This is the subject I've been working on for a year now. The basic research has been going on for 20 years. The key researchers are the brilliant Prof Albena Dinkova-Kostova in Dundee UK for the cellular and genetic processes, the neuroscientist Antonio Cuadrado in Madrid and Jed Fahey in US for plant chemistry. They all work together. I've been mostly working with Albena. The science is now established and mature. PD brains have too much oxidative stress and it increases with age. It is particularly strong in dopamine cells where it damages cell membranes and mitochondria. The system which controls this is deregulated in PD brains. We now know why and how to reset it using chemicals which attract electrons called electrophiles. You find these in food and the best are in broccoli. Yep! Eat your greens!
It's not that easy. You need high concentration which you get only in seeds and young sprouts. And a very specific extraction process to be strictly followed. The choice of seeds is also critical as is the dose. When you get it right it works, at least for me.
After 9 months of experimentation I now feel ok to tell the story.
The file below is an introduction for non-scientists. At the end of that article is a link to a long scientific article with all the source material.
Why not give them a try, but broccoli extracts don't contain sulforaphane but glucoraphanin and myrosinase. It's better to do the conversion to sulforaphane before ingesting to be sure of a good yield.
I tried it and it did not do anything for me, but was only 30 mg of sulforaphane per capsule and I took only one capsule per day. So perhaps I did not have enough.
I suggest you read the details of the article. The supplements don't contain sulforaphane but the precursors. They don't work for me either. The conversion requires very precise conditions that you don't get in the gut. It has to be done before ingestion. 30mg is probably enough if it's all converted. But it isn't!
Sulforaphane is unstable beyond a few days. I know Broccomax. The label says sulforaphane generater. And on the back it says sulforaphane glucosinolate which is glucoraphanin, the precursor molecule. They're not lying, just not being absolutely clear.
Wriga, thanks for your work. Is 30mg a good estimate of an appropriate daily dosage of sulforaphane? Jarrow's page for Broccomax says "demonstrated in vitro to yield approximately 8 mg of sulforaphane per DR capsule containing 30 mg of SGS." So if, for example, 30 mg of sulforaphane is a reasonable dose to try, might we at least approximate that by taking 4 capsules of Broccomax daily?
That's in vitro, not in your gut. In vitro you have the enzyme myrosinase, pH 7 and you control the temperature. In the gut, lots of other enzymes, T = 37 and pH 2. Not the same. ..
I have read your writings and gotten myself more up to speed on this. Firstly, kudos for all your good work.
I take it you question whether the broccomax supplement can be effective at all. I see there is a wealth of moringa products available on Amazon. According to what you've written, the version of sulforaphane available from moringa is more stable and more potent than the version available from broccoli. Why not use moringa?
This research paper has an extensive discussion of the use of moringa leaf powder for sulfurophanes:
Endogenous myrosinase in each of the moringa leaf powders was allowed to function as the powders became hydrated at ca. 23 C, forming the cold teas. Hydrolysis of glucomoringin to moringin (the biologically active ITC) was thus facilitated and moringin yield was estimated by performing the cyclocondensation analysis to measure total ITC (DTC). Maximum levels ranged from 25.9 umol/g (PA), to 18.4 umol/g (PB), and 7.7 umol/g (PC) (Figure 3), which paralleled the ranking of both the myrosinase activities and the glucomoringin levels of the respective powders (Table 1). There was a highly significant effect of incubation time for each powder(p < 0.0001), and a significant difference between the moringin yield of powders at 30 min (F1,6 = 221.38,p < 0.0001). The 30 min incubation (steeping) time reported herein (Figure 3) was based on previous work optimized using the PA powder (data not shown). The powder with the lowest level of myrosinase activity (PC) continued to convert GS to ITC, still increasing in linear fashion at 30 min. At least 25% of the hot water molar yield of glucomoringin was extracted (as moringin) into the cold-brewed tea."
Moringin weighs 311 g per mole. A concentration of 20 umol/g is therefore equivalent to about 6mg/g, - milligrams of morigin per gram of leaf powder. So to get about 60 mg of morigin you would need about 10 g of moringa leaf powder.
I ordered some powdered moringa leaf from Amazon. There are several good choices. I opted for this one:
A ‘cup of tea (8 ounces) could be expected to deliver about 200 μmol of glucomoringin, a theoretically therapeutic and/or preventive dose in clinical settings, based upon our extensive previous investigations of these compounds.’
With the commercial product, you are using, Table 1 on page five gives a yield for such product as 49.65 plus or minus 4.58 μmol glucomoringin per gram of leaf.
So if we assume 50 μmol glucomoringin per gram of leaf for commercial moringa, then we need 4g (200/50) of powder for a therapeutic dose.
So for a therapeutic dose you plan to use 10gm of powder and I plan to use 4gm.
Hydrolysis of the glucomoringin to moringin, the biologically active substance, is needed. Conversion is not one hundred percent which is why we end up with less moringin. I picked 20 umol/g because it was a round number in between 25.9 umol/g for (PA), and 18.4 umol/g for (PB).
Park and Caseyinsights, please note what I said about the activity of moringin compared to sulforaphane. Moringin would seem to be about 4 times more active than sulforaphane. I would prefer being cautious and sticking to sulforaphane. You don't have to grow sprouts, dry broccoli seeds are great and super easy to use. Please make a new post to organise yourselves into a group open to HU PwP who want to join so that we can then discuss and agree a protocol together.
I would like to continue this discussion here for a bit before creating a new post. If broccoli seeds can reliably supply the active substance, that is workable. However the issue I have with broccoli seeds is being sure they are the right variety for this purpose. Based on your experience it seems one can too easily be misled. This kind of problem does not exist for moringa leaf. Could you provide a link to a reliable source of right kind of broccoli seed, available in the US?
In the US, the best site for seeds seems to be True leaf market. I haven't bought from them because they warned me that it's illegal to import live seeds from US to EU without a licence and vice versa. What I found was
4 reasons I would like to stick with broccoli / sulforaphane
- So that we can compare notes when trying the same treatment under the same conditions with different PwPs.
