Luck based medicine: my resentful story of becoming a medical miracle

[Elizabeth]

Link post

You know those health books with “miracle cure” in the subtitle? The ones that always start with a preface about a particular patient who was completely hopeless until they tried the supplement/​meditation technique/​healing crystal that the book is based on? These people always start broken and miserable, unable to work or enjoy life, perhaps even suicidal from the sheer hopelessness of getting their body to stop betraying them. They’ve spent decades trying everything and nothing has worked until their friend makes them see the book’s author, who prescribes the same thing they always prescribe, and the patient immediately stands up and starts dancing because their problem is entirely fixed (more conservative books will say it took two sessions). You know how those are completely unbelievable, because anything that worked that well would go mainstream, so basically the book is starting you off with a shit test to make sure you don’t challenge its bullshit later?

Well 5 months ago I became one of those miraculous stories, except worse, because my doctor didn’t even do it on purpose. This finalized some already fermenting changes in how I view medical interventions and research. Namely: sometimes knowledge doesn’t work and then you have to optimize for luck.

I assure you I’m at least as unhappy about this as you are.

Preface to the Preface

I’ve had nonspecific digestive issues since before I have memories. In pre-school my family joked that I would die as a caveman because there were so few things I would eat, and they were mostly grains. This caused a bunch of subclinical malnutrition issues that took a lot of time to manage and never got completely better. And while I couldn’t articulate this until it went away, food felt gross all the time

It’s hard to convey just how bad this was for me, because it feels like it undermines everything I did to work around it. I’ve always been functional but decidedly less healthy than my friends. I got sick more often and it hit me harder. I was slower to heal from injuries and scrapes and that limited my interest in the more athletic sort of hobbies. I couldn’t work the same hours, and working hours traded off really sharply against energetic hobbies. I had to spend a lot of time managing food where other people can just show up and eat, which was a constant source of social stress. My genetics say I was destined to have anxiety issues, but the low level malnutrition and justified feelings of food insecurity despite apparent abundance did not help anything.

Eventually in my late 20s. I saw a nutrition-focused psychiatrist who listened to my observations (I could only eat protein with soda), immediately formed a hypothesis (I produced insufficient stomach acid), asked questions to rule it out (which I no longer remember), suggested a test (take stomach acid pills and see if they gave me heartburn), and when it came back positive (no heartburn) suggested a course of action (keep taking stomach acid pills) that showed immediate benefits in practice (indigestion removed, but only when I took the pills). My protein and produce intake increased enormously, and I felt overall much better.

This is exactly how I want medicine to work. I gathered good data and took it to an expert who immediately formed a model, definitively tested it, and prescribed a course of action that made mechanistic sense. If you forget that it took almost 30 years and I took those exact same symptoms to other doctors beforehand, it’s a stunning success.

But it was not a total success. My protein intake maxed out at 50 grams/​day, and that was if I made consuming protein a hobby and nothing went wrong. I was doing much better than I had been, but my nutrient tests showed I still had a lot of issues. Eventually the stomach acid pills stopped working, although that seems to be “my stomach started producing more acid and a different problem became the bottleneck” rather than the pills ceasing to contain acid. But the problem was not solved, and more of the existing treatment did not help.

Standard Preface

I worked with a number of doctors on fixing the remaining digestive, for ~another decade. I had a lot of conversations like the following:

Me (over 20 pages of medical history and 30 minutes of conversation): I can’t digest protein or fiber, when I try it feels like something died inside me.

Them: Oh that’s no good, you need to eat so much protein and vitamins

Me: Yes! Exactly!. That’s why I made an appointment with you, an expensive doctor I had to drive very far to get to. I’m so excited you see the problem and for the solution you’re definitely about to propose.

Them: What if you took a slab of protein and chewed it and swallowed it. But like a lot of that.

Me: Then I’d feel like something died inside me, and would still fail to absorb the nutrients which is the actual thing we want me to get from food.

Them: I can’t help you if you’re not willing to help yourself.

Or sometimes…

Me (over 20 pages of medical history and 30 minutes of conversation): I can’t digest protein or fiber, when I try it feels like something died inside me. If I make it my top priority I can get maybe 50 grams of protein a day.

Them: Oh that’s no good, you need 70 minimum, and really more like 100. Also because I’m a naturopath I’m morally obligated to tell you to give up eggs, dairy, and wheat.

Me: That’s gonna be hard seeing as those three are 90% of my protein intake and by far the easiest forms of protein to digest.
Them: What if you ate pea protein?

Me: Well that’s harder so…worse.

Them: What about hemp?

Me: That is even harder than pea protein.

Them: If you’re not going to try why are you even here?

These exchanges were incredibly draining for me, so I didn’t have them that often. Every year or two I’d get my hopes up for a new doctor, pay a shitton of money (these doctors are never covered by insurance) for several emotionally draining appointments, and then get told they couldn’t help me and this was a failure on my part.

After several years of that pattern I gave up and went back to my old PCP. She hadn’t solved the problem either, but she had solved other problems, had ideas to try for this one, and believed it was a physical rather than moral problem. Unfortunately she is very busy, and sometimes pawns me off on her assistant doctors, who are idiots. That second conversation was with one of those, although in the real conversation I was less witty, and was more like “*sob* no *sob* I told you *sob* I CAN’T”.

I refused to see that doctor again, but this left me little leverage when they assigned me a different sub-doctor to handle a post-covid rash back in April. You know how naturopaths complain about western medicine being mechanical and reactive and not taking the time to reach a systemic understanding? Well this guy, who we will call Dr. Spray-n-pray, was determined to fight for equality by taking the same approach with unregulated supplements. He guessed I had an allergic reaction and threw 5 different antihistamines of varying legitimacy at me, with no mention of testing the hypothesis, monitoring my progress, expected changes, duration of treatment…

And it worked.

Not on the rash; I eventually had to go to urgent care for that. But shortly after I started the pills, I found myself eating 50 grams of protein in a sitting and then going back for more the next meal. I also started chowing down on produce, and at some point realized I couldn’t remember the last time I’d had dessert. I had known I had some aversion issues with food but didn’t realize how gross I found it until the feeling went away and I could just eat without feeling contaminated. About here is when I started a food diary and found I was regularly hiting 100g of protein/​day. When I crashed my scooter I ate 350 grams of protein over two days, suggesting I could do that any time I wanted but chose not to, suggesting my body was getting all the protein it felt it needed, all of the time.

I’m not sure I can convey what a big deal this is either. I would have paid several years’ salary for this cure without thinking. It is now possible for me to feel okay at an emotional level it wasn’t before. Plus, you know, I can actually get the nutrients I need to run my body and stuff. My injuries after that scooter accident healed noticeably faster than past injuries. The fact that I haven’t caught an illness since April’s covid isn’t conclusive, since it’s summer and I haven’t done anything high risk, but it is interesting.

[I do have covid antibody results from the December (8 months after my vaccine) and August (4 months after catching covid) and my levels have gone way up, but that’s more likely due to the more recent and stronger immune stimulus.]

But that evidence came later. Back in May the timing of the miracle suggested that one of Dr. Spray-n-pray’s pills was responsible. This was more or less confirmed when I weaned off the various pills and the subtle grossness around food started to return. I could also feel growing sugar cravings. So it was important to figure out what the miracle pill was and get back on it immediately.

[If any of you are thinking “well it could have been a coincidence”: no it fucking couldn’t. I did not carry this around for 35 years and try everything to fix it only to have it suddenly go into remission for no reason. I’ll believe covid fixed it before I believe that.]

I had always assumed the reason doctors turned on me was that it was easier than accepting that they couldn’t solve my problem. But this one had fixed my problem! Not on purpose or anything, but I was fully prepared to pretend it was. Now we just had to figure out what had worked and why, in case it suggested any additional actions. I made a spreadsheet tracking the changes as best I could – when my diet changed (using grocery order data), when I’d started and stopped which pills. Surely my data plus his doctor ego would help us get to the bottom of this.

At the time of my follow-up appointment I had a strong guess which supplement had helped based on timing, but it didn’t make any sense. The active ingredient was Boswelia (specifically BosPro brand (affiliate link). I’m afraid to try another in case it breaks the spell). Boswelia is sometimes described by alt medicine websites as helping digestive issues, but in the same way they describe every supplement as helping digestive issues. “Helps anxiety, allergies, autoimmune disorders, inflammation, and digestion” should just be a stamp. This isn’t even necessarily illegitimate – the body is complicated and lots of things are entangled, especially with inflammation.

But I’ve tried a lot of these supplements at one point or another and there was absolutely no reason to predict this one would be different, even if I had researched it ahead of time. Examine.com is pretty positive on Boswelia but doesn’t list digestion as an issue it solves. Everything is connected to everything else in the body and it was still pretty hard for me to make a causal chain between Boswelia’s alleged mechanisms and improvements in my digestion. So I was extremely excited for Dr. Spray-n-pray to explain why it had worked.

All this was on my mind when I finally got to ask Dr. Spray-n-pray why his treatment had worked. He mumbled something about inflammation and moved on. He had zero interest in my spreadsheet or a more mechanistic understanding of what had changed. I confirmed the miracle was from BosPro when I resumed taking it and the digestive improvements returned (including the creeping feeling of grossness going away). It’s now 5 months since I started taking it and it still works but I have no idea why.

This is not how I want medicine to work, at all. A medic who clearly was not trying for a systemic understanding recommended a lot of stuff and one of them happened to fix a problem as unrelated as could be that I’d spent a decade+ searching for without success? Even knowing definitively that it works we have no idea why, and what would help or hinder it? And there’s ~0 evidence this would help other people with the same condition?

This is bullshit. But bullshit is working where logic feared to tread.

Other Evidence

This experience isn’t what got me on the path of luck-based medicine though. I was already at that point when the supplements were prescribed, which is why I took them instead of doing 5 hours of research and ignoring Dr. Spray-n-pray’s suggestions as the ravings of an idiot. There were a lot of contributors to my shift, but a few stand out.

A few years ago I ran a series of epistemic spot checks on various self-help books, and found that how helpful they were had no correlation with how rigorous or true their theoretical backing was.

Then last year I ran that ketone ester study. I and a handful of people I know get insane gains from using ketone esters – better than Ritalin with none of the side effects – but when I ran an RCT (n=8-12 depending on how you count) no one reported any benefits.

Or take Slime Mold Time Mold’s all-potatoes-all-the-time diet study (which happened after I started on the magic pills, but is too good an example to pass up). I have an extremely long list of complaints about their hypothesis and follow up study:

• They failed to contextualize it as a monodiet and discuss the classic monodiet problems.

• Potatoes aren’t nutritionally complete and don’t have enough protein for people to thrive. They gestured at some of the nutritional deficiencies but I think not hard enough, and believe potatoes have more protein than reported but have not pointed to any evidence to that effect.

• They tracked weight loss over 28 days but will not be doing a follow-up for six months. Since the default after rapid weight loss caused by an unsustainable diet is immediate regain, this is unconscionable.

• I haven’t had time to dig into the object-level facts in the argument between SMTM and a persistent critic, but with my monkey social brain it sure does look like SMTM is blowing off well-founded criticism (given in a super aggressive manner).

• They treat weight loss as an unalloyed good no matter how fast or what the person’s starting weight was.

  • I have not looked into the popular “weight loss not safe above 2 pounds per week” claim and it wouldn’t shock me if it were made up, but if I had an intervention with double that impact I’d spend an hour investigating the claim.

  • Weight loss beyond a certain body fat percentage is bad. You need that stuff.

• They did warn people about solanine poisoning but I think they should be more concerned about it.

• Analysis featured a lot of stories along the lines of “Did X on Wednesday and lost 2 pounds on Thursday” and fat loss does not work like that. Two pounds overnight is either water weight or has a lookback period longer than 24 hours.

  • I’m deeply confused about that second part, I don’t understand why or how weight-loss-that-is-definitely-not-changes-in-water-retention comes in chunks. If you have an answer I’m quite curious.

That’s a lot of epistemic sins. OTOH, their potato diet results inspired me to try the minimal potato diet, which consists of eating some potatoes every day (I started with ~100g of baby potatoes), and I’ve lost 15 pounds in 3 months. That level of weight loss with zero sacrifices buys you a lot of epistemic forgiveness, especially when my miraculous dramatic dietary improvements did fuck all to the number on the scale.

