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On Drug Repurposing and Nutrition Science

on damned lies, statistics, and "medical" research

Preface

Consider a scenario in the gray area, but not too gray, of medicine. So you are old, but not too old, but you have a condition which might hurt or kill you rather sooner than necessary, such as even mere age itself, since that is definitely going to kill you, but it might do so much sooner than necessary.

Now in this state of real vulnerability, suppose you don't have a perfect answer to your question, whether to follow a certain prescription or not. Your situation is uncertain, and the evidence is uncertain, and your doctors are uncertain, too. You have a medical decision to make to take a certain drug or even a nutrient, which might give you years of life, but it might not.

What are you going to do? I think:

You OUGHT to make the best decision you can make given the information CURRENTLY available to you.

Do you disagree?

Now this might or might not be the same as the Perfect Decision that might be proven years or decades in the future after perfectly designed studies have been done. Because by then you may be dead.

So you're stuck in the present, and it's either die helpless, or die trying. Obviously you should make the best practical decision available to you, which is the one using the best current information. And people and governments and systems and ideologies that say, Do nothing until perfect information arrives, are instead saying, Die patiently, or really, Just Die.

Sometimes there's a difference between Perfect Information and Best Information. Then what are you going to do?

What might this Best Information look like? Your intervention might appear quite safe and effective.

Safe: Let's suppose the intervention is used by 60 million Americans, who suffer no worse side effects than flatulence and having to switch to a slow-release version of it (metformin), or a billion people in the Third World (ivermectin), etc., so that it is obviously rather safe.

Effective: There might be a TON of suggestive evidence in favor. There might be a wide variety of animal data showing a consistent and enormous positive effect (rapamycin on lifespan). There might be geographic or population data, that countries or areas or islands where the people take that or eat more of this (vitamin K-2 on hip fractures in Japan) happen to live longer, or don't break their hips as much, or whatever. There might be strongly suggestive experimental data, such as dozens of small, international, randomized controlled trials, which show a strong positive effect for the intervention (Vitamin D3 on Covid).

Should it be okay, should it even be LEGAL, that you make your best decision? Or should you be legally prevented from making that decision by people who are paid to restrict choices?

That's today's question. It's about logic, the logic of medical decisions, and about politics and corruption, the legal structure around the medical decisions you are allowed to legally make. It's not simple, because it's in a gray zone, and the people on the other side might be doing their best, or might believe they are doing their best for everybody. But I hope we can tease out what is right and wrong here. To me, it looks like something is wrong here.

Will you agree? I don't know. Put your most critical thinking hat on, and let's find out together!

Introduction: Is our system broken?

This essay points out problems with the US medical information system at multiple levels, and ways to address them, also at multiple levels. Several examples of particular government policies are pointed out as suggesting the system is broken. The over-constrained, business-profitable, so-called logic of medical/scientific research, is pointed out as a particular stupidity that is killing lots of people. The 16 components of this logical system are brow-beaten in a detailed rant, below. Recommendations for policy-makers and private individuals are offered, as well as a business concept for a potential startup aiming to channel hungry money to underfunded, but socially recognizeable, research questions. Thank you for your interest, patience, continued interest, and support.

The Law of Sociopathy and the Logic of Medicine

What is this so-called logic? Faced with disease or death, one wants to make the best decision using the best currently-available information. Right? Anything less would be dereliction of duty, if not positive murder. Actually it is murder.

Instead, we have a system that says, IF you have a ton of money AND you will profit from a giant expensive study AND that study has 16 particular restricted characteristics which will produce a Final Answer, THEN you can have a government monopoly on your branch of the medical decision tree.

This approach, today's legal system, combines the wise Fundamental Dictum of Medicine, namely First, Do No Harm, with the Fundamental Law of Sociopathy, namely, Getting Paid Makes It Your Job.