- I have a good idea of the starting dose range for broccoli seeds when following my protocol for preparation. We can discuss this together as a group.
- I don't know the dose range for Moringa. I did a quick experiment with hot extracted 1g Moringa leaf powder + 4% white mustard for myrosinase added when cool. My pulse rate went up from 70 to 90 after 30 mins. Maybe I'm too sensitive, but ... Caution!!! I don't want any accidents.
- if we do well controlled experiments using Broccoli and get reasonably consistent results that we can document, we will have a chance to be taken seriously by the research community. We only have one chance to start from scratch, so let's not throw that away. They have years of research invested in sulforaphane.
You have set forth valid reasons to use the broccoli seed. However, I have concerns regarding this part of the extraction process:
"The seeds must first be ground to a coarse powder or the sprouts crushed and added to water at 60±2°C. The temperature is important to get a good yield, because different chemicals will be produced at lower temperatures."
I do have experience using a warming plate to heat a liquid to a desired temperature. Special measures like a double boiler would probably be required to maintain a uniform temperature within these bounds. Otherwise the temperature at the top edge of the reaction vessel will be noticeably lower than the temperature at the middle bottom. Also, to meet this requirement the water may need to be preheated to some temperature above 60° C so that when the cooler ground broccoli seed is added the resultant temperature is in the target range. Are you sure the temperature must be regulated so tightly? This would be a challenge for me and I can see this being a major problem for non-technical people.
If we can resolve this issue I agree broccoli makes the best sense for the reasons you set forth. I believe you are the proper person to design the protocol:
"I have a good idea of the starting dose range for broccoli seeds when following my protocol for preparation."
You have a good idea – I would only be guessing and you would almost certainly have to correct me.
Hi again Park before I go to bed. I have an induction cooker top and I use a small 11cm saucepan with a thick base. I put 120-140 ml water and heat on half power (6 on my cooker) on the smallest ring to 55-57C stirring with the thermometer. This cooker + pan has low inertia, so I cut the heating to level 1 and add the ground seeds which don't significantly affect the temperature. The temperature stabilises at 60+-2C which I hold for 5 mins and stir from time to time. I then let it cool and strain through a fine mesh tea strainer. I'm not sure how tight the temp range must be, but I try not to exceed 62C. 55 - 65 may still be ok I don't have any means to check except the taste. Going too high is more of a problem than too low. The 5 mins is to allow the seed content to disperse into the water. The hydrolysis is rapid. I find the result reproducible from day to day, which is important. If you don't have an induction plate, then use a bigger pan full of water at 60C to get stability and a small container inside to make the infusion.
For the dose, I don't think there's an absolute value. Remember, I started on the wrong seeds and still got a good initial result. That's what we should try to find out on drug-naive patients. I can't go back to square 1. When we get to that stage, which will be very soon I hope, I'll tell you my whole story and you make up your own mind where to start. It's a learning curve for us all.
As a first step, I just ordered (Quantity = 4 OZ to begin with) Broccoli - Waltham 29 - Microgreens Seeds ( Brassica oleracea var. italica) from the True Leaf Market Website. Did not order any mustard seeds for now.
Looking ahead and hoping to get started in a week to 10 days.
Using the water bath you recommended I was able to hit 60+-2C first try. The water bath overshot a couple of degrees and the suspended 100 mL of reaction water overshot by 1° but then dropped 3° upon addition of 10 g of chopped broccoli seed, for a reaction temperature of 58°
Failure to give guidance on dosages is prone to result in dangerous overdoses as we are witnessing right here and now. You are damaging your own cause by refusing to give dosage guidance. What do you regard as the safe upper limit of this substance?
An important point I don't have any way to get an answer for, that I am aware of, is your condition just before starting your self experiment. Would you be willing to share that information if it isn't too personal of a thing for me to ask? You are the only one on this forum that I think can accurately answer that question.
I has taken me months of trial and error to get to where I am now. I want to save everyone else from having to go through this complex and unsatisfactory process. It's also painful when you get it wrong, so you have to go through a washout and all your symptoms come back with a rush. Having gone through that, I finally realised that, in my case there were key symptoms that I could use as a guide to getting the dose right. Let's call these early markers or early responders. What I want to do is develop with you a protocol that helps us all identify our own early markers. If we can find an early marker for each individual who follows the protocol, this could signal the lowest functioning dose for their kind of PD, but only under the specific conditions defined by their source material and their preparation technique. Naturally, I want to minimise the variables due to source material and preparation technique. However my early marker symptom may not be the same as others. Once you find the minimum dose that affects one early marker symptom, my experience has been that others come along after some time without having to increase the dose. You may even be better on a slightly lower dose. To do this properly, you have to start with a very low dose and hold it for a week. If you don't see changes after a week, which is a very short time, can then you can either wait longer or modestly increase the dose week on week until you feel a change in an early marker symptom. Going too fast can get you into the overdose situation where you just feel generally bad, tired, nauseated, etc and some symptoms like tremor actually get worse, so you give up.
For information, my early marker was the "urgent urinary problem", but yours may be something else. The urgent pee problem for me was a real handicap. I couldn't leave the house without having to plan for pee stops every 30 mins, sometimes less. I was wearing protection and still had accidents especially when driving and unable to stop because of traffic. I first noticed a reduction in frequency, especially at night. Then the problem went away altogether. I don't even think about that any more. Other symptoms followed the same decline without increasing the dose. Mild overdosing can show up after a long time on the same dose. The effects of this treatment do not stop immediately when you stop taking the dose. There are short-term effects which continue for days and long term effects that may last weeks. If you stop the treatment and feel better after a couple of days, then you are overdosed and must cut down. That's how I got to the point of taking the equivalent of just 0.75g of seeds per day.
