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Lipid Soluble Alkaloids: Theobromine / Caffeine / Nicotine / Quinine

theobromine caffeine nicotine quinine alkalinization telomeres

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#1 Dorian Grey

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Posted 01 August 2025 - 03:09 AM


I became interested in Lipid Soluble Alkaloids (LSAs) while pondering the mysterious benefits of chocolate.  Jeanne Calment, the world’s longest lived human (122) was said to be very fond of chocolate (as well as cigarettes and port wine), consuming it a kilo per week, but what was the mysterious beneficial ingredient?  Flavanols?  Yes, but many foods are rich in flavanols, so how could this be what makes chocolate so special?  

 

Enter theobromine,, which has substantial effects on human physiology, and coincidentally is a lipid soluble alkaloid, which is fairly rare in  modern diets.  I’d read about those who feel shifting the body, which often becomes more acidic with age, back towards alkalinity, with some advocating drinking sodium bicarbonate in water; but I also read doctors opinions who claimed this would be futile, as it is too swiftly excreted to produce a lasting effect.  Theobromine however has a half life of 6-12 hours in humans, so perhaps this is a better way.  

 

Unfortunately, with chocolate being the only food rich in theobromine, and also very rich in sugar, this may present a compromising issue for many, as sugar is considered almost a poison to some (ME!).  

 

Looking at other / alternative LSAs, caffeine pops up, and coffee also is known to have some mysterious elixir of life ingredient that seems to ward off several chronic disease states and promote longevity; but once again, nothing really jumps out as unique to coffee except the caffeine, which is a lipid soluble alkaloid.  With a half life of 5-6 hours, twice per day dosing might be more effective than a single blast in the morning, and the caffeine side effects are unpleasant to some.  

 

Nicotine?  Well, it’s not for everyone, but I did note an unusual property regarding smoking and cancer.  Among smokers and ex-smokers, it seems the ex-smokers are more likely to get lung cancer than unrepentant / current smokers.  Tis a puzzlement!  Unless you consider smoking bathes the lungs in that lovely lipid soluble alkaloid nicotine, and this is somehow protective.  

 

I am also a believer in Ferrotoxic Disease…  That age related iron accumulation can promote accelerated aging and disease.  What’s this got to do with smoking?  Well, tobacco smoke particulate is fairly rich in IRON, which gets deposited in the lungs, causing oxidative stress, inflammation, and CANCER.  This iron persists long after quitting smoking, and likely may be what contributes to cancers that spring up many years after quitting.  

 

Interestingly…  Once you quit smoking and bathing your lungs in alkalizing nicotine, lungs can become more acidic which can render any iron to a very reactive state.  If you’re a blood donor, and/or chelating iron with IP6, this inflammatory iron will dissipate to leave a healthier pulmonary environment, but if you’re a male who’s been accumulating iron all his adult life, hepcidin (the bodies master iron transport hormone), will shut down iron transport, and lungs will remain full of highly reactive and inflammatory  iron.  If only there was a way to alkalize those poor lungs! 

 

There is yet another aspect to consider, and that is the alkalization of cellular organelles and autophagy.  Cellular lysosomes use acid to break down cellular garbage, and alkalizing them can inhibit this mechanism.  NOT GOOD one might think, but I have been unable to find just how much of a shift to alkaline moderate dietary LSAs do to lysosomes.  Quinine, Chloroquine & Hydroxychloroquine are all very powerful LSAs, some with a very long half life, with many who are treated with these for many years (even decades) for Rheumatoid Arthritis, Lupus, malaria prevention, etc, without much mention of the consequences of potent and persistent alkalization.  


Finally…  There is one more factor for consideration, and that is telomeres. I’m not an expert in this area, but I’ve read there is a delicate dance between autophagy and telomere health.  Cells burn brightly & hot in an acid environment, and also tend to burn out and be replaced rapidly, with telomeres shrinking a bit with every cell division. Shortening telomeres?  No Bueno!  


