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Taking Breaks from Supplements (Fusion vs Fission, etc)

supplements antioxidants frequency

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#1 Nate-2004

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Posted 30 May 2016 - 04:01 PM


I've read cogent arguments  here and elsewhere  for why you shouldn't take C60 every day and why consuming antioxidants all the time can be a bad thing. Aubrey de Grey also states that in some cases, such as AGEs, antioxidants actually make things worse and that trying to mess with free radicals is a futile approach that didn't work. That lead to research into AGE-breakers. There's also the argument that mitochondrial fission is just as important as fusion. I've read that too much vitamin E can actually accelerate the oxidation of LDL.  I've also read that your body benefits from oxidative stress as much as it benefits from antioxidants. That makes things really confusing for me.

 

To get to the point by asking an example question:

 

My stack includes C60OO, NR, Pterostilbene w/Resveratrol and honokiol.  Should I be taking these things continuously? I'm not asking for a prescription to take any particular thing, but rather in the context of this question regarding oxidation, in the context of what we understand now and my confusion above, what's the best way to go about it?

 

What's everybody's opinion at this point on antioxidants? Should people take breaks from NR and resveratrol and these other supps? Should they only take them on certain days of the week? What's the consensus? Is there any?


Edited by Nate-2004, 30 May 2016 - 04:11 PM.


#2 aconita

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Posted 30 May 2016 - 10:30 PM

C60oo everyday is a waste and possibly not a good idea, once a week seems way better since is a lipophilic compound and stays where it should (mitochondrial membranes) for quite a long time.

 

Free radicals are there for a reason, oxygen oxidize but without you would die right away...is really God that stupid?

 

Things are a bit more complex than good or bad, black or white...it is more a matter of balance than just trying to enhance or suppress.

 

Bad bacteria are bad but without any contact with them the first little naughty one we met will kill us, is a sterile environment good for us?

 

No, absolutely it isn't.

 

Free radicals seems bad, would we be better off scavenging them all with any sort of supplements?

 

I seriously doubt.

 

If you are unhealthy or old maybe your capabilities to keep things in balance with free radicals are diminished and some antioxidant supplement might help, but if you are healthy and young I seriously doubt overdoing with supplements will be smart, doesn't matter how fantastic they do look on paper.

 

 

 

 


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#3 Tom Andre F. (ex shinobi)

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Posted 30 May 2016 - 10:56 PM

Im not sure what you claim is science supported and Im not sure the importance of ROS.. already over generated by aging.. actually I would say more the importance to generate ROS in healthy cells more than their inner role. The good ones are just by product of mitochondria. And anyway.. you just cant even remove a fraction of ROS by using antioxidant.. its just not possible. To really face them you need endogen antioxidant (GSH, CAT, SOD.. that can trap million of free radical per ms instead of 1 for 1 for basic food antioxidants) such the one that young people express much more than older person. So this answer your question..

 

And regarding vitamin E its more their quinone form that makes problem it seems



#4 aconita

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Posted 30 May 2016 - 11:10 PM

We are talking about C60oo (among others) which seems to work a bit different than food antioxidant 1 for 1.

 

Anyway food antioxidants actually seems to do something since, for example, they do inhibit the super compensation induced by training, a proposed explanation is that the oxidative stress caused by training is taken care of by the antioxidants with no need for the organism to adapt. 

 

 

 

 



#5 Tom Andre F. (ex shinobi)

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Posted 30 May 2016 - 11:18 PM

We are talking about C60oo (among others) which seems to work a bit different than food antioxidant 1 for 1.

 

Anyway food antioxidants actually seems to do something since, for example, they do inhibit the super compensation induced by training, a proposed explanation is that the oxidative stress caused by training is taken care of by the antioxidants with no need for the organism to adapt. 

 

C60 is said to be a SOD like mimetics isnt ?

