Aspirin Comparable To DNP As Mitochondrial Uncoupler

[haidut]

This image is from the study I posted on the effects of aspirin on GI tract. As you can see from the attached image, aspirin increased mitochondrial respiration by 300% while DNP increased it by 400%. However, the authors stated that this concentration of DNP is not safe and in reality most people using DNP likely achieve uncoupling much closer to the one achievable with aspirin. In addition to its effectiveness, aspirin seems to be able to uncouple mitochondria over a much wider concentration range compared to DNP or indomethacin (which also uncouples respiration). This means that one can experiment with lower or higher doses of aspirin as needed, even though most people may end up trying a lower dose due to fear of GI side effects. As shown by the study, the fear of aspirin GI side effects is unfounded and if GI damage occurs it is likely caused by some other agent. Finally, aspirin has nothing close to the side effects observed with DNP.
As discussed several times on the forum, oral doses of aspirin needed to achieve the optimal concentration of 0.5mM (as shown on the image and other studies) are in the range of 1,000mg-1,500mg as a loading first dose, followed by 500mg every 4-6 hours.

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine. - PubMed - NCBI

And another similar study:
Inhibition of cardiac mitochondrial respiration by salicylic acid and acetylsalicylate. - PubMed - NCBI

 

[kineticz]

When I take 600mg aspirin it seems to increase my assertiveness and impatience? I feel really dominant

 

[schultz]

Amazing! Thanks for digging this up.

 

[RPDiciple]

i love it haidut. Thank you so much

 

[cantstoppeating]

This image is from the study I posted on the effects of aspirin on GI tract. As you can see from the attached image, aspirin increased mitochondrial respiration by 300% while DNP increased it by 400%. However, the authors stated that this concentration of DNP is not safe and in reality most people using DNP likely achieve uncoupling much closer to the one achievable with aspirin. In addition to its effectiveness, aspirin seems to be able to uncouple mitochondria over a much wider concentration range compared to DNP or indomethacin (which also uncouples respiration). This means that one can experiment with lower or higher doses of aspirin as needed, even though most people may end up trying a lower dose due to fear of GI side effects. As shown by the study, the fear of aspirin GI side effects is unfounded and if GI damage occurs it is likely caused by some other agent. Finally, aspirin has nothing close to the side effects observed with DNP.
As discussed several times on the forum, oral doses of aspirin needed to achieve the optimal concentration of 0.5mM (as shown on the image and other studies) are in the range of 1,000mg-1,500mg as a loading first dose, followed by 500mg every 4-6 hours.

So both aspirin and caffeine act as uncouplers to the same degree as DNP, but with lesser side effects. A few thoughts and questions: would you consider it wise to add aspirin (in doses mimicking DNP) to the caffeine doses also shown to mimic DNP?

I'm running a 4 week fat free experiment to rapidly deplete PUFA and get the liver lean again after years on keto/paleo. I'm already taking 800-1000mg of caffeine a day (thank god for l-theanine in helping restrain the negative effects) in the hopes of it acting as an uncoupler to speed up the process of getting the liver lean.

To me it makes sense to use one or the other for uncoupling. In the case of aspirin's known mechanism for inhibiting lipolysis -- does it matter? Mitochondrial uncoupling is inherently a different process than lipolysis and it can burn away fat in its own way, as said in an earlier study you posted:

The article claims that Type 2 diabetes is caused by fatty liver, and taking drugs that increase mitochondrial uncoupling can reverse the disease course.
Aspirin, caffeine, saturated fat, etc should do the job of uncoupling just as well.

http://news.rutgers.edu/research-news/a ... DIMWGeSz95

"...The modified medication – whose full name is niclosamide ethanolamine salt (NEN) – burned the excess fat in liver cells through a process known as mitochondrial uncoupling. ..."

A while ago, you posted something I too was thinking about:

..I have not answered for myself if it is best to just force through the fat burning period to get the liver lean and then refeed on proper carbs and moderate saturated fat, or if it is better to keep loading up on carbs (and block lipolysis) and hope the liver with get rid of the PUFA and excess fat through glucoronidation after several years like Peat suggests. Each method has its pros and cons and it will likely be a unique experience for each person...

In theory, perhaps the above is a false dichotomy and the solution is to take caffeine or aspirin in doses that induce uncoupling such that it burns away excess fat.

