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Condition

Schizophrenia

Schizophrenia is a serious mental illness in which brain signaling, including glutamate activity at NMDA receptors, is thought to go awry, shaping thoughts, motivation and emotion. Among supplements, the evidence is strongest for sarcosine, with moderate evidence for glycine and D-serine. Trials found overall symptoms improved with sarcosine and glycine, and cognition improved with D-serine. Still, these studies were small, the sarcosine finding rests on one trial, and people used them alongside usual antipsychotic medication.

Sources: PMID 16780811; PMID 14732596

Supplements studied
21
Graded outcomes
19
Trials
30
People studied
6,952

Evidence by supplement

  • Strong
  • Moderate
  • Limited
  • Very limited

21 supplements

Sarcosine

Sarcosine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Schizophrenia symptoms

Moderate Improvement

Improves (the measure goes down)Moderate effect1 study183 people

Studies that measured schizophrenia symptoms

Cognition

Small Improvement

Improves (the measure goes up)Small effect1 study98 people

Studies that measured cognition

Glycine

Glycine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Schizophrenia symptoms

Small Improvement

Improves (the measure goes down)Small effect3 studies50 people

Studies that measured schizophrenia symptoms

Cognition

Small Improvement

Improves (the measure goes up)Small effect17 people

D-Serine

  • Cognition: improves
  • Schizophrenia symptoms: improves
D-Serine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cognition

Small Improvement

Improves (the measure goes up)Small effect262 people
Schizophrenia symptoms

Small Improvement

Improves (the measure goes down)Small effect6 studies429 people

Studies that measured schizophrenia symptoms

and 3 more on the D-Serine page

Berberine

  • Apolipoprotein B: improves
  • Total cholesterol: improves
  • High-density lipoprotein (HDL): improves
Berberine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Apolipoprotein B

Small Improvement

Improves (the measure goes down)Small effect127 people
Total cholesterolImproves (the measure goes down)3 studies1,397 people

Studies that measured total cholesterol

High-density lipoprotein (HDL)Improves (the measure goes up)2 studies1,248 people

Studies that measured high-density lipoprotein (hdl)

TriglyceridesImproves (the measure goes down)1 study1,224 people

Studies that measured triglycerides

Low-density lipoprotein (LDL)Improves (the measure goes down)1,224 people

Chromium

  • HbA1c: improves
  • Weight: improves
  • Schizophrenia symptoms: improves
Chromium: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
HbA1c

Moderate Improvement

Improves (the measure goes down)Moderate effect4 studies20 people

Studies that measured hba1c

and 1 more on the Chromium page

WeightImproves (the measure goes down)12 studies20 people

Studies that measured weight

and 9 more on the Chromium page

Schizophrenia symptomsImproves (the measure goes down)20 people

Theanine

  • Anxiety Symptoms: improves
  • Subjective Well-Being: improves
  • Cortisol: improves
Theanine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Anxiety Symptoms

Small Improvement

Improves (the measure goes down)Small effect2 studies40 people

Studies that measured anxiety symptoms

Subjective Well-BeingImproves (the measure goes up)2 studies40 people

Studies that measured subjective well-being

CortisolImproves (the measure goes down)1 study60 people

Studies that measured cortisol

DHEASImproves (the measure goes up)60 people
InsulinChanges; see studies60 people
Schizophrenia symptomsImproves (the measure goes down)40 people
Serum BDNFImproves (the measure goes up)60 people
Serum DHEAImproves (the measure goes up)60 people
Total cholesterolImproves (the measure goes down)60 people

Saffron

  • C-Reactive Protein (CRP): improves
  • Hemoglobin: improves
  • Serum T3: improves
Saffron: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
C-Reactive Protein (CRP)

Small Decrease

Improves (the measure goes down)Small effect1 study66 people

Studies that measured c-reactive protein (crp)

HemoglobinImproves (the measure goes up)1 study66 people

Studies that measured hemoglobin

Serum T3Improves (the measure goes up)1 study66 people

Studies that measured serum t3

Erythrocyte Sedimentation RateImproves (the measure goes down)66 people
HematocritImproves (the measure goes up)66 people
Serum T4Improves (the measure goes up)66 people
Thyroid-Stimulating HormoneImproves (the measure goes up)66 people
White Blood Cell CountImproves (the measure goes up)66 people

Ashwagandha

  • Blood glucose: improves
  • Stress Signs and Symptoms: improves
  • Heart Rate: improves
Ashwagandha: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Blood glucose

Small Improvement

Improves (the measure goes down)Small effect1 study25 people

Studies that measured blood glucose

Stress Signs and SymptomsImproves (the measure goes down)3 studies68 people

Studies that measured stress signs and symptoms

Heart RateImproves (the measure goes down)1 study68 people

Studies that measured heart rate

High-density lipoprotein (HDL)Improves (the measure goes up)1 study25 people

Studies that measured high-density lipoprotein (hdl)

