kpfleger Posted October 3, 2018 Report Share Posted October 3, 2018 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?) Quote Link to comment Share on other sites More sharing options...
Gordo Posted October 5, 2018 Report Share Posted October 5, 2018 I don’t think flu shots are worth it and I never get them, latest Cochran’s review: https://www.ncbi.nlm.nih.gov/pubmed/29388196 Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted October 5, 2018 Report Share Posted October 5, 2018 Thanks Gordo. The review suggests flu vaccines are modestly effective but also pointed out most studies are industry funded. Research results can be biased in favor of the interests of those funding or conducting research and it makes me wonder to what degree that might be occurring here as well. While in general I find most anti-vaccine stuff absurd compared to the benefits rendered against diseases such as smallpox and polio I expect there are at least tiny merits to the arguments of the risks of vaccines. And in the case of flu vaccines I could see the risk/reward ratio being questionable. Quote Link to comment Share on other sites More sharing options...
Sibiriak Posted October 5, 2018 Report Share Posted October 5, 2018 (edited) Evidence-based medicine group in turmoil after expulsion of co-founder By Martin Enserink Sep. 16, 2018 , 5:10 PM https://www.sciencemag.org/news/2018/09/evidence-based-medicine-group-turmoil-after-expulsion-co-founder Quote A bitter dispute with one of its co-founders has plunged Cochrane, an international network of scientists promoting evidence-based medicine, into a crisis on the eve of an international gathering that marks its 25th anniversary. Late last week, a narrow majority of the organization's Governing Board apparently decided to end the Cochrane membership of Peter Gøtzsche, director of the Nordic Cochrane Centre in Copenhagen and a member of the board himself, for causing "disrepute" to the organization. Four other board members then resigned in protest. Gøtzsche announced his own expulsion in a three-page statement issued on Friday that said Cochrane was going through a "moral governance crisis." In a phone interview with Science, Gøtzsche speculated that some foundations funding the collaboration had pressured it to get rid of him because of his highly critical views about pharma. He says he had become increasingly unhappy with what he describes as a "more commercial and more industry-friendly direction" in the organization. Gøtzsche had also launched a broadside against a favorable Cochrane analysis of vaccines against human papillomavirus (HPV), charging it may have overlooked side effects—a position embraced by antivaccine groups. Quote Both within and outside of Cochrane, Gøtzsche is widely known for his fierce attacks on the pharmaceutical industry and his criticism of medical interventions he deems useless or harmful. He wrote a controversial book about what he says is the overuse of mammography in breast cancer screening, and, in another book, likened the pharmaceutical industry to "organized crime." He has often been critical of Cochrane as well. In a statement written for his 2017 election to the board, Gøtzsche listed a litany of "pretty widespread concerns" he wanted to address, including the concentration of power at the Central Executive Team in London and the fact that "collaboration" had been dropped from the group's name. "The Cochrane Collaboration is now run much more as a business with a brand than it was just a few years ago," he wrote. Quote Gøtzsche says the decision is likely related to a frontal attack on a Cochrane review about vaccines against HPV, a cancer-causing virus, that he and two co-authors published in July. The review, published in May in the Cochrane Library by researchers from Belgium and the United Kingdom, supported the mainstream view that such vaccines can prevent precancerous lesions in adolescent girls and young women. In their criticism, published in BMJ Evidence-Based Medicine, Gøtzsche, together with Lars Jørgensen of the Nordic Cochrane Centre and Tom Jefferson of the University of Oxford in the United Kingdom, argued that the review "missed nearly half of the eligible trials," "ignored evidence of bias," and did an incomplete assessment of the vaccine's side effects. The review didn't constitute the "trusted evidence" promised in Cochrane's official motto, they said. After an investigation, Cochrane Library editors acknowledged in a 30-page response that the review had missed some trials, but said this made little or no difference to the main outcome and that the criticism was wrong on many other points. "There is already a formidable and growing anti-vaccination lobby. If the result of this controversy is reduced uptake of the vaccine among young women, this has the potential to lead to women suffering and dying unnecessarily from cervical cancer," they wrote. In a response published on Friday, the editors of BMJ Evidence-Based Medicine defended publishing the trio's broadside, saying it "provokes healthy debate." Edited October 5, 2018 by Sibiriak Quote Link to comment Share on other sites More sharing options...
kpfleger Posted October 5, 2018 Author Report Share Posted October 5, 2018 (edited) 10 hours ago, Gordo said: I don’t think flu shots are worth it and I never get them, latest Cochran’s review: https://www.ncbi.nlm.nih.gov/pubmed/29388196 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. Edited October 5, 2018 by kpfleger Quote Link to comment Share on other sites More sharing options...
