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Multiple Sclerosis discovery could end disease's chronic inflammation (uvahealth.com)
234 points by elorant on Feb 24, 2023 | hide | past | favorite | 97 comments


Fulltext: https://journals.plos.org/plosbiology/article?id=10.1371/jou... Summary:

- Inflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is driven to some extent by aryl hydrocarbon receptor (AHR) activation in the gut.

- AHR knockout mice are resistant to, or recover more swiftly from, EAE.

- An investigation of AHR knockout mice revealed that their microbiomes were different from normal mice in that they produce more bile acids of a certain type, as well as more of certain short-chain fatty acids.

- It was hypothesized that these metabolites, which enter circulation generally, alter the disease course of EAE, and affect susceptibility to EAE.

- Taurocholic acid, a bile acid that's available as an OTC drug in certain nations, was the most effective AHR-knockout-boosted-metabolite at suppressing EAE, when administered orally. It is suggested as a potential treatment option for MS.

- The paper doesn't mention this, but taurocholic acid is hepatotoxic. I believe it remains to be seen whether or not liver-safe bile acids are effective, e.g. tauroursodeoxycholic acid.


tauroursodeoxycholic acid, aka TUDCA. I have M.S. Going to calculate a dose and give it a shot.


I sincerely hope you don’t try it without consulting your doctor. EAE mouse models are “like” MS but barely. Something working or not working in EAE models is only a vague suggestion that the same will work or not work on people. This thing can be a supplement but we don’t know how it’ll react with your other medication.

The linked article is a fluff piece written by the university PR. According to them every lab in their university is curing cancer and MS and AIDS every day.


I don’t have MS, but I have friends who do and I fully trust them to be appropriately cautious when they react to relevant medical news. They’re among the most medically informed and adept people I know, and not prone to flights of fancy in MS treatment. Maybe some caution is due in lecturing people about how they address dealing with their own illness.


That is wonderful for your friends, but I don't know what they have to do with this individual you have never met. My uncle has lived with MS for almost 50 years and is in the final stages of life unfortunately, which I guess gives me the same level of credibility. I would not advise a stranger on the internet to inject themselves with something based on one study done on mice.

I'm also not going to tell them what to do with their own body. But "run it by your doctor first" seems like a reasonable thing to suggest, even if they ultimately decide to do it anyway.


I'm not going to judge anyone (I have MS) but it's extraordinarily difficult to analyze evidence when the disease progression is random flares. If I have a flare, is it because a medication isn't working? Or is it working just fine and I would have had five otherwise? Not really any way to know.

I would not take anything my doctor didn't say would at least not cause harm. But the calculus is different for other people.

Among groups of people with MS I've chatted with there is kind of an unspoken rule to not advise treatment because we all know that we are all different in treatment, symptoms, probably cause... you can get off into the weeds pretty easily.

Lipolic acid, vinpocetine, curcumin, lots of things are anti-inflammatory or good for neuropathy. I've had people recommend getting controlled bee stings, hensbane, obviously meditation for reducing stress and cortisol, and if we go in the direction of alternative methods (which I know people with MS who have used) you get acupuncture and yoga and herbal medicines. CBD in Europe is a treatment, I'm sure other cannabinoids would help different people in different ways too. I just have to tune it out, I want to spend my attention on what I'm good at and enjoy, and trust my [MS specialist] doctor to let me know about new treatments.

Study says "inflammation decreased" which is great. But lots of things do that, so the question is how much... I wouldn't trust it without a fair bit of statistical evidence without my doctor telling me that whatever random supplement is safe enough to risk.


Do what's right for you, but never mind Europe, CBD is an accepted treatment in all US states. More specifically: there are no longer any states outright banning the use of CBD. This is not any sort of comment on MS and CBD, mind you.

https://cfah.org/cbd-legal-states/

I'm glad you have a specialist doctor whom you trust. MS is a relatively known quantity, having being first described by a neurologist in 1868. Not all diseases and not sufferers have such a privilege. For something newer at the edge of medical sience, like AIDs was in the 1980s or like Long Covid is now, patients are finding doctors of only limited use, and the FDA an impediment rather than helpful. If there was a cure for MS available in Mexico, would you not start a Dallas Buyers Club for others afflicted?


Honestly, I trust the FDA to mostly do a good job and would wait -- unless the time involved would mean that waiting would render the treatment moot.

