I don't think that I would trust a single epigenetic test to prove a negative causation between large dose Niacin and age. It could have been an unusual correlation. If we are to believe in the benefits of NAD, then Niacin's ability to raise it are too important to give up on that quickly. I'm taking 200 mg of Niacin a day and will continue to do so.
@VXingxu Right. Personally I think a single test return where that happened is more likely to be correlation than causation. Either that or the claim that raising your NAD level is good for you is false. He more that doubled his NAD with the Niacin. So, if that is healthy, then what did the Niacin do that was unhealthy or against longevity. Something is wrong in the analysis.
A study by (Niu et al., 2021) investigated the impacts of short-term NMN supplementation on several factors, including telomere length, in pre-aging mice and human volunteers. The study found that the telomere length of peripheral blood mononuclear cells was significantly elongated in NMN-administered mice and humans, suggesting a potential positive effect of NMN supplementation on telomere length.
I have had fenugreek almost every day for the last 5 years, so I am really interested in what your results will be. I make a curry. Turmeric, Fenugreek, Cumin and Cayenne. I use different amounts of the ingredients depending on what I am cooking, but I usually use a lot more Turmeric, and Fenugreek, than Cumin and Cayenne. And I may add other spices too. For scrambled eggs I add the curry, either all colors bell pepper pieces, or pimentos, one drop of iodine (Lugol's formula...that is not a brand), a tablespoon of flaxseed oil, salt, pepper, a little grated mozzarella cheese (cheddar tastes better, but I am trying to limit that). Scrambling and boiling eggs is superior to other ways of cooking eggs, at least it is lower in Advanced Glycation End-products. I eat around 4-5 eggs at a time, once or twice a week. Sometimes I throw in other things like potatoes, or black olives. If I put leftover beef or lamb in it, I use different spices. That happens maybe once a month. I use the curry on chicken, turkey burger, sardines + black beans, and several other dishes. It is good with dishes that are mostly potato, rice, beans, or lentils. If there is not much oil in the dish, I prefer less Cayenne. For garbanzos, I usually use more fenugreek, some milk, mozzarella and maybe some white pepper or ginger.
I believe NAD+ boosters need to be taken together with resveratrol. In young rodents resveratrol activated telomerase as much as telomerase positive cells, yet in older rodents it activated it less. I suspect this is due to age related NAD+ decline. If NMN reduces telomeres it may be that resveratrol can counter this. Resveratrol has been shown to lengthen telomeres and reverse near senescence physiology of old human cells restoring youthful phenotype.
Interesting. My problem with virtually ANY supplement is that they all (except Vit D and perhaps magnesium) tend to increase my ALT - i.e. liver enzymes. So I'm hoping diet and exercise are sufficient.
in my case, regular exercise training, fitness, and leanness (CR) haven't moved NAD from a relatively low 20-25uM. But, I'm hopeful that fenugreek seeds and its abundant trigonelline content can make a dent! that data is about 3 weeks away, experiment in progress...
Since this doesn't actually read your telomere length, I think this is not really any proof that nad speeds up speed of aging. Still thank your for the data you provided here
@@conqueragingordietrying123 I think I know what might be happening here. AS you increase NAD+ Via B3 (B3, NR, NMN, etc.) you also increase CD38 which is a NAD+ depended enzyme which actually could damage Pace of aging. Maybe increase NAD+ by inhabiting CD38 and do not forget about TMG for methylation. I don't know, let me know what you think sir
I got them from nuts.com, I'm not sure which brand is best. 16g/d, which approximates the trigonelline dose that increased NAD in the last video (Dr. Vincenzo Sorrentino's data). Definitely yes on the expectation, but we'll see what the data shows!
Interesting video, thought the high dose Niacin was an issue, but NMN can deplete methyl donors. Maybe try fixing the NAD salvage pathway, so the extra NAD is used for repair etc, rather than inflammation. I've done some content on it recently, need to do an update PACE now I'm starting the Time+ supplement!
Already on methyl-B12, folate is 3x the RDA, TMG intake is > 1g/d, and 3g of TMG doesn't impact methylation status (in my case). Easier said than done to expand the methyl donor pool I'm working on other ways to do that, including proline betaine. TMG isn't the only methylated amino acid...
Great video, glad I found your channel. Curious, if either of you have an idea why I would experience extreme fatigue from taking TMG? It’s not consistent but random. I’ve stopped taking TMG altogether. Sublingual NMN has an immediate effect on me.
hang on in regards to nicotinic acid can you take it for a period of time until flushing effect goes away and see if it is related to flushing effect, i have seen people reverse their epigenetic age by 2 years from taking 500mg nicotinic acid per day for 6 months
This highlights the importance of testing. In my case, the flush was strong, and DunedinPACE was terrible, not close to any other test. With 60 mg NA, no flush, NAD increase, no/marginal impact on DunedinPACE. Nonetheless, I'm working on ways to increase NAD without NAD precursors, which shouldn't mess up DunedinPACE, either (or maybe they will, we'll see!)
How do you intend on consuming the fenugreek seeds? Years ago I would drink sprouted fenugreek seed tea for female health issues. I would sprout them for ~ 3 days, refrigerate overnight (can't remember why) then boil them for a few minutes, let it sit for 20 min, strain and chug b/c it is terribly bitter. IDK if you can extract trigonelline this way. Sometimes I would save the sprouts (which surprisingly retained their firmness), refrigerate them and use them on top of salads with plenty of vinegar to cover up the bitterness. I would cycle use of the tea off and on and I recall that when I would start using again I would have to start at a low dose and work my way up, or I risked triggering a migraine. IIRC the tea seemed to improve muscle gains from weight training - a result I was not expecting since I had not heard of that use for fenugreek at the time.
I haven't tried this in a long time since I am now allergic to pretty much everything and react badly to all the legumes I've tried - even my beloved sprouted beluga lentils. I still have a bag of fenugreek seeds from Johnny's (good for sprouting, but expensive and don't get their broccoli seeds since they aren't actually broccoli).
Interesting result. 10.3389/fnut.2021.756243 - these guys say they doubled the telomere length over 90 days with 300 mg of NMN. But, as you said, trudiagnostic doesn't really measure the telomere length.
