I'd like to argue that it is possible to fight the balance game to an extent.

I've also fought a similar battle to you in a similar manner by "fix everything according to best practices."

When it comes to supplements and nutrition, it may be an impossible game, but what's important in finding the right approach is understanding at least the basic mechanism of action and knowing what you're targeting.

What I'm hearing you say is that you had an app with a performance issue, and you couldn't pinpoint whether it was CPU, Memory, Disk, Network, etc, so you solved it by doing a wholesale system upgrade by giving it all the basics that modern science says are the typical health best practices. Magnesium/Iron, exercise, gut biome, oral hygiene, etc to help. All the things you've listed are anti-inflammatory (of course there's other benefits) but generally, anti-inflammatory things are pretty good at making the body run better.

NAC on the other hand, is a precursor to glutathione, a significant anti-inflammatory molecule in the body, and usually the limiting reagent for glutathione synthesis. So it's also arguable that NAC had an anti-inflammatory effect on the body similar to the effects you received from your regimen.

Finding the right supplements are possible for sure. Usually what is needed though is a thorough analysis/observation of someone's diet and then working back the potential malnourishments that are most likely to occur and in alignment with the symptoms. But usually this takes months and years of learning and understanding to even know where to begin when it comes to suggesting a supplement.

It took a reading a few thousand pages of ncbi.nlm.nih.gov papers over a number of years (I made it a habit just to try to crack this thing), this is one of those traditional 'fall through the cracks' kinds of things. My PCP admitted to me that she felt ashamed at not being able to help any further and not knowing what to do, and she's internal medicine.

I have reactions to nearly every food group out there, even things traditionally safe for many (minus the ultra safe things like rice, lamb, etc).

It's definitely not a digestion/absorption issue, in fact I have a reasonable belief that I have barrier permeability issues as things like taking GABA will result in respiratory depression + temporary oxygen starvation for a few seconds - half a minute or so (yay) followed by that emergency contraction of blood vessels that the body does when trying to get oxygen to organs. That's one good indicator of systemic barrier dysfunction, for example, as that is certainly not supposed to happen in healthy people since GABA is not supposed to cross the intestinal barrier (or the BBB for that matter) in healthy individuals (though I wonder if one tiny benefit is making GABA slightly more effective for me for anxiety over, say, the average person due to potentially-increased BBB permeability). Additionally, things like P-glycoprotein inhibitors (like piperine, etc) cause me to react much more strongly to food/environmental things.

Apples would contain, say, the most pyruvate and malic acid (though I react to apples pretty badly, sadly, I'll get arthritis-like symptoms (which makes typing and manipulating objects difficult, for example), though I take an OTC 5-LOX inhibitor nowadays that is actually surprisingly quite effective at preventing things like that from happening in accidental food exposures. Still not enough to have apples straight though, lol).

So it's things like that. Most of this is things like looking at the Krebs cycle, finding upstream things to targets that I want that seem to perform well (like oxaloacetate, which is sold at an outrageous price), and then putting them through the empirical test pipeline to see if they hold up.

Things like niacinamide for example I'm taking 1.5-2. grams a day which would be hard to get from food, pyruvate is also hard to get from food as well. I love the idea of food as medicine, but unfortunately it's mostly calories in (and thankfully I don't seem to react to multivitamins, thank God).

I've tried several thousands of dollars worth of supplements over the last several years trying to find combinations that work. This is most certainly harder than most of the machine learning problems that I work on, as the loss signal is not all that clear, really (unfortunately)!

I am glad to have found something that seems to have a positive impact, however!

Yes I tend to consume half a pound to a pound of red meat per day (calories in -- rather extreme food sensitivities unfortunately), so my iron levels are good.

I have been struggling with many symptoms for close to a decade now. The worst one is acid reflux - only during the night, and when I wake literally every single morning my mouth tastes like I've been gargling concentrated vomit all night which is probably somewhat accurate. I think it's impacting my sleep as well.

Additionally I have seemingly incurable fungal infections on my feet, private areas etc. It's manageable but it makes me think a candida overgrowth could make sense. I also have what my doctor thinks is seborrheic dermatitis, causing a red rash that's spread over most of my face and scalp. Flakes a lot.