BrianA Posted October 5, 2018 Report Share Posted October 5, 2018 BTW, the Flumist nasal version of the vaccine is back to being available again. They tweaked one of the target strains in it to make it more effective. An option for those of us who prefer to avoid any preservatives+adjuvants that might be in the injected vaccine. Also for us cheapskates, I found the local Publix is giving away $10 gift cards for getting the vaccine. ? Quote Link to comment Share on other sites More sharing options...
kpfleger Posted October 5, 2018 Author Report Share Posted October 5, 2018 3 hours ago, BrianA said: BTW, the Flumist nasal version of the vaccine is back to being available again. They tweaked one of the target strains in it to make it more effective. An option for those of us who prefer to avoid any preservatives+adjuvants that might be in the injected vaccine. Also for us cheapskates, I found the local Publix is giving away $10 gift cards for getting the vaccine. ? 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. Quote Link to comment Share on other sites More sharing options...
JEC Posted October 6, 2018 Report Share Posted October 6, 2018 First post here so go easy on me I've never been a big fan of flu shots, but I suppose if they do cut risk without any potential downside, then it makes sense to consider. Kpfleger, you mention that it cuts risk by a half. I suppose that's true as far as the math goes, but going from an absolute risk of ~2% to just under 1% is much much different than having risk cut from say 40% to 20%. The other thing i find interesting in situations like this--most everyone seems to benefit by pushing for flu shots and overstating their efficacy The Cochrane collaboration seems to be the only group I know of that pushes back against the mainstream opinion. If you're unaware of what studies say about the flu shot, you probably think you're doing yourself a huge favour. Same thing with doctors, pharmacists, and even school administrators. Everyone seems to benefit by pushing for them. I guess my main point in writing is that there does seem to be evidence that they help, but it's quite minor. You'd prob be better off focusing on washing your hands or eating more garlic. Quote Link to comment Share on other sites More sharing options...
Saul Posted October 6, 2018 Report Share Posted October 6, 2018 Dear colleagues, I strongly agree with those who who favor vaccination against dangerous diseases, and also flu (Kefleger's reasoning is, IMO. correct -- ignoring the stuff about rapamycin). For example: We have an excellent vaccine research unit here at the University of Rochester Medical School: About two years ago, I was pleased to be a subject in a study testing the effectiveness of an experimental Norovirus vaccine; when Norovirus ravaged our campus several months later, I was much less concerned than my colleagues. This coming Tuesday, I will be taking an experimental vaccine against RSV (respiratory syncytial virus), and also receive my annual flu vaccine at the same time and place. This will take place at the Infectious Disease Unit of Rochester General Hospital (this is the second largest hospital in Rochester -- it is not a teaching hospital like URMC; my wife works at RGH, as an NP specialized in gastroenterology). For those who believe in avoiding vaccinations, consider the result of the foolish mass avoidance of measles vaccine in California: the (vritually extinct) disease has re-emerged, and killed many. LOL, -- Saul Quote Link to comment Share on other sites More sharing options...
Gordo Posted October 7, 2018 Report Share Posted October 7, 2018 I just want to clarify that I’m not an “anti-vaccine” person at all, I just don’t find the science compelling (yet) for the current flu vaccine (I’ve read that better vaccines are in the works and look more promising). Also in light of Siberiak‘s link above I think it’s worth looking at the PRIOR most recent Cochrane review on flu vaccines: https://www.ncbi.nlm.nih.gov/pubmed/20614424 WARNING: This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding. That review also described risks from getting the vaccine by the way (which are tiny, but not non-existent). Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted October 7, 2018 Report Share Posted October 7, 2018 How do we know there are no risks from the vaccine? I'm not against vaccines at all. There are MANY that are quite important to get (and I get them regularly), but I see no point in getting vaccines with extremely poor effectiveness. I don't get the flu shot. And I don't believe we know enough about possible negative effects - for example, perhaps challengeing or revving up the immune system (as vaccines do) is not an unalloyed good - a certain amount may be positive in that it keeps it tuned up, but do we know for sure that there isn't such a thing as overloading it unnecessarily, same as it's not always good to have inflammation - there is such a thing as too much inflammation. So I'm happy to take vaccines with proven benefits, but I'll pass on vaccines with marginal or zero benefits - that's an immune challenge I can do without. I have never had the flu, and I'm not super concerned about it, but if they do come up with a vaccine that is more effective - in the 90% range - I'd probably spring for it (especially as I get older and weaker). Quote Link to comment Share on other sites More sharing options...
