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Sulforaphane and Nicotinamide Riboside: The best combination for maximizing AMPK and the SIRTULINS?

sulfora sulforaphane nicotinamide riboside nad+ sirt1 ampk nrf2 pgc1a bioavailability potency

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#481 TMNMK

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Posted 23 April 2018 - 03:10 PM

I'm going to start growing again but to make the consumption more palatable I'm going to start experimenting with mixing in other foods/spices. Is there anything you should avoid mixing in with Broccoli sprouts that might ruin the benefits?

 

Good question! I'm not sure, but maybe avoid ingesting H2O2 with it? http://www.jbc.org/c.../3/555.full.pdf I don't think that's a real risk though, if you do take a page out of a mycology book and use H2O2 to kill pathogenic bacteria, just wash it off first and then crush/chew/ingest.

 

On another note, my wife put the kabosh on the broccoli sprouts after I stunk up my office with a mix of that and a significant amount of brown mustard seed powder for 12 hours. She just couldn't handle the smell anymore so I ordered Avmacol chewables and put away my poor little sprouts seeds.


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#482 bosharpe

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Posted 23 April 2018 - 06:26 PM

Good question! I'm not sure, but maybe avoid ingesting H2O2 with it? http://www.jbc.org/c.../3/555.full.pdf I don't think that's a real risk though, if you do take a page out of a mycology book and use H2O2 to kill pathogenic bacteria, just wash it off first and then crush/chew/ingest.

 

On another note, my wife put the kabosh on the broccoli sprouts after I stunk up my office with a mix of that and a significant amount of brown mustard seed powder for 12 hours. She just couldn't handle the smell anymore so I ordered Avmacol chewables and put away my poor little sprouts seeds.

 

Thank you for that. Haha, fair enough! Oh nice, I cannot budget for the sups on top of my monthly outgoings to I've got to grow instead. I don't use H2O2 when growing. When I started off I was a little paranoid about harmful bacteria but assumed heating the sprouts before consumption would kill all the bad stuff. 


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#483 TMNMK

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Posted 23 April 2018 - 07:17 PM

Thank you for that. Haha, fair enough! Oh nice, I cannot budget for the sups on top of my monthly outgoings to I've got to grow instead. I don't use H2O2 when growing. When I started off I was a little paranoid about harmful bacteria but assumed heating the sprouts before consumption would kill all the bad stuff. 

 

My pleasure :) Don't heat for too long (I seem to recall a couple minutes max being mentioned someplace, using steam) or it will deactivate myrosinase. However, you could heat as long as you want and then add something with active myrosinase like brown mustard seed powder back in after they've cooled off. You won't have pathogens on the mustard powder as it kills E. Coli itself.


Edited by TMNMK, 23 April 2018 - 07:21 PM.

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#484 mikela

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Posted 23 April 2018 - 08:08 PM

 Don't heat for too long (I seem to recall a couple minutes max being mentioned someplace, using steam) or it will deactivate myrosinase. 

 

I have been following Rhonda Patrick's guide to reduce nitriles and maximize sulforaphane.  I believe the nitriles impart a bad taste to the sprouts as well as the seed hulls which I remove.


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#485 tunt01

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Posted 28 April 2018 - 02:27 AM

McCarty, M. (2000). Co-administration of equimolar doses of betaine may alleviate the hepatotoxic risk associated with niacin therapy. Medical Hypotheses55(3), 189-194. doi:10.1054/mehy.1999.1011

 

McCarty suggests equimolar administration of niacin and betaine for methyl donors, because niacin administration can cause liver damage by burning through methyl/SAM sources.

 

Nicotinamide Riboside Chloride is 290.70 g/mol

Nicotinamide Riboside is 255.25 g/mol

Nicotinamide is 122.12 g/mol

 

Betaine is 117.148 g/mol

 

 

Therefore for 1 gram of nicotinamide riboside chloride, we should administer    (1 g / 290.70 g/mol  * 122.12 / 290.7 = 0.0014450961103698 mols of betaine, which is approximately 169 mg betaine for every 1 gram of NR)

 

This is consistent with Thorne Research's Resveracel product which has 300 mg NR Chloride and 50 betaine in a roughly equimolar amount or 16.7% of the weight.