In that case it seems like there's more reason to try, at first, but there is a real cost. The cost of time spent focusing on enjoying what you have in the search for a better that may or may not come. And the cost of spending your days dissatisfied that it's not better than it is.

I don't think chasing medical miracles is a good way to spend my days. If the treatment is safe and works I'm confused why you believe the FDA would prevent it's use, is that a common scenario?


Dissatisfied is one thing. Wouldn't you rather not spend your days having flares at all though? A trip down to Mexico and, like, $50k for a stem cell treatment (HSCT) could be the cure for your ills. It's definitely not got FDA approval, and your mainstream doctor definitely going to advise you against it. And I'm some random Internet commenter so definitely don't remotely read this as treatment advice. But next time you have a flare up, tell me what you wouldn't do to never have them again.


I think a lot of this is the feeling that one's own case is special or that you will get a better than median outcome. I want treatment that, for median cases similar to mine, improves things with a high enough success rate and low enough side effect rate that it's not a difficult call anymore.

And if the treatment is $50k in another country there's no reason that pharmaceutical companies in the US wouldn't pursue it as a treatment, so there's not the same argument as there is with supplements where they simply don't have funded studies. They'd want to upcharge it to $500k I'm sure, but I think the profit motive would be there for them to make it available.

If there's a complex and expensive surgery that might fix a problem, I guarantee there is funding available to make sure it's actually safe and won't give me a brain infection or something. If it could be solved with supplements, the issue is that there's no one funding such research but my doctor also doesn't object to taking stuff that might work. Like curcumin and R-Lipolic acid, and have been actively told to take D3. No harm likely, probably not helping but why not?

Neither of these cases seem like they involve the FDA, so I'm just super confused. The two people replying here seem to both be under the impression that the FDA drives the profit motives for pharmaceutical companies or stop people from taking random supplements so long as they aren't known to hurt you.*

I honestly do not have a problem trusting that the FDA uses a basically reasonable process to evaluate these things, and that if the treatment was available in the US I have vastly less objection to doing it elsewhere where it costs less.

But this is just me. I've lived through flare ups, and have had this since interferon was all we had to work with. I do not think it is a good idea to assume that you are somehow going to have a better outcome than median. Once my doctor agrees my prognosis is bad enough that the median outcome of a treatment is positive, my opinion changes.

I'm a scientist, maybe other people can't think this way. I think it is a very bad idea to think you are different from average, particularly about things that are certainly out of your control. It's just... it's gambling with your health, double or nothing... but if my family and doctor think it's worth the bet it's a much simpler choice.

I would not try to override my spouse or doctor or family if they felt it was too dangerous to be worth the potential benefit, I think they are much more objective than I am.

* Let's ignore DEA nonsense, it's important but tangential.


There is too much contradictory evidence from the medical community on the efficacy of vitamin supplements. However, enough circumstantial evidence exists to prove two things: 1) Diet studies are hard 2) Pharmaceuticals are not going to fund a study for a cheap supplement 3) If this is true then the FDA should fund a "good, big diet/supplement study" but they dont. For this, I would say the FDA can't be trusted with "doing a good job" when a possible cheap solution exists.


I completely agree about the incentives for supplement studies.

However, the FDA, critically, has totally different and vastly less difficult regulations for supplements as opposed to drugs. Where by drugs I mean things the manufacturer wants to sell as a treatment for a specific condition, for which they were required to provide evidence.

I totally agree that the funding incentives are not good for studying cheap supplements. I have no idea why you think that has anything to do with the FDA, just buy the supplements if you think the circumstantial evidence is good enough.

Edit: For instance, I have been trying R-Lipoic Acid lately. No one stopped me. No one advertised it as a treatment. I found some research papers that said it might help and my doctor said it wouldn't hurt. I don't think it helped, but certainly the FDA didn't get in the way.


" I have no idea why you think that has anything to do with the FDA, just buy the supplements if you think the circumstantial evidence is good enough."

Can the FDA turn the circumstantial evidence into real evidence? I think they can.


I've never heard of the FDA funding a drug study, that is more a NIH thing. If the FDA were sending out requests for proposals I would expect them to be about:

- testing food for contamination

- inspecting food facilities and farms for safety

- ensuring drugs are not contaminated and that safety reports are coordinated

The NIH is the one that provides funding for health studies... please understand that I'm not saying it's good or correct that studies of supplements aren't getting funding, I'm saying that the FDA is not involved. Direct frustration at the right target, pharmaceutical companies (i.e. capitalism) having no interest in unpatentable low cost treatments and NIH/government not funding such studies when they should.

