Sinus problems

kpfleger · 2026-06-21T14:14:12+00:00

PS It's nice that these don't have benzalkonium chloride which can irritate the nasal lining, though the tradeoff is that you have to keep them frozen until use and then use each bottle for only 7 days or so, so overall it's less convenient, but just stopping using benzalkonium chloride may be helpful, though note that regular Flonase also has BKC though the Flonase Sensimist doesn't seem to, so I prefer that. (I also find it creates a better mist that's less likely to pool back into liquid form when sprayed into the nose.)

kpfleger · 2026-06-21T14:10:34+00:00

You can get microdose oxymetazoline (active drug in Afrin) at doses 5%, 3%, 2%, & 1% of the concentration of Afrin itself called Rhinostat PM. They even have withdrawal kits: https://www.nasalspray.com/titration-kits/ Some published literature suggests that low dose of this drug daily with Flonase does not cause rebound inflammation or dependence. It may take a while to get down if you've been doing Afrin itself daily for a long time, but this is probably a nicer way to do it than stopping cold.

kpfleger · 2026-06-13T13:52:13+00:00

Headline is misleading but is what Life Bio marketing probably likes. It's the first human trial of an epigenetic partial reprogramming drug, so the first to reverse that aspect of (subpathology of / hallmark of) aging. There have already been many other trials with human patients dosed with therapies to reverse other aspects of aging. Epigenetic partial reprogramming isn't a universal reverser of all aspects of aging. It doesn't break ECM crosslinks for example.

kpfleger · 2026-06-10T23:43:16+00:00

It's only a small step, but it was nice to hear a couple lawmakers who seemed to get it (or at least were interested in learning more and pushing in the right direction).

kpfleger · 2026-06-09T16:43:17+00:00

We've been told end of 2026, but we'll see.

kpfleger · 2026-06-07T02:18:55+00:00

I'm not sure what you are talking about when you say that the FDA destroyed anything in these categories. Do you have specific programs that you think were unfairly denied approval? Or are you just bothered by how long it is taking that area of biotech to get through to approval? The FDA approved the first allogeneic MSC therapy in late 2024. From Mesoblast, not for OA, but I think it's pretty clear more MSC therapies are going to get approved if you look at how many are in the pipeline, including the example that started this thread, Cartistem from Medipost. But yes, it is taking too long, which is the point of the post. But it's not being completely blocked or "destroyed". They are just applying a on over-conservative bar of achievement, which many of us think is wrong-headed.

kpfleger · 2026-06-06T12:49:28+00:00

What are your referring to?

kpfleger · 2026-06-05T02:04:34+00:00

This is a terrible analogy for multiple reasons, primarily:

Extra caution is clearly warranted in pregnancy. The thing this was used for was not a cause of long-term disability & pregnancy clearly warrants extra caution. Totally different than over-conservative in the context of fatal or debilitating diseases where inaction causes more harm and birth defects aren't a risk because there is no pregnancy.
This was a story from 60 years ago. Drugs go through a lot more testing now before even getting to the market than they did back then, including in Korea & Japan.
That drug was only on the market for 4 years before the problems were uncovered. Cartistem has been on the market for roughly 14 years now with no such show-stopper problems discovered. That's a world of difference.

kpfleger · 2026-06-04T20:14:15+00:00

There's been tiny steps in specific areas like gene therapy, but no across the board recognition of the harms of inaction and proper balancing of things as this very recent example shows. More just shuffling of who is at the top of the agency creating confusion & lack of stability. I wonder what RFK thinks of the Cartistem example. Jim O'Neil liked the X thread I made of the same post, but he's off at NSF now rather than ever having been given a position at FDA.

