Commentary on Nutritional Treatment of Mental Disorders

from Willam Walsh, Ph.D., Senior Scientist, Walsh Research Institute

(The following information is taken from Dr. William Walsh’s discussion on Safe Harbor’s “Integrative Psychiatry” email list for professionals. To preserve Dr. Walsh’s wealth of information, we have posted his comments here, with the notation of added commentary [with the date] as discussion goes on.)

Alzheimer’s Disease
Amino Acids
Antidepressants and Cancer
Asperger’s Syndrome
Bipolar Disorder
Celiac Disease
Coral Calcium
Crime &Violence
Essential Fatty Acids

Fetal Alcohol Syndrome
Hair Analysis
Head Injury
Learning Disabilities

Metabolic Types
Nutrient Therapy
Obsessive Compulsive Disorder (OCD)
Oxidative Stress
Placebo effect
Post Partum Depression
Psychiatric Medications
Pyrrole Disorder

Womb Trauma



We’ve treated more than 6,000 children & adults diagnosed with ADHD, ADD, or LD. There is a great variety of biochemical phenotypes within these broad classifications & completely different treatment approaches are needed. About 60% of these patients are high dopamine, low choline persons and thrive on choline-enhancing supplements. (10 Jan, 2003)

After testing & treating more than 6,000 ADHD patients, I’ve learned that most of these patients exhibit chemical imbalances which impact neurotransmitter concentrations and brain function. In this sense, ADHD actually is a brain disorder. In countless cases, we have seen the ADHD disappear after treatment for the imbalances. Also, there clearly is a strong genetic component to ADHD. To me, this is good news, since genetic differences are usually expressed as chemical differences…. and chemistry can be adjusted. Just because ADHD is a brain disorder does not mean that drug therapy is indicated. In my experience, more than 80% of ADHD patients respond beautifully to nutrient therapy aimed at normalizing brain chemistry & body chemistry. ADHD usually involves disturbed brain chemistry & imperfect brain function. However, drugs are not the answer in most cases.

We have seen more than 5,700 children diagnosed with ADD/ADHD and most of them were mis-diagnosed & didn’t have it at all. Hundreds of these kids were extremely bright with terrific concentration for things they cared about. The major problems they experienced were boredom (number 1) and authority issues. Quite a few had OCD and oppositional/defiant tendencies which have nothing to do with ADD/ADHD. (6 Jan, 2003)

Is there a simple combination that’s generally effective for ADHD?

Not really, since there are several phenotypes comprising ADHD and the treatments may be completely different and in some cases opposite. (13 Jan, 2003)

A classic component of ADHD is impulsivity. Impulsivity leads to accidents & injuries. It would be very surprising if an ADHD population didn’t have a higher incidence of injuries. To complicate things, bumps on the head resulting in brain trauma can worsen ADHD. (Feb 10, 2003)

We’ve known for more than 20 years that the metallothionein protein system does not perform well in most ADHD patients. About 68% of them exhibit very poor control of Cu & Zn, based on lab data from more than 6,000 patients diagnosed with ADD/ADHD. Autism is different in that about 90% of patients exhibit Cu/Zn imbalances that are generally much more severe than in ADHD.

For several months, we have extended our metallothionein-promotion protocol to ADHD, behavior, depression, and schizophrenic patients who exhibit Cu/Zn imbalance. The informal results so far are very encouraging. However, we’ve not yet done a formal outcome study for these populations, and thus have no statistics yet.

We are considering applying MT-Promotion to Alzheimers & Parkinsons patients in the near future. Both disorders involve serious oxidative stress and abnormal trace metal levels. In addition, recent research has revealed a striking metallothionein deficiency in the brains of Alzheimers patients. (Feb 25, 2003)

The two primary ingredients for paranoid schizophrenia are (a) elevated copper levels and (b) over-methylation. In our database of more than 6,000 ADHD kids, 68% have elevated copper in blood serum. Since most ADHD individuals have one of the two SZ prerequisites, it would be a surprise if the SZ incidence were not relatively high in the ADHD population. Fortunately, very few ADHD kids become schizophrenic. (March 10, 2003)

ADHD is a real condition, but grossly overdiagnosed in the USA. NIMH estimates that the incidence is about 4.75%. However, there are states like Utah and Virginia in which more than 20% of all children are receiving Ritalin or other stimulant medication. Many parents prefer a diagnosis of ADHD to having to focus on family dynamics that might be a contributing factor…… the prospect of a “magic bullet” drug is very seductive. I agree that most children labelled ADHD don’t really have it! (March 25, 2003)

Overdiagnosis of ADHD. The incidence of ADHD has been determined by NIMH to be approximately 4.75%. However, there are many areas of the country (including entire states) where more than 20% of school children are taking Ritalin or other stimulant medication for ADHD. Many children who simply have behavior problems are misdiagnosed with ADHD.

Alzheimer’s Disease

It is becoming increasingly clear that Alzheimer’s Disease is a condition of oxidative stress. Niacin has good antioxidant properties, thus it protects against AD. Many other antioxidant nutrients also protect against AD.

Amino Acids

If a person is low across the board in amino acids, supplementation with mixed AA’s could be beneficial. However, if an individual is known to be deficient in one or two AA’s, it might be better to supplement these apart from each other and from food.

There is a large volume of published literature that indicates competition between amino acids in passage through the intestinal mucosa….. the highest levels of absorption are achieved in the absence of other AA’s.

Genetic differences in persons can result in great variations in nutrient requirements. If a genetic tendency for low AA levels is present, it might be impossible to eat enough food to supply what’s needed. (Aug 18, 2003)


We’ve treated many anorexics and find most of them to be undermethylated and zinc deficient. Our standard treatment regimes for these two imbalances are usually very successful, especially in concert with quality counseling. (July 22, 2003)

Antidepressants and Cancer

The FDA requires that all psychiatric medications be tested in animal studies for possible enhanced cancer risk. These are usually done with rodents. However, medications are often approved even if the medication causes cancer in rats. The box score on three drugs is as follows:

Paxil: Male rats exhibited increased incidence of lymphoreticular tumors & cell sarcomas.

Prozac: No evidence of carcinogenesis.

Zyprexa: Mammary gland adenomas and adenocarcinomas found in rats, suggesting possible increased risk of breast cancer. Increased prolactin levels which has been associated with increased risk of hormonal cancers….breast, ovarian, etc. Also one of two studies indicated increased incidence of liver cancer. (Feb 24, 2003)

Asperger’s Syndrome

Asperger’s Syndrome. True Aspergers is a striking and disabling disorderwhich often involves “Rainman-Type” abilities and terrible social skills. We’re now seeing that many bright kids with poor social skills (often called “nerds”) are inappropriately labeled with this autism-spectrum disorder.

One of the “treatments of choice” for autism is Risperdal, and it is given freely to tens of thousands of children under the age of 5 years. I’m especially concerned about its frequent use for autistics under the age of 3, when their little brains are still developing and maturing. There are legitimate concerns about Risperdal for teens, but the situation in autism is even more alarming.


Autism involves a powerful genetic component, so the real question is whether these genetically autism-prone children are hypersensitive to mercury. Recent research has shown that autistics are severely depleted in metallothionein, a protein needed for the body & brain to cope with mercury & other toxic metals. There is a definite possibility that a mercury preservative in a vaccine could harm such a child.

The concordance of autism in identical twins is 60%. The recipe for autism appears to be (1) a genetic predisposition plus (2) an environmental insult. We’ve had a set of identical twins at our clinic in which one was a productive, high-functioning adult and the sibling was a mute autistic with wild mood swings who was institutionalized. (9 Jan, 2003)

We have seen more than 2,000 autism-spectrum children…. and agree completely about the value of sensory imputs. I’ve become convinced that the primary problem in autism is not so much a damaged brain, but rather a brain that has not completely matured. PT, OT, etc shower the brain with stimuli which enhance development of new neuronal connections which are especially needed in the hippocampus & amygdala of autistics. Biochemical therapies which normalize the pruning, development, and growth inhibition processes in the brain are also vital. (Feb 3, 2003)

My clinic has seen more than 2,500 autism-spectrum children and I’m convinced that most of these kids have above average intelligence. We’ve seen many who were labeled “retarded” with IQ scores below 50….. who later had IQ scores above 120 following therapies such as CF/GF diets, metallothionein-promotion, normalization of the G.I. tract, behavioral therapies, etc. The problem is with the test methods, not the innate intelligence of the children.

Unfortunately, DSM-IV itself is perpetuating this myth! Page 67 of DSM-IV, Fourth Edition, Section 299.00 Autistic Disorder ……states the following: “In most cases there is an associated diagnosis of mental retardation, commonly in the moderate range (IQ 35-50). Approximately 75% of children with Autistic Disorder function at a retarded level.”

DSM-IV should not give currency to the high incidence of inappropriate diagnoses of retardation nor to incorrect IQ scores for these difficult-to-test children.

Most traditional autism experts believe that autism is “incurable” and that the associated “mental retardation” cannot be reversed. This is so wrong!!! There are tens of thousands of families that despair upon hearing this pronouncement….. and just give up! Please continue your efforts to get the truth out — It could make a big difference in the life of many of these children. (Feb 20, 2003)

For years, autism was the most difficult population for our clinic to work with, compared to persons diagnosed with behavior disorders, ADHD, depression, anxiety disorders, bipolar, or schizophrenia. However, this has changed following our discovery of the central importance of the metallothionein protein in ASD and development of metallothionein-promotion therapy

At Dr. Rimland’s request, we carried out a small outcome study about 6 months ago which measured the impact of MT-Promotion for 46 patients. I presented the results at a D.A.N. “Think Tank” at which Dr. Amy Holmes’ outcome results for MT-Promotion were presented by Stephanie Cave. There is no doubt that autism outcomes are far better at the Pfeiffer Center since MT-Promotion. Our group of 46 patients ranged from ages 3 to 18. A few of the families were unable to achieve compliance & a couple others gave up after a couple of days. More than 85% of the 41 families that achieved compliance reported impressive gains in cognition, speech, and socialization. More than 20% reported irritability and sleep problems, usually coincident with improved cognition or speech. Only 10% of the compliant families reported zero progress.

We found the greatest improvements were obtained with younger children, including a significant number whose autism was rapidly disappearing. However, our data showed definite (but slower) improvement in the autistic teenagers. A few examples: A mother from New Hampshire reported that her mute 17 year old daughter began speaking after 6 weeks of MT Promotion. A 13 year old girl from Virginia began talking after the first month. A 4 year old in Illinois who could only say a few words…. began speaking in complex sentences after 5 days of MT-Promotion. A socially isolated 7 yr old son of a doctor became very friendly & communicative during the first month. We now have many dozens of such outcomes.

Dr. Holmes’ population was much younger than ours, and her results indicated even higher efficacy than we had achieved. It was nice to have efficacy confirmed by an independent third party. Early intervention is essential, but benefits are possible for the older children also.

We are organizing a much larger and more scientific outcome study which should begin in a couple weeks.

Children between 2-4 years of age generally respond within a week or two. Since their little brains are still actively engaged in the brain-cell pruning, development, and growth inhibition processes….. the impact can be much greater. Families of ASD persons over the age of 20 have reported nice partial improvement after our treatment, but we’ve yet to experience a case in which a 20+ year old became completely free of autism symptoms.

My guess is that once MT normalization is attained, a simplified maintenance therapy can be implemented. Also there is a very good chance that CF/GF diets, yeast therapies, digestive enzymes, etc, will become unnecessary at that time. However, at present we recommend these therapies be continued….. just in case the genetically-weak MT system cannot be fully normalized. We should know a lot more within a year or so. (Feb 22, 2003)

I believe this can all be explained by the fact that estrogen and progesterone enhance metallothionein, whereas testosterone suppresses it. Therefore, given the same genetic tendency for weak metallothionein function, females would be more protected against environmental stresses which can trigger autism as they would have more MT to combat stresses.

Also, if the environmental triggers of autism have increased in recent years, you would expect the disparity in male/female incidence to drop. In essence each autism-prone child has a threshold with respect to environmental insults. In boys the threshold in lower. As the environment worsens, we get higher up on the statistical bell curve in both males and females & the disparity should moderate.

In my opinion, a wide variety of environmental triggers can trigger autism, including oxidative stress (e.g., mercury), immune crises (e.g. multiple vaccines or serious illness), severe emotional or physical stress, etc. It is very possible that the stress of circumcision could cripple metallothionein & impair brain development, at least temporarily. I’m not aware of peer-reviewed evidence of differences in autism incidence between circumcised and non-circumcised children.

Stresses of all kinds deplete metallothionein….. In persons without metal-metabolism disorders, the stress automatically induces production of more metallothionein. In autism, the metallothionein system has gone AWOL. (May 17, 2003)

There is no longer any doubt that autism results from a combination of genetic predisposition and environmental factors. Identical twins reared apart have an autism concordance of 60%…… This shows a powerful genetic influence, but the fact that the concordance isn’t 100% clearly shows that environment factors are also involved. I once tested a pair of identical twins (age 38) in which one was a successful professional writer & the other was an institutionalized severely-autistic mute young man who needed to be physically restrained. They were quite different from the day they were born.

In our database of 2,500 autistics, about 30% of the families reported autism symptoms from birth with the remaining 70% of autistics exhibiting “regressive autism” with typical onset between the ages of 16 to 22 months.

