Study Shows Aspirin Inhibits Mitochondrial Complex I

[zarrin77]

So I know Peat says that aspirin increases oxidative glucose metabolism, however this study (and if you read the full text, other studies as well) shows that all NSAIDs, including aspirin, inhibits mitochondrial complexes (especially complex I).

This study shows that quercetin can be used to mitigate this effect by allowing normal electron flow, and I'm aware of all the benefits to aspirin, but perhaps we should take steps to hamper this effect when using aspirin regularly? (Such as taking quercetin with it)

Any thoughts or ideas from you guys?

http://fulltext.study/download/2580725.pdf

Full text if you scroll down and click full text. Also attached.

 

[haidut]

So I know Peat says that aspirin increases oxidative glucose metabolism, however this study (and if you read the full text, other studies as well) shows that all NSAIDs, including aspirin, inhibits mitochondrial complexes (especially complex I).

This study shows that quercetin can be used to mitigate this effect by allowing normal electron flow, and I'm aware of all the benefits to aspirin, but perhaps we should take steps to hamper this effect when using aspirin regularly? (Such as taking quercetin with it)

Any thoughts or ideas from you guys?

http://fulltext.study/download/2580725.pdf

Full text if you scroll down and click full text. Also attached.

As the study says, these chemicals have uncoupling effects. So, if I am reading this right, taking aspirin increases need for CoQ10 as an electron carrier. Maybe another reason to take vitamin K with aspirin.
"...In fact, NSAIDs have been shown to uncouple oxidative phosphorylation, dissipate mitochondrial membrane potential (MMP), inhibit mitochondrial oxygen consumption and lower ATP synthesis."

"...This inhibitory effect was concentration-dependently reverted by increasing the concentration of added CoQ10 beyond 32.5uM. A full recovery was attained with concentration of 520uM."

 

[Such_Saturation]

You can't have your cake and eat it

 

[zarrin77]

Thank you for your reply. I understand the need for more co Q 10 with aspirin (ps. Why would K increase coQ10?)

However, dissipating energy as heat (uncoupling) and lowering the ATP of the cell does not sound like a positive thing. Is this just something we need to accept that aspirin does then and take proper steps to mitigate it (take vitamin K or quercetin, as they used in the study)?

 

[haidut]

Thank you for your reply. I understand the need for more co Q 10 with aspirin (ps. Why would K increase coQ10?)

However, dissipating energy as heat (uncoupling) and lowering the ATP of the cell does not sound like a positive thing. Is this just something we need to accept that aspirin does then and take proper steps to mitigate it (take vitamin K or quercetin, as they used in the study)?

No, vitamin K is a quinone and can serve as the electron carrier when CoQ10 is depleted. Vitamin K also happens to reduce the risk of bleeding with aspirin use and since Peat recommends taking K with aspirin, given this study we have another reason to do it - to prevent the complex I inhibition by aspirin.
I would not say uncoupling is a bad thing. Most metabolic boosters like caffeine, DNP, thyroid, etc will uncouple in higher doses. Producing a lot of heat from food is usually a biomarker of youthful metabolism. There are some bad exceptions but for most intents and purposes, temperature goes down with aging and is very low in old people. So, old age is quite literally like "freezing", both physically and mentally.

 

[zarrin77]

Thank you Haidut! Extactly the type of response I needed to interpret this study correctly. :)

 

[DaveFoster]

We need stickies on this forum.

 

[Such_Saturation]

We need stickies on this forum.

Like le reddit?

 

[DaveFoster]

Like le reddit?

Oh gawd. Anything but reddit.

 

[energyandstruct]

No, vitamin K is a quinone and can serve as the electron carrier when CoQ10 is depleted. Vitamin K also happens to reduce the risk of bleeding with aspirin use and since Peat recommends taking K with aspirin, given this study we have another reason to do it - to prevent the complex I inhibition by aspirin.
I would not say uncoupling is a bad thing. Most metabolic boosters like caffeine, DNP, thyroid, etc will uncouple in higher doses. Producing a lot of heat from food is usually a biomarker of youthful metabolism. There are some bad exceptions but for most intents and purposes, temperature goes down with aging and is very low in old people. So, old age is quite literally like "freezing", both physically and mentally.

In his early work, like Mind and Tissue, ray seems to see uncoupling as a negative thing. Is this something he's changed his mind on?

