Arginine and Depression


A new study has linked major depressive disorder (MDD) to low bioavailability of arginine, an amino acid which the body converts to nitric oxide to control vascular dilation. 

What is arginine?

Arginine is an amino acid necessary for protein synthesis and the production of nitric oxide. It is mostly found naturally in meat, poultry and dairy products. Nitric oxide is used in vascular regulation (dilation/relaxation of veins and arteries). Whilst low levels of arginine is associated with cardiovascular disease and is generally used for cardiovascular diseases such as coronary artery disease, angina or hypertension etc, arginine is also required for immune defence mediation and the support of the nervous system.

Arginine and Depression

A new study has found that arginine levels are low in those suffering with major depressive disorder (MDD). With lowered arginine bioavailability, nitric oxide production is impaired resulting in lack of circulation and risk of oxidative stress overload in the central nervous system is increased. The study took 99 people with diagnosed MDD and 253 non-depressed control patients. Amino acids such as arginine, orinthine and citruline were tested from fasting blood glucose samples and those with MDD were found to have reduced arginine bioavailability. There is no definitive cause found however, as to suggest why this is. Interestingly though, levels or arginine were slightly higher in those recovered from MDD than those still suffering.

Researchers over the years have tried to determine the cause of psychological disorders such as bipolar and depression, linking them to the L-arginine-nitric oxide pathway.

Arginine is converted to nitric oxide by nitric oxide synthase and up-regulates vasodilation (the blood vessels widening), thus improving blood flow. As we age, nitric oxide declines making it harder for oxygenated blood to reach vital organs and tissues.


As a speculation, lack of oxygenated blood and circulation of nutrients needed to combat depression in brain could be a contributing factor to depression and therefore exhibit a link between arginine and MDD.

Human growth hormone is increased by the presence of arginine. Insufficient HGH from the pituitary can lead to decreased energy and low mood. It governs other hormones in the body as well as metabolism. A sign of low HGH is depression, and there has been a fair amount of research to suggest that HGH can help those suffering with mood disorders such as this.

Arginine is needed to expel ammonia and reduce it’s toxic load in the liver. If the liver is congested, it can expedite toxins throughout the body, including the brain and nervous system and cause chemical imbalances and mood disorders.


Whilst we can make connections to the nitric oxide cycle, the author of this recent study has stipulated that ‘…we don’t know yet what exactly causes reduced arginine bioavailability in people with depression’. The author goes on to say that although those with MDD are found to have low arginine, there is no evidence yet to suggest supplementation is going to protect against depression. Testing to see if arginine will support MDD patients should be an area for further research.

Whilst we are constantly discovering more about the human body and science every day we are yet to determine a great deal yet. We do however know, that the vitamin B family, as well as vitamin C and magnesium are all recognised to contribute to normal psychological function and help energy levels, stress and inflammation leading to many diseases.

If you feel you may have a symptoms of depression, always seek medical advice before supplementing.

Ali-Sisto T, Tolmunen T, Viinamäki H, et al. Global arginine bioavailability ratio is decreased in patients with major depressive disorder. Journal of Affective Disorders, 2018; 229: 145 DOI: 10.1016/j.jad.2017.12.030
Wu G, Meininger CJ. Arginine nutrition and cardiovascular function. J Nutr 2000;130:2626-9.
Parker JO, Parker JD, Caldwell RW, et al. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. J Am Coll Cardiol 2002;39:1199-203.
Yanik, M., Vural, H., Tutkun, H. et al. European Archives of Psychiatry and Clinical Neurosciences (2004) European Archives of Psychiatry and Clinical Neuroscience. 254: 43.
Mahajan T, Crown A, Checkley S, et al. Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life. Eur J Endocrinol. 2004 Sep;151(3):325-32.

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