I decided not to nerd out completely on the statistics, because it would have led to a boring video, but here is some added nerding out for the few that are interested: If you look at any of the data shown (like @2:43), the data is displayed as a ‘relative change from baseline’ and does not show the absolute values. So, the baseline is roughly the same in these graphs, but if we look at the absolute values (as shown @4:18), we can see that they are not the same. This way of displaying the data allows the researchers to indicate a change (as we see comparing placebo vs NMN); however, if we were to use the absolute values and re-test the statistics, I’d wager that there wouldn’t be a difference between the two groups, because the absolute values would actually be closer together between groups after 28 days of supplementation. Second thing - the researchers rely on ‘between treatment’ statistical comparisons, but they don’t do any ‘within-treatment’ comparisons, which would be useful to see. I’d guess that there would be little to no change in either condition (statistically speaking). Ultimately, both of these issues aren’t deal breakers or anything, but they call into question how meaningful these statistically significant effects really are (my point in the video). Maybe I should have gone into it more, but I’m always playing a delicate game of balancing video time and not getting too bogged down in the minutia - hope this helped.
Yea I'm not buying it. Conflict of interest anybody? Not conclusive enough not much of a difference that I see so I don't see any benefit of supplementing with NMN. Whats your take?
I commented on your last video to discuss why there studies are not relevant to the NAD+ supplements effect. Suprised Sinclair did this study. Probably wanted to be right most of all. Though he has different, more promising, projects to look into.
Since changes in liver fat, LDL, and total cholesterol were all known primary outcome variables for the study, I am disturbed they didn't make sure that these variables were comparable for the NMN and placebo groups. The differences in these variables negate their results since the changes could also be explained by a regression to the mean.
So I took the leap of faith with NMN. I'm a 48 yr old male. I've been taking 500mg daily now for about 6 mos. I have begun to notice things such as improved exercise performance and sustained energy levels throughout the day. Blood work reflects improved liver function as well since being on it. The biggest surprise has been the drastic reversal of greying on my head with little change thus far to facial hair. Also, skin health appears to be improving as well. I'll emphasize again that exercise and energy levels have improved as I've pushed to make diet and health changes via exercise and walking for the past 3 yrs now. I'm going on 3 mile brisk walks with ease now and I mix in 4-6 hard 60-80 meter sprints once or twice a week within the daily walking regimen. Prior to NMN it felt like I'd been hit by a train 2-3 days after trying to sprint. I've also noticed heart rate is much lower during intense exertion. Above all, I was very skeptical, but what I'm experiencing currently is shocking to say the least...so I'm going to continue with NMN daily and possibly look to bump to a gram a day.
Have been taking it for a month now and haven't noticed much difference, have bought the next batch for the next couple of months hopefully it works for me.
@@Danny-mg1hu I always try a bunch of different supplements and I'm totally skeptical about them. Also, they usually take time to start showing effects, if any. On the first day, I took NMN I felt something different, then on the second day I felt an amazing increase of energy and also my eyesight improved (I see colors more vibrant now). Seems to be more effective when I'm also exercising.
Excellent analysis. Anyway "the rub" was a term used in lawn bowling in the 1600s, the "rub in the green" which was any defect in the lawn that caused the ball to deviate or altogether stop the ball along its intended path. (Yes, made famous in Hamlet, Shakespeare's audience in that day likely knowing full well the context)
@@moonstrukk126 Ha, I have never heard that one! I'll bet "dollars to cobwebs" some country hick literally tried putting socks on a rooster, and whoever that was is the origin.
My take on it... Given that the entire purported mechanism of effect for NMN is its supposed ability to raise NAD+ levels, there would be no additional intrinsic value to NMN over nicotinic acid other than avoidance of the flushing effect and maybe some improvement in NAD+ conversion rates due to the shorter metabolic pathway with less potential for blockade due to rate limiting steps, although some of this benefit may be negated by absorption issues. So, with that in mind, there is an extremely long history of people taking high does niacin in excess of 1 gr for cholesterol health. Given that, any benefit that we would see with high dose NMN would have also been seen in these patients. This gives us a much bigger sample size against which to determine if raising NAD+ levels actually has any significant health benefits. In my research, just like almost every single other health promoting compound I've ever looked at, there are some benefits, but the effect in isolation is much more modest than the hype makes it out to be. In fact, taken at high doses in isolation, just like everything, it can actually do more harm than good. I'm now straddling opinion here, but there is good evidence to support the view that the body requires a BALANCED intake of nutrients and co-factors. It's basically a VERY finely tuned ULTRA complicated series of interdependent chemical reactions. In order for these reactions to continue unimpeded and at optimal efficiency, the correct ratio of all the reagents need to be in place and are restricted to whatever the rate limiting reagent is. adding more of the other reagents in excess of the buffering capacity will only imbalance the reactions and compromise the bodies ability to maintain homeostasis. This is why, in my opinion, we will never see a single "magic bullet" (unless we genetically engineer ourselves at some point). Any attempt to extend life and healthspan needs to take into consideration all the these systems in consort. If you just raise NAD+ levels you will likely also raise cd38 levels, increasing inflammation. In addition, raising NAD+ levels without increasing NAMPT levels ultimately leads to an excess build of NAM as the NAD+ degrades, increasing the load on the clearance pathway, stressing the liver and kidneys, creating methylation issues, and raising homocysteine. So if you are going to take steps to raise NAD+, you must also address these issues as well. Your requirements for choline intake go up, as does your requirements for b12 and folate and methionine, just to scratch the surface. Anyway.. you get the point.. I'm not disparaging NMN, or saying that you won't see benefits using it, especially if you have heavily depleted levels of NAD+, but there's no such thing as a magic bullet anti aging pill/shot... nor is it likely there ever will be, not as so long as we are walking talking insanely complex chem labs.
@@denofpigs2575 YES..Eggs are freaking amazing.. They definitely rank in y top ten super foods! Unfortunately, not to be contrary, but although they do stack up favourably in terms of nutrient density, they aren't perfect as they still lack many of our required nutrients and the concentrations are still quite low compared to our requirements. Lets take Choline as an example.. Eggs are one of the hands down best sources with a few generally quite expensive exceptions (and liver), but even still you will need to eat between 4-5 eggs every day just to get enough choline.. For me that would be a big chunk of how much I can eat in an entire day. And if you do eat 5 eggs a day, you still are only getting 345mg of your required 3500-4000mg a day of potassium, 0 of your 25-30gr a day of fiber, 140mg of your required 1400mg of calcium, and on and on... So while I definitely do not disagree that eggs are one of the best things you can eat... as much as it sucks to say this, they're still not a magic bullet... not trying to be argumentative, just realistic.
@@denofpigs2575 i love pastured eggs, and used to eat four at a time. But unfortunately I'm one of those people who have an intolerance to dietary cholesterol. Through trial and error and monthly blood tests, I've determined that I can't eat eggs. My ApoB is much better when I don't eat eggs or red meat, and do it fiber rich foods like legumes along with my fatty fish and chicken breast/
The CD38 levels rise with the build up of senescent cells, as well as in large part due to aging in general. It has nothing to do with NAD+ levels causing its rise, as CD38 itself is a leading consumer of NAD+, and is associated with age related decline in the body.
Boredom is the last thing that comes to mind with your videos, thank you for your hard work, brilliant content. Please know that you are having an impact and adding value to society.
"Rub" is an old term from the game of bowls. The term is used often in Shakespeare to refer to something that is in the way of a goal or solution or perhaps something that deserves more attention.
Love your videos🙌 Honestly feels like the internet is just a bombardment of ads, and ads disguised as factual information. Glad to have somewhere to get a real take on it 👏🙏
Dr. Sinclair has long stated that TMG (trimethylglycine) should always be taken with NMN, since NMN uses up methyl groups, which TMG replenishes. In fact, Dr. Sinclair has said that he always takes TMG with NMN. So it's surprising that they didn't that give TMG along with the NMN in this human study.
Yes, TMG or some other supplement that contains methyl. Sinclair also takes a much larger does of NMN than in these studies. I think he takes 1,000mg per day.
Interesting video, Nicolas! It's refreshing to see someone questioning the credibility of Dr. Sinclair's NMN study, especially considering the controversies surrounding his previous ventures with Glaxo. It's essential to remain critical of claims, especially when big money and reputations are at stake. Keep up the skepticism!