Yes, the ratio of boys/girls has declined in the past 6 decades & the causes for the lessened maleness are certainly environmental. Also, there is mounting evidence that the overall incidence of autism has increased rapidly since 1990….. Again, environmental factors must be responsible. There is great public debate over the possible role of vaccinations or mercury preservatives in the vaccines. My personal opinion is that a wide variety of environmental stresses and toxins can contribute to the onset of autism. Your suggestion that circumcision and infant separation may be among them….. appears quite plausible. (June 9, 2003)

At the request of an autism parent group about 6 months ago, I checked out iron levels in our population of 3,000 autism patients. We found that autistic children exhibited higher serum iron levels than controls (non-autistic, healthy children). However, all of the differences occurred in about 1/3 of the autism population with the other 2/3 resembling the controls. The high iron kids were extremely high, the rest of the autistics were quite normal, and there was little or no “middle ground”. It appears that a segment of the autism population has very abnormal iron metabolism (and abnormal ceruloplasmin).

My data essentially confirms the findings of the M.H. article. Iron free radicals (ions) represent the primary oxidative stress in the brain of most humans. Autism involves oxidative stress during early brain development. In theory, elevated iron in the brain could result in autism. A genetic inability to regulate iron might be causative in 1/3 of autism cases. (Sep 15, 2003)

We are engaged in a foundation-funded study measuring estrogen, progesterone, testosterone, and other hormones in autistic subjects and age/gender matched controls. We expect to have the first data in a few weeks.

This is an area of interest since (a) there have been several reliable reports of efficacy using progesterone cream for autistics, and (b) progesterone and estrogen promote synthesis of metallothionein & testosterone inhibits MT. If autistics exhibit consistently abnormal levels, we plan to develop a hormone-normalizing therapy. (Oct 29, 2003)

After studying 3,200 autism-spectrum children & adults at our clinic, I am convinced that autism is caused by a genetic inability to cope with oxidative stress, involving weak functioning of the neuroprotective metallothionein/glutathione system. This condition results in inability to regulate Cu and Zn, hypersensitivity to metal toxics, extremely poor immune function & hypersensitivity to vaccines, yeast overgrowth, inability to break down casein & gluten, and worst of all….. incomplete maturation of brain cells and synaptic connections…. especially in hippocampus, amygdala, Purkinje cells, inferior olives, and pineal gland.

There are many environmental insults which can trigger autism in a genetically predisposed child. Mercury is just one of the many possibilities. Mercury (Thimerosal) is an unnecessary health risk and should be banned forever. However, I expect that elimination of mercury from infant vaccines will not stop the epidemic in autism cases, because of the other environmental triggers which remain.

I once met a health-conscious mother who had been hypervigilant prior to her pregnancy. She had avoided all amalgams & had her husband’s amalgams removed 2 years before conception. Her diet was exemplary before and during the pregnancy, and she & her husband carefully avoided potential environmental insults including vaccines. She was crushed to discover that her baby exhibited severe autism soon after birth. She stated that she was amazed and horrified that this had happened. A little digging revealed that she had a severe infection during the 7th and 8th months of gestation. This apparently was sufficient to cripple the MT/GSH system during a critical phase of brain development. A very sad case.

Our Center’s autism outcomes have greatly improved since beginning metallothionein-promotion therapy. It’s no longer a surprise when a young autistic child becomes free of all traces of autism. We are a public charity and have made this protocol available to more than 100 doctors, many of whom report treatment successes. MT-Promotion must be done very carefully to avoid zinc depletion which can result in temporary worsening of behavior, stimming, enuresis, etc.

We are beginning a funded study which we expect will provide strong evidence of severe oxidative stress/damage in 100% of autism subjects. We’ll be measuring isoprostanes, levuglandins, and pyrrole adducts, etc., in autistics and age/gender controls. (Nov 3, 2003)

ASD usually involves multple chemical imbalances, including….

1. Metallothionein Deficiency
2. Extreme Oxidative Stress
3. Undermethylation (more than 50% of ASD)
4. Overmethylation (about 10-15 % of ASD)
5. Maldigestion and/or malabsorption
6. Elevated GSSH/GSH ratio
7. Elevated Cu/Zn ratio….. etc.

Most ASD individuals exhibit a genetic tendency for undermethylation. A relative few exhibit a genetic tendency for overmethylation. However, it’s important to consider the impact of (1) inadequate diet and (2) inefficient digestion/absorption which is present in most of these individuals. Regardless of innate tendency for methylation, many ASD individuals are starved for all components of the SAM cycle and MTHF. In other words, they are deficient (across the board) in most nutrients. Two of the greatest deficiencies in ASD appear to be B-12 and methionine. B-12 is one of the most difficult vitamins to assimilate in healthy persons, and the situation is much worse if significant G.I. tract problems exist. The principal source of methyl groups is methionine from dietary protein. However, most ASD children receive inadequate amounts of dietary protein AND are very inefficient in cleaving the complex proteins into the amino acid units to enable absorption. Folic acid is also in a deficiency state in many ASD children…… including children with a genetic tendency for overmethylation and folic acid overload.

Supplementation of any nutrients which are in a deficiency state leads to better health and overall functioning. However, care must be taken to limit the supplementation of nutrients which tend toward overload (for genetic reasons).

Therefore supplementation of folic acid and B-12 can help an undermethylated ASD child who is deficient in these nutrients. However, these same children TEND to develop excessive levels of folates…. and vigilance is needed to avoid going beyond correctioon of the folate deficiency.

The same is true with respect to supplementing methionine to malabsorbing persons with a genetic tendency for overmethylation. A patient can benefit from overcoming the deficiency, but you have to be careful not to overshoot the methyl levels.

Managing methyl/folate levels is complicated enough, without adding the factor of severe maldigestion/malabsorption. Autism is the most complex disorder in our clinical population. We find it very helpful to address a person’s biochemical individuality in determining the best therapeutic protocol.

We have seen more than 3,500 patients in the autism spectrum. It’s clear that most of them suffer from some degree of gluten intolerance and most families report significant improvements following gluten-free diets. In
this case, severe zinc deficiency and intestinal oxidative stress cripple the synthesis of the enzymes needed to break down gluten.


The dangers of B-6 have been greatly overexaggerated. The original concerns began with a university study 25 years ago in which volunteer students were paid to take B-6 (pyridoxine hydrochloride) doses ranging from zero to 10,000 mg daily. After a few weeks, a number of the students taking doses higher than 5,000 mg/day reported a loss of sensation in areas of the skin. The study was stopped and in every case the symptom completely disappeared. This result became widely known & the side effect was identified as neuropathy.

Within a few years, similar neuropathy was observed in a small fraction of persons taking megadoses of 2,000 mg/day and for a while B-6 dosages were limited to 1,000 mg/day. Later, there were rare cases of persons who experienced temporary neuropathy with doses of a few hundred mgs. In the hundreds of neuropathy cases, the neuropathy completely disappeared after stopping the B-6. The effect a temporary one, and I’m unaware of
anyone ever being permanently “hurt” by B-6.

Persons who have normal metabolism of B-6 need only a couple of milligrams daily, which is easily obtained from their diet. However, there are many persons with metabolic disorders which result in innate B-6 deficiency…..These persons may need 100 to 1,000 mg/day of B-6 to normalize B-6 levels in the body. An example is provided by the genetic disorder pyroluria, in which B-6 is stripped from the bloodstream by kryptopyrrole/hemepyrrole molecules.

In a nutshell, most persons have no need for B-6 supplements, whereas innately B-6 deficient persons may need hundreds of mg/day to normalize B-6 activity. B-6 toxicity occurs only in persons who already have sufficient or elevated B-6 levels.

Another indicator of B-6 overload is the onset of vivid, troubling dreams. When that occurs in a patient, the B-6 dose can be lowered before neuropathy begins.

There are many nutrients that have serious dangers associated with overdose…… B-6 is not one of them. Examples of potentially-dangerous nutrients include the fat-soluble vitamins (A, D, E), copper, and selenium. (Feb 19, 2003)

In the 1980’s, I was collaborating with the late (and great) Dr. Carl Pfeiffer in developing nutrient programs for troubled individuals. In1986 we discovered that certain malabsorbers didn’t respond well to B-6 in the form of pyridoxine hydrochloride, but were helped greatly by the P-5-P form of B-6. For about a year we used P-5-P exclusively in treating B-6 deficiencies….. However, we later discovered that certain patients responded better to pyridoxal hydrochloride than to P-5-P. Thereafter, we provided both forms of B-6 in treating B-6 deficiency. A typical B-6 deficient patient might receive 300 mg pyridoxine hydrochloride and 50 mg P-5-P daily.

This practice has continued at the Pfeiffer Treatment Center over the past 13 years, with most patients receiving both “regular” B-6 and P-5-P. We tend to emphasize P-5-P for persons with malabsorption, maldigestion, or other gut problems…… with other patients receiving a balanced mix of the two forms of B-6. (Feb 20, 2003)

I’ve worked with more than 3,000 patients who received at least 500 mg/day of B-6. I know of only 2-3 dozen cases in which neuropathy symptoms occurred….. In these cases we had incorrectly believed there was severe B-6 deficiency. In every case, the neuropathy disappeared after stopping the B-6. Nobody was harmed.

The incidence of skin neuropathy after megadoses of B-6 is rare, but real. The specter of permanent harm from B-6 appears to be a myth. I am unaware of a single case. (Feb 22, 2003)

Bipolar Disorder

Bipolar disorder is not a single condition, but an umbrella term which includes a number of very different biochemical abnormalities. I’m bothered by any attempt to generalize over the bipolar phenotypes & to blindly recommend any formulation or therapy for all of them. The key is to determine a patient’s biochemical individuality, and to provide focused appropriate treatment. In our database of 1,500 bipolar patients, about 25% are overmethylated, 35% are undermethylated, and the remaining 40% do not exhibit a methylation disorder.

The three primary biochemical classifications of bipolar disorder are the following:

A. Undermethylation: This condition is innate & is characterized by low levels of serotonin, dopamine, and norepinephrine, high whole blood histamine and elevated absolute basophils. This population has a high incidence of seasonal allergies, OCD tendencies, perfectionism, high libido, sparse body hair, and several other characteristics. They usually respond well to methionine, SAMe, calcium, magnesium, omega-3 essential oils (DHA & EPA), B-6, inositol, and vitamins A, C, and E. They should avoid supplements containing folic acid. In severe cases involving psychosis, the dominant symptom is usually delusional thinking rather than hallucinations. They tend to speak very little & may sit motionless for extended periods. They may appear outwardly calm, but suffer from extreme internal anxiety.

B. Overmethylation: This condition is the biochemical opposite of undermethylation. It is characterized by elevated levels of serotonin, dopamine, and norepinephrine, low whole blood histamine, and low absolute basophils. This population is characterized by the following typical symptoms: Absence of seasonal, inhalent allergies, but a multitude of chemical or food sensitivities, high anxiety which is evident to all, low libido, obsessions but not compulsions, tendency for paranoia and auditory hallucinations, underachievement as a child, heavy body hair, hyperactivity, “nervous” legs, and grandiosity. They usually respond well to folic acid, B-12, niacinamide, DMAE, choline, manganese, zinc, omega-3 essential oils (DHA and EPA) and vitamins C and E, but should avoid supplements of methionine, SAMe, inositol, TMG and DMG.

C. Pyrrole Disorder: This condition, also called pyroluria, is a genetic stress disorder associated with severe mood swings, high anxiety, and depression. The biochemical signature of this disorder includes elevated urine kryptopyrroles, a double deficiency of zinc and B-6, and low levels of arachidonic acid. Pyrolurics are devastated by stresses including physical injury emotional trauma, illness, sleep deprivation, etc. Symptoms include sensitivity to light and loud noises, tendency to skip breakfast, dry skin, abnormal fat distribution, rage episodes, little or no dream recall, reading disorders, underachievement, histrionic behaviors, and severe anxiety. They usually respond quickly to supplements of zinc, B-6, Primrose Oil, and augmenting nutrients.

To me, a bipolar patient who becomes “well” with greatly-reduced medication requirements may have achieved complete success. I don’t believe that medication doses need to go to zero, as long as side effects are absent and long-term effects are minimal or absent.

Incidence of bipolar depression (diagnosis during lifetime):


We have seen more than 1,500 patients diagnosed with bipolar disorder, including a few hundred who presented with a diagnosis of “rapid-cycle” bipolar disorder. Many of the rapid cycle patients exhibited a severe pyrrole disorder as their primary imbalance. The key lab test is urine kryptopyrroles. Most “pyrolurics” are prone to high anxiety, severe mood swings, depression, and may be famous for their temper. Classic symptoms include aversion to eating breakfast, poor dream recall, sensitivity to bright lights & loud noises, abnormal fat distribution, poor short-term memory (often coincident with good long-term memory), and very poor stress control. (Feb 27, 2003)

We have worked with more than 1500 bipolar patients & found that most have an atrocious diet. I remember one young man whose only dietary intake for the past month consisted of Pepsi and potato chips.

In our experience, best results are achieved with a two-step procedure: (1) biochemical treatment followed by (2) life-style changes including a better diet. We learned the hard way that most bipolars are incapable of life-style changes until after their chemical imbalances have been corrected (or at least lessened). Once real biochemical progress has been made, the patient is more functional and real dietary improvements can be achieved. Trying to everything at once tends to overwhelm the patient, and they usually give up. (March 6, 2003)

About 20% of patients labeled as bipolar have a pyrrole disorder (genetic) which is associated with (a) fatty acid abnormalities, especially depressed arachidonic acid, (b) strikingly weak immune function, and (c) severe metal oxidative stress. The definitive test for the pyrrole disorder is urinalysis for kryptopyrroles (Direct Healthcare Access is the lab, 847/299-2440). These patients might benefit greatly from therapy concentrating on zinc, B-6, and primrose oil (or borage oil). Omega-3 oils can make things worse because of the competition for Zn & B-6 between delta-5 desaturase and delta-6 desaturase.