[ People already writing their “potatoes can’t possibly be the cause it must be psychosomatic” comments in their head: I see you. Your hypothesis is perfectly reasonable; in your position it would be my first reaction too. But in this particular case you’re going to need to explain why potatoes caused that magic mental shift when giving up soda, a dramatic improvement in diet and removal of dessert entirely, complete emotional reorientation to food, a mild prescription stimulant, and varying levels of exercise did nothing, and ketone esters worked better than all of those but much worse than potatoes. Comments not attempting this will be deleted or mocked as I see fit.]

If you are thinking “ah, but clearly those all did contribute and the potatoes were just the last step”: I agree that’s likely. If I’d started minimal potato diet before BosPro it either wouldn’t have worked or would have been extremely bad for me. But since it seems to work for at least some other people who didn’t have all this baggage I think we need to update in that direction.]

Or take every person who got a second opinion on their cancer and was recommended diametrically opposing treatment plans. Doctors as a class are not as epistemically virtuous as I’d like, but that’s not (always) why they propose wildly divergent treatment plans. In most cases it’s because the answer isn’t obvious, or at best has only been obvious for a few years.

And then there’s the absolute shitshow that is nutrition research. No one knows what the average optimum nutrient level is and even if we did it wouldn’t be that helpful for figuring out the optimum level for a given individual, because humans are so unbelievably variable.

I could go on here, but if you’re reading my blog you’re probably already on board with shit being extremely complicated and I don’t want to belabor the point.

Moral of the story: when intellect fails, try luck guided by intuition

Some medicine is very deterministic. Antibiotics, most of the time. That daylong IV drip when I had norovirus that probably turned the infection from deadly to a kind of annoying 36 hours. We may not know the optimum level of a given nutrient but most severe deficiency diseases can be solved by giving you the thing you’re severely deficient in. My impression is statins work pretty reliably.

But a lot of medicine just seems to be kind of random. People go through 10 antidepressants and then somehow the 11th one works great. Ketone esters increase my energy level so much I gave up soda and caffeine entirely but do nothing for most people. All those books where the cure was a miracle for someone, and it can’t just be a placebo because there’s no reason for the 35th placebo to be the one that works but nothing else makes sense.

All of which leads me to conclude that once you have exhausted the reliable part of medicine without solving your problem, looking for a mechanistic understanding or even empirical validation of potential solutions is a waste of time. The best use of energy is to try shit until you get lucky.

Not at random or anything. My guess is the world contains metis and you do better-than-chance preferentially trying things that helped one guy on a message board for your condition (even though it was shown to make no difference in real studies) or going to alt-modality practitioners (even the one with proactively stupid justifications they insist on sharing). The latter is especially true if you can find a practitioner that accepts that their treatments don’t always work and have a system to notice that and change course, but I think maybe even the really gung-ho ones sometimes have good ideas (you just have to set up your own system for deciding when to quit). Just don’t get hung up on “do we understand why this works?” or “does this work for other people?”

Also please remember that side effects and drug interactions are a thing. Anything with a real effect can hurt you. I gave a very caveated suggestion of BosPro to someone on Twitter and it caused something akin to niacin flush in them. This is the same brand that does nothing to me but makes me better at digestion and uninterested in sugar.

So I guess the full and accurate statement of my beliefs is “Try solving problems with understanding first, but accept when you’ve hit diminishing returns and consider if your energy isn’t better spent increasing your surface area to luck”.

Parting shots

Fuck you every doctor who told me my digestive problems were in my head or my fault for being a bad patient and you couldn’t help me until I solved the problem that drove me to you. You were factually incorrect and you should feel terrible.

For potential clients in particular

People sometimes approach me for medical literature reviews aimed at their specific problem. There are forms of these I will do, but those forms do not include producing a mechanistic model and high-probability treatment for someone’s persistent, sub-clinical, amorphous problem that medicine has failed to solve. There are a few reasons accepting these commisions would be wasting the clients’ money, and one of them is that by the time they come to me they have found all the low hanging deterministic fruit. The best I can do is spend a ton of time generating lists of things that might work. Sometimes I do offer that, but people tend to prefer my other offer of a referral to a researcher that’s better at individualized treatment.

[Elizabeth]

Overall I’m delighted with this post. It gave me a quick encapsulation of an idea I now refer to a lot, and I’ve received many reports of it inspiring other people to run helpful tests.

A number of my specifics were wrong; it now looks like potatoes were irrelevant or at least insufficient for weight loss, and I missed the miracle of watermelon. I think this strengthens rather than weakens the core philosophical point of the post, although of course I’d rather have been right all along.

[Heron]

This ‘medical miracle’ story engenders hope. To suffer a chronic illness and to have no tangible answers regarding (diagnosis for too many), treatment, or treatment that works, is disheartening, frustrating and draining. Here is a detailed account of one quest that, having exhausted the standard intellectual-medical approach, remarkably results in relief. This writer gets deeply into her specific experience, and the reminder that there is a case for exploring intuition, along with unlikely luck, is uplifting.

[DiamondSolstice]

This post is really important as a lot of other materials on LessWrong (notably AI to Zombies) really berate the idea that trying out things that haven’t been tested via the Scientific Method.
This post explains that some (especially health) conditions may go completely outside the scope of testable-via-scientific-method, and at some point turning to chance is a good idea, reminding us that intuition may be often wrong but it can work wonders when used as a last resort.
This is something to remember when trying to solve problems that don’t seem to have one perfect mathematical solution (yet).

[habryka]

This post is really important as a lot of other materials on LessWrong (notably AI to Zombies) really berate the idea that trying out things that haven’t been tested via the Scientific Method.

This sounds to me like a deep misunderstanding of R:A-Z. The whole point of essays like Scientific Evidence, Legal Evidence, Rational Evidence is that there are tons of valid non-scientific forms of evidence. Posts like Einstein’s Arrogance are explicitly about how you can come to high credence in propositions without much scientific evidence.

“berating the idea of trying out things that haven’t been tested via the Scientific Method” really sounds like a hilarious strawman of LessWrong, and if anything the opposite of what the culture of this site usually endorses (including the writing in R:A-Z).

[Elizabeth]

I haven’t checked but believe you that R:A-Z actively argues against that mistake. But DiamondSolstice is correct that there are strains of RCT-or-nothing and if-formal-science-doesn’t-understand-it-it-doesn’t-exist on the site. All the examples on this post are low karma, but I’ve seen them do better elsewhere.

[Gordon Seidoh Worley]

My own similar story like this:

I had a bunch of weird symptoms starting several months after I was really sick with what was maybe COVID, maybe some kind of SARS, and at least the worst flu of my life by 3 orders of magnitude. Symptoms kind of matched pericarditis, but there was no evidence of that. I wore a heart monitor for two weeks, turned up nothing either. I would occasionally get diabetes in the sense that diabetes is a symptom (excessive, unquenchable thirst), but blood glucose monitoring proved that I was, if anything, unusually healthy in that regard. I also experienced occasional vision blurriness, palpitations, and pain extending into my next and left arm. Probably some other minor things too that I’ve forgotten.

After almost a year of going to doctors and ruling things out my PCP recommended a dietitian, in part because I think he was out of ideas and dealing with a patient who had been reasonable for years but was now complaining about mystery symptoms that couldn’t be explained.

After two very expensive hours the dietitian recommended I go on an elimination diet because it was “probably gluten”. I rolled my eyes. I had eaten gluten just fine for years, no family history of gluten issues, DNA testing negative for celiac, etc.

Well one week into the elimination diet my problems cleared up. After 3 weeks I ate a loaf of bread. I was okay. I ate another loaf of bread the next day. Symptoms returned.

What’s even more annoying is trying to understand the mechanism of action. Nothing authoritative I’ve found has a good model. The best I’ve put together from scrounging forums and combining with the evidence I have is this:

At least in my case, gluten sensitivity is being caused by an allergic reaction in the villi of the small intestine. Gluten, or something that comes with gluten, locks into them and makes them swell. This causes referred pain that in my case mimics pericarditis symptoms. Because they’re swollen they can’t take up other nutrients, and if enough enough of them are swollen they can’t even process enough water for my body to be convinced it’s hydrated (in all cases of excessive thirst I was clinically fine other than some slightly lowered electrolytes from drinking so much water).

Now the weirdest part: drinking coconut water will make the symptoms go away, and I can basically eat gluten if I drink coconut water at the same time. My best guess is that the high levels of magnesium in coconut water are doing something here, but that’s really just a guess. On the model, somehow the coconut water probably gets any gluten bound to the villi and causing inflammation to release and out of my small intestine and maybe also does something to help the inflammation to go down.

I can’t find any papers documenting this sort of mechanism, though I’ll admit I might just not know enough to be able to find them, and maybe the mechanism I’ve proposed is all wrong and it’s better to just think of by body as something like a black box that has something like an threshold response to gluten where under some threshold I’m fine but then past some threshold I’ve “taken too much damage” to function normally and that I can get back under the threshold by drinking coconut water.

I just mostly avoid gluten now, but it was pretty frustrating that the only way to figure this out was to try something that we didn’t have any good evidence a priori to think was the cause, other than some vague stats that gluten sensitivity tends to develop in middle age. I’m not sure if we could have done better but man I sure wish we could.

[EGI]

The Mg hypothesis is easy to test: Get some MgCl or MgCO3 and take some with gluten containing food. Use a quantity similar to the Mg dose found in the amount of coconut water you found to help you. If it helps it is the a tive ingredient. If not, it may still be invloved but not sufficient.

[M. Y. Zuo]

I had eaten gluten just fine for years, no family history of gluten issues, DNA testing negative for celiac, etc.

Methods of growing and processing wheat have changed dramatically in the last few decades. Especially for pre-packaged sliced bread, buns for fast food, and anything else bought by a serious cost cutting purchaser.

i.e. The gluten found in any product you can buy for a few dollars in the U.S. or Canada is almost certainly different then the gluten any of your parents or grandparents had eaten.

This isn’t really talked about outside of industry experts and enthusiasts, and maybe some very agitated celiac adjacent folks, because there is no feasible way to go back to the old way of wheat growing and processing without bread doubling or tripling in price.

There are probably niche growers for luxury markets, and of course ‘gluten free’ bread, if you really want to eat bread regardless.

[Gordon Seidoh Worley]

I’ve gotten the advice from a few people that I might be able to eat things made with “heritage” wheat, but realistically I’m not going to make my own bread, cakes, etc. in general to try this out.

If this pans out maybe over decades we could effect a shift to different varieties that more people can eat, but I think that’s going to require some strong evidence to get food industry players to align around the choice.

[Tiuto]

Isn’t making your own bread really easy, you just need a bread maker put a bunch of ingredients in, press the button and wait. Seems like it might be worth a try. But obviously you know more about your situation than me.

[Gordon Seidoh Worley]

That it involves many more steps than put a thing in the microwave and pressing buttons means it’s a cooking task I’m only going to perform for special occasions, if ever. I realize others like cooking a lot more and would love an excuse to “have to” make their own bread, but not me.

[juliawise]

I don’t know what the supposed changes in growing and processing wheat are, but a lot of that will presumably have happened by the stage it’s flour. So doing the mixing and baking yourself might not change anything.

[Portia]

At least if the factor involved is gluten, afaik, the heritage forms are often even higher.

I have heard anecdotally from a bunch of people that they do better on heritage flours, but I do not think gluten can be the cause of that. Notably, a bunch of people who do badly on wheat do perfectly fine when eating pure gluten (seitan), so I think they are avoiding whatever is the trigger only indirectly, and in the process, likely missing out on a lot of joy and wasting a lot of money.

But then, I also understand that anyone who has found something that works for once really no longer cares to make any experiments.

[Morpheus]

Now the weirdest part: drinking coconut water will make the symptoms go away, and I can basically eat gluten if I drink coconut water at the same time. My best guess is that the high levels of magnesium in coconut water are doing something here, but that’s really just a guess. On the model, somehow the coconut water probably gets any gluten bound to the villi and causing inflammation to release and out of my small intestine and maybe also does something to help the inflammation to go down.

How on earth did you privelege the hypothesis that coconut water helps? Is that common?

[Gordon Seidoh Worley]

It was an accident mostly. I drank some coconut water when I had extreme thirst because I thought maybe something something electrolytes and it cleared it right up even though similar things that should have worked if it was an electrolyte imbalance didn’t.

Also, I’m not sure where you live, but where I am in the Bay Area coconut water is everywhere and a pretty common thing that lots of people drink, so it wasn’t even like I had to try very hard to find it. Before I found it had this medicinal property, I was probably already drinking coconut water several times a month just because I liked it, and drinking water from fresh coconut whenever I could get ahold of one also because I like it.

[Morpheus]

Yeah makes sense. I sort of pictured you stopping your glutenfree diet to test this, which didn’t make any sense.

