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💫 Summary
The video discusses the reasons why Dr. Brad Stanfield decided to stop taking NMN, a popular longevity supplement, due to concerns about its effects on inflammation and cancer, while also highlighting the benefits of NAD+ supplementation in combating age-related decline and chronic diseases. The speaker suggests strategies such as clearing out senescent cells, exercising, and inhibiting CD38 to maintain NAD+ levels, but emphasizes the need for more research and precision in supplementation.
✨ Highlights📊 Transcript
Dr. Brad Stanfield explains his decision to stop taking NMN due to concerns about the potential link between NAD+ levels and inflammation, SASPs, and cancer.
00:00
Dr. Stanfield believes that the science behind NAD+ precursors like NMN is still new and there is much that is unknown.
He references papers that suggest an increase in the ratio of NAD+ to NADH can worsen inflammation caused by SASPs.
NAD+ metabolism is linked to the pro-inflammatory effects of SASPs, which can contribute to inflammation and potentially cancer.
CD38 acts as an enzyme that consumes NAD+ to limit the harmful impact of NAD+ on inflammation, and NAMPT levels decline with age, potentially increasing the risk of cancer.
02:51
CD38 is found on immune cells and increases in inflammation.
CD38 consumes 100 molecules of NAD+ for every molecule of cADP ribose it creates.
NAMPT, the enzyme that converts NAM to NMN, declines with age.
NAD+ may increase the risk of cancer and worsen SASP-associated inflammation.
Dr. Brad Stanfield stopped taking NMN due to the decline in NAD+ levels, which can lead to chronic diseases and aging.
05:44
Aging causes a decline in NAD+ levels and an increase in cellular senescence.
Rising levels of inflammation caused by cellular senescence contribute to the decline in NAD+ levels.
CD38, released by SASPs, consumes NAD+ at a high rate, exacerbating SASP-associated inflammation.
Decreased activity levels result in a drop in NAMPT, leading to less NAD+ recycling and a loss of homeostasis.
The speaker discusses the correlation between NAD+ and inflammation, emphasizes the need for more research, and suggests strategies for promoting longevity.
08:32
The age-related decline in NAD+ levels may lead to under-activation rather than over-activation of sirtuins.
Clearing out senescent cells can reduce chronic inflammation and preserve the NAD+ pool.
Exercise, especially aerobic exercise and resistance training, can increase NAMPT levels and potentially mitigate the decline in NAD+.
More research is needed to fully understand NAD+ metabolism and its impact on aging.
The speaker discusses the challenges of monitoring NAD+ levels and the need for precision in administering NAD+ precursors.
11:22
Eliminating senescent cells and inhibiting CD38 are methods to prevent NAD+ decline.
NAD+ testing is currently limited and expensive, with only a few tests available.
Future technologies, such as liquid chromatography and bioluminescent biosensors, may make NAD+ level monitoring easier and cheaper.
The speaker plans to use age as a guide for trying more aggressive interventions.
00:00A few weeks ago, a YouTuber named Dr. Brad Stanfield posted a video
00:05in which he explained why he’s decided to stop taking NMN,
00:10one of the most popular supplements in the longevity community.
00:13I watched the video, and decided that I needed to post my own video in reply.
00:25This week, I’m gonna respond to a video that Dr. Brad Stanfield posted on his YouTube channel a few weeks ago.
00:32He posted this video to explain his decision to stop taking NMN.
00:38He feels that the science is new, there too much we don’t know,
00:43and there are some studies that might possibly point to some factors
00:47that contradict taking NAD+ precursors. And I have some thoughts on that.
00:55So, I want to start out by stating that I’m not a doctor, or a scientist, or a researcher.
01:01I’m just a lay person whose passion is longevity science.
01:05Dr. Brad Stanfield on the other hand, is a doctor.
01:08And I’m pretty sure that he’s more qualified than I am to be having any opinion of the subject of NAD,
01:14and NAD+ precursors like NMN or NR.
01:19That said, Dr. Stanfield explained, in great detail, why he’s decided to stop taking NMN.
01:26And he made some pretty good points.
01:28In his video, he referenced some papers that linked NAD+ levels with inflammation,
01:34with SASPs, and with cancer.
01:36So, as I understand it, here’s the case that the papers make, or at least, the conclusions that they came to.
01:43NAD+ metabolism governs the pro-inflammatory effects of
01:48senescent-associated secretory phenotypes, or SASPs. SASPs can cause inflammation
01:56and it’s been discovered that NAD+ can cause this SASP-associated inflammation to become worse.
02:02And what’s driving it is an increase in the ratio between NAD+ and NADH.
02:09NAD is a molecule that transfers electrons,