If a patient has a pyrrole disorder he/she likely would have at least half of the following symptoms:

Poor stress control
Sensitivity to bright lights and/or loud noises
Preference for spicy or heavily flavored foods
Significant growth after age 16
Morning nausea
Tendency to skip breakfast
Poor dream recall
Emotional outbursts
Poor short-term memory, perhaps coincident with excellent L.T. memory
Diagnosis of “rapid-cycle” bipolar
Much higher capability & alertness in the evening, compared to mornings
Dry skin
Reading disorder. (March 27, 2003)

DMAE passes the blood-brain barrier and converts to choline in the brain. Therefore it has cholinergic action & enhances formation of acetylcholine. As a result DMAE is generally very useful in treatment of high dopamine (low histamine, overmethylated) persons, but can seriously harm low dopamine, high histamine, undermethylated persons. We’ve seen more than 1,500 bipolar patients and confirmed that DMAE is generally effective for the overmethylated phenotype (25% of bipolar cases), but causes great worsening for those who are undermethylated (40% of bipolar cases). DMAE definitely should not be used indiscriminately for persons with serious mental illness. (Aug 15, 2003)

Childhood Bipolar Disorder. There has been an explosion in this dubious diagnosis in the past 5 years. It represents an attempt to predict which children are headed for a bipolar-type mental breakdown — The usual result is early intervention with powerful atypical antipsychotic medication.

A very high percentage of our incoming bipolar patients exhibit elevated liver enzymes, undoubtedly a result of the added stress on the liver due to powerful psychiatric medications. There is plenty of published data showing that many psychiatric meds can cause cirrhosis of the liver.

The benefits of psychiatric medications are often exaggerated and the risks minimized. A very common side effect of psychiatric medications is death.


Another effective way to combat candida is using zinc therapy. Candida is killed by metallothionein (MT) proteins which are normally in high concentration in intestinal mucosa. MT is induced by zinc. Many persons with candida are low zinc and low MT persons. They usually exhibit low zinc in plasma, serum, or packed cells, but high zinc in hair. You can expect chronic candida problems until zinc is normalized. In a sense, zinc can be an effective weapon in your anti-candida arsenal. Typical anti-candida therapies (including dietary restrictions) can manage the problem for a while……. Maintenance supplementation with zinc (after these interventions) can permanently fix the problem, in many cases, without the need to continue dietary vigilance. (Feb 5, 2003)

Celiac Disease, Wheat and Dairy Sensitivity

There are classic symptoms/markers of gluten intolerance which enable you to determine the small percentage that have symptoms consistent with this disorder. Examples are (1) compulsive, ritualistic behavior, (2) family history of malabsorption, (3) frequent, explosive bowel movements, (4) lethargy, (5) abdominal pain, and (6) Dermatitis Herpetiformis (skin disorder). One could screen the population for the presence of some of these markers of celiac disease & then perform diagnostic tests to nail it down. (11 Jan, 2003)

Severe wheat gluten intolerance can cause classic symptoms of schizophrenia, and amounts to about 4% of all schizophrenia diagnoses in the U.S. These persons usually become quite normal when placed on a gluten-free diet. Psychiatry continues to ignore the small, but significant, population, estimated at 100,000 to 300,000 Americans. These people are usually treated with atypical anti-psychotic medications, but simply need a dietary change to become free of symptoms. (11 Jan, 2003)

Our Center has evaluated and treated nearly 20,000 persons. About 1,500 of them have reported terrible reactions to wheat and/or dairy. The wheat/dairy sensitive population is composed of two major groups:

Group A consists of those people who are truly allergic to these foods & must make the lifetime commitment to total avoidance of these foods. Failure to accomplish this could result in irritability, violent behavior, ADD, depression, anxiety, bipolar disorder, delusional disorder, schizophrenia, not to mention malabsorption & terrible physical health.

Group B consists of persons who have severe reactions to wheat and/or dairy solely because of a genetic or acquired oxidative stress condition. Fix the oxidative stress in the G.I. tract & the food sensitivities disappear. Moreover, merely avoiding wheat/dairy will provide only partial benefits to this group….. because the untreated oxidative stress could result in toxic metal overload, yeast overgrowth, copper dysregulation, weakened immune system, abnormal levels of dopamine and norepinephrine, impaired hippocampal and amygdala function, etc. The net result can be behavior disorders, depression, severe mental illness, frequent infections, and an increased tendency for cancer.

In summary, most Group A persons can be successfully treated with dietary restrictions alone. Persons in Group B must have therapy which focuses of normalizing the level of oxidative stress. (Sep 2, 2003)


Phosphatidyl choline is also very effective in protecting DHA/EPA from free radical oxidative stress….. another good reason to take it. In my experience DMAE is especially effective for increasing acetylcholine levels in the brain, since it passes the blood/brain barrier & converts to choline. I like to use this for overmethylated persons who have excessive dopamine and norepinephrine levels. However, enhancing acetylcholine activity must be avoided in persons who genetically are overloaded in this NT. Choline, DMAE, and phosphatidyl choline can cause nasty symptoms in these persons (about 10% of the population).

Persons with innately high acetylcholine levels tend to be very tense and sometimes nearly catatonic. They have very high anxiety, but usually keep it inside. They also usually have a history of seasonal allergies, perfectionism, and OCD tendencies. Increasing acetylcholine activity can be a disaster for them.

Those deficient in acetylcholine usually present with nervous legs, are prone to pacing, and are quite voluble. Their misery is plain to everyone. Therapies to increase acetylcholine activity can be extraordinarily helpful for this population. (March 6, 2003)


A complication is that blood levels of copper can be very low in persons who have severe copper overload. The classic example is Wilson’s Disease in which the liver accumulates huge amounts of copper. These same Wilson’s patients usually exhibit very LOW levels of Cu in blood…..also the exhibit extraordinary low levels of ceruloplasmin. Is essence their blood contains little copper, but the blood Cu is predominantly in “unbound” form.

Years ago, we mistakingly thought low blood serum or RBC copper levels meant Cu deficiency….. and in a few cases we cautiously gave Cu supplements in an attempt to correct the situation. Most of these patients reacted badly to the Cu. Proper evaluation of copper status requires both serum Cu and serum ceruloplasmin tests.

Hair mineral copper is very valuable for behavior disorders and ADHD patients, but is of far less clinical value for autism, bipolar, and schizophrenia populations.

Giving supplemental Cu to patients is a risky business. It should be considered only in those who exhibit sufficient ceruloplasmin to accomadate between 80 and 95% of the Cu present. (April 10, 2003)

Selenium deficiency itself could result in a nasty copper elevation. Metallothionein at the intestinal mucosa and in the liver is the primary agent which regulates copper in the body. Selenium is needed for efficient metallothionein functioning.

Carl Pfeiffer of Princeton, NJ tested more than 25,000 persons for copper & reported that Cu toxicity was common, but Cu deficiency extremely rare. We have investigated the metal-metabolism of about 20,000 persons & found the same thing. I admit there are theoretical rationale for expecting copper deficiency, but it rarely actually happens.

Hair analysis ALONE is a very poor way to assess copper status. I say this after (a) evaluating more than 100,000 hair analyses, (b) developing the first high-quality hair standards (loaned to NIH and other researchers), and (c) performing numerous double-blind, controlled experiments involving hair chemistries. Findings of high Cu levels in hair are compromised by the many external sources of Cu which cannot be completely removed by washing. Low levels of Cu in hair and/or blood often are coincident with dangerous overloads of Cu in liver. Hair Cu values can provide information of clinical significance, but by itself
is not clinically decisive.

Serum Cu indicates the total amount of Cu in serum. Serum ceruloplasmin indicates the fraction of serum Cu that is bound as ceruloplasmin. A simple calculation (paying attention to the assay units) yields the numbers for comparison. Most copper experts agree that the normal or “healthy” situation is to have about 80 to 95% of the serum Cu present as ceruloplasmin.

A high fraction of “unbound” Cu is a good indicator of oxidative stress and low metallothionein activity…… and also a warning to NOT to supplement with Cu, even if serum/RBC/hair levels of copper are low. In addition, one should consider possible environmental sources of Cu, especially drinking water and swimming pools/jacuzzis treated with copper sulfate (to kill algae.) (April 11, 2003)

The ceruloplasmin analysis indicates the amount of Cu properly bound to this protein (Should be 80-95% of total serum Cu). If serum and hair Cu are low, a high proportion of “unbound” Cu is a warning signal that there might be a Wilson’s Disease-like situation…… Low serum/hair copper, but severe Cu overload in the liver. In some cases, testing for possible Wilson’s Disease is indicated.

Usually, the question is whether there is a Cu overload. The incidence of true Cu deficiency/depletion is very low. (April 14, 2003)

High copper females respond very well to therapy with zinc, B-6, P-5-P, C, E….. However the Zn should be introduced slowly….. for example 25 mg….50 mg…. 75 mg….. and given either at bedtime or after the evening meal. B-6 and P5P should be given before noon. Failure to phase in the Zn slowly would be likely to result in temporary worsening of symptoms over the first few weeks.

She should avoid estrogen therapy, drink bottled water, and limit high-Cu foods like chocolate, carob, and shellfish.

If her primary imbalance is the Cu overload, very little improvement is likely during the first 3 weeks….. followed by striking improvement thereafter. If the patient is clearly better during the first week, this is probably due to overcoming the pyrrole disorder. In her case, you might get a nice initial improvement which is partial in nature….. followed by a plateau of several weeks before more progress is made. (April 14, 2003)

The ideal ratio of serum copper to plasma zinc is in the range 0.8 to 1.0. About 15-20% of Americans have levels above 1.2.

The Cu/Zn ratio is especially high in certain populations; for example,

Post-partum depression: 95%

Autism: 85%

Hormonal cancers: 75%

ADHD: 68%

Intermittent explosive disorder: 50%

(October 14, 2015)

Crime & Violence

We’ve spent the past 25 years studying behavior disorders and have accumulated the world’s biggest & best chemistry database for behavior. We have about 100 separate chemical assays of blood, urine, and hair for more than 12,000 behavior-disordered persons, including participation in 28 forensics studies of folks like Charles Manson, Richard Speck, Henry Lee Lucas, and James Oliver Huberty. This database clearly shows violent, delinquent persons to have striking biochemical differences, compared to the general population. The late & great Carl Pfeiffer helped me over the last 12 years of his life to development biochemical, non-drug treatments for these chemical imbalances.

The Pfeiffer Treatment Center was named for Carl Pfeiffer, MD, PhD of Princeton, NJ …. for his great contributions to our work. He died 6 months before the Center opened in 1989.

The Pfeiffer Center has completed several outcome studies measuring efficacy of this treatment system. The latest one involves 207 consecutive patients in which we carefully determined the frequency of physical assaults and destruction of property before & after treatment. I’ve completed a manuscript for this study which will be published in the journal, Physiology and Behavior, hopefully within 4-6 months. The results are quite spectacular

This study indicates excellent efficacy for young persons…. 0-16 yrs of age…. with sharply declining efficacy at older ages. The decline seems to coincide with the onset of drugs & alcohol abuse. I am sorry to say that our experience with adult ex-convicts is not very good & the information you received about 95% success in overcoming recidivism in violent criminals is not true. However, about 90% of compliant YOUNGER violent/delinquent persons respond very nicely to the Pfeiffer therapy…. About 60% of these report complete elimination of assaults and property destruction, with the other 30% reporting excellent partial improvements. Maybe some day we’ll be smart enough to help the older offenders too.

We believe that America’s best hope for effective crime prevention is early identification of at-risk youths and effective treatment before their lives are ruined. I’m certain that stimulant drugs and/or psychiatric medications are not the answer. (Feb 6, 2003)

Many years ago I did a study examining chemistry differences between male siblings in which one was a violent delinquent and the other a well-behaved child. We balanced age and birth order and accepted only those who lived in the same household and attended the same school.

I clearly remember a family living in the squalor of Chicago’s south side black ghetto…… The father was in Stateville Prison for murder…. the mother was a prostitute who sometimes entertained her “guests” at home in the presence of the children. The boys were age 10 and 11 and both had suffered physical and sexual abuse from the customers. I’ve never seen a worse environment….. I remember being very nervous just driving into the neighborhood.

The 10 yr old was oppositional, defiant, cruel, truant, and was already in a violent gang. However, his 11 yr old brother was quite amazing…… a well-behaved, polite young man who was an excellent student and also class president. For years I wondered how such a miracle could have happened.

We eventually found 24 families that included an “all-American boy” and a “child from hell”. The ill-behaved children had clear chemistry abnormalities whereas the well-behaved ones generally exhibited expected trace-metal levels.

This experiment was a watershed experience for me. For the first time I knew that environment wasn’t the only causative factor in behavior disorders and ADHD….. that disordered biochemistry (probably genetic) also played a role.

In studying nearly 10,000 behavior-disordered children & adults since that time, I’ve learned the following:

1. A child born with ideal body/brain chemistry is nearly indestructible, and may thrive in a terrible environment.

2. A child with a MILD chemical predisposition to violence may turn out fine, if the environment is good and there are resources for counseling, etc. The same child might wind up in prison if born into poverty or an otherwise terrible environment.

