@@Physionic I appreciate your sacrifice by removing ads. You make it harder to click away from your channel if no ads pop up. You have chosen an excellent career for your self and for humanity that may benefit from your work. I thank you and Rimon for the hard work you both have invested your life’s in.
Thank you so much for the chapters and summary! They really help. I don't personally mind the adds because they make me feel like I give a little bit back. It's too bad the effect doesn't seem to be bigger and dosages have to be so high, because I have the kilo of NMN lying around, lol. Does the administration method matter? For instance, is sublingual powder more potent?
I’m one of the folks who follows both of you, so this podcast is how I’m spending part of my Saturday. 😁 I’m already over an hour in, it’s a great discussion, and just want to say thank you to both!
Thanks for breaking this all down. I've had alot of crazy people saying I'm on this longevity mission taking these supplements like im some marvel. And I said it's BS.
I’m an old retired scientist (octogenarian). Thanks for the excellent discussion with two of my favorite analysts. I watch both TH-cam channels. My goal is healthy longevity. I study this topic and test molecules on my aging body with surprisingly good results. I notice effects on old people are more profound than on younger people. I find senescent cell build up causes most diseases, including aging, that result in death. Excellent Nutrition is number one. I view exercise as a means to push nutrients around to cells in need and to carry unwanted material away from cells. My father in law is 105yo and still gets around on his own. He has a full head of white hair but otherwise looks, talks and acts like the avid tennis player I have known for over half a century.
Thanks for sharing. You and your father-in-law seems to know something about Health and longevity and I would love to learn more about both your protocols.
@@haveitalll Absolutely! I went to a new dermatologist 2 days ago ( previous one retired after 40 years) He couldn’t believe how good my skin was for my age. Meeting strangers in stores etc. When the topic comes up I’m usually looked at in disbelief when someone finds out my age. A Home Depot check out lady greets me as the octogenarian that looks 60 and feels 40!
@@royaltyentertainment I’ve never smoked, drank alcohol, used illicit drugs or drank coffee in my life. I grew up on a farm in the 1940s and learned how to eat natural food. I moved to California in 1955 and found fast foods came into existence like Swanson’s TV dinners were convenient after McDonalds hamburger. I did intense studying for about 10 years and found my body was degrading fast. I watched Jack LaLane in 1950s began studying exercise and nutrition. I found nutrition is number one because we cannot out exercise poor nutrition. Good sleep follows. So I don’t eat any foods with chemicals in them that would not be there from nature. Nuts, seeds, herbs , vegetables, fruit and blue fish are my diet. I exercise to move blood past all my 40 trillion cells. I do HIIT to keep my heart strong. I sleep 6 + hours per day. At my age I don’t have time to wait for double blind studies on human longevity, so I began studying molecular medicine 3 years ago to improve my knowledge on the cellular, molecular, atomic and subatomic levels. I find it is more complex than I ever imagined. With dementia setting in I’m doing everything I can to stop and reverse my aging. My lab rat buddy “Pinky” is my 105yo father in law. He’s doing great! So am I! He calls me “Brain”. He has always told me he learns something new every time I talk to him. We have fun when we are together.
What i would like to see is actually a list of supplements sorted from the cheapest to the most expensive to figure those i can safely reserve part of my budget. A table with some basic but vital info.For example: 1. Niacin. Price- low. Effect on longevity- medium. Daily dose- N gr. Side effects-hairy palms. 2. Getbacktoyoutwentiatorol. Effect on longevity- enormous. Daily dose- N gr. Side effects-not eligible for pension anymore. etc
Thank so much for this fabulous collab on NAD+, NMN, B3 with Rimon. Are you aware that Sinclair has actually caused NMN to be banned from sale in the US by the FDA by saying it has drug effects of which he is studying, instead of just being an ordinary supplement? Anyway, so cool to know that it has some effects for female mice on longevity. I heard of some anecdotally reversing menopause in humans and would love to understand why or any studies.... PS if you take B3 or NR or NMN you need to also take TMG or combo of B12 and folate to make up for the methyl groups that have been consumed in the NAD+ pathway.
@@WellnessMessiah It's so cool you are on here and thanks for your reply. I follow you so I have seen that video..I was actually meaning if Nicolas was aware about the issue with NMN.
I’ve been taking precursors to NAD like NMN or NR since I was 18 and it’s been the main thing I’ve been taking as a supplement that I actually felt a big difference with. No I don’t think it will solve aging, but I do believe it’s a strong way to boost NAD levels in the body. I’m 23 and have energy like never before. Not like a stimulant, but just consistent energy throughout my day
If the role of an important molecule (such as NAD+, cAMP) or even an ion (such as Ca++) in aging is discussed without referring to its location and time of action, it's often meaningless. At one single moment inside a cell, numerous biological reactions are going on at hundreds of microdomains simultaneously. The concentration of those molecules, taking cAMP and Ca++ as two well-known examples, can be INCREASED and DECREASED at the SAME time within a single cell at different microdomains, depending on which receptors they are associated. Also, Ca++ can be an important micronutrient, a second messenger, or even a potent neural toxin. In fact, intracellular Ca++ dysregulation is likely the single most critical factor that accelerates aging by causing mitochondria malfunction/injury and overproduction of ROS and RNS, which in turn plays a major role in the pathogenesis of neurodegenerative diseases, such as AD and PD. An abnormal amount of NAD+, if near CD38, could lead to intracellular Ca++ overload and mitochondria injury and therefore is NOT beneficial.
