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NEUROENDOCRINOLOGY LETTERS
including Psychoneuroimmunology, Neuro
psychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology
ISSN 0172–780X

NEL Vol.23 No.4, August 2002

ORIGINAL ARTICLE

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2002; 23:303308
pii: NEL230402A02
PMID: 12195231


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Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: A pilot study
Derrick Lonsdale 1, Raymond J. Shamberger 2 & Tapan Audhya 3

1. Preventive Medicine Group, Westlake OH, USA.
2. Director, King James Medical Laboratory, Inc., 24700 Center Ridge Rd. Westlake, OH 44145, USA.
3. Vitamin Diagnostics, Inc, Rt 35 & Industrial Drive, Cliffwood Bch, NJ 07735, USA.

Key words:
Autism; thiamine tetrahydrofurfuryl disulfide; urinary arsenic; sulfur metabolism

Submitted: Febrary 17, 2002
Accepted: May 24, 2002

ABSTRACT

OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were investigated.

SUBJECTS AND METHODS: Ten children were studied. Diagnosis was confirmed through the use of form E2, a computer assessed symptom score. For practical reasons, TTFD was administered twice daily for two months in the form of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses were determined through the use of the computer assessed Autism Treatment Evaluation Checklist (ATEC) forms *. The erythrocyte transketolase (TKA) and thiamine pyrophosphate effect (TPPE), were measured at outset and on completion of the study to document intracellular thiamine deficiency. Urines from patients were examined at outset, after 30 days and after 60 days of treatment and the concentrations of SH-reactive metals, total protein, sulfate, sulfite, thiosulfate and thiocyanate were determined. The concentrations of metals in hair were also determined.

RESULTS: At the beginning of the study thiamine deficiency was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine samples containing arsenic in greater concentration than healthy controls. Traces of mercury were seen in urines from all of these autistic children. Following administration of TTFD an increase in cadmium was seen in 2 children and in lead in one child. Nickel was increased in the urine of one patient during treatment. Sulfur metabolites in urine did not differ from those measured in healthy children.

CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically. We obtained evidence of an association of this increasingly occurring disease with presence of urinary SH-reactive metals, arsenic in particular.

 

ABBREVIATIONS:

TTFD Thiamine tetrahydrofurfuryl disulfide
TKA Erythrocyte transketolase
TPPE Thiamine pyrophosphate effect on TKA
ATEC Autism Treatment Evaluation Checklist
Delta ATEC Final ATEC score subtracted from baseline ATEC

Introduction

The hypothesis that TTFD might have a beneficial effect on autistic spectrum disease was suggested from studies by Waring and associates who reported sulfur depletion in the plasma [1] of these children and abnormal concentrations of sulfur in their urine [2]. One of the urinary abnormalities was a decrease in the concentration of thiocyanate and these authors hypothesized that this might be due to decreased activity in the enzyme rhodanese that converts toxic cyanide ions to non-toxic thiocyanate. Japanese investigators [3] had previously shown that thiamine disulfides partially protected pretreated mice from cyanide poisoning by increasing the activity of rhodanese. In addition, it was hypothesized that TTFD would act as a donor of sulfate since sulfur depletion had been observed in autistic children [1].
Although TTFD is usually given by mouth in capsules, autistic children are notorious for the difficulties involved with oral administration. When we attempted to administer the powdered contents of a capsule to any children of this age, the excessively unpalatable taste caused instant rejection. It was then decided to provide the TTFD in the form of rectal suppositories.
Since there is no reliable biologic test to indicate treatment effect in autistic patients, the form E2 was used to confirm the diagnosis and the ATEC forms used to measure the response to treatment.

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