Can Ringer’s Lactate be a Mood Stabilizer?
Main Article Content
Abstract
The exploration of the lactate shuttle has led to the understanding that lactate is a metabolic fuel, including in the central nervous system. In addition to being an intercellular messenger, it also plays a role in gene expression. Bipolar disorder, specifically, exhibits features of a biphasic energy dysregulation. Cognitive impairment is observed even during remission periods. Mitochondrial dysfunction is a current and important area of research in the etiology of this neuroprogressive disorder. In our studies, we demonstrated a band-specific metabolic/oxidative coupling between electrophysiological brain dynamics, quantified by Entropy Doubling and Ruzsa Distance derived from EEG data and serum lactate levels in patients diagnosed with bipolar disorder. We suggest that band-specific metabolic coupling is different between patients with mania predominant polarity and those with depression predominant polarity. This article asks whether Ringer's lactate may be a mood stabilizer.
Keywords:
Bipolar disorder, mitochondrial dysfunction, EEG, band specific metabolic/oxidative coupling, lactat, mood stabilizer
Article Details
How to Cite
KESEBIR, Sermin.
Can Ringer’s Lactate be a Mood Stabilizer?.
Medical Research Archives, [S.l.], v. 13, n. 11, nov. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7061>. Date accessed: 06 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i11.7061.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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19. Hagihara H, Shoji H, Hattori S, Sala G, Takamiya Y, Tanaka M, et al. Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment. Elife, (2024) 26;12:RP89376.
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21. Swartz CM, Breen KJ. Multiple muscle enzyme release with psychiatric illness. J Nerv Ment Dis, (1990) 178(12):755-9.
22. S Kesebir, RM Demirer. Serum lactate and LDH are related with Teta and Gama activities in Bipolar Disorder: A Band-Specific Metabolic Coupling. Frontiers in Psychiatry (2025) 16, 1695916, 2025
23. Hu Y, Boillat Y. Real-time lactate imaging of the brain during functional activation. J Neurosci, (2022) 42(10), 2012–2024.
24. Butler JL, Hay YA, Paulsen O. Comparison of three gamma oscillations in the mouse entorhinal-hippocampal system. The European Journal of Neuroscience, (2018) 48(8), 2795–2806.
25. Melloni L, Molina C, Pena M., Torres D., Singer W, Rodriguez E. Synchronization of neural activity across cortical areas correlates with conscious perception. The Journal of Neuroscience, (2007) 27(11), 2858–2865.
26. Martina M, Schultz JH, Ehmke H, Monyer H, Jonas P. Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus. The Journal of Neuroscience, (1998) 18(20), 8111–8125.
27. Kann O, Papageorgiou IE, Draguhn A. Highly energized inhibitory interneurons are a central element for information processing in cortical networks. Journal of Cerebral Blood Flow and Metabolism, (2014) 34(8), 1270–1282.
28. Gluckman PD. Metabolic acidosis and EEG slowing: linking lactate to cortical dysfunction. Neurology, (2024) 102(5), 455–463.
29. Dworak M. Sleep and brain lactate: EEG power predicts the rate of decline of lactate concentration during NREMS. Sleep, (2010) 33(7), 909–917.
30. Kesebir S, Demirer RM. Mitochondrial Dysfunction on EEG: HighBeta specific Metabolic/Oxidative Coupling in Mania-predominant Polarity. In Review.
31. Kann O. Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations. J Neurochem, (2024) 168(5):608-631.
32. Galow LV, Schneider J, Lewen A, Ta TT, Papageorgiou IE, Kann O. Energy substrates that fuel fast neuronal network oscillations. Frontiers in Neuroscience, (2014) 8, 398.
33. Kesebir S. Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res. 2018 Jun;10(6):453-460.
2. Brooks GA. "Lactate: Glycolytic End Product and Oxidative Substrate During Sustained Exercise in Mammals — The "Lactate Shuttle". Circulation, Respiration, and Metabolism. Proceedings in Life Sciences. Berlin, Heidelberg: Springer Berlin Heidelberg. (1985) pp. 208–218.
3. Brooks GA. The science and translation of the lactate shuttle theory. Nutrition & Metabolism, (2023) 20, 22.
4. Gladden, LB. "Lactate metabolism: a new paradigm for the third millennium". The Journal of Physiology. (2004) 558 (Pt 1): 5–30.
5. Hollnagel JO, Cesetti T, Schneider J, Vazetdinova, A, Valiullina-Rakhmatullina F, Lewen A, Rozov A, Kann O. Lactate attenuates synaptic transmission and affects brain rhythms featuring high energy expenditure. iScience, (2020) 23(7), 101316.
6. Hollnagel JO, Elzoheiry S, Gorgas K, Kins S, Beretta CA, Kirsch J, Kuhse J, Kann O, Kiss, E. Early alterations in hippocampal perisomatic GABAergic synapses and network oscillations in a mouse model of Alzheimer's disease amyloidosis. PLoS ONE. (2019) 14(1), e0209228.
7. Hollnagel JO, Maslarova A, Haq RU, Heinemann U. GABAB receptor dependent modulation of sharp wave-ripple Complexes in the rat hippocampus in vitro. Neuroscience Letters, (2014) 574, 15–20.
