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  1. TomBAvoider

    TMAO & Cardiovascular Disease

    Here is a super interesting study, showing another method of bypassing the TMAO problem: https://ahajournals.org/doi/abs/10.1161/circ.130.suppl_2.13412 Abstract 13412: 24-Hour Water-Only Fasting Acutely Reduces Trimethylamine N-Oxide: the FEELGOOD Trial Benjamin D Horne, James E Cox, Joseph B Muhlestein, Viet T Le, Amy R Butler, Heidi T May, John F Carlquist and Jeffrey L Anderson Originally published27 Mar 2018Circulation. 2014;130:A13412 "Abstract Background: Routine, periodic fasting is associated with lower risk of diabetes and coronary artery disease (CAD), and may reduce weight and improve metabolic parameters. Multiple related biological pathways are acutely affected by water-only fasting, potentially leading to long-term health improvements including lower CAD. Trimethylamine N-oxide (TMAO) is produced by intestinal bacteria and may increase CAD risk. This study evaluated the change in TMAO due to fasting in apparently healthy people. Methods: The FEELGOOD Trial (clinicaltrials.gov NCT01059760) included subjects free of cardiovascular disease who had never fasted for more than 12 hours (N=24). All individuals participated in a randomized cross-over trial of 24-hour water-only fasting and 24 hours of ad libitum eating. In this secondary analysis of stored samples, TMAO was measured by liquid chromatography-mass spectrometry. Results: Age averaged 43.6±13.5 years, 66.7% were female, and baseline TMAO averaged 27.1 ng. TMAO was reduced at the end of the 24-hour fasting intervention compared to the eating day (14.3 ng vs. 28.2 ng, p=0.034). The change in TMAO during the fasting day averaged -10.8 ng compared to an average increase of +2.6 ng during the eating day (p=0.23). For those randomized to fast the first day, the difference in TMAO change on the fast day vs. eating day (-12.1 ng, n=12) was similar to the TMAO change of those randomized to eat on the first day (-14.6 ng, n=12). For those who fasted the first day, TMAO levels were found to have returned to baseline after the full 48 hours of the study (baseline: 22.5 ng, 48 hours: 28.8 ng, p=0.55). Conclusion: Water-only 24-hour fasting reduced plasma levels of TMAO, a potential risk factor for CAD. The rapid resumption of TMAO production after renewed caloric intake suggests that fasting-reduced TMAO likely resulted from elimination of the substrate for TMAO production. Elimination of TMAO-producing bacteria may also account for this, but recolonization likely would take more time than it was observed to take for resumption of TMAO production. These findings suggest that routine, periodic fasting (multiple episodes over time on a regular basis) may have long-term impact on TMAO levels and related CAD risk, but this requires further investigation." I'm on a combination of 5:2 and 16:8 diet - I attempt to leave at have 16 hours of fasting every single day, usually closer to 18 hours, so I skip breakfast and eat lunch and dinner within 6-8 hour span; additionally on two days a week (Monday and Thursday), I only eat lunch and skip dinner altogether, i.e. very low calorie days 400 cal. more or less (which also then results in a 22 hour fast). I was already thinking about transitioning from eating anything on those two days - i.e. fasting for a total of 40-42 hours on those days. That gives me two water only fasting periods a week. Now it seems might even be useful wrt. TMAO. YMMV.
  2. TomBAvoider

