NEUROTRANSMITTER TESTING AND AMINO ACID THERAPY

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NEUROTRANSMITTER TESTING

 

And

 

AMINO ACID THERAPY

 

 

 

CONTENTS

 

QUICK GUIDE TO LAB AND AMINO ACIDS

 

3 Laboratory values, normal, optimal and therapeutic

 

4 Amino acid dosing and Laboratory testing recommendations

 

TECHNICAL HELP AND NeuroResearch

 

5 Technical support and contacting NeuroResearch

 

5 NeuroResearch history

 

6 Why has this not been done before?

 

NEUROTRANSMITTER CONSIDERATIONS

 

7 What are neurotransmitters

 

8 Synaptic model

 

10 Disease caused by low levels of neurotransmitters

 

11 Catecholamine and serotonin synthesis pathways

 

12 Neurochemistry overview.

 

13 Size of serotonin neurons

 

NEUROTRANSMITTER DEPLETION

 

13 Both systems must function properly

 

18 Cause of neurotransmitter depletion

 

19 Drug depletion

 

20 Neurotoxicity

 

21 Drugs do not work if there is not enough neurotransmitters

 

22 The healthy American diet

 

23 A list of neurotransmitter depleters

 

24 Causes of neurotransmitter dysfunction

 

NEUROTRANSMITTER TESTING

 

25 Testing for drug induced depletion with time considerations

 

26 Phentermine and Bontril testing

 

27 Phentermine depletion theory

 

28 Prozac testing

 

28 Thoughts on drugs that cause depletion

 

29 CNS stimulant testing

 

29 Hyperactivity testingTUAL PROPERTY STATEMENT

 

30 Obesity initial testing

 

30 Testing for appetite suppression

 

AMINO ACID THERAPY

 

32 GI upset

 

33 GI upset on start up = depletion

 

33 GI upset weeks into treatment = carbohydrate intolerance.

 

35 USDA RDA

 

35 Amino acid side effect profile

 

36 Critical balance

 

37 5-HTP that does not work

 

37 Peak-X

 

37 Most sensitive to B6

 

37 Switch theory

 

38 Dosing needs

 

39 So, how much do you use?

 

39 Aggressive adjusting of amino acids.

 

40 Time between dosing changes

 

40 Extra in the PM

 

40 Never adjust " one pill "

 

40 Find the lowest dose

 

41 Pills quit working

 

41 The tired patient

 

41 The anxious patient

 

42 Long hours

 

42 Alcohol intake

 

42 Tapering off medications

 

43 Amino acids / drug interactions

 

43 Use in pregnancy

 

43 5-HTP supports tryptophan

 

44 A story of tryptophan

 

NEUROCHEMISTRY

 

44 Neurochemistry of serotonin

 

45 Neurochemistry of catecholamines

 

48 SAMe

 

50 Dopamine and SAMe

 

50 Selenium

 

52 Glutathione

 

53 Central and peripheral serotonin correlation

 

DISEASE CONSIDERATIONS

 

53 Was man doomed to suffer?

 

54 Treatment of depression

 

55 Treatment of migraine headaches

 

55 Fibromyalgia

 

55 Incidence of neurotransmitter disease

 

56 The 1A Survey

 

WHAT ARE NEUROTRANSMITTERS

 

Neurotransmitters are naturally occurring chemicals in human

 

beings and animals. They relay electrical messages between nerve

 

cells known as " neurons " . This is not a simple process.

 

In the foods that we eat there are 4 basic components:

 

1) Vitamins

 

2) Minerals

 

3) Amino acids

 

4) Calories

 

Neurotransmitters are built in the body from amino acids with

 

the assistance of vitamins and minerals known as " cofactors " . If

 

the body does not take in enough of the amino acids, vitamins, or

 

minerals to build neurotransmitters, a neurotransmitter deficiency

 

state develops. Over time this leads to the development of diseases

 

and illnesses caused by or associated with low levels of

 

neurotransmitters.

 

Treating the illness that develops from low levels of

 

neurotransmitters by giving the patient oral or IV neurotransmitters

 

will not work since neurotransmitters will not cross the blood brain

 

barrier and enter the brain. Drugs such as Zoloft, Prozac, and other

 

drugs that work with neurotransmitters do nothing to increase the

 

overall level of neurotransmitters in the brain. They work by a

 

process known as " redistribution, " where neurotransmitters are

 

simply moved from one place in the brain to another in order to

 

trick the brain into thinking there are more neurotransmitters in the

 

system. In fact, there are no more neurotransmitters in the already

 

depleted brain. As discussed in this manual, drugs that work with

 

neurotransmitters, over time, actually deplete the already low

 

levels of neurotransmitters in many people, effectively making the

 

real cause of the problem worse.

 

The only way to actually increase the level of neurotransmitters in

 

patients suffering from neurotransmitter deficiency disease is by

 

giving them amino acid precursors, vitamins, and minerals the

 

body needs. Unlike neurotransmitters, precursors cross freely into

 

the brain where the body converts them to neurotransmitters and

 

actually increases the overall level of neurotransmitters in the

 

deficient system as verified by laboratory testing.

 

So this begs the question, " Why don’t we simply train people to

 

eat properly in order to get rid of their diseases? " As you will see

 

by reading this booklet, simply designing the perfect diet is not

 

practical or possible. We know from our database research as

 

based on data from almost 100 clinics, that the perfect diet would

 

involve eating the amount of protein found in 35 ounces of red

 

meat or 18 eggs each day. 35 ounces of meat has 2,440 calories

 

and would never keep a 140-pound female at 140 pounds,

 

therefore we looked to nutritional supplements for help.

 

Supplements are used within USDA guidelines and obtain results

 

that cannot be achieved on a practical level from diet alone.

 

When neurotransmitters are excreted into the synapse, in response

 

to an electrical stimulation traveling down the pre-synaptic neuron,

 

the process is best thought of as one of modulation of the post

 

synaptic neuron. Low levels of neurotransmitters in the synapse

 

will cause ineffective firing of the post-synaptic neuron and high

 

levels of neurotransmitters will cause an excited firing of the post

 

synaptic neuron. The post-synaptic neuron has the potential to fire

 

an electrical charge. It is the magnitude and the rate of firing that

 

are controlled by the neurotransmitters as they come in contact

 

with the receptors of the post-synaptic neuron.

 

SYNAPTIC MODEL

 

Even though the NeuroResearch drawing on the next page depicts

 

serotonin flow between the pre-synaptic and post-synaptic neurons,

 

the same is basically true regarding the catecholamines (dopamine,

 

norepinephrine, and epinephrine) as follows.

 

NEUROCHEMISTRY OVERVIEW

 

BLOOD BRAIN BARRIER

 

A curtain of blood known as the " blood brain barrier " surrounds

 

the brain. In general, water-soluble things cross the blood brain

 

barrier and get into the brain, whereas fat-soluble things do not

 

cross the blood brain barrier.

 

NEUROTRANSMITTERS

 

Neurotransmitters are the chemicals in the nervous system that

 

relay and modulate electrical impulses between nerve cells known

 

as " neurons. " Low levels of neurotransmitters cause diseases and

 

illness. Neurotransmitters are fat soluble and do not cross the

 

blood brain barrier, when given to a patient with low levels of

 

neurotransmitters orally or IV, they will do nothing to increase

 

neurotransmitter levels at the point of the problem, the brain.

 

AMINO ACIDS

 

The body builds neurotransmitters from amino acids. The

 

building of neurotransmitters requires vitamins and minerals,

 

which are known as cofactors, in order for the appropriate

 

chemical reactions to occur in the brain. Only by giving the body

 

what it needs to build neurotransmitters can the problem be

 

properly addressed and the levels of neurotransmitters in the brain

 

be increased. Through laboratory testing, we are now able to

 

demonstrate this increase.

 

SIZE OF SEROTONIN NEURONS

 

The common conception is that serotonin neurons are extremely

 

small. The fact is that the serotonin neurons in the adult human can

 

be up to 12 inches long. The lines on the follows brain represent

 

one serotonin neuron arising from the base of the brain.

 

MIXED NEUROTRANSMITTER

 

DYSFUNCTION THEORY

 

Based on clinical observations, NeuroResearch has formulated

 

the following theory known as the " mixed neurotransmitter

 

dysfunction theory " . 5% of patients with a given neurotransmitter

 

dysfunction disease are purely a serotonin dysfunction, 5% of

 

patients with a given neurotransmitter dysfunction disease are

 

purely a catecholamine dysfunction and the remaining 90% of

 

patients are a mixture of both serotonin/catecholamine dysfunction

 

and lie along a spectrum between the two extremes.

 

BOTH SYSTEMS MUST FUNCTION PROPERLY

 

The serotonin system and the catecholamine system (dopamine,

 

norepinephrine, epinephrine) must both be functioning properly

 

for the entire system to be healthy and free of neurotransmitter

 

disease. This appears to be reflected in neurotransmitter testing by

 

the fact that patients with dysfunction of the catecholamine system

 

tend to need higher serotonin levels to compensate and obtain a

 

clinical response.