So telemere length grew from ~Oct '22 to ~Jan23, then ~flat till ~Sep '23 then grew again till ~Nov '23 (approximates from pausing this vid). Those 2 growth periods did they correspond with more CR than other times? Or with something else notable? Also, were you taking the 60mg NA during one of the growth periods? Thanks!
Hi @geode232, on the channel there's a playlist with telomere videos, where one of the strongest correlations with TL in my data is for body weight. I've gotten leaner over the past year+, which may explain the TL improvement in 2023 vs 2022.
Hi Mike, great video, been waiting for this one! Do you think this telomere length result is significant enough to conclude NMN is a net harm? As I understand, it's only loosely correlated to health outcomes, and maybe this NMN change will unlock pathways (eg, change dietary correlations) to improve telomere results long-term
Thanks @the123apz. I'm not sure about a potential NMN-telomere length link, but I do find it interesting that TL was > 7.1kb for 7 consecutive tests, but shorter with high-dose NMN.
Do you think the DunedinPACE effect is a simply a chemical effect on the test or is it actually promoting aging? I mean is the NA somehow interfering with the test or is actually impacting a biological process negatively.
I think high dose NA in my case is bad for biomarkers. It's not interfering with the test, as lower doses (60 vs 600 mg/d) of NA have a minimal effect on DunedinPACE.
The trigonelline experiment is so interesting. I believe that 16 or 25g may be overkill as when translating the nmn dose from mice to humans, some sort of correcting factor was used. Either scaled by metabolic rate differences, surface area instead of weight or something of that sort. Some early self experimenters in longecity tried translating the mice dose like you did and ended up with 18g/day If I recall correctly, noticed benefits and no ill effects but eventually dropped the dose to around 1g with the same benefits. So I hope this could work and that your experience ends up being that you just need 1 or 2 grams of seeds.
Thanks @eruiluvatar236. Unfortunately, trigonelline content in fenugreek seeds may be as low as 2.6 mg/g (that data is coming this Sunday), so 24g of fenugreek seeds may only yield ~60 mg of trigonelline/day. The only way to know is to test, and I'm sending blood for NAD and metabolomic analysis on Feb 2/2...
@@conqueragingordietrying123 I thought that you scaled by body weight from mice and was using a much larger dose. If that is the case fenugreek seeds are not that good of a source. Indeed I googled it and they seem to go from 2mg/g to 3.8mg/g. Trigonelline seems interesting to me because of the half life, lower doses and because it should be cheaper to make than nmn. Also personally I have bad MTHFR so the extra methyl seems like a good thing. Anyway lets see the results.
Even low dose NA and then NMN didn't work for me, it gave me leg pains in joints and connective tissue something like a kind of neuropathy. I've been athletic all my life and never experienced anything like that. Pain didn't go away until months after cessation. It's not for everyone apparently.
I got that from high dose nicotinamide. I had difficulty figuring out what was doing it, because I take something like 50 different pills, and it takes time to develop symptoms and time to have the symptoms go away after cessation. I was very lucky, I heard about it from Sinclair on some random video. It can stop or slow collagen synthesis. I quit that immediately. Took around 9 months to recover, but it left wrinkles on my face that were not there before. Joints are all good, now. Actually, they are very good. I tried a bunch of things to try to get them to build. The combo that actually worked for me was glycine and TMG. I think my recovery was extra slow because I think I cleared out too many senescent cells that are needed for healing. I took large doses of senolytics while "fasting mimicking." It was probably fine the first or second time, but I should have waited a year for the next time. I think once a year to year and a half is probably best, or possibly even longer. The first time just had such amazing results, I was eager to make it part of my life once every few months. But that was way too frequent. I think my ability to heal is back to normal, but that took a couple years. Despite all the missteps, I am happy with my journey toward dealing with aging and health. And I feel good. My labs are mostly very good, and much better. And I can't help but get better, as I still have a lot I can work on, especially in the exercise and body composition areas.
@@ChessMasterNate Hmm I can't figure out the pathways to nicotinamide stopping or slowing collagen synthesis and never heard Sinclair mentioning that. Is there evidence behind that? And, didn't SInclair, by any chance, explain the details behind it? I mean anything specific related to collagen. Otherwise, all NAD-boosters used alongside unhealthy diet and life style potentially increase the inflammation in the body where it is already present because it also (beneficially in normal conditions) powers the immune cells and helps to clear out pathogens, foreign material, BUT if there is depletion of useful nutrients for effective immune system (like butyrate and magnesium from fiber-rich foods for example) and metabolic issues, depletion of cofactors to enzymes important in NAD cycle, the NAD would fuel the chronic inflammation.
TMG is overrated, at least for me. I already get about 1g/d via diet, and I've supplemented with up to 3g in the past with no effect on methylation, using homocysteine as an example.
Niacin, the B vitamin that was previously used to improve lipid profile and reduce the risk of heart disease, promotes arterial inflammation and cardiovascular risk through its metabolites
@@conqueragingordietrying123 Might be worth asking some researchers, I don't have any contacts but it could possible be an interesting discussion topic. Great video, I appreciate the work you put into these presentations.
@@bowser2005 I have no idea what biological pathways regarding aging that nicotinic acid might contribute to, but we already know from cardiovascular/lipidology research that *high dose* nicotinic acid has not reduced overall, heart-related, or non‐cardiovascular mortality, in spite of it increasing HDL-C, lowering LDL-C, and lowering triglycerides. @conqueragingordietrying1797 could be right that there is a relatively lower dose sweet spot.
nice work. If the telomer length proxied by methylation appears shorte, then there was less methyl groups in/at the telomers., making them to oappear shorter. High dose NA or NMN, without raising the capacity of NAMPT (rate limiting) would mean that a lot of methyl groups would be used for expelling meNAM, and methyls then missing for the DNA. This could mean that telomers are actually not shortened. Hence a couple of of direct measurements of telomer length and trudiagnostics' proxy length would be indicated for calibration. on the one hand, too little methylation can result in impaired gene activation regulationo, but on the other hand, the OSK rejuvenation also works by decreasing the methyl lad of the DNA... Everything not that linear i am afraid ...
