144 replies to this topic

[niner]

A few weeks ago, I read (at Longecity, I think) about a new anti-cancer strategy. It was based on the idea that cancer cells have a higher metabolism than normal cells, and create more ROS. If you inhibit natural antioxidant defenses (e.g. SOD, etc) then cancer cells will be harmed more than normal cells. I think the compound they were looking at as the inhibitor was berberine, but I might be mis-remembering that. I've looked around for the post, or paper, or whatever it was, and haven't found it. If anyone remembers what this was, please post a link.

At any rate, this got me thinking: What if C60, a potent antioxidant, were therefore a pro-cancer agent? What do we know about the relationship between C60 and cancer? We know via Anthony's interview of Fathi Moussa that Baati's rats had no tumors at the end of their very long lives. We also saw that one of AgeVivo's mice, started on c60-oo in middle age, died several months later with a large tumor that appeared to be on the surface of a lung. The general assumption is that AgeVivo's mouse already had the tumor before it was given c60-oo, and that c60-oo didn't kill the tumor. Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

Why would this be a problem for daily dosing, but less of a problem for intermittent dosing? When a cancer cell divides, the c60 content of the daughter cells will probably be split into two pools, perhaps of equal size, perhaps not. After several splits, the c60 content of most daughter cells should fall below the effective level, and the cells will again be susceptible to oxidative stress. With intermittent dosing, there will be a period where the daughter cells are relatively free of c60 and more susceptible to apoptosis. With daily dosing, the cancer cells would constantly be given a new dose of c60.

There is probably an optimal dosing schedule for avoiding this hypothetical risk. The dose should be large enough to allow enough time between doses for daughter cells from the tumor to lose enough c60 to be injured by their own ROS. At the same time, we don't want it to be so high that cells are overloaded, and daughter cells continue to have an effective dose even after a number of doublings.

From my muscle fatigue experiment (here, also see first post of thread), it appeared that a total dose of 0.09mg/kg was enough to provide good ROS coverage for a week. That suggests that 0.36mg/kg would be a reasonable monthly dose. I don't know that the assumption of linearity is valid here, but it's a starting point. The doubling time of different cancers is going to be highly variable; we would mainly be concerned with rapidly dividing cells. The faster a cell divides, the faster it loses C60.

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

[mikey]

Interesting. Turnbuckle has his own theory about intermittent dosing.
I tend towards using high doses of "nutrients" that exhibit no toxicity while also being highly beneficial, so I'll keep watching the two of you as your theories evolve.

Thank you.

[Andey]

A few weeks ago, I read (at Longecity, I think) about a new anti-cancer strategy. It was based on the idea that cancer cells have a higher metabolism than normal cells, and create more ROS. If you inhibit natural antioxidant defenses (e.g. SOD, etc) then cancer cells will be harmed more than normal cells. I think the compound they were looking at as the inhibitor was berberine, but I might be mis-remembering that. I've looked around for the post, or paper, or whatever it was, and haven't found it. If anyone remembers what this was, please post a link.

At any rate, this got me thinking: What if C60, a potent antioxidant, were therefore a pro-cancer agent? What do we know about the relationship between C60 and cancer? We know via Anthony's interview of Fathi Moussa that Baati's rats had no tumors at the end of their very long lives. We also saw that one of AgeVivo's mice, started on c60-oo in middle age, died several months later with a large tumor that appeared to be on the surface of a lung. The general assumption is that AgeVivo's mouse already had the tumor before it was given c60-oo, and that c60-oo didn't kill the tumor. Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

Why would this be a problem for daily dosing, but less of a problem for intermittent dosing? When a cancer cell divides, the c60 content of the daughter cells will probably be split into two pools, perhaps of equal size, perhaps not. After several splits, the c60 content of most daughter cells should fall below the effective level, and the cells will again be susceptible to oxidative stress. With intermittent dosing, there will be a period where the daughter cells are relatively free of c60 and more susceptible to apoptosis. With daily dosing, the cancer cells would constantly be given a new dose of c60.

There is probably an optimal dosing schedule for avoiding this hypothetical risk. The dose should be large enough to allow enough time between doses for daughter cells from the tumor to lose enough c60 to be injured by their own ROS. At the same time, we don't want it to be so high that cells are overloaded, and daughter cells continue to have an effective dose even after a number of doublings.

From my muscle fatigue experiment (here, also see first post of thread), it appeared that a total dose of 0.09mg/kg was enough to provide good ROS coverage for a week. That suggests that 0.36mg/kg would be a reasonable monthly dose. I don't know that the assumption of linearity is valid here, but it's a starting point. The doubling time of different cancers is going to be highly variable; we would mainly be concerned with rapidly dividing cells. The faster a cell divides, the faster it loses C60.

