I'm 80 and have been taking 1-2 gm / day of NMN and TMG for about 10 years. I am very healthy with no chronic health issues and no prescription drugs. I walk 3-10 miles every day, have not been sick for many years and feel great. I travel between Mexico and Florida almost monthly. Interestingly, my hair is now brown again! I think it may be important that I walk in full sun daily so have sun exposure in tropical and near tropical areas. People tell me I look and act 60. My greatest fear is balance and falling. I have been specifically concentrating on lower leg and foot strength.
Physionic, would really love to see a dive into TMG (betaine). Is there any point taking it for overall health benefits and/or physical performance? Is the reduction of homocysteine it provides gonna affect an individual's health in any noticeable manner? And given that at least I personally didn't notice any studies longer than 6 weeks, does that mean that it might not be safe to take it long-term? Otherwise, great content as usual, love the scientific approach!
And another video idea in case you ever need one: videos just generally explaining the mechanisms by which things work in the body. I myself have a degree in economics, so whilst I can read papers, some of the core understanding of exactly how enzymes or cofactors work is missing. Or gene transcription from hormones. Would be very interesting to see just a biochemistry/physiology crash course or something like that on the channel.
liposmal NAD+ does change the fact that it will have to be digested in your gut and broken down into it's building blocks. NAD+ is found in your food as well and also broken down. Very expensive practice for what is most likey zero benefit.
I'm 69. Adding a second gram of NMN in the late afternoon has helped me tremendously with my energy, I have the ME/CFS and feel almost normal now. Of course, I still have the condition, have to be careful that I don't use the extra energy to overdo it big time for a bigger crash... not hard. I am getting my money's worth. I also take apigenin at night, a reputed CD38 inhibitor. Still loving this channel.
@@CraigHocker Would never want anyone to have ME/CFS, I think for us people with normal energy levels would be hard to see benefits . But if you only have 2 hours on energy per day, then any variation would be noticeable. Many with CFS can't even read or concentrate while sitting for any length of time if on servere end. Adrenalin I think can give a big boost, but not viable ongoing option
I decided to take Niacin (or Nicotinic Acid) instead of the expensive NMN. There are studies showing lower doses of Niacin will raise NAD even higher than NMN. Unfortunately, people folllow the hype.
@@godsofthesingularity8308 It's powder not pills, so around 100 grams. I used to take more but I read some studies saying lower doses was enough. With this dose I also avoid the flushing although it doesn't bother me.
hey, i'm just making this comment to talk about the super high pitched noise that keeps repeating in the audio, it is very randomly spaced out but between 00:31 - 00:35 it happens 3 times and it makes the video quite hard to watch because of how high pitched and loud the sound is, ignoring that the video is really well done!
Good content, love the way you explain quite complex subjects. Would love to hear your take on how the blood pressure standard came about and why so much importance is placed on it.
I found Nuchido's Time+ supplement some time ago. I really liked their study (I had the ppt from their site). I've replicated their formula in the past for long periods using affordable supplements. It includes parsley (Apigenin - a CD38 inhibitor), rutin (Quercetin), alpha-lipoic acid, green tea extract, vitamin c, and zinc. Their study is fascinating. It found that taking the compounds that decrease NAD usage actually increased NAD levels more than NR. They also believe that the whole plant is better than the extract, which can be seen in their formulation. I've switched to 50 mg Niacin from 250 mg Niacinamide to reduce the required dosage (Niacinamide is less efficient, so more is required, and I had concerns with prolonged high dosage Niacinamide.). I'm sure there are problems with my logic because I'm not an expert.
I also try to replicare Nuchido Time +, I drink green Matcha tea every day and I take all other supplements. I take Nicotinamide (niacinamide) but only 50 mg. Maybe I will take B complex instead every other day. But honestly I do not feel any boost, while who is taking NMN says they feel a lot of energy
@@liviacotto7647 yeah I’ve switched back to NMN also for a little bit. But I’ll go back again. I switch it around. I feel much more of a boost from niacin than from nicotinamide. From the niacin studies results it’s much more effective than niacinamide at boosting NAD levels. Based on my calculations, I only need 50 mg niacin to bring NAD levels up to where they were 10 years ago. If you send me your age and your desired target age, I could do the calculation (based on public data) for you.
Thank you very much for your analysis of the work by Dr. Nichola Conlon. Her thought line is amazing! I agree that further investigation must be applied to ensure the efficacy of this so-called second generation of NAD+ boosters. Personally, I take the ingredients of this supplement, and in combination with exercise and intermittent fasting, my quality of life has significantly improved in just three months. I will continue on this path. 💚🙏🙏🙏
There are studies like Dr. Michael Lustgarten's which show that Niacin is more effective in raising NAD, if you dont mind the flushing effect. Dr. I also read that NMN is mostly converted into Niacin in your gut. Unfortunately, there's a lot of hype with NMN and NR. Probably because there's more $$$.
Niacin also raises NAD+ levels. But it has some side effects to be aware of. One is that it raises blood glucose. Another is that high doses have (sometimes) been found to do damage the retina (retinal swelling) (cystoid macular edema of the retina). I sometimes take a low to moderate dose of niacin at night because (for me) it seems to promote a better night's sleep. But I try to avoid doses higher then 400 mg.
I prefer real world examples , Bryan Johnson has tried NR & NMN and has reported both raised his NAD levels. I have a friend who has had a shoulder issue for 15 years which disappeared after NMN supplementation. My own experience is similar ,I'm in my 60s ,no aches or pains , I exercise regularly which has been shown to enhance NMN supplementation and this year my VO2 Max has gone from 44 to 48 as measured on my Garmin watch. As I said real world examples but I do not understand anyone taking a precursor who is under 50 !