[Morpheus]

I live in Germany, coconut water is easily available, but I did not know people actually consuming that regularly.

[GeneSmith]

This is kind of a crackpot theory, but I wonder if it could explain your experience:

Novel viral infections trigger the formation of new kinds of antibodies. We have strong evidence that some viruses can trigger the formation of antibodies that bind to human cells in addition to those of the virus. Two examples of this are bites from the Lone Star Tick causing red meat allergies and the Epstein-Barr virus causing multiple sclerosis.

In the case of the latter, only a very small subset of people who get Epstein-Barr go on to develop MS.

Maybe your viral infection caused your immune system to produce antibodies that happened to bind to gluten along with the viral proteins they were designed for.

[Portia]

I think anyone with a severe diet issue should try a proper elimination diet with carefully documented reintroduction at least once, also taking into account things like food storage times (affects histamines) and processing (affects FODMAPs).

For me at least, symptoms follow about three days after I consumed the thing in question (in the form of inflammation rising and me getting severely sick), and I need to eliminate for a while for it to quiet down, and the quantity and context matter. Until I went on an elimination diet, it seemed completely random and impossible to make sense of, because too much was varying all at once, and I never actually felt okay. I also grouped together a bunch of things that were importantly different. (E.g. whether I tolerate soy depends on how it was processed. Whether I tolerate fructose depends on whether it is paired with glucose. Etc.) There were symptoms I was barely even aware of because I had never been without long enough for them to fade.

[DirectedEvolution]

Drug development and genomics already use luck-based approaches. I wonder if doctors just worry about not looking respectable. A psychiatrist I know always seems a little defensive when the problem of finding the right med for a patient comes up, as if he were afraid others might see it as a bit seedy that he just tries things until something works.

Geneticists will silence every single gene in C. elegans to see the effect on longevity, then construct mechanistic hypotheses based on the the genes that had an effect.

If you read descriptions of how a genome-wide association study (GWAS) works, the field’s very clear that the method has trouble with:

1. Traits heavily determined by a small number of rare but but powerful alleles

2. Traits determined by a very large number of common but individually weak alleles

In animal studies, GWAS can be conplemented with QTL mapping to address these problems. Otherwise, you’re stuck with doing massive, massive studies on genetically diverse populations to try and get a full picture of the genetic architecture of a given trait.

In nutrition, it would not surprise me at all if Boswelia occasionally has a powerful effect for a small number of patients, but that studies of it in humans are underpowered. Boswelia is an herb containing multiple potential active ingredients, and I fully expect that different production processes and batch-to-batch variability would tend to confound studies, not to mention selection of different conditions, measured in different ways, among different patient populations—if the studies are done at all.

At some point, I’d like to consider whether there’s value in developing a protocol + software + device for facilitating personalized randomly controlled trials beyond whatever is the Pareto frontier for current enthusiasts. For example, do devices exist to facilitate self-blinded pill administration? Is there a way to help users collect and analyze the data without needing to be a statistics expert? Is it possible to make a logical list of things to try that’s better than an alphabetized list of herbs, medications, and other supplements?

It’s unlikely that I’ll have time to do this in the next year, but I do think about it from time to time.

[Elizabeth]

At some point, I’d like to consider whether there’s value in developing a protocol + software + device for facilitating personalized randomly controlled trials beyond whatever is the Pareto frontier for current enthusiasts

I know someone who’s working on this and I love the idea, although thus far his app is absolutely useless for something that doesn’t kick in and wear off the same day and I haven’t verified it for that use case either. I also have an entrepreneur client whose very interested in this and would plausibly provide support to someone working on it, but it’s not his own top priority.

[DirectedEvolution]

Tl;dr is tl;dr

Let’s say your problem is reliable and obvious. Get a sample pack of pills and remedies. Take 1 pill at a time. If it’s a miracle cure, keep taking it. If not, try the next one. No fancy stuff required. Does anyone sell a sample pack like this?

Tl;dr

If your mystery malady is obvious, reliable, and rare in the general population, then you can simply try pills one at a time, one pill at a time, to see if they provide a reliable treatment. If so, then this will become apparent right away, and you can keep taking it a few more times to confirm it works reliably. It should only take a few trials to show the pill works for you. If the pill doesn’t work, you can set it aside after one try and try the next one.

This would not help you if the problem is a deficiency or excess of some compound that takes time to build up. It would only help if the pill had an immediate, obvious effect for your condition—a “miracle cure.”

This approach requires no fancy statistics, devices, or complexities of taking multiple pills at once. The easiest way to overcome the bottleneck would be if a company sold “sample packs” containing 1 pill of eat type. You’d take them one at a time, see if they fixed the problem, and if they did, you’d buy a larger quantity of that specific pill and keep experimenting to confirm the result.

Long:

I could imagine a fruitful collaboration between a mechanical engineer, a statistician, a programmer, and a biomedical researcher/​doctor. The approach could be Bayes’ law-based. Using your problem as an example, here’s how it might work:

Does eating meat (cooked, store-bought, fresh, 50g) make me nauseous?

• P(H): You specify how common it is in the human population for eating meat to cause nausea

• P(E): You also specify how common it is for a member of the human population to eat meat and get nauseous, whether or not there’s a causal relationship

• P(E|H): Finally, you specify how likely it would be for you to get nauseous after eating meat if eating meat makes you nauseous.

If you don’t have a good way to estimate these likelihoods, the app would give you suggestions for ways you could find reasonable numbers to plug in.

Then, every time you ate meat and got nauseous, you could enter another data point and it would update the likelihood that eating meat causes nausea.

Once you’re adequately confident that eating meat causes nausea, you could then repeat the exercise for a range of herbs.

Given that eating meat causes nausea, does taking Boswelia (BosPro) before eating prevent nausea from meat consumption?

• P(H): You specify how common it is for people who get nauseous after eating meat to not get nauseous if they take Boswelia first.

• P(E): You also specify how common it is for people who get nauseous from eating meat to take Boswelia, then eat meat, and not get nauseous.

• P(E|H): Finally, you specify how likely it would be for you to not get nauseous after taking Boswelia, then eating meat, if taking Boswelia prevents nausea from meat consumption.

With a very reliable and unusual effect, as in your case, it’s possible to update a very low prior to a very confident prior in just a few trials.

I think the statistics would be doing most of the heavy lifting here. Being able to do a blinded placebo-controlled trial is important if you’re testing a relatively subtle/​sporadic effect or testing a single compound.

But if you’re testing an obvious, reliable effect and experimenting with a range of compounds, I don’t think the self-blinding aspect is as important.

Here’s my attempt (not trained in this, correct me if I’m going about it wrong) to apply Bayesian inference to the problem.

For example, let’s say:

• P(H), the chance that meat gives you nausea, is one in a million (.000001)

• P(E), the likelihood of you just randomly feeling nauseous after eating meat, is one in a thousand (.001)

• P(E|H), the likelihood you feel nauseous after eating meat, given that the meat causes you nausea, is 0.98

Then P(H|E), the chance that eating meat causes your nausea, given you ate meat and felt nauseous afterward, is 0.00098 after one time eating meat and getting nauseous. Feeding this back in as the new P(H), the chance that meat causes your nausea, P(H|E) becomes .9604, or 96.04%, the second time this happens (assuming you don’t eat meat and not feel nauseous). Realistically, we’d want to check if there’s something about the way you cooked the meat, the animal it comes from, the store you bought it from, the knowledge that you’re consuming meat, etc, that is confounding the result.

To deal with some of the confounds, you could repeat the experiment using different types of meat from different stores, and figure out how robust the effect is. It seems difficult to self-blind eating meat, since 50 g is about a sandwich’s worth of deli meat. Possibly you could try incorporating it into another more flavorful dish and eating the food with your eyes closed. But this is just to rule out the possibility that the result is from the perception of eating meat, as opposed to something primarily physiological about meat-material being in your digestive tract. If you weren’t concerned about this possibility, you could skip it.

But if the user is self-testing to find a treatment for a very reliable, obvious effect (as with your meat->nausea problem), and if our prior on any random pill just randomly working to prevent the nausea is low, then these results show you can probably figure out whether any random supplement works or not in just a few tries. That sort of obviates the need for fancy statistics or an app. You might be able to get much of the same result by just directing the user to “Try taking this pill, then eating 50 g meat. If the pill doesn’t work on the first try, move on to the next pill. If it does work, continue taking it. If it helps but doesn’t entirely eliminate the problem, explore dosing, timing, and manufacturer, to see if you can achieve significant improvements.”

I’m not sure if it makes sense to try multiple pills at once. Balancing the possibility that you stumble upon an effective treatment faster is the possibility that an effective treatment is disguished by a drug interaction, as well as the possibility that the average user just struggles to manage the added complexity, gets confused, and quits.

But this then becomes very simple.

If you have a reliable, obvious mystery malady that no doctor has treated effectively, systematically take 1 pill at a time until you find one with an effect. Then keep taking it, exploring dosage, timing, and manufacturer, until you maximize the effect. If satisfied, problem solved. If not fully satisfied, continue exploring other pills (unless it’s possible to devise a mechanistic hypothesis as to why the effective pill works, then use that to find likely alternatives more efficiently).

[Elizabeth]

TBC: the client is interested scaleable software that people intuitively find useful for experimenting on themselves and can combine selfishly motivated individual data into useful aggregate data. But there’s a point here I want to argue.

I’m not sure if it makes sense to try multiple pills at once. Balancing the possibility that you stumble upon an effective treatment faster is the possibility that an effective treatment is disguished by a drug interaction, as well as the possibility that the average user just struggles to manage the added complexity, gets confused, and quits.

It seems like you’re assuming all drug interactions are bad. What if you need three things in combination to see the effect, and then it works really well?

[DirectedEvolution]

That’s entirely possible. However, it introduces a level of risk that isn’t as present when you take one at a time. It’s unlikely that a given supplement will kill you at normal doses. Such a severe side effect would have been detected and the supplement most likely wouldn’t be sold.

But it’s not impossible that certain rare combinations of drugs might have lethal side effects in combination, and that you might stumble across such a combination by chance. The risk of this happening seems in my judgment to outweigh the potential benefit of finding the right drug for a chronic condition faster.

Examples: https://​​www.google.com/​​amp/​​s/​​www.news24.com/​​amp/​​health24/​​medical/​​backache/​​news/​​7-medication-combinations-that-could-be-deadly-20160829

I’m not certain if it’s plausible an interaction between supplements could kill you in a few days. Even the examples here seem to take a while to work. The only potentially instantly lethal drugs I’ve seen are things like alcohol and heroine. But I would shy away from taking combinations—that’s just where my risk budget is at. I could be persuaded otherwise.

[mcint]

The blinded aspect is hard.

• If you’re concerned about supplement interactions, you should be concerned about supplements effects at all. People should seek based on possible luck, but should know (and be able to tell doctors) what they’re putting into their bodies, and take contextual advice from relatives, friends, and community.

• Collecting individuals susceptible to effective treatment with intervention X and having them ready for researchers to talk to, test more directly—is this already done? I suppose around individual notable conditions: celiac disease and gluten intolerance, or n=1 genetic issue self-diagnosis.

• Some conditions have an intermittency, that makes it hard to assess interventions with unknown timing.

Perhaps blinded timing studies, self-studies, after something is found to work. Perhaps helping people to log and journal symptoms and effects during the blinded periods, as well as analyze, interpret, and share them—especially in ways that make it easier for others to trust.

[degrews]

At some point, I’d like to consider whether there’s value in developing a protocol + software + device for facilitating personalized randomly controlled trials beyond whatever is the Pareto frontier for current enthusiasts

Wow, yes. I’ve thought about this before and it feels like this would be so valuable. It’s been a while since I’ve looked into this space but as far as I’ve been able to tell the Pareto frontier is terrible.

I’m going to try to spend some time on this over the next few days.

[rain8dome9]

Is there a way to help users collect and analyze the data without needing to be a statistics expert?

Collection is really just a matter of finding the right devices and taking the time to use them. Analysis outside of immediate obvious effect can become difficult. If the effect is subtle and drowned in other effects, or hard to measure. If the intervention is not something user can easily or wants to reproduce. If the effect take long time to build up, or is shifted in time from intervention. If the successful effect only happens under several conditions or several interventions together. If the spray and pray approach is dangerous. If the spray and pray approach only hits gold once in a while. Multiple comparison problem (see wikipedia). If user is bad at keeping records. There are probably more. There are many many apps that just do correlation and none that do anything more. Here is a list of both problems and apps.