I agree, the NIH should study all these things -- and does if you look at their budget, via tens of thousands of individual academic research groups with less incentive to not study supplements. Capitalism is still there, but if anywhere can study it without worrying as much about profit motive it'd be academia or a national lab.

I also agree that NIH should have more money targeted at low-profit drug studies. That's unfortunately the kind of thing that gets determined by congress unless they decide to do it on their own.

The best situation is one where the legislature requires a minimum amount be spent by an agency to support certain kinds of research (for instance, they do this across the federal government through the SBIR program for small businesses).

https://www.nih.gov/ABOUT-NIH/WHAT-WE-DO/BUDGET

> The NIH invests most of its $45 billion budget in medical research for the American people.

> Over 84 percent of NIH’s funding is awarded for extramural research, largely through almost 50,000 competitive grants to more than 300,000 researchers at more than 2,500 universities, medical schools, and other research institutions in every state.

> In addition, over 10 percent of the NIH's budget supports projects conducted by nearly 6,000 scientists in its own laboratories, most of which are on the NIH campus in Bethesda, Maryland. The remaining 6 percent covers research support, administrative, and facility construction, maintenance, or operational costs.


> I would not advise a stranger on the internet to inject themselves with something based on one study done on mice.

I wouldn’t either.

> But "run it by your doctor first" seems like a reasonable thing to suggest, even if they ultimately decide to do it anyway.

Sounds like we’re mostly on the same page. I just trust the people I know with serious illness to know this stuff already, even if they get zealous about something that might improve their lives. Because even my friend with MS who has a long history of impulsive mistakes isn’t just injecting random things just based on news stories.


Not trying to denigrate your response, people do need to make informed decisions. However, "trust your doctor" / "ask your doctor"? People always say this phrase as a knee-jerk reaction. I think that a scientifically minded board like HN can corroborate my experiences in that: MDs are not scientists, in most cases not up to speed on current research (or any form of "science" or what one might believe as science) and many times the most inept at anything other than following their training. Its a reason medicine is moving at a snails pace and we need more open source or civilian science initiative.

Among our community I say, make your calculations and take your dose. Don't talk to your doctor, you'll receive no usable feedback, instead, report your results.


> MDs are not scientists

?

Medicine is science.

The definition of “scientist” includes someone learned in science, and so a physician absolutely is a scientist. Traditionally trained physicians learn physics and chemistry, biology, biochemistry and molecular biology, and later, anatomy and physiology basics.

But I suppose if MDs had any brains they would have forgone medical school and just got an HN account. Then they could have known everything instead of merely diseases and drugs.


Its hardly a science, you can look up the arguments but I'm not the only one that says this. Covid is over, we can stop worshiping the medical field..

And if trying to take physics and organic chem at a community college during the summer so that the "hard classes" dont pull down their GPA is hardly a training in what you think science is.

I'm not trying to demean them, but its not their job to understand the complexities of these drugs. I know alot of MDs and I can guarantee you they would agree. I've had these conversations with them before. Bottom line, they wouldn't be the first ones to ask if I wanted to experiment on myself with some new chemical.


If you trust your doctor so little, go find one you trust? A good doctor should be able to have a level headed conversation about things like this. If you have MS and are not in touch with an MS specialist what are you doing? If you are, do you really think that specialist wouldn’t know this supplement? Even if a supposedly good MS specialist doesn’t know about this compound, at the least they will look it up and tell you if it’s okay to try.

I myself don’t trust most doctors and do my own research. But I make it a point to find ones I can trust. I did a PhD in biomedical engineering and know a metric ton of biology and still wouldn’t trust myself to decide stuff like this myself. A good doctor will bring a ton of experience, a keen understanding of human physiology, and a network he can tap into for more tips. Underestimate them at your own bodily peril.

For this compound in particular, here’s my amateurish warnings already: it’s clearly hepatotoxic, it’ll likely not even have an effect (EAE models have no real relevance to human MS) and will likely interact with other drugs you take as well.


Its not that I don't trust MDs, its that I don't trust them to be at the forefront of their field.


This is quite interesting to me also. I have a neuro and inflammatory disease with elevated liver enzymes since getting sick. It seems TUDCA is fairly safe.

How does one calculate their dose?

Looks like I need to find a reputable brand and seller, that's lab made (rather than bear bile) if anyone has suggestions.

