Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation
Open accessAbstract
Aim: We investigated the uptake and pharmacokinetics of l -ergothioneine (ET), a dietary thione with free radical scavenging and cytoprotective capabilities, after oral administration to humans, and its effect on biomarkers of oxidative damage and inflammation. Results: After oral administration, ET is avidly absorbed and retained by the body with significant elevations in plasma and whole blood concentrations, and relatively low urinary excretion (<4% of administered ET). ET levels in whole blood were highly correlated to levels of hercynine and S-methyl-ergothioneine, suggesting that they may be metabolites. After ET administration, some decreasing trends were seen in biomarkers of oxidative damage and inflammation, including allantoin (urate oxidation), 8-hydroxy-2′-deoxyguanosine (DNA damage), 8-iso-PGF2α (lipid peroxidation), protein carbonylation, and C-reactive protein. However, most of the changes were non-significant. Innovation: This is the first study investigating the administration of pure ET to healthy human volunteers and monitoring its uptake and pharmacokinetics. This compound is rapidly gaining attention due to its unique properties, and this study lays the foundation for future human studies. Conclusion: The uptake and retention of ET by the body suggests an important physiological function. The decreasing trend of oxidative damage biomarkers is consistent with animal studies suggesting that ET may function as a major antioxidant but perhaps only under conditions of oxidative stress. Antioxid. Redox Signal. 26, 193–206.
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A number of high-dose studies indicate ERG is safe for mammalian consumption at levels far in excess of those likely in foodstuffs, and it has been declared safe by EFSA.
“Notwithstanding the highly variable intake between individuals(358), however, a number of high-dose studies have indicated that ERG is safe for mammalian consumption at levels far in excess of those likely to be encountered in foodstuffs(125,131,359,360), and it has been declared safe by relevant committees such as those of the European Food Standards Agency(361,362).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [360]
ERG is metabolised and excreted only slowly.
“ERG is metabolised and excreted only slowly(360,371,401,402).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [360]
In human volunteers given 5-25 mg daily doses of ERG for 7 d, urinary excretion was <4%, and main metabolites were hercynine and lesser amounts of S-methyl-ERG, correlated with ERG level and dose.
“In a recent and detailed study, Cheah et al. (360) administered 5–25 mg daily doses of ERG to human volunteers for 7 d. There was little urinary excretion (<4 %), and the main metabolites were hercynine, plus lesser amounts of S-methyl-ERG, whose concentrations were well correlated with the level of ERG and the dose of ERG given.”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [360]
Studies of the effects of ERG have in general been rather descriptive in nature and at the level of processes rather than mechanisms.
“studies of the effects of ERG have in general(449) been rather descriptive in nature. Many have been at the level of processes rather than mechanisms”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [360]
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Cites
Jacob, C. (2006) · Natural Product Reports · doi:10.1039/b609523m · Cited by 373 · see citing works
The antioxidant action of ergothioneine
Akanmu, D., Cecchini, R., Aruoma, O. I., & Halliwell, B. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90158-f · Cited by 251 · see citing works
Self-citationGene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1
Kato, Y., Kubo, Y., Iwata, D., Kato, S., Sudo, T., Sugiura, T., Kagaya, T., Wakayama, T., Hirayama, A., Sugimoto, M., et al. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0076-z · Cited by 206 · see citing works
Ergothioneine protects against neuronal injury induced by β-amyloid in mice
Yang, N.-C., Lin, H.-C., Wu, J.-H., Ou, H.-C., Chai, Y.-C., Tseng, C.-Y., Liao, J.-W., & Song, T.-Y. (2012) · Food and Chemical Toxicology · doi:10.1016/j.fct.2012.08.021 · Cited by 123 · see citing works
Zhu, B.-Z., Mao, L., Fan, R.-M., Zhu, J.-G., Zhang, Y.-N., Wang, J., Kalyanaraman, B., & Frei, B. (2011) · Chemical Research in Toxicology · doi:10.1021/tx100214t · Cited by 122 · see citing works
COLOGNATO, R., LAURENZA, I., FONTANA, I., COPPEDE, F., SICILIANO, G., COECKE, S., ARUOMA, O., BENZI, L., & MIGLIORE, L. (2006) · Clinical Nutrition · doi:10.1016/j.clnu.2005.10.005 · Cited by 81 · see citing works
Cheah, I. K., Ong, R. L. S., Gruber, J., Yew, T. S. K., Ng, L. F., Chen, C. B., & Halliwell, B. (2013) · Free Radical Research · doi:10.3109/10715762.2013.848354 · Cited by 44 · see citing works
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Butterfield, D. A., & Halliwell, B. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0132-6 · Cited by 1,954 · see citing works
Self-citationThe biology of ergothioneine, an antioxidant nutraceutical
Borodina, I., Kenny, L. C., McCarthy, C. M., Paramasivan, K., Pretorius, E., Roberts, T. J., van der Hoek, S. A., & Kell, D. B. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422419000301 · Cited by 296 · see citing works
Feng, L., Cheah, I. K.-M., Ng, M. M.-X., Li, J., Chan, S. M., Lim, S. L., Mahendran, R., Kua, E.-H., & Halliwell, B. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-180959 · Cited by 112 · see citing works
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Servillo, L., D'Onofrio, N., & Balestrieri, M. L. (2017) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000464 · Cited by 81 · see citing works
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Self-citationEFSA Panel on Dietetic Products, N. A. A. (., Turck, D., Bresson, J., Burlingame, B., Dean, T., Fairweather‐Tait, S., Heinonen, M., Hirsch‐Ernst, K. I., Mangelsdorf, I., McArdle, H. J., et al. (2016) · EFSA Journal · doi:10.2903/j.efsa.2016.4629 · Cited by 39 · see citing works
Specificity of the ergothioneine transporter natively expressed in HeLa cells
Tucker, R. A. J., Cheah, I. K., & Halliwell, B. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.122 · Cited by 38 · see citing works
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- Authors
- Cheah, I. K., Tang, R. M. Y., Yew, T. S. Z., Lim, K. H. C., & Halliwell, B.
- Affiliations
- National University of Singapore (SG)
- National University Cancer Institute, Singapore (SG)
- Corresponding author
- Halliwell, Barry
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2017-02
- Volume
- 26
- Issue
- 5
- Pages
- 193-206
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W2487967273
- Cited by
- 196
- References
- 7
- Citations by year
- 2026: 34 · 2025: 31 · 2024: 22 · 2023: 17 · 2022: 25 · 2021: 20 · 2020: 20 · 2019: 11 · 2018: 10 · 2017: 4 · 2016: 2
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Antioxidants and Redox Signaling (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- National Medical Research Council (NMRC/1264/2010/082/12, NMRC/1264/2010)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- L-ergothioneine, pharmacokinetics, oral administration, oxidative damage biomarkers, inflammatory markers, DNA damage, lipid peroxidation, protein carbonylation, C-reactive protein, antioxidants, free radical scavenging, urinary excretion
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Allantoin, Antioxidants, Betaine, C-Reactive Protein, Deoxyguanosine, Ergothioneine, Histidine, Humans, Inflammation, Biomarkers, Drug Monitoring, Oxidative Stress, Healthy Volunteers
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