02:12and as it goes from picking up an electron to dropping one off,
02:15it constantly changes between NAD+ and NADH.
02:20This increase in the ratio of NAD+ to NADH can convert
02:26SASPs with pro-inflammatory factors that are relatively low into highly pro-inflammatory SASPs.
02:33So, NAD+ can make inflammation caused by SASPs worse.
02:39If the ratio of NAD+ to NADH increases.
02:44Now, one of the pro-inflammatory compounds that SASP’s secrete is CD38.
02:51CD38 is found on the surfaces of immune cells, and inflammation causes an increase in macrophages,
02:59which is an immune cell, so this make sense.
03:02CD38 can also act as an enzyme, creating cADP ribose from NAD+.
03:09And CD38 consumes NAD+ at a voracious rate,
03:14consuming 100 molecules of NAD+ for every molecule of cADP ribose that it creates.
03:21So it’s theorized that CD38 acts to limit the harmful impact of NAD+ on SASP-associated inflammation.
03:31One way that NAD+ metabolism is thought to impact both tissue aging and cancer is through NAMPT,
03:39the rate-limiting enzyme that’s part of the salvage pathway in recycling NAD+.
03:45When NAD+ is used by a variety of enzymes, including CD38,
03:50but also by sirtuins and PARPs, which repair DNA, the NAD+ is converted to nicotinamide, or NAM.
03:59NAM is converted into NMN by the enzyme NAMPT
04:05before being further converted back into NAD+.
04:09And like a lot of other things. NAMPT levels go into decline as we age.
04:15And it’s believed that the culprit is inactivity which, in most of us, increases as we grow older.
04:22It’s also thought that NAD+ might increase the risk of cancer.
04:28In mice that had been especially bred to form cancers, NAD+ elevated levels of pre-cancerous markers.
04:36Now, while it did not have the same effect on wild mice,
04:39these cancer-inducing mice might be compared to people who have a family history of cancer. Like me.
04:48So, as we age, we produce more and more senescent cells.
04:52These senescent cells secret pro-inflammatory SASPs.
04:57NAD+ makes this SASP-associated inflammation worse,
05:02and might even increase the risk of cancer.
05:05But these same SASPs also secrete CD38,
05:09possibly in an effort to mitigate the inflammation-heightening effects of NAD+.
05:16So maybe it’s a self-correcting system, trying to balance things out and maintain homeostasis.
05:23So the paper recommends that dietary supplementation of NAD+ precursors,
05:28like NMN and NR, should be administered with precision.
05:34That means that NMN and NR are not supplements that everyone should be taking.
05:39And this seems to be the point that Dr. Stanfield is also making,
05:44and why he’s decided to stop taking NMN.
05:47However, there’s a wealth of other papers that demonstrate several things conclusively.
05:53They’ve demonstrated that as we age, our levels of NAD+ go into serious decline.
05:59They’ve demonstrated that these declining levels of NAD+ can lead to chronic diseases, like cancer.
06:07They’ve demonstrated that the age-related rise in cellular senescence contributes
06:13to this decline in NAD+ levels, as does both declining levels of NAMPT and rising levels of CD38.
06:22OK, we’ve got high levels of NAD+ causing more SASP-associated inflammation to become worse,
06:30but at the same time rising levels of inflammation caused by
06:34cellular senescence causes a decline in NAD+ levels, through the action of CD38 released by SASPs.
06:43So, here that way that I think it works.
06:46When we’re younger, our NAD+ levels are optimal and our NAD+ metabolism is cranking along
06:54tickety-boo.
06:55NAD+ fuels a lot of youth-persevering processes in our bodies.
07:00But apparently it can also fuel SASP-associated inflammation…
07:06which is a bad thing.
07:07But that’s OK.
07:09We’re still young, we don’t have that many senescent cells,
07:13so we don’t have much SASP-associated inflammation.
07:17But as we age, our load of senescent cells get bigger and bigger,
07:22we have more and more of them. And they’re cranking out more and more SASPs.
07:27And suddenly, issue of NAD+ making SASP-associated inflammation worse, is a big deal.
07:35So…CD38 is secreted along with the SASPs, the CD38 consumes NAD+ at a voracious rate,
07:44and it’s no longer a problem.
07:46Added to that is the fact that as we become less and less active, our levels of NAMPT drop.
07:52And so we recycle less and less NAD+.
07:56Unfortunately, while NAD+ is no longer fueling SASP-associated inflammation,
08:03it’s also not fueling repair of our DNA or the activation of sirtuins.
08:08And since repairing damaged DNA and activating sirtuins helps to maintain homeostasis,
08:14homeostasis is lost and we age.
08:18Now, Dr. Stanfield makes the case that while mild activation of sirtuins can lead to a reduction in chronic disease,
08:27over activation can have the opposite effect, leading to a rise in chronic disease.
08:32I’m guessing that this is a correlation of NAD+ making SASP-associated inflammation worse.