8. Kesebir S, Demirer RM, Tarhan N. CFC delta-beta is related with mixed features and response to treatment in bipolar II depression. [Heliyon 5 (6) (June 2019) e01898] Heliyon (2019) 6;5(9): e02286.
9. Kesebir S, Yosmaoglu A, Tarhan N. A dimensional approach to affective disorder: The relations between Scl-90 subdimensions and QEEG parameters. Front Psychiatry. (2022) 15;13:651008.
10. Demirer RM, Kesebir S. The entropy of chaotic transitions of EEG phase growth in bipolar disorder with lithium carbonate. Sci Rep. (2021) 4;11(1):11888.
11. Kaymak Koca E, Durmaz O, Füsun Domaç S, Kesebir S. Neuropsychological and Neurophysiological Assessment in Different Phases of Bipolar Disorder. Psychiatry Clin Psychopharmacol. (2022) 1;32(1):9-16.
12. S Kesebir, RM Demirer. Reclassification of Mood Disorders with Comorbid Medical Diseases based on Sinai-Ruelle-Bowen/SRB Entropy Measures. Medical Research Archives (2023) 11 (12).
13. Kesebir S. Projection of Bipolarity to Mitochondria: GABA Shunt is relatedwith Self pathology and Medical Comorbidity in Bipolar Disorder. Med Res Arch. (2024), 12(6).
14. Kesebir S. Electrophysiology of Self and Mood Disorder as an Energy Shift: Mitochondrial Dysfunction and Medical Comorbidity beyond the Metabolic Syndrome. Med Res Arch. (2025) 13(7).
15. Kuang H, Duong A, Jeong H, Zachos K, Andreazza AC. Lactate in bipolar disorder: A systematic review and meta-analysis. Psychiatry Clin Neurosci, (2018) 72(8):546-555.
16. Guo Q, Jia J, Sun XL, Yang H, Ren Y. Comparing the metabolic pathways of different clinical phases of bipolar disorder through metabolomics studies. Front Psychiatry, (2024) 8; 14:1319870.
17. Machado-Vieira R, Zanetti MV, Otaduy MC, De Sousa RT, Soeiro-de-Souza MG, Costa AC, Carvalho AF, Leite CC, Busatto GF, Zarate CA Jr, Gattaz WF. Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study. J Clin Psychopharmacol, (2017) 37(1):40-45.
18. Jeong H, Dimick MK, Sultan A, Duong A, Park SS, El Soufi El Sabbagh D, Goldstein BI, Andreazza AC. Peripheral biomarkers of mitochondrial dysfunction in adolescents with bipolar disorder. J Psychiatr Res, (2020) 123:187-193.
19. Hagihara H, Shoji H, Hattori S, Sala G, Takamiya Y, Tanaka M, et al. Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment. Elife, (2024) 26;12:RP89376.
20. Zachos KA, Choi J, Godin O, Chernega T, Kwak HA, Jung JH, et al. FondaMental Academic Centers of Expertise in Bipolar Disorders (FACE-BD) Collaborators. Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder. Psychiatry Res, (2024) 339:116063.
21. Swartz CM, Breen KJ. Multiple muscle enzyme release with psychiatric illness. J Nerv Ment Dis, (1990) 178(12):755-9.
22. S Kesebir, RM Demirer. Serum lactate and LDH are related with Teta and Gama activities in Bipolar Disorder: A Band-Specific Metabolic Coupling. Frontiers in Psychiatry (2025) 16, 1695916, 2025
23. Hu Y, Boillat Y. Real-time lactate imaging of the brain during functional activation. J Neurosci, (2022) 42(10), 2012–2024.
24. Butler JL, Hay YA, Paulsen O. Comparison of three gamma oscillations in the mouse entorhinal-hippocampal system. The European Journal of Neuroscience, (2018) 48(8), 2795–2806.
25. Melloni L, Molina C, Pena M., Torres D., Singer W, Rodriguez E. Synchronization of neural activity across cortical areas correlates with conscious perception. The Journal of Neuroscience, (2007) 27(11), 2858–2865.
26. Martina M, Schultz JH, Ehmke H, Monyer H, Jonas P. Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus. The Journal of Neuroscience, (1998) 18(20), 8111–8125.
27. Kann O, Papageorgiou IE, Draguhn A. Highly energized inhibitory interneurons are a central element for information processing in cortical networks. Journal of Cerebral Blood Flow and Metabolism, (2014) 34(8), 1270–1282.
28. Gluckman PD. Metabolic acidosis and EEG slowing: linking lactate to cortical dysfunction. Neurology, (2024) 102(5), 455–463.
29. Dworak M. Sleep and brain lactate: EEG power predicts the rate of decline of lactate concentration during NREMS. Sleep, (2010) 33(7), 909–917.
30. Kesebir S, Demirer RM. Mitochondrial Dysfunction on EEG: HighBeta specific Metabolic/Oxidative Coupling in Mania-predominant Polarity. In Review.
31. Kann O. Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations. J Neurochem, (2024) 168(5):608-631.
32. Galow LV, Schneider J, Lewen A, Ta TT, Papageorgiou IE, Kann O. Energy substrates that fuel fast neuronal network oscillations. Frontiers in Neuroscience, (2014) 8, 398.
33. Kesebir S. Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res. 2018 Jun;10(6):453-460.