[mcint]

Your link is broken, and while Wikipedia may be a guide to problems, generically, I’m curious about the apps, and the problems specifically relevant.

[rain8dome9]

https://​​wiki.openhumans.org/​​wiki/​​Finding_relations_between_variables_in_time_series This is the link I meant to post.

[DirectedEvolution]

I agree that the highest-leverage place to start is probably the paradigm of encouraging people with obvious long-lasting chronic problems to look for immediate obvious effects by doing maximal spray n pray. Equivalents of “have nausea from cancer/​chemo daily → medical marijuana → no more problems.”

Once we get away from that, I think that systems for collection, analysis, and self-blinding become important. There are a lot of details and trivial inconveniences in any research project, and most people just aren’t equipped to work them out on their own. There’s a lot you can do to smooth the path.

For example, I can imagine a nootropics test kit. It would come with:

• A standardized questionnaire that you fill out for every nootropic you try

• A sample of nootropics to try along with placebos. Placebos would mimic the appearance of various drugs so it’s impossible to tell which is which without deliberately unblinding yourself. the supply would be large enough to give you adequate power given the number of drugs you’re trying.

• An analytic framework that takes multiple comparisons etc. into account and lets you see if any correlations are statistically significant.

• Perhaps packaging drugs in different ways so that you can order more of the things that work, but with a different appearance, to do a more focused experiment on the likeliest candidates.

There’s a lot of detail to work out in designing such a kit, but it’s easy for me to see that it could convert an intractable problem into a do-able puzzle for a motivated and reasonably intelligent user.

[rain8dome9]

An analytic framework that takes multiple comparisons etc. into account and lets you see if any correlations are statistically significant.

Blinding.

Two issues, one of which I did not think of, out of like 20.

EDIT: I suspect, including from my own experience, that many problems can be solved without resorting to advanced statistics. Often by using through experimental procedure instead. Like eliminating a food type for a month then not doing an intervention for a month. Repeat. Trying out medications sounds like it should be done safely. This safety can only be achieved by monitoring vital signs and analyzing them using advanced statistics.

[wslafleur]

I’ve had gastrointestinal issues all my life. They started when I was a newborn; doctors diagnosed me as ‘withholding’, which is a polite way of implying that somebody is causing their own indigestion by refusing to take a shit. My distraught parents consulted several doctors who reaffirmed the original ‘diagnosis’ and finally resorted to administering enemas after other approaches had failed.

Presumably driven to innovation, half-mad with pain, sometime during my toilet training I arrived at a hack solution on my own. Rather than sitting on the toilet, I adopted an improvised ‘squatting’ posture with my feet planted on the seat, which my mother affectionately christened ‘The Spider-Man pose’. I had no way of knowing at the time, of course, that a good chunk of the modern world does their business in a similar-if-somewhat-less-elevated position.

The new posture was a winner in the sense that I could actually move stool. Unfortunately, it did fuck all for my chronic constipation and extreme pain. So my adolescence was full of grueling, agonizing bowel movements that persisted into my teens. For me, it was ordinary to go six or seven days without shitting and then spend a tortured 2-3 hours in the bathroom, passing a frankly terrifying amount of stool in a single sitting and then recuperating for several hours afterwards. This sounds like a gross exaggeration: Let me assure you it is nothing of the sort.

Things proceeded without much fanfare in this fashion for years. I saw several doctors during high school and they amended the consensus diagnosis from Withholding to ‘Irritable Bowel Syndrome’, the less-glamorous-but-equally-nebulous baby sibling of IBD (Irritable Bowel Disease). I was prescribed laxatives, antibiotics and steroids in approximately equal portions on the whim of the prescribing physician. I was directed to the food pyramid and instructed to adjust my intake towards more fiber and grains.

None of this helped and my condition worsened. It wasn’t until after I had graduated high school that things became truly intolerable. By this time I had developed a bad case of hemorrhoids, was occasionally shitting blood, and suffering from chronic abdominal pain and persistent fatigue. My parents trucked me around to several specialists (gastroenterologists), each of whom reaffirmed that I had IBS. I had two colonoscopies, both of which were inconclusive because my body wouldn’t properly flush even when I was following the cleansing instructions zealously (I imagine they weren’t written with people who only shit bi-weekly in mind).

It was about this time I started to get seriously desperate. All my life I’d been pretty athletic, but I was running out of energy to do anything and that worried me. I broke out the laptop and started digging, trying to keep my wits about me but willing to try more-or-less anything for which I could imagine a plausible mechanism. At this point I had moved out of my parents house and was poorer than most readers here will be able to properly envision, so I didn’t have access to a doctor. The only lever I had was my lifestyle, so I adjusted my diet and tried several supplements (the promising few I could afford). After running the gamut, I hit a bit of good luck.

On a hunch, after reading Gary Taubes’ Good Calories Bad Calories, I started pulling grains out of my diet: The effects were immediate and powerful. My energy levels returned to nearly normal and, for the first time in my twenty-something years of life, my bowel movements got a little easier. I remember running downstairs, tears streaming down my face, to tell my roommate that I had figured it out: I was allergic to gluten.

My initial conclusion was, of course, embarrassingly wrong. Removing wheat had been a good first step, but it wasn’t a cure. My symptoms had been consistent (and consistently worsening) my entire life, but now they came and went, seemingly at the whims of a capricious god, with no rhyme or reason whatsoever. Anybody reading this who knows anything about the reward systems of the brain is going to understand immediately how this engendered in me a sudden, insatiable interest in anything nutrition or gut-health related.

The rabbit hole deepens...

Over the course of much experimentation and several years worth of research I had developed a tenuous control over my condition. The flare-ups and remissions were at least explicable if not fully predictable, and I had become convinced that I was suffering from Ulcerative Colitis (a form of IBD which is really a fancy way of saying Colon Bad: Causes Unclear). Along the way I’d developed a cynical distrust of medical practices (especially in the US and especially where the gut is concerned) as I learned how little is truly known about the human microbiome and how large a role it plays in our health.

Then I had the worst flare-up of my life. I had no energy. I couldn’t get off the couch, and I was losing copious amounts of blood to the toilet. I lost something like 20lbs and if it weren’t for the generosity of my roommates helping to take care of me, I have no idea what I would’ve done.

This went on for about six months until I decided that I would try getting on the formerly useless Medical Carousel again. As it happened, I was able to afford a specialist this time around. They set me up for a colonoscopy and, since I was practically starved already, the results were conclusive this time around: I had Ulcerative Colitis. One of my friends had to explain to the nurse who gave me the news when I came around that—no—she hadn’t upset me, and that I was just excited to be proven right.

The feeling was elation followed by anti-climax; they’d confirmed what I’d already known. Ulcerative Colitis is more of a syndrome than a disease, which is to say that it’s a constellation of symptoms that we frequently see together: It says nothing whatsoever about the underlying mechanism.

What nobody ever tells you about these gut conditions is that they are basically a very slow, unattractive death sentence with a lot of discomfort to look forward to in the interim. The prognosis is something like this: many rounds of consistent steroids, antibiotics and NSAIDS (whichever you don’t react to, if any) to hopefully induce periods of remission followed by unexplained flare-ups until your intestines finally give out, at which point your options are death-by-sepsis or surgically removing them in favor of an ostomy-bag.

Having plunged deep into the available literature, I was resolved to fight the inevitable. By this time, however, I had already tried every fanatical lifestyle change that seemed likely to help. Perhaps you will think less of me for this, but having pored over hundreds of medical journals and listening to specialists discuss what little we know of the gut (which—in its own way—is rather a lot), I have concluded that antibiotics ought to be the very last line of defense, ranked up there with chemotherapy in terms of how much damage they do for the benefit of alleviating your symptoms. At least with chemotherapy, you hope to reduce/​remove the underlying problem—antibiotics for an IBD flare-up is really more of a band-aid solution.

Anyway, I was desperate to try something with a little more promise and a little less side-effect. Enter FMTs: It was vexing to discover that here in the United States, FMTs (Fecal Matter Transplants) are an approved treatment to repopulate the gut biome post-chemo, but otherwise unsanctioned; it is apparently a sanctioned treatment for IBD in at least a few other countries. It seemed promising albeit gross. Honestly, most of the pushback seemed to stem from this singular fact: it’s basically disgusting. Having neither the money nor the requisite knowledge to make the arrangements, I discarded flying to another country as an option.

You know what they say about desperate people… (please don’t try this at home I guess)

I’ll attempt to skip the gory details here, but I arranged to perform a homebrew FMT, utilizing a cough-donation-cough from a generous friend of mine who was a stellar specimen of gut health. At the time, he was in the military which meant that he’d recently been screened for all the relevant parasites. In any case, I’d done my homework thoroughly enough to feel confident that I wasn’t going to get myself killed.

The results were immediate. My energy levels came back from all-time-low to better-than-ever, and (sorry) my bowel movements were easy and picturesque for the first time in my life. I stopped bleeding. For those who are curious, there were some unexpected side-effects. Namely, during the subsequent two weeks everything smelt like my friend’s poo (this was apparently an internal thing, nobody else could smell it—WEIRD) and I had sudden, serious carb-cravings; I’d been low-carb for years and this was very noticeable.

It’s been 4-5 years since then and my condition—while not always perfect—hasn’t been nearly that bad since. I occasionally have flare-ups but they tend to resolve themselves and my diet/​lifestyle seems to be holding my condition in check approximately 95% of the time. That being said, things seem to be slowly worsening over time and I wonder what I’ll do the next time around. I’ve got no delusions about being cured, since IBD seems to have some sort of underlying genetic component and we’re still pretty foggy on the mechanism.

The whole thing has soured me considerably on the medical mainstream though, and I’m somebody who is staunchly against hokey bullshit like homeopathic remedies. I suspect there’s truth in the nuance here. It’s not as though the scientific method is a bunch of shit, but there’s a lot more that goes into medicine than simple, on-the-ground experimentation. Individual practitioners are experiencing information overwhelm to an extent that was formerly unimaginable and we all know that there are Incentive Structure Issues around drug research and manufacturing.

I don’t know what the moral of the story is. Perhaps that it’s an odd time to be alive. I felt compelled to share my story after reading, but I will admit that—looking it over—I feel pretty exposed. Nonetheless, if there’s a place to share this, it would be here.

I wish every single one of you the best of luck. It seems like we may need it.

[ChristianKl]

That being said, things seem to be slowly worsening over time and I wonder what I’ll do the next time around. I’ve got no delusions about being cured, since IBD seems to have some sort of underlying genetic component and we’re still pretty foggy on the mechanism.

Have you seen https://​​www.lesswrong.com/​​posts/​​i48nw33pW9kuXsFBw/​​being-a-donor-for-fecal-microbiota-transplants-fmt-do-good ?

If doing FMT once helped maybe doing it more frequently with even higher-quality material would help?

[wslafleur]

That’s super useful. Thank-you, I’ll definitely follow-up on this. I imagine it would be.

[Portia]

Mad respect. Hope you are okay now.

It is bizarre how large an impact the microbiome has on human health. You have probably long tried this (in this case, feel free to ignore to hell and back), but for me, adding a probiotic with B. infantis in particular, supplementing psyllium (start low on that one) and consuming a lot of live, wild ferments (e.g. kimchi) made a huge difference.

[Steven Huang]

I’m very curious about your homebrew FMT.. I’m assuming this was via a capsule of some sort and you ingested it? Or did you perform a self colonoscopy?

[wslafleur]

The latter, although I don’t think the gruesome details (beyond that) are really topical. I suspect that oral supplementation of this nature is significantly less effective and, other than a little mechanical discomfort, I don’t know why anyone would opt for an oblique approach. The desired bacterial translocation is pretty straight-forward and you can achieve it in a similarly direct manner.

If your desire for details extends beyond mere curiosity, I’ll respond to a DM. Just trying to be courteous to other uses.

[theme_arrow]

Very interesting story. One question: you said that the prognosis is “many rounds of heavy-duty antibiotics to hopefully induce periods of remission,” but my understanding was that UC was autoimmune, and that the standard treatment was steroids or other immune system modulators? That’s certainly what the Mayo Clinic says. Did the specialist mention any of these kinds of medications to you?

[wslafleur]

Oh, yeah. I should probably amend that. It’s basically steroids, antibiotics, anti-inflammatories (whichever flavor you can handle) and a strong recommendation that you increase your fiber intake. I mentioned having been given each of these in roughly equal portions, but then failed to include it as a part of the prognosis.

My experience with corticosteroids was hit-or-miss, and I had severe, acute depression as a side-effect (I have never experienced anything like depression before or after, so it was pretty blatant). In any case, I don’t really see steroids as being much better, since AFAIK, pretty much everyone relapses w/​ steroids as well, and then they have to be adjusted.

