Fisetin to Clear Senescent Cells

Joe smith Fairy8i8  Thats terrible information. If the content of products are so missleading then a link about the fake content must be spread. Do you have a link to Dr Rhonda Patrik so we can refer directly to her statement?

Staffan Olsson Maybe not so terrible - from a twitter tweet "

Dr. Rhonda Patrick

@foundmyfitness·

Apr 7, 2017

Avmacol has high concentration, broccomax has much less but is ok." 

Dr. Rhonda Patrick

@foundmyfitness

Dec 13, 2016

Broccoli sprouts are most concentrated form. Supps are not as good...avmacol is best one in U.S. Broccomax is decent."

From a February 2017 Joe Rogan podcast with Rhonda Patrick"

"Supplements: Hard to do right, only 1 in France  – Prostaphane with 70% bioavailability

• Avmocal has 40% bioavailability, Crucera only 10% bioavailability
• Broccomax isn’t great."

She said Broccomax is "ok" and "decent", and "isn't great".  The "isn't great" is concerning bioavailability".  Her favorite is Prostaphane but it is only available in France.  You can buy it using a shipping service because someone has either order it or go to a store where it is sold.  Then they ship it to you.  Those service fees are high. 

David H You are good at research 🙂 . Net net when you can get Avmacol for $24.95 for 60 capsules off Nutramax website and Broccomax on iherb for $18.87 as of today the choice at least for me is clear. I go with the readily available product used in multiple studies with good bioavailability vs isn't great.

Joe smith Thank you, I am a fan on Dr. Rhonda Patrick and am a member of FoundMyFitness. (I consider her my paid researcher - members join so we can benefit from her research.) Also I have a premium account with podcastnotes.org where I found the notes I cited from the Joe Rogan podcast.

Joe smith I agree. I would be very interested to know who did the testing and under what conditions. I would also be interested to see how it compares to broccoli sprouts, which she personally takes. The Broccomax bottle has testing claims, so it would be interesting to see if there is an independent study. 

Fairy8i8 Hi, see my follow up below. Basically the tests were done by Dr Jed Fahey lab at John Hopkins, #1 authority on the subject in the world. I didn't dig deeper into how they test and under what conditions. Perhaps  David H  as he is a member of FoundMyFitness could reach out to Dr Patrick and find out more? My understanding is  based on what she said is that broccoli sprouts are more effective/better. That said I'm curious too and we don't know for sure. It would be interesting to conduct the study of efficacy of broccoli sprouts vs Prostaphane/Avmacol. With respect of BroccoMax testing claims, let's find out more. Could you reach out to Jarrow and get the test(s) results?

David H I looked up the podcast. The Alpha Brain reference is linked to Onnit's Alpha Brain supplement. I would be cautious of relying on a competitor's testing as a reliable source for potency. I would take more stock in an independent lab. A PhD, especially a popularized one, citing a competitor's study doesn't make it more reliable. Note: I do enjoy her videos. It's true that Broccomax is less potent per capsule than some. However, I take several things that turn on the NRF2 pathway, and as the resveratrol researchers found, too much of a good thing is actually just toxic to the body. Sulphoraphane is a toxin that stimulates a certain response, but I used standard mouse to human scaling to get human equivalencies from the studies, so the amount you take depends on what you are looking at it doing, and also assumes you are not taking other things. I am taking other things, hence the conservative dose. I am looking for more of a nutritional boost effect than a drug effect from it, as I take it daily and have just started in the last month and want to see how I do. Ideally, I will feel no change. 

Joe smith Sorry, did not see this sooner. I found a 2.5 hour interview Dr. Patrick did with  with Fahey. 

https://youtu.be/Q0lBVCpq8jc

I haven't looked at it yet, but figured it would be interesting to some here.

Here is his FAQ page in response to all the questions he got from the interview.

http://chemoprotectioncenter.org/frequently-asked-questions/

I can see if Jarrow does batch testing. Even Fahey admits that potency levels will vary based on crop and growing conditions that naturally vary from year to year, even just buying and sprouting seeds.

Fairy8i8 You make two interesting points : 1) The more sometimes is not more effective 2) Interaction with the other supplements/drugs.