 

Prior to his retirement, the head of the clinical science department

 

at the local medical school on many occasions said, " The serotonin

 

and catecholamine systems must both be functioning properly for

 

the system as a whole to function properly and be healthy. "

 

Coming from the head of the clinical science department we took it

 

as gospel truth. It was only after working with patients extensively

 

in weight loss for several years did I fully appreciate what he

 

meant.

 

There is one final truth to the equation and that is, " 5% of

 

patients with neurotransmitter disease relating to the serotonin and

 

catecholamine system are purely a serotonin dysfunction, 5% are

 

purely a catecholamine dysfunction, and the remaining 90% are a

 

mix of serotonin and catecholamine dysfunction lying somewhere

 

along the spectrum between the two ends.

 

If you understand the two concepts above and use them as

 

reference points in working with patients who have

 

neurotransmitter dysfunction, eventually you too will come to see

 

the patients who are purely a catecholamine or serotonin

 

dysfunction as well as the rest of the patients.

 

HOW DO YOU SEE THE PATIENTS?

 

In this discussion, I will turn to clinical experience in treating

 

patients with depression and obesity, although the approach for

 

other diseases are similar.

 

The head of the clinical science department at the medical school

 

had a strong interest in the treatment of obesity and his assertion

 

was that weight problems were caused by dysfunction of serotonin

 

and/or norepinephrine. This assertion seems simple enough but the

 

ramifications are profound. Since the head of the clinical science

 

department at the medical school said it, I took it as true and in

 

retrospect he hit the nail on the head. Along the way, I have come

 

in contact with many physicians who did not have the benefit of a

 

medical school department head as they started treating obesity

 

and advocated numerous other things as being the cause, many of

 

them not even related to neurotransmitters. Sure there are other

 

things that affect weight loss, but from an appetite control and

 

suppression stand point, it is ONLY serotonin and norepinephrine

 

that have the ability to function.

 

So how do we know this? First, let’s answer this question from a

 

clinical standpoint. The only prescription drugs that we have in

 

medicine that induce appetite suppression are the drugs that work

 

with serotonin and/or norepinephrine. There is no appetite

 

suppression associated with any of the drugs that work with

 

dopamine, epinephrine, or anything else for that matter.

 

The weight loss drug phentermine, for example, works in a very

 

powerful way with norepinephrine and induces appetite

 

suppression. Appetite suppression, in turn when used properly with

 

proper patient positioning causes weight loss to occur.

 

Amphetamines have a very strong effect on serotonin.

 

Fenfluramine was a very well known amphetamine that produced

 

appetite suppression by increasing serotonin levels in the synapse.

 

Tim Seaton, MD, the medical director for Meridia at Knoll

 

pharmaceuticals personally told me of an animal experiment they

 

had performed where mico-electrodes were wired into the synapses

 

of rat brains and the rats were subsequently fed fenfluramine. The

 

intersynaptic levels of serotonin went up 2,500 times.

 

Certain norepinephrine drugs and certain serotonin drugs can

 

induce appetite suppression, but there is a third type of drug known

 

as the serotonin norepinephrine reuptake inhibitors (SNRI), which

 

works on both the serotonin and norepinephrine system. The

 

prototype drug in weight loss is Meridia, which works on both

 

systems and induces appetite suppression.

 

Over-the-counter preparations that work to induce appetite

 

suppression include Ephedra and Phenylpropanolamine (which

 

was recently pulled from the market). Both again exert their effects

 

on the serotonin and norepinephrine systems.

 

So what did the first patient with norepinephrine dysfunction only

 

look like? I was in the clinic seeing patients and we were having

 

the patients fill out a form relating to serotonin diseases. The

 

patient came into the clinic for weight loss, and by way of the

 

survey she had filled out, indicated that she had no problems with

 

serotonin disease. The real lynch pin was the history obtained. She

 

previously had dieted on phentermine alone, lost 48 pounds and

 

never was hungry. Anyone who has worked with phentermine

 

only in weight loss knows what a feat that is. I had before me a

 

pure norepinephrine dysfunction patient.

 

I have seen very few patients, who on 5-HTP alone lose all the

 

weight they want. Obviously these people are a serotonin only

 

dysfunction.

 

I hope I have planted the seeds here to, at least, get you thinking

 

about neurotransmitter dysfunction in patients as lying along a

 

spectrum, and who knows, maybe some day you too will see your

 

first norepinephrine only dysfunction patient.

 

TREATING ONLY ONE SYSTEM

 

WILL NOT WORK IN ALL

 

5-HTP has gained recognition as being helpful in and of itself in

 

the treatment of neurotransmitter disease and we have studied its

 

chemical properties and clinical applications extensively. Based on

 

our experience and research from our large database, I would make

 

the following observations on the use of only 5-HTP.

 

Only 35 to 40% of patients get some results using 5-HTP alone,

 

the rest get no response. Sure there is the 10 to 15% of patients

 

who get spectacular results from 5-HTP when used alone and are

 

held up for all to see. The remaining 85 to 90% who get only a

 

marginal response, or no response, are swept under the rug.

 

So, why do not all patients respond to 5-HTP only? Remember

 

the assertions at the beginning of this section, " Both systems have

 

to be functioning properly for the system to be healthy. " In using

 

5-HTP only to treat a group of patients, you are ignoring many

 

things and many people do not get better. Hence the need for both

 

5-HTP and tyrosine with all the cofactors and supporting elements

 

we have put in place. With the right combination (like we have put

 

in the supplements) and proper training on how to treat with amino

 

acids, 95%+ of patients will do as well as and arguably much

 

better than any treatment available with prescription drugs.

 

DEPRESSION THE SPECTRUM MODEL

 

We have talked about the treatment of obesity as it relates to

 

mixed neurotransmitter dysfunction, but the basic concepts just

 

discussed are the same for virtually all neurotransmitter diseases

 

relating to serotonin and catecholamines. To make the point, we

 

will now explore the treatment of depression.

 

Focusing first on 5-HTP, if you treat patients with depression

 

with 5-HTP only about 10 to 15% of patients will get good results

 

with the rest getting marginal or no results. In medicine, there are

 

prescription drugs that work almost exclusively with serotonin in

 

the brain such as Celexa. Celexa is a highly selective serotonin

 

drug that is effective in the treatment of depression, but again not

 

in all cases. So what do doctors do in treating patients who do not

 

respond to Celexa? Usually start a catecholamine drug such as

 

Wellbutrin.

 

On the other side of the coin are patients with depression who are

 

started on Wellbutrin only and do not respond. In these cases,

 

doctors will add a serotonin drug such as Celexa. If you imagine

 

the prescription drugs available for the treatment of depression as

 

lying along a spectrum with Wellbutrin on the far catecholamine

 

end of things and Celexa on the far serotonin end of things with

 

other drugs such as Effexor, Prozac, Zoloft, Luvox (in that order

 

from catecholamine to serotonin) lying on the spectrum in between

 

the two extremes, you will have a clear picture. These drugs do not

 

simply work on one system or the other. They all to some degree

 

exert their effects on both systems.

 

Then there is Effexor, an SNRI drug that is in the middle of the

 

spectrum that works on both the serotonin and norepinephrine

 

system and is used extensively for depression in medicine.

 

There are older antidepressants such as tricyclic antidepressants,

 

which work primarily on the norepinephrine system and the MAO

 

drugs that work in depression on both the serotonin and

 

catecholamine system.

 

The point is, medicine for a long time has known that depression

 

is not caused by only the serotonin system or only the

 

catecholamine system. It has to be viewed as a " mixed disease

 

process " when treating a group of patients or not all patients will

 

get relief.

 

Yes, you can treat with things that only work primarily with one

 

system or the other, but you will not get optimal results in a group

 

if that is the only approach you use. With all the work that we have

 

done with amino acids in treatment of neurotransmitter disease, we

 

know that treating everyone in the group with amino acids that

 

cover both ends ends of the spectrum is the only way to achieve

 

optimal results and have all patients in the group do well.

 

So, what about sorting out those patients who simply need 5-HTP

 

or tyrosine with cofactors and not giving all the patients everything

 

needed to cover both ends of the spectrum? We have simply found

 

it too difficult to sort accurately the very few that can get by on

 

treating only one end of the serotonin/catecholamine spectrum,

 

although we have seen it. Besides, " Why would you need to do it? "

 

The side effect profile of the amino acid formula that we have

 

developed is similar to placebo.

 

CAUSES OF

 

NEUROTRANSMITTER DYSFUNCTION

 

Patients with neurotransmitter diseases are suffering from low

 

levels of serotonin and/or catecholamines. But how do these low

 

levels of neurotransmitters develop? A number of years ago, I

 

wrote papers for my patients on the genetic basis of

 

neurotransmitter disease such as obesity. From a common sense

 

standpoint it made sense. Certainly there are families where the

 

grandparents, parents, and children are all suffering from obesity.

 

As time passed and we began to work with amino acids, the results

 

were astounding. Now I believe that the primary cause of

 

neurotransmitter disease is from long-term dietary deficiency. I

 

still come in contact with people who expound the genetic theory

 

of neurotransmitter dysfunction as I once did, to them I answer,

 

" Where did they learn to eat, from their parents. " This usually ends

 

the conversation on genetics.

