144 replies to this topic

[mikey]

After reading the many intelligent and complicated considerations about dosing I've decided to maintain dosing at 8 - 16 mg/day and wait until the study that Fathi said was in progress - where they were to dose the rats continuously - and see how long they live concludes.

The idea being taken from the first study that they didn't know if the rats would live much, much longer if they had kept dosing them daily rather than decreasing dosing frequency.

I'm betting on the consistent high dose daily dosing as being most successful at increasing lifespan.

Like vitamins and minerals, take an optimal dose every day and receive optimal benefits.

That's my bet. Let's see how that study does as well as seeing how I do taking a 8-16 mg a day every day consistently.

So far, I've had two major scars fade and my hair, even on the sides, which were quite white, is darkening.

I have startling before and after photos, which I've been reluctant to post because of all the variables that render the improvements as inconclusive - and then knowing how some of the posters on Longecity can be caustic, nasty and mean-spirited.

Aren't moderators supposed to keep the nasty stuff to a minimum and keep the "forward" idealism happening?

Edited by mikey, 22 November 2012 - 08:40 AM.

[niner]

After reading the many intelligent and complicated considerations about dosing I've decided to maintain dosing at 8 - 16 mg/day and wait until the study that Fathi said was in progress - where they were to dose the rats continuously - and see how long they live concludes.

That trial isn't in progress, it's only been proposed. I thought Moussa was pushing for a replication of his dosing protocol; at least we've seen it work once. My own choice would be to use a similar intermittent schedule, but continue it throughout the life of the animal. If I were to devote as many animals to the study as they're talking about (I think 200 in each of three sites is the norm for the ITP) then I'd want to use some of them as part of a dose-response study. With an effect as large as Moussa saw, I think it's frankly idiotic to use 600 animals on the exact same protocol, thus ensuring that you learn the minimum amount.

The idea being taken from the first study that they didn't know if the rats would live much, much longer if they had kept dosing them daily rather than decreasing dosing frequency.

I'm betting on the consistent high dose daily dosing as being most successful at increasing lifespan.

Like vitamins and minerals, take an optimal dose every day and receive optimal benefits.

That's my bet. Let's see how that study does as well as seeing how I do taking a 8-16 mg a day every day consistently.

Well, ok, but it's an experiment. There's no way at this point to know whether it's better or worse to do continuous versus intermittent dosing, but all the evidence (Baati's paper) is for intermittent, and there's my hypothetical concern...

So far, I've had two major scars fade and my hair, even on the sides, which were quite white, is darkening.

I have startling before and after photos, which I've been reluctant to post because of all the variables that render the improvements as inconclusive - and then knowing how some of the posters on Longecity can be caustic, nasty and mean-spirited.

Aren't moderators supposed to keep the nasty stuff to a minimum and keep the "forward" idealism happening?

Well, I'd certainly like to see pics, particularly if they are in focus and are well and identically lit. It is astonishing to me how many people try to draw conclusions from blurry cell phone pics with wildly different lighting conditions.

Moderators have several different needles to thread. We try to keep nastiness to a minimum, particularly of the ad hominem variety. However, we also try to keep the scientific accuracy of the forums from falling too far into the gutter. We also try to look out for the safety of the large numbers of people who read these forums, most of whom aren't posting.

[mikey]

After reading the many intelligent and complicated considerations about dosing I've decided to maintain dosing at 8 - 16 mg/day and wait until the study that Fathi said was in progress - where they were to dose the rats continuously - and see how long they live concludes.

That trial isn't in progress, it's only been proposed. I thought Moussa was pushing for a replication of his dosing protocol; at least we've seen it work once. My own choice would be to use a similar intermittent schedule, but continue it throughout the life of the animal. If I were to devote as many animals to the study as they're talking about (I think 200 in each of three sites is the norm for the ITP) then I'd want to use some of them as part of a dose-response study. With an effect as large as Moussa saw, I think it's frankly idiotic to use 600 animals on the exact same protocol, thus ensuring that you learn the minimum amount.

The idea being taken from the first study that they didn't know if the rats would live much, much longer if they had kept dosing them daily rather than decreasing dosing frequency.

I'm betting on the consistent high dose daily dosing as being most successful at increasing lifespan.

Like vitamins and minerals, take an optimal dose every day and receive optimal benefits.

That's my bet. Let's see how that study does as well as seeing how I do taking a 8-16 mg a day every day consistently.

Well, ok, but it's an experiment. There's no way at this point to know whether it's better or worse to do continuous versus intermittent dosing, but all the evidence (Baati's paper) is for intermittent, and there's my hypothetical concern...

So far, I've had two major scars fade and my hair, even on the sides, which were quite white, is darkening.

I have startling before and after photos, which I've been reluctant to post because of all the variables that render the improvements as inconclusive - and then knowing how some of the posters on Longecity can be caustic, nasty and mean-spirited.

Aren't moderators supposed to keep the nasty stuff to a minimum and keep the "forward" idealism happening?

Well, I'd certainly like to see pics, particularly if they are in focus and are well and identically lit. It is astonishing to me how many people try to draw conclusions from blurry cell phone pics with wildly different lighting conditions.

