I was diagnosed with lupus a few years ago. My mom also had it and passed away after 10 years due to complications. My initial symptoms were severe joint pains, which made daily activities difficult. This happened during the COVID lockdown, which helped me maintain my job.
I did a lot of research and tried various treatments. Functional medicines and expensive vitamins didn’t help. I read about long-term fasting and tried different routines at home. I did several 1-day, 3-day, and 7-day fasts. During the 7-day fasts, my pain disappeared, but it returned once I resumed eating. This led me to believe that food was causing inflammation.
Previously, I ate a lot of lean meat and occasional red meat. I then cut down to eating meat once a week and ate mostly raw leafy vegetables the rest of the time. My pain would come back after eating meat and decrease over the week. I eventually stopped eating meat entirely and consumed a ton on greens, and within six weeks, I was pain-free.
I also tried Benlysta for months, but it didn’t help much. Vegetables seemed to reduce my inflammation more effectively. I stopped taking Benlysta but continued regular blood tests. After a year, my doctor agreed I could stop the medication. I’ve been in remission for the last two years with no pain or inflammation.
I hope this helps, though it’s just my personal experience.
I have crohn's disease which is also autoimmune and directly related to ingesting certain things. I think a lot of autoimmunity has to do with intestinal bacteria and their relationship to our innate immune system. And to a lesser extent it seems that almost every aspect of life is effected by what we eat, how we feel, how we act, how we grow and die. Maybe in 100 years we'll have fecal tests and bacteria pills to catch and prevent a paradigm shifting amount of ailments.
I know I've tried tons of different diets and exclusions and things. I've got a pretty good list in my head of what i can and can't eat but it seems to change q bit every couple years. I used to not tolerate bread but eat sugar and it seems to have switched some time in the last decade. Anyways, i wish you luck with your journey and I'm glad you've found something that works for you
Quite a few of my friend's that were diagnosed with chron's disease found out that the main culprit seemed to be flour and other foodstuff that had been treated with glyphosate (Roundup). After switching to sourdough bread made from organic flours, and similar choices for masa harina (nixtamilated corn) their issues went away. This was after years of not eating anything with fiber, gluten, or nightshades.
Their theory was that the herbicides would kill off their gut's natural biome and cause an inability process carbohydrates, fiber and maintain a intestinal mucus layer.
YMMV...but just passing along what has worked for a few of my friends.
Hmmm...I recently had my gut biome die off but could not identify any suspects. I bake a lot.
The most noteable thing about the whole experience was how amazing my bowel functions are after having to restore the gut biome. They are functioning far better than the many years before I experienced the die off. I used pills from Amazon that had good reviews (Physicians Choice) with a strict raw vegetable diet, and they definitely worked. I noticed another uptick in bowel function after taking some pills my wife purchased that had more strains. You can't just eat yogurt and dust off your hands.
California banned potassium brominate as a food additive last year, but it doesn’t go into effect until 2027.
The FDA finally banned brominated vegetable oil very recently so maybe they’ll get to the rest of it too. Assuming they can make rules anymore, anyway.
I was struggling with digestive issues from about 2019 after a severe work burnout (I think triggered by sleeping with a belly full of casein powder and also don't eat gas station sushi) but finally got to the bottom of them only this year. The solution was holistic, but basically my body's inflammation was so high from stress that my gut couldn't handle a piece of bread or a cup of milk, much less beans or nightshades.
Specifically I have sleeps apnea, my cortisol was 1.5 times the max upper range, my thyroid wasn't getting signals from my brain, I had adrenal fatigue, my B12 levels were low (the liver stores 3 years worth of B12, that's why vegetarians often crash the third year), my D3 was low, my BMI was way too high so aromatase was turning my T to estrogen, basically my levels were all off. My nurse gave me some prescriptions and a supplement cocktail and I found relief within just a few days. My joint pain went away, my patchy hair filled in after a couple of months, no more brain fog, etc. If IBS is a spectrum, then my experience has been that it is curable even if it's been going on for 5 years or more, although Crohn's disease probably has immune system markers that require specific treatments.
Now my digestive issues are in remission and I can eat everything I did before (edit: including gluten), although spicy food maybe overstimulates my peristalsis. So that's just the onset of oldtimers disease I guess.
For some level of immediate relief, try eating mainly big looseleaf salads for a few days, drink kefir, and drink a scoop of organic turmeric powder to calm the inflammation, all daily. I also found 2-4 psyllium husk capsules and a large glass of water daily to be highly beneficial, but watch for flares since there are different types of IBS. And stop all multitasking (edit: choose the path of least anxiety), add slack to your schedule, make 20 minutes per day to meditate, and stop believing that you are stuck and this will last forever. I believe that night terrors and bodily symptoms are our subconscious trying to get our attention so that we do the healing work to address the pain of our isolation and suffering.
Yes, there is a whole subsection of the internet that seems to think that vegetables are a net negative. They site doctors that suggest that fiber causes irritation in individuals with compromised intestines (leaky gut syndrome, etc.). It's exhausting having conversations with them as a vegetarian as they seem to think the only healthy way to eat is bone broth, butter, mct oil, and meat.
It’s common for someone in a flare of an IBD to be unable to eat vegetables without irritation. You should seek to understand the root cause of an individual’s experience instead of invalidating their experience due to your own.
If they become healthier then they should be able to increase vegetable intake which will further increase their health.
I got fecal tests and used expensive supplements and vitamins as recommended by a functional doctor, but they didn't help. I looked into how immune suppression medicines like Benlysta work and tried to mimic their effects naturally to get relief and hopefully stop using medicine. I think food can help manage many side effects of immune-related diseases, even if it can't cure them.
You might want to try the Wim Hof Method. I don't believe in everthing Wim Hof attributes to his method but when it comes to immune response, there is scientific evidence that it does indeed result in an increase of IL-10, which is anti inflammatory.