Why didn't they cover stamina and muscle recovery? It was brought up in his podcast with Andrew Huberman, and it's something that is often referred to by others in the discussion of NMN. It appears to have helped me a lot. I can't speak to the longevity qualities Sinclair talked about, but the positive effects on endurance and recovery have been consistent with my experience. I think the benefits are getting lost in the hyperbole. I was a professional ballet dancer and have exercised consistently for most of my adult life, so I'm pretty in tune with my body. I love to run now, but ballet took a toll on the muscles in my legs, and for the past five years, I have constantly battled injury, most notably when the weather turns good, and I transition from the treadmill to the outdoors. Rarely was I out of physical therapy, and when I was, it was always temporary. I would run into the same soft tissue injuries every spring, except this past spring, after starting NMN in March. This year, when I got outside, I was running a mile further than normal at a good pace for me, and while I did experience the initial onset of my typical injuries, they didn't progress beyond the initial discomfort. The discomfort was gone quickly and did not impede my running. And every once in a while, when that familiar discomfort returns, it goes away quickly, whereas in the past, it would lead to injury and a return to PT. I've been taking 1gr of NMN, sublingually, since March, and I haven't been back to PT since or have had to back off my running. In the past, to compensate for being injury-prone, I'd spread the workout between the treadmill, stationary bike, and elliptical to move around the burden on my legs. I don't have to do that anymore. NMN was the only change to my routine.
I took part in a smokers study once and being made more aware of my smoking I reduced the amount of daily cigarettes by about 75% I almost quit smoking entirely and I suspect the same applies for people made aware of their fatty liver values - I mean who wouldn't address their dietary habits after this information, and perhaps even more so when they know more quantitative tests are incoming.
Even if Sinclair has an motive for money, Im glad he is bringing more light to longevity research. More light, means more scrutiny. We need more people like you looking at and discussing the research. Overall, this is still a plus for science. I havent tried any of the MNM supplements yet, just fasting and removing most sugar from diet. The only thing that is widely accepted across the board is the benefits of fasting.(under observation from your PCP, not everybody can fast) Anyways, thank you for your work. I hope you can continue doing what you do.
It’s comical when people try to say Sinclair is in it for the money. He doesn’t have any company that makes NMN. And isn’t associated with nor endorses any company that makes NMN. He DOES have labs and companies related to epigenetics, which is also not related to NMN.
@@Jessica-kk1czdo you realize he is a cofounder (and owner) of the company that is trying to get NMN banned as a supplement because that company wants to offer it as a prescription drug? He sounds nice in videos, but he has a financial history that speaks for itself.
@@moonstrukk126i wish that were true. He is the cofounder of the company that is trying to get nmn banned as a supplement because that company wants to sell it as a prescription drug.
#1 I love this content and sense of humour of the content creator. The timing of this video is perfect. #2 I'm 58yo male human. I've dropped 40lb over the past 6 months (I was probably on that sugary road to Type-2 diabetes so I had to do something). I've been supplementing with ALCAR and GlyNAC for 6 months, as well NMN for 3 months. I ran out of NMN a week ago and haven't repurchased. The only noticeable difference is recovery time for muscle building and to an extent energy enthusiasm for exercise. #3 I've supplemented my dog (11yo M, texas heeler) with the same ALCAR, GlyNAC and NMN but in smaller doses (the dog weighs 3.3 time less than me). He remains energetic towards exercise. #4 I'm going to invest in blood biomarkers and a new pair of walking/running shoes instead of NMN while continuing with ALCAR and GlyNAC. #5 Unless the drop off in exercise interest/physical "gotta do it" continues and the increase in muscle soreness continues for the month of October, I'm probably not going to rebuy NMN. #6 David Sinclair's "show" reminds me of con-artistry. He reminds me of a very smooth-non-threatening version of Trump and as well Nichola Conlon seems of the same stripe (nothing like a cute, sweety to sell ya some shyt). The marketing is palpable on NMN. Conlon and Sinclair look like the smartest MFers on Earth in those lab coats.
you would never know after 1 week of stopping NMN what it does for you! It's not a drug like coffee or alcohol that's supposed to change your mood right away. You;d notice after a month or 2.
Where's the niacin vs NMN and NR study? Note they don't seem to compare NMN or NR to cheap niacin. Under some conditions, it mat be that NMN or NR are more effective/efficient, at increasing NAD+ levels, but where's the comparative data?
I’m 58 and have never experienced anything like taking NMN. Energy levels, endurance, strength, flexibility….. I feel like I’m 30. I’ve taken all the supplements, ie vitamins, resveratrol, protein powder and never noticed anything. Nothing has made a difference like NMN. My blood pressure dropped. This stuff is amazing! I will never stop taking.
Hey - congrats - I personally am happy for you. But - it would be helpful to comment on how long have you been taking it, in what amount, and in what form (sublingual or pill). All of these are important factors… I took NMN for about a year - stopped a couple months ago - was suffering from fatigue (I was taking TMG). I am about ready to restart.
The cliffhanger on the last one had me rollin. I love your humor. And the way you disassociate yourself when speaking of humans😂 I completely concur with your conclusions of the data. Also, as someone in the category of those whom "may benefit" and who has personally tried NMN, I say don't bother. Especially when those benefits(and more) are easily gained elsewhere. I saw someone in the comments mention niacin, and I myself after many trials & errors am sticking with NAD+(Niagen).
Wasn't David Sinclair the guy who sold something for millions, boasting it to be the holy grail, but turned out the effect was due to the dye used to analyze the results?
For what it’s worth, I’ve used niacin (nicotinic acid full flush) at 1 g daily, and I’ve trialed NMN at 1 g daily. I’m in my late 40s and went on niacin because I noticed my gym sessions were starting to suffer and I felt sluggish. I was also starting to put on a little visceral fat despite changing nothing in my diet and lifestyle. Niacin had tremendous benefits in my gym performance, energy, and metabolism. And I lost that visceral fat. Plus, my blood panels were amazing on niacin with the highest HDL score and lowest triglyceride score in my entire life, which was awesome. So niacin was boosting my NAD levels and improving my lipid profile and improving my gym and body shape. As for NMN, I tried it for two months before giving up and restarting niacin. I had no improvements on NMN at all. Even my bloods returned to pre-niacin baseline. Niacin absolutely destroys NMN. No comparison at all for me. And niacin is one of the cheapest and most readily available supplements.
curious what brand of nmn you tried. Initially i bought two different brands of nmn. Tried the first one that arrived in the mail, noticed huge improvement in just 3 days. When i ran out of it i tried out the other brand. Noticed a decline in a few days and by the end of 2 weeks was back to where i had started before i took the first brand. Definitely not all NMN is created equal. The good brand i took was from NMN Bio the other one was off of amazon. I have heard that donotage nmn has the highest lab rated results, but NMN Bio has similarly high lab results too. I haven't yet tried DOnotage nmn so cannot personally attest to it for myself
According to World Wide Words, the term "the rub" refers to an obstacle or difficulty and its origin is the ancient game of bowls (lawn bowling). A rub is some fault in the surface of the green that stops a bowl or diverts it from its intended direction.
Really appreciate the nominally unbiased reviews of studies and supplementation. It's difficult to cut through the noise without diving into papers, but I also enjoy your deeper dives into the weeds, as it were. Thank you!
Hmmm, the Stapler can get the same effect taking M&M's. They are cheaper, raise colesterol just as well and make me happy with their serotonin release.
I recently used NMN for 2 months and thought I perceived an increase in energy. I did no testing other than how I felt because I believe I am. pretty sensitive to my body in general and I trust that. I am healthy and fit at 75. I've been off it for a month and now I think I will try again and see if, once again, I perceive a difference. I don't generally continue taking any supplements unless I notice some change. I understand that most people are not particularly sensitive to their bodies but years of practicing yoga and qigong have attuned me my ability to feel deeply inside.
I started taking nmn. Key benefits: Dewey sleep of youth, More steady energy throughout the day. Even when I’ve had little sleep. Taking 1.5 to two grams the day after a heavy night of drinking meant little to zero hangover. Better alcohol tolerance Improved eyesight I likened it to going from standard definition to high definition. Note must be taken with tmg otherwise you will crash after about 1 to 2 weeks.
I love your channel and your flawless impression of a bugs bunny crime boss. I've been taking MNM for over a year and noticed a pretty significant increase in energy. I do struggle with fatigue and pain so it makes sense that it has helped me. As for all the Sinclair bashing in the comments, I've learned over the years that it's never wise to throw away an entire person and ignore anything they might have to offer. I believe he is very sincere in his desire to treat aging as a disease. I appreciate his contribution to my increased energy levels, and the hope that someday age related diseases will be a thing of the past. I'm not naive...just a bit of an optimist. Thanks again mugsy...