Moderators have several different needles to thread. We try to keep nastiness to a minimum, particularly of the ad hominem variety. However, we also try to keep the scientific accuracy of the forums from falling too far into the gutter. We also try to look out for the safety of the large numbers of people who read these forums, most of whom aren't posting.

Well, the study authors posed the question that results might have been even better if dosing was maintained. So, it seems that they were pointing at what they thought might produce more optimal effects -- even longer lifespans by giving it to the rats ongoing.

They did not make a statement indicating that there was a benefit to reducing dosing frequency. He said that the reason they reduced the frequency of dosing is because the rats would experience lipid overload, too much olive oil.

That notion that there is a reason not to dose continuously has only come up on this site, and I find it to be a curiously questionable hypothesis that is based on the notion that C60 might cause some kind of toxicity to mitochondria, which is contrary to what Dr. Moussa said.

He explicitly said there is no toxicity, "This is absolutely sure." And he said this after studying fullerenes for 18 years.

What I take away from the study - and Fathi's interview - is that C60 is just plain good for you.

Logically if something is non-toxic and good for you it would seem best to take it every day for optimum life-extension effects and mitochondrial protection.

I, for one, have not perceived any negative effects taking it every day, only beneficial effects.

If there is anyone who has a hypothesis that is grounded in independent science - not someone's personal anecdote about how they feel, please weigh in, because so far all I've seen are individuals making statements that contradict Dr. Moussa's statement that C60 simply not toxic.

[niner]

Well, the study authors posed the question that results might have been even better if dosing was maintained. So, it seems that they were pointing at what they thought might produce more optimal effects -- even longer lifespans by giving it to the rats ongoing.

I completely agree with them. However, they never looked at daily dosing, only intermittent. I'm arguing for intermittent dosing that continues throughout the life of the animal.

They did not make a statement indicating that there was a benefit to reducing dosing frequency. He said that the reason they reduced the frequency of dosing is because the rats would experience lipid overload, too much olive oil.

That notion that there is a reason not to dose continuously has only come up on this site, and I find it to be a curiously questionable hypothesis that is based on the notion that C60 might cause some kind of toxicity to mitochondria, which is contrary to what Dr. Moussa said.

No, they didn't, but they might have stumbled on the ideal protocol. Maybe bigger doses are better, or maybe smaller. Maybe more frequent dosing is better. At this point, we have no evidence either way. Since this is the only site on the internet where c60 is being discussed in an ongoing and significant way, I'm not surprised it's the only place my intermittent dosing hypothesis has come up. Or maybe you meant that no one else thinks it's worth worrying about... Anyway, you are misunderstanding the hypothesis. I'm not saying that c60 harms mitochondria. On the contrary, it helps mitochondria withstand ROS. The problem is that this may protect cancer cells from something that should be making them go apoptotic.

He explicitly said there is no toxicity, "This is absolutely sure." And he said this after studying fullerenes for 18 years.

What I take away from the study - and Fathi's interview - is that C60 is just plain good for you.

Hmm. Sounds a little bit like boosterism. Has he done reproductive and developmental tox tests? Any tests whatsoever in humans?

Logically if something is non-toxic and good for you it would seem best to take it every day for optimum life-extension effects and mitochondrial protection.

I, for one, have not perceived any negative effects taking it every day, only beneficial effects.

If there is anyone who has a hypothesis that is grounded in independent science - not someone's personal anecdote about how they feel, please weigh in, because so far all I've seen are individuals making statements that contradict Dr. Moussa's statement that C60 simply not toxic.

There's not much independent science out there regarding c60-oo in humans. None, in fact, as far as published work goes. If we aren't willing to deal with people's experiences and hypotheses, then there's not much to talk about.

Dr. Moussa seems like a good researcher, but I just don't buy that we know for certain that c60-oo has no toxicities whatsoever. We're messing with some very fundamental free radical chemistry that our bodies use in a variety of ways. Without doing a LOT of experiments in humans, there's just no way that anyone can claim it is utterly harmless.

[Kevnzworld]

After reading the various opinions about dosing regimens and the logic behind them I've started dosing 1.6 mg C60 daily for two weeks. I will then take two weeks off, then on continuously. I do see value in letting the C60 clear from my system ( for the most part given what is known ), before redosing.
I took a fairly comprehensive blood test prior to supplementing with C60, and I will retest in six weeks. I will be looking at everything but especially liver and kidney function.
I also take PQQ, 20 mg daily.

Mikey wrote :
" He explicitly said there is no toxicity, "This is absolutely sure." And he said this after studying fullerenes for 18 years.
What I take away from the study - and Fathi's interview - is that C60 is just plain good for you.
Logically if something is non-toxic and good for you it would seem best to take it every day for optimum life-extension effects and mitochondrial protection. "

I don't have complete confidence in any one mans opinion, especially in something not tested extensively in humans. I am preceding, but with caution and as of now with a lower dosage.

Edited by Kevnzworld, 24 November 2012 - 12:09 AM.