Did you ever do an Igg food sensitivity test-food panel to check if there were any inflammatory Igg markers from specific foods you were eating? E.g. they can test for 200+ most common foods, which you would of had to have eaten within the last 2-3 months for the Igg markers to still be present - otherwise they breakdown and obviously won't be detected.
To note, you need to eat high fat meat in order to properly digest the meat.
It's possible to also be allergic to certain types of meat, e.g. there's a protein in duck that bothers me.
Another factor to seriously consider is if consuming high quality organic meat vs. whatever else.
Also, meat requires a lot of energy to break down due to its [nutrient-calorie] density - of course you get back much more energy than it consumes, but it is an intensive process, so if there are other foods you're eating that are causing irritation then digesting meat could be problematic - and so then while of course reducing or stopping eating meat will then stop symptoms, it's possible that if removing the other foods that may be causing problems would then allow the meat consumption without causing any problems.
There's really been no properly done research on diet.
I'm curious if you've looked into N-Glycolylneuraminic acid and whether that could be the issue? Does chicken cause an issue for you?
I'm sorry to hear about your Lupus diagnosis, and glad it's in remission. My doctor wanted to diagnose me with Lupus due to the facial rash and arthritis/joint pain, but I came back negative in all the bloodwork, which I think means about 98% sure don't have it. I found that I can treat the joint pain effectively with SSRIs (Fluoxetine, 20 mg is enough to wipe it out after a few weeks). My mother has MCAS and my sister and aunt have UC, so I feel like I'm tripping through a minefield trying to navigate whatever autoimmune issue this is....and I have a PhD in biochemistry.
I haven't looked into N-Glycolylneuraminic acid specifically. For me, all types of meats, including eggs, chicken, and lamb, increased my inflammation levels. From what I understand, correctly diagnosing immune diseases can be quite challenging. My doctor once said it’s more of an art than a science. Because my mother had lupus it was easy in my case. While I’m not against medications, they often come with side effects. For example, immunosuppressants are necessary for high inflammation but can increase the risk of cancer. Even SSRIs have side effects.
When I had pain, I tried both medications and dietary changes, using an engineering mindset to isolate variables. Although I listened to my doctor, I also took matters into my own hands and did my research. My doctor initially doubted that changing my diet would help but did recommend the Mediterranean diet. He still doesn’t believe that food helped since there’s no clinical research backing it, and it’s not something commonly taught in medical schools.
The best part about experimenting with food is that it's easy and inexpensive to test on oneself. In my case, I was fortunate that my joint pains allowed me to observe the effects of my dietary changes within a week or less. Initially, I expected results in a day or two, but I soon realized that I needed to experiment for at least a few weeks to see the full effects. These days, I consume small quantities of eggs every few weeks and haven't noticed any significant increase in inflammation.
One of my friends has APLS (antiphospholipid antibody syndrome), which can also occur as a secondary symptom of Lupus. All of her blood tests always come back negative due to the way APLS affects coagulation -- unless the bloodwork is cultured for at least two days. So if you have reason to suspect the test results may be incorrect, ask them to re-do the bloodwork as a long-term culture rather than the normal fast screening.
In the vegan community there is lost of discussion of animal products causing auto immune issues. A compromised gut lining will let intact animal proteins into the body. The immune sees the animal foreigners but also attacks our body; us being animals too.
Type 1 diabetes, aka childhood diabetes, is thought to be from casein in A1 milk; where the immune system attacks the beta cells of the pancreas. Seems plausible to me; rates of dairy consumption seem to correlate with type 1. (see Finland).
So this is where the people come from who responded to my MS diagnosis with diet plans…I can tell you, despite their clearly good intentions, it was really annoying. Same kind of thing with faith healers. Come at me after you’ve got some reliable data from repeated double-blind controlled trials. Until then, I’m really not interested what kind of kale smoothies might help nerve pain and paralysis.
They also used really unhelpful citations, like “see: Finland”.
Feel free to continue this discussion here and within nutrition enthusiast groups, but please consider the perspectives of someone who’s struggling with a fresh, serious diagnosis before telling them all the hidden secrets of raw diets. Part of getting diagnosed is, at least for me, doing a shit ton of research to know better what my body is doing to me. Part of that research is sifting through all the scams and B.S. NaturalNews[TM] crap that, relevant or not, reads just like this thread. So when people tried to respond to the news of my illness with recipes it felt really patronizing and minimized my experience for the purposes of highlighting their hobby.
Just for an outside perspective. If any of this is backed with reliable data, I’m happy to read it.
This is a classic example, frequently paired with a bunch of pseudoscience and smart sounding nonsense. Even if it weren’t personally offensive to me as an MS patient (diagnosed in 2001, when I in my late teens, and not for nothing—a soccer player and vegetarian in otherwise very good physical shape) this kind of speculative alternative health stuff muddies the water so that when looking for legitimate, bonafide information for autoimmune disorders and treatments, one has to sift through vast torrents of frequently difficult to distinguish bullshit. They go out of their way to appear legit, spend tons of money to push dis-/misinformation, and/or poison the well of mainstream science and research.
I’m not suggesting that’s what’s happening in all of these comments, but I’ve seen a lot already that absolutely is. It’s really disappointing to see, but I’ve learned HN comments are great…until the topic of discussion departs from the usual tech-specific ideas, then it’s Dunning, Kruger, et al.
Unfortunately, role of food in human health isn't studied properly because of won't make anyone money.
Traditional Indian medicine and grandma's wisdom have a long list of foods to eat or not depending on disease/pregnancy/breast feeding etc. But there isn't enough scientific research on it.
Unfortunately the Internet has made it worse now everybody is peddling something or other.
I eat a lot of legumes such as lentils, chickpeas, black beans, and peas. I also include tofu made from soy, and nuts like almonds, peanuts, as well as seeds like chia, flaxseeds, and hemp. I use plant-based protein powders too specifically (https://lovecomplement.com/products/complement-organic-vegan...) when I drink green smoothies (3 to 4 meals a week).