Saul Posted October 7, 2018 Report Share Posted October 7, 2018 It's never good to have inflammation. But it is good to rev up the immune system through vaccinations. Of course, exercise is also important -- and this causes very brief localized imflammation, which is quickly taken care of by a healthy body. -- Saul Quote Link to comment Share on other sites More sharing options...
Gordo Posted October 7, 2018 Report Share Posted October 7, 2018 The flu vaccine also commonly causes Soreness, redness, and/or swelling from the shot Headache Fever Nausea Muscle aches Quote Link to comment Share on other sites More sharing options...
Saul Posted October 7, 2018 Report Share Posted October 7, 2018 And protects you from the flu! ? -- Saul Quote Link to comment Share on other sites More sharing options...
AlPater Posted October 8, 2018 Report Share Posted October 8, 2018 21 hours ago, Gordo said: The flu vaccine also commonly causes Soreness, redness, and/or swelling from the shot Headache Fever Nausea Muscle aches Commonly?: https://www.ncbi.nlm.nih.gov/pubmed/2294762 : "These symptoms did not result in a decreased ability to perform usual daily activities" versus getting the flu. How many get the flu: https://www.webmd.com/cold-and-flu/flu-statistics . Quote Link to comment Share on other sites More sharing options...
JEC Posted October 8, 2018 Report Share Posted October 8, 2018 (edited) Strange--it seems the original study referenced a much lower incidence of the flu. Edited October 8, 2018 by JEC Quote Link to comment Share on other sites More sharing options...
Gordo Posted October 9, 2018 Report Share Posted October 9, 2018 5 hours ago, JEC said: Strange--it seems the original study referenced a much lower incidence of the flu. Could be linked to the rise in obesity and diabetes: https://www.telegraph.co.uk/news/0/rise-obesity-diabetes-could-exacerbate-future-flu-pandemics/ Quote Link to comment Share on other sites More sharing options...
mccoy Posted October 9, 2018 Report Share Posted October 9, 2018 I never thought about flu vaccination; in my case, the immunity boosting trinity (Whole diet, exercise and cold exposure) seems to work far better than any vaccine. When taken together, these three practices seem to be a pretty powerful combo. Of course, that may be not true for everyone. Also, I noticed that not everyone is able to expose consistently to cold . Quote Link to comment Share on other sites More sharing options...
kpfleger Posted October 10, 2018 Author Report Share Posted October 10, 2018 On 10/9/2018 at 4:33 AM, mccoy said: I never thought about flu vaccination; in my case, the immunity boosting trinity (Whole diet, exercise and cold exposure) 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. Quote Link to comment Share on other sites More sharing options...
mccoy Posted October 10, 2018 Report Share Posted October 10, 2018 (edited) KP, I fully agree, fact is that trinity sounded better than quaternity, LOL But of course quaternity it is, sleep is king! Edited October 10, 2018 by mccoy Quote Link to comment Share on other sites More sharing options...
Gordo Posted October 11, 2018 Report Share Posted October 11, 2018 kpfleger - cold exposure can be used to improve sleep (that's what I do), this is also discussed in the cold exposure thread (search that thread for "sleep"). This can result in very deep restorative sleep which boosts immune function. Its funny because just yesterday the company I work for sent out an email to all employees promoting the flu shot (its free, no copay, go get it)... A long-lasting flu shot that you'd only have to get once every 5-10 years could be on its way The hope is that such a broad-spectrum vaccine also could protect against rare but potentially deadly pandemics The most vexing thing about the annual flu vaccination is that it's annual. The most vexing thing about the annual flu vaccination is that it’s annual. You have to get it every year, and many people don’t do so. In fact, the Centers for Disease Control and Prevention recently reported that only 2 out of 5 Americans have received the shot so far this flu season. Wouldn’t it be easier if a flu shot were a once-in-a-lifetime event, or even once or twice in a decade? Public health officials see that as a potential game-changer. “If we had an effective universal vaccine, it would take a huge dent out of health-care costs [and] disruption of work, school attendance and social activities,” says William Schaffner, a professor of medicine at Vanderbilt University and medical director of the National Foundation for Infectious Diseases. “It could change the entire way we prevent influenza.” It could change the entire way we prevent influenza The idea no longer seems so elusive, says Barney Graham, deputy director of the vaccine research center at the National Institute of Allergy and Infectious Diseases. Modern molecular technology enables scientists “to