[mikey]

No, they didn't, but they might have stumbled on the ideal protocol. Maybe bigger doses are better, or maybe smaller. Maybe more frequent dosing is better. At this point, we have no evidence either way. Since this is the only site on the internet where c60 is being discussed in an ongoing and significant way, I'm not surprised it's the only place my intermittent dosing hypothesis has come up. Or maybe you meant that no one else thinks it's worth worrying about... Anyway, you are misunderstanding the hypothesis. I'm not saying that c60 harms mitochondria. On the contrary, it helps mitochondria withstand ROS. The problem is that this may protect cancer cells from something that should be making them go apoptotic.

He explicitly said there is no toxicity, "This is absolutely sure." And he said this after studying fullerenes for 18 years.

What I take away from the study - and Fathi's interview - is that C60 is just plain good for you.

First, since the rats that lived extended lifespans in the end had no tumors I wonder that anyone has a question about C60's effects on cancers. Obviously, it is anti-cancer - it is not protecting cancer cells from going apoptotic. I'm not sure where you got that. And remember, I have tremendous respect for your insights. But this doesn't make sense.

Then - I wasn't referring to your hypothesis as to C60 potentially harming mitos. Turnbuckle hypothesized that - so it's his notion that C60 could cause toxicity to mitos and his notion of intermittent dosing that I find at odds with Dr. Moussa's statement that C60 is "absolutely" not toxic.

As to all the notions, hypotheses and theories voiced here about potential adverse effects caused by C60, I have to go back to Dr. Moussa's eighteen years of studying C60.

Eighteen years makes me think that the Dr. has considered many more aspects of C60 biochemistry than have been rendered here.

As well, I found that he seemed to be very relaxed and sure of what he was saying when he said that C60 was not toxic.

"This is absolutely sure," he said.

Any researcher who has spent a major part of his career studying one area must surely be enlightened as to every possible aspect of that area.

And any respected scientist who makes an absolute statement like that must surely be certain of their words. It's like using the word "cure" related to a disease. The word cure is not to be taken lightly.

I have to thank Anthony again for doing that interview. It answered many questions that I think will extend my lifespan significantly.
Plus Anthony has a great sense of humor! Kudos, Anthony!

[Anthony_Loera]

I was impressed by his statements as well.

The thing that impressed me was that he made it a point, even after we had left the question of toxicity, to come back again... And reiterate that C60 was not toxic, even for long term use.

I was impressed by his definite assertion of it.

Again, we interviewed him at one of the many Paris Hospitals where he lends his expertise to doctors. At the hospital where he was interviewed, his expertise was provided regarding patient's tests in the Department of Biochemistry. I believe in another Hospital, he also provides his expertise in genetics.

A

[mikey]

After reading the various opinions about dosing regimens and the logic behind them I've started dosing 1.6 mg C60 daily for two weeks. I will then take two weeks off, then on continuously. I do see value in letting the C60 clear from my system ( for the most part given what is known ), before redosing.
I took a fairly comprehensive blood test prior to supplementing with C60, and I will retest in six weeks. I will be looking at everything but especially liver and kidney function.
I also take PQQ, 20 mg daily.

Mikey wrote :
" He explicitly said there is no toxicity, "This is absolutely sure." And he said this after studying fullerenes for 18 years.
What I take away from the study - and Fathi's interview - is that C60 is just plain good for you.
Logically if something is non-toxic and good for you it would seem best to take it every day for optimum life-extension effects and mitochondrial protection. "

I don't have complete confidence in any one mans opinion, especially in something not tested extensively in humans. I am preceding, but with caution and as of now with a lower dosage.

Well, Dr. Moussa operates with teams of like-minded scientists, so knowing how scientists of his stature function, his words carry great and carefully considered weight.

However, I wouldn't tell anyone to do what I do. Always go with your own sense of caution. It's just my analysis and my decision.

I view C60 as an agent that protects me at the mitochondrial level. It's antioxidant potential -- 172 times more than vitamin C - could well save me lots of cell death, which is the definition of aging.

And as my goal to extend my lifespan goes back 45 years to when I began my journey at 14 years of age perhaps I am overly enthusiastic about C60's potential, but then I have a documented history of locating potent agents that optimize metabolism going back many years.

I am not a genius, but i have historically shown a unique talent for finding things that solve specific health problems that others do not recognize as quickly as I do.

And that's what I see C60 doing, safely saving cells from death.

[niner]

First, since the rats that lived extended lifespans in the end had no tumors I wonder that anyone has a question about C60's effects on cancers. Obviously, it is anti-cancer - it is not protecting cancer cells from going apoptotic. I'm not sure where you got that. And remember, I have tremendous respect for your insights. But this doesn't make sense.

The rats were dosed from early adulthood, while we are starting in middle age. If many years of oxidative stress increases your odds of developing cancer, then it would make sense that c60 started early would reduce the odds of developing cancer, but if you already have some incipient cancers, that's a different situation. There's no evidence that c60-oo will kill an existing cancer. We could test that by injecting tumor cells into animals on both c60-oo and placebo. No one has done that as far as I know. We could also start a c60-oo dosing experiment with middle aged animals. AgeVivo did exactly that, and one of his mice died with a tumor on its lung. Dysfunctional mitochondria can lead to apoptosis, which is something we want cancer cells to do. If we rescue dysfunctional mitochondria with c60, that might interfere with apoptosis. Cancer cells generate more ROS than normal cells, so they are closer to the edge of apoptosis; I just don't want to help them out any more than necessary.