08:39But I suspect that the age-related decline in NAD+ levels gets so bad that sirtuin over-activation is no longer a concern.
08:49I think the concern is under-activation.
08:53So, what do we do with this information?
08:56How do we apply it to our longevity strategy?
08:59he first thing to keep in mind is that there’s a lot that we still don’t know.
09:03The research is not very old, and there’s not very much of it.
09:07We need a lot more of it.
09:08We don’t really understand NAD+ metabolism and it’s effect on the aging process.
09:15So anything we do needs to be tempered by this knowledge of what we don’t know.
09:20We don’t want to do anything that we might learn later was a huge mistake.
09:25So, how we apply this information to our longevity strategy kinda depends on how old we are.
09:32My strategy is different now than it would have been when I was in my 20’s or 30’s.
09:37I think the first thing that I would do, at any age, is to try to clear out senescent cells.
09:43Cellular senescence causes chronic inflammation,
09:46and you want to eradicate that as much as possible.
09:50If you can clear out senescent cells, you don’t have as much chronic inflammation.
09:55And you also don’t have as much CD38, which eats into the NAD+ pool.
10:02The next thing that I’d do is start exercising.
10:06Remember earlier when I mentioned that declining levels of NAMPT,
10:10the rate-limiting enzyme of the salvage pathway, is caused by inactivity?
10:15Well, it’s been demonstrated in studies that declining levels of NAMPT can be reversed by exercise.
10:22Aerobic exercise can raise NAMPT levels by 12% and resistance training can raise them by 25%…
10:31in young people.
10:32But in older people, you get an even more pronounced effect,
10:36raising NAMPT levels by 20% with aerobic exercise and 30% with weight training.
10:42I’m guessing that it doesn’t raise the levels as much in younger people because
10:48the levels haven’t gone into as much of a decline.
10:50As I aged, I’d probably start taking CD38 inhibitors like apigenin and quercetin.
10:56There’s a whole lotta science demonstrating that CD38 is inhibited by
11:02both apigenin and quercetin, and that either one of these polyphenols can result in increased levels of NAD+.
11:10I recently did a video on this, and I’ll link to it in the description and in this card up here.
11:16My longevity strategy would start out with trying to plug the hole in my NAD+ pool,
11:22to inhibit or prevent that things that are causing my NAD+ levels to go into decline.
11:28Eliminate CD38, first by eliminating as many senescent cells as I could,
11:35then by inhibiting the effects of CD38.
11:38And by increasing my NAMPT levels so that I was recycling more and more NAD+.
11:45Supplementing with an NAD+ precursor, like MNM or NR,
11:50would be the last type of intervention in my longevity strategy.
11:56So, earlier, I was talking about how one of the papers referenced in Dr. Stanfield’s video
12:01concluded that supplementation with NAD+ precursors should be administered with precision,
12:07and I’d like to revisit that opinion.
12:09That type of precision would require a pretty sound knowledge of my present NAD+ levels.
12:16But NAD+ testing is in it’s infancy.
12:19We would need to constantly monitor our NAD+ levels throughout the day,
12:24because they’re constantly changing throughout the day.
12:27Right now, there’s very few tests available to the consumer that can determine NAD+ levels.
12:33The only one that I know of is offered by BioViva and it costs about $200, although there may be others.
12:41Now, there are some technologies in development that might make it
12:45easier and cheaper to monitor NAD+ levels in the future.
12:49There’s one test that uses liquid chromatography and another that uses a bioluminescent biosensor.
12:56They’re both in development and they both test for NAD+ levels.
13:01But that’s in the future. Which makes that kind of precision kinda difficult.
13:06So, I guess I’d use age as a guide.
13:09If I was younger, I’d wait for the science and technology to catch up
13:13and I’d probably only exercise and maybe try to clear senescent cells.
13:18But as I got older, I’d be more willing to try more aggressive interventions.
13:23But at what age would I be willing to try everything, as aggressively as I could?
13:28Well, I’m 71 and I feel I’m pretty much there.
13:33I don’t know what my NAD+ levels are, but I’m guessing that they’re probably pretty low.
13:38I’m really looking forward to those cheap and easy NAD+ test,
13:43so that I can bring some precision to my strategy.
13:46In the meantime, I’ll guess I’ll try to estimate or test my biological age and us that as a guide.
13:53If any of you guys have a better way of figuring out what your NAD+ levels are,
13:59I’d love to hear about them. Leave me a comment.
14:01That’s it for this video. Check out this playlist of NAD and NAD+ precursors.
14:08I’m outta here, catch ya next week.
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FAQs about This YouTube Video