 

we have SOD in many foods... and yeah I also support an antioxidant rich diet


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#6 gamesguru

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Posted 30 May 2016 - 11:29 PM

c60 I would cycle, but honokiol, lipophobic, a modest dose should be safe for near continuous use.

there's a lot to be said for glycation blockers, both natural and synthetic

whether the oxidant effects crop up at higher doses depends on the supplement, many have a biphasic curve, such as curcumin and selenium. even piracetam has oxidative effects above a certain threshold. do all antioxidants behave like a double edged sword? probly not always, but it may be hard to find a counterexample.
a repeating theme here may be that as the dose is increased by 10x or more, that a new spectrum of effects become active... often including undesirable effects.

as mentioned, vitamin e may diminish in return at high doses for the reason of increasing quinones
"quinones are oxidants and electrophiles"

#7 Nate-2004

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Posted 31 May 2016 - 02:30 AM

We are talking about C60oo (among others) which seems to work a bit different than food antioxidant 1 for 1.

 

Anyway food antioxidants actually seems to do something since, for example, they do inhibit the super compensation induced by training, a proposed explanation is that the oxidative stress caused by training is taken care of by the antioxidants with no need for the organism to adapt. 

 

Yeah I'm not talking about just C60OO. Though it helps to know which ones to cycle based on this hypothesis and which ones not to. Not sure what you mean by 1 for 1.

 

I'm not sure what you claim is science supported and Im not sure the importance of ROS.. already over generated by aging.. 

 

I assume you mean reactive oxygen species?

 

 

C60 is said to be a SOD like mimetics isn't?

 

we have SOD in many foods... and yeah I also support an antioxidant rich diet

 

I Googled SOD but I get grass and the old band Stormtroopers of Death. LOL But then I found this and this. So now I understand a little bit.


Edited by Nate-2004, 31 May 2016 - 03:04 AM.


#8 Nate-2004

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Posted 31 May 2016 - 02:38 AM

c60 I would cycle, but honokiol, lipophobic, a modest dose should be safe for near continuous use.

there's a lot to be said for glycation blockers, both natural and synthetic

whether the oxidant effects crop up at higher doses depends on the supplement, many have a biphasic curve, such as curcumin and selenium. even piracetam has oxidative effects above a certain threshold. do all antioxidants behave like a double edged sword? probly not always, but it may be hard to find a counterexample.
a repeating theme here may be that as the dose is increased by 10x or more, that a new spectrum of effects become active... often including undesirable effects.

as mentioned, vitamin e may diminish in return at high doses for the reason of increasing quinones
"quinones are oxidants and electrophiles"

 

Thanks. This video here from this thread however seems to indicate that the reason they were limiting dosage in the Baati experiment was because they thought the rats would die from the lipids in olive oil, there are apparently some studies being run independently with 200 rats per group, some of whom will be dosed continuously.  That thread linked is also talking about how "megadosing" C60 may be bad because a similar "SOD" caused a 50% decrease in lifespan at high doses. I don't know what they consider to be a "megadose" however. What is megadosing for a human compared to what the rats were receiving? How many days in a row of 14mg is megadosing? If I dosed continuously for 5 days in a row at 14mg per day and then stopped for 2 weeks to recycle, would that be megadosing?  

 

Lipophobic?

 

Glycation blocker? Something that blocks AGEs? I didn't think we knew how to do that yet or knew how to break them down either. I assumed researchers are still looking for that.

 

I take it that supps like pterostilbene, honokiol and NR are more SIRT1/3 activators and fuel than they are antioxidants? 


Edited by Nate-2004, 31 May 2016 - 03:37 AM.


#9 normalizing

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Posted 31 May 2016 - 03:36 AM

there are quite a few AGE blockers if you check on wikipedia alone but im pretty sure a lot of research has been done and likely they have found more and might be available in medical journals. one that has very good literature behind it is easy to obtain and cheap, its benfotiamine.


Edited by normalizing, 31 May 2016 - 03:37 AM.

