Serine
OTHER NAME(S): (2S)-2-Amino-3-Hydroxypropanoic Acid, 3-Hydroxyalanine, Beta-Hydroxy-D-Alanine, Beta-Hydroxy-L-Alanine, Beta-Hydroxyalanine, D-3-Hydroxy-Alanine, D-Ser, D-Serine, L-3-Hydroxy-Alanine, L-Ser, L-Serine, Serinum, Serine, Serina, Sérine
Overview
Serine is an amino acid. It comes in two forms: L-serine and D-serine. L-serine is consumed in the diet and D-serine is made in the body from L-serine.
The body uses D- and L-serine to make proteins. D-serine also sends chemical signals in the brain. This might help with schizophrenia and other brain conditions.
People use serine for schizophrenia, Parkinson disease, memory and thinking skills, depression, insomnia, and many other conditions, but there is no good scientific evidence to support most of these uses.
Uses
Possibly Effective for
- Schizophrenia. Taking D-serine by mouth along with standard antipsychotic therapy might improve symptoms of schizophrenia. But taking D-serine alone doesn't work as well as standard treatments.
There is interest in using serine for a number of other purposes, but there isn't enough reliable information to say whether it might be helpful.
Side Effects
When taken by mouth: L-serine is commonly consumed in foods. The typical diet provides about 3.5-8 grams daily. Serine is possibly safe when used in higher doses as medicine. L-serine in doses up to 25 grams daily for up to 1 year, or D-serine in doses of 2-4 grams daily for up to 4 weeks, have been used safely. Side effects might include upset stomach and bloating.
Serine is possibly unsafe when taken in very high doses, such as 25 grams or more of L-serine daily or 8 grams or more of D-serine daily. High doses might lead to increased stomach side effects and seizures.
Precautions
When taken by mouth: L-serine is commonly consumed in foods. The typical diet provides about 3.5-8 grams daily. Serine is possibly safe when used in higher doses as medicine. L-serine in doses up to 25 grams daily for up to 1 year, or D-serine in doses of 2-4 grams daily for up to 4 weeks, have been used safely. Side effects might include upset stomach and bloating.
Serine is possibly unsafe when taken in very high doses, such as 25 grams or more of L-serine daily or 8 grams or more of D-serine daily. High doses might lead to increased stomach side effects and seizures.
Pregnancy and breast-feeding: L-serine is commonly consumed in foods. But there isn't enough reliable information to know if L- or D-serine is safe to use as a medicine when pregnant or breast-feeding. Stay on the safe side and stick to food amounts.
Kidney disease: High doses of D-serine might worsen kidney disease. Stay on the safe side and avoid use.
Interactions
We currently have no information for Serine overview.
Dosing
L-serine is found in many foods. The typical diet provides about 3.5-8 grams of L-serine daily. There isn't enough reliable information to know what an appropriate dose of L-serine might be when used as medicine. D-serine has most often been used by adults in doses of 2 grams by mouth daily for up to 16 weeks. Speak with a healthcare provider to find out what form of serine and dose might be best for a specific condition.
References
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Micronutrients). Washington, DC: National Academy Press, 2005. Available at: http://www.nap.edu/books/10490/html/.
- Avellar M, Scoriels L, Madeira C, et al. The effect of D-serine administration on cognition and mood in older adults. Oncotarget. 2016;7(11):11881-8.
- Biemans EA, Verhoeven-Duif NM, Gerrits J, Claassen JA, Kuiperij HB, Verbeek MM. CSF d-serine concentrations are similar in Alzheimer's disease, other dementias, and elderly controls. Neurobiol Aging. 2016;42:213-6.
- Billard JM. D-Serine in the aging hippocampus. J Pharm Biomed Anal. 2015;116:18-24.
- Bradley WG, Miller RX, Levine TD, Stommel EW, Cox PA. Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of L-Serine. Neurotox Res. 2018;33(1):192-198.
- Cho SE, Na KS, Cho SJ, Kang SG. Low d-serine levels in schizophrenia: A systematic review and meta-analysis. Neurosci Lett. 2016;634:42-51.
- D'Souza DC, Radhakrishnan R, Perry E, et al. Feasibility, safety, and efficacy of the combination of D-serine and computerized cognitive retraining in schizophrenia: an international collaborative pilot study. Neuropsychopharmacology. 2013;38(3):492-503.
- Ermilov M, Gelfin E, Levin R, et al. A pilot double-blind comparison of d-serine and high-dose olanzapine in treatment-resistant patients with schizophrenia. Schizophr Res. 2013;150(2-3):604-5.
- Fridman V, Suriyanarayanan S, Novak P, et al. Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. Neurology. 2019;92(4):e359-e370.
- Garofalo K, Penno A, Schmidt BP, et al. Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest. 2011;121(12):4735-45.
- Gelfin E, Kaufman Y, Korn-Lubetzki I, et al. D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease. Int J Neuropsychopharmacol. 2012;15(4):543-9.
- Heresco-Levy U, Javitt DC, Ebstein R, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. 2005;57(6):577-85.
- Heresco-Levy U, Vass A, Bloch B, et al. Pilot controlled trial of D-serine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol. 2009;12(9):1275-82.
- Ishiwata S, Hattori K, Sasayama D, et al. Cerebrospinal fluid D-serine concentrations in major depressive disorder negatively correlate with depression severity. J Affect Disord. 2018;226:155-162.
- Ito Y, Takahashi S, Shen M, Yamaguchi K, Satoh M. Effects of L-serine ingestion on human sleep. Springerplus. 2014;3:456.
