The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity

Summary

Autism is a neurodevelopmental disorder that according to the Centers for Disease Control and Prevention (CDC) affects 1 in 150 children in the United States. Autism is characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. Recently emerging evidence suggests that mercury, especially from childhood vaccines, appears to be a factor in the development of the autistic disorders, and that autistic children have higher than normal body-burdens of mercury. In considering mercury toxicity, it has previously been shown that testosterone significantly potentates mercury toxicity, whereas estrogen is protective. Examination of autistic children has shown that the severity of autistic disorders correlates with the amount of testosterone present in the amniotic fluid, and an examination of a case-series of autistic children has shown that some have plasma testosterone levels that were significantly elevated in comparison neurotypical control children. A review of some of the current biomedical therapies for autistics, such as glutathione and cysteine, chelation, secretin, and growth hormone, suggests that they may in fact lower testosterone levels. We put forward the medical hypothesis that autistic disorders, in fact, represents a form of testosterone mercury toxicity, and based upon this observation, one can design novel treatments for autistics directed towards higher testosterone levels in autistic children. We suggest a series of experiments that need to be conducted in order to evaluate the exact mechanisms for mercury–testosterone toxicity, and various types of clinical manipulations that may be employed to control testosterone levels. It is hoped by devising therapies that address the steroid hormone pathways, in addition to the current treatments that successful lower heavy metal body-burdens of mercury, will work synergistically to improve clinical outcomes. In light of the fact that there are a number of other diseases that may have a chronic mercury toxicity component, such as Alzheimer’s disease, heart disease, obesity, ALS, asthma, and other various forms of autoimmune disorders, it is imperative that further research should be conducted to understand mercury–testosterone toxicity.

Introduction

Autism is a neurodevelopmental disorder characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. According to the most recent estimates published by the Centers for Disease Control and Prevention (CDC), it has been reported that approximately 1 in 150 children in the United States suffers from an autistic disorder [1], [2]. Recent studies have reported that exposure to mercury can cause immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with autism, and the similarities extend to neuroanatomy, neurotransmitters, and biochemistry [3], [4], [5].

Thimerosal, a preservative added to many vaccines, has become a major source of mercury among children in the United States who, within their first two years of life, may have received a quantity of mercury that exceeded Federal Safety Guidelines [6], [7]. According to the CDC recommended immunization schedule in the United States during the 1990s, infants may have been exposed to 12.5 μg of ethylmercury at birth, 62.5 μg of ethylmercury at two months, 50 μg of ethylmercury at four months, 62.5 μg of ethylmercury at six months, and 50 μg of ethylmercury at 18 months, for a total of 237.5 μg of ethylmercury during the first 18 months of life, if all thimerosal-containing vaccines were administered [6], [7].

Redwood et al. have estimated hair mercury concentrations expected to result from the recommended CDC childhood immunization schedule during the 1990s utilizing a one compartment pharmacokinetic model. The authors determined that modeled hair mercury concentrations in infants exposed to vicinal thimerosal were in excess of the Environmental Protection Agency (EPA)’s safety guidelines of 1 part-per-million (ppm) for up to the first 365 days, with several peak concentrations within this period. We have evaluated doses of mercury from thimerosal-containing childhood vaccines administered in accordance with the recommended CDC childhood immunization schedule during the 1990s in comparison the EPA and the Food and Drug Administration (FDA) safety guidelines for the oral ingestion of methylmercury, a similar compound to the ethylmercury [6]. We have reported that children received instantaneous doses of mercury from thimerosal-containing childhood vaccines that were many-fold in excess of the Federal Safety Guidelines [8], [9].

Epidemiological studies conducted in the United States have examined the relationship between thimerosal-containing childhood vaccines and neurodevelopmental disorders. It has been shown that children receiving thimerosal-containing childhood vaccines were two- to sixfold statistically significantly more likely to develop neurodevelopmental disorders, depending upon the specific conditions or symptoms examined, in comparison to children receiving thimerosal-free childhood vaccines [8], [9], [10], [11], [12].

Several recent studies have clinically evaluated the body-burden of heavy metals present in children with autistic disorders in comparison to normal children. Bradstreet et al. have evaluated urinary heavy metals following three days of oral chelation with meso-2,3-dimercaptosuccinic acid (DMSA) in children with autistic disorders in comparison to a control population [13]. It was determined that autistic children had statistically significantly approximately sixfold higher urinary mercury concentrations than matched normal controls, whereas other heavy metals were present in similar urinary concentrations following three days of oral chelation with DMSA. In addition, in this study, urinary mercury concentrations were compared following three days of oral chelation with DMSA in matched vaccinated and unvaccinated normal children. It was observed that there were similar concentrations of urinary mercury in both groups following DMSA treatment. Holmes et al. have evaluated mercury excretion rates in autistic and normal children by evaluating mercury levels in first baby haircuts [14]. It was observed that the mercury levels in the first baby haircuts of children were inversely related to the severity of the autistic disorders of the children (i.e. the more severely affected the children were – the less mercury levels were present in their first baby haircut). It has been hypothesized that these results are consistent with autistic children having biochemical differences than normal children, possible as a result of genetic polymorphisms, resulting in children with autistic disorders have an increased body-burden of mercury in comparison to normal children [13].

Boris et al. have recently conducted genomic studies of children with autistic disorders in comparison to normal control populations [15]. The authors have examined genes in pathways that are responsible for the synthesis of key biochemical molecules that are of functional relevance in the excretion and/or oxidative stress protection of mercury from the body. Specifically, the authors demonstrated that there was approximately a twofold statistically significant increase in the homozygous methylenetetrahydrofolate reductase (MTHFR) 677TT gene among children with autistic disorders in comparison to controls. This of particular relevance because MTHFR 677TT is one of the key genes in the biochemical pathway involved with the synthesis of glutathione, a key molecule in the body’s natural defenses against mercury, and those with the MTHFR 677 TT gene have been found to have an enzyme with only 32% of the activity of normal [16].

The understanding of the cause of the autism epidemic has allowed for the design of treatment modalities that address the mercury toxic component of these disorders. These therapies include methods to remove the mercury by such techniques as the use of chelating agents and by corrections in various biochemical pathways that lead to sulfhydryl-containing compounds that the body uses to rid itself of the mercury [17], [18]. Clearly much more clinical research in this area is needed. However, even at this early stage in the development of these types of therapies, it is clear that many if not most children only have a partial response or do not respond at all to such therapies. What is needed is another modality of clinical treatment to complement the work on eliminating mercury from these mercury toxic individuals.

We believe that the data from the autism epidemic itself suggests another method of attacking the problem in affected individuals. This potential therapeutic mode stems from the observation that autism affects males four to five times as often as females [1], [2]. In fact, closer observation indicates that the more severely affected the group of autistics studied the higher the male to female ratio. In very severe autistics males may outnumber females by 15 to 1 or even more [14].