The prevention aspect of the Do No Harm rule supports the idea of ruling things out, along with the nay-saying temperament typical of the bureaucratic personality, while the Sociopathy aspect rules out even safe alternatives so long as they feed the financial status quo. So this is what we have.

On one hand, even reasonably safe, reasonably effective solutions are to be made actually illegal, and on the other hand the way to make even not very safe, not very effective things legal is to be sure to get us paid, where "us" is government regulators and pharmaceutical companies together. It's a commercial-legal monopoly, highly profitable to the monopolists, which is built upon a very specific, and only somewhat immoral and wrong, logic of medical decision-making.

It's only somewhat immoral and wrong. It could be worse, since the current system gets some nice research done for patentable medicines. At the same time it could hardly be worse, since the current system strongly, excessively, downregulates use of safe, effective, but non-patentable options.

Who cares? Everyone who will die cares, and everyone who loves someone who will die cares: if not now then later. This is not a niche concern.

The Inappropriate So-Called Logic of FDA Approval

So, what is this so-called logic, over-constrained, and business-profitable, and why is it inappropriate, medically, scientifically, and as a matter of public policy and personal decision-making?

The US FDA seems to require a certain standard of proof for its recommendations. Practically speaking, they seem to need (1) multiple, (2) prospective, (3) US-based, (4) multi-center, (5) NIH or Big-Pharma funded, (6) two-treatment-comparing, (7) double-blinded, (8) randomized, (9) placebo-controlled (10) trials (DBRCTs), (11) comparing standard of care with an alternative, ((12) financially-) sponsored, (13) prescribable, treatment to achieve (14) a standard outcome (cure or survival) in contrast with (15) a standard endpoint (non-cure, death), for (16) a recognized disease.

DBRCTs are nice because they seem to constitute a Final, Perfect Answer, and the blockheaded among us don't just love, they actually cannot live without, Final Answers. FDA-spec DBRCT = Final Answer.

Look, I'm not so airheaded as to not admit that a Final Answer is nice if you can get it. It is nice, and would be nice. But life is full of intermediate states of knowledge which do not admit of Final Answers before decisions must sometimes actually be made, even decisions of life and death. And life is full of burning questions which are not of the form that an FDA-spec DBRCT could even answer in principle.

What if Final Answers are practically unattainable? Is that even possible? Yes, it's possible.

(1) and (4), the multiple centers, multiple studies requirements, might fail where there isn't funding to do multiple studies or get multiple centers involved.

(2) prospective studies, might fail because prospective studies might take a generation (of human lives) to complete, whereas retrospective data might give such strong indications as to constitute the best current knowledge on a question. Nice to have, and good to aim for, for later. But not having these is not a basis to avoid thinking about the best current plan.

(3) US-based, might fail if the research had to be done in some other country where it is practically affordable, again due to financial limitations. Yet good answers, or the best answers we have so far, may be found there, and medical decision-making should be based on the best currently-available knowledge, not just what landed in the US.

(5) NIH or Big-Pharma funding, might fail because the NIH has its constrained view of what's interesting today, not free from financial influence since the regulators get 2/3 of their funding from Big Pharma. And Big Pharma might fail to be interested in the question if it fails to lead to patent protection for their future businesses.

(6) two-treatment-comparison, might fail in several ways. (a) Big Pharma's idea of a comparison might involve something almost indistinguishable from the standard treatment, such as a tiny but proprietary chemical modification which makes little to no difference in the treatment results for most patients, but with a large enough study looking at a small enough fraction of the patient population might show an absolutely tiny yet statistically significant result. Here the two treatments are in practical terms one treatment, and the purpose is to protect future business, rather than make something that is a real step forward for the broad population of patients. (b) Or the comparison might be with a defunct standard of care still on the books, but already obsoleted by other recent research. (c) Sometimes multi-variate studies are necessary to understand a biological phenomenon. In such cases, logistic regression or even neural-network or AI-based assessments can draw out the separate effects of even many simultaneous influences on a particular outcome. Using rich data is how one properly understands complex systems, after all, but the binary experiments of FDA acceptability are somewhat designed to prevent, or require ignorance of, such science.

