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Comment by tysam_and | Hacker News Reader

I have chronic fatigue issues that go in and out of remission, and the buildup of glutamate seems to by far be the biggest factor for me.

N-acetyl Cysteine and other blood glutamate scavengers (BGS) like malic acid and pyruvate are indispensable in these scenarios. They don't solve the issue but dampen it a bit.

Additionally, a ketogenic diet helped me a lot.

Most of all, high dose niacinamide holds it in remission at times, though I have a theory it's caused by a well-set-in, chronic infection as the reduction in symptoms with niacinamide correlates with the symptoms of fighting off an infection (very swollen lymph nodes, histamine release, sometimes nausea &etc, headaches, some other clear indicators, etc). I've been on it for about 7-8 weeks or so and we're still going!

That said, having energy is a gift that is hard to quantify. Chronic fatigue takes away your ability to think about anything, so you have to have discipline to not think about anything sometimes...which also takes mental energy. It's a bit of a living hell, for suresies.

Here's hoping I get to stay in remission. <3 :')))))

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I used to have CFS, but apart from the occasional temporary post viral fatigue that many get, it’s gone. And what is CFS but long term post viral fatigue?

One thing I learned is to ignore figuring out the exact supplements, because you’re playing an impossible balancing game with poor feedback mechanisms. There’s too many inputs.

What helped me was a combination (no one thing can solve it) of therapy (being able to listen to and not suppress emotions), key supplements (magnesium/iron - check out lactoferrin and anaemia of chronic infection), exceptional oral hygiene to reduce inflammation (4 minutes per brush), exceptional gut health (many viruses cause problems with the gut), exercise (eventually), and more…

I never used niacinamide or any of the supplements you used, which shows you that there’s no single approach. I agree that it appears to correlate with an unaddressed infection.

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.

Have enough supplements to cover your bases and ideally cover it off with whole foods when possible.

To be clear, I found it wasn't a good use of time to spend years experimenting with many supplements that end up working temporarily and then having an antagonist effect on something else that appears months down the line.

The best use of time was taking a holistic approach. Supplements didn't save me - but without some basic supplements I wouldn't have been saved. And I agree, some basis in nutrition is important.

I'm curious how you came to start taking these supplements? Were they prescribed by a doctor? Several of these appear to be abundant in food (according to quick search results) so I wonder if it's more of a digestion/absorption issue for you?

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!

It sounds like you’ve looked into it thoroughly, but have you had a blood iron test as well? My iron levels were not below the normal range, but taking an iron supplement (Proferrin) was profoundly impactful for me. I went from needing daily 1-2hr naps back to a normal sleep cycle (and can even go on <7hrs without feeling fatigue during the day).

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 a theory it's caused by a well-set-in, chronic infection

Have you looked into fungal overgrowth / candidiasis? Keto seems to work for that too https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583754/

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.

Obligatory "this is not medical advice", the human body is a wonderful, horrible mess of incomprehensible, interrelated systems, etc. etc.

For sebderm check out r/sebderm. From what I understand sebderm is also a fungal overgrowth, albeit a different species. (The apparent overlap between sebderm and candidiasis would point to an immune deficiency, which suggests mineral deficiency. (Which suggests digestive issues or food sensitivities, the way celiac damages the gut and severely reduces mineral uptake, issues digesting dairy can also result from undiagnosed celiac...) Have you had blood work done?

Digestive issues may also point to a Thiamine (B1) deficiency. There's some interesting work with thiamine megadoses. (I know megadoses trigger the pseudoscience alert bells, but there's real science behind this.) Something about how the mechanisms responsible for Thiamine uptake can stop working when you have a deficiency, which causes the deficiency to persist even if you return to eating normal levels. This can then be resolved with a megadose (which are considered harmless).

Also, are you getting enough sun? I have found this does wonders for me. (Alternatively supplement with Vitamin D and make sure you research the right dose, because the recommended dose was too low for many years).

If it's some sort of infection, did you try a round of broad spectrum antibiotics?

Also, read up on the "carnivore diet" if you haven't already specifically the anicdotes of people online. I found it removed basically all my chronic health issues, which tells me I've become intolerant of certain foods. Re introducing is tedious though.

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.

For what it's worth, I've had a great experience with sauna/cold therapy. You seem well researched on the topic, so im sure you're aware of the plethora of studies correlating reduced inflammatory response and heat/cold therapy, but if you've never given it a shot yourself I'd highly reccomend. I went so far as to build a small sauna for myself, and have found that my energy has increased drastically day to day, and I have had significantly reduced inflammation generally. (GI and dermatitis issues previously.)

This is an excellent idea, and I haven not visited this one in a long while. I've been interested and have access to an infrared sauna now, so I will be trying this!

Thank you so very much for the recommendation, this is a great one! <3 :')))) <3 :D

I'm waiting for diagnosis of me/cfs or long covid, although it could be some kind of allergy fatigue as my symptoms are much more severe during april to late october.

Been looking at pushing the button to buy some niacinamide for a while now and I may have to go for it to try.

All the best for you!

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

Have you been tested for Lyme? This is textbook Lyme disease.

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

It's spreading rapidly. Worth a shot. Undiagnosed Lyme is horrible and can cause serious long-term damage.

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.

Whoa, thank you for the comprehensive answer. I reach for Lyme since it's one of the most common and under-diagnosed diseases in this category, but you are definitely in your own category here. Good luck, having something outside the reach of standard antibiotics already makes doctors afraid, and this would probably give an immunologist nightmares.

I want you to know that this was a fantastic HN comment, and I truly hope you figure this out.

I don't have any chronic infections that I'm aware of (maybe the athletes foot) but I have experienced a stark enough improvement in overall sense of wellbeing from taking NAC that I sort of characterize my own recent history in to pre-and-post NAC phases. It's a great molecule.

Thank you for your kind words. Having my comment praised as a fantastic HN comment is one of the highest honors I could ask for, I do put the effort in and you made my afternoon with your compliment. Thank you so much and much love! <3 :'))))

NAC is quite fantastic. Not just for energy, but for autism too, in which glutamate dysfunction is also implicated! Some people do just as well with sulforaphane as well, which I really need to do.

Jarrow has a great NAC extended release brand, I've been spotty with it recently but it feels really good when I take it. Feels like my autism symptoms go down half a notch (i.e. the opposite direction of aspartame, lol), my energy goes up, and I just sorta feel more 'real', for lack of a better word.

Very great medication/molecule, all around, it does so much more than that, too (for example, NAC is just glutathione without the glutamate component IIRC, and that's how it binds the glutamate out of your bloodstream. 2 huge birds, one spicy sulfurey stone). Let's hope it stays open access, for all of the benefits it has.

I'm skeptical of potentially dangerous Internet medical advice. What are your qualifications?

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