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Thursday, 13 August 2015

Sulforaphane Research in Japan – Cognitive Deficits and Schizophrenia






I recently received some papers about Sulforaphane from a reader of this blog and also comments from people with schizophrenia looking for therapies

Sulforaphane is already a valued part of my autism Polypill for Monty, aged 12 with ASD.  Just google "Sulforaphane Epiphany", or use the site index tab on this blog.

Sulforaphane has been patented for various purposes by John Hopkins, however even after twenty years they have not brought to market a standardized product.  The Sulforaphane (SFN) used in their research is made in the lab and then has to be kept deep frozen.

Sulforaphane is not a stable substance and so you are wasting your money buying most supplements.  Even most types of broccoli powder, which should be a precursor to Sulforaphane (SFN), were shown to be ineffective in independent lab tests.

In Japan it seems they are far more advanced, they already have a standardized SFN-glucosinolate tablets, no mention of the need to keep them frozen.


Japanese Sulforaphane (SFN) research

What is interesting in the Japanese research into cognitive deficits in schizophrenia is that SFN shows has both prophylactic and therapeutic effects.  This suggests that even if there is no immediate benefit from taking SFN in some people, there may be some long term preventative/protective benefits.




Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

  


After giving written informed consent, participants received 3 tablets of SFN prepared by Kagome Co., Ltd. (Nagoya, Japan), totaling 30 mg of SFN-glucosinolate per day, for 8 weeks. It is known that SFN-glucosinolate is metabolized to SFN in the body.

Objective

Schizophrenia is a mental disorder characterized by severe cognitive impairment. Accumulating evidence suggests a role for oxidative stress in the pathophysiology of schizophrenia. Sulforaphane (SFN) extracted from broccoli sprout is an agent with potent anti-oxidant and anti-inflammatory activity. In this study, we attempted to evaluate the effect of SFN on cognitive impairment in medicated patients with schizophrenia.

Methods

We recruited a total of 10 outpatients with schizophrenia, all of whom gave informed consent. Participants took 3 tablets of SFN, consisting of 30 mg of SFN-glucosinolate per day, for 8 weeks. Clinical symptoms using the Positive and Negative Syndrome Scale (PANSS) and cognitive function using the Japanese version of CogState battery were evaluated at the beginning of the study and at week 8.

Results

A total of 7 patients completed the trial. The mean score in the Accuracy component of the One Card Learning Task increased significantly after the trial. However, we detected no other significant changes in participants.

Conclusion

This result suggests that SFN has the potential to improve cognitive function in patients with schizophrenia.

   
I do get comments from people with schizophrenia on this blog and there is clearly a big overlap between some schizophrenia and some autism.  More and more therapies are being shown to be effective in both; it seems to be the SFN is one of those therapies.

What would be nice would be a commercially available, standardized product that genuinely could be relied upon to produce SFN in the body.  The Japanese appear to have already mastered this.  No need for Johns Hopkins patents.

For the time being, I am happily using my Supersprouts broccoli sprout powder which does indeed seem to produce SFN.  If one day they stop making it, I have already found that you would just need to add heat stable myrosinase (in the form of daikon radish root) to otherwise ineffective broccoli sprout powder.

For those of you who tried other products claiming to contain/produce SFN, and found them ineffective, you do not know whether the child does not respond to SFN, or your product produced none.

  
Conclusion

SFN really does look worth a try, or perhaps even a second try for those who tried one of those “false” supplements.  Price does not always indicate quality.


One day I hope that the Japanese firm Kagome, chooses to sell its SFN tablets worldwide and not just their tomato ketchups and juices.  




23 comments:

  1. HI Peter, I am using the Australian company Super Sprout. Their Broccoli Sprouts in capsule form. Do you think that is effective? It seems good to me.

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    1. My son is using the same product and it really does work. We use the powder form and mix 2.5ml of powder in water.

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  2. Peter,
    Have you heard any feedback on Enduracell's powder? I tried it for 4 months with my 8 year old son (I gave him a daily 1/2 tsp= 6mg of SFN), but I stopped it because it didn't seem to help. I put it in applesauce and then immediately fed it to him per Enduracell's recommendation to use it within 30 minutes after adding water. Thanks.


    I tried Enduarcell's powder with my 8 year old son for 4 months- but it didn't appear to help. Have you

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    1. No, I have had no feedback on that brand.

      Supplement companies are not drug firms and if they do not test each batch, one jar might work and the next not.

      There are lots of comments about SFN for other uses on the web, where users are not happy.

