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TomBAvoider

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  1. TomBAvoider

    Bottle of Lies

    None so blind as those who don't want to see.
  2. TomBAvoider

    Water Kefir

    Our household (wife & I) has had a kefir operation going for close to 10 years now. We bought a kefir starter kit on Amazon (I think it was MR's recommendation), and it came with 2 packets of kefir grains. We used exclusively non-fat milk and we're still on the very first grains packet... I don't even know where the second packet is! Amazing. Even when we go on very lengthy vacations (2-3 months), we just stash the grains in the fridge and it keeps there no problem. For many years we used only distilled water to wash the grains, but as of a couple of years or so, I've been using ordinary tap water, and it has not killed 'em! We don't drink kefir every single week, but most weeks. But again, that's non-fat milk, so as a vegan that might not work for you. In my experience, kefir grains are extremely hardy (at least in milk). I can't speak to how the composition of the grains organisms may have changed over the years, but I can't taste any difference. FWIW, we've been using the same TJ's non-fat milk all these years (hormone free, blah, blah etc.). We make shakes with the kefir - adding some frozen berries from TJ's (blueberries, blackberries, raspberries, strawberries and so on). Occasionally my wife adds a banana or some protein powder. We drink this 1-2 times a week, most weeks. The idea is that we're hoping it's good for the gut biome - what the actual effect is... who knows; it's a gamble, like most dietary interventions. YMMV. Bottom line, kefir grains are hardy and quite versatile in prepared shakes/drinks.
  3. TomBAvoider

    Supplements Thoughts

    Association of habitual glucosamine use with risk of cardiovascular disease: prospective study in UK Biobank.Ma H, Li X, Sun D, Zhou T, Ley SH, Gustat J, Heianza Y, Qi L.BMJ. 2019 May 14;365:l1628. doi: 10.1136/bmj.l1628.PMID: 31088786AbstractOBJECTIVE:To prospectively assess the association of habitual glucosamine use with risk of cardiovascular disease (CVD) events.DESIGN:Prospective cohort study.SETTING:UK Biobank.PARTICIPANTS:466 039 participants without CVD at baseline who completed a questionnaire on supplement use, which included glucosamine. These participants were enrolled from 2006 to 2010 and were followed up to 2016.MAIN OUTCOME MEASURES:Incident CVD events, including CVD death, coronary heart disease, and stroke.RESULTS:During a median follow-up of seven years, there were 10 204 incident CVD events, 3060 CVD deaths, 5745 coronary heart disease events, and 3263 stroke events. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, drug use, and other supplement use, glucosamine use was associated with a significantly lower risk of total CVD events (hazard ratio 0.85, 95% confidence interval 0.80 to 0.90), CVD death (0.78, 0.70 to 0.87), coronary heart disease (0.82, 0.76 to 0.88), and stroke (0.91, 0.83 to 1.00).CONCLUSION:Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events.
  4. TomBAvoider

