2523 replies to this topic

[Turnbuckle]

I've never seen any evidence stem cells (other than embryonic stem cells) can re-elongate their telomeres. At best some residual telomerase activity can slow the rate of loss.

 

 

Adult stem cells express telomerase, and telomerase elongates telomeres. How much it does this is stochastic: some may shorten and some may lengthen, depending on factors like the amount of telomerase, the antioxidant status, etc. But there is an optimum--

 

"This work shows that the optimal length for telomeres is a carefully regulated range between two extremes," says Jan Karlseder, a professor in Salk's Molecular and Cell Biology Laboratory and senior author of the work. "It was known that very short telomeres cause harm to a cell. But what was totally unexpected was our finding that damage also occurs when telomeres are very long."

 

...As telomeres shorten over time, the chromosomes themselves become vulnerable to damage. Eventually the cells die. The exception is stem cells, which use telomerase to rebuild their telomeres, allowing them to retain their ability to divide, and to develop ("differentiate") into virtually any cell type for the specific tissue or organ...

 

Perhaps not surprisingly, cells with too little telomerase had very short telomeres and eventually the cells died. Conversely, cells with augmented levels of telomerase had very long telomeres. But instead of these cells thriving, their telomeres developed instabilities.

 

https://medicalxpres...y-telomere.html

 

 

In fact, stem cells trim back telomeres if they get too long. From the same article--

 

The team observed that very long telomeres activated trimming mechanisms controlled by a pair of proteins called XRCC3 and Nbs1. The lab's experiments show that reduced expression of these proteins in ESCs prevented telomere trimming, confirming that XRCC3 and Nbs1 are indeed responsible for that task.

 

[QuestforLife]

I don't think telomere trimming is relevant in vivo - in the paper you quote the researchers augmented telomerase activity beyond what even ESCs can do. It's certainly not relevant to adult stem cells.

 

Also contrary to what the researchers state it is unsurprising excessively long telomeres are harmful, as telomeres have less protection against ROS than the rest of the chromosome. As an aside, this is a strategy for attacking cancer that uses the ALT mechanism of telomere elongation - which results in very long telomeres. Upping the DNA damage response is very harmful to such cells.

 

I will continue my research but I still believe stem cells do suffer from short telomeres - but we can agree to disagree on that point for now.

 

Going back to my other point - do you think In addition to upregulating fusion (and perhaps downregulating fission) we could temporarily inhibit normal ATP production with something like Berberine, Meformin or Glucosamine to encourage symmetric division? Come to think of it, Honokiol is known to open the transition pore:

 

https://www.ncbi.nlm...pubmed/17510419

Edited by QuestforLife, 14 June 2018 - 01:48 PM.

[Turnbuckle]

Going back to my other point - do you think In addition to upregulating fusion (and perhaps downregulating fission) we could temporarily inhibit normal ATP production with something like Berberine, Meformin or Glucosamine to encourage symmetric division? Come to think of it, Honokiol is known to open the transition pore:

 

https://www.ncbi.nlm...pubmed/17510419

 

 

Stem cells remain quiescent because their mitochondria are shut down, and they are shut down because they are loaded up with UCP pores that allow protons to escape and thus short-circuit ATP production. My hypothesis is that C60 has the right size to plug those pores, and thus stem cell mitochondria suddenly wake up and begin the process of proliferation--

 

UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells

 

Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential.

 

https://www.ncbi.nlm...les/PMC3243621/

 

 

While mito fusion biases the stem cell to symmetric division, it's the sudden increase in ATP production that gets the process rolling. Thus you don't want to decrease it.

Edited by Turnbuckle, 14 June 2018 - 04:34 PM.

[Turnbuckle]

Another apparent benefit of this protocol —

 

For a couple of decades I’ve seen a distortion in the Amsler grid -- wavy lines in one area of one eye. This was stable so I didn’t worry about it, and last year it was still there. Yesterday I noticed it was gone. Now the grid looks regular and flat in both eyes.   