(1) I have been taking a NAD precursor for a long time. Each day, I take a 500 NAM just before exercise (e.g., weight training or cardio). There is a clear increase in muscle output - its effect lasts about an hour or two. It also seems to aid in recovery from exercise. (2) I have looked at studies on NMN, After one ingests NMN, the gut seems to extract and absorb NAM from the NMN. In other words, most of NMN is not absorbed. (3) Regarding the study discussed in the video, I note that one should be skeptical of any claims on health benefits that involve energy expenditure or distribution (e.g., lipid profile). For example, if the body is suffering from a metabolic syndrome (e.g., type 2 diabetic), a drug that stresses the body energetically is likely to lead to a short-term, minor improvements in the lipid profile. If you give the same drug to a healthy individual, you may not see the desired result.
NMN benefits have alot of variables behind it which makes difficulty to measure! For example, younger people dont need NMN supplementation nearly as much as older individuals! And NMN supplementation is expected to only return people to youthful levels of ATP production. I would like a see a study to see if ATP levels increased, or not. Also, NAD gets consumed by CD38, which also increases with age in older adults thereby further reducing NAD and ATP production. I see NMN supplementaion as a strategy to raise cellular energy, not to effect cholesterol or blood sugar levels, etc or other biological markers you sited in those studies, in fact there was never a claim on those markers made about NMN at all. - I am 58 yrs old, my energy levels have increased, my workouts are stronger, and I dont get tired halfway through the day anymore, I'm more alert, my hair and nails grow faster, and I heal quicker from cuts and bruises! I was able to reduce CD38 using the strategy of supplemtating with apigenin so that NAD+ with NMN supplementaion wont be consumed as much, and ATP could be maximized. But hey, maybe thats just me. . . . .I will continue to supplemant NMN.
Yup, Sinclair rubs me wrong. At 65 after having COVID three times I have worked to increase glutathione and NAD. Vitamin approach for NAD seems more economical, but since I've collected NMN I'll be using that as well.
NMN has been life changing for me. I don't care if Sinclair cuts corners or is a money grubber, just get nmn to the masses with the best delivery system.
Same here, Im 63 year old male and work 12 hour shifts lifting most of that time, i found after taking NMN just for 2 days i feel just as energized @ the end of my shift. As a matter of fact I would say NMN has been life changing for me.
I have tried all of niacin, NMA, NR, and NAM. Except for niacin, they have similar effects. Niacin causes flushing for about an hour or two, depending on the dosage.
Yep, it definitely makes a difference in my body when taken along with Resveratrol, unless its just working because I believe its working, in which case it may not after watching this video:)
In my experience, I didn't experience greater effects however taking more than 500mg made me feel more energized but in that time I was taking vitamins b, and vitamins b cause the same effect as NMN, I noticed that my abdomen was flat in the morning after taking NMN at night in the previous day, I was 20 years old and I haven't taken NMN since then.
Hey me comment was deleted? SO here is the paper without the link: "NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension" Outcomes: Outcomes and laboratory measurements The primary outcome was the group differences of vascular function including FMD and baPWV before and after NMN treatment. The secondary outcomes were the group differences of PBMCs NAD+ level, blood pressure, body weight, issues with tolerability or treatment-emergent adverse events (AEs) before and after NMN treatment. Moreover, plasma inflammatory cytokines were also compared between two groups using ELISA. Body mass and BMI were recorded by anthropometry.
Thank you Nick. Love your candid & ability to “simplify” the heavy duty “ pass the fork & gouge my eyes out” data sets. I’m confident you could present the scientific data & process on watching grass grow into a palatable & interesting presentation 🙏
"aye, there's the rub" From Shakespeare's To Be or Not To Be speech in Hamlet's nunnery scene. Meaning 'there's the friction' between sleep and death, as though sleep could be death but without a long term commitment. - Among other 16th/17th century uses.
Many thanks. Nic, for this comprehensive analysis, so far have been only bits and pieces of info about NMN, my question: I heard conflicting views on how NMN may affect existing cancer cells and I wonder if you have found enough evidence for or against NMN in such case; I have a prostate cancer and got NMN + TMG ++ AEON pills that I put on the shelf before I know more about potential risks - THANKS!
more great data, i think something is important is doing studies looking for synergy of effects. I also realize doing studies with multiple variables makes proof harder to come by. I think nmn works, in liposomal form, but in regular powder form it didn’t do anything for me. the NMN Lozenges seemed to help but i didn’t take them alone, I took them along with the liposomal NMN. it is only my experience of the last 4 months. My daughter in college has noticed the benefits. but, both of us also take a gly-nac supplement. together this combo seem to really boost energy and also helps to suppress appetite. almost completely off sugar for two months now. before i couldn’t drink enough soda. tried quitting before and just couldn’t do it. so it is possible, if the NMN and Gly-NAC combo only helped me get off my sugar addiction and then correct my normal energy pathways, well that still made it worth what i spent on it.
Thanks Nick. I’d love to hear your take on anecdotal evidence popping up here. At least for those taking it who do not meet the criteria where (possible) effect was found.
I think anecdotal evidence is essential for something like nmn because those who take it know more than these inadequate tests. So far independent himan trials have been based on low doses in some cases, no consideration for participants health at the start, age, and long term. I've been taking it for almost 4 years now and my results are incredible, my skin is amazing, my walking speed is fast...I'm 61...I have heart disease and angina and kept on having ischemic strokes/tia's, but since starting nmn i've had no more tia's/strokes, angina has stabilised and I don't need to take isosorbide mononitrate as often as before. NMN needs more longer term trials.
2:55 the rub comes from betting it’s how the house always wins. No casino goes into business to lose money the rub is like the difference between the real stats and the betting stats
*_the rub_* The difficulty or problem, as in _We'd love to come but there's the rub-we can't get reservations._ This expression may come from lawn bowling, where rub refers to an unevenness in the ground that impedes the ball. *Its most famous use is in one of Hamlet's soliloquies (Hamlet, 3:1): “To sleep, perchance to dream-ay, there's the rub, For in that sleep of death what dreams may come ... Must give us pause.”* [Late 1500s]
question, if NMN raised NAD levels which increases cellular energy, does this mean your basal metabolic rate decreases since your cells are producing more energy outside of normal caloric measures? or are those two completely different systems of energy
NICK - isn’t there an important distinction between blood NAD levels and intercellular NAD levels? I thought the real question is whether MNM (or NR) supplements can raise NAD levels in the cells, not the blood.
True, but the NAD has to be produced from NMN in some cells, perhaps in the liver. I think that indicates, indirectly at least, that it raises the NAD+ in cells too, not just in the blood.
I followed Sinclair taking MNM for two years and at age 66 developed a very large melanoma on my scalp… first time ever, and luckily it was found in time. So I stopped taking NMN immediately… scared all the hype out of me.
Rub: seems an early English idiom for friction, as in it reduces the easy flow. In 3 Shakespearean plays so well known. That is how we use it even today in the sense you mentioned.
I would appreciate the reference to the study. The molecular structures of NMN and NR are roughly the same, except NMN has an added phosphate group. This added phosphate group makes NMN a larger molecule than NR. Some scientists believe NMN is too large to cross cellular membranes and must convert to NR before entering cells, where NAD+ biosynthesis occurs.
If it did in fact raise NAD levels,the study is just not long enough to show how beneficial the clinical improvement could be. Does it activate the longevity genes, is what we need to know. The mitochondria should be working at top capacity with NAD levels saturated, but we need longer studies.
My understanding is simple and it is supported by data: NMN increases NAD+ levels, which is often good; yet, it’s also good for cancer cells, which are often in your body way before you notice (and are often eliminated so that you never notice them). That’s what needs to be weighted.