 

Over time we have begun to focus on three major causes of

 

neurotransmitter dysfunction:

 

1. Nutritional deficiency.

 

2. Drugs and substances that deplete neurotransmitters.

 

3. Neurotoxicity.

 

NUTRITIONAL DEFICIENCY

 

The drug companies studying animal models have known for

 

many years that feeding animals a diet that is void of a specific

 

nutrient will induce a deficiency. For example, if the researchers

 

want to deplete serotonin in animals, they will feed the animals a

 

tryptophan free diet. The same is true with animals where

 

depletion of the catecholamine system is desired and a tyrosine

 

free diet is fed.

 

In weight loss successful people eat about 1/3 of the food they

 

were prior to dieting and thus a nutritional deficiency can develop

 

which in turn causes what we describe to the patients as, " bringing

 

on the big appetite " and causes them to fail in weight loss.

 

Based on our experience in patient care over the last 4 years, we

 

now firmly believe that the number one cause of neurotransmitter

 

dysfunction in patients is long-term dietary deficiency.

 

DRUG DEPLETION

 

We will use the SSRI medications as the prototype for discussing

 

neurotransmitter depletion induced by drugs. At the end of this

 

booklet is a discussion of neurotransmitter testing results which

 

specifically demonstrate depletion by drugs.

 

So why do drugs like Prozac, Zoloft, Paxil, Luvox, Celexa,

 

Effexor, Welbutrin, and many others cause further depletion of

 

neurotransmitters in many people?

 

We start with the assumption that the patient was depleted at the

 

start of treatment as evident by the fact that they were suffering

 

a depletion disease that was treated with one of the drugs listed on

 

page 10. So the patient is put on Zoloft which acts by blocking

 

serotonin reuptake and in the process of not letting the serotonin

 

back into the pre-synaptic neuron, the synaptic levels of serotonin

 

rise, tricking the brain into thinking there is more serotonin in the

 

system and their brains starts functioning normally. But the real

 

fact is that the drug has not created one additional molecule of

 

serotonin in the system, it has merely worked by moving

 

neurotransmitters from one place to another in the brain.

 

So now the serotonin molecules are subjected to being outside of

 

the store in the pre-synaptic neuron on a much longer basis. The

 

longer the molecules are outside the store, the more likely they are

 

to come in contact with the Monoamine Oxidase System (MAO)

 

which is the enzyme system that breaks down neurotransmitters

 

(both catecholamines and serotonin).

 

For the patient who presented for treatment with a

 

neurotransmitter deficiency disease, in many cases it was

 

secondary to a dietary deficiency and by putting the patient on a

 

drug that accelerates MAO metabolism without increasing nutrient

 

intake gives the net effect of further depletion.

 

From a clinical standpoint, the most prominent thing seen is that

 

the drugs quit working or a disease that gets worse (see page 21).

 

Now briefly back to the original weight patients that we were

 

working with. 46% of patients under treatment with prescription

 

medications found that the drugs quit working in weight loss on an

 

average of 3.3 months into treatment. The problem here was twofold.

 

First, the patients became depleted on a lower intake diet.

 

Second, the drugs used to treat the patients further depleted the

 

patients and aggravated the picture. Both caused further depletion.

 

NEUROTOXICITY

 

Drugs with neurotoxic effects induce changes in the nervous

 

system, " THAT ARE PERMANENT! " There are many things that

 

are neurotoxic but they generally fall into one of three categories;

 

heavy metals, chemicals and drugs. From a clinical standpoint, the

 

effects of neurotoxicity look exactly the same as depletion and a

 

neurotransmitter dysfunction is seen. Not all neurotransmitter

 

dysfunction is a depletion issue; exposure to neurotoxins in the

 

past may be the problem. The issue of neurotoxicity is an academic

 

one. The symptoms, clinical presentations, and treatment with

 

amino acid therapy are the same as depletion.

 

The prototype drug for inducing neurotoxicity is amphetamine.

 

Damage with neurotoxins occurs at the receptors of post-synaptic

 

neuron and the net effect is a dysfunction in the proper firing of the

 

post-synaptic neuron. The same problem is seen with depletion.

 

Since 1975, articles have appeared in the literature regarding

 

fenfluramine being neurotoxic in animals, but until now there has

 

been no evidence of how it affects humans. Our data shows that

 

people who took fenfluramine need 28% more amino acids in

 

treatment to attain the proper clinical response. A fact that is even

 

more significant considering it has been over 4 years since any of

 

them have taken fenfluramine.

 

In the 1960’s and early 1970’s, doctors prescribed amphetamines

 

to patients for diet. Today, many of these patients are suffering

 

from neurotransmitter dysfunction disease. One patient in our

 

practice, who is 43 years old, reported taking up to 100 white

 

crosses (a form of street amphetamine) per day in her early and

 

mid 20s. When she presented, she was suffering from extreme

 

neurotransmitter disease. After only one week of treatment, her

 

symptoms resolved.

 

DRUG THAT WORK WITH NEUROTRANSMITTERS DO

 

NOT WORK IF THERE IS NOT ENOUGH

 

NEUROTRANSMITTERS TO WORK WITH!!!

 

We started working with amino acids in an attempt to get

 

prescription medications that were no longer working to work

 

again. They indeed did start working again. Within 6 to 8 months

 

we had fixed the initial process that we had set out to correct. For

 

almost 3 years we have been saying, " Drugs that work with

 

neurotransmitters do not work if there is not enough

 

neurotransmitters to work with " . We had no basis in literature,

 

only our research and experience. Then in the spring of 2000, the

 

following was published by Dr. Delgado in the Journal of Clinical

 

Psychiatry:

 

" NE-selective (norepinephrine-selective) antidepressant

 

drugs appear to be primarily dependent on the

 

availability of NE for their effects. Likewise, 5-HT-selective

 

(serotonin-selective) antidepressants appear to be primarily

 

dependent on the availability of 5-HT for their effects. "

 

In this paragraph, it would appear that the author is saying the

 

same thing we have been saying for almost 3 years, " Drugs need

 

neurotransmitters to work " . This whole thing seems simple now,

 

but the fact is it has large implications. We did indeed get the drugs

 

working in the weight patients again, but this can be applied to any

 

situation where drugs that work with neurotransmitters quit

 

working or do not work from the start of treatment. For the

 

depressed patient who literally wakes up one day to find their

 

Zoloft or other similar drugs are not working, amino acid therapy

 

can restore the clinical picture.

 

We began using amino acids to get prescription drugs properly

 

working. As time progressed we found we could get the same job

 

done with amino acids alone, without using prescriptions drugs.

 

The training and skill of the caregiver is critical to the outcome. If

 

things are not turning out as you think they should, get in touch

 

with NeuroResearch, we can help.

 

For now, we see only limited applications of prescription drugs;

 

these are discussed in the section on disease management. In

 

general, using depression as the prototype, we still recommend

 

prescription drugs with patients who are suicidal, or in whom the

 

depression is severe enough to interfere with day-to-day activities.

 

In most of these cases, drugs are needed with amino acid therapy

 

for only 4 to 8 weeks.

 

THE HEALTHY AMERICAN DIET

 

Many Americans believe that the following is a " healthy diet " :

 

1. Avoid red meat.

 

2. Lots of vegetables.

 

3. Lots of fruit.

 

4. Low fat foods.

 

5. Some white meat to include fish.

 

The fact is, this is a tryptophan and tyrosine deficient diet. It is

 

little wonder so many people are suffering from diseases and

 

illnesses caused by or associated with neurotransmitter deficiency.

 

DEPLETERS OF NEUROTRANSMITTERS

 

Luvox

 

Zoloft

 

Prozac

 

Celexa

 

Paxil

 

Trazodone (Deseryl)

 

Sinequan (Doxepin)

 

Serzone

 

Effexor

 

Meridia

 

Phendimetrazin

 

(Bontril)

 

Phentermine (Adipex)

 

Phenylpropanolamine

 

(Dexatrime)

 

Tenuate

 

Mazindol

 

Fenfluramine

 

(racemic)

 

D-fenfluramine

 

Amphetamines (all to

 

include Ritalin)

 

Ephedra

 

Caffeine

 

Alcohol (ETOH)

 

Nicotine

 

Imitrex

 

Zomig

 

Maxalt

 

Amerge

 

Amitriptyline (Elavil)

 

Nortryptyline

 

(Norpramin)

 

Remeron

 

Wellbutin (Zyban)

 

Thioridazine (Mylan)

 

Cheeses

 

Chocolate

 

Citrus fruits

 

Tomatoes

 

Potatoes

 

Strawberries

 

Eggs

 

Onions

 

Mustard

 

Shell fish

 

Red wine

 

Monosodium Glutamate (MSG)

 

Anything strongly cultured or fermented

 

Nitrates & Nitrites

 

Meat tenderizers

 

Salad bars that spray with sulfites

 

Aspartame (nutrasweet)

 

Saccharin

 

Smoked/cured meats

 

Cold cuts containing nitrates, etc.

 

Frankfurters containing nitrates, etc.