Your early marker symptom may be quite different from mine. I think we will do a service to everyone if we can identify the most frequently observed early marker symptoms. Some symptoms may be refractory at first or only show change after a long period of treatment. We will just ignore these for the time being and concentrate only on the early ones.
I will to call this method PD symptom tracking. I now have a bunch of symptoms that have practically gone away, or are now very infrequent. My feeling is that once you find one early marker symptom and the treatment reduces that, it is also working on all the others, so be patient!
My initial experimentation was messy because I had not conceived this Symptom Tracking method at the start. It's too, late for me to do it now. You have to start from zero. For the people who sign up to use the protocol, this will be their training course for symptom tracking. To be useful, the first group of pioneers must do it properly and follow the rules. We may still make mistakes but hopefully a second group can learn from that. These results of this could be important for further development.
This is awesome! I can see why you didn't want to unleash this all at once since the dosing can be so fine and adjustments need to be made slowly so as not to get into a state of overdose as that just slows the whole process down and can make for a worsening of symptoms.
I see some similarities in what people have gone through trying to get their B1 dose to optimal.
You've done the leg work for the forum and have discovered the pitfalls already. It sounds like once the person has obtained the proper source of seeds, it is down to a "low and slow" start watching carefully for a modest change in any of their early symptom responses and then you are on track, but low and slow is still the way forward.
Hello Albert, before using « your broccoli protocol », did you use classic Parkinson medication like sinemet, madopar or else ? For a Parkinson patient using sinemet or madopar, is it possible to start your protocol and then, slowly reduce them ? Thank you very much for all your work
Thank you for your reply and your extensive work Albert! Our community is most grateful for the time and effort you have put into this! And your willingness to share it with all of us! Connie😊
I use a coffee grinder. A blender could be used but for the small amount of seed involved the coffee grinder is better. I use a kitchen digital thermometer to confirm the water bath temperature, which has been quite accurate.
Here is an interesting possibility I came upon. I found this supplement with a combination of ingredients and the claim that it contains 9.7mg sulforaphane per capsule. In answer to a customer question on Amazon the company says, "we had the end supplement tested for actual sulforaphane content. That testing showed our supplement to contain about 9.7mg per capsule."
"Question about your sulforaphane product. In answer to a shopper's question on Amazon, one of your representatives says, "we had the end supplement tested for actual sulforaphane content. That testing showed our supplement to contain about 9.7mg per capsule." My question is... is that 9.7mg the amount of sulforaphane *produced*, as in in vitro testing, or is it the amount of sulforaphane actually existing in the capsule from the outset? If it's the latter, then I would assume *additional* sulforaphane is produced as the sulforaphane glucosinolate is converted? Thanks!"
Here is their answer:
"The ladder is correct, this is the amount of sulforaphane in the capsule. Additional sulforaphane will be produced and that is the reason we included Myrosinas."
So if I'm understanding correctly. It sounds like we could count on something more than 10mg sulforaphane per capsule here, the exact amount remaining a bit unclear.
I looked at the link provided and the info detailed is as follows -
“Activated BroccoRaphanin® 75mg (broccoli seed extract providing 8.5% Sulforaphane Glucosinolate / 20% of the Sulforaphane Glucosinolate is converted to Sulforaphane by the Myrosinase Enzyme).”
Feel free to believe what you wish, but the information comes straight off the Amazon account of the product.
I cross checked to ensure we are speaking of the same product.
So let’s look at the Supplement Facts for this product. It says ‘BroccoRaphanin® 75mg (broccoli seed extract providing 10% Sulforaphane Glucosinolate)’
So here we get a different claim as to the amount Sulforaphane Glucosinolate’ encased in the broccoli seed extract.
10% of 75mg gives us 7.5mg.
And if 20% of that Sulforaphane Glucosinolate is converted by Myrosinase Enzyme we have have 1.5 mg Sulforaphane.
And let’s be clear Sulforaphane Glucosinolate is not Sulforaphane.
Sulforaphane Glucosinolate is a precursor to Sulforaphane. 🌺
I haven't formed any conclusion. I just pasted what the company provided in answer to my email asking for clarification. (see the two quotes I pasted above) Before coming to any conclusions maybe we should account for the mustard seed powder as well? It likely provides additional Sulforaphane. (see Wriga's document) Also, is it possible there is something else we're not understanding? If each capsule provides only about 1.5mg of Sulforaphane then, by claiming ~9.5mg (both on the Amazon page and more clearly in email), even before the conversion of Sulforaphane Glucosinolate, either the company is lying or they just don't know what they're talking about. Certainly possible!
Seeing the claim of 9.5mg Sulforaphane on the Amazon page but I just don’t know how it adds up. And they don’t say. Oh yes they do - third party testing 😒
I really think that this is important. I had good results way back in January, but at that time my understanding was only superficial. Then I had a relapse that I couldn't understand. I now believe that was a dosing error, but I responded then by increasing the dose. When that didn't work, I changed to a stronger molecule!
I lost 6 months and had a very bad time with those mistakes. In fact isothyocyanates and especially Sulforaphane are very powerful drugs that can easily over activate the Redox Balance system and create a rebound. I'm now on 1/6 of the dose I first started on. I am almost symptom free.
Steven, Actually I was thinking of making it a little artistic touch with this recipe with turnip tops. unadonna.it/ricette/cime-di...
Albert I know a way to go more direct on Nrf2 / ARE: niacin B3 NA flush. Niacin solves deficiencies and could help much used from time to time synergistically with electrophiles. The searches are on google..
I do not understand this paragraph because the last sentence seemed to contradict the preceding text. Can you please clarify?
" Some isothiocyanates found in Brassica seeds are harmful to health. The most important of these is goitrin which can block the uptake of iodine into the thyroid gland and reduce thyroid function if ingested over long periods. It is important that progoitrin, the precursor glucosinolate of goitrin is not present in significant quantities in the Brassica source."
I am finding I still need clarification of the above cited passage in your writing. I am concerned about the goitrin issue. This may be a reason to go with the moringa instead of the broccoli seed.
