Metallothionein and Autism Update

by Kelly Dorfman, MS, Co-founder, Developmental Delay Resources

Healthcare professionals treating children with autism spectrum disorders have shown considerable interest in metallothionein (MT) in the last few years because of pioneering research by William Walsh, PhD of the Walsh Research Institute.

I feel that Dr. Walsh is correct that the copper-to-zinc ratio is abnormally high in individuals with autism. However, I believe that the reason for this abnormal ratio involves the complex interaction among MT, zinc, copper, as well as ceruloplasmin and glutathione.

Metallothionein (MT)

Metallothionein is a family of small proteins containing 61-68 amino acids that play a major role in heavy metal detoxification. MT deficiency could explain why individuals with autism respond unfavorably to heavy metals like mercury.

MTs function as intracellular distributors and mediators of copper and zinc. MT also contains an unusually high (30%) concentration of cysteine, which reacts with a number of metals including zinc, mercury, copper and cadmium. However, the most important factor in the regulation of MT is the amount of zinc intake.


Zinc deficiency is common in children with autism and also associated with growth retardation, poor wound healing, hair loss, night blindness, weak immune function and delayed sexual maturation. As zinc levels fall, skin rash, abdominal pain, diarrhea, loss of appetite and impaired taste and smell can occur.

When the body’s stores of zinc are depleted, it must break down MT and take zinc from plasma proteins. Many practitioners prescribe heavy loads of zinc for periods of several weeks to several months.

I have found that MT increases six-fold after only 10 days of zinc supplementation, then plateaus. If you give too much zinc for too long, it can cause depigmentation of hair and skin.

Excess zinc can also lead to copper deficiency. A parent I know gave her child high doses of zinc daily for over a year. She reported that the child’s hair turned grey.

Chelation should begin once zinc levels are sufficient. Since zinc regulates MT, the body will release some zinc along with the heavy metals. It is important to continue zinc loading during chelation.

Because zinc is a co-factor in hundreds of biochemical reactions, it is impossible to know which symptoms are associated with which reactions. I believe that some of the benefits of long-term zinc supplementation might be completely unrelated to MT.


Copper produces energy in the cells, assists in neuro-transmitter production, nerve conduction, and in the healthy function of both the immune and cardiovascular systems. Symptoms of excess copper include hyperactivity, irritability, poor concentration and joint pain.


A large protein called ceruloplasmin plays an important role as a “transporter” in copper metabolism. While most copper in the blood is bound to ceruloplamsin, some is bound to albumin, MT or other proteins. If ceruloplasmin is low, free copper can rise to toxic levels. Reduction of free copper may be the reason for improvement seen in autistic symptoms on zinc loading.


The body’s level of glutathione (GSH) determines absorption of toxins from heavy metals. Glutathione can be low for a number of reasons, including exposure to toxic hydrocarbons such as DDT, PCB’s, or chloroform because it combines with these toxins and is eliminated with them.

When levels of metallothionein and zinc bound by metallothionein are appropriate, glutathione mediates the transfer of zinc to metallothionein. Conversely, glutathione oxidizes the sulfhydryl groups of MT and releases zinc to enzymes.

Metallothionein, glutathione and other regulatory proteins are thus very important in maintaining zinc in the brain at non-toxic levels.

New Lab Test

I have responded to Dr. Walsh’s desire for a metallothionein screening test with the Advanced Metallothionein Profile (AMP). This blood test measures not only metallothionein, but also serum zinc, copper, ceruloplasmin, free copper, and glutathione. It is evident that either an excess or deficiency of any of these substances may be harmful. The print-out also includes a copper/zinc ratio, a GSH/MT ratio, and a zinc/MT ratio.

With the Advanced Metallothionein Profile, professionals can determine whether a patient has zinc, copper, glutathione, ceruloplasmin and metallothionein deficiencies or excesses, and thus provide the appropriate treatment. Doctors can order test kits, available overnight, from Great Plains Laboratory.

My staff and I provide test interpretation training by phone or in person. I urge all health care professionals to use the AMP to monitor the effectiveness of detoxification treatments, and as a guide for modulating immune deficiencies.

For more information about the AMP go to For Dr. Walsh’s work go to

Categories: Autism | Nutrition