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Article Written by Amy S. Holmes, M.D.
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Reprinted with the kind permission of the author and William Walsh, Ph.D. -
Co-Founder and Senior Scientist - the Health Research Institute and Pfeiffer Treatment Center
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Heavy Metal Detoxification and Metallothionein Promotion
Background:
Recent developments have been made to promote metallothionein (MT) in the G.I. tract, brain, and elsewhere. This protocol is based on 1,200 published articles describing MT synthesis, activation, and redox mechanisms. A total of 22 nutrients that enhance MT production were identified and tested in informal clinical trials involving staff and volunteer autism families.We found that aggressive zinc loading must precede full-scale MT Promotion therapy for best results. Each molecule of MT requires 7 atoms of zinc (Zn) for proper functioning. Premature synthesis of MT at intestinal mucosa can temporarily prevent Zn transport into the bloodstream, resulting in severe irritability. Our best clinical outcomes were achieved using a two-phase protocol:
- Preloading with Zn and augmenting nutrients, followed by:
- Cautious, gradual introduction of MT promotion nutrients.
William Walsh, Ph.D. and staff at the Pfeiffer Treatment Center in Naperville, Illinois developed the protocol for the induction of metallothionein production itself.
The advantage of MT induction itself over DMSA/LA is that it does not promote the large overgrowths of unfriendly organisms in the intestines so often associated with the use of lipoic acid. If a child is doing well on DMSA/LA with no overgrowths of unfriendly organisms, then it may be best to stick with this treatment, however if a child is found to have large overgrowths of unfriendly organisms at initial evaluation or experiences overgrowths of these organisms once lipoic acid is added, it is probably best to use the protocol of MT induction instead.
The scientific literature clearly indicates that most of the body's MT is induced by zinc, with glutathione (GSH) needed for loading apo-MT with zinc and glutathione disulfide (GSSH) required for redox exchange. Selenium and the GSH/GSSH redox couple enhanceMetallothionein - MT Promotion Nutrient
The equilibrium constants for binding of MT to heavy metals are remarkably large; with the net result that Zn-MT is a "magnet" for these toxic metals.
- delivery of Zn to cells
- sequestering of mercury and other heavy metals
MT proteins are composed of 14 amino acids and zinc. Many autism-spectrum patients are unable to efficiently cleave dietary proteins into the individual amino acids needed for MT synthesis. Our formulation provides all 14 amino acids, in the proportion found in MT. The large amounts of cysteine required for MT synthesis can be supplied in the form of oral GSH which breaks down in the G.I. tract with minimal side effects.
The Health Research Institute - HRI Pharmacy has patented various MT-promotion formulations in order to ensure that they will be widely available at low cost. Because of risks associated with improper use, these formulations will be available by prescription to medical professionals, but not to the general public.
The various MT-promotion formulations are available only from the HRI Pharmacy. The original prescription written by your physician must be mailed to the HRI Pharmacy directly. It cannot be called or faxed into the pharmacy.
MT-promotion therapy is recommended only for patients with disturbed metal metabolism. Key laboratory tests include serum copper, plasma zinc, and serum ceruloplasmin. In healthy individuals, the Cu/Zn ratio usually ranges between 0.8 and 1.2, and the amount of free copper (unbound by ceruloplasmin) ranges from 5 to 25 mcg/dL. In addition, the presence or absence of symptoms of copper overload and zinc deficiency can also aid diagnosis. Meaningful assays require acid-etched trace-metal-free sample tubes and avoidance of trace mineral supplements for 24 hours before sampling.Clinical Testing Procedures
Other essential tests required for full evaluation include blood counts, tests of liver and kidney functions, along with an evaluation of thyroid function. Testing plasma ammonia is highly recommended prior to treatment because of the high prevalence of elevated ammonia levels in patients with autism/PDD and related disorders.
Also, a full evaluation of intestinal microflora, including both stool comprehensive parasitology (aerobic bacteria, yeast, and parasites) and urine organic acid test is recommended prior to the initiation of any therapy.
Other tests that may be useful include plasma sulfate and plasma reduced glutathione levels prior to the initiation of therapy.
A good trial of the gluten-free, casein-free diet (at least 6 months) is highly recommended. The best source of information about this diet is the book written by Lisa Lewis, Ph.D., Special Diets for Special Kids.Treatment for Patients Found to Have Metallothionein Dysfunction
- Step 1
- Gut Clean-up - restore good levels of friendly bacteria and reduce overgrowths of unfriendly organisms such as Clostridia and yeast
- Supporting Nutrients - exact nutrients determined by testing
- Reduction of elevated plasma ammonia (if necessary)
- Aggressive zinc pre-loading
- DMSA alone until very little mercury, lead or tin is excreted in urine (if necessary)
- Step 2 - MT Promotion Protocol
- Phase 1: Zinc Loading: Aggressive supplementation with Zn and augmenting nutrients for 4 to 8 weeks is recommended. Sensitive patients may require gradual build-up of Zn dosage. Plasma zinc levels should be greater than 100 mcg/dL prior to Phase 2 to minimize irritability side effects. Zinc dosages vary with body weight. A helpful rule of thumb for small patients is to provide a daily mg dosage of Zn equal to weight (lbs) plus 15-20 mg. For example, a 40 lb child would receive 55-60 mg/day during Phase 1. In addition, we recommend the following augmenting nutrients be given with the Zn: Pyridoxal-5-Phosphate, Manganese Gluconate, and Vitamins C and E. Also, Taurine may be used for patients with seizure tendencies. We have developed a compounded supplement for Phase 1, which we call the "Metabolic Primer".
- Phase 2: After Phase 1 is completed, GSH, Se, and the 14 amino-acid constituents of MT are introduced gradually, as tolerated. These nutrients are available in a compounded blend called the MTP supplement. Continuation of casein/gluten-free diets, probiotics, the Metabolic Primer, and other ongoing therapies is recommended.
Promotion of the MT protein system is expected to provide many benefits to autism-spectrum patients, including:Objectives of MT-Promotion Therapy
- elimination of toxic metals
- protection against future toxic exposures
- normalization of the G.I. tract
- improved behavior control
- improved immune function
- enhanced development of brain neurons and synaptic connections
The first 5 benefits may be attainable in the first year of treatment, regardless of the patient's age. However, the rate of formation of new synaptic connections declines rapidly with age, and early intervention is critically important for development of speech, cognitive advancement, etc. Great patience is needed in treatment of older children who can be expected to progress at a relatively slow rate. For example, it may require years for a 10 year old to achieve the same cognitive progress achieved by a 2 year old in a few weeks. Behavioral therapies, which shower the brain with impulses and promote neuronal development are especially recommended in conjunction with Metallothionein Promotion therapy.
Amy S. Holmes, M.D.
March 5, 2002
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