Thanks. I stopped taking this supplement a while back. They got ahead of themselves selling this product for years based on skimpy original data then when their "clinical" data finally came out there was, to me, some sleight of hand. Example - their graph shows about 17 ng/ml increase in NAD+ for intracellular NAD+ but did not show baseline value. I asked but did not receive and to my knowledge they have never published the "baseline" value. If I did the math correctly normal intracellular NAD+ is over 30,000 ng/ml. As a check I asked Jinfiniti, a company who tests for intracellular NAD+, to convert 50 microM to ng/ml as they indicated that a good value was 50 microM. They came back with 33,000 ng/ml. similar to my conversion. This seems to make a rise of 17 ng/ml irrelevant, as is data with no reference value. In any case, the ingredients are natural products which are already in my diet for most part. Plus I exercise which has been shown to increase NAD+ as does fasting to some degree. Please correct me if I'm wrong on this in any way.
50 uM = 50e-6 mol/liter * (663.43 g/mol) * (1 liter/1000 ml) * (1e9 ng/g) = 33,000. That checks out. I agree that 17 ng/ml seems trivial in this context.
I wish the de novo pathway got as much attention as the salvage pathway - yes, I use NA as my NAD booster, I am almost 67yo retiree living leisurely with excellent diet, sleep and exercise and maintain a VO2max of 54ml/min/kg
I’ve been taking NR for the past 4 years everyday and I’ve felt much better because of it. I’m gonna still take my NR. Maybe I’ll even switch to NMN now
I am 70 and I have been taking 3 grams of NMN a day for the past 10 months. I have been building muscles at the gym and am stronger than at any time in my life! My health is phenomenal and all issues have disappeared. I am learning new languages and feel decades younger. I have learned a new profession and am milking cows, a very strenuous job. NMN studies should cover higher doses. I strongly recommend NMN, especially after the age of 50.
Mustard Hurl. 😂 Enjoyed that quip. Sir, forget parcely. look up Quercetin and its inhibition of CD38. I believe quercetin alone raises NAD levels more and longer than any of the NAD boosters (including niacinimide which is absolutely the most effective NAD booster). Most of the studies with NMN and NR don't compare their precious sales pitch to Niacinimide or Quercetin. You've done a great job on your talks and this channel. Good luck to all
The problem with NAD isn't that it is unstable, but that it is too big a molecule to enter cells and replenish NAD. Therefore, it only works to the extent that it breaks down into precursors NR and NAM in circulation.Also, each metabolic pathway requires different enzymes at the different steps. So adding NAMPT will help you get from NAM to NMN, but it isn't necessary for NR to get to NMN. For that, you need NRK, which is not in short supply.
Can you do an episode on niacinamide? I've seen conflicting reports on how it helps people who have started getting skin cancers. A while back I started taking it 500mg 2 times a day. I went a full year without any new spots. Recently I lowered the dose to 1x and then stopped for a bit. Then I got 9 new spots. I'm intrigued that something so simple could make such a difference.
Does it matter if it’s the injectable available at a wellness clinic vs orally dosed? Injectable has been claimed to be superior. Any real world users in the chat?
The NAD+ supplement conversation has a problem. Adding a precursors (the Niacin family) is a great idea, but more NAD+ production is dependent on demand. If we don't increase demand (aerobic and resistive exercise, heat shock, cold shock, fasting, etc), there is no reason to produce more NAD+. Also, our daily requirement for a NAD+ precursor is something like 37mg. Adding multiples of that only adds more work for our liver to break it down and excrete the excess.
This would have been better with a standard NAD precursor too - so three groups. And I would suggest a precursor would have been better than a placebo to better test the effects of the cocktail.
Is increasing NAD+ a good thing? Increased levels of NAD+ boost glycolysis and allow for the quick proliferation of cancer cells. I do have cancer, and I certainly don't want to have it grow faster or metastasize.
Most of the data I've seen suggest uncertainty. Knowing what kind of cancer and how it may proliferate given increase NAD+ levels and then also the benefits to your own body, if autophagy even "works" to any degree against your variant, will go a long way.
Besides the Quercetin mentioned, I would definitely look into Fisetin, it's a closely related Senolytic to Quercetin, but has it has a stronger effect. Dr James Kirkland at his Mayo Lab is one of the leading researchers on Senolytics, the human trials are underway but it will be a few years before the results. I take both for Pulmonary Fibrosis, I do definitely feel improvements, but I need more time and follow up CT scans and Lung Function tests, to know for sure. I also supplement with NMN, Pterostilbene, Zinc, and high Strength DHA / EPA Omega-3. My condition is very different than Prostate Cancer, both are not good. I hope it's a very slow growing type, the type not worth operating on because you'll die of old age before the Prostate cancer gets to you. 🙏
interesting. Although I don't do things exactly the same way, for example, I take nicotinic acid, which would increase NAD synthesis via the Preiss-Handler pathway, I do use a similar multi-targeted approach similar to the one proposed... including eating A LOT of dried parsley everyday!... lol... instead of Rutin, I take Quercetin, closely related, although not identical, but both have been shown to increase NAMPT (Along with exercise, which has the best demonstrated effect on NAMPT levels). I do take ALA and EGCG, as well as Q10 and PQQ, but I also focus on a number of upstream and down steam systems as well, ensuring a very well rounded and balanced approach that takes everything from methylation to gut health into consideration.... It's been working wonders so far... fingers crossed.
I’ve been lowering my metabolic age through diet, a combination of cardio and resistance training, and masturbating between 2-6 times per day. I know these numbers might seem challenging but remember that nothing happens overnight, it took me time to get here.
Hey Physionic, I love your vids. Do you have any thoughts on Mercola's comment that 200 mg of Nicotinamide is as good as it's more expensive metabolites: NMN & NR? I respect your academic approach and would love to hear your opinion, if you have one?
@@grmalinda6251 It doesnt really itch for me that much.. and i dont know how to help you, because i like it. Good info for you is that you will eventually build some sort of "tolerance" where it no longer appears at that dosage you are using.
Haven't other studies shows NAD boosts (ALA if i recall) improved glucose burning ? because NAD is necessary for Crebs cycle. Simply burning off more glucose could explain the improvement in glycation measurements.