To sum up on (6) then, I will stand up for research comparing two (or more) treatments, as long as the comparison is *meaningful*. Meaningless comparisons as between a soon-out-of-patent drug and its barely-distinguishable sister synthetic demonstrating small absolute differences in outcome, do not justify expensive changes in medical recommendations and requirements. Options are okay, and the FDA shouldn't be in the business of especially protecting the new-and-expensive when the difference in benefits are tiny while the difference in costs are large.

(7) double-blinding, might fail in principle. There exist medically significant options, you might call them treatments, which are impossible to even single-blind, much less double-blind. Can you hide the fact that they are exercising from the patient who is in the exercise arm of an experiment intended to show that exercise extends life? Who doesn't know they are exercising, when they are exercising? Duh. Yet this question to which the FDA rejects the possibility of an answer, answers itself: exercise is widely considered to be the closest we have to a panacea, the universal cure. Do we rule out that recommendation because the treatment arm is not blinded or double-blinded?

(8) randomization, fails a lot. Folks do one-sided studies, or pre-select the outcomes by selecting the subjects, and such studies don't really tell you anything more than the prejudices or hopes of the experimenter. We need a real comparison, so I'll stand by the FDA with respect to randomization. So let's not throw out the baby with the bathwater. Hear hear.

(9) placebo control, is a nice to have, not a must have. If you were treating a bunch of dying patients in your study, then you ought to be offering reasonable, acceptable options to each one, and the control treatment of nothing whatsoever might be a morally unacceptable prescription. So long as you compare at least two things, you should learn something.

(10) trials. Lots of studies are not trials, but they do say something and not nothing. Retrospective cohort studies, for example, suggest something, not nothing. That's how we know about most nutritional questions, as in, Does the Standard American Diet reduce lifespan as compared with a whole foods diet? We look at things and draw the best, natural conclusions for now, and then we also launch prospective trials and animal studies, to the degree that we can get the funding. That's the best we can do. Do we give up, because it's not good enough, will never be good enough in our lifetimes, for the FDA? No, because we actually want to live longer and healthier, as best we can, and without being limited by the FDA's drug approval process.

(11) standard of care. Let me not repeat myself. I ripped that issue a new a**hole under (6) above.

(12) Financially. Well, isn't that actually the crux of everything, the driver of every loophole and constraint of this systemic corruption? Yes it is.

Since Final Answerers often like to track the money, let's notice: the FDA-spec DBRCT requires multiple Phase III studies for risk profiling, and that's after the already-expensive Phase I and Phase II studies are done for safety and dosing and some level of effectiveness. These are the domain of multi-million-dollar investments. This rules out expired-patent drug treatments and anything in the category of nutrition. Who would spend huge money on what they can't make the real money from, on what can never become a patent-protected, monopoly product. Exactly: nobody would. So we have large classes of potential valid treatments which are untested and unpursued, in principle. Rejected out of hand, for no reason related to their effectiveness, they aren't getting looked at.

In comparison, those that do, drive our half-broken system. Factor (12) above financially enables (1), (3), and (4). I guess it buys you something. But Item (12) also presumes that the study will complete soon and lead to a patent-protected monopoly status for the sponsor's treatment. Soon means that lifetime studies are not fundable in practice, because no investor will wait a lifetime for a study outcome; they need their profits soon.

It is easy to invent lifetime studies to answer any given question. Will X help me live longer? Easy to ask, desireable to know, hard to answer. Such a study might require a lifetime to unroll before the findings can be known, particularly under the constraint that the accepted experimental outcomes are limited to death or survival. Your particular medical decision must be made today, when you face your own immediate death or disease, not a generation from now. In that most common case, Non-Final Answers might be all you can find, and you will have to make your best decision in the gray light of ambiguity. Sorry, that's reality, O my dear Blockheads, get used to it, open up to it; in fact since death is coming even for you, at least, please, consider it, since it will then even for you be the Best We Can Do. Aim at least that high, won't you?