On the flip-side, alkalized cells tend to run cooler, with less autophagy and live longer lives, which may not sound too bad, but longer lived cells can have more accumulation of DNA breaks and damage, which may potentiate CANCER?  Perhaps…  But I would expect this would mean those on long term hydroxychloroquine therapy for RA & Lupus, would have a greatly increased proclivity for cancer, and I haven’t heard this to be so.  


What am I doing?  Well…  Moderation in all things!  I don’t smoke, and resist daily chocolate intake due to the sugar (and NO, I’m not forcing dark choc on myself or anyone else).  I do have a large, 22oz black, fresh brewed coffee most every day after lunch.  Coffee on an empty stomach is supposed to spike cortisol, so avoid that, but any time after you break your morning fast is fine, so long as you can sleep at night.  


I also switched from my old red wine evening tipple to Gin & Light Tonic.  I loved my cabernet, but the sulfites were a problem, and I switched to G & T during the plague for the quinine, and found I really liked it.  You must be careful to avoid full sugar tonic water, as it really is loaded with more sugar than even sodas to counteract the bitterness of the quinine.  Sugar free tonic has very little quinine, so this defeats the whole G & T benefit.  There is one Light Tonic I have found with only 30 calories per 6.8oz bottle, and a good natural quinine content, and that is FEVER TREE Light Tonic Water.  


I sip on two (or three) of these between dinner and midnight, and have found the 30 calorie per hour consumption rate does not create a sugar bomb or insulin flood/poisoning.  Quinine is in fact known to lower blood glucose, so there’s another reason to enjoy!  The quinine also seems to alkalize my stomach, and I don’t get reflux if I sleep on my right side anymore, like I did during my wine days.  .  


Please let me know your thoughts on this, and if I’ve made any erroneous assumptions.  

 


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#2 pamojja

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Posted 01 August 2025 - 12:57 PM

 

I don’t smoke, and resist daily chocolate intake due to the sugar (and NO, I’m not forcing dark choc on myself or anyone else)

 

I smoke, ferritin has been consistently low (avg. 75 ng/ml) and had been taken 20 g of organic cocoa powder and as much 85% dark chocolate for over a decade, only recently I quit the powder. Still do take the dark chocolate voluntarily, no need of force. ;-)

 

For quitting sugar - also in bitter things like pure cocoa powder - stevia extract helped me. Also used gymnea sylvestre extract against pre-diabetes, Meshashringi in India, there known as killer of the sweet taste. How that worked for me, I found out on my last recuperating vacation to an Indian beach, when I forgot the stevia extract at home. It didn't kill my sweet taste, but at least the most bitter, pungent and astringent tastes don't bother me anymore. Stevia extract actually, for the first time, was available at that place as a mix with xylitol. I did without this time.

 

Beside theobromine from cocoa products, berberine, caffeine and nicotine probably make the bulk of my daily alkaloids for me, summing up to a few 100 mg/d. Some piperine too. Blood pH has been about 7.46 average for many years. And experienced remission of a walking-disability from PAD, symptoms of COPD, and post-excertional malaise (PEM, otherwise the hallmark of ME/CFS).

 

 

 

 


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#3 Dorian Grey

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Posted 01 August 2025 - 04:17 PM

Thanks for the input pamojja.  I smoked a pipe for many years, but started feeling a bit of angina hiking up hills so had to lay it down a few years back.  The heart issue surprised me, as my lungs have always been great.  I'm a long term blood donor, so any iron in my lung tissue hopefully got tapped to replace all those red cells. I used to hike up and over the 200 steps at the convention center without coughing or even getting winded.  

 

I'm having trouble finding the ex smokers get more lung cancer than unrepentant/current smokers, so I may have to retract this.  I recall seeing it on the Forces International (smokers rights) site, and was impressed.  As I recall, it pertained to lifetime smokers who quit in their later/senior years, but I can't find it now.  I would have kept puffing till they nailed me into a box, but angina has a way of getting one's attention.  

 

I tried berberine, but it inflamed my colon, so I had to punt.  Perhaps I'll give the dark chocolate another try.  

 

Good to hear your PAD and other issues are under control! 