I agree with you. In those situations, you need "end point" data. What happens in the body over many years, and this is what they did in this Sinclair study, measuring lifespan and healthspan therefore it is useful.
@WellnessMessiah You are right. As for the supplements to boost the intracellular NAD+ without inducing intracellular Ca++ overload, a better way to do it, in my opinion, is to take CD38 inhibitors, such as apigenin.
Conflict of interest is only a red flag; it is not an indictment. Heck, even crookedness does not imply incorrectness. Look at the Robot series of Asimov, when R. Giskard could have prevented the destruction of Earth, but doesn't, because although the evil perpetrator thought he was lying, he was unknowingly speaking truth, and Giskard knew he was right. And to say "[his] research['s] been questioned HEAVILY" is the mother of all appeals to authority. Appeal to Authority is probably the oldest fallacy in Philosphy, and you are applying this appeal to a collection of unnamed critics, and with special attention placed on numbers, (un-specified number at that), as if the truth of 2+2 should take notice of how many people say 5. That's a garbage argument. It's like saying that free speech should be denied to anyone who says anything that a number of people disagree with .... ?!?!?! I have my own set of reservations about Synclair, but I'd never demand that he not be discussed. In fact I want him to be discussed, which is why this post angers me so much.
Don't throw the baby out with the bathwater... there is value in any researcher's work. Technically, any research should be questioned-that's what science is all about, isn't it?
That is the worst thing about the society right now. Attacking the messenger instead of the message. If Dr Sinclair said chocolate is delicious it doesn’t mean chocolate doesn’t taste good any longer. A broken clock is right twice a day. Science requires skepticism and counterpoints, running from it is the opposite of science. This desire to silence opposition is horrible for society.
Science is about questioning and challenging all data and authority. Not to prove your opinion, but to seek truth and it allow science to change when evidence points in a different direction. This is not a religious venture where laws are set in stone. It is about discussions, experiments and questioning.
Thanks for the neutral analysis ! Always interesting to understand the last details of the research on NAD ! For me NMN works well for the daily energy (it was even huge when I started so I assume I was at a low level)
On Nuchido Time+ - assuming users with high Blood levels are good responders might be the wrong way around. If it assumes it's equally absorbed by the gut then low blood levels indicate it's well absorbed by cells. Similar to glucose sensitive people have lower blood levels because they absorb it into cells.
Why eat mostly protein to extend life. It bears strong resemblance to Peter Attias stance on longevity. To slam protein and build muscle in a big gamble to keep frailty away. Which yes in studies people who ate more protein experienced less sarcopenia or had at least less issues from it. But this was a correlation not causation. Studies have shown that restriction of amino acids such as methionine can improve longevity. Also it seems that in the absence of exercise high protein diets don't help with age related frailty. A greater emphasis should be put on simply staying active especially strength training to ward off age related frailty. Especially sense exercise increase not just muscle but greatly effects bone density.
Great content Nic. I’m glad you pushed back on the weight loss and longevity topic. There’s such strong evidence that long term weight loss (I.e. not a short term fluctuation) requires a calorie deficit, it seemed odd he spoke as if it could be done without caloric reduction.
Thanks Dave! Sure thing. I didn’t want to derail the conversation by discussing insulin in an NAD+ podcast, but I wanted to make sure we frame that point correctly (from my eyes, of course).
You're right. My answer wasn't sufficient. Weight loss and long-term health implications are complex topics where tissue types, methods of weight loss, and other factors need to be taken into account. I couldn't formulate a proper answer. I was also concerned that people over 65 might hear this and assume that losing weight would automatically help them live longer, when it could actually increase mortality if done incorrectly. That's why I was hesitant to make a conclusive, all-ages statement. Additionally, statements like "losing weight is beneficial in most cases, although you can reach this generally positive goal through less-than-optimal routes (compared to what's possible) that may have negative consequences later" are very difficult to explain in one sentence. I needed a full podcast on that subject to answer, but it's my fault since I raised it.
I learned that low blood pressure is a possible risk factor for dementia/Alzheimer's. I hadn't read that. So thank you. Fwiw, I gravitate toward science information that is based in solid evidence (or lack thereof) and from sources I can trust are broadly knowledgeable, honest & include citations. Anything else is frustrating & a waste of time.
This brings me back to the days of journal club in pharmacy school. If we trust our fellow nerds, then we get all the info using the critical view hive mind!
Perhaps the NMN disappears because the intestine is prioritizing its own consumption of it. Specially people who consume wheat products containing gluten, which damages the intestines of everybody; not just those of us diagnosed celiac. I think most people's intestines are badly damaged along the scale from perfect health to leaky gut syndrome, but remain un-diagnosed. It would be interesting to prioritize markers of intestinal health, in studies of NMN.
I’m in this position with damaged intestines without any symptoms until my 73rd year. It’s a slow process to repair. The bpc 157 might be a good option. No gluten/ grains also suspect adult FPIES so no fish or beef. I’m only 18 mins and finding it interesting.
@ plus you can purchase it online I’ve used with great success orally it sealed a cavity I had went to a dentist they said you have a cavity forming I dribbled Bpc 157 on it twice a day 6 months later dentist was like ware did it go I just smiled
I have a request. Could you cover what we currently know about allulose in our metabolic pathways? I have heard there is some evidence that allulose competes with fructose via fructokinase, which would seem to have some pretty big implications if true.