 

Any chemists pls check my math.

 


Edited by tunt01, 28 April 2018 - 02:39 AM.

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#486 pone11

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Posted 06 June 2018 - 06:55 AM

If I remember correctly, myostatin was inhibited strongly at 5 umol, but the inhibition began at 1 umol. To achieve around 2 umol in-vivo in plasma, four or five ounces of sprouts is enough. Probably less would be enough if you heated them to 60C-70C for a couple minutes first to destroy the enzyme that would produce inactive nitrils. I don't think any in-vivo human testing have been done (the above testing was done in pigs), but I think the results would transfer over.

 

The really cool thing about sulforaphane is that you can get very good results with VERY low toxicity in "normal" cells until the 10 umol range. Beyond that, limited toxicity starts to build, but the toxicity is FAR FAR less to human cells than it is to cancer cells. Some cancer cells -- although probably not all -- seem to die very rapidly around 10umol or above. However, the cytotoxic effects on cancer cells begin all the way down at 1 umol.

 

Just to calibrate to doses of sulforaphane, are your references above supposed to be the number of micromoles per kilogram of body weight for a human?   

 

Most human studies have been done with between 30 mg and 60 mg of sulforaphane.   Assuming a molecular weight of sulforaphane of 177.29 grams per mole, that yields something like:

30 mg = 30/1000 grams 

30/1000 grams / 177.29 grams/mol = 0.000169214 moles ~= 0.169 millimoles ~= 169.2 micromoles

For a 70 kg human, that is about 2.4 micromoles per kg of body weight.    So that seems to agree with the order of magnitude of your statements if we assume that the human ingested 30 mg of sulforaphane.


Edited by pone11, 06 June 2018 - 06:58 AM.


#487 pone11

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Posted 06 June 2018 - 12:03 PM

Is there a fundamental error in the procedure that Dr Rhonda Patrick is suggesting for brewing broccoli sprouts at 70C to maximize sulforaphane production?   In Rhonda's method, she is brewing the intact sprouts for 10 minutes at the target temperature, then at the end she is blending them.  The problem with that is the myrosinase enzyme is actually trapped in the fiber structure of the sprouts, and it is the chewing and blending of the glucoraphanin and myrosinase together that starts the chemical reaction that then produces sulforaphane.

 

The correct procedure should be to raise a water bath to 70C, then blend the sprouts in that water bath and leave the blended material at the target temperature for 10 minutes.   That gives you 10 minutes with the two critical chemicals in contact and undergoing chemical reaction.



#488 Nate-2004

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Posted 06 June 2018 - 05:57 PM

Is there a fundamental error in the procedure that Dr Rhonda Patrick is suggesting for brewing broccoli sprouts at 70C to maximize sulforaphane production?   In Rhonda's method, she is brewing the intact sprouts for 10 minutes at the target temperature, then at the end she is blending them.  The problem with that is the myrosinase enzyme is actually trapped in the fiber structure of the sprouts, and it is the chewing and blending of the glucoraphanin and myrosinase together that starts the chemical reaction that then produces sulforaphane.

 

The correct procedure should be to raise a water bath to 70C, then blend the sprouts in that water bath and leave the blended material at the target temperature for 10 minutes.   That gives you 10 minutes with the two critical chemicals in contact and undergoing chemical reaction.

 

I agree and this is actually what I do but not with sprouts, just with regular broccoli, which with grown florets the water should be at 60c not 70. I put it in my Epica boiler and set it to the target temp of 70c, I then pour it into a measuring cup and again into the blender with the broccoli. Whenever you pour water, each time, it consistently loses 2 degrees celsius until a certain point (room temp?). By the time I blend the water should lose another 4 degrees just from blending, so I'd be roughly around 62 and let it sit for 10 mins before adding other ingredients like blueberries, banana, tomato, flaxseed, walnuts, etc.

 

Also know that, at least at my house, the hot water comes out of the faucet at around 52 to 58 celsius so that in itself may be enough but pouring risks losing a lot of that heat.

