26 replies to this topic

[Dstein]

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

Low-dose nicotine can activate NAD+ salvage pathways.

[Jesus Evola]

Sublingual or inhaled nicotinic acid.  

[Dstein]

Sublingual or inhaled nicotinic acid.  

 

In the study, they put the nicotine into the drinking water.
 

[Dstein]

Quick update:

As the article states, the dose response is an inverted u-curve.  If you use too much, it loses its NAD+ boosting effect. I did some arithmetic that included adjusting for the metabolic differences between mice and humans (allometric scaling) and concluded that the sweet spot for humans is one 4 mg nicotine lozenge spread out over 15 days.  After about 6 weeks, I was sleeping a lot less, but I wasn't tired from lack of sleep. My energy levels and mental clarity was as good or better than before I started the nicotine.  Since I felt less tired, I kept going to sleep later and later, and my sleep cycle shifted twelve hours forward.  I've discontinued the nicotine, and I'm struggling to get back to a normal sleep schedule.

Edited by Dstein, 09 June 2023 - 02:15 AM.

[LawrenceW]

Quick update:

As the article states, the dose response is an inverted u-curve.  If you use too much, it loses its NAD+ boosting effect. I did some arithmetic that included adjusting for the metabolic differences between mice and humans (allometric scaling) and concluded that the sweet spot for humans is one 4 mg nicotine lozenge spread out over 15 days.  After about 6 weeks, I was sleeping a lot less, but I wasn't tired from lack of sleep. My energy levels and mental clarity was as good or better than before I started the nicotine.  Since I felt less tired, I kept going to sleep later and later, and my sleep cycle shifted twelve hours forward.  I've discontinued the nicotine, and I'm struggling to get back to a normal sleep schedule.

 

Thank you Dstein for volunteering to validate the study's premise that taking too much nicotine has its downside.

 

 Nicotine dose.png   29.03KB   1 downloads

 

By my calculations the daily dose for a 200 lb. human is 0.019 mgs. and not the 0.266 mgs. per day that you were taking.

[Dstein]

By my calculations the daily dose for a 200 lb. human is 0.019 mgs. and not the 0.266 mgs. per day that you were taking.

 

Interesting.  I did my calculation a long time ago, and didn't write them down (I may have just done them in my head).  One thing I noticed in your numbers is that you didn't adjust for differences in the metabolic rate between mice and humans.  Doing so, would have made your numbers even smaller (and mine would be even more excessive).

 

Could explain a lot.

Edited by Dstein, 11 June 2023 - 04:36 AM.

[LawrenceW]

One thing I noticed in your numbers is that you didn't adjust for differences in the metabolic rate between mice and humans.  

 

But I did.  Take the 2,567 ng/KG mouse dosage and divide by 12.3 to convert mouse dosage to human and you get 208.7 ng/KG human dosage.

[Dstein]

But I did.  Take the 2,567 ng/KG mouse dosage and divide by 12.3 to convert mouse dosage to human and you get 208.7 ng/KG human dosage.

Oops-missed that.  Looks like I made a lot of mistakes here--thanks

[LawrenceW]

Dstein, I would also like to thank you for bringing this study to everyone's attention. I have been taking a 19 mcg (0.019 mg) daily nicotine dose since the end of February and am very impressed with the results.  This is in addition to the NMN based formulation I first began taking in July 2015.

Edited by LawrenceW, 12 June 2023 - 12:47 AM.

[joesixpack]

Where can I find a 19 mcg dose of nicotine?

[LawrenceW]

Where can I find a 19 mcg dose of nicotine?

 

Please PM me.

[LawrenceW]

Where can I find a 19 mcg dose of nicotine?

 

I did a group buy of nicotine for everyone on our NMN based anti-aging formulation.

 

PM me if you want some.

[MikeDC]

Thank you Dstein for volunteering to validate the study's premise that taking too much nicotine has its downside.

Nicotine dose.png

By my calculations the daily dose for a 200 lb. human is 0.019 mgs. and not the 0.266 mgs. per day that you were taking.

The paper has 2 micrograms per mL. Here is my calculations.

2ug/mL Nicotine water
7.7 mL. Mice water consumption
15.4 ug daily consumption
0.51mg/kg Mice dose
0.0425 mg/kg human dose
Human weight 75kg
3.18mg human dose

[LawrenceW]

The paper has 2 micrograms per mL. Here is my calculations.

2ug/mL Nicotine water
7.7 mL. Mice water consumption
15.4 ug daily consumption
0.51mg/kg Mice dose
0.0425 mg/kg human dose
Human weight 75kg
3.18mg human dose

 

From page 5 of the study. "The results also showed that 1 ng/mL of nicotine slightly

enhanced NAD+ levels, whereas 10 ng/mL significantly increased NAD+

levels. Surprisingly, 100 ng/mL of nicotine had no significant effect, and

500 ng/mLof nicotine inhibited NAD+ levels in the cells (Supplementary

Fig. 3c)."

 

According to the study the best measured results came from 10 ng/mL and not the 2 ng/mL quoted by MikeDC

 

Also, from MikeDC calculation above:

 

"15.4 ug daily consumption" =

0.1054 mcg daily consumption =

0.0001054 mg daily consumption.