I wonder if there's something in this thread that could help. I asked my physician about antifungal pills as I haven't had any luck with creams etc but he wanted me to try to remove dairy from my diet. That seems to have had some effect, but the only manifestation of that effect is that if I do consume dairy my digestion acts up for a day or two. Hasn't helped the reflux or face/scalp rashes.

If anyone has any suggestions I'm open for anything.

I currently eat half a pound to a pound of meat per day as it seems to currently be the most reliable way to get calories in for me with minimal reaction. It feels rather horrible from the 'yuck, bleh' feeling of eating a little more unhealthfully compared to that lovely glow (by comparison) that having vegetables will sorta bring on.

I can have some vegetables (yay salads! I love certain kinds of salads, have to be picky about dressings and toppings though), but at the very minimum meeting caloric needs is the core goal for me.

As far as infection goes, I've had many antibiotics over the years of different classes. I believe it's fungal (mayyyybe with a parasitic co-infection of some kind?) as that anti-parasitics/antifungals are the classes that seem to introduce the strongest response in me.

Also, I cultured some of the skin from my foot and it grew yeast, in great abundance! (not the most reliable test, but it works okay...ish, lol).

Additionally, I had the same systematic spike in pain in my leg when taking niacinamide originally as I did when surface-treating the fungal foot infection, which cleared up pretty rapidly underneath it.

Things like thujone/juglone/etc seem to be quite helpful too, though, so I do worry about a potential opportunistic parasitic component to it as well, as I seem to respond in some way to drugs in that class (even the ones potentially without apparent antifungal activity). Parasitic infections actually are quite common in the US compared to our expectations -- just look at pinworms or toxoplasmosis (even though it is quite low here in the US compared to the rest of the world)!

I think something that I've slowly been finding is hard about epidemiology is that immunocompromised individuals can be subject to a whole host of odd infections & etc in comparison to a standard, healthier population.

Of course, and much love! Pyruvate is fantastic too, and w/ niacinamide if you're going for the nicotinamide riboside route don't forget to try taking ribose with it -- it apparently _really_ makes the difference for some!

So much mitochondrial implication in any post-viral fatigue syndrome, it seems like somewhere in the stack is oftentimes disrupted, thankfully it can be managed though!

Night and day for me. On the Appalachian Trail, I had to count steps and watch my heartrate on the climbs to keep from triggering PEMS (you don't want that out in the semi-wilderness). I had extra food and would take days off when I did trigger PEMS/go mildly hypoxic/lactic acidosis, whatever. Not fun, but boy was it a pristine place to take break days, in the perfectly gorgeous wilds (surrounded by interesting and talkative, friendly people. heaven).

In any case, on the AT it took so much discipline. I switched to keto after getting norovirus because why not on the momentum of not eating for several days, and some of the ridge runners helped me out as well (they are true trail angels I think). The keto really softened my PEMS a lot, I think basically by preventing the lactic acidosis spiral because...yay, no glycogen in the energy cycle anymore. That was my motivation/thought at least, and it did really pay off, it seems (for whatever reason!).

Pyruvate was my second best shot, it would really reverse a lot of problems to a manageable degree so I could do more basic stuff and focus on rest days, etc.

Eliminating free glutamates was _huge_ for me. Maybe not for everyone, but for me, absolutely. This is yeast extract, miso, soy sauce, hydrolyzed corn protein, anything that is umami basically is glutamate or glutamate-related in some form or fashion. For whatever reason, blood glutamate scavengers seem to be well-implicated in reducing symptoms of me/cfs quite well (and fatigue in general? i think?), this is not quite as well-known as I think it should be, but check the research out on that for yourself!

I'd have energy crashes after having, say, beef jerky (which already has glutamate, just competing with the other amino acids during breakdown), which often has tons of soy sauce or the like. Everything seemingly has MSG (or the equivalent), though they can legally lie if they put it in via a different source, apparently.

(Don't get me wrong, I love MSG. But it can make the lives of me and other people with fatigue stuff absolute freaking hell).

All that to say, niacinamide sorta waltzed up and smashed the delicate glass wall that I'd been balancing things around. I'm very grateful for it, it sorta feels like easy mode (minus all of the symptoms lol) compared to the other stuff.