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

Am I understand you right that you propose to do a month rest period between dosages ?
Or use weekly dosage ? It looks unclear to me what your final conclusion about it )

Edited by Andey, 05 November 2012 - 11:38 AM.

[niner]

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

Am I understand you right that you propose to do a month rest period between dosages ?
Or use weekly dosage ? It looks unclear to me what your final conclusion about it )

Yes, I'm thinking of taking a single dose of 0.36mg/kg, which for me would be about 23mg, then waiting 4 weeks before taking it again. This could get revised either up or down in the future, but monthly dosing is very convenient because it's synchronized with the calender. I could just dose on the first day of every month, for example, which would be easy to remember.

[Andey]

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

Am I understand you right that you propose to do a month rest period between dosages ?
Or use weekly dosage ? It looks unclear to me what your final conclusion about it )

Yes, I'm thinking of taking a single dose of 0.36mg/kg, which for me would be about 23mg, then waiting 4 weeks before taking it again. This could get revised either up or down in the future, but monthly dosing is very convenient because it's synchronized with the calender. I could just dose on the first day of every month, for example, which would be easy to remember.

But in your 'minimum dosage thread' your experienced a kind of withdrawal symptoms (if it not a coincedence). Are you ok with it if it would be every month ?

Also some common thoughts - may be I didnt understand you completely but it looks to me that your concern is about already existing cancer cells. and in this state C60 would not help and may harm.
But it may be not relevant to case when no cancer in body yet and C60 prevents its appearance. This thought can be supported by Baati experiment with weekly doses. Obviously metabolic rate may differ in rats and humans but I dont sure that rats cells are dividing much often or get rid of C60 quicker.

Edited by Andey, 05 November 2012 - 02:08 PM.

[taho]

I am leaning towards the idea, that if you remove ROS damage to the cell, you prevent 6 changes that need to occur to become cancerous. The rats that were given regular dosages of c60-oo, haven't gotten any of the billions of cells to the point where they become cancerous. So, the less ROS, the less of a probability of a cancer.

But, if the cell is already cancerous, then it doesn't really matter if it they are more damaged from ROS that are produced. It is constantly growing by uncontrolled division of cells that still can do that. It might grow a little bit slower or faster, but it's still a blob of cancerous cells that will end up killing you.

I think that mouse was unlucky or have gotten c60-oo too late (damage was already done). c60-oo doesn't fix the things that are already broken.

[Turnbuckle]

Since cancer cells shut down their mitochondria, anything that promotes mitochondrial health ought to prevent cancer. So the best C60 protocol would be one that best rejuvenates aged mitochondria.

Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

I wouldn’t build a theory on one data point.

[Andey]

Since cancer cells shut down their mitochondria, anything that promotes mitochondrial health ought to prevent cancer. So the best C60 protocol would be one that best rejuvenates aged mitochondria.

Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

I wouldn’t build a theory on one data point.

I see in your profile that you change dosage from 2 on/5 off to every other day - is it works for you ?


What do you think about once a week dosage ? It was used for Baati rats so it probably safe and beneficial.
'Baatis' weekly dosage is also on the larger side so rats was probably oversaturated with C60 during active intake phase of experiment.

P.S. For last 2 weeks I use kind on intermediated protocol as you suggest ) I choose 1 tablespoon of C60oo two times a week. So I am liitle bit surprised that you are trying every other day dosage )

Edited by Andey, 05 November 2012 - 05:23 PM.

[niner]

Yes, I'm thinking of taking a single dose of 0.36mg/kg, which for me would be about 23mg, then waiting 4 weeks before taking it again. This could get revised either up or down in the future, but monthly dosing is very convenient because it's synchronized with the calender. I could just dose on the first day of every month, for example, which would be easy to remember.

But in your 'minimum dosage thread' your experienced a kind of withdrawal symptoms (if it not a coincedence). Are you ok with it if it would be every month ?

Assuming that was real, this dosing schedule should keep c60 levels high enough to avoid it. The withdrawal symptoms (if that's what they were) didn't happen until later.

Also some common thoughts - may be I didnt understand you completely but it looks to me that your concern is about already existing cancer cells. and in this state C60 would not help and may harm.
But it may be not relevant to case when no cancer in body yet and C60 prevents its appearance. This thought can be supported by Baati experiment with weekly doses. Obviously metabolic rate may differ in rats and humans but I dont sure that rats cells are dividing much often or get rid of C60 quicker.

Right. For younger people who aren't likely to have any cancer in their body, C60 might help them avoid cancer. You're also correct that the pharmacokinetics of C60 in rats might be very different than in humans. Without looking at more some sort of redox marker in rats, or doing a radiolabel experiment, we really don't know how long it takes for c60 to leave their system completely, although we do know about the first phase of rat C60 pharmacokinetics, which shows rapid clearance from plasma.