NNM i tested and NR! NMN does improve my fatigue more than NR. Clearly it has an effect , and rising NAD levels prove that too, but its long term effects are unknown
I must say, your analyses are extremely well-conducted and highly entertaining. There's a lot to be said about Dr Sinclair's business efforts too, not least what he's been trying to do in the US with the FDA and NMN "yes supplement/no supplement" diatribe (Marcel of The Pulse has published several videos about this). Regardless, I have been taking NMN and I have been a believer since day one, because - well, it FEELS good, and the feeling is enough (if we could master the placebo effect, we would overcome every ailment but death - would you agree with me on this?). Plus, you've said yourself in the other video, NAD levels are demonstrably higher. So now the "rub" is to find out what that actually means, higher NAD levels, but as you pointed out, there is no conclusive evidence yet. I think in this case a more holistic approach should be taken. Is NMN the Holy Grail? The sacred fruit of the Tree of Life? No it ain't. Something else must be done. In one of his very first videos (at Joe Rogan's), Sinclair pointed out that NMN is not enough to grant benefits by itself: it must be combined with Resveratrol, calorie restriction, and physical activity. No such complex studies have been conducted, have they? So in a more "alchemic" vein, I venture to hypothesize - NMN may be just like a rare spice, like Thyme or Tamarind, that adds a unique flavor to a number of dishes but is of little significance as a main course.
Dr Sinclair also states tmg and resveratrol are to be combined for full activation of cirtuins. But also have heard you shouldn't take resveratrol all the time
Also look at the daily dosage: 2000 mg per day! That will run you well over $210 CAD per month. That maybe too expensive for most ppl to take on a regular basis
It came from Shakespeare - Hamlet said in a soliloquy in which he was considering topping himself, " To sleep, perchance to dream - now there's the rub," - as in, "there's tbe catch," - in his case meaning what happens after, we are not to know and it might not be a relief from this life anyways.
It's like they don't want to get any firm research results! Such small changes in an underpowered study, with large differences in initial values between the groups. It's not exactly a conclusive study. You mentioned the size of the placebo group, 9 persons. But not the size of the NMN group. Too small to mention, was it? I'm still wondering why NAD in the blood is there, since we don't know if it can get into the cells where it would do something. I guess it's the liver which produces it. That would mean that the liver itself take up NMN (or NR from it) and an effect there seems likely. But what about the rest of the body? I understand the reason for looking at things an effect in the liver would do. But what about that "energy increase" all these proponents on UA-cam talks about. That would require something more than reducing a fatty kiver and some blood fat levels! The body wouldn't increase the level of NAD in the blood if it hadn't any purpose, would it? So I would expect that there were some way to use it. I would look for a NAD transporter to make sense of that!
In my view, the transition from rats to humans presents a significant challenge, primarily because of the differences in lifespan. The chosen measurement points may not be dependable indicators in this context. While I maintain that the hypotheses remain valid, they have not yet risen to the level of becoming a recognized theory, and I have doubts whether they ever will. Only time will tell.
But, what does “the rub” mean and from where did it originate? “Rub” in this sense means drawback or impediment. Most sources say it comes from the ancient game of bowls-the ancestor of the game bocce ball-in which a ball (known as a bowl) is rolled toward a smaller stationary ball, called a jack. The object is to roll one’s bowls so that they come to rest nearer to the jack than those of an opponent. A rub is a flaw in the playing surface that interferes with the ball’s trajectory.
I'm confused now! Should I believe those graphs from the studies or should I believe on the positive results after taking NMN for a month. Well I'm 60 years old male who can do 30 pull ups now from 15 reps before taking NMN. It could be the hype or NMN real effect. What do you think Nick? Like what I've said, I'm confused😝
Thank you Nick. This is a constant source of consternation for me. I understand that these studies are expensive, but why perform Important investigations with such small numbers of test subjects. Like it or not this comes up often (many times thanks to your diligence) and casts shadows on the out comes. Personally I like Dr. Sinclair and don’t like to see him vilified, but why create a study that from its inception, before a single subject is tested, already gives us reason to doubt? Anyway like I said Thank you!
I heard that there's a big difference between blood levels vs levels found in actual body tissue, such as muscle tissue. The latter can indicate absorption into body tissues in general.
What's the rub? : I went looking for the answer. I thought it was related to the phrase "Rubbing the wrong way" but it actually isn't: " In Shakespeare’s “Hamlet,” when Hamlet was contemplating suicide, he said, ““To sleep; perchance to dream: ay there’s the rub: for in that sleep of death what dreams may come?” But, what does “the rub” mean and from where did it originate? “Rub” in this sense means drawback or impediment. Most sources say it comes from the ancient game of bowls-the ancestor of the game bocce ball-in which a ball (known as a bowl) is rolled toward a smaller stationary ball, called a jack. The object is to roll one’s bowls so that they come to rest nearer to the jack than those of an opponent. A rub is a flaw in the playing surface that interferes with the ball’s trajectory. "
Hello! I want to begin by thanking you for your rewarding posts! But I, along with many, want to know why TMG is lifted high to the height!? Sincerely Martin
It blows my mind that it is possible to publish results with a control size of 9 participants... it's just useless noise, not worth the time to write up, let alone read. How can you possibly compare that many variables with such a small sample size? Multiple comparison bias will dominate anything you find.
I've noticed only one effect from NR and NMN. The hair pigmentation is noticabley increased, but still far from to youthful levels. So it has some effect on the stem cells at the hair follicles producing that.
I saw a video made by people using NMN and one of them used vitamin B-12 and the result was a far greater improvement of the items measured compared too the people using only MNM. Could this mean something you think?
So, if the placebo group didn’t have enough members we can still look at the NMN group results. Those results are that there was no significant change in weight or triglycerides or LDL. Right? Based on that alone NMN does not show a meaningful benefit. Right?
I decided not to nerd out completely on the statistics, because it would have led to a boring video, but here is some added nerding out for the few that are interested:
If you look at any of the data shown (like @2:43), the data is displayed as a ‘relative change from baseline’ and does not show the absolute values. So, the baseline is roughly the same in these graphs, but if we look at the absolute values (as shown @4:18), we can see that they are not the same. This way of displaying the data allows the researchers to indicate a change (as we see comparing placebo vs NMN); however, if we were to use the absolute values and re-test the statistics, I’d wager that there wouldn’t be a difference between the two groups, because the absolute values would actually be closer together between groups after 28 days of supplementation.
Second thing - the researchers rely on ‘between treatment’ statistical comparisons, but they don’t do any ‘within-treatment’ comparisons, which would be useful to see. I’d guess that there would be little to no change in either condition (statistically speaking).
Ultimately, both of these issues aren’t deal breakers or anything, but they call into question how meaningful these statistically significant effects really are (my point in the video).
Maybe I should have gone into it more, but I’m always playing a delicate game of balancing video time and not getting too bogged down in the minutia - hope this helped.
Yea I'm not buying it. Conflict of interest anybody? Not conclusive enough not much of a difference that I see so I don't see any benefit of supplementing with NMN. Whats your take?
I commented on your last video to discuss why there studies are not relevant to the NAD+ supplements effect. Suprised Sinclair did this study. Probably wanted to be right most of all. Though he has different, more promising, projects to look into.
Since changes in liver fat, LDL, and total cholesterol were all known primary outcome variables for the study, I am disturbed they didn't make sure that these variables were comparable for the NMN and placebo groups. The differences in these variables negate their results since the changes could also be explained by a regression to the mean.
Thank you for the extra breakdown. If it helps for future videos, I find the “weeds” very useful. You are very good at explaining stats!
Someone's probably already mentioned this, but the phrase, "there's the rub" is best known as a quote from Shakespeare's Hamlet.
So I took the leap of faith with NMN. I'm a 48 yr old male. I've been taking 500mg daily now for about 6 mos. I have begun to notice things such as improved exercise performance and sustained energy levels throughout the day. Blood work reflects improved liver function as well since being on it. The biggest surprise has been the drastic reversal of greying on my head with little change thus far to facial hair. Also, skin health appears to be improving as well. I'll emphasize again that exercise and energy levels have improved as I've pushed to make diet and health changes via exercise and walking for the past 3 yrs now. I'm going on 3 mile brisk walks with ease now and I mix in 4-6 hard 60-80 meter sprints once or twice a week within the daily walking regimen. Prior to NMN it felt like I'd been hit by a train 2-3 days after trying to sprint. I've also noticed heart rate is much lower during intense exertion. Above all, I was very skeptical, but what I'm experiencing currently is shocking to say the least...so I'm going to continue with NMN daily and possibly look to bump to a gram a day.
yeah, they just don't know how to measure it on a blood level.
Have been taking it for a month now and haven't noticed much difference, have bought the next batch for the next couple of months hopefully it works for me.
mostly placebo. i believe that will die off and you will feel the same again.
@@Danny-mg1hu what makes you say that?
@@Danny-mg1hu I always try a bunch of different supplements and I'm totally skeptical about them. Also, they usually take time to start showing effects, if any. On the first day, I took NMN I felt something different, then on the second day I felt an amazing increase of energy and also my eyesight improved (I see colors more vibrant now). Seems to be more effective when I'm also exercising.
