Nicotine Uncouples Mitochondria

[Dopamine]

The mitochondrial uncoupling effect of caffeine, thyroid, and other substances has been discussed on the forum. Nicotine also uncouples mitochondrial proteins- specifically: Uncoupling Protein 1 (UCP1)

Fasting and food restriction lowers expression of UCP1
Nicotine increases expression of UCP1

Effects of caffeine on the uncoupling protein family in obese yellow KK mice. - PubMed - NCBI
Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs.

Cigarette Smoking and Brain Regulation of Energy Homeostasis
Fasting or chronic food restriction normally results in the downregulation of UCP1 expression in brown fat (Champigny and Ricquier, 1990) while nicotine induces UCP1 mRNA expression, which likely leads to enhanced energy expenditure (Yoshida et al., 1999; Arai et al., 2001). In mice directly exposed to cigarette smoke, both UCP1 and three mRNA expression was increased compared with pair-fed animals (Chen et al., 2006, 2008), suggesting that increased energy expenditure occurred despite their reduced energy intake. This theory has also been supported by data from humans, where energy expenditure was increased by nicotine administration (Perkins et al., 1989).

It should also be noted that nicotine has been demonstrated to significantly increase fat loss in rats when they are fed a low fat diet but only marginally increase fat loss when they are fed a high fat "cafeteria style" diet. The high fat diet likely being high in PUFA. Nicotine + a diet lower in fat would likely aid in fat loss. Indeed their is a correlation between nicotine intake and leaner mass.

 

[Parsifal]

It should also be noted that nicotine has been demonstrated to significantly increase fat loss in rats when they are fed a low fat diet but only marginally increase fat loss when they are fed a high fat "cafeteria style" diet. The high fat diet likely being high in PUFA. Nicotine + a diet lower in fat would likely aid in fat loss. Indeed their is a correlation between nicotine intake and leaner mass.

Isn't it because of the lipolysis prometed by nicotine?

Do you know if nicotine would increase cytochrome oxydase C activity and if it is a carbonic anhydrase inhibitor? I think that caffeine does all that but not sure.

 

[Drareg]

Nicotine uncoupling has been discussed on the forum many times.

Nicotine will leave you with severe withdrawals.
Ray Peat recommends far safer substances to uncouple mitochondria that won't leave you in severe withdrawals.

Withdrawal effects have been known to cause increased susceptibility to suicide.

 

[Dopamine]

Isn't it because of the lipolysis prometed by nicotine?

Do you know if nicotine would increase cytochrome oxydase C activity and if it is a carbonic anhydrase inhibitor? I think that caffeine does all that but not sure.

Caffeine similarly promotes lipolysis and FFA release in the presence of inadequate glucose.

Nicotine is a carbonic anhydrase inhibitor in many tissues:
Effects of nicotine and vitamin E on carbonic anhydrase activity in some rat tissues in vivo and in vitro. - PubMed - NCBI

Here is an interesting study examining how chronic nicotine effects the mitochondria:
http://naldc.nal.usda.gov/download/30138/PDF

It seems nicotine potentially increases electron transport chain activity, Cytochrome C Oxidase activity, and NADH dehydrogenase activity (Formation of COQ10)- in some parts of the brain while potentially reducing it in others.

I'm wary of studies that force dosing on the animals rather than allowing them to self administer as much as they want. The nicotine was given constantly via implanted pumps so the rats would not have gotten a break from the stimulant even at night which would very likely disturb sleep. Sleep deprivation itself impairs mitochondrial function:
Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice. - PubMed - NCBI

So nicotine has significant effects on cytochrome c oxidase activity but it is hard to find evidence as to how exactly it effects it. The fact that nicotine has been shown preventative against Parkinsons, Alzheimers, and other diseases involving brain oxidative stress and decreased energy metabolism tells me that nicotine likely has a balancing or protective function on brain metabolism.

Here is a study showing nicotine protects brain mitochondria
Nicotine protects rat brain mitochondria against experimental injuries. - PubMed - NCBI

I don't think it is as simple as saying "caffeine/nicotine increases/decreases cytochrome c oxidase activity" it depends on the context and what tissues you are looking at.

 

[Dopamine]

Nicotine uncoupling has been discussed on the forum many times.

Nicotine will leave you with severe withdrawals.
Ray Peat recommends far safer substances to uncouple mitochondria that won't leave you in severe withdrawals.

Withdrawal effects have been known to cause increased susceptibility to suicide.

It has never been discussed on the forum as far as i'm aware. I will say anecdotally that I have started vaping nicotine between sets when I workout and have not found it addictive whatsoever. I am much more addicted to my morning coffee than my several times a week nicotine usage. Nicotine in isolation has not been found to be particularly addictive when self administration is allowed and when it isn't forced on the subject.

 

[postman]

Nicotine uncoupling has been discussed on the forum many times.

Nicotine will leave you with severe withdrawals.
Ray Peat recommends far safer substances to uncouple mitochondria that won't leave you in severe withdrawals.

Withdrawal effects have been known to cause increased susceptibility to suicide.

