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Impacts the function of the Aryl Hydrocarbon Receptor, which improves Tryptophan / Kynurenine metabolism, too. Unless you are exposed to pollution like Benzopyrene during exercise, then it goes the other way. Don't exercise near exhaust fumes or bushfires.
This sounds like a promising device. It would be great to get these researchers together with a group trying to connect blood NAD and tissue NAD levels (Maybe in mice? This is probably well-conserved.) For example, it would be interesting to know if the spike in NAD after exercise is really describing an attempt to make tissues that need NAD absorb them. I imagine the hard part of these studies is that blood NAD can change very quickly, whereas if you wanted tissue NAD, you would probably have to start by buying old mice, and then run an experiment on them for a couple months.
Hi Jeff, thanks for your comment. It would be great to see in a mouse model how well NAD levels in the blood correlates with NAD levels in other tissues.
Thanks for the great video. This seems to be very good clinical trial that seems to definitively prove that niacin is a very effective NAD booster. They test mad levels in the blood and muscle tissue
The confusion seems to be that tissue levels apparently do not increase…also, there is no way to test the brain tissue until you’re dead…so the NMN folks can only point to blood levels. I take NMN but the jury is out as to whether it actually impacts human health in a meaningful way.
Hi Scott, thanks for the comment. As a note they are measuring intracellular NAD levels in the blood cells (not in the plasma) but it is still a valid point that the level in the blood is not the most important. I think that they are the best proxy that we have. NAD levels are localized to different tissues and also to different places in the cell (in our most recent interview with Dr. Baur he talked about the importance of getting the NAD into the mitochondria rather than just into the cell). So talking of "NAD levels" is a very high level generalization. The current way of measuring NAD levels in a tissue requires a biopsy and grinding up the tissue. We can do these in mouse models, which gives an idea of the relationship between the levels in the blood and in other tissues. I do see a paper which shows that NMN can get into the brain (Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain)
Hi thanks for your comment. It would be good. I think it has been shown that there is a correlation between having higher NAD levels and being healthy, though raising NAD levels through supplementation has had mixed results.
If they didn't use the Salvage pathway NAD+ will be reduced to NADH. The salvage pathway recycles NAD+ by keeping it in the oxidized state. These are classified as simple oxidation reduction reactions.
As other people commented here, it seems that Blood NAD levels are meaningless. What matters is raising NAD level in the different tissues, which as far as I know was not detected in any trial so far. It corresponds with the poor results so far of NAD supplementation in humans.
Hi thanks for the comment. I don't think that raising NAD levels in blood cells is meaningless, but it is not the most important figure. Certainly seeing the levels raised in specific tissues would be good but that does require biopsies. I find the varying responses to the supplementation interesting. One of the points that Dr She made about NMN (and other NAD boosting studies) is that the dose should not be standardised, rather the NAD level should be. So a participant should be given the amount of NAD precursor required to reach a certain blood NAD concentration and then the outcome measured.
They aren't overall as disappointing as he made them out to be. He missed numerous studies too. So many studies also use NMN without resvertatrol or pterostilbene for which many health benefits are essential
Hi Ken, thanks for the comment. The test does look at NAD levels in the blood cells not in the plasma. However, it does not look at NAD levels in specific tissues as that would require biopsies. It is also true that NAD levels can differ in different tissues so this is a proxy, but I think it is the best one that we have at the moment.
I’m concerned about NMN being banned by the FDA. Safety is very important to me. Seeking advice on legally approved supplements adhering to stringent regulatory standards.
I would like to see this same study with NA and NR as well. There is no reason to believe NMN is superior to either of those when raising NAD blood levels.
Hi thanks for your comment. This is probably true. It would be great to see head to head comparisons of the various NAD precursors but just because of the way clinical trials work it does not seem likely that we will get them.
Well, I’m only taking it because NMN has been proven with Dr. Sinclair on animal studies. But yes you’re right we need thorough investigation with NR also.
This gives me the impression that focusing too much on NAD boosting might cause problems for DNA methyl groups long term. I wonder if it's best to reduce NMN dosage and focus on boosting the salvage pathways instead.
I think it is more important to see significant measurable gains in muscle mass, strength and overall physical improvement than increases in NAD levels. Not seen any studies that show that yet. Dr. Brad Stanfield hasn't found any either.
There is no magic pill. NMN does work in a molecular level and promotes mitochondrial health and repair mechanisms. This is already very important isn’t it?
Hi George, thanks for the comment. It is important to see measurable improvements though I don't think it needs to be muscle mass necessarily. NAD is also required for DNA repair and many other vital functions. If improvements in these were seen would that not be worthwhile?
it would be valuable to see appropriate increased NAD levels at a cellular level via gold standard double blind studies, but by then it would be probably classified as a drug. Sadly.
