Restore NAD+ Level without NR or NMN
To keep NAD+ levels high, almost everywhere I look, it is suggested that we must supply precursors (NR or NMN), so that we can induce "production" of NAD+. Both NR & NMN are not cheap.
I wonder why the other side of the equation is mostly ignored. Namely, to cure the root cause of the reduced levels of NAD+ with age.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911708/
In this study, it is claimed that the root cause of NAD+ level reduction is the increase of CD38 with age. If this is true, inhibiting CD38 should be the target.
There are many inhibitors. One that I find interesting, is apigenin.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609577/
Apigenin is a flavonoid that is inexpensive, safe and has numerous other benefits. You can even avoid buying the supplement if you are willing to eat plenty of parsley.
Of course, other CD38 inhibitors might also be utilized.
To me, this appears to be a better approach. We cure the problem (elevated CD38 that causes lower levels of NAD+), rather than the symptom (force feed precursors hoping that NAD+ will eventually be produced)
Any feedback will be appreciated
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It might be more productive to remove senescent cells than trying to boost NAD.
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Larry
Here I am not trying to compare boosting NAD+ with other interventions.
Instead, for those that are interested in boosting NAD+, we suggest that there might be an alternative to supplementing with precursors such as NR or NMN.
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Larry
Having read the content of the link you provided, I noticed that they also suggest that the "CD38 expression is believed to be the key modulator of lowered NAD+ levels with aging".
This supports my suggestion that an intervention inhibiting CD38 might be useful for boosting NAD+
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Zisos Katsiapis Nicola Conlon agrees with your conclusions and started Nuchido. Check out her blog, supplement and presentation during 2019 undoing aging. I didn’t try it myself yet; but, the test results showing 3 fold nad increase without nad precursor and nearly 10 fold with nad precursors are impressive.
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Joe smith
Wow!
That is truly amazing.
In fact, I have been supplementing with NMN and 50mg Apigenin (also consuming lots of Parsley). I expected some synergy, but did not expect such amazing benefits!
A question:
What tests are you referring to? Can you provide a link?
Thanks
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Here is the link to her research https://cdn.shopify.com/s/files/1/0029/5449/4052/files/Undoing_ageing_poster_2019_-_Correct_size.pdf . The doc has the test results but is not specific with respect of what the chemicals they used in their tests. The chemicals and what they do to achieve the network effect are explained in this blog post https://nuchido.com/blogs/articles/ageing-nad-and-biological-complexity. In summary yes you can achieve good boost of nad+ even without nad precursors and it takes apigenin and other chemicals as she explains to do so. Amazingly she achieves her 10x nad+ boost utilizing the cheapest nad+ precursor out there Niacinamide.
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Joe smith
Very interesting. So it is possible to boost NAD+ substantially at a very low cost.
Example:
Supplement with Apigening (or consume substantial amount of parsley)
Supplement with EGCG (or drink lots of Green Tea)
Supplement with Rutin (inexpensive, with many extra benefits)
Supplement with inexpensive Niacinamide (instead of expensive NR or NMN)
Thank you for these links.
I currently take NMN, Apigenin (and consume plenty of parsley), and drink 5-6 cups of green tea per day.
Based on those links, I will replace expensive NMN with inexpensive Niacinamide, and add Rutin (also inexpensive). This will probably increase benefits and will reduce cost.
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Joe smith
Thank you for sharing the interesting poster. A poster from scientists that tackle the issue of complexity of the human organism. When it comes to promotion of long and healthy life through supplements the usual approach (the reductionist way) is to study one substance at the time. This is of course the correct way to study and learn how the single substance effects the human body. But the results we get from that approach are not automatically translated the persons that use several other supplements. I have read about Nuchido before but never seen any researchpapers or posters. I hop there is more on the way.
Like they say in the poster “all functional systems in biology are composed of complex sets of pathways, feedback loops, signaling sequences, homeostatic balancing mechanism, redundancies, sub-networks and competitive interactions. This means that complex biological processes such as ageing cannot he understood through the application of a single target reductionist approach.”
I remember reading a report from quite a long time ago (I can not find it now). It was a mouse/rat study and it might have been flawed, who knows? But what they did and the results they got startled me. They gave rats/mice many different kinds of antioxidants. Up to 25 – 30 different kinds of supplements. The end result was surprising (at least then). The supplemented animals had a shorter life. Antioxidant overlaod? Negative interactions? Who knows?