Green leafy vegetables also has a lot protein (Kale, Broccoli and Brussels).
I use supplements for B12 which is missing from vegetable foods.
I used to eat fish but when I stopped all animal products I gave up fish as well. I guess if I have fish once in a while it won't hurt me but I have a tendency to overdo it. The main thing for me was to reduce the inflammation when I had the imbalance. This meant stopping everything I thought might cause inflammation until it went away.
My diet was also free of all salts, sugars and oils for few months though I do use them now.
I never understood why the British had such a hardon for split pea soup until I looked at the nutrition. "Split peas" have a lot more protein than regular peas. Like two or three times as much.
As for the fish, you could try making yourself miso soup. Properly made, it contains bonito flakes, and it's impossible to overdo bonito flakes.
>I use supplements for B12 which is missing from vegetable foods.
Just in case you're looking for an inexpensive vegan whole food source, seaweed sheets (like those used in sushi) have a relatively high amount of B12. I took a look at the brand in my pantry and it has 60% RDA per sheet.
> A 2014 study reported that dried purple laver ("nori") contains vitamin B12 in sufficient quantities to meet the RDA requirement (Vitamin B12 content: 77.6 μg /100 g dry weight).[19] By contrast, however, a 2017 review concluded that vitamin B12 may be destroyed during metabolism or is converted into inactive B12 analogs during drying and storage.[20] The Academy of Nutrition and Dietetics stated in 2016 that nori is not an adequate source of vitamin B12 for humans.[21]
Thanks, I was only going off the nutrition label, it shows 60% RDA per sheet. However, the reference link for the academy is broken; I wonder if they’ve changed their stance? Other references indicate raw nori has B12 but the drying process may turn it to an inactive form.
Kudos to them for landing a nature publication but I really would temper this level of excitement (??a top link on HN??) at a basic science research publication discussed in a press release from a university highlighting it's researchers.
My read is it is down to decreased CXCL13 expression and type I interferon expression in blood of a small number of patients, controls, and cell culture which gives direction for further study. CXCL13 was published as a possible RA biomarker half a decade ago and crickets since then clinically. Is it causal or a consequence of chronic inflammation? Type I interferon signature has been looked at heavily for over a decade and is clearly relevant in SLE but still only just over about half of lupus patients have it and the signature is by definition broad expression of hundreds of genes that affect innate and adaptive immune system components.
We DO need better treatments for lupus patients but it's a very variable disease in severity, clinically, and in terms of biomarkers making it difficult. I mean the best drug that everyone with lupus should be on barring a good reason is an old antimalarial (that doesn't treat COVID) and then we add to it. If you are interested in other new-ish therapies for lupus take a look at anifrolumab, belimumab, voclosporin, and even newer CAR T stuff. Important to consider the manifestations being treated with those in the studies e.g. belimumab with skin, joint, kidney but nothing for hematologic/cardiac/neurologic manifestations.
Exactly. When our car doesn't run well, a car with perhaps 20,000 parts, we take it to the mechanic who says "yup, issue was your spark plug, fixed". And even then, of course, the car issue may have been multifactorial. Maybe the spark plug failed because the fuel/air mix was off, for example, the spark plug was the symptom.
But then we leap from the car with 20,000 parts to a body with a trillion cells each cell with a trillion molecules. The calculus of the fuel/air mix and the spark plug has now been blown out of proportion, as challenging as conceiving a 20 dimensional manifold or the size of the universe. And so my reservation with a paper like this, and in general, is people say, "yup, sure was the spark plug" and then get accolades and a Nature paper, when the core issue was the air fuel mix, the air fuel mix that is, times a trillion cells, times a trillion molecules.
And I can't blame the authors. No shame in shooting for Nature and succeeding. No shame in these simplistic models, each one takes us a step further. But somewhere along the lines we're going to have think about the R&D of the big picture in non-hand-wavey ways.
The thing about a car is when the bumper gets detached you can't just strap it down to the front of the car and wait until it reattaches itself.
It may be (surely is) that something like lupus is multifactorial and impossibly complex, but knocking out the largest cause of something can be a reliably cure.
Look at antibitoics - a truly "replace the sparkplug" fix for let's say treating a MRSA infection. Doesn't treat cell damage, doesn't treat inflammation, doesn't treat pain, doesn't treat hormonal imbalance through the body. It doesn't even target the specific infection it kills indiscriminately. Yet "give them antibiotics until the MRSA goes away, or if it doesn't give them more antibiotics until it does" it super hand-wavy.
Sure, a car has a lot of parts, but when one of them is leaking oil where it's not supposed to, you don't have to check every part to see where the problem is.
Likely nanotechnology. Sensors that can reside in your body and give up to the moment details, and chemical factories that we can programmatically make adjustments to the body's existing pathways (reprogramming the immune system, etc.).
In other words, better integration and faster feedback loops.
When dealing with code we say refactor and simplify. Superintelligence my (rightfully) consider us too complicated and a 'big ball of mud' and replace us with version 2.0.
Autoimmune diseases, of which lupus is but one of many, are essentially black boxes. It’s proven extraordinarily difficult to develop therapies in this area. As such, this is great news. Hopefully this research will encourage pharmaceutical and biotech companies to invest more resources into translating research findings into effective therapies.
I haven’t read the paper yet, so I can’t comment on how this discovery might generalize to other autoimmune diseases, but one interesting bit about autoimmune diseases is that they tend to run in packs. This is suggestive there may be underlying mechanisms that are shared across autoimmune diseases.
The aryl hydrocarbon receptor (AhR), which is key to this discovery, appears to be super relevant to psoriasis, another autoimmune disease.
AhR has been known for a long time, but it seems it's been somewhat mysterious until a series of recent breakthroughs. In 2022, an AhR inhibitor called tapinarof, sold as VTAMA, was launched, and has shown itself to be one of the most effective treatments for psoriasis to date. It's also unique in that it appears to have the ability to bring lasting remission. In the main clinical trial, patients who used VTAMA for one year and then stopped had a mean remission duration of 4 months until their psoriasis returned. That is unheard of for any topical medication used on psoriasis.
