Spondylitis Association of America Forums General Discussion General Message Board for Ankylosing Spondylitis and Related Diseases Potential "Patch" for AS

Update: After reading about those compounds, of which punicalagin was one I hadn't read about before...I have purchased Life Extensions Pomegranate Complete and will resume taking my AlliMax. Thanks for a wonderful reminder and addition to this post.

Hey guys! I have a pretty huge update! I want to detail an experience and some thoughts below.

Candibactin AR/BR and other natural antimicrobials have worked pretty well for me when I need to control increasing pain. However, I've had a recent experience that I am going to post about that has pretty much ended any doubts in my mind that HLA-B27 related disease is strictly triggered by bacterial insult. In short, I believe that the Candibactin helped eradicate a subset of bugs that was causing me issues from my initial infection in Mexico that triggered my genetics to move into a diseased state. The more I've read about HLA-B27 and its binding groove, the more I realize that B27 is simply "unstable" in its bonding. It will bond peptide fragments, however, they are not firmly bonded. Thus, they can "wiggle" and it is this "wiggling" that allows these peptides to interact and bond with other things they normally wouldn't. This would explain why HLA-B27 also slowly builds up inflammatory responses in the body over time, but an acute interaction of just the right type can cause a very rapid progression if there is some form of "mimicry" or interaction in that unique peptide the invader presents to the immune system in comparison to other self-antigens, etc. The HLA-B27 variants 06 and 09 are resistant to the disease and they lack this "wiggling" due to a different set of amino acids at certain locations along the chain.

No, back to relating this back to my experiences. I would take rounds of my natural antimicrobials when my pain would increase over time (eating and growing more and more bacteria over time and taking psyllium fiber would usually result in increased pain over weeks to months). However, recently I got an infection from bad food being delivered from Amazon (Whole Foods). It ended up being a blessing in disguise. I had to go to the ER and got an ultrasound, which found I had an acute case of diverticulitis. They forced me to take antibiotics while I was there in the hospital, even though I was reluctant to do so given my reactivity to antibiotics normally. The antibiotic they gave me was Metronidazole. I had ZERO reaction to it but had the normal metallic taste and loss of appetite. I finished the course of that antibiotic but ditched the second one they gave me and substituted it with FC Cidal and Dysbiocide (my shipment of Candibactin that I reordered was stolen because FedEx is stupid and left my packages out in the open in the mailroom). After 10 days I decided to slowly start eating heavier and heavier foods. However, it was also Thanksgiving, so I ended up cheating at a friend's small gathering. What shocked me was that I did not react to ANY of the food at all. It is now ~3 weeks later and I am pain/reactivity free and eating whatever I want! I have a feeling there was some other resident that was creating byproducts that, upon eating complex carbs, I was reactive to that byproduct. I can't be 100% sure of this, as it could have just been a specific bacteria that was growing more and more by eating carbs and going dormant when I ate keto. All I can say is...I can eat anything right now and am basically in 0 pain. I have eaten rice, bread, starchy veggies like potatoes, super sweet deserts during Thanksgiving, etc. I still have some other symptoms that have persisted from my disease getting worse (heart palpitations...my heart literally stops beating...or beats like crazy on simply standing up or doing mild exercise. This is autonomic nervous system dysfunction, which can occur in people with AS and ReA.) However, the amount of times my heart skips or feels fluttery has significantly decreased within the last 3 weeks, which tells me the inflammatory response that is causing the heart valve/nerve damage is reduced quite a lot. All in all, I feel much better and I am happy to have taken this round of antibiotics.

My next project is going to be reducing my reactivity by trying to work with a select few peptides, like Thymosin Alpha 1, to try and normalize my immune response. There are a few other things I am planning to try but at the moment I am just enjoying no pain and a massively expanded diet!

Thanks for the update. Did the effect of the metronidazole persist or did things go back to baseline after a while?

Metronidazole gains have persisted! I am still relatively pain-free and eating most anything I want. I am not trying to go too crazy but I will say I just ate a whole bag of chips yesterday lol...no pain.