So did the NAD supplementation include the CD38 inhibitor? All I saw was parsley on one of the diagrams which does act like a CD38 inhibitor. The Nuchido lady/researcher says there's significant results saying that her and her team's formula works. And anecdotally, I heard one needs to consume unrealistic amounts of natural parsley to get the CD38 inhibition necessary. And agreed, older folks over 50 would likely benefit the most. i'm over 50 and being older has its benefits because I believe I can detect changes (good and bad) better than a younger person who has less aging damage IMHO. I take NR, NMN, and niacin on different days. They do seem to help when taken with other supplements. And exercise is essential to feel the energy boost. It seems to activate them, especially with heavy cardio. And finally, it's super important to keep a running log of one's observations to manage all the variables -- dose, combos, and timing.
Interesting, Armando. Yes, the parsley extract was part of the formulation. I find it interesting they said there's significant results - maybe statistically significant? But, then again, the CD38 levels didn't budge, so... I'm not sure where they got that from.
I dont trust that Nuchido lady. She a pretty, charming sales person. You can get alot of Apigenin by buying dried parsley and blending it into a protien shake. I just take Niacinamide it's the same thing.
@@richardbreeze7898 Isnt it easier to take Apigenin supplements directly & skip the blender & nasty taste experience? Long term Apigenin intake may not be a great idea because it inhibits the NRF2 pathway, I believe.
Physionic, I'm a relatively new subscriber, so apologies if you've already covered this, but, I would love to hear your take on the efficacy of taking colostrum for overall general good health reasons. I've been taking the Sovereign Labs liposomal colostrum for about 2 weeks now, but it's absolutely CRAZY expensive, so I'd rather not waste money on something if there isn't good solid research to justify the expense. Especially if the long term use safety data isn't solid.
Please look into Liposomal NAD, am wondering if it also raises NAD in the blood, especially if combined with TMG. I had great results with MNM and NR but I am now running low on energy again after taking the above supplement instead of NMN.
I take NR (Niagen). I know 6 people who got rid of restless legs syndrome completely after 6 to 8 weeks of 600 mg to 1000 mg supplementation. I know of two who get relief from neuropathy, one from carpal tunnel syndrome, and one from lupus. It took care of my mild psoriasis and I get only brief and mild colds since I started taking 1000 mg. (I also take luteolin and quercetin to control CD38 accumulation.). In all of these examples, the people benefiting are over 55 years of age, and most over age 70.
Possibly the effect off the supplement on decreased glycation has nothing to do with the NAD+ increasing effect of it. For example EGCG (one of the main component of the supplement if understand well) decrease the absorption and digestion of carbs (sugars and starches too) therefore decrease blood glucose spikes. That itself decrease glycation... (also it is a strong antioxidant which also decrease glycation).
What I don't see addressed here is any mechanisms linking NAD+ to any of the metrics the study looks at. My understanding about NAD+ is that it is an energy transporter, like ATP, but that is used by a smaller number of energy delivery cases, such as for example, the so-called "3-way enzymes", which are not enzymes that put together or take apart 3 constituents, but rather enzymes that put together or take apart 2 constituents, much like any other enzyme, but do so where the reaction requires energy input, and they receive energy from an NAD+ molecule. Now, if these markers the study looks at are substances that require the action of 3-way enzymes to put together, then MARVELOUS!; but this should be stated and explained in detail. This is not criticism about this video in particular, but generally about everything written or blogged about NAD+ across the entire Internet. In general, any study, or video about a study, involving NAD+ needs to start tackling the detailed mechanisms that justify the choice of metrics for presence, for absorption and utilization, for a welcome change; otherwise the whole article, paper, study or blog is pure gobbledygook.
NAD+ is also used in the Electron Transport Chain where we get most of our ATP. This is why people who focus on the energy theory of aging like a combination of Glutathione precursors, Ergothioneine, and NAD support.
@@jefflittle8913 Thanks for the clarification. Makes a bit more sense now. Still, I think there should be a test that is specific to NAD+ presence/action that we could use, instead of standard blood panel items.
Only thing about NMN and TMG I definitely see is, and cannot attribute to placebo is, whenever I try to get drunk, I need huge amounts of alcohol. I also suffer little to none hangovers from said amounts. Of course when I took couple of months off, I felt "older". But that could be just placebo.
Is cd38 really a bad thing? Sure it uses up lots of nad but maybe it’s going good work eg to reduce inflammation and we shouldn’t be trying to stop it?
Great video, the fact that data can be manipulated to present better. I feel is exactly what’s wrong with science today. What happened to the good old days of making an observation and reporting your observation?
I’m looking for reasons to dump NMN. Didn’t like the “unless you’re older 50,60,70” not your fault … too many times around the sun. My plasma NAD+ went from 26 to 88 no idea of that’s good or not but 88 is teenage levels. I may swap,to niacin. I blended boat loads of parsley in my daily kale goo and it made no difference and made a disgusting tasting potion even worse.
@@frankasafscimone3920 Most NMN is converted into Niacin in your gut. Also, there are tests showing Niacin raises your NAD more than NMN. NMN is more hyped because of $$
@@pattersonellen several years ago I needed to use a cane and my knee pain kept me awake at night. I no longer have the pain or need a cane. Boron and MSM also helps.
The benefits of NMN supplementation on health markers is so small it is debatable if it does anything. Spending large amounts of money on a supplement that provides health benefits so small that they are hardly detected does somewhat suggest puke gold. At the very least people should cycle this puke gold to save money. It's my understanding that after about two weeks of continuous supplementation the NAD levels max out and then gradually fall to baseline over two weeks if you were to stop so you could try cycling the puke gold two weeks on and two weeks off to save on the 🤮 💰💰
Off-topic question: Can cross-over studies be double blinded? Off the top of my head, I can't figure that one out. I guess it can, and the mechanism must be somewhat special ?
Niacin at 50-60mg daily was just as good as 1000mg NMN at raising NAD levels. There's a guy on YT doing monthly blood tests gauging the epigenetic effects of diet and supplements.
are you still using some kind of voice audio filter? I thought that was just temporary after a bad mic, but the sound has been kind of messed up since then
It's been messed up for 3 months. However, literally today I fixed it (editing video as I type this). So, not next week, but the following week, audio will be nice and crisp anew.
i was afraid of the result …. but i assume Nutrido will have to come up with more scientific convincing results. I am sorry for her but it is a 1 - 0 now.
