Arginine is an amino acid that the body uses to produce nitric oxide. Decreased arginine bioavailability (for which global arginine bioavailability ratio (GABR) is a key biomarker), may result in impaired nitric oxide production. This may in turn increase oxidative stress and inflammation of the central nervous system (CNS), which is thought to be involved in MDD, explained the research team led by the University of Eastern Finland, Kuopio.
The scientists found that baseline levels of both serum arginine and GABR were lower in MDD patients than in non-depressed controls.
This relationship remained valid after adjusting for confounding variables including smoking, physical exercise, gender and age. The association was seen both in patients taking anti-depressants and those not on medication.
Contrary to the researchers’ hypothesis, at follow-up, individuals who had achieved remission had only marginally higher levels of arginine bioavailability than those who remained depressed.
"Arginine bioavailability was slightly higher in people who had recovered from depression than in people who remained depressed. However, a more extensive set of data and a longer follow-up period are necessary for estimating arginine's role in depression recovery," commented PhD student Toni Ali-Sisto, the lead author of the study.
The study, published in the Journal of Affective Disorders, included 99 adults diagnosed with MDD and 253 non-depressed controls. Scientists measured blood concentrations at baseline of three amino acids (arginine, citrulline and ornithine), and from which they calculated GABR.
The researchers also analysed symmetric and asymmetric dimethylarginine concentrations. Both are known to inhibit nitric oxide synthase, an enzyme which catalyses the production of nitric oxide from arginine.
The levels of the various amino acids were compared between depressed patients and the non-depressed controls. Participants were followed-up after eight months. The scientists again measured amino acid levels to identify any differences in concentrations between those with continuing depression, compared with those in remission.
Causal mechanism undetermined
"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," said Ali-Sisto.
"Although our study shows that people with depression have reduced arginine bioavailability, this doesn't mean that taking an arginine supplement would protect against depression. That's an area for further research," he added.
Source: Journal of Affective Disorders
Volume 229, Pages 145–151. DOI: 10.1016/j.jad.2017.12.030
“Global arginine bioavailability ratio is decreased in patients with major depressive disorder”
Authors: Toni Ali-Sisto et al