      Well over half the people who replied to me found that Supersprouts SFN was effective and from the first dose. But in some case it had no apparent effect.

      I did buy daikon radish powder, which is cheap, and if the powder had not worked I would have added a small amount. This is in effect what Johns Hopkins are doing in the lab.

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  3. Hi Peter
    I wanted to know if any of your readers have used it for younger kids
    My son is 3 and I wanted to try bumetanidw before sulphorophane as both work on mood
    Thanks
    BK

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    1. Readers seem to represent a wide range of ages. Three is young since most people are not diagnosed before then.

      Bumetanide and Sulforaphane (SFN) are different. SFN really does affect mood almost immediately. Bumetanide primarily affects cognition, and so once the brain starts to work better many other things also change.

      Bumetanide is used in babies. One reader gave it to his 3 year old until the age of 5, at which point the diuresis became a problem, since the child was still not toilet trained.

      SFN has only recently been suggested for use in autism. The dose is small and it really is just like eating a small plate of broccoli sprouts each day.

      I would recommend trying both, but first one (see if it works) and then the other. You will know within a few hours in SFN is effective. Bumetanide may take a month or two to take effect, but it was about 10 days for us.

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  4. Neurobiologix have released a capsule claimed to contain 60mg sulforaphane glucosinolate. That would appear to be a strong claim in respect of the active ingredient itself. But, I'm a little cautious about claims re sulforaphane. Whats the best question(s) to ask them? We've tried super sprouts but couldn't get the boy to take it for a long enough trial period, so I'm trying to find a capsule (and apparently, the neurobiologix formula is quite as strong tasting for those who can't take a capsule).

    Cheers Peter.

    By the way, we've just got back from a US visit with a US MAPPS/DAN doctor who is very much into off-label/second indication use of existing drugs, particularly regarding GABA and NMDAr management, etc. Much more encouraging

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    1. If your son can swallow capsules you can put the supersprouts powder in gelatin capsules, they do also sell it in capsules.

      There is no way to know which products produce SFN because, as with all supplements, they are not made with the quality controls and testings that is required by law from drug firms. The independent testing showed that most products produced no SFN, regardless of what was claimed.

      Great that you have found a helpful autism doctor.

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  5. Peter, Your blog is terrific and much appreciated. This might be too concrete a question: You often mention cognitive gains globally -- but the areas my child is hardest hit is processing speed and spatial issues. In your research, have you come across specific studies, drugs, or therapies, etc that particularly helped those areas specifically? I hope that is clear? thank you again!

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    1. That may be too specific question, since people do seem to get different benefits from the same drug. To improve cognition you could try piracetam, which some people respond very well to. There are other related nootropics.

      In my son the cognitive benefit is from Bumetanide, Atorvastatin and now cinnamon. There may be a response to PAK1 inhibitor BIO30 propolis, and at least one reader notes a positive response.

      Processing speed may be slow because he is not 100% "present", this might be rectified by bumetanide. Well worth a try.

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    2. Bumetanide seems to have helped with spatial issues with regards to writing. Also, my daughter was standing on one side of a bookcase and was looking for her headphones. I pointed to the case from the other side where she could not see me fully. So, she bent down, stuck her head close to one of the open sections and looked at my finger to see where it was pointing and then got her case. She has never been able to do this before.

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  6. Hey there Peter,

    So I've been doing some research to try and determine which broccoli sprout powder is effective so I can give it another try. I've tried Cell-Logic Enduracell but have not noticed any real changes. I was just about to order some SuperSprout (the one you give your son) when I happened to read the John Hopkin's article again and realized something in the last paragraph:

    "U.S. patent applications have been filed by The Johns Hopkins University for inventors Smith, Talalay and Zimmerman. Talalay and Zimmerman have divested themselves from all potential financial benefits. The sulforaphane-rich broccoli sprout extract is not a commercial product. Broccoli sprouts and seeds rich in glucosinolates have been licensed by Johns Hopkins to Brassica Protection Products LLC"

    So I went to brassica's website and under products, it took me to trubroc's website, and they only sell a variety of teas but there is a list of a few different products that contain at least some amount of trubroc (which is GLUCORAPHANIN, which once consumed apparently meets intestinal microflora and is converted to sulforaphane). Now I am not as educated on this topic as you, so maybe you can give me some insight on this whole situation.