According to Charles Brenner there is no correlation between blood NAD and biological aging. He also argues that NMN needs to be turned into nicotinic acid to be absorbed into cells, so if that's true, I would think that a high dose of NMN would have the same effect as a high dose of nicotinic acid?
There are plenty of studies showing that blood intracellular NAD levels correlate with tissue levels I'm on the side of resisting age-related NAD changes, with the goal of improving mitochondrial metabolism. To test that, I'm also sending blood for metabolomic analysis on the same day as NAD tests, which is the closest that we can get to a tissue biopsy Whether that impacts longevity in people, we'll see
I have been considering fenugreek seed extract as well as I don't do well with coffee. After doing some research it appears there is very little standardization from the supplement manufacturers for fenugreek extracts. I like to be precise, how did you decide on dose and brand?
I put roughly zero weight on their telomere length estimate. DunedInPace minimum counts as something! Because it's the best predictor of all cause mortality (outside of Levine phenotypic age, which is also very strong in this area). If I were you, I'd double down on NMN supplementation --- experiment to find the minimum effective dose, or just continue 2g/day to get confirmation?
I'm sorry, Michael, but only in one case - there is no statistical power at all. I think it's too early to draw any conclusions about correlation on N=1. It could be a false positive. At least repeat your experiment several times to be sure of the result.
Different people also might react differently too. Talking from personal experience with NMN, NR, Nicotinamine. Every time I used any of these I would get a growth (chalazion) and once when I did not stop in time it grew out of control and had to surgically remove it. Usually they get sucked back by the body upon cessation. I personally am N=1 but it’s N=10 for the times I tried and it’s always repeatable. Some have suggested I might have the MTHFR mutation which is on my plan to test for. It does make sense though. (I did take it with TMG too)
Hi @justsaying7065, potentially yes-the plan is to send blood for NAD and metabolomic analysis on 2/2. if NAD isn't impacted by 24g of fenugreek seeds/d (I've increased it from 16g/d!), that experiment will end before the full blood panel, scheduled for 3/4.
Say goodbye to mnm folks! I have feeling that was not just an outlier. I am happy however, that there exist a cheaper alternative. My only concern is that the brand is listed on Amazon as prop 65 for heavy metals. Do you have any thoughts on that Micheal?
Can hexanicotinate be used instead of nicotinic acid? Also, how do you consume the fenugreek seeds? Can they be swallowed without chewing (unlike flaxseeds, which can't be digested when intact)?
I'm not sure about hexanicotinate, as I haven't done the experiment-the best way to know would be to measure NAD levels Initially, I started with whole seeds, and almost broke my teeth, so I ground them. Then, after eating the raw ground seeds for 1 day, there's a weird taste to it, so I boiled them with other stuff for about 10 minutes this morning. There's still a bitter taste after cooking-I'm in the process of sorting out how to best mask/get used to that
Hey @paulfiedler9128, there are a few videos in the NAD playlist that provide more context. For example, ruclips.net/video/SwggBuuamCk/видео.html Also, 300 mg of NMN didn't increase my NAD, so I'd recommending testing to see if that's true for you...
I'll cover this in a future video, but there are a lot more methyl donors besides TMG (proline betaine, tryptophan betaine, methyl-nicotnate, others), which didn't work to reduce homocysteine in my case with doses up to 3g/d, so I'm not sold on its potential impact on methylation in my case.
Does trigonelline eventually turn back into nicotinic acid? If so maybe a high dose of trigonelline would have the same negative effect on pace of aging
It does, Dr. Vincenzo Sorrentino showed that in this video: ruclips.net/video/nd4rOop_08U/видео.html Ah, the question is dose-it's hard to get more than 100 mg (or more) of trigonelline/d via diet
Hmm, thats a good question. But even if high dose of trigonelline used, we can't be sure it reaches the receptors that pure nicotinic acid otherwise would reach (like the GPR109A receptor), depending how it would be compartmentalized in our cells and tissues. Also, the half life of nicotinic acid is quite short, like 0.5-1 hour or something, can't remember atm exactly, but even at large doses of trigonelline, it would probably not be converted to high levels of nicotinic acid in the body but used more continuously instead. The latter makes a difference, because even the GPR109A receptor signaling depends on the concentration of nicotinic acid in the body.
In the last video, we saw that trigonelline increased NAD at a dose of 300 mg/kg BW in mice. The human equivalent dose is 1.6g/d, and to get that, I'm currently eating 16g of fenugreek seeds.
Is this just a methylation problem, where you need methyl donors? Methylation pathways are pretty complicated to balance especially if you have gene mutations.
I don't have MTHFR SNPs, as homocysteine was < 7 in my early 30s. It's likely a methyl donor issue, but which one is the challenge. In my case, TMG, methyl B12, and methyl folate are a lot higher than the RDA but haven't made much of a dent on methylation markers.. Proline betaine and trigonelline are potential methyl donors that I expect to be beneficial.
He takes fenugreek seeds as a source of trigonelline which hopefully will boost his NAD without negatively effecting his epigenetic pace of aging or his telomere length.
Isn’t it true that coming into contact with a virus can temporarily raise biological age? That’s always a possibility to consider, even if you’ve never gotten sick it is flu season so the body can be busy fighting things
Study the integrated stress response the body uses in response to viruses. The body lowers protein quality control when infected so viruses can't hijack protein production machinery to efficiently replicate. It compromises or lowers the 'fitness' of most cells in the process, though. As we get older it tends to get overactivated or stuck activated. Loss of protein production quality control via the integrated stress response is a major driver of aging via EIF2A and EIF2B, ATF4, ATF6 and various other genes.
@@SamiSami-sb3ze The most common pathway to that is NMN fueling inflammation. You need to fuel health instead. :) That's why I'm sure NAD-boosters only work when accompanied with otherwise heathy diet and life style :) The stuff that directs the NAD use. The stuff that controls NAMPT enzyme, inhibit inflammatory NAD-consumers etc. Thats the way, but a crucial way, we definitely wanna be on that way and NAD-boosted.
Also, we need to be sure our NMN is top quality product. It's easier with nicotinic acid (if it worked) - because we know the quality of it, somewhat, by the taste already and it has excellent heat and humidity tolerance.
I will take Peter Attia’s critism point here on these age test. Can a couple of gram NMN or any other supplement for that matter really slow your age speed that much down?
