Tobacco Smoke And It's Effect On PUFA

[Stryker]

If by pufa depletion, you mean low fat, I wouldn't recommend it.

Low fat and tobacco is an awful combination, in my experience. I'm a regular smoker and in combination with a super low fat diet, cigarettes gave me a low mood, jitters, nervous feeling... one cigarette had me feeling like I had just ripped a hookah for a half hour.

However the buzz provided without restricted fat intake is a totally different experience. Mellow, uplifting, makes me sociable, etc.

yeah i know that feeling.... somedays when stressed to the balls like not having eaten or less than 4 hours sleep or whatever. Two drags of a cigarette would absolutely floor me. Cold sweats, tunnel vision , sense of impensing doom , ringing ears etc. LOL

IMO i think its just the metbolic enhancing effects of tobacco pushing your body too far when it cant handle it

 

[tyler]

yeah i know that feeling.... somedays when stressed to the balls like not having eaten or less than 4 hours sleep or whatever. Two drags of a cigarette would absolutely floor me. Cold sweats, tunnel vision , sense of impensing doom , ringing ears etc. LOL

IMO i think its just the metbolic enhancing effects of tobacco pushing your body too far when it cant handle it

Tobacco can be so good, but when it's bad it's BAD. "Sense of impending doom" is spot on haha.

 

[tyw]

If by pufa depletion, you mean low fat, I wouldn't recommend it.

Low fat and tobacco is an awful combination, in my experience. I'm a regular smoker and in combination with a super low fat diet, cigarettes gave me a low mood, jitters, nervous feeling... one cigarette had me feeling like I had just ripped a hookah for a half hour.

However the buzz provided without restricted fat intake is a totally different experience. Mellow, uplifting, makes me sociable, etc.

In mice models, Nicotine activation of nicotinic-acetylcholine receptors reliably induces higher SIRT1 activity.

Ref:
- Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibr... - PubMed - NCBI
- Modulations of sirtuin 1 protein levels by nicotine and β- cryptoxanthin can be mediated by miR-34a in A/J mice lung cancer model
- Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain

This will put acute depletion pressure on NAD+ stores in the cells which are affected by nicotine. Some evidence will also point toward a "fat burning phenotype", whereby fatty acid use in the mitochondria is further enhanced, but IMO, this is a secondary side effect of SIRT1 activation.

Practically speaking, in the people that I've seen use nicotine regularly, some form of NAD+ precursor seems to fix all negative issues related to nicotine consumption.

This will require some experimentation between forms (each column in the image below represents a distinct pathway for NAD+ replenishment).

The above figure is taken from 'The dynamic regulation of NAD metabolism in mitochondria' (Liana Roberts Stein and Shin-ichiro Imai, 2012)-- The dynamic regulation of NAD metabolism in mitochondria

Niagen (NR), needs to be converted to Nicotinamide (NAM) before it can be pushed towards NAD.

IMO, it is this contribution to total NAD pool that is responsible for the effects of any of these related compounds (Niagen, niacinamide, niacin, etc ...).

We have 2 more potentially rate-limiting enzymes NRK and PNP when trying to affect NAD via the NR pathway. This will mean more regulation, but also a less direct impact.

There may be cases where more endogenous regulation is preferred, and there may be cases where specific enzymes are not working, that will prevent the use of one substrate over the other.

Note that in any case, if the NMNAT enzyme is screwed, none of these pathways will work.

In any case, there are clear differences even at the nuclear level, the most significant probably being that Nicotinamide Riboside (NR) increases SIRT1 expression, while Nicotinamide (NAM) decreases SIRT1 expression.

Mechanism of NR activation of SIRT1 and SIRT3 (see the section 'NR treatment enhances SIRT1 and SIRT3 activity') -- The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

NAM inhibition of SIRT1

- Nicotinamide Prevents NAD+ Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD+ Consumption by SIRT1 may Endanger Energetically Compromised Neurons
- https://www.ncbi.nlm.nih.gov/pubmed/22198152

The effect of NAM is very quick-acting (and quick-clearing), and suppression of SIRT1 activity comes within 1 hour of supplementation -- http://www.anti-agingfirewalls.com/...acinamide-supplementation-–-good-or-bad-idea/

See this answer for commentary -- https://www.researchgate.net/post/H..._to_inhibit_SIRT1_and_how_long_until_it_stops

At my current stage of knowledge, I believe that SIRT1 activation is a sort of switch that indicates availability of easily available resources.

