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kpfleger

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Everything posted by kpfleger

  1. Some here may be interested in a new table I've just put up on AgingBiotech.info that collects aging/longevity related diagnostic tests that are currently available: https://agingbiotech.info/diagnostics/ It covers aging clocks (methylome & others) / various -omic panels, but also other things like the AgingSOS NAD & cell-senescence tests, plus multi-cancer screens. List of things out of scope or on the fence can be found in the sub-sheet about scope to the right of the main sheet (tabs at bottom). Feedback welcomed, Karl, AgingBiotech.info creator
  2. I've been building a list of blood biomarkers to track for long-term health, along the lines of the CRSociety tests and biomarkers page, but with target recommendations that are more specific than ref ranges and with the source of each rec linked. My main concern is long-term health and mortality risk rather than short-term performance. The set of vendors offering direct-to-consumer blood tests seems to be exploding. So I've also made a list of a bunch of these with specific test packages to compare them on comprehensiveness and cost. Here is the resulting table: https://docs.google.com/spreadsheets/d/1G65NGyMbIWr72QY7w00iobZ_IMXxQbC_Lhaxbss4ALk/edit?usp=sharing The top half of the table is the list of tests and which biomarker each includes (based on the vendor's website). The bottom half of the table explains why each marker is included and gives the recommendations for specific target ranges. I welcome suggestions on both the list of biomarkers or the list of tests/vendors (or the set of linked sources of recommended target ranges), either here or by email. The table also has comments enabled, so anyone with the link can insert a comment into any cell. Does anyone have any knowledge of significant differences of accuracy or customer service or other factors besides just tests and price to use to choose between the test providers? Most (all) providers are just using LabCorp (or maybe Quest) so I would expect accuracy to be the same for everyone. InsideTracker and WellnessFX seem to provide their own proprietary interfaces to the results rather than only a typical LabCorp report (at least I think WellnessFX does this too). InsideTracker wraps into their report some explanations for lay-audiences about why each biomarker is important and how some of them interact, plus also an "optimal" range for each narrower than the lab-ref-range, plus also food (and maybe other lifestyle) recommendations, which most of the others seem not to do (not sure exactly what WellnessFX provides). Neither of these seem to provide a sample report linked directly from their test package page, though Googling them does find some reviews with some sample screenshots. Other than these things, I'm not sure what else there is to judge on other than price and set of tests. Good deals: Based on the prices I just found on their websites in late Sept 2016 (after the recent LifeExtension sale), the following seem like particularly good deals based on the set of biomarkers I am currently most interested in: The ~$250 LifeExtension "Healthy Aging Panel (Comprehensive)" gets a lot of good stuff for a not high price, a good bit cheaper than their "Male Elite Panel" recently discussed in the recent sale thread. That test is now $643 w/ B12 added on. The $250 test loses IGF1, testosterone, PSA vs. the more expensive one. A better deal for getting those other tests included than the LEF Male Elite Panel seems to be the PrivateMDLabs "Male Anti-Aging Ultimate w/ Free (Direct) Testosterone" for $535, which has been Dean's go-to test. Also note-able for value is LifeExtension's basic "Chemistry & CBC" test which includes all 4 basic panels (CBC, lipids, metabolic, & liver) for only $35! But another take-home is that there are at least a half-dozen places to order a fairly comprehensive set of blood tests direct-via-web with only minor variations in packaging of different individual tests. If many of them have sales from time to time it may be worth shopping around each time one wants a new test. OTOH, if you can live with testing the more expensive markers less frequently, the price differences for different levels of comprehensiveness dwarf the discounts available with even big sales. Eg, the non-sale $250 price for the LEF Healthy Aging Panel is still much less than the $431 price Dean reported getting for the more expensive Male Elite Panel. -Karl Disclaimer: I generated this info by hand from looking at the test webpages and it hasn't been double-checked. Feel free to let me know if you find an error. Also, I didn't look at every test package and especially didn't try to find the best deals at the sub-$100 level.
