Mercury Detox - Autism Protocol - Vaccines - Amalgam

[Guest guest]

http://www.mercola.com/2001/jun/2/mercury_autism.htm

Mercury Detox Autism Protocol

Part 1 of 3 (Part 2, Part 3)

DR. MERCOLA'S COMMENT:

This is such a long article I wanted to put my comment at the beginning so

my newsletter subscribers can view my perspective prior to reading the

document.

First of all the professionals who put this protocol together are to be

strongly congratulated. They did a tremendous effort in getting together

and developing a consensus statement among some of the top clinicians

treating this problem in the country.

This is exactly what is required if we are going to advance natural

medicine in this country and I am grateful to these professionals for their

dedication, commitment and hard work in developing this document.

I was part of the Great Lakes Chelation Panel on mercury toxicity, and have

co-authored one of the leading papers in clinical mercury detoxification,

and have worked with hundreds of patients with mercury detoxification

issues, so I have some experience in this area.

In general, the panel's review of this subject is thorough and I would

strongly recommend reading it if you have an interest in this area.

However, I cannot endorse a number of the panel's recommendations and I

will provide my objections to the protocol at the beginning.

The major objection to the recommendation is the use of DMSA for mercury

detoxification. My affinity for the use of DMPS is likely one of the

reasons I was not invited to participate in this panel.

However, one needs to know that in the overall treatment of this problem

our approaches are very similar. The KEY strategy to improve children with

brain injury is to optimize their gut flora and diet and this is something

the panel makes very clear.

Mercury detox with DMSA or DMPS is not a huge magic bullet, it is just one

of many strategies that can be implemented to help these children. If one

uses either of these chemicals without first properly preparing the child,

there can be great harm and damage.

The panel refuses to support the DMPS recommendation, despite the fact that

it is, as they admit, a clearly more effective agent, due to DMPS's history

of complications in adults and its lack of FDA approval in children.

The issue of DMPS, and for that matter DMSA, toxicity, is not related to

the direct toxicity of the drugs, but to the drug's ability to take the

heavy metals out of the body. It is actually the heavy metals that cause

the side effects. If one does not properly prepare the body to address

these heavy metals then one will have complications from the chealting agent.

DMPS was, and still is, frequently improperly used in many adults.

Primarily by well-intentioned physicians who provide DMPS when the person

still has amalgam fillings in their mouth. Because DMPS is so effective at

removing mercury, it will actually pull the mercury right out of the

fillings and cause huge problems in some patients.

It has been my and Dr. Klinghardt's combined thirty year experience that

DMPS when used properly is far safer then DMSA.

The other issue the panel raises of FDA approval is really moot as DMSA,

although approved for lead chelation, clearly is not approved for removing

mercury.

Additionally, please pay special attention to the huge list of

complications of DMSA that are listed in this protocol. They require that

the child have regular blood draws for a chemistry profile and a CBC to

monitor for these complications.

This is not necessary for DMPS, which is another reason I prefer it.

Through my use of IV secretin I have become very proficient in drawing

blood from children. But after doing that for several years I realized that

I was inflicting emotional trauma and scaring that was worsening their

problem overall.

For this reason, at this time I cannot endorse any protocol that requires

regular blood draws on children below the age of 6.

Other areas of disagreement are in the negative recommendation for

chlorella. Their information on chlorella is seriously flawed. It is based

on a small study done by Doctor's Data. They never demonstrated increased

absorption of mercury from the chlorella, only that mercury was present in

the chlorella. Since hundreds of tons of mercury are deposited into the

oceans every year, this is not surprising.

However, what the investigators failed to account for was that the binding

coefficient of chlorella to mercury is far in excess of its potential to

release mercury into the body. It only ABSORBS mercury, it does NOT release

it into the body.

The other issue of potential for contamination with toxic dinoflagellates

is only true for blue green algae and NOT for chlorella since chlorella is

a cultured product and is NOT contaminated with it.

Mineral replacement is a critical element of mercury detoxification when

using chelating agents. Monitoring the child's mineral status prior to and

during chelation is essential.

The panel recommends the use of the more expensive blood tests for

monitoring mineral status. As I wrote in my letter in JAMA, I believe that

hair analysis from specific labs is far less expensive, more clinically

valid and clearly less traumatic on the child then the blood tests.

With those objections aside, I invite you to review the Panel's outstanding

compilation of an effective Autism Protocol.

----------------------------------------------------------------------------

----

Autism Panel Report

An enormous, alarming, and unexplained increase in the prevalence of autism

is being reported, on an almost daily basis, in the U.S., the U.K., and

elsewhere.

California maintains what is probably the world's best and most systematic

database on autism and other developmental disabilities. In California the

reported increase in the prevalence of autism over a 20-year period is over

one thousand percent.

