Plasma Metabolites Of A Healthy Lifestyle In Relation To Mortality And Longevity
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- Опубліковано 30 бер 2024
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Papers referenced in the video:
Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population pubmed.ncbi.nlm.nih.gov/29712...
Association of dietary quality indices with glycemic status in korean patients with type 2 diabetes pubmed.ncbi.nlm.nih.gov/23908...
Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies pubmed.ncbi.nlm.nih.gov/38366... - Наука та технологія
Hey everyone, I made a mistake, and my apologies! CE 22:6 contains DHA, not EPA as shown in the video.
Thanks! The "brain" one.
I was going to write this :) EPA is the one C20:5, it is good too but DHA is better.
For me, modest drinking no longer works, if it ever did. Repeated testing, based on my Oura data and simply how I feel, shows that even moderate drinking negatively impacts my sleep, especially REM. Given that I'm older (69) and have suffered from sleep issues for over a decade, my self prescription is zero alcohol. Zero alcohol combined with no food within 3 hours of sleep significantly improves total sleep time as well as duration of deep and REM sleep.
Yep, same, on the zero alcohol (but not never, I'm still open to it on "special" occasions), but for many people it may have a small (to neutral) benefit in relatively low doses based on large epi studies. For ex., pubmed.ncbi.nlm.nih.gov/37000449/
Same here.
I believe that this is an artifact of epidemiological studies. Anyone find a RCT, or plausible mechanism for alcohols health benefits?
Mendelian randomisation studies shows alcohol damages brain age from >0g/day.
There is no safe dose of alcohol.
what do you understand by "moderate drinking"? 2 whiskeys each on Fridays and Saturdays? 350 ccm red wine for consecutive 3 days? or already 50 ccm once every week?
note that the form\type of the beverage matters a lot, because of the other ingredients. I could not sleep with white wine or champagne after 6pm, while red wine sends me to bed earlier than scheduled by habits
@@monnoo8221 My tolerance may just be lower now due to age. But 1/3 rd of a bottle of red wine which is 250 mls or about 9 ounces affects me. Occasionally have a single glass (approx 150 mls) with an early meal and usually fair OK. Just can't do it daily. I'm coming from a place of bad sleep already though so all I can do is rely on my own data. I would love to be able to routinely drink a couple of glasses of wine with dinner or a couple of beers and be able to sleep well, but just doesn't work. So now limit myself to a little wine or beer when my kids visit. Don't recall a problem in my 40s and 50s but I wasn't tracking sleep data so don't really know.
Dr here. routinely look at labs. I really appreciate your quality evidence based presentation on the true comlexity of even a seemingly banal result like a serum triglyceride level . For instance i learnt today that TG esters levels do matter . All this detail is one more piece to the puzzle, tks
Wealth has a big impact. Having access to good healthcare and dental care is crucial. Also air quality.
Kind of surprised that quality sleep was not one of the factors. Very interesting!
Possibly an oversight. But is it subjective?
I took a break from longevity research and YT. Back now, looking forward to catching up on your excellent content. Glad to see I can swap annoying NMN for 60mg nicotinic acid.
Hitherto life long Gin & Tonic man here . Unfortunately had to go Xmas and birthday only treat now due to underlying AFib . My own 24 hr ECG monitor would read from occ baseline atrial ectopic to about 6 or so an hour with occ couplet after a few G&Ts . Interestingly never got ventricular ectopics .Repeated the experiment many times unfortunately the same result. Great collection of Gins now sitting in my cupboard going to waste. Fear of stirring up my Afib keeps them there .
Superb insights!
Thanks @andrewpawley8883!
I wish this study also looked at irreversible metabolites which accumulate in the body forever and when the amount is great enough, interferes with mitochondrial function. Glucosepane is a known AGE (Advanced Glycation End-product) which results from excess Glucose in the blood (high-carb diet.) Lipofuscin Compounds appear to be the result of excess Unsaturated Fats (both Poly- and Mono-) in the blood. It is said that we need some minimum level of glucose and unsaturated fats (both Omega-3 and Omega-6, even though the latter is considered inflammatory) but no one agrees on what these minimum amounts are. I try not to be an absolutist so I eat some carbs (average somewhere between 50 to 100g/day) and I take a fish oil supplement (2.4 g/day) but no more than that. The idea of irreversible metabolites piling up like a landfill bothers me. 😊
I highly doubt sfa contribute towards the formation of lipofuscin. If anything, it's just the opposite. Not being in a ketotic, catabolic state long enough for meaningful autophagy to occur
@@Ardentic-aa Saturated Fat won’t form Lipofuscin Compounds. They’re saturated and that’s why lard and tallow can sit at room temperature and not spoil. It’s the Unsaturated Fats that will readily combine with whatever is in the bloodstream near it. Autophagy can’t help with irreversible metabolites because we have no enzymes to take them apart. There are many researchers looking for enzymes that will take apart Glucosepane and Lipofuscin Compounds but for now, at least to me, it seems safest to minimize the formation of these compounds in the first place. Have I chosen The Right Path? No way to know until I live out my life.