Nice one, glad to hear the results have been long lasting.

I came across a study from China recently that found that 89% of AS patients had SIBO based on hydrogen breath testing with lactulose - https://ard.bmj.com/content/78/Suppl_2/1482.2

Another smaller study in Mexico found 33% of AS patients had SIBO and that hydrogen breath levels were negatively correlated with sulfasalazine intake which makes sense as it contains sulfapyridine which is an antibiotic - https://ard.bmj.com/content/78/Suppl_2/483.2

So it's possible that SIBO could be an important factor in a large percentage of people with SpA. I'm of the opinion that anything that causes chronic gut inflammation could cause SpA so it may be that there's different types of gut inflammation in SpA - Crohn's type, UC type, and SIBO type. They aren't mutually exclusive either as around 20% of Crohn's and 30% of UC patients have SIBO.

There's been a lot of interesting research on SIBO in the last few years. In many cases it seems that food poisoning initiates SIBO. Bacteria that cause food poisoning release cytolethal distending toxin B (CdtB) and the body then produces anti-cbtB and anti-vinculin antibodies. Having anti-cbtB or anti-vinculin antibodies is 90% predictive of IBS.

The anti-vinculin antibodies seem to cause an autoimmune type reaction against the gut which affects the migrating motor complex, slowing down the motility of the small intestine and diminishing the cleaning wave of the gut that clears bacteria out between meals, resulting in SIBO. This has been experimentally verified in rats with campylobacter which leads to SIBO. Interestingly, people with the antibodies are more likely to get food poisoning again which increases the antibodies further and perpetuates the vicious cycle.

Do you think it's plausible that SIBO could explain the increase in disease activity after contracting a water/food-borne pathogen in Mexico and the positive response that you had to restricting starch and fermentable fibre and taking herbal antimicrobials, rifaximin, and metronidazole?

100%. Also, you've definitely brought up very important mechanisms that have a very important mechanical action to worsen the environment and cause dysfunction. One thing to note, that isn't noted in that analysis is that any bacteria (good or bad) regulate cytokine expression through interleukin modulation in the gut. Thus, any kind of SIBO is likely going to cause you to house invaders that upregulate IL-17 (the interleukin pathway that deals with insults to epithelial linings - gut, lungs, etc) The IL-17 pathway is massively implicated in AS/SpA's. Thus, we have mechanical issues you mentioned, the immune memory formed that makes infection more likely and inflammation much more potent, and then we have the driving of the inflammatory pathways through the communication the bacteria have with the gut lining itself. All of these things are extremely important in creating the "profile" of an AS sufferer.

To further your line of reasoning, and demonstrate is indeed valid, check out: Link.

Basically, I've treated myself under two assumptions:

1) I have massive SIBO due to dysfunction in the immune system, so treat SIBO
2) Keep the number and type of bacteria lower than in normal/healthy people since the number of interactions with the intestinal wall drives the inflammatory pathway. The LPS coating (lipopolysaccharide) of bacteria is one of THE most potent initiators of acute inflammatory (TNF-alpha) response.

So, I may not have as diverse a gut microbiome as I used to, but mainly because my immune system is too hypersensitive to allow it anymore. This might make me more susceptible to various infections (but nowhere near as susceptible as blunting my immune system with biologics), but at least I am more mobile and able to eat a wider variety of food. I think, in the long-run, this is more important as I won't have as many nutritional deficiencies and I can enjoy a more normal/mobile life.

Just wanted to update this post with an article that basically summarizes my concern with the general approach of trusting clinical trials for big pharma drugs and why I said medicine moves too slowly, and the information also doesn't make it to doctors very quickly on top of that. This aims more to speak about the former, but the latter is a subsequent result of how the system works at the research level. Doctors push these pills because they get incentives to do so, and these people running the trials...well you can read the article =)

Link

TLDR: PainintheAS is absolutely on the right track. These posts and his support have accelerated my personal research towards a "cure" by years. I have put into practice much of what he has recommended and have reaped the benefits in symptom reduction, better understanding of the pathogenesis and mechanics of the disease, as well as improved tactics for disease management.