    Colonoscopy Pro and Con

    If a test can definitely detect pre-cancerous polyps, then the advantage of a colonoscopy drops significantly. Accordingly to the article Mike linked to, sDNA is supposedly such a test, but I don't know how accurate it is - does it definitely flag a polyp 100% of the time? I don't know. Keep in mind that a colonoscopy does not guarantee 100% polyp detection either - not only does it depend on the physician administering the test, but there are regions of the colon that the colonoscopy does not properly reach. *If* a test would definitely discover polyps, then the only advantage a colonoscopy would have would be the ability to immediatly excise that polyp. Removing polyps seems a good idea, because according to studies this kind of prevention is key to reducing CC, as merely catching CC early seems to confer no survival advantage :( - either way, whether discovered by a test like sDNA or colonoscopy, you still should remove any pre-cancerous polyps ASAP. It might be that if you've already have had at least one colonoscopy, and it detected no polyps, then it's probably quite fine to just rely on tests such as the fobt or sDNA - assuming you are not at high risk due to lifestyle factors or family history. In any case I've had my colonoscopy, so I'm good for awhile. It is my understanding that it takes an average of about 10 years for a polyp to develop into cancer, so if you've had a colonoscopy that showed you have zero polyps, even if you got a polyp the next day, presumably it would get caught on your next scheduled colonoscopy (every 10 years) before it turned fully cancerous. Anyhow, if there's a reliable test that definitely detects pre-cancerous polyps, I'm quite happy not to have another colonoscopy what with its attendant risks and disruption to the gut biome. YMMV.
  3. Scientists have been sounding the replication crisis alarm for quite a while. While not much seems to have been done to correct for that, we can now focus on a brand new crisis - the INFERENCE CRISIS. Frankly, it doesn't seem particularly surprising - perhaps the only surprising thing is that it took so long to formally study this issue - after all, everyone has had this takeaway more than once "how on earth does this 'conclusion' follow from this study?!". I know I have this reaction almost daily. But how to quantify this? Well, here it is, and it's even worse than we might have suspected: https://www.sciencedaily.com/releases/2019/10/191010161540.htm "For the past decade, social scientists have been unpacking a 'replication crisis' that has revealed how findings of an alarming number of scientific studies are difficult or impossible to repeat. Efforts are underway to improve the reliability of findings, but cognitive psychology researchers say that not enough attention has been paid to the validity of theoretical inferences made from research findings. "Rotello reports that about one-third of responders "seemed to be doing OK," one-third did a bit better than pure guessing, and one-third "made misleading conclusions." She adds, "Our jaws dropped when we saw that. How is it that researchers who have used these tools for years could come to completely different conclusions about what's going on?""
  4. That's a fair, but very complicated question. I have a bunch of baseline tests, full blood panel, urin analysis and a record of blood pressure, oximeter readings, blood sugar, weight, and so on gathered over many months or years. That was before any statin or metformin (and obviously rapa). I also have a very detailed health diary listing every symptom, dietary tweak, exercise protocol, supplement regimen, doctor visit, sleep length, even bowel movement, and crucially how I felt subjectively - a record of close to 20 years. Following the taking of a statin, I had very frequent (every 3 months) blood and urine tests with special focus on the liver and kidneys. This was to establish the effect of the statin - it appears to have had no real effect on those biomarkers that were measured, except for blood lipids, where the LDL and triglycerides were lowered. I have now been on the statin - lowest dose of 10 mg atorvastatin (Lipitor) for some 18 months. I have been on metformin for 13 months - for 12 months daily, and the last month pulsed. I go to a diabetes specialist every three months for tests (liver, kidneys, blood sugar) - I have never been diagnosed with diabetes, but my fasting blood sugar has always been somewhat high 90-95 (although it was between 80-85 for a few years), however my post meal blood sugar levels have always been very good. It's just the first thing in the morning where it's in the 90's. In all the tests so far, metformin appears to have had no effect whatsoever on the markers being observed. I have not as yet had any tests with the pulsed metformin protocol. My next visit is scheduled for early December. Btw. the statin doesn't seem to have effected my blood sugar levels so far. But what is the function of all those tests - they can't really tell me anything about whether my aging has been affected. All they can do is record the biomarkers tested. What do those markers mean for health is not clear, although if something went suddenly wrong (say, elevated liver enzymes), presumably that would point to problems. I have not had my Horvath clock measured. I am left with purely subjective observed effects - how I feel, energy levels, sleep duration, skin appearance, hair quality, friend's spontaneous observations etc. This naturally is subject to all the biases and potential inaccuracies, placebo/nocebo effects etc. I attempt to be as objective as I can be, but I can't prove anything. I have my health diary for comparison to before/after. Still subjective and prone to placebo/nocebo effects. That said, I try my best. So far, I have not observed any effects of the statin on exercise capacity, energy levels, muscle/tendons, cramps, mental confusion etc. - commonly listed side effects. Same for metformin, no subjective effects, no gastric issues, not even extra gas which is commonly reported - however ONE possible metformin effect - loss of about 2-3 lbs of weight. However, I cannot vouch that this is due to metformin - it just coincided with the time of my metformin taking. Time frame - indefinite. I will simply monitor my health, objective marker measurements, and subjective evaluations of how I feel (compared to my diary records). This will not tell me whether the drugs are having any effect other than subjective. It is my understanding that you can use certain proxies for the aging process - the state of your skin and hair (obviously extremely rough) - there is the skin pinch test for example. Same for reflex tests (f.ex. the ruler test), balance tests etc. But even if you do record a change (so far none), how would you know it was the drug that was responsible? You won't. Unless there are pretty immediate deleterious effects that come up on blood/urine tests, or subjective evaluations, you really won't know anything. In effect, it's a negative test - "we'll see" whether the combo met/stat/rapa results in something immediately negative. What else will it do? No way to know. Taking such drugs is a gamble that they are having a good effect - but you can't verify that, you can only tell if immediate disaster results.
  5. Yes, Peter Attia also suggested that pulsing metformin - not taking on days you exercise - might be the way to go. And like Gordo says, not taking meds every day might be a good idea in general. Certainly Sinclair thinks so - in that interview with Attia, he explicitly says that we should probably pulse most medication, which he claims to do for all supplements except I think resveratrol. Btw. I have finally broken down and I've gone on metformin. I did so, because I'm also on atorvatstatin (and statins in general can elevate your chances of getting DMT2). But based on this, for the past month or so, I've been pulsing my metformin, taking it on non-exercise days. Unfortunately, in my case, I exercise 4 times a week, so I only take metformin 3 times a week. Who knows the utility of that. It could all be goofy as Gordo says, and honestly we just don't know, because there are no human studies that tell us any of this. It's all 100% pure speculation and a gamble. So far I'm on a statin and metformin and I'll be adding rapa soon (which I'll pulse for sure!). It might not do anything, it might be deleterious, or it might give me a small boost. I'm rolling the dice. We'll see!
  6. TomBAvoider