Blocking AhR has also shown promise in treating MS [1].
I haven't read the lupus paper, but often with papers like these, the "cause" turns out not to be the actual origin, but some cytokine or other protein that is more disease-specific than current drug targets. This lupus discovery appears to identify an imbalance that may be compensated for, but we still don't know what triggers the imbalance in the first place.
In some cases diseases turn out to be a genetic fault, but my money is on pathogens acting as the initial triggering event, which then spins the immune system into a vicious cycle of autoimmunity. In psoriasis we see this with strep bacteria, for example, but the exact mechanisms are not well understood. However, the mechanism that makes psoriasis chronic has been identified, a type of T-cell called a tissue-resident memory (TRM) T-cell. This type of cell acts as a kind of biological memory for infections.
Good post. One small correction: Tapinarof isn't an AhR inhibitor, it's an AhR activator, an agonist.
Interestingly, tapinarof is a natural product -- a sort of bacterially-modified stilbene, a chemical cousin of resveratrol and pterostilbene -- and several other natural products also activate AhR. (Though perhaps not exactly in the same way.) The most potent and readily available of these is probably 3,3'-diindolylmethane.
Ah, thanks. I assumed tapinarof was an inhibitor, as the papers on its mechanism describe it as downregulating cytokines. It appears the exact mechanism isn't quite clear. Bissonette et al 2021 [1]:
Tapinarof was found to bind directly to AhR, resulting in
downregulation of inflammatory cytokines, regulation of
skin barrier protein expression, and antioxidant activity
... In a T-cell polarization assay, tapinarof markedly
inhibited T-cell expansion and Th17-cell differentiation
and reduced the production of IL-17, while also reducing
IL-17A and IL17F levels in a CD4 T-cell assay.
It looks like tapinarof modulates the signaling behaviour of AhR, but so far the precise mechanisms are educated guesses.
The story of tapinarof's discovery is fascinating. It's produced by a bioluminescent (!) bacillus P. luminescens that (quoting from the paper) "lives symbiotically within parasitic, soil-living entomopathogenic nematodes." It was observed in the 1950s that "the nematode did not putrefy once dead, in contrast to the rapid decay seen in the absence of the nematode," leading to the idea that the bacillus' metabolites had antimicrobial activity — which turned out to include what is now synthesized as tapinarof.
Coal tar is another semi-natural substance that is thought to act on AhR.
And, yeah, good point re coal tar. AhR was once thought to be a toxin or junk receptor that activated liver enzymes for clearance of environmental waste and other chemical byproducts. The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) were, at one time, thought to be very similar. That might still be the case with respect to PXR and CAR, but I'm thinking that the way to bet is that there's more to them than was once thought...
I don’t have any particular point to this post, just tossing out that resveratrol itself seems to be an antagonist of AhR, as it seems to compete with and block agonists.
Also of note for those curious since I haven’t seen it mentioned yet, Dioxins are potent agonists of AhR.
My own interest in AhR is that it seems to play a role in metabolism. Lower levels of exposure to AhR activators seems to kick off a complicated series of effects that seem to ultimately lower metabolism, potentially being a factor in obesity. Higher levels of exposure to dioxins however results in wasting. AhR is poster child for hideously complicated biochemical relationships, so do be careful of simple summaries of exposure/response relationships.
I would be cautious of AhR agonists though, I recall coming across a number of potential negative associations in regards to cardiovascular health.
Thanks for posting this. My doc just prescribed vtama for me a month ago and my psoriasis was gone in less than a week. I didn’t even finish the sample tube he gave me. Far more effective than the steroid topical cream I was using before. I had no idea what vtama was until reading your post.
Yep. The nice thing about VTAMA is that it can be used continuously, unlike steroid creams. And it's unique among current topical meds in that it can provide sustained remission.
It may be that VTAMA reduces TRM cells in the skin, which are the T-cells responsible for relapse. There's is an ongoing clinical trial right now called KNOCKOUT [1] that gives patients a "megadose" of Skyrizi, an IL-23 inhibitor that has, like VTAMA, been shown to reduce TRM cells. The idea is that a single huge dose could effectively cure psoriasis, or at least suppress it for a very long time. The results so far show that 83% of patients achieved complete clearance after six months, which was sustained throughout the trial period. I'm confident it will be a game changer. Here [2] is an interview with the main researcher.
Among new psoriasis drugs, there is also Zoryve, a PDE4 inhibitor (same mechanism as Otezla) as a cream or foam, which has a different mechanism of action.
This is a great response. I tapped out something longer about not being as particularly impressed with the paper and the headline here on HN, but as an rheumatologist just wanted to say your last two paragraphs well said.
Hi @zeagle, sorry to hijack the thread (didn’t see a way to DM you)
I'm a PhD student working on a new lupus diagnostic blood test approach [1]. Hoping to steer the project towards true clinical needs.
I'd love to ask for your feedback as a technologist + rheumatologist on a few lupus + RA diagnostic directions we're considering. Would they actually be useful in your practice?
Would you be open to a quick chat? My email is maximz@stanford.edu.
I have a good feeling we're going to make a fairly big impact on cancer in our lifetimes with mRNA and other new discoveries in our lifetime. Autoimmune issues I'm feeling much less confident about. It seems like so many of the therapies are "turn down the immune system". I wish there was wider study into autoimmune derived mental health complications too. Maybe I'm totally wrong on this (and I'm very OK to be proven wrong) but maybe there's something to find here.
I am here to restore your confidence about autoimmune issues.
Recently (and still in many cases) "turn down the immune system" was the treatment for most cancers. Of course, the purpose of anti-cancer drugs isn't to turn down the immune system. It just happens that the side effect of drugs that target cancer cells also target other rapidly-dividing cells like hair, endothelial, and immune cells.