design things at atomic resolution,” which “really wasn’t possible until the last few years,” says Graham, who is trying to develop what scientists call a universal, or long-lasting, vaccine. Several groups of scientists, including Graham’s, have reported progress toward a vaccine that could protect against flu permanently with a single injection or with a shot given every five to 10 years. Either approach would be a big advance over current practice, which requires health officials to predict major flu viruses nine months in advance so manufacturers can adjust the vaccine each year. With a universal vaccine, “we wouldn’t have to worry about that,” Schaffner says. “Each year we could go after people who hadn’t been vaccinated before. It could be a year-long, daily vaccination activity, not just focused in the fall.” The hope is that such a broad-spectrum vaccine also could protect against rare but potentially deadly pandemics. “It would be the single most important thing we can do in public health today,” says Michael Osterholm, a professor of public health and the director of the Center for Infectious Disease Research and Policy at the University of Minnesota. While flu can strike anyone, it is most dangerous for the very young, the elderly and the chronically ill. Globally, seasonal flu epidemics produce 3 million to 5 million cases of serious disease every year, resulting in 250,000 to 500,000 deaths, according to the World Health Organization. Symptoms include fever, dry cough, headache, muscle and joint pain, severe malaise, sore throat and runny nose. The two major types of seasonal influenza viruses that can infect humans are A and B. Type A viruses, which are constantly changing, are the ones usually responsible for yearly epidemics. Scientists classify type A viruses into subtypes based on the combinations of the two molecules that cover the surface of the virus, hemagglutinin and neuraminidase. Vaccines work by stimulating the production of antibodies against pieces of the virus. A universal vaccine would need to provoke antibodies that bind to “conserved” regions of the virus – that is, areas that stay the same and are common to most flu viruses. Currently, seasonal vaccines are designed to respond to the hemagglutinin head, which changes every year. Researchers are using different strategies that target the common areas. Some very impressive scientific efforts are underway to make this real Two groups working separately, for example, are focusing on hemagglutinin’s stem, or stalk, which, unlike the head, doesn’t change. To do so, each team had to first figure out how to stabilize the stalk after lopping off the head. (The head is removed because it draws key immune system cells – those needed to make antibodies – away from the stem.) Each using a different approach, the teams have found a way to anchor the stem once the head is eliminated. Another team built an entirely new virus in the lab by using recombinant DNA techniques, then designed a vaccine based on its conserved elements. “We hope that by doing that, our immune system will remember the conserved regions . . . so that changes in the head won’t matter,” says Peter Palese, chair of the microbiology department at the Icahn School of Medicine at Mount Sinai in New York. Finally, another group has developed an experimental multiyear vaccine based on the genetic sequences of flu strains that have appeared in the past century. These researchers believe it is unrealistic to assume that any experimental vaccines, including theirs, will last a lifetime without requiring an update; thus, they are reluctant to predict the effectiveness of their own beyond five to 10 years – but even that would be an improvement over having to get an annual shot. “We can go back in history and make vaccines that protect against all the variants for the last 100 years,” says Ted Ross, director of the Center for Vaccines and Immunology at the University of Georgia’s College of Veterinary Medicine. “That doesn’t mean we can do 100 years in the future, but we still can prevent a lot of disease. We just don’t know when and if one approach will have longer staying power than another. We’ll find out.” While animal studies of various prospective vaccines are promising, it probably will be years before researchers start testing them in humans. Still, public health officials are excited. The idea of a universal vaccine seemed a pipe dream until recently. “But now, or very soon, it may no longer be a flight of fancy,” Schaffner says. “Some very impressive scientific efforts are underway to make this real.’” ‘I can’t rewrite history’: She didn’t think a flu shot was necessary — until her daughter died at 12 Sorry kids: Docs urge flu shots, not nasal spray, this year Flu nose spray doesn’t work for kids and needles are more effective, U.S. health panel says Quote Link to comment Share on other sites More sharing options...