Please feel free to ping me on twitter if you ever want to! <3 :'))))) Happy to chat further about this, and much love! Thank you so very much for your encouraging words, ME/CFS, long covid, post viral stuff is a hellhole of a syndrome as it basically feels like it sucks your soul out of you physically (experientially, at least, lol), and leaves you dead-alive. There is hope, and much CFS does not last forever! And even if it is there, I can assure you that there is a way to enjoy and love life, it just becomes much more of an inward and spiritual (if necessary regardless of the requiring circumstances) journey.

Sorry, that was a lot, I, er, maybe am recalibrating to my energy levels. Also, I'm very passionate about this particular topic! <3 :')))) :'))))) :'))))) :')))) <3

The world is much more complex than this, unfortunately, there are a significant number of etiologies which result in CFS-like symptoms, it's one of the less studied umbrellas out there.

Lyme, babesiosis, rocky mountain spotted fever, etc, all negative. I also did a urine Lyme DNA test a while back but looking back on it, apparently that was not an extremely reliable test (though the western blot has a decent amount of false negatives as well).

I believe it's a chronic yeast infection that's slowly traveled up under the skin of my left leg for the last 7 years or so. It started out as athletes foot in college, and then when I got past the point of being too overwhelmed to treat it, it had set in pretty well.

I wondered if the two were correlated, but over the past few years I've had increasing leg pain in that area, and the same pain in my toe where the infection was. Of course, the nature of this infection is that it seems to be resistant to many OTC classes of antifungals, so it did not budge. The most effective agent was carvacrol/thymol, which is extremely broad range (even against MRSA), but it macerated the skin to a point of strong pain, bleeding, etc, all that jazz. Even when it cleared up on the outside, there was a deep white patch under the skin that you could see under the (healthy-seeming) skin, which, of course, is its own unique class of horror.

About a year ago or so, I finally broke and decided to get rid of the skin infection no matter what. I basically mixed isopropyl alcohol and table vinegar and put it in the skin after removing the top layer of dead skin, which as it was an open wound was extremely painful. I used the reasoning that I could temporarily damage the nerves with overexcitation via the isopropyl alcohol stimulation, and that reasoning panned out after an excruciating several days, after which my nerves were damaged enough to no longer hurt under the raw vinegar and alcohol combination.

That at least cleared up the surface infection until I was on the Appalachian Trail this year (which, yes, I did my two months on it with chronic fatigue + post exertional malaise (!!!!) !), where, more than a year later, the infection inexplicably came back again.

I found niacinamide in my search for treatment-resistant infections, and it cleared up the surface infection within an astounding 2-3 days. I started taking it orally, and became extremely sick, it felt like I was being poisoned and doing a mini-chemotherapy of sorts, so I slowed down and began taking silymarin and NAC to help preserve liver and kidney function (which seems to still remain okay so far).

The process of treating it has been painful, as the initial days caused a huge flare in leg pain in my left leg corresponding with swelling of the lymph nodes almost exclusively on the left side of my body, oddly enough (though it seems to have balanced out, a bit). I was in the emergency room on my birthday last year due to the leg pain, and they couldn't figure it out so they offered a potential umbrella diagnosis of complex regional pain syndrome.

It's hard to keep up with dosing as I do have a bit of an aversion to feeling sick -- it quite literally feels like I'm being poisoned! -- but, my CMP from even this week came back okay, and I'm getting a feeling of underlying 'rightness' despite the transient negative symptoms (including having to pee every 2-3 hours...not fun).

I've had maybe two dozen doctors, both in and out of the ER (6 visits in the last year or so), or so give me that look of not quite being able to know what to do. I applied to the internal medicine program at the Mayo Clinic a few months ago and got a form letter turning me down. It's not due to incompetence, it's just that there is a long tail of extremely complicated conditions that categorically fit an umbrella of symptoms, but are extremely hard to actually track down (and the semi-binarization of medical specialties makes cross-disciplinary diagnosis extremely difficult for these vague kinds of conditions).

I'm sitting here now and can feel the leg pain when I focus on it, for example. But I think treating it is worth it -- especially as one has to work to live in many circumstances! That said, this does not underpin how grateful I am to at least have one avenue -- whether it's temporary or not -- where I can have energy.

