*** In this video, there may be some distortion on my audio, sorry for causing any distraction. We shall improve in our next interview series. Thank you for your understanding *** Prof Joseph Baur - NAD Interview Series Playlist ua-cam.com/video/4z3540vldBk/v-deo.html Modern Healthspan Newsletters Playlist ua-cam.com/video/wNeuqs15JcQ/v-deo.html If you would like to support our channel, we’d love a coffee…thank you! www.buymeacoffee.com/mhealthspan
The finding that NMN and NR are breaking down to NAM and reforming feels really significant. I checked his paper afterwards and it seems like high quality science. Full instructions for replication are included. 👏 Obvious question : does NAM alone raise NAD in humans? Proving this would make a shockwave in the supplement industry
I know this is an old interview now and things have probably moved on, but I'm just going through and summarising some of these videos to better get my head around the content over time. Posting a summary of the main points from this one in case it's useful for others: • NMN and NR do boost NAD but when oral doses were traced they found most got converted to nicotinamide before being used in tissues to make NAD. The molecules are broken down both by the intestinal microbiome and the liver. • Baur hypothesises that when people take NMN and NR orally at high doses, it is the small amount of intact NMN or NR which gets into the blood or peripheral organs and makes a difference. NMN and NR are better than nicotinamide once in tissues as they bypass the pathway that is the most energetically costly. They are now doing trials of giving smaller doses intravenously to see if this hypothesis is correct. He mentions that it has been demonstrated in heart failure that giving nicotinamide to boost NAD may not be effective as the first enzyme that uses nicotinamide is down-regulated, so the other boosters are indicated in certain scenarios. • There have been very few comparisons of NMN and NR. Baur’s team has done some unpublished work on kidney injury where it seems they are working almost equally. Also found they worked more or less equally in the kidney and liver, as per published tracer study. The tracer study also showed, however, there may be a divergence when it comes to the two molecules. When they gave them intravenously, so they would get to the target tissues mostly intact, they found that NR goes into muscle and the heart much more effectively than NMN (note: he mentions this finding wasn’t included in the published paper). • He mentions, with regard to NMN, there’s an argument you need a certain enzyme that breaks it down to NR on the outside of the membrane for it to cross. Someone may not have that enzyme active and therefore won’t be able to get it into certain tissues. It looks like that is the case for muscle. • Richard asks if when taking NMN or NR in a large single dose in order to (theoretically) flood the liver, if there is a critical amount that will ensure enough NMN/NR gets into tissue (i.e. not all converted to nicotinamide). Baur just says that he thinks it’s pretty high. He doesn’t give an amount but refers to the large dosage given in mouse studies, which is as high as 500mg per kg, much higher than you could go in humans. Even for mice on those high doses, they see a very small amount of NMN/NR spilling over and being detectable in tissues like muscle, which is not to say the molecules aren’t effective at those doses (see second dot point above). • It is not known yet if taking nicotinamide inhibits sirtuins in vivo. • In relation to the above point, the level of nicotinamide you get from taking nicotinamide is pretty much equivalent to the level you get from taking NR. That is, if nicotinamide does inhibit sirtuins, it’s probably going to be an issue for any NAD booster, not just nicotinamide.
Richard, thanks for the video. I found this video just after I ordered NR from Tru Niagen today. It sounds like what Dr. Baur was saying was that we will have little success getting enough NR through the gut and liver to really make any meaningful difference in NAD+ levels. Did I understand correctly.....if so, I admit to being pretty bummed. Tru Niagen is not cheap and more importantly than price is that it might not work after all. Your thoughts will be greatly appreciated.
Hey Richard, good to see you asking questions around nicotinamide :) I am aware of another study which found the gut microbiome could convert NMN to another NAD precursor called NAMN (on the niacin nad pathway). Would be great if we could control our gut microbiome to get the most from our supplements and diet.