3. A child born with a SEVERE chemical imbalance will exhibit terrible behavior, even in an ideal environment. You can’t just “love away” a severe brain chemical imbalance. My group once visited and tested Charles Manson at San Quentin prison….. his chemistry was so extraordinarily aberrant that I am convinced that if adopted into a different family, Manson would have turned out the same. (July 28, 2003)

In the beginning, we had no way of knowing if the biochemical differences were a causative factor or simply an association. I decided the quickest way to find out would be to correct the aberrant chemistry of the violent children to see if the behaviors changed. 10,000 behavior patients later, I can report that the bad behavior in young children usually disappears completely when the chemistry is balanced. Children under the age of 10 usually correct beautifully without counseling of any kind. However, older children (14+) benefit greatly from counseling, behavior mod, conflict resolution, etc after the chemistry is corrected. I’m not sure if this is because of an ingrained negative self-image, poor social skills, or problems in breaking the bad behavioral habits. All I know is that counseling/therapy seems necessary with teens, even after the chemistry has been normalized. We’ve also learned that adult criminals generally fail to achieve enduring benefits with our biochemical (non-drug) therapies. Most are back in jail within 5 years. We are on a mission to identify the at-risk children and intervene with effective therapy before their lives are ruined. The window
of opportunity (for severe cases) begins to close in the early teen years. Drug and alcohol abuse may be major factors in this phenomenon.

Most children with a predisposition to bad behavior have chemistry imbalances which are fairly mild, and for this large group….. environment and life experiences rule. For them, early traumae might be the deciding factor. (July 28, 2003)

Coral Calcium

The calcium in Coral Calcium is mostly calcium carbonate, which provides the highest amount of calcium absorbed per unit volume. CaCO3 is 40 w/o calcium and is quite dense. Many manufacturers claim higher calcium absorption on a percent basis for low density products like calcium glycinate. A lot of this is deceptive marketing. A capsule of calcium carbonate will result in more calcium in your bloodstream than a same-size capsule of any other form of

That’s the good news about CaCO3. The bad news is that CaCO3 can result in nasty stomach & intestinal problems in sensitive persons. In some cases, all hell can break loose. In my opinion, CaCO3 (not Coral Calcium) is the best option for persons who don’t experience side effects….. lowest volume to swallow down and lowest cost. For sensitive persons, some of the calcium blends are very absorbable with reasonable volume, low cost, and minimal
side effects.

A significant advantage of Coral Calcium is the presence of a multitude of micro-nutrients that are unavailable in most supplements. Things like praesodymium, erbium, etc. Every year we discover another micro-nutrient with a vital function in the body. The “good” impurities in a natural product like Coral Calcium could be significant. Of course the “bad” impurities such as lead or mercury MUST be at a negliglble level for the supplement to provide benefits. (April 17, 2003)


After getting extensive biochemical data on more than 3,000 persons diagnosed with clinical depression, we found that 95% of them fit neatly into one of 5 separate biochemical classifications. Depression is not a single condition, but an umbrella term covering several completely different conditions. Anyway, we believe we have identified the 5 primary phenotypes….. each with their own classic symptoms and each with completely different treatment needs.

1) High Histamine (under-methylated)

40-70 is optimum histamine range for mental health considerations. Histamine is an important neurotransmitter which affects human behavior. This syndrome often involves seasonal variations in depression, obsessive-compulsive behavior, inhalant allergies, and frequent headaches. In severe cases involving psychosis, the dominant symptom is usually delusional thinking rather than hallucinations. They tend to speak very little and may sit motionless for extended periods. They may appear outwardly calm, but suffer from extreme internal anxiety. Most OCD patients with both obsessive thoughts and compulsive actions are in this category. Associated with under-methylation, which results in low levels of important neurotransmitters such as serotonin, dopamine and norepinephrine. Treatment focuses on the use of antifolates such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and folic acid. Three to six months of nutrient therapy are necessary to correct this chemical imbalance. Symptoms will return if treatment is stopped. Two good labs for whole blood histamine are LabCorp and Quest. Also use a special absolute basophil count as a methlyation marker. The count must be direct and not differential. Alcian blue dye is the preferred staining agent. Best lab for this test is Direct Healthcare Access in Glenview IL 847 299 2440

2) Low Histamine (over-methylated)

Low-histamine depressives are usually nervous, anxious individuals who are prone to paranoia and despair. No seasonal allergies, but many food allergies and chemical sensitivity. Low libido. Obsessions but not compulsions. Heavy body hair. Nervous legs. Grandiosity. Many have a history of hyperactivity, learning disabilities and underachievement. They are over-methylated which results in elevated dopamine and norepinephrine levels. Treatment focuses on B3, C, B12 and , with about 2-4 months required for correction of the imbalance.. Also DMAE, choline, manganese, zinc, omega-3 essential oils, C and E. They should avoid methionine, SAMe, inositol, TMG and DMG.

3) Pyroluria

A stress disorder characterized by pronounced mood swings, temper outbursts, anxious depression. Inability to eat breakfast, absence of dream recall and frequent infections. The biochemical signature of this disorder includes elevated urine kryptopyrroles, a double deficiency of zinc and B-6, and low levels of arachidonic acid. Devastated by stresses including physical injury, emotional trauma, illness, sleep deprivation. Sensitivity to light and loud noises, dry skin, abnormal fat distribution, rage episodes, histrionic behavior. They also have low levels of arachidonic acid. Treatment centers on correcting a double deficiency of B-6, zinc essential fatty acids and augmenting nutrients. It is believed to result from abnormal hemoglobin synthesis which depletes the body of these nutrients. A positive response often occurs within the first seven days of treatment, with 1-2 months usually required for correction of the imbalance.

4) High Copper (Hypercupremia)

If your level is above 140 mcg/dL, you would profit from getting rid of the excess copper. The most common depression phenotype for women. History of hyperactivity, tinnitus, and skin sensitivity to metals. Females with this condition usually have significant PMS and are prone to heightened depression during hormonal events such as puberty, gestation, childbirth and menopause. A woman’s copper level more than doubles during the 9 months of pregnancy, apparently to enhance angiogenesis in the fetus. Women with an innate tendency for copper overload are prone to post-partum depression or post-partum psychosis. Estrogen increaases creuloplamin and copper levels and results in zinc depletion. Very elevated norepinephrine levels, elevated copper and low ceruloplasmin. Elevated norepinephrine/dopamine ratio. Most get worse after chocolate which is very high in copper. This condition is non-existant in males. Serum copper levels above 140 mcg/dl High NE and ADR levels can result from overmethlyation, probably genetic, elevated serum copper, and low folate/B12 levels. Hypertension is associated with high NE and ADR levels. Using folate/B12 will reduce hypertension and anxiety and depression. They often report a worsening of depression after estrogen or multiple vitamins. Most hypercupremics get worse if they overdose on chocolate. Treatment focuses on release of excess copper from tissues, promotion of copper excretion, and stimulation of metallothionein (a metal-binding protein). Many patients report a worsening for three weeks followed by steady improvement. Nutrient support is zinc, manganese, vitamin C and B6. Nutrients should be introduced gradually to avoid side effects. Use 25mg of zinc initially, then 50 then 75 as tolerated. A total of 60 to 90 days is usually required to correct this imbalance.

The list of things to avoid include the following:

1. Multiple vitamins/minerals containing Cu

2. Enriched foods with Cu added (learn to read the labels)

3. I recommend that she drink bottled water.

4. She needs to avoid swimming pools/jacuzzis treated with algicides containing copper sulfate.

5. The primary foods to avoid are chocolate, carob and shellfish.

5) Toxic Overload

This syndrome often involves a sudden, prolonged bout of depression without apparent reason and without a prior history of depression. Toxic substances which are capable of producing depression include lead, cadmium, mercury, and a wide variety of organic and inorganic chemicals. Treatment varies with the type of toxic material involved, and care must be exercised to avoid flooding the kidneys with toxins during the early stages of treatment. Heavy-metal overloads can be corrected quickly by in-hospital chelation, or more slowly using biochemical treatment. Organic chemical overloads require liberal use of antioxidants along with avoidance of the offending substances.

BTW, chocolate has 4 separate ingredients that can worsen malaise/depression in some people: (1) sugar, (2) caffeine, (3) copper, and (4) milk. The most significant of these for females is usually copper. Unfortunately carob has even more copper than chocolate.

Many depression patients experience striking cycles in which their depression may wax for months or wane for months. It’s really hard to evaluate treatment efficacy for such persons since the patient may deteriorate during effective treatment or improve while experiencing placebo or a harmful therapy. (30 Dec, 2002)

Histamine assays for depression were introduced by Dr. Carl Pfeiffer of Princeton, NJ in the 1970′ and 1980’s. My clinic has found whole blood histamine to be very useful & has used this assay more than 30,000 times.

First of all, the analysis must be done for whole blood (not plasma, serum, etc), strictly adhering to the sampling protocol. We presently use LabCorp but in the past Quest also had proficiency for this assay.

The reference “normal” range for mental health is 40 to 70 ng/dL. Levels above 70 indicate undermethylation, whereas levels below 40 suggest overmethylation.

Undermethylated depressives thrive on l-methionine, calcium, magnesium, B-6, Zinc, and Vitamin C. In severe cases, up to 3,000 mg/day of methionine and 2,000 mg/day of Ca may be needed. However, we also like to routinely run a homocysteine test to assure the safety of the methylation protocol. This population is believed to result in low serotonin activity. This methylation therapy is quite slow in taking effect…. and often 6-8 weeks pass before
progress is obvious

Overmethylated (low-histamine) depressives thrive on folic acid, B-12, niacin (or niacinamide), B-6, Zinc, Manganese, DMAE, and Vitamins, C and E. In severe cases, up to 5,000 mcg/day of FA may be needed. Response is more rapid with this phenotype, with clear progress usually by week 4. This population is believed to have an innate tendency for elevated serotonin, dopamine, and norepinephrine levels.

This test can also help guide psychiatrists in selection of psychiatric medications. For example high histamine persons may do quite well on SSRI’s, but low-histamine persons usually reactly very badly to SSRI’s and are better candidates for benzodiazapines.

We like to augment the histamine blood test with an “absolute basophil” test offered by Direct Healthcare, Inc. The histamine assay can be affected by antihistamines and other medications with AH properties. The reference range for ABC’s is 30-50.

We have an enormous chemistry database for depression….. more than 90 chemical assays for each of 3,200 persons with clinical depression. We find that 90% of depressives may be divided into five biochemical classifications, each requiring a different treatment approach. Two of these depression phenotypes are undermethylation and overmethylation. (June 2,

Estimated incidence of hypercupremia in our depressive population:

Females: 45%
Males: 3%
Overall: 30% (We have more females than males in our depression database)

As you can see from the numbers, hypercupremic depression is generally a female event. We are about to publish a database study which shows that hypercupremic feamles are especially prone to post-partum depression and post-partum psychosis. Many of these high-Cu females get worse on anti-depressants, but respond beautifully to nutrient therapy which normalizes Cu and Zn levels. (June 11, 2003)


We are not a Down’s clinic, but I have researched Down’s biochemistry in past years. One common factor is elevated levels of serum copper and insufficient levels of serum ceruloplasmin. We did an exploratory outcome study following treatment of 24 Down’s patients about 10 years ago and the results were the following:

1. Better general health
2. Much better behavior control and moods
3. No detectable improvement in cognitive function.

If this person were in my family, I would have the following tests run: serum copper, serum ceruloplasmin, and plasma zinc. If the expected metal-metabolism imbalance were evident, a simple and inexpensive formulation of vitamins and minerals could normalize the metals. I would expect that the violence would disappear and that he would have a better life. (Aug 21, 2003)

Essential Fatty Acids

Borage Oil is a good source of omega-6 oils. I think the widespread use of Primrose Oil results from widely publicized treatment successes with schizophrenia in England & the USA in the 1970’s and 80’s. I would choose the one with the highest arachidonic acid level. (Sep 28, 2003)

I once collaborated with Dr. Doug Bibus, a Minnesota fatty-acid expert, on a study of 87 schizophrenics. Bibus’ lab provided reliable chemical analysis for about 60 fatty acids.

We reported the results at a national meeting of the Americal Oil Association (not petroleum) & plan to publish the results in a journal. We found that 75% of schizophrenics were somewhat elevated in omega-6 oils, and significantly depleted of omega-3 oils. However, the pyroluric schizophrenics comprised the other 25% and exhibited severe deficiency of arachidonic acid and other omega-6 oils.

We’ve had considerable success in using PUFA’s (poly-unsaturated fatty acids) to treat persons with mental illness, but have found that omega-3 and omega-6 oils can cause clear worsening if given inappropriately. Pyrolurics need omega-6….. whereas most other patients need omega-3. There is a competition between o3 and o6 for zinc, B-6, and the delta 5,6 desaturases. The ideal would be to identify a person’s biochemical individuality, with respect to PUFA’s, then treat accordingly.

We’ve met several pyrolurics patients who reported a setback after omega-3 supplements. Most of them turned out to be pyroluric.

Kennedy-Kreiger Institute in Bethesda has a lab that performs a reliable PUFA assay. Direct Healthcare Access in the Chicago area has an excellent kryptopyrrole assay for determining presence or absence of pyroluria. (Oct 14, 2003)

If you look at the reaction cascades for omega-3 and omega-6 beginning with ALA and LA…. both cascades require B-6 and Zn, which may be in limited supply. If a person is overloaded in one of the omega’s and depleted in the other…. supplementation with the omega already in excess will result in less B-6 and Zn availability and a worsening of the levels of the depleted omega.