Why take nmn over niacinamide if it converts into niacinamide. It was probably discussed but flew over my head. And is niacinamide really silencing sirt to a meningfull degree. AKA when nad did not extend male mice span. Did it also shorten it or was there no difference. Currently taking niacinamide to counter methyl groups from betaine hcl. For stomache issues.
The end results is NAD+ in the cell. That's highly tissue specific and recycling specific. But yes, you will get blood NAD+ but that's not end result like you asked.
There are some reports of women in menopause regaining their menstrual cycles after taking NMN. The fastest aging organ are the ovaries so I’m interested to hear about what NMN does for the ovaries. I’m curious about topical NMN for skin health. It’s being marketed as some anti aging skincare product but I really question the absorption NMN is to the skin. Have you ever looked into sirtuin 6 and Vera Gorvunova’s work on longevity?
Shouldn't we just eat the correct food types rather than taking supplements of NAD+, NMN, or NR? Seeds, nuts, green vegetables, etc all contain niacin (vitamin B3). That's the conclusion I came to but watching this and reading a bit of materials. Of course I'm not a sceintist at all, but I have way more energy since I started eating healthier.
This was interesting. So it sounds like there's a hypothetical benefit to boosting NAD on one of the hallmarks of aging but so far no supplements have shown any benefits.
Correct. But, they never used in the studies like nature designed it too. It's unnatural use when you think about it instead of augmenting nature/DNA in preserving youth.
I have heard anecdotes where after stopping nmn there is rapid aging and feeling much worse than before supplementing. Is it possible supplementation severely down regulated natural production if stopped
I’m about an hour in and is feeling very touchy-feely unlike your normal “just the data” shows. I was surprised you didn’t jump all over the CIco/insulin/igf weight loss comments,it seemed you wanted to.
Noted. Thanks. I think it might feel that way, because a lot of it is speculation based on the data we have. Still, I’ll keep that in mind for the future.
You're right. My answer wasn't sufficient. Weight loss and long-term health implications are complex topics where tissue types, methods of weight loss, and other factors need to be taken into account. I couldn't formulate a proper answer. I was also concerned that people over 65 might hear this and assume that losing weight would automatically help them live longer, when it could actually increase mortality if done incorrectly. That's why I was hesitant to make a conclusive, all-ages statement. Additionally, statements like "losing weight is beneficial in most cases, although you can reach this generally positive goal through less-than-optimal routes (compared to what's possible) that may have negative consequences later" are very difficult to explain in one sentence. I needed a full podcast on that subject to answer, but it's my fault since I raised it.
48:30 both are pragmatic decisions. It’s easier for a human to take a pill once a day. It’s easier to mix a supplement in a lab animal’s chow to eat throughout the day.
Could the higher need of niacin at fasting be because of our gut microbes? That's my first thought. They want niacin as well and when we are fasted they might be more prone to consume it at higher rates. At fasted the passage through our intestine is often faster as well, right? So it could pass by more microbes at fasting before we absorb it all in to the blood compared to when we have eaten a couple of meals. Right?
I've been on Niacin, NAD, and NR (most recently) since 2018, and I feel no improvement or difference. In 2020, I was diagnosed with fibromyalgia and tests show my oxidative stress and mitochondrial dysfunction are high. My #1 fibro symptom is fatigue followed by post exertional malaise. I'm only 40. So, I think my issues are too far gone to be helped by one of these supplements.
I was hoping you guys would include how glutathione might fit into this discussion? .....or is this an entirely different discussion? I tried NMN supplementation for about 3 - 4 months+ and sincerely did not find any perceptible physiological benefits in the gym. So I stopped taking it and opted instead for the GlyNac +TMG supplements, in an effort to increase Glutathione levels instead. After careful consideration of Rimon's advice here, I am now also going to include his 50mg niacin every 6 hours! Especially to Rimon's point on the budget consideration, niacin is WAYYyyyyy less expensive than NMN!!
@@Physionic Thank you, that's what I figured. And that definitely makes sense. I guess I was just wondering more along the lines of if there was any direct connection between glutathione levels vs. NAD levels, or if these are two totally distinct discussions. Specifically, from a life-extension focus, should I be focusing more on one vs the other? But, I can gather from your reply that this would be a whole other discussion!
Would really like you to assess the research on anatto derived Vit. E tocotrienols and Geranylgeraniol, as, per Dr. Barrie Tan and their effects on chronic illness.
Why don’t they discus direct I.v. Of NAD I’ve done Iv bad in two cycles and it seemed to give me more energy and clear my mind having said that it’s not a comfortable experience
Some of the stuff that dude said doesn't make any sense if you're heavy I don't care what age you are if you work hard and lose weight and you do it healthy way how could that not improve your health I know for a fact that it improves your health because I've done it and I feel much better now
You're right. My answer wasn't sufficient. Weight loss and long-term health implications are complex topics where tissue types, methods of weight loss, and other factors need to be taken into account. I couldn't formulate a proper answer. I was also concerned that people over 65 might hear this and assume that losing weight would automatically help them live longer, when it could actually increase mortality if done incorrectly. That's why I was hesitant to make a conclusive, all-ages statement. Additionally, statements like "losing weight is beneficial in most cases, although you can reach this generally positive goal through less-than-optimal routes (compared to what's possible) that may have negative consequences later" are very difficult to explain in one sentence. I needed a full podcast on that subject to answer, but it's my fault since I raised it.
