#51

My suspicion for a while now, all the scientific papers on NMN the last couple of years has been grasping at straws to put it mildly. supplement companies and YouTubers love it though, NMN and Resveratrol, two things that does nothing for anti aging…is pumped to be the best anti aging strategy, go figure.

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#52

Low dose nicotine?

https://www.nature.com/articles/s41467-023-36543-8

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

Previous studies showed that supplementing NAD+ precursors, such as nicotinamide mononucleotide (β-NMN), nicotinamide riboside (NR), nicotinamide (NAM), or Niacin (NA), were efficient for anti-aging8,9,10. In mammalian cells, most NAD+ precursors were “reclaimed” to NAD+ via the rate-limiting enzyme nicotinamide phosphoribosyl transferase (NAMPT) of the salvage pathway. As NAMPT activity decreases with age, it results in NAD+ depletion and cognitive impairment11. Consequently, the NAMPT enhancers can effectively increase NAD+ levels and prevent neuronal degeneration12,13,14. Moreover, supplementing the high active extracellular NAMPT (eNAMPT) also increases NAD+ biogenesis and aging-related symptoms15,16,17. Therefore, the enhancement of NAMPT activity could be a potential strategy for preventing aging and age-associated diseases arising from NAD+ decline11,18,19.

Interestingly, nicotine is a secondary metabolite of the NAD+ biosynthesis and the NAD+ pathway is also coordinately regulated with nicotine biosynthesis20,21. Furthermore, the NAD+ salvage pathway is conserved across a variety of species, including bacteria, plants, yeasts, and mammals20. Consequently, we hypothesized that nicotine may play a role in the NAD+ salvage pathway. It has been discovered that minuscule amounts of nicotine, as an activator of NAD+ biogenesis, can markedly improve NAMPT activity and NAD+ synthesis, leading to improved glucose metabolism and cognitive function, as well as aging symptoms, in male mice.

Vape liquid provides nicotine.

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#53

I suppose it has to do with dose, but nicotine is bad for blood vessels. I wouldn’t vape it. Maybe use a small chunk of a patch or chew a tiny piece of gum.

I grew a few tobacco plants in my garden once just for the hell of it. Touching the leaves gives you a little nicotine. Great plants to grow! Knew a guy that smoked and he made them into cigarettes.

#54

I meant drink the vape liquid. I have to check if it is edible. Probably is.

If not, there would be the nicotine gums, for those who want to stop smoking.

#55

Nicotinamide extends replicative lifespan of human cells

https://onlinelibrary.wiley.com/doi/full/10.1111/j.1474-9726.2006.00234.x

Summary

We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

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#56

In another thread, World_Traveler says he takes nicotinamide and riboside powder to make his own precursor.

There is evidence for that approach, below:

The increase is modest, maybe because the doses used in the study are conservative - 240 mg nicotinamide plus 1 gram riboside powder, twice a day.

Compared with the mild increase in NAD+ level, an unexpectedly dramatic increase in NADP+ concentration was observed (Figure 2b). Significant within-group increases of 19.1%, 27.6%, and 19.6% were recorded with RiaGev group at Days 3, 5, and 8 over baseline, respectively (p ≤ 0.008). The NADP+ concentrations for the RiaGev group are also significantly greater than that of Placebo group at Day 5 and 8 (p ≤ 0.04).

Don’t know what the effect of hefty doses (that World_Traveler takes) would be.

1 Like
#57

Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study

If one clicks “Show More” on authors, included as co-author is derided-guy-number-one for many members here - David Sinclair.

Body weight (difference −1.9 [−3.3, −0.5] kg, P = .008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P = .034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P = .004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P = .007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 (microcrystalline β-nicotinamide mononucleotide ) group than placebo.

Due process.

Below is the Jan 2023 study on NR.

Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study

There are 17 authors. If you expand it, co-author is the Sinclair nemesis, Charles Brenner.

https://www.science.org/doi/10.1126/sciadv.add5163

NR boosted whole-blood NAD+ levels by 2.3-fold

In conclusion, NR supplementation is a potential treatment option to be tested in individuals with decreased muscle mitochondrial biogenesis and dysbiosis. As possible adverse effects, we report a declining muscle satellite cell number and a possibility for impaired glucose metabolism. As patients with chronic muscle disease typically exhibit satellite cell dysfunction, muscle performance and regeneration are important endpoints to be monitored in future NR clinical trials. Overall, our data underscore the role of NR as a potent modifier of systemic NAD+ levels, muscle mitochondrial biogenesis, satellite cell function, DNA methylation, and the gut microbiota in humans. Notably, NR modulated these metabolic processes similarly in both leaner and heavier cotwins, i.e., regardless of BMI.

I’m not into muscle-building. I prefer to try to improve TC, LDL, and blood pressure.

Maybe it is snake oil. But I have unfinished doses of NMN that I have parked somewhere. It is what accountants call sunk-in cost. So will dig them up and restart dosing.

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#58

I have been using NR on and off, primarily because it is made by a US company and it helps. NMN is mostly sourced from China I believe and so are most of the earlier research. Sinclair is using NMN and has said NMN is superior to NR. But at a molecular level, it does not quite make sense to me NMN is better than NR, as Brenner has stated many times.

2 Likes
#59

I like NMN. I just finished a 25 hour trip from Hong Kong to the USA. Took 1 g of NMN and no jet lag. For those of you who travel, you know how rare that is. IMHO NMN is great for keeping my energy levels up.

As for helping me live longer, I am unsure. But it has its uses.

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#60

When did you take 1g of NMN - before the flight or after?

#61

I took it after the flight when I arrived.

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#62

what brand you would recommend?

#63

The only brand I used is DoNotAge. Too many of the other brands have no NMN in them. There was a report done about the percentage of NMN in Amazon products and it was amazing how many were fake.

To save on costs, I buy the powder and mix it with EVOO.

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#64

This youtube video that goes through all human studies of NMN is pretty negative on the effects on this overpriced and overhyped supplement. I am definitely never going to spend any more money on this.

5 Likes
#65

The most interesting takeaway from this video is that it may be of benefit to overweight and older (50+) individuals. It probably doesn’t make sense to take NMN unless you belong to one of these groups.

I’ll be switching to NR when my current supply runs out. I still think there’s enough positive data on NAD. But, no need for NMN when NR will do the same.

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#66

I take lipo nmn/apigenin mainly for the energy/libido kick, not for longevity though apigenin might have a hand (though liposomal delivery is controversial and I’m guessing untested)

#67

What is the advantage of taking one of the expensive NAD+ boosting supplements like NR or NMN vs niacin or nicotinamide? Don’t they all boost NAD?

#68

No, I believe NR or NMN are superior. But you can pick the cheaper of the two.

#69

“Superior” as in bigger effect for lower dose? I take niacin and nicatinamide (rotate) anyway so would I also need to take NR or NMN? I’m betting no so far. Let me know if I’m wrong.

#70

50-100mg of niacin is all you need. NR has failed the ITP, NNM/NR have failed most human trials, extended release niacin can cause liver damage and high dose niacin did not lower all cause mortality in clinical trials done decades ago.

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