    Supplements Thoughts

    I fully understand the reasons why one could decide to take glucosamine - after all, I too take it. However, I'm not as optimistic as you are regarding how valid our justifications are. Sure glucosamine up-regulates AMPK, but that's classic biomechanistic reasoning, which is extremely poor grounds for any prescriptive actions - the only valid measure is long term health/longevity outcomes. The history of supplements and drugs is littered with promising sounding biomechanical justifications and poor outcomes. AMPK is not like an on-off switch - there are at least 3 major pathways to upregulating AMPK, and they are not all equivalent. And merely upregulating AMPK does not tell you much about ultimate outcomes. Note, f.ex. that metformin is a famous AMPK upregulator, as is exercise. So people naturally thought that metformin and exercise would be additive. The opposite is true. Metformin - an AMPK upregulator - blunted the effect of the other AMPK upregulator, exercise. So how do you know that glucosamine, an AMPK upregulator is not working at cross purposes to exercise or any other element of your supplement, diet, exercise or lifestyle regimen - after all, metformin an AMPK regulator does that too! For that matter, did you know that statins also upregulate AMPK? See this study of atorvastatin (which I take!): https://www.ncbi.nlm.nih.gov/pubmed/17116771 Statins activate AMP-activated protein kinase in vitro and in vivo. Abstract BACKGROUND: Statins exert pleiotropic effects on the cardiovascular system, in part through an increase in nitric oxide (NO) bioavailability. AMP-activated protein kinase (AMPK) plays a central role in controlling energy and metabolism homeostasis in various organs. We therefore studied whether statins can activate AMPK, and if so, whether the activated AMPK regulates nitric oxide (NO) production and angiogenesis mediated by endothelial NO synthase, a substrate of AMPK in vascular endothelial cells. METHODS AND RESULTS: Western blotting of protein extracts from human umbilical vein endothelial cells treated with atorvastatin revealed increased phosphorylation of AMPK at Thr-172 in a time- and dose-dependent manner. The AMPK activity, assessed by SAMS assay, was also increased accordingly. The phosphorylation of acetyl-CoA carboxylase at Ser-79 and of endothelial NO synthase at Ser-1177, 2 putative downstream targets of AMPK, was inhibited by an adenovirus that expressed a dominant-negative mutant of AMPK (Ad-AMPK-DN) and compound C, an AMPK antagonist. The positive effects of atorvastatin, including NO production, cGMP accumulation, and in vitro angiogenesis in Matrigel, were all blocked by Ad-AMPK-DN. Mice given atorvastatin through gastric gavage showed increased AMPK, acetyl-CoA carboxylase, and endothelial NO synthase phosphorylation in mouse aorta and myocardium. CONCLUSIONS: Statins can rapidly activate AMPK via increased Thr-172 phosphorylation in vitro and in vivo. Such phosphorylation results in endothelial NO synthase activation, which provides a novel explanation for the pleiotropic effects of statins that benefit the cardiovascular system. Now, statins famously are muscle-unfriendly - again, you'd think that since exercise upregulates AMPK, you'd have statins being additive to exercise, but no. And yet statins can certainly be very good for your vascular system through - as the study indicates - your endothelial cells. The point being is that just because a given supplement does something that's considered "good" biomechanically, like "upregulates AMPK" doesn't mean much without seeing the full spectrum of interactions. Statins may still be an overall good for someone like me, who has uncontrollably high LDL cholesterol that is not amenable to diet/exercise interventions - but statins may be a big negative for someone who has naturally low LDL. Your individual physiology, your genetic/epigenetic profile, your dietary, exercise and other supplementary regimes all determine whether adding supplement "X" in a specific protocol will transpire to be a net positive. Here is a fascinating talk given by a scientist who studied the effect of exercise - especially glucose transport - and zeroed in on AMPK, metformin, aicar ("exercise in a pill") - this was before the effect of metformin on exercise was illuminated, so it's an amazing experiment in time showing how our understanding has evolved: If you want to jump straight to AMPK, you can start from minute 18:50.
  5. TomBAvoider

    Supplements Thoughts

    As I said, glucosamine looks a bit tempting. Does anyone else here (besides Ron and Clinton) take it or have an opinion on it? I take glucosamine. But let's face it - as I said in a post about metformin: we simply do not know, period. There are so many interactions with other drugs, your diet, lifestyle, genes, individual physiology, age, gut microbiota and so forth, that it's almost impossible to make additive recommendations about an individual supplement such as glucosamine (as opposed to subtractive, such as "don't smoke" and "don't shoot yourself in the head"). The fact that glucosamine seems to work for people in aggregate is a statistically derived effect which may mean absolutely nothing by the time you are looking at a particular individual - and Dean is absolutely correct in pointing out that folks participating on these boards are a whole other kettle of fish compared the cohort from which that statistcal glucosamine effect was gleaned. I am acutely aware that taking glucosamine, is a gamble on my part, as it is with pretty much all my interventions - and worse, a gamble the result of which I cannot ever know, it being a n-1 experiment without a corresponding control - it is essentially unknowable (at least at this stage of medical science, and I suspect probably for the next 100 years to come too). You asked about "opinions" - well, that's mine; it looks interesting, and I'm rolling the dice on it /shrug/, but don't ask me to "prove" anything, as that's impossible at this point in time and any speculation is going to be for entertainment purposes only. YMMV.
  6. TomBAvoider

    Eating Natto for Bone, Artery & Brain Health

    Well, there is a link between arthritis and osteoporosis - prominently the inflammatory variant: https://creakyjoints.org/comorbid-conditions/inflammatory-arthritis-osteoporosis/ And the study I cited does claim greater BMD for natto (see the title!) - and if you scroll up to the post you made and from which I extracted the study I referenced, you yourself titled is as such: Natto Once Again Shown to Increase Bone Mineral Density Now, of course I don't think that OA somehow inherently is a health-positive thing - it's an illness and quite debilitating. All I'm saying is that something odd is going on and something worth investigating.
  7. TomBAvoider