I have had confirmation from plant experts that goitrin is not a problem with regular broccoli. This is especially true for the quantities I'm using now which are particularly low. In my opinion getting the dose right is the bigger issue.
I am also very interested in the complete dosage range you have tested and the different responses at each dose and what you have concluded so far regarding dosing and timing of dosage if you can share?
I followed this thread with interest and I thought that I saw several publications on the effects of the sulforaphane as a neuro protective agent in pd. In the context of this discussion I thought that this source would be interesting: intechopen.com/books/a-mast...
Three is some very interesting info regarding selegeline and how it modules nrf2.
To get a bit more info on this science, check out Dr. Jed Fahey on youtube. As far as I know he has been studying this science since at least 2017 so he is well versed and can give you many of the highlights of what's going on in this science. Check out Albert's two papers that he wrote on this subject if you haven't already. Both goodreads!
I saw your post last night, but it was late and I was headed to bed so I only got to start reading the link to your paper. I'm going to go finish reading it right now. You have me intrigued!
As long as you don't have to watch your vitamin K intake. And one can easily create toxic amounts of NAC, which breaks into the somewhat dangerous-when-excessive cysteine, without meaning to...which can be dangerous. I wouldn't rush to claim my "you can trust me, just don't blame me" diploma just yet.
The only serious NAC toxicity I am aware of are rare anaphylactic reactions after massive amounts are infused by IV to treat acetaminophen -induced liver toxicity. I wrote about potential adverse effects of NAC here: NAC May Reduce the Severity of Coronavirus Respiratory Illness
It's not a very big deal, in fact my own use of it is moderate and I've found it helpful. But some people have risks and you have to know your own conditions pretty well. Anti-oxidants are supposed to achieve a balance, not an overbalance, with oxidants.
I'm really horrified by what happened to my daughter. They put her on a very high dose of a PPI when she was hospitalized for intractable vomiting. I knew then thatat high doses PPIs inhibit the V-ATPase, but I said nothing about it since I figured I had better leave things up the the experts. I should not have. She was given olanzapine (they thought the vomiting was caused by anxiety - turns out she has Celiac) and it really had a bad effect (turned her into a zombie) and I had them discontinue after 3 days. Later she was given Reglan and suffered an episode of Neuroleptic Malignant Syndrome. Pretty sure it was partly due to the PPI - though there are also likely genetic factors.
I'm so upset. I'll never get over this.
~
I take NAC, though, it has helped with sleep and aches and pains. I'll try to do a lower dose.
I applaud your scientific background which you put it to work, not just for yourself but for all the PwP. I read your post very carefully. In your previous post, you had written to unleash the power of broccoli, you added mustard powder. I have been doing this ever since I read that post. After reading this post, I ordered this supplement:
I just got done reading your first paper and it is very interesting ! I feel like you and I have been researching different molecules that have somewhat similar effects in terms of reducing oxidative stress and reducing excess inflammatory levels. You are looking at isothiocyanate (specific type) and I am looking at melatonin, but for a bit longer.
I have been very interested in melatonin for awhile as I can see you have been with isothiocyanate. I am also interested in melatonin because it is naturally produced in the body, but that production drops off with age and I feel that this may partially be explained by increased and ever brighter lighting at night which suppresses natural melatonin production and secretion. You are seeking rebalance of the redox system, as am I and melatonin can at least partially do this in PD. In PD it is known that the total antioxidant capacity(TAC) is down and well below healthy controls. The bodies response to this is to produce more melatonin, to increase TAC, but the body does not seem to be able to produce enough melatonin on its own to complete this task.
Melatonin is known to increase gene expression and production of the body's own natural and potent antioxidants such as glutathione, glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and heme oxygenase 1 (HO-1). Melatonin itself is a potent scavenger of multiple radicals such as reactive oxygen species(ROS)/hydroxyl radicals, reactive nitrogen species (RNS), H2O2 and importantly, peroxynitrite (ONOO) as it is also known to be at elevated levels in the PWP brain where it induces death and dysfunction of dopaminergic neurons. Melatonin can neutralize up to 10 oxygen radicals while common antioxidants, vitamin C and vitamin E can only reduce 1 each. This all makes melatonin the most potent antioxidant in the body and melatonin readily enters all tissues and easily crosses the blood brain barrier.
It is interesting to note that melatonin declines in humans beginning around age 7 until puberty when the decline in melatonin increases at a much more rapid pace. By the 50's, melatonin has declined to the level of a newborn and the decline continues at a lesser rate from 50 and beyond. Many diseases seem to begin in our 40's and increase right along with melatonin decline. Perhaps just a coincidence, but an interesting one. Consider that at least up to age 7 parents make sure their kids are in bed by 8:00 ~9:00 pm and then start to gradually slack off on that requirement. Very similarly to the decline of melatonin and then by puberty teenagers are staying up later and later and are being exposed to more and more night lighting increasing the reduction in melatonin production???
As I mentioned in the previous post, melatonin suppresses Keap1 and induces Nrf2.
In a post I did earlier this year regarding a human randomised, double blind, placebo controlled study involving melatonin and PWP, it was shown that TAC and glutathione were down in PWP compared to controls. Just 10 mg of melatonin/night for 12 weeks was able to raise TAC and glutathione and was able to improve some PD symptoms such as gastrointestinal issues, significantly reduced UPDRS part 1 score, improve PSQI measured sleep scale, significant reduction in hs-CRP, significant increase in plasma TAC, increased total glutathione levels, significantly decreased serum insulin levels, decreased HOMA-IR/reduced insulin resistance, reduced TNF-alpha and reduced LDL cholesterol.
So overall, I feel that melatonin, within its limited means of production in humans, attempts to achieve homeostasis within the organism including mitochondria and this would include a rebalance of redox status. Unfortunately, the body is not able to produce enough melatonin on its own and the 10 mg melatonin study in PWP begs the question of whether even more melatonin or a longer study or both may derive an even better response from a common molecule like melatonin. In the following study, involving athletes who generate significant amounts of ROS and other oxidants, were given 100 mg melatonin/night for 4 weeks and it was determined that the melatonin helped to significantly reduce the oxidative damage. Here is a quote from the study which is behind a paywall.