(12) really means, Buy Our Drug, and is a business-competition issue. If the system is set up as a purchase recommendation system, then the choices are your purchase options, and businesses are purposed to compete against each other in the question of whether you are to be their customer or someone else's. Being noone's customer, because the Actual answer is, Eat your Vegetables, Get some Sunshine, Sleep plenty, and Exercise: well, those answers are Unprofitable and therefore Not part of the government-industrial recommendation system, which even avoids updating the Vitamin D recommendations, which arguably constitutes racist genocide within today's medical/nutritional public policy. Wow.

(13) prescribability, is more about the prevention of consumer-led choice than about the containment of the option in a pill-bottle. The FDA rules illegal those supplements that are about to become FDA-approved, such as, recently NMN, now that funded work is underway to put a patent-protected minor variant under the FDA umbrella. This protection or expansion of the prescribability constraint makes for good business both for the pharma sponsor, and for the FDA which gets so much of its income from pharma. This is corruption and only-slightly-indirect self-dealing, pure and simple: Abominable.

(14) standard positive outcome of cure or survival, and (15) standard negative outcome, of non-cure or death. Oh please don't get me started. Really? Let's look at the aging issue again. Noone will be cured of aging, we will all die eventually, though most of us earlier than necessary, according to the emerging research on aging. So cure is off the table in principle. Leaving us with survival versus death. So: How many years before we nervous and declining old folks have to wait for a survival-based experiment to conclude? Don't you think a decade ought to pass before some new life-extension recommendation would be persuasive? Well some people don't have a decade. So this FDA requirement says in effect, We Have No Place For Your Questions: Go Die.

Yet on the other hand we have excellent and improving biological clock measurements taken from blood samples which track the aging process to some remarkable degree of precision, and we could look at studies which associate various treatments with improvements in so-called biological age. Oh, but those are not the "Standard Outcome", so let's ignore that work. This is the policy, at present. The Ostrich hides its head in the sand, to be sure not to see things. Must we be Ostriches, as a society? Let's not. Let's allow alternative outcomes which are meaningfully supported. Let them prove out their biological clocks; then let's use them!

Similarly in nutritional studies, you take some vitamin and check your blood levels. If the blood levels are at unhealthy levels, that means something, not nothing. Yet it's not a Standard Outcome of Death or Disease or Cure or Survival, so it is required to be ignored in the FDA reasoning universe. That limitation just happens to fit in with a financially motivated system of medical information recommendations. That system fails to benefit from recommendations about, for example, vitamins; that system (?therefore?) suppresses medical recommendations about them. Why else would Vitamin D's RDA still be at 600UI despite the proofs that the studies which put that number there were mistaken and should have specified a level 10x higher? Because we don't want to change recommendations, and we don't want to admit mistakes. That's the approach of a frightened 12-year-old, not a society of adults. Sorry for the rant.

(16) a recognized disease. This is a particular loophole for a lot of sins to enter our world. What exactly is or is not a recognized disease?

It is no mere curiosity that the FDA fails to recognize aging as a disease. This is a out-of-date, traditional view which incuriously but profitably fails to take notice of the commonality of all the so-called diseases of aging, for which age, hello, is the strongest predictive factor. They seem to say, "Our ignorance is exceeded only by our lack of interest." And, "If all that happens is that you die, that won't be changing our minds."

Instead, cancer is one thing, diabetes another, CVD/heart disease a third, Alzheimer's disease a fourth, Parkinson's disease a fifth, etc., etc., each with its own body subsystem, its own set of medical specialists, conferences, industry lobbyists, its own medicare billing codes, established business channels and profit streams, and none shall interfere on the turf of any other. And yet inflammation, a.k.a. inflammaging, is characteristic of all of them, and correlated with age. Things like Vitamin D deficiency predict several of them. Or sugary diets, which give you more frailty, CVD, diabetes, Alzheimer's disease, (via obesity) cancer, and cancer progression: several things. They aren't necessarily that different.