Users happy with NMN are reporting positive psychological effects that induce them to become ambitious, get into shape and with workouts and jogging, etc. Where are the lab reports that measure this effect? Why are there so many users paying the big bucks if this substance is not producing results?
This is a common study run by supplement companies -- small participant numbers and measuring lots of biomarkers, searching for some claim they can make. I can only assume it was powered by NAD+ increase, because it is underpowered to detect differences in the interleukins and other quantities as you can see by the CIs on the two arms. As Nick mentions the statistical analysis is technically wrong and at best severely lacking. By taking the mean of the two baseline values you throw away information (in this case variance and ordering) which is a big no no. Nor did they explain how descriptive statistics were reported or assumptions checked in the paper. The t-test vs ANOVA comment is possibly unfounded because you can see missing values in the dataset in the supplemental, and ANOVA can't handle missing values directly. But how this was managed was not explained. The biological age result on glycosylation has CIs that overlap in the figure, so it is not a significant effect. Possibly "trending" in a frequentist interpretation (p around 0.1 I would guess). In summary this is typical study run by a small supplement company. They should have hired an expert to dredge this correctly and reported everything. Instead we have a series of methodological issues that cloud the results.
I highly disagree with the “vomit gold” color nomenclature. Vomit can have so many different colors and hues, could be homogenous or heterogenous, etc. I urge you to please consider a different way to address it. Perhaps consider diving deeply into some research on the topic.
The only thing im interested in anti againg is if they make something the can make us look like baby faced teenagers again with smooth skin and fast skin turn over to me thats real anti aging
Dr. Nic is by his prestigious qualifications and his body of work on UA-cam indisputably a highly qualified scientific professional. If his demeanour was perhaps a tad more casual or jocular in this video that seems to me irrelevant as his thorough and clearly highly informed scientific analyses are of the highest standard. I rest my case.
I want to know about the carcinogenic potential of tinkering with telomeres. Of all of the supplements I've tried, NAD has been the only one where I've thought I *know* it's doing something (one brand, another brand nothing). To the extent that I've stopped, it freaked me out a bit: after a few days i noticed at the end of the day *I didn't feel tired*. I know that's probably not telomere related in that time span, but I've taken B3 before and not had such an obvious effect.... So I'm discounting that, which leads me back to "I'd like to take it again but it's safety seems unknown".
![Ergothioneine: New Supplement discovered to Improve Mitochondrial Function [Study 295]](http://i.ytimg.com/vi/VX8qvLytsJs/mqdefault.jpg)
I'm 80 and have been taking 1-2 gm / day of NMN and TMG for about 10 years. I am very healthy with no chronic health issues and no prescription drugs. I walk 3-10 miles every day, have not been sick for many years and feel great. I travel between Mexico and Florida almost monthly. Interestingly, my hair is now brown again! I think it may be important that I walk in full sun daily so have sun exposure in tropical and near tropical areas. People tell me I look and act 60. My greatest fear is balance and falling. I have been specifically concentrating on lower leg and foot strength.
For balance get vibration plate.
@@daveoatway6126 I thought NMN came on the market some 5 years ago.
NMN has been remarkable for me in helping recover from a long term pattern of not sleep enough and using too much caffeine. I am 48
Physionic, would really love to see a dive into TMG (betaine). Is there any point taking it for overall health benefits and/or physical performance? Is the reduction of homocysteine it provides gonna affect an individual's health in any noticeable manner? And given that at least I personally didn't notice any studies longer than 6 weeks, does that mean that it might not be safe to take it long-term? Otherwise, great content as usual, love the scientific approach!
yes!
And another video idea in case you ever need one: videos just generally explaining the mechanisms by which things work in the body. I myself have a degree in economics, so whilst I can read papers, some of the core understanding of exactly how enzymes or cofactors work is missing. Or gene transcription from hormones. Would be very interesting to see just a biochemistry/physiology crash course or something like that on the channel.
It’s one of my “must take” supplement stack but I’m > 60
TMG makes me feel bad and that may be a COMT gene problem. If you get that issue (weird mood, irritable) you can just take plain glycine, at night
Also, does TMG have an impact on muscle protein synthesis? And does it have any negative side effects, for example, related to overmethylation?
would love a video on TMG/betaine especially for muscle mass (which is it alleged to increase)
We need your insights on TMG !
For me, the takeaway is daily green tea with generous parsley, in addition to the liposomal NAD+ I'm already taking.
liposmal NAD+ does change the fact that it will have to be digested in your gut and broken down into it's building blocks. NAD+ is found in your food as well and also broken down. Very expensive practice for what is most likey zero benefit.
I've shared the link to this video with Dr. Nicola from Nuchido. Lots of great work here...Love this channel. Thank you
I'm 69. Adding a second gram of NMN in the late afternoon has helped me tremendously with my energy, I have the ME/CFS and feel almost normal now. Of course, I still have the condition, have to be careful that I don't use the extra energy to overdo it big time for a bigger crash... not hard. I am getting my money's worth. I also take apigenin at night, a reputed CD38 inhibitor. Still loving this channel.
What supplement brand do you use ?
happy for you, but a placebo could do the same for such a vague metric.
Just take flush niacin
@@CraigHocker Would never want anyone to have ME/CFS, I think for us people with normal energy levels would be hard to see benefits . But if you only have 2 hours on energy per day, then any variation would be noticeable. Many with CFS can't even read or concentrate while sitting for any length of time if on servere end. Adrenalin I think can give a big boost, but not viable ongoing option
I take my NAD precursor in the afternoon also. Better than a nap! ;-) Thanks
I am using it for over a year and the results are 🤯🤯🤯
I decided to take Niacin (or Nicotinic Acid) instead of the expensive NMN. There are studies showing lower doses of Niacin will raise NAD even higher than NMN. Unfortunately, people folllow the hype.
what dosage?
