Abstract
Purpose
Accumulation of ammonia causes central and peripheral fatigue. This study aimed to investigate the synergistic effect of tea catechins and low-dose ornithine in activating the urea cycle to reduce blood ammonia levels during exercise.
Methods
We used hepatocyte-like cells derived from human-induced pluripotent stem (iPS) cells to assess the effect of tea catechins combined with ornithine on urea cycle activity. The urea production and expression of key genes involved in the metabolism of urea were investigated. We then examined the synergistic improvement in ammonia metabolism by tea catechins in combination with ornithine in a human pilot study.
Results
Tea catechins combined with ornithine increased urea cycle activity in hepatocyte-like cells derived from human iPS cells. Intake of 538.6 mg of tea catechins with 1592 mg of ornithine for 2 consecutive days during exercise loading suppressed the exercise-induced increase in the blood ammonia concentration as well as stabilized blood glucose levels.
Conclusion
Controlling the levels of ammonia, a toxic waste produced in the body, is important in a variety of situations, including exercise. The present study suggests that a heterogeneous combination of polyphenols and amino acids efficiently suppresses elevated ammonia during exercise in humans by a mechanism that includes urea cycle activation.
Trial registration
This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (No. UMIN000035484, dated January 8, 2019).
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Availability of data and materials
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ARG:
-
Arginase
- ASL:
-
Argininosuccinate lyase
- ASS:
-
Argininosuccinate synthase
- AUC:
-
Area under the curve (total)
- BMI:
-
Body mass index
- cDNA:
-
Copy deoxyribonucleic acid
- CPS:
-
Carbamoyl-phosphate synthase
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- GOT:
-
Glutamic-oxaloacetic transaminase
- HRmax:
-
Maximum heart rate
- iPS:
-
Induced pluripotent stem cell
- mRNA:
-
Messenger ribonucleic acid
- OTC:
-
Ornithine carbamoyltransferase
- PCR:
-
Polymerase chain reaction
- qRT-PCR:
-
Quantitative real-time polymerase chain reaction
- RNA:
-
Ribonucleic acid
- SD:
-
Standard deviation
- SE:
-
Standard error
- TCA:
-
Tricarboxylic acid
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Acknowledgements
The authors thank Shu Chen and Mizuki Tsunakawa for their valuable discussions on this study and their technical assistance with the experiments. They also thank Masanobu Hibi and Koichi Misawa for proofreading this manuscript.
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This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.
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TH designed the study, conducted the experiments, and wrote the draft of the manuscript with support from YM and NO. TH and YM contributed to the analysis and interpretation of data with support from NO. KK designed and manufactured the test beverage and supported the design of the human study. TH revised the manuscript with support from YM. All the authors read and approved the final version of the manuscript.
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TH, KK, YM, and NO are employees of Kao Corporation, a chemical, cosmetic, and food company headquartered in Tokyo, Japan. Kao Corporation had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Ethics approval
The experimental protocol was approved by the Human Research Ethics Committee, Kao Corporation (Approval No. T153–180720, dated October 15, 2018).
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Written informed consent was obtained from all participants prior to enrollment in accordance with the Declaration of Helsinki.
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Communicated by Michalis G Nikolaidis.
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Hasumura, T., Kinoshita, K., Minegishi, Y. et al. Combination of tea catechins and ornithine effectively activates the urea cycle: an in vitro and human pilot study. Eur J Appl Physiol 124, 827–836 (2024). https://doi.org/10.1007/s00421-023-05310-4
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DOI: https://doi.org/10.1007/s00421-023-05310-4