Hypothesis on Vancomycin 'brand' differences for PSC effectiveness

I’ve read a lot about PSC’ers on Vanco finding certain brands work and certains ones don’t. The ‘theory’ is that somehow they are subtly different at the molecular level and certain ‘brands’ by luck work on PSC (by - theoretically - killing one or two bad guy gram positive bacteria in the gut). It is not a problem I’ve had personally, and use multiple brands of IV powder taken orally - whatever is available. Since my rPSC is so early (no damage) I know from experimentation (going off Vanco) takes over 2 years for LFT evelavation again - so mixing in a new supposedly inneffective Vanco brand or two along the way would never get noticed because my gut would respond maybe to the next brand change. Maybe, or maybe all the powder is exactly identical, and no different from whats inside the pills on the oral form (why would it be?). It has been mused somewhere on this site, that IV Vanco (powder) tend to be more ‘bioequivalent’ and effective for PSC across the IV brands (??). Again why can they manufacture a Vancomycin molecule to put in a wee bottle but somehow wreck it by knocking an atom off when they put it in the pill. OK, so fundamentally it doesn’t make sence that a generic drug molecule is different from brand to brand and that always confounded me - if its not a Vanco molecule as pictured on the box insert - well it isn’t Vanco, right? So I’m getting to the point, no one complains about powder or liquid forms of Vanco not working due to brand difference (unless I’ve missed something). I’ve picked up a few reports of experiences including reports from Dr. Ken Cox (below) that sometimes there is a ’ bioavailability problem with certain ORAL Vanco brands - plain speak the damn jell capsule doesn’t disolve and you end up pooping out most of the dose. It would be rather an unforgivable R and D faux pas on the part of the manufacturer but people are reporting, if they open the capsule on non working vanco - they suddenly begin to work on the PSC. You can see where I’m going here. Is the brand kerfuffle -‘this one works, this one doesn’t - try it for 3 months then finds another brand and then another’ - all because the frickin jell cap on the oral drug, doesn’t dissolve? And the powder inside is perfectly good PSC-treating vanco for all brands? Some supporting discussion on the ‘open the capsule’ recommendation in these that I scooped the the facebook PSC-support page by a very helpful poster on that forum. RoundTable w/Drs. Kenneth Cox and Dr. Mounif El-Youssef at 11/2018 AASLD Liver Meeting, Part 1 of 3. - YouTube
RoundTable w/Drs. Kenneth Cox and Dr. Mounif El-Youssef at 11/2018 AASLD Liver Meeting, Part 2 of 3. - YouTube
RoundTable w/Drs. Kenneth Cox and Dr. Mounif El-Youssef at 11/2018 AASLD Liver Meeting, Part 3 of 3. - YouTube

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Yes, this is due to gel caps not dissolving. People for example have different levels of stomach acid, and therefor gel caps are dissolved differently in different people. This doesn’t have anything to do about the vancomycin. This can easily be solved by just buying liquid vancomycin. :slight_smile:

I’m so glad you sent this message. I just listened to that panel of doctors discuss their studies… and there were some good pointers in there. My teenage son has PSC and Chron’s. He has been on a strict SCD diet for over 2 years now and he is on Remicade. Chron’s appears to be stable at this point - no pain, super low stool calprotectin. PSC was found to be in the early stages when diagnosed 1 yr ago with MRI & livery biopsy, and he responded well to the first found to Vanco (500 mg tid), as his GGT and other liver enzymes normalized within weeks. The brand of Vanco switched a while back, with the new capsules feeling very thick and almost glass-like. His liver enzymes (ALT/AST) have incresed again since switching to this brand… plus his GGT started to increase again. I wonder if this has something to do with the the new capsules! I tried picking them apart last night, and there was NOT powder inside (the original vanco was powder filled), but rather a hard lump of something that looked like hard, dry taffy. Weeeird. Will definitely be discussing this with his GI doc in the near future. I’m wondering if switching to a liquid form would be indicated at this point. - Oh, I also found it interesting that Dr. Kenneth Cox only considers reducing the dose of Vanco after confirmation of no more inflammation upon biospy/colononscopy and after at least 12 months of vanco. And that all those patients who have PSC and IBD are no longer on biologics, as the Vanco seems to help control their IBD, too. Feeling a little more hopeful because of your post. I truly appreciate this forum. Thank you!

