References

Bio Balance Health trains doctors in assessing mental health symptoms and treatment response, using biomarkers. This significantly improves the capabilities of current psychiatric care.  The use of conventional pathology tests is not common in the management of mental health. Yet, a very simple search shows there is extensive research between mental health and essential nutrients. Investigation of the need for these essential nutrients is not common practice in treatment of mental health symptoms.

Published Articles Google Scholar Pub Med
Zinc, depression 297,000 11,860
Magnesium, depression 240,000 1,548
B6, depression 65,000 242
Folic Acid, depression 68,000 724
Vitamin D, depression 632,000 878
SAMe, depression 3,400,000 18,684
Vitamin B12, depression 67,100 535
Minerals, depression 276,000 511

Bio Balance Health has actively supported and funded the following research papers:

Dr Fryar-Williams’ work has developed an above 90% statistical probability of diagnosis of certain schizophrenic conditions by using a combination of biomarkers.

  • Biomarker Case-Detection and Prediction with Potential for Functional Psychosis Screening: Development and Validation of a Model Related to Biochemistry, Sensory Neural Timing and End Organ Performance.
    https://www.ncbi.nlm.nih.gov/pubmed/27148083
    Fryar-Williams S, Strobel JE.
  • Fundamental Role of Methylenetetrahydrofolate Reductase 677 C → T Genotype and Flavin Compounds in Biochemical Phenotypes for Schizophrenia and Schizoaffective Psychosis
    Fryar-Williams S, Strobel JE.
    https://www.ncbi.nlm.nih.gov/pubmed/27148083

This study demonstrated that Micronutrients can reduce violent behaviour:

  • Micronutrient Therapy for Violent Aggressive Male Youth
    Jessica L. Hambly, MPharm (Hons),1 Kelly Francis, MBBS, FRACGP,2 Sohil Khan, PhD,1,3 Kristen S. Gibbons, PhD, AStat,3 William J. Walsh, PhD,4 Brett Lambert, MAppSc,5 Chris Testa, BPharm, BBus,6 and Alison Haywood, PhD1,3
    https://www.ncbi.nlm.nih.gov/pubmed/28481642

Epigenetic modifications may play a major role in schizophrenia pathophysiology:

The study demonstrated that patients who followed the program had an average of 2 days hospitalisation compared to 22 days for those who did not follow the program:

Mental health symptoms and oxidative stress

The following list of research studies is a glimpse into some of the research exploring the relationship between mental health symptoms and oxidative stress:

  • Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nano materials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.
    Archives of Toxicology 98:1323-1367.
    Jomova, K. Alomar, S. Alwasel, S. Nepovimova, E. Kuca, K. Valko, M. (14 March, 2024).

Mental health and nutrients

The following list of research studies is a glimpse into some of the research exploring the relationship between mental health and nutrients:

This history of research in South Australia documents how Australian soils lack nutrients and how scientists discovered what to do to recover health of sheep and crops.  The analogy to human health should be clear yet the medical world dismisses these issues in mental health. The link to this paper is here to provide information for all.

Zinc

  • Zinc in CNS: From Molecules to Behaviour. “Biofactors” 2012 Mar 31
    https://pubmed.ncbi.nlm.nih.gov/22473811/
    Covered role of zinc in transcription factors, gene regulation, transporters, neurogenesis, neurotransmission, AD, Depression, Stroke, Epilepsy. This paper alone had 81 references
  • Zinc supplementation in Major Depression: A RCT.
    Iran J Psychiatry. 2013 June 8, 73—79
    SSRI plus zinc is more effective than SSRI plus placebo in treating depression. This paper alone had 26 reference articles
      • Zinc concentrations 1.85micm/l lower in depressed patients.
      • The lower the zinc concentration the more severe the depression.
      • Low zinc levels are a marker of treatment resistant depression.
  • Do the Micronutrients Zinc and Magnesium Play a Role in Adult Depression?
    Top Clin Nutr.2011 Jul-Sep;26(3):257-267. doi: 10.1097/TIN.0b013e3182260d86.
    Dickerman B1Liu J1
  • Do the Micronutrients Zinc and Magnesium Play a Role in Adult Depression?
    Top Clin Nutr.2011 Jul-Sep;26(3):257-267. doi: 10.1097/TIN.0b013e3182260d86.
    Dickerman B1Liu J1.