In practise however, the route you took (and a route I've taken that's also produced similar results) was to not block lipolysis:

...I have lost most of my extra weight I gained on Peat by stopping niacinamide and aspirin, avoiding PUFA whenever possible, keeping vitamin E levels close to the upper normal range in labs, keeping protein normal (80g-100g), and not really restricting sugar except making sure I consume no starch like bread, rice, potatoes, etc. It actually worked quite easily and it took about 3 months to drop the 30 extra pounds I had, and the only exercise I do is walk several miles a day at a slow pace and do pushups 3 times a week. Not exactly a hardcore exercise schedule...

Looking back, would you say you could have replicated the drop in 30 extra pounds by taking aspirin or caffeine in doses known to induce mitochondrial uncoupling?

In any case, I'm going to experiment and document my results whichever way I decide to go.

 

[RPDiciple]

Ive tried taking 1-1.5 grams now but i dont feel much from it. I have tried different dosages.

I was wondering if you could explain why some need more and some need less of aspirin for it to take effect? like what stuff in the body is the reason why some need more aspirin for it to get the super effects from it. Like is there some "chains" that just need to be broken that is harder in some then in others. Like higher estrogen, serotonin or stress in general will just need more aspirin for it to reduce?

 

[RPDiciple]

cantstoppeating: im in the same boat as you, i want to drop some fat fast without to much harm. Im only consuming skimmed milk atm and carrot salad. And want to speed things up with aspirin and caffeine. I only do coffee now since i dont have my caffeine powder. I dont have the l-theanine ***t tho but i can go super high on caffeine so thats no worry without it

 

[nikotrope]

I am in the same boat too. I want to drop some fat but nothing works. Currently I eat skimmed milk, oj, coke and sugar and don't lose fat at all. I tried 2000kcal for several days (I usually eat 2700-3000kcal) and it did nothing. I think I should be more patient though.

Anyway I am asking the same question, is aspirin will block fat lost or help it? There seem to be contradictory opinions.

 

[haidut]

This image is from the study I posted on the effects of aspirin on GI tract. As you can see from the attached image, aspirin increased mitochondrial respiration by 300% while DNP increased it by 400%. However, the authors stated that this concentration of DNP is not safe and in reality most people using DNP likely achieve uncoupling much closer to the one achievable with aspirin. In addition to its effectiveness, aspirin seems to be able to uncouple mitochondria over a much wider concentration range compared to DNP or indomethacin (which also uncouples respiration). This means that one can experiment with lower or higher doses of aspirin as needed, even though most people may end up trying a lower dose due to fear of GI side effects. As shown by the study, the fear of aspirin GI side effects is unfounded and if GI damage occurs it is likely caused by some other agent. Finally, aspirin has nothing close to the side effects observed with DNP.
As discussed several times on the forum, oral doses of aspirin needed to achieve the optimal concentration of 0.5mM (as shown on the image and other studies) are in the range of 1,000mg-1,500mg as a loading first dose, followed by 500mg every 4-6 hours.

So both aspirin and caffeine act as uncouplers to the same degree as DNP, but with lesser side effects. A few thoughts and questions: would you consider it wise to add aspirin (in doses mimicking DNP) to the caffeine doses also shown to mimic DNP?

I'm running a 4 week fat free experiment to rapidly deplete PUFA and get the liver lean again after years on keto/paleo. I'm already taking 800-1000mg of caffeine a day (thank god for l-theanine in helping restrain the negative effects) in the hopes of it acting as an uncoupler to speed up the process of getting the liver lean.

To me it makes sense to use one or the other for uncoupling. In the case of aspirin's known mechanism for inhibiting lipolysis -- does it matter? Mitochondrial uncoupling is inherently a different process than lipolysis and it can burn away fat in its own way, as said in an earlier study you posted:

The article claims that Type 2 diabetes is caused by fatty liver, and taking drugs that increase mitochondrial uncoupling can reverse the disease course.
Aspirin, caffeine, saturated fat, etc should do the job of uncoupling just as well.

http://news.rutgers.edu/research-news/a ... DIMWGeSz95

"...The modified medication – whose full name is niclosamide ethanolamine salt (NEN) – burned the excess fat in liver cells through a process known as mitochondrial uncoupling. ..."