Vanco has a complicated history of generic therapeutic equivalence issues and for a time had a special FDA rule requiring generics perform in vivo testing in addition to the usual in vitro testing. I don’t think the drug itself is the issue in this case and am in the gel cap is the problem camp as there are numerous accounts of people popping open or chewing the caps and seeing significantly improved results. The issue, as I believe has been articulated by Dr. Cox, is that at certain pH (particular patients) generic brand gel caps have slower dissolution compared to Vancocin. Notably, the C. diff community isn’t complaining about the efficacy of oral vancomycin (aside from reinfection due to ongoing gut dysbiosis). The PSC community appears to be uniquely sensitive to slower dissolving vanco gel caps and, to me, this is fascinating.

The old thinking was that the bile ducts were a sterile environment (no bacteria) under normal conditions. The theory was that a leaky gut down around the lower small intestine and beginning of the large intestine could cause translocation of bacteria to the biliary tract. More recent research shows that the bile ducts have a robust microbiome, even under normal conditions. The biliary microbiome is typically closer in composition to the microbiomes seen between the mouth and the upper small intestine compared the microbiomes in the lower GI tract. The thinking is that the biliary microbiome is likely populated by the duodenum and sphincter of oddi.

Our accidental experiment with slower dissolving gel caps suggests that the cause of and solution to PSC is potentially found in this upper GI tract rather than further downstream. Slower dissolving generic caps may be missing the major window of opportunity to affect the bacterial composition of the biliary tract.

You’re right, I’ve looked into this too. It seems like one study a bunch of years ago pointed to differences in potency of brand vs non-brand vanco. This got the FDA to act. However, this conclusion was contested because the original study used a mouse model which supposedly isn’t a good model for determening the potency. More recent studies on a rabbit model (which supposedly is the best way to evalute this) havn’t shown any significant difference for brand vs non-brand and therefor these FDA requirements were removed. :slight_smile:

Occassionally the IV (10ml bottle) powder vanco I get is clumpy - like clumped sand but immediately breaks apart when I stir it up. But a consistency distinctly different from other brands which is a fine powder from the start. I wonder if its an age or process thing. I’ve not seen anything like the solid you describe - (even with long expired vanco I’ve had come to think of it.). And I also got a lot out those AASLD Liver meeting posts that a good person on the the PSC-support facebook page shared. Its like sitting in the room with the experts (cause you are) - it is gobbsmackingly hard to imagine given the way these experts, researchers and physicians, from some of the highest rep medical research clinics in the world - casually talk about their overwhelming successful treatment experience with Vanco , and it is their routine first line therapy for years if not decades; its frustrating that acceptance in the wider medical community is so slow.

It has occurred to me as well that I had never heard of brand differences for C-diff treatment, therefore supporting that the drug is still effective Vanco, regardless of brand. Also, one correction to my first post based on your input; logically the stubborn jell caps are not ‘pooped out’ completely uselessly, just theoretically takes longer to dissolve and seems to do so lower in the gut as you describe. What you say makes sense, it is then fine for C-Dif but somehow doesn’t do the business for PSC. I recall reading, if I’m not mistaken, they are closing in on 3 bacteria species implicated in the PSC effect (I presume gram positive types) that Vanco kills off at least one of them. I am wondering aloud if there any interesting correllations with that finding; for instance, It would be interesting if their is any gut locality knowledge to any of those specific species in reinforcement to your theory.

I agree. Plain craziness. This needs to be acknowledged as a real course of treatment. It’s literally a life saver and nuts how it’s not widespread knowledge.


I have not experienced any clumps. It should be fine (crystal looking) powder. If it doesn’t look like intended, return it to the pharmacy. :slight_smile:

The vanco treatment for PSC is not really comparable to c-diff. C-diff infections are in the colon (and not in the small intestine). Also, c-diff is extremly sensitive to vancomycin (in theory, 500mg/day of vanco is 1000 times more than what’s needed to kill 90% of c-diff). We don’t know which bacteria we’re trying to kill when we take vanco for PSC, so it’s hard to compare doses. Furthermore, most bacteria aren’t known by man, so that doesn’t make it easier.