Since cancer cells shut down their mitochondria, anything that promotes mitochondrial health ought to prevent cancer. So the best C60 protocol would be one that best rejuvenates aged mitochondria.

How do cancer cells generate energy if they shut down their mitochondria? It probably is the case that healthy mitochondria should help to prevent cancer, but I'm not worried about preventing it, I'm worried about accelerating the growth of existing cancer. This is a bit like the telomerase inducer issue.

Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

I wouldn’t build a theory on one data point.

It's not a theory. It's a hypothesis. Those are very different. And it's not a single data point- there's the bit about inhibiting endogenous antioxidant systems harming cancer cells, and I suppose you could add the large study where smokers given antioxidant vitamins got more cancer instead of less. My hypothetical concern is a little bit like Junk Master's hypothetical concern that c60 might affect adaptation to exercise. That is based on more, but more conflicting data, and is a concern that I also share.

[Turnbuckle]

Since cancer cells shut down their mitochondria, anything that promotes mitochondrial health ought to prevent cancer. So the best C60 protocol would be one that best rejuvenates aged mitochondria.

Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

I wouldn’t build a theory on one data point.

I see in your profile that you change dosage from 2 on/5 off to every other day - is it works for you ?


What do you think about once a week dosage ? It was used for Baati rats so it probably safe and beneficial.
'Baatis' weekly dosage is also on the larger side so rats was probably oversaturated with C60 during active intake phase of experiment.

P.S. For last 2 weeks I use kind on intermediated protocol as you suggest ) I choose 1 tablespoon of C60oo two times a week. So I am liitle bit surprised that you are trying every other day dosage )

As I say on my profile page, I consider 1/2 mg every other day a maintenance dose, by which I mean it’s probably too low to act as an epigenetic agent, but still providing some antioxidant value.

I varied the schedule quite a bit over the past 7 months, but I feel that a dose of 2.5 to 7.5 mg (for a 86 kg subject) on one or two successive days once every week or two is good. And perhaps, were I to do this again, I'd add in the 1/2 mg every other day as a background dose.

Edited by Turnbuckle, 05 November 2012 - 05:36 PM.

[Andey]

As I say on my profile page, I consider 1/2 mg every other day a maintenance dose, by which I mean it’s probably too low to act as an epigenetic agent, but still providing some antioxidant value.

I varied the schedule quite a bit over the past 7 months, but I feel that a dose of 2.5 to 7.5 mg (for a 86 kg subject) on one or two successive days once every week or two is good. And perhaps, were I to do this again, I'd add in the 1/2 mg every other day as a background dose.

Thanks for explanation. I will look at your profile for updates.

Maybe you consider to start a log thread ? Its interesting to read about your observations and experiments on c60 )

[Turnbuckle]

How do cancer cells generate energy if they shut down their mitochondria? It probably is the case that healthy mitochondria should help to prevent cancer, but I'm not worried about preventing it, I'm worried about accelerating the growth of existing cancer. This is a bit like the telomerase inducer issue.

The Warburg Effect. According to Wikipedia--

The Warburg Theory of Cancer or "Warburg hypothesis" (as distinguished from the Warburg effect) postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria. The Warburg Effect describes the observation that cancer cells, and many cells grown in-vitro, exhibit glucose fermentation even when enough oxygen is present to properly respire. In other words, instead of fully respiring in the presence of adequate oxygen, cancer cells ferment . . .

Warburg's hypothesis was postulated by the Nobel laureate Otto Heinrich Warburg in 1924. He hypothesized that cancer, malignant growth, and tumor growth are caused by the fact that tumor cells mainly generate energy (as e.g. adenosine triphosphate / ATP) by non-oxidative breakdown of glucose (a process called glycolysis). This is in contrast to "healthy" cells which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end-product of glycolysis, and is oxidized within the mitochondria. Hence, according to Warburg, the driver of cancer cells should be interpreted as stemming from a lowering of mitochondrial respiration . . .

In recent years, Warburg's hypothesis has re-gained attention due to several discoveries linking impaired mitochondrial function as well as impaired respiration to the growth, division and expansion of tumor cells . . .

. . . The body often kills damaged cells by apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells where the mitochondria are shut down. The reactivation of mitochondria in cancer cells restarts their apoptosis program . . .

[maxwatt]

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

Am I understand you right that you propose to do a month rest period between dosages ?
Or use weekly dosage ? It looks unclear to me what your final conclusion about it )

Yes, I'm thinking of taking a single dose of 0.36mg/kg, which for me would be about 23mg, then waiting 4 weeks before taking it again. This could get revised either up or down in the future, but monthly dosing is very convenient because it's synchronized with the calender. I could just dose on the first day of every month, for example, which would be easy to remember.