Similar enormous increases have been reported from studies in New Jersey

and elsewhere in the US, in the UK, in the Middle East, and in Asia. While

the reality of the increase is beyond doubt, there is great controversy

over the cause. Many experts believe the primary cause is the increase in

the number of vaccines given to children from birth to age two, which has

risen from 8 in 1980 to 22 in the year 2001.

The increased number of vaccines has brought with it an increased exposure

of young infants to mercury intoxication. The preservative thimerosal,

which is used in many vaccines, consists of approximately 50% mercury.

In 1998 the Food and Drug Administration requested the vaccine

manufacturers to begin the process of removing thimerosal from the

vaccines. Thimerosal containing vaccines are still being used in 2001.

Mercury is highly toxic in even very small doses, and some individuals are

exquisitely sensitive to mercury.

Some infants have been given, in one day, as much as 100 times the maximum

dosage of mercury permitted by the Environmental Protection Agency's

standards, based on the weight of an adult. An infant's system is much less

capable of dealing with toxins than an adult's.

In early 2000, parent Sallie Bernard and several other concerned and

inquisitive parents began looking into the mercury issue. They learned that

thimerosal was used in most vaccines at levels that greatly exceeded the

upper limits decreed safe by the US Environmental Protection Agency (EPA).

The scientific paper by Bernard et al. may be found on the website of the

Autism Research Institute (www.autismresearchinstitute.com).

In her testimony before the US House of Representatives in July, 2000,

Sallie, the primary author of the report, testified: " The symptoms which

are diagnostic of or strongly associated with autism itself are found to

arise from mercury exposure, as described in available literature on past

cases of mercury poisoning. "

" These similarities, " she testified, " include the defining characteristics

of autism - and they include traits strongly associated with autism and

found in nearly all cases of the disorder - sensory disturbances such as

numbness in the extremities and mouth, aversion to touch, and unusual

response to noise; movement disorders like toe-walking, hand flapping,

clumsiness, and choreiform movements; and cognitive impairments in specific

domains like short-term, verbal and auditory memory and in understanding

abstract ideas. "

In addition, she noted, mercury poisoning can cause many of the same

biological abnormalities as are seen in autism, including immune system

dysfunction and anomalies in the cerebellum, amygdala, and hippocampus.

Bernard noted that the growing prevalence rate of autism closely matches

the introduction and spread of thimerosal-containing vaccines and that

autistic symptoms generally emerge at the time the child is given these

vaccines.

She added " Our group has also documented a number of cases of autistic

children with toxic levels of mercury in hair, urine and blood. " In

addition, she noted, mercury is more toxic to males than to females, and

the male-to-female ratio in autism is 4 to 1.

Noting that low doses of mercury tend to harm genetically susceptible

individuals, Bernard pointed out that " autism has been recognized as one of

the most heritable of all neurological disorders and is strongly associated

with familial autoimmune disorders. "

Bernard and her colleagues called for an immediate ban on

thimerosal-containing childhood vaccines in October 2000. The meeting was

attended by a number of physicians and scientists. One of the physicians,

Dr. Cave of Baton Rouge, Louisiana, told the group that in her

experience over a number of years in treating over 400 autistic children

with various modalities, she had found no modality which was more effective

in a great many autistic children than mercury detoxification.

Other physicians who also had experience with mercury detoxification in

autistic children, including several who were themselves parents of

autistic children, strongly supported Dr. Cave's remarks.

The Autism Research Institute convened a weekend Consensus Conference on

the Detoxification of Autistic Children in Dallas, Texas in February, 2001.

The attendees were 25 carefully selected physicians and scientists

knowledgeable about mercury and mercury detoxification.

The 15 physicians present included 7 who were parents of autistic children

and who had detoxified their own children with good results. The physician

attendees present had treated well over 3,000 patients for heavy metal

poisoning, about 1,500 of them being autistic children. The chemists,

toxicologists and other scientists present had a combined total of almost

90 years of experience in research on the toxicology of mercury.

The purpose of the meeting was to arrive at a consensus document that would

delineate the safest and most effective methods of detoxifying autistic

children. Nine candidate detoxification protocols, including five submitted

by non-attendees, were considered in detail by the conferees.

R. Laidler, M.D.

The DAN! mercury detoxification consensus group met in Dallas, Texas on

February 9 - 11, 2001 to gather some of the top scientists and

practitioners in the field to develop a protocol for mercury detoxification

in the autistic child.

Rationale

Many of the features of autism bear striking similarity to certain features

of mercury poisoning, especially the immune dysfunctions1,2, visual

disturbances3,4, and motor/coordination defects5 seen in a growing number

of autistic children. Treating autistic children with agents to remove

mercury and/or other heavy metals has brought about significant improvement

in many of them, sometimes dramatic improvement.

This improvement is coincident with increased excretion of mercury and/or

other metals in most but not all patients. Some have theorized that those

who improve without increased mercury excretion are suffering from some

other metal toxicity. Another possibility, which also explains those

patients who improve without significant heavy metal excretion, is that the

chelating agents are working in some other fashion and that the heavy metal

excretion is coincidental to this other effect.