I've had severe withdrawals from very high doses of coffee. I'm not trying to knock coffee but I don't think responsible nicotine intake is all that different. I tried it for a couple of weeks with great results but then i built tolerance and I didn't want to increase the dose so I stopped. It was not addictive at all to me.

 

[Drareg]

It has never been discussed on the forum as far as i'm aware. I will say anecdotally that I have started vaping nicotine between sets when I workout and have not found it addictive whatsoever. I am much more addicted to my morning coffee than my several times a week nicotine usage. Nicotine in isolation has not been found to be particularly addictive when self administration is allowed and when it isn't forced on the subject.

Generally people who are addicted try to justify it.
Your claim that nicotine has not been particular addictive has been shown to be your own fallacy in your other thread on nicotine.

Nicotine has severe withdrawals on the same level of phenibut.

 

[Drareg]

I've had severe withdrawals from very high doses of coffee. I'm not trying to knock coffee but I don't think responsible nicotine intake is all that different. I tried it for a couple of weeks with great results but then i built tolerance and I didn't want to increase the dose so I stopped. It was not addictive at all to me.

If it wasn't addictive why did you feel like a tolerance building?
What you say points to it being addictive.

 

[Dopamine]

Generally people who are addicted try to justify it.
Your claim that nicotine has not been particular addictive has been shown to be your own fallacy in your other thread on nicotine.

Nicotine has severe withdrawals on the same level of phenibut.

I currently use nicotine twice a week during a workout. If you think I am addicted then you are severely deluded.

Also your claim that nicotine has withdrawal symptoms on par to phenibut must be based on your own abusive drug experiences because there are no studies demonstrating this... You accuse me of being an addict while simultaneously admitting that you have been severely addicted to both phenibut and nicotine. Correct?

 

[Drareg]

I currently use nicotine twice a week during a workout. If you think I am addicted then you are severely deluded.

Also your claim that nicotine has withdrawal symptoms on par to phenibut must be based on your own abusive drug experiences because there are no studies demonstrating this... You accuse me of being an addict while simultaneously admitting that you have been severely addicted to both phenibut and nicotine. Correct?

Strawman. A very poor one at that.

Your deluded for even bothering with nicotine when the other substances Peat recommends are far superior, if you need nicotine for a workout it's telling you something here, you should look into it.

In your other post on nicotine this point was put to you about nicotine and phenibut with the research.
Here it is again, both can be switched out as they are highly addictive hdac inhibitors.

Histone deacetylase inhibition decreases preference without affecting aversion for nicotine. - PubMed - NCBI

 

[postman]

If it wasn't addictive why did you feel like a tolerance building?
What you say points to it being addictive.

Developing tolerance is not the same as it being addictive. I could stop taking nicotine without any difficulty what so ever, I didn't feel a "thirst" for nicotine when I went off it. There are plenty of studies that show that nicotine isn't addictive unto itself, it's the other chemicals in cigarettes that are addictive. It's also those other chemicals that cause disease.

 

[postman]

Generally people who are addicted try to justify it.
Your claim that nicotine has not been particular addictive has been shown to be your own fallacy in your other thread on nicotine.

Nicotine has severe withdrawals on the same level of phenibut.

This is some serious alcoholics anonymous type reasoning

 

[Drareg]

Developing tolerance is not the same as it being addictive. I could stop taking nicotine without any difficulty what so ever, I didn't feel a "thirst" for nicotine when I went off it. There are plenty of studies that show that nicotine isn't addictive unto itself, it's the other chemicals in cigarettes that are addictive. It's also those other chemicals that cause disease.

Can you clarify your reasoning in how developing tolerance is different to being addictive in relation to a hdac inhibitor?
I'm not taking about cigarettes but nicotine, this is your starwman.

There is plenty of research not done on isolated nicotine currently and plenty from the past pointing to isolated nicotines addictiveness.
Current research is pointing to it being a hdac inhibitor which can make addictive based on the level it as at.

 

[Drareg]

This is some serious alcoholics anonymous type reasoning

No it's not achoholic anonymous type reasoning ,that's your brain projecting that.

 

[postman]

Can you clarify your reasoning in how developing tolerance is different to being addictive in relation to a hdac inhibitor?
I'm not taking about cigarettes but nicotine, this is your starwman.

There is plenty of research not done on isolated nicotine currently and plenty from the past pointing to isolated nicotines addictiveness.
Current research is pointing to it being a hdac inhibitor which can make addictive based on the level it as at.

Tolerance and addiction are two completely different concepts. Tolerance means you have to take a higher dosage to get the desired effect. Addiction means you have a physical craving for the substance in question. Those two things are not necessarily related.

Painkillers: Tolerance vs. Addiction

 

[jyb]

Nicotine has severe withdrawals on the same level of phenibut.

Have you ever tried nicotine? It is a bit like coffee and alcohol in terms of withdrawal: if you use it reasonably, you can probably stop cold turkey and not even notice. That was my experience anyway. In fact, reading the anecdotes about coffee usage and withdrawal experiments on this forum, I am tempted to conclude coffee is worse. But honestly I doubt there are huge differences in dependence between these three substances when taken at "normal" doses.