Hi Bob, thanks for the question. Well, increase NAD rather than NMN, but yes. Exercise has been shown to increase NAD levels and this study's findings agreed with that.
lol yeah we’ll wait till you hit 68. Number changes for everyone but sooner or later your body changes and as you get older aging speeds up, efficiency crashes, and you will be looking for something to help.
@@BK-dy8jk Sinclair's work also suggests that exercise ultimately fails in the end (and you get severe sarcopenia to shrink down to the same 40-55% body fat mass just like everyone else) because of anabolic resistance caused by vascular aging and NAD decline (immunosenescence+CD38). A elderly friend of mine was unable to sprint and lift due to joint pains until they tried IF, 72 hour monthly pure fat FMD cycles and then finally lipo NMN+resveratrol+apigenin+quercetin. Even then we're still working on the visceral fat belly. that's how important NAD and SIRT1 are in combating anabolic resistance in MTOR-overactivated, chronically inflamed sarcopenic muscles. -Meat based KD sprinter
Renue By Science 10% Lipo NMN : tinyurl.com/3wr8pr3t , New Lipo Vitamin C: tinyurl.com/yva673b7
ProHealth 15% discount NMN Pro 1000 Code MODERN : prohealth.pxf.io/DKeEmd, NR Pro 500 prohealth.pxf.io/jry3N6
DoNotAge 10% discount code MHS Pure NMN tinyurl.com/5bhsh5vn, Pure NR tinyurl.com/27seu943
NOVOS Core & Boost novos.sjv.io/QyWP7o code 5offmodernhealth1026
☕If you would like to support our channel, we’d love a coffee…thank you! www.buymeacoffee.com/mhealthspan
It's fascinating that exercise causes nad to rise rather than falling!
Hi thanks for your comment. I believe the mechanism may be that exercise activates AMPK which stimulates NAMPT to increase the salvage pathway.
Impacts the function of the Aryl Hydrocarbon Receptor, which improves Tryptophan / Kynurenine metabolism, too.
Unless you are exposed to pollution like Benzopyrene during exercise, then it goes the other way.
Don't exercise near exhaust fumes or bushfires.
Excellent presentation, thank you Richard!
Hi thanks Sparkling!
This sounds like a promising device. It would be great to get these researchers together with a group trying to connect blood NAD and tissue NAD levels (Maybe in mice? This is probably well-conserved.) For example, it would be interesting to know if the spike in NAD after exercise is really describing an attempt to make tissues that need NAD absorb them.
I imagine the hard part of these studies is that blood NAD can change very quickly, whereas if you wanted tissue NAD, you would probably have to start by buying old mice, and then run an experiment on them for a couple months.
Hi Jeff, thanks for your comment. It would be great to see in a mouse model how well NAD levels in the blood correlates with NAD levels in other tissues.
Thanks for the great video. This seems to be very good clinical trial that seems to definitively prove that niacin is a very effective NAD booster. They test mad levels in the blood and muscle tissue
But do NAD blood levels matter? I thought it was only intracellular NAD that benefits us.
The confusion seems to be that tissue levels apparently do not increase…also, there is no way to test the brain tissue until you’re dead…so the NMN folks can only point to blood levels. I take NMN but the jury is out as to whether it actually impacts human health in a meaningful way.
Hi Scott, thanks for the comment. As a note they are measuring intracellular NAD levels in the blood cells (not in the plasma) but it is still a valid point that the level in the blood is not the most important. I think that they are the best proxy that we have. NAD levels are localized to different tissues and also to different places in the cell (in our most recent interview with Dr. Baur he talked about the importance of getting the NAD into the mitochondria rather than just into the cell). So talking of "NAD levels" is a very high level generalization. The current way of measuring NAD levels in a tissue requires a biopsy and grinding up the tissue. We can do these in mouse models, which gives an idea of the relationship between the levels in the blood and in other tissues. I do see a paper which shows that NMN can get into the brain (Oral Administration of Nicotinamide Mononucleotide Increases Nicotinamide Adenine Dinucleotide Level in an Animal Brain)
Great review and encouraging results, thank you!
Great review. I appreciate the concise presentation.
Hi thanks!
Now if only it can be shown that increased nad correlates with improved health then we’d have something
Hi thanks for your comment. It would be good. I think it has been shown that there is a correlation between having higher NAD levels and being healthy, though raising NAD levels through supplementation has had mixed results.
If they didn't use the Salvage pathway NAD+ will be reduced to NADH. The salvage pathway recycles NAD+ by keeping it in the oxidized state. These are classified as simple oxidation reduction reactions.