For example, there are clinical studies showing that autistic children with

significant allergy problems have elevated cysteine/sulfate ratios in their

blood, and there are other indications of disordered sulfur amino-acid

chemistry. Sulfhydrylbearing agents, such as DMSA and others, remove

cysteine6 and thereby improve some sulfur amino acid imbalances.

Yet another possibility under investigation is the anti-oxidant effect of

the drugs and supplements used and their ability to compensate for

deficiencies in the native anti-oxidant systems. Quite a few autistic

children have laboratory evidence of anti-oxidant deficiency; low

intracellular glutathione is commonly found in these children.

What may be happening in these children is that the DMSA7 and other agents

" put out the fire " of intracellular oxidation and help restore the 7 normal

anti-oxidant functions. Whatever the action may be, DMSA therapy has been

shown to help a large number of autistic children. It is important to

remember that autism is a syndrome, not a disease.

The " diagnosis " of autism covers a wide spectrum of children, many as

different from each other as they are different from " typical " children. No

one causative factor has been identified for autism and the possibility

exists that autism is not a single disease but several individual diseases

that share a similar presentation.

With that in mind, it is not surprising that no single treatment has been

found that works for all children with autism. Preparatory treatment Many,

if not most, autistic children suffer from some degree of intestinal

dysbiosis, abnormal intestinal permeability and nutritional derangements

which must all be corrected as much as possible prior to any attempt at

detoxification.

Without this preparatory treatment, the adverse side effects of therapy may

be magnified. Without the correction of their intestinal dysfunctions, any

improvement from the treatment may be hard to detect. Many of the drugs and

supplements used for mercury detoxification are rich sources of nutrition

for bacteria and fungi.

If treatment is started while the child is suffering from overgrowth of

abnormal or pathogenic organisms, they will experience explosive growth of

these organisms with subsequent worsening of their symptoms. This monograph

is but a part of the DAN! treatment protocol for autistic children, so this

is not the place for a detailed discussion of how to correct their

intestinal problems. However, a brief outline of the process is included

(Appendix to help practitioners who are not familiar with the process.

Inclusion testing

Urine, blood and hair mercury are typically normal or negative unless the

mercury exposure has been fairly recent. On occasion, urinary mercury will

be elevated if the child is in a catabolic state due to growth or

malnutrition. In these situations, the mercury stored in tissues may be

released as those cells are broken down.

Provoked excretion of mercury and heavy metals is the only accurate way to

estimate the total body burden of heavy metals. This is performed by

administering a chelating agent prior to collection of urine for heavy

metal analysis. The usual provoking agents are 2,3-dimercaptosuccinic acid

(DMSA) and 2,3-dimercapto-propane-sulfonate (DMPS). Of these two, DMSA is

safer, but DMPS is somewhat more effective8,9.

The usual way to gather a provoked urine specimen is to administer the

chelating agent and then to collect the next six to twelve hours of urine

produced. The usual DMSA dose for a single-dose provocation is 10 mg/kg. No

reference ranges exist for provoked urinary heavy metal excretion, so the

interpretation of the results is problematic.

Given that the problem in autistic children may be excessive sensitivity to

mercury or other heavy metals, any level over the reference range for

unprovoked urine heavy metals may be sufficient indication for a trial of

therapy. In addition to mercury, lead, cadmium, arsenic, antimony and many

other metals are extracted by DMSA10, so the urine metal analysis may show

a number of toxic metals. 8

Other than looking for the heavy metals directly, one can look for evidence

of their effects. Mercury and other heavy metals suppress the effect of a

number of enzymes, some of which can be easily tested. The most commonly

available of these is glucose-6 phosphodiesterase (G-6PD); a quantitative

G-6PD activity may reveal levels intermediate between normal and deficient

in heavy metal poisoning11.

Of note, there has been one report of hemolysis in a patient with absolute

G-6PD-deficiency12, but DMSA has been used extensively in populations with

a high incidence of G-6PD deficiency and sickle cell disease without

problems. Less commonly available is glutathione reductase, which is also

reduced in heavy metal poisoning13.

Low glutathione levels in the red cells are not specific for heavy metal

toxicity, but may be supporting evidence. Another commonly available test

is blood or urine pyruvic acid. Pyruvic acid can be elevated for a number

of reasons, but mercury is notorious for interfering with the mitochondrial

pyruvate dehydrogenase complex, where it binds to and deactivates the

lipoic acid coenzyme, resulting in elevated pyruvic acid.

Mercury and other heavy metals interfere with heme synthesis, leading to

urinary excretion of uroporphyrin and coproporphyrin. Mercury also causes

production of pre-coproporphyrin, which may be considered a specific marker

for mercury poisoning14,15. Analysis of uroporphyrin and coproporphyrin can

be done at most clinical laboratories; pre-coproporphyrin analysis can also

be done, but most laboratories do not routinely have that test available.