Excellent analysis. Anyway "the rub" was a term used in lawn bowling in the 1600s, the "rub in the green" which was any defect in the lawn that caused the ball to deviate or altogether stop the ball along its intended path. (Yes, made famous in Hamlet, Shakespeare's audience in that day likely knowing full well the context)
Ay! There's the rub! For in that sleep of death, what dreams may come?
Thanks, Hamlet! Who knew that etymology lovers would also be etiology lovers?
I love when people whip out obscure facts about sayings!😁
Ok... I've got one for you..."Like socks on a rooster"
Origin?
@@moonstrukk126 Ha, I have never heard that one! I'll bet "dollars to cobwebs" some country hick literally tried putting socks on a rooster, and whoever that was is the origin.
@@kylelochlann5053 lol
I'm a little disappointed...I was hoping you'd have names/dates/region information 😔🙃
Great. Science was hard enough, but now you also need to decipher papers from marketing, political and lawyer manipulations.
Always has been...🤺
@JohnnytNaturalyup, time to start fighting against the quackery that’s infringing on evidence based medicine, turning medicine into big placebo
My take on it...
Given that the entire purported mechanism of effect for NMN is its supposed ability to raise NAD+ levels, there would be no additional intrinsic value to NMN over nicotinic acid other than avoidance of the flushing effect and maybe some improvement in NAD+ conversion rates due to the shorter metabolic pathway with less potential for blockade due to rate limiting steps, although some of this benefit may be negated by absorption issues.
So, with that in mind, there is an extremely long history of people taking high does niacin in excess of 1 gr for cholesterol health. Given that, any benefit that we would see with high dose NMN would have also been seen in these patients. This gives us a much bigger sample size against which to determine if raising NAD+ levels actually has any significant health benefits.
In my research, just like almost every single other health promoting compound I've ever looked at, there are some benefits, but the effect in isolation is much more modest than the hype makes it out to be. In fact, taken at high doses in isolation, just like everything, it can actually do more harm than good.
I'm now straddling opinion here, but there is good evidence to support the view that the body requires a BALANCED intake of nutrients and co-factors. It's basically a VERY finely tuned ULTRA complicated series of interdependent chemical reactions. In order for these reactions to continue unimpeded and at optimal efficiency, the correct ratio of all the reagents need to be in place and are restricted to whatever the rate limiting reagent is. adding more of the other reagents in excess of the buffering capacity will only imbalance the reactions and compromise the bodies ability to maintain homeostasis.
This is why, in my opinion, we will never see a single "magic bullet" (unless we genetically engineer ourselves at some point). Any attempt to extend life and healthspan needs to take into consideration all the these systems in consort.
If you just raise NAD+ levels you will likely also raise cd38 levels, increasing inflammation. In addition, raising NAD+ levels without increasing NAMPT levels ultimately leads to an excess build of NAM as the NAD+ degrades, increasing the load on the clearance pathway, stressing the liver and kidneys, creating methylation issues, and raising homocysteine. So if you are going to take steps to raise NAD+, you must also address these issues as well. Your requirements for choline intake go up, as does your requirements for b12 and folate and methionine, just to scratch the surface.
Anyway.. you get the point.. I'm not disparaging NMN, or saying that you won't see benefits using it, especially if you have heavily depleted levels of NAD+, but there's no such thing as a magic bullet anti aging pill/shot... nor is it likely there ever will be, not as so long as we are walking talking insanely complex chem labs.
The closest you're gonna get to a "Magic bullet" is gonna be pasture raised eggs. So so delicious and nutritious!
@@denofpigs2575 YES..Eggs are freaking amazing..
They definitely rank in y top ten super foods!
Unfortunately, not to be contrary, but although they do stack up favourably in terms of nutrient density, they aren't perfect as they still lack many of our required nutrients and the concentrations are still quite low compared to our requirements.
Lets take Choline as an example.. Eggs are one of the hands down best sources with a few generally quite expensive exceptions (and liver), but even still you will need to eat between 4-5 eggs every day just to get enough choline.. For me that would be a big chunk of how much I can eat in an entire day. And if you do eat 5 eggs a day, you still are only getting 345mg of your required 3500-4000mg a day of potassium, 0 of your 25-30gr a day of fiber, 140mg of your required 1400mg of calcium, and on and on...
So while I definitely do not disagree that eggs are one of the best things you can eat... as much as it sucks to say this, they're still not a magic bullet... not trying to be argumentative, just realistic.
Well stated.
@@denofpigs2575 i love pastured eggs, and used to eat four at a time. But unfortunately I'm one of those people who have an intolerance to dietary cholesterol. Through trial and error and monthly blood tests, I've determined that I can't eat eggs. My ApoB is much better when I don't eat eggs or red meat, and do it fiber rich foods like legumes along with my fatty fish and chicken breast/
The CD38 levels rise with the build up of senescent cells, as well as in large part due to aging in general. It has nothing to do with NAD+ levels causing its rise, as CD38 itself is a leading consumer of NAD+, and is associated with age related decline in the body.
Boredom is the last thing that comes to mind with your videos, thank you for your hard work, brilliant content. Please know that you are having an impact and adding value to society.
"Rub" is an old term from the game of bowls. The term is used often in Shakespeare to refer to something that is in the way of a goal or solution or perhaps something that deserves more attention.
Love your videos🙌 Honestly feels like the internet is just a bombardment of ads, and ads disguised as factual information. Glad to have somewhere to get a real take on it 👏🙏
Dr. Sinclair has long stated that TMG (trimethylglycine) should always be taken with NMN, since NMN uses up methyl groups, which TMG replenishes. In fact, Dr. Sinclair has said that he always takes TMG with NMN. So it's surprising that they didn't that give TMG along with the NMN in this human study.
Since this is the first human trial, maybe they want to see the isolated effects? Perhaps they will do both in follow up studies?
Yes, TMG or some other supplement that contains methyl. Sinclair also takes a much larger does of NMN than in these studies. I think he takes 1,000mg per day.
@@MW-100he does take 1000mg per day. Or at least that’s what he says in his book, and various videos I’ve seen.
@@MW-100To earn more money by the fools who buy it.
Also be sure to take your 2 grams of bullshit and donate 5 grams from your wallet, thank you.
Interesting video, Nicolas! It's refreshing to see someone questioning the credibility of Dr. Sinclair's NMN study, especially considering the controversies surrounding his previous ventures with Glaxo. It's essential to remain critical of claims, especially when big money and reputations are at stake. Keep up the skepticism!
Why didn't they cover stamina and muscle recovery? It was brought up in his podcast with Andrew Huberman, and it's something that is often referred to by others in the discussion of NMN. It appears to have helped me a lot.
I can't speak to the longevity qualities Sinclair talked about, but the positive effects on endurance and recovery have been consistent with my experience. I think the benefits are getting lost in the hyperbole. I was a professional ballet dancer and have exercised consistently for most of my adult life, so I'm pretty in tune with my body. I love to run now, but ballet took a toll on the muscles in my legs, and for the past five years, I have constantly battled injury, most notably when the weather turns good, and I transition from the treadmill to the outdoors. Rarely was I out of physical therapy, and when I was, it was always temporary.
I would run into the same soft tissue injuries every spring, except this past spring, after starting NMN in March. This year, when I got outside, I was running a mile further than normal at a good pace for me, and while I did experience the initial onset of my typical injuries, they didn't progress beyond the initial discomfort. The discomfort was gone quickly and did not impede my running. And every once in a while, when that familiar discomfort returns, it goes away quickly, whereas in the past, it would lead to injury and a return to PT.
I've been taking 1gr of NMN, sublingually, since March, and I haven't been back to PT since or have had to back off my running. In the past, to compensate for being injury-prone, I'd spread the workout between the treadmill, stationary bike, and elliptical to move around the burden on my legs. I don't have to do that anymore. NMN was the only change to my routine.
I agree about recovery with NMN
Two of the biggest snake oil salesmen online right now.
Huberman is a shill.
@@scottk1525 It's like the nonsense around it is driving the research. Makes no sense.
@@ginzo666 AG1 (overpriced spirulina powder) and LMNT (overpriced salt) does seem to enhance your snake oil salesmen skills. 😁
I took part in a smokers study once and being made more aware of my smoking I reduced the amount of daily cigarettes by about 75% I almost quit smoking entirely and I suspect the same applies for people made aware of their fatty liver values - I mean who wouldn't address their dietary habits after this information, and perhaps even more so when they know more quantitative tests are incoming.