  3. kpfleger

    Vitamin D Recommendations

    Ron, that's a very old study in the world of vitamin D research (2012). Lots has come out since then. There remains disagreement about the exact optimal level. Many knowledgeable doctors & researchers quote 40-60ng/ml. Few to no people advocate 30ng/ml as better than 40ng/ml though some claim that 40 should be the upper end of the optimal range, but most of the uncertainty and debate is about where the upper end of optimal range is. As the reverse-J-shaped curve Michael R posted on the 1st or 2nd page of this thread in 2016-2017 showed, the steepness of the all-cause mortality graph is lower in the higher blood level direction than the lower level, so it makes sense there is more debate about the upper end of the optimal range. And there may be tradeoffs such as increases in some kinds of mortality vs decreases in others. But it's also important to note that there is ample evidence that low vitamin D levels worsen COVID-19 and in fact lots of evidence that vitamin D supplements directly help against this virus (more than others) and good mechanism arguments as well (including direct action against the virus particles). For a review, see my review http://agingbiotech.info/vitamindcovid19/ or its 1-pager summary: http://agingbiotech.info/vitamindcovid19facts/ So here in the year 2020 the optimal blood vitamin D (25OHD) range has probably temporarily shifted to a higher range than the previous optimal due to a higher short-term risk from COVID-19.
  4. kpfleger

    Testosterone, Luteinizing Hormone and Mortality

    So far no replies to my Feb 28 message with any compelling evidence-based reasons for those on (near)CR diets not to try to combat age-related testosterone loss by boosting it back to former personal levels. (Perhaps the timing is such that everyone quickly got distracted by the pandemic and this topic suddenly seemed less important.)
  5. kpfleger

    Testosterone, Luteinizing Hormone and Mortality

    The forums give me an error message on this way of attaching a whole file to a message, if I'm not logged in. Works fine if logged in. For those not logged in, the paper is: https://www.sciencedirect.com/science/article/pii/S1090023313004486?via%3Dihub or https://doi.org/10.1016/j.tvjl.2013.09.020 So this study showed no advantage for neutered male dogs. This quote: "In the UK, neutering was associated with increased longevity for females but not males (Michell, 1999), while neutered males outlived entire males among US military dogs (Moore et al., 2001)." shows another UK study showed the same and a US study showed an advantage (in military dogs specifically). I wonder if that's explainable based on more risky behavior, as supposed as a confounder for the human eunuchs.
  6. kpfleger

    Testosterone, Luteinizing Hormone and Mortality

    This is the most recently active of many CRSociety threads on testosterone (T). Some others: 1, 2, 3. There are several related but somewhat different topics: (A) Is the low-T that results from CR bad? Does boosting it reduce the benefits of CR? (B) In those not doing CR but also not obese / suffering from metabolic syndrome, is age-related decline of T bad and is boosting it back to earlier levels net long-term healthy? (C) In those doing CR is the (perhaps slower) age-related T decline bad & boosting it back to youthful CR levels (but not back to non-CR levels) net long-term healthy? I'm most interesting in the question of whether boosting T to stop age-related decline has clearcut health risks for those without metabolic syndrome / obesity, whether case B or C above, i.e. deep in CR or borderline (eg, WFPB or generally healthy obesity-avoiding lifestyle). I'm curious what everyone (especially Michael) thinks are the best arguments not to intervene to raise T to prior youthful levels (for whatever level of CR / leanness one maintains) as one ages, assuming one has records of prior levels going back some years? Is there really much trustworthy data to make any informed decision about this? Are there any studies that boost T in aging CR'ed mammals to maintain non-declining levels with age? Michael mentioned that castration lengthens the life of dogs. I haven't tried to dig up the studies. Which ones do you find most compelling? Do the castrated dogs have lower overall leanness? Any data on whether castrated, CR'ed dogs live longer than non-castrated but CR'ed dogs? More details..... It's clear there is controversy about whether low T is bad & boosting it good, both in the wider medical community for the general population and here on these forums. General population: Pro-T example: StemTalk podcast just had interviewed Abe Morgantaler, an human T expert with long Harvard credentials. The episode discusses history of the the subject from the medical community perspective, eg risk of prostate cancer, also CVD. I don't have a broad enough view to know how one-sided the presented history is, but clearly he is an advocate of T therapy. Positive evidence is discussed as well as quality of life patient anecdotes. A lot of time is spent discussing flaws in studies that caused negativity for T therapy (and some of this is generally interesting from on the issue of science errors & publishing). This interview just came across my podcast feed and isn't meant to be the best single summary of the pro-T case. Anti-T example: Michael, in one of the other threads, pointed out this article that summarizes a lot of evidence against T therapy. The author of this article is accused in the comments of the article of being biased against T therapy (opposite of the podcast interviewee above). [Note that Michael originally linked to the printable version of the article, possibly just to get to the unpaginated 1-HTML page version, but