Edited by Dorian Grey, 01 August 2025 - 04:19 PM.

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#4 pamojja

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Posted 01 August 2025 - 05:34 PM

I smoked a pipe for many years, but started feeling a bit of angina hiking up hills so had to lay it down a few years back.

 

I also had angina like chest pain before starting supplementing, but in my case related to physical or mental stress only, before starting to supplement comprehensively more than 16 years ago. Along with life-style changes against the PAD. Found simply 160 mg/d of CoQ10, or half of that of Ubiquinol, ceased them. Also reanalyzing all my intake, interestingly realized intake had been highest at about 200 mg/d CoQ10+Ubiqunol during my last and most difficult remission of PEMs.
 

I'm having trouble finding the ex smokers get more lung cancer than unrepentant/current smokers, so I may have to retract this.  I recall seeing it on the Forces International (smokers rights) site, and was impressed.  As I recall, it pertained to lifetime smokers who quit in their later/senior years, but I can't find it now.  I would have kept puffing till they nailed me into a box, but angina has a way of getting one's attention.

 

It sure does. I was completely surprised with my diagnosis of PAD, and following the advice of my MDs about daily walking-exercise (for which I quit regular commuting by cycling; a huge mistake) and to quit smoking, that only with those 2 intervention my walking-disability got worse. Down to 3-400 meter painfree walking distance only.

 

Therefore, I started to search for any evidence that quitting smoking could improve a PAD walking disability. Or at least some benefit in quitting for life-long smokers in mortality. Found nothing, but 2 long term randomized controlled trials with life-long smokers, where the groups supported in quitting had no improved outcome. Less lung-cancer, sure, but more colon cancer instead. Almost no difference in mortality. That was the end of me quitting, and start to improve again.

 

I'm still certain not smoking would of course be better, to begin with. But after decades of it? -  The self-medication aspect, for someone with so many health issues from birth onward, certainly plays a role too.

 

I tried berberine, but it inflamed my colon, so I had to punt.

 

Took only a low dose. Like 110 mg/d during the last 16 years. Probably my high ascorbic acid intake quelled inflammation there too.

 


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#5 bullGenteel

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Posted 20 September 2025 - 06:00 AM

https://www.sott.net...nst-Lung-Cancer

"a thin mucous layer in the lungs, "which forms a protective layer stopping any cancer-carrying particles from entering the lung tissue."

I was in a community college class close to 20 yeara ago to give witness of an instructor gave a "Dr Gregory House, MD", type persuasive rhetoric formed on the spot to more less cover the crux of the theme. I have severe OCD it drove me a little crazy. I was on some meds that slowed my cognitive function, absence of serotonin booster SSRI, just my luck.

I vaguely remember googling it and finding a Canadian researcher that must have confirmed this article with some quantitative analysis and a similar conclusion in humans. I could be wrong about the details of the Google paper since I have a poor memory. I have had suspicions powers that remove papers they will to be removed. I can't find the paper I recalled on a web search. In the same way I saw multiple papers saying that notrphic agents could safely offset cognitive deficits attributed inlarge part by psychotropic meds and some part by psychiatric illnesses. I could imagine that would not be a avenue of investigation big pharma would want opened.

Might be a little TMI, little off-putting Im sure. I remember coughing up mucus whenever I wasn't alone, imaging radioactive particles trapped in mucus. Results were it did have the unintended serendipitous manifestation of a chronic inflammation with actual mucus layer seemed to be built up just in throat. I felt this may give me some protection as a blockade against any foreign infiltration.

I like to think I have made a lot of stide in personal transformation, as a
result I have less fear of dealth replaced with a higher purposes. But still have a healthier fear of dealth.

So it is probably is a good idea to prevent toxic exposure through lungs. Perhaps there are multiple toxic agents in the environment that increase cancer. Plastics and teflons were put into high use around the same time as nuclear testing. Perhaps a mucous layer can prevent microplastics from entering the lungs as well as any number of toxins we are exposed too. Prostate and breast cancer have greatly increased in the same time period as lung cancer. Two cancers I presume are hormonal in nature to a degree with plastics being a hormonal disruptor as far as I know.