Fun fact, that's called the Hawthorne effect :).
Good research can, should and will take it into account.
It’s very hard to even if you know; I have fatty liver and lord knows I want to improve my health but I can’t get those calories under control
ty :) @@mikelbesil6946
That's in part what the placebo group does
That's easy my Grandmother.
Even if Sinclair has an motive for money, Im glad he is bringing more light to longevity research. More light, means more scrutiny. We need more people like you looking at and discussing the research. Overall, this is still a plus for science. I havent tried any of the MNM supplements yet, just fasting and removing most sugar from diet. The only thing that is widely accepted across the board is the benefits of fasting.(under observation from your PCP, not everybody can fast)
Anyways, thank you for your work. I hope you can continue doing what you do.
Sinclair’s reputation sadly speaks for itself. More about the $$ than the actual science. Buyer should ALWAYS be aware with anything he’s attached to
It’s comical when people try to say Sinclair is in it for the money. He doesn’t have any company that makes NMN. And isn’t associated with nor endorses any company that makes NMN. He DOES have labs and companies related to epigenetics, which is also not related to NMN.
Sinclair isn't selling anything except for the idea that aging should be treated as a disease.
@@Jessica-kk1cz Let's also not mention his role in the resveratrol debacle and the money he swindled off from that.
@@Jessica-kk1czdo you realize he is a cofounder (and owner) of the company that is trying to get NMN banned as a supplement because that company wants to offer it as a prescription drug? He sounds nice in videos, but he has a financial history that speaks for itself.
@@moonstrukk126i wish that were true. He is the cofounder of the company that is trying to get nmn banned as a supplement because that company wants to sell it as a prescription drug.
#1 I love this content and sense of humour of the content creator. The timing of this video is perfect.
#2 I'm 58yo male human. I've dropped 40lb over the past 6 months (I was probably on that sugary road to Type-2 diabetes so I had to do something). I've been supplementing with ALCAR and GlyNAC for 6 months, as well NMN for 3 months. I ran out of NMN a week ago and haven't repurchased. The only noticeable difference is recovery time for muscle building and to an extent energy enthusiasm for exercise.
#3 I've supplemented my dog (11yo M, texas heeler) with the same ALCAR, GlyNAC and NMN but in smaller doses (the dog weighs 3.3 time less than me). He remains energetic towards exercise.
#4 I'm going to invest in blood biomarkers and a new pair of walking/running shoes instead of NMN while continuing with ALCAR and GlyNAC.
#5 Unless the drop off in exercise interest/physical "gotta do it" continues and the increase in muscle soreness continues for the month of October, I'm probably not going to rebuy NMN.
#6 David Sinclair's "show" reminds me of con-artistry. He reminds me of a very smooth-non-threatening version of Trump and as well Nichola Conlon seems of the same stripe (nothing like a cute, sweety to sell ya some shyt). The marketing is palpable on NMN. Conlon and Sinclair look like the smartest MFers on Earth in those lab coats.
voted you up for implementing protocols for your dog
you would never know after 1 week of stopping NMN what it does for you! It's not a drug like coffee or alcohol that's supposed to change your mood right away. You;d notice after a month or 2.
Where's the niacin vs NMN and NR study? Note they don't seem to compare NMN or NR to cheap niacin. Under some conditions, it mat be that NMN or NR are more effective/efficient, at increasing NAD+ levels, but where's the comparative data?
Sinclari is not exactly a trustworthy person in my opinion...
I feel like he’s trying to build a reputation as the “longevity researcher” for “tv doctors.”
I enjoy the way your mind works
I’m 58 and have never experienced anything like taking NMN. Energy levels, endurance, strength, flexibility….. I feel like I’m 30. I’ve taken all the supplements, ie vitamins, resveratrol, protein powder and never noticed anything. Nothing has made a difference like NMN. My blood pressure dropped. This stuff is amazing! I will never stop taking.
Nice placebo
@@volos_olympus You clearly haven’t read the research studies. I take a blood test to confirm my levels.
@@BravoZulu12 I have seen the rcts and the failed ITP result. Your blood levels mean jack shit because of cofounding factors and placebo.
Hey - congrats - I personally am happy for you. But - it would be helpful to comment on how long have you been taking it, in what amount, and in what form (sublingual or pill). All of these are important factors… I took NMN for about a year - stopped a couple months ago - was suffering from fatigue (I was taking TMG). I am about ready to restart.
Oh - I am 70 - should have included that…. And very fit…
Awesome video. Im glad your channel is getting traction
The cliffhanger on the last one had me rollin.
I love your humor.
And the way you disassociate yourself when speaking of humans😂
I completely concur with your conclusions of the data.
Also, as someone in the category of those whom "may benefit" and who has personally tried NMN, I say don't bother.
Especially when those benefits(and more) are easily gained elsewhere.
I saw someone in the comments mention niacin, and I myself after many trials & errors am sticking with NAD+(Niagen).
Wasn't David Sinclair the guy who sold something for millions, boasting it to be the holy grail, but turned out the effect was due to the dye used to analyze the results?
Resveratrol but other studies seem to show it works
$720, MILLION!! When he sold his Resveratol company to KlaxoSmithKline in 2008. He reinvested it in his other companies.
I do not trust Dr Sinclair
For what it’s worth, I’ve used niacin (nicotinic acid full flush) at 1 g daily, and I’ve trialed NMN at 1 g daily. I’m in my late 40s and went on niacin because I noticed my gym sessions were starting to suffer and I felt sluggish. I was also starting to put on a little visceral fat despite changing nothing in my diet and lifestyle. Niacin had tremendous benefits in my gym performance, energy, and metabolism. And I lost that visceral fat. Plus, my blood panels were amazing on niacin with the highest HDL score and lowest triglyceride score in my entire life, which was awesome. So niacin was boosting my NAD levels and improving my lipid profile and improving my gym and body shape. As for NMN, I tried it for two months before giving up and restarting niacin. I had no improvements on NMN at all. Even my bloods returned to pre-niacin baseline. Niacin absolutely destroys NMN. No comparison at all for me. And niacin is one of the cheapest and most readily available supplements.
Are you also eating foods high in niacin? Because I wasn't under the impression a typical person who isn't a vegan would be deficient in it.
Which brand niacin did you buy?
curious what brand of nmn you tried. Initially i bought two different brands of nmn. Tried the first one that arrived in the mail, noticed huge improvement in just 3 days. When i ran out of it i tried out the other brand. Noticed a decline in a few days and by the end of 2 weeks was back to where i had started before i took the first brand. Definitely not all NMN is created equal. The good brand i took was from NMN Bio the other one was off of amazon. I have heard that donotage nmn has the highest lab rated results, but NMN Bio has similarly high lab results too. I haven't yet tried DOnotage nmn so cannot personally attest to it for myself
Niacin when mixed with statins do nothing …according to the you tuber above
So no undesirable side effects with niacin then? Can't decide one negative reviews other day positive
According to World Wide Words, the term "the rub" refers to an obstacle or difficulty and its origin is the ancient game of bowls (lawn bowling). A rub is some fault in the surface of the green that stops a bowl or diverts it from its intended direction.
Aye, there’s the rub.
Really appreciate the nominally unbiased reviews of studies and supplementation. It's difficult to cut through the noise without diving into papers, but I also enjoy your deeper dives into the weeds, as it were. Thank you!
Thank you. :)
@@Physionic how can they say that baseline is same between placebo and NMN and then release values that says otherwise??
“ay, there’s the rub” comes from the play Hamlet, Act III, Scene I - the “To be, or not to be” soliloquy by Hamlet.
Thank you :)
There's a video of Dr. Sinclair stating that niacin supplementation alone will also boost NAD levels.
Hmmm, the Stapler can get the same effect taking M&M's. They are cheaper, raise colesterol just as well and make me happy with their serotonin release.
Lol!
I recently used NMN for 2 months and thought I perceived an increase in energy. I did no testing other than how I felt because I believe I am. pretty sensitive to my body in general and I trust that. I am healthy and fit at 75. I've been off it for a month and now I think I will try again and see if, once again, I perceive a difference. I don't generally continue taking any supplements unless I notice some change. I understand that most people are not particularly sensitive to their bodies but years of practicing yoga and qigong have attuned me my ability to feel deeply inside.
Thank you for another fun analysis. I really admire your patience! 🙌🏻
I started taking nmn.