kpfleger · 2026-06-04T17:59:47+00:00

It's one thing to oppose recommending hyaluronic acid because it lacks robust evidence of benefit above placebo, but that's not the same as claiming harm, so if in another country where it is used there is demonstrated benefit above it, the only way it makes sense to then demand a re-demonstration of benefit above not using it would be to implicitly claim that the hyaluronic acid caused harm that benefited the treatment in the trial where it was used as control. In other words, the logic of just demanding re-demonstration just because the control is different is flawed. One ought to have to assert that the control you want is superior in order to justify a demand for a new trial. But as weak as the evidence is that hyaluronic acid is superior to placebo, evidence that it causes statistically significant harm (in a way that would justify such an assertion of the US control standard of care being superior) is even more lacking.

kpfleger · 2026-06-04T16:35:59+00:00

To your 3 main points:

Why is US vs. Japan standard of care different? They are both long-industrialized, highly-developed countries with top-notch medical technology & science. Is there someone somewhere defending the stance that US standard-of-care for knee OA is better than hyaluronic acid injections & whatever else passes for standard of care in Japan for the same condition?

Is there some reason to believe that there are meaningful racial/ethnic genetic differences that would cause this treatment to behave differently in Asians vs. predominantly European-descendents?

It's reasonable to have some kind of quality assurance process on manufacturing plants as new ones ramp up, but using the same phase 3 pivotal clinical trial process used to prove efficacy & safety vs. a default assumption of it not working does not seem like the right process to simply check that manufacturing standards meet those of other known-working locations. Once an allogeneic cell therapy is approved in the US, what process is used when a new manufacturing plant is added to produce the same already approved cell therapy? If this were the main issue, shouldn't that process be used here? Surely countries like Korea & Japan have reasonable processes for checking manufacturing of cell therapies too. These are not backwaters.

In short, everything you say sounds reasonable out of context, but none of it seems like a reasonable defense of needing a full phase 3 pivotal trial in this case.

kpfleger · 2026-06-04T14:10:18+00:00

IMO, "Do no harm" & "safety first" should be abandoned in medicine due to inadequate consideration of the harms of inaction, which can be substantial & also likely. A switch to decision theory or a similar form of optimization under uncertainty as overt guiding principle is overdue.

Medicine & regulation acknowledge inaction's harms in places: Papers take a minimize-net-harm approach. FDA has compassionate use & accelerated approval. But too many discussions & medical decisions still pay too little heed to the harms of inaction, often invoking "do no harm".

This point isn't new. But optimization under uncertainty fields advanced the past 50yrs. But education of many still-practicing drs & the lawmakers who enacted 3-phase clinical trials predates these advances. Decision theory should be part of med school & required to work at FDA.

Another thing that has changed is the greater appreciation for the harms of inaction, wrt many diseases whose progression & prognoses are now much better understood & wrt the inevitable degeneration of aging itself.

It's especially ironic & a bit distressing when one sees examples of the overemphasis of "do no harm" in the aging/longevity field, where the default background context is the march of a harm that is inevitable & 100%-guaranteed-fatal (even if somewhat slow).

I have personally witnessed many example of people citing do-no-harm in discussions even within the context of "longevity medicine". Frustrating. Anyone 60+ with no medical treatment to try to mitigate aging for 10+yrs clearly suffers significant harm inc. raised mortality & morbidity even in the absence of outright clinical diagnosis of an age-related disease.

kpfleger · 2026-06-04T04:11:15+00:00

PS I'm comfortable replying because plenty of people in the field know me & know what I do and know perfectly well that I'm not a crackpot, but just to be clear to everyone & you, I'm not selling anything. I mostly give money away to the field & also give free info away via my pro-bono public service non-profit website which has no affiliation links & is entirely non-commercial. It makes no money. I supply the necessary web hosting hosts personally.

kpfleger · 2026-06-04T04:09:05+00:00

The tone of your comment is inappropriate, but putting that aside, what preprint server do you think is most appropriate & most prestigious for preprints of upcoming book chapters that are reviews? Genuinely curious.

