Creatine’s Unexpected Link to Depression
Physionic
May 25, 2026
Episode description
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0:00 - Introduction
0:46 - Dude, where’s my Creatine?
3:20 - 7 Studies Disagree
6:46 - Something critical is missing here…
Creatine Dosing for the Brain: https://www.youtube.com/watch?v=nEjWqUTwMQA&t=2s
References*
*Full Funding/Conflicts are provided in the free article (found in email list and Physionic Community Article Library)
[Study 760] Lu CL, Ren J, Lei Y, et al. Cell Metab. 2026;38:1-17. doi:10.1016/j.cmet.2026.03.002
[Study 761] Eckert I, Lima J, Dariva AA. Br J Nutr. 2025;134(11):947-959. doi:10.1017/S0007114525105588
[Study 762] Sherpa NN, De Giorgi R, Ostinelli EG, Choudhury A, Dolma T, Dorjee S. Eur Neuropsychopharmacol. 2025;90:28-35. doi:10.1016/j.euroneuro.2024.10.004
[Study 763] Brooks SJ, Candow DG, Roe AJ, et al. J Int Soc Sports Nutr. 2023;20(1):2193556. doi:10.1080/15502783.2023.2193556
[Study 764] Butchart S, Candow DG, Forbes SC, et al. Int J Exerc Sci. 2022;15(2):1117-1132.
[Study 765] Toniolo RA, Silva M, Fernandes FBF, Amaral JAMS, Dias RDS, Lafer B. J Neural Transm (Vienna). 2018;125(2):247-257. doi:10.1007/s00702-017-1817-5
[Study 766] Kondo DG, Forrest LN, Shi X, et al. Amino Acids. 2016;48(8):1941-1954. doi:10.1007/s00726-016-2194-3
[Study 767] Writing Group for the NINDS Exploratory Trials in Parkinson Disease Investigators, Kieburtz K, Tilley BC, et al. JAMA. 2015;313(6):584-593. doi:10.1001/jama.2015.120
[Study 768] Alves CR, Merege Filho CA, Benatti FB, et al. PLoS One. 2013;8(10):e76301. doi:10.1371/journal.pone.0076301
[Study 769] Nemets B, Levine J. Int Clin Psychopharmacol. 2013;28(3):127-133. doi:10.1097/YIC.0b013e32835ff20f
[Study 770] Lyoo IK, Yoon S, Kim TS, et al. Am J Psychiatry. 2012;169(9):937-945. doi:10.1176/appi.ajp.2012.12010009
[Study 771] Roitman S, Green T, Osher Y, Karni N, Levine J. Bipolar Disord. 2007;9(7):754-758. doi:10.1111/j.1399-5618.2007.00532.x
[Study 772] Kondo DG, Sung YH, Hellem TL, et al. J Affect Disord. 2011;135(1-3):354-361. doi:10.1016/j.jad.2011.07.010
[Study 773] Hellem TL, Sung YH, Shi XF, et al. J Dual Diagn. 2015;11(3-4):189-202. doi:10.1080/15504263.2015.1100471
[Study 774] Kious BM, Sabic H, Sung YH, Kondo DG, Renshaw P. J Clin Psychopharmacol. 2017;37(5):578-583. doi:10.1097/JCP.0000000000000754
[Study 775] Yoon S, Kim JE, Hwang J, et al. Biol Psychiatry. 2016;80(6):439-447. doi:10.1016/j.biopsych.2015.11.027
[Study 776] Toniolo RA, Fernandes FBF, Silva M, Dias RDS, Lafer B. J Affect Disord. 2017;224:69-75. doi:10.1016/j.jad.2016.11.029
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Mindsip insights from this episode:
Utilize creatine supplementation for clinically diagnosed depression
A review of 17 studies suggests creatine supplementation is effective for depression only in people with a clinical diagnosis, not in other populations like those with Parkinson's.
Consider higher creatine doses to boost brain levels
There is an argument for using higher doses of creatine, closer to 20 grams, to more effectively raise brain creatine levels based on some studies.
Combine creatine and gut bacteria to enhance depression treatment
A small clinical trial showed that combining creatine with a specific gut bacterium resulted in a sizable improvement in depression scores.
Investigate gut microbiome's impact on blood creatine levels
Transplanting the gut microbiome from depressed patients into mice causes a reduction in the mice's blood creatine concentrations.
Address gut bacteria to enhance creatine absorption
Differences in specific gut bacteria in depressed individuals are implicated in reduced creatine absorption at the intestinal level, leading to less creatine reaching the brain.
Investigate creatine levels in individuals with major depression
People with major depression have been found to have reduced creatine in their blood and cerebrospinal fluid, but increased levels in their feces.
Combine creatine with medication to reduce depression severity
Creatine appears to reduce depression severity only when used in combination with depression medication, not as a standalone treatment.
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