High-dose nicotinic acid likely made DunedinPACE much worse than my baseline (0.98 vs < 0.8), so supplements can definitely impact it. Whether it can be improved via supplements, I'm not sure, and skeptical, too
I don't think Attia's point is valid. Yes, the markers are malleable, but this is the point actually - staying healthy, fit and young takes daily work to change them! Vo2max is also malleable, but Peter somehow doesn't think vo2max is invalid.
@@erastvandoren I am confused? You write: "but this is the point actually - staying healthy, fit and young takes daily work to change them!" This is what Peter Attia says and what I agree on aswell. Moreover, he (Peter) don't believe a single supplement will decrease you aging proces by 1/3.. as claimed in the video. In my eyes it seems you agree on this?
@@conqueragingordietrying123 I appreaciate your work and it is so nice that you show your numbers! big fan! I just think when NMN has such a big effect on your speed of age.. we should question these test.
This feels like a bait and switch based on the title....in the title you list NMN but then proceed to talk about Niacin/Nicotinic Acid. They are not the same thing. NMN does not have the same drawbacks of Niacin.
No. It's a nad salvage and electron transport chain issue. If NAD salvage is dysfunctional then high dose NAD precursors just rapidly convert to NADh. Overloads the electron transport chain, resulting in a buildup of H202 and depleted mitochondrial catalase. H2O2 is an important epigenetic signalling molecule in small amounts. In large amounts, it will mess you up. Greying hair and fatty liver is the tip of the iceberg of what will happen. Telomere depletion and rapid aging can result. Especially if you don't have appropriate inositol pyrophosphate metabolism to maintain telomeres.
@HateDietPepsi This is precisely what tens of thousands of studies into the electron transport chain, mitochondrial membrane complexes, nad salvage, and Nad+ / NadH ratio tells us. Yours is an echo chamber of a complex idea explained quite badly. I bet you don't even know the epigenetic modulators of methylation and demethylation, how the TET and DNA methyltransferase genes work.
watch out for the smell that fenugreek gives u i was also all hyped up years ago when i heard about their supposed strength and testosterone benefits and dr greger showing science sugggsting that they make u smell like "maple syrup" was even more promising however turns out that was just some biased vegan pink glasses view: the supposed "maple syrup" body smell in my opinion is WAY closer to "fresh urine smell", i discontinued the fenugreek, later i did fenugreek extract tho, which didnt have that smell issue, however they were a bit pricy so i discontinued them for the time being, maybe later when they cheaper i add the extract back in 😋normal fenugreek not viable tho ;S just like with cumin (makes u smell like sweaty female genitalia) and roasted "coffee stank" (as u would say it xD)
Definitely interesting comparison! I wish we could see these replicated in more than one test only - for both, negative effect for nicotinic acid or any effects of NMN. I think I can't be too sure otherwise :D because I think even some cold viruses or the recent lab-leaked bioweapons may mess with the DuneinPace value - this is certainly true for the recent SARS viruses - I mean I can visibly see people hair turn grey quickly. AND I wanna point out that this could happen even without the major symptoms of the disease tbh. So, that's why these NAD+ boosting results could be fluctuating a lot I am afraid :) and nibble away on youthful markers, temporarily, even when the NAD+ levels are healthy.
I don't think that I would trust a single epigenetic test to prove a negative causation between large dose Niacin and age. It could have been an unusual correlation. If we are to believe in the benefits of NAD, then Niacin's ability to raise it are too important to give up on that quickly. I'm taking 200 mg of Niacin a day and will continue to do so.
I think he took 600mg of Niacin daily, which apparently raised his aging rate, but Niacin 60mg daily did not.
@VXingxu Right. Personally I think a single test return where that happened is more likely to be correlation than causation. Either that or the claim that raising your NAD level is good for you is false. He more that doubled his NAD with the Niacin. So, if that is healthy, then what did the Niacin do that was unhealthy or against longevity. Something is wrong in the analysis.
A study by (Niu et al., 2021) investigated the impacts of short-term NMN supplementation on several factors, including telomere length, in pre-aging mice and human volunteers. The study found that the telomere length of peripheral blood mononuclear cells was significantly elongated in NMN-administered mice and humans, suggesting a potential positive effect of NMN supplementation on telomere length.
Well, Niu used qPCR to measure telomere length, while trudiagnostic makes an educated guess,
I have had fenugreek almost every day for the last 5 years, so I am really interested in what your results will be. I make a curry. Turmeric, Fenugreek, Cumin and Cayenne. I use different amounts of the ingredients depending on what I am cooking, but I usually use a lot more Turmeric, and Fenugreek, than Cumin and Cayenne. And I may add other spices too. For scrambled eggs I add the curry, either all colors bell pepper pieces, or pimentos, one drop of iodine (Lugol's formula...that is not a brand), a tablespoon of flaxseed oil, salt, pepper, a little grated mozzarella cheese (cheddar tastes better, but I am trying to limit that). Scrambling and boiling eggs is superior to other ways of cooking eggs, at least it is lower in Advanced Glycation End-products. I eat around 4-5 eggs at a time, once or twice a week. Sometimes I throw in other things like potatoes, or black olives. If I put leftover beef or lamb in it, I use different spices. That happens maybe once a month.
I use the curry on chicken, turkey burger, sardines + black beans, and several other dishes. It is good with dishes that are mostly potato, rice, beans, or lentils. If there is not much oil in the dish, I prefer less Cayenne. For garbanzos, I usually use more fenugreek, some milk, mozzarella and maybe some white pepper or ginger.
you sound hot
I believe NAD+ boosters need to be taken together with resveratrol. In young rodents resveratrol activated telomerase as much as telomerase positive cells, yet in older rodents it activated it less. I suspect this is due to age related NAD+ decline. If NMN reduces telomeres it may be that resveratrol can counter this. Resveratrol has been shown to lengthen telomeres and reverse near senescence physiology of old human cells restoring youthful phenotype.
