Depression Linked to Reduced Arginine Levels

Arginine is an amino acid which the body uses to produce, for example nitric oxide. Nitric oxide, in turn, is a nervous system and immune defense mediator, and it also plays a role in vascular regulation.

The global arginine bioavailability ratio (GABR) is an indicator of the body's arginine levels, and the ratio has previously been used to measure the body's capacity to produce nitric oxide. Reduced arginine bioavailability is also known to be an independent risk factor of cardiovascular diseases.


Scientists at the University of Eastern Finland (Kuopio, Finland) and their colleagues enrolled 99 adults with diagnosed major depressive disorder (MDD) and 253 non-depressed controls. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine.

The concentrations of the three amino acids were analyzed from their fasting glucose samples, and this data was used to calculate their GABRs. Symmetric and asymmetric dimethylarginine concentrations were measured, as they both play a role in the production of nitric oxide. The findings were then compared between the depressed and the non-depressed controls. The study also analyzed whether these concentrations changed in people with depression during a follow-up of eight months, and whether remission of depression had an effect on the concentrations.

The scientists found lower arginine levels (OR 0.98, 95% CI 0.97–0.99) and lower GABR (OR 0.13, 95% CI 0.03–0.50) were associated with the MDD versus the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups.

Toni Ali-Sisto, MD, the lead author of the study, said, “It is possible that depression-induced inflammatory responses lead to reduced arginine levels. This may result in insufficient production of nitric oxide for the needs of the nervous system and circulation. However, we don't know yet what exactly causes reduced arginine bioavailability in people with depression.” The study was published in the March 2018 issue of the Journal of Affective Disorders.

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University of Eastern Finland