Copyright © 2008, Dr. Raymond J. Pataracchia B.Sc., N.D.
The Naturopathic Medical Research Clinic
20 Eglinton Avenue East, Suite #441, Toronto, Ontario, M4P 1A9 
(416) 944-8824 (T); (647) 439-1551 (F);  
Biochemical imbalances that compromise neurotransmitter production, availability, regulation, and signal transduction are directly or indirectly affected by protein intake, sugar imbalance, zinc availability, heavy metal toxicity, methylation status, B6 loss, vitamin C deficiency, thyroid/adrenal imbalance, essential fatty acid deficiency, and food allergies.
Most neurotransmitters are made from amino acids obtained from the proteins in our diet. Many psychiatric patients improve when they start eating regular protein meals. 40% protein, 40% carbohydrate, and 20% fat with every meal is a good guideline to follow.
Without adequate B6 and zinc, neurotransmitter manufacturing is compromised. B6 and zinc are involved in basic protein manufacturing processes of transamination and transcription, respectively.
In the late 1960’s Dr. Abram Hoffer, Dr. Carl Pfeiffer M.D., Ph.D., and others discovered a common psychiatric imbalance – pyroluria - that depleted vitamin B6 and zinc. B6 and zinc deficiency is associated with acne, white spots on nails, joint problems, poor dream recall, and stress intolerance.
Zinc is probably the most important mineral for brain function as it is involved in over 200 enzyme pathways. Supplementation of high doses of zinc for prolonged periods however, can aggravate brain function because zinc can initiate heavy metal release. A good percentage of the mentally ill patients are toxic with copper, mercury, lead, aluminum, or cadmium.
Zinc excess can deplete copper and, if your copper stores are already depleted, you can acquire copper deficiency symptoms. Without copper, mood and motivation can be disrupted because copper is needed for catecholamine neurotransmitter production. Other common copper deficiency symptoms include frequent bacterial infections, bleeding gums, and easy bruising.
Conversely, copper can be detrimental in excess because it can act as a brain stimulant. Copper toxicity is very common in schizophrenia, mood, and behavior disorders. Overproduction of dopamine can be a causative factor of psychosis.
Dopamine over-stimulation was deemed to be the classic presentation of schizophrenia. This “dopamine hypothesis” was disputed and it is now accepted that a diverse imbalanced brain neurotransmitter profile exists in schizophrenia. Major sedatives are used to treat schizophrenia conventionally. Major sedatives are also called tranquilizers, neuroleptics, or anti-psychotics. All atypical first or second generation neuroleptics have an affinity for dopamine receptors.
Excess amounts of copper can come from external sources including the food chain, dental fillings/appliances, cigarettes, water pipes, and birth control pill use. Animal feed and plant sprays (in vegetarian diets) infiltrate our food supply. Hard water is another source of copper but it is especially a problem when water softeners are used because these can leach the copper out. Since WWII, copper water pipes began to be used universally in schools, homes, and offices. The birth control pill (estrogen) was also introduced universally post-WWII. Estrogen elevates copper and the copper can pass in utero to offspring. Often the copper is retained post-partum and copper toxicity is therefore important to rule out in post-partum depression and post-partum psychosis.
Many people with copper toxicity retain copper because they have weak thyroid function. Copper is also known to weaken thyroid function. Copper toxic patients therefore can not easily rid copper without first having intact and healthy thyroid function. Thyroid function in turn, typically can not be optimized without also optimizing adrenal function because these glands work together by negative feedback.
The route of removal of copper is mainly via liver à gall bladder à bowel. Often you can not efficiently remove heavy metals without first ensuring that the digestive tract is intact and healthy.
Copper is essential for development. Right brain copper dominance is associated with visuo-spatial creativity versus left brain dominance with verbal-analytical-intellectual thinking. Learning disabilities are often associated with copper elevations because the curriculum and testing is focused on verbal and analytical skills.
Mobilizing heavy metals is easy to do and can aggravate patients unless their body is healthy and ready to remove it. If you have a heavy metal, it is probably being retained in part because elimination routes are not intact and healthy. Elimination routes typically involve the liver, kidney, bowel, and lymphatic system. Heavy metal removal is essential to regain intact and healthy brain function.