@@gekizai I think I might have speed read your comment and was somehow left with the impression you were against sfas. Sorry about that.
@gekizai I'd add, though, that there are plenty of young people gulping unhealthy seed oils and they don't develop spots. I'm not sure if I want to go with: it's probably just defenses and no active cleanup. I think the lysosomes do a poor job at something. But hey, thanks for the feedback!
As far as I remember DAGs are the fats which mechanically resist insulin in insulin resistance (blocking GLUT4)
This is very interesting.
Thanks!
Thanks for your support, @cravarc!
just rewatched it , the years of MV use as a component of AHEI score was to parapharase Sergeant Schulz , very interesting .
Thank you for another thought provoking presentation. “Less unsaturated” is a double negative suggesting that saturated fat triglycerides code for longevity? The other curiosity was the 5-fruit portions per day. In one of your earlier study analyses presentations suggested that lowest ACM was associated with an intake only 1.5 portions of fruit per day. Both statements cannot be correct!
Thanks @davidgifford8112. The opposite-having more SFA-containing FAs would be found in the TAG > 56 and < 3 double bond metabolite class. Higher levels of this TAG-containing group were associated with a reduced odds of living > 85y and had an increased all-cause mortality risk.
In contrast, there were a couple of TAGs > 56 carbons and > 3 double bonds (i..e containing more unsaturation) that were associated with the healthy lifestyle score, which suggests those TAGs as potentially good for longevity (TAG 58:9, TAG 56:8 as examples).
The strength of this study is that it combines the 5 factors, including diet, which is a likely better approach than only looking at diet-mortality associations.
“Less unsaturated” might be a double negative syntactically, but not semantically.
I assume it simply means "Less of unsaturated triglycerides".
Without checking it, I think the idea is that low triglycerides in general is healthy. But here he tells us that we especially want low unsaturated triglycerides. So thinking that we want more saturated triglycerides is surely wrong!
General practice doctors are so fachinated about blood fats, such as LDL. I usually ignore them on that issue, and care only for high HDL and low triglycerides of what they meassure. So Im used to think low triglycerides is good for me.
If I got it right, that's simply because excessive carbs is turned into fat, and low triglycerides means that doesn’t happen too much.
But I might have some delusions about that. Theres so much confusion about blood lipids!
Thanks again. This quite entertaining tho' too old for it to be of benefit personally. I'm also impressed by how much you follow the literature for example your fenugreek intervention come at the threshold of this release: "Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. Nature Metabolism, 2024"
Thanks @bhut1571. I've been waiting for that paper to be published, as Vincenzo Sorrentino presented that data at ARDD...
Very interesting video again, thanks! What is your take on rapamycin? And what about Matt Kaeberlein Optispan, he seems to follow your philosophy on being conservative on supplements.
Thanks @mannmstorm. Whether it's rapamycin or anything else, supplementation should occur with objective biomarker testing (many, not a few), to see if the net systemic effect is positive, neutral, or detrimental. Not tesitng is simply making an educated guess based on animal studies or RCTs in other people...
Compared to LUSTGARTEN, Matt Kaeberlein is not so conservative on supplements as he seems to be.😊
Is that DEXA scan mentioned near 16 months ago in the works? I am curious about the effects of reducing your calorie intake.
Hey @ChessMasterNate, yep, I did another one in December 2023, but there are so many videos to make!
Unfortunately I used 2 different DXA machines for 2022 and 2023, so there is a disparity in the results-according to that analysis, the 11lb weight loss was almost entirely lean mass. But that doesn't make sense because I didn't experience any strength or functional decline (which would be expected with a loss of muscle mass), and bone density was almost identical year-over-year.
If muscle mass was down, BMD should also be down, but that's not the case. Nonetheless, I'm thinking about a repeat DXA using the same machine as 12/2023 in June/July, or at the latest Dec 2024.