that doesn't include the comments.] The comments also point out some purported flaws in some of the studies discussed (eg differences in plaque scores in treatment vs. control groups before therapy was initiated in one study). The podcast interview above also discusses flaws in several studies---I didn't go back and try to match up the studies but I suspect many are covered in both places. I didn't try to dive into each study and its criticisms to try to decide each case myself. Michael's summary was: It should be noted that "otherwise health" here means healthy by the definition of the normal medical healthcare system that defines lack of full blown clinical disease as "healthy", but many (most?) of the studies used people who had high BMIs, ate typical diets, and thus mostly had underlying molecular accelerated aging that meant that they were already well on the road to chronic diseases and metabolic syndrome given their ages. We could dive into the studies of such people as they are and discuss the details to figure out which studies are most trustworthy and try to guess at which conclusions carry over somewhat to leaner humans---that's one direction this thread could go if anyone cares to. For CR or low-BMI healthy diet/lifestyle: The T threads here discuss many things, including whether CR lowers T, whether CR or near-CR causes the age-related rate of decline of T to be slower. [Note: Below I will just say (near)CR as a shorthand catch-all abbreviation for all of CR and other generally healthy obesity-avoiding diets, such as WFPB, Okinawans, etc. CR vs. these others is obviously different, but for the purpose of this discussion the difference between all of these and typical western diets in the important distinction.] The thing most everyone agrees on is that typical bad diets lead to obesity / metabolic syndrome (metS) and simultaneous reduction of T (in humans, and seemingly in other animals too I think). Consequently, there is naturally much epidemiological data showing correlations between low T and bad health outcomes, but this correlational data is (near-)worthless for arguing that low T in the context of (near)CR is bad. It seems to me, even randomized trials in which T is artificially lowered or raised in high-BMI subjects eating bad typical diets should be viewed with caution as to relevance for those doing (near)CR. Unsurprisingly, there is little to no data from well-done studies of (near)CR humans randomized to interventions that raise or lower T and then followed for long-term health. There just aren't enough (near)CR'ed humans in long-term studies let alone ones with this particular kind of randomized intervention. Are there good studies in rodents or other mammals that are CR'ed and then randomized to T-lowering or T-boosting interventions? My read of the existing threads on these forums and everything else I've found so far is that there is insufficient evidence to conclude that age-related low T in (near)CR is clearly bad, nor that it definitely is safe. No one really tried to discuss whether intervening to increase T (via supplements or direct use of T therapy) to correct age-related T decline would be bad for (near)CR humans. I don't see much evidence at this point to conclude it would be bad (nor that it would be safe). The best argument presented against boosting T so far seems to be the increased CVD risk, but even to the extent true in high-BMI/bad-diet individuals, how relevant is that for those doing (near)CR, whose CVD risk should be very low? What's the best argument that someone doing (near)CR would likely or possibly be doing harm to their long-term health by trying to slow or fully correct for age-related T decline by intervening to boost T? If there is insufficient evidence to conclude that low T is bad, and insufficient to conclude that boosting T back to youthful levels is bad, then it becomes at matter of intuition & guesswork played off against personal preference for how someone wants to live their life (and strength of that personal preference vs. width of the error bars on the best estimate one can come up with from the data available). Michael in one of the other threads pointed to a non-scientific episode of This American Life discussing some of the huge life changes that low vs. high T can have on a person's life (quality of life, tastes and desires, even personality). These are things reasonable people may have strong personal preferences about. I'm not having any particular low-T problems, but I see my free T levels starting to decline over time (in the context of stable diet & BMI) and personally don't have a desire to roll the dice on a changing personality---I like the one I have now thank you very much, nor roll the dice on some of the problems the patients in the Abe Morgantaler podcast episode talked about. Nor do I welcome energy level decline and I wonder whether caffeine use and variability may mask my ability to perceive a slow energy decline over time. Karl