As to all the notions, hypotheses and theories voiced here about potential adverse effects caused by C60, I have to go back to Dr. Moussa's eighteen years of studying C60.

Eighteen years makes me think that the Dr. has considered many more aspects of C60 biochemistry than have been rendered here.

I've spent thirty years working and studying in the biomedical field. When it comes to the effects of xenobiotics in man, I wouldn't use the phrase "absolutely sure" about anything.

[zen]

...
The rats were dosed from early adulthood, while we are starting in middle age. If many years of oxidative stress increases your odds of developing cancer, then it would make sense that c60 started early would reduce the odds of developing cancer, but if you already have some incipient cancers, that's a different situation. There's no evidence that c60-oo will kill an existing cancer.
...

I have added added BIO30 Propolis (available on Amazon.com) to my daily diet. It looks like it has some interesting anti cancer properties
http://www.ddtjourna...c.php?docid=482
http://www.bio30.com/Research/


HTH

Edited by zen, 24 November 2012 - 04:10 PM.

[Kevnzworld]

...
The rats were dosed from early adulthood, while we are starting in middle age. If many years of oxidative stress increases your odds of developing cancer, then it would make sense that c60 started early would reduce the odds of developing cancer, but if you already have some incipient cancers, that's a different situation. There's no evidence that c60-oo will kill an existing cancer.
...

I have added added BIO30 Propolis (available on Amazon.com) to my daily diet. It looks like it has some interesting anti cancer properties


HTH

Propolis with CAPE looks interesting after glancing at some of the pubmed studies. I need to look into it further. Post this in the supplement area for others to view and comment.

[motorcitykid]

I jumped on the propolis train 3 months ago:

http://www.ncbi.nlm....les/PMC2781777/

http://www.proteomes...9/1/74/abstract

[Raza]

Would it be reasonable to assume that, being the powerful lipophilic antioxidant-catalyst that it is, C60-oo might confer some protection against the oxidation of LDL in the bloodstream; and following from that, and considering the half-life of lipoprotein particles, that daily dosing might be preferable for those who are more concerned with atherosclerosis than with existing cancers?

[solarfingers]

I like Niner's idea and I know that Turnbuckle cycles his c69-oo yet for different reasons. Does it hold that I should load myself with telomerase inhibitors during the second half of the cycle when c60's effects are at it's weakest to further inhibit cancer senescence or differentiation?

[niner]

Would it be reasonable to assume that, being the powerful lipophilic antioxidant-catalyst that it is, C60-oo might confer some protection against the oxidation of LDL in the bloodstream; and following from that, and considering the half-life of lipoprotein particles, that daily dosing might be preferable for those who are more concerned with atherosclerosis than with existing cancers?

I think this is quite a good idea. If your main concern was CVD rather than cancer, a shorter dosing interval might be helpful. A bit of mindless googling suggests that the half life of an LDL particle is 3 days or longer. To get good coverage, it looks like you'd want a dosing interval of 2 days or less. At this point, this is purely hypothetical, but then it's hypothetical thread... It would be pretty easy to measure ox-LDL under various dosing regimes. We can add that to the list of experiments that we wish someone would run.

[solarfingers]

Niner, please tell me if I am wrong but didn't you say you were cycling your c60 once a month? I believe Turbuckle said that he recently went to once a week. I was considering every two weeks to follow my telomere cycling regimen but if what you are saying is a factor in dealing with cancer then I would need to take it once a month. I would subsequently load myself with polyphenols and telomerase inhibitors during the second two weeks of my cycle. The CVD/ox-LDL concern is a bit over my head and I am mostly concerned with cancer. Would a two day cycle be enough for c60 to loose it's potency in the body? It seems to stick around longer than that.

I now see that Turnbuckle is on a day on day off cycle...

Edited by solarfingers, 19 June 2013 - 09:49 PM.

[solarfingers]

I had another thought about this. The Wistar rats used in the Baati study were rats genetically prone to tumors and are commonly used in cancer research. At the beginning of the study mature rats were selected for the study. Would it not be likely that some of the rats on the c60-oo would have had some cancer cells at that age? I'm just thinking out loud.

[niner]

Niner, please tell me if I am wrong but didn't you say you were cycling your c60 once a month? I believe Turbuckle said that he recently went to once a week. I was considering every two weeks to follow my telomere cycling regimen but if what you are saying is a factor in dealing with cancer then I would need to take it once a month. I would subsequently load myself with polyphenols and telomerase inhibitors during the second two weeks of my cycle. The CVD/ox-LDL concern is a bit over my head and I am mostly concerned with cancer. Would a two day cycle be enough for c60 to loose it's potency in the body? It seems to stick around longer than that.

I now see that Turnbuckle is on a day on day off cycle...