    Eating Natto for Bone, Artery & Brain Health

    Right. It's a correlation or association - anything could be responsible; perhaps calcium as you suggest; or - to be cheeky, lower intake of K2 (with the additional complication that perhaps some K2 which appears in abundance f.ex. with cheese might also mean you take in a lot of saturated fat and that's a negative etc. - so if your K2 is high, it's good for bones, but it's at the cost of taking in a lot of saturated fat which might be a negative, etc.). There are tons of confounders, so it's very difficult to know why OA is associated with lifespan/cognition preservation in such a counter-intuitive way. But given how astoundingly huge this effect is - 10 times(!) the number of centenarians, I think it would be very useful to investigate this OA effect.
  8. TomBAvoider

    Eating Natto for Bone, Artery & Brain Health

    Yes, Dean, I noticed that study this morning (thanks Al!) - and wondered if anyone would comment, given the natto threads around here. But there is another study that Al posted yesterday which I've been puzzling over ever since - and in a roundabout way, it's tangentially related to the natto study. In one sense, the natto study is a morbidity and biomarker study - it tells us that you'll have less bone breakage and osteoporosis. If you go up in this thread there is also a study which recommends natto: https://www.jstage.jst.go.jp/article/tjem/239/2/239_95/_pdf "In particular, natto intake is recommended for preventing postmenopausal boneloss on the basis of current evidence." Which says directly that natto should prevent or ameliorate osteoporosis. This is where Al's puzzling study comes in from yesterday: Increased lifespan, decreased mortality, and delayed cognitive decline in osteoarthritis.Mayburd AL, Baranova A.Sci Rep. 2019 Dec 9;9(1):18639. doi: 10.1038/s41598-019-54867-8.PMID: 31819096AbstractIn absence of therapies targeting symptomatic dementia, better understanding of the biology underlying a cognitive decline is warranted. Here we present the results of a meta-analysis of the impact of osteoarthritis (OA) on cognitive decline and overall mortality. Across 7 independent datasets obtained in studies of populations in the USA, EU and Australia (NBER, NSHAP, TILDA, NACC, Kaiser Permanente, GRIM BOOKS, OAI, with a total of >7 × 107 profiles), OA cohorts demonstrated higher cognitive scores, later dementia onset as well as longer lifespan and lower age-specific all-cause mortality. Moreover, generalized OA with multiple localizations is associated with more significant reduction of mortality and dementia than a singly localized OA or no arthritis. In OA patients with younger ages, all-cause mortality was disproportionally reduced as compared to that in controls, while exponential term of Gompert'z hazard function was increased, accelerating mortality accrual at later ages. Up to 8-10% of poly-osteoarthritic patients are predicted and observed to reach centenarian lifespan, while in matched non-OA population the same benchmark is reached by less than 1% of patients. These results point at a possibility of life-extending and cognition preserving impacts of OA-conditioned immune system. Ain't that something? Quite a humdinger. Note, that they speculate - again speculate - as to why OA seems to be associated with life extending effects and cognition preservation (i.e. it's immune system driven). But the study can show us no grounds for such speculation - no proof of mechanism. All it can ascertain is the correlation. Why that is, who knows. But that effect is very robust - it is pretty astounding: 8-10% of poly-osteoarthritic patients are observed to reach centenarian lifespan, while matched non-OA population is only at 1% - that's 1000% - or TEN TIMES the rate. That's eye-wateringly high. If we were to go only with this, you should be down on your knees praying for poly-osteoarthrisis. Note again - we have no idea what the mechanism is in the case of OA being life prolonging/cognition preserving. And on the other side - we actually don't know what life-expansion effect natto intake has, all we have is a morbidity marker. And ironically a morbidity marker (OA and bone breakage) that's in direct opposition to lifespan, at least according to the study Al posted - which means that if you were to look at just that, you should avoid natto precisely because it inhibits OA. All you can say is that natto prevents OA - and nobody can prove that that's desirable rather than undesirable from a life-extension and cognitive preservation point of view. Now what?
  9. TomBAvoider

    Metformin Benefits May Result from "Crypto-CR"

    Thanks, Dean. Yep, that's definitely a downer. Insulin sensitising was certainly a major consideration for me. Now I have to re-think the utility of this. There are pleiotropic effects, but this one was a big one. Ouch.
  10. TomBAvoider