I'm 53 I used to be almost 270 pounds now I'm like 190 I know that it's helped my cholesterol I know that it's helped me from not having sleep apnea anymore and I'm hoping that it's done a lot more for my health thank you for your info
There are still a bunch of Okinawa centenarians that are still consuming goats head soup and sea snake soup for health reasons and they have no access to synthetic vitamins, supplements or fortified foods and they won't post comments on here since they don't use computers and other such things that can destroy your health.
nanograms of nicotine complete fix the salvage pathway issues that come with age, one reason why super centenarians lived so long is because they all heavy smokers and avoided cancer. a 5mg daily patch of nicotine is more than enough and you avoid the downsides of smoking.
I love you guys and I don't have a scientific background but I feel like this was totally unfocused. I could have distilled this all down to 20 minutes. I'm a fair way in and I don't know whether you love or hate Sinclair
wish you could trim this interview down to 20 minutes or so for better attention span issue and better information obversion rather than 1 1/2 continuous talk.
@@johnny9072 you are ignorant. and your thing is not having the capacity to comprehend the issue. length of time no matter how much attention you can give to a particular thing can still impact how much you can observe and digest and can remember which clinically known as sustained attention span vs cognitive function which is related to amount of continuous time a person can focus. also attentions span varies based on age group specially in the digital landscape. how much of one's attention can lead to productivity which in this case translates into how much you can learn is based on how much you can remember measured by how much you can take away as a solid understanding of any of the key concepts. furthermore, who has time to watch a scientific discussion that its concepts are hard to understand let alone trying to focus on it for 1 1/2 hours.
I've heard enough about Sirtuins and David Sinclair. Check out Dr Been's recent youtube video about inflammation caused by the accumulation of misfolded protein aggregates that build up over your whole lifetime. Could this be the simple answer to it all? I'm a natural "breakfast skipper" and am going back to time restricted eating. Lunch and dinner only.
Taking NAD+ precursors might be treating the symptoms, and not the cause! Diminishing levels of NAD+ with age probably is something we should try to manage. But is hefty doses of vitamin B3, such as NA, NAM, NR, and NMN the solution to that? I suspect tha we should look at the NAD+ consumers instead. We know that CD38 is one important such which increases with age. We also know that Apigenin (or parsley) reduces it. But is that the right way? I suspect that we should look into why CD38 increases (inflammation perhaps), and get rid of the causes of that. I have never seen any real research of what does that. So, that's what I want! To take NAD+ precursors might not be bad, but to me it looks like treating the symptoms and not the cause!
I don’t listen to you guys on longevity. You are too skinny. Muscle mass is an indicator of longevity. I only listen to Tren users. They have lots of muscle mass so they are way more healthy.
Ummm ... You think Physionic is too skinny!? If you can't tell by looking at his arms, have a look at his legs in the podcast before this one. (Titled "Age Reversing Antibodies, Glycine and Longevity, Ergothioneine and Mitochondria and More" dated 9/21/24.) Have a look, I'll wait.
I removed ads throughout and there’s timestamps to skip around. Also, there’s a summary Rimon provides at the end. Hope it’s informative.
that shows character and that you care about your audience, bravo!
@@Physionic I appreciate your sacrifice by removing ads. You make it harder to click away from your channel if no ads pop up. You have chosen an excellent career for your self and for humanity that may benefit from your work. I thank you and Rimon for the hard work you both have invested your life’s in.
So what to supplement now?
Thank you so much for the chapters and summary! They really help. I don't personally mind the adds because they make me feel like I give a little bit back.
It's too bad the effect doesn't seem to be bigger and dosages have to be so high, because I have the kilo of NMN lying around, lol. Does the administration method matter? For instance, is sublingual powder more potent?
Thanks for having me, Nic!
I’m one of the folks who follows both of you, so this podcast is how I’m spending part of my Saturday. 😁 I’m already over an hour in, it’s a great discussion, and just want to say thank you to both!
Excellent discussion.
Thanks for sharing your perspective on the matter!
Thanks for breaking this all down. I've had alot of crazy people saying I'm on this longevity mission taking these supplements like im some marvel. And I said it's BS.
this messiah doesnt actually know anything he just follows along what that mouse looking dude sinclaire says
I’m an old retired scientist (octogenarian). Thanks for the excellent discussion with two of my favorite analysts. I watch both TH-cam channels. My goal is healthy longevity. I study this topic and test molecules on my aging body with surprisingly good results. I notice effects on old people are more profound than on younger people. I find senescent cell build up causes most diseases, including aging, that result in death. Excellent Nutrition is number one. I view exercise as a means to push nutrients around to cells in need and to carry unwanted material away from cells. My father in law is 105yo and still gets around on his own. He has a full head of white hair but otherwise looks, talks and acts like the avid tennis player I have known for over half a century.
Thanks for sharing. You and your father-in-law seems to know something about Health and longevity and I would love to learn more about both your protocols.
More info please
Do you think you also look younger than your actual age?
@@haveitalll Absolutely! I went to a new dermatologist 2 days ago ( previous one retired after 40 years) He couldn’t believe how good my skin was for my age. Meeting strangers in stores etc. When the topic comes up I’m usually looked at in disbelief when someone finds out my age. A Home Depot check out lady greets me as the octogenarian that looks 60 and feels 40!