Schizophrenia symptomsImproves (the measure goes down)1 study68 people

Studies that measured schizophrenia symptoms

Blood PressureImproves (the measure goes down)68 people
C-Reactive Protein (CRP)Improves (the measure goes down)68 people
Interleukin 6Improves (the measure goes down)68 people
TriglyceridesImproves (the measure goes down)25 people
WeightImproves (the measure goes down)68 people

Panax Ginseng (Korean Ginseng)

  • Depression Symptoms: improves
  • Schizophrenia symptoms: improves
  • Working Memory: improves
Panax Ginseng (Korean Ginseng): outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Depression Symptoms

Small Improvement

Improves (the measure goes down)Small effect1 study64 people

Studies that measured depression symptoms

Schizophrenia symptomsImproves (the measure goes down)1 study64 people

Studies that measured schizophrenia symptoms

Working MemoryImproves (the measure goes up)64 people

Folic Acid (Vitamin B9)

  • Cognition: improves
  • Depression Symptoms: improves
  • Schizophrenia symptoms: improves
Folic Acid (Vitamin B9): outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cognition

Small Improvement

Improves (the measure goes up)Small effect1 study55 people

Studies that measured cognition

Depression SymptomsImproves (the measure goes down)2 studies123 people

Studies that measured depression symptoms

Schizophrenia symptomsImproves (the measure goes down)2 studies340 people

Studies that measured schizophrenia symptoms

Ginkgo Biloba

  • Anti-Oxidant Enzyme Profile
  • Schizophrenia symptoms: improves
  • Tardive Dyskinesia Symptoms: improves
Ginkgo Biloba: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Anti-Oxidant Enzyme Profile

Mixed effect

35 people
Schizophrenia symptomsImproves (the measure goes down)3 studies228 people

Studies that measured schizophrenia symptoms

Tardive Dyskinesia SymptomsImproves (the measure goes down)1 study157 people

Studies that measured tardive dyskinesia symptoms

Serum BDNFImproves (the measure goes up)157 people

Inositol

  • Depression Symptoms
  • Schizophrenia symptoms: improves
Inositol: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Depression Symptoms

No effect

NoneNo effect5 studies21 people

Studies that measured depression symptoms

and 2 more on the Inositol page

Schizophrenia symptomsImproves (the measure goes down)2 studies44 people

Studies that measured schizophrenia symptoms

L-Tyrosine

  • Memory
  • Schizophrenia symptoms: improves
L-Tyrosine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Memory

No effect

NoneNo effect11 people
Schizophrenia symptomsImproves (the measure goes down)1 study11 people

Vitamin B12

  • Cognition
  • Schizophrenia symptoms: improves
Vitamin B12: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Cognition

No effect

NoneNo effect55 people
Schizophrenia symptomsImproves (the measure goes down)55 people

N-Acetylcysteine

  • Processing Speed
  • Schizophrenia symptoms: improves
  • Working Memory: improves
N-Acetylcysteine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Processing Speed

No effect

NoneNo effect136 people
Schizophrenia symptomsImproves (the measure goes down)1 study354 people
Working MemoryImproves (the measure goes up)136 people

Resveratrol

  • Body Fat
  • Weight: improves
  • Body Mass Index (BMI): improves
Resveratrol: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Body Fat

No effect

NoneNo effect516 people
WeightImproves (the measure goes down)3 studies1,265 people
Body Mass Index (BMI)Improves (the measure goes down)1,418 people
Waist circumferenceImproves (the measure goes down)753 people

Probiotics

  • C-Reactive Protein (CRP): improves
Probiotics: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
C-Reactive Protein (CRP)Improves (the measure goes down)2 studies239 people

Cannabidiol (CBD)

  • Schizophrenia symptoms: improves
Cannabidiol (CBD): outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Schizophrenia symptomsImproves (the measure goes down)2 studies124 people

Fish Oil

  • Oxidative Stress Biomarkers: improves
Fish Oil: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Oxidative Stress BiomarkersImproves (the measure goes down)1 study71 people

Omega-3 Fatty Acids

  • Schizophrenia symptoms: improves
Omega-3 Fatty Acids: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Schizophrenia symptomsImproves (the measure goes down)1 study765 people

Creatine

  • Schizophrenia symptoms: improves
Creatine: outcomes studied for Schizophrenia
GradeOutcomeEffectSizeStudiesPeopleStudies list
Schizophrenia symptomsImproves (the measure goes down)1 study12 people

