Microdosing nicotine increases NAD levels and rejuvenates old mice

[Mauritio]

This study looked at the effect of microdoses (2 μg/mL drinking water) of nicotine on mice.

Nicotine was able to rescue the rate limiting enzyme for NAD synthesis, NAMPT, and improve NAD levels.
This comes of course with all the goodies of a higher NAD/NADH ration, in this case: increase in anti-oxidant enzymes, lowering of inflammation and oxidative stress, improvement of cognition and neurogenesis, etc...

Nicotine restores the NAMPT to levels to those of young mice. In some organs even above that.

The interesting thing about nicotine was that higher or lower doses were not as effective or even ineffective.
So there seems to be a sweet spot at a tissue level of about 10ng/ml of nicotine.

In the in-vivo study the oral dose was about 8mcg /day/rat (2mcg/ml drinking water). A mouse weighs about 20g, so 0.4mcg/1g or 400mcg/kg.
Divided by 12 for the usual conversion to humans equals 33,33mcg/kg. Multiplied by 75 for average human weight equals a HED of almost exactly 2.5mg/day.
(I might have screwed up the calculation, so correct me if I'm wrong.)

As it is completely water-soluble, it should be relatively easy to dilute nicotine and take microdoses. Worth a try.

- Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity

 

[alephx]

2.5 is about the amount in a cigarrette if I remember correctly. Obviously not all is absorbed but you know. Anecdotally, many people in my family smoke a cigarrette after lunch and they all have lived to 88, 99, etc... with good quality of life.

 

[ecstatichamster]

great find, thank you!

 

[Mauritio]

2.5 is about the amount in a cigarrette if I remember correctly. Obviously not all is absorbed but you know. Anecdotally, many people in my family smoke a cigarrette after lunch and they all have lived to 88, 99, etc... with good quality of life.

Yeah nicotine also has a strong anti-endotoxin effect, so they might be self-medicating unknowingly.

Whenever I take nicotine I only take a mg ,although topically . The study used oral nicotine, which might matter because of slowed absorption and first pass metabolism.

"It has been reported that nicotine, when ingested in drinking water, is slowly absorbed through the gastrointestinal tract and is rapidly metabolized in the liver63–66, which might explain why the concentration of nicotine in the body is extremely low (Supplementary Figs. 1a and 3c)."

Btw I'm not 100% sure if I calculated the HED right ,so if anyone could confirm me on that, that'd be great. I can't find a flaw myself, the thing that makes me suspicious is, the authors keep talking about how tiny the dose is in mice but 2.5mg for a human actually isn't really a microdose anymore. So I hope the HED is right.

great find, thank you!

You're welcome:)

 

[youngsinatra]

Interesting find!

 

[LeeLemonoil]

So the usual Nicotine-chewing Gums come with 2mg usually. A cheap and convenient way to reap the benefits? Would be quite a hack I didn’t think of before

 

[LeeLemonoil]

So the usual Nicotine-chewing Gums come with 2mg usually. A cheap and convenient way to reap the benefits? Would be quite a hack I didn’t think of before

But Lots of bull**** additives in those. Maybe better to use chewing tobacco

 

[Mauritio]

But Lots of bull**** additives in those. Maybe better to use chewing tobacco

You can simply use liquid nicotine.
I use this one.

Nicotine – Solution (USP) (30mL / 100mL)

Warning: This product is only for use in non-clinical research scenarios.

mitolab.com

 

[LeeLemonoil]

You can simply use liquid nicotine.
I use this one.

Nicotine – Solution (USP) (30mL / 100mL)

Warning: This product is only for use in non-clinical research scenarios.

mitolab.com

Ah great, Mitolabs. Gotta order fresh MB anyway

 

[Jam]

You can simply use liquid nicotine.
I use this one.

Nicotine – Solution (USP) (30mL / 100mL)

Warning: This product is only for use in non-clinical research scenarios.

mitolab.com

What is the ph of that solution? I would tend to think that very little of this is absorbed through the skin. Under the tongue or on the gums would work a bit better. Raising the ph would increase absorption.

 

[bloooeh]

You can simply use liquid nicotine.
I use this one.

Nicotine – Solution (USP) (30mL / 100mL)

Warning: This product is only for use in non-clinical research scenarios.

mitolab.com

Thanks for sharing. Didn’t know liquid form is available. I got the lozenge but only used twice because it gives me a little headache. Maybe takes time to get used to. Gum and the vape has harmful ingredients.

 

[Mauritio]

What is the ph of that solution? I would tend to think that very little of this is absorbed through the skin. Under the tongue or on the gums would work a bit better. Raising the ph would increase absorption.