EDIT: I’m not specifically trying to be overly pessimistic/​fatalist here, it’s just that I’ve had a very bad time w/​ traditional approaches to treatment for IBD. Take everything I say with a grain of salt, obviously. I think that people should do whatever they can to feel better.

I’ll update the post, and thank-you for the reply.

[Ruby]

Curated. I appreciate this post for what I see as pushing on a frontier of reasoning, epistemics, and practical life advice. On LessWrong, we love well-researched, epistemically virtuous analyses of topics, and this post, to me, says something like “in some domains we really have a very poor idea, and you might want to try something different”. And it’s not an abstract point, I expect that this will change my behavior in future medical scenarios. Kudos.

[MondSemmel]

Fuck you every doctor who told me my digestive problems were in my head or my fault for being a bad patient and you couldn’t help me until I solved the problem that drove me to you. You were factually incorrect and you should feel terrible.

I sympathize so much with this and other sections of this post.

Here’s a somewhat related story of my own.

Part 1

I developed sudden strong stomach cramps in 2017, and while I did get a relatively quick appointment for an endoscopy, it was still a few weeks of suffering. In the meantime I was told that my problem was likely work-related stress or something. And it ultimately turned out to have been work-related stress helicobacter pylori, a stomach bacterium for which there is a well-known treatment (taking two different antibiotics and a proton pump inhibitor) which worked quickly and completely.

Side note: Supposedly a significant chunk of the developing world has this bacterium. (Wikipedia: “In 2015, it was estimated that over 50% of the world’s population had H. pylori in their upper gastrointestinal tracts[6] with this infection (or colonization) being more common in developing countries.”) But if that’s true, the vast majority of cases must be asymptomatic or mild; the world presumably doesn’t look like debilitating stomach issues are anywhere near that common.

Part 2

Around two years later, I again experienced stomach cramps. I figured that I was well-prepared this time, knew exactly what the problem was, and how to get rid of it. Unfortunately, this time I tested negative for helicobacter and other obvious problems, so I had no idea what to do. (Helpful diagnoses included stuff like irritable bowel syndrome, which essentially means “we don’t know what’s wrong with you, but we still needed a label to bill health insurance”.) My stomach issues lasted for months and got worse until a strategy eventually worked (probably probiotics, maybe assisted by removing lactose from my diet; I never entirely found out).

Also unfortunately, the beginning of my new stomach issues coincided with visiting some new mental health professionals for unrelated reasons. Several of them were all but convinced that my problems were psychosomatic. Again, infuriating and unhelpful. But not surprising—if all you have is a hammer (i.e. a therapist can’t diagnose stomach problems), then everything looks like a nail (i.e. psychosomatic).

And none of those doctors will have or could have learned anything from this episode. After all, it’s not like there’s any feedback channel that would have informed them that their hypothesis was wrong.

[EGI]

The cool thing about the “psychosomatic” diagnosis from the doctor’s perspective is that it is a convenient, utterly non-disprovable “diagnosis” that offers closure to the doctor: “I found out what is wrong with the guy” instead of admitting failure: “Well, there is a problem but I don’t know what it is.” It also sends the patient on a long (month to years) therapy loop which offers plenty of time for the problem to resolve on it’s own (which happens frequently). An additional perk is that any question or doubt of the patient can be chalked up to “being defensive /​ in denial” or “uncooperative” which is of course a symptom of the underlying psychopathology.

[Marion Z.]

Yes. My uncle, who is a doctor working in gastroenterology, was talking about basically the exact same topic last week. He said that they’re highly confident a significant number of patients are having entirely or near-entirely psychosomatic illnesses, but it’s incredibly difficult to identify when that is specifically happening, and unfortunately due to time and money constraints they have a tendency to just slap the label on difficult cases. We just do not know enough about the human body and how the brain affects it to be confident outside of extremely obvious cases. Even a lot of what we do know is being reexamined in the last two decades due to edge cases being discovered and lack of rigor in earlier testing.

[Portia]

That label also just does not achieve anything.

Sure, absolutely, poor mental health worsens physical health, and some debilitating condition have no apparent physical causes.

But this doesn’t make them hurt less. It doesn’t provide a resolution.

My episode beginings have a significant correlation with stressful events. I am perfectly aware of this. I would still, really really, like a way to interrupt the resulting destructive cascade other than going “well, it would have been better not to have been stressed”.

[RedMan]

I had a severe health problem that I treated myself with broscience (doing research like a gymbro buying supplements to get hyooge) and some alt medicine that needed a clinic. I have pre and post treatment test results showing a problem and the problem in remission, with a degree of success that was unheard of, even in that particular clinic for that particular issue.

Had this conversation:

“So Dr, you’re saying that either I have done something medicine believes to be impossible, or I was never sick”

“That’s correct”

I looked into commercialization of my protocol, but unfortunately, I used mostly stuff available OTC, which would no longer be available OTC if it were determined to be ‘a drug’ by success in a RCT, and I would thus lose access.

So the process of getting good data is explicitly counterproductive to my goal of staying healthy.

[Elizabeth]

Can I encourage you to write it up on a patient forum somewhere? Or I’d host it on my blog if you want. If luck matters this much I think it’s worth recording every success, even if they rarely replicate.

[RedMan]

Description of the thought process and general techniques used to generate an answer for myself puts those techniques at risk. Discussion of the specifics definitely my access at risk, and no I don’t need a second opinion.

I’ve thoroughly investigated disclosure, to the point of talking to industry VCs and CEOs about the challenges I’d hit spinning out a biotech startup to commercialize it. For a number of reasons, such a startup is a lame idea.

Since I don’t do social media, the possible exposure/​engagement from simple disclosure isn’t valuable to me.

Instead, I’ll offer an unrelated anecdote, if the structural/​market issues that cause the following issue are fixed, I assert that my therapy will rapidly emerge from a more credible source with no effort on my part required, so work on this one instead:

I met someone who was involved in an attempt to commercialize ‘cell therapy for diabetes’. Someone else can go find the papers if they care.

Basically, they sat in the lab and tried ‘start with stem cells, convert into beta cells, implant in mouse; diabetes fixed’ they then moved to ‘peripheral blood cells, treat blood to turn into stem cells, treat again to turn into beta cells, inject in mouse, cells float through blood and park in the pancreas; diabetes fixed’

At this point they said ‘hey let’s see about spinning this out for commercialization’, and failed hard. I literally met people who were in the meetings. For market reasons, the project is simply not viable as a business. They talked to everyone who could listen, found no investors, gave up, and went back into the lab.

Last I checked the state of the research was ‘make gmo mouse that can’t produce beta cells period, pull off blood, make stem cells, gene edit stem cells to fix missing gene, turn into beta cells, inject into mouse; diabetes fixed’

Scientists are literally stunting on diabetes in the lab while people die because they can’t afford insulin.

[RedMan]

Thankfully, the Chinese seem to have figured out how to thread this needle: https://​​economictimes.indiatimes.com/​​industry/​​healthcare/​​biotech/​​healthcare/​​chinese-scientists-develop-cure-for-diabetes-insulin-patient-becomes-medicine-free-in-just-3-months/​​articleshow/​​110466659.cms?from=mdr

Edit: paper here https://​​www.nature.com/​​articles/​​s41421-024-00662-3

[RedMan]

https://​​www.nature.com/​​articles/​​d41586-024-03129-3 this is separate research. It looks like this will happen, and it will come from somewhere other than the west.

[romeostevensit]

My own frustrating story: had weird skin issues diagnosed as a variety of things for years and unsuccessfully treated with a variety of prescription and OTC remedies. During the pandemic I built up some spare capacity to overcome my usual maintenance helplessness around it and decided to throw literally every internet intervention for every possible diagnosis at it at the same time and then do binary search for specific things that worked. What wound up working? Hydrogen fucking peroxide. Something that many people say has no chance of working. It’s been 2 years now and my symptoms are 80+% better. My belated hypothesis is that the underlying cause is something to do with skin ph and just regularly using more acidic washes and lotions (eg salicylic or uric acid) also seems to help and make the peroxide less necessary. This seems to have fallen into the hole of ‘because there’s an adjacent woo thing (ph is often the domain of BS fake medicine) doctors were incapable of thinking anything near it’.

[methree]

Wouldn’t it be nice if there were a way to at least document random cures? Someone I know used to have problems doctors could not diagnose (lingua geographica was a symptom… one of those things nobody knows much about). Biopsies were made, blood levels were checked, a heroic efforts was put into trying to match the symptoms with something known. They disappeared all at once after a coloscopy, which requires, lo and behold, an intestinal cleansing that seriously disrupts the gut ecosystem. The moment the symptoms disappeared, doctors forgot about the issue. We learned that doctors are there to treat and have no time for research or curiosity. I feel an important bit of information is being left on the table, and it’s not their fault, it’s the system they are trapped in.

[Portia]

Case study reporting is a thing doctors occasionally do, if a documented severe issue significantly resolved after an unconventional, novel cure that still entails a plausible working mechanism.

But I think the issue here is often that doctors aren’t sure what it was in the first place, and if it resolved spontaneously, which does happen.

And I think a lot of patient solutions work indirectly. The patient will say “I quit gluten” or “I started yoga” or “I used a cream with x”, but this entails a long sequence of other changes as well, which the patient may not necessarily be aware of, and which may have made the actual difference.

And because a lot of these solutions are done by the patient, hence not blind, there are massive placebo effect distortions.

[Alex_Altair]

Loved this post. Both because I think this is a valuable set of reasoning heuristics, and because I read it in your voice, which made it feel something like a rationalist standup routine.

[Ben Pace]

“Luck-based medicine” is a phrase I will now be using.

[Stephen Bennett]

This reminds me of Scott Alexander’s post on Pascalian Medicine: https://​​astralcodexten.substack.com/​​p/​​pascalian-medicine

The gist of that post is that if you take dozens-hundreds of medications for something, each of which is unlikely to work but carries basically no risk, the net effect of the medicines is in theory positive. I think this is probably false for acute illnesses, but might be true for chronic illnesses since the net damage of the illness is larger (barring consequences like death from acute illness) and the odds of a negative interaction between medications is lower when you’re only taking a handful at a given time (again, so long as nothing kills you—I don’t know how to account for that because I don’t know how likely it is). As a result, while for each medication you take you might have negative expectations for that dose—a couple of random side effects with no effect on your condition—the information you gain means that the lifetime consequences of taking the dose are positive. I have no idea how to even guess at the frequency that a given medication will solve a given problem through pure luck, which is unfortunately the central number in this calculation.

I’m glad you found something that works for you!

[Elizabeth]

Yeah, I would only make the case for this when a cure will be obvious. Medicine that insists its lack of effect is a sign you need more, ad-infinitum, is the worst- but I’d apply this to standard medicine too, and standard doctors take it worse than alt practitioners.

I also think Scott is mostly but not entirely right on the Algernon effect- that it’s easier to hurt yourself than help. That is mostly true, but often chronic problems are caused by your normal homeostasis mechanisms getting caught in a bad equilibrium, and knocking yourself out of that equilibrium can be a step into an adaptive valley. But that can only possibly hold for things where there’s a good equilibrium to be had, which I think is much more true for digestion and inflammation than for e.g. aging.

[DirectedEvolution]

I just want to note the origin and context for “Algernon effect” for anyone who might stumble across this. Eliezer Yudkowsky based the term “Algernon’s Law” on the SF book Flowers for Algernon and used it loosely to refer to the idea that evolution has probably found most of the simple ways to increase human intelligence in ways that benefit transmission of the genes involved. Then Gwern built on Eliezer’s writing and others in his coverage of purported intelligence enhancing drugs and other practices. Scott cited Gwern in redefining Algernon’s Law to mean “your body is already mostly optimal, so adding more things is unlikely to have large positive effects unless there’s some really good reason,” and now it’s being used here to mean “it’s easier to hurt yourself than help.”

I haven’t looked much into intelligence research, but the mainstream understanding of this idea in aging research is based on antagonistic pleiotropy and diminishing selection pressure with age.

• Genes that cause disadvantages at later ages (which impact fewer organisms) may give a reproductive advantage at a younger age, and thereby achieve a net reproductive advantage.

• The optimizing pressure of natural selection diminishes with age, particular in the post-reproductive part of the life cycle.