A while ago, you posted something I too was thinking about:

..I have not answered for myself if it is best to just force through the fat burning period to get the liver lean and then refeed on proper carbs and moderate saturated fat, or if it is better to keep loading up on carbs (and block lipolysis) and hope the liver with get rid of the PUFA and excess fat through glucoronidation after several years like Peat suggests. Each method has its pros and cons and it will likely be a unique experience for each person...

In theory, perhaps the above is a false dichotomy and the solution is to take caffeine or aspirin in doses that induce uncoupling such that it burns away excess fat.

In practise however, the route you took (and a route I've taken that's also produced similar results) was to not block lipolysis:

...I have lost most of my extra weight I gained on Peat by stopping niacinamide and aspirin, avoiding PUFA whenever possible, keeping vitamin E levels close to the upper normal range in labs, keeping protein normal (80g-100g), and not really restricting sugar except making sure I consume no starch like bread, rice, potatoes, etc. It actually worked quite easily and it took about 3 months to drop the 30 extra pounds I had, and the only exercise I do is walk several miles a day at a slow pace and do pushups 3 times a week. Not exactly a hardcore exercise schedule...

Looking back, would you say you could have replicated the drop in 30 extra pounds by taking aspirin or caffeine in doses known to induce mitochondrial uncoupling?

In any case, I'm going to experiment and document my results whichever way I decide to go.

Aspirin and caffeine are additive in their effect on mitochondrial uncoupling. Hence the reason the (in)famous stack ECA had ephedrine, caffeine and aspirin in it. If you can handle the high dosages of caffeine combined with aspirin then by all means go for it. I think the effects of aspirin would depend on the dose. In smaller doses it likely blocks lipolysis and in higher doses it increases fat oxidation. All I know is that when I was taking 500mg a day and 500mg-1,000mg niacinamide a day (without caffeine) I was not losing weight but felt like gaining instead. But this could be due to me being hypothyroid at the time.
For people trying to lose weight, I'd still focus on caffeine and K2 until their liver function normalizes (as measured by both enzymes and tolerance to caffeine).
If I had to reproduce my experiment, I'd still go the caffeine route and add niacinamide only after losing excess fat.

 

[haidut]

Ive tried taking 1-1.5 grams now but i dont feel much from it. I have tried different dosages.

I was wondering if you could explain why some need more and some need less of aspirin for it to take effect? like what stuff in the body is the reason why some need more aspirin for it to get the super effects from it. Like is there some "chains" that just need to be broken that is harder in some then in others. Like higher estrogen, serotonin or stress in general will just need more aspirin for it to reduce?

I don't think anybody can answer that question definitively for you - why people need different dose of aspirin for the same effect. Considering how different we are metabolically, the "right" dosage for mitochondrial uncoupling probably varies quite a bit. That's why I posted a range, which is based on human studies. Even in those human studies the plasma levels of aspirin varied widely after taking the same dose. One thing you can do to improve absorption is take aspirin with glycine. The glycine will also protect your stomach.
There is no reliable way of knowing if your mitochondria was uncoupled unless somebody does measurements on your oxygen consumption, exhaled CO2, perspiration, etc. Temperature and pulse gives you some info, but they can be elevated by adrenalin too. In some studies they use rectal temperature as the only reliable measure of thermogenesis and to make it even more efficient sometimes they even block adrenalin with drugs to remove any possibility that the increased temperature was caused by stress.
So, aspirin could have been working for you and you didn't notice.

 

[Strongbad]

So since aspirin will improve mitochondrial respiration by 300%, then I need to jump into this aspirin bandwagon :) To give my hair some growth again.

So do you think Aspirin + Vitamin E + Vitamin K + Vitamin A (since E makes A more efficient) + Bone broth (it has glycine) is a good combo or should I add other things? I have to avoid caffeine for now since it stresses my adrenal function. I get jitters, adrenaline, fast heartbeat and anxiety from coffee, even after mixing it with milk, cocoa and raw honey

 

[RPDiciple]

haidut: how much caffeine and K2 would you aim for to clean fatty liver or get liver back to optimal function?

 

[RPDiciple]

Also back to aspirin dosages.
Will higher dosages always be better or work better or will to much be worse then say a small dose for some people in terms of the effect it will give?