  7. Tis the season to think about flu shots. What's the optimal practical stuff one can do to optimize effectiveness? A few early studies have shown improved immune response to influenza immunization in humans by taking rapamycin around the time of the vaccination. There has been enough work to think that the effect is real, but not enough for optimal dose, timing, etc. to be confidently worked out, nor enough for this to have translated to standard-of-care in common clinical use yet, especially given rapamycin's other negative side effects. CR and fasting hit many of the same pathways as rapamycin, so it is reasonable to hypothesize that maybe temporarily entering CR or doing some fasting around a flu shot might also help optimize immune response and effectiveness of the shot. I think there has been no direct work testing this yet. Would love to hear people's opinions or any pointers if there has been respectable work on this that I don't know about. Should one fast before and/or after a flu shot, or enter CR / deepen CR around it? There has been science recently on fasting vs. feasting's differential effects on infectious agents depending on whether the infection is viral vs. bacterial, essentially backing up the old saying to "feed a cold, starve a fever", except the general version would be feed a virus, starve a bacterial infection. That doesn't exactly square with fasting or downregulating mTOR for a viral vaccination. The reconciliation seems to be that the eating in the face of an infection didn't affect the immune response itself. The additional glucose allowed cells to fight a viral infection better than without the glucose. Since the flu shot is inactivated, no cells actually get infected so no benefit to more available glucose. This suggests that possibly the best thing to do is fast near the flu shot but eat more if you actually get the flu (regardless of whether you had the shot). Separately from the above, AHCC seems to have some evidence that short-term use around a vaccination improved immune response. Matt covered this in his AHCC post (nice post Matt). But this seems to be based on a single paper published in 2013 and maybe earlier work. I don't see much work since then and clearly the intervening 5 years haven't caused this to be a widespread recommendation. I haven't search Google scholar for more recent papers citing this one to see what recent thoughts are on this study, but that's a next obvious thing to try. Certainly AHCC seems to have some other good work showing that it helps the body during certain kinds of infections, or even treatments like chemo. Michael Rae pointed out to me once that it is commonly used for people with low neutrophil WBC counts (neutropenia), but it did nothing for me personally to increase my WBC when I tried it for 6-9 months. So perhaps it helps taking around the flu shot, and perhaps it would help to take it if one were actually fighting a flu. Anything else? And what do people think of this list so far? Should we fast and take AHCC around the flu shot but then eat a lot and take more AHCC if we nonetheless later get a bad flu? And then stop eating again but take more AHCC if we get a secondary bacterial infection after the flu, such as bronchitis? (But alas, one can get viral or bacterial bronchitis and consumers and individual clinics/doctors don't yet have good tests to distinguish the type of infectious agent I think, though there are people working on this. Fever by itself I think is not a reliable indicator, though maybe it is decent for just a chest infection if the flu has cleared up?)
  8. I made a website to track all aging/longevity companies, in an interactive (sortable, etc.) and quantitative way: agingbiotech.info The aging/longevity field has grown to where it's hard to follow. There are books, journals, blog, some industry reports, and a few website with forums like this one, but few structured info sources for broad context or targeted queries, particularly few focused on aging defined as the underlying molecular causes of multiple age-related diseases. The web had no comprehensive & precise list of companies with therapies or diagnostics for underlying aging in this sense. Hope this is helpful to some. For those here, it's particularly worth noting that many interventions being pursued within the aging/longevity communities (both in academic labs and companies) are focused on correcting or making up for age-accelerating factors, either genetic disorders that accelerate some aspect of aging or lifestyle factors that do so such as bad diet, lack of exercise, etc. including their downstream manifestations such as obesity. There is even a new buzz-phrase that succinctly describes a subpart of the field focused on these kinds of things: metabesity (with a conference this month in the DC area even). Interventions that are best categorized into this bucket include category buzz-phrases like CR-mimetics, exercise-mimetics, Rapalogs, etc. Metformin probably goes in this bucket. For those on a CR diet, or even just eating high micro-nutrient, obesity-avoiding, relatively healthy diet (much healthier than average Westerner), there is a question about how much such interventions will do to improve health & healthspan. The website includes companies working on such interventions, but also many working on things that should be important even to those on CR or living close to optimal long-term-health preserving lifestyles. Figuring out the exact boundary of that split is debatable and will only be answered definitively with further science so until then you have to decide which companies and which of their clinical trials are more worth paying attention to than others. But there is certainly important work being tracked. Hopefully this site is a useful way to check out the current state every now and then. Feedback welcomed (see contact link at the site). Karl
  9. Don't forget that that applies only to some of the interventions these companies are working on. CR and other lifestyle habits at most slow aging relative to population average. They don't stop it. So many of the anti-aging efforts will be important to even those on the most optimal levels of CR. CR in humans probably slows aging by at most 30% (and that's probably wildly optimistic). Senolytics, partial epigenetic reprogramming, stem-cell therapies (which may work through signaling that does reprogramming), therapies to protect mitochondria from damage, persistent AGE cross-link breaking, immune system regeneration, etc. will all probably be beneficial to even those on CR.