 

I realize with full broccoli the sulforaphane content will be lower but not by much, and I'm taking BroccoMax with it.


Edited by Nate-2004, 06 June 2018 - 06:03 PM.


#489 pone11

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Posted 07 June 2018 - 03:24 AM

I agree and this is actually what I do but not with sprouts, just with regular broccoli, which with grown florets the water should be at 60c not 70. I put it in my Epica boiler and set it to the target temp of 70c, I then pour it into a measuring cup and again into the blender with the broccoli. Whenever you pour water, each time, it consistently loses 2 degrees celsius until a certain point (room temp?). By the time I blend the water should lose another 4 degrees just from blending, so I'd be roughly around 62 and let it sit for 10 mins before adding other ingredients like blueberries, banana, tomato, flaxseed, walnuts, etc.

 

Also know that, at least at my house, the hot water comes out of the faucet at around 52 to 58 celsius so that in itself may be enough but pouring risks losing a lot of that heat.

 

I realize with full broccoli the sulforaphane content will be lower but not by much, and I'm taking BroccoMax with it.

 

So now I am going to innovate and ask why aren't people heating a water bath to 70C, then powderizing a BroccoMax or Avmacol tablet and then putting that powder into the bath for 10 minutes?   Rapidly cool that liquid and then drink it.

 

First, we would increase the conversion to Sulforaphane from those tablets by 250%, given the study that Rhonda quotes in one of her Youtube videos.  

 

Second, we would get 70% bioabsorption of the sulforaphane instead of 35% bioabsorption of the precursors.    

 

These two effects together might turn an effective sulforaphane dose for two Avmacol tablets from 8 mg sulforaphane to 40 mg sulforaphane, applying the two adjustments above.

 

Why would this not work?



#490 pone11

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Posted 07 June 2018 - 03:36 AM

I should mention that sulforaphane at high doses did a number on my libido.  In addition to the DHT inhibition it also decreases androgen receptor levels.  This has been demonstrated in prostate cells but I imagine it could occur elsewhere (in the brain this would certainly have anti-sexual effects).

 

At what specific dose did you perceive a negative sexual side effect from sulforaphane?   How were you taking it?



#491 hamishm00

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Posted 07 June 2018 - 09:59 AM

So now I am going to innovate and ask why aren't people heating a water bath to 70C, then powderizing a BroccoMax or Avmacol tablet and then putting that powder into the bath for 10 minutes?   Rapidly cool that liquid and then drink it.

 

First, we would increase the conversion to Sulforaphane from those tablets by 250%, given the study that Rhonda quotes in one of her Youtube videos.  

 

Second, we would get 70% bioabsorption of the sulforaphane instead of 35% bioabsorption of the precursors.    

 

These two effects together might turn an effective sulforaphane dose for two Avmacol tablets from 8 mg sulforaphane to 40 mg sulforaphane, applying the two adjustments above.

 

Why would this not work?

 

No need. The Broccomax product has already been heat treated to 70 degrees I believe, after reading their patent.


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#492 Jesuisfort

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Posted 07 June 2018 - 03:53 PM

Hi, Can we take Sulforaphane + NAD +  Metformin   ?  will we get a synergistic effect ? 


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#493 pone11

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Posted 07 June 2018 - 10:35 PM

No need. The Broccomax product has already been heat treated to 70 degrees I believe, after reading their patent.

 

I guess they are doing that to the broccoli sprouts before separating out the glucoraphanin and myrosinase enzyme that they ship to us?    My guess is they are targeting destruction of the epithiospecifier protein (ESP), which is the enzyme that would create the nitrile form of sulforaphane that has no clinical value for us.    So by heat-treating they destroy what is bad and preserve what is good.

 

So that then raises the question what is the optimal temperature for brewing glucoraphanin and myrosinase to produce sulforaphane.   If we no longer need to worry about ESP being present in the mix that means the sulforaphane production curve may be different than the one I am attaching, from the study that Rhonda has been quoting.

 

  Attached File  Antioxidant_Sulforaphane-Production-Temperatures.jpg   97.82KB   0 downloads



#494 mikela

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Posted 08 June 2018 - 05:18 AM

So that then raises the question what is the optimal temperature for brewing glucoraphanin and myrosinase to produce sulforaphane. 