- Kantrowitz JT, Epstein ML, Lee M, et al. Improvement in mismatch negativity generation during d-serine treatment in schizophrenia: Correlation with symptoms. Schizophr Res. 2018;191:70-79.
- Kantrowitz JT, Malhotra AK, Cornblatt B, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res. 2010 Aug;121(1-3):125-30.
- Lane HY, Chang YC, Liu YC, Chiu CC, Tsai GE. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry. 2005;62(11):1196-204.
- Lane HY, Lin CH, Huang YJ, Liao CH, Chang YC, Tsai GE. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol. 2010;13(4):451-60.
- Lemmon ME, Grados M, Kline T, Thompson CB, Ali SF, Singer HS. Efficacy of Glutamate Modulators in Tic Suppression: A Double-Blind, Randomized Control Trial of D-serine and Riluzole in Tourette Syndrome. Pediatr Neurol. 2015;52(6):629-34.
- Levin R, Dor-Abarbanel AE, Edelman S, et al. Behavioral and cognitive effects of the N-methyl-D-aspartate receptor co-agonist D-serine in healthy humans: initial findings. J Psychiatr Res. 2015;61:188-95.
- Levine TD, Miller RG, Bradley WG, et al. Phase I clinical trial of safety of L-serine for ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(1-2):107-111.
- Lin CH, Yang HT, Lane HY. D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer's disease or mild cognitive impairment. Pharmacol Biochem Behav. 2019;185:172760.
- Tuominen HJ, Tiihonen J, Wahlbeck K. Glutamatergic drugs for schizophrenia. Cochrane Database Syst Rev. 2006;(2):CD003730.
- Malkesman O, Austin DR, Tragon T, et al. Acute D-serine treatment produces antidepressant-like effects in rodents. Int J Neuropsychopharmacol. 2012;15(8):1135-48.
- Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs. 2011;25(10):859-85.
- Metcalf JS, Dunlop RA, Powell JT, Banack SA, Cox PA. L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential. Neurotox Res. 2018;33(1):213-221.
- Moaddel R, Luckenbaugh DA, Xie Y, et al. D-serine plasma concentration is a potential biomarker of (R,S)-ketamine antidepressant response in subjects with treatment-resistant depression. Psychopharmacology (Berl). 2015;232(2):399-409.
- Montesinos Guevara C, Mani AR. The role of D-serine in peripheral tissues. Eur J Pharmacol. 2016;780:216-23.
- Nagamachi S, Nishigawa T, Takakura M, et al. Dietary L-serine modifies free amino acid composition of maternal milk and lowers the body weight of the offspring in mice. J Vet Med Sci. 2018;80(2):235-241.
- Nagasawa M, Otsuka T, Togo Y, et al. Single and chronic L-serine treatments exert antidepressant-like effects in rats possibly by different means. Amino Acids. 2017;49(9):1561-1570.
- MacKay MB, Kravtsenyuk M, Thomas R, Mitchell ND, Dursun SM, Baker GB. D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression? Front Psychiatry. 2019;10:25.
- Seif T, Simms JA, Lei K, et al. D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats. Neuropsychopharmacology. 2015;40(10):2357-67.
- Tsuda Y, Yamaguchi M, Noma T, Okaya E, Itoh H. Combined Effect of Arginine, Valine, and Serine on Exercise-Induced Fatigue in Healthy Volunteers: A Randomized, Double-Blinded, Placebo-Controlled Crossover Study. Nutrients. 2019;11(4). pii: E862. doi: 10.3390/nu11040862.
- Verhoef P, Steenge GR, Boelsma E, van Vliet T, Olthof MR, Katan MB. Dietary serine and cystine attenuate the homocysteine-raising effect of dietary methionine: a randomized crossover trial in humans. Am J Clin Nutr. 2004;80(3):674-9.
- Weiser M, Heresco-Levy U, Davidson M, et al. A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia. J Clin Psychiatry. 2012;73(6):e728-34.
- Chang CH, Kuo HL, Ma WF, Tsai HC. Cerebrospinal Fluid and Serum D-Serine Levels in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis. J Clin Med 2020;9(12):3840.
- Sasahara I, Yamamoto A, Takeshita M, et al. L-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. J Nutr 2020;150(9):2278-2286.
- Asakawa T, Onizawa M, Saito C, et al. Oral administration of D-serine prevents the onset and progression of colitis in mice. J Gastroenterol 2021;56(8):732-745.
- Miura N, Matsumoto H, Cynober L, et al. Subchronic tolerance trials of graded oral supplementation with phenylalanine or serine in healthy adults. Nutrients 2021;13(6):1976.
- Yulug B, Altay O, Li X, et al. Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial. Transl Neurodegener. 2023 Jan 26;12(1):4.
- Umeda K, Shindo D, Somekawa S, et al. Effects of Five Amino Acids (Serine, Alanine, Glutamate, Aspartate, and Tyrosine) on Mental Health in Healthy Office Workers: A Randomized, Double-Blind, Placebo-Controlled Exploratory Trial. Nutrients 2022;14(11):2357.
- Ohashi M, Lee SI, Eto T, et al. Intake of L-serine before bedtime prevents the delay of the circadian phase in real life. J Physiol Anthropol 2022;41(1):31.
- Sehatpour P, Iosifescu DV, De Baun HM, et al. Dose-Dependent Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia: A Double-Blind, Placebo-Controlled, Randomized, Target Engagement Clinical Trial of the NMDA Glutamate Receptor Agonist d-serine. Biol Psychiatry 2023.