The long version:
I've had Ankylosing Spondylitis since I was 19 (I am nearly 35) but did not have a diagnosis until around age 27. I also discovered that I had Crohn's disease right around the same time. To be fair, the Crohn's never really manifest any symptoms itself but some unfortunate health issues allowed for a diagnosis around age 25. AS, however, suuuuuucccckksss. My twenties were rough. God bless my wife for putting up with me.

I tried biologics against my better judgement with no improvements and was honestly relieved when recurring fevers prompted my doctors to take me off of them. Daily NSAIDs (diclofenac 50mg 3x daily) and muscle relaxers (cyclobenzaprine) for emergencies (once someone would prescribe them to me chronically) were the ONLY thing that allowed me to function as a (relatively) normal human being. I'll spare the gory details for now but let's just say it was very, very bad.

I had convinced myself that there was nothing I could do but accept my fate until around Spring 2018 I decided to experiment with a ketogenic diet to "prove" to my overzealous friend that it was a fad and wouldn't help me or anyone else lose weight (note that this activity had NOTHING to do with AS when it began). I could not have been more wrong. This single act of facetiousness was probably one of the best things I ever did for myself. Yes - I lost weight. But more importantly I realized around day 2-3 that "Oh, wow! My back doesn't hurt today!". It was the beginning of a personal health renaissance that has driven me to accept nothing but a cure for this nasty disease. I now had a powerful knob to turn for a disease I wrongly presumed as a constant. We're not victims of our bodies. Our bodies are incredible pieces of biological machinery that evolved over millions of years and they respond logically to the signals we provide to them. To be clear: keto is not a fad and, if done right, is a phenomenal tool in the AS (and general health) toolkit. More keto stories for another day.

My experience using a ketogenic diet continued through 2018 and 2019. The next big leap came when I started experimenting with long term fasting during COVID. I was really enamored with David Sinclair's work on longevity and was eager to do as much as I could through lifestyle changes as opposed to more dramatic interventions. So, I gave fasting a try. HOLY COW! I cannot say enough good things about fasting. It's like a OFF SWITCH for AS symptoms. To be clear, when I say fasting, I literally mean I do not eat or drink anything except water and unsweetened herbal tea. Over time I progressed from 24 hour fasts to 36 hour, 72 hour, and eventually 7 day fasts. The longest I ever went was 8 days (shooting for a 10 day) but pulled the plug due to an injury that would require nutrients to heal. After this I was hooked. I dove headfirst into many books and articles in an attempt to understand the veritable magic I had stumbled onto and why it worked so well against my disease. I put special effort in trying to understand the true pathogenesis of AS, as well. Happy to share my reading list another day.

I've experimented a TON with nutrition beyond keto and fasting but this post is getting too long already!

Around the same time, a friend of mine unfortunately contracted long COVID (a nasty, nasty disease) and so we spent many conversations talking shop. He, like PainintheAS, went "full nerd citizen scientist" and turned to the web and the broader community for help in curing his ailments. He encouraged me to be brave and do the same. To be honest, I was discouraged from turning to the web AGAIN. I found zero answers in the past (2014-2016) and most of what I found recently was people looking for emotional support. Not my thing. I want answers. I want action.

My friend's continued persuasion translated to my following of several different forums/channels/subreddits/etc. I actually found this post and this forum while browsing on related Reddit channels in July 2021. PainintheAS had shared a summary and link to this series of posts over there. I read the first post and my gut (no pun intended) reaction was "Oh sh*t, this guy has learned everything that I have learned and has taken it many, many steps farther. I want more". The general framework that PainintheAS lays out fully encompassed all of my research and observations from personal experiments/experience.