 

 

Room temperature for 40 minutes according to this.  Start at the 1:35 mark.



#495 pone11

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Posted 12 June 2018 - 10:55 AM

Room temperature for 40 minutes according to this.  Start at the 1:35 mark.

 

The 38C figure comes from this study on PubMed.  There are all kinds of problems with using this study to answer my question.

 

First, the study was homogenizing broccoli sprouts, not using the substrate and enzyme in powder form.

 

Second, the table 1 in this study shows they never tried any temperature above 38C.

 

Third, the table 1 in the study shows that the 38C optimization required a pH adjustment and required three hours in the bath.   Who has three hours to spare every time they want to take a sulforaphane supplement?

 

I strongly suspect that the optimal processing for the isolated substrate and enzyme would occur at a higher temperature, which would potentially dramatically reduce the required processing time.

 

So far I have not been able to find any study that investigates this.



#496 pone11

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Posted 12 June 2018 - 11:51 AM

I am seeing almost 1000 studies on sulforaphane on PubMed in the last 20 years, and not one of these appears to be an animal study looking at life extension.   Does anyone know of any sulforaphane study tracking effects on lifespan of any organism?



#497 pone11

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Posted 12 June 2018 - 12:22 PM

From the OP--

 

 

I think it's likely to be the opposite. NR and other NAD+ precursors get the mitochondrial quality control system running, whereby dysfunctional mitochondria are tagged, engulfed by lysosomes, and digested. To fit them into lysosomes they must be fissioned into the smallest possible size, and then later they fuse together to produce mitochondria that are more robust than before. So anything that prevents fission is going to reduce or eliminate the effectiveness of NR. And sulforaphane is a promoter of "hyperfusion," which means they are even larger than normal. Thus these supplements are working at cross purposes.

 

See this paper--

 

 

So unless someone is getting amazing results with this combination (I doubt it), I wouldn't take them at the same time. And I wouldn't take either supplement all the time.

 

These are great points, but this begs the question how often should we go on and off therapeutic doses of sulforaphane.  What is the optimal protocol?   We simply do not have the science or the empirical studies to know the answer to this.

 

This really emphasizes the need for some lifespan studies in animals, where they change the dose and the frequency to try to determine where sulforaphane achieves optimal results, and equally important where it starts to reduce lifespan.


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#498 Harkijn

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Posted 12 June 2018 - 12:38 PM

I am seeing almost 1000 studies on sulforaphane on PubMed in the last 20 years, and not one of these appears to be an animal study looking at life extension.   Does anyone know of any sulforaphane study tracking effects on lifespan of any organism?

I don't think we have much on that. Well, the lifespan of beetles....

https://www.foundmyf...ane?t=00h38m06s



#499 mikela

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Posted 12 June 2018 - 02:00 PM

These are great points, but this begs the question how often should we go on and off therapeutic doses of sulforaphane.  What is the optimal protocol?   We simply do not have the science or the empirical studies to know the answer to this.

 

This really emphasizes the need for some lifespan studies in animals, where they change the dose and the frequency to try to determine where sulforaphane achieves optimal results, and equally important where it starts to reduce lifespan.

 

This thread has some interesting information on alternating fission and fusion.

 

#500 pone11

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Posted 12 June 2018 - 07:18 PM

I don't think we have much on that. Well, the lifespan of beetles....

https://www.foundmyf...ane?t=00h38m06s

 

This is the beetle lifespan study.



#501 pone11

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Posted 13 June 2018 - 01:19 AM

 

To those opposed to eating sprouts, I thought of a way that might make consuming sulforaphane easier. In the rhonda patrick interview, Dr. Fahey mentioned that when you freeze sprouts, it breaks down the cells so need to make sure to get all the juice into the blender along with the sprouts, because the juice will contain sulforaphane. It occurred to me that one could possibly drink just the juice and discard the sprouts. Upon drinking the juice, it tastes potent, but I can't tell how potent it is compared to the the whole sprouts. Blending fresh sprouts seems to be more potent (made my stomach hurt), but blending is a chore.
 