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#10 gamesguru

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Posted 31 May 2016 - 01:53 PM

generally to convert rat mg/kg to human, divide by 6.

the lipophobic vs lipophilic but was touched on by aconita, and he explained his idea on why megaadosing c60 daily may be bad (it accumulates in mitochondrial membranes and begins to interfere with basic cellular respiration and other "diffusion" processes needing oxygen or radicals)

honokiol also affects gaba. and safer for continued use because theyre mostly lipophobic and don't accumulate in the mitochondrial membranes, things that accumulate there take a long time to get broken down, and can interfere long-term with membrane activity. the water soluble compounds in food are generally cleared out much faster, and dont pose this sort of concern.

Edited by gamesguru, 31 May 2016 - 01:58 PM.

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#11 Nate-2004

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Posted 31 May 2016 - 06:34 PM

there are quite a few AGE blockers if you check on wikipedia alone but im pretty sure a lot of research has been done and likely they have found more and might be available in medical journals. one that has very good literature behind it is easy to obtain and cheap, its benfotiamine.

 

I'm not sure that's the case.

 

generally to convert rat mg/kg to human, divide by 6

 

So for me that's 119mg/6 = 19mg. I've been taking 7-14mg for 7 days in a row, I plan to go with 14mg for 5 days in a row with one or two week breaks. I'm not sure if that counts as megadosing but I have trouble in light of the video and thread I linked determining what would be considered megadosing.

 

the lipophobic vs lipophilic but was touched on by aconita, and he explained his idea on why megaadosing c60 daily may be bad (it accumulates in mitochondrial membranes and begins to interfere with basic cellular respiration and other "diffusion" processes needing oxygen or radicals)

 

Do you have references? According to Fathi Moussa C60 is completely non-toxic and the reasoning behind the breaks in the mouse studies. The reasoning behind the dosing was about the olive oil lipids. 

 

Some people decided like the mouse trials they'd stop dosing altogether after 6 months, following the exact methods in the trial. Unfortunately they were off by 17.5 years. 6 months in a rat's life is about 18 years in a human life. By that same reasoning, two weeks apart in that sense is almost a year.


Edited by Nate-2004, 31 May 2016 - 06:42 PM.


#12 normalizing

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Posted 31 May 2016 - 09:32 PM

nate 2004 did you even go through the whole thread on benfotiamine? i used to check it years ago (its quite outdated now) and conclusion was that it works for AGEs and diebetics have been taking it for many years with actual positive results so im not sure how linking to a thread you didnt even bother researching thoroughly makes benfotiamine automatically a bad thing to take


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#13 aconita

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Posted 31 May 2016 - 09:38 PM

Nobody knows what a normal C60oo dosing would be, including Fathi Moussa.

 

Fathi Moussa might claim that with his protocol and those mouses he wasn't able to detect any sign of toxicity and since the average life span greatly improved the claim is very reasonable, that's all.

 

To claim that C60oo is completely non-toxic in humans at any dosage is totally out of context and I doubt Fathi Moussa intention was to claim such a thing.

 

 

 


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#14 normalizing

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Posted 01 June 2016 - 02:17 AM

i think this guy needs cognitive stack more than anything, he just managed to do search and find one single outdated thread on benfotiamine and trashed it without even going through in it with detail and examination. bro, you need something much bigger than what you are aiming at in this thread sorry maybe you are still a teenager though which there is still hope


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#15 Nate-2004

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Posted 01 June 2016 - 02:39 AM

I read through the entire thread, I even linked you to the end of the thread. I did not see a single good argument for using benfotiamine and saw many solid arguments against. The thread may be old but nobody's updated it with anything convincing.



#16 normalizing

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Posted 01 June 2016 - 03:04 AM

well i guess that showed me. you are looking for the miracle herb, good luck young fellow


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#17 Skyguy2005

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Posted 01 June 2016 - 04:16 PM

In my opinion everything herbal is worth cycling off occasionally. The only question would be how much. Also, some things have very sharp drop-off like CoQ10, Vitamin D, I would argue that something like CoQ10 is simply a vitamin in all but name (vitaminish?). The more vitaminish it is, the simpler this would be. My consideration of CoQ10 as a vitamin is basically because of this cliff-like drop-off in feeling from taking it, similar to vitamin D. 