In fact, chemotherapy drugs like Methotrexate are prescribed - at lower doses than for cancer patients - to people with Lupus and other autoimmune diseases.
There are similar challenges with cancer and autoimmune diseases, so progress in one might help progress in the other.
From the article: "They are now working to find ways to deliver these molecules safely and effectively to people." This is a challenge for many potentially effective cancer treatments as well.
It should inspire confidence that we have moved beyond that for many types of cancer. And if it can be done with cancer treatment, we are closer to doing it with autoimmune and anti-virus treatments.
> pro-inflammatory drugs can induce people to become depressed, which suggests a causative link. In one seminal study published in the New England Journal of Medicine, Miller and his colleagues conducted a double-blind study of 40 cancer patients undergoing treatment with interferon-alpha, an inflammatory cytokine.
> Though none of the patients had depression to begin with, the inflammatory agent had a striking effect: Many became depressed, a finding that has been consistently replicated.
However the causality is not clear. Inflammatory agents cause depression. And most depressed people have higher pro-inflammatory markers. It could also be the case that the inflammation is a result of something completely different.
I don’t believe there is any evidence that vitamin C reduces inflammation or helps with depression. Vitamin C is an antioxidant, not an anti-inflammatory agent.
There is evidence that things that reduce systemic inflammation help with depression. Fish oil, or more generally a balanced omega-3/omega-6 intake is one example. Curcumin is another. However the effects are modest, which is probably to be expected with a condition as diverse as depression.
„Vitamin C supplementation attenuates the oxidative stress (lipid peroxidation) and inflammatory response (IL-6) to a single bout of exercise.“[1]
Vitamin C is essential and gets consumed by the body and needs to be replenished. For example during sickness the Vitamin C consumption is higher which could lead quickly to low levels.
> Autoimmune issues I'm feeling much less confident about. It seems like so many of the therapies are "turn down the immune system".
The immune system has many branches, and you can effectively deplete one branch of the immune system while preserving the other branches to fight infection. For example with MS a very effective treatment is CD20+ B cell suppression, as rituximab does. For many people diagnosed with MS this has been effectively a "cure," in the sense that while they need to continually deplete their CD20+ B cells, their disease doesn't progress in any meaningful way, and their immune systems remain largely able to fight infection.
So we don't need to wholesale "turn down" the entire immune system for many autoimmune diseases. Rather, we need to surgically target specific parts of it and either suppress those parts or modify their behavior. Given the success we've seen with ritixumab and MS I'm more optimistic about our prospects for finding effective treatments for autoimmune conditions.
And all of this is controlled by your microbiome which is always ignored. I really wish more money was put towards researching that. It's literally our body's bioreactor.
No, the immune system is not controlled by our microbiome. The microbiome interacts with, and modulates the immune system in various ways, but it's hardly "controlling" it. There are germ-free animal models with sterile guts, which demonstrate that you can live without a microbiome - of course not 100% healthy, but they can still live and reproduce.
The immune system is modulated by a lot of things: circadian rhythm, environmental stress, nutrients, etc. Yes, the gut microbiome is one of them. But let's be a bit more nuanced than Joe Rogan or The Liver King.
" insufficient activation of a pathway controlled by the aryl hydrocarbon receptor (AHR), which regulates cells’ response to environmental pollutants, bacteria or metabolites. Insufficient activation of AHR results in too many disease-promoting immune cells, called the T peripheral helper cells, that promote the production of disease-causing autoantibodies.
To show this discovery can be leveraged for treatments, the investigators returned the aryl hydrocarbon receptor-activating molecules to blood samples from lupus patients. This seemed to reprogram these lupus-causing cells into a cell called a Th22 cell that may promote wound healing from the damage caused by this autoimmune disease.
“We found that if we either activate the AHR pathway with small molecule activators or limit the pathologically excessive interferon in the blood, we can reduce the number of these disease-causing cells,”
On the other side quick search on AHR activation brings for example cancer related stuff like this :
Both reactions make sense to me. Too much AHR activation suppresses immune response leading to cancer proliferation due immune cells not culling cancerous cells, but too little leads to auto-immune conditions. It's definitely like a large sloppy code base with lots of implicit overlaps and global effects.
"Autoimmunity and cancer as two sides of the same coin. The figure depicts how tuning of immune system regulatory mechanisms can contribute to autoimmunity, health, or cancer development."
One can wonder if induction of some autoimmune condition may be used as a treatment of some cancers.
> One can wonder if induction of some autoimmune condition may be used as a treatment of some cancers.
This is one of the bases of the checkpoint inhibitor revolution in immunotherapy. [1] The checkpoint is there to prevent immunity excesses. Temporarily turning it off is effectively an autoimmune disorder [2], one that can take out the cancer.
Similarly checkpoint inhibitors can cause autoimmune conditions that look a lot like lupus, arthritis, inflammatory bowel, endocrine disorders, etc. and it's sometimes difficult to be able treat both as it can be antagonistic. E.g. one of the checkpoint inhibitors has the opposite effect of a drug used to treat rheumatoid arthritis.
Fascinating stuff, it's interesting to read that the main ligands of the AhR (Aryl hydrocarbon receptor) are PAHs (Polycyclic aromatic hydrocarbons) and that activation of the AhR receptor improves the markers of Lupus.
Polycyclic aromatic hydrocarbons are nasty, carcinogenic, molecules that are commonly found in smoke, tar, and char. Basically burnt organic matter. On the other side of the coin AhR is also activated by a bunch of Polyphenols, which are found in a variety of plant derived foods.
Does this mean, it is possible that Lupus (and Psoriasis) are diseases of affluence caused by processed food (low in Polyphenols), and a reduced exposure to smoke byproducts in the environment?
There's definitely a genetic component but it would be interesting if those environmental factors impacted prevalence or severity.