An ounce or so of C60 once a month should be manageable. Maybe with a little garlic and some pasta.

WRT apoptosis of cells with damaged mitochondria, resveratrol is thought to restart the process in at least some cancer cells.

[Logic]

Turnbuckle you have a hypothesis that mitos need to be given a chance to die off??

[Turnbuckle]

Turnbuckle you have a hypothesis that mitos need to be given a chance to die off??

It's not allowing them to die off, that's just part of the normal process. The half life of mitochondria is on the order of 2 days. My theory is that several half lives are needed before mitochondrial epigenomes that have been randomly improved by C60 treatment can increase their numbers sufficiently before you tweak them again. If you let them multiply for two weeks, that would be 7 doublings and 1 would become 128, which would take over 13% of the population if the cell had a thousand to begin with. If you went three weeks instead, it would take over the entire population. That's a bit simplistic, but it gives you the general idea.

[mikey]

Turnbuckle you have a hypothesis that mitos need to be given a chance to die off??

It's not allowing them to die off, that's just part of the normal process. The half life of mitochondria is on the order of 2 days. My theory is that several half lives are needed before mitochondrial epigenomes that have been randomly improved by C60 treatment can increase their numbers sufficiently before you tweak them again. If you let them multiply for two weeks, that would be 7 doublings and 1 would become 128, which would take over 13% of the population if the cell had a thousand to begin with. If you went three weeks instead, it would take over the entire population. That's a bit simplistic, but it gives you the general idea.

I greatly respect your insights, Turnbuckle.

Please tell me - what do you perceive that isn't optimal when you've done continual dosing and what do you perceive is improved with intermittent dosing?

[zorba990]

Epitalon might be another method to slow or eliminate potential tumor issues:
http://iv.iiarjourna.../2/253.abstract

I'm somewhat floored that supplement companies have not yet jumped on the epitalon bandwagon ...

[Turnbuckle]

Turnbuckle you have a hypothesis that mitos need to be given a chance to die off??

It's not allowing them to die off, that's just part of the normal process. The half life of mitochondria is on the order of 2 days. My theory is that several half lives are needed before mitochondrial epigenomes that have been randomly improved by C60 treatment can increase their numbers sufficiently before you tweak them again. If you let them multiply for two weeks, that would be 7 doublings and 1 would become 128, which would take over 13% of the population if the cell had a thousand to begin with. If you went three weeks instead, it would take over the entire population. That's a bit simplistic, but it gives you the general idea.

I greatly respect your insights, Turnbuckle.

Please tell me - what do you perceive that isn't optimal when you've done continual dosing and what do you perceive is improved with intermittent dosing?

If you dose continuously by this theory, and your dose is high enough to hypomethylate the mtDNA, then you aren't allowing time for better mitochondria to be selected. My own experience is consistent with that. When taking it for more than 5 days, I felt that I was moving back to baseline. That's to say, less energy and poorer performance in the gym.

[Anthony_Loera]

Having taken the Baati doses a few times, and now taking the daily reduced doses, i had always felt i was going back to 'normal' at between 7 to 9 days after a week of taking the large doses.

At the daily reduced doses, it really didn't feel it was doing anything ... In the beginning. Now as i simply continued the regimen, i am changing my mind. I do think we get rid of the C60 over time.

However, the daily dose may slowly accumulate the C60 over time at a faster rate than your body gets rid of it.

I am just wondering how to measure a 'top off' point in a practical terms.

It maybe that some people may be able to get rid of it faster than others, so dosing may vary for each individual. Finding a good way to measure the C60 in plasma at least would be a nice start.

A

[niner]

Having taken the Baati doses a few times, and now taking the daily reduced doses, i had always felt i was going back to 'normal' at between 7 to 9 days after a week of taking the large doses.

At the daily reduced doses, it really didn't feel it was doing anything ... In the beginning. Now as i simply continued the regimen, i am changing my mind. I do think we get rid of the C60 over time.

However, the daily dose may slowly accumulate the C60 over time at a faster rate than your body gets rid of it.

I am just wondering how to measure a 'top off' point in a practical terms.

It maybe that some people may be able to get rid of it faster than others, so dosing may vary for each individual. Finding a good way to measure the C60 in plasma at least would be a nice start.

Boy, after a week of getting half your calories from olive oil, I'm surprised you felt normal that soon. You sure hadn't run out of C60 after a week-long megadose. I can't really say that I felt "great" on c60, but I had two different disease states that seem to have improved, and I was happy about that. One was the symptoms of postural hypotension that I frequently get, which were much reduced with c60, and the other was an improvement in persistent eczema and a couple other skin lesions. I never felt any stronger, but I could completely obliterate the old maximum number of reps on the one exercise that I regularly got to the point of muscle fatigue on. I was able to use the rep count as a marker for how much c60 effect I was still getting a number of days after the last dose. After resuming dosing, I'm continuing to see the positive effects I noted; not really much change there.