———————

 

Stem cell self-renewal protocol, update 3

 

 

Time 0 (suggested 3 hours before bedtime, on empty stomach) —

Astragalus root extract powder — 5 g

 

Optional —

Cycloastragenol — 10 mg

 

Time 1:00 —

Stearic acid — 10 g, in brownie or hot chocolate (post #7)

 

Time 2:00 —

TUDCA — 500 mg

Jiaogulan — 800 mg (or LEF brand AMPK activator)

L-Threonine — 5 g

Taurine — 5 g

ALA — 600 mg

Vitamin C — 2 g (extended release)

NAC — 600 mg (extended release)

 

Time 3:00 —

C60 — 1 teaspoon of .6 mg/ml in oil, 3 mg C60

———————

 

Notes:

 

1. Since stem cells shut down their mitochondria, creating new mitochondria during the protocol might be a mistake, thus I eliminated the PQQ. This increased the transient fatigue that comes hours later, yet the results seem better. Conversely, when I added one supplement that eliminated fatigue, I got no apparent benefit.

 

The fatigue may be from low blood pressure.

 

2. I’m now using extended release C & NAC. I like this combination for general purposes.

 

 

Edited by Turnbuckle, 17 June 2018 - 08:07 PM.

[Turnbuckle]

Something to watch out for--

 

The protocol of post post 214 above (where I'd removed PQQ) dropped my blood pressure dramatically. Normally it runs about 135/85 with drugs (and a systolic of 160-180 without drugs), but several hours after the last step it began to fall, ultimately reaching 80/50, then slowly began rising over 2 days to 100/60 (with no antihypertensive drugs). Subsequent PQQ had no apparent effect. 

Edited by Turnbuckle, 19 June 2018 - 06:06 AM.

[Fafner55]

Turnbuckle, do you have insight into which supplement or what mechanism caused your drop in blood pressure?

[Turnbuckle]

Turnbuckle, do you have insight into which supplement or what mechanism caused your drop in blood pressure?

 

 

I cut the PQQ in the suspicion that it might be limiting the self-renewal of stem cells. It's known that stem cell treatments can lower BP, but that is normally seen after months of treatment, and is not this dramatic. It's also possible the BP drop has something to do with mitochondria. Last year I had a similar experience while doing my fission/fusion protocol, as mentioned in this post. It wasn't nearly to this degree, however, nor was I able to repeat it. I'd found that fission generally lowered BP and fusion raised it, so this is the first time I've seen a drop in BP with fusion. And the biggest one ever, by far.

 

The causes of hypertension are poorly understood and thus the treatments are symptomatic. If this stem cell treatment were somehow getting at the root cause, that would be a great advance. Still, before getting ahead of things by creating hypotheses, the first step is to see how long it lasts, and the second is to repeat it.

[QuestforLife]

Vasodilation may have be caused by all the antioxidants you are taking (combined with lower ROS from mito fusion). Or you may even have succeeded in causing proliferation of endothelial progenitor cells and rejuvenated your vasculature. If the effects are short lasting I suspect the first explanation; if they endure they the latter explanation becomes more likely.

 

I've pointed out this study before, which achieves something similar by a short term (1-month) cycle of low dose sartan and statin treatment. A blood pressure drop was not reported (the dose of sartans was intentionally kept below the threshold that would cause this), but flow-mediated dilation of the brachial artery was reported, along with decreases in vascular adhesion molecule concentration and C-reactive protein, and increased total antioxidant status. The effects lasted much longer than the treatment duration. The mechanism is obscure but seems to be linked to an increase in telomerase activity. The authors note they do not know whether this increase was caused by an increase in telomerase activity in endothelial cells, or an increase in their number.

 

https://www.ncbi.nlm...pubmed/26214555

 

 

 

 

[Kentavr]

QuestforLife, pls, see it:

https://m.youtube.co...h?v=frzpQONNX0o

The best of sartans - telmisartan:

https://en.m.wikiped...iki/Telmisartan

The drug "Mikardis" is widely known, but it has a diuretic in its composition. This is dangerous because it lowers the level of the potassium element in the blood (it is washed out with a diuretic).

I recommend finding telmisartan and without a diuretic.

Temilsartan in its pure form is very good as a geroprotector.