@@godsofthesingularity8308 It's powder not pills, so around 100 grams. I used to take more but I read some studies saying lower doses was enough. With this dose I also avoid the flushing although it doesn't bother me.
I've read a couple of studies confirming what you say. But breathless hype sells mountains.
@@godsofthesingularity8308 around 100 mg
Yeah what dose
hey, i'm just making this comment to talk about the super high pitched noise that keeps repeating in the audio, it is very randomly spaced out but between 00:31 - 00:35 it happens 3 times and it makes the video quite hard to watch because of how high pitched and loud the sound is, ignoring that the video is really well done!
Good content, love the way you explain quite complex subjects.
Would love to hear your take on how the blood pressure standard came about and why so much importance is placed on it.
I found Nuchido's Time+ supplement some time ago. I really liked their study (I had the ppt from their site). I've replicated their formula in the past for long periods using affordable supplements. It includes parsley (Apigenin - a CD38 inhibitor), rutin (Quercetin), alpha-lipoic acid, green tea extract, vitamin c, and zinc. Their study is fascinating. It found that taking the compounds that decrease NAD usage actually increased NAD levels more than NR. They also believe that the whole plant is better than the extract, which can be seen in their formulation. I've switched to 50 mg Niacin from 250 mg Niacinamide to reduce the required dosage (Niacinamide is less efficient, so more is required, and I had concerns with prolonged high dosage Niacinamide.). I'm sure there are problems with my logic because I'm not an expert.
This sounds reasonable. I'd add mitotaur to that mix.
@@johnolaoluwa I looked into Mitopure, but it's expensive. I'm poor. Any suggestions? I take a pomegranate extract hoping for the best. ;-)
@@Schu2505I take 50 mg of Nicotinamide (niacinamide), it's cheap
I also try to replicare Nuchido Time +, I drink green Matcha tea every day and I take all other supplements. I take Nicotinamide (niacinamide) but only 50 mg. Maybe I will take B complex instead every other day. But honestly I do not feel any boost, while who is taking NMN says they feel a lot of energy
@@liviacotto7647 yeah I’ve switched back to NMN also for a little bit. But I’ll go back again. I switch it around. I feel much more of a boost from niacin than from nicotinamide. From the niacin studies results it’s much more effective than niacinamide at boosting NAD levels. Based on my calculations, I only need 50 mg niacin to bring NAD levels up to where they were 10 years ago. If you send me your age and your desired target age, I could do the calculation (based on public data) for you.
I'm 68 and have been taking Nuchido Time+ for about 9 months... l plan to continue taking it... n=1
Thank you very much for your analysis of the work by Dr. Nichola Conlon. Her thought line is amazing! I agree that further investigation must be applied to ensure the efficacy of this so-called second generation of NAD+ boosters. Personally, I take the ingredients of this supplement, and in combination with exercise and intermittent fasting, my quality of life has significantly improved in just three months. I will continue on this path.
💚🙏🙏🙏
Hi Nic, thank you for your work! It would be great, if you might consider making a video about the effects of aspirin on people with high Lp(a)
While NMN being actually expensive, how does good old Niacin (the flush one) compares to it? Its completly diffrent pathway from what i remember.
There are studies like Dr. Michael Lustgarten's which show that Niacin is more effective in raising NAD, if you dont mind the flushing effect. Dr. I also read that NMN is mostly converted into Niacin in your gut.
Unfortunately, there's a lot of hype with NMN and NR. Probably because there's more $$$.
Niacin also raises NAD+ levels. But it has some side effects to be aware of. One is that it raises blood glucose. Another is that high doses have (sometimes) been found to do damage the retina (retinal swelling) (cystoid macular edema of the retina). I sometimes take a low to moderate dose of niacin at night because (for me) it seems to promote a better night's sleep. But I try to avoid doses higher then 400 mg.
Is noacinimide or nad+ better for long covid?
I prefer real world examples , Bryan Johnson has tried NR & NMN and has reported both raised his NAD levels. I have a friend who has had a shoulder issue for 15 years which disappeared after NMN supplementation. My own experience is similar ,I'm in my 60s ,no aches or pains , I exercise regularly which has been shown to enhance NMN supplementation and this year my VO2 Max has gone from 44 to 48 as measured on my Garmin watch. As I said real world examples but I do not understand anyone taking a precursor who is under 50 !
Thanks. I stopped taking this supplement a while back. They got ahead of themselves selling this product for years based on skimpy original data then when their "clinical" data finally came out there was, to me, some sleight of hand. Example - their graph shows about 17 ng/ml increase in NAD+ for intracellular NAD+ but did not show baseline value. I asked but did not receive and to my knowledge they have never published the "baseline" value. If I did the math correctly normal intracellular NAD+ is over 30,000 ng/ml. As a check I asked Jinfiniti, a company who tests for intracellular NAD+, to convert 50 microM to ng/ml as they indicated that a good value was 50 microM. They came back with 33,000 ng/ml. similar to my conversion. This seems to make a rise of 17 ng/ml irrelevant, as is data with no reference value. In any case, the ingredients are natural products which are already in my diet for most part. Plus I exercise which has been shown to increase NAD+ as does fasting to some degree. Please correct me if I'm wrong on this in any way.
50 uM = 50e-6 mol/liter * (663.43 g/mol) * (1 liter/1000 ml) * (1e9 ng/g) = 33,000. That checks out. I agree that 17 ng/ml seems trivial in this context.
I wish the de novo pathway got as much attention as the salvage pathway - yes, I use NA as my NAD booster, I am almost 67yo retiree living leisurely with excellent diet, sleep and exercise and maintain a VO2max of 54ml/min/kg
I’ve been taking NR for the past 4 years everyday and I’ve felt much better because of it. I’m gonna still take my NR. Maybe I’ll even switch to NMN now
Physionic, great video. Have you ever looked at the NR inflammation studies? The is a well supported indication NR reduces inflammation.