We certainly get rid of the c60 over time. And yeah, if we took a daily dose that was greater than the amount we lose, we should accumulate it over time. The best thing I can come up with for measuring c60 status would be various measures of antioxidant status, but those are fairly expensive to do on a regular basis, not to mention the annoyance of a blood draw. Dosing might well vary on an individual basis, although because it's mostly just physics- diffusion and partitioning, rather than a receptor mediated phenomenon that might be more subject to genetic differences, I'd expect most people to be pretty similar. It would be nice to have a method to measure c60 in blood. It should mostly be in the cells rather than the plasma. You'd want to purify the membrane fraction, then you'd need a very sensitive assay for c60 analogs. Redox status would be more indirect, but the assays are already well developed.

[Anthony_Loera]

You know, durring the large dose days.. I really didn't feel hungry that much.

While on the low doses... (A tablespoon in the morning and one in the evening...) I do get hungry.

On the subject of measurement, are we talking... a biopsy?

A

[niner]

No, no biopsy, just a blood draw. Probably leukocytes. I suppose you could use a tissue biopsy, but I don't think you'd need one.

[hav]

A few weeks ago, I read (at Longecity, I think) about a new anti-cancer strategy. It was based on the idea that cancer cells have a higher metabolism than normal cells, and create more ROS. If you inhibit natural antioxidant defenses (e.g. SOD, etc) then cancer cells will be harmed more than normal cells. I think the compound they were looking at as the inhibitor was berberine, but I might be mis-remembering that. I've looked around for the post, or paper, or whatever it was, and haven't found it. If anyone remembers what this was, please post a link.

At any rate, this got me thinking: What if C60, a potent antioxidant, were therefore a pro-cancer agent? What do we know about the relationship between C60 and cancer? We know via Anthony's interview of Fathi Moussa that Baati's rats had no tumors at the end of their very long lives. We also saw that one of AgeVivo's mice, started on c60-oo in middle age, died several months later with a large tumor that appeared to be on the surface of a lung. The general assumption is that AgeVivo's mouse already had the tumor before it was given c60-oo, and that c60-oo didn't kill the tumor. Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

Why would this be a problem for daily dosing, but less of a problem for intermittent dosing? When a cancer cell divides, the c60 content of the daughter cells will probably be split into two pools, perhaps of equal size, perhaps not. After several splits, the c60 content of most daughter cells should fall below the effective level, and the cells will again be susceptible to oxidative stress. With intermittent dosing, there will be a period where the daughter cells are relatively free of c60 and more susceptible to apoptosis. With daily dosing, the cancer cells would constantly be given a new dose of c60.

There is probably an optimal dosing schedule for avoiding this hypothetical risk. The dose should be large enough to allow enough time between doses for daughter cells from the tumor to lose enough c60 to be injured by their own ROS. At the same time, we don't want it to be so high that cells are overloaded, and daughter cells continue to have an effective dose even after a number of doublings.

From my muscle fatigue experiment (here, also see first post of thread), it appeared that a total dose of 0.09mg/kg was enough to provide good ROS coverage for a week. That suggests that 0.36mg/kg would be a reasonable monthly dose. I don't know that the assumption of linearity is valid here, but it's a starting point. The doubling time of different cancers is going to be highly variable; we would mainly be concerned with rapidly dividing cells. The faster a cell divides, the faster it loses C60.

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

I'm trying to follow the logic of all this. From presuming c60 is a potent antioxidant through using a measure of muscle fatigue to gauge the antioxidant effect level with the idea of modulating it to allow cancer cells to self destruct from pro oxidative stress. Although I'm pretty convinced c60/evoo is a potent antioxidant, mainly from the Baati observation of the protective effect it had on the rats treated with carbon CCl4, I'm still not clear on how muscle fatigue would be a clear measure of antioxidant effect. Granted, some antioxidants seem to enhance my endurance. I'm thinking of resveratrol. But many do not. Like vitamin C, E, and a host of other antioxidants I take like GSE, Jiagulan, Milk Thistle, etc. I've got to say, resveratrol may be the only other antioxidant I've ever noticed an endurance enhancing effect from.

But I did try to do some searching through the literature relating to antioxidants and muscle fatigue. Came up with this interesting paper that summarizes what seems to be allot of research related to muscle fatigue:

http://physrev.physi.../88/4/1243.full

I found it interesting because it covers quite a few subjects that have been kicked around in this thread, like ROS, SOD, and singlet oxygen . And some that I don't remember seeing much of, like RNS. In any event, I got the impression after reading this that oxidative stress is only one of many factors that cause muscle fatigue. Furthermore, this paper has a whole section on markers of oxidative stress, and muscle fatigue is not one of them. Which just make me doubt that muscle fatigue can be used as a dosage measure of an antioxidant, unless improving muscle performance is your primary objective.