[Turnbuckle]

The observation in post #215 does repeat. By following my BP hour by hour, I saw a relatively rapid rise for the first few hours after the C60 dose, then a slow drop off to below baseline. Trying it a second day in a row, it dropped again, in this case reaching 90/60. (It might have dropped lower, but I wasn't monitoring it as closely at that point). Then it began to slowly rise again. The initial rise can be ascribed to fusion, which I've noted before raises BP, then the drop can be attributed to the decline in fusion as the stearic acid burns off, with an additional and much greater drop due to some unknown effect, possibly having to do with stem cells.  

[Fafner55]

... then the drop can be attributed to the decline in fusion as the stearic acid burns off, ...

 

If stearic acid burns off after a few hours, does it make sense to modify the protocol to take it 3 times per day?

[Turnbuckle]

If stearic acid burns off after a few hours, does it make sense to modify the protocol to take it 3 times per day?

 

Why? So I can have higher BP?

Edited by Turnbuckle, 22 June 2018 - 02:28 PM.

[Fafner55]

Why? So I can have higher BP?

 

Not for that reason. It would be to stimulate greater fusion. Not everyone has a problem with high BP, and for those with healthy BP more fusion could lead to an increased bias towards symmetric division. Do you think this would be the case?

[Turnbuckle]

Not for that reason. It would be to stimulate greater fusion. Not everyone has a problem with high BP, and for those with healthy BP more fusion could lead to an increased bias towards symmetric division. Do you think this would be the case?

 

I expect C60 blocking the UCP pores (hypothetical) will be the limiting factor (see post #17). That won't last long, but will commit stem cells to symmetric or asymmetric division based on the morphology of the mitochondria at that point. Once set in motion, the entire process should be complete at 24 hours, so you would not want to stimulate them more frequently than that with more C60. More stearic acid after stem cells have made the initial commitment should have no effect.

 

Bottom line: you want the mitochondria in a state of fusion before taking C60. Not afterward.

 

During development and in the context of tissue regeneration, there are molecular mechanisms in place, at the transcriptional and translational levels, to regulate stem cell function. We now uncover that the state of an organelle, namely mitochondria, has the capacity to coordinate self-renewal versus differentiation of stem cells. Mitochondria are dynamic organelles that undergo morphological changes through fission and fusion. Although major changes in mitochondrial structure have been generally attributed as a cellular response to stress, we now present evidence that mitochondrial dynamics can act as a functional regulatory factor, beyond ATP generation, in the context of physiological and developmental processes. In fact, mitochondrial dynamics serves as a regulatory point for the coordination of a nuclear developmental program in NSCs, by dictating the cellular redox state... we present a model whereby changes in mitochondrial structure direct the fate of stem cells. In this model, elongated mitochondria in NSCs maintain low ROS levels and promote self-renewal, while a transition of mitochondria to a more fragmented state results in a modest increase in ROS levels, thereby inducing the expression of genes that inhibit self-renewal (Botch) and promote commitment and differentiation.

https://www.scienced...934590916300820

 

[triguy]

and the division of bone marrow cells increases starvation (due to increased expression FOXO1). The number of bone marrow stem cells increases 6 times:



Controlled fasting should be 5-6 days, then a break of 25 days (within 25 days there is a recovery of the body, during this period one should eat well). The procedure must be repeated 8 times.
And not a penny of money.

 

 

 

what is considered "CONTROLLED FASTING"??

 

% of 

fat

carbs

protein

 

total number of calories???

[HaplogroupW]

Turnbuckle: are you sure you want that Jiaogulan/AMPK activator in there before the C60?

 

https://www.ncbi.nlm...les/PMC4852862/

 

Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress.

 

Another thought: perhaps this protocol would do well to break your light-speed fast, since fasting induces fused mitochondria:

https://www.ncbi.nlm...les/PMC3121813/

https://www.ncbi.nlm...ubmed/21478857/

 

 

Edited by HaplogroupW, 23 June 2018 - 04:33 AM.

[Turnbuckle]

Turnbuckle: are you sure you want that Jiaogulan/AMPK activator in there before the C60?

 

https://www.ncbi.nlm...les/PMC4852862/

 

Another thought: perhaps this protocol would do well to break your light-speed fast, since fasting induces fused mitochondria:

https://www.ncbi.nlm...les/PMC3121813/

https://www.ncbi.nlm...ubmed/21478857/

 

Thanks. I will take delete Jiaogulan from the protocol. As for the second reference, this may explain why my attempt at fission during a fast was a bomb.