>>> ' We conclude that melatonin supplementation at doses of 100 mg.day-1 during four weeks, 30-60 min before bedtime, enhances the efficiency of the endogenous antioxidant defence system leading to """"redox equilibrium"""", and yields skeletal muscleprotection against exercise-induced oxidative damage, without adverse effects (Zhangand Zhang 2014). These data agree with the efficacy of the same dose of melatonin toimprove the circadian system during exercise elsewhere reported (LeonardoMendonça et al. 2015). Thus, chronodisruption and oxidative damage, both events that could reduce the exercise efficiency, can be simultaneously prevented by melatonin, a unique molecule involving chronobiotic and antioxidant properties. ' <<<
There are many many more health benefits to melatonin in terms of protective qualities of all major organs which is very important in PWP because heart disease is more common in PWP, so a molecule that is also protective of the heart is of significant importance also and melatonin meets that need.
Albert, now you have me wondering if the two together would be better than either one alone. You say you are almost symptom free and that in itself is extremely impressive with this disease and sounds like you are really close to remission! I have to wait on further melatonin studies to find out if melatonin can offer more at higher dosing or longer duration of supplementing or both in PD specifically. Melatonin is also purported to have life promoting effects and that too would be very useful with an improved quality of life!
Albert, you have reinvigorated me with your paper as I have been somewhat out of sync of late. Long may it last! On that note, I leave you with this :
How can you get 100mg Melatonine a day ?? I take already capsule of 3mg before going to sleep...but 100mg..,.? or in the form of a suppositorie (I know a company who sells "zetpills" of 400mgs (but is that not to much ??)
The largest capsules I have seen are 60 mg and there is bulk powder but it is not a good taste. The suppositories are 200 mg or 400 mg and they are expensive. I imagine those doses are likely for cancer treatment regimens or ALS which can both advance quickly.
I think now that melatonin is worth looking closer...had a chat with a neurologist who thinks there is some traction in higher doses of melatonin (though we didn't get into the 100mg environs.
Well I feel like an idiot. I have REM Sleep Behavior Disorder and am trying as hard as I can to figure out what I can do to stop it from progressing to something worse.
One of the main points I always make is I am not interested in Melatonine as I don't want to mask the symptoms, I want to treat them! I want to stop disease progression.
And here you come along and show that Melatonin might be exactly what is needed!
So correct me if I'm wrong, but eat heaps and heaps of green leafy type vegetables and plants, as naturally soursed as you can , in your diet. And reduce the amount of food intake that any human hand has had interference with? Which is potentially cheaper and easier and easily obtained than adding another supplement to an ever growing list ?
I mean no disrespectful feelings toward the study or anyone's feelings. And I don't mean to play devils advocate, however, taking say 5-10 supplements in any diet, in a consentrated amount will inevitably create growth in one area but weakness in other areas, either that or your body gets so much of a supplement dosage and only uses what it needs, and on top of that doesn't your body only use the supplements if it's in deficit of that particular vitamin etc?
So my question is this, if getting your homeostasis in your body buzzing thru the things we have readily available ( rich coloured fruit vegetables and plants and regular exercise) wouldn't this be a more longer lasting beneficial course of action for your body? Which would also boost bodily functions such as neuroplasticity and also reducing overall oxidive stress thru the body?
Once again am I missing something or do I need education?
My reasoning behind this is practical when I was younger pumping iron in the gym . Taking supplement after supplement after bloody supplement. And in all honesty I obtained better results in training really hard and consistency, resting and eating more but the food was good quality with minimal crap.
I read your paper and am impressed with the research but I live in an assisted living facility and don't have too much control of my diet. Buckholt in his reply says there are supplements available for sale. Have you reviewed any of them and can you make some recommendations? I see one product on Amazon.com that says Sulforaphane Supplement 75mg with Myrosinase, Broccoli Seeds, Broccoli Sprouts & Mustard Seed Extract - 60 Capsules - Glucoraphanin SGS, Sulforaphane Glucosinolate - Anti-Inflammatory* & Antioxidant. Is this what I should look for?
First, I would like to thank you for the work you have put into both papers, your self experimenting and have shared with us so generously!
I have just started reading your second paper and it is much slower going because it makes me want to look for studies in the general idea of what you have written. For example, it made me look up other supplements and minerals that I am very interested in, one being zinc, which at first glance appears to be a fairly potent Nrf2 activator at relatively low dose, but I need to check to have a bit more certainty. All interesting though, and now back to your paper!
I would like to thank you all for your interest in these articles and in my work. It really does make the effort worthwhile. What you see in this thread are just the public exchanges. Then there are the private HU messages and direct emails from people on Researchgate. My Inbox is overflowing.
The messages I most appreciate are those which say" I will take the next few days or weekend to read the articles and then get back to you".
It has taken me a year of very hard work to get this far and I'm sure it's only the beginning. I made a lot of mistakes on the way. I started by going down the ultra-antioxidant diet route to fight oxidative stress... polyphenols in red fruit etc. until I realised that you could only fight against endogenous ROS (generated inside cells) by using the endogenous anti-ROS system. It is not possible to deliver external antioxidant molecules fast enough to do the job.
I did not want to go down the road of genetic signalling pathways such as Nrf2 (and that is just one of many such pathways), the language all seemed just too foreign and difficult to grasp. I was dragged into it by the increasing pressure of PD.
And then comes the practical stuff. Well surely broccoli is broccoli isn't it? Not when you're talking seeds it isn't. My first (and very successful) trial used "broccoli bio" seeds found in all organic food shops in France for growing shoots for salads. You never grow them to maturity, so nobody sees that they don't grow into broccoli. But I did just that afterwards. They just shoot up very fast and grow pretty yellow flowers like mustard, then seeds. It's all over in 6 weeks. Great for producing seeds fast and economically, 3 or 4 crops a year. Except it's not broccoli. It's a special cross between chinese cabbage, turnip and broccoli, genetically closer to turnip tops. Latin name, Brassica rapa cymosa. and guess what? the seeds don't produce any sulforaphane, none at all, zero!