@@conqueragingordietrying1797 Perhaps fat within the muscles was lost? If you made circumference measurements, you could probably rule that out. But, yes, most likely inconsistency between machines. My plan was to do DEXA once and use that as correction for my Amazon listed " GE Smart Scale for Body Weight and Fat Percentage with All-in-one LCD Display, Digital Bathroom Weight Scales Bluetooth Rechargeable Body Fat Scale, Accurate Weighing Scale, 396 lbs ," correcting all the data going backward and forward, and use the scale from then on. Maybe another correction a few years later. I like the daily feedback. The app also has a place for body circumference measurements. I have done that 3 times, and plan to do that for every 10 lbs lost. I did lose some size in the extremities as well, but it says I have not lost any muscle while losing ~30 lb (I actually have lost 60, but I have only had the scale for the last 30). I had another body comp scale. It was all over the place. I bought the new one because it has a phone app, so I don't have to record the data, and it has more parameters. I will probably do the DEXA when I am close to my composition goals according to the scale. Of course, it would be nice to have a better, before vs after. But that is just pride nonsense, and I don't have money to toss away on that.
I was wondering about your thoughts on pentadecanoic acid (C-15) supplementation, and on Pulse Wave Velocity measurements. Amazon has this device that is supposed to evaluate your cardiovascular age: " Internal Age Health Monitor, Fingertip Health and Fitness Tracker. Measure Biological Age, Pulse Wave Velocity, Aortic Stiffness, Sp02 and Heart Rate BPM with our iOS and Android App " There seem to be some pretty grand claims on these, and I don't want scammed. I don't hear other age-hackers mentioning these, so that makes me skeptical.
And it would be great to have a video of all the abandoned attempts you have made. Not necessarily in detail, just the things that did not seem to work for you. This is as much what the show is about, as anything. I was going through a bunch of your old videos from before I found the channel, and you were working on lungs because of the correlations with longevity, but the exercise did not seem to work. Have you tried just blowing out or just sucking in? Developing one may interfere with the other. I suspect blowing out is the important one. That helps people cough up stuff that gets in their lungs. Inability to cough strongly, kills a lot of very old. My mom (88-years-old) still has a very strong voice because she was a soprano that sang in various things like the Master Coral for the San Diego Symphony. Also, when I looked at what around 150 centenarians ascribed their longevity to, there were 2 surprises to me: dancing and singing were near the top (I tabulated everything they mentioned in a spreadsheet). I think dancing prevents falls or reduces the risk of breaks, and singing keeps those lungs strong. I also looked deeply into what actually killed people at different ages...which is why singing and dancing stood out to me. I think we run a gauntlet, and have to get by all these things. I am not a big believer in delayed compressed mortality, where supposedly the very elderly die of the same things later. The data says that is bunk. Only a small percentage of 100+ for example die of cancer, and likely they die of a different kind of heart disease: Wild-type ATTR. The only areas where that might be true, to some degree, are lucky people with genetic variants of the gene that makes SERT6 and people with a lower core body temperature...even a tenth of a degree makes a difference. I think everything else is dodging. Raising NAD+ seems to have a lot of false steps and wack-a-mole fails. I bet there are a bunch of other things that fell flat, that are being touted by companies and agehackers, who are not doing the necessary measurements. I really like the objectivity of measures. Too bad, there is no easy, cheap way of making tests N of 20 or 200.
Another video I really want to see is the lowest all-cause mortality point on each of the 50-60 usual biomarkers. Though, if you are saving that for a book, I understand. Pretty hard to dig them all out of the videos, though. And you may have gotten better info over the years.
@@conqueragingordietrying1797 The comment I made disappeared. I think it was my fault. Instead of editing my comment, I replied to my comment, and I think that killed the real comment.
what was your Kynurenine/Tryptophan on this test?
My best yet, 0.02
Michael, have you experimented with Sirolimus (Rapamysin)?
Hey @paulfiedler6820, not yet
@@conqueragingordietrying1797 I've been following Professor Matt Kaeberlein's research (Optispan UA-cam) with rapamycin and it looks promising. Before it became available as Sirolimus with medical insurance, people would have to go to one of the three NYC docs that prescribe it and pay around $399.00 for a 20-minute interview and one-month supply. I am a subscriber to your channel and think you are doing interesting work. I grow microgreens in my Brooklyn apartment and on your recommendation, I'm using fresh parsley and dill in my protein smoothies. Waiting to see my Primary doc in May to see if he'll prescribe sirolimus for me. He had no idea what rapamycin was last time I had a physical and he kind of looked at me like I was nuts while I was telling him about the history of rapamycin. Maybe I shouldn't have started with the soil samples from Easter Island during a 20-minute appointment. I'm a practitioner at FullScript (CUNY Health Coach Certification) and for the time ever I ordered NMN. I'm 67 with painful osteoporosis in my lower back and looking for something to help. The boswellia, turmeric, and gut-killing Advil aren't doing the job. Thanks for your work. I'm going to be a $ Patreon member soon.
thank you very much for presenting that study. Good mental food on this cold Easter sunday :)
For me, the most surprising part of it is about the unusual triacylglycerides >C56:3+ . They are strongly correlated, meaning you can have too little of them and having more is helpful for longevity. An article from 2012 "Very long-chain fatty acids: elongation, physiology and related disorders" does not mention them.