The lack of quick energy substrates (like glucose) demands higher SIRT1 activation, which in turn, stimulates programs that mobilise energy from various stores, while upregulating fatty acid metabolism.

This is thus going to be a very dynamic sate, with the present state of the person having a huge factor in which compound is going to work best.

For example, immediately after a significant amount of exercise, SIRT1 is going to be up-regulated, presumably due to the energetic stress of consuming substrate.

When we are dealing with Nicotine, which stimulates the Nicotinic-Acetylcholine receptors, I view this state as being a "forced excitatory state".

Whether the cell should be relaxed (via Sirtuin activation) or primed (via fast NAD+ replenishment), is going to depend on the existing energetic capabilities of the cell.

In a case of high insulin sensitivity and habitual high carbohydrate low fat consumption (ie: when we can assume no issue with carbohydrate metabolism), and probably some genetic propensity to use carbohydrate, it would make sense that SIRT1 activation is NOT a good load management strategy.

With a habitual higher fat intake, and likely less eager insulin signalling, one may benefit from higher SIRT1 activation to manage cellular energy capacity.

And of course, circadian variation will play a role. Midday, after significant light exposure and enough food, would generally be a well-fed, low SIRT1 state, while early morning and evenings would be the opposite.

-----

FINAL NOTE

None of the above discusses whether or not one should use nicotine. It assumes that nicotine is already going to be present in the system.

Nicotine is a potent drug, and should be treated as such. Avoid it if the effects are unknown.

I have no comment on cigarettes, and personally do not recommend any habitual consumption of substances that require smoke or vapour delivery through the lungs.

.....

 

[schultz]

Smoking increases ACTH and cortisol. Studies have shown that cortisol drops a few days after an individual stops smoking. This is possibly one of the reasons people find it hard to quit.

On the plus side it's an aromatase inhibitor. It also lowers 3a-HSD activity which is the enzyme responsible for turning DHT into another metabolite. 3a-HSD also makes allopregnanolone. However smokers have been shown to have higher allopregnanolone, so it doesn't seem to matter. Smokers also have higher DHEA (probably from the ACTH) and pregnenelone. Plus, I am told that it makes you look cool.

The idea of breathing smoke into my lungs seems counter-intuitive. I'd be worried about the carbon monoxide myself. Interesting topic!

 

[DaveFoster]

In mice models, Nicotine activation of nicotinic-acetylcholine receptors reliably induces higher SIRT1 activity.

Ref:
- Effects of sirtuin 1 activation on nicotine and lipopolysaccharide-induced cytotoxicity and inflammatory cytokine production in human gingival fibr... - PubMed - NCBI
- Modulations of sirtuin 1 protein levels by nicotine and β- cryptoxanthin can be mediated by miR-34a in A/J mice lung cancer model
- Effects of Chronic Nicotine Exposure and Lack of High Affinity Nicotinic Receptors on Cortico-Hippocampal Areas in the Aging Mouse Brain

This will put acute depletion pressure on NAD+ stores in the cells which are affected by nicotine. Some evidence will also point toward a "fat burning phenotype", whereby fatty acid use in the mitochondria is further enhanced, but IMO, this is a secondary side effect of SIRT1 activation.

Practically speaking, in the people that I've seen use nicotine regularly, some form of NAD+ precursor seems to fix all negative issues related to nicotine consumption.

This will require some experimentation between forms (each column in the image below represents a distinct pathway for NAD+ replenishment).

View attachment 4482

The above figure is taken from 'The dynamic regulation of NAD metabolism in mitochondria' (Liana Roberts Stein and Shin-ichiro Imai, 2012)-- The dynamic regulation of NAD metabolism in mitochondria

Niagen (NR), needs to be converted to Nicotinamide (NAM) before it can be pushed towards NAD.