They produce another isothyocyanate called 3-butenyl ITC, a volatile, bitter tasting and smaller molecule than sulforaphane that rapidly gets to the brain, but is less active as a keap1 inhibitor.
Its effect was remarkable, all symptoms, except tremor, knocked out in 10 days. Nothing, no pain, full energy, felt like I was 25. I cut down on PD pills, then I tested cutting down on the "broccoli" extract. All fine. No pills, no broccoli, no PD. This lasted 25 days. Then I had to go back on pills and on "broccoli " extract. It didn't work. I increased the dose and that made things worse. I had no choice but to stop the treatment and try to go back to square one. That was when I learnt that the seeds were not broccoli. So what was happening? 3-butenyl ITC works on Keap1, but also on another route by changing epigenetics as does sulforaphane. I wont go into that here, it's another big chapter, but as with Nrf2 once you start some changes, you can't easily undo them.
What I want to say is that once you start this process, you can never fully go back to square one. As I understand it, and I may be utterly wrong here, activating Nrf2 triggers a healing process which runs it's own path and is partly self driven. Nrf2 triggers antioxidant enzyme synthesis and GSH and Trx maintenance which triggers mitochondrial healing which triggers more energy and better GSH and Trx supply etc.
Everytime you cycle through this cascade of events you get an upgrade. It's exponential like Covid19 infection with R >1. The original vicious circle is transformed into a virtuous circle. So what happens if you continue to boost Nrf2? You will eventually reach saturation and get a rebound effect due to the negative feedback loops which include Bach1. The virtuous circle then turns back into a vicious circle and you start a downward path.
This is where dosing becomes critical. Less is better once you start the process. It's a tricky route to follow and it took me a while to find it.
That's all for now. But I hope that when some people ask what dose should I take, I can't answer. I'm no longer what is called drug naif, and when I was, I used the wrong seeds even if they worked, we don't know enough about 3-butenyl ITC. So for all of you who are interested, we have to start this right when you are drug naif, or Nrf2 naif. You don't get a second chance to make the right start. There are also dose related safety issues that I'll come back to later. They are all dealt with in the scientific paper.
And here comes the most difficult part: communication and correct application by others, well my advice is forget the forums, because you probably won't find two people doing the same thing out of a thousand, misunderstanding leads to alteration and is the door to failure by others, but never say never. You would sooner to form a small group of pwps and follow it in person.
What I will be proposing is that PwP on this forum as on others must organise themselves into small groups with at least 2-3 people who have made the effort to thoroughly learn the science as we currently understand it and can start a learning curve based on experience with the group. We can then agree a protocol with the group, established via email or WhatsApp groups. I will then communicate with the group until it becomes autonomous and the group can give feedback that can be used by other groups.
I will not give advice to individuals on the forum. I'm not accredited to give private medical advice.
This is a complex multifaceted subject. It is evident that several people here have different yet related pieces of the puzzle. Breaking up into small groups of 2 to 3 people is a prescription for failure. Everyone with an interest in this subject needs to be able to participate in a single group.
We are all grown-ups here. No one is asking you to be liable.
I did not mean that we should break up into groups of 2-3, but that at least 2-3 people who have made the effort to try to understand the science as it stands, should seriously discuss amomg themselves how best to go forward. This can only be envisaged in the knowledge that there are still many unknowns and that many PwP have different health conditions that need to be considered.
As MarionP said, some people will take general statements at face value without trying to understand that these may be simplification that may not apply in all cases.
Take this statement from the scientific paper :
Caution: Nrf2 expression in different tissues Although Nrf2 is expressed in all tissues, it is most strongly expressed in brain, heart, urinary tract, gastrointestinal and endocrine tissues [53]. All of these tissues are therefore “On-target” for Nrf2 activation. Consequently, any therapy that targets the activation of Nrf2 in the brain, will also affect other tissues which strongly express Nrf2....
This is critically important But:
My statistics tell me that more than 200 people from the forum have read the short article for non scientists, which does not have this information. Only about 40 have chosen to have access to this information in the scientific article.
There is no way that concerns a forum like HU. Like all forums the information here is taken out of context. I am sorry, but the only way I know how to carry out this type of study is not on a forum for the simple fact that the theoretical part must be followed by a practical part where, under supervision, the data and procedures are applied giving weight and correct importance to the most relevant steps that only practice can give and supervision can correct. Like the example you have just given.
I'll tell you my opinion and it's pretty hard: apparently you've reached a dead end. And always the same mistake that we make with cellular life, that is, we assume it is not intelligent and the mechanisms are not governed intelligently by cells. Actually you are not in a dead end, but on the starting line, all the others have not even got there.
IMHO A different approach, which takes this point into account, will solve the question of doses. Maybe!
.
I have grown many plants in my life and have experimented with all possible hormones, pesticides, fertilizers. Only an approach that takes into account the Life factor present in every organism that transcends the simple mechanics work: otherwise "there is water, but the horse does not drink".
Firstly, thank you for clarification - as I understand it you are concerned people will do themselves damage. This is a valid concern of a highly ethical person.
I am not knocking it, but as a warning the passage you cited is of limited use because it does not tell us what signs to look for. I found your personal account of symptoms getting worse instead of better to be much more compelling. A narrow therapeutic index is commonplace in Parkinson's - it seems a bit too much of anything helpful is detrimental. I believe most of us are used to this.
As to off target effects I am not overly worried because this is a food product and because sulforaphane has been popularized by Rhonda Patrick for several years now. She has over 300,000 followers. If it did something awful it is likely we would have heard about it by now.