EDIT: Okay this is quite shocking to me so had to share, in searching for reliable sources of TUDCA it looks like pharmaceutical versions are now being approved in Canada and the US for treatment of ALS that cost $13,000 per month!

https://biopharma.media/amyotrophic-lateral-sclerosis-new-dr...


TUDCA is not perfectly safe. Studies show that while it does prevent damage from ethanol and AAS abuse when taken during or after, it can also cause/exacerbate damage when taken prior to ethanol/AAS or by healthy individuals.

Long term TUDCA use seems like it also lowers good cholesterol.


To be clear, if you’re not taking alcohol/ethanol etc then TUDCA seems fairly safe for short term use


For <8 weeks, yes. But year-round general supplementation for no indicated reason can be harmful. TUDCA is known to lower HDL cholesterol (good cholesterol).[0]

NAC would be a more appropriate year-round liver support for general supplementation.

0: https://pubmed.ncbi.nlm.nih.gov/8674405/


NAC chelates metals like zinc and copper, so you got to watch out for low levels of those when supplementing NAC.


Even that has issues. It can promote lung cancer growth and initiation. The gist is it is too good at keeping cells alive and keeps alive some that should have died.

https://www.science.org/content/blog-post/n-acetyl-cysteine-...


Oh that’s not good. Thanks for letting me know.


What is AAS?


Anabolic steroids, it’s popular in that community as a harm reduction supplement for liver support.


> In early January 2022, Amylyx has submitted a Marketing Authorization Application (MAA) for Relyvrio/Albrioza to the European Medicines Agency (EMA).

I hope this wont end the same way like edaravone.


Most brands you can buy online are not made from bear bile. But since it’s an expensive supplement, there’s lots and lots of counterfeit (in my experience). I never buy off eBay or Amazon market place, but directly from manufacturers. Some I‘ve tried and which seem to work for me: BodyBio, Everychem, Nutricost


Buy tudca from purebulk or any bulk type stores and have it tested in a lab which is fairly easy process . If it's 99% pure changes in dosage won't need to change much


“Due to the complexity of the gut flora, probiotics are difficult to use clinically. This receptor can easily be targeted with medications, so we may have found a more reliable route to promote a healthy gut microbiome,”

Probiotics would likely be a safer thing to play with. Journaling and isolating specific things the first time you try it can allow an individual to track more complex processes than clinical trials can handle.


Or a stool transplant.


Can you share your result?


It's been in study for a wide variety of neurodegenerative diseases, with good early results (ALS is one).


If you haven't already done so, I'd recommend trying the Coimbra Protocol [1] before chasing after brand new research. It has been a game changer for those I know that tried it.

[1] https://www.coimbraprotocol.com/the-protocol-1


Surely if given people vitamin D can’t actually cure MS. Surely someone would have tried it and done case studies?


Having read the page, this is particularly high doses, along with a clinical protocol to determine the both correct dose, and other treatments required to avoid serious problems that would normally accompany such a high dose.

Simply supplementing with D3 would run into problems without that. Nevertheless, they do cite studies showing improvements with lower doses.

Normally I'm pretty sceptical about 'named doctor' websites as they are usually some kind of grift, but this one doesn't seem to be.


It's not a cure, it's a very effective therapy. It has ~10 years of history and trials. The doctors I've spoken with mention interesting new studies and research associated with the therapy often, so it's still a developing area of research... research that has moved past the "...in mice" caveat.


interesting. this is already used for ALS


> taurocholic acid is hepatotoxic.

Taurocholic acid is a huma bile acid. I may increase liver enzyme levels with some patients, but to say it is toxic to the liver is fear mongering.

https://www.ncbi.nlm.nih.gov/books/NBK548276/

Not that I think their research is useful in anyway. Anytime you want to treat a disease through a receptor you always end up with changes in receptor density which make the drug useless.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106030/


>taurocholic acid is hepatotoxic

Excuse my rudimentary question but does this mean it would still be possible for administration intravenously?


It would still wind up in the liver. In a 1966 paper -- "the metabolism of intravenously injected isotopic cholic acid in Laennec's cirrhosis," by Blum et al. -- it was discovered that "when isotopic cholic acid was administered intravenously to normal subjects, there was a rapid and permanent disappearance of isotope from the systemic plasma, reflecting the essentially complete localization of bile acids in the liver, biliary apparatus, intestinal content, and portal blood."