I am 70 and I have been taking 3 grams of NMN a day for the past 10 months. I have been building muscles at the gym and am stronger than at any time in my life! My health is phenomenal and all issues have disappeared. I am learning new languages and feel decades younger. I have learned a new profession and am milking cows, a very strenuous job. NMN studies should cover higher doses. I strongly recommend NMN, especially after the age of 50.
Can you let me know what brand are you using please?
Thank you
Placebo effect is 💪
@@Biewtiful DoNotAge powder
@@larryc1616 I have been going to the gym, on and off, for 35 years. It cannot possibly be a plaçebo effect.
@@Biewtiful DoNotAge powder
Perhaps you could get a side gig naming paint colors for Sherwin Williams - Mustard Hurl, Vomit Green, what a laugh.
Mustard Hurl. 😂 Enjoyed that quip.
Sir, forget parcely. look up Quercetin and its inhibition of CD38. I believe quercetin alone raises NAD levels more and longer than any of the NAD boosters (including niacinimide which is absolutely the most effective NAD booster). Most of the studies with NMN and NR don't compare their precious sales pitch to Niacinimide or Quercetin.
You've done a great job on your talks and this channel. Good luck to all
Looking at that protein gel results you showed and the other results, you are being very kind to what is pretty much garbage generated for marketing.
The problem with NAD isn't that it is unstable, but that it is too big a molecule to enter cells and replenish NAD. Therefore, it only works to the extent that it breaks down into precursors NR and NAM in circulation.Also, each metabolic pathway requires different enzymes at the different steps. So adding NAMPT will help you get from NAM to NMN, but it isn't necessary for NR to get to NMN. For that, you need NRK, which is not in short supply.
Can you do an episode on niacinamide? I've seen conflicting reports on how it helps people who have started getting skin cancers. A while back I started taking it 500mg 2 times a day. I went a full year without any new spots. Recently I lowered the dose to 1x and then stopped for a bit. Then I got 9 new spots. I'm intrigued that something so simple could make such a difference.
Does it matter if it’s the injectable available at a wellness clinic vs orally dosed? Injectable has been claimed to be superior.
Any real world users in the chat?
The NAD+ supplement conversation has a problem. Adding a precursors (the Niacin family) is a great idea, but more NAD+ production is dependent on demand. If we don't increase demand (aerobic and resistive exercise, heat shock, cold shock, fasting, etc), there is no reason to produce more NAD+. Also, our daily requirement for a NAD+ precursor is something like 37mg. Adding multiples of that only adds more work for our liver to break it down and excrete the excess.
This would have been better with a standard NAD precursor too - so three groups. And I would suggest a precursor would have been better than a placebo to better test the effects of the cocktail.
It would be great if you could wrap your big brain around PQQ, and let us know what you think. Thanks!
is it worth taking Apigenin to reduce CD38 marker?
Is increasing NAD+ a good thing? Increased levels of NAD+ boost glycolysis and allow for the quick proliferation of cancer cells. I do have cancer, and I certainly don't want to have it grow faster or metastasize.
Most of the data I've seen suggest uncertainty. Knowing what kind of cancer and how it may proliferate given increase NAD+ levels and then also the benefits to your own body, if autophagy even "works" to any degree against your variant, will go a long way.
@@MajorCanada It is prostate cancer.
Have you looked at quercetin?
@@1134gh I take quercetin, and fisetin as well. Thanks.
Besides the Quercetin mentioned,
I would definitely look into Fisetin, it's a closely related Senolytic to Quercetin, but has it has a stronger effect.
Dr James Kirkland at his Mayo Lab is one of the leading researchers on Senolytics, the human trials are underway but it will be a few years before the results.
I take both for Pulmonary Fibrosis, I do definitely feel improvements, but I need more time and follow up CT scans and Lung Function tests, to know for sure.
I also supplement with NMN, Pterostilbene, Zinc, and high Strength DHA / EPA Omega-3.
My condition is very different than Prostate Cancer, both are not good.
I hope it's a very slow growing type, the type not worth operating on because you'll die of old age before the Prostate cancer gets to you.
🙏
interesting. Although I don't do things exactly the same way, for example, I take nicotinic acid, which would increase NAD synthesis via the Preiss-Handler pathway, I do use a similar multi-targeted approach similar to the one proposed... including eating A LOT of dried parsley everyday!... lol... instead of Rutin, I take Quercetin, closely related, although not identical, but both have been shown to increase NAMPT (Along with exercise, which has the best demonstrated effect on NAMPT levels). I do take ALA and EGCG, as well as Q10 and PQQ, but I also focus on a number of upstream and down steam systems as well, ensuring a very well rounded and balanced approach that takes everything from methylation to gut health into consideration.... It's been working wonders so far... fingers crossed.
Please make a video on what supplements you take on a daily/weekly basis
I think he did. Creatine is one of the few he does take.
@@MajorCanada hey im in Canada too! Can you drop a link brother!
I’ve been lowering my metabolic age through diet, a combination of cardio and resistance training, and masturbating between 2-6 times per day. I know these numbers might seem challenging but remember that nothing happens overnight, it took me time to get here.
Have you ever considered stand-up? 😅
Hey! Would you be willing to implement a student discount for the Physionic Insiders subscription?
Hey Physionic, I love your vids. Do you have any thoughts on Mercola's comment that 200 mg of Nicotinamide is as good as it's more expensive metabolites: NMN & NR? I respect your academic approach and would love to hear your opinion, if you have one?
Test your NAD levels and supplement accordingly. I tested and my levels were perfect. In fact, you should do this before any supplementation.
How do you test?
Even then supplementing, good old, and cheap niacin (the flush one) wouldnt hurt , even if your NAD is in proper range
@@SoilworkWThow do you deal with the itch? Please
@@grmalinda6251 It doesnt really itch for me that much.. and i dont know how to help you, because i like it. Good info for you is that you will eventually build some sort of "tolerance" where it no longer appears at that dosage you are using.
@@grmalinda6251what a problem?)) Massage with a small towel is extremely good thing at that moment of hot flash.
Haven't other studies shows NAD boosts (ALA if i recall) improved glucose burning ? because NAD is necessary for Crebs cycle. Simply burning off more glucose could explain the improvement in glycation measurements.