Since then, I've been chatting with PainintheAS frequently, have done the homework to understand the underlying mechanisms at play, and have put into practice many of his suggestions including:

1. I have performed oral bacteria cultures to rule out mouth as the source (I had a terrible, undiagnosed 6 month infection in the root of a molar around age 24)
2. I have worked through my doctors to get an insurance covered prescription of Rifaxamin (3x14 days 550mg 3x daily). This is great stuff. I am practically asympomatic in combo with NSAIDS. I can eat whatever I want (though I won't - LOL - I am not stupid). I do have a plan for long term.
3. Experimented with Baicalein. This stuff is also like magic. I take a much as 1200mg per day with water.
4. Experimented with shilajit. Mostly for micronutrients due to frequent fasting.
5. Using the bread from Uprising Foods

The game isn't over but I definitely feel like I am winning. I see a clear line of sight to the goal line. There are uncertainties for sure but everything is converging on a clear model of the disease and a growing set of tools that I hope will converge on an effective cure over time.

I'm glossing over TONS of details. TONS. TONS.

I'm also realizing that some of you probably want some proxy credentials in order to take me seriously. Without being too specific, I have a Ph.D. in Electrical Engineering that I finished at age 25 and I now run a 60+ person technology organization in the energy industry with a focus on remote sensing of infrastructure and time-series data analytics. That's right - I'm a nerd, too.

I'd like to close with a direct "Thank you!" to PainintheAS for literally saving me years of research and symptoms. He's has gone out of his way to teach and support me in my efforts. My "pay-it-forward" is that I'm happy to share from my personal experiences for those that are open to it.

Warmest regards,

It has been my pleasure to help someone who wants to jump in the fray with me and begin tackling this disease by getting to and understanding the root causes and mechanisms of action. Not only has it been my pleasure to help you, but it has also become a pleasure getting to know you and finding a friend both through adversity and in our mutual love of science and understanding. Looking forward to our continual climb upward!

To the rest of the community, there are a LOT of peptides that are extremely beneficial for the intestinal inflammatory arm of this disease. I have been recently experimenting with some peptides that have been very beneficial to my overall level of gut inflammation. While I have not had a lot of back pain in quite a long time, my gut continued to be a source of continual stress and pain. This is due to the progressive nature of the disease. I was doing fairly decent before, but things began to progress despite intervention, which I believe relates to a loss of various signaling molecules (as damage and increased inflammation decreases their genetic encoding, which can force a feedback loop of increasing inflammation). The peptides I have been looking into and utilized are below:

BPC-157 (I may have mentioned this before. A general catchall for damage in soft-tissues and mild reduction in systemic inflammation)
KPV (A tripeptide known ONLY to interact in cells overexpressing inflammation and targets the gut)
KdPT (Another derivative like the above)

Daily usage of these three peptides has reduced my overall sensation to gut pain by approximately 60-80%. Mechanical pressure on the intestinal sections that feel irritated or hurt still causes pain, but that pain has also been reduced by 40-60%.

I have been studying the interplay of mechanisms in the gut along with the mechanisms of inflammatory signaling in AS. My general model of leaky guts being the primary driver of a whole host of immune dysregulation is essentially confirmed in this paper I have recently found. It demonstrates that the leaky gut (permeability) precedes the disease state of ulceration or inflammation in the intestines. Since Spondyloarthropies also contain IBD/IBS within, this is a very relevant model to pay attention to. The link below elucidates much of what I've been saying about loss of tolerance in the gut and TLR signaling, etc.

Link

Some other peptides are also mentioned, which I will be looking to find a way to custom synthesize and test. They are:

APOA1 Mimetic 4F and Tg6F
D-4F
Stable analog of LXA4 (BML111)

The study shows these even worked in human cells, which I am honestly tired of having to prove that animal studies of IBD/AS frequently carry over to human models and are some of the best models we have for the development of drugs...but for anyone who needed that level of assurance...these compounds DO work in humans and were tested to do so in the study.

Hi, interesting thread - any updates? How are you doing now?