This helps explain why people age, which is just another word for the development of health problems over time and the mortality risk they cause. It may also help explain evolutionary limits on intelligence. A gene that enhances intelligence, but lowers the chance of reproduction overall in the ancestral environment, will be selected against. For example, if a gene increases intelligence, but delays puberty, causing the organism to suffer more brushes with death in the wild, evolution may select it out of the gene pool—even though this particular form of evolutionary cost may not be one that we particularly care about, or that even impacts us very much in our modern, low-risk environment.

None of this is to necessarily contradict Elizabeth’s comment—just to add context.

[Dentin]

So much yes to this post. This tracks with about everything I’ve experienced so far. It also makes me appreciate even more the close friends I have in the medical profession; I know I can trust them to review ideas, think about them, theorize, and suggest other areas for research at a level that is appropriate for my skillset. In private, they admit to proposing numerous luck based treatments that panned out. Our hardware is complicated, and we have extremely limited monitoring and visibility on it. Doctors that aren’t burned out and are curious know that painfully well.

Personally, I’ve been doing a lot of investigation and understanding into my own health. Understanding my biochem, understanding the various subsystems, keeping good records myself instead of relying on our piss poor medical facility information management to do it. In the current environment, the only person that’s going to take care of you is yourself, and it’s best to train that up as a skill even if you’re lucky enough to have a good doctor. You won’t have that doctor forever.

Personalized medicine is a long way away; when I get to the point that I need substantial medical care, I plan to shop around for a doctor that I can spend time with, and hire them on a retainer basis as a personal physician. If nothing else, I’ll have them as an advocate to help me deal with specialists who don’t know me and don’t care.

[Big Tony]

A lot of gut issues are a combination of:

• Allergies to food. Diagnose and treat by cutting the most common offenders from your diet first: gluten, eggs, nuts, dairy. If there’s no improvement and you’re desperate, cut everything from your diet except rice and water, and add foods one-by-one until you isolate the culprit.
  You may have an intolerance to food which isn’t an allergy, e.g. coeliac disease. These can be diagnosed by a colonoscopy.

• Allergies to other things in the environment that are causing issues, e.g. fragrances.

• SIBO (small intestinal bacterial overgrowth). Diagnose by doing a SIBO breath test, and treat with a combination of antibiotics for the initial cull, pre and probiotics until you develop a healthy flora, then be very wary of having antibiotics from then on.

• SIBO is often caused by a hereditary inability to absorb a certain type of dietary sugar, e.g. fructose (fructose malabsorption) or lactose (lactose malabsorption). When eating foods containing that sugar, you don’t digest it, which leads to an overgrowth in bacteria which consume that sugar. Diagnose by doing a SIBO test, treat by avoiding that food and/​or taking enzyme supplements to help you digest it.

• (I don’t know any scientific basis for this point, but it seems to be this way from observation) There seems to be certain ‘types’ of people: red meat people, white meat people, no meat people or it-doesn’t-matter people. If your diet is heavily slanted towards one of the ‘types’, it’s worth trying out the other types to see if you do better on that diet.

There’s a few supplements which are generally useful, and good to have in the toolkit:

• Slippery elm powder in capsule form is a great soother, forming a mucus-like material in your guts.

• Activated charcoal capsules are useful for soaking up toxins in the gut, which is an issue experienced with SIBO-related bacterial die off. Be careful with over-supplementing with these, because it will soak up nutrients also.

[Elizabeth]

I mostly want to let 1000 flowers bloom on this, but activated charcoal is on my list of “only use if you have a very specific model of exactly what you are solving and what the costs are, with numbers”. To the extent it works, it does not discriminate between toxins, nutrients, and medicines.

[Celarix]

I mostly want to let 1000 flowers bloom on this

I am not sure what you mean by this. Do you mean this comment is great and worth the recommendation, or should be buried so that its corpse produces a thousand flowers? Genuinely unsure.

[Aiyen]

Normally that’s an idiom for “We’re not sure of the best approach here, so let everyone try whatever approach they like, and hopefully among a thousand methods, some will be useful”.

[habryka]

It sadly also was used by Mao, possibly to lull dissenters into a false sense of security, to then be cracked down upon:

During the campaign, differing views and solutions to national policy were encouraged based on the famous expression by Mao: “The policy of letting a hundred flowers bloom and a hundred schools of thought contend is designed to promote the flourishing of the arts and the progress of science.”[3] The movement was in part a response to the demoralization of intellectuals, who felt estranged from the Communist Party.[4] After this brief period of liberalization, the crackdown continued through 1957 and 1959 as an Anti-Rightist campaign against those who were critical of the regime and its ideology. Citizens were rounded up in waves by the hundreds of thousands, publicly criticized, and condemned to prison camps for re-education through labor, or even execution.[5] The ideological crackdown re-imposed Maoist orthodoxy in public expression, and catalyzed the Anti-Rightist Movement.

[Elizabeth]

Yeah I’d love to have a less loaded phrase for “encourage people to try a bunch of stuff” but Mao did a great job optimizing his.

[Celarix]

Makes sense, thanks.

[birdy]

woah. thanks a lot for mentioning SIBO, because somehow i was not aware this was a thing until you mentioned it, much less that sugar malabsorptions can cause this.

i’ve had weird digestive issues for years now, and i always sort of blamed them on my fructose malabsorption (as did my parents and doctors), even though the timing and symptoms didn’t really fit, so i guess i will get a test for SIBO now.

it would be fitting to randomly find a solution to a health problem under a post that specifically says that sometimes blind luck fixes problems where actual medicine can’t/​won’t.

[pinkgothic]

Hmm, from the literature I’ve consumed so far, I had the impression that SIBO isn’t actually that common, and it’s just one possible (and not particularly wide-spread) reason for irritable bowel syndrome. That said, evidence is mounting that SIBO was absolutely [my problem](https://​​www.lesswrong.com/​​posts/​​fFY2HeC9i2Tx8FEnK/​​luck-based-medicine-my-resentful-story-of-becoming-a-medical?commentId=FXit9XoHTjevw6goD), so I have no anecdata leg to stand on. (Personally I’m gradually experimenting with the carbs my gut is okay with it, since it has such a strong dislike for most of them (especially starches, for some reason).) Thanks for the tip with the elm powder!

(Edit: Erk, sorry, I can’t seem to make that link work. This is what I get for not commenting here often!)

[Adam Zerner]

The way I think about this is more “sometimes it makes sense to lower your standards for trying things”. Ie here the upside is incredibly large: if trying the thing works, it means a significant improvement to quality of life. OTOH, the downside is relatively small: some non-crazy amount of money and/​or weeks of unwanted side effects. With that as the upside/​downside, I think an eg. 1% chance of something working is plenty.

Related: Pascalian Medicine

When I reviewed Vitamin D, I said I was about 75% sure it didn’t work against COVID. When I reviewed ivermectin, I said I was about 90% sure.

Another way of looking at this is that I must think there’s a 25% chance Vitamin D works, and a 10% chance ivermectin does. Both substances are generally safe with few side effects. So (as many commenters brought up) there’s a Pascal’s Wager like argument that someone with COVID should take both. The downside is some mild inconvenience and cost (both drugs together probably cost $20 for a week-long course). The upside is a well-below-50% but still pretty substantial probability that they could save my life.

[gwern]

The broader problem here is more one of predictive validity, and only accidentally or as a special-case ‘you should try more things’ (the value of that is doing it in a human, not the more-things per se). Appropriately, a new Scannell paper just came out, further discussing the logic of pipelines/​screening/​selection.

Why did they discover so many amazing drugs back in the 1930s-1950s? Why do we discover so few now? Why is the late Shulgin so influential? Well, it’s because they were ‘testing’ all of the drug candidates (where the n is extremely, extremely small by contemporary standards of various kinds of in vitro or in silico screening) in humans. (The secret ingredient to both Soylent Green, useful COVID vaccine trials, and good drugs? It’s humans. Always has been.)

The key point being any humans, not necessarily yourself. When you feed random wacky chemicals to humans and one of them tells you it did something funny, this has low predictive validity, as it is bare anecdote afflicted by all sorts of biases… but it still has way more predictive power than poking some mutant cells in a petri dish, and that’s why you can look impressive and brute force thousands of those petri dishes and write papers and in the end, still get back fewer useful drugs in the end than the quack irresponsibly dosing patients at random because ‘inflammation’ & listening to their complaints.

So as a general principle, you want to push your samples as far ‘up the stack’ as possible, and be willing to trade off a lot of samples to move up a bit. Better randomized than correlation; better in vitro than in silico; better in vivo than in vitro; better mice than worms; better dogs than mice; better random humans than dogs; better you than random humans...

[yagudin]

I think it might be good to normalize “just try stuff until they fix your condition” as one of the treatment strategies. I guess it’s a bit ironic that Dr. Spray-n-pray’s indifference toward which pill worked and why seems so epistemically careless, while actually maybe being a correct way to orient towards success when you optimize for luck and have little reliable information.

[ChristianKl]

If the problem with proteins appears, it would be worth experimenting with whether you can replace protein requirements with consuming amino acids directly. If you consume them directly, there’s no need for the stomach to break down proteins and you still get the nutritional value.

[Elizabeth]

That does seem a good bit more likely to work than mediocre plant proteins. Interestingly the first and only medic to recommend it to me did so after the bospro started working, shortly after I shared that news. It ended up giving me digestive side effects that would have been worth working through before the miracle but pretty borderline right now.

[joey]

Really apprecitate you sharing your story. I read through most of the comments and it seems most of them are centered around diet/​illness and finding miracle cures almost by accident. Has anyone here had mysterious musculoskeletal issues (nerve issues, chronic pain, etc. - I know those examples are vauge...) that no doctor was able to diagnose regardless of imaging but were able to fix through self-experimentation and trial and error?

[Shmi]

Wonder how much of this is due to variation in gut flora and finding something that your picky gut bacteria could be happy with. Certainly made a difference for me, accidentally, when I apparently picked up a different gut flora strain that changed things that have been persistent for decades.

[Elizabeth]

I’m pretty sure gut biome renovations were somewhere between pointless and insufficient for me but agree that they should be very high on the list of things to try for many problems. I’d put them in luck based rather than model based only because we don’t really know how to do them.

[Shmi]

Yeah, figured you’d have tried, just that I didn’t see you mentioning it, so brought it up.

[Nanda Ale]

Gut biome was my first thought too as an explanation.

As far as I can tell fixing gut biome with things you swallow is extremely difficult. Probably not impossible, but fragile as heck.

The only thing that can somewhat reliably do it is a fecal transplant. Probably because you are moving in a whole ecosystem at once so the odd of it sustaining are higher.

This post makes me want to try ketone esters because I do notice I am very productive when fasting, where I am in ketosis. But I only do it a day or two a month because I like food too much.

[sclmlw]

This points to the biggest contradiction for evidence-based medicine: it’s often at odds with personalized medicine. We like to say that the plural of anecdote is not statistics, but we squirm a bit when asked to contemplate that the opposite is also true.

Yet our best tools for understanding how the body works require n>>1 for us to learn anything meaningful. You can’t do statistics on a single event, be it an actual literal miracle or just an unexpected one-off effective treatment. How often do we directly observe the limits of our epistemic system, and then complain that reality isn’t adjusting to the tools we prefer to use for measuring it?

[Eir]

I’d like to thank you for sitting down and writing this. I’ve been thinking about this post post for a few days now and I can’t say that I have anything worthwhile to add (yet at least), but I’d like you to know that on the other side of the screen this sparked a bigger curiosity of a doctor-in-training somewhere.

[Going Durden]

I have a somewhat similar story. I have been struggling with ADHD all my life, and only recently started using anti-ADHD medicines. Unfortunately, these gave me stomach issues and tremendous reflux, which was only tolerable if I took them in small doses...which in turn barely helped with my ADHD.

After testing pretty much every anti-ADHD drug with combination of every anti-reflux drug, I gave up, and tried my aunt’s suggestion of Ashwaghandha. I was beyond skeptical, and only gave it a try to please a concerned relative. I was mentally prepared to anti-placebo it, determined to prove it will not work (I even pre-planned my smug and condescending speech about how I did my best to test it and how obviously it did nothing, being just another woowoo herbalist nonsense with no scientific proof behind it).

It goddamn worked. By itself, ashwaghandha did precisely nothing. By themselves, ADHD medicine did something, but at the cost of me belching acid like an overfed xenomorph. Combined, it resulted in a far, far greater mental focus, and no digestion issues at all. Absurdly, combining ashwghanda with smaller dose of amphetamine salts gave better and stabler mental results than just doubling the amph intake.

AFAIK, there are no studies that conclusively prove ashwaghanda really works. Those that do, suggest it as a sleeping aid of all things. And yet. I talked it out with my psychiatrist, and as far as she knows (and she is likely THE expert on adult ADHD in my country) ashwaghanda should do nothing at all.