Hi, thanks for sharing. Yes, I think I know the study. As Prof Baur mentioned his study only looked at the amount of the NR/NMN that got through made it to the liver. The gut microbiome adds another layer of complexity.
Interesting interview Richard. You had mentioned that you have started taking AKG, can you kindly do a small video on which brand, how much, what time and so on. Thanks.
Hi Ankur, thanks for you comment. We are still trying different AKG options, but will do a video on it soon. Can I ask, are you or your dad taking it at the moment?
Recent review suggests exercise the most effective for supporting NAD levels with age, and where's the niacin vs NR or NMN studies? I suspect exercise, a good diet, and niacin, is going to support NAD levels. Precursors may have utility in some specific clinical populations.
What I got from this video was that supplementation with the cheaper niacinamide is most likely just as good (or possibly even better) than NR/NMN supplementation, as the end result in the body is NR/NMN converts to niacinamide which then ends up boosting NAD+. Not a biologist, so wondering if I am understanding this correctly?
There’s new information about high dosages of NMN and NR of 1000mg and higher. Apparently, less is more. The excess NMN causes epithelial inflammation per those studies.
@@justlookattheflowers4239 I just wanted to add that most people have been scared away from niacinamide - because it has the reputation of being SIRT1 inhibitor. In vitro, niacinamide definitely has been shown to inhibit SIRT1.
Hi Falcon, thanks for your comment. Similar feelings here. It is encouraging that they all raise NAD levels but there does seem a need for further investigation.
Greetings from Singapore. Interesting as always. I am taking a sub-lingual lozenge of NMN 250mgs daily along with other supplements. It would be interesting to find out whether this is more bio available than oral dosage (which I also do). Thank You
Hi Robert, thanks for sharing. there is certainly logic to the sub-lingual administration. Would be very interested to see if you notice any difference.
Sublingual administration of NMN is definitely better as it directly gets to the blood stream 100% and intact. So you don't need to take a high dose as NMN is expensive. I would like to know where can I purchase the NMN sublingual lozenges that you are taking?
Hi Bill, thanks for your question. So just for reference as I cannot offer advice: Thinking about what Prof Baur said there are a couple of things. We did not talk about niacin (and it was not in the paper that Prof Baur co-authered) so we don't know whether it is converted to Nicotinamide. But he did say that 3g of Nicotinamide is toxic to the liver, and 1.5g is half way there. I think the other relevant part is that he said that probably we cannot take enough nicotinamide based supplements to go over the liver's ability to handle them, so it is not clear that taking everything in one go would allow the supplement to get into the blood stream.
Hi Ben, thanks for your question. I had a look in pubmed but cannot find any papers that talk about liposomal delivery of NMN (or NR). I will do some investigation.
@@ModernHealthspan - I don't know if it's ever been researched in this area. But getting nutrients where they need to be is quite important. So, maybe it's not being discussed because it's not being studied. Or maybe it's not being studied because it's not being discussed. In either case, it represents massive whole in our knowledge. Liposomal could be the most effective transport of NMN, NR, etc. It is known to work well for other nutrients. I'd think researchers might have some mild interest in finding out.
If you refrigerante it and take it outside the refrigerador and open the bottle dayly, the air humidity from outside will condense on the capsules etc and that could me more harmfull then not to refrigerante it. That' s what I heard.
Everybody says something else…and they are all scientifics. So l decided to follow the example of the scientific also taking one of these substances, in my case it’s Dr. Sinclair. How kind of him to keep us informed about his and his fathers health and the long term effects of the supplementation. All the others talk about yeast, mice and worms and maybe have never taken them themselves.
Thanks for this video. It is a real peek into the lab, and it seems to be very important ! Can you furnish a reference on the body chemistry involved ? I intend to transcribe this video word for word to try and get the gist if it. I would like to hear it translated for lay understanding. Dr. Brad Stanfield referred to a paper he read about this topic wherein the paper's authors claimed that NMN and NR are converted to nicotinic acid early, before interacting with the NAD thing. I have been using 100mg of nicotinic acid (flushing niacin or vitamin B3) every night before bed for 25 years. There is a full body flush which passes in about 20 minutes, after which I feel cool and tired and go right to sleep. Is it possible that I have been boosting NAD+ this whole time ? Is puzzlement.