Key benefits:
Dewey sleep of youth,
More steady energy throughout the day. Even when I’ve had little sleep.
Taking 1.5 to two grams the day after a heavy night of drinking meant little to zero hangover.
Better alcohol tolerance
Improved eyesight I likened it to going from standard definition to high definition.
Note must be taken with tmg otherwise you will crash after about 1 to 2 weeks.
I love your channel and your flawless impression of a bugs bunny crime boss.
I've been taking MNM for over a year and noticed a pretty significant increase in energy.
I do struggle with fatigue and pain so it makes sense that it has helped me.
As for all the Sinclair bashing in the comments, I've learned over the years that it's never wise to throw away an entire person and ignore anything they might have to offer.
I believe he is very sincere in his desire to treat aging as a disease.
I appreciate his contribution to my increased energy levels, and the hope that someday age related diseases will be a thing of the past. I'm not naive...just a bit of an optimist.
Thanks again mugsy...
Thanks for the input. I appreciate it. :)
This is a very good critique of the data. Good video. :) Thank you Physionic.
Ok, man, you are truly having (too much) fun! Keep up the good work!
(1) I have been taking a NAD precursor for a long time. Each day, I take a 500 NAM just before exercise (e.g., weight training or cardio). There is a clear increase in muscle output - its effect lasts about an hour or two. It also seems to aid in recovery from exercise.
(2) I have looked at studies on NMN, After one ingests NMN, the gut seems to extract and absorb NAM from the NMN. In other words, most of NMN is not absorbed.
(3) Regarding the study discussed in the video, I note that one should be skeptical of any claims on health benefits that involve energy expenditure or distribution (e.g., lipid profile). For example, if the body is suffering from a metabolic syndrome (e.g., type 2 diabetic), a drug that stresses the body energetically is likely to lead to a short-term, minor improvements in the lipid profile. If you give the same drug to a healthy individual, you may not see the desired result.
NMN benefits have alot of variables behind it which makes difficulty to measure! For example, younger people dont need NMN supplementation nearly as much as older individuals! And NMN supplementation is expected to only return people to youthful levels of ATP production. I would like a see a study to see if ATP levels increased, or not. Also, NAD gets consumed by CD38, which also increases with age in older adults thereby further reducing NAD and ATP production. I see NMN supplementaion as a strategy to raise cellular energy, not to effect cholesterol or blood sugar levels, etc or other biological markers you sited in those studies, in fact there was never a claim on those markers made about NMN at all. - I am 58 yrs old, my energy levels have increased, my workouts are stronger, and I dont get tired halfway through the day anymore, I'm more alert, my hair and nails grow faster, and I heal quicker from cuts and bruises! I was able to reduce CD38 using the strategy of supplemtating with apigenin so that NAD+ with NMN supplementaion wont be consumed as much, and ATP could be maximized. But hey, maybe thats just me. . . . .I will continue to supplemant NMN.
That thing on your wall had me rubbing my screen 😂
I have no faith in Sinclair after that whole Resveratrol scandal and then the more recent debacle with the FDA with NMN.
Yup, Sinclair rubs me wrong. At 65 after having COVID three times I have worked to increase glutathione and NAD. Vitamin approach for NAD seems more economical, but since I've collected NMN I'll be using that as well.
Thanks Nick as always informative and excellent analysis,
NMN has been life changing for me. I don't care if Sinclair cuts corners or is a money grubber, just get nmn to the masses with the best delivery system.
Same here, Im 63 year old male and work 12 hour shifts lifting most of that time, i found after taking NMN just for 2 days i feel just as energized @ the end of my shift. As a matter of fact I would say NMN has been life changing for me.
I have tried all of niacin, NMA, NR, and NAM. Except for niacin, they have similar effects. Niacin causes flushing for about an hour or two, depending on the dosage.
@@codasmWhich brand of NMN have you tried? Sinclair or DoNotAge?
@@codasmBut does it interfere with your sleep if it's so energizing?
@@whoatethechocolate It depends when you take it...take it in the mornings or midday and it shouldn't interfere with your sleep.
Yep, it definitely makes a difference in my body when taken along with Resveratrol, unless its just working because I believe its working, in which case it may not after watching this video:)
NMN by itself is far less potent than if taken with resveratrol
100% .Sinclair has explained this synergy in detail for years!!!
What is your opinion on gyl/nac vs NMN head-to-head? If that's a loaded question, could it possibly be a topic for a video of it in the near future?
What other ingredients on the bottle should we look for? Im noticing some brands have other ingredients with nmn
Due to conflicts of interest, I view it as a promotional brochure.
In my experience, I didn't experience greater effects however taking more than 500mg made me feel more energized but in that time I was taking vitamins b, and vitamins b cause the same effect as NMN, I noticed that my abdomen was flat in the morning after taking NMN at night in the previous day, I was 20 years old and I haven't taken NMN since then.
Hey me comment was deleted? SO here is the paper without the link: "NAD+ exhaustion by CD38 upregulation contributes to blood pressure elevation and vascular damage in hypertension" Outcomes: Outcomes and laboratory measurements
The primary outcome was the group differences of vascular function including FMD and baPWV before and after NMN treatment. The secondary outcomes were the group differences of PBMCs NAD+ level, blood pressure, body weight, issues with tolerability or treatment-emergent adverse events (AEs) before and after NMN treatment. Moreover, plasma inflammatory cytokines were also compared between two groups using ELISA. Body mass and BMI were recorded by anthropometry.
Thank you Nick. Love your candid & ability to “simplify” the heavy duty “ pass the fork & gouge my eyes out” data sets. I’m confident you could present the scientific data & process on watching grass grow into a palatable & interesting presentation 🙏
"aye, there's the rub" From Shakespeare's To Be or Not To Be speech in Hamlet's nunnery scene. Meaning 'there's the friction' between sleep and death, as though sleep could be death but without a long term commitment. - Among other 16th/17th century uses.
Thank you!
Thank you for the work you do man!
Great work. Thanks
Many thanks. Nic, for this comprehensive analysis, so far have been only bits and pieces of info about NMN, my question: I heard conflicting views on how NMN may affect existing cancer cells and I wonder if you have found enough evidence for or against NMN in such case; I have a prostate cancer and got NMN + TMG ++ AEON pills that I put on the shelf before I know more about potential risks - THANKS!
more great data, i think something is important is doing studies looking for synergy of effects. I also realize doing studies with multiple variables makes proof harder to come by. I think nmn works, in liposomal form, but in regular powder form it didn’t do anything for me. the NMN Lozenges seemed to help but i didn’t take them alone, I took them along with the liposomal NMN. it is only my experience of the last 4 months. My daughter in college has noticed the benefits. but, both of us also take a gly-nac supplement. together this combo seem to really boost energy and also helps to suppress appetite. almost completely off sugar for two months now. before i couldn’t drink enough soda. tried quitting before and just couldn’t do it. so it is possible, if the NMN and Gly-NAC combo only helped me get off my sugar addiction and then correct my normal energy pathways, well that still made it worth what i spent on it.
Can you plz add links you forgot to insert at the end when pointing finger?
Thanks Nick. I’d love to hear your take on anecdotal evidence popping up here. At least for those taking it who do not meet the criteria where (possible) effect was found.
I think anecdotal evidence is essential for something like nmn because those who take it know more than these inadequate tests. So far independent himan trials have been based on low doses in some cases, no consideration for participants health at the start, age, and long term. I've been taking it for almost 4 years now and my results are incredible, my skin is amazing, my walking speed is fast...I'm 61...I have heart disease and angina and kept on having ischemic strokes/tia's, but since starting nmn i've had no more tia's/strokes, angina has stabilised and I don't need to take isosorbide mononitrate as often as before. NMN needs more longer term trials.
I know resveratrol isn't good for a fatty liver buy is NMN any better?
something to add to your list of topics is a deep dive on mTOR including the mechanisms and best practices to improve metabolic health.
I would like that ad well, also best way to pulse it - because we dont want it on all the time at all..
2:55 the rub comes from betting it’s how the house always wins. No casino goes into business to lose money the rub is like the difference between the real stats and the betting stats
*_the rub_*
The difficulty or problem, as in _We'd love to come but there's the rub-we can't get reservations._
This expression may come from lawn bowling, where rub refers to an unevenness in the ground that impedes the ball. *Its most famous use is in one of Hamlet's soliloquies (Hamlet, 3:1): “To sleep, perchance to dream-ay, there's the rub, For in that sleep of death what dreams may come ... Must give us pause.”* [Late 1500s]
question, if NMN raised NAD levels which increases cellular energy, does this mean your basal metabolic rate decreases since your cells are producing more energy outside of normal caloric measures? or are those two completely different systems of energy
NICK - isn’t there an important distinction between blood NAD levels and intercellular NAD levels? I thought the real question is whether MNM (or NR) supplements can raise NAD levels in the cells, not the blood.
