“In two tumor models of the mouse, inhibition of serotonin signaling consistently impaired tumor growth”[1]
“As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities”[2]
Recent development has postulated that omega 3 and vitamin D are essential for the production of serotonin from the amino acid tryptophan. While it was found that vitamin D was involved in serotonin production if serotonin was already high, vitamin D lowered serotonin levels[3] ( Omega 3 have not been shown to lower serotonin levels).
Serotonin has been made popular as an antidepressant working as an LSD opposer. It was in the 1960s that it was found that serotonin was inhibiting mitochondria’s function and caused a decrease in energy as it decreased phosphorus and oxygen uptake[4]. Serotonin is a key player in the formation of colitis[5] (omega 3 can exacerbate colitis by itself[6], while saturated acids were found to be protected[7]), anti-serotonin lowers context-conditioned immobility (learned helplessness) in males[8] and genetically altered mice displaying no serotonin in the brain displayed anti-depressive effects[9].
Anti-serotonin drugs are useful in treating aspects of depression[10][11], and are anti-fibrosis[12] serotonin is heavily involved in learned helplessness[13], diabetes type 2[14] compulsive disorders[15] and is involved in coronary artery disease and occurrence of cardiac events[16]. Serotonin is a key player in hibernation and is increased when temperature decreases, serotonin is highest at the beginning of hibernation and decreases at the end of hibernation[17]. Estrogen can increase serotonin[18] while vitamin A will lower serotonin[19].
If you want to know more about the serotonin-fish oil connection, please look into the book “fishy business” here
[1] Serotonin Promotes Tumor Growth in Human Hepatocellular Cancer Christopher Soll, Jae Hwi Jang,Marc-Oliver Riener, Wolfgang Moritz, Peter Johannes Wild, Rolf Graf, Pierre-Alain Clavien.
[2] Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Justin D Crane, Rengasamy Palanivel, Emilio P Mottillo, Adam L Bujak, Huaqing Wang, Rebecca J Ford,Andrew Collins, Regje M Blümer, Morgan D Fullerton, Julian M Yabut, Janice J Kim, Jean-Eric Ghia, Shereen M Hamza, Katherine M Morrison, Jonathan D Schertzer, Jason R B Dyck,Waliul I Khan, Gregory R Steinberg.
[3] Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior. Rhonda P. Patrick Bruce N. Ames.
[4] The Influence of Serotonin on Oxidative Metabolism of Brain Mitochondria. D. J. Mahler. F. L. Humoller Biochemical Research Laboratory, Veterans Administration Hospital, Omaha, Nebraska 68105
[5] Gastroenterology. 2009 Nov;137(5):1649-60. doi: 10.1053/j.gastro.2009.08.041. Epub 2009 Aug 23. Serotonin has a key role in pathogenesis of experimental colitis. Ghia JE1, Li N, Wang H, Collins M, Deng Y, El-Sharkawy RT, Côté F, Mallet J, Khan WI.
[6] Inflamm Bowel Dis. 2008 Oct;14(10):1348-57. doi: 10.1002/ibd.20491. Omega-3 fatty acids exacerbate DSS-induced colitis through decreased adiponectin in colonic subepithelial myofibroblasts.Matsunaga H1, Hokari R, Kurihara C, Okada Y, Takebayashi K, Okudaira K, Watanabe C, Komoto S, Nakamura M, Tsuzuki Y, Kawaguchi A, Nagao S, Itoh K, Miura S.
[7] Lipids – Immunology. Jennifer Lee, Pedro M. Moraes-Vieira, Angela Castoldi, Pratik Aryal, Eric U. Yee, Christopher Vickers, Oren Parnas, Cynthia J. Donaldson, Alan Saghatelian, and Barbara B. KahnBranched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses. J. Biol. Chem. 2016 291: 22207-. doi:10.1074/jbc.M115.703835
[8] Psychopharmacology (Berl). 2016 Apr;233(8):1513-21. doi: 10.1007/s00213-016-4246-5. Epub 2016 Feb 24. Serotonin depletion eliminates sex differences with respect to context-conditioned immobility in rat. Pettersson R1, Hagsäter SM1, Eriksson E2.
[9] ACS Chem Neurosci. 2014 Oct 15;5(10):908-19. doi: 10.1021/cn500096g. Epub 2014 Aug 12. Mice genetically depleted of brain serotonin do not display a depression-like behavioral phenotype. Angoa-Pérez M1, Kane MJ, Briggs DI, Herrera-Mundo N, Sykes CE, Francescutti DM, Kuhn DM.
[10] Arch Gen Psychiatry. 1986 Feb;43(2):177-81. Anorexia nervosa. Treatment efficacy of cyproheptadine and amitriptyline. Halmi KA, Eckert E, LaDu TJ, Cohen J.
[11] Pharmacotherapy. 1995 May-Jun;15(3):357-60. Treatment of depression with cyproheptadine. Greenway SE1, Pack AT, Greenway FL.
[12] Ruddell RG, Oakley F, Hussain Z, et al. A Role for Serotonin (5-HT) in Hepatic Stellate Cell Function and Liver Fibrosis. The American Journal of Pathology. 2006;169(3):861-876. doi:10.2353/ajpath.2006.050767.
[13] Brain Research 826 1999 35–43. Research report. Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor R.E. Grahn ), M.J. Will, S.E. Hammack, S. Maswood, M.B. McQueen, L.R. Watkins, S.F. Maier. Department of Psychology, BehaÕioral Neuroscience Program, UniÕersity of Colorado, Boulder, CO 80309, USA. Accepted 2 February 1999
[14] Cell Metab. 2007 Nov;6(5):398-405. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Zhou L1, Sutton GM, Rochford JJ, Semple RK, Lam DD, Oksanen LJ, Thornton-Jones ZD, Clifton PG, Yueh CY, Evans ML, McCrimmon RJ, Elmquist JK, Butler AA, Heisler LK.
[15] Nutritional up-regulation of serotonin paradoxically induces compulsive behavior. Brett D. Dufour, , Olayiwola Adeola, , Heng-Wei Cheng, Shawn S. Donkin, Jon D. Klein, , Edmond A. Pajor, Joseph P. Garner, Department of Animal Sciences and USDA-ARS, Purdue University, West Lafayette, Indiana, USA, school of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
[16] Circulation. 1999 Aug 3;100(5):483-9. Serotonin is associated with coronary artery disease and cardiac events. Vikenes K1, Farstad M, Nordrehaug JE.
[17] Bulletin of Experimental Biology and Medicine. November 1994, Volume 118, Issue 5, pp 1208–1210. Seasonal dynamics of serotonin in the duodenum of hibernating animals. ShestopalovaM. S. VinogradovaE. V. Dubinin
[18] BMC Womens Health. 2005 Dec 20;5:12. An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology. Rybaczyk LA1, Bashaw MJ, Pathak DR, Moody SM, Gilders RM, Holzschu DL.
[19] Oral Administration of Retinoic Acid Lowers Brain Serotonin Concentration in Rats. Anne Lorraine Smazal and Kevin Lee Schalinske. April 2013The FASEB Journalvol. 27 no. 1 Supplement635.6