 

Food preservatives

 

Paint fumes & other chemical fumes

 

Excessive use of coffee or tea

 

Tempeh, Tomari, Tofu, Yogurt, Umbusi,

 

Soy sauce, (fermented)

 

Nuts and nut butters

 

Tobacco

 

Frequent use of amphetamines

 

Frequent use of barbituates

 

Frequent use of recreation drugs

 

Beer

 

Chemically processed decaffeinated

 

coffee

 

Excessive exposure to fluorescent

 

lighting

 

NEUROTRANSMITTER DYSFUNCTION

 

There are three principle causes of neurotransmitter dysfunction:

 

1) nutritional deficiency 2) depletion 3) neurotoxicity. The results

 

of all three are the same: disease.

 

TESTING FOR DRUG INDUCED DEPLETION

 

Drugs that work with neurotransmitters have a very powerful

 

ability to move neurotransmitters around through processes such as

 

excretion and reuptake inhibition. Many patients on long-term

 

prescription drugs that work with neurotransmitters may have

 

normal neurotransmitter levels during the initial testing on the

 

drug. To gain a true picture of the neurotransmitter status

 

underlying the drug, it is important to obtain two sets of

 

neurotransmitter tests. The first set should be obtained, if possible,

 

when the patient is still taking the drug. The second set of tests

 

should be taken once the patient has been off of the drug for a

 

period long enough that the drug has been completely removed

 

from the system. In medicine, it is recognized that after stopping a

 

drug, it takes " 4 half-lives " for the drug to be completely removed

 

from the system. " One half-life " is the amount of time needed to

 

remove 50% of the drug from the system. In some cases, the

 

symptoms displayed by the patient, who is off of the medication,

 

are severe. In these cases, it may be necessary to test and place the

 

patient back on the drug before it is able to get fully out of the

 

system. Symptoms always take priority over depletion testing.

 

TIME OFF A DRUG FOR DEPLETION TESTING

 

Note: These are " mean half lives " , 50% of patients took longer

 

50% of patient took less to clear the drug.

 

DISCUSSION OF

 

PHENTERMINE AND BONTRIL RESULTS

 

We feel the following is the best embodiment of thinking on the

 

actions of phentermine and Bontril.

 

FROM U.S. Patent 4,885,312 (Wurtman)

 

Indirect-acting sympathomimetic amines (such as phentermine

 

and Bontril) function by releasing stored norepinephrine from

 

sympathetic nerve endings. The major problem with their use is

 

that after a few doses, they often stop functioning, i.e.,

 

tachyphylaxis sets in. Tachyphylaxis is known to be associated

 

with the partial depletion of norepinephrine in the nerve

 

endings. This leads to the supposition that there are releasable

 

and non-releasable pools of norepinephrine and when the

 

drugs cease functioning, it is because the releasable pools have

 

been severely depleted.

 

THE PHENTERMINE DEPLETION THEORY

 

As we started testing patients who had been treated with

 

phentermine or Bontril and were off the drugs for 5 days, we

 

expected to see low norepinephrine levels. This was not the case.

 

In all cases, the norepinephrine level remained about the same or

 

increased, while the epinephrine level uniformly decreased (see

 

page 26). The next step was to explain why this happened. In doing

 

so, the " Phentermine Depletion Theory " came into existence. The

 

theory is as follows:

 

The ability of norepinephrine to be excreted into the synapse

 

takes precedence over the ability of norepinephrine to act as a

 

precursor. In the process, depletion of norepinephrine shows up

 

through depletion of epinephrine.

 

We have seen similar results with dopamine drugs that are

 

suspected of causing depletion of dopamine. Once the dopamine is

 

stopped, the dopamine levels remain normal or elevated, but the

 

norepinephrine and epinephrine levels fall. It was suggested along

 

the way that phentermine may act as a reuptake inhibitor, but the

 

fact is that the T1/2 of phentermine is 20 hours meaning it should

 

be fully out of the system at testing 5 days (120 hours) later.

 

RESULTS OF TESTING Prozac

 

The following lab results are from a female reportedly being on

 

Prozac for 10 years. It was reported that she quit the Prozac

 

because it was no longer working and she saw no point in taking it

 

anymore. The neurotransmitter test was performed approximately

 

3 weeks after stopping the Prozac. Looking at the " half-life chart "

 

on the preceding page, it is quite possible the patient still had

 

Prozac in the system. These values may have been even lower 2 to

 

3 weeks after this test was performed. Most notable in the lab

 

results reported is the fact that the Serotonin level of 15.5 is the

 

lowest level seen in over 600 patients in the study so far.

 

As previously noted in this booklet, " drugs that work with

 

neurotransmitters do not work if there is not enough

 

neurotransmitters to work with " . In reviewing the testing, you can

 

see the state that 10 years of Prozac therapy left this patient in and

 

why her drugs were no longer working.

 

MORE THOUGHTS ON DRUG DEPLETION

 

The following is from the NeuroResearch patient orientation

 

manual for high performance weight loss.

 

The appetite center of the brain is controlled by neurotransmitters.

 

When neurotransmitter levels become low, diseases can occur.

 

Prescription drugs work by moving neurotransmitters from one

 

place to another in the brain. They do nothing to actually increase

 

the overall number of neurotransmitter molecules in the brain. At

 

the start of treatment there is still the same amount of

 

neurotransmitter molecules. They have simply been redistributed

 

from one place to another.

 

In the process of moving neurotransmitter molecules from one

 

place to another in the brain, further depletion of neurotransmitters

 

can take place effectively, making the cause of the problem worse.

 

Drugs that work with neurotransmitters do not work if there are

 

not enough neurotransmitters to work with. This is why

 

prescription drugs quit working in some people, do not work from

 

the start of treatment in other patients or why some people feel

 

worse when they stop the drugs.

 

Drugs like Phentermine, Phendimetrazin, Tenuate, Prozac, Zoloft,

 

Paxil, Celexa, Effexor, Meridia, Trazodone, Serzone, Ephedra, and

 

many more, can cause depletion of neurotransmitters in people.

 

If we had a drug that made the real cause of the problem worse,

 

while making the symptoms better for a while, should we use it?

 

This is exactly what happens in many people with these drugs.

 

CENTRAL NERVOUS SYSTEM STIMULANTS

 

The following test is from a patient taking the central nervous

 

system stimulant Ritalin for hyperactivity on a long-term basis. Of

 

importance here is the fact that the norepinephrine level is low

 

with a normal epinephrine level. The use of central nervous system

 

stimulants such as Ritalin and amphetamines are the only

 

applications where we have seen a low norepinephrine level with

 

normal epinephrine level. In all other cases, when the

 

norepinephrine level is low, the epinephrine level is also low. It is

 

noted that this patient was actively taking Ritalin. It is theorized

 

that Ritalin acts as a sympathomimetic agonist, and in the process,

 

it blocks excretion of norepinephrine. Testing patients on and off

 

central nervous system stimulants shows a similar pattern that is

 

distinctly different from phentermine testing on page 26.

 

HYPERACTIVITY

 

Hyperactivity in pediatric patients has shown results that are

 

again unique. The following is from a 10-year-old male patient

 

with a history of hyperactivity. As noted, the catecholamines are

 

increased uniformly across the board. Dopamine, norepinephrine,

 

and epinephrine are markedly elevated. The twist is as follows: the

 

boy responded to amino acid therapy, the elevation in urinary

 

catecholamines was due to an undetermined mechanism that

 

enhances excretion of neurotransmitters from the kidney. This

 

caused low systemic levels of neurotransmitters, which responded

 

to treatment. Pediatric hyperactivity is the only circumstance so far

 

identified where urinary neurotransmitter levels are not correlating

 

with systemic levels.

 

This appears to be a very important finding out of the

 

neurotransmitter testing work being done by Pharmasan Labs and

 

NeuroResearch. Obviously the next step is to explain why the

 

increased excretion of neurotransmitters is occurring.

 

RESULTS IN OBESITY INITIAL TESTING

 

The obese patient is considered to have a neurotransmitter

 

deficiency disease, but at the start of treatment many of these

 

patients have normal serotonin and dopamine levels. 20% have low

 

norepinephrine levels. 79% have low epinephrine levels. If obesity

 

is a combination of serotonin and norepinephrine deficiency in

 

90% of patients, " Why doesn’t it show up in more patients at the

 

start of treatment? "

 

About 5 years ago we formulated " The strainer theory " . The

 

main cause of neurotransmitter deficiency is from nutritional

 

deficiency. The theory is: " In order for the 300-pound female to

 

function on a nutritionally poor diet found on intake to the weight

 

programs, the patient needs to eat enough calories to keep her at

 

300 pounds in order to get the nutrients needed.

 

TESTING FOR APPETITE SUPPRESSION

 

In the last 4 years, as we have worked to induce appetite

 

suppression with amino acids, we knew all along that 5-HTP was

 

not subject to a chemical regulatory feedback loop meaning that

 

higher than normal serotonin levels could be obtained in the

 

system. Suppose you take a group of 100 people and treat them

 

with only 5-HTP. We know for a fact that only 30% or so will get

 

some response. The rest will no have a clinical response. Both the

 

catecholamine system and the serotonin system have to be

 

functioning properly for the entire system to obtain a clinical

 

response. In the catecholamine system, tyrosine and cofactors are

 

loaded; in the process the body has ample supplies of nutrients. It

 

builds catecholamines whenever it needs them.