Autoimmune disorders in general might be worse/more common in countries where kids grow up in clean environments. There's already some discussion on this with regard to allergies that I think has some credibility.
I've encountered an individual who had fibro, me/cfs, pots diagnosis. Turns out his small nerve fibers were fried by an antibiotic. His skin punch biopsy showed reduced fibers. This may not be the case in everyone, but SFN is extremely under diagnosed.
He was a chemist, and he ended up healing all his symptoms with pirenzepine. If I recall correctly they did the skin punch biopsy again and his physician was stunned when they saw regrowth of the fibers.
Today, WinSanTor is in stage 3 trials with their drug. They designed a cream with main ingredient being pirenzepine. They are targeting diabetes but the med appears to work for small nerve fibers as well.
Small nerve fibers control so much that any time people have weird unexplained symptoms it should be explored.
Indeed Pirenzepine[1] is a muscarinic receptor antagonists. “The muscarinic receptor is a protein involved in the transmission of signals through certain parts of the nervous system, and muscarinic receptor antagonists work to prevent this transmission from occurring.“[2]
I could imagine that a let’s say relaxed nervous system recovers better.
Yes, he did take an oral dose, I believe it was higher than recommended dose, so some risk involved. I don't really see any studies on oral administration, but the new cream showed systemic relief.
Very likely. All of these illnesses are diseases of the cells. We're entering the golden age of immune cell science. You figure out what immune cells are causing disease and how to restore them.
Here the T cells are imbalanced and a specific protein is found to regulate the imbalance but the interferon is countering the protein's effects. Now you can target that in many ways and run all sorts of clinical trials.
It seems to me that as we've gone layers deeper into organic processes we've repeatedly recapitulated Galenic theory: "rebalancing" more and more precisely-targeted "humours". Not saying this is bad - in fact, quite the contrary: it seems like a necessary stage on the way to more-sophisticated mechanitistic understanding.
Maybe but the immune dysfunction goes further in ME/CFS its not just a problem of reduced CD4 and heightened CD8 (which are the two cell types they seem to be talking about) its a wider set of oddities that seem related to exhausted cells with not enough energy stuck in "there is infection near by" operation mode. It might help reduce symptoms that are caused by the imbalance so it would certainly be worth a trial when they work out the details.
>stuck in "there is infection near by" operation mode
There are bunch of articles on successful treatment of CFS with methotrexate (which causes B-cells depletion whereis original CFS was associated in particular with B-cells over-presence after say viral infections/etc.)
Isn't thiamine tissue deficiency at the bottom of dysautonomia? Potentially leading to Alzheimer, MS, ALS over long periods of time if untreated depending on one's genetics and the way their body tries to adapt to it? I understand nobody tracks this over 30 years though. I think it's low-risk to try to address long-term tissue B1/B2/B3 deficiencies first and see if it helps.
"The initial symptoms of thiamine deficiency beriberi are those of dysautonomia [1], a broad term that describes any disease or malfunction of the autonomic nervous system. This includes postural orthostatic tachycardia syndrome (POTS), inappropriate sinus tachycardia (IST), vasovagal syncope, mitral valve prolapse dysautonomia, pure autonomic failure, neurocardiogenic syncope (NCS), neurally mediated hypotension (NMH), autonomic instability and a number of lesser-known disorders such as cerebral salt-wasting syndrome. Dysautonomia is associated with Lyme disease, primary biliary cirrhosis, multiple system atrophy (Shy–Drager syndrome) Ehlers–Danlos syndrome and Marfan syndrome for reasons that are not fully understood [2]. It has been hypothesized that the association of dysautonomia with so many different diagnoses is because a common form of dysautonomia originates from high calorie malnutrition. This leads to loss of oxidative efficiency (pseudo hypoxia) and subsequent disorganization of ANS controls that are mediated through the limbic system and brainstem."
Yes for some cases and any doctor who knows anything about dysautonomia tests and treats for it. It’s not root cause for many though because dysautonomia is a syndrome with potentially hundreds of reasons with the biggest being post-viral (autoimmune hypothesis) and EDS (vein elasticity hypotheis).
It has been my hope that the number of me/cfs cases would finally drive enough research into autoimmune disorders in general, that we might finally figure it out. It seems very poorly understood from an outside perspective.
There is no funding and since Long Covid appeared the funding for ME/CFS has completely vanished. If Long Covid ME like illness is the same then ME/CFS is getting lots of research right now, on the other hand if they turn out to be different ME/CFS patients are getting completely ignored.
Many ME experts are doing both. RECOVER is considering adding ME/CFS arms to its huge clinical trial platform. UCSF just added ME/CFS as a priority in their LIINC program.
SARS-CoV-2 therapeutics won’t work on both but immune cell based ones may given they haven’t been tested in either yet.
Both suggest a root cause of persistent viral antigen. Time will tell what works here.
RECOVER is the biggest scam when it comes to research unfortunately. 90% of their studies are focusing on various form of "brain exercises", CBT therapy and exercise therapy. Things that are not only proven to not work, but actually proven to harm people with ME/CFS (of which long covid patients make up a large amount).
They fund and do a lot of work beyond the horrible choices for initial RCTs. This fall we should hopefully see actual pharmaceutical interventions and a plethora of research they’ve been publishing.
The more important parts of their programs are the omics and tissue biopsy programs.
For what’s it’s worth, autoimmune drugs are amongst the highest grossing due to their cost. Rheumatoid arthritis, psoriasis, MS all do have a lot of study. I wouldn’t say it’s enough, but I don’t think the prevalence of me/cfs alters anything due to the high prevalence of the other diseases. Immune disorders are definitely mysterious though
HLA-B27 is directly related to a number of autoimmune disorders, including lupus. I hope this research can expand to other conditions associated with HLA-B27, like psoriasis, psoriatic arthritis, ankylosing spondylitis, etc.