For what it is worth here is how I plan to proceed:
Use the cold tea extraction process from the paper I cited above to obtain approximately 60 mg of the sulforaphane moringin, from powdered moringa leaf. I will consume this daily. If my symptoms start to improve, I will decrease the dosage to a lower maintenance amount. I chose this instead of broccoli because no sprouting is necessary - just let the powdered leaf steep for 30 minutes in room temperature water..
Hi Park and everyone who's getting addicted to this remarkable adventure to the point of really trying to understand what might be going on. Let me say that I am still learning from my experiences and there are lots of unanswered questions for which we can only hope to get clear answers if we do well prepared tests. And then it's not so sure because we all have different types of PD at different stages. Some of you have indicated that you're taking the weekend to get up to speed, so let's give everyone time. And many of the important details can be found in the references. If you add all that up you're talking 1000 pages of incredible detail that's not easy to read and understand in one go. Of course, not every page is relevant, but some will become essential to defining how we proceed.
I'm also getting HU private messages that are pertinent to the discussion, so could I ask you at this stage to make these public when they are of general interest.
Some of you are making calculations related to dose and putting that into mg. I would like to point out that we should all be thinking in micromol (umol) , which is a measure of the number of molecules. In a perfect conversion, 1 umol of glucoraphanin is converted into 1 umol of sulforaphane. The weight in mg changes because the MW of glucoraphanin is 437 g/mol and that of sulforaphane is 177 g/mol, so 437 mg of glucoraphanin will produce a maximum of 177 mg of sulforaphane. But the conversion is of course far from perfect.
The isothyocyanate from Moringa has a MW of 311. Equally as important is the activity of the molecule to double the induction of NQO1. This is the CD value referred to in fig. 3, smaller CD means greater activity. The CD of sulforaphane is about 200 nM (nano mol), that of Moringin from Moringa is about 50 according to Fahey, ref 39 although we don't have independent confirmation of this number. This brings Moringa into the range of the cyano-enones shown in fig 3. Remember that a phase III trial for kidney disease of a cyano-enone CDDO -Me was stopped because patients suddenly dropped dead from heart attacks. Ref 51.
For this reason, I remain cautious of Moringa until we get more data.
One way we can do this is to monitor critical Nrf2 active tissues during our tests. A key control to avoid accidents should be on cardiovascular effects. I would like to suggest getting a list of checks done before starting : electrocardiogram, resting BP and pulse rate, fibrillation, cardio inflammation markers etc. It's then easy to monitor BP, fibrillation and pulse rate during the test with a home BP monitor. My experience was that too much sulforaphane caused increased pulse rate 30 mins after ingestion that lasted 2 hours.
If you take a look at the molecular structure shown in figure 1 you will see that
CDDO-me is NOT an isothiocyanate. Even worse, " CDDO-Me contains α,β-unsaturated carbonyl groups on rings A and C that can generate reversible adducts with the thiol groups of Cys residues in target proteins such as Keap1 and IκB kinase."
This is bad because carbonyl groups are highly reactive and are prone to creating adducts in any vulnerable molecule they encounter. Carbonyl groups react with amine groups as well as thiol groups. When molecules with carbonyl groups, or their adduct byproducts, get into circulation they can damage blood vessels and thereby cause cardiovascular disease. I wrote about this here: A Tale Of Two Studies Leads To A Deeper Understanding Of Cardiovascular Disease tinyurl.com/y6agl45j
Comparing structures, moringin bears no resemblance to CDDO-me. As stated, CDDO-me is not even an isothiocyanate. Moringin IS an isothiocyanate and has no carbonyl groups.
Of course, it is still important to affirmatively establish the safety of moringin. We have:
Review of the Safety and Efficacy of Moringa oleifera
"various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published,"
From the full paper, behind paywall:
"In summary, the previous human studies indicate that whole leaf powders of M.oleifera given orally exhibit significant anti-hyperglycemic, anti-dyslipidemic, and antioxidant effects in human subjects without production of adverse effects."
While there are no safety studies specifically of moringin, it comes from moringa leaf powder which was the subject of the above studies.
It is good to bring up potency because it is an important consideration in establishing dosing. Agree on the validity of using molar instead of weight measures.
I'm very pleased that you are taking such an interest in my comments and holding me to task. I know full well that CDDO-Me is not an isothyocyanate. It's a cyano-enone and works via a Michael reaction which is a much stronger electron transfer process than with isothyocyanates. The borrowed electron is transferred to the other side of the molecule!!! This is described in the article and there's a ref to the mechanism. They say it's reversible but I not so sure. One ref from memory talks of an Nrf2 spike when CDDO molecules are administered. The comparison I was making was about the NQO1 potency compared to Moringa. They are quite similar which is a concern. The extra potency of Moringa compared to sulforaphane is independent of the isothyocyanate group, but related to the other end of the molecule which probably binds to the basic amino acids of C151 and keeps it in place. If this makes it more selective to C151, that will be good but we don't know that yet. In my opinion sulforaphane is quite potent enough, but Moringa should be kept in mind for PwPs that may not respond to sulforaphane.
I'm very pleased to be having this discussion with you.
I too am pleased to be having this discussion and excited at the prospect of a disease modifying treatment.
In our other comment thread I have tentatively agreed that the protocol should use broccoli seed.
That said, I think the greater specificity and therefore the greater potency of moringin is a good thing. By your own account the mechanism of moringin specificity is different from that of CDDO. I do not believe that the off target and nonspecific adverse effects of exposed carbonyl groups of CDDO can be ignored as its cause of cardiovascular disease. I continue to believe that the similar on target potency of these two substances is not related to the off target adverse effects of CDDO.
I agree with holding moringin in reserve in case sulforaphane does not work out for one reason or another.
I do broccoli sprout smoothies and they seem to help with gut motility and also reflux. In addition to being an Nrf2 inducer, sulforaphane can inhibit H. pylori growth; I tested negative for H. pylori, but I expect sulforaphane can affect other microorganisms and I think dysbiosis is what causes my reflux. I also include raw cabbage as it seems to have beneficial effect also - not sure if it just adds extra myrosinase, or if cabbage has another isothiocyanate that has benefit (maybe an entourage effect), or maybe it's the indoles.