Mercury and other heavy metals (such as lead) can cause progressive myelin

degeneration with the development of antibodies to myelin basic protein

(MBP) and glial fibrillary acidic protein (GFAP)16,17. While these changes

are not diagnostic of mercury intoxication, they point to ongoing

degeneration in the central nervous system.

Depletion or deficiency of the cellular antioxidant systems is seen in a

number of autistic children. A common finding in autistic children is an

abnormally low erythrocyte glutathione level. The potential causes for this

deficiency in cellular antioxidant substances are myriad, ranging from

congenital deficiency to toxins; heavy metals are well-documented causes of

intracellular antioxidant depletion.

Whether the cause is too little production, rapid consumption or a

combination of the two, many of these children can benefit from exogenous

antioxidant support. Since DMSA and many of the other supplements used to

treat mercury and heavy metal intoxication are powerful antioxidants, this

may be mechanism of action in some children who improve, especially those

who show little excretion of toxic metals.

Since it is possible that neither removal of metals nor supplementing

cellular antioxidants are the mechanism of action, an empiric trial of DMSA

therapy may be warranted. This trial should be done for a limited time and

without changing any other therapy, including physical therapy,

occupational therapy, speech therapy, etc. If no definitive results are

seen in four to six weeks, discontinue therapy and look again for any changes.

Pre-treatment testing

DMSA can cause bone marrow suppression and is potentially hepatotoxic18.

There have been no reports yet of permanent bone marrow suppression or

liver damage, but the literature has many case reports of significant

neutropenia and thrombocytopenia during therapy with DMSA.

Prior to starting therapy, it is important that a complete blood count

(CBC) with platelet count be 9 checked, both to provide a baseline as well

as to detect any pre-existing abnormalities. Blood levels of liver

transaminases (ALT and AST) are also important for the same reasons. DMSA

is primarily excreted in the urine19, so kidney dysfunction will cause it

to accumulate in the blood.

To prevent serious toxicity, it is important to detect any decreased renal

function prior to starting therapy. In the absence of any signs or symptoms

of renal insufficiency, blood urea nitrogen (BUN) and creatinine levels

should be adequate to document normal renal function. If there are any

reasons to suspect renal insufficiency, creatinine clearance should be

measured.

Periodic checks of blood urea nitrogen and creatinine should also be

performed when other blood studies are done. Several investigators have

found that autistic children are typically low in blood zinc and high in

blood copper. Many other minerals, such as selenium and magnesium, are

often low as well.

The body stores of these minerals can be estimated by measuring the red

blood cell mineral content. Serum copper and plasma zinc levels are

considered to be the most accurate reflections of total body content of

these two minerals, but not many laboratories can perform this assay

consistently. Other options are platelet and erythrocyte copper and zinc

levels.

Practitioners who decide to use copper and zinc levels routinely are

advised to closely monitor their analytical laboratory and to perform

periodic quality-control checks with known samples.

Detoxification Of the chelating agents available at present, DMSA

(succimer, Chemet®) provides the optimal combination of safety and

efficacy. DMSA has been used extensively for nearly fifty years and is

approved by the USFDA to treat lead poisoning in children; its safety

record is exemplary20.

There is far less experience using DMPS, especially in children, and the

adult experience with it has shown that it is significantly more toxic than

DMSA. DMPS is currently not approved for any use by the USFDA.

Several animal studies have shown that DMSA is capable of removing a

portion of the mercury bound in the brain21,22. Some of these studies have

also shown that, months after exposure, mercury still moves between the

blood and brain in both directions23.

It should be noted that, to date, no studies have definitively shown any

chelating agent capable of removing mercury from the human brain, no doubt

due to the reluctance of human subjects to have their brains removed for

analysis. One autopsy study has demonstrated that, despite urine and blood

mercury levels in the normal range, mercury will persist in the brain and

other organs for many years without adequate chelation therapy24.

DMSA should be given in doses of no more than 10 mg/kg/dose and no more

than 30 mg/kg/day with a maximum dose of 500 mg (1500 mg/day maximum).

Exceeding these limits has been associated with a significantly higher

incidence of side effects and toxicity.

The dosing interval can be any convenient period, as long as the dose

limits are not exceeded. There is no convincing evidence to suggest that

dosing intervals shorter than eight hours provide any inherent benefit,

although a lower dose given more frequently may help to reduce troublesome

side effects.

In addition, the subset of children who experience improvement only while

receiving DMSA may benefit from more frequent dosing. Clinical experience

supporting 3- or 4-hour dosing intervals is matched by equally good results

with 8-hour dosing. As always, the dosing interval should be based on the

clinical response of the individual patient. 10 DMSA is usually given

orally but it can, if necessary, be given intravenously.

