8 ms·

Multiple Sclerosis discovery could end disease's chronic inflammation

234 points by elorant 4y ago

Nomentatus 4y ago
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-study 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.
startupsfail 4y ago
I don’t remember, was it sugar that was bad for your memory?
- loa_in_ 4y ago
  I believe the lack of memory excercise is bad for memory.
- treeman79 4y ago
  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
  - TedDoesntTalk 4y ago
    I looked I the AIP diet on your suggestion. It looks very difficult. Good luck to you.
    - cjdell 4y ago
      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.
    - datavirtue 4y ago
      Difficult? You control what you shove down your neck, no?
- JPLeRouzic 4y ago
  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/ https://pubmed.ncbi.nlm.nih.gov/36625082/
loa_in_ 4y ago
...in mice.
- whatshisface 4y ago
  It already does end the inflammation in mice, it could end it in humans.
  - rzzzt 4y ago
    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.
    - doctor_eval 4y ago
      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.
  - atombender 4y ago
    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.
    - devin 4y ago
      One way of knowing is, y’know, trying.
      - xkcd-sucks 4y ago
        And that's how all the Alzheimer's drugs that do absolutely nothing get approved :)
A_D_E_P_T 4y ago
Fulltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002000 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.
- drcross 4y ago
  >taurocholic acid is hepatotoxic Excuse my rudimentary question but does this mean it would still be possible for administration intravenously?
  - Ovah 4y ago
    Nah blood gets filtered through the liver and so would this compounded even if it was intravenously administered.
  - A_D_E_P_T 4y ago
    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.
odyssey7 4y ago
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.
- Waterluvian 4y ago
  Wait until I see Pliny’s dad, Pliny, and drop this bombshell. He’s going to find it… humorous.
- jfengel 4y ago
  I was briefly thought to have hemochromatosis, an excess of blood iron, for which the standard treatment is phlebotomy. Which is to say, bloodletting.
  - pfannkuchen 4y ago
    What did it turn out you actually had?
    - jfengel 4y ago
      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.
- metamet 4y ago
  Dr. Terry Wahls addressed the role of diet and MS over a decade ago: https://www.youtube.com/watch?v=KLjgBLwH3Wc https://www.youtube.com/watch?v=KLjgBLwH3Wc
  - 4y ago
treeman79 4y ago
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.
- flumpcakes 4y ago
  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.
- voldacar 4y ago
  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?
  - treeman79 4y ago
    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.
  - cjbgkagh 4y ago
    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.
obert 4y ago
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” :-( :-(
- sourcelabs 4y ago
  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?
deleted 4y ago
[deleted]
antonchekhov 4y ago
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.
- Shaggy2000 4y ago
  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.
oifjsidjf 4y ago
Some people have improved MS on a carnivore diet. Perhaps keto would also do.
- alphazard 4y ago
  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.
moremetadata 4y ago
> 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?
FollowingTheDao 4y ago
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.2020.00823/full 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.
mo_42 4y ago
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis https://www.science.org/doi/10.1126/science.abj8222 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.

234 points by elorant 4y ago

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-study 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.

startupsfail 4y ago

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

loa_in_ 4y ago
I believe the lack of memory excercise is bad for memory.
treeman79 4y ago
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
- TedDoesntTalk 4y ago
  I looked I the AIP diet on your suggestion. It looks very difficult. Good luck to you.
  - cjdell 4y ago
    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.
  - datavirtue 4y ago
    Difficult? You control what you shove down your neck, no?
JPLeRouzic 4y ago
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/ https://pubmed.ncbi.nlm.nih.gov/36625082/

loa_in_ 4y ago

...in mice.

whatshisface 4y ago
It already does end the inflammation in mice, it could end it in humans.
- rzzzt 4y ago
  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.
  - doctor_eval 4y ago
    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.
- atombender 4y ago
  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.
  - devin 4y ago
    One way of knowing is, y’know, trying.
    - xkcd-sucks 4y ago
      And that's how all the Alzheimer's drugs that do absolutely nothing get approved :)

A_D_E_P_T 4y ago

Fulltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002000 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.

drcross 4y ago
>taurocholic acid is hepatotoxic Excuse my rudimentary question but does this mean it would still be possible for administration intravenously?
- Ovah 4y ago
  Nah blood gets filtered through the liver and so would this compounded even if it was intravenously administered.
- A_D_E_P_T 4y ago
  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.

odyssey7 4y ago

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.

Waterluvian 4y ago
Wait until I see Pliny’s dad, Pliny, and drop this bombshell. He’s going to find it… humorous.
jfengel 4y ago
I was briefly thought to have hemochromatosis, an excess of blood iron, for which the standard treatment is phlebotomy. Which is to say, bloodletting.
- pfannkuchen 4y ago
  What did it turn out you actually had?
  - jfengel 4y ago
    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.
metamet 4y ago
Dr. Terry Wahls addressed the role of diet and MS over a decade ago: https://www.youtube.com/watch?v=KLjgBLwH3Wc https://www.youtube.com/watch?v=KLjgBLwH3Wc
- 4y ago

treeman79 4y ago

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.

flumpcakes 4y ago
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.
voldacar 4y ago
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?
- treeman79 4y ago
  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.
- cjbgkagh 4y ago
  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.

obert 4y ago

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” :-( :-(

sourcelabs 4y ago
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?

deleted 4y ago

[deleted]

antonchekhov 4y ago

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.

Shaggy2000 4y ago
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.

oifjsidjf 4y ago

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

alphazard 4y ago
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.

moremetadata 4y ago

> 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?

FollowingTheDao 4y ago

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.2020.00823/full 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.

mo_42 4y ago

Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis https://www.science.org/doi/10.1126/science.abj8222 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.