Combination of L-lysine and L-arginine reduces stress and lowers cortisol levels

Supplementation with 2.34 g L-lysine and the same amount of L-arginine daily reduces psychological stress and lowers cortisol amounts in men’s bodies. Researchers at the Japanese Ajinomoto amino acid manufacturers announced this in Biomedical Research.

Miro Smriga, the first author in the article that was published in Biomedical Research in 2008, has studied the effect of the lysine-arginine combination on anxiety and stress for years. He’s observed the effect in mice [Nutr Neurosci. 2003 Apr;6(2):125-8.] subjected to a stressful situation in a laboratory, in pigs being transported [Nutr Neurosci. 2003 Oct;6(5):283-9.] and in humans with a stress-sensitive personality [Nutr Neurosci. 2005 Jun;8(3):155-60.].

At least part of the explanation for the stress-reducing effect of the lysine-arginine combination is probably that lysine interacts with the receptor for GABA. [Neurochem Res. 1995 Aug;20(8):931-7.] Sleeping pills and alcohol also work via the same receptor.

In the study that was published in Biomedical Research, the researchers gave a group of about one hundred healthy test subjects 2.34 g L-lysine and 2.34 g L-arginine daily for seven days. The subjects took the amino acids twice a day, at breakfast and the evening meal.

After the supplementation period the researchers got their subjects to complete a questionnaire, the State-Trait Anxiety Inventory. Psychologists use this to measure how sensitive you are to stress in daily life. The figure below shows that this sensitivity decreased in the subjects that had taken the lysine-arginine combination.



Cortisol is the main hormone associated with stress. The researchers measured the cortisol concentration in the subjects’ saliva and saw that this did not decrease significantly in the women that had taken lysine and arginine supplements. In the men however this did happen, as the figure above shows.

The amino acids reduced the men’s cortisol concentrations by 18 percent. The researchers took their measurements between 9 and 10 in the morning.

The Japanese also studied the effect of a stressful event – in this case exposure to noise – on the subjects. They noticed that lysine/arginine supplementation had no effect on the cortisol concentration in the women, but that in the men this speeded up the return of cortisol concentrations to normal levels.

Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans.

Smriga M1, Ando T, Akutsu M, Furukawa Y, Miwa K, Morinaga Y.


Dietary supplementation with an essential amino acid L-lysine has been shown to reduce chronic anxiety in humans with low dietary intake of L-lysine. A combination of L-lysine and L-arginine has been documented to normalize hormonal stress responses in humans with high trait anxiety. The present study was carried out in one hundred eight healthy Japanese adults. The aim of study was to find out whether a week-long oral treatment with L-lysine (2.64 g per day) and L-arginine (2.64 g per day) reduces trait and stress-induced state anxiety and basal levels of stress hormones. We confirmed that, without regard to gender, the amino acid treatment significantly reduced both trait anxiety and state anxiety induced by cognitive stress battery. In addition, we found that the treatment with L-lysine and L-arginine decreased the basal levels of salivary cortisol and chromogranin-A (a salivary marker of the sympatho-adrenal system) in male subjects. These results of this double-blind, placebo controlled and randomized study confirm the previous findings in humans and animals and point to a combination of L-lysine and L-arginine as a potentially useful dietary intervention in otherwise healthy humans with high subjective levels of mental stress and anxiety.

PMID: 17510493 [PubMed – indexed for MEDLINE]