[Portia]

There are a lot of studies on ash, it absolutely does work. https://​​examine.com/​​supplements/​​ashwagandha/​​ And I have myself experienced, and anecdotally heard, of massive improvements in areas not yet tested here. In light of how cheap, harmless and relatively healthy it is, I think it is a damn solid thing for people in this symptom cluster to try. It is the only thing that ever helped me with anxiety without making me more fatigued, for one, and also had far more significant effects for me.

[Elizabeth]

Someone PMed me reporting that this post led them to try Osteo Biflex (which contains Boswellia plus some other stuff) and it ~cured their lifelong knee pain.

[AnthonyC]

Yes, this sounds completely right. One unusually good doctor I had told me, “In the right patient, any drug can have any effect.” It took me another four years to solve that particular problem, ten years in total, and I’m still concerned that when I see my new PCP (previous one retired) he might try to change my meds that’ve been working for 5 years.

Most doctors are too cautious, for whatever (often justified) reasons, to just try things. Most really don’t know how to respect what patients know about themselves or to interact with an actually-intelligent patient. I’ve had doctors tell me, “I don’t know what to do with what you’re telling me. Most patients wouldn’t even be able to notice these kinds details and put them together, so none of the research captures them.” And then they usually decline to try anything based on best guesses after first- and nth-line interventions fail.

It’s also true for veterinarians, btw. My cat gets chronic bacterial UTIs. We spent years having vets and specialists tell us, “Nope, unless you spend hundreds of dollars on a cystocentesis every six weeks, we’ll insist the problem is behavioral and stress related and not give antibiotics. No, it doesn’t matter that the $20 course of amoxicillin worked the last 10 times and that if it did again the symptoms would be mostly gone before the cysto results even come back. No, we don’t count it as evidence that you can tell a flare up is coming a few days in advance by the change in urine smell. Your cat just needs to suffer until the culture comes back and you have to deal with her being completely incontinent and dripping blood,” (we diaper her at night and when she’s infected). “Also, you should have us do a cystoscopy even though we probably can’t because they don’t make a scope small enough for a six pound cat but you’d have to pay anyways if we try and can’t, and you should do an MRI that if it shows anything we almost certainly won’t be able to fix it surgically so it won’t give any new treatment options,” (we’ve done ultrasounds and they don’t find anything). Finally our own vet gave us as many bottles as we wanted and said to use them as needed, and everything was fine for a few years. We also cleaned up her diet and found out a big part of the problem was a prescription gastrointestinal health food she’d been on for a previous condition (or at least, the food interacted with a suspected anatomical defect that no one can find because she’s too tiny for tests to show it) (we think she can’t tolerate brewer’s yeast? maybe?). She only had two infections the whole next year. She’s now 13, and just had to switch antibiotics because she started showing signs of resistance to amoxicillin after 5 years, but we honestly hadn’t thought she’d make it even to 10.

They tell doctors, when you hear hoofbeats, think horses, not zebras. But there are also deer, and elk, and antelope, and buffalo, and lots of other hoofed animals. And sometimes there are zebras!

[pinkgothic]

I flippantly summarise my version of this as “Prevent dementia, drink Coca Cola.” My own story is that I was B12 deficient because of (at the end of a chain of causation) low gut motility.

I’d drunk Coca Cola like other people drink water for my teenage years and the caffeine in it was plenty to keep my gut motility up enough to not cause issues. Eventually I went off Coca Cola for all the usual sane health reasons (but never picked up coffee or some other caffeinated drink!), my gut bacteria spilled over into my small intestine (SIBO) and increased irritable bowel syndrome (IBS) symptoms I had (yep, I am one of those people who could report that cola makes my stomach feel better—now I finally know why, and I know why it usually doesn’t replicate! Most people don’t have SIBO). I unsuccessfully tried to change my diet around several times trying to figure out what the issue was, made it worse by being flexitarian or vegetarian for a few months (very little B12!), eventually was so light- and sound-sensitive due to degraded myelin sheaths on my nerves that I could barely sleep properly and became severely depressed and increasingly mentally challenged (thankfully not to the point of dysfunctionality), until I was begging my doctors to do something.

The doctors correctly figured out the B12 deficiency (although there was some luck in that as well), but I only came across the link to my IBS by accident. I was reading The End of Alzheimers to see what I could do to fix my (mild) neural damage, decided to try a low-carb diet, noticed my IBS disappeared, and for many, many months (well over a year) did not think anything more of it, other than being happy that I had a way to manage my IBS now.

...then I looked into why low-carb would even fix IBS, came across SIBO, noticed it made the observation that I should be fine with sushi rice (indeed, I am! That was an observation I’d made a long time ago already) but not basmati rice (indeed, this is bad!), and also that it can cause B12 deficiency.

Once I realised that SIBO is caused by low gut motility, I realised I’d done this to myself by no longer drinking colas, and laughed out loud.

(To be clear, I am sticking to the low-carb diet and do not drink excessive amounts of cola, and I still don’t drink coffee, but I’m now using the SIBO self-diagnosis to carefully explore which carbs I can ingest so I can avoid some of the unfortunate side-effects of a high-protein diet (which low-carb pretty much maps to), such as kidney stones. Ow, kidney stones are bad. Do not recommend!)

[Portia]

Just curious… why didn’t you inject B12? At the point of nerve damage, that seems certainly more than warranted.

[carrots]

I had severe fibromyalgia/​chronic fatigue syndrome for a couple of years, as diagnosed by two independent rheumatologists. It was so bad I couldn’t sleep at night and I couldn’t get out of bed during the day. Around that time, a few pilot studies came out of Spain with excellent results from CoQ10 supplementation. I had had little success with the regular prescriptions, so I decided to give CoQ10 a try. I felt much better after a week. Eventually I also started supplementing with other stuff known to be used by mitochondria, and 6 months later, I was back to my old self.

I spoke to my rheumatologist about how well I was feeling since taking the supplements. This guys was supposed to be one of the experts on fibromyalgia. He just laughed at me and said that these supplements were nonsense. I tried showing him the pilot studies but he wasn’t interested AT ALL.

I continue to wonder what I could have done differently to make this doctor give me the benefit of the doubt and hear me out. In case something like that ever happens again.

[Portia]

Nothing.

I have literally walked into the office with several double-blind, peer-reviewed, large n studies printed out, the relevant sections carefully highlighted, to argue for the treatment I wanted, only for the doctor to repeat that this treatment does not work, like his conviction would somehow undo the data stating that it clearly bloody does.

I take Q10 as well. Crucial supplement for me.

There is this weird thing where some doctors believe that a substance that was not synthetically derived from scratch and created as a novel substance in a lab, but instead isolated from plants, or even delivered in the form of whole plants, can somehow not have any effect on your body, good or bad, as though such substances had an intrinsically different ineffective character. I have doctors go “no need to note the supplements, just the meds” and me telling them that they have significant interactions with other medications and blood values that they should really keep equally in mind does absolutely nothing. They’d want to know if you have taken aspirin, but not if you have taken willow bark. They group together proven cures with fucking homeopathy. It’s the same mindset that leads to people poisoning themselves because “it is just herbs”. “Just herbs” can heal you, or kill you.

[CronoDAS]

My own weird medical story: apparently I inherited my father’s issues with heartburn and acid reflux. We share an unusual heartburn trigger: sugary drinks. I can have just about any artificially sweetened beverage under the sun, regardless of how acidic it is, and be perfectly fine, and I have no problem with tomato products or many other acidic foods that give other people heartburn, but just about anything that contains both water and a lot of sugar makes my chest hurt something fierce.

I’ve only found two exceptions: orange juice is pretty safe for me, and Diet Minute Maid Lemonade is almost as bad as the non-diet stuff. (Minute Maid Lemonade gives me heartburn basically 100% of the time.)

[Ben Pace]

Hm, I also inherited my father’s issues on this (though not the same triggers as you), and I was really hoping you were going to give me a random cure to try.

[CronoDAS]

Well, although the triggers are unusual, I haven’t had any need to resort to unusual treatments to keep the heartburn itself under control; avoiding my triggers is generally enough, and I use antacids when it isn’t.

[Arshad Hosein]

Reading your experience with the medical world was hard for me. I have ARFID and have been down the same ringer for my entire life. I’ve come away from those experiences with a lot of the same conclusions about medical treatment and have also found myself into that try-a-new-doctor-every-couple-years loop. But in my case, I am now reasonably convinced it’s psychosomatic. I’m happy you were able to find something that helped you!

[Dambi]

Condition: Dry Eye Syndrome (AKA: your eyes are dry and we don’t know why)

Treatments that doctors did not recommend that work well for me:
Moisture-trapping night mask: https://​​www.eyeeco.com/​​eyeseals-40-hydrating-sleep-mask-charcoal-black.html?cat-id=

Moisture-trapping glasses: https://​​www.zienaeyewear.com/​​products/​​kai

If the cause is unknown, might as well treat the symptoms.

[Tim Freeman]

I tend to have itchy eyes. An optometrist suggested “derm dry eye relief mask” by eyeeco. Heat it in the microwave 20 seconds or so and then lay down with this lump of warm stuff on your eyes for 10 minutes until it isn’t warm anymore. Gently rub once afterward.

This seems to help and I do it fairly reliably.

The theory is that there are glands on your eyelids that secrete some magic substance that makes your eyes dry out slower. Those glands get clogged up if you stare at a computer screen and don’t blink enough. Rubbing at them does a poor job of removing the cloggy stuff and the warm compress is better because the compress melts it. The optometrist claimed to be able to see the cloggy stuff.

This theory predicts that I would have dry eyes if I didn’t rub them when they itched.

https://​​www.eyeeco.com/​​derm-warm-compress-mild-dry-eye-relief.html says they only sell to eye care professionals, but Google finds lots of equivalent competing products I could buy directly. I loathe that business model and I hope the competitors win.

They sell it for use with moist compresses, but I don’t add any moisture.

[Dambi]

Yeah warm compresses are nice and I guess I recommend them as well, especially for relief when symptoms are severe. They are a bit of a hassle though so I recommend looking for other solutions.

The best product for compress that I have found:
https://​​www.thea-pharmaceuticals.co.uk/​​products/​​blephasteam

It gently steams your eyes, so it makes them both warm and moist. I think I do recommend some form of moisture when you do warm compresses.

[kparker]

There really should be an aggregator for medical knowledge found on disease forums and posts of this kind (is there one?)

[Elizabeth]

Crazymeds used to do this for psychiatric meds but no longer exists. I think it’s hard to formalize because it’s a lot of work, hard to capture the value of ethically, but very easy to capture the value of doing unethically.

[kparker]

how so? forum members submit info voluntarily and anonymously

natural experiments of your kind i.e. spontaneous resolution with some unexpected agent or lifestyle change—and other best practices based on n,000′s of years living with a condition—there has to be value there for drug developers and clinicians. The work is authenticating claims and maybe matching people to scientists?

[Tim Freeman]

In response to “how so?”: If this catches on, you can sell a drug by infiltrating the forum and posting fake news of miracle cures under many different names.

For schemes like this to work, you need some way of guessing who trusts whom. The spammers might claim to trust each other, and you never really know who the spammers are. The best you can hope for is for the real people to get good information from other real people they trust, and the spammers get garbage information from other spammers but that doesn’t matter because they are spammers.

I don’t know of any implementations of this.

[Portia]

Because at the point where people browse these forums, they are so desperate they will try literally anything, and are surrounded by people who feel the same, and a lot of the things being reported cannot possibly work, are extremely tied to very specific conditions, and possibly very dangerous. People will also select the meds they hear people report cures of in ways that emotionally resonate, not because there is good evidence it would transfer for their case, or at least be safe.

[Maxwell Peterson]

What form/​brand/​dose do you take the ketone esters in?

[Elizabeth]

I use KE4. Now it’s typically 5ml before bed and sometimes I forget that, but when I was doing longer intermittent fasting I’d do 10-15ml at night, 5-10 in the morning, and 5-15 before work outs.

My ability to fast has increased, relative to what I did pre-ketone-esters, even when I don’t take them or take less. I also quit soda when I started them and never restarted, even when I was taking almost no ketones. I think there might have been durable changes from it.

[Maxwell Peterson]

Thanks!

[TekhneMakre]

Re/​ ketone esters, is it plausible that they increase variance in productivity, but not mean productivity? That is, for some people (or for the same person at different times) they increase productivity and for some they decrease it, in a way that balances out in expectation?