True, but the NAD has to be produced from NMN in some cells, perhaps in the liver.
I think that indicates, indirectly at least, that it raises the NAD+ in cells too, not just in the blood.
I followed Sinclair taking MNM for two years and at age 66 developed a very large melanoma on my scalp… first time ever, and luckily it was found in time. So I stopped taking NMN immediately… scared all the hype out of me.
Rub: seems an early English idiom for friction, as in it reduces the easy flow. In 3 Shakespearean plays so well known. That is how we use it even today in the sense you mentioned.
What about NMN --> NAD --> Cancer? 😅😅😢😢
Thank you.
I would appreciate the reference to the study.
The molecular structures of NMN and NR are roughly the same, except NMN has an added phosphate group. This added phosphate group makes NMN a larger molecule than NR. Some scientists believe NMN is too large to cross cellular membranes and must convert to NR before entering cells, where NAD+ biosynthesis occurs.
It's linked. Please look in the description.
If it did in fact raise NAD levels,the study is just not long enough to show how beneficial the clinical improvement could be. Does it activate the longevity genes, is what we need to know. The mitochondria should be working at top capacity with NAD levels saturated, but we need longer studies.
My understanding is simple and it is supported by data: NMN increases NAD+ levels, which is often good; yet, it’s also good for cancer cells, which are often in your body way before you notice (and are often eliminated so that you never notice them). That’s what needs to be weighted.
NNM i tested and NR! NMN does improve my fatigue more than NR. Clearly it has an effect , and rising NAD levels prove that too, but its long term effects are unknown
I must say, your analyses are extremely well-conducted and highly entertaining. There's a lot to be said about Dr Sinclair's business efforts too, not least what he's been trying to do in the US with the FDA and NMN "yes supplement/no supplement" diatribe (Marcel of The Pulse has published several videos about this).
Regardless, I have been taking NMN and I have been a believer since day one, because - well, it FEELS good, and the feeling is enough (if we could master the placebo effect, we would overcome every ailment but death - would you agree with me on this?). Plus, you've said yourself in the other video, NAD levels are demonstrably higher. So now the "rub" is to find out what that actually means, higher NAD levels, but as you pointed out, there is no conclusive evidence yet.
I think in this case a more holistic approach should be taken. Is NMN the Holy Grail? The sacred fruit of the Tree of Life? No it ain't. Something else must be done. In one of his very first videos (at Joe Rogan's), Sinclair pointed out that NMN is not enough to grant benefits by itself: it must be combined with Resveratrol, calorie restriction, and physical activity. No such complex studies have been conducted, have they?
So in a more "alchemic" vein, I venture to hypothesize - NMN may be just like a rare spice, like Thyme or Tamarind, that adds a unique flavor to a number of dishes but is of little significance as a main course.
Dr Sinclair also states tmg and resveratrol are to be combined for full activation of cirtuins. But also have heard you shouldn't take resveratrol all the time
Can you look at the nuchido time+ study?
The image of 'Nick' and I skipping hand in hand, in our new Easter dreseses through the field of flowers .... will haunt me for many years to come ...
😂
Also look at the daily dosage: 2000 mg per day! That will run you well over $210 CAD per month. That maybe too expensive for most ppl to take on a regular basis
It came from Shakespeare - Hamlet said in a soliloquy in which he was considering topping himself, " To sleep, perchance to dream - now there's the rub," - as in, "there's tbe catch," - in his case meaning what happens after, we are not to know and it might not be a relief from this life anyways.
How about "nuchido", Dr Nichola Colon's nicotinamide based alternative?..
2:38 scared the crap out of me 💀
Sorry, I'll make a note not to use that again.
It's like they don't want to get any firm research results!
Such small changes in an underpowered study, with large differences in initial values between the groups.
It's not exactly a conclusive study.
You mentioned the size of the placebo group, 9 persons. But not the size of the NMN group. Too small to mention, was it?
I'm still wondering why NAD in the blood is there, since we don't know if it can get into the cells where it would do something.
I guess it's the liver which produces it. That would mean that the liver itself take up NMN (or NR from it) and an effect there seems likely. But what about the rest of the body?
I understand the reason for looking at things an effect in the liver would do. But what about that "energy increase" all these proponents on UA-cam talks about. That would require something more than reducing a fatty kiver and some blood fat levels!
The body wouldn't increase the level of NAD in the blood if it hadn't any purpose, would it?
So I would expect that there were some way to use it.
I would look for a NAD transporter to make sense of that!
AYO, this is the last guy I would’ve expected a “pause” from.
Wild.
Can we know how did you get to access to that scientific paper? I could not access it 😢.
In my view, the transition from rats to humans presents a significant challenge, primarily because of the differences in lifespan. The chosen measurement points may not be dependable indicators in this context. While I maintain that the hypotheses remain valid, they have not yet risen to the level of becoming a recognized theory, and I have doubts whether they ever will. Only time will tell.
But, what does “the rub” mean and from where did it originate?
“Rub” in this sense means drawback or impediment. Most sources say it comes from the ancient game of bowls-the ancestor of the game bocce ball-in which a ball (known as a bowl) is rolled toward a smaller stationary ball, called a jack. The object is to roll one’s bowls so that they come to rest nearer to the jack than those of an opponent. A rub is a flaw in the playing surface that interferes with the ball’s trajectory.
the second I saw n=9 at placebo I was like "yup this is way underpowered and not at all representative of the general population"
How do you know you can trust the data in his report?
'Where's the rub?' Means 'where's the catch?'
Thanks.
Did you review Dr Conklin human NMN study?
I'm confused now! Should I believe those graphs from the studies or should I believe on the positive results after taking NMN for a month. Well I'm 60 years old male who can do 30 pull ups now from 15 reps before taking NMN. It could be the hype or NMN real effect. What do you think Nick? Like what I've said, I'm confused😝
Thank you Nick. This is a constant source of consternation for me. I understand that these studies are expensive, but why perform Important investigations with such small numbers of test subjects. Like it or not this comes up often (many times thanks to your diligence) and casts shadows on the out comes. Personally I like Dr. Sinclair and don’t like to see him vilified, but why create a study that from its inception, before a single subject is tested, already gives us reason to doubt? Anyway like I said Thank you!
thanks for your videos :)
I heard that there's a big difference between blood levels vs levels found in actual body tissue, such as muscle tissue. The latter can indicate absorption into body tissues in general.
What's the rub? : I went looking for the answer. I thought it was related to the phrase "Rubbing the wrong way" but it actually isn't:
" In Shakespeare’s “Hamlet,” when Hamlet was contemplating suicide, he said, ““To sleep; perchance to dream: ay there’s the rub: for in that sleep of death what dreams may come?”
But, what does “the rub” mean and from where did it originate?
“Rub” in this sense means drawback or impediment. Most sources say it comes from the ancient game of bowls-the ancestor of the game bocce ball-in which a ball (known as a bowl) is rolled toward a smaller stationary ball, called a jack. The object is to roll one’s bowls so that they come to rest nearer to the jack than those of an opponent. A rub is a flaw in the playing surface that interferes with the ball’s trajectory. "
Hello!
I want to begin by thanking you for your rewarding posts! But I, along with many, want to know why TMG is lifted high to the height!?
Sincerely Martin
It blows my mind that it is possible to publish results with a control size of 9 participants... it's just useless noise, not worth the time to write up, let alone read. How can you possibly compare that many variables with such a small sample size? Multiple comparison bias will dominate anything you find.
I've noticed only one effect from NR and NMN. The hair pigmentation is noticabley increased, but still far from to youthful levels.
So it has some effect on the stem cells at the hair follicles producing that.
What about niacin?
" Aye, that's the rub." Shakespeare. Hamlet.
I saw a video made by people using NMN and one of them used vitamin B-12 and the result was a far greater improvement of the items measured compared too the people using only MNM.
Could this mean something you think?
So, if the placebo group didn’t have enough members we can still look at the NMN group results. Those results are that there was no significant change in weight or triglycerides or LDL. Right? Based on that alone NMN does not show a meaningful benefit. Right?