Defeat Autism Now! (DAN!)

MERCURY DETOXIFICATION
CONSENSUS GROUP
POSITION PAPER 

May 2001 

AUTISM RESEARCH INSTITUTE
4182 Adams Avenue
San Diego, California 92116

autismresearchinstitute.com

© Autism Research Institute 2001

General Disclaimer

This monograph is not intended as medical advice. Its intention is solely informational and educational. Please consult a qualified medical or health professional if you wish to pursue the ideas presented.
Every effort has been made to ensure that the information contained in this monograph is a complete and accurate representation of a consensus opinion of the listed contributors. However, neither the authors, contributors not the sponsoring organization, The Autism Research Institute, is engaged in rendering professional advice or services to the individual reader. The ideas, procedures and suggestions contained in this monograph are not intended as a substitute for consulting with your physician and obtaining medical supervision as to any activity, procedure or suggestion that might affect your health.
Neither the authors, nor contributors, nor the sponsoring organization shall be liable or responsible for any loss, injury or damage allegedly arising from any information or suggestion in this monograph.

—The Consensus Position Paper—

This consensus position paper represents the current views of the undersigned physicians and
research scientists. The consensus process was initiated at a conference convened for this purpose by the
Autism Research Institute on February 9-11, 2001 in Dallas, Texas. The participants continued their
discussions by telephone, fax, e-mail and, in some cases, in-person discussions. The final version was
approved on April 20, 2001.
No one is more aware than the undersigned that this document represents merely a beginning step
in our long-term efforts to solve an exceedingly difficult problem. We have much to learn.

a: Not present at Dallas conference b: Conference coordinator c: Project organizer

TABLE OF CONTENTS

3...... Background and Introduction

7...... Position Paper on Mercury Detoxification

18..... Appendix A: Detoxification Regimen

20..... Appendix B: Treating Gut Dysbiosis

22..... References

25..... Follow-Up Research: Treatment Evaluation Form

THE AUTISM RESEARCH INSTITUTE

“Research That Makes a Difference”

The Autism Research Institute (ARI) has been in the forefront of research on the causes and treatment of autism since its founding in 1967. In that era, autism was considered to be a psychological disorder caused by the mother’s emotional rejection of the child. Bernard Rimland,
Ph.D., the founder of the ARI (as well as the founder of the Autism Society of America), is credited with destroying the “blame the mother” theory and setting autism research on its present course of seeking answers in the biomedical domain.

The ARI’s Defeat Autism Now! (DAN!) project, initiated in 1995, is ARI’s response to the abysmally slow rate of progress in autism research. ARI has enlisted a consortium of cutting-edge scientists and physicians from around the world to seek answers at an accelerated pace. The
Mercury Detoxification Position Paper is one of many ARI/DAN! initiatives directed toward defeating autism as quickly as possible.

ARI depends upon the generosity of concerned individuals and organizations. Your help will speed the day when the horror of autism fades into history.
All donations are tax-deductible and are acknowledged.

ARI is a 501(c)(3) organization. Federal ID No. 95-2548452.
Autism Research Institute • 4182 Adams Ave., San Diego, CA 92116 • www. autismresearchinstitute.com
Fax: 619-563-6840

This project was supported in part by a grant from:
Kirkman Laboratories
1-888-KIRKMAN
www.kirkmanlabs.com

Background and Introduction to the
Position Paper of the Consensus Conference
On The Mercury Detoxification of Autistic Children

Bernard Rimland, Ph.D., Director
Autism Research Institute

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 U.S., in the U.K., 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. Thimerosalcontaining 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.

During the late 1960s, my then graduate-student assistant, Dale Meyer, became interested in the fact that mercury poisoning mimicked many of the symptoms of autism. She wrote a research paper on the subject which is no doubt still somewhere in my files. She wrote that acrodynia and pink disease were puzzling ailments which caused numerous symptoms, including those of autism that had baffled medical investigators for many decades, until the cause, mercury in teething lotions and diaper powders, was discovered. “Interesting,” I remember thinking.
“Another mystery solved. But only of historical interest.” How wrong I was!

I had assumed, very naively as it turned out, that the FDA and the drug manufacturers would thenceforth scrupulously avoid using mercury. I was aware that minute amounts of mercury, along with other toxins, such as aluminum and formaldehyde, were used as preservatives in vaccines, but, after all, I assumed, since everyone now knew that these substances are extremely toxic, those highly sophisticated vaccine-makers would not possibly use amounts which even approach dangerous levels. Bad guess!

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 I attended a meeting called by the National Institute of Environmental Health Sciences, on the possible role of mercury in the causation of autism. The meeting was attended by a number of physicians and scientists. One of the physicians, Dr. Stephanie 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.

I was very much aware that there was a great deal of disagreement among physicians as to the most appropriate procedures for mercury detoxification and decided that it would be highly desirable to call a consensus conference - a think tank - of experienced physicians and scientists to review the available evidence and come up with a position paper presenting the safest and most effective methods of treating autistic children for mercury intoxication.

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.

The meeting was an outstanding success. Despite my initial concern that the various areas of
disagreement would prove divisive, the participants discussed the controversial issues
harmoniously and agreed that it would be feasible to arrive at the consensus position that was
hoped for.

