Now, the history of medicine is littered with the dessicated corpses of treatments that had been vigorously promoted but failed to live up to their promise. Some of these now-dead treatments had long and full lives before they were brought down and others had only a short time on the stage. A key feature in the eventual downfall of most (if not all) of these ex-treatments is that they were "killed" by the scientific method.
"Balancing the humors" had a good long run as a medical therapy, first formulated by Hiipocrates, Plato and Aristotle in the 4th and 5th centuries BCE and lasting (in some form) until well into the 16th century CE. Fortunately, it is now dead - although it sometimes pops up in various "alternative" medicine explanations. It was killed by the growing understanding of how the body actually operated.
More recently, we have (through scientific investigation) found that homeopathy is just water (or lactose) and that acupuncture "works" no matter where you stick the needle. And on the way, we have learned that the bleeding, purging and blistering of "heroic medicine" also don't work (and more often kill or injure). We've also learned that electroshock is not a useful treatment for homosexuality (although it does help depression) and that treating alcoholism with morphine and opiate addiction with cocaine is - at best - a short-lived solution.
In short, although there have always been some practitioners who have clung to the old ways, modern medicine (i.e. 20th and 21st century medicine) has been fairly quick to drop therapies that either don't work or that have been superceded by better or safer treatments. The same cannot be said of "alternative" medicine, which - almost by definition - refuses to reject any therapy except (ironically) those used by "mainstream" medicine.
Back to autism therapies.
On the advice of a reader, I went to Dr. Bernard Rimland's "Autism Research Institute" (ARI) website and found the following therapies recommended for the treatment of autism:
DMG (dimethly glycine, Betaine) - Among the benefits claimed for DMG are:
"For over 20 years ARI has been hearing from parents who have tried DMG on their autistic children. In many cases remarkably good results have been seen, especially in enhancing speech."
"Many parents have reported that, within a few days of starting DMG, the child's behavior improved noticeably, better eye contact was seen, frustration tolerance increased, the child's speech improved, or more interest and ability in speaking was observed."
"In some cases, drug-resistant seizures have been stopped by DMG. (See New England Journal of Medicine, 10-21-82, pgs 1081-82)." [also see Epilepsia. 1989 Jan-Feb;30(1):90-3, which found no effect]
"Many studies have shown that DMG enhances the effectiveness of the immune system, improves the physical and athletic performance of humans and other animals (e.g. race horses) and has, all in all, a very wide range of beneficial effects." [no references given]
A quick stroll through MedLine revealed that a few clinical trials (as opposed to parental anecdotes) have been completed on DMG. Their results:
 A study of 37 autistic children 3 - 11 years of age -
"...the quantitative changes in the dimethylglycine behavioral assessments were not significantly different from what was observed among children who received placebo."Kern JK, Miller VS, Cauller PL, Kendall PR, Mehta PJ, Dodd M. Effectiveness of N,N-dimethyl-glycine in autism and pervasive developmental disorder. J Child Neurol. 2001 Mar;16(3):169-73.
 A pilot study of eight autistic people 4 -30 years old (small number, large age spread!) -
"Analysis of all three scales revealed no statistically significant differences, and parent reports were equally distributed."
Bolman WM, Richmond JA. A double-blind, placebo-controlled, crossover pilot trial of low dose dimethyl-glycine in patients with autistic disorder. J Autism Dev Disord. 1999 Jun;29. (3):191-4.
 A review of the performance-enhancing effects of DMG (NB - Pangamic acid is a combination of DMG and calcium gluconate):
"Multivariate analysis of variance (MANOVA) revealed no significant differences (P greater than 0.05) between groups after treatment. It was concluded that ingestion of pangamic acid does not produce significant changes in short-term maximal tread-mill performance."
Gray ME, Titlow LW. The effect of pangamic acid on maximal treadmill performance. Med Sci Sports Exerc. 1982;14(6):424-7.
 Finally, a claim that has been substantiated - in one study:
"A double-blind study in 20 human volunteers showed a fourfold increase in antibody response to pneumococcal vaccine in those receiving DMG orally as
compared with controls (P less than 0.01)."
"The in vitro responses of lymphocytes from patients with diabetes and those with sickle cell disease to phytohemagglutinin, convanavalin A, and pokeweed mitogen were increased almost threefold after addition of DMA [sic]. These results suggest that DMG enhances both humoral and cell-mediated immune responses in humans."