[Turnbuckle]

Stem cell self-renewal protocol, update 4

 

 

Time 0 —

Astragalus root extract powder — 5 g

 

Optional —

Cycloastragenol — 10 mg

 

Time 1:00 —

Stearic acid — 10 g, in brownie or hot chocolate (post #7)

 

Time 2:00 —

TUDCA — 500 mg

L-Threonine — 5 g

Taurine — 5 g

ALA — 600 mg

Vitamin C — 2 g (extended release)

NAC — 600 mg (extended release)

 

Time 3:00 —

C60 — 1 teaspoon of .6 mg/ml in oil, 3 mg C60

Edited by Turnbuckle, 23 June 2018 - 08:49 AM.

[lost69]

i was not taking pqq but mitoq and i made protocol without it yesterday but instead of BP lowering like previously and like my baseline values (baseline around 104-115/84-74) i got a small increase to 124/92.i also didn t take milk thystle and went swimming after the protocol, i had less energy than usual swimming but i cannot tell if it is the protocol or the fact i didn t swim this week.no fatigue or sleepy like first rounds of protocol

i still use gdf11 once a week and hydrogen pills+C60 and thinking to add back mitoQ

 

i m at 6th or 7th round and i m getting sudden muscles growth, shoulder growth while swimming much less due to my job, this week only 30min swim

 

i need to take 2 weeks of antibiotics for a mild infection i have since 1 year, i have no symptoms now but only lowering of vocal range like when you have a bad throatache and a swollen tonsil but if i get immune system down i can get some throatache.

do you think this is a problem with the protocol or with stemcells activity?results are so amazing week by week that i prefer not to take antibiotics now if there is interference with stemcells or this protocol

 

do you think that protocol might lower vocal range like during puberty?i have soprano range despite being male but vocal range has got extended to very low range and high range notes are not there anylonger or bad sound, dont know if this is the mild infection or if protocol might do this

Edited by lost69, 23 June 2018 - 08:58 AM.

[Turnbuckle]

i need to take 2 weeks of antibiotics for a mild infection i have since 1 year, i have no symptoms now but only lowering of vocal range like when you have a bad throatache and a swollen tonsil but if i get immune system down i can get some throatache.

 

do you think this is a problem with the protocol or with stemcells activity?results are so amazing week by week that i prefer not to take antibiotics now if there is interference with stemcells or this protocol

 

 

 

do you think that protocol might lower vocal range like during puberty?i have soprano range despite being male but vocal range has got extended to very low range and high range notes are not there anylonger or bad sound, dont know if this is the mild infection or if protocol might do this

 

According to one paper, this will vary according to the antibiotic. However, all those tested showed lower in vitro viability after 24 hours, so I would not mix the two. What's 2 weeks, anyway?

 

Impact of Antibiotics on the Proliferation and Differentiation of Human Adipose-Derived Mesenchymal Stem Cells

 

As for lowering your voice, that certainly seems a possibility. Professional singers should be wary.

[lost69]

it s a chronic infection by now and all antibiotics used did not work to clear it definitively even if used for 2-3 weeks it keeps coming back as mild infection/throatache after i stop.all tests even dna tests in the troat are negative and tests were done during throat infection.i found cumin oil can keep it in check like when i take antibiotics and i found out about its potency on studies for antibiotics resistance

 

immune system is good because i never get flu or viral infections even when exposed to them due to all family sick but it is weak on all bacterial infections and i think mercury could be the reason

 

i removed 2 amalgamas few weeks ago and the infection got immediately weaker (and many other little problems like refulx, metallic taste, candida mouth sores and so on) and the plan was amalgamas removal and combo of new antibiotic plus cumin oil and hopefully clear it once and for all.but i can also wait since it is now very weak and also wait to see if it clears on its own as C60 slowly removes mercury

Edited by lost69, 23 June 2018 - 09:58 AM.