There is also some experience with rectal administration via suppository.

Despite the sulfurous smell, most children will take it if it is mixed with

a suitable masking liquid, such as orange juice or other sweet beverage.

One study has shown that mercury-intoxicated rats prefer water containing

DMSA to pure water, while the control animals would shun the water with

DMSA25; this phenomenon has been seen in some children as well.

Acidic or neutral liquids are best to maintain the activity of the DMSA

while in solution. DMSA will retain approximately 80% of its activity after

24 hours in solution, but prolonged storage in solution may result in

significant degradation and loss of effectiveness26. If the child will

swallow capsules, the whole issue of taste and smell can be neatly bypassed.

The treatment period can last from three to five days with a " rest period "

of at least as long as the treatment period. A treatment of three days

followed by a rest period of eleven days provides adequate time for bone

marrow suppression to resolve and yet is short enough for rapid removal of

tissue mercury. A three-day treatment period allows the drug to be

administered over the weekend (Friday evening through Monday morning),

which can be a tremendous convenience.

Common side effects of DMSA are nausea, diarrhea, anorexia, flatulence and

fatigue. If these become serious enough, reducing the dose will usually

make the symptoms tolerable. Occasionally, patients develop a maculopapular

rash during treatment; this should not to be confused with an allergic

reaction27. Some autistic children are reported to experience a transient

regression in language and behavior during and shortly after treatment.

Reducing the dose may also make these symptoms less bothersome.

Clinical experience suggests that most children who experience regression

at the start of therapy will have less regression with each subsequent

cycle of treatment. Serious side effects of DMSA are extremely rare and

include allergic reaction, toxic epidermal necrolysis (TEN) and erythema

multiforme (s- syndrome)a. Potentially dangerous neutropenia

and thrombocytopenia may also occur28. While reducing the dose may reduce

the severity of the neutropenia and thrombocytopenia, truly dangerous

reductions in cell count are a contraindication to continued therapy

without a compelling reason to do so.

Obviously, allergic a No cross-sensitivity between DMSA and the sulfa

antibiotics has been reported. If the patient has a history of sensitivity

or allergy to other dithiol chelating agents (e.g. DMPS, DMPA,

dimercaprol/BAL), they may not be a candidate for DMSA therapy, depending

on the severity of the reaction. If the reaction was mild or ambiguous, a

small test dose can help resolve the issue. Toxic epidermal necrolysis and

erythema multiforme occur without predictable pattern and their etiologies

are poorly understood. Both may occur with the initial treatment or may

appear after several months of therapy.

Both have been reported only a few times in connection with DMSA even

though tens of thousands of children have received the drug. Erythema

multiforme (s- syndrome) is a selflimited inflammatory

disorder of the skin and mucous membranes. It is thought to be induced by

immune complexes and mediated by lymphocytes. It is characterized by

distinctive target-shaped skin lesions, sore throat, mucous ulcers and

fever. It usually begins a week or more after therapy starts and will

usually resolve spontaneously if the inciting medication is stopped.

Toxic epidermal necrolysis (TEN) is the most serious cutaneous drug

reaction and may be fatal if not recognized. Its onset is generally very

acute and characterized by epidermal necrosis without significant dermal

inflammation. Its pathology is poorly understood but it also usually

resolves when the inciting agent is stopped. There are no other specific

treatments other than supportive therapy and symptom relief. 11 reaction,

TEN and s- syndrome are absolute contraindications to

continued therapy.

More beneficial " side effects " reported with DMSA therapy in autistic

children include rapid progression of language ability, improved social

interaction, improved eye contact, and decreased self-stimulatory behaviors

( " stimming " ). Children with motor problems have experienced significant

improvement in both strength and coordination.

Mineral supplements

Because of poor nutrition (often due to idiosyncratic food preferences),

poor absorption, and other, poorly understood factors, autistic children

usually have numerous mineral deficiencies. Chief among these deficiencies

is zinc. Zinc supplements should be given prior to, during and after

detoxification therapy.

Zinc given with DMSA will complex with it and will be more readily absorbed

as a consequence29,30. Supplementation with 1 - 2 mg/kg/day of zinc is

recommended (maximum of 50 mg/day unless guided by laboratory evidence of

marked deficiency); more may be needed and plasma, erythrocyte or platelet

zinc levels can be used to guide doses higher than this.

Autistic children are also often deficient in selenium. Since this mineral

is one of the few that can cause a significant toxicity if it is present in

excess, caution should be exercised. In the absence of laboratory evidence

of a profound deficiency, selenium supplementation should be limited to 1 -

4 mcg/kg/day.

Magnesium, molybdenum, manganese, vanadium and chromium are all among the

minerals that are deficient in autistic children; these can be supplied by

a multi-mineral supplement. Be sure that this supplement does not contain

copper. Copper is the one mineral that autistic children often have in

excess and additional supplements will only worsen the excess.

