurs with a number of other disorders.

Genetics, brain biology and chemistry, and stressful life events could cause depression. It is treated with counseling (cognitive behavioral therapy and interpersonal therapy) and medications. There are conflicting results for the effectiveness of antidepressants for acute, mild to moderate depression. The pills might work better in cases of severe depression.

References:

Sheng-Min Wang, Changsu Han, Soo-Jung Lee, Ashwin A. Patkar, Prakash S. Masand, and Chi-Un Pae. “A review of current evidence for acetyl-l-carnitine in the treatment of depression”. Journal of Psychiatric Research, June (2014), Volume 53, Pages 30–37
Depression: What You Need To Know - (https://www.nimh.nih.gov/health/publications/depression-what-you-need-to-know/index.shtml)

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