Look: If the Huns are breaking down the castle walls, they'll eventually get through at some location first, but the problem isn't the relative slight weakness of one or another part of the walls but the primary fact that Huns are attacking in the first place. Aging is the attacking Huns, while the different "diseases of aging" are the walls, towers and drawbridge, the bailey and the motte.

You can't just ignore the Huns, folks.

The science of aging as its own, unitary topic does currently exist and is moving rapidly forward, having already achieved such milestones as

Matt Kaeberlin and Pankaj Kapahi are a couple names I'm following at present in this space. These are serious people, not wild-eyed lunatics.

No, this is not nothing, I hope you will agree. But all of this is off the table at the FDA, because aging is not a "recognized disease". Imagine that we had a treatment that adds five years of productive healthspan to the average life. We might be there today. But the FDA wouldn't recognize it, the NIH and Big Pharma won't fund it (where are the rapamycin studies?!), and there it sits, in a black eddy of policy ignore-ance.

Okay that was approximately 16 factors of brokenness in the current medical information recommendation system, which is largely the state medical establishment and the FDA. Have I got you on my side here, yet? I hope so; I think so.

Indeed I hope the blockheaded among us are not so blockheaded that they destroy too many lives through their decisive and grinding inaction -- more, their prevention of action on the part of others -- before deciding to wake up and do their actual, morally-required homework. Thus we stare with mistrust if not hostility at each other, the Explorer and the Decider, uneasily occupying the same actual universe.

Medical Decision-making Under Imperfect Information

Certain stupidities are ignored in the current medical scientific space regarding aging. First, the alternative outcome we are talking about is death, unnecessarily early death, massive, enormous, genocide-level, millions and tens of millions per year of potentially preventable or postponeable human death. That's what's actually going on, and that's what old folks are actually facing as they get, hello, older.

But that's not the way "they" think about it. Instead it's: Death from aging is normal and unpreventable and therefore insignificant and ignoreable. If metformin, for example, might make you live longer, well that has to be proven with a FDA-spec DBRCT contrasting against some other treatment on the standard endpoint, which is death. But metformin is off-patent, so nobody is going to make money if it is proven to directly impact aging, and it'll take a long time for people to die in a standard-endpoint study, so even if it were fundable the time for a study might be way longer than your life expectancy. So the system just says No to this perfectly valid research question, and a million like it. As in, No we won't be thinking about what we won't think about, and we won't let you either. Even if it kills you.

That's what kills me, the idiot complacency of the bureaucrats here. In the metformin case, I don't care if it turns out to solve aging or not, the point is it might, and some partial data at the moment suggests it's not just a fantasy. So here we have a treatment that 90 million Americans are already taking for its approved use, let's consider that maybe that's on the safe side, in fact, let's call it, could we just call it, safe? The complications are things like burping and farting if your dosage isn't right, or you didn't get the slow-release form, or you didn't take it with meals. 90 million Americans figure it out. On the other hand, the benefits are that you have an apparent likelihood, let's downgrade that to be nice to a possibility, a mere possibility, that it MIGHT make you live a few years, or one year, longer. So you weigh in the balance, the benefit of years of living instead of being dead, as compared with the risk of having a little intestinal discomfort while you get your dosage adjusted. So what does the FDA say? They say, Hell no, noone can get Metformin, since it's off label, without a prescription, which isn't forthcoming to non-diabetics, which is still most of us, even though the risk is THAT small and the benefit is THAT large.

To me this indicates a broken system.