From your comment it seems you are using nicotinic acid/ vitamin B3 to help you sleep better, is it effective? And do you feel more energetic after talking it?
@@MRT-co1sd I use nicotinic acid because I believe it helps circulation, esp the skin, and puts me to sleep reliably. I take very hot herbal cayenne pepper, about 40,000 Heat Units, because it stimulates the circulatory system all over the body (Dr.John Christopher). I feel weak after both of these so use at night. Herbal cayenne has been said to stop a heart attack long enough for people to get to the ER. Also reduces bleeding. I once had a girl who was just an acquaintance tell me "You have very healthy pink skin". I am a man. I told her it was due to hot-hot herbal cayenne pepper by mouth daily, and I gave her some to try. Later she said she could never use it because it stung her mouth badly for about 2 minutes. It does not upset a healthy stomach.
Here is a wild thought. Perhaps the NMN benefits the gut microbes and when they thrive, there can be a domino effect on us. By the time it gets to the liver, not much of the good stuff is left. Baur thought it possible we only need a tiny amount and if he is right, that could explain the “age reversals” seen by some. This did not seem right to me, so I wondered about the microbes.
So niacinamide also increase nad in the heart? Tought it was only in liver n blood. Have no idea how you can increase nad in the blood without increase it in the heart Also, pomgranate extract inhibbit NMNT/NNMT or how its spelled, and increase the nmn created by the niacinamide, makes more nad Niacinamide + d ribose + tmg + pomgranate extract = best nad booster on earth
pomegranate is so good, you can also get 'urolithin a' from it via gut bacteria converting ellagic acid, check it out, it restores mitochondria via mitophagy-would be good to see Richard cover this :)
What the video is hinting is that all the precursors end up as niacinamide. Niacin is likely to end up as niacinamide - just look at the salvage pathways.
*** In this video, there may be some distortion on my audio, sorry for causing any distraction. We shall improve in our next interview series. Thank you for your understanding ***
Prof Joseph Baur - NAD Interview Series Playlist
ua-cam.com/video/4z3540vldBk/v-deo.html
Modern Healthspan Newsletters Playlist
ua-cam.com/video/wNeuqs15JcQ/v-deo.html
If you would like to support our channel, we’d love a coffee…thank you! www.buymeacoffee.com/mhealthspan
Prof. Baur’s interviews have been terrific! Thanks for bringing him online - lots of good information. Much appreciated…
Hi Dan, thanks for your kind comments, glad that you found it helpful!
The finding that NMN and NR are breaking down to NAM and reforming feels really significant. I checked his paper afterwards and it seems like high quality science. Full instructions for replication are included. 👏
Obvious question : does NAM alone raise NAD in humans? Proving this would make a shockwave in the supplement industry
I know this is an old interview now and things have probably moved on, but I'm just going through and summarising some of these videos to better get my head around the content over time. Posting a summary of the main points from this one in case it's useful for others:
• NMN and NR do boost NAD but when oral doses were traced they found most got converted to nicotinamide before being used in tissues to make NAD. The molecules are broken down both by the intestinal microbiome and the liver.
• Baur hypothesises that when people take NMN and NR orally at high doses, it is the small amount of intact NMN or NR which gets into the blood or peripheral organs and makes a difference. NMN and NR are better than nicotinamide once in tissues as they bypass the pathway that is the most energetically costly. They are now doing trials of giving smaller doses intravenously to see if this hypothesis is correct. He mentions that it has been demonstrated in heart failure that giving nicotinamide to boost NAD may not be effective as the first enzyme that uses nicotinamide is down-regulated, so the other boosters are indicated in certain scenarios.