    Magnesium

    • Association between magnesium intake and depression:
      Australian & New Zealand Journal of Psychiatry: Volume 43, 2009
      5708 patients. “There is an inverse statistically significant association between dietary magnesium intake and depression score”
      There seemed to be a similar association with anxiety but not statistically significant.
    • Magnesium in addiction – a general view.
      Magnes2018 Aug 1;31(3):90-98. doi: 10.1684/mrh.2018.0443.
      Nechifor M1.
    • Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus.
      Biol Psychiatry, 2004, 55, 781–784.
      Kajdanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H
    • Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action
      Bernadeta Szewczyk1,*, Ewa Poleszak3,*, Magdalena Sowa-Kuæma1, Marcin Siwek4, Dominika Dudek4, Beata Ryszewska-Pokraœniewicz5, Maria Radziwoñ-Zaleska5, W³odzimierz Opoka7, Janusz Czekaj6, Andrzej Pilc1,6, Gabriel Nowak1,2
      Pharmacological Reports 2008, 60, 588–599 ISSN 1734-1140
    • The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review.
      2017 Apr 26;9(5). pii: E429. doi: 10.3390/nu9050429.
      Boyle NB1Lawton C2Dye L3.
    • Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials.
      Adv Ther.2018 Mar;35(3):261-288. doi: 10.1007/s12325-018-0680-6. Epub 2018 Mar 5.
      Barić H1Đorđević V2Cerovečki I3Trkulja V4.

    Folic Acid

    • Treatment of depression: time to consider folic acid and B12.
      Journal of Psychopharmacology, Jan 1 2005
      “There is now evidence of a common decrease in folic acid and B12, an increase homocysteine and polymorphism of MTHFR C677T being overrepresented in depressive patients”
    • Folate in depression: efficacy, safety, differences in formulations, and clinical issues.
      J Clin Psychiatry 2009;70 Suppl 5:12-17. [Full text]
      Fava M, Mischoulon D.
    • The role of folic acid in the prevention and treatment of depression: An overview of existing evidence and implications for practice
      Chrystalleni Lazarou a,*, Margarita Kapsou b
      https://pubmed.ncbi.nlm.nih.gov/20621278/

      a Harokopio University, Department of Nutrition and Dietetics, Athens, Greece
      b University of Cyprus, Department of Psychology, Nicosia, Cyprus

    Pyridoxine

    • Antidepressive effect of pyridoxine in neuroleptic treated schizophrenic patients with co-morbid depression
      Harefuah [Israel] May 2001: 140 [5]; 369—373.
      Conclusion: A subgroup of schizophrenic patients with co-morbid depression may benefit from pyridoxine added to their anti-psychotic treatment

    Vitamin D

    • Efficacy of vitamin D supplementation in major depression: A meta-analysis of randomized controlled trials.
      J Postgrad Med.2018 Jun 21. doi: 10.4103/jpgm.JPGM_571_17. [Epub ahead of print]
      Vellekkatt F1Menon V1
    • Association of antepartum vitamin D deficiency with postpartum depression: a clinical perspective.
      Public Health Nutr.2019 Jan 18:1-6. doi: 10.1017/S136898001800366X. [Epub ahead of print]
      Szpunar MJ1
    • Database Analysis of Depression and Anxiety in a Community Sample-Response to a Micronutrient Intervention.
      2018 Jan 30;10(2). pii: E152. doi: 10.3390/nu10020152.
      Kimball SM1,2Mirhosseini N3Rucklidge J4
    • Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.
      FASEB J.2015 Jun;29(6):2207-22. doi: 10.1096/fj.14-268342. Epub 2015 Feb 24.
      Patrick RP1Ames BN1
    • Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.
      Psychiatry Res.2018 Dec;270:104-110. doi: 10.1016/j.psychres.2018.09.024. Epub 2018 Sep 13.
      Fond G1Godin O2Schürhoff F et al
    • Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.
      EBioMedicine.2017 Dec;26:138-145. doi: 10.1016/j.ebiom.2017.11.027. Epub 2017 Dec 2.
      Krivoy A1Onn R2Vilner Y3, et al
    • Hypovitaminosis D is associated with depression and anxiety in schizophrenia: Results from the national FACE-SZ cohort.
      Psychiatry Res.2018 Dec;270:104-110. doi: 10.1016/j.psychres.2018.09.024. Epub 2018 Sep 13.
      Fond G1Godin O2Schürhoff F et al
    • Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.
      EBioMedicine.2017 Dec;26:138-145. doi: 10.1016/j.ebiom.2017.11.027. Epub 2017 Dec 2.
      Krivoy A1Onn R2Vilner Y3, et al
    • Vitamin D levels, brain volume, and genetic architecture in patients with psychosis.
      PLoS2018 Aug 24;13(8):e0200250. doi: 10.1371/journal.pone.0200250. eCollection 2018.
      Berg AO1,2Jørgensen KN1,3Nerhus  M et al