In 2005, industry as a whole in the US (~23,500 U.S. facilities) released about 4.34 billion pounds of some 89,300 chemicals into the atmosphere. This represents an increase of 117 million pounds of chemicals over the previous year.
Lead is toxic to patients with behavior disturbances, mood disorders, insomnia, learning disability, and immune compromise. Lead accumulates in the body and persists in the environment for long periods of time. In the United States, in 2005, lead released compounds totaled about 469 million pounds.
Mercury is toxic and commonly found in patients with schizophrenia, mood, and behavior disorders, nervous irritability, and memory decline. In the United States, in 2005, mercury released into the environment totaled about 4.4 million pounds. Mercury is also found in dental fillings, fluorescents, some vaccines, thermometers, fish, animals, and plants.
Oxalate buildup is found to be associated with heavy metal deposition. Oxalates bind to copper, mercury, and iron, and, trap them in the tissues (brain, etc) and prevent their release. Lowering oxalate buildup can be important in the process of heavy metal removal. Oxalates found in the gastro-intestinal tract bind to zinc, magnesium, and calcium. High oxalates in the urine are associated with mal-absorption syndromes.
Aluminum toxicity is also not uncommon in mental health problems. Aluminum can be toxic in patients with digestive pathologies, mood and behavior disorders. Aluminum sources include aluminum cookware (especially when you heat and deglaze with an acid such as vinegar or wine), drinking boxes, processed cheese, deodorants, and drinking water.
Drinking 2L of water per day is good for an average adult. This helps to keep bowel contents hydrated and allow for an efficient route of elimination of toxins, including heavy metals.
Bad gut bacteria flourish when heavy metals are present. Removing the metal is therefore an important step in resolving fungal and parasitic imbalances that often disrupt brain function.  
“Minerals in Health and Disease” is an excellent book with heavy metal monographs that explain associated symptoms, heavy metal sources, and incurred biochemical imbalances. This book reviews all clinically relevant elements and can be used as a desk top reference for practitioners and patients. This book was published in 2005 by Dr.’s K-G Wenzel and R.J. Pataracchia.  
Vitamin B3 and C are physiological antagonists of copper. Copper is a cofactor in dopamine production. A copper-overload metabolism can benefit from vitamin B3 and C by diminishing, in a regulated fashion, dopamine overproduction. This is important because a portion of schizophrenics have dopamine over-stimulation of the frontal cortex. Reduced copper availability can be important for mood and behavior disorders because dopamine can down-regulate the serotonin feel-good neurotransmitter system.
The lowest effective dose of vitamin B3 should be used in schizophrenia. The vitamin B3 protocol is typically, though not exclusively, provided as an adjunct to neuroleptic medication with optimal dosing strategy (Pataracchia RJ: Optimal Dosing in Schizophrenia. J Orthomol Med, 2005; 20(2): 93-99).
Vitamin B3 comes in 3 main forms: as pure niacin, niacinamide, or inositol hexaniacinate. The latter two forms are non-flushing. Niacin in doses up to 6 grams per day has been used as an effective cholesterol lowering agent. Inositol hexaniacinate retains some of the vascular and cholesterol lowering benefits of niacin and it has been FDA approved for intermittent claudication. All types of vitamin B3 have been used effectively by orthomolecular practitioners in the treatment of schizophrenia. NIASPAN® is a recent prescription medication used for its ability to raise ‘good’ HDL cholesterol lower ‘bad’ LDL cholesterol and triglycerides. NIASPAN® is an extended release form of niacin.
For $40 a month, a schizophrenic could obtain a monthly supply of vitamin B3 from a local nutrition store. If all schizophrenics were put on vitamin B3 alone at onset, we would have less homeless people in the street and less certifiable inmates in our jails.
The first double blind in psychiatry using vitamin B3 in neuroleptic-naïve schizophrenia was done in the 1950’s (Hoffer A, Osmond H, Callbeck MJ, Kahan, I: Treatment of schizophrenia with nicotinic acid and nicotinamide. Journal of Clinical and Experimental Psychopathology & Quarterly Review of Psychiatry and Neurology, 1957(Jun); 18(2): 131-158).