  10. Thanks, I hadn't seen those. There were only ~26 companies mentioned (vs ~110 that I already had). There were a couple new to me so I added them to the sub-tab of my table that has companies to consider adding when I get a moment. In some ways the site I made is the answer to the site he said at the top of his part-ii post that he couldn't find anywhere. And my counts sub-sheet answers some of the money questions he lays out in his first paragraph (of part ii). I added a comment to his post but it's waiting for him to approve it.
  11. Yes, I saw that he wrote an long post about it, didn't notice any discussion of FOXN1 nor of error bar methodology for small n use of methylation clocks (but I didn't read the whole thing carefully after seeing no discussion of FOXN1).
  12. There is a lot to like about Fahy's trial and a lot to dislike. The main 2 points made in this thread so far are both right: (1) It's nice to have this data in humans despite the obvious negatives of small n and uncontrolled and (2) the press regrettably but predictably over-hyped its coverage. Let's move on from those points and let me add a few other points that haven't been brought up in this thread: I'm disappointed that Fahy thought that the right order in which to do this science was human n=1 trial followed by uncontrolled human n~=10 trial without any work in mice or any other mammal. The thymus involutes in mice too. A controlled mouse trial with much larger n could have been could have been done for less than (I presume) the cost of the n~=10 human trial, and it could have included followup for a long fraction of mouse lifespan to watch for long-term negative effects (or even been a lifespan study with similar total real-time study duration, eg, start with 2-year-old naturally aged mice like the Oisin trial and follow until death roughly a year later). A big question in this work is how long will the regenerated thymus remain more effective before re-shrinking. It's possible the negative effects of GH/DHEA are not so bad if only pulsed every 5 or 10 years, but if the thymus recovery is very short-lived then that is much more worrying. Followup with scans multiple years later will be very important. (And a mouse study would have been because this could have been tested on timescales relevant to how quickly the thymus shrinks in that model organism.) Fahy is attempting to commercialize this protocol to make it available as widely as possible as quickly as possible through the company Intervene Immune. Good luck to him and his team! They observed that FOXN1 was up-regulated as one of the consequences. FOXN1 is known from other work to stimulate thymus growth. Repair Biotechnologies (disclaimer: I am an investor) is working on thymus regeneration more directly via FOXN1 upregulation (via gene therapy). If all the benefit observed in the TRIIM trial is through the intermediate of FOXN1 increase,. then other direct interventions through that can avoid the HGH/DHEA/etc. Clearly an important space to watch in coming years. A lot was made about the Horvath age-clock reversal. Morgan Levine (former Horvath lab member now Yale professor doing great work on pushing methylation clocks forward) has said that she believes that though DNA methylation clocks are useful on a population level, she thinks they are too noisy on an individual level for changes in the age they report for an individual across a time interval to be reliable. She thus believes it's not useful to have one's methylation clock age tested and then retested after an intervention. If this is right (and she's clearly an authority), then it's not clear for n~=10 how much change you would expect to get due to random chance. Presumably Horvath himself could characterize this math but I haven't seen that done and presented for comparison to these results. I didn't read the paper directly. Did it present error bars on its Horvath clock averages (and cite the data and methodology by which they were computed)? Karl
  13. TomBAvoider, Michael Rae's post that started this thread provided a pretty long list of links that look pretty scientifically respectable. That post by itself seems to disagree with any claim that this is all hype hype hype. I come at this with default skepticism about the therapeutic effects and view those as just bonus if they do exist. To me this is the long-awaited successor to the Zeo headband, the first sleep measuring device that actually had EEG. This and its Philips competitor (which seems to require regularly replacing something consumable and thus seems less desirable to me) are the first sleep things that can potentially do a reasonable job at sleep phase classification. After a big analysis of all the best sleep things on the market a couple years ago, including taking 2 of the same model of one of the best devices and measuring them against each other) I concluded that movement + pulse and the other things one gets easily from wrist-based on under-mattress type sensors are just not going to be able to classify sleep phases accurately. I default assume that this will be more accurate than the Oura ring, any watch, or any ballistocardiography device. I think this is a reasonable default position until data says otherwise (rather than requiring data to prove this). Even if it's not perfect and classifying deep vs. shallow vs REM perfectly, the EEG should mean it is better at hitting sleep vs wake than the other categories of device. 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. Karl
