The Causes of Autism

BMC Clinical Pharmacology 2009, 9:16

Who are the authors?

James B Adams, Matthew Baral, Elizabeth Geis, Jessica Mitchell,
Julie Ingram, Andrea Hensley, Irene Zappia, Sanford Newmark,
Eva Gehn, Robert A Rubin, Ken Mitchell, Jeff Bradstreet, and Jane
El-Dahr

What is the study about?

This study investigated the effect of oral Dimercaptosuccinic acid (DMSA) therapy on children with autism spectrum disorders (ASD) aged 3-8 years who had evidence of significant heavy metal exposure. The study aimed to evaluate the safety and efficacy of DMSA therapy to remove toxic metals, normalize glutathione, and improve platelet levels in children with ASD.

It also aimed to quantify the amount of toxic metals excreted by children in the DMSA and placebo groups after multiple rounds of therapy and determine whether multiple rounds of DMSA chelation therapy would lead to clinical improvements in autism-related symptoms.

The study was conducted in two phases. In Phase One, each child received a screening round of DMSA to determine whether they had high excretion of toxic metals, which is an indicator of heavy metal toxicity. Participants who had high urinary excretion of toxic metals were selected to continue onto Phase Two. Phase Two was a randomized, double-blind, placebo-controlled study of six additional rounds of either DMSA or a placebo.

What is DMSA?

DMSA is an abbreviation for Dimercaptosuccinic Acid, a medication that can remove toxic heavy metals such as lead and mercury from the body. In this particular paper, DMSA therapy was being evaluated on children with autism spectrum disorders who have evidence of significant heavy metal exposure. The study investigated the safety and efficacy of DMSA therapy to remove toxic metals, normalize glutathione, and improve platelet levels in children with ASD.

What previous research is there on this topic?

Many epidemiological studies have investigated the possible link between thimerosal-containing vaccines and autism since it was discovered in 1999 that the amount of thimerosal in US childhood vaccines was far in excess of FDA and EPA guidelines.

Eleven studies have reported a significant link, while 5 studies by other groups failed to establish a link, and another study was inconclusive. There is also evidence to suggest that lead, mercury, and other toxins can impair child development at levels commonly encountered by most of the US population.

What methods were used in the study?

Phase One

Phase One was a screening round of DMSA chelation therapy that each child received to determine if they had high excretion of toxic metals, which is an indicator of heavy metal toxicity. The criteria for Phase One were: each child first received a physical examination to determine that he/she was in sufficiently good health to participate in the study. Then a blood draw was conducted to test for blood chemistry and complete blood count (CBC), and red blood cell (RBC) glutathione. If liver and renal function were normal, and CBC’s were not below the normal range, then the child was eligible to participate in Phase-One. In the screening round, each child received nine doses of DMSA (over three days) to remove toxic metals from their body. After the screening round of DMSA in Phase One, each child was assessed based on their urinary excretion of toxic metals, and only those who had high excretion of toxic metals were selected to continue into Phase Two.

Phase Two

Phase Two was a double-blind, placebo-controlled study involving six additional rounds of DMSA or placebo treatment for children with high urinary excretion of toxic metals following the Phase One DMSA therapy. The study enrolled 49 participants who were randomly assigned to either the DMSA or placebo group. The primary objective of Phase Two was to quantify the amount of toxic metals excreted by the children after multiple rounds of therapy. The secondary objective was to evaluate whether multiple rounds of DMSA chelation therapy would result in improvements in autism-related symptoms.

What were some findings of the data?

Phase One Findings

In Phase One, the screening round of DMSA resulted in a significant increase in mercury excretion, with a slight increase at the 9th dose that was not statistically significant. The study also found significant increases in excretion of thallium, antimony, and tungsten. Furthermore, the study showed that there was no significant deterioration in renal function in any of the participants.

Phase Two Findings

Multiple rounds of DMSA chelation therapy led to a significant increase in the excretion of lead, tin, bismuth, mercury, and thallium. Possible increases were observed in excretion of uranium, antimony, tungsten, and nickel. Conversely, the study found a decrease in the excretion of cadmium and arsenic.

The study observed a possible trend of a small decrease in eosinophils (-18%) and a potential increase in triglycerides (+47%). Eosinophils decreased from initially 3/21 high to 2/21 high at the end of the study. Similarly, initially all triglyceride levels were normal, and at the end of the study, 2/21 showed elevated levels.

The study found that most of the metals had one or more correlations with other metals, making it difficult to distinguish the effect of one metal from another when doing regression analysis.

During Phase One, one case of mild adverse reaction (lethargy, decreased appetite) was observed, and one child had a history of gaining and losing skills, and the parents thought that the child did permanently lose some skills during the study. However, the ADOS scores on that child were either unchanged (Communication, Sociability) or improved (Play, Stimulatory Behavior/Restricted Interests) from the beginning to the end of the study.

It should be noted that the study was largely exploratory, and future studies should be larger and true placebo-controlled, double-blind studies of DMSA chelation therapy in children with autism spectrum disorders.

What were the conclusions drawn from the findings?

The study data suggests that initial glutathione levels can be partially predicted based on the excretion of cadmium, lead, tin, thallium, and arsenic. Furthermore, the change in glutathione levels can be partially predicted by the excretion of cadmium after the 9th dose in phase 1.

The BUN/Creatinine ratio can also be partially predicted by urinary metal excretion at baseline and after the 9th dose of Phase 1. The study found significant increases in excretion of thallium, antimony, and tungsten, and a small decrease in excretion of arsenic at the 9th dose.

It is important to note that a larger study is needed in the future to conduct a true placebo-controlled, double-blind study.

What are the limitations of the study?

The study had a small sample size, with only 65 children completing Phase One and 49 children continuing to Phase Two. Additionally, the study was not designed to evaluate the long-term safety and efficacy of DMSA chelation therapy. Moreover, the lack of a true placebo group in Phase One makes it difficult to determine the effectiveness of DMSA therapy.

The study also failed to measure urinary porphyrins, a more specific marker for heavy metal toxicity than urinary excretion of toxic metals. Furthermore, potential confounding factors such as diet and environmental exposures were not controlled for.

The study was conducted on children with autism spectrum disorders who were taking a vitamin/mineral supplement for at least two months before and throughout the study, which could have influenced the results. Finally, the study involved multiple comparisons, increasing the risk of Type I errors.

What should future studies research based on the findings in this study?

Future research directions could include conducting larger, randomized, and controlled trials with a genuine placebo group to establish the safety and effectiveness of DMSA chelation therapy in children with ASD. Additionally, future studies may consider longer treatment periods and compare the efficacy and safety of DMSA with other chelators.

Another important step is to measure urinary porphyrins as a more specific marker for heavy metal toxicity and conduct pre-screening for metal toxicity using urinary porphyrins. Researchers should also control for potential confounding factors such as diet and environmental exposures. Furthermore, investigating the long-term effects of DMSA chelation therapy on the physical and cognitive development of children with ASD is necessary.

It is also worth considering the effects of chelation on non-heavy metal toxins. Lastly, improving study design techniques to minimize errors from multiple comparisons can help ensure the validity of results.

Can I find the full study somewhere?

You’re so beautiful when you want to read the full study.

Check it out right here: Full Text Article.