IMO, it is this contribution to total NAD pool that is responsible for the effects of any of these related compounds (Niagen, niacinamide, niacin, etc ...).

We have 2 more potentially rate-limiting enzymes NRK and PNP when trying to affect NAD via the NR pathway. This will mean more regulation, but also a less direct impact.

There may be cases where more endogenous regulation is preferred, and there may be cases where specific enzymes are not working, that will prevent the use of one substrate over the other.

Note that in any case, if the NMNAT enzyme is screwed, none of these pathways will work.

In any case, there are clear differences even at the nuclear level, the most significant probably being that Nicotinamide Riboside (NR) increases SIRT1 expression, while Nicotinamide (NAM) decreases SIRT1 expression.

Mechanism of NR activation of SIRT1 and SIRT3 (see the section 'NR treatment enhances SIRT1 and SIRT3 activity') -- The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

NAM inhibition of SIRT1

- Nicotinamide Prevents NAD+ Depletion and Protects Neurons Against Excitotoxicity and Cerebral Ischemia: NAD+ Consumption by SIRT1 may Endanger Energetically Compromised Neurons
- Nicotinamide, a SIRT1 inhibitor, inhibits differentiation and facilitates expansion of hematopoietic progenitor cells with enhanced bone marrow hom... - PubMed - NCBI

The effect of NAM is very quick-acting (and quick-clearing), and suppression of SIRT1 activity comes within 1 hour of supplementation -- http://www.anti-agingfirewalls.com/2010/03/30/niacin-or-niacinamide-supplementation-–-good-or-bad-idea/

See this answer for commentary -- How long does it take for Niacinamide to inhibit SIRT1 and how...

At my current stage of knowledge, I believe that SIRT1 activation is a sort of switch that indicates availability of easily available resources.

The lack of quick energy substrates (like glucose) demands higher SIRT1 activation, which in turn, stimulates programs that mobilise energy from various stores, while upregulating fatty acid metabolism.

This is thus going to be a very dynamic sate, with the present state of the person having a huge factor in which compound is going to work best.

For example, immediately after a significant amount of exercise, SIRT1 is going to be up-regulated, presumably due to the energetic stress of consuming substrate.

When we are dealing with Nicotine, which stimulates the Nicotinic-Acetylcholine receptors, I view this state as being a "forced excitatory state".

Whether the cell should be relaxed (via Sirtuin activation) or primed (via fast NAD+ replenishment), is going to depend on the existing energetic capabilities of the cell.

In a case of high insulin sensitivity and habitual high carbohydrate low fat consumption (ie: when we can assume no issue with carbohydrate metabolism), and probably some genetic propensity to use carbohydrate, it would make sense that SIRT1 activation is NOT a good load management strategy.

With a habitual higher fat intake, and likely less eager insulin signalling, one may benefit from higher SIRT1 activation to manage cellular energy capacity.

And of course, circadian variation will play a role. Midday, after significant light exposure and enough food, would generally be a well-fed, low SIRT1 state, while early morning and evenings would be the opposite.

-----

FINAL NOTE

None of the above discusses whether or not one should use nicotine. It assumes that nicotine is already going to be present in the system.

Nicotine is a potent drug, and should be treated as such. Avoid it if the effects are unknown.

I have no comment on cigarettes, and personally do not recommend any habitual consumption of substances that require smoke or vapour delivery through the lungs.

.....

Tldr: niacinamide and nicotine may synergize and the former may eliminate negative effects of the latter. Nicotine mitigates some of the harm with a high-fat diet, which may explain the mention by Edward J Edmunds of centenarians who smoke and consume a high-fat diet.

 

[BigYellowLemon]

@Stryker
@tyler

I usually don't get "nic-sick" unless I use a large amount right in the morning before I've had breakfast. I used to do this a lot and it always felt weird.

Being nic-sick is probably one of the worst feelings.

Also, today I ate extremely low fat, under 1.5g of PUFA at most, just the hydrogenated fat in skittles, and I smoked a couple times, and I feel pretty good. This of course means nothing haha, I haven't used that much nicotine today anyways.