    Top Mortality causes from heart disease?

    Thanks, Sibirak, this is helpful. As Todd points out, this is not precisely causes of death from heart disease, insofar as high blood pressure is not a cause of death in and of itself, except for very special circumstances such as: I imagine that the blood pressure at that moment must have far exceeded 120/80 which is the cutoff for high BP. I'll try to hunt around for more data, but it's not easy. If anyone wants to jump in, by all means, join!
  7. Does anyone know off hand where to find statistics for deaths from heart disease in the U.S. ranked by frequency? F.ex. if a-fib is #1, congestive #2 etc.? I'm having trouble finding such rankings. TIA!
  8. I hope it works this time! Sinclair is definitely super enthusiastic and quite confident... same way as he was when he was hawking resveratrol. But hey, hope springs eternal! The other day I was talking to my friend's son, who is 20, and I made a reference to a certain trope, and I was gobsmacked that he was not familiar with it... it really told me just how old I am! Kids no longer understand references I thought everybody knew! But, anyway, I think that reference is super applicable in this thread, and since so many old people read this board, I figure everyone will get it with no problem: Will Anti-Aging Research finally get to kick the football? "Inquiring minds want to know" (btw., this saying will soon be obscure to the young generation too, as nobody young reads magazines/print press these days lol).
  9. Looking over all of Fernando Gabriel's posts, I conclude that the boards on crsociety.org are not likely to have the answers Fernando Gabriel is seeking. Fernando Gabriel, I think this website is where your intellectual curiosity will be richly rewarded: https://timecube.2enp.com I urge you to spend your time there. Best of luck!
  10. Same here, I'm about a third way in. It's quite an engaging book, and a good writeup as to where we are today, but as I mentioned before, a note of caution - David Sinclair tends to let his enthusiasm carry him beyond where the evidence leads. So when it comes to his claims as to how close we are to conquering aging and how this one way is the sure to be the way, you should probably treat it the same way we treat all such big problems, energy from controlled fusion, real general AI, cure for cancer (despite his claim that solving aging is easier than curing cancer)... i.e. it's perpetually just around the corner (whatever the case may be 5, 10, 15, 20 years)... that time frame will continue to move as we approach it. Having said that, I'd be the last one to discourage anyone's efforts in that direction - if by some miracle we get there, I'll be the first to celebrate; I just sadly doubt we'll see any such thing within our lifespans, or the lifespan of anyone living today or over the next century and probably more. YMMV.
  11. TomBAvoider