  14. Dreem2 headband is now on sale for $500. This appears to be the summary list of changes from Dreem 1.
  15. I quick Google Image Search for the query sleep mortality shows the widely reported U-shaped curve, with optimum near 7 hours. Has anyone dug into the studies that have examine this to focus on how sleep duration of the subjects was collected? Or has anyone looked into this enough to find which such studies specifically differentiated between hours spent in bed vs. hours spent actually sleeping as determined by some kind of sensor? My expectation and vague memory is that some fraction of these studies use self-reported sleep durations. Even if all the various watches, clips, ballistocardiography, smartphone-on-mattress, etc. sensors are not perfect at measuring sleep stages, I think some of them are decent approximations for total time spent in a sleeping state vs. awake (though they vary, eg my Emfit QS seems much better at realizing how long it takes me to go back to sleep after getting up in the middle of the night than my Garmin FR235). In my case, I seem to only spend an average of about 80% of my time between going to bed and finally waking actually sleeping. So this makes a big difference in terms of where the optimum is for hrs/night. Eg, if I try to hit 7hrs/night real sleep, then I'm at nearly 9hrs/night in bed, but maybe the studies are actually just reporting associations with in-bed time. I haven't had a chance to dig into the studies myself, so I figured I'd ask if anyone else has looked at any of them in enough detail to know, or found any that specifically used a trustable sensor to determine actual sleep time in the subjects. Karl
  16. This is surprising: the study did report results at finer-grained breakpoints (8 sleep ranges instead of 3), but it was not a U-shaped curve with mortality. The lowest and highest sleeping groups survived much better than the 2nd lowest and 2nd highest, and not that much worse than the groups in the middle ranges (with confidence intervals that don't go way into bad territory so it doesn't look like just randomness due to low n). The differences between adjacent groups may not have been statistically significant, but when graphed the overall 8-group bar-chart still represents a striking departure from what you would expect for a U-shaped dose-response (see attached bar chart, fig 1 of the paper). In numbers, those sleeping >7.5hr (n=15) had 89% survival (95% CI 81-91%) vs those sleeping 7-7.5hr (n=31) having 58% (45-71%). The 81-91% range for >7.5hr doesn't seem that much worse than the 85-94% CI for the pooled 5-6.5hr group. If this were some weird quirk due to the low n, I would expect a bigger CI that ranged down further into bad survival %s. I didn't see any discussion of this turning down of the ends of the U curve in glancing very briefly through the later parts of the paper. But this doesn't match any of the other sleep research I've ever heard about. It seems so odd, it's hard for me to take this paper as a reason to think that >6.5hr is the point at which more starts to become bad, as suggested by their pooled 3-group analysis (and the figure 2 that Ron posted above). So until I see some study that replicated this, I'm still going to go with 7.5hr of actual sleep measured by a tracking device as the rough amount where more sleep may start to become a negative, as suggested by the hunter gatherer research reported in the Walker book and the studies described by Parsley. My own sleep averages around 6.5hrs (measured w/ Emfit QS under mattress + Garmin Fr235 at wrist). Karl
  17. Ron, thank you for the https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010336/#!po=1.21951 study. This is the best direct answer yet to the question I posed in the 1st post. As Michael said, it will be some time before we have lots of studies using actual sleep measurement and long-term health followup because we didn't have measurement a long time ago and what measurement we had (sleep studies) were very sleep disruptive. We obviously didn't have FitBits and Apple Watches in the 1970s, but even if whatever wrist actigraphs we did have were systematically different than what people use now, it is clearly a strict improvement on self-reported time-in-bed, and the study demonstrates exactly what I hypothesized in the 1st post: It's notable that getting too little sleep is much worse than getting too much, based on the pasted graph. It seems odd that the highest breakpoint they used was 6.5hrs. Given the other science suggesting 7-7.5hr as optimal (the studies Kirk Parsley described in the linked podcast above) or 6-7.5hr as optimal (some of the modern hunter-gatherer studies described in Matthew Walker's book I recommended above), it seems strange they wouldn't separate the above 6.5hr group with a breakpoint at ~7.5hr. I haven't had a chance to read the paper yet, but will look at this when I do. Maybe there weren't enough subjects in the above 7.5hr range. But if there were, one hopes their outcomes don't drag down those in the 6.5-7.5hr range. Tangentially, I note that Dreem's website homepage says the Dreem2 is available now, but when you click through to the order page, it still says not available yet and has a place to register your email to be notified when that changes. Karl