The prognosis of orthomolecular treatment for neuroleptic-naïve schizophrenia has been determined in six double blind studies in the 1950’s and 1960’s and, in 1000 of clinical cases treated by Dr. Abram Hoffer and other ND’s, MD’s, and practitioners (Natural Medicine J, 1999, p.14-15; Hoffer A: Vitamin B-3 and Schizophrenia: Discovery, Recovery, Controversy. Kingston, ON, Canada. Quarry Press. 1998).
Later clinical trials conducted by the Psychiatric Association Task Force failed to repeat these results. Their study methods were largely of insufficient duration, with insufficient doses of vitamin B3, with dissimilar patient cohorts (theirs were more chronic), and without the implementation of optimal neuroleptic dosing (Pataracchia RJ: Optimal Dosing in Schizophrenia. J Orthomol Med, 2005; 20(2): 93-99; Hoffer A: Healing Schizophrenia: complementary vitamin & drug treatments. Toronto, Ontario. CCNM Press. 2004).
In the lifetime of every schizophrenic patient, the government calculates an economic loss of about $2,000,000 to account for patient services and lost income, etc.
The goal of the Canadian Alliance for Research on Schizophrenia (CAROS) is to improve the current health model of psychiatric care. To meet this goal, research funding should be organized to monitor the outcome of existing complementary therapies. This would entail reproducing the original work of Hoffer with a current orthomolecular protocol on neuroleptic-naïve schizophrenic patients.    
Many neuroleptic side effects are associated with decompensation – when neurotransmitter metabolism is unable to compensate for the synthetic changes induced at the receptor level (e.g. receptor number changes).
Neurotransmitter deficiency syndromes are common in central nervous system disorders (psychosis, mood dysfunction, etc.).
Depression is used here as a classic example of a neurotransmitter deficiency syndrome. Based on current research, mixed neurotransmitter theory states that depression (including bipolar depression) is caused by reduced numbers of the brain neurotransmitters serotonin and/or dopamine, norepinephrine, and epinephrine (the later 3 are catecholamines). This is a neurotransmitter deficiency problem. Serotonin and the catecholamines are master neurotransmitters. SSRI’s, NRI’s, and SNRI’s can increase the synaptic availability of one or both neurotransmitter pathways.
SSRI’s, NRI’s, and SNRI’s trick brain cells into complacency by making them ‘think’ they have neurotransmitter when they don’t and, inadvertently, neuronal tracts shut down neurotransmitter making processes -- processes that are already weakened due to the multi-factorial etiology of mood dysfunction.
SSRI’s, NRI’s, and SNRI’s depend on brain cells having enough neurotransmitter to do the job (Delgado PL, Moreno, FA. Role of norepinephrine in depression. J Clin Psychiatry. 2000; 61 Suppl 1:5-12). Conventional medication does not act to increase the total number of neurotransmitters and, in an attempt to increase synaptic levels - by keeping neurotransmitters in the cleft - there is further neurotransmitter depletion. As these drugs increase the synaptic concentration of neurotransmitters, there is an opposing natural breakdown of neurotransmitters mediated by MAO and COMT homeostatic regulation. The end result is a further depletion of already low neurotransmitter levels! This is why, in clinical practice, we see so many psychotropic drugs that either quit working or do not work at all and in such cases, the MD either, changes the medication, increase its dosage, or adds another drug.
The term “Orthomolecular” simply means using the correct molecules to address disease. This is a facet of nutritional medicine. Over the past 60 years, dedicated orthomolecular practitioners and investigators have developed protocols that are deemed orthomolecular in origin.
In the early 1950’s one of the most significant contributions to mental health evolved as Dr. Abram Hoffer M.D., Ph.D. and Dr. Humphry Osmond M.R.C.P., D.P.M. theorized a vital link between niacin (B-3) deficiency and schizophrenia – the adrenochrome hypothesis - the first biochemical theory of schizophrenia presented in psychiatry.