I had a few deviations, but I'm still on the monthly dosing scheme. I'm not sure that a telomerase inhibitor will do anything if you don't have an active cancer with a runaway telomerase system, and I have a feeling that most of what get called telomerase inhibitors would require impossibly high doses to work in vivo. The idea behind a two day cycle is to have c60-oo in the blood stream often enough that the LDL particles get dosed not too long after they're created. When c60-oo partitions into cellular and mitochondrial membranes, then it's no longer going to be as available to the LDL particles, since it will have been cleared from the plasma. It's still in the body, just tucked away in the membranes.

I had another thought about this. The Wistar rats used in the Baati study were rats genetically prone to tumors and are commonly used in cancer research. At the beginning of the study mature rats were selected for the study. Would it not be likely that some of the rats on the c60-oo would have had some cancer cells at that age? I'm just thinking out loud.

I'm not a rat expert, but my impression is that Wistar rats are not particularly worse than other typical rats as far as cancer goes. It's more a matter of rats and mice just being susceptible to cancer in general. Baati's rats were mature, but they weren't particularly old when started on c60. Ten months, as I recall. My guess is at that age, they would be in pretty good shape.

[solarfingers]

I guess there is more than one way to look at an inhibitor. 1) It inhibits growth of telomeres or 2) It inhibits telomere length from shortening. It's not always clear to me when reading sources which they are referring to. I need to ponder this question a bit more when looking at supplementation. I would prefer the later be true yet I would think that you want to prevent runaway telomerase in cancers. Would that not be cancer prevention or a killer? I think you first mentioned that unregulated telomerase could potentially cause cancer and that's why you were cycling c60 in the first place. Is that my misconception or is this your thinking?

From what I gather we are looking to neutralize LDL's ability to affect cancer. There seems to be a difference of opinions as to whether or not LDL is responsible for cancer. This article suggests some researchers have it wrong and LDL actually protects from cancer and that the push to reduce LDL is actually from the pharmaceutical companies who wish to cash in on the sale of statins. I'm not sure how the picture for CVD comes into the discussion of c60-oo. Has it been demonstrated to affect cholesterol?

The more I dig into this business of Microbiology the deeper the rabbit hole gets...

Edited by solarfingers, 20 June 2013 - 03:57 AM.

[solarfingers]

Now that I have slept on it I believe your original concern was with c60's antioxidant effect aiding cancer instead of hampering it.

[hav]

From what I gather we are looking to neutralize LDL's ability to affect cancer. There seems to be a difference of opinions as to whether or not LDL is responsible for cancer. This article suggests some researchers have it wrong and LDL actually protects from cancer and that the push to reduce LDL is actually from the pharmaceutical companies who wish to cash in on the sale of statins. I'm not sure how the picture for CVD comes into the discussion of c60-oo. Has it been demonstrated to affect cholesterol?

As I read that article I thought to myself, "How would I prefer to go? A slow death with cancer or a nice quick heart attack?" That too is an over simplification, but at least a more balanced one. Although still slanted in the direction of my own personal preference if those were really the only choices available.

From the discussion above it seems c60-oo was proposed as relevant to cardiovascular health because of a possible effect of protecting LDL and I presume, raising LDL levels. I think that's contrary to mainstream thinking which preaches lowering LDL and raising HDL to promote CV health. In fact, that's one of the exact effects of olive oil and I doubt that combining olive oil with c60 would reverse that property. I would expect it would enhance that effect. But I don't know that it has been proved in a study yet.

It's possible that the c60-oo in the bloodstream will protect both HDL and LDL for the reasons theorized above and be a neutral factor. I doubt it, however, because its not clear how much of the c60-oo which is absorbed by the body actually makes it into the bloodstream or how far what does make it into the the bloodstream actually gets before its removed. My own conception is that most of the c60-oo gets absorbed from the lymphatic system before what's left over gets dumped into the bloodstream. I'm not sure where the brain is along the pathway but it must pull a significant amount of anything left over out of the bloodstream.

I think another connection relates to the healthy effect of other antioxidants on CV health and the assumption that c60, being such a powerful antioxidant, might be even better. Not sure that tracks for me. Resveratrol, another antioxidant, seems to get its positive effect on cv health from a beneficial effect on the elasticity of vessel walls it comes into contact with. Like the portal vein. But it comes into contact with this and other vessels only because it doesn't usually get absorbed via the lymphatic system; instead it follows a route similar to mct's and alcohol: through the portal vein to the liver and on into the bloodstream. I suppose you could dissolve c60 in an oil rich in mct's like coconut oil. But I'd be careful with that idea because I saw one resveratrol study that did that (it used neobee oil plus alcohol) and observed an increase in tumor growth, rather than the inhibitory effect the same researcher observed when using corn oil instead on a different breed of mice. It was discussed in this other thread. A larger c60-oo dosage might be a safer bet for dumping more left over c60-oo into the bloodstream; perhaps something closer to the the dosage used in the Baati study.

Howard

Edited by hav, 20 June 2013 - 03:50 PM.

[solarfingers]

Well I have not heard of anyone testing c60-oo having a rise in cholesterol. Where does this concern come from? As far as cancer fighting is concerned I'm pretty sure the answer lies in the ingestion of plenty of polyphenols. I am even more convinced after reading Vince G's article on Slaying Two Dragons with One Stone this morning. It seems that polyphenols would also add a great deal of antioxidants to the system yet there seems to be no concern of stimulating cancer proliferation with too many of them. Granted there are other mechanisms at play than just antioxidants here.

