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Cholestyramine
Haven't gone very far into the literature yet on this, but found something worth reporting in this 1971 paper.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1930848/pdf/canmedaj01613-0030.pdf
I can't find the 1965 paper they reference, but here's the quote:
"Longenecker and Basu showed that when 8 g. of cholestyramine was administered with 250,000 units of vitamin A to four normal men, the resultant increase in serum vitamin A levels over the next nine hours was significantly reduced. No significant effect was noted with a dose of 4 g. Whiteside et. al. showed that a 2% cholestyramine diet containing growth-limiting amounts of vitamin A retarded growth in weanling rats and impaired liver storage of vitamin A."
I wonder if the "growth-limiting" had anything to do with depletion of D, K, E, or other nutrients.
Ritchie Shoemaker, MD noted in a lecture that cholestyramine's binding-polarity (anion exchange) set it apart from charcoal/clay/zeolite. So, I wondered about VA. I'm ingesting some lately due to mold-exposure, so I'm motivated to learn more about it. One thing I ran across from a Shoemaker-trained D.O. in Wisconsin, is that if someone is sensitive to the coloring and sugar in the cholestyramine packets (Sandoz), they can get it compounded at pharmacies that do that sort of thing. One thing that comes to mind about the Shoemaker Protocol (he likes to call it the Surviving Mold protocol) is that the cholestyramine part of the treatment is the first thing at the base of the pyramid of getting someone well from mold or other biotoxin illness. The treatment is 4 times a day for a month or two, sometimes a bit longer. It just has to be the case that not only are they binding mycotoxins, but VA as well, and some of the inflammatory improvement is due to retinoid-clearance, even if they're not aware that's the case. I haven't heard any of them talking about it so far. I'd be interested to hear what Dr. Shoemaker thinks about this angle.
Here's another early study from 1973 that confirms and expands on the Longenecker and Basu paper.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412596/pdf/gut00629-0074.pdf
Discussion
In this study we have shown that cholestyramine, in an amount equivalent to a modest daily dose, markedly reduces vitamin A absorption as assessed by the vitamin A tolerance test. It acts presumably by removing bile acids from solution and so preventing the formation of a micellar phase in the small bowel lumen. This finding was predictable and confirms earlier preliminary studies (Longenecker and Basu, 1965).
Although cholestyramine is not very palatable, it is unlikely that delayed gastric emptying played a significant role since adding this agent to the test meal did not delay the peak rise in serum vitamin A. It is probable that cholestyramine also impairs the absorption of the other fat-soluble vitamins D, E, and K.
Direct studies of this question are lacking, but cases are on record in which cholestyramine appeared to cause osteomalacia (Heaton, Lever, and Barnard, 1972) and hypoprothrombinaemia (Gross and Brotman, 1970), which were reversed by treatment with vitamins D and K respectively.
Although the vitamin A tolerance test is crude and unphysiological, the results with cholestyramine show that it can be used to detect pharmacological binding of conjugated bile acids. The failure of lignin, even when given in an amount two or three times greater than the suggested daily dose (Thiffault et al, 1970; Eastwood and Girdwood, 1968), to have any significant effect on the rise in serum vitamin A suggests that in vivo lignin does not bind conjugated bile acids to an important extent.
Cholestyramine is a polybasic anion exchange resin which is believed to act mainly by exchanging chloride ions for bile acid ions, though a lesser non-electrostatic component has been postulated (Johns and Bates, 1970).
So this is a medicine and not a naturally occurring thing?
In the discussion on this blog post cholestyramine is mentioned 3 times I think. One person said it helped with HVA but that they thought it caused bad side effects. https://www.treasuredtips.com/how-i-got-vitamin-a-toxicity/
Quote from lil chick on December 13, 2019, 5:38 pmSo this is a medicine and not a naturally occurring thing?