About 60% of schizophrenics exhibit low omega-3 levels. About 20% of SZ patients (those with severe pyroluria) exhibit extremely low AA and DGLA levels and thrive on Primrose Oil or other forms of omega-6. The remaining 20% do not exhibit PUFA anomalies.

The low omega-6 patients are very different from other schizophrenics and the general population. Classic symptoms include: Extremely dry skin (remember that the oils are the waterproofing of the skin), raised nodules on the back of the upper arm, abnormal fat distribution, plus the symptoms of pyroluria itself…. These include severe mood swings, stress dyscontrol, sensitivity to light and loud noises, poor immune function, little or no dream recall, reading disorder in childhood, craving for spicy/salty foods, poor appetite in the AM, etc.

My preference is the RBC membrane assay for the PUFA’s. (Oct 20, 2003)

Articles F-L

Fetal Alcohol Syndrome

We have seen dozens of patients with a diagnosis of fetal alcohol syndrome. Most of them had an associated diagnosis of ADHD or a behavior disorder. We’ve never done a formal outcome study on this group, so I have no treatment efficacy statistics. However, I remember years ago being surprised that so many of these children were responsive to our treatments and turned out so well. An even bigger surprise to me was learning that many cocaine babies become highly-functioning, well-adjusted children. It looks like the dire predictions of severe dysfunctions for these persons have been grossly exaggerated. (Feb 20, 2003)


As described in my book Nutrient Power, there are five major phenotypes (chemical classifications) of depression. Two of them involve low serotonin activity & represent slightly more than 50% of depressives….. and most report lessening of depression after SSRIs, albeit often with nasty side effects. Approximately 20% of depressives are in the “low-folate depression” group & generally report great worsening of depression after SSRI antidepressants. I’ve worked with about 600 such cases. They have distinctive symptoms and traits that assist in diagnosis and exhibit very low whole-blood histamine levels along with low functional folate and low SAMe/SAH ratios.

These SSRI-resistant patients thrive on treatment with folates in any form (folic acid, folinic acid, etc) together with Vitamin B-12 and a few augmenting nutrients. They often report difficulty over the first 2-3 weeks, and steady improvement thereafter. My outcome studies showed efficacy in 85% of cases. After treatment, about 80% reported the ability to completely wean off antidepressant medication without a return of depression — 20% reported they needed a low dosage of the antidepressant to be at their best.

You will find that folic acid works as well as the other folate forms, but folinic acid has the advantage of passing the blood-brain barrier more rapidly than folic acid. The best way to get B-12 is with 1000 mcg IM injections. Next best is sublingual B-12 at about 2,000 mcg/day.

These patients suffer from elevated serotonin activity. The folates act in an epigenetic mechanism to increase gene expression of SERT and DAT transport proteins that regulate neurotransmission activity. In effect folates are serotonin reuptake PROMOTERS.

If you try this approach, most of your SSRI-resistant patients will love you. However, this same treatment would greatly worsen depressives with low activity at serotonin receptors. If uncertain of the diagnosis, I recommend a cautious trial at half dosages. Also, beware of patients whose SSRI resistance relates to the side effects, and not depression itself….. These persons are not candidates for folate therapy. (March 7, 2013)

Hair Analysis

I’ve done hair analysis proficiency testing for more than 25 years. I’ve never yet found a lab that can reliably assay barium in hair. The same is true of more than 10 other elements routinely reported by the hair analysis labs. Strontium has a history of strange results since typical levels are close to the detection limit for most labs.

In contrast, you can usually depend of hair assays for copper, zinc, magnesium, calcium, iron, manganese, lead, cadmium, phosphorus, chromium, sulfur, and a few others. (April 22, 2003)

The Johnson’s baby shampoo recommendation is intended to minimize exogenous contamination from shampoos. Bob Smith who was previously president of Doctor’s Data and later Great Smokies hair analysis efforts…. has a lot of data which shows this is the best approach.

Uranium is an analysis that I have very little confidence in. I’ve done quality assurance testing of hair analysis labs and find some of the elements assays to be highly reliable and others to be nearly worthless. Uranium is NOT one of the good elements. (July 1, 2003)

I’ve done proficiency testing on Doctor’s Data, Inc and Great Smokies hair analysis facilities and believe that they are the two best commercial HA labs in the world. They both report findings for 35 to 40 elements, but only about half of their assays have precision, accuracy, and clinical significance. I’ve complained to both labs about releasing meaningless levels….. they maintain that these speculative elemental levels may eventually have research significance…. so they provide the data.

The “good” elements are Ca, Mg, Zn, Cu, Na, K, S, Mn, Fe, Pb, Se, P, and Cd.

Others that are decent (qualitative relevance) are Sb, As, Hg, Cr, Mo, Li, Ba, Ni, Sr, and Co.

Terrible assays (according to my tests) are: Al, Be, Bi, Pt, Th, Tl, U,Ag, Sn, Ti, V, B, I, Ge, Rb, and Zr. However, it’s certainly possible that individual labs may have improved their capabilities in the past two years.

On the positive side, hair analysis is actually a very valuable tool & I love the ability to obtain meaningful assays of a dozen or so metals with non-intrusive sampling and very low cost. (July 3, 2003)

Head Injury

Many years ago, the great Carl Pfeiffer told me that head injury patients often respond well to supplements of octacosanol (2,000 to 4,000 micrograms daily), taken together with zinc, B-6, and Vitamin C (common daily dosages 50 mg Zn, 300 mg B-6 and 2,000 mg Vitamin C). He said that it helped repair damage to myelin sheaths in the brain. I’ve used this many times over the years with apparent excellent success, based on anecdotal case histories (which of course have limited scientific value).

A few years ago, we collaborated with a doctor from the Schwab Rehabilitation Hospital which specializes in head and spinal injuries. We provided the above nutritional supplements to about a dozen persons with severe brain injuries. About 2/3 of them reported very nice improvements. One man who had been on a plateau after 2 years of Schwab’s physical therapies was able to walk again after 3 months of octacosanol, etc. Another head injury client with aphasia was able to talk coherently after a few months. (June 2, 2003)


Histamine is a neurotransmitter itself, and Carl Pfeiffer originally believed that innate histamine abnormalities in the brain were responsiblefor many mental problems. However, it now appears that whole blood histamine is really a “marker” for methylation, in an inverse relationship. High bloodhistamine indicates undermethylation, low serotonin levels, etc….. low blood histamine the opposite.

The five groups refers to the biochemical classification of depression that I developed a few years ago. At that time, I observed that 90% of all new patients who presented at the clinic with a diagnosis of clinical depression fit into one of 5 chemical classes:

1. Overmethylated
2. Undermethylated
3. Hypercupremic
4. Pyrrole Disorder
5. Toxic Metal Overload

Each of these conditions is associated with a syndrome involving specific personality traits, physical markers, and symptoms. (June 16, 2003)

We use whole blood histamine as a marker for methylation. Persons with high histamine ( > 70) are believed to be undermethylated; persons with low histamine (< 40) are considered overmethylated. We believe that methylation imbalances have a major impact on synthesis of serotonin, dopamine, and norepinephrine. The reason is that methyl status isn’t easy to decisively determine…… and is very important clinically. For example, more than 40% of all clinically depressed men are undermethylated and benefit from therapies which enhance methylation. Another 15% or so are overmethylated and need to head for the other goal line…… namely avoidance of methylating supplements and use of folate therapy.

In many cases, this is the dominant innate factor predisposing to depression (or other disorder)….. Blood histamine is one of the best ways to get hard evidence regarding this factor. (July 1, 2003)


Most persons who develop hives are undermethylated persons who have a genetic tendency for elevated blood histamine. Often the hives occur after outdoor physical activity, especially during times of high levels of ragweed or other inhalation allergins. Temporary relief can often be achieved using Benedryl….. A long-term preventative approach involves therapy with methionine, calcium, magnesium, B-6, and Vitamin C. (Aug 9, 2003)

Learning Disabilities

In my experience, the most effective nutrient for speech stimulation is Dimethylglycine (DMG). This is especially effective for undermethylated children.

Many anxious children are overmethylated and thrive on DMAE which passes the blood-brain barrier and enhances acetylcholine (which suppresses dopamine). Since DMAE tends to lower Dopamine, Norepinephrine, and Noradrenaline….. anxiety may be lessened and expressive language improved. Of course, DMAE is effective only for children who have a genetic tendency for elevated levels of these three neurotransmitters.

DMAE is usually indicated for children who are “space cadets” who have high anxiety, little motivation for learning, and poor organization. DMG is usually indicated for intense children who are strong willed, competitive, and exhibit obsessive/compulsive tendencies. (Oct 1, 2003)

Articles M-P

Metabolic Types

About 7 years ago, I developed a classification system which subdivides the entire population into 26 metabolic types (Types A through Z). A small company in Illinois carried out a pilot study of this system (which they called “Bio-Logic”) and provided compounded nutrients to more than 1,000 clients who paid for this service. The use of this system was limited to “wellness” clients who were free of serious mental problems. The company found that the results were generally very positive, with many loyal users. At least 26 types are needed to enable consideration of key factors including methylation, metal metabolism, glucose control, absorption, neurotransmitter synthesis, etc. For example, I am a Type L….. which means my genetic metabolic makeup results in a need for supplements emphasing methoinine, calcium, magnesium, zinc, and vitamins B-6, C and E…… and a need to completely AVOID supplements of folic acid, DMAE, choline, copper, etc. Proper typing requires identification of nutrients in overload (because of genetics) as well as nutrients in deficiency.


The average amount of mercury we get from breathing is 1 mcg/day. The typical American diet provides another 15-20 mcg/day. If one eats tuna or other large ocean fish daily…. an intake of 60-80 mcg/day is possible.

For persons with normal metal metabolism (metallothionein, glutathione, etc), only 5% of ingested mercury gets into the bloodstream and less than 1% into the brain. Also, there are natural neuroprotective chemical factors in the brain which can sequester mercury & prevent damage.

All bets are off if a person has a serious metal-metabolism disorder……such persons may be hypersensitive to Hg. (Oct 30, 2003)


The metallothionein (MT) theory seems more likely to be at the center of ASD. Children having a genetic weakness in MT activity would perforce have yeast overgrowth. MT kills candida, and helps regulate bacterial levels in the mucosa.

A genetic MT weakness is consistent with (1) casein/gluten intolerance, (2) presence of dense, undeveloped brain cells evident in autopsy studies, (3) hypersensitivity to mercury & other toxic metals, (4) high autism incidence after thalidomide, (5) hypersensitivity to vaccines, (6) poor immune function, (7) low stomach acid, (8) higher incidence in males, (9) taste/texture sensitivities, (10) tendency for yeast overgrowth, (11) leaky gut, (12) behavior problems. (July 24, 2003)


Effective “markers” for methylation are (1) whole blood histamine (ref. levels 40-70 mcg/dL), available from Quest and LabCorp; (2) Absolute Basophils (ref. levels 30-50), available from Direct Healthcare, Inc in the Chicago area.

Elevated histamine and/or elevated basophils indicate undermethylation. Review of symptoms and medical history can bolster the diagnosis. For example, most undermethylated persons exhibit seasonal allergies,
perfectionism, strong wills, slenderness, OCD tendencies, high libido, etc. Overmethylated persons generally exhibit anxiety, absence of seasonal allergies, presence of food/chemical sensitivities, dry eyes, low perspiration, artistic/music interests/abilities, intolerance to Prozac and other SSRI’s, etc.

Conditions associated with undermethylation: Anorexia, Bulemia, shopping/gambling disorders, depression, schizo-affective disorder, delusions, oppositional-defiant disorder, OCD.

Conditions associated with overmethylation: Anxiety/Panic disorders, anxious depression, hyperactivity, learning disabilities, low motivation, “space cadet” syndrome, paranoid schizophrenia, hallucinations. (Oct 3, 2003)

One-carbon (methyl) groups are involved in numerous important biochemical reactions in the body, including genetic expression, neurotransmitter synthesis and metabolism, etc. Methylation (more properly, the methyl/folate ratio) is a major factor in the rate-limiting step (the tetrahydrobiopterin reaction) in the synthesis of serotonin, dopamine, and norepinephrine in the brain. Undermethylated persons tend to be depleted in these 3 neurotransmitters, and the opposite is true for overmethylation.

The SAM cycle in which dietary methionine is converted to SAMe (the primary CH3 donor in the body), and then to homocysteine, is a dominant cascade of reactions in methylation and also is very important in production of glutathione, cysteine, and other aspects of sulfur chemistry.

Most persons with depression, oppositional defiant disorder, OCD, bipolar disorder, or schizophrenia exhibit a genetic abnormality in methylation….. which appears to be central to their illness. Carl Pfeiffer, MD, PhD of Princeton, NJ was a pioneer in this field. (Oct 3, 2003)

About 25 years ago, Dr. Carl Pfeiffer (Princeton, NJ) identified the condition he called “histapenia” or histamine deficiency. After studying the metabolism of more than 20,000 schizophrenics he learned that this
“low histamine” syndrome was common in anxiety, panic disorders, and classical paranoid schizophrenia. His enormous biochemistry database revealed that most histapenics suffered from (1) copper overload and (2)
deficiency of folic acid and/or B-12. More importantly, he found that aggressive therapy using folic acid, B-12, and B-3 usually produced dramatic improvements in these persons. Pfeiffer thought the improvements were largely due to elevating histamine levels in the body & brain.