My routine:
1.scoop several tablespoons of seeds into mason jar (make batches in bulk to save time).
2. pour heated water and/or heated hydrogren pyroxide over seeds to kill any possible ecoli (this paper recommends heating at 140F for 5 minutes http://anrcatalog.uc...u/pdf/8151.pdf)
3.Let grow for 3 - 4 days (sufloraphane content shown to peak at 2-3 days, also I don't like the sprouts to get too big)
4. Pour 168F water on the sprouts for 10 mins to dissolve EPS and increase sulforaphane, also to kill any bacteria that could survive.
measure out how much you want per serving, put your desired amount into ziplock baggies and freeze.
5.Once you let your baggie thaw, squish the sprouts with your hands (maybe even use something to smash them if you like), then pour out the juice out in a cup, mix with whatever juice you want.

 

 

That procedure will not work.  The 2003 study that Rhonda used as a basis for her video cooks the sprouts at around 65C for 10 minutes only to deactivate the ESP enzyme.   If you read the full text of the study, they actually appear to then wait EIGHT HOURS to produce the sulforaphane.

 

What might work is to cook the sprouts to disable ESP, then homogenize the sprouts and cook those at 38C for three hours. 

 

NOW you can take the juice.   The problem with storing it is the sulforaphane rapidly degrades.

 

See a post I made today for links to studies.


Edited by pone11, 13 June 2018 - 01:20 AM.


#502 pone11

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Posted 13 June 2018 - 02:48 AM

Thanks tintinet.

 

http://tim.blog/

 

Well worth a listen as Dr. Patrick talks for over 2 hours. Tim Ferriss allows the mp3 file to be downloaded. . Nate, she talks extensively about water only fasting, intermittent fasting and time restricted feeding starting at 13 minutes in. 

She practices time restricted feeding which she counts only water as being allowed. She explains why. She is taking NR at a dose of 125 mg, if I heard correctly.

 

I had to slow the podcast down to 90% of full speed to just keep up with Rhonda's verbal pace.    If I didn't know better, I would think she took 10 amphetamine pills before this interview.  Wow.


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#503 pone11

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Posted 13 June 2018 - 06:16 AM

Maybe, but there's little proof of this and no rationale. If sulforaphane in cruciferous veggies, specifically broccoli because it's the plant with glucoraphanin, is the active ingredient giving such good results in numerous studies in several areas, then what would be the difference, specifically, of taking it in a supplement vs taking it in a plant? What's the actual difference? Why must sulforaphane come in plant form for it to be any good? 

 

This is the question that I can't seem to get an answer for when it comes to people criticizing the use of supplements. The arguments are that it's not the same thing and could be dangerous, and the other is that people will take supplements so they can eat badly. To both arguments I ask, what's the difference?

 

Facts of each specific case matter, but there is a decent generalization to be made that for some supplement types the manufacturers do not produce the right substance to get the desired effect.   A great example of this is urolithin production from pomegranate seeds.   The urolithin is metabolized in the gut based on a specific tannin profile in the ingested pomegranate.   Urolithin has nearly miraculous research behind it and is a big deal.  So along come the supplement makers who realize that the industry standardized on just one marker "ellagic acid" and they all certify their supplements based on the ellagic acid component.   This study shows how most pomegranate supplements do not actually contain the required tannin ingredients at all.   From that study's abstract:

 

To compare the phytochemical contents and antioxidant activities of commercially available pomegranate extract dietary supplements beyond their content of ellagic acid, a total of 27 different supplements in the form of capsules, tablets, and soft gels were studied. Total phenolics were measured using both gallic acid equivalent (GAE) and ellagic acid equivalent (EAE) assays. Punicalagins, punicalin, and ellagic acid contents were determined by HPLC, whereas antioxidant capacity was measured using the Trolox equivalent antioxidant capacity (TEAC) assay. Of the 27 supplements tested, only 5 had the typical pomegranate tannin profile by HPLC, 17 had ellagic acid as the predominant chemical with minor or no detectable pomegranate tannins, and 5 had no detectable tannins or ellagic acid. Therefore, standardization of pomegranate extract supplements based on their ellagic acid content does not guarantee pomegranate supplement authenticity.