The digestive tract of many psychiatric patients is compromised and they may require intensive rebuilding at a structural and functional level.
Mal-absorption is very common in schizophrenia, mood, and behavior disorders. Main causes of mal-absorption include food allergies (especially dairy/gluten/eggs/soy/nuts), heavy metal toxicity, low thyroid function, dehydration, low adrenal function, parasitic infiltration, low stomach acid, and gastro-intestinal pathology.
Many hormonal cyclic changes in women are alleviated when thyroid and adrenal function are restored along with heavy metals elimination. Cyclic depressions, postpartum or otherwise, are often linked to copper and zinc imbalances. Copper dominant metabolisms in females are highly estrogen dominant. Zinc is related to progesterone metabolism.
The thyroid is responsible for neurotransmitter regulation in the brain. ‘Brain hypothyroidism’ is becoming a clearly identifiable syndrome due to the advancement of recent proteomic studies. Schizophrenics and mood dysfunction patients have the biggest compromise in the ability to transport inactive thyroid hormone T4 into the brain.
It is said ‘if you have energy, you can’t be depressed’. Energy levels of most psychiatric patients are severely depleted. Energy improvements are an important sign of treatment success. Low energy can be due to, among other things, low thyroid, low adrenal, poor dietary intake, vitamin B3 deficiency, food allergies, inadequate methylation, and dysglycemia.  
Many patients do not eat 3 meals a day and if they do, they eat mainly carbohydrates. Carbohydrate dominant North American diets release glucose to the bloodstream quickly. This influx of glucose is followed by a sharp decline. The sharper the decline, the greater the effect on brain cells that demand a substantial amount of glucose to function. About 20% of the total blood volume circulates in the brain although it represents 2% of the body weight. The body vents so much blood to the brain because of its high metabolic rate and its high demand for glucose.    
A support network is encouraged for all patients with schizophrenia, mood, and behavior disorders. This includes family, friends, social workers, counselors, psychologists, general practitioners, psychiatrists, and other naturopathic and orthomolecular doctors. Many government-funded social work programs are available to monitor symptoms and help maximize quality of life.  
Evidence-based medicine is the best that medicine can offer. Protocols should be based on a wide scope of research involving case studies, database research, and longitudinal research on quality of life (QOL) parameters.
QOL criteria should be harsh and include recovery definition that involves patients returning to a level of functioning that allows them to be symptom free, get along well with family, friends and society, and pay taxes or return to a previous level of vocation.
Naturopathic medicine is an umbrella term for medical alternatives including clinical nutrition and supplementation, botanical medicine, etc.
Naturopathic services are covered by most health insurance policies with extended or supplemental health care.
Food-allergen responses are seen in schizophrenia, mood, and behavior disorders and, can be of such magnitude that they provoke severe mental symptoms within minutes of ingesting an intolerant food. Often the pulse races during such episodes and this can be a good indicator. Symptoms such as full blown psychosis, severe negative thought rumination, extreme compulsivity, and criminal behavior are not uncommon in this subgroup. Food intolerance responses that severely effect mental ability are more appropriately called brain or cerebral allergies. Other food intolerances are more subtle in their physiological reaction and the allergen has a milder influence on brain chemistry: symptoms here include fatigue, irritability, headache, grumpiness, weakness, mild insomnia, and digestive upset. 
Most vitamins are dosed with meals. Conversely, herbs or botanicals are usually dosed away from meals for increased absorption.
Magnesium deficiency is extremely common. Magnesium deficiency is associated with anxiety, sleep disturbance (problems staying asleep), clumsiness (dyspraxia), depression, muscle cramps/tension of skeletal muscles, blood pressure changes, and bladder enuresis. Too much fiber (contains phytates), and too few vegetables (magnesium is the central ion in chlorophyll) will deplete magnesium.
Iron deficiency is also common. Iron deficiency symptoms include fatigue, poor attention & cognition, difficulty swallowing pills, and sallow complexion. Copper toxic patients often exhibit iron deficiency because these minerals are physiologically antagonistic. Iron deficiency is more common in women due to menstrual blood iron loss.