I do take two tablespoons of Olive Oil a day but mostly for brain health during my second phase. I have never had a cholesterol issue so I would be curious to see if there were any change when I start my c60-oo. I'm patiently waiting to begin. I do take Resveratrol, Milk Thistle on the second half of my cycle and I juice raw vegetables during that time. I'm also looking to adding ECCG and possibly Grape Seed extract to my diet then. Jim Green had a similar concern to cancer cell proliferation so he prescribes the two two week cycles of telomerase inhibitory and activation phases. Vince Giuliano cycles daily taking his telomerase inhibitors in the morning and the activators at night. He says activation at night helps him to sleep better.

Turnbuckle on the other hand sees a different issue. He is concerned that the c60 may energize stem cell mitochondria and cause them to differentiate with no proliferation. He prescribes a cycle to ensure the good stem cells have time to proliferate else one would deplete their stem cell supply.

The concern for cancer is viable but until I hear of c60-oo users having higher cholesterol then I won't be alarmed. Can cycling c60-oo alone account for with all the variables that cause cancer? If I already have mechanisms in my diet to address this concern for cancer then should have reason to be alarmed... Especially since the Baati c60-oo induced rats did live a cancer free life.

The idea of cycling does sound like a prudent measure and I am hearing different voices with distinctly different viewpoints. Who is to know which voice has the right idea about cycling and what it actually means? Perhaps the answer does not lie in the timing but the cycling itself. What happens when the body is pushed in a particular direction, say with a new supplement? Eventually it can become accustomed to it and the net effect is lost. Cycling in this context would allow the body to take the supplement more effectively if cycled. I know there has to be some optimal timing for cycling but is that the same for everyone? I think it interesting that Turnbuckle adjusts his cycle based upon his overall sense of well being. Perhaps we can just trust what our bodies are telling us.

[hav]

Here's a study that focused on the CV effect of polyphenols in olive oil:

In vivo nutrigenomic effects of virgin olive oil polyphenols (full-text)

It found that if they washed the polyphenols out of Spanish evoo using water, that inflammation markers and atherosclerosis related gene expression were all higher and similar to the control group. They mention hydroxytyrosol as the prime active polyphenol in olive oil which they believe reduces the risk of atherosclerosis.

Note that in Baati, the evoo control group got the same olive oil as the evoo+c60 group so polyphenols are unlikely too be the explanation for their difference in lifespan. Also, in Baati they filtered and centrifuged the evoo+c60, a process that most olive oil connoisseurs would find objectionable because it tends to remove any water-soluble polyphenols that would be in suspension in the oil. It's not clear if they did the same for the olive oil control group. I suspect not. If not., the olive oil control group would have gotten more polyphenols than the evoo+c60 group! I do filter my olive oil before (and after) mixing in the c60 and quite a bit of solids are removed before mixing.

Howard

Edited by hav, 20 June 2013 - 07:57 PM.

[niner]

There's some confusion here. The idea of using c60-oo to reduce oxidation of LDL (hypothetically speaking) has nothing to do with cancer. The issue is that oxidized LDL is more atherogenic than non-oxidized LDL. The AMOUNT of LDL in the system would not be changed by this, just the QUALITY of it. Reducing the level of LDL oxidation should result in less atherosclerosis, i.e. less CVD. Keep in mind that this hinges on the hypothesis that c60-oo will protect LDL against oxidation. That is plausible, but it hasn't been demonstrated.

I don't think that centrifugation and filtration would make much of a difference in polyphenol level. I suppose if the oil was very wet or if the polyphenols were adsorbed onto solids then you might see some loss, but I think most oils are homogeneous when sold.

[niner]

I guess there is more than one way to look at an inhibitor. 1) It inhibits growth of telomeres or 2) It inhibits telomere length from shortening. It's not always clear to me when reading sources which they are referring to. I need to ponder this question a bit more when looking at supplementation. I would prefer the later be true yet I would think that you want to prevent runaway telomerase in cancers. Would that not be cancer prevention or a killer? I think you first mentioned that unregulated telomerase could potentially cause cancer and that's why you were cycling c60 in the first place. Is that my misconception or is this your thinking?

A telomerase inhibitor can only inhibit telomerase that is present and functional. If telomerase isn't being expressed, then telomerase inhibitors will do nothing. They will not prevent telomerase from being expressed. There is no inhibitor that keeps telomere length from shortening, because telomere shortening is not an ezymatic process. Random oxidative damage is responsible for a lot of (possibly most) telomere shortening, so a highly effective antioxidant (like c60-oo) should slow the shortening of telomeres.

Telomerase inhibitors can't prevent the initiation of cancer, but if they are sufficiently bioavailable and the cell isn't using the alternative telomere-lengthening system that doesn't involve telomerase, then a telomerase inhibitor should slow cancer down once it has been initiated. My hypothetical concern about daily dosing isn't related to telomerase, it's related to the reports that cancer cells are oxidatively challenged and might be helped more by antioxidants than healthy cells would be.