@tyw

haha I was gonna say that: that nicotine favors/enhances a fatty acid based metabolism.

So what you're saying is that because NAD+ is lowered, a carbohydrate based metabolism will be less efficient?

I don't really know jack ***t about SIRT1, but from reading people who eat lots of fat seem to like nicotine better, like Edward. Nicotine is as you know a complex 1 inhibitor but you say that it wouldn't normally be allowed to hit the ETC. I'm not sure... How strong are the mitochondria defenses to such things? And does nicotine increase SIRT1 like resveratrol?

A common remedy for getting "nic-sick", or slightly overdosing on nicotine, is to consume sugar. People often recommend soda or candy to cure nausea from nicotine, which in my experience works kinda well. Maybe that is a quick way for people to replenish NAD+?

I've read that tobacco/nicotine could replenish NAD+, not only because nicotine can possibly be turned into niacin, but because tobacco also contains similarly structured pyridines that could possibly have an effect. The dose would be very small though.

As well nicotine/tobacco increases catecholamines. Having high FFA and glucose in the blood at the same time would probably lead to feeling like ***t.

Edit: Wait is that why niacinamide inhibits lipolysis, because it inhibits SIRT1?

I'm gonna have to read this all.

-

Something to add, I just found out about "cembranoids". Apparently they inhibit prostaglandins...

This post on Longecity by nightlight also contains a good argument as well as a list of studies showing tobacco having protective effects in animals.

 

[Stryker]

@Stryker
@tyler

I usually don't get "nic-sick" unless I use a large amount right in the morning before I've had breakfast. I used to do this a lot and it always felt weird.

Being nic-sick is probably one of the worst feelings.

Also, today I ate extremely low fat, under 1.5g of PUFA at most, just the hydrogenated fat in skittles, and I smoked a couple times, and I feel pretty good. This of course means nothing haha, I haven't used that much nicotine today anyways.

yeah i cant say i can relate it too any part of eating "low-fat" and yeah the worst time for me was waking up at 3am to travel somewhere and immediately lighting one up..

that feeling is up their with solanine poisoning for me and make me shudder thinking about

 

[mujuro]

I'll +1 to that. Smoking first thing upon waking is a really awful feeling. It's a very adrenergic sensation. Smoking in the afternoon after being well fed and hydrated is a hell of a lot more relaxing.

 

[BigYellowLemon]

And as a by the way, throughout my 1+ year long smoking "experiment" I never once developed a cough or any sign of respiratory distress.

I also didn't really use filters at all. nightlight on Longecity makes the case that if you are gonna smoke, to not use filters, as the filters are made from some fibrous material like cotton, and is cut unevenly, so when you inhale, you are inhaling microfibers.

I wish they had carbon-filter cigarettes in the US like in Japan. Apparently lung cancer rates in Japanese people who smoke are far less than in Americans who do.

I bet they think it's from all the "protective" DHA and soy isoflavones lol.

 

[BigYellowLemon]

yeah i cant say i can relate it too any part of eating "low-fat" and yeah the worst time for me was waking up at 3am to travel somewhere and immediately lighting one up..

that feeling is up their with solanine poisoning for me and make me shudder thinking about

They're both from the nightshade family... So it makes sense in a way.

Solanine is an acetylcholinesterase inhibitor so that makes perfect sense, they both work through a similar mechanism, solanine is just more direct and poisonous.

 

[Stryker]

They're both from the nightshade family... So it makes sense in a way.

Solanine is an acetylcholinesterase inhibitor so that makes perfect sense, they both work through a similar mechanism, solanine is just more direct and poisonous.

yup , nictoine felt more systemic... solanine felt focused in the gut, i was hoping i would pass out or die because that was absolutely excruciating

 

[BigYellowLemon]

yup , nictoine felt more systemic... solanine felt focused in the gut, i was hoping i would pass out or die because that was absolutely excruciating

That sounds horrible, sorry

 

[BigYellowLemon]

I'll +1 to that. Smoking first thing upon waking is a really awful feeling. It's a very adrenergic sensation. Smoking in the afternoon after being well fed and hydrated is a hell of a lot more relaxing.

