I support the development of experimental treatments that are grounded on theory as long as practitioners and researchers do not jump the gun and present the treatment as a validated and effective method before there is compelling scientific evidence that the treatment works. For this reason, I’m always excited when I see well conducted research studies of experimental treatments, as these studies help clarify whether such experimental treatments are effective or not. This week I was particularly excited when I read one study examining the effectiveness of an alternative treatment for autism disorder. Specifically, a study conducted in Australia examined the effectiveness of an enzyme supplement for the treatment of children with an autism.

One theory about autism suggests that children with autism have abnormalities within their intestinal system.  This ‘leaky gut’ theory is based on the belief that the abdominal barrier in these children is defective and allows specific substances and toxins to leak into the child’s bloodstream. This has led to the development of a large industry that offers assistance to families in a variety of forms, from helping them create gluten free diets to providing supplements that help breakdown the proposed toxins. Some of these practices (i.e. gluten free) have been studied scientifically and unfortunately have been shown not to be as effective as their proponents claim. Other practices, such as enzyme supplementation, simply have not been properly examined.

The study examined the effects of Peptizyde, a dietary supplement, on the core symptoms of autism among 43 properly diagnosed children. This study was simple and elegant, and used a double blind randomized placebo controlled cross over methodology. In brief, this is how it worked: about 40 kids with autism were randomly assigned to either receive the enzyme supplement for 3 months or receive a placebo for 3 months. After the 3 months, the groups switched so that those receiving the placebo would now receive the supplement and those first receiving the supplement would now receive the placebo. The parents, teachers, and most of the study staff did not know who was receiving the placebo and who was receiving the supplement. Under this method all children received both the treatment and the placebo in 2 controlled sequences.

The authors then compared parental and teacher reports of symptoms during the time the children were taking the supplement as compared to the time the children were taking the placebo (Remember that the parents didn’t know when their kids were taking the real supplement). If the supplement has an effect on autism symptoms or functioning, it is sensible to expect that parents would correctly identify changes when their children were taking the supplement but not when the children were taking the placebo.

The results:

No significant differences between the placebo and the supplement condition were noted on:

· Core symptoms as reported by parents

· Gastroinstestinal Symptoms

· Sleep Quality

· Social Engagement as reported by the therapist

· Vocabulary

· Sentence length

The only statistically significant effect was an increase in food variety during the supplement condition. That is, during the time the children were taking the supplement their parents rated them as having statistically significantly more food variety than during the time they were taking the placebo. However, the authors did not believe that this statistical finding was clinically significant because their mean scores of the two groups, 4.06 (placebo) and 4.42 (supplement), was small and clustered around the score 4, which means “no change”. I’m not sure I agree with that last conclusion because determining “clinical significance” is a complex process that is based on whether the difference in scores translate to meaningful differences in the day to day life of these children. In this case for example, clinical significance would mean that the difference between such scores, even if small, results in real changes in the child’s diet, such as wanting to eat 3 more variety of vegetables, etc. That question of ‘clinical significance’ can not be easily answered by simply examining the numeric difference of the scores and their location in the scale (near the ‘no change’ mark).

So unfortunately this study failed to provide evidence that enzyme supplementation is effective in the treatment of children with autism. I must mention however, that the study was conducted with a very small sample (less than 20 participants per group by the end of the study) which certainly impacted the researchers’ ability to find statistically significant differences between the groups. It would be reasonable for someone to argue that a larger study should be conducted before we can form a final conclusion regarding the effectiveness of this experimental intervention.

The reference:
Munasinghe, S., Oliff, C., Finn, J., & Wray, J. (2010). Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-010-0974-2

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10 Responses to Enzyme supplements for autism. Do they work?

  1. Liz Ditz says:

    There’s an article up today by Peter Lipson, M.D., on another of digestive enzymes in the treatment of autism


    ….The study is designed to evaluate the affect of “CM-AT”, made by Curemark, LLC, on the symptoms of autism in children. CM-AT is an enzyme with a proprietary delivery system that is supposed to help digest proteins….

    There are a number of things I find disturbing about this study. While it appears to be well-run, it fails to conform to an important scientific and ethical standard: plausibility….

    Fallon and Curemark have not convinced me that there is any science that would justify their study. It’s certainly reasonable to take some risks based on sound science, but in this case, all that underlies this study is a handful of very questionable studies. Citing literature to justify your research is not just some bureaucratic hurdle to leap; it is fundamental to the ethical design of clinical trials. There is no reason to expect that delivering an oral protease to children with autism should improve symptoms of autism. There is no putative mechanism by which this should work, ….

  2. DSC says:

    Did they test Peptizide for diarrhea? We couldn’t get our son potty trained until we put him on GFCF diet, and 10 days later he was potty trained. He has had no diarrhea since as long as he is either on enzymes or GFCF. As far as behaviour, very little difference, but no diarrhea is huge!

  3. Neuroskeptic says:

    A disappointing result, but it’s good to see some high quality (if small) studies being done in this area.