Key findings

  • Schizophrenia symptomsSarcosineImproves (the measure goes down)
  • CognitionSarcosineImproves (the measure goes up)
  • Apolipoprotein BBerberineImproves (the measure goes down)

The Schizophrenia protocol

2 primary supplements · 5 supporting supplements

See the full protocol

Studies cited

78 studies from PubMed

  1. Efficacy and Safety of Berberine Alone for Several Metabolic Disorders: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.Front Pharmacol, 2021 · PMID 33981233
  2. Effects of berberine on lipid profile in subjects with low cardiovascular riskExpert Opin Biol Ther, 2013 · PMID 23441841
  3. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center studyJ Clin Psychiatry · PMID 21208586
  4. Serum levels of brain-derived neurotrophic factor and cortisol to sulfate of dehydroepiandrosterone molar ratio associated with clinical response to L-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patientsClin Neuropharmacol · PMID 21617527
  5. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stressesJ Physiol Anthropol · PMID 23107346
  6. The Effects of Green Tea Amino Acid L-Theanine Consumption on the Ability to Manage Stress and Anxiety Levels: a Systematic Review.Plant Foods Hum Nutr · PMID 31758301
  7. L-Theanine reduces psychological and physiological stress responsesBiol Psychol · PMID 16930802
  8. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophreniaBiol Psychiatry · PMID 16780811
  9. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophreniaBiol Psychiatry · PMID 15023571
  10. An evaluation of the effect of saffron supplementation on the antibody titer to heat-shock protein (HSP) 70, hsCRP and spirometry test in patients with mild and moderate persistent allergic asthma: A triple-blind, randomized placebo-controlled trialRespir Med · PMID 30509713
  11. Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophreniaAvicenna J Phytomed · PMID 26468460
  12. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteersPhytomedicine · PMID 18693099
  13. A Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Impact of Resveratrol Supplementation on Anthropometric Indices in Patients With Type 2 Diabetes.Phytother Res · PMID 40842160
  14. Efficacy of Resveratrol Supplementation on Glucose and Lipid Metabolism: A Meta-Analysis and Systematic ReviewFront Physiol · PMID 35431994
  15. Resveratrol supplementation significantly influences obesity measures: a systematic review and dose-response meta-analysis of randomized controlled trials.Obes Rev · PMID 30515938
  16. Probiotic Supplementation and Inflammatory Status in Coronary Artery Disease: A Systematic Review and Meta-Analysis.Microorganisms · PMID 41156763
  17. Effect of probiotics on C-reactive protein levels in schizophrenia: Evidence from a systematic review and meta-analysis.Complement Ther Med · PMID 39798817
  18. HT1001, a proprietary North American ginseng extract, improves working memory in schizophrenia: a double-blind, placebo-controlled studyPhytother Res · PMID 22213250
  19. Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative Medicine GroupInt J Clin Pharmacol Res · PMID 10761538
  20. Effect of n-3 polyunsaturated fatty acids on the treatment of schizophrenia: an updated systematic review and meta-analysis.BMC Psychiatry · PMID 41219779
  21. Meta-analysis of randomised controlled trials with -acetylcysteine in the treatment of schizophrenia.Aust N Z J Psychiatry · PMID 31826654
  22. L-tyrosine pharmacotherapy of schizophrenia: preliminary dataClin Neuropharmacol · PMID 8149360
  23. Myo-inositol in the treatment of premenstrual dysphoric disorderHum Psychopharmacol · PMID 22031267
  24. CSF inositol in schizophrenia and high-dose inositol treatment of schizophreniaEur Neuropsychopharmacol · PMID 7894259
  25. Lack of effect of inositol treatment in chronic schizophreniaBiol Psychiatry · PMID 8329500
  26. Inositol addition does not improve depression in SSRI treatment failuresJ Neural Transm · PMID 10907738
  27. Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidoneAm J Psychiatry · PMID 16449473
  28. Double-blind, controlled trial of inositol treatment of depressionAm J Psychiatry · PMID 7726322
  29. Inositol for depressive disorders.Cochrane Database Syst Rev · PMID 15106232
  30. Glutamatergic drugs for schizophrenia.Cochrane Database Syst Rev · PMID 16625590
  31. High-dose glycine added to olanzapine and risperidone for the treatment of schizophreniaBiol Psychiatry · PMID 14732596
  32. Efficacy of pharmacological agents for the management of treatment-resistant schizophrenia: a network meta-analysis.Expert Rev Clin Pharmacol · PMID 38269529
  33. Brain-derived neurotrophic factor levels and its Val66Met gene polymorphism predict tardive dyskinesia treatment response to Ginkgo bilobaBiol Psychiatry · PMID 22695185
  34. A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophreniaJ Clin Psychiatry · PMID 11775047
  35. The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophreniaPsychiatry Clin Neurosci · PMID 16401239
  36. A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophreniaInt Clin Psychopharmacol · PMID 18545061