I'm not sure what alternative to suggest. I note that in the Baati study treatment started at 10 months of age, olive oil alone increased average life spans from 20 to 22 months, after which treatment for all groups ceased. C60/evoo treated rats lived on average another 20 months without further treatment. If those rats had died of cancer and/or tumors, like the others, I would infer that it took 20 months for the c60 effect, whatever it was, to wear off. But they died of old age. So maybe the effect which prevented the cancer and/or tumors, if it was an antioxidant one, would have lasted longer than 20 months if their boody parts had not worn out first. In any case, I'm not sure where that leaves us on an optimal dosage guestimate. Or the theory that cycling off until the c60 effect dissapears might be beneficial. I can only observe that perhaps following the Baati dosage timeline exactly for 12 months followed by a 20 month timeout would be consistent with the study. And then what? Start over again? Hopefully at some point a followup study will give us a clue but it might take 4 or more years.

Howard

[hav]

A few weeks ago, I read (at Longecity, I think) about a new anti-cancer strategy. It was based on the idea that cancer cells have a higher metabolism than normal cells, and create more ROS. If you inhibit natural antioxidant defenses (e.g. SOD, etc) then cancer cells will be harmed more than normal cells. I think the compound they were looking at as the inhibitor was berberine, but I might be mis-remembering that. I've looked around for the post, or paper, or whatever it was, and haven't found it. If anyone remembers what this was, please post a link.

At any rate, this got me thinking: What if C60, a potent antioxidant, were therefore a pro-cancer agent? What do we know about the relationship between C60 and cancer? We know via Anthony's interview of Fathi Moussa that Baati's rats had no tumors at the end of their very long lives. We also saw that one of AgeVivo's mice, started on c60-oo in middle age, died several months later with a large tumor that appeared to be on the surface of a lung. The general assumption is that AgeVivo's mouse already had the tumor before it was given c60-oo, and that c60-oo didn't kill the tumor. Could c60-oo have accelerated the growth of the tumor via an antioxidant mechanism? That is my hypothetical concern.

Why would this be a problem for daily dosing, but less of a problem for intermittent dosing? When a cancer cell divides, the c60 content of the daughter cells will probably be split into two pools, perhaps of equal size, perhaps not. After several splits, the c60 content of most daughter cells should fall below the effective level, and the cells will again be susceptible to oxidative stress. With intermittent dosing, there will be a period where the daughter cells are relatively free of c60 and more susceptible to apoptosis. With daily dosing, the cancer cells would constantly be given a new dose of c60.

There is probably an optimal dosing schedule for avoiding this hypothetical risk. The dose should be large enough to allow enough time between doses for daughter cells from the tumor to lose enough c60 to be injured by their own ROS. At the same time, we don't want it to be so high that cells are overloaded, and daughter cells continue to have an effective dose even after a number of doublings.

From my muscle fatigue experiment (here, also see first post of thread), it appeared that a total dose of 0.09mg/kg was enough to provide good ROS coverage for a week. That suggests that 0.36mg/kg would be a reasonable monthly dose. I don't know that the assumption of linearity is valid here, but it's a starting point. The doubling time of different cancers is going to be highly variable; we would mainly be concerned with rapidly dividing cells. The faster a cell divides, the faster it loses C60.

At the moment, I'm leaning toward something like 0.36mg/kg per month as my own dose, but that's not cast in stone. Thoughts?

Although I am pretty convinced c60/evoo is a potent antioxidant, mainly from the Baati observation of the protective effect it had on the rats treated with CCl4, I'm still uneasy about using muscle fatigue to measure antioxidant effect and determine optimal c60/evoo dosage. Granted, some antioxidants seem to enhance my endurance. I'm thinking of resveratrol. But many do not. At least not for me. Like vitamin C, E, and a host of other antioxidants I take like GSE, Jiagulan, Milk Thistle, etc. I've got to say, resveratrol may be the only other antioxidant I've ever noticed an endurance enhancing effect from.

But I did try to do some searching through the literature relating to antioxidants and muscle fatigue. Came up with this interesting paper that summarizes what seems to be allot of research related to muscle fatigue:

http://physrev.physi.../88/4/1243.full

I found it interesting because it covers quite a few subjects that have been kicked around in this thread, like ROS, SOD, and singlet oxygen . And some that I don't remember seeing much of, like RNS. In any event, I got the impression after reading this that oxidative stress is only one of many factors that relate to muscle fatigue. Furthermore, this paper has a whole section on markers of oxidative stress, and muscle fatigue is not one of them. Which I think confirms my doubts. Unless improving muscle performance is your primary objective.