The more I dig into this business of Microbiology the deeper the rabbit hole gets...

It is a very very deep hole. No one knows where the bottom is.

[solarfingers]

Here's a study that focused on the CV effect of polyphenols in olive oil:

In vivo nutrigenomic effects of virgin olive oil polyphenols (full-text)

It found that if they washed the polyphenols out of Spanish evoo using water, that inflammation markers and atherosclerosis related gene expression were all higher and similar to the control group. They mention hydroxytyrosol as the prime active polyphenol in olive oil which they believe reduces the risk of atherosclerosis.

Note that in Baati, the evoo control group got the same olive oil as the evoo+c60 group so polyphenols are unlikely too be the explanation for their difference in lifespan. Also, in Baati they filtered and centrifuged the evoo+c60, a process that most olive oil connoisseurs would find objectionable because it tends to remove any water-soluble polyphenols that would be in suspension in the oil. It's not clear if they did the same for the olive oil control group. I suspect not. If not., the olive oil control group would have gotten more polyphenols than the evoo+c60 group! I do filter my olive oil before (and after) mixing in the c60 and quite a bit of solids are removed before mixing.

Howard

Is it not notable that the control group who were administered only Extra Virgin Olive Oil lived longer and had fewer expressions of tumors than did those only administered water? The secoiridoids found in EVOO only account for nine mechanisms of silencing that inhibits cancer proliferation. There are roughly 26 of these mechanisms according to VG. From his long list of inhibiting supplements I can gather 8 of them which will cover the 22 signals that can be addressed. Specifically:

EGCG (Green Tea)
Curcumin
Resveratrol
SAMe
EVOO (secoiridoids) ~ Could be Olive Leaf Extract for this is what VG takes.
PQQ
Fish Oil
Fisetin

Note that this is only 8 of approximately 26 + supplements that he identifies. I narrowed the list down to 26 because these are easily obtainable. The majority of these expressions are also hindered by exercise, fasting, caloric restriction or glucos restriction. None of this has any bearing on our thread but I wanted explain my thinking here. I will post a spreadsheet of VGs results in the supplements section soon.

Edited by solarfingers, 21 June 2013 - 02:46 AM.

[Logic]

Dysfunctional mitochondria can lead to apoptosis, which is something we want cancer cells to do. If we rescue dysfunctional mitochondria with c60, that might interfere with apoptosis. Cancer cells generate more ROS than normal cells, so they are closer to the edge of apoptosis; I just don't want to help them out any more than necessary.

While Niner and I have had his discussion in another thread, I feel its important to mention it here too.

It seems that mitochondria send out an apoptosis, 'kill this cell' signal when cells become pre/cancerous.
Because of this pre/camcerous cells suppress or 'turn off' their mitochondria and turn to glycolysis for energy so as to stop the apoptosis signal from being sent and thus survive.

The above info comes from studies done with DCA.
DCA has the ability to 'kickstart' suppressed mitochondria, allowing them to send out the apoptosis signal and thus kill the defective cell:
http://www.ncbi.nlm....pubmed/20533281
http://www.ncbi.nlm....pubmed/21132264
http://www.ncbi.nlm....pubmed/21557214


My Hypotheses based on the above:

C60oo may prevent mitochondria from being 'switched off' in pre/cancerous cells causing the apoptosis of said cells.
As C60oo is known to be a mitochondrial anti-oxidant and mitochondria are 'turned off' in cancerous cells; C60oo no longer has a job in them and is thus anti-cancer overall.

So based on Baati and Avevivo's results it seems possible that C60oo will kill of pre/cancerous cells, but do very little in already cancerous cells.


Based on these hypotheses it seems like a good idea to take mitochondrial 'kickstarters' prior to and/or during taking C60oo.
Apart from DCA; Mebendazole, a de-worming Medication, and most other microtubule destabilizers, has also been shown to boost OXPHOS expression while suppressing ROS levels.
Deoxysappanone B, found in Green Tea, does so too.
http://www.ncbi.nlm....les/PMC2715872/


Also worth considering is PQQ which is known to stimulate motochondrial biogenesis.
http://www.google.co....47810305,d.ZGU

Resveratrol has a similar effect to PQQ???

Edited by Logic, 21 June 2013 - 01:48 PM.

[solarfingers]

Logic, What about Alpha Lipoic Acid, isn't it noted for energizing mitochondria as well?

Based on these hypotheses it seems like a good idea to take mitochondrial 'kickstarters' prior to and/or during taking C60oo.
Apart from DCA; Mebendazole, a de-worming Medication, and most other microtubule destabilizers, has also been shown to boost OXPHOS expression while suppressing ROS levels.

Let me see if I understand what you're getting at. Are you attempting to up-regulate ATP by boosting OXPHOS expression to keep healthy cells alive while suppressing ROS to choke out cancer cells? Being that Green Tea, PQQ and Resveratrol are all on my list, it might hold that a good time to take c60 is while I'm taking my phytochemical supplements. Sounds logical. Also, anything else that might fall into the MitoSENS category should booster this effect.

Edited by solarfingers, 21 June 2013 - 02:05 PM.