I think both of these have to do with the fact that we are trying to act on complex human organism. Hence there is a braking point. The drugs/interventions may be good by themselves with limitations of diminishing or even negative returns when saturation point is reached. This is even more complex and need to be adjusted when combined e.g. too much exercise may be counter productive where risk of injury goes up and benefits go down. The same with calorie restriction. When you combine two it is very beneficial but the amounts of exercise and calorie restriction need to be adjusted downward. Also clearly you wouldn't exercise and fast every day unless you want to die prematurely. We understand CR/exercise fairly well but much less so with respect of supplements/drugs and their combined effects. For instance, is it beneficial to combine fisetin (senolytics + NRF2 activator in strawberries) and broccoli (  sulforaphane NRF2 activator and senolytic) in megadoses at the same time? My gut feeling is that it will be counterproductive. Nature just didn't make humans to be so responsive with respect of such interventions like CR/exercise demonstrates. I'd bet everything on that eating 10 pounds of broccoli (or equivalent supplement) and 10 pound of strawberries (or equivalent supplement) per day won't make you live longer. Further it will most likely shorten your lifespan. Perhaps smaller doses are beneficial and/or rotating supplements to mimic mother nature and your specific epigenetics (i suspect that optimal doses of chemical compounds may be different depending on where you grew up and what you ate then) . Basically personalized medicine which starts with personalized testing.

Joe smith The only problem is that it takes 2 capsule of Avmacol to get at least the same listed amount as Broccomax. I looked a little deeper, and Broccomax used to not have myrosinase, so it used to be much less effective. They now have it. Also, Avmocol made their to suit Fahey's needs in that it is a tablet that can be crushed, which was beneficial for his research on autistic children who couldn't swallow a pill. Broccomax has recently been used in clinical trials and is currently the product of choice for a trial in prostate cancer patients in the US. Fahey never directly said that Broccomax didn't have it's claimed amount to Patrick, but insinuated it wasn't the best to her. The purity comment was an add on in podcast discussion and wasn't necessarily directed at Broccomax. They have since changed their supplier and how it's formulated to include myrosinase. Also, Fahey supplies broccoli seeds and was in the business. He has since had to distance himself from executive decisions of his company because of conflicts of interest, but he does hold a financial stake. Fahey did test various products, but I do not think he will give out the data or make a specific statement because of the legal ramifications. 

Fairy8i8 Thank you for your effort in bringing clarity to this issue. it looks like broccomax after all is an ok product. I have been looking for Avmacol on sites here in Europe but I have not found it.  Broccomax is much easier to buy.

Staffan Olsson Glad to hear you can get Broccomax, although if you are ever in France, Prostaphane could be even better.

Joe smith I agree with you on combining things. Fahey did do a study comparing sulphoraphane with curcumin, but I haven't looked at it yet. High doses of curcumin have some senolytic effects, but I do not know the dose used in the study or the results. Apparently many things activate the Nrf2 pathway, like even the omega-3 fish oil I take. Initially, I thought I was taking things that worked on different pathways, but there is a lot of crossover. One Broccomax has about as much sulphoraphane as 100mg of broccoli sprouts. I take as much fish oil as is in about a serving or two of salmon. I'm comfortable with those amounts, as it's comparable to food levels, but more convenient for me. It's hard to know the best route.

My dad (70 years old) got deep vein thrombosis. His doctor couldn't figure why because he has an awesome cardiovascular system. However, he was taking high doses of Vitamin K to get the various forms like MK-4 amd MK-7- thought to have no known upper limit- and guess what blood thinners block? Vitamin K uptake in the body. Here he thought he was doing something good for his body getting a variety of Vitamin K and improving calcium absorption and reducing calcification of blood vessels, even promoted by the likes of Dr. Patrick, and his doctor thinks it contributed to his deep vein thrombosis. Now he is on blood thinners for a year and gets terrible headaches from them. When self experimenting, you have to be comfortable with significant risk, and sometimes it may indeed cause more health problems than it fixes. That's why I appreciate this forum- people looking out for me on a possibly bad product, shared experience. I don't discuss this much with people around me because I know most won't bother to inform themselves and understand that there is some risk involved. That said, trials in children are very difficult to get approved, so I feel much more comfortable taking a product that has shown to improve many children's lives.

Fairy8i8 Joe smith I lookad at that interview some time ago and I remember that Fayey mentioned that when broccoli sprouts (or supplements) activate the Nrf2 pathway the pathway will stay activated for 48 or 72 hours.  When I learned that, I started to take sprouts or supplements intermittently every two or every third day.