[Turnbuckle]

it s a chronic infection by now and all antibiotics used did not work to clear it definitively even if used for 2-3 weeks it keeps coming back as mild infection/throatache after i stop.all tests even dna tests in the troat are negative and tests were done during throat infection.i found cumin oil can keep it in check like when i take antibiotics and i found out about its potency on studies for antibiotics resistance

 

immune system is good because i never get flu or viral infections even when exposed to them due to all family sick but it is weak on all bacterial infections and i think mercury could be the reason

 

i removed 2 amalgamas few weeks ago and the infection got immediately weaker (and many other little problems like refulx, metallic taste, candida mouth sores and so on) and the plan was amalgamas removal and combo of new antibiotic plus cumin oil and hopefully clear it once and for all.but i can also wait since it is now very weak and also wait to see if it clears on its own as C60 slowly removes mercury

 

 

Try EDTA and/or liposomal cucurmin for the mercury. I doubt that 3 mg C60 will do much in that regard.

[lost69]

Try EDTA and/or liposomal cucurmin for the mercury. I doubt that 3 mg C60 will do much in that regard.

 

thanks i didn t know about curcumin, i use it in liposomal form every day except on protocol days, can it be used when on protocol?

 

i had also plans to chelate by ALA but it is too hard to take it every 3 hrs (ala half-life)

[aribadabar]

Stem cell self-renewal protocol, update 4

 

 

Time 0 —

Astragalus root extract powder — 5 g

 

Optional —

Cycloastragenol — 10 mg

 

Time 1:00 —

Stearic acid — 10 g, in brownie or hot chocolate (post #7)

 

Time 2:00 —

TUDCA — 500 mg

L-Threonine — 5 g

Taurine — 5 g

ALA — 600 mg

Vitamin C — 2 g (extended release)

NAC — 600 mg (extended release)

 

Time 3:00 —

C60 — 1 teaspoon of .6 mg/ml in oil, 3 mg C60

 

Is each successive iteration of the protocol a "better" version i.e. some of the constituents now removed were deemed not as important/necessary and only essential/core elements are retained?

What is your experience between the 4 different combos so far?

[Turnbuckle]

thanks i didn t know about curcumin, i use it in liposomal form every day except on protocol days, can it be used when on protocol?

 

i had also plans to chelate by ALA but it is too hard to take it every 3 hrs (ala half-life)

 

Since curcumin is another ampk activator, you are probably right to use it on non-protocol days. Still, taking it a few hours after C60 would likely be fine.

[Turnbuckle]

Is each successive iteration of the protocol a "better" version i.e. some of the constituents now removed were deemed not as important/necessary and only essential/core elements are retained?

What is your experience between the 4 different combos so far?

 

 

All you really need to make this work is stearic acid and C60. Stearic acid drives mitochondria to fusion, and C60 (I've hypothesized) blocks UCP pores and begins the proliferation of stem cells, with a bias to symmetric division (self renewal). This is clearly better than taking C60 alone, as the initial positive results faded with passing months, presumably the result of depletion of the stem cell pool. Fusion via stearic acid brings that back. All the rest is bells and whistles, and most of that is being done based on research papers which have been addressed all through this thread. One big concern is that that telomeres of stem cells are maintained, because otherwise we could end up back where we started with C60 in 2012, with a protocol that looks good at first and then fades. Ideally with symmetric division no somatic cells would be created at all during a treatment, and thus it would be impossible to tell right away if something is working or not. It's not like the fission/fusion protocol for mitochondria where the fission state was obvious in the gym. This is a gradual process with the SC pool is being replenished and used by the body as needed, and so it is necessarily dependent on best guesses, backed up as much as possible by research papers. I don't believe I've moved anything in or out without giving a reason, with a possible exception of the form of a given supplement, such as using an extended instead of immediate release pill.

Edited by Turnbuckle, 23 June 2018 - 09:14 PM.

[Graviton]

 

 

I’m presently using 10 g of stearic acid (120 mg/kg) and 1 teaspoon of C60 in olive oil half an hour later, doing this once a week or so. The oil is my own mix from 2016, which I’d stored in the freezer. It contained 0.6 mg/kg of C60 in Frantoio Pruneti EVOO which tested at 608 mg/polyphenols (mostly oleuropein), to which I added 1400 mg/kg hydroxytyrosol (HT). This oil with extra HT proved to be one of the better of my olive oil experiments for exercise.