NAD+ ? To pin or not ? Local clinic offers it but it’s expensive. Is it worth a short cycle for a 60 yr old wknd gym dad?
So did the NAD supplementation include the CD38 inhibitor? All I saw was parsley on one of the diagrams which does act like a CD38 inhibitor. The Nuchido lady/researcher says there's significant results saying that her and her team's formula works. And anecdotally, I heard one needs to consume unrealistic amounts of natural parsley to get the CD38 inhibition necessary. And agreed, older folks over 50 would likely benefit the most. i'm over 50 and being older has its benefits because I believe I can detect changes (good and bad) better than a younger person who has less aging damage IMHO. I take NR, NMN, and niacin on different days. They do seem to help when taken with other supplements. And exercise is essential to feel the energy boost. It seems to activate them, especially with heavy cardio. And finally, it's super important to keep a running log of one's observations to manage all the variables -- dose, combos, and timing.
Interesting, Armando. Yes, the parsley extract was part of the formulation. I find it interesting they said there's significant results - maybe statistically significant? But, then again, the CD38 levels didn't budge, so... I'm not sure where they got that from.
I dont trust that Nuchido lady. She a pretty, charming sales person. You can get alot of Apigenin by buying dried parsley and blending it into a protien shake. I just take Niacinamide it's the same thing.
@@richardbreeze7898 Isnt it easier to take Apigenin supplements directly & skip the blender & nasty taste experience?
Long term Apigenin intake may not be a great idea because it inhibits the NRF2 pathway, I believe.
@@coffeebreakchat2450 Well. I didn't know about the inhibition of Nrf2. I will look into that.
Physionic, I'm a relatively new subscriber, so apologies if you've already covered this, but, I would love to hear your take on the efficacy of taking colostrum for overall general good health reasons. I've been taking the Sovereign Labs liposomal colostrum for about 2 weeks now, but it's absolutely CRAZY expensive, so I'd rather not waste money on something if there isn't good solid research to justify the expense. Especially if the long term use safety data isn't solid.
Been doing a similar combo for almost a decade for this reason.
Please look into Liposomal NAD, am wondering if it also raises NAD in the blood, especially if combined with TMG. I had great results with MNM and NR but I am now running low on energy again after taking the above supplement instead of NMN.
I take NR (Niagen). I know 6 people who got rid of restless legs syndrome completely after 6 to 8 weeks of 600 mg to 1000 mg supplementation. I know of two who get relief from neuropathy, one from carpal tunnel syndrome, and one from lupus. It took care of my mild psoriasis and I get only brief and mild colds since I started taking 1000 mg. (I also take luteolin and quercetin to control CD38 accumulation.). In all of these examples, the people benefiting are over 55 years of age, and most over age 70.
Capers?
@@grmalinda6251 - I think capers are rich in luteolin.
@@grmalinda6251 - I understand that capers are rich in luteolin.
@@grmalinda6251 I think capers are rich in luteolin.
An 78, NMN works for me.
2 key take aways - retch gold and mustard hurl
Possibly the effect off the supplement on decreased glycation has nothing to do with the NAD+ increasing effect of it. For example EGCG (one of the main component of the supplement if understand well) decrease the absorption and digestion of carbs (sugars and starches too) therefore decrease blood glucose spikes. That itself decrease glycation... (also it is a strong antioxidant which also decrease glycation).
An excellent point
Could you look into stemregen? is it all hype or?
What I don't see addressed here is any mechanisms linking NAD+ to any of the metrics the study looks at. My understanding about NAD+ is that it is an energy transporter, like ATP, but that is used by a smaller number of energy delivery cases, such as for example, the so-called "3-way enzymes", which are not enzymes that put together or take apart 3 constituents, but rather enzymes that put together or take apart 2 constituents, much like any other enzyme, but do so where the reaction requires energy input, and they receive energy from an NAD+ molecule. Now, if these markers the study looks at are substances that require the action of 3-way enzymes to put together, then MARVELOUS!; but this should be stated and explained in detail.
This is not criticism about this video in particular, but generally about everything written or blogged about NAD+ across the entire Internet.
In general, any study, or video about a study, involving NAD+ needs to start tackling the detailed mechanisms that justify the choice of metrics for presence, for absorption and utilization, for a welcome change; otherwise the whole article, paper, study or blog is pure gobbledygook.
NAD+ is also used in the Electron Transport Chain where we get most of our ATP. This is why people who focus on the energy theory of aging like a combination of Glutathione precursors, Ergothioneine, and NAD support.
@@jefflittle8913 Thanks for the clarification. Makes a bit more sense now. Still, I think there should be a test that is specific to NAD+ presence/action that we could use, instead of standard blood panel items.
My question now is it safe for me to keep supplementing the NMN since I see a lot of improvement in my health,or should I stop.
Only thing about NMN and TMG I definitely see is, and cannot attribute to placebo is, whenever I try to get drunk, I need huge amounts of alcohol. I also suffer little to none hangovers from said amounts. Of course when I took couple of months off, I felt "older". But that could be just placebo.
Ok but if we want a potent NAD booster, which compound should we look for ?
Why would they use IgG glycosylation for biological age instead of the newer epigenetic clocks??
Would you please do a video on C60?🙏
The picture on the wall is crooked.btw nice article
The world is crooked, and the picture is the only thing straight.
1.5x speed big brain fam unite 🎉
Is cd38 really a bad thing? Sure it uses up lots of nad but maybe it’s going good work eg to reduce inflammation and we shouldn’t be trying to stop it?
Great video, the fact that data can be manipulated to present better. I feel is exactly what’s wrong with science today. What happened to the good old days of making an observation and reporting your observation?
I’m looking for reasons to dump NMN. Didn’t like the “unless you’re older 50,60,70” not your fault … too many times around the sun. My plasma NAD+ went from 26 to 88 no idea of that’s good or not but 88 is teenage levels. I may swap,to niacin. I blended boat loads of parsley in my daily kale goo and it made no difference and made a disgusting tasting potion even worse.