Staffan Olsson Thanks for reminding me! I only take 1 Broccomax capsule a day, which is a low dose (autistic children were given more daily than me), so I won't be in a hurry the increase my dose. I think Fisetin has a much faster half life, if I remember correctly.

Fairy8i8 It sounds like we came to similar realization with respect of supplements and their interactions. They can be very useful but you need to be very cautious and conservative while applying sound overall principles like homeostasis. Also as you pointed out optimal dosing for some supplements is unclear we do know a bit about D3 optimal dosage curve but clearly not so much about K2. Interestingly that you brought up K2 . I have Innovixlabs K2 (MK4+MK7) 750% daily RDA. The last bottle I finished, I put it aside a couple of weeks ago to take a break from over supplementation.

Staffan Olsson Very useful piece of information. I think we should put more precision and engineering approach to the supplementation if we ever want to achieve repeatable and predictable results. A following spreadsheet, could be a start, showing:

1. compound (e.g. fisetin)

2. What we are trying to achieve: short , medium , long term

3. human activation amount

4. half/time and/or how long pathway stays activated

5. Interaction(s) with other compounds

6. Any advice on what to do and not to do when taking the supplement: e.g. take it with olive oil for better absorption, don't take it a day before or after going to gym, etc.   

7. Frequency of supplementation: e.g. once a week, supplementation cycle 

8. Side effects, things to watch out, etc.

9. What to do if you encounter such side effect e.g. stop supplementation for 2 weeks

Feel free to contribute. If you guys think it make sense, I will set it up on google docs so we can all edit it and contribute as needed.

Fairy8i8 Joe smith

yes the half life of fisetin is short. But its effects are long lasting because the effect of the "fisetin punch" produce a structural change in the human body by knocking out senescent cells. A bit like when surgery or the editing of genes are done there are long lasting effects of those kinds of procedures.

And yes, it is very logical that we should use different strategies when it comes to finding the optimal dosing for different purposes. Like when it comes to using broccoli extracts for treating autism or when we use the extract for improved general health and as a preventive measure.

There are many questions that we cant find answers to in our lifetimes so we have to rely on the research at hand and apply concepts of physiology. I will try to locate the segment in the interview with Fahey were Dr Patrick and him tlk about the long lastning effecs by broccoli extracts on the Nrf2 pathway

Fairy8i8 I read this post several times because one point confused me.  You stated, "However, he was taking high doses of Vitamin K to get the various forms like MK-4 amd MK-7- thought to have no known upper limit- and guess what blood thinners block? Vitamin K uptake in the body. "  Did you mean he was taking blood thinners at the same time he was taking the vitamin K2 (MK-4 and MK-7) or only after he experienced the DVT?  Was he taking any doctor prescribed medicines during the time he was taking the high dose vitamine K2( MK-4 and MK-7)?  

I've been taking high dose vitamin K2 + high dose vitamin D3 for over two years with no bad side effects, but I want to be aware of potential bad side effects.    

Jay Orman He wasn't on blood thinners at all before getting deep vein thrombosis. I was saying that blood thinners work by blocking vitamin K. He got deep vein thrombosis- a blood clot. His doctor was surprised that he got one. He has chronic fatigue syndrome, but takes good care of himself. He has excellent cardiac stress tests results and is a healthy weight, but he does have elevated cholesterol that he manages with careful diet. The only thing the doctor thought could be a factor in his getting DVT was the very high vitamin K and sitting in a car driving across country. He had to go on blood thinners for a year afterwards to get rid of the clot, and the doctor told him to stop taking his vitamin K supplement because the blood thinners work by blocking the Vitamin K receptors (which means that part of Vitamin K's action in the body is to assist in clotting). 

I would say to just watch for clot symptoms. Also, get up and move around frequently and if you are traveling, take frequent stops to move around. 

I get a ton of Vitamin K through diet, so I have never felt the need to supplement.

Jay Orman Also, he us was not taking any prescription medications during the time he took vitamin K. He did take the blood thinners for a year after DVT, but is now off them. I don't think he will supplement with Vitamin K again, though, and he has an alarm on his watch to make sure he gets up and moves around frequently because he is the type to get lost researching something on the computer and sit all day.

Fairy8i8 Thanks very much for both clear and precise answers.  I suspect inactivity and sitting may play an important role in DVT.  The K2, maybe?  I'll investigate further.  It reminds me of the death of Tim Russert a few years ago after he passed a stress test, but was sitting for an extended period on a long flight.  Very unfortunate.