I have trouble focusing on more than one complex topic. Just because it is on my mind. I wonder how much the member Questforlife's theory of aging and larger cells not being as efficient and reducing cellular waste might be beneficial on many fronts if addressed. I don't know if smaller cells may even have a better chance to lessen microplastics, forever chemicals or radioactive particles. It likely need to be examined by someone othe than me. I have no medical or science knowledge.
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#6 Dorian Grey

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Posted 20 September 2025 - 03:12 PM

Thanks for visiting my little rant bull, and thanks for the link. 

 

The paper I once saw about cancer rates lower in current compared to former smokers has vanished.  That google MEDIC update back in 2018 has a lot of work obscured by clouds now.  I probably should have looked before my original post in this thread, as now I've dinged my credibility.  

 

The secret behind the magical properties of coffee, chocolate, & perhaps to a lesser extent quinine, still present intrigue.  Even the polyphenols in resveratrol are better absorbed when combined with the lipid soluble piperine. 

 

I was hoping this might catch someones eye.  Thanks for noticing!  



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#7 Dorian Grey

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Posted 20 September 2025 - 05:02 PM

Here's a link to a page: https://www.longecit...rm/#entry564686

 

About 3/4 of the way down a post by "nightlight" has all the links, many of which have been banished.  

 

The highlight of one of nightlight's old posts was what was supposed to be the definitive study proving tobacco smoke caused cancer.  It seems though they had been able to cause cancer smearing tissue with concentrated tobacco tar, they hadn't actually proven tobacco smoke itself could cause cancer.  

 

The study exposed golden hamsters to high dose tobacco smoke for extended periods, but backfired spectacularly, when not only were cancer rates similar to controls, but test hamsters exposed to the smoke actually lived slightly (though not statistically significantly) longer than the controls.   

 

Tobacco smoke particulate does contain iron though, which is known to be highly inflammatory and in certain circumstances carcinogenic, which may become more reactive once the lipid soluble alkaloid (nicotine) is discontinued and tissues become more acidic.  

 

This study may be in one of the links he provides, though many of them are dead now.  Lets see if the way back machine can help: 

 

https://web.archive....s-good-for-you/

 

Bottom line...  It appears nicotine may have some remarkable properties regarding keeping iron deposits from tobacco smoke quiet and benign (via alkalinization).  Take away the nicotine, and tissues acidify, rendering the iron deposits highly reactive and toxic.  


Edited by Dorian Grey, 20 September 2025 - 05:19 PM.

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#8 bullGenteel

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Posted 20 September 2025 - 08:23 PM

That's interesting about nicotine perhaps having some cancer preventive properties thru promoting alkalinity. It seems either way tobacco smoke whether it is just the modern tobacco with all toxic additives likely causes some local trauma and/or DNA damage. Based off the fact that vitamin A apparently increases risk of cancer in smokers to enhace tumorgensis.

To prevent a spark in this case, no pun inteneded, smoking may protect against the tissue with DNA damage and/or scarring inflammed damage of lungs from progressing into cancer. I remember the research paper I read and maybe that article I posted stated having some thin mucous could act as a shield preventing particles that could be pro cancer from taking root. A google search did mentuon there is a radioactive particle released in burning tobacco. I don't know if that is fact or fiction. It was proposed smokers may still get cancer if weaker lungs make dislodging mucus more difficult for themselves.

Of course your work sounds like another interesting research angle. I never smoked myself but have some family members and friends of course who do. Myself, I am interested in cancer prevention and anti aging health through promoting more stem like cells and maintaining telomeres. Based off questforlife and turnbuckles work. I am figuring out how senitoics might be handled successfully, mostly based off quests theories. I am thinking along lines of a way to trick the body by replicating as near perfect the conditions that are present in our younger bodies that allow for replacement of cells. I had some intresting results experimenting that may point to this. I don't think current use of seniotic protocols actually replace cells. They may have u shaped postive response by lowering inflmmation by thier removal, but remove too many... I will make an inquiry on Quests thread when I get my thoughts together. I only focus on one topic at a time, I know my limitations.