Bile acids might be less toxic if administered via IV infusion, in comparison with oral administration. Then again, they might be more toxic. (Due to rapid excretion or poor absorption via the oral route.) I don't know offhand if one delivery method or the other would be preferred in this regard.

But though most bile acids are toxic, not all of them are. TUDCA and UDCA are not only liver-safe, they're first-resort drugs for resolving drug-induced liver damage and promoting liver health. If these "healthy bile acids" can combat MS, that would be a very interesting result. TUDCA and UDCA are very cheap, and their safety profiles are well established.


From other thread: [the tested drug] taurocholic acid is hepatotoxic

You: TUDCA and UDCA are not only liver-safe, they're first-resort drugs for resolving drug-induced liver damage

Me: I think I have a stupid idea


I have no idea what its metabolic pathways are, but it's possible that by bypassing first pass metabolism might mean that more of the substance reaches the liver versus its metabolites.


Nah blood gets filtered through the liver and so would this compounded even if it was intravenously administered.


Unsure which of these gets me more.

"an immune system controller found in 'barrier tissues' such as the intestine"

This sounds like academic wording for "leaky gut."

"doing so had a dramatic effect on the production of bile acids and other metabolites in the microbiomes of lab mice. With this receptor out of commission, inflammation decreased and the mice recovered."

Who might have guessed MS could be caused by an imbalance in a bile humor? Physicians from antiquity.


Leaky gut is a real medical term, but one that unfortunately has been picked up by the woo/toxin/alternative medicine crowd. Some researchers use the term intestinal permeability instead.

Both terms refer to barrier dysfunction in the tight junctions that make up the cell wall of the intestines. By becoming more permeable, the gut wall lets bacteria through and allows them to either colonize the surrounding tissue and/or enter the blood stream, a phenomenon known as bacterial translocation. Patients with intestinal permeability may have detectable levels of bacteria in their blood. A healthy gut absorbs nutrients and water through the gut wall, but protects the body against pathogens.

Studies show that some autoimmune conditions like psoriasis and Crohn's are associated with increased intestinal permeability. Unfortunately, "leaky gut syndrome" took this idea and ran with it, and as a result we have a lot of snake oil going around.

As for this paper, the connection is really interesting, and seems to fill in some gaps. For example, one of the newest medications for psoriasis, Vtama, is an aryl hydrocarbon receptor agonist. Psoriasis has also been successfully treated with bile acids in at least two studies.


Wait until I see Pliny’s dad, Pliny, and drop this bombshell. He’s going to find it… humorous.


I was briefly thought to have hemochromatosis, an excess of blood iron, for which the standard treatment is phlebotomy.

Which is to say, bloodletting.


What did it turn out you actually had?


Just a slightly high ferritin measure. The concern was that I was already a very frequent donor (platelets, which you can donate more often), and if I stopped it could potentially be really bad.

But it was nothing. Just a slightly off scale number, unusual but not dangerous.


Dr. Terry Wahls addressed the role of diet and MS over a decade ago: https://www.youtube.com/watch?v=KLjgBLwH3Wc


Dr Terry Wahls isn't going off of research. She wanted to sell books - and has. She's commonly known as a fraud/snake oil salesmen to all but the folks that buy into her scam.


She reversed her RRMS! How is that fraudulent? Or is it that you just cannot come to believe it?

She is a clinical professor of medicine at the University of Iowa Carver College of Medicine.

https://terrywahls.com/about/about-terry-wahls/


Yeah, she's a doctor going around telling people they need to eat an assload of a wide variety of fresh vegetables each day. This can't stand.


I have no issue with folks telling others to eat more vegetables and otherwise have a generally healthy diet.

I do have an issue with telling folks to eat a specific style of diet, which is difficult to maintain, especially with the promise that it'll cure a disease, one that leaves some folks with little hope. There is no quality research proving her right.


> There is no quality research proving her right.

If you were as sick as we are would you wait for research that is never going to happen because capitalism?

What we do know is that oxidative stress seems to play a huge role in MS, and we also know that eating certain diets reduces oxidative stress.


I have Sjogrens and would easily qualify for MS. Burning pain throughout nervous system. LDN has been fantastic in reducing pain from extreme to near zero. Got off all my painkillers.

All the support forums rage about how awesome it is. I had a nightmare of a time finding a doctor that had heard of it. Finally had to get an online doctor.

Diet changes also work, but I have to be really strict without LDN. Or a little strict with LDN.