 

The only references I can provide are: Skyguy2005. Sorry. 


Edited by Skyguy2005, 01 June 2016 - 04:40 PM.

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#18 gamesguru

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Posted 01 June 2016 - 04:28 PM

Telmisartan/micardis
it has antihypertensive and antiglycation properties

Edited by gamesguru, 01 June 2016 - 04:30 PM.

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#19 Nate-2004

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Posted 01 June 2016 - 07:17 PM

In my opinion everything herbal is worth cycling off occasionally. The only question would be how much. Also, some things have very sharp drop-off like CoQ10, Vitamin D, I would argue that something like CoQ10 is simply a vitamin in all but name (vitaminish?). The more vitaminish it is, the simpler this would be. My consideration of CoQ10 as a vitamin is basically because of this cliff-like drop-off in feeling from taking it, similar to vitamin D. 

 

The only references I can provide are: Skyguy2005. Sorry. 

 

I'm quite skeptical about CoQ10 given all the debunking of claims around its usefulness. I recall reading into it a while back before deciding not to waste money on it. There was a lot of hype about it years ago and then a ton of research was done showing it did absolutely nothing.

 

WebMD gives it a C in evidence around most of the claims and a B with blood pressure conditions. The only A it gets is in very rare conditions of deficiency. NIH says the evidence is limited and inconclusive.

 

This guy gives it a little more credit for heart conditions while this guy blasts it as a money scam.  As experimental as I like to be, I prefer strong evidence before I spend any money. I'm with Tim Minchin on alternative medicine. "What do we call alternative medicine that works? We just call it medicine."

 

Nearly every meta review of the stuff says it's not worth it unless you're on statin drugs or beta blockers.  I take beta blockers occasionally for essential tremor but not enough to warrant spending money on this.

 

 

 

Telmisartan/micardis
it has antihypertensive and antiglycation properties

 

I'll have to look into that thanks. I'm only skeptical about the anti-glycation stuff because the latest news from SENS is that there's just no funding for research on AGE-breakers or anything of the sort. They only cited one project to develop an AGE-breaking drug and also mention every kind of attempt they made in this process and none of them were successful once human trials began. They could be in the dark about these other alternatives but I doubt it. If there were something out there that works I imagine they'd be on it.  If it works in rats, the likelihood of it working in humans is slim, because from what I understand, rats don't have the same kind of glucosepane based AGEs that we do.

 

This thread has gone way off topic though, but the question I had has been answered for the most part. Cycling is useful for C60OO but the idea that some ROS is needed or that we can be too antioxidant has little supporting evidence. The exception being Vitamin E and Beta Carotene. Though this meta analysis concludes otherwise.  I take vitamin A but only once every few days. My vitamin E comes from almonds and almond milk. My beta-carotene, or carotenoids in general will come from actual carrots, tomatoes and stuff. 


Edited by Nate-2004, 01 June 2016 - 07:31 PM.

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#20 gamesguru

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Posted 02 June 2016 - 02:15 AM

the idea that some ROS is needed or that we can be too antioxidant has little supporting evidence.

the whole universe is dark to the blind man...

"The effect of the mitochondrial membrane on the oxygen supply to the interior of mitochondria was analyzed with a cylinder model of diffusion... The predicted oxygen gradient suggests a non-uniform distribution of oxygen in the myocardial cell and may be of importance in understanding the relationship between oxygen supply and myocardial function in hypoxia."


"Due to the potential beneficial role of ROS demonstrated by several lines of research, ranging from their role as signaling molecules [2] to the more unexpected role in improvement of certain cancers [3], the term “redox regulation” might prove to be more accurate than “redox stress”; there have been even some situations where antioxidants are described to be “bad” [4]. However, the term “redox stress” is more commonly used."
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#21 niner

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Posted 02 June 2016 - 04:47 AM

An AGE blocker is not the same thing as an AGE breaker.  The blocker stops it from forming, the breaker cleaves it after it has formed.  There are lots of compounds that interfere with AGE formation, nothing that breaks glucosepane at this time.