 

[Drareg]

Have you ever tried nicotine? It is a bit like coffee and alcohol in terms of withdrawal: if you use it reasonably, you can probably stop cold turkey and not even notice. That was my experience anyway. In fact, reading the anecdotes about coffee usage and withdrawal experiments on this forum, I am tempted to conclude coffee is worse. But honestly I doubt there are huge differences in dependence between these three substances when taken at "normal" doses.

You can do the same thing with phenibut or benzodiazepines, I'm sure many do the same with cocaine regularly.

I found nicotine to be terrible all round, nausea and stomach upset from tiny amounts. The nootropic effect was more hyper vigilance, I personally don't equate that to intelligence, quick on the uptake but not much dept going on.
Far better substance to take imo, Nicotine seems pointless when put into that conetext.

 

[DaveFoster]

This reminds me of the HyperLipid guy who recommends ketogenesis to uncouple mitochondria.

 

[jyb]

You can do the same thing with phenibut or benzodiazepines, I'm sure many do the same with cocaine regularly.

I found nicotine to be terrible all round, nausea and stomach upset from tiny amounts. The nootropic effect was more hyper vigilance, I personally don't equate that to intelligence, quick on the uptake but not much dept going on.
Far better substance to take imo, Nicotine seems pointless when put into that conetext.

Funny, I never equated nicotine with vigilance. Coffee yes a bit, but never nicotine. I did a few experiments taking high doses of nicotine and would never get the hyper vigilance side effect that I could get from coffee if I overdosed it. I did get nausea from nicotine but only when I took an unreasonable dose. I do associate nicotine with creativity, however.

I disagree with you when you say nicotine is pointless, because it is slightly different from the rest. Just like coffee is slightly different from thyroid. They have similar effects but different uses. And just like the rest, some people don't do well on them. Just look on this forum at those who do absolute ***t with cyproheptadine for example. Ray has cited nicotine a number of times (search on his website: in some articles, nicotine is sitting right next to progesterone or other familiar molecules), it is pretty clear that in some doses it has its uses for reducing stress and improving metabolism but it should not be surprising that some people don't do well on it. It seems to me very arbitrary to declare it to be pointless.

It would a bit like if I said coffee is pointless for thyroid effects because it can give adrenaline. It can indeed increase adrenaline, but only when it is not used correctly and unsuitable for the metabolism. For some, the correct use is "never", and it's not necessarily a bad thing at all. Nicotine is very similar in that respect. I always expected pre-nausea from nicotine when my metabolism was that of stress, when it is unsuitable to increase metabolism. Coffee is to jitteriness what nicotine is to nausea, is the way I think about it. This is my experience only - I know some people who use nicotine regularly and in high doses, and never experienced nausea.

Note that I'm no more fan of nicotine than many other things discussed on this forum. I don't even use it, I only replied to this thread for the reasons I mentioned. So I'd like to think I'm not so biased.

 

[Drareg]

Funny, I never equated nicotine with vigilance. Coffee yes a bit, but never nicotine. I did a few experiments taking high doses of nicotine and would never get the hyper vigilance side effect that I could get from coffee if I overdosed it. I did get nausea from nicotine but only when I took an unreasonable dose. I do associate nicotine with creativity, however.

I disagree with you when you say nicotine is pointless, because it is slightly different from the rest. Just like coffee is slightly different from thyroid. They have similar effects but different uses. And just like the rest, some people don't do well on them. Just look on this forum at those who do absolute **** with cyproheptadine for example. Ray has cited nicotine a number of times (search on his website: in some articles, nicotine is sitting right next to progesterone or other familiar molecules), it is pretty clear that in some doses it has its uses for reducing stress and improving metabolism but it should not be surprising that some people don't do well on it. It seems to me very arbitrary to declare it to be pointless.

I declared it pointless in my opinion, please put it into context. Within context it's not arbitrary.

I fully understand how all people are different, I have been clear in many of my posts on nicotine that Peat mentions it, I have also pointed to an understanding of how it works, Im fully aware of it.
Ray Peat also mentions niacin at times and other substances. He cites many different substances so context is necessary.
Few of his recommendations within context leave people addicted from daily use, I don't know of anyone who is addicted to cyproheptadine and needs a hit every 1 to 2 hours.

When metabolism is doing ok thyroid can be taken fewer times per day, coffee can be taken once in the morning,since beginning some of Peats ideas I have little interest in coffee anymore other than experiment.
Coffee has a half life of a few hours as does thyroid.
Nicotine has a half life of 1 to 2 hours.

If nicotine has a similar effect to phenylbutyrate acting as a hdac inhibitor its liable to have higher addictive potential, looking through the threads on nicotine by the op you can see this is what I'm pointing to.
Withdrawals come with this. Keep in mind the half life of nicotine is 1 to 2 hours.
Claiming it has no addictive potential and currently recommending nicotine in relation to other adaptive substance is what seems pointless imo.