Subsequent research has indicated that the improvements are due to normalizing the methyl/folate ratio. This ratio is important in the BH4 rate-controlling step in catecholamine synthesis (dopamine & norepinephrine). Also, methyl/folate abnormalities can impact genetic expression of many biochemicals. At any rate, too much methyl results in overproduction of DA and NE, and vice versa.

Also, a serious overload of homocysteine (homocysteinuria) can result in symptoms quite identical to paranoid schizophrenia. Folic Acid & B-12 serve to lower HCy levels.

One thing that is absolutely certain is that methionine and/or SAMe usually harm low-histamine (overmethylated persons)….. but are wonderful for high-histamine (undermethylated) persons. The reverse in true for histadelic (undermethylated) persons, who thrive on methionine, SAMe, Ca and Mg….. but get much worse if they take folates & B-12 which can increase methyl trapping.

I guess the bottom line is that undermethylated persons generally exhibit very elevated folate levels…. and these persons get worse if additional folate is given.

This is a fairly complex subject, and some of my medical staff are still struggling with the concept. However, they have the solace of knowing the clinical impact of methylation or folate therapy on persons with specific methylation/histamine disorders.

It’s certainly true that whole blood histamine is compromised by AH treatments (including antigens and many psychiatric medications). We’ve gotten quite proficient in taking these factors into account. Fortunately, the ABC test doesn’t suffer from this disadvantage. Also, the syndromes of over-methylation and under-methylation are well defined…. and a medical history & review of symptoms greatly aids the diagnosis. (Oct 6, 2003)

The generalization that perfume and other chemical sensitivities are associated with overmethylation, low blood histamine, and elevated norepinephaine… is exactly that…a general rule with many exceptions. However, the correlation seems to be above 90 percent in the case of perfume sensitivity. Whenever a patient enters our clinic wearing a mask to filter out inhalant chemicals, we immediately suspect the overmethylation syndrome. The chemical testing usually confirms this diagnosis, but there definitely are a few persons who have severe perfume sensitivity for other reasons. We’ve evaluated about 19,000 persons, including about 1500 with anxiety disorder or panic disorder. Hundreds of these patients reported sensitivity to perfumes. Nearly 90 percent of the perfume-sensitive group were overmethylated, and reported multiple chemical and food sensitivities. usually in the absence of seasonal inhalant allergies. Perfume sensitivity is a classic symptom of these high nonepinephaine persons, who usually respond beautifully to folate/B-12 therapy [1 Dec -03]

Inositol is especially helpful for undermethylated persons (for example most persons with OCD), but can cause negative side effects in those who are overmethylated. Since Inositol is one of the primary second messengers in neurotransmission, it’s surprising is isn’t more commonly used. It’s especially useful in reducing anxiety and enhancing sleep.

To enhance sleep for a 160 lb person, we usually recommend 650 mg tablets, 1-3 as needed for sleep. Persons who have difficulty falling asleep should take it 30-60 minutes before sleep. Persons whose main problem is waking up in the middle of the night should take it at bedtime.

We’ve often given as much as 3-4 grams/day to undermethylated persons who respond beautifully to Inositol, and these persons take it morning, noon, and evening.

I once gave an invited presentation at a symposium at an APS annual meeting… in which data on megadoses (15-30 g) of Inositol were reported by another speaker. The volume of Inositol used seemed extreme to me, and would present daunting compliance problems. I believe such huge doses of Inositol are unnecessary, if methionine, calcium, B-6, and other nutrients to combat undermethylation are used. However, massive doses of Inositol might be needed if one tries to combat OCD with Inositol alone.

Regardless of the form of inositol, its use should be started as a trial, with close monitoring of patient. We’ve found that persons who achieve improved sleep after inositol are excellent candidates for taking it throughout the day also. I recommend you be alery for adverse side effects, especially with persons with severe anxiety or panic symptoms

Trichotillomania has been associated with OCD and undermethylation. If you can confirm the presence of undermethylation, the patient should benefit from (1) aggressive doses of l-methionine, calcium, magnesium, along with augmenting nutrients zinc, B-6, Inositol, Vitamin A & C and (2) strict avoidance of folic acid, choline, DMAE, and copper supplements

Aggressive methylation therapy can be very successful, but usually involves a very slow response. Typically, treatment with methionine, calcium, magnesium, B-6, etc requires about 2 months before the patient before any progress is evident — and 6-12 months are required for all of the benefits to be attained. Please note that whole blood histamine is a marker for innate methylation tendency, but is not an indicator of wellness or the degree to which undermethylation has been overcome. Undermethylated patients can become quite well without their histamine lab results changing at all.

One way to speed up the process of recovery is to use SAMe supplements in the beginning. Undermethylated patients usually report nice progress after the first week or two. SAMe is quite expensive, and can be gradually
replaced by methionine after a couple of months.

Nearly all severely undermethylated persons have low serotonin levels and present with a history of depression, internal anxiety, and OCD. Many have a history of perfectionism and high accomplishment in the early years.
Unfortunately this population also has a tendency for non-compliance with any treatment.

The late and great Carl Pfeiffer would occasionally resort to use of the anti-histamines Benedryl or Dilantin in high-histamine persons who were slow to respond. Avoidance of folate supplements is essential for most undermethylated persons, an exception being autism

Some practitioners like to tinker with the SAM cycle to promote conversion of homocysteine to methionine, but this can deplete the cystathione pathway and result in deficiencies of glutathione, cysteine, etc. Some persons have
a genetic enzyme weakness which can disrupt the SAM cycle

Undermethylated adults typically require 2,000 – 3,000 mg/day of methionine for several months to see good results. Also, augmenting nutrients such as calcium, magnesium, B-6, and zinc are essential.

TMG generally provides some benefits to undermethylated persons, but tends to make oxidative stress protections worse by diminishing the amount of homocysteine which converts via the cystathione pathway of the SAM cycle.
TMG certainly is a promising nutrient for such persons, and adding some cysteine or glutathione can overcome the cystathione pathway deficit.

Personally, I believe the use of SAMe is the quickest way to help an undermethylated, high-histamine person.

Learning Disabilities

There are many possible causes of serotonin deficiency including severe B-6 deficiency, folate overload, undermethylation, malabsorption, tryptophan deficiency, weak activity of tetrahydrobiopterin, etc. It would help a lot if the underlying reason for the low serotonin activity could be identified. The rate-limiting BH4 step in serotonin synthesis deserves special attention.

Oxidative stress can also increase serotonin requirements. However, I believe that chelation for serotonin enhancement is a very bad idea. The patient might be better served by supplements of glutathione, selenium, metallothionein-promotion nutrients, etc, to reduce oxidative stresses.


Most mentally ill patients have a lousy diet, and aren’t functional enough to achieve a major life-style change, such as fixing their diet. We’ve learned that the recipe for success is to first correct the primary chemical imbalance, and then fix the diet.

We’ve also learned to never attempt to take away their cigarettes, until AFTER they begin to respond to treatment….. for the same reason. Sometimes medical care (like politics) is the art of the possible.

We have major compliance problems with mentally-ill patients who hate medications. They become revulsed with swallowing capsules of all kinds, and it’s hard to convince a paranoid patient that there really are nutrients inside.

Very few of our SZ or bipolar patients have any money or any insurance other than medicare. At present, about 65% of patients with private insurance receive coverage for our fees. PPO’s pay about 20% of the time, but HMO’s almost never cover our services. As a public charity, we provide financial assistance for most of our seriously mentally ill clients.

Compliance with nutrient therapy is a big problem even in cases of 100% recovery. Eventually a patient will wonder if they really need to continue swallowing those capsules daily, and may stop for a few days. They don’t realize that it may take several weeks/months for their brain chemistry to revert to the original condition….. Often they are ok for about a month and then relapse. Nutrient therapy is much slower in response than medications.

We learned that best results are achieved if the patient continues their medication(s), if any, during the first few months of treatment. After the patient is significantly improved, we suggest that the medication be slowly reduced “to determine the optimum dosage of the medication”. Many psychiatrists will agree to this….. but often are astonished to discover that the patient is just fine with zero medication.

Medications can usually take away a patient’s psychosis, but the resulting over-sedation and “zombie-like” condition is repulsive to many. (March 18, 2003)

Obsessive Compulsive Disorder (OCD)

Most OCD patients (both obsessive thoughts AND compulsive actions) exhibit undermethylation and associated low levels of serotonin, dopamine, and norepinephrine. Choline is anti-dopaminergic and often makes OCD patients worse. Generally OCD patients respond nicely to methionine, SAMe, calcium, magnesium, B-6, inositol, TMG, and zinc. Most OCD patients get worse if given supplements of DMAE, choline, copper, or folic acid. 500 to 1000 mg/day of inositol will probably be needed to provide good response. (9 Jan, 2003)

We have corrected the disordered chemistry of hundreds of conduct disorder & ODD children & teens. We’ve learned that the older patients have a rotten self-image and terrible social habits, even if the original cause of the behavior disorder is eliminated. They usually profit greatly from quality counseling, once the chemistry is fixed. (1 Jan, 2003)

In my experience, counseling is often unsuccessful until the “edge” of the OCD tendency is overcome with methylation therapy….. but thereafter quality counseling can be helpful. (21 Dec, 2002)

My clinic has used inositol with thousands of patients & learned the following:

A) Inositol is usually very helpful for UNDERMETHYLATED, HIGH HISTAMINE patients. This includes nearly every OCD patient we have seen. Inositol usually provides calming throughout the day and ability to settle down to sleep at night, for these patients.

B) On the other hand, OVERMETHYLATED patients usually derive little or no benefit from Inositol, and may experience very nasty side effects from it.

C) Although a couple thousand milligrams may be needed to do the job & the tablets are often quite large, Inositol has the great advantage of being palatable….. Many of our patients chew it before swallowing, and report it “doesn’t taste bad at all”.

I’m quite surprised that Inositol isn’t more popular due to its effectiveness and its role as a major “second messinger” in neurotransmission.

Anorexia and bulimia

We have found that nearly all anorexic and/or bulemic patients are very undermethylated, low serotonin persons. Most of then respond very well, albeit slowly, to aggressive doses of methionine, Vitamin B-6, and calcium. A positive response can usually be achieved more rapidly with SAMe. In severe cases we often start with SAMe to get a quick improvement, and than gradually convery to methionine/B-6/calcium.

I certainly agree that a lousy food choices can aggravate an eating disorder, and might even trigger it in a person with a tendency for OCD and delusional thinking. An excellent dietary & nutritional program is an important component of success for these persons. (7 Jan, 2003)

In my experience, most anorexics are perfectionistic, obsessive-compulsive, high-histamine, low serotonin persons. Most have a history of high accomplishment in school and were never discipline problems. Most anorexics also have a history of being overweight, at least in their eyes. When they begin to diet, their OCD takes over and they go to great extremes. Also, when these emaciated skeletons of people look in the mirror, they tell me that all they see is FAT. It seems to involve a nasty combination of obsessive/compulsive disorder plus delusional thinking. I’ve never noticed a correlation with lousy diets. The anorexic I know best at present is a dedicated nutritionist/dietician….. who eats only the finest nutrient-dense whole foods. Her condition is still serious. (Jan, 2003)

I’ve observed that most anorexic and bulemic patients benefit greatly from a combination of biochemical therapy and counseling/psychotherapy. (30 Dec, 2002)

I’ve researched the biochemistry of hundreds of OCD patients, many of whom had comorbidity for schizo-affective disorder or delusional disorder. Typical characteristics for this patient population include undermethylation, weak functioning of the BH4 rate-limiting steps in synthesis of serotonin, and dopamine, low calcium levels, excessive folate levels, and high oxidative stress. (Aug 4, 2003)

Other helpful nutrients for OCD are methionine, calcium and magnesium…… since virtually all OCD patients are undermethylated, low-serotonin persons. (Aug 8, 2003)

Inositol is especially helpful for undermethylated persons (for example most persons with OCD), but can cause negative side effects in those who are overmethylated. Since Inositol is one of the primary second messengers in neurotransmission, it’s surprising is isn’t more commonly used. It’s especially useful in reducing anxiety and enhancing sleep.

To enhance sleep for a 160 lb person, we usually recommend 650 mg tablets, 1-3 as needed for sleep. Persons who have difficulty falling asleep should take it 30-60 minutes before sleep. Persons whose main problem is waking up in the middle of the night should take it at bedtime.

We’ve often given as much as 3-4 grams/day to undermethylated persons who respond beautifully to Inositol, and these persons take it morning, noon, and evening.

I once gave an invited presentation at a symposium at an APS annual meeting… in which data on megadoses (15-30 g) of Inositol were reported by another speaker. The volume of Inositol used seemed extreme to me, and would present daunting compliance problems. I believe such huge doses of Inositol are unnecessary, if methionine, calcium, B-6, and other nutrients to combat undermethylation are used. However, massive doses of Inositol might be needed if one tries to combat OCD with Inositol alone.

A word of caution — Manganese supplements tend to aggravate Tourette’s Syndrome, and can also worsen the symptoms of OCD.