Technically they are kind of waxes, but as waxes they are unusual as well. My guess is that they are related to the well-functioning of the endoplasmatic reticulum and the capability to produce sphingomyelins.
I discussed the subject with Gemini and it mentioned: "The emerging information supports the possibility that these unusual TAGs play a role in organelle membrane structure and function, particularly in the ER and Golgi."
I find it comical where AHEI (and many other recent WHO based vegitarianistic) advocate low fatty acids intakes yet, (yet again), saturated fats are more beneficial (if I'm reading the ester charts of what is benefical) then fats in the middle (the recently debated problem of linolenic and better known problem of aracadonic). Ancestrally for humans, and typical for hibernating species, the rise in PUFAs in the food chain approaching the season of Fall, initiates tupor, insulin resistance leading to the seasonally beneficial weight gain, to survive over wintering. Except today PUFAs are a majority of the SAD macros, 365, and we now have type II diabetes and obesity 365. IE thanks to poly unsaturated fats and an abundance of carbs, both of which ancestrally where scarce thus most species where evolved to grab on to both and not let them go. Us health oriented types are finding it difficult to excret PUFAs and improve our Linolenic : Omega 3 ratio and percent Linolenic. ;( We test via OmgaQuant several times a year as we try to reduce our life time burden of Linolinic, as we desire to improve insulin resistance Its tough.
@@MsElaine122 do you mean linolEIc, not linoleNic acid?
@@MsElaine122 lipid metabolism as an entirety is incredible complex, and I think we barely scratched the surface. One theme which gets more and more obvious is that even for the three categories energy carriers, or what we thought to be so, like C16:0, information matter, aka messengers, building material many compounds can change their roles. E.g. I did not find a convincing study as t why C16:0 can "be" inflammatory, triggers inflammation, or has negative effects on the metabolic network,...sometimes.
What about peptides and rapamycin or metformin? Why don’t you use these?
Which of my biomarkers would you expect them to improve?
Isn't DHA docosahexanoic acid= (22:6) and eicosapentanoic acid = (20:5)? Therefore 22:6 fatty acid should be DHA, not EPA as depicted?
You're right, @williamthompsoniii4337, what a stupid mistake! Now in the pinned comment as an apology.
No worries! You are conducting an amazing experiment very well. Carry on!
Can you make a note about the association of CE with high density lipoprotein? Some controversy suggests HDL is good, others bad without considering VLDL. And people are prescribed statins for controversial reasons...
Got some papers for me to check out in terms of CEs and HDL?
@@conqueragingordietrying1797 Unfortunately your guess is a good as mine. These publications are all over the place. It might be worth your time to scan the horizon to see what you can come up with...
That list of healthy lifestyle factors seems very short!
It's interesting that a healhy lifestyle has a clear effect, though. But I think I have to find my own version of it.
Isn't it rather odd that we all know what a healthy lifestyle is, much better than research do, I think!
But still, we have some difficulty living it. Especially since obsessing about it surely Isn't healthy either.
I'm surprised that C15:0 didn't make it to the list after all the latest hype and research it got. And after all, if im not mistaken, it belongs to the family.
Great video👍
Thanks @etielahat9414. It's because of studies like this that I think the C15:0 longevity story is overhyped, at least for now, until more data is published.
C15:0 may be advantageous for dolphins, but for us they are not. They have an issue with membrane stability, as they ingest a lot of DHA. The effect is stiffening of high performance cell membranes like myelin sheaths, neuronal synapses, kidney glomeruli, and RBC. In humans we usually have the problem that those are too stiff anyway, because of malnutrition by ingesting too little DHA. technically, C15:0 would correct an overload of omega-6, but hats a bad idea. Too much C15 can result in triggering MS, and AD, or heavy symptoms resembling those
Hi! Your reply is too complex for me to follow. In my case, my MCV is on the 100s and I think it's because my red blood cells are dying too early. The thing is that in a later test, my numbers improved maybe due to O3 supplementation. Could this be correct? I'm further increasing the dose to check my theory.
@@viracocha2021 high MCV is pointing to folate or/and B12 deficiency, or (true) hypothyroidism. Together with the variability of the size, expressed as RDW = rbc distribution width, the doctor can assess the severity of the issue, or influence of other factors.