Don't know if it is helping my brain, but it should.
Sulforaphane also acts on TMPRSS2, which regulates the epithelial sodium channel (ENaC) (btw the name is a lie - it's not just found on epithelial cells):
You seem to know a lot about this and maybe your background is more suited to it than mine. Could I ask you to read through the scientific paper and look for errors or areas where it might be made more understandable?
I'm sure your sprout smoothies will do you some good but pls check to be sure they are truly broccoli, Brassica oleracea var. Italica and if you modify the preparation temperature to 60C you will optimise the conversion to sulforaphane.
I read over it quickly and it looks really good to me, but I will read it again more closely on Sunday. Tomorrow is the Defeat MSA Conference: msa-conference.org/agenda/
This is my seed source (I like that they test for the major pathogens):
Sorry, I still have not had a chance to sit down and give your article a good long read. I had a migraine and am now trying to catch up on chores. I will try in the next few days.
Why don't you just add a bit of grapefruit juice? So people who lack your knowledge and experience don't get the idea that naive experimentation is without risk? Consuming research competently is not for the untrained.
I appreciate what you say MarionP. The articles carry these warnings and that's why I don't give personal advice here and would like to see PwP forming groups with well informed members before taking any action. Supplements are however just as dangerous and freely on sale.
Well supplements have their risks, just like meds do...but also their legitimate uses...that's a should-be-known caveat emptor...whereas uninformed use or use that is coloured by making too many unwarranted assumptions on one's own is the real problem we can deal with, without throwing out the baby with the bathwater. A bigger risk, because it is not so obvious, or is hidden or implied, is assuming the information or message you receive is always good to use or apply at face value, uncritically; and not being critical of your own thinking and deciding process. Humans aren't built to efficiently examine their own selves for error as they are efficiently able to examine others. Have to watch out for that.
Ha, I wondered if you were there, Bass, maybe I missed your intro. You should have played us a few chords. Maybe next time.
I'm on an upward trajectory right now. Lets hope it lasts and that it can help others. You didn't see the slight left hand tremor, but it's gradually getting less. A pretty good advert for magic seeds, dont you think ? Pity they're so cheap. I'm not going to get rich on this.
Thanks to your priceless post, I am posting this video for the benefit of everyone. Gives a nice history and background about the subject matter. Once again with due regard to you and all those who are interested.
(it is a rather long video )
Jed Fahey, Sc.D. on Isothiocyanates, the Nrf2 Pathway, Moringa & Sulforaphane Supplementation
Eating a bowl full of broccoli sprouts, inspired by my good friend Cool Hand Wriga! A little Cesar dressing and it almost tastes palatable. Thanks for the advice! I think I speak for all of us when I say, We love you!!!
Next steps on Nrf2 activation therapy for Parkinson's disease.
I have thought long and hard about what to do next. I am currently writing a protocol about what I think will be the best way to proceed. I will not be posting the protocol here, but will send it those who sign up by email to receive it and agree to provide feedback to the whole group who have signed up. I may initially limit the number of participants in order to be able manage the responses and put a time limit on the feedback period. This feedback will be used to refine the protocol after discussion with the group. The protocol is therefore likely to change over time. That's why I will not post it here.
The protocol will be based on the identification of key symptoms that respond to the treatment.
Rather than trying to measure all PD symptoms, I have found that for me, some symptoms could be identified as early markers of Nrf2 acting on PD. In my case, the first marker I identified was "absolute urinary urgency " . This was the first symptom to be reduced and subsequently eliminated in my case. The feedback I'm looking for will be to list other early markers of Nrf2 activity identified by the group as a function of dose.
Other observations to be followed will be non-PD markers such as hypertension, pulse rate, general feeling of wellbeing or feeling off-colour, nausea etc. I hope that through discussion with you these will help us to find the useful dose range and the max dose not to be exceeded as the treatment progresses.
I will start a new post next week to launch this idea if there is sufficient agreement. Please don't email me until the launch date is announced.
I have now ordered my seeds from the italian provider and I am ready to start using them as soon as I receive them. I will be please to share my experiment with others and also hope to learn from others experimentation
I am using the water bath device recommended by John Morris above. Makes preparation really easy - just set for 60° C and the temperature is taken care of. I immerse a smaller jar with just water until it reaches temperature, then add the ground broccoli seed.
It may be better to try spouts as it has been reported that ‘broccoli sprouts contain 100 times as much glucoraphanin compared with the mature broccoli plant’ 🌺
Thank you. The reason I ask is because I have so little energy. Just reading all these scientific papers and posts of which I can only glean some basic understanding of what needs to be done in this extraction process exhausts me. Until we get more results, and a simple step by step receipe, I will do the fastest/easiest/safest thing and start growing, and eating tons of brocolli sprouts....
Here then, is the leading proponent on the use of Broccoli sprouts on how to ensure maximum bioavailability of sulforaphane from your sprouts and indeed all cruciferous vegetables
Fresh broccoli sprouts are going to be more potent than broccoli florets - raw, cooked, or cooked with a sprinkling of mustard seed powder at the dinner table.
And taste your ground mustard seeds or store bought mustard powder for potency. It should have a peppery/bitter taste🌺
Thanks for the new links. Ever since you last told me that the sprouts were more nutritious than the brocolli heads I've been net surfing on growing broccoli sprouts. When I stumbled on the word microgreens and PD, a whole new world opened up. I also found a great source for live grown broccoli sprouts, and until I can gett mail and get sprouts ( I'm not home) I've been eating about 2 cups of fresh raw brocolli heads with dip every day.
I hadn't thought of joining the extract group because I didn't think I could offer anything to it, also wouldn't be in a position for another 3-4 weeks to order the necessary equipment anyway. Is there a place on this forum where I can keep up with the discussions ? Thanks Caseyinsights for helping me out again !
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