@@jp7357 Why dump NMN? Niacin does not have the same effect by a long shot. NMN has made me feel decades younger.
@@frankasafscimone3920 Most NMN is converted into Niacin in your gut. Also, there are tests showing Niacin raises your NAD more than NMN. NMN is more hyped because of $$
any chance you can reveal the link to this study🙏
It’s linked
@@Physionic sorry I was looking for something highlighted in blue...
I notice niaciamide helps my knees
ribose helps my energy.
How does it help your knees?
@@pattersonellen several years ago I needed to use a cane and my knee pain kept me awake at night. I no longer have the pain or need a cane. Boron and MSM also helps.
what is the difference between NAD and NAC?
I love your videos but they are very hard to watch due to the background noise and the low audio quality :(
I’m working on it - thanks for the feedback
I can hear an echo too. Curtains and sound absorbers needed off camera.
how much apigenin did they introduce?
The benefits of NMN supplementation on health markers is so small it is debatable if it does anything. Spending large amounts of money on a supplement that provides health benefits so small that they are hardly detected does somewhat suggest puke gold. At the very least people should cycle this puke gold to save money. It's my understanding that after about two weeks of continuous supplementation the NAD levels max out and then gradually fall to baseline over two weeks if you were to stop so you could try cycling the puke gold two weeks on and two weeks off to save on the 🤮 💰💰
So how do we reduce CD38? I thought apigeon and parsley was the way, but this cocktail didn't have a result?
Quercetin and Apigenin are CD38 inhibitors.
Off-topic question:
Can cross-over studies be double blinded?
Off the top of my head, I can't figure that one out.
I guess it can, and the mechanism must be somewhat special ?
Definitely can be double blind - you simply have a third party that keeps track of which tablets are given when
@@Physionic Off course ... I'm sure you can tell, that I'm no scientist :D
Niacin at 50-60mg daily was just as good as 1000mg NMN at raising NAD levels. There's a guy on YT doing monthly blood tests gauging the epigenetic effects of diet and supplements.
are you still using some kind of voice audio filter? I thought that was just temporary after a bad mic, but the sound has been kind of messed up since then
It's been messed up for 3 months. However, literally today I fixed it (editing video as I type this). So, not next week, but the following week, audio will be nice and crisp anew.
@@Physionic 🙌!
According to Dr. Stanfield the data shows that older adults who exercise have normal NAD levels. Exercise!
A new study shows that high NAD levels lead to paintings being hung very very crooked
(edit: Yes probably an illusion. Just a meager attempt at humor)
There's a conclusion to my illusion I assure you this ...
-"Younger", by Seinabo Sey
That painting is askew.
Nuchido time+ won the reverse age competition beating bryon johnson
The idea of supplementing NAD because it's low in aging, is flawed if you consider that aging cells might be reducing it in order to *survive* aging.
i was afraid of the result …. but i assume Nutrido will have to come up with more scientific convincing results. I am sorry for her but it is a 1 - 0 now.
Users happy with NMN are reporting positive psychological effects that induce them to become ambitious, get into shape and with workouts and jogging, etc.
Where are the lab reports that measure this effect? Why are there so many users paying the big bucks if this substance is not producing results?
This is a common study run by supplement companies -- small participant numbers and measuring lots of biomarkers, searching for some claim they can make. I can only assume it was powered by NAD+ increase, because it is underpowered to detect differences in the interleukins and other quantities as you can see by the CIs on the two arms.
As Nick mentions the statistical analysis is technically wrong and at best severely lacking. By taking the mean of the two baseline values you throw away information (in this case variance and ordering) which is a big no no. Nor did they explain how descriptive statistics were reported or assumptions checked in the paper.
The t-test vs ANOVA comment is possibly unfounded because you can see missing values in the dataset in the supplemental, and ANOVA can't handle missing values directly. But how this was managed was not explained.
The biological age result on glycosylation has CIs that overlap in the figure, so it is not a significant effect. Possibly "trending" in a frequentist interpretation (p around 0.1 I would guess).
In summary this is typical study run by a small supplement company. They should have hired an expert to dredge this correctly and reported everything. Instead we have a series of methodological issues that cloud the results.
You can take NAD in an IV. I think rich people do this.
I highly disagree with the “vomit gold” color nomenclature. Vomit can have so many different colors and hues, could be homogenous or heterogenous, etc. I urge you to please consider a different way to address it. Perhaps consider diving deeply into some research on the topic.
What is this comment even??
@@tor4472 The relevant section of the video is at 5:37
Bizarre individual
Read a lot about nuchido time+ a while back. Parsley and green tea.. Seems underwhelming.
The only thing im interested in anti againg is if they make something the can make us look like baby faced teenagers again with smooth skin and fast skin turn over to me thats real anti aging
Why does this guy have a sense of humor of a 70 year old baby boomer?
Not much of a study, n=28? Add 4 zeros and we're talking.
Aeon supplement is better...
TINY study again…😢
Demeanor less scientific and professional.
Thank you for your assessment
Dr. Nic is by his prestigious qualifications and his body of work on UA-cam indisputably a highly qualified scientific professional. If his demeanour was perhaps a tad more casual or jocular in this video that seems to me irrelevant as his thorough and clearly highly informed scientific analyses are of the highest standard. I rest my case.
@@Physionic your demeanor was perfect. don't change anything
@rush - people could call me a trashcan and I wouldn't change a thing, haha
than normal.
First
🥇
no one cares
@@george6252 You cared enough to comment lol
5:25 the megaNerd in you really broke thru that chad image you have going there!
I want to know about the carcinogenic potential of tinkering with telomeres. Of all of the supplements I've tried, NAD has been the only one where I've thought I *know* it's doing something (one brand, another brand nothing). To the extent that I've stopped, it freaked me out a bit: after a few days i noticed at the end of the day *I didn't feel tired*. I know that's probably not telomere related in that time span, but I've taken B3 before and not had such an obvious effect.... So I'm discounting that, which leads me back to "I'd like to take it again but it's safety seems unknown".