@@royaltyentertainment I’ve never smoked, drank alcohol, used illicit drugs or drank coffee in my life. I grew up on a farm in the 1940s and learned how to eat natural food. I moved to California in 1955 and found fast foods came into existence like Swanson’s TV dinners were convenient after McDonalds hamburger. I did intense studying for about 10 years and found my body was degrading fast. I watched Jack LaLane in 1950s began studying exercise and nutrition. I found nutrition is number one because we cannot out exercise poor nutrition. Good sleep follows. So I don’t eat any foods with chemicals in them that would not be there from nature. Nuts, seeds, herbs
, vegetables, fruit and blue fish are my diet. I exercise to move blood past all my 40 trillion cells. I do HIIT to keep my heart strong. I sleep 6 + hours per day. At my age I don’t have time to wait for double blind studies on human longevity, so I began studying molecular medicine 3 years ago to improve my knowledge on the cellular, molecular, atomic and subatomic levels. I find it is more complex than I ever imagined. With dementia setting in I’m doing everything I can to stop and reverse my aging. My lab rat buddy “Pinky” is my 105yo father in law. He’s doing great! So am I! He calls me “Brain”. He has always told me he learns something new every time I talk to him. We have fun when we are together.
What i would like to see is actually a list of supplements sorted from the cheapest to the most expensive to figure those i can safely reserve part of my budget. A table with some basic but vital info.For example:
1. Niacin. Price- low. Effect on longevity- medium. Daily dose- N gr. Side effects-hairy palms.
2. Getbacktoyoutwentiatorol. Effect on longevity- enormous. Daily dose- N gr. Side effects-not eligible for pension anymore.
etc
Thank so much for this fabulous collab on NAD+, NMN, B3 with Rimon.
Are you aware that Sinclair has actually caused NMN to be banned from sale in the US by the FDA by saying it has drug effects of which he is studying, instead of just being an ordinary supplement? Anyway, so cool to know that it has some effects for female mice on longevity. I heard of some anecdotally reversing menopause in humans and would love to understand why or any studies....
PS if you take B3 or NR or NMN you need to also take TMG or combo of B12 and folate to make up for the methyl groups that have been consumed in the NAD+ pathway.
I'm aware - check my comment here: 1:38:37
@@WellnessMessiah It's so cool you are on here and thanks for your reply. I follow you so I have seen that video..I was actually meaning if Nicolas was aware about the issue with NMN.
More podcasts please, this is such a great format. I bet Aubrey de Grey would be happy to have one as well.
I’ve been taking precursors to NAD like NMN or NR since I was 18 and it’s been the main thing I’ve been taking as a supplement that I actually felt a big difference with. No I don’t think it will solve aging, but I do believe it’s a strong way to boost NAD levels in the body. I’m 23 and have energy like never before. Not like a stimulant, but just consistent energy throughout my day
Very interesting. Thanks for sharing.
Naturally, you should have an abundance of energy at your young age! I wonder what your supplementation regime would look like at age 60😅
two of the youtube greats on science this was fantastic
Thanks for the compliment, lots of love back!
Ramon is awesome! Great collaboration.
so resveratrol was star wars & nmn is the empire strikes back - can't wait to see what sinclair discovers next to round out his snake oil trilogy.
Tsk tsk. In 120 years when Dr Sinclair is still slam dunking basketballs and you are in the grave you’ll see.
Excellent deepdive! Thanks for this accessible breakdown 🌟
I also thoroughly enjoyed the discussion and took notes along the way.
If the role of an important molecule (such as NAD+, cAMP) or even an ion (such as Ca++) in aging is discussed without referring to its location and time of action, it's often meaningless. At one single moment inside a cell, numerous biological reactions are going on at hundreds of microdomains simultaneously. The concentration of those molecules, taking cAMP and Ca++ as two well-known examples, can be INCREASED and DECREASED at the SAME time within a single cell at different microdomains, depending on which receptors they are associated.
Also, Ca++ can be an important micronutrient, a second messenger, or even a potent neural toxin. In fact, intracellular Ca++ dysregulation is likely the single most critical factor that accelerates aging by causing mitochondria malfunction/injury and overproduction of ROS and RNS, which in turn plays a major role in the pathogenesis of neurodegenerative diseases, such as AD and PD.
An abnormal amount of NAD+, if near CD38, could lead to intracellular Ca++ overload and mitochondria injury and therefore is NOT beneficial.
I agree with you. In those situations, you need "end point" data. What happens in the body over many years, and this is what they did in this Sinclair study, measuring lifespan and healthspan therefore it is useful.
@WellnessMessiah You are right. As for the supplements to boost the intracellular NAD+ without inducing intracellular Ca++ overload, a better way to do it, in my opinion, is to take CD38 inhibitors, such as apigenin.
Nice! Looking forward to this one.
Hasn't Dr. Sinclair's research been question HEAVILY? Should anyone be citing him anymore? Am I missing something? Tx, jt
That’s what we discuss
Conflict of interest is only a red flag; it is not an indictment.
Heck, even crookedness does not imply incorrectness.
Look at the Robot series of Asimov, when R. Giskard could have prevented the destruction of Earth, but doesn't, because although the evil perpetrator thought he was lying, he was unknowingly speaking truth, and Giskard knew he was right.
And to say "[his] research['s] been questioned HEAVILY" is the mother of all appeals to authority. Appeal to Authority is probably the oldest fallacy in Philosphy, and you are applying this appeal to a collection of unnamed critics, and with special attention placed on numbers, (un-specified number at that), as if the truth of 2+2 should take notice of how many people say 5. That's a garbage argument. It's like saying that free speech should be denied to anyone who says anything that a number of people disagree with .... ?!?!?!
I have my own set of reservations about Synclair, but I'd never demand that he not be discussed. In fact I want him to be discussed, which is why this post angers me so much.
Don't throw the baby out with the bathwater... there is value in any researcher's work. Technically, any research should be questioned-that's what science is all about, isn't it?