Not sure. Judging by the ingredients (glycerol and nicotine) I would say the pH is slightly alkaline.
I definitely notice an effect, but I rarely take it orally so I can't really compare it. I think I'll try orally though, because that was the MoA of this study.
Glycerol might function as an absorption enhancer:

"An addition of glycerol, an osmotherapeutic agent, in the physiological receptor solution seemed to enhance the percutaneous absorption of RA by affecting the partition coefficient of RA."

Effects of glycerol on the in vitro percutaneous absorption of all-trans retinoic acid - PubMed

The nature of the receptor solution plays an important role in in vitro percutaneous absorption of highly lipophilic compounds having limited solubility. In vitro permeation studies of a lipophilic compound, all-trans retinoic acid (RA), through the rat dorsal skin were performed with the...

pubmed.ncbi.nlm.nih.gov

 

[GTW]

Simplest way to scale up to human dose is use the same 2 ugm/ml drinking water. That's 2 mg/liter. With no other source of water, how much would a human consume over the course of a day? That's the physiological scaling factor built in. Would seem to be important that the dose is spread over the day.

 

[LeeLemonoil]

There are liquids offered in pharmacies as alternatives for the chewing gums. Only agent for ph-adjustment seems to be sodium hydroxide:

(Inci other than Nicotine (1mg per pump)

• Die sonstigen Bestandteile sind: Propylenglycol, Glycerol, Ethanol, Poloxamer 407, Glycin, Natriumhydrogencarbonat, Levomenthol, Minze-Aroma, flüssig (enthält Benzylalkohol, Propylenglycol, Pulegon), Frische-Aroma, flüssig (enthält Menthol, Mentholcarboxamid, ätherisches Öl, Propylenglycol), Sucralose, Acesulfam-Kalium, Natriumhydroxid und Gereinigtes Wasser.

 

[ecstatichamster]

I wonder about sublingual use.

 

[GTW]

High local tissue concentration of nicotine as a result of bucal absorption is probably not healthy.

 

[Mauritio]

Simplest way to scale up to human dose is use the same 2 ugm/ml drinking water. That's 2 mg/liter. With no other source of water, how much would a human consume over the course of a day? That's the physiological scaling factor built in. Would seem to be important that the dose is spread over the day.

Good point.

The smartest thing is to just put one or two drops of nicotine in a water bottle and simply drink that over the course of the day, as you normally would.

As the authors said the nicotine concentration in the mice's body was really low, probably because of the low continuous doses through the drinking water and extensive first pass metabolism.

So, low, continous, oral doses are the way to go, if you want to replicate this study-design.

Sublingual/buccal/topical or even one big oral dose might have very different effects.

 

[GTW]

Consistent with the desired dose and administration another option would be infusion of tobacco leaf. Grow your own free of pesticides. N rustica
is prolific. Would need to establish the nicotine content.

 

[mm33]

This study looked at the effect of microdoses (2 μg/mL drinking water) of nicotine on mice.

Nicotine was able to rescue the rate limiting enzyme for NAD synthesis, NAMPT, and improve NAD levels.
This comes of course with all the goodies of a higher NAD/NADH ration, in this case: increase in anti-oxidant enzymes, lowering of inflammation and oxidative stress, improvement of cognition and neurogenesis, etc...

Nicotine restores the NAMPT to levels to those of young mice. In some organs even above that.
View attachment 48905

The interesting thing about nicotine was that higher or lower doses were not as effective or even ineffective.
So there seems to be a sweet spot at a tissue level of about 10ng/ml of nicotine.
View attachment 48906

In the in-vivo study the oral dose was about 8mcg /day/rat (2mcg/ml drinking water). A mouse weighs about 20g, so 0.4mcg/1g or 400mcg/kg.
Divided by 12 for the usual conversion to humans equals 33,33mcg/kg. Multiplied by 75 for average human weight equals a HED of almost exactly 2.5mg/day.
(I might have screwed up the calculation, so correct me if I'm wrong.)

As it is completely water-soluble, it should be relatively easy to dilute nicotine and take microdoses. Worth a try.

- Nicotine rebalances NAD+ homeostasis and improves aging-related symptoms in male mice by enhancing NAMPT activity

Great find Mauritio thanks so much!! I think I could take this in water as suggested. I’ve read other positive things about nicotine so may have to give this a try now that I’ve officially reached old - 65 and can use anything that helps rejuvenation lol

 

[Mauritio]

Great find Mauritio thanks so much!! I think I could take this in water as suggested. I’ve read other positive things about nicotine so may have to give this a try now that I’ve officially reached old - 65 and can use anything that helps rejuvenation lol

You're welcome. Keep in mind that the mice (not a human study) took the nicotine daily, so that would be required to replicate the study design. I'm not saying it wouldn't have any benefits occasionally but that's what they did.

I'm trying a drop in my water bottle today as well.