[hav]

I don't think that centrifugation and filtration would make much of a difference in polyphenol level. I suppose if the oil was very wet or if the polyphenols were adsorbed onto solids then you might see some loss, but I think most oils are homogeneous when sold.

I expect it would only lower the amount of water soluble polyphenols in suspension which I would have thought are not the majority of the polyphenols in olive oil. But maybe they are. The water washing process done in the CV study measured the following:

WOO [washed olive oil] was similar to VOO, but with a lower polyphenol content (55 vs. 328 mg/kg, respectively

Granted their method was a little extreme and probably more effective, repeatedly mixing with water, centrifuging, and separating the water off. But I'd expect a 22 micron filter would remove some of it too. I know when I filter a liter of olive oil before mixing that it leaves about 1/64 of an inch of golden residue on the filter. Which I wipe off with a piece of bread so it doesn't go to waste.

Howard

Edited by hav, 21 June 2013 - 04:08 PM.

[taho]

I was thinking about a hypothesis that could explain well basically everything. Let’s call it an unified theory of free radicals and disposable soma with an answer why those rats lived 15% longer on olive oil and 90% longer on C60-oo.

Ok, ROS are bad guys. They leak from complex I, III and IV in mitochondria and either damage mitochondria itself or the cell itself. Some of them are very reactive (HO) some of them are quite stabile (H2O2), unless they hit Fe/Cu and become 2 very reactive ones (HO). The rate of production of ROS is somewhere between 0,1 and 10% of consumed 02, but it is generally in the 2-4% range. That generally means 60K "liters of oxygen per kilogram consumed" = death from all those random ROS hits. The exception to that rule are birds which have better mitochondria because of flight and naked mole rats, humans and few deep diving animals that have evolved better defenses against ROS. The reason is hidden in the evolutionary race between high reproducing (low ROS) and long living (high ROS) but handicapped with all those resources that are needed for better ROS defenses. We live only as long as we can improve chanses that "our" genes will live longer then competing ones.

That 60K liters/kg is not a hard limit even in the specific organisms. We can extend that limit by either calorie restriction or with specific chemicals that target some genes. mTOR, FOXO and sirtuins come to my mind. But if you look closer one gene pops up almost always and it’s a nrf-2. Nrf-2 is a strange gene. Type almost any “antioxidant” and it is somehow related to Keap1-Nrf2-ARE pathway. http://onlinelibrary.../med.21257/full lists following substances as activatos: propolis (CAPE), garlic, bardoxolone methyl, diethyl maleate, quercetin, onion, coffe, resveratrol, green tea, rosmarin, broccoli, cabbage, brussel sprouts, arsen, ALA, selen, carrots, tomatos,.. The list goes on if you search pubmed the list goes on.. olive oil, metformin, chocolade, curumin, ashwaganda, boswellia, ginger,.. and let’s not forget exercise, toxins, radiation,..

So what is Nrf2?

It’s a peptide/gene that gets activated when things get oxidized or come under some kind of stress. For example, Bardoxolane methyl oxidizes glutathione. In response the Nrf2 upregulates about 200 cytoprotective genes. Keap1 is it's antagonist making it a homeostatis system. The interesting thing about Nrf2 is that it is inhibited by NAC, E vitamin and C vitamin. It makes sense. Lower ROS = lower Nrf2 activation. What all that means? Well.. if you eat your greens and eat “antioxidants” (toxins!) then you will have higher ROS protection, high free iron neutralization and upregulated gene and system repair. You will live longer, but since those things are everywhere nobody notices that, except if you have rats that eat boring food that just happens to have none of if. In that case small amounts of olive oil will make your rats live 15% longer. And if you test E vitamins (on humans) you will notice that it increases mortality and you will stop test and declare “E vitamin will kill you”. Nope. Lower Nrf2 activation will kill you.

Ok, now, what happens if you discover super-vitamin-E that is catalytic, does not wear out and happens to embed itself into mitochondrial lipid wall and into any other lipid wall (nucleoid wall?), but other than stopping ROS chain reactions and not wanting to leave lipid wall doesn’t do anything. Well, Nrf2 downregulates. It is upregulated only by all those chemical activators, but from ROS; NOTHING. If this would be your E vitamin test, your mice would die from ROS made from H2O2 catalised by Fe/Cu and by low running DNK and system repair. But, our super-vitamin reduces ROS damage to such a low level that it doesn’t matter. Rats live longer. And remember olive oil that is used to “dissolve C60” still has Nrf2 activators. That should help a little on that subject.

Our super-vitamin-E has changed “regular” mitochondrion into “super efficient, more bird like” mitochondrion. In our rats lifespan went from 60K liters/kg oxygen to 114K liters/kg oxygen before death.

Prediction: C60-oo with potent Nrf-2 activators that cause genetic removal of free iron and upregulate repair as much as possible should increase “liters/kg oxyen before death” even higher. And this could be testable even in short lived animals (yeast, flies, worms) since they all have mitochondria that produce ROS, regulate apoptosis (when x of them die, cell kills itself) and have nrf-2 pathway.

Edited by taho, 22 June 2013 - 01:49 AM.