That is the worst thing about the society right now. Attacking the messenger instead of the message. If Dr Sinclair said chocolate is delicious it doesn’t mean chocolate doesn’t taste good any longer. A broken clock is right twice a day. Science requires skepticism and counterpoints, running from it is the opposite of science.
This desire to silence opposition is horrible for society.
Science is about questioning and challenging all data and authority. Not to prove your opinion, but to seek truth and it allow science to change when evidence points in a different direction. This is not a religious venture where laws are set in stone. It is about discussions, experiments and questioning.
Thanks for the neutral analysis ! Always interesting to understand the last details of the research on NAD ! For me NMN works well for the daily energy (it was even huge when I started so I assume I was at a low level)
On Nuchido Time+ - assuming users with high Blood levels are good responders might be the wrong way around. If it assumes it's equally absorbed by the gut then low blood levels indicate it's well absorbed by cells.
Similar to glucose sensitive people have lower blood levels because they absorb it into cells.
CONGRATULATIONS on getting your PhD!!! 🎉
Why eat mostly protein to extend life. It bears strong resemblance to Peter Attias stance on longevity. To slam protein and build muscle in a big gamble to keep frailty away. Which yes in studies people who ate more protein experienced less sarcopenia or had at least less issues from it. But this was a correlation not causation. Studies have shown that restriction of amino acids such as methionine can improve longevity. Also it seems that in the absence of exercise high protein diets don't help with age related frailty. A greater emphasis should be put on simply staying active especially strength training to ward off age related frailty. Especially sense exercise increase not just muscle but greatly effects bone density.
Great content Nic. I’m glad you pushed back on the weight loss and longevity topic. There’s such strong evidence that long term weight loss (I.e. not a short term fluctuation) requires a calorie deficit, it seemed odd he spoke as if it could be done without caloric reduction.
Thanks Dave! Sure thing. I didn’t want to derail the conversation by discussing insulin in an NAD+ podcast, but I wanted to make sure we frame that point correctly (from my eyes, of course).
You're right. My answer wasn't sufficient. Weight loss and long-term health implications are complex topics where tissue types, methods of weight loss, and other factors need to be taken into account. I couldn't formulate a proper answer.
I was also concerned that people over 65 might hear this and assume that losing weight would automatically help them live longer, when it could actually increase mortality if done incorrectly. That's why I was hesitant to make a conclusive, all-ages statement.
Additionally, statements like "losing weight is beneficial in most cases, although you can reach this generally positive goal through less-than-optimal routes (compared to what's possible) that may have negative consequences later" are very difficult to explain in one sentence.
I needed a full podcast on that subject to answer, but it's my fault since I raised it.
I learned that low blood pressure is a possible risk factor for dementia/Alzheimer's. I hadn't read that. So thank you. Fwiw, I gravitate toward science information that is based in solid evidence (or lack thereof) and from sources I can trust are broadly knowledgeable, honest & include citations. Anything else is frustrating & a waste of time.
This brings me back to the days of journal club in pharmacy school. If we trust our fellow nerds, then we get all the info using the critical view hive mind!
I will take that an compliment haha! Great to meet you here
Perhaps the NMN disappears because the intestine is prioritizing its own consumption of it. Specially people who consume wheat products containing gluten, which damages the intestines of everybody; not just those of us diagnosed celiac. I think most people's intestines are badly damaged along the scale from perfect health to leaky gut syndrome, but remain un-diagnosed. It would be interesting to prioritize markers of intestinal health, in studies of NMN.
It maybe cheaper and easier to heal the gut with bpc 157 used for two months I’d like to see studies on that for gut health
I’m in this position with damaged intestines without any symptoms until my 73rd year. It’s a slow process to repair. The bpc 157 might be a good option. No gluten/ grains also suspect adult FPIES so no fish or beef. I’m only 18 mins and finding it interesting.
@ plus you can purchase it online I’ve used with great success orally it sealed a cavity I had went to a dentist they said you have a cavity forming I dribbled Bpc 157 on it twice a day 6 months later dentist was like ware did it go I just smiled
@@intuitivesean443 I'd give it a try, but I'm in Canada. They'd send it back at the border for sure.
Nicotinic Acid (NA)
↓
NA → NAMN (Nicotinic Acid Mononucleotide)
↓
NAAD (Nicotinic Acid Adenine Dinucleotide)
↓
NAD+
↓
NADH (when used in redox reactions)
↓
Nicotinamide (NAM) [as breakdown product]
Great podcast but really having trouble with the volume for me, it's too low compared to others. Keep up the great work!
Hey Sean, about the volume - I will post a segment from that interview in my channel too... I will take into account what you said and will raise it.
I have a request. Could you cover what we currently know about allulose in our metabolic pathways? I have heard there is some evidence that allulose competes with fructose via fructokinase, which would seem to have some pretty big implications if true.
Why take nmn over niacinamide if it converts into niacinamide. It was probably discussed but flew over my head. And is niacinamide really silencing sirt to a meningfull degree. AKA when nad did not extend male mice span. Did it also shorten it or was there no difference.
Currently taking niacinamide to counter methyl groups from betaine hcl. For stomache issues.
Would you happen to know if taking niacin you would get the same end result same as NAD, thank you
Discussed :)
No, he does not know and neither does the guest. It’s discussed around 1:06:00. The guest mentions that he staggers low dose niacin at 25mg increments
Also how about the studies that show increased supplementation of niacin increase heart attacks
The end results is NAD+ in the cell. That's highly tissue specific and recycling specific. But yes, you will get blood NAD+ but that's not end result like you asked.