Insant headrush and a feeling of anxiety in the morning, walking is difficult because you're so intoxicated, you feel almost drunk and sick

After dinner on a relaxing night = reminisce and enjoy

 

[BigYellowLemon]

It hasn't made me feel better today. I wouldn't recommend it currently. It makes me sharper but it is definitely dirty.

The CO2 is appealing...

 

[Aspekt]

Insant headrush and a feeling of anxiety in the morning, walking is difficult because you're so intoxicated, you feel almost drunk and sick

After dinner on a relaxing night = reminisce and enjoy

Personally, it seems like smoking gives me a potent adrenaline response, if I'm not fueled up I get anxiety/heart rate increase/cold extremities/clamminess. Inhibiting adrenaline seems to make smoking more pleasant, it's better if I've had b6 (and food) before. Something with alcohol has an interesting synergy, smoking after drinking feels really good, and I don't seem to get as much of a stress cascade, but I can still overdo it. Smoking on a beta blocker (proponol) was super relaxing/energizing which would support the adrenaline idea.

 

[damngoodcoffee]

I'll +1 to that. Smoking first thing upon waking is a really awful feeling. It's a very adrenergic sensation. Smoking in the afternoon after being well fed and hydrated is a hell of a lot more relaxing.

Yeah i never understood why everybody else said morning cigarette is the best one.

 

[ecstatichamster]

Theanine neutralizes nicotine if I take it.

 

[schultz]

Personally, it seems like smoking gives me a potent adrenaline response, if I'm not fueled up I get anxiety/heart rate increase/cold extremities/clamminess. Inhibiting adrenaline seems to make smoking more pleasant, it's better if I've had b6 (and food) before. Something with alcohol has an interesting synergy, smoking after drinking feels really good, and I don't seem to get as much of a stress cascade, but I can still overdo it. Smoking on a beta blocker (proponol) was super relaxing/energizing which would support the adrenaline idea.

Effects of low- and high-nicotine cigarette smoking on mood states and the HPA axis in men. - PubMed - NCBI
"After high-nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.88+/-5.34 pmol/l within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r=0.85; P<0.0001), DHEA (r=0.66; P=0.002), and epinephrine (r=0.86; P<0.0001). Cortisol and DHEA increased significantly within 20 min (P<0.05) and reached peak levels of 424+/-48 and 21.13+/-2.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones and subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking."

Cortisol is highest in the morning upon waking. Maybe further increasing cortisol levels, and epinephrine, by smoking can cause someone to feel sick? @BigYellowLemon mentioned sugar as a remedy which is interesting since Ray has said sugar is the best thing for lowering cortisol.

"... sugar happens to be the best thing for lowering cortisol to normal." - Ray Peat

Glucose and sucrose for diabetes.
"Sucrose consumption lowers ACTH, the main pituitary stress hormone (Klement, et al., 2009; Ulrich-Lai, et al., 2007)"

EDIT: The "nic-sick" symptoms described are actually similar to the symptoms of high epinephrine. ACTH raises both cortisol and epinephrine and sugar lowers ACTH.

Epinephrine side effects:
Nausea or vomiting, difficulty breathing, pounding, fast, or irregular heartbeat, pale skin, headache, sweating, dizziness, nervousness, anxiety, or restlessness, weakness, uncontrollable shaking.

 

[Jarman]

My uncle developed lung cancer after years of being an avid smoker. For 2 years he had to sit on wheelchair and breath via oxygen tanks for 2 years before he passed away. His lungs went completely caput.

My buddy is an avid smoker, too. Tried to quit so many times but always came back even after using vape as substitute for months. He can barely do a short morning run.

I won't touch tobacco ever, even if nicotine has health benefits. That thing is too addicting to quit and I've seen it destroying people's health with my own eyes.

 

[ecstatichamster]

I'm happy smoking cigars, occasionally. Ray is okay with a little tobacco for "older" people he says. I think a cigar now and then can be beneficial.

Not very enthused about inhaling smoke.