A question I threw at AI about the bodies production of AhR and how it relates to food
Glucosinolates seems to be a key compound for the production of AhR. Has anyone tried Sulforaphane Glucosinolate supplements?
This was its response.
AhR itself is not found in food, but certain foods contain natural compounds that can activate or modulate the activity of the aryl hydrocarbon receptor. Here is a list of foods that are known to contain high concentrations of AhR activators:
Cruciferous Vegetables
* Broccoli: Contains glucosinolates, which are converted to indole-3-carbinol, an AhR activator.
* Brussels Sprouts: Rich in glucosinolates and indole-3-carbinol.
* Cabbage: Contains glucosinolates and their breakdown products that can activate AhR.
* Cauliflower: Another cruciferous vegetable high in glucosinolates.
* Kale: Contains a variety of phytochemicals, including indole-3-carbinol.
Berries and Fruits:
* Blueberries: High in polyphenols, particularly anthocyanins, which can activate AhR.
* Strawberries: Contain a variety of polyphenols and antioxidants.
* Blackberries: Rich in anthocyanins and other polyphenols.
* Grapes: Especially red and purple varieties, which are high in resveratrol and other polyphenols.
Spices and Herbs:
* Turmeric: Contains curcumin, a known AhR modulator.
* Garlic: Contains organosulfur compounds that can influence AhR activity.
* Ginger: Contains gingerols and shogaols, which can modulate AhR.
Legumes and Beans:
* Soybeans: Contain isoflavones like genistein, which can activate AhR.
* Black Beans: High in various polyphenols.
Nuts and Seeds:
* Walnuts: Contain a variety of polyphenols and antioxidants.
* Flaxseeds: High in lignans, which can have AhR-modulating effects.
Teas and Beverages:
* Green Tea: Contains epigallocatechin gallate (EGCG), a potent polyphenol that can activate AhR.
* Red Wine: Contains resveratrol and other polyphenols.
* Coffee: Rich in various polyphenols that can modulate AhR activity.
Other Foods:
* Olive Oil: Particularly extra virgin olive oil, which contains polyphenols like oleocanthal.
* Dark Chocolate: High in flavonoids and polyphenols.
The Nightshade family of plants, which are very common in our diets, can mimic the symptoms of Lupus. That food sensitivity needs ruled out when diagnosing the cause of Lupus.
Yes. Also "inflammation and pain in the joints" can be mistaken for Rheumatoid Arthritis (RA).
We discovered the hard-way that my late wife had issues with this.
Multiple doctors diagnosed her with both RA and Lupus.
When we got the Nightshades out of her diet and switched to more natural based cleaning products, such as Hemp based soap, shampoo and vinegar for cleaning, her symptoms of RA and Lupus went away. An good allergist finds things like this.
My girlfriend has lupus, so I showed her the article. It sparked a bit of hope. She has a science background and always asks in awe "how do you find such good papers on the day they get released". She's not really the HN audience though :*)
I wonder if allergies can eventually be fixed somehow as well. There has to be an immune or autoimmune reason why some people have tons of allergies and other people are perfectly fine.
Allergies are caused by an overactive immune system. The way to overcome them is to train the immune system by exposing yourself to low doses of the allergen. Doctors do this and it’s called allergen immunotherapy. Interestingly this has been done since 1911.
I used to be allergic to 100s (I could not even walk 1 meter of certain weeds and I would get blisters etc) of things until I moved away from my country 20+ years ago. I suddenly was allergic (as far as I know still now) to nothing; I accidentally came in contact with some of the worst allergens of old (as I live in nature since then) and they did nothing to our surprised. My wife who was allergic to seafood (passing out to needing epi levels) and that’s gone too, shortly after the move. I don’t know why; our doctor then didn’t know, but we chalked it up to stress; we went from depressing commute ratrace city jobs to sitting in a forest in nature doing whatever we liked. I work more hours now but they are stressless. Don’t know whatever is true, but one mistake I made was not moving earlier.
I've had some sort of autoimmune thing hitting me almost every decade of my life (and then clearing up): eczema, asthma, vitiligo and most recently psoriasis. Usually quite mild, but I worry that the next one in the progression will be arthritis. Most doctors' explanations can be summarised into a shrug. Would be a relief to know what's going on in there.
Hey: do you have any stomach problems? Because that was me (up to and including the arthritis part) and then my "IBS" turned out to be Crohn's disease and once I started treating that 90% of my other shit vanished. Things were so bad back then that I was seriously considering a hip replacement to make the pain stop, but today I just hopped off the exercise bike and feel totally fine.
Oh dear, I hope not. I do tend to have the occasional need to visit the mens room several times a day (but only at a level where it's just the mildest of inconveniences). I'd be really worried if it was IBS. The prospect of that getting "upgraded" to Crohn's is downright terrifying. Maybe I'll ask my GP next time.
It could very well not be that, but I always feel compelled to mention it just in case I can spare someone else the same "three years of confusion to figure out what was wrong" fate that I suffeed :P
And even more broadly speaking, if your immune stuff does progress, the good news is that treating the biggest baddest one (in my case, the Crohn's) usually treats the myriad smaller ones with it. So if you ever end up arthritic enough to get treated for that, the treatment should knock down your psoriasis and other stuff too!
^ Likewise if certain foods set you off and those foods are actually "good for you". If you feel like crap after eating a ball of grease, that's one thing, but it turns out leafy greens aren't supposed to give you a nuclear-level stomachache.
At first, a mix of mesalamine and oral steroids; then I graduated to Remicade and a low dose of methotrexate to stop my immune system from creating antibodies against the Remicade. And that's basically it.
I should also note that even when I was only taking mesalamine (a drug that works in your GI tract and basically nowhere else), my arthritis pain improved drastically, so it wasn't just the result of steroids having a general anti-inflammatory effect. Treating my intestines alone was enough for me to stop walking with a cane.
Autoimmune disorders all have a common root of gut dysfunction. I suffered from chronic inflammation for five years, the ultimate solution was a double capsule probiotic and eating more fiber. Most probiotics have a single capsule that opens in the stomach and all those CFUs are killed by stomach acid.