Trichotillomania has been associated with OCD and undermethylation. If you can confirm the presence of undermethylation, the patient should benefit from (1) aggressive doses of l-methionine, calcium, magnesium, along with augmenting nutrients zinc, B-6, Inositol, Vitamin A & C and (2) strict avoidance of folic acid, choline, DMAE, and copper supplements

Oxidative Stress

It’s essential of course for digestive exzyme preparations (such as AbsorbAid) to survive stomach acid. However, this won’t help if there is too much oxidative stress in the gut, as this can wipe out many of the key enzymes (such as DPP-IV). Oxidative stresses often are the cause of the malabsorption or maldigestion problems….. Sending in more enzymes can have limited effect in this case. It’s a little bit like Pickett’s charge in the Civil War: The new soldiers are killed off as soon as they enter the fray.

We find that zinc therapy and metallothionein-promotion therapy can be effective in easing oxidative stress in the G.I. tract and overcoming these problems.

Tests for plasma zinc, serum copper and serum ceruloplasmin can give a good indication of “metal” oxidative stress. A Cu/Zn ratio greater than 1.20 or an excessive amount of “unbound” copper….. that is, copper not bound to ceruloplasmin….. are indicators of excessive free radical metal ions which can suppress or destroy many digestive enzymes, cause diarrhea, digestive pain, maldigestion, malabsorption and multiple food sensitivities. The levels will be abnormal in the presence of toxic overloads of mercury, cadmium, lead, antimony, etc. A hair analysis for the metals can provide some information also.(March 6, 2003)

Biochemical individuality is the key since there are many different biochemical abnormalities which may be at the root of the disorder….and each requires different clinical intervention.

However, one common thread which is present in most cases of SZ, ODD, ADHD, etc…… is excessive oxidative stress. As a result most of these patients exhibit high-normal (or worse) levels of toxic elements. The toxic metals are not the cause of the condition, but rather a consequence of genetic abnormality in metal-metabolism. Use of oral chelation is a short-term solution since DMSA, DMPS, etc do nothing to prevent lead, cadmium, mercury, etc from accumulating in the body again due to natural environmental exposures. Personally, I greatly favor metallothionein promotion therapy which can provide enduring benefits.

Many patients report a very nice improvement within a few days after oral chelation….. the improved symptoms usually last about 3 weeks, after which most patients return to the original state. Most practitioners who supervise chelation focus on driving toxic metals out of the body. However, I’m convinced that the improved symptoms are really due to the fact that the patients had severe oxidative stress, and DMSA, DMPS, etc are terrific antioxidants. I’ve known of many cases of autistic children who improve dramatically after DMSA, but lose the benefits in a very short time…… The same scenario may occur after more than 1.5 years of chelation. This clearly indicates that the improvements achieved were due to antioxidative benefits, rather than exit of toxic metals.

Occasionally we encounter a patient who has actually been severely poisoned by a toxic metal, and chelation is the first option. However, this is really quite rare. (Aug 4, 2003)

Another factor to consider is the high incidence of oxidative stress in the G.I. tract. This environment can destroy key digestive enzymes such as DPP-IV (needed to break down casein & gluten)….. This condition is especially common in autism-spectrum disorders.

Failure to correct the oxidative stress would doom supplemented enzymes to an early death. The result can be similar to Pickett’s Charge at the battle of Gettysburg…. The digestive enzymes are mowed down as soon as they enter the G.I. tract.

On the other hand, amino acid supplements can be quite helpful, even if digestive enzymes are absent. The reason is that the enzymes act to cleave (break down) proteins into the individual amino acids before the AA’s can be absorbed. “Free-form” amino acids need no further digestion or conversion….. They are already completely broken down to the form needed for efficient absorption.

Of course, proper enzymatic action is needed for effective processing of dietary protein and other foods, a requisite for good G.I. tract health. (Aug 20, 2003)

The casein-free, gluten-free diet often results in rapid striking improvements. However, nutritional supplements which overcome G.I. tract oxidative stress can make the CF/GF diet unnecessary.

Normalization of zinc, metallothionein, and glutathione in the G.I. tract isn’t difficult to accomplish. It’s a lot easier to take a couple of capsules daily than this difficult diet. It takes about 6-8 weeks for the G.I. tract to get “fixed” using this therapy.

We’ve had many patients who were extremely sensitive to dairy and wheat…. and did marvelously after the CF/GF diet. Many of these same patients completely lost their sensitivity to casein and gluten after the antioxidant supplementation….. and now can eat a normal diet without a problem. (Aug 21, 2003)

It’s becoming increasingly clear that oxidative stress has an important role in mental illness. Since psychic stress increases oxidative stress in the brain, sudden easing of emotional traumae would be expected to have a direct and beneficial chemical effect on the brain.

It’s true that mercury can be devastating to the brain and chelation cleans up peripheral mercury. However, most of us have a very effective system to protect us from mercury, namely glutathione & metallothionein in intestinal barriers, liver, blood/brain barrier, and the brain itself. Chelation to remove metals should be helpful only (a) in cases involving massive poisoning by heavy metals, or (b) in cases in which the normal protective systems fail to function properly. However, chelation can provide 2-3 weeks of benefits just from the antioxidant effect, whether or not there are nasty metals present.

Did you know that nearly all psychiatric medications are powerful anti-oxidants? I don’t think this is a coincidence.


Paranoia is a symptom rather than a specific disease condition, and is associated with a number of biochemical imbalances. First of all, it is clear that paranoia generally involves a genetic predisposition. In my experience paranoia usually involves either highly elevated norepinephrine or diminished GABA levels. The recipe for paranoid schizophrenia is (1) overproduction of dopamine due to an innate tendency for overmethylation, (2) excessive conversion of dopamine to norepinephrine due to high copper levels, and (3) depressed levels of GABA (which tends to quench the paranoia & anxiety associated with elevated norepinaphrine. The patients are usually afflicted with multiple medications which can provide some relief, albeit with very unpleasant side effects. Complementary medicine techniques to balance body/brain chemistry may involve therapies using folates, zinc, manganese, and vitamins B-3, B-6, C, and E and can be very successful This treatment should be individualized to reflect the individual’s array of chemical imbalances…. for best results. In many cases paranoia is exacerbated by estrogen therapy, environmental sources of copper, well-intentioned (but wrong) vitamin/mineral supplements, and/or chelation therapy. For females, paranoia tends to flare up during hormonal events including puberty, childbirth, and menopause. (Feb 10, 2003)

Placebo effect

I believe there are 4 major factors at work here: (1) improvements resulting from environmental changes, (2) true placebo effects in which a caring practitioner supplies hope, encouragement, and a positive attitude to the patient, (3) a Hawthorne effect in which the family and medical practitioners are giving attention & are monitoring the patient, and (4) cycles of improvement and relapse which are so strong that they overwhelm the therapies. (30 Dec, 2002)

Post Partum Depression

We have seen more than 3,500 persons with clinical depression including several hundred with a history of post-partum depression. Most PPD females exhibit a copper overload and zinc deficiency. Most PPD females report major improvement after nutrient therapy aimed at balancing Cu & Zn levels. Most normals have Cu/Zn ratios in the 0.75 to 1.15 range, whereas most PPD females exhibit a Cu/Zn ratio in the 1.5 to 2.0 range. The cause appears to be a genetic weakness in regulation of Cu & Zn which may involve weak functioning of the metallothionein/glutathione system.


Depression, anxiety, panic episodes, and paranoia in pregnancy are often caused by an inborn inability to regulate copper and zinc in the body. During pregnancy, a woman’s blood copper level more than doubles….. in order to provide sufficient copper to the fetus to support angiogenesis. Persons who have a genetic tendency for copper overload get into real trouble during and immediately after pregnancy since elevated Cu levels in blood result in diminished dopamine and elevated norepinephrine in the brain. This is a recipe for panic attacks, depression, etc.

I suggest a blood serum test for copper and a plasma test for zinc. If the levels are severely abnormal, there are natural treatments which can decisively correct the problem. The first step is to discontinue pre-natal vitamin supplements that contain copper. We’ve guided dozens of anxiety/panic/depression prone women through pregnancies, but one must be careful to avoid aggressive therapies (including natural ones) which might adversely affect the fetus. (Sep 8, 2003)

Psychiatric Medications

Individual psychiatric medications can impact methylation, histamine levels, oxidative stress, and can result in depletion or accumulation of specific proteins, enzymes, neurotransmitters, vitamins, and minerals. (Aug 1, 2003)

A published article of interest is one by John Crayton (research psychiatrist, then at U. of Chicago). Crayton measured dendrite populations with and without psychiatric medication. He found that psychiatric medication (I think he focused on Prolixin) caused a proliferation of dendrites on peripheral neurons. This, of course, is a
permanent change….. and possibly the cause of Tardive Dyskinesia. This article received very little attention, despite its striking finding….. namely, permanent damage caused by psychiatric medication.
(Sep 2, 2003)

Pyrrole Disorder

Omega 3s can worsen mental symptoms in bipolar or schizophrenic patients…. if they have a pyrrole disorder. This phenotype is dramatically short of arachidonic acid & giving omega 3 oils aggravates the situation since omega 3 and omega 6 EFA’s are in competition for delta 5,6 desaturases. We use red blood cell membrane analysis for EFA’s
if we suspect this problem.

Pyroluric mental patients will usually get worse if given fish oils, DHA, EPA, etc. They thrive on Primrose Oil, a good source of AA and other omega 6s. (June 23, 2003)

Most persons with pyroluria respond very quickly to the B-6, Zn, C, E therapy….. Major improvements are often seen by the 2nd day, and almost always by the end of the first week. The exceptions are: (1) persons with severe mental illness (schizophrenia or bipolar), (2) persons with other significant chemical imbalances, and (3) patients with a major malabsorptive condition. When pyroluria is diagnosed along with another chemical imbalance, I like to track a patient during the first 6-8 weeks to determine which is the dominant imbalance. If major improvement occurs immediately, it’s because pyroluria has been corrected. Some patients report a nice early improvement followed by a plateau, and then another advance.

Schizophrenic and bipolar pyrolurics usually report some progress after a few weeks, but it may take 3-6 months to get to steady state. The biggest problem with the Kp analysis is getting a proper sample to the lab. The kryptopyrrole molecule is unstable and will disappear rapidly at room temperature or if exposed to bright light. The urine sample must be placed in a freezer immediately after acquisition. Kp can be lost in the freezer if the temperature isn’t well below 32 degrees F. We’ve also learned that exposure to bright light results in breakdown of the Kp molecule. Finally, the sample must be maintained in a frozen condition during shipment. I would greatly suspect any Kp value below 3.0. Usually this means the sample didn’t get to the lab in proper condition.

With respect to reference levels: We consider a healthy level to be between 4-8 mcg/dL. We consider persons between 10 and 20 to have mild pyroluria, and a good response to treatment is usually reported. Persons exhibiting 20 to 50 mcg/dL have moderate pyroluria, which can be a devastating condition. Persons above 50 mcg/dL have severe pyroluria.

Longitudinal testing of pyrolurics has shown that major variations can occur during a day. For example, Arthur Shawcross (famous NY serial killer) had levels ranging from 35 to 203, with higher levels observed during stressful periods in prison. However, he always tested as pyroluric in multiple tests. Stresses, illnesses, injury, etc can be expected to elevate Kp levels. Medical history and review of symptoms are vital to this diagnosis.

The major challenge in differential diagnosis of pyroluria is the similarity in symptoms between pyroluria and overmethylation (low blood histamine). Another problem is that symptoms of pyroluria are greatly muted in undermethylated, obsessive/compulsive persons. These persons may be high achievers, with great internal tension….. Persons with pyroluria alone tend to underachieve, partly because of a poor short term memory and associated reading problems. (Nov 10, 2003)

We’ve obtained hair Zn and plasma Zn levels (simultaneously) about 40,000 times. Low hair zinc correlates beautifully with low plasma levels. However, very elevated Zn in hair nearly always means Zn deficiency and loss plasma Zn levels. Most of the time this involves a Pyrrole disorder which results in very high Zn excretion in urine (and hair). In a healthy person without metal-metabolism problem, only about 4 percent of excreted Zn leaves through the kidneys. [28 Nov 03]

Symptoms of pyroluria include (1) stunting of growth, (2) unpleasant body odor, (3) delayed puberty, and (4) skin stretch marks. This family’s symptoms are certainly consistent with pyroluria.