Nic, you are the best. Ever. ❤
There are some reports of women in menopause regaining their menstrual cycles after taking NMN. The fastest aging organ are the ovaries so I’m interested to hear about what NMN does for the ovaries.
I’m curious about topical NMN for skin health. It’s being marketed as some anti aging skincare product but I really question the absorption NMN is to the skin.
Have you ever looked into sirtuin 6 and Vera Gorvunova’s work on longevity?
Do you plan on discussing The Virus That Must Not Be Named in relation to niacin and nad at any point? Have you read those studies?
So which supplements are the best to increase NAD+?
Shouldn't we just eat the correct food types rather than taking supplements of NAD+, NMN, or NR? Seeds, nuts, green vegetables, etc all contain niacin (vitamin B3). That's the conclusion I came to but watching this and reading a bit of materials. Of course I'm not a sceintist at all, but I have way more energy since I started eating healthier.
1:09:50 I have never heard anyone make this distinction before and I really really appreciate it @WellnessMessiah!!!!
This was interesting. So it sounds like there's a hypothetical benefit to boosting NAD on one of the hallmarks of aging but so far no supplements have shown any benefits.
Correct. But, they never used in the studies like nature designed it too. It's unnatural use when you think about it instead of augmenting nature/DNA in preserving youth.
Nick..speaking of collaboration.. are you at least advising Dr Stanfield in his rappamycin study?
No. Looks like he’s working with some high caliber scientists, though (based on the published study protocol).
I have heard anecdotes where after stopping nmn there is rapid aging and feeling much worse than before supplementing. Is it possible supplementation severely down regulated natural production if stopped
I’m about an hour in and is feeling very touchy-feely unlike your normal “just the data” shows. I was surprised you didn’t jump all over the CIco/insulin/igf weight loss comments,it seemed you wanted to.
Noted. Thanks. I think it might feel that way, because a lot of it is speculation based on the data we have. Still, I’ll keep that in mind for the future.
You're right. My answer wasn't sufficient. Weight loss and long-term health implications are complex topics where tissue types, methods of weight loss, and other factors need to be taken into account. I couldn't formulate a proper answer.
I was also concerned that people over 65 might hear this and assume that losing weight would automatically help them live longer, when it could actually increase mortality if done incorrectly. That's why I was hesitant to make a conclusive, all-ages statement.
Additionally, statements like "losing weight is beneficial in most cases, although you can reach this generally positive goal through less-than-optimal routes (compared to what's possible) that may have negative consequences later" are very difficult to explain in one sentence.
I needed a full podcast on that subject to answer, but it's my fault since I raised it.
@ yes, I take nmn, my plasma nad+ rose from 26uM o 88um. I’ll,probably switch to niacin as per “conquer aging” as buying nmn pisses me off.
Brilliant opening 😂😂😂
😆
Have you thought about methylated Niacin (Trigonelline)?
48:30 both are pragmatic decisions. It’s easier for a human to take a pill once a day. It’s easier to mix a supplement in a lab animal’s chow to eat throughout the day.
Could the higher need of niacin at fasting be because of our gut microbes? That's my first thought. They want niacin as well and when we are fasted they might be more prone to consume it at higher rates. At fasted the passage through our intestine is often faster as well, right? So it could pass by more microbes at fasting before we absorb it all in to the blood compared to when we have eaten a couple of meals. Right?
I've been on Niacin, NAD, and NR (most recently) since 2018, and I feel no improvement or difference. In 2020, I was diagnosed with fibromyalgia and tests show my oxidative stress and mitochondrial dysfunction are high. My #1 fibro symptom is fatigue followed by post exertional malaise. I'm only 40. So, I think my issues are too far gone to be helped by one of these supplements.
I was hoping you guys would include how glutathione might fit into this discussion? .....or is this an entirely different discussion? I tried NMN supplementation for about 3 - 4 months+ and sincerely did not find any perceptible physiological benefits in the gym. So I stopped taking it and opted instead for the GlyNac +TMG supplements, in an effort to increase Glutathione levels instead. After careful consideration of Rimon's advice here, I am now also going to include his 50mg niacin every 6 hours! Especially to Rimon's point on the budget consideration, niacin is WAYYyyyyy less expensive than NMN!!
We take 500mg Nicain 2 times a week.
I just wanted to limit the discussion to NAD+, because I think podcasts gloss over too many details once they start moving from topic to topic.
@@Physionic Thank you, that's what I figured. And that definitely makes sense. I guess I was just wondering more along the lines of if there was any direct connection between glutathione levels vs. NAD levels, or if these are two totally distinct discussions. Specifically, from a life-extension focus, should I be focusing more on one vs the other? But, I can gather from your reply that this would be a whole other discussion!
Would really like you to assess the research on anatto derived Vit. E tocotrienols and Geranylgeraniol, as, per Dr. Barrie Tan and their effects on chronic illness.
This is where resveratrol plays as it mimics exercise
What if you increase absorption of nr or nmn with a combination of tmg and piperine. Would this increase tissue absorption?
Why don’t they discus direct I.v. Of NAD I’ve done Iv bad in two cycles and it seemed to give me more energy and clear my mind having said that it’s not a comfortable experience
Some of the stuff that dude said doesn't make any sense if you're heavy I don't care what age you are if you work hard and lose weight and you do it healthy way how could that not improve your health I know for a fact that it improves your health because I've done it and I feel much better now
You're right. My answer wasn't sufficient. Weight loss and long-term health implications are complex topics where tissue types, methods of weight loss, and other factors need to be taken into account. I couldn't formulate a proper answer.