Again, we cannot fail to notice that the FDA-spec DBRCT plan is a fabulous way of doing business for Big Pharma. They can afford the multiple, large, expensive trials which themselves constitute a moat against smaller competitors in their space; their treatments exist as binary options in the treatment space (standard-of-care versus use-theirs-instead); and their standard endpoints (survival) for short-term fatal diseases are within the time-range of reasonable and practical if expensive studies. Plus, incidentally, they pay the regulators 65% of the regulator's own budget in the US of A (and more in the UK).

This system is NOT great for non-Big-Pharma treatments, such as expired-patent drugs or nutraceuticals. Consider a nutritional supplement, like say NMN (Niacinamide Mono-Nucleotide). Suppose taking it reduces the biological age of 60 year olds, measured by a blood test or assay, on average, by five years after one year of use. I'm just making up an example. For an example. Well, blood levels are not a "standard endpoint" (death is), and aging is not a disease so it's not a "recognized serious or life-threatening condition" which would justify "surrogate endpoints" like a biological age blood test. So the FDA chucks it out. No results forthcoming, no research will be looked at, no good, give up, go away, we don't recognize your condition, so shut up: and go die. See? The alternative is death.

When the alternative is death, the FDA should back up a little bit.

In particular, if something is SAFE and MIGHT HELP, then it should NOT BE ILLEGAL.

Here. Do the risk-benefit analysis, counting aging as an actual disease. If the risk is small, like for Metformin or Rapamycin or whatever, properly dosed and medically supervised, and the potential benefit is enormous, like the percent reaped by the Grim Reaper for people of that age every year, then reconsider what quality of information you need to allow something. Maybe you can't afford an FDA-spec DBRCT. Maybe you have a ton of population data or retrospective data or the treatment can't actually be hidden from the user so it can't be blinded, or whatever, so it's not the gold standard of data but it's still quite suggestive, like the Vitamin D and Covid data, for example, in 2/2023. Anyone betting on the market using this kind of information might bet money on it with that amount of information, but the FDA has a different standard: "Do no harm", so to speak. Maybe surrogate endpoints like blood levels would give you an excellent idea of treatment performance without waiting decades for everyone to die sooner or later, but the FDA will not acknowledge such arguments. (Nobody is paying them to, so why should they? The regulators in the US get more than half their budget from Big Pharma, why wouldn't they derail or slow-track changes if it protects their accustomed ways of doing business? Getting paid is called doing your job, hello -- for sociopaths, irrespective of the public welfare.) Especially with financially unprofitable treatments, the FDA is not set up to do the morally right or intellectually correct thing.

"Do no harm" is the medical motto, but "Balance today's risk and reward assessment given today's information" is a better standard for those who risk death soon. These are slam-dunk arguments, tiny risk versus huge reward situations, but noone seems to be listening.

If aging isn't a disease, then people aging out and dying sooner isn't a "serious and life-threatening condition" which would justify "surrogate endpoints". This is their argument. But what madness is that? Since when is death not life-threatening?

Decisions might need to be made sooner than FDA approval arrives. Decisions are often made, must be made, in the gray light of incomplete certainty and evolving knowledge. We might not be able to get a good answer today, yet folks are aging year by year today, and dying at their current actuarial rate even this year, while they could potentially be living quite a bit longer at some rather high probability which has been estimated in poorer-quality data which happens to be the best we have, traded against near-zero risks. These are the questions that doctors should answer with their patients, and the FDA should back the f*** away slowly from them, should allow them, instead of pretending that the only reasonable decisions are those backed by 100% FDA-spec DBRCTs, and everyone who has a question not answered by those should go ahead and die so we don't have to stretch our brains to think about them. That's not really acceptable.

Tomorrow there may be a FDA-spec DBRCT on some treatment option, sure, but that may be too late for a dying patient (and we who are aging are indeed dying, on some schedule or other), who has to bet his or her life today, this year, and should be guided by the best data available today, even if that's not the full and perfect final data that the FDA demands. It's as if they are unable to consider that information accumulates and knowledge evolves and therefore recommendations might change. If new data comes, people take it into consideration. That's called learning. But the FDA won't allow uses that are based on best current estimates if the FDA-spec DBRCT is not done.