    CR: My Story

    Congrats, and I'm very happy that you are doing well! The whole point of all of this is to enhance health so that you enhance the QOL, and any additional longevity is a bonus. I did enjoy your post and particularly the previous one where you mentioned that Dr. McDougall spoke fondly of valve replacement surgery. I'm reading David Sinclair's book that just came out "Lifespan" - and last night I read about the problems with foot wounds. Just amazing stuff, how you can walk around with nails in your feet and not know about it and how it's practically impossible to avoid serious foot wound problems and amputations if you have DMT2. Horrifying - yet, I read it with as you put it "fondness", because it's so fascinating. Best of luck, and keep on rockin'!
  12. For the sake of argument, let us assume that the band will give you 100% accuracy in measuring sleep time and phases. Why is good passive recoding of sleep important without therapeutic effect? Because there are dozens of known ways to influence sleep quality (blue-light blocking glasses, get bright light during the day, don't eat late, keep bedroom dark, keep bedroom cool, just go to bed earlier, etc.---just Google sleep hygiene, or if more time read Why We Sleep by Walker). A tool to measure how you are doing and track that over the years as you age and sleep quality naturally gets worse with age is useful to help dose doing all of these things. But this assumes several things, which are by no means obvious - in fact, they are highly disputable: 1) Science today, in 2019 fully understands the function of each phase of sleep. Simply untrue - there's more that we don't know, than we do know. 2) Science today can tell us exactly which pattern of sleep is optimal for a given individual. Absurdly obvious that we know no such thing. We can't even figure out the major components of sleep function overall, let alone individual variation and the optimal mix of sleep phases. 3) Any given individual can in fact influence the time/phases of their sleep. Sorry, but that is just not true for vast numbers of people. If it were as simple as sleep hygiene, there would be no sleep problems in the population - instead, there are vast numbers of people who do all they can, but it is of no help, and I put myself into the same category. I dare say I know more about sleep hygiene and indeed about sleep itself (from reading books and papers), and yet my sleep continues to be quite fragmented, as it has increasingly been for me in the last 20 years. I don't even know if that is deleterious in my case, as I as yet don't experience any negative effects that I noticed (such as being tired during the day, or functioning subpar) - but I suspect (without proof), that eventually it will be negative and uninterrupted sleep is superior, which is why I've tried to change it. The original objection to the band has been: 1) It does not measure anything accurately enough. For the sake of argument, let us say it measures it with platonic ideal of 100% accuracy - I grant this, simply because we are in no position to say one way or another. 2) The numbers it comes up with mean nothing to us, because we don't know their meaning (see my points above) - since we don't know what sleeping patterns are optimal, it's data whose meaning is unknown 3) Even if the meaning were known, there are vast numbers of people who are unable to affect those numbers by voluntary actions. 4) Lacking in the ability to affect those numbers, the band's utility is reduced to nothing. As far as I can see, the last three objections still obtain: the headband does nothing except measure numbers the meaning of which we don't understand and can't influence anyway. To me - 100% platonic ideal of useless. YMMV.
  13. TomBAvoider

    Bottle of Lies

    ...maybe due to other factors than drugs, and had they had non-fraudulent drugs, they'd live even longer.
  14. TomBAvoider

    Bottle of Lies

    Thanks, Todd, I subscribe to Attia's podcasts, but have not listened to this one yet. But I've raised alarms in other threads about the shockingly abysmal situation wrt. generics - and where they're produced in places like China and India, and according to data, some 80% of them are tainted by fraud. It's terrifying. This is a situation of "no kidding, if you are taking generics, look into what you're getting".
  15. Thanks, Todd - that sounds pretty much like my suspicions confirmed. Useless numbers, which are neither understandable, nor precise, nor actionable. In other words - wait for it, my favorite: "HYPE, HYPE, AND MORE HYPE, AMEN". Back to the salt mines.