  18. FYI, 2nd generations of the Dreem and Philips sleep enhancing headbands announced/shown at CES this week: https://www.usatoday.com/story/tech/columnist/2019/01/08/sleep-tech-ces-2019/2505688002/ ...along with a new 3rd sleep enhancing headband called Urgonight from another French startup, this one interestingly designed to be used during the day in order to enhance slow-wave sleep at night. The USA Today article I happened upon didn't include references to scientific studies supporting the idea the way a post from Michael would. 🙂
  19. Great find Michael---thanks for sharing. All cause mortality would be nice instead of just CVD. Is there a price in terms of increased diabetes or dementia, or increased death from infectious diseases?
  20. kpfleger

    Cadmium contamination in cacao products

    It's true that I expect both the bad heavy metals and the good flavanols to vary and CL doesn't explicit address this variability that I noticed. I'm sure it's expensive to run the lab test and thus to test everything multiple times to get a range would be harder. It'd be nice if they tested some example products multiple times (eg buying national brands in different geos and over different seasons and showing a distribution to get a sense of the kind of variability) but I haven't seen it if they have done this. Still, they do often test the same products in different years and I trust them a lot more than I trust some customer service representative from Trader Joe's. In fact, they tested Trader Joe's unsweetened powder and found it exceeded acceptable thresholds in both 2014 and 2017 (1.2+ mcg cadmium / g of powder both years). I don't know what their quoted "ppm" means in this context but either it's a misleading metric or their quality control isn't as good as the rep claims. Navitas Naturals nibs only had 0.32mcg/g of cadmium. Since Trader Joe's 85% bar had 0.73mcg/g (vs Endangered Species 88% with 0.06mcg/g and several other bars with low levels), this doesn't seem to be an issue isolated to their powder. I personally will stay away from Trader Joe's branded chocolate, at least until they improve on future updates of these reports.
  21. One more with evidence of making flu vaccine more effective: ginseng: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659611/ (but also a study just in mice) Still, add this to AHCC and Rapamycin (and maybe fasting/CR). And probably sleep around the immunization is important too though I haven't seen a study on that, but intuitive given the other reading on sleep and immune system. Note: Timing is different for each of these. Eg, AHCC was given for a few weeks after immunization vs. Rapamycin was given for weeks but stopped 2 weeks before vaccination.
  22. I believe the science showing immune boosting of healthy sleep (equivalently the immune compromising of lack of sufficient sleep) is more compelling than for cold exposure, and probably more compelling than for exercise, so I'd put the list as healthy diet & sufficient sleep, then moderate exercise, then if you want to include it (not a topic I've dived into personally yet) cold exposure. Eg, see the sleep book I recommended IIRC in another thread recently: Why We Sleep by Walker. But it's probably easy to find primary studies too.
  23. I read a bit about why it didn't work in previous years. The short version is that it has live but weakened viruses, multiple strains. They have to carefully balance the strains so that some don't get outcompeted in the body and thus not provide protection by not being present in sufficient number for an immune response to be learned. For a few years one of the strains got out of whack and outcompeted some or all of the others. They think they've fixed this and the CDC is convinced this year based on data so far, but the AAP is not convinced and wants to wait until the data is more numerous and so these 2 orgs recommendations don't agree on this form of the vaccination this year. But even AAP agrees that the mist is better than not getting either form.