 

Appetite suppression can be induced by either norepinephrine

 

drugs, such as phentermine, or by serotonin drugs, which increase

 

the synaptic levels of neurotransmitters above normal levels. In the

 

case of our amino acid formula, it is the 5-HTP supported by

 

tyrosine which induces the appetite suppression. The following are

 

the results of actual lab testing at the start of treatment and 4 weeks

 

into treatment of obesity.

 

In treatment of disease and illness other than weight, we have

 

defined the " therapeutic range for serotonin " as being 600 to 1,200.

 

For the treatment of obesity, we have defined the therapeutic range

 

as being 1,200 to 2,400, although, we have seen patients with

 

optimized catecholamine levels doing well in weight loss with

 

serotonin levels as low as 600. In weight loss, levels above 2,400

 

appear to be of no benefit. In fact, it may distract from the patient’s

 

ability to be successful in weight loss. Serotonin has a very

 

powerful effect. It induces a " laid back feeling of well being, " and

 

it appears that the patient’s motivation to monitor calorie intake

 

may be affected by serotonin levels that are too high.

 

Neurotransmitter testing really comes into its own in the patient

 

who is on high dose amino acid therapy and is not responding

 

clinically. In almost all cases, neurotransmitter testing can verify if

 

the patient needs more amino acids and establish a need to increase

 

amino acids even further without overloading the system. Prior to

 

amino acid therapy, we set the highest dosing of 5-HTP needed in

 

patients at 900 mg per day. Since we have started using

 

neurotransmitter testing, we have found a few patients who need as

 

high as 1,400 mg per day in order to get into the desired

 

therapeutic range.

 

At present, I have one patient under active treatment for

 

fibromyalgia who is on 1,400 mg. of 5-HTP with 6,000 mg. of

 

tyrosine a day, lab testing showed a serotonin level of 925.

 

Some people simply have the ability to metabolize and excrete

 

neurotransmitters and precursors more than others.

 

Amino acid therapy is highly effective in weight loss, but only if

 

proper patient guidance is put in place. The NeuroResearch

 

database has an excess of 111,000 patient days of treatment with

 

phen-fen, which was pulled from the market in September of 1997.

 

Results obtained with amino acid therapy in weight loss are much

 

greater than the weight loss results obtained with phen-fen.

 

So how could this be? We know from the NeuroResearch

 

database that 46% of patients taking phen-fen plateaued and quit

 

losing weight an average of 3.3 months into treatment. This

 

appears to have occurred secondary to the depletion of

 

neurotransmitters by the phen-fen and by nutritional deficiency due

 

to fewer nutrients being taken in.

 

Amino acid therapy in weight loss is not the cure in and of itself.

 

Proper positioning of patients is the key once appetite suppression

 

is achieved..

 

Calorie counting is controversial in weight loss programs, but we

 

have no doubt in asserting, " If you want to maximize the number

 

of patients making goal weight, you need to have your patients

 

count calories. " In appetite suppression on amino acids, patients

 

can eat comfortably at 900 calories per day or 3,000 calories per

 

day. It is up to the patient to monitor food intake for maximum

 

results. For a complete set of orientation materials in weight loss

 

see, www.USAweightloss.com and click the " literature hyperlink " .

 

GI UPSET

 

GI upset is divided into two groups, " start up " and " carbohydrate

 

intolerance " . It would appear, in the past, that problem has not

 

been fully understood. Once the causes of these problems are

 

understood, they are easily managed, allowing patients the full

 

ability to use natural amino acid therapy in place of prescription

 

drugs in the treatment of disease. GI upset is easy to manage if you

 

explain it to the patient at the start of treatment. If you do not tell

 

your patients about this, you may not have a patient once treatment

 

is underway.

 

USDA

 

Recommended

 

Our use in

 

general

 

Tyrosine 2,500 to 5,000 mg Up to 5,000 mg

 

5-HTP None 100 to 900 mg

 

Vitamin C 45 mg 1,000 mg

 

Vitamin B6 3 mg 75 mg

 

Calcium

 

Male: 1,000mg

 

Female: 1,500mg

 

1,000 mg

 

Folate 400 mcg 1,600 to 2,400 mcg

 

Lysine 500 to 1,500 mg 500 mg

 

THE CRITICAL BALANCE

 

There are prescription drugs, when used in combination the

 

undesirable effects of one drug are cancelled out by the other drug.

 

This appears to be true with the use of tyrosine and 5-HTP in

 

combination. If you treat a group of patients with a higher dose 5-

 

HTP alone, complaints of tiredness develop. If you treat a group of

 

patients with higher dose tyrosine alone, complaints of headaches,

 

anxiety and anxiousness develop. When the two are used in proper

 

balance, these complaints seem to vanish.

 

5-HTP THAT DOES NOT WORK

 

In 1997, as we started working with amino acids and prescription

 

drugs that did not work, we sent our patients out with shopping

 

lists so they could buy the things they needed at local health food

 

stores and pharmacies. The initial 6 patients we worked with went

 

to the same health food store and bought the same brand of

 

products. This was a lucky stroke for us, results were good and by

 

the end of 1997, we were sending all patients out with shopping

 

lists. But the luck was not to continue. Of the first 40 or so patients

 

started on the list of nutritional supplements, most were not doing

 

well. We soon identified a small sub-group of patients who were

 

doing well. We found that all were going to the same health food

 

store and buying the same products. As we looked further, we

 

found that 90%+ of the 5-HTP sold in retail stores did not work.

 

Since then, we have found the problem is the lack of uniform set

 

standard for the manufacturing of 5-HTP in the

 

United States. Many of the products in retail stores contained 10%

 

or less 5-HTP. The 5-HTP in our products is processed in

 

Switzerland and is manufactured under the European guidelines,

 

which have stringent pharmaceutical standards (99.5%+ pure).

 

PEAK-X

 

In August of 1998, Mayo clinic released a report indicating that

 

most of the 5-HTP tested contained a substance known as " Peak-

 

X " . Tryptophan was pulled from the U.S. and Canadian markets in

 

1989, secondary to the contaminant that formed during the

 

fermentation process, causing an outbreak of a disease known as

 

" Eosinophilia Myalgia Syndrome " . It was speculated by Mayo

 

clinic that " Peak-X " could have the potential to cause symptoms

 

similar to Eosinophilia Myalgia Syndrome, although none had

 

been reported. The 5-HTP used in our products has been assayed

 

by the University of Minnesota, and is certified as " Peak-X free " .

 

If you have patients who raise concerns about " Peak-X, " contact us

 

and we can fax you a copy of the assay. In the past, this has

 

effectively dealt with the concerns.

 

MOST SENSITIVE TO B6

 

As we sent the initial patients out with shopping lists to pick up

 

the nutritional supplements, not all patients bought everything on

 

the list. We immediately began keeping data on which supplements

 

the patients were taking. In analyzing this data, it became apparent

 

the whole system was most sensitive to Vitamin B6. In some

 

patients, this need was so great that you could give them all the

 

tyrosine and 5-HTP you wanted, but if there was not enough B6

 

the system would not work.

 

SWITCH THEORY FORMULATED

 

I was originally trained as an Industrial Chemist and thoroughly

 

indoctrinated with the ability to understand and formulate chemical

 

models. I wrestled for a long time with the concepts of Serotonin

 

and Norepinephrine regulating the appetite center.

 

What was the basic chemical model that held the two together in

 

appetite regulation? The following theory is the best explanation I

 

can offer for the interrelationship between Serotonin and

 

Norepinephrine in the appetite center of the brain. This theory is

 

used as a working model and serves as a reference point until

 

something better comes along.

 

SWITCH THEORY

 

If the regulation of appetite by the neurotransmitters Serotonin

 

and Norepinephrine are like a light bulb with two switches, then

 

the light bulb needs to shine brightly in order for the appetite to be

 

gone.

 

SWITCH THEORY DISCUSSION

 

Serotonin, by virtue of properties observed in weight loss, has an

 

absolute threshold property that acts like an " on-off " switch.

 

Patients with low levels of Serotonin experience more time where

 

the switch of light bulb is off, than those with normal levels of

 

Serotonin, leading to increased hunger and weight problems.

 

Norepinephrine acts like a dimmer switch hooked to the light

 

bulb. While the Serotonin switch may be fully on, lower levels of

 

Norepinephrine contribute to the dimming of the light bulb.

 

This is why Serotonin takes the spotlight so much in weight loss.

 

Its dramatic " on-off " effect is more readily observed and

 

appreciated than the subtle effects of the Norepinephrine dimmer

 

switch.

 

It is our experience that some patients (5%) only have a problem

 

with the dimmer switch (Norepinephrine) causing eating and

 

weight problems. While other patients (5%) only have problems

 

with the " on-off " switch (Serotonin) causing eating and weight

 

problems. Most patients appear to have a combination problem

 

with both neurotransmitters.