 

How do you know taking stearic acid about an hour before C60 can work?

Usually, fat digestion takes time, and how do you get the pharmacology data of stearic acid?

 

Also, you seem to think C60 becomes inactive in a few days, why do you think in a such way? Isn't that no one knows?

Do you guess that there seems to be some kind(s) of enzyme(or something else) to inactive metabolite(s)?

 

 

 

 

Edited by Graviton, 24 June 2018 - 08:12 AM.

[Turnbuckle]

How do you know taking stearic acid about an hour before C60 can work?

Usually, fat digestion takes time, and how do you get the pharmacology data of stearic acid?

 

Also, you seem to think C60 becomes inactive in a few days, why do you think in a such way? Isn't that no one knows?

Do you guess that there seems to be some kind(s) of enzyme(or something else) to inactive metabolite(s)?

 

 

You are quoting the initial post with an early experiment. I soon changed that to two hours, recommending that it be taken baked in a brownie or dispersed in hot chocolate with lecithin, and on an empty stomach. If you are making the argument that more time should be allowed, perhaps you are right. However, by post #83 I was suggesting doing this 3 days in a row. As for C60, the mechanism vis-a-vis stem cells is entirely hypothetical, and is based on research showing that C60 stimulates stem cells, and that other nanoparticles such as silver and gold do so as well, suggestive of a possible physical rather than chemical mode of action. It's known that mitochondria of stem cells are quiescent, kept that way by UCP pores that short circuit oxidative processes by allowing protons to escape, and that coincide with the activation of stem cells, these pores disappear. Thus is was my hypothesis that C60 is blocking these pores and kick-starting SC mitochondria and thus stem cell proliferation. This also explains why many users (including myself) saw a distinct bump in energy levels just half an hour after taking C60 dissolved in olive oil, as UCP pores in all mitochondria would be blocked, not just those in stem cells. My own experience is that the bump in energy with a 3 mg dose lasts only a few hours, which suggests that regardless of how long it takes for C60 to be cleared from the body, the effect on UCP pores has a rather limited time frame.

Edited by Turnbuckle, 24 June 2018 - 09:35 AM.

[orion22]

1 how much time does it take for a stem cell to devide?

2 can the same stem cell start deviding again right after if we raise nad what about the newly made one?

3 how much time from when we raise nad+ do stem cells start to devide and does nad+ level have to be mentained 

Edited by orion22, 24 June 2018 - 07:11 PM.

[lost69]

You are quoting the initial post with an early experiment. I soon changed that to two hours, recommending that it be taken baked in a brownie or dispersed in hot chocolate with lecithin, and on an empty stomach. If you are making the argument that more time should be allowed, perhaps you are right. However, by post #83 I was suggesting doing this 3 days in a row. As for C60, the mechanism vis-a-vis stem cells is entirely hypothetical, and is based on research showing that C60 stimulates stem cells, and that other nanoparticles such as silver and gold do so as well, suggestive of a possible physical rather than chemical mode of action. It's known that mitochondria of stem cells are quiescent, kept that way by UCP pores that short circuit oxidative processes by allowing protons to escape, and that coincide with the activation of stem cells, these pores disappear. Thus is was my hypothesis that C60 is blocking these pores and kick-starting SC mitochondria and thus stem cell proliferation. This also explains why many users (including myself) saw a distinct bump in energy levels just half an hour after taking C60 dissolved in olive oil, as UCP pores in all mitochondria would be blocked, not just those in stem cells. My own experience is that the bump in energy with a 3 mg dose lasts only a few hours, which suggests that regardless of how long it takes for C60 to be cleared from the body, the effect on UCP pores has a rather limited time frame.

 

i posted in the past that i had extreme fatigue sleeping all day at a previous round of the protocol, today i found out that it happens only if i mix stearic acid+raw cocoa+boiling oat milk and soya lectine while avoiding lectine i dont have any or very mild fatigue.

 

is it possible lectine makes such a huge difference?can we say more fatigue equals to more stemcell activity?

 

extreme fatigue happens few hours after c60 and keeps getting worst for many hours.this time i took c60 at 19:00 and fatigue is hitting max at 22:00 which is ok since i can go to sleep now