 

[schultz]

In his early work, like Mind and Tissue, ray seems to see uncoupling as a negative thing. Is this something he's changed his mind on?

I'm of the opinion that chronic mild uncoupling is a pro. It seem to increase lifespan, possibly through reduced oxidative stress.

I think Ray thinks it can be benecicial (uncoupling) but I think he thinks thyroid will do something even better and that is an increase in meaningful oxidation without causing oxidative stress.

Uncoupling is increasing oxidation but wasting oxygen and calories. Thyroid will increase oxidation and create useful energy. The latter will also help keep the repair mechanisms running strong.

This is the way I currently understand it anyway.

Low dose DNP for life does increase lifespan in mice at least. I think the comparitive dose for a human is somewhere between like 1-10mg (I figured it out once), whereas bodybuilders will take like 1g of the stuff and generally people say you need to take 200mg a day for any effect. Aspirin can probably do the same thing as low dose DNP. Aspirin can actually do the same thing as larger doses of DNP but it requires quite a bit of aspirin. In the old research they call it aspirin fever lol.

This study is a really fun read.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1474-9726.2008.00407.x
"Because many of the characteristics of caloric restriction were found in DNP-treated mice, we evaluated whether long-term DNP treatment could extend lifespan. We found (Fig. 4) that DNP treatment in itself was capable of promoting an extension in murine longevity. Median longevity in the control group was 722 days, vs. 771 days in the DNP group, while mean lifespan was 718.8 days in the control and 769.7 days in the treated group. Although the change in lifespan promoted by DNP was not large, it is statistically significant."

 

[ilikecats]

@debored13 one of rays favorite studies is “uncoupled and surviving” where they show that mice with higher metabolisms have greater mitochondrial uncoupling and a longer lifespan. I think that mitochondrial uncoupling goes hand in hand with a higher metabolism and we all know what Ray thinks of a higher metabolic rate. I have a data base of a bunch of his old newsletters and I recall searching “uncoupling” and I’m pretty sure each time he mentioned it, it was in a positive light. Mind and tissue was written about 40 years ago I believe so it’s not unusual that he changed his position on the subject. Also most of peats favorite substances uncouple mitochondria: T3, Aspirin, Caffiene. I’m still trying to fully understand mitochondrial uncoupling myself and obviously at first glance it seems maybe not ideal because it seems like less ATP is produced when mitochondria are uncoupled .But obviously it goes deeper then that and I have a lot of studying to do haha.

@schultz thanks for that gem very good stuff.

 

[schultz]

If you haven't read the old papers on aspirin poisoning, they are fun to take a look at. The doses people used to take could be quite high. They measure it by "grains of aspirin" which I think is like a baby aspirin, or something close, 65-70mg?

This article is fun.
Aspirin Poisoning

I remembering reading the first case report and thinking "Wow that lady took 100 grains of aspirin, that's quite a bit (6.5g?)" then I read the second case report of a lady taking 435 grains of thyroid lol. Um... 28g? Apparently, she became quite dehydrated from massive sweating and salicylic acid was found in abundance in her spinal fluid. She didn't die though. They drained her spinal fluid, which they think saved her.

I think the poisoning is sort of amplified by dehydration.

 

[Momado965]

As the study says, these chemicals have uncoupling effects. So, if I am reading this right, taking aspirin increases need for CoQ10 as an electron carrier. Maybe another reason to take vitamin K with aspirin.
"...In fact, NSAIDs have been shown to uncouple oxidative phosphorylation, dissipate mitochondrial membrane potential (MMP), inhibit mitochondrial oxygen consumption and lower ATP synthesis."

"...This inhibitory effect was concentration-dependently reverted by increasing the concentration of added CoQ10 beyond 32.5uM. A full recovery was attained with concentration of 520uM."

Will aspirin do the things you stressed in bold black or only the other NSAIDS?

 

[haidut]

Will aspirin do the things you stressed in bold black or only the other NSAIDS?

Since the study also tested aspirin and I also mentioned aspirin in my post, what do you think? You could have easily checked this by opening the PDF and doing Ctrl-F for "aspirin".

 

[Momado965]

Since the study also tested aspirin and I also mentioned aspirin in my post, what do you think? You could have easily checked this by opening the PDF and doing Ctrl-F for "aspirin".

I dont know this is why I asked you.