There is a study that claims that genes associated with autoimmune diseases increased survival during the black death epidemic by 40% and frequency of these genes increased a lot in the 14th century Europe [1]. I haven't yet seen independent confirmations but I can imagine that paranoid immune system can be beneficial depending on circumstances. If we eradicate autoimmune diseases then there's a chance we won't survive the next big pandemic.
> If we eradicate autoimmune diseases then there's a chance we won't survive the next big pandemic.
IMO it seems more likely that we'd find effective treatment which mitigates symptoms of autoimmune disease than a treatment that irreversibly eradicates the disease (including from subsequent generations, even?).
This is a preprint of the abstract to the paper and I know there are some very smart people on HN but if you can grasp this you are in an entirely much higher orbit
Lupus is kind of lousy for the punchy scientific format because it has as a nickname "The Great Imitator." (Note that the porphyrias are known as the "little imitator.") Because of this somewhat Protean nature, lupus can masquerade as quite a lot of things, leading it to be a casual element one would have to bring up and then eliminate in episode after episode. Thus, for screenwriting reasons, it needs a kind of general dismissal which would stick in the mind of viewers ...
Time to bring it back for an special episode where House say's it's not lupus, but it turns out it is and they find out thanks to an intern, and then they cure it using this new therapy.
Out of sheer boredom, I started watching this, and got as far as an argument about whether or not some set of symptoms was lupus. Then I closed my laptop, tired of wasting my time. I sat quietly on the couch in my living room for a moment. My wife was watching television in the next room over, at a volume where the dialogue was clearly audible, and what do I hear but a woman state, "At that time, I was diagnosed with lupus"!
they aren’t cell diseases. It is plant toxins either leaking into the blood stream through intestinal permeability or a problem with peoples livers being fatty and not able to do their job anymore resulting in the bodies inability to remove plant toxins. The toxins cause an immune reaction wherever they build up , rheumatoid arthritis if it’s the joints of the legs and arms etc.
Plant toxins include pesticides, fungicides, herbicides, both human created and sprayed on and natural ones to stop animals and bugs eating them. They also include glysophate
Thousands of people on Reddit have put Rheumatoid arthritis and other Auto immune diseases into remission using the carnivore diet. Ie manually removing Plant toxins from their food and not letting the toxins enter their damaged bodies
Funnily enough you have another poster [1] saying the exact opposite, that meat makes their symptoms worse, and eating plant foods makes their symptoms go away.
Whenever the carnivore diet comes up as a panacea (which it does, a lot), I wonder if people tried anything else. Did they try reintroducing plant foods to test their hypothesis?
Personally, I bet that it's not the diet itself that helps in most cases, but that the very act of changing one's diet radically alters the gut microbiome. People with autoimmune diseases usually have a dysbiotic gut flora, so it makes sense that a radical change would "reset" it. However, this would suggest that reintroducing foods should work, unless you reintroduce things that bring back the imbalance.
Anecdotally, my psoriasis disappeared after I switched to a strict vegetarian diet. I can't prove it, though, so I don't go on Reddit making unscientific claims I can't back up with evidence.
If these toxins build up in animal cells - why would you eating meat (that must then have a much higher concentration) not expose you to the same toxins?
For me, it was the opposite. Cutting out meat and eating a lot of organic greens helped calm my immune system and reduce inflammation. In my experience, meat increased my inflammation, while greens decreased it. I think everyone is different, and it's not hard to test on yourself if you have noticeable symptoms like joint pain, as I did.
This idea that plants are toxic and meat is healthy is absurd in the extreme. Historical evidence shows humans at mostly a plant based diet for most of our evolution. And the various large and strong herbivores are completely contradictory to your thesis. It's similar to flat-earth in how easy it is to debunk.
the reason that this bro science works for people is that change can effectuate change EG what you’re doing isn’t working change what you are doing and that can have affect with anything, mind, immune system, you name it, I had RA and it went into remission when I just changed my diet and started eating totally different foods. Now we can say that those foods were the cure all and that everyone eat them, but maybe just change your life a bit You’re doing right now ain’t working
Wouldn't then the cure just be to eat organic food, rather than meat of animals that were fed way worse crap than the average person? The whole premise makes no sense...
Some meats like chicken do cause flare ups for auto immune people because the chickens diets are full of crap food yes. Pork also causes a lot of people in these communities issues.
Cows on the other hand just eat grass or plain grains ... and have 7 stomachs filtering and cleaning their food.
I believe no one diet works equally for every single individual with Autoimmune conditions. For some, a plant-based diet reduces symptoms, for others like Jordan B. Peterson, and his daughter (I believe she suffered from RA) a purely meat-based diet reduced all of their symptoms. Personally, I struggle with Hashimotos, Ankylosing Spondylitis and Crohn's Disease and have to stay away from sugary foods, alcohol and caffeine or else one of the conditions will flare up. Any type of meat is fine for me however.
I did a lot of research and tried various treatments. Functional medicines and expensive vitamins didn’t help. I read about long-term fasting and tried different routines at home. I did several 1-day, 3-day, and 7-day fasts. During the 7-day fasts, my pain disappeared, but it returned once I resumed eating. This led me to believe that food was causing inflammation.
Previously, I ate a lot of lean meat and occasional red meat. I then cut down to eating meat once a week and ate mostly raw leafy vegetables the rest of the time. My pain would come back after eating meat and decrease over the week. I eventually stopped eating meat entirely and consumed a ton on greens, and within six weeks, I was pain-free.
I also tried Benlysta for months, but it didn’t help much. Vegetables seemed to reduce my inflammation more effectively. I stopped taking Benlysta but continued regular blood tests. After a year, my doctor agreed I could stop the medication. I’ve been in remission for the last two years with no pain or inflammation.
I hope this helps, though it’s just my personal experience.