    So of the 8 or so products, 2 of them caught my attention because they had the highest content of this ingredient and are broccoli based. They are:

    1-Avmacol® 60 Tablets (containing 350 mg broccoli extract blend containing 25mg of glucoraphanin)

    2-Crucera-SGS (containing Sulforaphane Glucosinolate (from Broccoli extract (seed) (Brassica oleracea italica)) 50mg )


    So my question to you is, would these supplements be of higher quality and effectiveness than, say, SuperSprout or Enduracell? The only reason they caught my attention is because of the indirect association to John Hopkin's product used during their research. SuperSprout doesn't give any real numbers or percentages of ingredients and Enduracell claims 1000mg of pure broccoli sprout powder yielding sulforphane.


    I am somewhat overwhelmed with the conflicting information and my budget is pretty tight so I don't want to get an ineffective product, but I have read so many health benefits of sulforphane and how effective it is for some individuals on the spectrum. I am just curious to hear your thoughts/opinion on all of this since I'm a big supporter of your research and findings. Baclofen, NAC and Bumetanide have made big differences for me and I'm hoping this may be yet another piece to my puzzle.

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    1. This comment has been removed by the author.

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    2. It would be great if someone tested all these products. A while back when someone did just that, they found that most produced no Sulforaphane. Then you are left wondering is it that the powder was not effective, (no Sulforaphane) or the powder worked but the Sulforaphane had no effect on that person.

      I choose Supersprouts because they seem to be somewhat in control of the production process (the powder does not come in big sacks from China) and it was not so expensive. They do not say how much Sulforaphane is produced and, even if they did, you have no way of knowing whether it is true.

      Enduracell is not a cheap product and I expect it will produce Sulforaphane, so perhaps it is a case that you are just not a responder. Not everyone is. From the same jar of Supersprouts, some people with ASD responded and others did not.

      I would save your money and try something totally new.

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    3. I'm thinking what if I used daikon radish powder to mix with whatever I end up choosing to buy? Is there any radish powder available online you would recommend? I might just und up purchasing and trying both the supersprout and Crucera-SGS separately along with the daikon radish root powder. If that still doesn't work than I guess I'm just one of those non responders to sulforphane. Do you buy daikon root powder and just mix it with the broccoli powder or take them as capsules? I can't seem to find a good source of it looking through supplant stores, only in capsules which I am not sure are effective either.

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    4. I bought online Swansons Daikon Radish powder, but never needed to use it. You would only need a tiny amount, much less than a capsule, but I do not think too much would do any harm. This is heat stable and can even be frozen. Good luck.

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  7. I just bought some brocco max from Amazon and I'm wondering if I should get something different at this point. I bought it because my HFA daughter shed her autism symptoms (what she describes as constant videos in her head) when she has a low grade fever due to a cold this past week. It was amazing so I researched remedies to mimic a fever and found this. I want to made sure I give her the right thing and I see lots of different information here. So my question is, what exactly do you recommend and where can I purchase it?
    Thank you!!

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  8. Some people do really benefit from the sulforaphane produced by some broccoli powder. The problem is that most powders tested actually do not produce sulforaphane. The powders that do seem to work produce a mood improvement. It is well worth having, but it really is not the same as the famous "fever effect". It is clear that nobody has figured out what is behind this effect, lots of ideas but just that.

    One powder that does work is from Australia and is called Supersprouts, just google it. They ship everywhere. The dose is only half a teaspoon a day. In the people who respond there is a profound effect in about 30 minutes from the first dose.

    It is worth a try and may indeed help, but it does not match the fever effect.

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  9. Hellow this is for all who read about brocoli sproud.I have buy by mistake 2 of supersprouts.If somebody is thinking to buy it and live in Europe,i can sell one.If someone is interested please write to:vicencomgi@hotmail.com.Thanks Peter and excuse me for posting here but I don,t know what to do with too much broccoli.

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  10. I helped to develop Avmacol, one of the products referenced in a prior October posting. I was lucky enough to be part of a fantastic research team that carried out clinical studies investigating the chemopreventive efficacy of sulforaphane (Carcinogenesis. 2007 Jul;28(7):1485-90). I have spent more than a decade researching this wonderful compound and can gladly put together a WebEx for those interested. I can share a bit of background and then open it up to Q&A. (Peter - if you get a chance to read this please let me know how I can contact you).

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    1. Hi
      I am interestes in knowing what is the special in Avmacol.
      How it stabilize the active compounds?
      Please explain. Thanks!

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  11. We spent many years developing (and testing) Avmacol formulations that would consistently deliver both glucoraphanin (the sulforaphane precursor) and an active myrosinase enzyme. It is important to store the product in a cool and dry environment.

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    1. I am wondering how the enzyme works after entering the stomach. Should it be inactivated by low pH?

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