A high MCV means a larger surface, which can raise the hba1c simply because the chance of getting glycated is higher. proportional to the %difference of your MCV to the mid of the standard range. example: your MCV is 108, which would be 20% larger than 90, hence your hba1c is up to 20% higher than it would be with a normal MCV. if you would measure 6.5 Hb1ac = 6.5% of RBC are glycated, your true sugar load is apprx. 20% lower, that is 5.2 in this example.
folate/B12 deficiency usually also can be seen vi elevated homocysteine levels
Does Iollo measure plasmalogens?
Unfortunately not yet
@@conqueragingordietrying1797 Is there a valid way to decompose the study's findings into its individual components? Something like: phosphatidylcholine plasmalogens explained x% of the association..
'The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity.
Only think I'm missing in this lifestyle factors is moderate alcohol which is 0 g for me currently. So, I will start taking at least 5 g of alcohol daily. Thanks.
Keep in mind the limitation that all these recomendations are based on large averages over populations and nobody knows if that is good specifically for you.
We also should ask "well why would alcohol be beneficial in any amount?"
@@arihaviv8510 Likely the same reason low dose radiation, moderate exercise and many plant toxins are. This j-curve hormesis response shows up a lot.
in the light of ppl that are 65 and older have a protein rda of 1.2g/kg bodyweight (instead of the usually recommended 0.8g/kg bodyweight):
it might be worth considering to check out one's small intestinal permeability/absorption capacity (if there even is such a test) to estimate how strong one's guts are compared to the ones of young ppl 🤔
More fish oil
I guess you are talking about the US which is 47th on the list of life expectancy for males and females, lower than Costa Rica and even Reunion which is a major indictment for a country that spends so much on health car compared to those in Europe and Asia that do far better. So it is more pertinent for you to ask what are the factors that depress US longevities so far below the others and one can start with your junk food that you have foisted on the rest of the World along with your false nutrition standards and obsession with cholesterol. One of the most important factors in longevity is the microbiome which controls the immune and inflammation responses as well as diabetes and atherosclerosis via uptake of LPS particles and the impact of zonalins on gut wall permeability. Not all fruits, vegetables and grains are beneficial in this respect so advice to eat so many servings is not helpful. Finally we need to know the epigenetic effect of the diet components and their effect on mitochondrial function as well as energy intake and eating pattern. Nutrition is more complex than a few charts drawn from an observational study fraught with errors from people not remembering what they ate accurately.
This man is showing a study and is trying to explain it for free!You just throwing some unverified words!
i got 4/5 guess i need to become an alcoholic :(
Ha, alcohol intake is associated with a modest life expectancy increase, 2-3y, so I'm not worried about it.
I'm also at 4/5
It is because people who never drink usually have some other problems. Thats the problem with these observational studies i think you are referring to.
I bet that never drinkers (voluntarily) who had never drunk alc have a better life expectancy.
So... I am not.
I'm interested in AHEI defining 0 Alcohol servings per day as a criterion for minimum score and it improving with higher doses (up to a certain limit). Why could that be?
Low dose alcohol intake is associated with a small reduction for all-cause mortality risk in many studies, relative to non-drinkers. But not significant in a large meta-analysis (video on the to-do list), so it's still a debatable association.
@@conqueragingordietrying1797Basically it can be highly biased - people who drink 0 alkohol can have underlying condition, that prevents them from drinking it (assuming a study is done after exlcluding religious purposes)
@@danielwiczew Yep, that's true-it was included in the analysis for this relatively recent paper:
pubmed.ncbi.nlm.nih.gov/37000449/
The AHEI scoring looked like it was written by the religious backed Dieticians Accoc/WHO thats slanted toward vegetarianism. Vs recognizing humans historical roots. Nuts, Soy have many antinutrients, too low a protein. Blue zones ate pork of all things.. Blue zone questionaires asked; "do you eat meat" they largely said no. LOL the pollsters didn't ask; what protein do you eat? Alot of pork, lamb, goat. Local historical animal types. Alot of disinformation. But great channel and efforts by this poster!!
None of the diet indices is perfect, which is why I advocate for one weighing and tracking one's intake (as I do every day).
Fish oil is deadly. Brian Peskin. MIT
Do you have any paper?
@@viracocha2021 My Google searches come up multiple papers retracted, conflicts of interest, and an injunction by the State of Texas for unsubstantiated claims.
@@viracocha2021 UA-cam. Brian Peskin Fish Oil. 🤮🤮🤮
Rancid pill fish oil would be a problem. Eating canned sardines is a different story