I have no idea about the quality of that particular report but it brings forward the idea that we should understand that our good intentions can backfire. Yes, there are science behind many supplements but how to optimize their effect? More of a substance is not automatically better and a combination of many different kinds of supplements is not automatically better that fewer. This is true in spite of the fact that there are sound research showing that every supplement is very beneficial on its own. But together they might create a negative effect on health. Or they can counteract each other and the sum of a massive effort is a Zero effect on healthspan.
That is why I appreciate the functional approach that is done by Conlon et el, and what they bring forward in the poster. But I also appreciate what "vitality in aging" seem to aim for - Maximum effect on specific targets with a minimum of substances -. And also what is done by life extension and Insilco with their deep learning models aiming at finding synergistic substances to improve specific cellular functions.
Thank you for sharing the poster.
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Zisos Katsiapis
Have done some further reading, and realized that Niacinamide might not be a good choice, because in large doses it inhibits sirtuins. So, I will stick to sublingual NMN for now.
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Staffan Olsson Couple of comments. First I’m not surprised that antioxidant study you are referring to shortened a lifespan. I think antioxidant theory of aging just doesn’t have support in the scientific research. It kind of sounded convincing in the nineties until researchers started testing it and found that antioxidants actually reduce lifespan. So no surprise that piling up bunch of antioxidants would produce even worse results. Second I really like the approach of computer simulation in uncovering action of molecules on body cells and as next step of interaction between chemicals. In that vein, I have seen some recent very interesting computer simulation research on chemical molecules and coronavirus. my thinking is that one at a time reductionist approach was just simply only one option available because we didn’t have large scale computer simulation. Now we can do more.
@Zisos Katsiapis I think Nuchido is trying to show that if you combine these other molecules with niacinamide, it doesn’t stick around to negatively affect sirt1 and instead gets converted to nad+ and then properly salvaged so you don’t have to use nmn. Also my thinking here is that it just may be better to take the other chemicals she lists to conserve nad+ and improve recycling and avoid taking any nad+ precursors at all. If nuchido is right then it may be possible to avoid age related degradation while restoring nad+ to youthful levels without any precursor. Adding precursor to the mix may push your nad+ levels above normal and hence increase cancer risk. To keep check and balances your body maintains homeostasis. Hence, extra precursor I suspect will encounter your body resistance and may have negative side effects. It is of course all speculations as there are 0 nmn studies in humans. So instead, I much more like increasing nad+ levels through more systemic approaches like cr and/or intermittent fasting.
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Joe smith
I was not aware that "too much" NAD+ increases cancer risk. So this is one more thing to worry about. I would assume that this is a function of age. If Sinclair is right in saying that at age 50 the NAD+ levels are half than at age 20, and by age 90 there is almost no NAD+ left, then someone 50 years old should not increase levels by a factor of 10. At age 90, there would be no such worry. Unfortunately, there is no easy way to test NAD+ levels, so we have to guess. Being almost 70 years old, I am inclined to keep NAD+ higher, rather than lower. My inclination is not based on scientific evidence. Maybe I am just influenced by the fact that everyone is trying to increase NAD+.
I find the information that you have provided about the combinational approach extremely useful. Now I know that I can increase NAD+ very much without spending an arm and a leg supplementing large quantities of NMN or NR, which might even be less effective, and might even cause more side effects. At the same time, I need to make sure that I do not overdo it. Thank you for your contribution.
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Zisos Katsiapis Note that anything that makes you live longer increases your chance of cancer. There needs to be some sort of age control to see if it's excess cancer, or just living long enough to reach the vulnerability.
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Inhibiting CD38, sounds like a logical approach to correct for low NADH. However, after a little searching, I found this recent article, that describes the MANY roles CD38 has with the immune system. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017097/ Some inhibition MAY get the desired effect, but overdosing could lead to reduced immunity.
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Henry walker
Hm... I guess we do need to be careful. I wish there was an easy way to measure CD38 and NAD+. Then we could adjust utilization of supplements to calibrate for the appropriate levels. In the absense of easy testing, I guess we should be careful with dosing of CD38 inhibitors, as you suggested. Also, we might want to avoid inhibitors of CD38 if we have been infected, or if there is a high probability of being infected. It also depends on age. As the paper suggests, for older HIV patients, low CD38 is beneficial, but for young patients detrimental. This might be the case for other deseases. Inhibition in old age makes sense, because levels of CD38 are very high, whereas in younger people, they are lower. So, it is much more complicated than what I thought when I made my first comment about CD38 inhibitors.
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i have been using the 4 hour patch 1/x wk. Wondering if I should be supplementing on other days as well with some form of NAD? Looking into NAD Gold by Quicksilver?
Do others supplement in addition to wearing the patch?