 

[haidut]

So since aspirin will improve mitochondrial respiration by 300%, then I need to jump into this aspirin bandwagon :) To give my hair some growth again.

So do you think Aspirin + Vitamin E + Vitamin K + Vitamin A (since E makes A more efficient) + Bone broth (it has glycine) is a good combo or should I add other things? I have to avoid caffeine for now since it stresses my adrenal function. I get jitters, adrenaline, fast heartbeat and anxiety from coffee, even after mixing it with milk, cocoa and raw honey

I would ask this in separate thread, this one is about aspirin specifically. You are asking for a combination of food and supplements and many of these things have been discussed before. I will just say that if you are taking aspirin, then adding vitamin E may thin your blood too much. Try not to think of a "good" or "bad" combo, I am just posting various studies on various options for boosting metabolism. What will work for you can be decided only by your own experimenting and keeping track of temperature and pulse.

 

[haidut]

haidut: how much caffeine and K2 would you aim for to clean fatty liver or get liver back to optimal function?

There is a separate thread where people discuss specifically this topic and dosages. Just search the forum for "K2 aspirin".

 

[haidut]

Also back to aspirin dosages.
Will higher dosages always be better or work better or will to much be worse then say a small dose for some people in terms of the effect it will give?

The dosages I mentioned is what has been shown to achieve and sustain levels of 0.5mM in humans. This is what was shown boost metabolism the most. Whether higher or lower dosages would work I have no idea. The study on cellular respiration was done on cells (in-vitro) and it was easy for them to measure effects of specific aspirin dosages. What specific dosage of aspirin will boost YOUR respiration by 300% can only be determined by experimenting and measuring some surrogates like CO2, glucose load response, free fatty acids etc. It is not easy to determine effects of aspirin on metabolism of a living human being. Start with the mentioned dosages and adjust based on evidence of aspirin helping or not.

 

[Strongbad]

So since aspirin will improve mitochondrial respiration by 300%, then I need to jump into this aspirin bandwagon :) To give my hair some growth again.

So do you think Aspirin + Vitamin E + Vitamin K + Vitamin A (since E makes A more efficient) + Bone broth (it has glycine) is a good combo or should I add other things? I have to avoid caffeine for now since it stresses my adrenal function. I get jitters, adrenaline, fast heartbeat and anxiety from coffee, even after mixing it with milk, cocoa and raw honey

I would ask this in separate thread, this one is about aspirin specifically. You are asking for a combination of food and supplements and many of these things have been discussed before. I will just say that if you are taking aspirin, then adding vitamin E may thin your blood too much. Try not to think of a "good" or "bad" combo, I am just posting various studies on various options for boosting metabolism. What will work for you can be decided only by your own experimenting and keeping track of temperature and pulse.

Fair enough

 

[cantstoppeating]

Almost the end of my first day using aspirin as an uncoupler and I can report that my early morning temp quickly reached 36.6 Celsius and peaked at 37.2 Celsius with it hovering around 37 (+/- 0.1) throughout the rest of the day. Pulse increased in unison with temp.

Tomorrow I'll add caffeine to mix and note changes.

 

[haidut]

Almost the end of my first day using aspirin as an uncoupler and I can report that my early morning temp quickly reached 36.6 Celsius and peaked at 37.2 Celsius with it hovering around 37 (+/- 0.1) throughout the rest of the day. Pulse increased in unison with temp.

Tomorrow I'll add caffeine to mix and note changes.

Excellent. Btw, I think for testing purposes you can increase the aspirin to 1,000mg every hours instead of the 500mg every 4 hours boosting dose. It may work even better.

 

[cantstoppeating]

Almost the end of my first day using aspirin as an uncoupler and I can report that my early morning temp quickly reached 36.6 Celsius and peaked at 37.2 Celsius with it hovering around 37 (+/- 0.1) throughout the rest of the day. Pulse increased in unison with temp.

Tomorrow I'll add caffeine to mix and note changes.

Excellent. Btw, I think for testing purposes you can increase the aspirin to 1,000mg every hours instead of the 500mg every 4 hours boosting dose. It may work even better.

So 1000-1500mg as an initial dose then 1000mg every 4 hours? I'll give it a try since I expect my temp to exceed 37 C if I'm using an uncoupler.