I think we have some work to do.

Community capitalism applies to medical research

Long ago I conceptually developed a project, Community Capitalism, a.k.a. PFFS, which seems to me to apply nicely to medical research. The idea is to crowdfund and kickstart research to answer questions that people do care about, which Big Pharma and the NIH don't. Quality research driven by motivated contributors, that's what the Community Capitalism concept offers. With or without CC, the obvious targets we must aim at are these:

Two main categories of research that corporate capitalism doesn't support (non-Big-Pharma, non-NIH) are nutrition and repurposing of expired-patent drugs. Neither pays anyone's bills, because noone can patent either kind, so they are all wallflowers, all dolled up but noone asking for a dance.

Nutritional Science.

Nutrients are intrinsically hard to study. People like to eat all kinds of stuff, from snails to Coke. Who knows whether it was the snails or the Coke or something else that did you in, thirty years later!? You can't tell.

International comparison studies like the Ansel Keys' bullshit, manipulated, 17 country study are at best suggestive. Get 'em where you can, and use 'em if you must, but aim higher if you want any kind of confidence.

There was a diet study of prisoners in Minnesota decades ago, you couldn't do that study today with our ethics standards.

The trick is endpoints. The standard endpoint is survival. So if you eat snails instead of Coke you survive how many years more or less, well that's a question that can't be answered in a few months, it needs something like a lifetime. Maybe we should start up those long, long-term studies (with better questions), as fast as we think of them. But since we are all dying soon, we might also want to get as good information as can soon-enough be got. So we might look for "surrogate endpoints", which we can correlate with the standard endpoints, and which we can more easily measure in the near term. Blood levels, hair loss, skin wrinkles, cognitive tests, etc. etc. Those might be surrogates for early death, or disease, which will give us scientific leverage on the problem.

I would like to see ODAs, Optimum Daily Allowances, studied for a wide variety of potential nutrients against biological age markers. See the argument in tomveatch.com/diet.php, that Optimal Daily Allowances might far exceed the Recommended Daily Allowances for the essential Vitamins and Minerals as well as an expanded list of optimizing nutrients. The decision tree of the uses of nutrients needs to be fully explored, so we know that a little more of X actually makes no difference in the short term to prevent bleeding out, say, but in the long term it enables better quality of life in one's 90's (those are long term studies, hard to control, and slow to ripen), or in the measureable short term reduces, especially, biological age markers, but also particular disease markers. It's a big space, with lots of X's, markers, durations, prioritizeable uses, and priorities. Very big.

But the case of Vitamin D with its 10X underestimated RDA and its 800 copies of the gene for the lock that the Vitamin D key opens up, is compelling. There is a potentially large decision tree of nutrient-use prioritization for a large list of nutrients, and if the body is capable of taking all it gets of a given nutrient for one priority before it allocates any of that nutrient to a lower-immediate-priority but still long-term-impactful purpose, then we need to know that decision tree if we are to optimize human living. We are so ignorant that our studies have, like, three categories, carbs + proteins + fats, while the list of nutrients is multiple dozens, and the list of foods is uncounted. We can't even get answers whether "good fats" include coconut oils (phytosterols from vegetable oils play a role in atherosclerosis) or not (low-fat high-carb diets tend to be unhealthy); or lard (no phytosterols: good) or not (obesogenic high fat diets, i.e., too many calories so you get fat, do lead to the consequences of, well duh, obesity).

I am hoping that CommunityCapitalism will enable ODA research. It won't be paid for otherwise, apparently, is what I'm saying. And it'll optimize human lifespan and healthspan, at least as far as nutrition can make a difference. So we should work on it!

Are you curious about any particular nutrient, vitamin, mineral, or therapy, or disease? Here, I hope, is a path to finding out more, for yourself and for everybody.