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#22 Nate-2004

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Posted 02 June 2016 - 05:37 AM

An AGE blocker is not the same thing as an AGE breaker.  The blocker stops it from forming, the breaker cleaves it after it has formed.  There are lots of compounds that interfere with AGE formation, nothing that breaks glucosepane at this time.

 

Do you think telmisartan or benfotiamine have any strong evidence for blocking AGEs from forming? If so how do they block AGEs? Do they interfere with crosslinks? 



#23 normalizing

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Posted 02 June 2016 - 04:13 PM

carnosine is AGE blocker or breaker, not sure, but it has been mentioned here and on various article i have seen in the past years. maybe check on this one



#24 gamesguru

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Posted 02 June 2016 - 05:10 PM

New Generation AGE Blockers Inhibit Final Glycation Reactions and Prevent AGE Formation

A new class of anti-aging supplements, called AGE blockers, works by stopping the glycation chain reaction started by glucose metabolism just prior to the formation of the AGE molecules.

Although stopping glycation reactions at the Advanced Stage does not break up cross-links that have already formed, it does limit the formation and accumulation of AGEs throughout the body without interfering with normal bodily function.

There are a few drugs that are in various stages of approval that are purported to actually be cross-link breakers. One such drug, called ALT 711, appears to do just that but may not be available on the market for some time. Another drug, aminoguanidine, is also in the midst of drug approval trials, but it has only been shown to be an inhibitor of AGE, not a cross-link breaker.

An array of substances have been tested for effectiveness at preventing AGE formation. Many of those tested work well in vitro (in the laboratory test tube) but fail in vivo (in living organisms).

#25 Nate-2004

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Posted 02 June 2016 - 05:25 PM

I should probably change the thread title to AGE blockers lol.  

 

I looked into carnosine. The primary concern with that is the incredibly short half life.

 

ALT711 was Alagebrium. It will never be on the market as it did not translate to humans. It was talked about in Aubrey de Grey's 2008 book on Ending Aging. It also required users to take it continuously. I linked above to the article on that.

 

 



#26 Graviton

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Posted 24 November 2016 - 07:18 AM

I just found this thread. I am not sure which reference you read for "Aubrey de Grey also states that in some cases, such as AGEs, antioxidants actually make things worse and that trying to mess with free radicals is a futile approach that didn't work".

Can you link for the above reference you read?

 

Most antioxidants in plants act as pro-oxidants that lead to a hormetic effect, which results in the net beneficial effect by inducing antioxidant enzymes in the body. In this context, I would like to clarify the source for "consuming antioxidants all the time can be a bad thing". Which antioxidants do you mean?

 

Currently, I would be more interested in how c60oo works in the combination of other hormetic supplements in regards to whether they share the same pathway or choose different pathways.

 



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#27 RWhigham

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Posted 25 November 2016 - 12:37 AM

This article presents evidence that AGE-preventers largely act by chelating metals (such as iron and copper) which are implicated in AGE formation.  https://www.ncbi.nlm...les/PMC3282805/ "Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications"

It talks quite a bit about benfotiamine.

 

Table 1 "IC50 of various compounds that inhibit metal-catalyzed oxidation of ascorbate"

https://www.ncbi.nlm...805_549tbl1.jpg 

 

This table shows that carnosine inhibits at a far lower concentration than everything else on the list.

(I believe there is a typo in the text where it says otherwise.)

 

If you accept this article, then reducing iron and copper will reduce AGE formation.

 

I've been drinking distilled water for many years to avoid the iron, copper, lead, etc from the plumbing, and run off of fire fighting chemicals into mountain reservoirs, and now fracking.  My ferritin is 56 ng/ml..


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