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Trial sprouts doubts about broccoli extract for autism

by  /  10 November 2014

Broccoli boost: A compound in broccoli sprouts may counteract oxidative stress and inflammation — molecular processes implicated in autism — but some experts are skeptical.

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The newest entrant in the list of unusual autism therapies is a chemical mixture extracted from broccoli sprouts. The extract seems to improve social skills in young men with autism, a small pilot study has found1. But scientists caution that the study is too small to say whether the findings are reliable.

The extract is rich in sulforaphane, a compound that guards against oxidative stress, inflammation and DNA damage2. All of these are implicated in autism.

Sulforaphane also induces the ‘heat-shock response,’ a cellular defense mechanism against temperature extremes3. Some children with autism show behavioral improvements during bouts of fever, which trigger the heat-shock response4.

This led Andrew Zimmerman, clinical professor of pediatrics at the University of Massachusetts Medical School, to investigate whether sulforaphane eases some symptoms of autism.

Zimmerman teamed up with Paul Talalay, who discovered sulforaphane 25 years ago and founded Brassica Protection Products, a Baltimore-based company that sells products containing broccoli sprout extract.

Talalay acknowledges that sulforaphane is just one component of the extract, which contains a “huge” number of other compounds.

The team enrolled 40 males with autism aged 13 to 27 years, 26 of whom received a daily dose of the extract for 18 weeks. The remaining participants received a placebo pill. The trial was double-blind, meaning that neither the participants and their caregivers nor the researchers knew who was receiving the extract.

The people who got the extract showed improvements in various behaviors, such as interacting with others and communicating verbally, as reported by parents and clinicians. These improvements disappeared four weeks after the treatment ended. Those in the placebo group did not show any significant improvements. The results were published 13 October in the Proceedings of the National Academy of Sciences.

The findings hint at potential therapies for autism, but the researchers caution against drawing big conclusions. “I really want to stress to people that this study needs to be replicated to demonstrate that it’s valid,” Zimmerman says.

Cruciferous caution:

Some independent researchers have similar reservations, noting that the control group showed an unusually small placebo response.

“You always see a 20 to 25 percent improvement in placebo,” says John Jay Gargus, director of the Center for Autism Research and Translation at the University of California, Irvine. For example, the placebo effect plagued trials of the gut hormone secretin and antidepressants for autism.

“It’s stunning that they’ve managed to have found a placebo that doesn’t give the placebo effect that we see in every other neuropsychiatric drug trial,” Gargus says.

“I really want to stress to people that this study needs to be replicated to demonstrate that it’s valid.”

Still, the study opens new doors in the search for autism’s molecular origins, some say.

“This is an excellent exploratory study,” says Judith Miles, emerita professor of child health at the University of Missouri, who was not involved in the study. “It exemplifies a shift to studies that identify physiological or cellular mechanisms that produce autism symptoms.”

The researchers used two parent questionnaires to assess behavior: the Aberrant Behavior Checklist, which measures irritability, lethargy, stereotypic behavior and hyperactivity, and the Social Responsiveness Scale, which measures social abilities. They also used the Clinical Global Impressions Scale to measure autism severity.

They took baseline measurements and repeated the tests 4, 10 and 18 weeks into the trial and 4 weeks after the trial ended. By 18 weeks, nearly half of the study participants receiving broccoli sprout extract showed significant improvements in social functioning and verbal communication, as measured by the Clinical Global Impressions Scale. These are two core features of autism that are not treated by existing medications for the disorder.

“It doesn’t change the diagnosis,” Zimmerman says. “But it changes a lot of the characteristics.”

Roughly 60 percent of participants in the treatment group showed improvements on the Aberrant Behavior Checklist, compared with 20 percent of those in the placebo group. About 35 percent of those in the treatment group showed improvements on the Social Responsiveness Scale, compared with none in the placebo group.

Scores on all of the tests returned to near baseline levels four weeks after the trial ended.

None of the study participants experienced adverse side effects, although those in the treatment group gained an average of 4 pounds during the 18-week trial. Two participants in the treatment group experienced seizures during or shortly after the trial. However, both had a history of seizures that they did not disclose to the researchers before the study began.

“I think that the results are really quite intriguing,” says Jeremy Veenstra-VanderWeele, associate professor of psychiatry at Columbia University in New York, who was not involved in the study. “I love the idea of a potential treatment that causes minimal side effects.”