 

DOSING NEEDS

 

Average dosing needs for the group can be calculated from the

 

database, but individual needs vary widely. At the extreme low end

 

of things, we have seen a few patients lose large amounts of weight

 

on 75 mg of 5-HTP per day with 750 mg of tyrosine per day. On

 

the extreme high end of things, we have seen patients

 

who needed 1,400 mg of 5-HTP per day with 6,000 mg of tyrosine

 

in order to have their appetite under control. (It is noted at this

 

higher level that neurotransmitter testing verified that the patient’s

 

system was not over loaded and the need was actually there.)

 

In general, group dosing needs can be divided into 2 categories:

 

1) Treatment of obesity

 

2) Treatment of diseases other than obesity.

 

In studying the NeuroResearch database in the treatment of

 

obesity, the average group dosing was 425 mg of 5-HTP per day

 

and 4,250 mg of tyrosine per day. For diseases other than obesity,

 

the average dosing was 300 mg of 5-HTP per day and 3,000 mg of

 

tyrosine per day. In treating diseases other than obesity, in general

 

less amino acids are required but not always on an individual basis.

 

SO, HOW MUCH SHOULD YOU USE?

 

First, follow the dosing schedule on page 2. If after one week the

 

desired clinical response is not seen, increase the patient to the next

 

step on the dosing schedule. How much do you use in the end?

 

ENOUGH!!!

 

Using too much amino acids is not needed and may even be

 

detrimental in some treatments. The ability to measure

 

neurotransmitter levels is very helpful in establishing where the

 

patient is at and what is needed next. Do not be afraid to push your

 

patients to a higher dosing level, they probably need it. As we

 

started to evaluate neurotransmitter testing, we were amazed to see

 

patients on 900 mg of 5-HTP per day with low serotonin levels.

 

AGGRESSIVE ADJUSTING OF AMINO ACIDS

 

In assisting clinics over the last 2½ years, one of the largest and

 

most consistent problems we have seen is, " Not adjusting the

 

supplements aggressively enough. " If the clinical response you are

 

looking for is not present after 7 days, increase the dose. The

 

ingredients are not toxic. Aggressive adjusting of the dose, until

 

the clinical response is seen, is very beneficial in the end. On the

 

extreme end of things, we have seen clinics that simply started a

 

patient on the starting dose and the patient was kept there for 3

 

months even though a clinical response was not seen.

 

TIME BETWEEN DOSE CHANGES

 

Once you start to change a dosing, it takes 4 to 5 days to observe

 

the full effects of the new dosing. Working with amino acids is not

 

like taking an aspirin, where you take a pill and see the effects 30

 

to 45 minutes later. Be patient and do not increase the dosing more

 

than once every 7 days. We have seen clinics and patients " chasing

 

their tail, " by increasing doses every 2 or 3 days.

 

EXTRA IN THE PM

 

Referring now to the dosing schedule on page 4, at visit number

 

two the RepleteExtra is added in the PM (before the evening meal).

 

From an amino acid stand point:

 

1 pill of " RepleteExtra " = 2 pills of " NeuroReplete "

 

We made this recommendation due to the fact that

 

neurotransmitter levels drop off as the day progresses. Feeling

 

worse in the evening or feeling hungrier in the evening is seen as

 

neurotransmitter levels drop off later in the day. Higher dosing of

 

amino acids later in the day has proven to be very beneficial.

 

NEVER ADJUST BY " ONE PILL "

 

So you have a patient who seems to be much better at times, but

 

is not quite there all the time, " What do you do next? " Remember

 

the " switch theory, " the patient is probably sitting on the threshold,

 

" clicking in and out. " Your next step should be to continue to

 

adjust the patient’s amino acid dosing. If you are going to adjust

 

the patient in the future, add at least 2 pills per day to the patient’s

 

dosing regime. As a rule thumb:

 

If you only want to add one pill to the patient’s

 

daily dosing, you do not need to do any adjustments.

 

FIND THE LOWEST DOSE

 

After the patient has been stable for 6 to 8 weeks, with no

 

symptoms, you may try and find the lowest dose of amino acids to

 

maintain the patient on. To do this, have the patient cut back at the

 

rate of 1 pill every two weeks until symptoms

 

return, then increase to the dose needed to keep symptoms under

 

control.

 

SUPPLEMENTS QUIT WORKING

 

From time to time, we encounter patients who have been under

 

treatment for several months who claim that the supplements have

 

quit working. In virtually all cases, the problem was the patient

 

was not taking the supplements properly. Remember the " switch

 

theory? " If a patient misses 1 or 2 doses and is sitting just above

 

the threshold needed for symptoms to resolve, the patient can find

 

the symptoms return for a few days. If the patient repeatedly

 

misses supplements throughout the week, from the patient’s

 

perspective the supplements have quit working. To manage a

 

patient who believes the supplements have quit working, we have

 

the patient carry a notebook and journal all times and doses of

 

supplements taken. It is amazing how many patients return in a

 

week or two with the supplements once again working.

 

Another thing you should do for the patient in whom the

 

supplements have quit working is, " Evaluate the importance of the

 

supplements in the patient’s mind. " Some patients think the

 

supplements are not important and subsequently, do not take them

 

properly.

 

THE TIRED PATIENT

 

You may encounter the rare patient who, at the start of treatment,

 

reports that he or she is, " Too tired to function " . Out of all the

 

clinics, NeuroResearch has 6 to 8 reports of this happening each

 

year. To manage this problem, it is recommended you cut back on

 

the NeuroReplete dosing to the maximum level where symptoms

 

resolve, and simply titrate the patient up using plain tyrosine and

 

do follow-up neurotransmitter testing as outlined on page 4.

 

THE ANXIOUS PATIENT

 

Should you encounter the rare patient that complains of feeling

 

anxious or jittery at the start of treatment, cut back the

 

NeuroReplete to the maximum dose that keeps symptoms under

 

control and titrate up from there using plain 5-HTP.

 

LONG HOURS

 

In general, the response to amino acid therapy in the system starts

 

to taper off after 4 to 5 hours. This is important in patients who

 

work long hours, such as nurses doing double 8 hours shifts and

 

long haul truck drivers. If you have such a patient and they

 

complain of the effects of the amino acids wearing off late in the

 

day, simply give them one or two additional doses later at night.

 

For people like nurses who work odd hours and ask, " When

 

should I take my supplements? " The answer is, " When you get up

 

is the AM dose. Ten hours before bed is the Noon dose. Six hours

 

before bed is the PM dose. "

 

ALCOHOL USE

 

We tell our patients that one or two drinks are OKAY but four or

 

more drinks are not. Alcohol can reverse the effects of the amino

 

acids. This observation has been most pronounced in the use of

 

amino acid therapy in weight loss. We have seen patients who

 

were doing well for several months that " partied hearty " one night,

 

only to find their hunger had returned for 4 or 5 days. If the patient

 

is not doing well, evaluate their alcohol intake.

 

" 1 or 2 drinks is OKAY, 4 or more is not "

 

TAPERING OFF MEDICATIONS

 

If the patient is on a serotonin or catecholamine medication for

 

the treatment of neurotransmitter dysfunction disease, the

 

recommendation for tapering medications is as follows: in general,

 

wait until the patient has been on the amino acid therapy for 6 to 8

 

weeks and is doing well prior to tapering. The goal of tapering is to

 

have the least impact on the patient while working for a positive

 

outcome. In tapering most medications such as Zoloft, Prozac, etc.,

 

step down one dose every 2 weeks. In general, drugs that work on

 

the catecholamine end of things such as Effexor and Wellbutrin are

 

harder to stop and require vigorous use of cysteine and patience.

 

We have cared for patients on Wellbutrin that required 4 months of

 

slow taper. Paxil is another drug that is difficult to taper. In

 

extreme cases, custom formulation of Paxil by a pharmacist may

 

be needed in order to decreased dosing at the

 

rate of only 1 or 2 mg every two weeks. If you have problems with

 

tapering meds, call NeuroResearch.

 

AMINO ACID / DRUG INTERACTIONS

 

From time to time, we get questions about the use of amino acids

 

with various prescription drugs. We know of no amino acid / drug

 

interactions that would preclude the use of amino acids. All drugs

 

appear to be safe and have no interactions or contraindications that

 

we know of when used with amino acids.

 

USE IN PREGNANCY

 

Should you have a female patient who becomes pregnant, you

 

may advise her that the use of amino acids in pregnancy appears to

 

be safe. But, due to the lack of studies, it is recommended the

 

amino acid formulation not be used during the first trimester of

 

pregnancy (first 13 weeks). The fact is, they are already getting

 

these thing to some degree from their food.

 

Amino acids are water soluble and not excreted in high doses into

 

breast milk which concentrates fat soluble things. We know of no

 

studies indicating that there have been any problems with their use

 

in the nursing mothers.

 

5-HTP SUPPORTS TRYPTOPHAN

 

Tryptophan 5-HTP serotonin

 

Tryptophan hydroxylase

 

Regulation of the conversion of tryptophan to serotonin is via the

 

5-HTP regulatory feedback loop. As more 5-HTP is available in

 

the system, further deactivation of tryptophan hydroxylase takes

 

place and less 5-HTP and serotonin is made. 5-HTP is turned

 

freely into serotonin without being subject to regulation. This is

 

why we can achieve serotonin levels above normal by taking 5-

 

HTP. In the process, 5-HTP shuts down tryptophan hydroxylase

 

making more tryptophan available for other needs in the body.