My father had MS and had to get an online doctor/private prescription to get LDN. It was pretty much the only drug that helped him, but the general practitioners would not prescribe it on the NHS.


Are there any side effects to LDN? Or just general unusual effects from having it in your body constantly? Is it rough on the liver at all?


The LD is for Low Dose and it has a short half life of 4 hours, though sensitive can vary by an order of magnitude so how long it lasts can depend. Typically people start low and slowly build up. You don't notice the initial effects (unless you're unfortunate enough to need opioids during that time), it's the subsequent bodies reaction overnight that has the real effect. Most healthy people don't notice anything good or bad. Sick people can get a variety of effects and some quite strong but very rarely an emergency.

Anecdotally it appears that if you get a strong effect then it is likely it'll be more beneficial long term. Most common effects are nausea which generally subsides in a few weeks, extremely vivid dreams that you can remember which lasts longer. Basically low grade serotonin sickness and perhaps some dopamine dysregulation - some people do get dopamine surges. It helps normalize neurotransmitter levels and your brain might not be used to it. Usually you sleep less but feel more refreshed. I had one of the rarer reactions which was extreme energy, I started LDN for ME/CFS and thought it had cured me and that I now had a new problem of too much energy. Unfortunately it wore off after a few weeks, but it did plateau to a higher baseline.


I should add LDN can normalize thyroid function so if someone is on medication it’ll likely need to be adjusted.

And the dreams are next level crazy vivid, it’s probably the most common complaint. Sometimes it can be hard to go to sleep knowing there is a dragon waiting to eat you again. There can be a dissociative feeling when you wake up as you try to work out what was real and what isn’t. Was I really just storming the beaches in Normandy? Hmm seems unlikely, but it feels like I was just there.


Oh yes. I forgot how vivid the dreams were. Those calmed down after a few months for me


Naltrexone metabolizes into methylnaltrexone which lasts longer in the blood and has stronger but slightly different binding profiles than its parent. Is the response from LDN the result of naltrexone, its metabolites or both?

I ask because I'm genuinely curious, I'm ignorant of its use for this condition.


I’ve read at these doses it lasts < 4 hrs but I don’t know the mechanism. It is usually taken at night an hour before going to bed and the post inhibition reaction can be felt the same night during sleep so it must be a matter of hours.


Naltrexone gave me the rarest side effect - seizures, and that's extremely rare because it generally bolsters seizure threshold. It surprised my doctor. About 3 months into taking it I had a complete absence seizure at work while operating a 1kW LASER. The thing's supposed to fire for a split second, I had it happen just as I was hitting the fire button, kept the fire button held with my body for just short of a minute. I came to from the smell of vaporizing metal hitting my nose. Whoops, $10K experimental board wrecked.

As soon as I got off the medication and let it clear out of my body for a month, I quit having auras or any other odd seizure-related symptom. Damn glad that didn't happen while driving.


The one side effect I’ve heard from my doctor who has patients on LDN, that fortunately seems fairly rare, but that can catch people off guard is sudden depression. People a few days to a week into starting it suddenly having uncontrollable crying and other things. Apparently corrects quickly after stoping so not something to be afraid of so long as aware. LDN seems to help a lot of people.


I think this is a reversal of emotional blunting. I consider becoming overly emotional a good indication that LDN will really help and heightened emotional sensitivity will wear off as the brain adjusts. Stiff like crying over spilt milk. Certainly people should be warned that they could be in for a bit of an emotional roller coaster.


Can’t take it with any opioids. Plus side. I no longer needed opioids (tramadol) to manage pain.

I wake up with energy in the morning. First few months it was like viagra on steroids in morning. That eventually calmed down.

Otherwise I’ve had no side effects, and I tend to get all the crazy side effects of almost every medication.


This could be consequential for a number of diseases. I suffer from Rheumatoid Arthritis, and have tried innumerable solutions (diets, supplements, etc) to reduce the fundamental inflammation that is the core of R.A. - if this discovery is applicable to multiple types of inflammation, it may be a huge help to R.A. sufferers as well.