  24. You are entitled to your value judgement of course, but I am surprised to find this sentiment. (A) I disagree and think that flu shots are worth it in the same way that wearing seatbelts and having insurance is worth it. Small expected benefit (because benefit unlikely) but much much smaller negatives (statistically hard to distinguish from zero). (B) To the extent that you believe the studies about rapamycin, AHCC, or other things making the vaccine more effective, this clearly changes the balance of pros/cons from studies just looking at taking the vaccine the normal way. (C) It is the job of the CDC, the AAP, etc. to review all the studies and make recommendations. While the groups sometimes differ on the details (like whether to recommend the nasal spray version), they all strongly recommend most people to get the flu vaccine. Multiple different groups of scientists have reviewed many studies and surveys. Do you think all these bodies have all been captured by corporate interests? (D) The main numbers in the very link you cited seems to disagree with your point. In more detail: A year ago a relative emailed out a link expressing anti-flu-vaccine opinion, so I Google'd around a bit and this was my summary at the time: ------------------ There is a lot of anti-vaccine stuff out there in general (not just for flu shots specifically) and for the other (non-flu) vaccines the weight of the evidence is so strongly in favor of vaccination that it is sad that so much negative is written about them as to make it seem like there is still an actual debate. Flu vaccines are different in that the benefits are very clearly less strong. But because of the amount of mis-information out there about vaccination in general, whenever anything comes up about vaccines/immunizations I always try to start with as unbiased of a Google query as I can think of that tries to get at the underlying scientific evidence. So for this I typed the following into Google: science OR evidence flu OR influenza shot OR vaccine OR vaccination risk benefit FWIW, I read through the first 10 results. The summary seems to be that there is some debate about the magnitude of the benefit. It's clear that it's much less of a benefit than vaccines that almost completely prevent really bad diseases. And some reasonable sounding things claim little to no benefit. But almost none of that material suggests any significant negative---1 exception for pregnancy but with lots of cautions, and 1 link mentioning febrile seizures but at a really low chance, so no mention of any scientifically credible worry for older kids, adults, or elderly. And lots of credible stuff suggesting the benefit though small still clearly greater than zero. ------------------ Now I didn't re-do that search in late 2018, but I'd be surprised if the results flipped. As for the 2018 Cochran paper you cited, it's main conclusion is "Healthy adults who receive inactivated parenteral influenza vaccine rather than no vaccine probably experience less influenza, from just over 2% to just under 1% (moderate-certainty evidence)." Reducing the chance by half with no downside mentioned seems pretty compelling to me. Also, to me the big value of the flu shot isn't actually avoiding the flu, it's making it much less severe if it should occur and thus significantly decreasing the chance of nasty secondary infections or other more severe consequences. The article mentions hospitalizations (and notes of the reduction in them that "the CI is wide and does not rule out a large benefit") but there are less severe complications of flu that are probably more common, such as secondary lung infections. These can be more than annoyances---they can cause lasting damage. Certainly antibiotics are not uncommon (and probably more common than hospitalization) and these of course damage one's gut microbiome. I wish the review had presented statistics on the reduction in antibiotic need for secondary infections. This is the main reason I like to get a flu shot. For those of us with low WBC this is an even more compelling rationale. One could conceivably believe as a result that flu shots are thus more important for those on CR. But again, if we have ways of making the flu shot more effective by creating a better immune response, then the balance of the statistics of these previous studies shifts in favor of vaccination. Thus, the original reason for my post that started this topic.
  25. kpfleger

    Cadmium contamination in cacao products

    There are no cocoa powders that have a better flavanol to bad metals ratio than the Navitas Naturals nibs. In particular note that the Navitas Naturals powder has much more cadmium than the nibs. So you'd be much better off crushing the nibs yourself. (Of course, if you really like crushing, you could maybe crush a 100% bar that has even less cadmium.) There was one powder that had low cadmium, but it had high lead, so that's no help. Even without paying or having a login, you can read the teaser page about the report here: https://www.consumerlab.com/reviews/Cocoa_Powders_and_Chocolates_Sources_of_Flavanols/cocoa-flavanols/ There is some info in the teaser page, and there is an 11min video that explains some of the basic topics like what levels of flavanols are therapeutic and what levels of cadmium are bad. The video does also talk a bit about dutching chocolate and how that can allow for darker % but lowers flavanols. The video mostly doesn't talk specific brands but does mention Aduna Super-Cacao, which had the highest flavanol and flavanol/cadmium ratio in their chart, but the ratio is still worse than the Navitas Naturals nibs, and the video discusses how there is a reformulation of that product that decreases the flavanols so they don't recommend it.
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