However, he and others say they are skeptical about whether the results will hold up in other trials and in the broader population of people with autism. One concern is that 80 percent of the participants have a history of behavioral improvements during bouts of fever. Surveys estimate that roughly 30 percent of people with autism show this ‘fever effect.’ “That makes this population a little different than the typical population,” Veenstra-VanderWeele says.

What’s more, the improvement seen with the extract is comparable to that seen with placebo in a previous trial that involved hundreds of people with autism5. The benefit is probably too low to hold up in a bigger trial, says Veenstra-VanderWeele.

Still, the study findings are intriguing and warrant follow-up in a larger population, he says. “If this replicates, it’s really exciting, in part because it seems very unlikely to do harm.”

References:

1. Singh K. et al. Proc. Natl. Acad. Sci. USA 111, 15550-15555 (2014) PubMed

2. Zhang Y. et al. Proc. Natl. Acad. Sci. USA 91, 3147-3150 (1994) PubMed

3. Gan N. et al. J. Biol. Chem. 285, 35528-35536 (2010) PubMed

4. Singh I.S. and J.D. Hasday Int. J. Hyperthermia 29, 423-435 (2013) PubMed

5. Marcus R.N. et al. J. Am. Acad. Child. Adolesc. Psychiatry 48, 1110-1119 (2009) PubMed


33 responses to “Trial sprouts doubts about broccoli extract for autism”

  1. auitsm parent says:

    naysaying and negative spin is not what we need. if Sulforaphane even helps a subset of kids on the spectrum then it is worthy of a larger study

    so thumbs down on the title of this article. thumbs up on the comments.

    “This is an excellent exploratory study,” says Judith Miles, emerita professor of child health at the University of Missouri, who was not involved in the study. “It exemplifies a shift to studies that identify physiological or cellular mechanisms that produce autism symptoms.”

    I think that the results are really quite intriguing,” says Jeremy Veenstra-VanderWeele, associate professor of psychiatry at Columbia University in New York, who was not involved in the study. “I love the idea of a potential treatment that causes minimal side effects.”

    Still, the study findings are intriguing and warrant follow-up in a larger population, he says. “If this replicates, it’s really exciting, in part because it seems very unlikely to do harm.”

  2. Seth Bittker says:

    Dr. Gargus makes an interesting observation on the absence of a placebo effect in this trial. The placebo was cellulose. Depending upon how much was consumed, it could have marginal effects on digestion. Cellulose tends to sequester minerals, and this in itself might have decreased the mineral absorption of some of those in the placebo group. As many with ASD have mineral deficiencies this could have had a negative effect thereby contributing to the absence of a placebo effect.
    I think the improvement the authors found was real though and likely due to the sulfur content of sulforaphane. If you look at autism research historically there have been some studies as well as anecdotal evidence of improvement in symptoms when those with autism are given sulfur containing compounds. For example, in 2012 Hardan et al. found in a randomized trial that NAC resulted in substantial improvements in irritability: http://www.ncbi.nlm.nih.gov/pubmed/22342106. Pangborn and Baker in their book on autism treatment also mentioned that taurine resulted in significant improvement in some with autism. In addition Adams found that supplementation with DMSA resulted in substantial improvements in behavior: http://www.biomedcentral.com/1472-6904/9/17. Adams interest was in the effect of DMSA on chelating toxic metals but DMSA like taurine and NAC are sulfur containing compounds.
    Why are sulfur containing compounds helpful in many with autism? There is significant evidence of a sulfur deficit in most with autism and high levels are excreted in the urine. See Waring’s work for this: http://informahealthcare.com/doi/abs/10.1080/13590840050000861. Another connection is that in autism we frequently see low levels of metallothionines, which are sulfur containing proteins. See Walsh’s work for this: http://www.biobalance.org.au/articles/17. So it makes sense that sulforaphane as well as other sulfur containing compounds would be helpful to many with autism.
    Another interesting possibility is that the sulforophane is acting as an anti toxicant. Evidently sulforophane can mitigate effects of toxicants from pollution: http://carcin.oxfordjournals.org/content/33/1/101.full. Other sulfur containing compounds are effective in chelating toxic metals. DMSA and ALA come to mind.
    In my view the issue with most of these compounds is not whether they can improve symptoms over the short term but whether it is sustainable over the long term. For example the NAC trial cited above had very high levels of gastrointestinal symptoms in the treated group and exacerbation of gastrointestinal symptoms can have very negative effects on behavior of those with autism. I think what tends to happen when you give these sulfur compounds is that side effect from sulfur consuming bacteria often counteracts the positive effects. If the sulforaphane form of sulfur mitigates this issue, then I think it may be an advance. In addition Andrew Zimmerman and company should be commended for conducting this trial. We desperately need more trials of compounds like this to guage effectiveness in those affected by autism. Dr. Zimmerman thank you for your work!
    One more thought on this is that broccoli is not the only vegetable with promising sulfur containing compounds. Asparagus contains S-Methyl methanethiosulfinate which has significant antibacterial properties. Given the dysbiosis that is common in autism and the sulfur deficit that seems to characterize it, I would think a trial of this compound in autism may have interesting results.