If you have ever had a sore gut or a known sensitivity to gluten you should try the carnivore diet like Mikhaela Peterson. It has put my RA into remission and I hypotasize gluten causes leaky gut and other plant toxins are entering my blood stream causing the fundamental inflammation. RA does not exist for me if I only eat beef and butter along with supplementing electrolytes. Without carnivore I was on crutches, hospital boot, crippled. If I try to do keto and eat a few nuts or an avocado I immediately reactivate the disease. Semen Retention also had a positive effect before I did carnivore so take what I say with a pinch of salt and investigate for yourself. I'm going to try and take glutamine to heal my gut soon.


it’s been 20+ years some doctors keep bringing up a correlation between gut bacteria and MS, and I don’t see anything new here, again. Always hoping for the best, but the trend is not promising well, at this pace it will take another 100 years of “news” :-( :-(


Agreed. These types of articles read like “pop-sci” nowadays… How many more decades will it take for any sort of commercialization of this research to take place?


Unless they are looking at each individuals genetics and ways to control their oxidative stress I do not want to hear about any thing that might "help" MS patients.

https://www.frontiersin.org/articles/10.3389/fnins.2020.0082...

There will never be a singe treatment for MS. Never. Because genetics and exogenous influences. The only reason that MS has not been cured in anyone is they refuse to use Personalized Medicine.

If you have RRMS or know someone who does, I advise you to take this route, investigating sources and resolution of your own oxidative stress, to limit relapses.

By the way, most bile acids, like taurocholic acid, are antioxidants.


This fits with a previous study showing that soluble fiber altered biota and reduced symptoms. https://www.inverse.com/mind-body/diet-rich-in-beans-legumes...

FWIW, other research shows that without soluble fiber, we can't absorb choline; we need a bacteria in the gut to transform it into a bioavailable form, apparently.

Choline is getting a lot more attention recently, from researchers.

Notoriously, MS is a disease of the last couple centuries, so far as we can tell, it simply didn't exist before that.


Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis

https://www.science.org/doi/10.1126/science.abj8222

I think this was a major breakthrough in recent years but no one mentioned it here so far.


Some people have improved MS on a carnivore diet. Perhaps keto would also do.


This is likely related to the significant decrease in gut bacteria (of all kinds good and bad) on a low carbohydrate diet, and a corresponding decrease in intestinal permeability.

Another proposed mechanism is inadvertent calorie restriction, which is common on high protein diets (because protein is so satiating), and on diets with few foods (because eating the same thing is boring). The effects of fasting on autoimmune diseases are well documented. It's thought that calorie restriction may be sufficiently similar.


...in mice.


It already does end the inflammation in mice, it could end it in humans.


The problem is that mice can't get MS. When researchers experiment on mice, they do so using animal models. With MS these models are Experimental Autoimmune Encephalomyelitis (EAE) and Theiler’s Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD). Neither is MS. So if you cure a mouse with EAE, you've cured them of EAE, not MS, and there's no knowing if the same treatment works on MS in humans.


> The problem is that mice can't get MS.

Correct.

Why do you think mice with EAE are a reference in the research of MS?


One way of knowing is, y’know, trying.


And that's how all the Alzheimer's drugs that do absolutely nothing get approved :)


Is there a study on how many discoveries made on animal models could be turned into practical treatment for human subjects (percentage-wise)? I can't find one easily.


For MS the number of treatments that made it to the clinic is depressingly low, however (a) that's changed recently, and (b) in this case it's a new pathway. So maybe this is interesting.


Sure, but that's what folks say about all of the mice studies. Any of them could end x in humans.

Most mice studies don't go further.


> Due to the complexity of the gut flora, probiotics are difficult to use clinically.

I have no trouble at all with ursolic acid. I go to AliExpress.com place an order and 14 days laters, it in my hands, going down my neck.

Now whats hard about that?


I don’t remember, was it sugar that was bad for your memory?


Sugar is a huge trigger for inflammation for many people.

Look up AIP diet if you want to reduce inflammation a lot. Changed my life


I looked I the AIP diet on your suggestion. It looks very difficult. Good luck to you.


AIP is tough but you don't have to do it forever, just long enough for your body/gut to heal and for your immune system to calm down. Maybe 3 months.

I had such bad IBS at one point I thought I was dying. Doctors weren't interested in helping me because they couldn't see anything wrong. The AIP diet turned my life around. Now eat most normal foods but still avoid gluten.


Difficult? You control what you shove down your neck, no?


There are many publications on this topic, yet "as of today there is no clinical trial indicating a relation between sugar and Alzheimer"

But some publications are really impressive like this one, which says that sugary drinks are particularly harmful:

https://pubmed.ncbi.nlm.nih.gov/36625082/


I believe the lack of memory excercise is bad for memory.




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