Graber CD, Goust JM, Glassman AD, Kendall R, Loadholt CB. Immunomodulating properties of dimethyl-glycine in humans. J Infect Dis. 1981 Jan;143(1):101-5.
This sounds like a great deal until one considers the many people claiming an autoimmune component to autism. Would increasing the immune response be such a good idea, if this is the case?
Vitamin B6 and Magnesium
This one goes 'way back - back to when Dr. Rimland was a contributor to Linus Pauling's book "Orthomolecular Psychiatry: Treatment of Schizophrenia". On the ARI website, the following claims are made about the therapy:
"All 18 studies known to me in which vitamin B6 has been evaluated as a treatment for autistic children have provided positive results. This is a rather remarkable record, since the many drugs that have been evaluated as treatments for autism have produced very inconsistent results." [this study must be the 19th study on B6 and magnesium]
A number of anecdotes are also relayed, although the results of Dr. Rimland's largest (and earliest that I can find) B6 and magnesium study are only briefly mentioned in passing. This study, which apparently involved over 200 autistic children, was mentioned in the book "Orthomolecular Psychiatry: Treatment of Schizophrenia" (Hawkins and Pauling, eds). Although I have not yet received a copy of the book (through the miracle of interlibrary loan), a previous reading of the chapter by Dr. Rimland disclosed to me a revealing aspect of the study.
Some of the children in this study were institutionalized and Dr. Rimland found that these children had a much lower improvement rate. Although he did not test for compliance (by testing the urine, as he did in later studies), Dr. Rimland's assumption was that the staff of the institutions were not being compliant because they didn't believe that the therapy would be effective.
Interestingly, my (extremely limited) experience with long-term care facilities (as institutions are now called) is that once a medication order is written, it will be carried out religiously - sometimes in the face of ample reason to stop giving it. I find it odd, therefore, to blame institutional non-compliance for the poor results in these children. An alternative hypothesis is that the staff of the institutions did not have a "stake" in the outcome and so were more objective.
The secretin story is pretty much a classic for alternative medicine. The story begins in April 1996, when an autistic child underwent an endoscopy and received - as is routine - an injection of secretin to confirm the continuity of the pancreatic duct (it causes pancreatic juice to squirt out of the duct, which can easily be seen during endoscopy). Following this procedure, he demonstrated "remarkable" improvement in language and social skills. His mother, Victoria Beck, determined that the only medication he had received that could be responsible for this improvement was the secretin.
Ms. Beck not only wrote a book (Confronting Autism) on the subject of secretin and autism, she (and Dr. Rimland) patented the treatment. This patent was subsequently sold to the Repligen corporation, which proceeded to make secretin (human secretin, using recombinant technology) and test it on autistic children.
Interestingly, part of the sale included Repligen stock - Ms. Beck reportedly donated her portion to the Autism Research Institute (run by Dr. Rimland out of his home), as did Dr. Rimland. So the Autism Research Institute has a financial interest in making secretin "work" for autism, since that product promised to be Repligen's biggest seller.
This story "broke" in early October 1998, after appearances by Ms. Beck on "Dateline" and "Good Morning America". The demand was so great that the one company making secretin - Ferring - was sold out by October 16th. In late 1998, Dr. Rimland recorded in the ARI Newsletter that:
"The good news is that confirmatory evidence of the power of secretin keeps coming. A national newspaper told of Florida pediatrician Jeff Bradstreet's own four-year-old son, Matthew, shocking his parents by holding his first normal conversation with them the day after his first secretin infusion. And Virginia pediatrician Lawrence Leichtman told me of his 'miracle case:' a five-year-old who had previously said only two words amazed all in the office by saying, 15 minutes after his infusion, 'I am hungry. I want to eat.' Most cases are much less dramatic, but the autism world is excited, and for good reason."
Many of the initial clinical studies on secretin were promising, but only small numbers of patients were treated in these studies. The clouds began to gather when larger, more rigorous studies were done, including Repligen's own studies to earn an FDA-approved indication for autism.
One of the first "bad news" studies was the following:
Lack of Benefit of a Single Dose of Synthetic Human Secretin in the Treatment of Autism and Pervasive Developmental Disorder. Adrian D. Sandler, M.D., Kelly A. Sutton, M.A., Jeffrey DeWeese, B.S., Mary Alice Girardi, P.N.P., Victoria Sheppard, M.D., and James W. Bodfish, Ph.D. N Engl J Med. 1999 Dec 9;341 (24):1801-6.