  3. Gerry Fischbach says:

    The title of this article does a disservice to an interesting observation that deserves further study. One objection cited seems to be that the placebo effect was not large enough. That is not strong negative evidence. Another concern raised was that the most profound effects were in individuals that exhibited a positive response (diminished autistic behaviors) in individuals that also exhibited a positive response to fever. I am a skeptic by nature, but I find that observation interesting and promising rather than a n reason for concern. We must stratify the autism phenotype by whatever criteria may provide clues.

  4. ASD Dad says:

    “That makes this population a little different than the typical population,” Veenstra-VanderWeele says.

    I don’t know why there’s a slow uptake that autism is not just one pathway but has a differing etiopathology, for different children and adults, and thus differing subgroups. But perhaps it is because of siloing of knowledge.

    We have to start an intelligent dialogue instead of fruitless criticism of what has been some really quite astounding work made in beginning to tease open real treatment and care options.

    The take home message is there is no one treatment for Autism or co-occurring medical and psychological issues you need a Swiss Army knife of options.

    • Katie says:

      Agree. Where has he been? The massive amount of research by Rossingnol, Frye and Jill James has long demonstrated that these are COMMON problems among ASD population.

  5. Shree says:

    Though with less reason of analysis, the observation seems to be promising.Still more observation and analysis is needed.

  6. Katie Wright says:

    This is really terrific and a great example of the kind of out of the box thinking we need more of in autism treatment research. Thank you Dr. Zimmerman. All too often autism treatment research is based on only early diagnosis, anti-psyhoctics or treatment tailored to rare chromosomal abnormalities, which do not translate to the other 98% of people with autism.

    Finally here we have a biomedical treatment aimed to combat the VERY common problem of oxidative stress and inflammation. My son and countless others with autism (especially regressive autism) have horrendous ox stress problems. Finally someone is paying attention to this problem. Autism is not only behavioral! Far from it. The reason that even high quality early intervention really works for only 20% of kids is because all the autism issues below the neck (inflammation, GI problems, autoimmune dysfunction) remain unaddressed.

  7. Sam says:

    After all autism could be much simpler than all this genetic hype behind it:

    We need researchers who have closely looked at autism from individual basis and not people working closed up in laboratories…lookin at vials and makeing the shots.

    What I love wbout this research is that expression which says a lot about autism and THE RESEARCH TODAY: The diagnosis of the kids stayed the same but the charcteristics softened up. How can that be if the genetics are behind autism, how can it be brain connection, if theses characteristic can be modified. It just goes to show you two understanding of autism…one by mainstream doctors and the other alternative …with different views of which one is closer to reality than other

  8. Rene Anand says:

    Some subtypes of autism may be a protein folding disorders.

    Here is my thinking and it comes from personal experience. I am a non-obese type II diabetic. In an effort to find natural remedies for my diabetes I discovered by accident that broccoli soup would significantly drop my fasting sugar levels! As a scientist I followed the trail and discovered that type II diabetes is also considered a protein folding disorder, and the culprit is misfolded and aggregated amylin in beta pancreatic insulin producing cells.
    http://www.nature.com/nrm/journal/v15/n6/full/nrm3810.html

    Ever since, I have been taking broccoli capsules with great results.

    So its is likely that sulphoraphanes in broccoli through their known “heat shock” effect, may be enhancing proper folding of proteins by augmenting the ER stress responses.

    Note that many of the proteins implicated in autism (neuroligin, neurexin, others) are “synaptic” membrane proteins and as such are processed by the ER (as is amylin because it is a secreted protein).

    This article suggests that autistic individuals have comorbid diabetes (reminds me of a similar issue with schizophrenia which has overlapping risk genes with autism)
    http://journal.frontiersin.org/Journal/10.3389/fendo.2011.00054/full

    Hence a possibility to consider is that many subtypes of autism may more broadly result from an ER processing defect that is a common factor and especially in those with autism responsive to sulphoraphanes (and fevers).