 

A STORY OF TRYPTOPHAN AND PROZAC

 

Tryptophan is classified as an essential amino acid. Meaning, it

 

needs to be supplied in adequate amounts in the diet and cannot be

 

synthesized within the body.

 

In the 1980’s, tryptophan was available over-the-counter. People

 

used it for depression and other neurotransmitter diseases.

 

In 1989, a batch of tryptophan from Japan was brought into the

 

United States and Canada. The batch contained a contaminant that

 

caused an outbreak of a disease known as, " Eosinophilia Myalgia

 

Syndrome. " The source of the contaminant was a by-product of the

 

fermentation process used to produce tryptophan. Tryptophan was

 

not the problem; it was a contaminant in the tryptophan.

 

A few months later, after tryptophan was pulled from the market,

 

Prozac, the first serotonin drug, came on the market. The rest is

 

history.

 

At present, tryptophan is only available for human use in infant

 

preparations. It is the only essential amino acid that we cannot buy

 

off the shelves. I have always marveled at the coincidence of

 

tryptophan being pulled from the market within months of the first

 

serotonin drug becoming available in the U.S. At present, the SSRI

 

industry in the U.S. is a $10 billion a year industry.

 

NEUROCHEMISTRY OF SEROTONIN

 

On page 11 is the serotonin synthesis pathway. The whole

 

process is very simple in comparison to the catecholamine

 

pathway. The precursor tryptophan is used for the synthesis of

 

serotonin. It is subject to the " 5-HTP

 

tryptophan hydroxylase

 

feedback loop " . The implications of the feedback loop are that the

 

body will only produce a certain amount of serotonin (usually in

 

the normal range). With the use of 5-HTP, two important things

 

happen:

 

1. 5-HTP is not subject to a feedback loop of any other

 

regulation and in the process higher than normal levels

 

of serotonin can be achieved.

 

2. With an abundance of 5-HTP in the system, the

 

tryptophan hydroxylase is virtually 100% inhibited

 

meaning that none of the tryptophan in the system will

 

be converted to 5-HTP making it exclusively available for

 

other bodily needs such as protein synthesis.

 

NEUROCHEMISTRY OF CATECHOLAMINES

 

Both the catecholamine system and the serotonin system have to

 

function properly for the system as a whole to be disease free.

 

In our study of neurotransmitters, through Pharmasan Labs, we

 

have found that 79% of patients have low epinephrine levels and

 

20% of patients have low norepinephrine levels. No patients had

 

low dopamine levels. This does not mean low dopamine levels do

 

not exist, they are just fairly rare on testing.

 

A key point to interpreting what is going on with the

 

neurotransmitters is the " Phentermine depletion theory " as

 

discussed on page 27. We believe this phenomenon occurs not

 

only with the norepinephrine – epinephrine system, but with the

 

dopamine – norepinephrine – epinephrine system as well. The

 

ability of the system to excrete neurotransmitters into the

 

synapse takes precedence over the ability for the

 

neurotransmitter to act as a precursor. So, when you see a low

 

epinephrine level there is a high probability there is also a problem

 

with norepinephrine. Taking this one step further, when you see

 

low norepinephrine and epinephrine levels there is a high

 

probability there is also a problem with dopamine.

 

Other factors come into play regarding catecholamine levels;

 

most notable is a system involving cysteine, homocysteine,

 

methionine, S-adenosylmethionine (SAMe), folate, vitamin B6 and

 

vitamin C. The key player in this system is SAMe.

 

In September of 2000, secondary to experiencing problems in

 

patients who were stopping phentermine and after being placed on

 

amino acid therapy, we began working with cysteine. Initial

 

results were very good and this led us into a whole new world of

 

amino acid therapy. Of the first 9 patients placed on cysteine for

 

the problem of amino acids not working after stopping

 

phentermine, 7 obtained dramatic results. We initially explained

 

the phenomenon as a dysfunction of the " tyrosine hydroxylase

 

enzyme " . We focused on tyrosine hydroxylase as a rate-limiting

 

step in the formation of catecholamines. We researched the

 

enzyme extensively, from the DNA to the feedback loop. The

 

decision to start cysteine was based on the fact that at the heart of

 

the tyrosine hydroxylase enzyme is a " heme-thiolate protein " made

 

up of a cytochrome P-450 iron complex and a cysteine molecule.

 

HEMETHIOLATE PROTEIN

 

The rate-limiting step in the formation of catecholamines is the

 

enzyme tyrosine hydroxylase. At the heart of the tyrosine

 

hydroxylase enzyme is the " heme-thiolate protein, " depicted

 

below. This protein is made up of a cytochrome P-450 iron

 

complex (Fe) and a cysteine amino acid. The " S " sulfur group is

 

from the cysteine (Cys). Depletion of cysteine can lead to

 

decreased production of the tyrosine hydroxylase enzyme, which

 

in turn leads to decreased production of catecholamines.

 

TYROSINE HYDROXYLASE REGULATION

 

The rate-limiting step in the formation of catecholamines is

 

tyrosine hydroxylase. Tyrosine hydroxylase activity is controlled

 

by the norepinephrine feedback loop. Norepinephrine via

 

phosphorylation inactivates tyrosine hydroxylase. The higher the

 

concentration of norepinephrine the more inactivation occurs.

 

Cysteine, Methionine, Homocysteine, SAMe cycle

 

Note, " S-adenosylmethionine (SAMe) in the upper right corner.

 

Folate, B12, and B6 are needed to turn homocysteine into

 

methionine.

 

SAMe

 

The fact that cysteine was at the heart of the rate-limiting enzyme

 

in the formation of catecholamines led to the use of cysteine.

 

Results were so good that we filed our eighth patent application

 

based on this fact. As time progressed, it became apparent there

 

was a much larger cysteine system in the picture.

 

S-adenosylmethionine (also known as SAMe " sam ie " ) is a

 

methyl donor in the formation of epinephrine from norepinephrine.

 

There is an abundance of literature on SAMe, methionine,

 

homocysteine and cysteine. Low levels of SAMe can cause low

 

levels of epinephrine and the synthesis is compromised

 

Homocysteine has taken a spotlight in medicine in recent years as

 

a risk marker for cardiac disease. It is still somewhat controversial.

 

I know a cardiologist who does not recognize it and family

 

practitioners who do. Folate, B6 and B12 are all needed for proper

 

conversion of homocysteine to methionine. If there is a deficiency

 

of any of the three, elevated homocysteine levels will occur. In

 

speaking with physicians who routinely screen for and treat

 

elevated homocysteine levels on patients over 40 years old, it was

 

the consensus that a full 50% of patients tested have elevated

 

homocysteine levels. Treatment is the use of folate and B6. B12 is

 

made naturally in the body and unless there is a deficiency with the

 

intrinsic factor, B12 problems do not enter the picture. The

 

physicians report, in general, it takes 4 to 6 months for

 

homocysteine levels to return to normal with this treatment.

 

So how does this relate to neurotransmitters? Again the literature

 

is clear that elevated homocysteine levels are associated with lower

 

levels of SAMe in the peripheral circulation and the CNS. (J

 

Neurol Neurosurg Psychiatry 2000 Aug;69(2):228-32 Bottiglieri

 

et. al.). Plugging up the cycle on the preceding page lowers levels

 

of SAMe. SAMe has far reaching implications. It is actively

 

involved in over 40 major pathways in the body as a methyl donor.

 

We believe this is another piece to the puzzle and why we now

 

have folic acid (folate) in the NeuroResearch products.

 

There are patients with normal homocysteine levels that respond

 

to cysteine therapy, " What is going on here? " Cysteine is involved

 

in many chemical pathways also. Until recently methionine was

 

considered to be an " essential amino acid. "

 

Cysteine to Methionine

 

Methionine was originally classified as an essential amino acid

 

meaning it could not be synthesized in the body and needed to be

 

supplied in the diet. With the discovery of the pathway below it

 

has been reclassified as semi-essential in some scientific circles.

 

The pathway shows methionine synthesis from cysteine.

 

When the pathway on the shown above was defined which

 

shows that methionine can be synthesized from cysteine. It also

 

shows that cysteine, methionine, homocysteine, and SAMe are in

 

balance and when a deficiency exists in the system, giving any one

 

of the 4 can get the whole system functioning optimally again. In

 

the patients who had normal homocysteine level and responded to

 

cysteine treatment, it is postulated that the system overall was in

 

fact low and the addition of cysteine to the system put it back in

 

balance.

 

Why not use SAMe instead of cysteine? We find full clinical

 

response in treating a group of patients with cysteine in dosing at

 

the 4,500 mg per day. SAMe is expensive, costing $40 at our local

 

health food store for 60-200 mg pills. We do not believe the

 

clinical response is different enough to warrant using many pills of

 

SAMe every day in place of cheap cysteine.