Edited by bullGenteel, 20 September 2025 - 08:51 PM.

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#9 Dorian Grey

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Posted 21 September 2025 - 05:13 AM

The U shaped curve is vexatious... 

 

Autophagy reduces senescence, but can increase cell turnover, and every time cells turnover telomeres get shorter;  yet senecent cells accumulate DNA damage and increase cancers?  

 

This dichotomy has always puzzled me.  I like to look at reptiles, with their slower metabolism and remarkable longevity (200 year old tortoises), and would like to think a cooler metabolism would be desirable, so long as DNA damage doesn't become too problematic.  

 

I've been very keen on "Ferrotoxic Disease", and its avoidance as a fountain of youth.  Blood donation and iron chelation both showing remarkable longevity promise.   

 

https://www.longecit...isease-omnibus/

 

Ferrotoxic Disease Omnibus

 

I recall during the pandemic reading about how quinine / chloroquine / hydroxychloroquine drugs alkalize cellular organelles, effectively reducing autophagy, and one would think increasing cellular senescence, and thinking YIKES this really should increase cancers in the patients that take hydroxychloroquine long term (decades!) for rheumatoid arthritis / Lupus, etc, but this does not appear to be the case...  Long term alkalinization, slowing autophagy, and increasing cellular senescence does not seem to kill these patients, though they don't live 200 years either.  

 

Does this mean this cooler running metabolism is more desirable than a hot autophagy and cellular turnover physiology?  I really don't know, but determining this would seem to be key to a lot of longevity theories.  

 

I'm going with a cooler metabolism, through lipid soluble alkalinization, and reduction of ferrotoxic DNA damage through blood donation and iron chelation to minimize DNA damage in my slower cellular turnover bodkin.  I just don't see how running hot (and clean) would promote longevity over a cooler and slightly slower metabolism, when every time these hot running cells turnover, telomeres grow shorter.  


Edited by Dorian Grey, 21 September 2025 - 05:27 AM.


#10 bullGenteel

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Posted 22 September 2025 - 05:02 AM

Sounds like you bring up two opposing approaches to longevity as I see members presnet here. One side might want to kep the body at peak functioning with clearing out old cells, optimizing as many systems as possible like mitochondria to achieve an increase health span to increase life span. Other option being conserving energy and slowing down the system at a metabolic level to conserve resources and slow degradation to achieve longevity at the cost of vitality. The second strategy might use something like calorie restriction.

I am still working on neurogenisis to overcome a brain injury and also some developmental deficits I believe I had when born. Also, I am on a 13 day of a water fast. The fast is for neurogeneratuon after taken a few weeks to make my cells more stemlike. Perhaps to transform some sencient cells into stem like cells. I havent reached a stage where I am rwsdy toctscjle sencinet cells directly. I'd esnt to rescue as many damaged scient like cells first, if possible. I forget thebspecifics I rwad about a reason why keto and perhaps calorie restriction has a lot of good parameters involved, except for one that kills it as an idea. It was on another users long thread. I am trying to be practical and wrap my head around enough to allow me to practice protocols just to treat my disability successfuly. I seem to be slowly making progress, with some missteps causing me to fall behind while moving forward overall.

But fasting does not get rid of sencient cells. I believe an expert on here named Michael stated that before. A theory states that damage can shorten cells and make them sencient like. I seem to have a lot wirh my physical injuries. Fasting never made a dent in them, pun intended since swelling seems to be the presentation in my ankle. But this newest protocl to restore cells to younger type by increase in stemness has made a considerable improvement. I made a mistake int he first round and am still on the second round. My stem cell treatments, previous to my latest protocol, did reduce swelling before it stalled. I never used much sencient cells killing agents because of worries that it wouldn't work effectively. Actually from quests work, being in a fed state tells your cells to not grow anymore. That is the state your body has to be in to intitate the process of cell repair and or replace. So opposite of fasting. But it needs help or optimal conditions as we have in youth.