    Just thought I would share this possibility and its great that broccoli sprouts may have given us a lead into the kind of drugs that could effectively treat autism. I agree with Dr. Fischbach, this is a great study!

    Rene Anand
    The Ohio State University

    • RE says:

      We don’t need a new drug. Just use the extract. I don’t want to get into the drug subject…It’s all for $$$$.
      Thanks for the info though…The extract seems to be working well for my son, very impressive change in him. And I am pre-diabetic so I’ll see how it works for me too. It sounds logical what you are saying because I have also been trying things that supposedly help autism for my son. I’ve been noticing that a few things they say are good for autism, they also say is good for diabetes….something to think about.

  9. MMichael says:

    My son is 19 and was diagnosed at age 2. From the very first time he had a fever to today my wife and I have maintained that his behavior improves. Not once every other fever, or just a few times, but EVERY time. We have asked our physicians what the body produces when we are sick with a fever with no reply. Stay with it Dr Z

  10. John Schaut says:

    I agree with comments criticizing the article title and lumping it in with other past approaches that were found ineffective. Dr Zimmerman presneted that study in a balanced,informative and ethical manner true to his role as a scientist and practitioner who has treated many children with autism.

  11. VICKY says:

    Hi I have a 4 year old son who is autistic i have been putting broccoli in my stews which he use to love and eat every day. there is great improvement from him in the last 10 months but as a mum after the happy phase i always want more and look for remedies. we live in South Africa where the facilities are not as available as they are in the states but i still research. when i came across this article which my ABA therapist forwarded I realized his broccoli intake has dropped. Can i give him broccoli supplements as we get them at the local pharmacy or should i give him the fresh cooked version?

    • Seth Bittker says:

      I am a father of a boy with ASD as well. You can do either. If you go the supplement route, be careful and try an extremely low dose. In the trial two participants had seizures. There is some question as to whether these were coincidental or not. My personal view is that they were related to the sulforophane. With broccoli that is not concentrated it seems this is much lower risk.

      You mention in South Africa the facilities for autism treatment are not as available. I live here in the US and with respect to autism treatment beyond ABA I don’t think you are missing much. Unfortunately very few physicians have an understanding of this disease and often their suggested treatments are detrimental.

      • Megan says:

        If you look at the study, the kids that had seizures during the study actually had a history of seizures, so I don’t think you can blame it that on the broccoli. And, just giving the kid broccoli isn’t going to get him anywhere near the levels he needs to be at. In fact, most broccoli supplements on the market today lack the key components to replicate this study. By all means, feed him more broccoli, but don’t expect anything but a healthier gi tract from it.

  12. kimr says:

    I bought enduracell’s powder which has the myrosinase enzyme that most broccoli supplements lack (they claim 1000mG of powder yields 1.2% or 12 mg of sulforaphane). My son has been on it for almost 4 weeks now- I’m seeing some improvement- but I’ve no idea if it’s due to the supplement.

  13. ASD Mom says:

    I have a 4 yr old son who is autistic. I am interested in trying the broccoli supplement. Did any of you consult with your doctor before trying the supplements.

  14. RE says:

    I’ve been giving my 12 year old son the extract twice a day now for a few weeks and just started noticing a very big difference in him. He’s so much calmer, not as much scripting, More eye contact, he seems to sleep better, goes to sleep right away. He seems so much more mature now. This is the biggest difference I’ve seen so far, compared to all the other things I’ve tried over the years. Of course he has been on a very good diet most of his life, low sugar, no gluten, recently started him on sprouted grains and organ meats, etc this last year.

  15. JD says:

    I am giving enduracell once a day since December 3, 2014 to my 7 yrs old ASD son. I notice more language, More NT moments, tells me if he doesn’t want things, answer the phone for the first time ever. use new words and longer sentences. no longer robotic. expressive language. Some kids do not do well at a high dose of the enduracell so you can start with a sprinkle and go from there. Some use swanson brand which is a bit weaker.

  16. BRF says:

    Has anyone attempted to contact (or gotten the assistance of a health provider) Brassica Protection Products which is the company that produced the sulforaphane supplements used in the study? I am interested in starting a trial but want to match the study as much as possible.

  17. TD says:

    What kind of dosage are you guys giving?

  18. FTS says:

    Wow, thank you so much to all the knowledgeable folks who have commented here, especially Seth and Rene for taking the time to be so detailed. I really appreciate it. My integrated medicine GP prescribed broccoli extract for me to replace consumption of soy milk, which I found regulated my extreme moods/PMS. Ran across this great study on the NIH website and then this article. Family and friends have suggested that I may be on the autism spectrum; I get by. Will try the extract.