Interesting. My problem with virtually ANY supplement is that they all (except Vit D and perhaps magnesium) tend to increase my ALT - i.e. liver enzymes. So I'm hoping diet and exercise are sufficient.
in my case, regular exercise training, fitness, and leanness (CR) haven't moved NAD from a relatively low 20-25uM. But, I'm hopeful that fenugreek seeds and its abundant trigonelline content can make a dent! that data is about 3 weeks away, experiment in progress...
might want to check some liver complex supp to assist your liver
@@conqueragingordietrying123 Maybe this is obvious, but you want to grind the fenugreek seeds into a powder, to use it as a spice in your food.
Since this doesn't actually read your telomere length, I think this is not really any proof that nad speeds up speed of aging.
Still thank your for the data you provided here
appreciate the explanations of the nuances involved in even simple supplementation
Excellent - thanks. Please keep us updated.. 👍
Thanks @kst157, and I plan on doing this for the next 72+ years, so definitely!
@@conqueragingordietrying123 I think I know what might be happening here. AS you increase NAD+ Via B3 (B3, NR, NMN, etc.) you also increase CD38 which is a NAD+ depended enzyme which actually could damage Pace of aging. Maybe increase NAD+ by inhabiting CD38 and do not forget about TMG for methylation. I don't know, let me know what you think sir
What brand of Fenugreek and what dosage will you be trying? You hope for this to increase your NAD, anything else?
I got them from nuts.com, I'm not sure which brand is best. 16g/d, which approximates the trigonelline dose that increased NAD in the last video (Dr. Vincenzo Sorrentino's data).
Definitely yes on the expectation, but we'll see what the data shows!
Interesting video, thought the high dose Niacin was an issue, but NMN can deplete methyl donors. Maybe try fixing the NAD salvage pathway, so the extra NAD is used for repair etc, rather than inflammation. I've done some content on it recently, need to do an update PACE now I'm starting the Time+ supplement!
Already on methyl-B12, folate is 3x the RDA, TMG intake is > 1g/d, and 3g of TMG doesn't impact methylation status (in my case). Easier said than done to expand the methyl donor pool
I'm working on other ways to do that, including proline betaine. TMG isn't the only methylated amino acid...
Nice to hear you are keeping up the homocysteine fight.@@conqueragingordietrying123
Great video, glad I found your channel.
Curious, if either of you have an idea why I would experience extreme fatigue from taking TMG?
It’s not consistent but random. I’ve stopped taking TMG altogether.
Sublingual NMN has an immediate effect on me.
Besides these data on NMN or Nicotinic acid, will nicotinamide (NAM) give same results?@@conqueragingordietrying123
@christophergaggo4088 TMG can increase SAMe, could be down to that.
hang on in regards to nicotinic acid can you take it for a period of time until flushing effect goes away and see if it is related to flushing effect, i have seen people reverse their epigenetic age by 2 years from taking 500mg nicotinic acid per day for 6 months
This highlights the importance of testing. In my case, the flush was strong, and DunedinPACE was terrible, not close to any other test. With 60 mg NA, no flush, NAD increase, no/marginal impact on DunedinPACE. Nonetheless, I'm working on ways to increase NAD without NAD precursors, which shouldn't mess up DunedinPACE, either (or maybe they will, we'll see!)
Why NMN and NA, and not NR?
There was a trial with NR with good results.
How do you intend on consuming the fenugreek seeds? Years ago I would drink sprouted fenugreek seed tea for female health issues. I would sprout them for ~ 3 days, refrigerate overnight (can't remember why) then boil them for a few minutes, let it sit for 20 min, strain and chug b/c it is terribly bitter. IDK if you can extract trigonelline this way. Sometimes I would save the sprouts (which surprisingly retained their firmness), refrigerate them and use them on top of salads with plenty of vinegar to cover up the bitterness. I would cycle use of the tea off and on and I recall that when I would start using again I would have to start at a low dose and work my way up, or I risked triggering a migraine. IIRC the tea seemed to improve muscle gains from weight training - a result I was not expecting since I had not heard of that use for fenugreek at the time.
I haven't tried this in a long time since I am now allergic to pretty much everything and react badly to all the legumes I've tried - even my beloved sprouted beluga lentils. I still have a bag of fenugreek seeds from Johnny's (good for sprouting, but expensive and don't get their broccoli seeds since they aren't actually broccoli).
Why are you using NA and NMN interchangeably? They do not have the same effects in the body...that's very strange..
I'm not sure why you think I'm using them interchangeably, I did separate experiments with NA and NMN
Interesting result. 10.3389/fnut.2021.756243 - these guys say they doubled the telomere length over 90 days with 300 mg of NMN. But, as you said, trudiagnostic doesn't really measure the telomere length.
So telemere length grew from ~Oct '22 to ~Jan23, then ~flat till ~Sep '23 then grew again till ~Nov '23 (approximates from pausing this vid). Those 2 growth periods did they correspond with more CR than other times? Or with something else notable? Also, were you taking the 60mg NA during one of the growth periods?
Thanks!
Hi @geode232, on the channel there's a playlist with telomere videos, where one of the strongest correlations with TL in my data is for body weight. I've gotten leaner over the past year+, which may explain the TL improvement in 2023 vs 2022.
Hi Mike, great video, been waiting for this one!
Do you think this telomere length result is significant enough to conclude NMN is a net harm? As I understand, it's only loosely correlated to health outcomes, and maybe this NMN change will unlock pathways (eg, change dietary correlations) to improve telomere results long-term
Thanks @the123apz. I'm not sure about a potential NMN-telomere length link, but I do find it interesting that TL was > 7.1kb for 7 consecutive tests, but shorter with high-dose NMN.
Do you think the DunedinPACE effect is a simply a chemical effect on the test or is it actually promoting aging? I mean is the NA somehow interfering with the test or is actually impacting a biological process negatively.
I think high dose NA in my case is bad for biomarkers. It's not interfering with the test, as lower doses (60 vs 600 mg/d) of NA have a minimal effect on DunedinPACE.
The trigonelline experiment is so interesting. I believe that 16 or 25g may be overkill as when translating the nmn dose from mice to humans, some sort of correcting factor was used. Either scaled by metabolic rate differences, surface area instead of weight or something of that sort.
Some early self experimenters in longecity tried translating the mice dose like you did and ended up with 18g/day If I recall correctly, noticed benefits and no ill effects but eventually dropped the dose to around 1g with the same benefits. So I hope this could work and that your experience ends up being that you just need 1 or 2 grams of seeds.