Vitamin supplements

Although the conventional wisdom is that the " average American " receives

all the vitamins and nutrients they require in a balanced diet, there are

several reasons why this is not true in autistic children. First, autistic

children rarely eat a balanced diet. They often have an extremely limited

number of foods they will accept and these rarely encompass all of the

major food groups.

Additionally, some of the vitamins are anti-oxidants and are depleted in

autistic children. Finally, many autistic children are deficient in vitamin

B6, vitamin B12, folate and niacin, either from poor diet, poor absorption

or both. Vitamin C: An important anti-oxidant, vitamin C can be a great

benefit to autistic children. Since it is a water-soluble vitamin, it is

rare to see true toxicity, although ascorbic acid crystals in the urine

(and the potential for renal stones) will result from sustained use of

extremely high doses.

More commonly (and usually at doses over 2000 mg/day), gastrointestinal

distress and diarrhea are the only side effects from vitamin C. Using the

buffered preparation or vitamin C esters can significantly reduce the

incidence of gastrointestinal side effects, as will dividing the dose.

Vitamin C supplementation should start at 5 -10 mg/kg/day and gradually

increase to tolerance. Some may tolerate and, in fact, need more than 50

mg/kg/day.

Vitamin E: Another of the anti-oxidant vitamins, vitamin E has received

more press lately than vitamin C. Since it is fat soluble, it can

accumulate if given to excess. Dosing in the range of 2 - 4 12 mg/kg/day (3

- 6 IU/kg/day) is within safe limits. Mixed tocopherols are the preferred

preparation. Many vitamin E supplements are prepared from soybeans and may

be a problem in children who are sensitive to soy products.

Since vitamin E is important in preventing fatty acid oxidation and

peroxidation, more may be needed if the child is also receiving essential

fatty acid supplements.

Vitamin B6: Vitamin B6 can be found as B6 (pyridoxine),

pyridoxal-5-phosphate (P5P), or a mixture of the two (rare). Up to 15

mg/kg/day of B6 or 3 mg/kg/day of pyridoxal-5-phosphate should be used (to

a maximum of 500 mg B6 or 100 mg P5P). Be aware that many of the

pyridoxal-5-phosphate preparations contain supplemental copper to prevent

pyridoxal retinopathy in copper-deficient people.

Since autistic children are typically high in copper, be sure to use a

copper-free preparation.

Other supplements Alpha-Lipoic acid: A dithiol fatty acid, alpha-lipoic

acid is a native chelating agent but is also a powerful anti-oxidant. It

has been extensively used in Germany to treat diabetic neuropathy with

excellent results31. Its anti-oxidant effects may be particularly helpful

in autistic children, since many of them show clear evidence of

anti-oxidant depletion. Start with 1 - 3 mg/kg/day of alpha-lipoic acid and

increase to 10 mg/kg/day as tolerated.

Alphalipoic acid is a natural product of human cells and so has minimal

toxicity; doses of up to 25 mg/kg/day given over more than three years have

been studied in adults with no detectable toxicity32. There is a

theoretical concern that alpha-lipoic acid may bind to DMSA and reduce the

availability of both, but this has not been seen clinically.

Another concern is that alpha-lipoic acid reduces the removal of

methyl-mercury by glutathione, which is a reason why it should be given

with DMSA. There is also evidence that alpha-lipoic acid reduces copper

excretion33. Since DMSA increases copper excretion34 (it has been used to

treat the copper intoxication of 's disease35), this should not be a

problem if alpha-lipoic acid is used with DMSA.

A serious concern with alpha-lipoic acid is that it can facilitate the

movement of mercury out of and into the cells. It can be very useful in

mobilizing mercury from within the cells and making it available for DMSA

to chelate. Without the DMSA to " grab " the mercury from lipoic acid, it may

readily enter other tissues.

Melatonin: The pineal hormone that helps to regulate the sleep/wake cycle,

melatonin is also an anti-oxidant. It is relatively unique among natural

anti-oxidants in that it is a terminal antioxidant: once oxidized, it

cannot be reduced36. This characteristic means that melatonin cannot

participate in destructive redox cycling, where an oxidized compound is

reduced by oxidizing another compound. One study has found that neurons are

protected from mercury damage by hormonal levels of melatonin37.

Melatonin is also concentrated in the mitochondria and protects them from

oxidative damage.38 Aside from its anti-oxidant properties, melatonin helps

to regulate the sleep/wake cycle, which is often seriously deranged in

autistic children. Its long-term use in institutionalized children has

established its safety39.