[Elizabeth]

Clearly there is high variance in response to ketone esters. If you’re asking if in my study there was high variance averaging out to zero the answer is no, I checked for that specifically. I do suspect this is problem with a lot of other research though.

[TekhneMakre]

Thanks. (I was asking both questions.)

[Portia]

I have so much fucking sympathy for this.

I suffer from a connected set of unusual and debilitating conditions that clearly, noone is capable of accurately diagnosing or making sense of. I understand aspects of them—inflammation makes them worse, for example, as do certain parts of my hormonal cycle, it also seems to be related to a genetic difference in how I respond to some nutrients and how my joints operate and a neurodivergence, and these aspects are reliable and helpful—but at the end of the day, noone knows why this is messing up my body so badly. And I mean badly, emergency room badly, randomly nearly dying badly, tanked quality of life for long periods badly. Characteristically, some of my values are terribly off in a way that they know from condition x, except condition x also has y, and I do not have y, while I do have z, which seems utterly unrelated and terrible in and of itself, and is common in condition a, for which I also do not test positive, continue indefinitely. I don’t know if it is an unusual presentation, or an unusual combination, or outright new, but I am no longer expecting to actually get an answer.

I’ve also had your experience of bringing detailed documentation of what has been tested, what I am taking, what triggers symptoms etc. and having that entirely ignored in favour of generic useless advice I tried years ago.

And at some point, when I realised we weren’t getting anywhere, but that some of these potential diagnoses had the same cures, and that the cures, if they would fail to work, would have less atrocious side effects than the current symptoms, and that I wouldn’t need to get the diagnosis to have them work, that them working was the goal in itself and testable, I switched to “fuck it, so let’s try all of these in sequence while carefully monitoring to see which work”. I’d have been delighted to set up double blind placebo trials.

Doctors thought this was a very bad idea, saying they could not prescribe without a diagnosis, even though I was clearly very ill and they saw no way to diagnose what made me so ill because my test results were so weird—I would have one alarming marker meaning one thing, but then not the other they would expect, etc. (And that was the ones that believed me, and were very sorry, but figured there was nothing they could do. There is also a special class of doctor who apparently believes that I can’t have possibly have had a heavy, unabating period for two full months, or spent a month with diarrhoea so badly I dropped 10 kg, or developed pain so crippling it made working or being happy or even getting decent sleep essentially impossible, because the test for whatever they thought would cause this came back negative, so clearly, I just like hanging out in hospitals for no fucking reason, maybe because hanging out with gaslighting idiots is so inherently wonderful.) We got nowhere. Even as I stressed that my quality of life was currently so bad that I was suicidal, so I literally could not see how it could get any worse from trying the wrong pill. It drove me nuts. I started actively avoiding medical care because it was so disheartening to have hope and have it be crushed each time.

I eventually trialed this, myself, through various roundabout ways. (I got a doctor friends to prescribe the trial meds, after showing her very carefully why I thought these would be good to trial, and how I would ensure my safety during the trial. And I went through a long list of potential supplements one can get online.) And a lot of stuff did nothing much in any direction, really. Some made me a little bad. Some made me briefly really bad, but was dropped and contained without further consequence. But some, and I say this with a relief I can barely express, some helped. Some helped, a lot.

I’m now on a pharmaceutical developed for fibromyalgia. I do not think I have fibro. But it did, massively, reduce my pain levels, so frankly, I do not care.

I’m also on a med I was prescribed years ago, an atypical antidepressant. The doctor involved told me it was forbidden to prescribe for my condition, but he suspected it would really help me, and that it would produce the effects I was seeking without the side effects I was worried about, and wanted to try. It really helped me, incredibly so. I have meanwhile been told that the diagnosis he gave me at the time reflected a medical misunderstanding of several other conditions, that I have a different condition, and that the recommended medication for that is… the one he already gave me, that I am already taking. I still think of that man fondly as a dude who actually helped me.

I am also on ashwagandha, which completely eliminated a severe psychiatric symptom I had, doing something no major medicine could for me. I am certain this is the cause, the correlation is rock solid, and the difference is major. Forgetting this supplement has it return. I have not seen this link documented anywhere. I have no idea why it works. But as long as it does, I do not care. A name for what I have, and understanding for it, would be neat, it really would. But at the end of the day, my goal is to fucking function.

And on 20 other things that make a significant difference, but do not stand out as much as the above.

Beyond pills, I have very, very elaborate documentation of nutrition rules and exercises and habits that help, and guidelines for when it gets bad.

I’m still alive, and getting my PhD, and working at university, and in a long-term relationship, and have savings, and manage to do some activism and have some impact, all in spite of the fact that I think the genes I got were a whole bunch of crap still causing me considerable grief. So I guess it worked, for some degree of “worked”.

But fuck, do I feel your anger. I’ve had to figure out and set this up all on my own, with the medical system for the most part not just failing to help, but making it worse. At this point, I only see doctors to access lab machines, scanning machines and prescriptions, and perceive them as hurdles more than anything else.

[Tim Freeman]

In response to: “I don’t understand why or how weight-loss-that-is-definitely-not-changes-in-water-retention comes in chunks. If you have an answer I’m quite curious.”

I too have observed that this happens. I read somewhere that if you lose fat, it is a few cells losing all of the fat instead of many cells each losing a little bit of the fat. The empty fat cells fill with water and your weight stays approximately constant. After there are enough empty fat cells that have been empty long enough, some of them do apoptosis and you pee out the water and you lose weight then.

I don’t remember where I read it.

[Elizabeth]

I read a similar thing on Reddit repeating something the author’s trainer said once. I have almost zero confidence in this explanation and it’s also the best I’ve found

[Tim Freeman]

Found a different, perhaps better explanation: salt intake leads to temporary weight gain from water. Restaurant food is salty. https://​​youtu.be/​​j314amPw4RQ 42:30

[Elizabeth]

That explains noise but at the time I had almost no variation and then sudden drops. I was also consistently high salt, and I expect the salt effect has a ceiling.

[wgb]

The potato diet reminds me of a brilliant professor, John PJ Pinel, who had a pet theory he could never publish.

He believed that the most effective diet was to limit yourself to no more than seven ingredients. You can pick any seven. It might be potatoes, eggs, beef, carrots, lettuce, blueberries and tomatoes. Any seven, and maybe a Vitamin C supplement if you don’t pick a citrus. You become so tired of each ingredient that you eat substantially less calories.

The interesting part was the theory that a limited diet allows your body to align cravings with the nutrients a body needs at any given time. Our bodies cannot align cravings with needs when there are hundreds of foods in our diet, but when theres only a few we can apparently manage it.

I highly recommend the chapter of his textbook on food and diet if you are into this kind of thing. Biopsychology by John PJ Pinel. To be fair, lot of his pet theories were probably wrong. He also believed that we needed almost no sleep, and that we would be healthier if we ate lots of very small meals.

He loved to tell the stories about how various drugs and treatments had been discovered. Nearly all of them were discovered by accident. Penicillin, Botox, Lithium, Rapamycin, Viagra, Birth control, Iproniazid, Warfarin, etc. They all have stories like yours.

[AnthonyC]

I can see how that might help me eat less, but unless you chose the seven very carefully to be potentially nutritionally complete, sustaining that seems like a path to the kinds of deficiencies that made the agricultural revolution cost humans half a foot of height for most of the last ten millennia.

[carrots]

I came to a similar conclusion about limited diet causing weight loss. I moved to a small remote town in Europe a few months ago and lost my excess weight with no effort, after having lived in large North American cities all my life. I shop mostly at a local mini grocery store that has limited stock, so my diet tends to be boring and my appetite small. As soon as I stock up from a supermarket with a variety of yummy unusual foods, I start gaining weight.

I don’t limit myself to 7 ingredients though. Rather, I eat the same thing for lunch everyday, and rotate through a handful of simple recipes for dinner. This also keeps my IBS-like symptoms under control, but I don’t know if my GI is happy due to the ingredients themselves, the lower volume of food, or the fact that it isn’t exposed to novel foods as often. Or a combination.

[Marion Z.]

The most effective diet for weight loss? Seems plausible. The most effective diet for being healthy, that sounds extremely unlikely. Even if your seven foods are nutritionally complete you’re not likely to be eating them in the right balances. Intuitive body regulation sounds good there but in general, our bodies are actually not so good at guessing that kind of thing.

[Portia]

No idea why you were downvoted. Humans have some correct intuitions on foods they need, but they are generally overwhelmed by wrong signals. My body certainly believes that it would profit from living off sugary fatty things, and that any multicoloured food has lots of nutrients, or that anything acidic is high in vitamins, which is why acidic, multicoloured candy is obviously a complete diet. I see why it thinks that and why that would help in a natural environment, but it really does not help with typical foods.

[rain8dome9]

In my case it turned out to be manufactured food and gluten. This post is very similar to Quantifed Self movement.

Also please remember that side effects and drug interactions are a thing. Anything with a real effect can hurt you. I gave a very caveated suggestion of BosPro to someone on Twitter and it caused something akin to niacin flush in them. This is the same brand that does nothing to me but makes me better at digestion and uninterested in sugar.

What if the problem or the negative consequence of some intervention is hard to detect? I know this is not a popular opinion but anyone trying spray and pray really really should track their basics like HRV, Mood and cognitive ability.

EDIT: The other way to spray and pray in one huge chunk is to move to a different country. A large number of variables change when you do. In my case moving to Mexico helped because there are many restaurants that make food from scratch and bakeries that seem to make food without gluten.

[sarahcone]

This was a very interesting account and I think more of medicine falls into this category that we’d like to admit.

I’m interested in companies like Radicle Science that are a “private FDA” that run clinical-grade trials of natural medicines, vitamins, diet, exercise, and OTC medications on a variety of indications.

[Nathan Helm-Burger]

One of the ideas I’m excited for once we get further with the aligned AI stuff (sub-AGI level, but needs more careful handling than current narrow AI) is chatbots that people enjoy talking to which can collect and analyze anonymized data from lots of people. Hopefully this could push forwards personalized medicine significantly. That, plus cheaper better genetic screens and body biome genetic screens.

[Semanticprion]

Regarding “Fuck you every doctor who told me my digestive problems were in my head”: psychosomatic illnesses are a real thing, and sometimes the solution to an apparently physical problem really is psychiatric. BUT if a non-psychiatrist physician believes this is what’s going on, THEY SHOULD REFER THE PATIENT TO A PSYCHIATRIST, not dismiss them. Imagine someone coming to a primary care doc with unstable angina and the doc said, “Ah, it’s in your chest, whaddaya gonna do” without referring to a cardiologist.

[Daniel V]

He guessed I had an allergic reaction and threw 5 different antihistamines

Not so much dumb luck after all! Allergic reactions often cause inflammation, and it’s the inflammation that is uncomfortable. Sure, it’s not very controlled (could have suggested one, then another, then another, until you got to Boswellia, preferably in order of prior belief for each more-specific hypothesis), and other things could cause inflammation, but it’s not completely luck either. (Though this did not detract from my enjoyment of the post!)

Some quick Googling says,

Current research showed that 3-O-Acetyl-11-keto-beta-boswellic acid (AKBA) is the one boswellic acid with strong pharmacological activity; for example, AKBA has a powerful inhibitory effect on 5-lipoxygenase (5-LOX)

The tissue, animal model, and animal and human genetic studies cited above implicate ALOX5 in a wide range of diseases...chronic inflammatory conditions such as rheumatoid arthritis, atherosclerosis, inflammatory bowel disease, autoimmune diseases

Helpfully, this study compared AKBA vs. NDGA, so maybe that could be a useful way to test the mechanism of action (they also differ in their specifics within that too, so that’s yet another question mark). Obviously not medical advice and just a curious wondering.

[Purged Deviator]

weight-loss-that-is-definitely-not-changes-in-water-retention comes in chunks

Source for my answer: for the last 10 months, I have fasted regularly, with various fasts from 16 hours to 7 days, with & without vitamins, including water fasts, electrolyte fasts, and dry fasts. During this time, I have weighed myself multiple times per day. [I have lost >100 lbs doing this, but that’s not important right now.]

How hydrated you are at any given time is a confounding variable whenever you weigh yourself. My body can hold plus or minus nearly a gallon of water without me feeling a difference. If I weigh myself while less hydrated one day, and then while more hydrated the next day, that hydration difference will completely overshadow any weight loss. When I was dry fasting there was no increase in hydration, so weight loss became extremely regular. Eating more carbohydrates also tended make me retain more water for a few days, and the amount of food in my gut at any one time were some other confounding variables.

[deleted]