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Typical Ron, simply ignore the counter-argument (including the link I provided about the history of loitering/vagrancy laws) and repeat the same absurd claims all over again. Never mind what the ostensible intent of the laws was - the plain fact of the matter is that the laws were weaponized to imprison human beings and corral them into forced labor, a practice that was an integral part of Jim Crow laws. The reason the SC had to get involved is precisely because of such a perversion of the use of these laws. You however blame that SC review of these abusive laws for homelessness. Nobody familiar with the history of civil rights and Jim Crow thinks anything other than that the SC was absolutely right to address such abuses of loitering/vagrancy laws - except you, of course... which is why you made a link between the SC decisions and homelessness. Congratulations! The reason shelters don't have full occupancy is because often they are not safe and people are afraid to stay there. Yes, mental health and drugs are a big part of the homelessness problem, but neither of those factors can account for such a rapid explosion in the size of the homeless population. The plain fact is, that a huge factor here is unaffordable housing driven by real estate speculation and capital parking. This sudden jump in the number of homeless is not an odd rise in mental illness and drugs, which have been around for decades - it is that the working poor have joined the ranks of homeless: https://laist.com/2018/09/03/thousands_of_angelenos_work_while_homeless_and_many_dont_want_their_boss_to_know.php You are a pretty typical type of guy who finds blame for social problems always with the victims. Somehow they're in drug gangs working the system and so on. Guys like you with your explanations have always been around - during FDR's time and during Reagan's time (here we'd have Ron talking about how bad social spending is, and examples are the mythical cadillac driving "welfare queen"), and today we've got Ron talking about the homeless really being in drug gangs and willingly homeless to bleed the system dry. Oh well, another day, another reason why it's never the fault of the system, and always the fault of the nasty humanity.
  11. TomBAvoider

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Well that's encouraging, if Ron disagrees that's a sure sign I'm on the right track. But Ron, perhaps you should read more closely. I said "it's like", meaning I'm comparing the policies, not saying that just cutting taxes was was the (sole) reason - otherwise I'd have said "it's because". I'm well aware of other reasons why homelessness exists, amongst them the closing of mental hospitals and changes to laws governing when someone can be committed. The reasons are complex and posts on this board are not a good medium to explore them, so I just reference things glancingly. And no, I don't believe vagrancy/loitering laws are to blame in the least - I believe there are policies with far greater impact, as just one example - the way capital has been encourged to buy up vast amounts of properties and then not be taxed for leaving them unoccupied (effectively a way to park capital): https://thehill.com/changing-america/respect/poverty/471675-in-los-angeles-vacant-homes-outnumber-the-homeless Meanwhile the old vagrancy/loitering laws were exploited to imprison folks based on racial grounds, often as a covert way to re-introduce forced labor, slavery in all but name: https://en.wikipedia.org/wiki/Black_Codes_(United_States) I'm glad these evil vicious laws were put under scrutiny - good riddance, too bad not more comprehensively as in fact they're still used to harrass people for purely discriminatory reasons feeding the industrial prison system. Vagrancy and loitering laws are hardly a factor in homelessness... people don't become homeless in the year 2019 or 2000, because someone in the 70's determined that you won't get arrested for loitering "hey, no loitering laws back since the 70's? Cool, I'm dropping my apartment today in 2019 immediately and going homeless! Whoowee! What a way to save on rent!"... and conversely, tougher loitering laws won't create housing, jobs and drug rehabilitation... if you want to understand why there's homelessness, follow the money... always a good rule... someone is getting rich and the rest are getting ripped off. But again, it's too complex to discuss in detail here. Glad you disagree though.
  12. TomBAvoider

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Yes, there's the issue of moral hazard. But in this case, it's on a much larger scale. My problem with charity giving in this scenario is not so much the moral hazard in the case of individuals, but rather the moral hazard of the whole enterprise. What I mean is this: homelessness is a societally created problem; it didn't use to exist in such numbers, and in some countries didn't exist at all for many decades (Sweden, when I lived there in the 80's). But as a result of various policies, homelessness has been created. Now I'm - as in Joe Schmoe - supposed to step in and clear up the mess while those who profited from such policies go scott free? It's like cutting taxes and social services with resultant massive money transfer to those who are already super wealthy and then turning around and saying "let charity fix the mess". It's the same moral hazard reason why I absolutely refuse to donate to any "veteran" cause - if you engage in aggressive wars, you should also finance the help veterans need. It can't be that when the soldiers come back from war it's not the war-monger's problem to support the veterans. That leads to the long term costs of war being offloaded on charity and so encouraging endless wars. Pay for your wars, don't cry "charity". Providing charity under such circumstances results in less political push to hold accountable those responsible for such disasters, because "charity will fix it". Instead I'd like to see a Bonus Army, veterans organizing politically to demand services instead of having to rely on handouts and charity. Veterans deserve our support in taxes paid, not having to rely on chance and charity. So the question is how to help the individual while not encouraging further abusive policies that will only multiply the problem.
  13. TomBAvoider