As other people commented here, it seems that Blood NAD levels are meaningless. What matters is raising NAD level in the different tissues, which as far as I know was not detected in any trial so far. It corresponds with the poor results so far of NAD supplementation in humans.
Hi thanks for the comment. I don't think that raising NAD levels in blood cells is meaningless, but it is not the most important figure. Certainly seeing the levels raised in specific tissues would be good but that does require biopsies. I find the varying responses to the supplementation interesting. One of the points that Dr She made about NMN (and other NAD boosting studies) is that the dose should not be standardised, rather the NAD level should be. So a participant should be given the amount of NAD precursor required to reach a certain blood NAD concentration and then the outcome measured.
Sound like its the exercise that makes the difference.
Great technology. I hope they test the effectiveness of other chemicals on NAD chemicals in the future.
Hi Julia, thanks! It is great to see some home testing technology coming out. More data is always good!
Ok that NMN can increase NAD blood levels, but does it also increase cells NAD ?
thoughts on brad stanfield's video on disappointing NMN human studies?
They aren't overall as disappointing as he made them out to be. He missed numerous studies too. So many studies also use NMN without resvertatrol or pterostilbene for which many health benefits are essential
Thanks Richard.
Hey Ron, thanks!
I thought blood NMN levels were not necessarily indicative of NMN in other tissues. I forget which study/youtube video where I saw that factoid.
Dr brad Stanfield...who also says it needs lots more research....this has been said by many doctors
Hi Ken, thanks for the comment. The test does look at NAD levels in the blood cells not in the plasma. However, it does not look at NAD levels in specific tissues as that would require biopsies. It is also true that NAD levels can differ in different tissues so this is a proxy, but I think it is the best one that we have at the moment.
I’m concerned about NMN being banned by the FDA. Safety is very important to me. Seeking advice on legally approved supplements adhering to stringent regulatory standards.
I would like to see this same study with NA and NR as well. There is no reason to believe NMN is superior to either of those when raising NAD blood levels.
maybe not so much demonstrably superior or more likely, no worse
Hi thanks for your comment. This is probably true. It would be great to see head to head comparisons of the various NAD precursors but just because of the way clinical trials work it does not seem likely that we will get them.
Well, I’m only taking it because NMN has been proven with Dr. Sinclair on animal studies. But yes you’re right we need thorough investigation with NR also.
This gives me the impression that focusing too much on NAD boosting might cause problems for DNA methyl groups long term. I wonder if it's best to reduce NMN dosage and focus on boosting the salvage pathways instead.
I think it is more important to see significant measurable gains in muscle mass, strength and overall physical improvement than increases in NAD levels. Not seen any studies that show that yet. Dr. Brad Stanfield hasn't found any either.
There is no magic pill. NMN does work in a molecular level and promotes mitochondrial health and repair mechanisms. This is already very important isn’t it?
Hi George, thanks for the comment. It is important to see measurable improvements though I don't think it needs to be muscle mass necessarily. NAD is also required for DNA repair and many other vital functions. If improvements in these were seen would that not be worthwhile?
it would be valuable to see appropriate increased NAD levels at a cellular level via gold standard double blind studies, but by then it would be probably classified as a drug. Sadly.
Those are important factors but there are more factors to consider to account for overall health and well-being
Seems the persons that check their EPG age clock get negative result if their NAD levels is to high.
So daily exercise increases nmn?
Hi Bob, thanks for the question. Well, increase NAD rather than NMN, but yes. Exercise has been shown to increase NAD levels and this study's findings agreed with that.
I must be a lucky super responder. NMN is basically anabolic steroids for me
Nmn + tmg is a waste for me. Exercise 2x per week is where its at for me
lol yeah we’ll wait till you hit 68. Number changes for everyone but sooner or later your body changes and as you get older aging speeds up, efficiency crashes, and you will be looking for something to help.
@@BK-dy8jk Sinclair's work also suggests that exercise ultimately fails in the end (and you get severe sarcopenia to shrink down to the same 40-55% body fat mass just like everyone else) because of anabolic resistance caused by vascular aging and NAD decline (immunosenescence+CD38). A elderly friend of mine was unable to sprint and lift due to joint pains until they tried IF, 72 hour monthly pure fat FMD cycles and then finally lipo NMN+resveratrol+apigenin+quercetin. Even then we're still working on the visceral fat belly. that's how important NAD and SIRT1 are in combating anabolic resistance in MTOR-overactivated, chronically inflamed sarcopenic muscles. -Meat based KD sprinter
Do not waste your money on Nmn it’s a con .