Mental Health

What is often not fully appreciated is that the neurotransmitters are made in the body. There are over 100 neurotransmitters now identified, though most research has focused on a few key ones. Serotonin is produced from the amino acid tryptophan (found in protein) and the final reaction requires vitamin B6 (The process also requires tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D). Dopamine can be made from either of 2 amino acids and requires iron and folate. Norepinephrine is made from dopamine and requires adequate copper. GABA requires adequate zinc and B6 for its synthesis and regulation. Good mental health requires proper neurotransmitter activity at the synapses. This means you need a healthy synapse as well as adequate levels of the neurotransmitters.

Many medications target these key neurotransmitters by impacting the “reuptake” of them at the synapse, such as SSRIs – Serotonin Reuptake Inhibitor antidepressants. The synapse is the gap between 2 neurons where the electrical signal is turned into a chemical signal that moves across the space. The “reuptake” is where the neurotransmitter chemicals are whisked from the synapse like a vacuum inhaling dust, which returns the brain cell to its original state. This process is performed by transporters that are embedded in the cell membranes, creating a form of passageway. The rate of production of these transporters can change, and is regulated by “epigenetic” expression of genes.

The methylation (adding a CH3 chemical group) of DNA can switch off genes that produce neurotransmitter proteins. This causes the person to have reduced serotonin activity and a tendency towards depression. The reverse process, over methylation could cause excessive dopamine and a tendency towards anxiety. Multiple researchers [1] have found “over methylators” tended to have distinct character traits compared to “under methylators” and the different groups required different treatments to get better. They also found urinary pyrrole excretion (a marker of oxidative stress) was higher in people with mental illness than those without, and this correlated with a certain pattern of character traits. We now know that urinary pyrrole is a marker of oxidative stress.

A person’s metabolism and nutritional status can and does impact their mental health. The main mechanism through which this occurs is epigenetics.

Countless environmental influences can cause these epigenetic changes, such as nutritional deficiencies or excesses, toxin exposures or stress. It makes sense then if we could optimise nutrition and neurotransmitter production, we could bring about new epigenetic changes and improve mental health.

This is the basis of the Pfeiffer-Walsh protocol (BioBalance)
in which we have been trained.

Dr.Walsh has had clinical experience with a massive number of patients and has analysed their biochemistry. He has worked with 10,000 patients with behaviour and ADHD issues, 3,500 people with Schizophrenia, 3,200 people with depression, and 1,500 Bipolar disorder patients.

Researchers such as Abram Hoffer, Dr.Walsh, Dr.Stuckey, Brett Lambert, Carl Pfeiffer and Dr.Mensah [2] have shown repeatedly that success is possible in treating mental illnesses using personalised high doses of selected nutritional supplements as they bring about epigenetic changes.

In a 12 month Australian study,[3] 567 patients with a range of serious conditions (Autism Spectrum, ADHD, Asperger’s Syndrome, Anxiety, Bipolar Disorder, Depression, Schizophrenia and Obsessive Compulsive Disorder), were treated with a personalised nutritional therapy. It resulted in 64% having improvement (45% had major improvement, 19% partial improvement, and 14% nil improvement).

The study used 3 nominated quality of life outcomes to measure these improvements though hospital admission was substantially lower in the treatment group as well, and 22% were able to reduce their prescription medication. In the comparison group not receiving the equivalent nutrient treatment 19% had a major improvement, 19% partial improvement, and 62% noted nil improvement.

The study highlighted that most patients with the best results used a combination of both pharmacological and nutritional interventions. Over time the amount of medication is often reduced, but this is only after the nutrient therapy has had time to work.

A 2018 paper [4] found people who suffer from mood and anxiety problems may benefit from improved nutritional status achieved with targeted nutritional supplements. Their year-long trial had 16,020 participants and found 49.2% (n = 7878) who reported any level of depression or anxiety at baseline improved at follow-up. Of those who reported severe/extreme depression at baseline (n = 829), 97.2% reported improvement after one year. Regression analyses revealed a significant association of improvement in depression and anxiety with higher vitamin D status (>100 nmol/L) and more strenuous physical activity. Researchers in 2019 did a a meta-analysis of randomized controlled trials and found that "vitamin D supplementation favourably impacts depression ratings in major depression. The effect sizes noted were in the moderate range for this outcome.”[4]

Another recent study [5] examining depression in mice demonstrated that 6 weeks of a Magnesium deficient diet induced depressive symptoms in mice, which was associated with changes in gut microbiota and neuroinflammatory marker hippocampal IL-6.

As Dr.Walsh says: “After clinical experience with thousands of mental health patients, I was surprised to learn that nutrient overloads usually cause more mischief than deficiencies. This explains why most multivitamin/mineral products are ineffective for mentally ill patients and can cause more harm than good. Patients with an overload of copper, methionine, folic acid or iron are likely to deteriorate if they take supplements containing these nutrients. In most cases, mentally ill persons cannot become well using a special diet or indiscriminately stuffing themselves with amino acids, vitamins and minerals.

“The challenge is to carefully identify the specific nutrient overloads and deficiencies possessed by an individual and to provide treatments that normalise blood and brain levels of these chemicals with rifle-shot precision. This is the essence of biochemical therapy.” (Nutrient Power: Heal your biochemistry and heal your brain”, William Walsh, PhD)

• Enhancement of antidepressant action of fluoxetine by folic acid: a randomised placebo control trial. Journal of Affective Disorders, Nov 2000, pp121—130

• 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”

• Enhancement of recovery from mental illness with L-methylfolate supplementation.  Perspective Psychiatric Care: 2018 April 54[2], pp331—334

• Folate in unipolar depressive illness, a systematic review and meta-analysis.  J Psychopharmacology: 2018. April:32 [4] pp377--384

• Pyridoxine and the premenstrual syndrome: a randomised crossover trial.  British Journal of General Practice. 1989: 39[326] 364—368
  Conclusion: There was a statistically significant benefit  in depression, irritability and tiredness in the treated group.

• Anti-depressive 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

• B Complex Vitamin Patterns in Geriatric and Young Adult In patients with Major Depression. Journal of American Geriatrics Society: March 1991: Vol 39 issue 3
  Conclusion: A poorer status of B Vitamins is present in major depression.

•  Zinc in CNS: From Molecules to Behaviour. “Biofactors” 2012 Mar 31
  Covered role of zinc in transcription factors, gene regulation, transporters, neurogenesis, neurotransmission, AD, Depression, Stroke, Epilepsy.  This paper alone had 81 references

• Vitamin D supplementation ameliorates severity of generalized anxiety disorder (GAD), Journal of Metabolic Brain Disease (2019), "Augmenting standard care with vitamin D resulted in significant improvement in symptoms, an increase in serotonin levels, and a reduction in neopterin levels"

• 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 in Depression, A Meta-Analysis: Biological Psychiatry: 2013, Dec15, pp872—878
  Considered 17 studies in 1643 patients. Concluded:
  - 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.

• 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”

• Magnesium and depression: A Systematic Review. Nutritional Neuroscience, Vol 16, 2013.
  21 cross sectional studies, 3 interventional studies, one prospective trial. “A higher dietary intake of magnesium is associated with lower depression symptoms.”

• High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression Human Psychopharmacology, July 20222

  Double-blind study found Vitamin B6 reduced anxiety and depression, as well as increased surround suppression of visual contrast detection. Vitamin B12 supplementation produced changes in anxiety and visual processing. Vitamins B6 and B12 are involved in metabolic processes that decrease neural excitation and increase inhibition.

• Meta Analysis of studies involving 10,951 individuals found "The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications."[6]