This study looked at 60 autistic children and found:
"As compared with placebo, secretin treatment was not associated with significant improvements in any of the outcome measures. "
"After they were told the results, 69 percent of the parents of the children in this study said they remained interested in secretin as a treatment for their children. "
The last quote forshadowed the events to come.
Dr. Rimland responded quickly to this first setback with an article in the ARI Newsletter titled: "Secretin: positive, negative reports in the 'top of the first inning' ". But the bad news just kept coming.
[April 200] - "Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children, overall it produced few clinically meaningful changes when compared to children given placebo injections."
Secretin and autism: a two-part clinical investigation.Chez MG, Buchanan CP, Bagan BT, Hammer MS, McCarthy KS, Ovrutskaya I, Nowinski CV, Cohen ZS. J Autism Dev Disord. 2000 Apr;30(2):87-94
[May 2001] - "A single dose of intravenous secretin does not appear to have significant effects on either parents' perception of autistic behaviors or language skills at 6 weeks after injection. Transient, marginally significant improvements in autistic behaviors may occur in some children."
A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism. Coniglio SJ, Lewis JD, Lang C, Burns TG, Subhani-Siddique R, Weintraub A, Schub H, Holden EW. J Pediatr. 2001 May;138(5):649-55
[May 2001] - "No evidence is provided for the efficacy of repeated doses of porcine secretin in the treatment of children with autism."
Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo-controlled trial. Roberts W, Weaver L, Brian J, Bryson S, Emelianova S, Griffiths AM, MacKinnon B, Yim C, Wolpin J, Koren G. Pediatrics. 2001 May;107(5):E71
[November 2001] - "There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial."
Multisite, double-blind, placebo-controlled trial of porcine secretin in autism. Owley T, McMahon W, Cook EH, Laulhere T, South M, Mays LZ, Shernoff ES, Lainhart J, Modahl CB, Corsello C, Ozonoff S, Risi S, Lord C, Leventhal BL, Filipek PA. J Am Acad Child Adolesc Psychiatry. 2001 Nov;40(11):1293-9.
[November 2002] - "No evidence that either biologic or synthetic secretin provided amelioration of symptoms beyond placebo was observed. This held true when children with and without gastrointestinal problems were examined separately."
A randomized, double-blind, placebo-controlled trial of porcine versus synthetic secretin for reducing symptoms of autism. Unis AS, Munson JA, Rogers SJ, Goldson E, Osterling J, Gabriels R, Abbott RD, Dawson G. J Am Acad Child Adolesc Psychiatry. 2002 Nov;41(11):1315-21
[December 2002] - "The results of this study do not support secretin as a treatment for autism."
Lack of benefit of intravenous synthetic human secretin in the treatment of autism. Molloy CA, Manning-Courtney P, Swayne S, Bean J, Brown JM, Murray DS, Kinsman AM, Brasington M, Ulrich CD 2nd. J Autism Dev Disord. 2002 Dec;32(6):545-51.
[August 2003] - "In a controlled setting, parents of young children with autism are unable to distinguish the short term behavioural effects of secretin from placebo."
Children with autistic spectrum disorders. II: parents are unable to distinguish secretin from placebo under double-blind conditions. Coplan J, Souders MC, Mulberg AE, Belchic JK, Wray J, Jawad AF, Gallagher PR, Mitchell R, Gerdes M, Levy SE. Arch Dis Child. 2003 Aug;88(8):737-9.
In 2004, the Repligen Corporation - partway through a Phase III study of secretin for autism - threw in the towel because the initial results were unfavorable. This should have been the end of it...but it wasn't. For full details, read Dr. Rimland's impassioned letter to the CEO of Repligen. The Autism Reseach Institute still claims that secretin is an effective treamtment for autism.
And don't miss Dr. Rimland's complaints about the double-blind, placebo-controlled method.
After reading all this, I was left to wonder how parents can continue to listen to the recommendation of people like this (and ARI is far more scientific and reasoned than some of the others). Of course, much of the reason is that the parents don't know the history of some of these treatments - they only know what the organizations like DAN! (tied with ARI) tell them unless people like me can get to them.
The practitioners who follow these therapies are the ones I have the most concern for (and about). The parents have only been exposed to this for a relatively short time, while the practitioners must have seen some of these therapies rise and fall. They must either have a severe memory disorder or be able to tolerate near-fatal amounts of cognitive dissonance. Either way, I think that there is a problem.