Its a complicated process to repair cells. I appreciate quests work. I believe he has done the work to show you can return your cells and behavior to a youthful state in order to successfully remove and replace sencient cells. I believe I may have srumbled on a way to direct your body to just replace cells that are not capable of being repaired. So to take a surgical approach vs a shotgun. Perhaps others have attempted this. I believe sencient agents will remove a lot more cells than is needed, especially datsnab. It would be super precise if the body could pick only worser cells to replace. You would then conserve the bodies resources like stem cells and reduce unnecessary cell turnover and telomere degradation. I know quest involved telomere enhancers in his protocol during this stage as well. I don't know how confident he is but it addresses the telomere quagmire with cell turnover. Perhaps if telomeres cannot be lengthened, atleast lessen attrition. A lot of things are still fuzzy for me. Perhaps that will lessen in the future.


Over the last few years I have incorporated as many practical and interesting theories I could that I found on this site. I think I felt better doing blood donation for a few years from reading your threads. I also wonder if just attempting to make cells younger and mote effcient might make the Krebs cycle more effcient and take care of waste products like iron. I barely understand any of this. Oh well. But effcient cells like younger version will be more effcient at removing waste in my layman understanding. Since young people have lower iron levels whether that's because the cells are more effcient, alternative premise being the body hasn't had time to buildup iron. But I believe it was mentioned that blood donation would also rssult in cell turnover to make mote blood.

For me I am just motivated to treat my brain injury and perhaps to be as healthy as possible. I wouldn't get drawn into considering all the longevity theories because it is hard enough to focus on my present endeavor.
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#11 QuestforLife

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Posted Yesterday, 10:08 AM

You may be interested that nicotine increases telomere length in treated mice.

 

See: https://www.longecit...-30#entry920902

 

They claimed that long term nicotine treatment reduced glucose dependence, but my experience with nicotine is that it increased my blood glucose and triglyceride levels, and this matches the literature on smokers/ex smokers. 

 

It may be that this can be overcome with a lower dose, (this is tricky as nicotine is pretty addictive), or perhaps by cleverly taking nicotine far away from any meals (particularly sugary or starchy meals).  


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#12 Dorian Grey

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Posted Yesterday, 04:21 PM

You may be interested that nicotine increases telomere length in treated mice.

 

See: https://www.longecit...-30#entry920902

 

They claimed that long term nicotine treatment reduced glucose dependence, but my experience with nicotine is that it increased my blood glucose and triglyceride levels, and this matches the literature on smokers/ex smokers. 

 

It may be that this can be overcome with a lower dose, (this is tricky as nicotine is pretty addictive), or perhaps by cleverly taking nicotine far away from any meals (particularly sugary or starchy meals).  

 

Thanks for the input QfL.  I've long been perplexed by the magical properties of tea & coffee, chocolate, and how some smokers seem to defy time.  Telomere maintenance might be the key.  I wonder if caffeine & theobromine protect telomeres too.  

 

The autophagy vs senescent cell conundrum may be involved.  Autophagy increases cell turnover and every cell turnover it is supposed to shorten telomeres, yet senescent cells, turning over more slowly accumulate DNA errors that likely increase incidence of cancer.  

 

Could it be the stimulating properties of caffeine, nicotine & theobromine help to stimulate autophagy while alkalizing cells reducing cell turnover that is normally inherent with high autophagy? 

 

This would be the best of both worlds if true.  


Edited by Dorian Grey, Yesterday, 04:22 PM.


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#13 QuestforLife

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Posted Today, 07:53 AM

I am not suggesting that everything comes back to telomeres, but from my thread:

 

Caffeine for telomeres:

 

https://www.longecit...-17#entry906174

 

Dark Chocolate for telomeres::

 

https://www.longecit...-17#entry906249

 

We might find there is a stimulant link in there somewhere. Nicotine is clearly a stimulant. As is caffeine and theobromine. 

 

As an aside, don't forget coffee (including decaf) us also a potent mTOR inhibitor, So slowing down cellular processes and cell turnover could also be part of the life extension/health effect it has.

 


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