Thanks @eruiluvatar236. Unfortunately, trigonelline content in fenugreek seeds may be as low as 2.6 mg/g (that data is coming this Sunday), so 24g of fenugreek seeds may only yield ~60 mg of trigonelline/day. The only way to know is to test, and I'm sending blood for NAD and metabolomic analysis on Feb 2/2...
@@conqueragingordietrying123 I thought that you scaled by body weight from mice and was using a much larger dose. If that is the case fenugreek seeds are not that good of a source. Indeed I googled it and they seem to go from 2mg/g to 3.8mg/g.
Trigonelline seems interesting to me because of the half life, lower doses and because it should be cheaper to make than nmn. Also personally I have bad MTHFR so the extra methyl seems like a good thing.
Anyway lets see the results.
Even low dose NA and then NMN didn't work for me, it gave me leg pains in joints and connective tissue something like a kind of neuropathy. I've been athletic all my life and never experienced anything like that. Pain didn't go away until months after cessation. It's not for everyone apparently.
Yep! Even more the reason to look for other ways to impact NAD (trigonelline, for ex)
I got that from high dose nicotinamide. I had difficulty figuring out what was doing it, because I take something like 50 different pills, and it takes time to develop symptoms and time to have the symptoms go away after cessation. I was very lucky, I heard about it from Sinclair on some random video. It can stop or slow collagen synthesis. I quit that immediately. Took around 9 months to recover, but it left wrinkles on my face that were not there before. Joints are all good, now. Actually, they are very good. I tried a bunch of things to try to get them to build. The combo that actually worked for me was glycine and TMG. I think my recovery was extra slow because I think I cleared out too many senescent cells that are needed for healing. I took large doses of senolytics while "fasting mimicking." It was probably fine the first or second time, but I should have waited a year for the next time. I think once a year to year and a half is probably best, or possibly even longer. The first time just had such amazing results, I was eager to make it part of my life once every few months. But that was way too frequent. I think my ability to heal is back to normal, but that took a couple years.
Despite all the missteps, I am happy with my journey toward dealing with aging and health. And I feel good. My labs are mostly very good, and much better. And I can't help but get better, as I still have a lot I can work on, especially in the exercise and body composition areas.
@@ChessMasterNate Hmm I can't figure out the pathways to nicotinamide stopping or slowing collagen synthesis and never heard Sinclair mentioning that. Is there evidence behind that? And, didn't SInclair, by any chance, explain the details behind it?
I mean anything specific related to collagen. Otherwise, all NAD-boosters used alongside unhealthy diet and life style potentially increase the inflammation in the body where it is already present because it also (beneficially in normal conditions) powers the immune cells and helps to clear out pathogens, foreign material, BUT if there is depletion of useful nutrients for effective immune system (like butyrate and magnesium from fiber-rich foods for example) and metabolic issues, depletion of cofactors to enzymes important in NAD cycle, the NAD would fuel the chronic inflammation.
Did you take double the dose of TMG with the Nicotinic acid? I was told to do this to reduce negative impact of the Nicotinic Acid.
TMG is overrated, at least for me. I already get about 1g/d via diet, and I've supplemented with up to 3g in the past with no effect on methylation, using homocysteine as an example.
@@conqueragingordietrying123 It may be for such a high dose of NMN you may need a higher dose of TMG to compensate.
what is the negative impact of Nicotinic Acid?
@@sobeck6900Methyl donors sink.
Niacin, the B vitamin that was previously used to improve lipid profile and reduce the risk of heart disease, promotes arterial inflammation and cardiovascular risk through its metabolites
What pathways did Nicotinic acid contribute to the faster rate of aging?
*high dose, and I have no idea
Were you flushing from the 600mg?@@conqueragingordietrying123
@@conqueragingordietrying123 Might be worth asking some researchers, I don't have any contacts but it could possible be an interesting discussion topic. Great video, I appreciate the work you put into these presentations.
@@bowser2005 I have no idea what biological pathways regarding aging that nicotinic acid might contribute to, but we already know from cardiovascular/lipidology research that *high dose* nicotinic acid has not reduced overall, heart-related, or non‐cardiovascular mortality, in spite of it increasing HDL-C, lowering LDL-C, and lowering triglycerides. @conqueragingordietrying1797 could be right that there is a relatively lower dose sweet spot.
So why not rake niacin instead of both of them 😅😅
Is aging dot AI still around? The links do not work for me.
Nope, unfortunately not, despite my best efforts to try to have it revived...
nice work.
If the telomer length proxied by methylation appears shorte, then there was less methyl groups in/at the telomers., making them to oappear shorter. High dose NA or NMN, without raising the capacity of NAMPT (rate limiting) would mean that a lot of methyl groups would be used for expelling meNAM, and methyls then missing for the DNA. This could mean that telomers are actually not shortened.
Hence a couple of of direct measurements of telomer length and trudiagnostics' proxy length would be indicated for calibration.
on the one hand, too little methylation can result in impaired gene activation regulationo, but on the other hand, the OSK rejuvenation also works by decreasing the methyl lad of the DNA...
Everything not that linear i am afraid ...
According to Charles Brenner there is no correlation between blood NAD and biological aging. He also argues that NMN needs to be turned into nicotinic acid to be absorbed into cells, so if that's true, I would think that a high dose of NMN would have the same effect as a high dose of nicotinic acid?
There are plenty of studies showing that blood intracellular NAD levels correlate with tissue levels
I'm on the side of resisting age-related NAD changes, with the goal of improving mitochondrial metabolism. To test that, I'm also sending blood for metabolomic analysis on the same day as NAD tests, which is the closest that we can get to a tissue biopsy
Whether that impacts longevity in people, we'll see
I have been considering fenugreek seed extract as well as I don't do well with coffee. After doing some research it appears there is very little standardization from the supplement manufacturers for fenugreek extracts. I like to be precise, how did you decide on dose and brand?
I put roughly zero weight on their telomere length estimate. DunedInPace minimum counts as something! Because it's the best predictor of all cause mortality (outside of Levine phenotypic age, which is also very strong in this area). If I were you, I'd double down on NMN supplementation --- experiment to find the minimum effective dose, or just continue 2g/day to get confirmation?
