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Commentary on Nutritional Treatment

of Mental Disorders

from Willam Walsh, Ph.D., Senior Scientist, Pfeiffer Treatment Center

www.hriptc.org

(The

following information is taken from Dr. 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.)

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Index

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.

Mercury

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)

Metallothionein

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)

Methylation

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.

Neurotransmitters

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.

Nutrient

Therapy

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.

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 ( 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

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.

Pregnancy

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 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

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