 

The MikeDC human dose was only off by a factor of 1,000 which per the study "inhibited NAD+ levels in the cells"

Edited by LawrenceW, 26 June 2023 - 05:45 PM.

[MikeDC]

Lawrence, the 15ng/mL concentration was obtained from organ tissue after 2ug/mL feed in drinking water. Since we are modeling the intake of nicotine, we should use 2ug/mL as nicotine concentration in water. You are quoting the in vitro studies as nicotine concentration in water. The in vitro studies models the in vivo concentration of nicotine.

Edited by MikeDC, 26 June 2023 - 07:25 PM.

[LawrenceW]

Lawrence, the 15ng/mL concentration was obtained from organ tissue after 2ug/mL feed in drinking water. 

 

 

Wrong.  "The nicotine content in the liver and brain were about 15 ng/g"  It is per gram not per mL.

[LawrenceW]

 You are quoting the in vitro studies as nicotine concentration in water. The in vitro studies models the in vivo concentration of nicotine.

 

 

Also, "Similar to in vivo studies, 10 ng/mL of nicotine increased NAMPT activities (Supplementary Fig. 3a). We also measured the content of β-NMN with LC-MS and found that nicotine increased β-NMN levels in a dose-dependent manner (Supplementary Fig. 3b). The results also showed that 1 ng/mL of nicotine slightly enhanced NAD+ levels, whereas 10 ng/mL significantly increased NAD+ levels. Surprisingly, 100 ng/mL of nicotine had no significant effect, and 500 ng/mLof nicotine inhibited NAD+ levels in the cells (Supplementary Fig. 3c)."

[MikeDC]

Wrong. "The nicotine content in the liver and brain were about 15 ng/g" It is per gram not per mL.

1 mL water is 1g. They translates weight content into volume content. But the important thing is the nicotine content in the tissue can’t be directly translated into oral dose. They are totally different things.

[MikeDC]

Also, "Similar to in vivo studies, 10 ng/mL of nicotine increased NAMPT activities (Supplementary Fig. 3a). We also measured the content of β-NMN with LC-MS and found that nicotine increased β-NMN levels in a dose-dependent manner (Supplementary Fig. 3b). The results also showed that 1 ng/mL of nicotine slightly enhanced NAD+ levels, whereas 10 ng/mL significantly increased NAD+ levels. Surprisingly, 100 ng/mL of nicotine had no significant effect, and 500 ng/mLof nicotine inhibited NAD+ levels in the cells (Supplementary Fig. 3c)."

The in vivo studies used 2ug/mL. This just means that if mice drinks water with 2ug/mL nicotine, their tissue will have 10-15ng/g nicotine.

If you want to model the oral intake of nicotine, you need to use 2ug/mL and not 15ng/mL.

[Dstein]

The paper has 2 micrograms per mL. Here is my calculations.

2ug/mL Nicotine water
7.7 mL. Mice water consumption
15.4 ug daily consumption
0.51mg/kg Mice dose
0.0425 mg/kg human dose
Human weight 75kg
3.18mg human dose

 

Hi Mike,

 

I found my original calculations on how I came up with the number that I came up with.  There are two differences.  The first difference is that I didn't use the standard mouse to human scaling that you and Lawrence used.  I didn't write down what my reasoning was and have no idea why I scaled it the way I did.  The second difference is in the water consumption.  How did you get 7.7 mL? Is that in the paper--I couldn't find it.  The number that I came up with is that a typical mouse consumes about 4 mL of water per day
 

[MikeDC]

I just used the number Lawrence used.

[Dstein]

Hi Mike,

 

I found my original calculations on how I came up with the number that I came up with.  There are two differences.  The first difference is that I didn't use the standard mouse to human scaling that you and Lawrence used.  I didn't write down what my reasoning was and have no idea why I scaled it the way I did.  The second difference is in the water consumption.  How did you get 7.7 mL? Is that in the paper--I couldn't find it.  The number that I came up with is that a typical mouse consumes about 4 mL of water per day
 

 

I figured out what I did.  I added an adjustment for bioavailability. I have that nicotine in water is 10% bioavailable; while, as a sublingual lozenge, it's 70%-80% bioavailable.

Edited by Dstein, 08 July 2023 - 03:13 AM.

[MikeDC]

I figured out what I did. I added an adjustment for bioavailability. I have that nicotine in water is 10% bioavailable; while, as a sublingual lozenge, it's 70%-80% bioavailable.

We just assume human and mice have similar bioavailability.

[Dstein]

I'm making the same assumption, but adjusting for the fact that I'm using a sublingual lozenge instead of putting it in my drinking water.  Bioavailability of nicotine seems to be even higher when inhaled.

[MikeDC]

I'm making the same assumption, but adjusting for the fact that I'm using a sublingual lozenge instead of putting it in my drinking water. Bioavailability of nicotine seems to be even higher when inhaled.

[MikeDC]

You are risking overdose with sublingual dosing. Some tissues can be exposed to higher nicotine concentrations. Dilution with water and slowly drink it over the course of the day is probably the best way to not overdose.

[Dstein]

You are risking overdose with sublingual dosing. Some tissues can be exposed to higher nicotine concentrations. Dilution with water and slowly drink it over the course of the day is probably the best way to not overdose.

 

Good point