Effects of an amino acid mixture on exercise-induced cortisol levels

Relation

Tsuda Y, Murakami R, Yamaguchi M, Seki T. Acute supplementation with an amino acid mixture suppressed exercise-induced cortisol response in recreationally active healthy volunteers: a randomized, double-blind, placebo-controlled, crossover study.J Int Soc Sports Nutr. 2020;17(1):39.

Study objective

To determine the effects of an acute single dose of an amino acid mixture containing arginine, valine, and serine on male participants with a demonstrated high cortisol response to exercise

Draft

Randomized, double-blind, placebo-controlled crossover study

intervention

Capsules containing either 1.8 g arginine, 1.1 g valine, and 0.1 g serine or placebo (empty capsules) 30 minutes before participants performed an exercise test on a bicycle ergometer (Aerobike 75XLIII) at 50% VO₂max for 80 min with a 3 minute break in the middle. Researchers gave participants a cup containing the amino acid mixture or placebo and instructed them to swallow all the capsules without touching them to maintain placebo blindness.

To prevent dehydration, subjects drank equal amounts of water during a 3-minute break.

According to the study authors, indirect effects of the amino acids could explain the decrease in training-induced cortisol.

After a one-week washout period, participants returned to cross over to the other arm of the study.

The researchers collected blood samples from the brachial vein immediately before and after exercise.

Participant

Twenty “leisurely active” men aged 20 to 39 years (mean 32.3 ± 1.2 years), mean body mass index (BMI) 22.3 ± 0.4. After removal of 5 participants due to abnormal blood analysis or protocol deviations, 15 participants contributed to the final analysis.

Study parameters assessed

• Plasmakortisol (mcg/dl)
• Adrenocorticotropes Hormon (ACTH, pg/ml)
• Cortisol/ACTH-Verhältnis
• Blutzucker (mg/dl)
• Plasmalaktat (mg/dL)
• Plasma-Ammoniak (mcg/dL)
• Serum-Kreatin-Phosphokinase (CPK, U/L)
• Gesamtketonkörper im Serum (µmol/L)
• Freie Fettsäuren im Serum (mEq/L)

Primary outcome measures

Changes in plasma blood cortisol concentration within each group (intervention and placebo) and between groups

Key insights

Internal group results:

Cortisol: In the placebo group, post-exercise plasma cortisol was significantly higher than pre-exercise cortisol (9.51 ± 0.85 vs. 14.39 ± 2.15,P<0.05), while there was no significant difference in the treatment group (9.71 ± 0.93 vs. 9.99 ± 1.23,P=0.846).

ACTH: In the placebo group, plasma ACTH increased significantly after training (24.21 ± 2.91 vs. 53.17 ± 6.97,P< 0.01), while the change in the treatment group was not significant (27.33 ± 3.60 vs. 46.92 ± 10.41,P=0.057).

Cortisol/ACTH ratio: Participants in both the placebo and treatment groups showed a significant increase in the cortisol/ACTH ratio post-exercise compared to pre-exercise (P<0.01).

Intergroup results:

Cortisol: The increase in plasma cortisol before and after training was significantly lower in the treatment group compared to placebo (0.28 [−2.75, 3.31] vs 4.87 [0.89, 8.86],P<0.05).

ACTH: There was no significant difference between the 2 groups for changes in plasma ACTH during exercise (28.96 [13.5, 44.4] for the placebo group vs. 19.59 [−0.7, 39.8] for the treatment group,P=0.454).

Cortisol/ACTH ratio: The changes in the cortisol/ACTH ratio before and after training were not significantly different between the two groups.

Blood glucose, plasma lactate, plasma ammonia, serum CPK, serum total ketone bodies, and serum free fatty acids all changed significantly post-exercise compared to pre-exercise (P<0.01) within each group. All of these analytes increased significantly after exercise, except for blood glucose, which decreased significantly in both groups (P<0.01).

However, when comparing the amino acid intervention group with placebo, there were no significant differences between groups for any of the above analytes.

Practice implications

Cortisol is released during intense physical exercise in response to a drop in blood sugar. The physiological effect of cortisol is to maintain circulating glucose by increasing glycogen breakdown (glycogenolysis) in muscles and liver. This is generally due to increased secretion of ACTH from the pituitary gland, which stimulates the release of cortisol from the adrenal gland.

Interestingly, the post-exercise plasma cortisol increase was attenuated in the amino acid group compared to placebo, although there was no significant difference in ACTH between the two groups. Since ACTH was not significantly reduced by taking the amino acid mixture, the mechanism of action leading to the suppressed cortisol response is unclear.

According to the study authors, indirect effects of the amino acids could explain the decrease in training-induced cortisol. Arginine promotes fat metabolism,^1.2which can help maintain glycogen or glucose levels in the blood. Valine (and leucine, but not isoleucine) has been shown to reduce exercise-induced cortisol increases in rats.³And serine can increase the production of phosphatidylserine, which has been shown in a clinical study to reduce exercise-induced cortisol.⁴

While there was a statistically significant reduction in post-exercise cortisol in those who took the amino acid combination, the clinical relevance is unclear. The researchers did not test VO₂max, fatigue, perceived exertion or recovery time. This would have provided additional data to understand whether the biochemical changes were also reflected in performance changes.

A previous study conducted by the same researchers evaluated chronic intake (14 days) of the same combination of amino acids and found a benefit.⁵In this study, volunteers took double the dose - 3.6g arginine, 2.2g valine and 0.2g serine - for 14 days. They then exercised on the bike, and as in the current study, measurements were taken after exercise. Subjective ratings of fatigue based on visual analogue scale (VAS) and rating of perceived exertion (RPE) improved significantly compared to placebo. Furthermore, increases in serum total ketone bodies during exercise and plasma tryptophan/branched-chain amino acids (BCAA) were significantly lower in the amino acid group compared to placebo. This implies that long-term and acute dosing of amino acids are likely to have different effects.