I'm not sure what alternative to suggest. I note that in the Baati study treatment started at 10 months of age, olive oil alone increased average life spans from 20 to 22 months. C60/evoo treated rats lived on average another 20 months without further treatment. If those rats had died of cancer and/or tumors like the others, I would infer that it took 20 months for the c60 effect, whatever it was, to wear off. But they died of old age. So maybe the effect which prevented the cancer and/or tumors, if it was an antioxidant one, would have lasted longer than 20 months if their body parts had given out first. In any case, I'm not sure where that leaves us on an optimal dosage guesstimate. Or the theory that cycling off until the c60 effect disappears might be beneficial. I can only observe that perhaps following the Baati dosage timeline exactly for 12 months followed by a 20 month timeout would be consistent with the study. And then what? Start over again? Hopefully at some point a followup study will give us a clue but it might take at least another 4 years.

Howard

[niner]

Although I am pretty convinced c60/evoo is a potent antioxidant, mainly from the Baati observation of the protective effect it had on the rats treated with CCl4, I'm still uneasy about using muscle fatigue to measure antioxidant effect and determine optimal c60/evoo dosage. Granted, some antioxidants seem to enhance my endurance. I'm thinking of resveratrol. But many do not. At least not for me. Like vitamin C, E, and a host of other antioxidants I take like GSE, Jiagulan, Milk Thistle, etc. I've got to say, resveratrol may be the only other antioxidant I've ever noticed an endurance enhancing effect from.

But I did try to do some searching through the literature relating to antioxidants and muscle fatigue. Came up with this interesting paper that summarizes what seems to be allot of research related to muscle fatigue:

http://physrev.physi.../88/4/1243.full

I found it interesting because it covers quite a few subjects that have been kicked around in this thread, like ROS, SOD, and singlet oxygen . And some that I don't remember seeing much of, like RNS. In any event, I got the impression after reading this that oxidative stress is only one of many factors that relate to muscle fatigue. Furthermore, this paper has a whole section on markers of oxidative stress, and muscle fatigue is not one of them. Which I think confirms my doubts. Unless improving muscle performance is your primary objective.

I'm not sure what alternative to suggest. I note that in the Baati study treatment started at 10 months of age, olive oil alone increased average life spans from 20 to 22 months. C60/evoo treated rats lived on average another 20 months without further treatment. If those rats had died of cancer and/or tumors like the others, I would infer that it took 20 months for the c60 effect, whatever it was, to wear off. But they died of old age. So maybe the effect which prevented the cancer and/or tumors, if it was an antioxidant one, would have lasted longer than 20 months if their body parts had given out first. In any case, I'm not sure where that leaves us on an optimal dosage guesstimate. Or the theory that cycling off until the c60 effect disappears might be beneficial. I can only observe that perhaps following the Baati dosage timeline exactly for 12 months followed by a 20 month timeout would be consistent with the study. And then what? Start over again? Hopefully at some point a followup study will give us a clue but it might take at least another 4 years.

Thanks for that link, Howard. I haven't read it all, but it looks pretty good. It looks to me like they think that ROS is a pretty big factor in muscle fatigue. If you haven't seen it, I posted this in my muscle fatigue thread:

J Appl Physiol. 2008 Mar;104(3):853-60. Epub 2007 Nov 15.
Muscle-derived ROS and thiol regulation in muscle fatigue.
Ferreira LF, Reid MB.

Department of Physiology, University of Kentucky, 800 Rose St., Lexington, KY 40536-0298, USA.

Muscles produce oxidants, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), from a variety of intracellular sources. Oxidants are detectable in muscle at low levels during rest and at higher levels during contractions. RNS depress force production but do not appear to cause fatigue of healthy muscle. In contrast, muscle-derived ROS contribute to fatigue because loss of function can be delayed by ROS-specific antioxidants. Thiol regulation appears to be important in this biology. Fatigue causes oxidation of glutathione, a thiol antioxidant in muscle fibers, and is reversed by thiol-specific reducing agents. N-acetylcysteine (NAC), a drug that supports glutathione synthesis, has been shown to lessen oxidation of cellular constituents and delay muscle fatigue. In humans, NAC pretreatment improves performance of limb and respiratory muscles during fatigue protocols and extends time to task failure during volitional exercise. These findings highlight the importance of ROS and thiol chemistry in fatigue, show the feasibility of thiol-based countermeasures, and identify new directions for mechanistic and translational research.