@lc - yes, it's a synthetic substance, what they call a bile-acid sequestrant. It fell out of use when statins were introduced according to Wiki. The 1965 study got me wondering; why did they design it that way, with such a high-dose of VA? One thought was, there had to be a lot of lab-work going on before the introduction of retinyl palmitate into the US food-supply. I wonder if anyone ever wrote a book on the history behind that decision. The dose of 250,000 IU they used (presumably retinol - but possibly retinyl palmitate) seems large. At .3 mcg/IU, that's 75,000 mcg, which equals 75 milligrams. Maybe they didn't know that our homeostatic serum-level of VA is supposedly "maintained" at around 2.5 milligrams, which is 50-times less than that whopper-sized dose. Maybe the 'Dr. Strangelove's' of the medical world were worried about Russia poisoning our water-supplies with VA? Ha!! Or, alternatively, they were looking for an effective antidote for VA-toxicity for some reason? Or, they were wondering how those people using cholestyramine at the time would respond to the VA-fortification of foods? Like we used to say in Ann Arbor, so many pedestrians, so little time. Using it requires some caution as multiple papers describe, mostly due to it's effect on the absorption of fat-soluble vitamin intakes other than Va. It seems like one would need to keep a precise schedule of supplementation to counter that effect of cholestyramine's binding of bile, and the fat-soluble E, K, D along with it; if for some reason they were using it long-term, as appears to be the case for those with particular liver and bowel issues. The Shoemaker Protocol doctors only use it for a couple of months to clear biotoxins being recirculated along with bile conjugates, which is so similar to VA-excretion issues. That's what got me thinking, wow, what if a person could speed-up the VA-detox? I'd much rather catch excess VA being dumped by the liver in my bowel, than be pissing foam for months on end via some other pathway that I'm not even sure about. I'm assuming that's an effect of retinyl palmitate or some degraded VA-metabolite affecting surface-tension, but I don't know if anyone has ever attempted to measure or identify exactly what's going on there, or the actual path from serum to urine. Maybe Grant could help out on that as a reminder if he sees this and has looked into it further since his post that discussed the foamy-urine thing. Is there a test for retinoids in urine that's available to the public via their GP? It's funny that I go off into the weeds of complicated papers and don't spend equal time on learning the basics. I've been trying to track what makes the foam go away, lately, 10-percent of the time. I'm just about ready to eat a bunch of VA foods for a few weeks to see what happens. My symptomology is pretty minimal, so that's not an issue. I'm making the assumption that the liver is tougher than the kidneys when thinking about all of this. Speaking of kidneys, do a search at PubMed for "Oxylate and Cholestyramine" and you'll find some old papers showing a benefit there as well.
@romaine - yup, I actually asked SK the question over there. I started to wonder shortly after that, how SK could be blowing-through all those trials of exotic substances like pioglitazone and reporting rather extensive negative results in literally a matter of days for some of them. I also wondered why SK never came over here. Whatever on that side of it. Thinking back, I must have had the cholestyramine thing in the back of my mind, ever since I used it for mold-toxicity a few years ago. I don't doubt there's a down-side that one has to be aware of to use it, as I mentioned above. Since it induces the liver to create new bile acids, by interrupting enterohepatic recirculation, it's possible that the liver might "see" that as an opportunity to dump more VA, which would be good for us, as long as it gets excreted. From papers on bile acid metabolism, it also looks like they do some signaling of their own, so maybe other organs are messaged that the time is right to "let go". Since nobody's doing Cholestyramine-VA research anymore, at least that we're seeing, who knows how much more there is to it? I've only used it for a few days so far and my ongoing peripheral nerve-tingling of the last few months is noticeably diminishing. That symptom is likely mold-related, but it confirms the usefulness of it. N equals one. Another thing that's interesting between VA-toxicity and the Shoemaker Protocol is that a simple test they perform to confirm a CIRS diagnosis, is called Visual Contrast Sensitivity. They wait until the cholestyramine has removed enough toxins for the patient to pass the VCS before moving on to the next step of therapy. It could be a whole separate thing, a nerve-related myco-toxin effect, and not a VA-related one, but who knows, maybe it's a bit of both. Some of us noticed significant vision-improvement in the first few months of VA-deplete diets. It has to be that the body knows when it's OK to get rid of the inflammatory burden of excess VA. Overall, I'm operating on the assumption that a significant proportion of people who are VA-toxic, are also genetically-susceptible to the ill effects of mold and other biotoxins. According to Dr. Shoemaker's genetic testing (I think N = 8,000), it would mean potentially upwards of 24% of us could be facing both problems, depending on exposure to biotoxins. Symptom-wise, it could also mean that some portion of those who think they are VA-toxic are actually reacting to biotoxin exposure, and vice-versa. The mold doctors are fixing Fibro and ME/CFS, so it's food for thought.