 

 

Sulforaphane is not different in principle, since you need a supplement that has both the precursor as well as the enzyme.   Since sulforaphane has become so widely discussed this fact is out there and many consumers look for that.   But - even then - how well preserved was the enzyme by a given manufacturer, particularly since it is heat sensitive.   You need to be aware of such issues with supplements and ask questions.



#504 pone11

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Posted 13 June 2018 - 06:32 AM

Is there a fundamental error in the procedure that Dr Rhonda Patrick is suggesting for brewing broccoli sprouts at 70C to maximize sulforaphane production?   In Rhonda's method, she is brewing the intact sprouts for 10 minutes at the target temperature, then at the end she is blending them.  The problem with that is the myrosinase enzyme is actually trapped in the fiber structure of the sprouts, and it is the chewing and blending of the glucoraphanin and myrosinase together that starts the chemical reaction that then produces sulforaphane.

 

The correct procedure should be to raise a water bath to 70C, then blend the sprouts in that water bath and leave the blended material at the target temperature for 10 minutes.   That gives you 10 minutes with the two critical chemicals in contact and undergoing chemical reaction.

 

So just to update my post here, I did not understand the reaction well enough.  Now that I read through the original 2003 study, it looks like the 10-minute procedure is only to disable the ESP enzyme that competes with myrosinase.   The actual production of sulforaphane is a three to eight-hour process depending on temperature and pH.  I link the studies in my new topic on this.



#505 Nate-2004

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Posted 13 June 2018 - 01:36 PM

So just to update my post here, I did not understand the reaction well enough.  Now that I read through the original 2003 study, it looks like the 10-minute procedure is only to disable the ESP enzyme that competes with myrosinase.   The actual production of sulforaphane is a three to eight-hour process depending on temperature and pH.  I link the studies in my new topic on this.

 

Can't that process just happen inside you after ingestion? Isn't that what happens anyway?

 

What I wonder is if this process is even worthwhile, maybe the nitrile producing enzyme just dies in the stomach?



#506 John250

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Posted 13 June 2018 - 04:05 PM

What supplement/brand/dose would you recommend for the best
Sulforaphane? Thanks

#507 APBT

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Posted 13 June 2018 - 08:08 PM

What supplement/brand/dose would you recommend for the best
Sulforaphane? Thanks

 

As pone11 has pointed out, there are questions about the efficacy of any of the sulforaphane supplements.  Perhaps someone could contact these companies and address the questions/concerns posted here.  Or contact Rhonda Patrick.

That said, I've used the following products:

https://www.cell-log...exd.asp?id=6940

https://www.cell-log...exd.asp?id=9685

https://www.nutramax...ablets#Wellness

https://www.iherb.co...ggie-Caps/68704



#508 John250

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Posted 13 June 2018 - 08:16 PM

What about bad monkey

https://www.badmonke...ch=Sulforaphane

#509 APBT

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Posted 13 June 2018 - 09:33 PM

Rhonda Patrick posted this recently on Instagram:  https://www.instagra...=foundmyfitness


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#510 pone11

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Posted 13 June 2018 - 11:04 PM

Can't that process just happen inside you after ingestion? Isn't that what happens anyway?

 

What I wonder is if this process is even worthwhile, maybe the nitrile producing enzyme just dies in the stomach?

 

No, the nitrile enzyme does not deactivate until about 60 centigrade.  It survives digestion.  That is why they go to the trouble to deactivate it in Broccomax and Avmacol.

 

The temperature of the body is very close to the target temperature if you process it outside the body.   But what is different is the bioabsorption.  You get about 35% bioabsorption eating the precursor glucoraphanin in Broccomax / Avmacol, based on Avmacol's studies.   You get 70% bioabsorption of sulforaphane.   So creating the sulforaphane in a test tube and ingesting it will give you a little more than twice the dose of sulforaphane.

 

That said, there is too much of a good thing too.   I started to follow this procedure and started to feel pretty bad.  That's just N=1, but I think I will have to spend some time to calibrate my dose.


Edited by pone11, 13 June 2018 - 11:06 PM.






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