During the next six weeks the participants were deluged with e-mails, faxes and phone calls as
the conferees discussed, rediscussed, thrashed out, modified, reviewed and revised each and every
aspect of the proposed position paper. Finally, the last details were agreed upon - with the clear
understanding on everyone’s part that there is much more to be learned.

The other attendee who demurred was also a chemist, but his reason was quite different. He sees
the problem in a different light than everyone else, and is working on a new and innovative
approach toward solving it. I have a great deal of respect for this scientist, and am looking
forward, with great anticipation, to learning more about his new ideas and procedures, when he is
ready to share them with us. Albert Szent-Gyorgy once said, “Genius is the ability to look at what
others have looked at, and see what they have not seen.” When our chemist friend is ready to
make his ideas public, we will present them in the Autism Research Review International. He just
may be right. I hope so!

I should mention several topics, discussed at the Dallas conference and in subsequent
communications, that did not reach consensus status but nevertheless commanded a significant
degree of attention and support. These topics, which will be raised again at future consensus
meetings, include:

• the use of intravenous vitamin C as a detoxicant
• improving pancreatic function through the use of secretin and by normalizing body
acidity with weak acids such as lemon juice or vinegar
• finding ways of using DMPS more safely
• causing transdermal excretion of toxins by saunas or epson salt baths

Any clinician with data or experience to share on these or related topics is encouraged to
communicate with us.

In the meantime, however, I am confident that the document on the following pages, even though
it is best described as still a “working paper,” provides the best information available at the
present time.

As the parent of an autistic adult son, and as a worker in the field of autism research for over 40
years, I feel privileged to have been a part of the Consensus Committee that produced the
following “Position Paper on the Detoxification of Autistic Children.”

MERCURY DETOXIFICATION OF AUTISTIC CHILDREN:
CONSENSUS POSITION PAPER

Purpose

A few years ago, several people began to explore the possibility that at least some of the children
with autism are manifesting a type of mercury poisoning. A landmark monograph written by
Sallie Bernard, Albert Enayati, B.S, Ch.E, M.S.M.E., Heidi Roger, Theresa Binstock, Lyn
Redwood, R.N, M.S.N, C.R.N.P., and Woody McGinnis, M.D. served as a call to action. Acting
on this theory, several practitioners began treating autistic patients with a variety of detoxifying
regimens to remove the mercury and try to reverse the damage. Although no outcome studies
have yet been published, the clinical experience of a number of practitioners has been extremely
encouraging.

Unfortunately, there are more autistic children who might benefit from this therapy than any of
the practitioners currently engaged in mercury detoxification therapy could treat in their lifetimes.

In addition, there is such divergence in the details of therapy among practitioners that comparison
of their outcomes is impractical. Finally, a number of practitioners have expressed an interest in
initiating detoxification therapy but need guidance in how best to begin. For all of these reasons,
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
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 B) 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.

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
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.

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 (Stevens-Johnson 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
reaction, TEN and Stevens-Johnson syndrome are absolute contraindications to continued
therapy.

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 (Stevens-Johnson 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.

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
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 Wilson’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.

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.

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
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
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.
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.

Appendix A: Detoxification Regimen

Appendix A: Detoxification Regimen (cont.)

Glutathione: Oral glutathione 250 – 500 mg per day may help gut anti-oxidant function.
Notes:

1. Vitamin C: Use the buffered preparation or the ester to minimize GI upset. Begin with the starting
dose and increase to the maximum tolerated. Be sure to keep well-hydrated. Dividing the dose may
decrease GI upset.

2. Vitamin B6: If you choose to use pyridoxal-5-phosphate (P5P) instead of B6, divide the dose by 5.

3. Vitamin B6: Be sure to use a copper-free preparation. Since vitamin B6 is very bitter, we suggest the
use of Super Nu Thera (flavored B6 and magnesium) from Kirkman Laboratories: 1-888-KIRKMAN,
www.kirkmanlabs.com.

Appendix B: Treating gut dysbiosis
A large number of autistic children have intestinal abnormalities, including abnormalities in gut
permeability, defects or deficiencies in intestinal enzymes, and abnormal intestinal flora. Many of
these factors are mutually reinforcing, so they are difficult to correct in isolation. The causes of
these intestinal dysfunctions are hotly debated, but the leading theories are congenital enzyme
dysfunction, secondary enzyme dysfunction due to toxins (e.g. mercury), viral injury, and yeast
overgrowth. There are other theories and their exclusion here does not reflect on their merit or
lack thereof.

Since no two autistic children are alike, the first step is to examine the stool to determine which
specific organisms predominate and whether there are imbalances or pathogenic flora present. A
stool culture (with fungal culture) will provide a great deal of information for a relatively minor
output of effort and at a reasonable cost. A common finding is yeast overgrowth, with a fair
number of children showing significant colonization with Clostridium species. Evidence of
Clostridium may be seen in the stool sample (C. difficile antigen) or it may be detected by urine
organic acid analysis. Elevated hydroxylated phenylproprionate (DHPPA) in the urine is a telltale
marker of Clostridium overgrowth. Other abnormal bacteria found include Pseudomonas and
other opportunistic pathogens.