 

DOPAMINE AND SAMe AND FOLATE

 

While SAMe is not directly involved in the conversion of L-dopa

 

to dopamine the system does appear to affect SAMe levels

 

according to the literature. There are several studies, which

 

indicate placing additional L-dopa in the system will lead to

 

decreased SAMe and epinephrine levels. This appears to be

 

primarily due to the fact that the main inactive metabolite of Ldopa

 

requires SAMe for conversion. There is other literature that

 

suggests the L-dopa may inhibit the conversion of norepinephrine

 

to epinephrine through these decreases in SAMe.

 

Another hint of the problems involve are from an article which

 

demonstrated that a decrease in SAMe levels caused an increase in

 

catecholamine metabolites in the system.

 

The bottom line of this discussion is the addition of folate to the

 

NeuroReplete formula. This is the first change in the original

 

formula in 2 years. The daily recommendation is 1,600 mcg to

 

2,400 mcg of folate per day.

 

SELENIUM

 

This discussion would not be complete without talking about the

 

selenium in CysReplete. As we began to work with cysteine, a

 

doctor made us aware of scientific world literature from the

 

late 1980s that talked about the ability of cysteine to concentrate

 

mercury in the body and into the brain. We found the literature.

 

Once mercury gets into the body, it is methylated. It is this

 

methylated mercury that cysteine has the ability to concentrate into

 

the brain. By giving 200 mcg per day of selenium, the mercury is

 

bound into an inactive biological form by the selenium and the

 

problem is solved.

 

GLUTATHIONE

 

Next to the importance of cysteine in the system is the

 

Glutathione system. There is much talk about anti-oxidants and

 

detoxification. The fact remains that the Glutathione system is the

 

most powerful system in the body for neutralizing toxins. The

 

synthesis of Glutathione is dependent on the availability of

 

cysteine. The sulfur group on the cysteine is the powerhouse of the

 

detoxification on the Glutathione molecule.

 

Overloading the system with toxins can deplete cysteine and the

 

Glutathione system, which in turn can lower catecholamine levels.

 

Extreme stress can deplete the catecholamine system affecting the

 

ability of the body to handle toxins.

 

As a practicing MD of 20 years, who was trained in the straight

 

and narrow of allopathic medicine, a few years ago I would not

 

have believed that fat-soluble toxins could cause such problems. I

 

have seen it with my own eyes in our weight patients. I’ve seen

 

patients, like firemen, who have 30 years on the job and who have

 

been repeatedly exposed to toxins in the work place. They

 

developed skin lesions in weight loss on the upper torso, proximal

 

arms, and face. When this first happened, a fire captain pointed out

 

that these were from fat-soluble toxins leaching out as the fat store

 

diminished and became supersaturated with toxins. Detoxification

 

took the lesions away. Later, as we started working with cysteine,

 

we found that cysteine was also effective in dealing with the

 

lesions. The whole experience leaves us asking the question; If

 

firemen and other people with toxic exposure are the extreme

 

cases, how many people have toxins but never develop skin lesions

 

in weight loss?

 

GLUTATHIONE SYNTHESIS

 

The Glutathione system is the primary system in all life for

 

handling toxins in the cells. Depletion of cysteine can lead to

 

depletion of Glutathione and increased toxin load in the body,

 

which in turn causes increased cell damage. Increased toxin load

 

can cause depletion of cysteine, which in turn affects the

 

production of SAMe and neurotransmitters.

 

PERIPHERAL AND CENTRAL SEROTONIN

 

The fact is, serotonin does not cross the blood brain barrier and it

 

has been speculated that peripheral testing of serotonin levels may

 

not correlate with central levels. As we approached

 

neurotransmitter testing, I did not know what the truth was other

 

than what we were doing worked.

 

Dr. Kellerman at Pharmasan Labs had literature showing that

 

there was indeed a correlation between peripheral and central

 

serotonin levels. Beyond that, the following facts are true. 5-HTP

 

crosses the blood brain barrier freely and once a steady state is

 

achieved, the central and peripheral levels of 5-HTP are indeed the

 

same. From the perspective of 5-HTP, there is no blood brain

 

barrier, only one body. It distributes equally throughout. 5-HTP is

 

not subject to regulation or a feedback loop, whenever it comes in

 

contact with a carboxylase enzyme it is converted to serotonin.

 

Over time, the system equilibrates and the peripheral and central

 

serotonin levels are indeed in equilibrium.

 

Reflecting on the nature of amino acid therapy, recommendations

 

for testing exists. Full effects of starting or changing the dose of

 

amino acids are not seen for 4 to 5 days. Next, do not perform

 

testing until 7 days have passed since the dosing of the amino acids

 

was started or changed. Time is the critical factor, allowing the

 

system to equilibrate. We also make the assumption that patients,

 

at the start of testing, are in steady state. If given time to

 

equilibrate, the central and peripheral serotonin levels do indeed

 

correlate. It is under conditions where there has been a recent

 

change that they might not.

 

WAS MAN DOOMED TO SUFFER?

 

There appears to be two distinct groupings of patients in the

 

treatment of neurotransmitter deficiency disease:

 

1. Obesity

 

2. Diseases other than obesity

 

In focusing on " diseases other than obesity, " it would appear that

 

in most patients, the symptoms of diseases could be brought under

 

control at the 300 mg of 5-HTP / 3,000 mg of tyrosine per day

 

dosing level. With this information in hand, in early 2000, we set

 

out to design a diet that might have the same effects. Such a diet

 

must contain protein as the source of amino acids. Nutritional

 

books were reviewed and the final conclusion was that such a diet

 

does not exist.

 

The two foods that were identified as leading contenders in the

 

diet were meat and eggs. To get the dosing equivalent of 300 mg of

 

5-HTP and 3,000 mg of tyrosine per day from red meat, the patient

 

would have to eat 35 ounces of red meat per day, which equals

 

2,440 calories per day. This would not keep a 140-pound female at

 

weight. To get the same dosing equivalent from eggs, the patient

 

would have to eat 18 eggs per day, which equals 1,440 calories per

 

day. You could keep the 140-pound female at 140 pounds, but

 

there would be nothing else she could eat other than eggs.

 

" Was man doomed to suffer? " became the question. As we stared

 

deeply at the question, we became aware of " The thing that is

 

broken. " There is something else in the system not working that

 

prevents us from controlling neurotransmitter diseases with food.

 

We could probably write an entire booklet on, " The thing that is

 

broken, " but for now will simply leave it here for you to ponder.

 

DEPRESSION

 

Treatment of mild to moderate depression with amino acid

 

therapy is excellent, but where it really excels is in the treatment of

 

severe and refractory depression.

 

For the most part, initiation of treatment of depression can be

 

done with amino acid therapy without the use of prescription

 

medications. In cases where suicidal thoughts exist or where there

 

is severe compromise in day-to-day function, it is recommended

 

that the patient be started concominently on prescription

 

medications and amino acid therapy. In general, with these more

 

severe cases medications can be tapered after two months of

 

therapy.

 

Our experience with the treatment of depression has shown the

 

ability to differentiate a small sub-group of patients, who in the

 

past were easily overlooked. If after 6 to 8 weeks of amino acid

 

therapy in treating the patient for depression, the clinical symptoms

 

have not improved markedly, consider the possibility that the

 

patient is suffering from the depressive form of bipolar disorder.

 

Other than the standard DSM IV criteria, other things that might

 

point you in that direction are a long standing (many years) history

 

of depression, where the patient has seen many physicians and has

 

been on many medications without success. Starting the patient on

 

Lithium or Depakote, in addition to any antidepressants or amino

 

acids the patient may be on, has shown dramatic results. Based on

 

personal practice experience in working with depressive bipolar

 

patients, there is reluctance on the part of the patient to taper the

 

antidepressant medication or amino acids once relief is gained.

 

MIGRAINE HEADACHES

 

Migraine headaches are mediated by the 5HT1BD serotonin

 

receptors in the temporal region of the head. Based on clinical

 

experience with amino acid therapy, it is our opinion that

 

approximately 15% of patients who present with a working

 

diagnosis of " migraine headaches " from other practices have been

 

misdiagnosed. With true uncomplicated migraine headaches

 

(where there is not a second source of pain present such as

 

temporal mandibular joint syndrome or herniated cervical disk)

 

most headaches resolve after the first day of amino acid therapy.

 

FIBROMYALGIA

 

Treatment results with fibromyalgia have been excellent and tend

 

to take 2 to 4 weeks for the full effects to be seen. In general, 80%

 

of patients with fibromyalgia are pain-free and the remaining 20%

 

are so much better that they no longer care about their pain. If you

 

find a fibromyalgia patient who seems to be refractory to

 

treatment, make sure you look for other causes of pain.

 

INCIDENCE OF NEUROTRANSMITTER DISEASE

 

We started using the " 1A survey " in 1997. At first we viewed this

 

as a simple survey of 24 neurotransmitter diseases and illnesses

 

caused by or associated with low levels of neurotransmitters.

 

Formal diagnostic criteria was not established. This is a survey of

 

diseases present for the perspective of the patient. In 70% of

 

patients starting a weight program, there are other diseases present.

 

In many cases, there are 5 to 7 of these diseases present. The

 

record at this time, is 18 of 24 diseases present. The following are

 

the incidence of some of the diseases surveyed in patients starting

 

medical weight management:

 

 

 

 

 

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