  37. Effects of folic acid supplementation on cognitive function and inflammation in elderly patients with mild cognitive impairment: A systematic review and meta-analysis of randomized controlled trials.Arch Gerontol Geriatr · PMID 38964091
  38. Folate and vitamin B12 supplementation in patients with schizophrenia and low serum folate level: A 24-week randomized, double-blind, placebo-controlled study.J Formos Med Assoc · PMID 39645464
  39. Folic acid/methylfolate for the treatment of psychopathology in schizophrenia: a systematic review and meta-analysis.Psychopharmacology · PMID 29785555
  40. Enhancement of recovery from psychiatric illness by methylfolateLancet · PMID 1974941
  41. Folate for depressive disordersCochrane Database Syst Rev · PMID 12804463
  42. Oxidative stress reduction related to the efficacy of n-3 polyunsaturated fatty acids in first episode schizophrenia: Secondary outcome analysis of the OFFER randomized trialProstaglandins Leukot Essent Fatty Acids · PMID 28651701
  43. High dose D-serine in the treatment of schizophreniaSchizophr Res · PMID 20541910
  44. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophreniaInt J Neuropsychopharmacol · PMID 19887019
  45. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophreniaBiol Psychiatry · PMID 15780844
  46. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled studyArch Gen Psychiatry · PMID 16275807
  47. A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophreniaJ Clin Psychiatry · PMID 22795211
  48. D-serine added to antipsychotics for the treatment of schizophreniaBiol Psychiatry · PMID 9836012
  49. Lack of efficacy of 5 grams daily of creatine in schizophrenia: a randomized, double-blind, placebo-controlled trialJ Clin Psychiatry · PMID 17592912
  50. A double-blind, randomized pilot trial of chromium picolinate for binge eating disorder: results of the Binge Eating and Chromium (BEACh) studyJ Psychosom Res · PMID 23751236
  51. Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitusEndocr Pract · PMID 20634174
  52. Chromium picolinate does not improve key features of metabolic syndrome in obese nondiabetic adultsMetab Syndr Relat Disord · PMID 19422140
  53. Chromium picolinate supplementation for overweight or obese adultsCochrane Database Syst Rev · PMID 24293292
  54. Lack of effect of chromium supplementation on mental state and body weight in people with schizophreniaJ Clin Psychopharmacol · PMID 16974208
  55. The effects of chromium and copper supplementation on mitogen-stimulated T cell proliferation in hypercholesterolaemic postmenopausal womenClin Exp Immunol · PMID 11966762
  56. Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitusJ Am Coll Nutr · PMID 11444416
  57. The effects of inorganic chromium and brewer's yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetesSaudi Med J · PMID 11376359
  58. Beneficial effect of chromium supplementation on glucose, HbA1C and lipid variables in individuals with newly onset type-2 diabetesJ Trace Elem Med Biol · PMID 21570271
  59. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetesDiabetes · PMID 9356027
  60. Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitusBiol Trace Elem Res · PMID 16632892
  61. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trialDiabetes Care · PMID 16505499
  62. Role of chromium supplementation in Indians with type 2 diabetes mellitusJ Nutr Biochem · PMID 12550067
  63. Chromium supplementation shortens QTc interval duration in patients with type 2 diabetes mellitusAm Heart J · PMID 15990745
  64. Effect of resistance training with or without chromium picolinate supplementation on glucose metabolism in older men and womenMetabolism · PMID 10337851
  65. Chromium picolinate supplementation in women: effects on body weight, composition, and iron statusNutrition · PMID 17291720
  66. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trialPsychopharmacology · PMID 29619533
  67. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled TrialAm J Psychiatry · PMID 29241357
  68. The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control Trials.Evid Based Complement Alternat Med · PMID 31915452
  69. Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials.Phytomedicine · PMID 36805484
  70. Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.Drugs · PMID 36941490
  71. The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis.Front Nutr · PMID 36313096
  72. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) rootIndian J Exp Biol · PMID 11116534
  73. Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical StudyCureus · PMID 32021735
  74. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adultsIndian J Psychol Med · PMID 23439798
  75. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trialsPhytother Res · PMID 36017529
  76. Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled TrialJ Evid Based Complementary Altern Med · PMID 27055824
  77. Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled StudyJ Clin Psychiatry · PMID 29995356
  78. Effects of Withania somnifera in patients of schizophrenia: A randomized, double blind, placebo controlled pilot trial studyIndian J Pharmacol · PMID 24014929

Supplement stack for Schizophrenia