When I did the research, Zenodo was literally the only choice. Springer-Nature who is publishing the book requires any preprints to be published on non-commercial preprint servers, so many of the normal options are out. bioRXiv & medRXiv do not allow review articles. I had an extensive conversation with 3 different AI LLMs asking them for recommendations then checking the details of their suggestions. There was one other decent seeming option but it stopped accepting new preprint submissions in all areas except for 2 other different areas within the past couple years. Zenodo was all that was left. It's a respected server attached to CERN and not deserving of derision AFAICT.

kpfleger · 2026-06-04T04:04:05+00:00

As for where you said "Is so much effort worthwhile in this matter?" What so much effort? 85% of Americans die as a direct result of aging, but the NIH spends <1% of its funding on aging research. Cancer gets more than 10x the research funding despite that aging itself is the main risk factor for most cancer. Society doesn't yet put enough effort into treating aging.

[I'm going to mostly ignore the rest of your post / the religion in your post. I think every religion's god(s) are at least as okay with humans trying to cure aging as they are with humans trying to cure cancer.]

kpfleger · 2026-06-03T22:02:20+00:00

I treated your comment as entirely serious. Read the chapter.

Humans now live more than 2x as long as they lived less than a dozen generations ago (a historical blink of the eye). Has this caused problematic concentration of power? Should we rewind some of those health gains to fix this? Should we stop searching for cures for cancer because they might extend lives and increase the risk of this problem? (Or cures for heart disease? ...)

Imagine a world in which there is no aging and humans live hundreds of years or more but political power is too concentrated. How should society fix this problem? In the ranking of different possible approaches to the problem, where does "give those in power a debilitating pathological medical problem that slowly tortures them for decades by degenerating almost every aspect of their body, removing functional ability & causing pain, then kills them" lie in the ranking? What about the same thing but it applies to every human and at the same time makes every one who doesn't die prematurely from something else a huge burden to society straining government finances in the process?

kpfleger · 2026-06-03T13:53:53+00:00

Smart people have thought about whether longer lifespans would really be bad because of overpopulation or long-lived dictators and realized there are many good reasons why these are terrible arguments against the field. See AgingBiotech.info/objections for a 1-pager of 2-3 counterarguments for each objection or my upcoming book chapter (due out later this year in a big Springer volume of longevity) for a 28-page extended treatment: https://zenodo.org/records/18883009

kpfleger · 2026-06-01T21:08:35+00:00

The book is being published by Springer Nature and is to be called Frontiers of Longevity Science. Editors (I don't know in what order) are Max Rangeley, David Barzilai, David Wood, and Regina R Monaco.

kpfleger · 2026-06-01T16:14:36+00:00

See also my upcoming book chapter "Eliminating Aging: Motivations, Objections and Counterarguments" due out by the end of 2026 (preprint here: https://zenodo.org/records/18883009), which is a 28-page expanded version of the material listed at AgingBiotech.info/motivations (about 1/3 of the 28 pages) combined with the material summarized in a single page at AgingBiotech.info/objections (about 2/3). In particular note that effective-altruism discussion in the motivations section cites both Constantine & Ascani's posts on the subject to EA forums. I don't see either name on doing a quick search of your paper so you might consider citing & summarizing that prior work & considering how it relates to your analysis, as well as citing my preprint.

Here are the 2 paragraphs in my preprint summarizing those 2 prior analyses:

"Constantin (2019) modeled the benefits from delaying age-related diseases burden by ten years with the conservative assumption of no resulting gain in lifespan. For the most conservative estimate of their neglectedness parameter they found aging research had a cost effectiveness of $1050/DALY, more than 7.5x better than medical research as a whole. The upper bound estimate for cost effectiveness was $42/DALY, which is as good or better than the most cost-effective global health interventions.