Michael R Posted October 14, 2018 Report Share Posted October 14, 2018 So first: Karl bounced his fasting-as-natural-mTOR-inhibitor-so-see-PMIDs 29997249 & 25540326 idea: at the time, I thought (and still think) it's damned clever, but thinking more on it I'm not sure how to operationalize it,nor run a feasible clinical trial without a whole bunch of prior work. The problem is that while we have evidence that people on chronic CR have inhibited mTOR signaling (PMID 26774472 — consistent with the mice — as usual ;) ), I'm not aware of any good data on the time-course of mTOR suppression in different tissues upon initiation of fasting, let alone the more specific intermediates you'd want to see to replicate the mice (improved HSC function leading to increased production of naïve T-cells). Longo reported (PMID 26094889) that after a cyclical 5-day fasting-mimicking diet, "Although not significant, the percentage of [mesenchymal stem and progenitor cells (MSPC)] in the peripheral blood mono-nucleated cell population showed a trend (p = 0.1) to increase from 0.15 ± 0.1 at baseline to 1.06 ± 0.6 at the end of FMD, with a subsequent return to baseline levels after re-feeding." So without further work, I don't know that it'd be worth it to try this: conceivably, if you do it too soon or too late, you might miss the potentially beneficial shifts in MSPC output (and thence hypothesized increase in naïve T-cells), or the energy deficit or other metabolic changes might counteract such a benefit. Subjects in Mannick's first trial were administered everolimus "0.5 mg daily, 5 mg weekly, or 20 mg weekly... for 6 weeks ... and, after a 2-week drug-free interval, were given a 2012 seasonal influenza vaccine", and a similar protocol in the second, ± resTORbio's BEZ235/RTB101. Second: I strongly urge people to get the flu shot. Aside from the general principle that some risk reduction is better than none (added on, of course, to all the other stuff you may do to protect yourself), at next to no risk (vide infra), and the fact that vaccines may work better in us (based on PMIDs 26774472 (mTOR inhibition in chronic human CR) and PMID 2071828), whereas CR folk may be at greater risk if they do contract flu (discussed many times before — studies by Christine Gardner and others), and the fact that neither the individual trials nor the meta-analyses capture the benefit of the residual immunity from being vaccinated one year that carries over into subsequent years — aside from all that, folks are forgetting that the individual vaccinee isn't the only person at risk. By lowering your own risk of the bug taking hold in you, you're reducing the risk of transmission to others, including the vulnerable immunosenesced elderly, young children (who are at elevated risk of serious flu-related complications), people with immune deficiencies (HIV/AIDS, congenital disorders, people who have just had their bone marrow ablated for cancer, etc etc). Each of us needs to step up to protect all of us. On 10/3/2018 at 10:18 AM, kpfleger said: 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 Yeah: there is prior work, but it's all in mice, alas. The incentives are not well-aligned for clinical trials of dietary supplements, alas. On 10/6/2018 at 9:44 PM, TomBAvoider said: How do we know there are no risks from the vaccine? Because we track side-effects in clinical trials, silly ;) . Gordo listed them; they're quite minor. Quote Link to comment Share on other sites More sharing options...
Todd Allen Posted October 15, 2018 Report Share Posted October 15, 2018 59 minutes ago, Michael R said: Because we track side-effects in clinical trials, silly ? How many of those trials are designed, conducted, analyzed and reported by people whose highest priority is the public interest? Quote Link to comment Share on other sites More sharing options...
TomBAvoider Posted October 17, 2018 Report Share Posted October 17, 2018 Yes, of course I understand that they must have conducted studies that looked at side effects - which you have to do for every medication to get it past the FDA. However, I wasn't referring to immediate side effects, but rather to more subtle and long term effects which might be hard to spot in shorter term studies - which, by the way, is the frequent downfall of a lot of medications pushed through the FDA review process by large pharma. Have you noticed how often these have to come back with black box warnings or are taken off the market altogether? If the studies you refer to were as reliable and comprehensive as you seem to have faith in, then recalls should never happen. Yet they happen with alarming frequency, and probably should happen even more often. I am simply applying the precautionary principle. I don't believe - I repeat - that we know all there is to know about the long term effects on f.ex. the immune system. Maybe it is harmless and maybe not. Not knowing for 100% means if I don't have to undergo a medical procedure or take a given medication, I elect not to, if the benefits are minimal. My attitude to taking the flu shot might change if I can be convinced that even if it is worthless or of limited utility to me personally it might protect the herd - but I'm not completely convinced of that either, so why should I take that sacrifice for no discernable benefit to anyone? Sorry, but unless the effectiveness of the flu shot improves dramatically - dramatically - I am not inclined at the present moment to get one. I might change my mind in the future, especially if a better vaccine comes along. Quote Link to comment Share on other sites More sharing options...
kpfleger Posted October 17, 2018 Author Report Share Posted October 17, 2018 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. Quote Link to comment Share on other sites More sharing options...
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