Doses of up to 0.1 mg/kg at bedtime should be adequate to help with sleep

disturbances. Some clinicians have noted that smaller doses of melatonin

(0.3 mg in adults) are just as effective for sleep and may cause fewer

problems with nightmares and/or night terrors. A sustained release form of

melatonin is currently under development and should help with those

children who awaken four to six hours after the dose of melatonin. 13

Taurine: Taurine is a sulfur-containing amino acid which is important in

the production of bile salts and, therefor, in the native excretion of

toxins and absorption of fats and fat-soluble substances. Many autistic

children are deficient in taurine and benefit from a supplementation of 250

- 500 mg/day. A maximum dose of 2 grams/day in adults and adult-sized

children is recommended.

Glutathione: Glutathione is the keystone of the cellular anti-oxidant

system and is often deficient in autistic children. Despite numerous rodent

studies that show good systemic absorption of oral glutathione, the two

human studies looking at oral absorption have shown it to be nil40. In

humans, oral glutathione is readily absorbed by the gut mucosa, repleting

its glutathione supply; the mucosa then breaks down the remaining

glutathione. This may explain why oral glutathione has been of help to

autistic children even when there is apparently no systemic absorption.

Given the gut dysfunction found in many autistic children, oral glutathione

250 - 500 mg/day may be of significant help.

Supplements to be wary of

Cysteine/cystine: As sulfur-containing amino acids (cystine is the dimer of

cysteine), both can bind to and mobilize mercury. Like alpha-lipoic acid,

cysteine and cystine may worsen mercury intoxication by spreading it to

other tissues. Furthermore, cysteine and cystine are excellent culture

media for the Candida genus of yeast and can promote or worsen intestinal

candidiasis.

In addition, many autistic children have high blood levels of cysteine.

N-Acetyl-L-Cysteine (NAC): NAC should not be used initially or by itself

with anyone suspected of having a significant body burden of mercury. Like

alpha-lipoic acid, cysteine and cystine, NAC can bind with mercury and

carry it across cell membranes.

NAC is also a good culture medium for yeast, like its parent molecule,

cysteine. Since many autistic children also have high cysteine levels,

giving them NAC will only exacerbate this problem. NAC is often recommended

because it can rapidly increase intracellular glutathione levels41,42. For

that reason, it can be tremendously useful in treating the antioxidant

deficiencies seen in so many autistic children.

NAC should be used either in conjunction with DMSA or after mercury

detoxification is well under way. In addition, NAC should be used with

extreme caution in children with elevated cysteine levels.

Chlorella/other algae: Often touted as an herbal remedy for mercury

poisoning, chlorella has a great affinity for mercury and other heavy

metals. Unfortunately, it will also readily extract mercury from the water

it is grown in. Analysis of at least one specimen of commercially available

chlorella has shown high levels of mercury. Other unicellular algae

preparations are available on the market, advertised as a remedy for a

variety of problems. They should also be viewed with caution, not only

because of possible mercury content but also because of the potential for

contamination with toxic dinoflagellates.

----------------------------------------------------------------------------

----

Note from Dr. Mercola:

This information on chlorella is seriously flawed. It is based on a small

study done by Doctor's Data. They NEVER demonstrated increased absorption

of mercury from the chlorella, only that mercury was present in the

chlorella. Since hundreds of tons of mercury are deposited into the oceans

every year, this is not surprising. However, what the investigators failed

to account for was that the binding coefficient of chlorella to mercury is

far in excess of its potential to release mercury into the body. It only

ABSORBS mercury it does NOT release it into the body.

The other issue of potential for contamination with toxic dinoflagellates

is only true for blue green algae and NOT for chlorella since chlorella is

a cultured product and is NOT contaminated.

----------------------------------------------------------------------------

----

Concurrent testing

Since DMSA has been reported to cause elevations in hepatic transaminases,

serum ALT and AST should be monitored during therapy. Likewise, white cell

and platelet counts should be followed. Both elevation of liver enzymes and

bone marrow suppression are dose-related and 14 have been, to date,

completely reversible.

Also, review of the literature indicates that, while some patients are more

sensitive, sensitivity appears to remain constant. This would suggest that

patients who tolerate DMSA well initially will rarely, if ever, develop

sensitivity later in therapy.

Complete blood count (CBC) with platelet count and liver enzymes should be

checked after the first or second cycle and, assuming no abnormalities are

found, rechecked periodically while therapy continues. If elevated liver

enzymes or depressed cell counts are found, the DMSA should be stopped and

the laboratory tests followed until the values return to baseline.

If the abnormalities were not too severe and they return to baseline

promptly, the DMSA can be resumed at a lower dose with careful monitoring.

Urine metal analysis for mercury and other toxic metals may help direct the

duration of therapy. The optimum time for collecting the urine specimen is

after the second dose of the cycle and within six hours of the last dose of

the cycle. Timed specimens are best, but may not be practical in children

who are not toilet-trained.

When a 24-hour specimen is not possible, 12- or 6-hour specimens are

completely acceptable. In children who are continent at night, the first

morning urine represents an 8-hour collection, on average. Random or spot

urine specimens are problematic, as they may miss the time of peak

excretion, especially when DMSA is given every eight hours.