Pyroluria definitely runs in families. We have a mother in Kane County, IL who has 15 children & all of them tested pyroluric. The mother had a Kp level of over 150 herself


SAMe is very promising for undermethylated persons and a bad idea for those who suffer from a genetic tendency for overmethylation. I don’t particularly like the “allopathic” method you referred to which is simply trial & error. SAMe can do great harm if given to the wrong person. I hate going to funerals. (17 Dec, 2002)

The mechanisms of action of SAMe and TMG are quite different. Most of our methyl groups come from dietary methionine. The methionine is converted to SAMe in a reaction with magnesium, ATP,
methionine-adenosyl-transferase, and water. SAMe is a relatively unstable carrier of methyl groups and is the primary source of methyl for most reactions in the body. Once the methyl group has been donated, the residual molecule is s-adenosyl-homocysteine which converts to homocysteine. TMG (betaine) is a biochemical which can donate a methyl group to homocysteine, thus converting it back to methionine. The TMG route is secondary to the 5-methyl-tetrahydrofolate/B-12 reaction which the primary route for restoring methionine. Methionine and SAMe supplements directly introduce new methyl groups into the body. TMG can provide a methyl group only to the extent that there is insufficient folate/B-12 to do the job. In some persons, the methylation effect of TMG is very minimal. In addition, persons who are undermethylated have a SAM cycle which is “spinning very slowly”, much like a superhighway with little traffic. The answer for them is NOT to more efficiently convert the small amount of homocysteine to methionine (using TMG), but rather to directly introduce more methionine or SAMe into the body. A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe — These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule. In most other cases, methionine supplements alone are sufficient. TMG is a great way to treat individuals with dangerously high homocysteine levels. TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine. Use of TMG is an “insurance policy” against this happening. (Jan 22, 2003)

A quick way to test for need for methylation therapy is to carry out a cautious trial of SAMe. Within a week or two you should have your answer. If she clearly is improving on the SAMs (which is frightfully expensive)….. you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6. This should be side-effect free unless (a) the methylation is begun too abruptly or (b) the patient has a rare genetic enzyme disorder which disrupts the SAM cycle. We’ve found that direct methylation is usually more successful than tinkering with the SAM cycle. The primary way humans receive most of their methyl groups is from dietary methionine. It’s often hard to improve on Mother Nature. (Jan 20, 2003)

SAMe is likely to cause great worsening of symptoms, including mania, if given to an OVER-methylated person. The incidence of overmethylation in our patient database of 1,500 bipolar cases is about 18%. Bipolar disorder is not a single condition, but a collection of very different biochemical disorders under the same umbrella diagnosis. SAMe works great for truly undermethylated patients, but all hell breaks out if given to someone who is
overloaded (genetically) with methyl groups. The right way to do this is to (a) first determine the person’s innate methylation tendency & then (b) act accordingly. (Jan 31, 2003)


Severe wheat gluten intolerance can cause classic symptoms of schizophrenia, and amounts to about 4% of all schizophrenia diagnoses in the U.S. These persons usually become quite normal when placed on a gluten-free diet.

I’ve done medical histories for more than 2,000 persons diagnosed with schizophrenia and have always been struck by the high frequency of schizophrenia in other relatives. Interestingly, the schizophrenia would often skip a generation. NIMH data suggests that the overall incidence of schizophrenia in the USA is between 1% and 4%, depending on the definitions. However, the incidence of schizophrenia for children who have a schizophrenic parent is about 16%. This number doesn’t change much for children of schizophrenics adopted at birth. I don’t think there is “a schizophrenia gene”, partly because this is a garbage term which encompasses several completely different conditions. There are a number of biochemical ingredients which predispose to each phenotype of SZ….. these may be either genetic or acquired. However, I’m absolutely certain there is a genetic component in most cases.

Carl Pfeiffer was the first to develop meaningful chemical classifications of schizophrenia (and separate treatments for each phenotype). Carl Pfeiffer of Princeton, N.J. saw more than 20,000 schizophrenics in his lifetime. He found that 90% of all SZ patients could be classified into 3 large groups, with completely different etiologies & treatment approaches. These he termed “histapenia”, “histadelia”, and “pyroluria”. The remaining 10% fit into several splinter groups. One of the splinter groups was gluten intolerance, which represents 4% (1 case in 25). This is a rare form of schizophrenia, but if you’ve got it, it’s everything!

Multiple food & chemical sensitivities are also associated with histapenia (low histamine, overmethylation), the largest of all SZ groups, amounting to about 48% of all cases. For this group, SZ symptoms often worsen if exposed to the offending substances, & nice improvements often occur if they are identified & avoided. However, the food sensitivities usually disappear after about 1 year of aggressive Folate/B-12/B-3 treatment, which is the primary route to a normal life for these patients.

We’ve known for more than 20 years that the metallothionein protein system does not perform well in most ADHD patients. About 68% of them exhibit very poor control of Cu & Zn, based on lab data from more than 6,000 patients diagnosed with ADD/ADHD. Autism is different in that about 90% of patients exhibit Cu/Zn imbalances that are generally much more severe than in ADHD.

For several months, we have extended our metallothionein-promotion protocol to ADHD, behavior, depression, and schizophrenic patients who exhibit Cu/Zn imbalance. The informal results so far are very encouraging. However, we’ve not yet done a formal outcome study for these populations, and thus have no statistics yet.

We are considering applying MT-Promotion to Alzheimers & Parkinsons patients in the near future. Both disorders involve serious oxidative stress and abnormal trace metal levels. In addition, recent research has revealed a striking metallothionein deficiency in the brains of Alzheimers patients. (Feb 25, 2003)

I’ve evaluated more than 3,500 patients with a diagnosis of bipolar or schizophrenia. The predominance of auditory hallucinations, serious self abuse, aggressiveness, inability to continue school, and social isolation…… all point in the direction of classic “paranoid schizophrenia”, although many of these patients are labeled “bipolar disorder with psychotic features”. Most severely mentally ill persons with a history of exceptional artistic or musical talent test as overmethylated. The biochemical recipe for these patients usually consists of (1) overmethylation, (2) low folate levels, and (3) elevated blood copper levels. All three of these chemical imbalances impact dopamine and norepinephrine in the brain, and together can cause rather extraordinary abnormalities in these important neurotransmitters. In my opinion, the key to successful treatment is biochemical treatment to overcome these chemical imbalances…… fortunately this can be accomplished using aggressive therapy with nutrients to normalize the chemical factors.

Most mental breakdowns are triggered by severe stress, but the underlying cause is genetic and involves brain chemistry. Many persons self-medicate with alcohol, marijuana, or other illegal drugs in a desperate attempt to feel better. Many patients and their families erroneously believe that the EtOH or drug experiences were the underlying cause of the condition. They are wrong! This adult-onset condition will strike eventually in most cases, even if substance abuse never occurs.

Traditional medicine can provide medication support which can usually eliminate (temporarily) most/all psychosis symptoms. However, these patients are usually plagued by drug side effects and are a mere shadow of their original selves. Common side effects are (a) fatigue, (b) inability to focus/concentrate for more than a few minutes, (c) change in personality, (d) massive weight gain, etc. The most popular drugs for these patients are Zyprexa, Seroquil, Risperdal, Geodon, and Clozaril….. the so-called atypical antipsychotics. Since most patients hate these medications, poor compliance is a major problem.

I’ve seen many young schizophrenics and bipolar patients achieve complete recoveries through biochemical (nutrient) therapy. This rarely occurs with traditional medication therapy. (May 12, 2003)

Some of schizophrenics who spontaneously get better are those who experience a toxic psychosis. I have a friend who had a toxic psychosis after an accidental overdose of a medication during childbirth. For 6 hours she was a full blown paranoid schizophrenic….. No symptoms in the following 20 years. Also, schizophrenia comes in mild, moderate, and severe versions. Many persons with a very mild genetic tendency for SZ can experience an environmental insult which pushes them into a temporary mental illness. Most will become quite ok with or without therapy.

The real problem is the millions of SZ persons who have moderate to severe SZ which does not go away easily. (May 27, 2003)

Based on epigenetic science, niacin should be beneficial to overmethylated SZ patients and harmful to undermethylated SZ patients. However, after working with thousands of patients we have learned that niacin is helpful for all forms of SZ — The overmethylated usually achieve a major benefit, but the undermethylated a mild improvement. Carl Pfeiffer was the first to observe this. Niacin biochemistry is complex and there’s more than epigenetics involved.

Niacin inhibits sirtuin, a major deacetylase inhibitor, and niacin enhances DAT (dopamine transporter) expression by this mechanism, thus lowering dopamine activity. However, we now know that the NMDA receptor system is also a major factor in SZ and it appears niacin improves glutamate activity at NMDA. (Sep. 30, 2015)



Yes, I’ve read a few articles and a book that talked about Taurine’s slow metabolism and tendency to build up over time. Because of this, I’ve believed that high doses of Taurine (1,000 to 2,000 mg/day) are ok in the beginning….. but that the dosages need to be reduced within 2 weeks to about 400 to 500 mg/day….. to achieve the same effect.

I believe that Taurine is especially effective for (1) combating seizure tendency and (2) reducing liver stress in processing fats. There have been several reports of intolerances and side effects from use of Taurine, and I feel that indiscriminant high doses are unwise.

About 12 months ago, there was a fad among several alternative practitioners in which high doses of Taurine were given to every autistic patient. One of the reasons given was “to assist the liver cope with stresses associated with toxic metal overload”. This seems to be a poor reason, since Taurine’s action in the liver appears to be limited to fat metabolism, and most autistics are slender malabsorbers with low lipid levels. (June 24, 2003)

Womb Trauma

There is an exquisite and fragile biological/biochemical process during gestation in which short, dense immature brain cells are pruned, grow into fully-developed brain cells, and then (remarkably) experience growth inhibition to complete the process. The molecular biology of this process is becoming very well defined, and it is clear that many environmental events can hinder or disrupt early brain development. The primary culprits are oxidative stress, teratological chemicals, and infections. The least appreciated of these harmful factors is oxidative stress which can deplete key proteins and enzymes required for normal brain development.

Environmental harm to a developing fetus can result from (a) biochemical inadequacies of the mother, and (b) external environmental insults. We’re all familiar with birth defects that can result from Thalidomide, Thorazine, Prolixin, Haldol, and other psychiatric medications. Also the dangers of mercury, lead, and other toxics are well established, and we know that a mother’s improper diet (e.g. inadequate folic acid) can be harmful. Although lower on the radar screen, fetal oxidative stresses can be equally devastating.

What I’m leading up to…. is the scientific fact that serious emotional or physical stresses experienced by the mother can impair early brain development, especially if the mother is not biochemically intact. For example high emotional stresses or physical trauma to the mother will weaken the activity of metallothionein (MT) and glutathione (GSH) proteins, and
increase oxidative stress in the brain. MT-1 and MT-2 are directly involved in growth of immature brain cells. MT-3 is a key protein required for pruning and growth inhibition. These proteins also have the job of defending against oxidative stress in the brain and are consumed in the process. Maternal emotional stresses and psychic traumae deplete the embryonic brain of MT proteins and can compromise brain development.

Womb trauma is real and the concept of “a cry so deep” is not psycho-babble guesswork. Rather, it is solidly supported by scientific fields such as embryology and molecular biology. (Aug 1, 2003)

If fetal or early infant traumae have resulted in a brain that hasn’t completely matured….. therapies to promote MT and GSH appear very promising….. especially in tandem with
behavioral therapies which stimulate the development of new brain cells.

If the net result of the traumae is biochemical or neurotransmitter differences, then biochemical therapy aimed at normalizing brain chemistry would be indicated.

If the traumae resulted in diminished ability to tolerate environmental toxins (for example an incompetent blood-brain barrier), then avoidance of such toxins would be an important aspect of treatment.

If the traumae resulted in an innate inability to cope with emotional stresses, then counseling or other psychological services could be very beneficial.

If the traumae resulted in a brain that is structurally different, this may represent “brain damage” that may be refractory to all treatments. (Aug 1, 2003)


There have been several recent published articles which indicate that zinc and zinc metallothionein proteins (1) tend to prevent brain strokes, (2) tend to assist brain recovery after strokes, and (3) that deficiency of Zn or Zn-MT is associated with increased stroke likelihood. An occasional test for plasma Zn could help identify the proper dosage. Most adults can safely start with 25 to 50 mg/day of Zn. Without indication of B-6 deficiency, it might be a good idea to limit pyridoxine hydrochloride (usual form of B-6) to about 200 mg/day. B-6 is very helpful in enhancing the utilization of Zn.

After use of these nutrients with thousands of persons, I’m not aware of a single case of harm. However, it is a good idea to introduce zinc gradually & to take Zn during the PM only. (June 3, 2003

Every 5 years or so, the zinc experts of the world convene for a symposium in which they share new advances in Zn technogy & research….. It’s usually headed up by the eminent Prof. Prasad.

One of the topics is laboratory testing to indicate an individual’s Zn status. They consider about 10 different methods including packed cells, taste tests, etc…… The last two symposia resulted in the consensus that none of the testing options is wonderful, but that the best of the commercially available tests is plasma zinc. Taste tests didn’t make the top three methods.

However the Zn experts also stated that the most definitive determination of zinc depletion is the presence of symptoms of Zn depletion which disappear after Zn supplementation.

My organization has evaluated the Zn status of 18,000 patients and we’ve tried all of these methods. Our standard protocol involves plasma Zn, being careful to use acid-etched, trace-metal-free tubes.

We find that virtually all treatment-naive ASD persons are very Zn depleted and overloaded in “free” (unbound by ceruloplasmin)copper. Our patient population for ASD is 2,800. Our database of 5,600 ADHD patients indicates that about 75% are depleted in Zn. The remaining 25% have problems associated with pyrrole disorders, methylation disorders, EFA disorders, toxic overloads, etc. (July 22, 2003)

The high level of zinc depletion in ASD appears to stem from a genetic weakness in the metallothionein protein system.

Cu/Zn ratios in hair are very helpful in ADHD and behavior disorders….. but far less useful in ASD, depression, and schizophrenia. Tracking plasma Zn, serum Cu and serum ceruloplasmin levels can be very helpful in guiding dosages aimed at normalizing Zn. Management of Zn & Cu levels is a challenging problem in ASD. Sometimes rather extraordinary Zn dosages are required to normalize blood Zn levels.

Virtually all ASD persons are Zn depleted., but not all exhibit an elevated Cu/Zn ratio. A minority of ASD patients exhibit normal or low Cu levels in serum, but have vastly inadequate levles of ceruloplasmin. Thus, the level of “unbound” Cu can be very high, even though all standard measures of Cu appear to be low. Some of these patients seem to have a mild version of Wilson’s Disesase. (July 24, 2003)