This also doesn't cover things like the mast cell sensitivity (diagnosed as not MCAS by _two_ separate immunologists, though they both fall in the tryptase-test-philosophy camp). I react to everything, including All Free and Clear detergent, for example, and with food and such sometimes it's just eating tons of meat (it's pure muscle protein and fat and doesn't have things I can react to like lots of plants do) and multivitamins to cover the nutritional gaps.

I wish it were as simple as just having Lyme disease, as I think that would be much, much easier for me personally. But, I suppose to keep living we have to accept the limitations that we have (and unfortunately this is not the only journey of limitation I'm on -- I also have autism to a mild-moderate degree! That would be enough challenge for a normal lifetime as it is. D'''':), and I had a number of years where I really struggled (like, really really struggled). But all of that said, I think although it's taken a few years, I've come around the bend in starting that process of eventually accepting the challenges I've been given, and I am on currently on that particular upward walk of learning to enjoy the life that I do have access to in the meantime. It's not perfect, and I have a lot of big bumps in the road, for sure, but the slope for me is pointed up, and that's what I wished for for years. And I'm enjoying life a lot more than I have in the past, on average! :')))) <3 <3 <3 <3 :'))))

Hope that answers your question.

If you don’t live in a Lyme-prone area, Lyme is unlikely and your risk of a false positive is high

Reminds me of Michael Phelps and his 12,000 calorie diet...

EDIT: https://en.wikipedia.org/wiki/Michael_Phelps#Training

To be clear, this wasn't Sapolsky's research. In one of his books he referenced the findings of another researcher (physicist, chess GM, and textbook author Leroy DuBeck), with caveats about that figure being extrapolated and thus not a direct measurement at all.

As per usual, this claim has been repeated all over sports/medicine journalism with improper attribution and no mention of the caveats.

Thanks for the write up. I always wondered about this.

But if they are eating less or triggering other mechanisms because of the thinking wouldn’t that be an indirect effect?

I’ve been tapping my foot ferociously since I was a kid and the most I’ve been “on” is caffeine. Lots of it, though, but the taping helps me even when I’m not drinking coffee.

You have to assume anything not tested for (that helps) is used at the top.

I would think large swings like that are water weight. They're probably really focused and not drinking or eating as much as usual

Does amphetamine help concentration?

Or maybe stimming?

It is a bit confusing to me because it is often said that the brain draws about the same amount of energy, no matter what. Perhaps people also eat less during tournaments.

> Obviously, our results are only correlational and cannot be taken as proof that what limits cognitive control exertion is the need to prevent glutamate accumulation.

I didn't read the original story but I wonder if it included that little gem

"Please submit the original source. If a post reports on something found on another site, submit the latter."

https://news.ycombinator.com/newsguidelines.html

Mine just sits around and worries all day.

I use to colloquially call this game "slap deck" as a kid. The general approach taken was to add a ton of house rules, such that it was a large test of working memory to keep all rules in your head. We kept some simple rules to keep the game approachable for younger children, and older children/teens would continue to add house rules to make the game more complex. In addition, game play would be very fast, and often times patterns would be missed because no one recognized it quick enough.

Some of the rules that would sometime appear that I can recall

* Put 1 or 2 jokers in. Jokers are slappable

* Doubles are slappable (3, 3)

* Three (or four) face cards are slappable

* Three (or four) cards of the same suite are slappable

* Three (or four) consecutive cards are slappable (2, 3, 4, 5) or (5, 4, 3, 2)

* A player without cards can 'slap in'

Ahh, thanks for the memories! If it weren't for my slow reflexes, I would have been much better at that game.

The difference is the reward afterward. Learning to play a complex piece on an instrument is mentally taxing, but getting it right gives you that sense of accomplishment that can't really be matched with anything else. Same with debugging a program you are writing, or solving other types of problems.

Doing hours of arithmetic homework as a child didn't give me that reward signal, so for me that was torture back then.

I took a similar one, I remember "trying" really hard to prove to myself that I wasn't faking but about 30 seconds later I was looking about the room and struggling to recall if the screen changed at all. Was a nice confirmation of my issues.