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  1. 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
  2. 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
  3. 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. 🙂
  4. 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?
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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?)
  11. 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.
  12. I continue to be disappointed that none of Longo's work that I've noticed has results stratified by BMI or any correlates such as various blood markers (CRP, etc.). In most cases the control rodents are ad-lib and the control humans are on average normal people in our culture who on average eat pretty close to Standard American Diet---i.e., both species of controls are not particularly healthy. And given Rhonda's readership/listenership, I continue to be disappointed that she doesn't press him on the question of how much benefit is there to someone who already does a bunch of what she recommends in terms of healthy lifestyle. How much benefit is there to FMD or IF for those with a BMI of say 22.5 who eat a mostly whole-foods, plant-based diet whose biomarkers are mostly good (eg most of the way to Fontana's profile of CR even if not all the way in CR)? I buy that there are some benefits for cancer avoidance to getting glucose super low and ketones up temporarily every now and then, but it's hard to swallow any all-cause mortality overall quantification of benefits of any variants of fasting with controls that are to my mind artificially unhealthy. I get that those controls are appropriate if you are trying to help the majority of typical Americans, but I assume that for the community of these forums and for Rhonda's followers a different baseline should be considered. Now I haven't dug into the details of all of Longo's work or all work on various forms of fasting and time-restricted eating, so if someone knows of some data that compares to healthier baseline controls, I'd love a pointer. BTW, this is a broader disappointment I have with Rhonda's interviews that applies to other topics as well (and is feedback I have only just recently shared with them). For example, I wish she had pursued the question of how much benefit saunas / heat-therapy provides relative to a similar amount of sweating exercise as the control rather than just sitting around. I assume that there is some overlap in the pathways mediating the health-positive effects of saunas vs exercise and thus that the addition of sauna use would not be purely additive on top of the more basic healthy lifestyle factors (good diet + exercise + sleep + not smoking) at the level indicated by most of the studies (whose controls probably don't achieve even that basic mix of healthy lifestyle).
  13. kpfleger

    Cadmium contamination in cacao products

    Note that CL has updated their flavanols/chocolate/cadmium report (probably paywalled; I paid). The top says, "last update 9/12/18". Cacao powders generally seem to have more cadmium than nibs. By lucky chance the nibs that they tested that had the best flavanol to cadmium ratio was what my family has been using anyway, Navitas Naturals (so maybe this got better since the 2014 report) and for the double-win my favorite dark chocolate, Endangered Species 88%, did the best of bars (excluding a 100% bar) and had an even better flavanol to cadmium ratio than the Navitas Naturals nibs, though with the disadvantage of some sugar.
  14. Since posting this I have read the excellent book, Why We Sleep by Matthew Walker. Highly recommended. And available as an audiobook. One of the best books on health relationship to any aspect of lifestyle that I've ever read. Better than any single book on nutrition/eating (including CR) that I've ever read, and I've read many more on that area of lifestyle. Similar for exercise. He specifically says in this book that the sleep recommendations of the National Sleep Foundation and CDC of 7-9 or 7+ are time-in-bed recs and that modern hunter-gatherers actually sleep 6-7.5 hrs/night. That CDC page cites a couple published studies (that I did not dig into). I now try to spend 8-9 hours in bed in order to get 6.5-7.5 hours actual sleep. [My sleep efficiency seems to hover around 80% based on my Emfit QS and on my Garmin Forerunner 235 after correlating it with my old Basis Peak (which I trust more for sleep than the Garmin and which agreed with the Emfit) when switching from the Peak to the Fr235.]
  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