PMID: 18006866 Free full text

If you aren't seeing an effect on muscle fatigue from antioxidants, there are two probable reasons: The first is that you are not really dealing with muscle fatigue, i.e. the point at which you can no longer move the weight no matter how hard you try. You might be looking at something that's more like aerobic fitness. The other reason for not seeing an effect may be from using antioxidants that aren't partitioning into the mitochondrial compartment or are just weak antioxidants. The markers of oxidative stress in the paper you referenced are the classic chemical markers which they've nicely categorized. Muscle fatigue onset isn't a good general purpose marker because you can't compare results from one muscle to another, or from one person to another. What I think you can do with it is follow your own redox status, once you've established a baseline in a trained muscle, in the absence of the antioxidant. (untrained muscles have other competing failure modes involving neural effects)

I don't know that we can say that the rats still had C60 on board when they died. The C60 might have washed out a year earlier, and they lacked a great deal of oxidative damage at that point, but then started accruing it. From the data we have in Baati, we really just don't know if or when the rats ran out of c60.

[Logic]

It's not allowing them to die off, that's just part of the normal process. The half life of mitochondria is on the order of 2 days. My theory is that several half lives are needed before mitochondrial epigenomes that have been randomly improved by C60 treatment can increase their numbers sufficiently before you tweak them again. If you let them multiply for two weeks, that would be 7 doublings and 1 would become 128, which would take over 13% of the population if the cell had a thousand to begin with. If you went three weeks instead, it would take over the entire population. That's a bit simplistic, but it gives you the general idea.

Thx Turnbuckle.

Another question:
You mentioned PQQ being sunergistic with C60?
How are you incorperating it into your regmn/schedule?

[Turnbuckle]

It's not allowing them to die off, that's just part of the normal process. The half life of mitochondria is on the order of 2 days. My theory is that several half lives are needed before mitochondrial epigenomes that have been randomly improved by C60 treatment can increase their numbers sufficiently before you tweak them again. If you let them multiply for two weeks, that would be 7 doublings and 1 would become 128, which would take over 13% of the population if the cell had a thousand to begin with. If you went three weeks instead, it would take over the entire population. That's a bit simplistic, but it gives you the general idea.

Thx Turnbuckle.

Another question:
You mentioned PQQ being sunergistic with C60?
How are you incorperating it into your regmn/schedule?

Nothing special with the PQQ. I take 10 mg in the morning.

As for the maintenance dose of C60 I've been taking--initially 1/2 mg every other day--I noticed a difference in taking it at night as compared to the morning or not taking it at all. Taking it at night I slept better because I didn't have any aches and pains. Or fewer, anyway. And thus it seems that the prompt effects of C60 seem to wash out quickly. I'm now taking 1/4 mg twice a day and so far I'm happy with it.

Notes:
I expect this low dose will have little epigenetic effect.
I'm actually taking C60/C70, but will later switch to C60 to compare.

Edited by Turnbuckle, 09 November 2012 - 08:32 PM.

[Turnbuckle]

It's not allowing them to die off, that's just part of the normal process. The half life of mitochondria is on the order of 2 days. My theory is that several half lives are needed before mitochondrial epigenomes that have been randomly improved by C60 treatment can increase their numbers sufficiently before you tweak them again. If you let them multiply for two weeks, that would be 7 doublings and 1 would become 128, which would take over 13% of the population if the cell had a thousand to begin with. If you went three weeks instead, it would take over the entire population. That's a bit simplistic, but it gives you the general idea.

Thx Turnbuckle.

Another question:
You mentioned PQQ being sunergistic with C60?
How are you incorperating it into your regmn/schedule?

Nothing special with the PQQ. I take 10 mg in the morning.

As for the maintenance dose of C60 I've been taking--initially 1/2 mg every other day--I noticed a difference in taking it at night as compared to the morning or not taking it at all. Taking it at night I slept better because I didn't have any aches and pains. Or fewer, anyway. And thus it seems that the prompt effects of C60 seem to wash out quickly. I'm now taking 1/4 mg twice a day and so far I'm happy with it.

Notes:
I expect this low dose will have little epigenetic effect.
I'm actually taking C60/C70, but will later switch to C60 to compare.

The low dose continuous trial with C60/C70 did not go well. I started getting weird pains so I stopped taking it. I'll stick with C60 in the future.

[somecallmetim]

Turnbuckle,


Do you mind describing the weird pains that you were experiencing while taking the C60/C70?



Edit: Scratch that request Turnbuckle, I just read your recent post in the "C60: Experiments @ Home" thread where you explained the pains.

It is here for those who wish to read it: http://www.longecity.org/forum/topic/57492-c60-experiments-home/page__st__1410#entry545987

Edited by somecallmetim, 13 November 2012 - 07:04 PM.

[lastdeadmouse]

Fwiw, I started taking 2mg yesterday, and again today. I haven't noticed anything. That's not to say nothing is happening, but no noticeable changes. Just adding an anecdote.

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