One way to overcome this problem is to obtain two or more random specimens

and combine them. This will " average " the mercury excretion over several

samples. The best time to get a spot urine sample is two to four hours

after a dose.

Some practitioners have found stool mercury analysis to be helpful, as much

of the mercury excreted with alpha-lipoic acid will be found in the bile.

The major limitation to stool mercury is that the stool contains both

mercury excreted in the bile as well as any mercury ingested in the diet

and not absorbed.

Without knowing the amount of mercury in the diet, it is impossible to

accurately interpret stool mercury levels. The best way to use stool

mercury levels is to obtain a level before treatment. Assuming that the

dietary mercury remains relatively constant, this will provide a baseline

for subsequent measurements.

End-of-treatment indications

If one could assume that the benefits seen in autistic children were

exclusively due to mercury detoxification, then treatment could stop when

mercury excretion dropped below detectable limits. Since this may not be

the sole mechanism of action, the decision to end treatment needs to be

based on both laboratory and clinical evidence.

One obvious indication to stop treatment is when improvement ceases. Halt

therapy when the child reaches a " plateau " and watch for any indication of

regression. Some parents and practitioners may want to continue treatment

for a few months after reaching a " plateau " in the hopes that a small

amount of additional progress may occur.

Also, the possibility of a " false plateau " due to illness or other stress

should be considered. Obviously, if the child shows no significant progress

during therapy or experiences regression, this would be another indication

to stop treatment. Keep in mind that a significant number of autistic

children will undergo some degree of regression during initial treatment

with DMSA while later experiencing significant gains.

If intestinal dysbiosis is not adequately treated prior to 15 starting

DMSA, any improvement from the DMSA may be masked when the intestinal

dysbiosis worsens on exposure to a rich culture medium. A number of

children have shown significant improvement while taking the DMSA, which

regresses when they stop, even for the " rest period " of each cycle. These

children need to be dealt with on a case-by-case basis, since there is

insufficient clinical experience so far to recommend a course of action.

----------------------------------------------------------------------------

----

Disclaimers:

1. The therapies outlined in this monograph should not be used except by

and under the supervision of a physician.

2. This is not a " stand-alone " protocol and must be preceded by correction

of intestinal dysbiosis and nutritional deficiencies.

3. These therapies may not help all autistic children and may potentially

make some autistic children significantly worse. Even those children who

will ultimately benefit from these therapies may show transient

deterioration during treatment.

4. The drugs and nutritional supplements discussed in this monograph, with

the exception of DMSA (Succimer, Chemet®), antibiotics and antifungals, are

not approved by the United States Food and Drug Administration (USFDA).

DMSA is currently approved by the USFDA only for lead poisoning.

5. The quality and purity of drugs and supplements that are not FDA

approved will vary with different suppliers. All such drugs and nutritional

supplements mentioned are allowed by the USFDA, but it does not guarantee

their safety, purity or effectiveness.

6. The theories and medical models on which these therapies are based are

not universally accepted in the medical community and are being vigorously

studied by a number of researchers. The clinical evidence supporting these

therapies is compelling but no wellcontrolled outcome studies have yet been

performed; the evidence is largely based on clinical experience at this point.

7. The theories and therapies discussed in this monograph are subject to

change without notice if significant clinical or research data indicates a

need for change.

Disclaimers for medical practitioners:

1. Attempting mercury or other heavy metal detoxification before the

patient's underlying gastrointestinal and nutritional problems are

corrected will likely be disappointing to you and to the patient's family.

2. The dosing of the drugs and nutritional supplements in this monograph is

within the limits supported by the majority of the peer-reviewed literature

published as of January 2001. The maximum limits should be exceeded only if

you have good reasons to do so.

3. At the present, it is impossible to determine which patients will

benefit from these therapies with great accuracy. Some patients who seem to

be perfect candidates will have no improvement and others who seem to have

little to recommend the therapy will show marked improvement

4. The treatment of autism is in a state of continual flux. 16

Disclaimers for parents and family members:

1. Many families are treating their autistic children with therapies

similar to those listed in this monograph without involving a physician or

other health care provider. That most of them do so without any adverse

consequences is a testament to the safety of the drugs and supplements

used. However, DMSA and some of the supplements present a small but nonzero

risk of serious side effects. Life, in general, is a series of risks; the

risk of serious side effects can be reduced by careful medical monitoring

during treatment.

2. Not every physician is able or willing to carry out the therapies

described in this monograph. Have a frank and open discussion with your

physician or other medical practitioner before embarking on these treatments.

3. Despite miraculous case reports heard on the grapevine and on the

Internet, these therapies will not work for every autistic person. Even

those who do improve may have slow or incremental improvement

4. In general, younger patients appear to respond more quickly than older

patients, but this has not yet been adequately investigated.

Autism Research Institute

References