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Thanks, Dean. Yes, we're still involved in animal rescue, although given that we're more pressed for time, we've upped our financial contributions to rescue organizations as a means of contributing. However - even that has been questioned, given the humanitarian crisis we witness on a daily basis here in LA, namely homelessness. Can we really justify expending as much resources on animals when humans are in such dire need? Shouldn't our priorities be inverted from the current 90% animal 10% human (at least as far as charitable giving)? Maybe it's just another sign of old age that I'm increasingly fretting about making/leaving a lasting contribution behind, rather than just having lived a life focused mostly on selfish pursuits.
  14. TomBAvoider

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Thanks, Dean - I think I've pretty much discussed most of the issues wrt. metformin identified by Reason in that link. However, I'd point out again that my metformin regimen is part of a complex of interventions, and therefore looking at that one compound in isolation is a mistake - again, that timely Al Pater post I mentioned above alludes to this. Metformin as tested in mice was a single drug intervention. But what happens if you combine metformin with other drugs (like rapa), or take metformin according to a different protocol (f.ex. pulsing)? We are all individuals in specific physiological situations, subject to a variety of interacting variables. After all, Reason himself mentions (and I've done so too) the fact that metformin is not additive when combined with exercise - so the idea that one intervention may impact another in non-obvious ways should not be a foreign concept. One of the undesirable side effects of rapa can be a tendency to DMT2 - and metformin counteracts this. Meformin by itself might be a net neutral or negative, but combined with something else, all of a sudden the sum is greater than the parts. Now, obviously, this gets out far into the sticks speculatively speaking. Ordinarily I stay far away from acting on biomechanistic speculations and much prefer outcome data, but in the absence of the latter and compelled to act, I have little choice but to venture along that path. So, my metformin adventure is in the context of looking at other aspects of how metformin acts, not simpy as an anti-aging agent. Metformin inhibits gluconeogenesis in the liver - in the last few years, my FBG has been edging up at the end of my longer non-feeding windows (currently approx. 18 hours out of every 24). Metformin might be useful here to me (but perhaps not to someone else - again, we're all in individual situations) - not as an anti-aging agent per se, but as a piece of the puzzle - you have to look at the whole picture, not just at individual pieces (i.e. every piece by itself is not the whole map of anti-aging, which is what people sometimes focus on). Perhaps no single drug in a given cocktail is anti-aging by itself, the effect happens only once all work in concert. You are also correct that it's possible such interventions might not buy us much in lifespan. I was struck by another study Al posted, where they tracked 40 variables and over a dozen conditions in a large group of elderly people and found that if you did everything right the difference between the best and worst individuals in lifespan was as little as 6 months (this was in a setting of a retirement home). My response is that part of why I do this is purely intellectual/hobby - you have to do something anyway (as I said, even if that something is "nothing"), you have to eat anyway, so why not do as good a job as you know how to, regardless of whether it'll actually buy me anything; the resources don't matter, and I can't take it with me, so if I can afford it, why not (we have no kids)... hey, hobbies have a cost in time, effort and money - this is no different :)... I also continue to believe that there isn't a perfect alignment of healthspan with lifespan 1:1 - and so even if I gain nothing with lifespan, I am hoping that perhaps it might be good for some gains in healthspan, which is nothing to sneeze at. On a completely different note, and perhaps it belongs in a different thread, but there's one psychological aspect to all of this that admittedly slightly troubles me, namely - what about the ethical implications of all this? Is it terribly self-indulgent? In a world of constrained resources, is such extravagant attention to ones own health and mortality not a wasteful and selfish pursuit? The health insurance my wife and I have allows for once-yearly general health exam. We very rarely go otherwise go to the doctor. Also, I believe research shows that such checkups are useless and should be only done about once every five years. Are we taking up time from our busy PCP, who has patients with actual problems - (this is what we think as we sit in the waiting room, surrounded by patients who are visibly struggling). Then we go in, and have to report no real problems - seems very wasteful and self indulgent to have this battery of tests for no real reason other than curiosity. When asked about what might trouble us, it's actually embarrasing to bring up niggling QOL issues such as "there's a persistent itching in my ears that wasn't there a year ago" - because other than cleaning them out (which resolves nothing), there's not much that he can do. Why even bring up such trivial stuff. My wife and I are gradually coming around to the idea that we won't go in for yearly checkups any more - it takes time away from other patients and the doctor. Instead, if we're so curious, we should pay for tests out of pocket in an external lab and not be a burden on a strained healthcare system. What's your view of this whole thing - are we all, life-extension hobbyists, being a bit self-indulgent, and shouldn't we all spend more of our time and resources helping out instead of focusing on ourselves? Or is this also self-indulgent overthinking? Inquiring minds want to know.
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