1. What are the concerns about the effects of NMN on inflammation and cancer?

The concerns about the effects of NMN on inflammation and cancer led Dr. Brad Stanfield to stop taking the popular longevity supplement. The speaker highlights the need for more research and precision in supplementation to address these concerns.

2. What are the benefits of NAD+ supplementation in combating age-related decline and chronic diseases?

NAD+ supplementation has shown benefits in combating age-related decline and chronic diseases. It is suggested as a strategy to maintain NAD+ levels and address age-related health issues.

3. What strategies are suggested to maintain NAD+ levels?

Strategies such as clearing out senescent cells, exercising, and inhibiting CD38 are suggested to maintain NAD+ levels. These strategies may help in combating age-related decline and chronic diseases.

4. What is emphasized regarding NAD+ supplementation?

The need for more research and precision in supplementation is emphasized when it comes to NAD+ supplementation. This highlights the importance of understanding the effects and benefits of NAD+ supplementation.

5. What is the speaker's perspective on the use of NMN and NAD+ supplementation?

The speaker discusses the concerns about NMN's effects on inflammation and cancer, leading to Dr. Brad Stanfield's decision to stop taking it. However, the benefits of NAD+ supplementation in combating age-related decline and chronic diseases are also highlighted, suggesting a balanced perspective on the use of these supplements.

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