    SAMe

    • Excessive S-Adenosyl-L-Methionine-Dependent Methylation Increases Levels of Methanol, Formaldehyde and Formic Acid in Rat Brain Striatal Homogenates: Possible role in S-adenosyl-L-methionine-induced Parkinson’s disease-like disorders.
      [LIFE SCIENCES; Lee,E; 83(25-26):821-827 (2008)].
    • Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder.
      J Clin Psychiatry.2009;70 Suppl 5:18-22. doi: 10.4088/JCP.8157su1c.04.
      Papakostas GI1
    • S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies.
      Acta Neurol Scand Suppl. 1994;154:7–14. [PubMed]
      Bressa GM.
    • Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies.
      Am J Clin Nutr. 2002 Nov;76(5):1172S–6S.
      Delle Chiaie R, Pancheri P, Scapicchio P.
    • Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial.
      Pharmacopsychiatry. 2015 Jul;48(4–5):141–4.
      Sarris J, Price LH, Carpenter LL, Tyrka AR, Ng CH, Papakostas GI, et al.
    • S-adenosylmethionine (SAMe) as treatment for depression: a systematic review.
      Clin Invest Med 2005;28(3):132-139. [Abstract]
      Williams AL, Girard C, Jui D, et al.
    • S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine.
      J Clin Psychopharmacol 2004;24(6):661-664Alpert JE, Papakostas G, Mischoulon D, et al.
    • Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive disorder: An 8-week double-blind, randomized, controlled trial.
      Eur Neuropsychopharmacol.2018 Oct;28(10):1126-1136. doi: 10.1016/j.euroneuro.2018.07.098. Epub 2018 Aug 14.Sarris J1Byrne GJ2Bousman C3, et al
    • Clinical use of nutraceuticals in the adjunctive treatment of depression in mood disorders.
      Australas2017 Aug;25(4):369-372. doi: 10.1177/1039856216689533. Epub 2017 Jan 31.
      Sarris J1
    • Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder.
      Levkovitz Y, Alpert JE, Brintz CE, et al. J Affect Disord. 2012;136(3):1174–1178.
    • Psychological distress during the puerperium: a novel therapeutic approach using S-adenosylmethionine.
      Ther. Res. 1993;53:701–716.Cerutti R, Sichel MP, Perin M, et al.
    • Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence.
      Am J Clin Nutr. 2002;76(5):1158S–1161S. [PubMed]
      Mischoulon D, Fava M.
    • S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies.
      Acta Neurol Scand Suppl. 1994;154:7–14. [PubMed] Bressa GM.
    • S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial.
      Am J Psychiatry. 2010;167(8):942–948. [PubMed]
      Papakostas GI, Mischoulon D, Shyu I, et al.
    • Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder.
      J Affect Disord. 2012;136(3):1174–1178. [PubMed]
      Levkovitz Y, Alpert JE, Brintz CE, et al.
    • Psychological distress during the puerperium: a novel therapeutic approach using S-adenosylmethionine.
      Curr. Ther. Res. 1993;53:701–716.
      Cerutti R, Sichel MP, Perin M, et al.
    • S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism.
      Drugs 1989;38(3):389-416. [Abstract]
      Friedel HA, Goa KL, Benfield P.