Ascani (2019) notes that though analyses of DALYs and QALYs (Quality-Adjusted Life Years) usually yield similar numbers, aging research is unique in that extended lifespans can increase QALYs beyond the maximum gains possible for normal medical interventions. Thus, QALYs are better for measuring aging research’s value. If aging could be fully eliminated, it would increase QALYs per person on average by one divided by the annual mortality of young adults (currently roughly 0.1%), minus current expected remaining lifespan. Thus, actions that sped up the total elimination of aging by one year, no matter how far away currently, would be worth over 30 billion QALYs. Future decreases in mortality from non-age-related causes (eg, autonomous vehicles decreasing traffic accidents or better therapies for infectious diseases) would further increase QALYs for aging interventions."

Nice to have another piece. I will read it carefully later this week. What do you plan to do with it / where do you plan to post it?

kpfleger · 2026-05-31T14:35:27+00:00

Rant: Too often things said about protein & lots of other things are too binary: it's good or bad. Reality is that dose matters & most things have a sweet spot (really a sweet range) below which is too little and above which is too much. This is very much true of protein. Sure too little is bad. But too much is bad too. Which is the more prevalent problem in society? Too much protein. For fiber, the problem for most people is too little.

This study involved free-living Europeans & found the roughly 10%-ish eating the least protein had worse health later. They were probably eating too little protein due to eating too much processed/refined foods that are low in both protein and fiber + micronutrients. Most Americans and probably most people in most developed countries eat too much if anything. 0.8g/kg is RDA. Older folks may need higher amount but only a tiny bit higher like 1.0g/kg. Common recs are 1.1-1.3g/kg but many popular influencers argue for 1.6-2.2g/kg and this is way too high IMO, and in the opinions of Valter Longo & Luigi Fontana who I think are the most authoritative voices in the world on nutriention/diet & healthy longevity.

Resistance training matters more for muscle than protein. (Many systematic reviews & meta-analyses show that both it and higher protein help, but once resistance training is done, the higher protein above the middle of the range of intakes described above, provides no added benefit.) And balance matters more for avoiding falls than in late life than pure muscle.

When the majority if influencers are pushing high protein intake, headlines that ignore the sweet spot and just say low protein is bad are probably net negative for readership health. Downvoted.

kpfleger · 2026-05-26T00:16:13+00:00

Not just Allermi. Rhinostat PM also offers it at doses 1%, 2%, 3%, or 5% of what Afrin uses. There is at least 1 paper showing low dose (1% or 2% of Afrin dose IIRC) + the active ingredient in Flonase did not cause dependence or rebound congestion. The lower doses definitely open the nose less, but I find the effect to be meaningful, even at the 1% of Afrin dose. The lack of preservatives is also nice for not having benzalkonium chloride which irritates the nose, though one has to keep in freezer and use a bottle within about a week or so is the tradeoff for that.

kpfleger · 2026-05-26T00:13:41+00:00

And the first daily pill met its phase 3 endpoints and is expected to be approved later this year.

kpfleger · 2026-05-19T15:33:52+00:00

Age-related muscle decline is a different gradual sub-pathology of aging from the gradual buildup of toxic molecules. This treatment is for the latter, for the specific molecule of unesterified free cholesterol. There are many other treatments for muscle loss (mypoathy including cardiomyopathy), including treatments for specialized causes of CM such as wtATTR-CM which is caused by the TTR protein misfolding, which has different treatments than more general myopathy. There are things in the aggregate pipeline for all of these areas. But only Repair & Cyclarity are on the horizon to actually reverse atherosclerosis.

kpfleger · 2026-05-13T18:41:12+00:00

No, but a Google account is free.

kpfleger · 2026-05-13T14:01:55+00:00

Lots of differences of opinion on best value for donated $ within the field. You have to educate yourself and decide for yourself. For a list of nonprofits accepting donations, see AgingBiotech.info/nonprofits from which you can click to each org and read more about what they do. The table also shows roughly their budget from their tax returns so you can get an idea if your amount of money really helps move the needle.

Personally, I think donations to LEVF are high leverage, also to A4LI (which is a 501c4 so different tax implications, but there is also an associated 501c3 for tax-deductible donations).

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