Expired-Patent Drug Repurposing

This category includes Metformin off-label use for anything outside diabetes, Rapamycin used for anti-aging effects rather than organ transplant rejection, the Ivermectin rage during Covid. The way you make the real money in drugs is a patented FDA-approved treatment in an improved standard of care. Without the patent which gives you a monopoly, everyone can copy it, make it, and sell it for cheap. That might help the users, the buyers, but it doesn't help the people who made a business out of it. It's a loophole in capitalism, otherwise so beneficial for humanity. Buyer and seller both have to gain for a transaction to happen, and here the seller doesn't gain, only the buyer does. So we have to construct a seller out of thin air, mainly by proving to the government that some treatment is safe and effective for some valuable purpose, even though no company will hold a monopoly on it to milk for 20 years using the patent system. It turns out that generic drug manufacturers are easy to find and easy to persuade to produce patent-unprotected drugs for economical prices at world-satisfying volumes. The market solves the problem of sellers producing low priced drugs at scale. The problem is the legality of the transaction. Which means we have to get past the FDA.

Well, we aren't going to be paying them bribes or regulatory oversight fees, like Big Pharma's 65%. But even as little folks banding together with smart scientists and experimentalists and chemists and statisticians and managers and report-writers and even lawyers we can design good studies, get quality researchers, do quality work, and write solid reports, which will satisfy any rational requirements. And we can use the power of the public welfare, of logic, and also of grass-roots politics and potentially even legal action, to clear and to clarify the paths forward and take projects forward along them. That's the promise of doing paid work, the promise of PFFS and Community Capitalism applied to medical research. Because when you get paid to do it, then that's your job. And when it's your job, you get it done.

I say, Let's fix this! Will you help?

May I put in a plug for help?

At the political level regarding public policy, I hope we could enact legal protections for Current Best Decision practices in medical decision-making, that is, to make it legal to choose a treatment option, in one's circumstances, that is *relatively* safe (in proportion to the danger of the non-treatment alternative), and that is presently supported by a *preponderance* of current evidence, even if that evidence does not constitute a Final Answer. Policies should be Expected to Change as experimental results come in, and Choices should not be limited to those supported by the 16 corruptions of the FDA-spec DBRCT requirements currently in place nationally.

Since the system needs reform so badly, yet is so deeply entrenched at the national level, such changes may only be possible to enact at the state or local level.

At the personal level, I do offer a path to those who want to have a long-term impact on humanity hereafter, to contribute in some way to my CommunityCapitalism.cc a.k.a. HumBlink project, or to projects within this project.

Money and Labor are two ways to help; Encouragement also helps!

The two or twenty major donors who fund the work that proves some new nutrient has a role in long-term survival will have an impact on humanity forever. Consider that when you write your will, or hope to have a meaningful impact in life. The downstream impacts of such Benefax optimization are greater, if more personally remote, than having children, if, say, your children's and grandchildren's years in the next century or two are fewer than the number of years in extended lifespans of those impacted by your funding. A result that extends the average life by a month, times a few billion people on this planet, or anyway 300M in the US, makes you, in the sense of Benefax, equivalent to Abraham being the father of nations. Bequeath significance, bequeath love, sure, but don't bequeath unnecessary waste and do, for your own sense of meaningfulness -- bequeath what will produce ripple effects downstream from your particular action to enabling other positive flows of goodness over and over hereafter. Three primary methods of downstream ripple effects from the goodness flowing out of you today to impact the future, are parenting, entrepreneurship, and knowledge creation. Here a check could drive a lot of important knowledge creation. Donations, I promise, will be carefully spent. Please consider it.

Labor will also help hugely. A mere word of encouragement goes a long way. We need a team of scientific advisers, coding for website, financial and workflow components, marketing and public relations, etc., etc. What can you do? Let's talk.

And I thank you. Find my contact information, or use the feedback form below, and get in touch. I look forward to talking with you.

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Created: February 3, 2023