• There have been very few comparisons of NMN and NR. Baur’s team has done some unpublished work on kidney injury where it seems they are working almost equally. Also found they worked more or less equally in the kidney and liver, as per published tracer study. The tracer study also showed, however, there may be a divergence when it comes to the two molecules. When they gave them intravenously, so they would get to the target tissues mostly intact, they found that NR goes into muscle and the heart much more effectively than NMN (note: he mentions this finding wasn’t included in the published paper).
• He mentions, with regard to NMN, there’s an argument you need a certain enzyme that breaks it down to NR on the outside of the membrane for it to cross. Someone may not have that enzyme active and therefore won’t be able to get it into certain tissues. It looks like that is the case for muscle.
• Richard asks if when taking NMN or NR in a large single dose in order to (theoretically) flood the liver, if there is a critical amount that will ensure enough NMN/NR gets into tissue (i.e. not all converted to nicotinamide). Baur just says that he thinks it’s pretty high. He doesn’t give an amount but refers to the large dosage given in mouse studies, which is as high as 500mg per kg, much higher than you could go in humans. Even for mice on those high doses, they see a very small amount of NMN/NR spilling over and being detectable in tissues like muscle, which is not to say the molecules aren’t effective at those doses (see second dot point above).
• It is not known yet if taking nicotinamide inhibits sirtuins in vivo.
• In relation to the above point, the level of nicotinamide you get from taking nicotinamide is pretty much equivalent to the level you get from taking NR. That is, if nicotinamide does inhibit sirtuins, it’s probably going to be an issue for any NAD booster, not just nicotinamide.
it would be great if you can summarize each episode with some key points of the interview, great work always, thanks, Richard!
Hi Tony, thank you for the suggestion. Our schedule is quite tight but we will see how we can add this.
What is the difference between NR and just plain Nicotinamide? Is there any benefit in taking just nicotinamide?
Richard, thanks for the video. I found this video just after I ordered NR from Tru Niagen today. It sounds like what Dr. Baur was saying was that we will have little success getting enough NR through the gut and liver to really make any meaningful difference in NAD+ levels. Did I understand correctly.....if so, I admit to being pretty bummed. Tru Niagen is not cheap and more importantly than price is that it might not work after all. Your thoughts will be greatly appreciated.
Same concern
Love this interview series! I have a more clear picture on NAD now. Thank you Richard.
Hi Susan, thanks for your comment. I am glad that you found the video helpful.
Hey Richard, good to see you asking questions around nicotinamide :) I am aware of another study which found the gut microbiome could convert NMN to another NAD precursor called NAMN (on the niacin nad pathway). Would be great if we could control our gut microbiome to get the most from our supplements and diet.
Hi, thanks for sharing. Yes, I think I know the study. As Prof Baur mentioned his study only looked at the amount of the NR/NMN that got through made it to the liver. The gut microbiome adds another layer of complexity.
Interesting interview Richard. You had mentioned that you have started taking AKG, can you kindly do a small video on which brand, how much, what time and so on. Thanks.
Hi Ankur, thanks for you comment. We are still trying different AKG options, but will do a video on it soon. Can I ask, are you or your dad taking it at the moment?
@@ModernHealthspan not taking AKG currently
Richard - I like your videos. Very informative!
Hi David, Thanks for your kind comments!
Recent review suggests exercise the most effective for supporting NAD levels with age, and where's the niacin vs NR or NMN studies? I suspect exercise, a good diet, and niacin, is going to support NAD levels. Precursors may have utility in some specific clinical populations.
so normal flush niacin is best?
What I got from this video was that supplementation with the cheaper niacinamide is most likely just as good (or possibly even better) than NR/NMN supplementation, as the end result in the body is NR/NMN converts to niacinamide which then ends up boosting NAD+. Not a biologist, so wondering if I am understanding this correctly?
what about flush niacin?