Upon advice from those with extensive experience, we use ANI brand capsules, which have worked very well for my son.

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Fecal concentrations of vancomycin are typically two orders of magnitude higher than what one would expect in the blood from IV administration. Taken orally, all but the most resistant organisms are eliminated, to include gram negative bacteria and even fungi, such as some candida albicans. In fact, at the phylum level the most sweeping change in the vanco gut is the complete elimination of gram-negative Bacteroidetes.

The gut pathobionts study is interesting. The idea is that if you can fix the problem if you cut off at least one of the three highlighted bacteria. Vanco won’t touch the klebsiella or proteus, but would take out the VRE-light E. gallinarum. The big caveat is that this study involves Japanese adults, a group that is unique in the overall PSC population (ex. IBD is rare). I don’t believe we’ve seen E. gallinarum in other PSC studies (with at least one looking at the biliary microbiome). We do see other species of enterococci, so what if we expand the study hypothesis to the whole genus and roll with the idea that vanco works by killing problem bacteria to include particular enterococci. Vanco users normalize over a wide spectrum of dosage, with a fairly specific breakpoint unique to each individual (eg. 2000mg normalizes, while 1750 does not). Enterococci vary from species susceptible to vanco to those with a wide range of vancomycin resistance (VRE). I’ve taken gut microbiome tests and compared results with other patients and controls. I get away with a low dose and don’t have any detectable enterococci in my gut. One treated patient, who needed a high level of vancomycin to normalize, showed trace amounts of enterococci. Was this VRE? Would VRE explain why some patients need high doses and others are unable to get the treatment to work?

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That’s a solid discussion! The conclusion is that it’s too advanced for us normal folkes to fully understand (at least for me haha). :sweat_smile:

Indeed, thanks JTB, I’m taking that information in as another puzzle piece - in a puzzle us patients should not have to solving for ourselves. But here we are - many of us here are at just that (a hobby?). Its self preservation, I need to be able to hold ground on hypothetical technical medical arguments against my continued script for Vanco - from Doctors or insurers. I also do failure investigation as part of my profession - and this is another such - only my experience is science and research applied to metal and equipment failure, not medical/bio. For each its like assembling a puzzle to try to see the whole picture with no photo on the box and no chance of all the pieces out there - for vanco/psc, each piece is knowledge provided by others. The microbiome - and it having any extended role in physiology - is even relatively new interest to the medical community, so it presents a challenge (quite a zoo down there). Grateful for your research on this. If I want to help understand the cause and effect here, I can no longer avoid those papers!.


You need to read this paper. It will explain some of your questions about brand issues. Also understand that there are 6 sources for the API (active pharmaceutical ingredient). We do not know exactly what has the efficacy for PSC – certainly if we had funding we could do a study. I actually have the former MD, PhD CEO of a pharma company interested in doing this study. Buness2020_Article_SuccessfulResponseOfPrimaryScl.pdf (1.3 MB)

here is a link that combines the 3 YouTube links you posted: Vancomycin for Primary Sclerosing Cholangitis (PSC) Roundtable: Featuring Dr. Cox and Dr. El-Youssef - YouTube

Actually the original Vancocin capsules had a solid inside and they still do. But they too may need to be opened. Opening the capsules increases bioavailability. We are speculating that some capsules dissolve at different pHs causing them to not dissolve in the “right” part of the GI tract. Studies need to confirm this but we need money to do so. So in the interim, I recommend opening the capsules.
see Buness2020_Article_SuccessfulResponseOfPrimaryScl.pdf (1.3 MB)

Let me know if you need more information.

No it is not likely VRE. As you stated, we have found that patients vary on their dosing needs. May be because of different phenotypes.

awesome info, thanks!

Thanks! I have been opening up my son’s hard vanco capsules since reading the original post… But his doctor just sent in a prescription for oral vanco, so we’ll be switching that that within the next couple days. I will report back on how things pan out with his labs… so we can keep the information flowing.

what do you mean “hard vanco capsules?” I am only aware of capsules that are openable. Also anything taken by mouth is “oral.”