The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Increase of total creatine in human brain after oral supplementation of creatine-monohydrate
Abstract
The effect of oral creatine supplementation on brain metabolite concentrations was investigated in gray matter, white matter, cerebellum, and thalamus of healthy young volunteers by means of quantitative localized proton magnetic resonance spectroscopy in vivo (2.0 T, stimulated echo acquisition mode sequence; repetition time = 6,000 ms, echo time = 20 ms, middle interval = 10 ms, automated spectral evaluation). Oral consumption of 4 × 5 g creatine-monohydrate/day for 4 wk yielded a statistically significant increase (8.7% corresponding to 0.6 mM, P < 0.001) of the mean concentration of total creatine (tCr) when averaged across brain regions and subjects ( n = 6). The data revealed considerable intersubject variability (3.5–13.3%), with the smallest increases observed for the two male volunteers with the largest body weights. A regional analysis resulted in significant increases of tCr in gray matter (4.7%), white matter (11.5%), and cerebellum (5.4%) and was most pronounced in thalamus (14.6% corresponding to 1.0 mM). Other findings were significant decreases of N-acetyl-containing compounds in cerebellum and thalamus as well as of choline-containing compounds in thalamus. All cerebral metabolic alterations caused by oral Cr were reversible, as evidenced by control measurements at least 3 mo after the diet. This work demonstrates that excess consumption of Cr yields regionally dependent increases of the tCr concentration in human brain over periods of several weeks.
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“Finally, a number of studies have shown that creatine supplementation can increase brain creatine content generally by 5 – 15% [218–220].”
From International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine (2017) · cites this paper as [218]
In the citing paper
“Creatine supplementation increases brain creatine content and the ratio of phosphocreatine to ATP.4,5”
From Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [4]
In the citing paper
“As such, higher doses of creatine supplementation may not be required to optimize brain creatine content4,5 and ATP (re)synthesis by mitochondrial creatine kinases.46”
From Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [4]
Citations
Cites
Estimation of metabolite concentrations from localized in vivo proton NMR spectra
Provencher, S. W. (1993) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910300604 · Cited by 3,659
Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation
Harris, R. C., Söderlund, K., & Hultman, E. (1992) · Clinical Science · doi:10.1042/cs0830367 · Cited by 1,168
Multinuclear NMR Studies on the Energy Metabolism of Glial and Neuronal Cells
Brand, A., Richter‐Landsberg, C., & Leibfritz, D. (1994) · Developmental Neuroscience · doi:10.1159/000111347 · Cited by 889
Birken, D. L., & Oldendorf, W. H. (1989) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(89)80048-x · Cited by 783
Creatine: Biosynthesis, Regulation, and Function
Walker, J. B. (1979) · Advances in enzymology and related areas of molecular biology/Advances in enzymology and related subjects · doi:10.1002/9780470122952.ch4 · Cited by 496
Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS
Pouwels, P. J. W., & Frahm, J. (1998) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910390110 · Cited by 470
Self-citationNeuroprotective Effects of Creatine and Cyclocreatine in Animal Models of Huntington’s Disease
Matthews, R. T., Yang, L., Jenkins, B. G., Ferrante, R. J., Rosen, B. R., Kaddurah-Daouk, R. F., & Beal, M. F. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00156.1998 · Cited by 431
Creatine deficiency in the brain: A new, treatable inborn error of metabolism
Stöckler, S., Holzbach, U., Hanefeld, F., Marquardt, I., Helms, G., Requart, M., Hänicke, W., & Frahm, J. (1994) · Pediatric Research · doi:10.1203/00006450-199409000-00023 · Cited by 417
Self-citationPouwels, P. J. W., Brockmann, K., Kruse, B., Wilken, B., Wick, M., Hanefeld, F. A., & Frahm, J. (1999) · Pediatric Research · doi:10.1203/00006450-199910000-00019 · Cited by 311
Self-citationCreatine supplementation and dynamic high-intensity intermittent exercise