Thank you for your information and your time
Great job
Thanks @mikeghafoori8227!
TA 65. Astragalus. Telomeres. Health Guru.
It seems that your fat loss/higher calorie restriction is what drives the DunedinPace improvement.
Definitely possible!
I'm sorry, Michael, but only in one case - there is no statistical power at all. I think it's too early to draw any conclusions about correlation on N=1. It could be a false positive. At least repeat your experiment several times to be sure of the result.
Yes, definitely @madpower2000, I agree
Different people also might react differently too. Talking from personal experience with NMN, NR, Nicotinamine. Every time I used any of these I would get a growth (chalazion) and once when I did not stop in time it grew out of control and had to surgically remove it. Usually they get sucked back by the body upon cessation. I personally am N=1 but it’s N=10 for the times I tried and it’s always repeatable. Some have suggested I might have the MTHFR mutation which is on my plan to test for. It does make sense though.
(I did take it with TMG too)
Hi Mike, Can you let us know if you experience other benefits from fenugreek, such as better blood sugar levels and higher testosterone? Thanks.
Hi @justsaying7065, potentially yes-the plan is to send blood for NAD and metabolomic analysis on 2/2. if NAD isn't impacted by 24g of fenugreek seeds/d (I've increased it from 16g/d!), that experiment will end before the full blood panel, scheduled for 3/4.
I'd be curious to know how CD38 affects telomeres, and how the interventions that you tried affected your CD38 level.
60g of fresh parsley is in the everyday approach...
Say goodbye to mnm folks! I have feeling that was not just an outlier. I am happy however, that there exist a cheaper alternative. My only concern is that the brand is listed on Amazon as prop 65 for heavy metals. Do you have any thoughts on that Micheal?
Can hexanicotinate be used instead of nicotinic acid? Also, how do you consume the fenugreek seeds? Can they be swallowed without chewing (unlike flaxseeds, which can't be digested when intact)?
I'm not sure about hexanicotinate, as I haven't done the experiment-the best way to know would be to measure NAD levels
Initially, I started with whole seeds, and almost broke my teeth, so I ground them. Then, after eating the raw ground seeds for 1 day, there's a weird taste to it, so I boiled them with other stuff for about 10 minutes this morning. There's still a bitter taste after cooking-I'm in the process of sorting out how to best mask/get used to that
Hexanicotinate in high doses can be liver damaging. 60-100g NA seems to produce a totally tolerable flush AND the desired bump in NAD+.
@@kkostadinof what is high doses? I have tablets of 250mg niacin equivalent each, and I'm taking a fourth daily. Haven't seen side effects.
Hmmm? I just ordered for the first time ever 300 mg of NMN. I haven't gotten them yet but I hope it's safe to just take one capsule a day?
Hey @paulfiedler9128, there are a few videos in the NAD playlist that provide more context. For example,
ruclips.net/video/SwggBuuamCk/видео.html
Also, 300 mg of NMN didn't increase my NAD, so I'd recommending testing to see if that's true for you...
Thanks for all the info 😃
What will your feenugreek seed dose be?
16g
@@conqueragingordietrying123 that is enough to make you smell strongly like maple syrup. My wife complained. Clover is also high in trig
Did you take TMG along with NMN? I understand that it's advisable.
I'll cover this in a future video, but there are a lot more methyl donors besides TMG (proline betaine, tryptophan betaine, methyl-nicotnate, others), which didn't work to reduce homocysteine in my case with doses up to 3g/d, so I'm not sold on its potential impact on methylation in my case.
Fenugreek unfortunately may increase prolactin and inhibit of leptin secretion.
Interesting, thanks for that, can you please share some links?
@@conqueragingordietrying123 When I post URLs my comments seem to disappear.
@@conqueragingordietrying123 I had made 2 attempts to reply, but the replies somehow disappeared.
Does trigonelline eventually turn back into nicotinic acid? If so maybe a high dose of trigonelline would have the same negative effect on pace of aging
It does, Dr. Vincenzo Sorrentino showed that in this video:
ruclips.net/video/nd4rOop_08U/видео.html
Ah, the question is dose-it's hard to get more than 100 mg (or more) of trigonelline/d via diet
Hmm, thats a good question. But even if high dose of trigonelline used, we can't be sure it reaches the receptors that pure nicotinic acid otherwise would reach (like the GPR109A receptor), depending how it would be compartmentalized in our cells and tissues. Also, the half life of nicotinic acid is quite short, like 0.5-1 hour or something, can't remember atm exactly, but even at large doses of trigonelline, it would probably not be converted to high levels of nicotinic acid in the body but used more continuously instead. The latter makes a difference, because even the GPR109A receptor signaling depends on the concentration of nicotinic acid in the body.
Do you take apigenin as well? Just ordered a nad test and should be interesting. I want to do the aging one, too!
Not as a supplement, but I eat 60g of fresh parsley/d, which = 100 mg apigenin
Please keep us posted on the NAD result!
What dosage of Fenogreek seeds would you suggest?
In the last video, we saw that trigonelline increased NAD at a dose of 300 mg/kg BW in mice. The human equivalent dose is 1.6g/d, and to get that, I'm currently eating 16g of fenugreek seeds.
@@conqueragingordietrying123 Excellent, Thank you very much.
Is this just a methylation problem, where you need methyl donors? Methylation pathways are pretty complicated to balance especially if you have gene mutations.
I don't have MTHFR SNPs, as homocysteine was < 7 in my early 30s. It's likely a methyl donor issue, but which one is the challenge. In my case, TMG, methyl B12, and methyl folate are a lot higher than the RDA but haven't made much of a dent on methylation markers.. Proline betaine and trigonelline are potential methyl donors that I expect to be beneficial.
I got Sneezing, runny nose from nmn 😮 why ?
Sorry, what kind of seeds do you take?
English isn't my mother tongue so I have some problems with strange nutrition names.
He takes fenugreek seeds as a source of trigonelline which hopefully will boost his NAD without negatively effecting his epigenetic pace of aging or his telomere length.
the scientific name of the plant is Trigonella foenum-graecum
Thanks! Intresstingly I already got a truckload of it in my kitchen
Can you try nigella sativa seeds and their effects on biological age
Hey @rianeon, do you mean DunedinPACE? Why would you expect that nigella seeds would specifically make an impact?