No mention of B3 (NMN &MR)using methyl groups.Depletion of the methyl group 'pool'?DR.David Sinclair...TMG?
There’s new information about high dosages of NMN and NR of 1000mg and higher. Apparently, less is more. The excess NMN causes epithelial inflammation per those studies.
What the research studies are showing is that most likely, NAM and not NR or NMN is the active NAD+ precursor (ones that are administered orally).
@@justlookattheflowers4239 A study shows that niacin also boosts NAD+.
@@justlookattheflowers4239 I just wanted to add that most people have been scared away from niacinamide - because it has the reputation of being SIRT1 inhibitor. In vitro, niacinamide definitely has been shown to inhibit SIRT1.
Great interview, not sure which direction to continue in; currently on team NMN however
Hi Falcon, thanks for your comment. Similar feelings here. It is encouraging that they all raise NAD levels but there does seem a need for further investigation.
@@ModernHealthspan yes I’m inclined to continue nmn, albeit quite expensive, at least to follow Dr S.... although niacinamide is sounding appealing
Great interview series, thank you Richard!
Hi Sharapova, Thanks for your comment
Isn't niacin more effective in boosting NAD than niacinanamide?
I believe it YES!
it seems both NMN and NMR are a waste of money when you can just take simple B3 (nicotinamide)
what about flush niacin?
Richard, your channel really has great guests & content!
Hi Shirley, thanks for your kind comments!
So what happens when you take Nicotinamide with MR or NMN?
Does normal nicotinamide do anything similar?
Love your topic and contents... you need good mics with pop filters and in a room with echo dampening...
So Nicotinic Acid a good precursor?
Excellent explanation on different forms of B3. thx.
Hi Kona, Thanks!
Greetings from Singapore. Interesting as always. I am taking a sub-lingual lozenge of NMN 250mgs daily along with other supplements. It would be interesting to find out whether this is more bio available than oral dosage (which I also do). Thank You
Hi Robert, thanks for sharing. there is certainly logic to the sub-lingual administration. Would be very interested to see if you notice any difference.
Sublingual administration of NMN is definitely better as it directly gets to the blood stream 100% and intact. So you don't need to take a high dose as NMN is expensive.
I would like to know where can I purchase the NMN sublingual lozenges that you are taking?
Based on your discussion would it be advisable to take my NR & NNM At the same time that I take my 1.5 g of flushing Niacin?
Hi Bill, thanks for your question. So just for reference as I cannot offer advice: Thinking about what Prof Baur said there are a couple of things. We did not talk about niacin (and it was not in the paper that Prof Baur co-authered) so we don't know whether it is converted to Nicotinamide. But he did say that 3g of Nicotinamide is toxic to the liver, and 1.5g is half way there. I think the other relevant part is that he said that probably we cannot take enough nicotinamide based supplements to go over the liver's ability to handle them, so it is not clear that taking everything in one go would allow the supplement to get into the blood stream.
1.5g niacin is way too high. Nor should you combine it with NR NMN all at the same time In high doses
Is it possible long term use may have a cumulative effect that wouldn't have been measured in this method?
I'm more confused than ever.
What about liposomal form that carries molecules across cell membranes and directly into cells? Why is this rarely discussed?
Hi Ben, thanks for your question. I had a look in pubmed but cannot find any papers that talk about liposomal delivery of NMN (or NR). I will do some investigation.
@@ModernHealthspan - I don't know if it's ever been researched in this area. But getting nutrients where they need to be is quite important.
So, maybe it's not being discussed because it's not being studied. Or maybe it's not being studied because it's not being discussed. In either case, it represents massive whole in our knowledge.
Liposomal could be the most effective transport of NMN, NR, etc. It is known to work well for other nutrients. I'd think researchers might have some mild interest in finding out.
David Sinclair says keep NAD supplements in the refrigerator but the ResveraCel bottle says don’t refrigerate. Any thoughts?