Clinical experience has shown that an important first step in treating gut dysbiosis is to correct
any coexisting constipation. Regular elimination will help reduce the fungal and/or bacterial load
and will reduce the amount of endotoxins and exotoxins that are absorbed from the intestine.

Diet modifications are also important during the treatment of documented or suspected yeast
overgrowth. Reducing the carbohydrate intake as much as possible has been correlated with
improved success and fewer recurrences. At least one study of Candida albicans showed that the
presence of sucrose, glucose, fructose, galactose or maltose in the culture media significantly
increased the surface adherence of the yeast, a major determining factor in its pathogenicity43. In
addition, Candida in the gut lumen, even without invasion of the intestinal mucosa, can decrease
the intestinal absorption of sugar and water in experimental animals44.

Yeast overgrowth can be treated in a number of ways; one reasonably gentle way is to administer
live Lactobacillus by mouth. In moderate yeast overgrowth, the Lactobacillus can restore normal
gut flora, which then suppresses yeast by competition. A number of herbal preparations, such as
garlic, have been used to suppress yeast as well, and may help the Lactobacillus regain a
foothold. When neither of these methods is sufficient, antifungal drugs are needed.

One drug commonly used is Nystatin, which is a polyene antibiotic produced by the bacteria
Streptomyces noursei. When given by mouth, it is not absorbed to any significant extent and
remains in the intestine; this keeps the drug where it is needed and minimizes any systemic
effects. The usual dose schedule is one to two million units a day, either as a single dose or in
divided doses. Doses of up to 10 million units a day or more may be needed initially to eliminate
yeast; maintenance doses of one or two million units a day for in excess of a year are common.
Side effects are limited to nausea and gastrointestinal upset, usually only seen at doses over 5
million units daily. Since it is not absorbed, the yellow color of the drug will modify the stool
color, which may alarm some parents if they are not forewarned.

For more persistent yeast overgrowth, the azole antifungals such as fluconazole (Diflucan®),
itraconazole (Sporanox®) and ketoconazole (Nizoral®) can be a great help. The azole antifungals
work by inhibiting the fungal cytochrome P-450 enzyme that catalyzes C-14 alpha-demethylation
in the production of ergosterols. The equivalent human enzyme is much less sensitive to
inhibition by azoles, but is affected somewhat. This inhibition may become clinically significant
when given with another compound that is metabolized by that enzyme. Specific drug
interactions have been reported with rifampin, coumadin, phenytoin, cyclosporine, theophylline,
oral hypoglycemics, terfenadine, cisapride, and astemizole.

Fluconazole is well absorbed when taken by mouth and so has the potential for systemic effects.
One of these systemic effects is to get into the deepest crypts of the intestine and eradicate any
yeast taking refuge there. Adverse reactions reported in children include vomiting (5%),
abdominal pain (3%), nausea (2%), and diarrhea (2%). Laboratory abnormalities of elevated
transaminases and alkaline phosphatase were seen in 1.4% of children without any clinical
findings. Adults undergoing prolonged fluconazole therapy reported headache (1.9%) and skin
rash (1.8%). Rare anaphylactic reactions have also been reported as well as Stevens-Johnson
syndrome and toxic epidermal necrolysis (TEN).

Fluconazole has been used in children as young as six months for oropharyngeal and esophageal
candidiasis. The recommended dosage is an initial loading dose of 6 mg/kg and doses of 3 mg/kg
once a day. The daily dose may be up to 12 mg/kg/day but should not exceed a maximum of 600
mg/day. The duration of treatment depends on the clinical findings, but should be at least fourteen
days. The longest reported therapy with fluconazole was 1,616 days.

Hepatocellular injury can be seen with any of the azole antifungals, but fluconazole has the
lowest reported incidence. Still, serum liver transaminase levels should be followed carefully for
any treatment lasting longer than 20 – 30 days. Side effects are not significantly different between
drugs in this class, although fluconazole and itraconazole are often reported to have a lower
incidence of side effects than ketoconazole45. Resistance to the azoles is becoming more of a
problem, especially in patients who have repeated or prolonged treatment. Resistance to one azole
drug usually, but not always, leads to resistance to them all46,47.

Like yeast, overgrowth with Clostridium spp. or Pseudomonas spp. may also resolve with
reintroduction of Lactobacillus. For those that do not resolve, oral therapy with vancomycin is
tremendously effective. Vancomycin is a tricyclic glycopeptide antibiotic produced by
Amycolatopsis orientalis (formerly Nocardia orientalis) which is not normally absorbed orally,
so there is minimal risk of systemic effects. An oral form is available, but the powdered form
used to prepare intravenous infusions is also readily available and is absolutely free of any
potentially harmful additives or fillers. The recommended dosage is 40 mg/kg/day divided into
three to four doses; the total daily dose should not exceed 2 grams. Treatment should last 7 – 10
days.

With the increased use of antibiotics, both bacteria and yeast are developing increasing drug
resistance. For this reason, the stool culture should include the antibiotic sensitivities and any
isolates.

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