Balsom, P. D., Ekblom, B., Söerlund, K., Sjödln, B., & Hultman, E. (1993) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/j.1600-0838.1993.tb00378.x · Cited by 282
Stöckler, S., Hanefeld, F., & Frahm, J. (1996) · The Lancet · doi:10.1016/s0140-6736(96)04116-5 · Cited by 240
Self-citationCreatine supplementation per se does not enhance endurance exercise performance
Balsom, P. D., Harridge, S. D. R., Söderlund, K., Sjödin, B., & Ekblom, B. T. (1993) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1993.tb09649.x · Cited by 183
Functional Aspects of Creatine Kinase in Brain
Hemmer, W., & Wallimann, T. (1994) · Developmental Neuroscience · doi:10.1159/000111342 · Cited by 166
Frahm, J., Michaelis, T., Merboldt, K. D., Bruhn, H., Gyngell, M. L., & Hänicke, W. (1990) · Journal of Magnetic Resonance (1969) · doi:10.1016/0022-2364(90)90051-a · Cited by 155
Self-citationCreatine Metabolism in Skeletal Muscle
Fitch, C. D., Shields, R. P., Payne, W. F., & Dacus, J. V. (1968) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)93544-1 · Cited by 134
‘Hot spots’ of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus
Kaldis, P., Hemmer, W., Zanolla, E., Holtzman, D., & Wallimann, T. (2009) · Developmental Neuroscience · doi:10.1159/000111452 · Cited by 99 · cited 1×
“In general, one might expect that cerebral Cr uptake is most pronounced in regions with high energy demands, such as cerebellum and thalamus, which have been shown to be rich in creatine kinase (11, 13) and the specific Cr transporter (9).”
BackgroundCarter, A. J., MULLER, R. E., Pschorn, U., & Stransky, W. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64062691.x · Cited by 83
Creatine Protects the Central Respiratory Network of Mammals under Anoxic Conditions
Wilken, B., Ramirez, J., Probst, I., Richter, D. W., & Hanefeld, F. A. (1998) · Pediatric Research · doi:10.1203/00006450-199801000-00002 · Cited by 67
Self-citationIn situ hybridization analysis of CHOT1, a creatine transporter, in the rat central nervous system
Happe, H. K., & Murrin, L. C. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903510109 · Cited by 48
Brain creatine phosphate and creatine kinase in mice fed an analogue of creatine
Holtzman, D. H., McFarland, E. W., Moerland, T. S., Koutcher, J. A., Kushmerick, M. J., & Neuringer, L. J. (1989) · Brain Research · doi:10.1016/0006-8993(89)90035-8 · Cited by 39
Hagenfeldt, L., von Döbeln, U., Solders, G., & Kaijser, L. (1994) · PubMed · Cited by 36
Research works printed but not linked: 3
- Frahm J., 1990, J. Magn. Reson., 90, 464
- Hagenfeldt L., 1994, Muscle Nerve, 17, 1236
- Walker J. B., 1979, Advances in Enzymology, 50, 177
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Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-017-0173-z · Cited by 1,057
Magnetic resonance imaging of glutamate
Cai, K., Haris, M., Singh, A. K., Kogan, F., Greenberg, J. H., Hariharan, H., Detre, J. A., & Reddy, R. D. (2012) · Nature Medicine · doi:10.1038/nm.2615 · Cited by 664
Rae, C. D. (2013) · Neurochemical Research · doi:10.1007/s11064-013-1199-5 · Cited by 524
Ohtsuki, S., & Terasaki, T. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9374-5 · Cited by 476
Clinical Pharmacology of the Dietary Supplement Creatine Monohydrate
Persky, A. M., & Brazeau, G. A. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01490-x · Cited by 333
Metadata
- Authors
- Dechent, P., Pouwels, P. J. W., Wilken, B., Hanefeld, F., & Frahm, J.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- University of Göttingen (DE)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1999-09-01
- Volume
- 277
- Issue
- 3
- Pages
- R698-R704
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2139463702
- Semantic Scholar
- 003706525d905e44e3829feebb7f2f8bf0f758c4
- Cited by
- 221
- References
- 21
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 5 · 2021: 10 · 2020: 4 · 2019: 10 · 2018: 10 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 6 · 2013: 8 · 2012: 13
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Physiology (medical) › Biochemical effects in animals
- Keywords
- creatine supplementation, creatine monohydrate, total creatine, brain metabolites, regional brain differences, gray matter, white matter, cerebellum, thalamus, choline-containing compounds, body weight
- MeSH terms
- Administration, Oral, Adult, Brain, Creatine, Diet, Female, Humans, Magnetic Resonance Imaging, Male
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