I was also concerned that people over 65 might hear this and assume that losing weight would automatically help them live longer, when it could actually increase mortality if done incorrectly. That's why I was hesitant to make a conclusive, all-ages statement.
Additionally, statements like "losing weight is beneficial in most cases, although you can reach this generally positive goal through less-than-optimal routes (compared to what's possible) that may have negative consequences later" are very difficult to explain in one sentence.
I needed a full podcast on that subject to answer, but it's my fault since I raised it.
I'm 53 I used to be almost 270 pounds now I'm like 190 I know that it's helped my cholesterol I know that it's helped me from not having sleep apnea anymore and I'm hoping that it's done a lot more for my health thank you for your info
What about tmg with niacin 1 to 1 and methylation?
There are still a bunch of Okinawa centenarians that are still consuming goats head soup and sea snake soup for health reasons and they have no access to synthetic vitamins, supplements or fortified foods and they won't post comments on here since they don't use computers and other such things that can destroy your health.
Great information
1:15:38 Did anyone else listen to this heat this called the “New Cheetos Time Plus” study. …thanks for the book mark with the real spelling.
nanograms of nicotine complete fix the salvage pathway issues that come with age, one reason why super centenarians lived so long is because they all heavy smokers and avoided cancer. a 5mg daily patch of nicotine is more than enough and you avoid the downsides of smoking.
I’m using 3 mg and I think it’s helpful but rarely does anyone discuss it on TH-cam. Maybe they might get censored.
@@jjperry3995 it also reduces risk of Parkinson's by 40%. The added energy is also a great = more exercise.
@ I do think it’s helped me. Been sick from late Dec for 6-7 mths slowly recovering now.
I love you guys and I don't have a scientific background but I feel like this was totally unfocused. I could have distilled this all down to 20 minutes. I'm a fair way in and I don't know whether you love or hate Sinclair
Thanks for the feedback, but does it matter if we love or hate a scientist? The science is what matters.
I targeted thyroid health and achieved weight loss as an incidental benefit.
The use of the sexy woman on the Real Therapy advertisement makes me skeptical of Real Therapy
slightly unscientific discussion on a controversial supplement
wish you could trim this interview down to 20 minutes or so for better attention span issue and better information obversion rather than 1 1/2 continuous talk.
If you can't pay attention, it's a you thing
@@johnny9072 you are ignorant. and your thing is not having the capacity to comprehend the issue. length of time no matter how much attention you can give to a particular thing can still impact how much you can observe and digest and can remember which clinically known as sustained attention span vs cognitive function which is related to amount of continuous time a person can focus. also attentions span varies based on age group specially in the digital landscape. how much of one's attention can lead to productivity which in this case translates into how much you can learn is based on how much you can remember measured by how much you can take away as a solid understanding of any of the key concepts. furthermore, who has time to watch a scientific discussion that its concepts are hard to understand let alone trying to focus on it for 1 1/2 hours.
Maybe I'm just not the intended audience being someone with a deep biochemistry background, but this guy is just an embarrassment.
Can you elaborate? Thanks!
I've heard enough about Sirtuins and David Sinclair. Check out Dr Been's recent youtube video about inflammation caused by the accumulation of misfolded protein aggregates that build up over your whole lifetime. Could this be the simple answer to it all? I'm a natural "breakfast skipper" and am going back to time restricted eating. Lunch and dinner only.
there is no simple answer, doesn't matter who says it....
Taking NAD+ precursors might be treating the symptoms, and not the cause!
Diminishing levels of NAD+ with age probably is something we should try to manage. But is hefty doses of vitamin B3, such as NA, NAM, NR, and NMN the solution to that?
I suspect tha we should look at the NAD+ consumers instead. We know that CD38 is one important such which increases with age. We also know that Apigenin (or parsley) reduces it. But is that the right way?
I suspect that we should look into why CD38 increases (inflammation perhaps), and get rid of the causes of that.
I have never seen any real research of what does that. So, that's what I want!
To take NAD+ precursors might not be bad, but to me it looks like treating the symptoms and not the cause!
🤔
The jokes get predictable after a while 😂
It's low in real scientific Information, you can do better
Thanks
When someone cites rat studies all i hear is ... "blah, blah, blah"
i'm surprised you hear anything at all....
@boossersgarage3239 if i was a rat, i d hear even more.
I don’t listen to you guys on longevity. You are too skinny. Muscle mass is an indicator of longevity. I only listen to Tren users. They have lots of muscle mass so they are way more healthy.
Ummm ... You think Physionic is too skinny!? If you can't tell by looking at his arms, have a look at his legs in the podcast before this one. (Titled "Age Reversing Antibodies, Glycine and Longevity, Ergothioneine and Mitochondria and More" dated 9/21/24.) Have a look, I'll wait.
@@TheCookiecupcakesdefinitely not “skinny” but definitely not on the longevity supplement Tren.
@@lozgod Just curious how big do you think people need to be (and what data are you basing that on)?
hahahahaha, sarcasm noted....
@@TheCookiecupcakesit was trolling. Tren is like the unhealthiest thing for longevity.
goddamn, the "wellness messiah" is so annoying. such an arrogance and boastfulness in his videos about him being doctor and bla bla bla ,pfffff
whatever....
Then, you and my mother are on the same page :)