Always fascinating!
Isn’t it true that coming into contact with a virus can temporarily raise biological age? That’s always a possibility to consider, even if you’ve never gotten sick it is flu season so the body can be busy fighting things
I did on a full blood panel on the day of the 0.98 test-no aberrations anywhere else, including hsCRP or immune cells
Study the integrated stress response the body uses in response to viruses.
The body lowers protein quality control when infected so viruses can't hijack protein production machinery to efficiently replicate.
It compromises or lowers the 'fitness' of most cells in the process, though.
As we get older it tends to get overactivated or stuck activated. Loss of protein production quality control via the integrated stress response is a major driver of aging via EIF2A and EIF2B, ATF4, ATF6 and various other genes.
Do you have your own lab? How often do you do bloodwork i imagine it adds up fast cost wise.@@conqueragingordietrying123
interesting results!
I’ve been taking 1g NMN for about 6 months before my yearly Trudiagnostic test and my pace of aging went from 0.85 to 0.97. 😢
I'm not surprized. Because 1mg is tiny and useless.
@@musaire oops I meant 1g.
@@SamiSami-sb3ze The most common pathway to that is NMN fueling inflammation. You need to fuel health instead. :) That's why I'm sure NAD-boosters only work when accompanied with otherwise heathy diet and life style :) The stuff that directs the NAD use. The stuff that controls NAMPT enzyme, inhibit inflammatory NAD-consumers etc. Thats the way, but a crucial way, we definitely wanna be on that way and NAD-boosted.
Also, we need to be sure our NMN is top quality product. It's easier with nicotinic acid (if it worked) - because we know the quality of it, somewhat, by the taste already and it has excellent heat and humidity tolerance.
Do i have right or not lets see
i was wrong but did you check the trigonella? i will be do this in next months
@@Anonymousextb Experiment currently in progress!
I will take Peter Attia’s critism point here on these age test.
Can a couple of gram NMN or any other supplement for that matter really slow your age speed that much down?
High-dose nicotinic acid likely made DunedinPACE much worse than my baseline (0.98 vs < 0.8), so supplements can definitely impact it. Whether it can be improved via supplements, I'm not sure, and skeptical, too
I don't think Attia's point is valid. Yes, the markers are malleable, but this is the point actually - staying healthy, fit and young takes daily work to change them! Vo2max is also malleable, but Peter somehow doesn't think vo2max is invalid.
@@erastvandoren
I am confused?
You write: "but this is the point actually - staying healthy, fit and young takes daily work to change them!" This is what Peter Attia says and what I agree on aswell.
Moreover, he (Peter) don't believe a single supplement will decrease you aging proces by 1/3.. as claimed in the video.
In my eyes it seems you agree on this?
@@conqueragingordietrying123 I appreaciate your work and it is so nice that you show your numbers! big fan!
I just think when NMN has such a big effect on your speed of age.. we should question these test.
This feels like a bait and switch based on the title....in the title you list NMN but then proceed to talk about Niacin/Nicotinic Acid. They are not the same thing. NMN does not have the same drawbacks of Niacin.
NMN is a part of the story, there's no bait and switch.
Your telomere length is weird. How come they have been growing over time? They should be shrinking.
In earlier videos, we saw that body weight reduction is significantly correlated with longer telomeres, so that's my best guess
Nicotinic acid, through its metabolism, get methylated and reduces the bodies methylation capability.
No. It's a nad salvage and electron transport chain issue.
If NAD salvage is dysfunctional then high dose NAD precursors just rapidly convert to NADh.
Overloads the electron transport chain, resulting in a buildup of H202 and depleted mitochondrial catalase.
H2O2 is an important epigenetic signalling molecule in small amounts. In large amounts, it will mess you up.
Greying hair and fatty liver is the tip of the iceberg of what will happen. Telomere depletion and rapid aging can result.
Especially if you don't have appropriate inositol pyrophosphate metabolism to maintain telomeres.
@@darkhorseman8263 😆. Impressive explanation, but not what most of the literature says.
@HateDietPepsi This is precisely what tens of thousands of studies into the electron transport chain, mitochondrial membrane complexes, nad salvage, and Nad+ / NadH ratio tells us.
Yours is an echo chamber of a complex idea explained quite badly.
I bet you don't even know the epigenetic modulators of methylation and demethylation, how the TET and DNA methyltransferase genes work.
@@darkhorseman8263 Bet you don't even realize that I'm much smarter than you.
@HateDietPepsi Dunning and Kruger are smiling right now.
watch out for the smell that fenugreek gives u
i was also all hyped up years ago when i heard about their supposed strength and testosterone benefits and dr greger showing science sugggsting that they make u smell like "maple syrup" was even more promising
however turns out that was just some biased vegan pink glasses view: the supposed "maple syrup" body smell in my opinion is WAY closer to "fresh urine smell", i discontinued the fenugreek, later i did fenugreek extract tho, which didnt have that smell issue, however they were a bit pricy so i discontinued them for the time being, maybe later when they cheaper i add the extract back in 😋normal fenugreek not viable tho ;S just like with cumin (makes u smell like sweaty female genitalia) and roasted "coffee stank" (as u would say it xD)
I guess it depends. When I drank fenugreek tea years ago it made me smell faintly of maple syrup and it was pleasant.
I also got sick of that smell, it wasn't unpleasant, but it was very strong and ended up overloading me
Or everything is fine and the issue is with the test.
Double blow. Ouch!
Definitely interesting comparison! I wish we could see these replicated in more than one test only - for both, negative effect for nicotinic acid or any effects of NMN. I think I can't be too sure otherwise :D because I think even some cold viruses or the recent lab-leaked bioweapons may mess with the DuneinPace value - this is certainly true for the recent SARS viruses - I mean I can visibly see people hair turn grey quickly. AND I wanna point out that this could happen even without the major symptoms of the disease tbh. So, that's why these NAD+ boosting results could be fluctuating a lot I am afraid :) and nibble away on youthful markers, temporarily, even when the NAD+ levels are healthy.