If you refrigerante it and take it outside the refrigerador and open the bottle dayly, the air humidity from outside will condense on the capsules etc and that could me more harmfull then not to refrigerante it. That' s what I heard.
Everybody says something else…and they are all scientifics. So l decided to follow the example of the scientific also taking one of these substances, in my case it’s Dr. Sinclair. How kind of him to keep us informed about his and his fathers health and the long term effects of the supplementation. All the others talk about yeast, mice and worms and maybe have never taken them themselves.
0ne would need a sublingual form of NMN or NR to bypass the liver
Hi Thanks for sharing.
Whenever there something useful for people to take action on their own, FDA steps in on behalf of vested interests to block it or so it seems.
Thanks for this video. It is a real peek into the lab, and it seems to be very important ! Can you furnish a reference on the body chemistry involved ?
I intend to transcribe this video word for word to try and get the gist if it. I would like to hear it translated for lay understanding.
Dr. Brad Stanfield referred to a paper he read about this topic wherein the paper's authors claimed that NMN and NR are converted to nicotinic acid early, before interacting with the NAD thing.
I have been using 100mg of nicotinic acid (flushing niacin or vitamin B3) every night before bed for 25 years. There is a full body flush which passes in about 20 minutes, after which I feel cool and tired and go right to sleep. Is it possible that I have been boosting NAD+ this whole time ?
Is puzzlement.
From your comment it seems you are using nicotinic acid/ vitamin B3 to help you sleep better, is it effective? And do you feel more energetic after talking it?
@@MRT-co1sd I use nicotinic acid because I believe it helps circulation, esp the skin, and puts me to sleep reliably. I take very hot herbal cayenne pepper, about 40,000 Heat Units, because it stimulates the circulatory system all over the body (Dr.John Christopher). I feel weak after both of these so use at night. Herbal cayenne has been said to stop a heart attack long enough for people to get to the ER. Also reduces bleeding.
I once had a girl who was just an acquaintance tell me "You have very healthy pink skin". I am a man. I told her it was due to hot-hot herbal cayenne pepper by mouth daily, and I gave her some to try. Later she said she could never use it because it stung her mouth badly for about 2 minutes. It does not upset a healthy stomach.
boost NAD ? But for what if you dont do anything
Here is a wild thought. Perhaps the NMN benefits the gut microbes and when they thrive, there can be a domino effect on us. By the time it gets to the liver, not much of the good stuff is left. Baur thought it possible we only need a tiny amount and if he is right, that could explain the “age reversals” seen by some. This did not seem right to me, so I wondered about the microbes.
What is better nmn capsules or powder that you put sublingual?
Niacin b3
Somewhat discouraging but it's better to be realistic than to believe the hype.
Hi Cybair, thanks for your comment. Agreed, though it is a still unfolding saga! I am grateful to Prof Baur for providing his info.
NMN OR TRU Nagen?
Thank you.
Hey Ron! Always good to see you. Thanks!
So niacinamide also increase nad in the heart? Tought it was only in liver n blood. Have no idea how you can increase nad in the blood without increase it in the heart
Also, pomgranate extract inhibbit NMNT/NNMT or how its spelled, and increase the nmn created by the niacinamide, makes more nad
Niacinamide + d ribose + tmg + pomgranate extract = best nad booster on earth
@@justlookattheflowers4239 its the ellagic acid that do what I just said, in the pomgranate
pomegranate is so good, you can also get 'urolithin a' from it via gut bacteria converting ellagic acid, check it out, it restores mitochondria via mitophagy-would be good to see Richard cover this :)
@@pelletey yes your correct !
Yes 🔥
niacin
What the video is hinting is that all the precursors end up as niacinamide. Niacin is likely to end up as niacinamide - just look at the salvage pathways.
Gives you flush. Take Nicotinamide if you dont believe the hype of expensive products.
@@markveen1373 flush niacin is cheaper than nicotinamide
@@davidchung1697Niacin and sport are the cheapest alternative to nmn expensive tablets
snake oil