    Vitamin B12

    • B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline.
      Neurosci Biobehav2014 Nov;47:307-20. doi: 10.1016/j.neubiorev.2014.08.006. Epub 2014 Aug 27.
      Mitchell ES1Conus N2Kaput J2.
    • Folate, vitamin B12, homocysteine, and the MTHFR 677C – > T polymorphism in anxiety and depression: the Hordaland Homocysteine Study.
      Arch Gen Psychiatry.2003 Jun;60(6):618-26.
      Bjelland I1, Tell GS, Vollset SE, Refsum H, Ueland PM.
    • One month of nitrous oxide abuse causing acute vitamin B 12 deficiency with severe neuropsychiatric symptoms.
      BMJ Case Rep. 2019 Feb 7;12(2). pii: bcr-2018-228001. doi: 10.1136/bcr-2018-228001.
      Lundin MS1,2Cherian J1,2Andrew MN1,2Tikaria R1,2.
    • Vitamin B12, folic acid, homocysteine and vitamin D levels in children and adolescents with obsessive compulsive disorder.
      Psychiatry Res.2017 Aug;254:232-237. doi: 10.1016/j.psychres.2017.04.032. Epub 2017 Apr 21.
      Esnafoğlu E1Yaman E2.

    Homocysteine

    • Homocysteine excess: delineating the possible mechanism of neurotoxicity and depression.
      Fundam Clin Pharmacol.2015 Dec;29(6):522-8. doi: 10.1111/fcp.12145. Epub 2015 Sep 17.
      Bhatia P1Singh N2.
    • Fundamental Role of Methylenetetrahydrofolate Reductase 677 C → T Genotype and Flavin Compounds in Biochemical Phenotypes for Schizophrenia and Schizoaffective Psychosis.
      Front Psychiatry.2016 Nov 9;7:172. eCollection 2016.
      Fryar-Williams S1.
    • Pseudodementia in a twenty-one-year-old with bipolar disorder and vitamin B12 and folate deficiency.
      West Indian Med J.2000 Dec;49(4):347-8.
      Reid SD1.
    • Malignant catatonia in a patient with bipolar disorder, B12 deficiency, and neuroleptic malignant syndrome: one cause or three?
      Psychiatr Pract.2009 Sep;15(5):415-22. doi: 10.1097/01.pra.0000361282.95962.9f.
      Lewis AL1Pelic CKahn DA.

    Iodine

    • Iodine deficiency in pregnancy: the effect on neurodevelopment in the child.
      2011 Feb;3(2):265-73. doi: 10.3390/nu3020265. Epub 2011 Feb 18.
      Skeaff SA1.

    Selenium

    • Importance of selenium and selenoprotein for brain function: From antioxidant protection to neuronal signalling.
      Inorg Biochem.2015 Dec;153:1-12. doi: 10.1016/j.jinorgbio.2015.09.003. Epub 2015 Sep 15.
      Solovyev ND1.
    • Association of total zinc, iron, copper and selenium intakes with depression in the US adults.
      J Affect Disord.2018 Mar 1;228:68-74. doi: 10.1016/j.jad.2017.12.004. Epub 2017 Dec 6.
      Li Z1Wang W1Xin X1Song X1Zhang D2.
    • Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications.
      2018 May 9;10(5). pii: E584. doi: 10.3390/nu10050584.
      Wang J1Um P2Dickerman BA3Liu J4.
    • Comparative Study on Serum Levels of 10 Trace Elements in Schizophrenia.
      PLoS2015 Jul 17;10(7):e0133622. doi: 10.1371/journal.pone.0133622. eCollection 2015.
      Liu T1Lu QB2Yan L2Guo J3Feng F3Qiu J3Wang J2.

    Manganese

    • Association of hair manganese level with symptoms in attention-deficit/hyperactivity disorder.
      Psychiatry Investig.2015 Jan;12(1):66-72. doi: 10.4306/pi.2015.12.1.66. Epub 2015 Jan 12.
      Environ Sci Pollut Res Int. 2019 Jan 7. doi: 10.1007/s11356-018-04066-1. [Epub ahead of print]
    • Genetic variants in nuclear-encoded mitochondrial proteins are associated with oxidative stress in obsessive compulsive disorders.
      Psychiatr2012 Feb;46(2):212-8. doi: 10.1016/j.jpsychires.2011.09.012. Epub 2011 Nov 8.
      Orhan N1Kucukali CICakir USeker NAydin M.
    • Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies.
      Surg Neurol Int.2015 Mar 24;6:45. doi: 10.4103/2152-7806.153876. eCollection 2015.
      Samsel A1Seneff S2.

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