  4. MJ says:


    The drug you are talking (CM-AT) about is already in Phase III trials with the FDA. That presumably means that it has been shown to be at least partially effective in earlier phases. I can’t see a company going to the time and expense of putting a drug through the FDA trials if they didn’t have some reason or data to show that it can work.


    I know one of the trial sites is UPMC, which I believe you used to be affiliated with, Nestor.

  5. DSC says:

    There is hope that maybe, maybe treatment for a lot of autistic people may be nearer, if the news about RORA and BCL-2 is true.

  6. Val says:

    My seventeen yr old daughter started using probiotic… I slowly started her on lesser daily dose of digestive enzymes while beginning a candida overgrowth intervention, because I was more intent on help the probiotic might provide with regard to the kind of balance one needs between good vs bad bacteria (85/15).What I found out in the process was that the probiotic helped with chronic throat constriction, a problem that was not helped with antibiotic. Also while using the probiotic program (which involved basic components of probiotic, enzymes and colostrum) my daughter’s blood sugar stabilized and her calcium level normalized and she stopped an alarming weight gain trend. This trend towards doing physically better was well timed because she needs to stay on the medications that may have contributed to her weight gain, in order not to suffer from severe psychotic symptoms. I would have had to take her off the Lithium. Risperdal if she developed diabetes…which they were pretty sure she was developing. She is followed at Mayo. She continues to lose weight, instead of gaining. And she has actually been able to control impulses to over eat since starting the program for candida overgrowth intervention.

    Unfortunately I do not have a professional understanding of the ingredients involved in the program. I just know that my daughter experiences some healthful benefits that were not present before utilization of them.

  7. Virginia says:

    Well, doctor didn’t help us much so I looked towards alternative medicine (someone with proper medical knowledge but specialized in treating with natural things), I doubted her but felt that had no choice but to try it.

    Result after few months of continously taking digestive enzimes and antioxidants made from natural sources: my child had better concentration, started to grow again (she stopped growing completely for a year but doctor thought is ok. because my child was tall enough), of course, she eats much more of what she used to.

    I find sometimes doctors are negligent and dismissive. My little one still needs lots of support mainly to focus in a non-self chosen task but is definetely better. Funny, that one of the things she takes to boost her immunosystem have been taken in ancient times and had been rediscovered. Iam not saying it will work for everyone but is worth to make some research and try it.

    I would feel better, though, if someone is in charge of supervising that the contents of the bottles of alternative medicine contains exactly what they say even if they don’t garantee the effects.

  8. My son is 7 and is in the CM-AT trial at Ohio State University. The average unit of CM-AT for is age is 23 units, we tested his bowel movement and it has 7.3 units of the enzyme. I am hopeful that being in this study helps, but not optimistic

  9. Antony Clarkson says:

    I’m not against medical sciences, and I’m not against well designed and well controlled research. In fact, this latter is what I do for a living.

    What I found disturbing, if you like, in many medical practice, autism in particular, is that professionals are not open to potential, and are stuck with textbooks. The very truth about autism is that we don’t know very much about the true causes of it. Let’s be honest, biological systems break down to chemistry at the molecular level. Everything will eventually make sense when chemistry works out, be it autism or not. The problem we have with autism is that we don’t understand the chemistry behind autism yet, period! The current practice in autism diagnosis is helpful because it identifies issues among kids with a general but very broad spectrum of disorders, however, this practice doesn’t have a chemistry basis! It is perhaps the best we can do with our very limited knowledge about this complex spectrum of disorder. Can anybody argue against that it might very well be that autism is in fact caused by different chemistry, but with rather similar clinical manifestation? With this in mind, it comes with no surprise that any medical studies (I’m talking about treatment with drugs), be it controlled or not, will give ambiguous results – because we don’t know the chemistry behind autism!

    With that said, I’m not against the behavioral intervention for children on the spectrum, it’s how we train animals and it works for some. The professionals involved in this disorder, however, need to keep in mind that we DON’T know the chemistry behind autism. Enzyme supplements, despite unproven due to the very reason outlined above, are worth a trial, as long as they don’t cause irreversible side effects. From a chemistry point of view, if one has an unidentified enzyme deficiency, it makes sense that one will have a problem, nobody can augur against this. A kid on the spectrum could very likely have been suffering from such deficiency, we don’t know, nobody does yet. If enzyme supplement works for a given individual but not another, it is perfectly understandable – autism could have been caused by different chemistry!

    In saying all this, I hope that professionals don’t simply dismiss possibilities based on their training, which is again based on unknown as far as autism is concerned. Parents with children on the spectrum are desperate. I’m not a snake oil salesman, but as long the enzyme supplement is not causing irreversible damage, such a possibility shouldn’t be dismissed. Don’t get me wrong, I’m not an uneducated individual, I just felt that many professionals involved in autism are too quick to act against things that we simply don’t know much about. My 15 years’ post-secondary training and 10 years’ practice in natural science tell me that I’m not going to jump to dismiss things for which we don’t know much about.

    I wish all kids on the spectrum and their parents all the best, as myself is one of you!

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