  19. SMS says:

    5 year old twin boys with autism, what brand of broccoli extract has worked for your kids and how much of it a day. My boys weigh 40 lbs.

  20. gregboustead says:

    Please note:

    SFARI.org is not a resource for medical information. We cover a range of autism science, including basic research as well as translational and treatment studies. However, the vast majority of potential treatments we describe are a long way from being comprehensively tested to ensure effectiveness, suitability, or safety. And although we welcome in the comments a diversity of perspectives on the research, as part of the scientific discourse, we discourage and will actively moderate any treatment recommendations based on experimental data.

    Thank you for helping keep comments on-topic and appropriate, per our community guidelines:
    http://sfari.org/terms-and-conditions#standardsofbehavior

    Greg Boustead
    SFARI.org, community manager

  21. Paulette says:

    I have been using this with my son for 3 months now. The results have been slightly astounding. No side affects, huge progress, small miracle for us. No extracts, straight broccoli sprouts. The “study is being replicated” in my home, successfully I might add. I use Enduracell.

  22. kimr says:

    After 5 months on Enduracell (1/2 tsp daily), I had to stop for over a week because my son had stomach flu. I finally decided to see if it was really helping him- so I’ve stopped now for a full month. Unfortunately, I don’t think it really had any significant impact, so I’m stopping it for good. It’s a big disappointment, but there was only a ~40% chance it would help based on the study.

    • Christine Houghton says:

      Hello Kimr. We are the manufacturers of EnduraCell 100% whole broccoli sprout powder and capsules. In some ASD patients, it is not uncommon for there to be significant gut dysbiosis (overgrowth of undesirable microbial species)and when starting EnduraCell, there can be a rapid die-off of these organisms, leading to gastric discomfort. We suggest stopping the product completely until the symptoms clear and then starting again at a lower dose – probably as much as will fit onto the tip of sharp knife blade and then increasing over the next 2 weeks or so; this is usually very effective. You dont mention the age or size of your child because the dose is dependent on body size. I suspect that 1/2 teaspoon is not enough to activate the expression of the relevant genes.

      After the clinical trial was published, it led to a lot of confusion associated with the amount required; we produced a 4-page handout which attempted to translate the findings of the study into a practical guide for parents trying to help their children.

      • gregboustead says:

        A general reminder:

        Although this article discusses a commercially available plant compound, we don’t vouch for guidance or advice offered in the comments for any potential treatments that have yet to be fully tested and approved.

        SFARI.org is not a resource for medical information. We cover a range of autism science, including basic research as well as translational and treatment studies. However, the vast majority of potential treatments we describe are a long way from being comprehensively tested to ensure effectiveness, suitability, or safety. And although we welcome in the comments a diversity of perspectives on the research, as part of the scientific discourse, we discourage and will actively moderate any treatment recommendations based on experimental data.

        Thank you for helping keep comments on-topic and appropriate, per our community guidelines:
        http://sfari.org/terms-and-conditions#standardsofbehavior

        Greg Boustead
        SFARI.org, community manager

  23. LBS- Pittsburgh, PA says:

    My 23 year old son’s doctor told me to try this as my son’s behavior also improved with a fever. He gave me the article and told me which brand to purchase. The doses in the article are different than the doses available. Since I am not supposed to ask about dosing here, is there a website or newsgroup where people are discussing this therapy. Thanks

  24. Christine Houghton says:

    I think it’s important to note that many contributors refer to a broccoli sprout ‘extract’. The supplements marked as ‘extracts’ are in fact devoid of the myrosinase enzyme needed to produced the bioactive compound, sulforaphane. The broccoli sprout contains a precursor compound ‘glucoraphanin’ and an enzyme, ‘myrosinase’. Both are needed for sulforaphane to be produced. What the ‘extracts’ contain is just the precursor compound glucoraphanin and no enzyme. If you look carefully at the label, you will not see mention of the enzyme – this is the clue, even if it mentions ‘sulforaphane glucosinolate’ which is a marketing term, not a chemical term. Best to look for a 100% whole broccoli sprout product which has retained its myrosinase enzyme. I know this is very confusing when all you want to do is to help your child.

  25. steve hancock says:

    It’s 2018… What’s the latest with Sulforaphane and Autism?

  26. steve hancock says:

    Is Sulforaphane safer/healthier than OREOs or McD French Fries? I would guess , yes

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