Here's a up-to-date summary of the contraindications and usage parameters of bile-acid sequestrants like cholestyramine.
Res Exp Med (Berl). 1977 PMID:410086
Intestinal oxalate absorption. I. Absorption in vitro.
(it's hard to imagine they misspelled hyperoxaluria twice in the abstract, but I can't find the other spelling online)
Enteric hyperoxaluria and oxalate urolithiasis in patients with ileal resection seem to be caused by intestinal hyperabsorption of oxalate. The mechanism responsible for hyperabsorption of oxalate is not known. Intestinal transport of oxalic acid was therefore examined by an in vitro technique in rat intestine. Oxalic acid was absorbed by a mechanism of simple passive diffusion. The rate of absorption decreased from the colon to the duodenum (colon greater than ileum greater than jejunum greater than duodenum). Bile acids enhanced oxalic acid absorption in the large and small intestine and increased extracellular space; calcium, however, markedly decreased mucosal-serosal transport of oxalic acid. Cholestyramine known to reduce oxalate excretion in hyperuxaluria associated with ileal resection did not directly affect absorption of oxalic acid, but decreased the enhanced absorption of oxalic acid induced by bile acids. The results suggest that the beneficial therapeutic effect of cholestyramine in hyperuxaluria is rather mediated by its bile acid binding activity than by direct binding of oxalic acid.
Can J Gastroenterol. 2000 PMID:10655026
Update on primary biliary cirrhosis.
The Toronto Western Hospital, Toronto, Canada.
[please excuse my editorializing on this one, just feeling kind of spunky this morning, maybe it's the cholestyramine, ha]
The diagnosis of primary biliary cirrhosis (PBC) is most often made in the asymptomatic phase, sometimes before the development of abnormal liver biochemistry. The antimitochondrial antibody remains the predominant hallmark, although not all patients test positive, even when the most sensitive techniques are used. The etiology of PBC remains elusive; studies suggest that the interlobular bile duct destruction is immune based, and associated autoimmune diseases are common. [Hmmm, wonder why that is. Hey, Grant, can you spare 5-minutes and give them a hand on that one? Must be genetics, right?]
There are no surrogate markers that predict outcome in asymptomatic patients, whose chance of survival is less than that of age- and sex-matched populations but much better than the median survival of eight years in patients with symptomatic PBC.
Symptoms common in this disease are fatigue, pruritus [chronic itchy skin] and xanthelasma, as well as complications of portal hypertension and osteoporosis. [Xanthelasma is a sharply demarcated yellowish deposit of cholesterol underneath the skin. It usually occurs on or around the eyelids]
[Wow, does that has VA-toxicity written all over it, or what? I wonder how many 'uncommon' symptoms occur. Is it worth a search? Would they include some large-percentage of the multitude of "autoimmune" symptoms?]
Treatment includes symptomatic and preventive measures, as well as specific therapeutic measures. Immunosuppressive therapy has yielded disappointing results in the long term management of PBC, and the only therapy shown to improve survival is the hydrophobic dihydroxy bile acid ursodeoxycholic acid. Treatment at a dose of 13 to 15 mg/kg/day is optimal, given in separate doses or as a single dose at least 4 h from giving the oral anion exchange resin cholestyramine, which may be used to control pruritus.
[Hmmm, that sounds like a bit of a clue there. I'll bet that among the 23,278 papers on pruritis at PubMed, there's a mess of VA-toxicity evidence. I wonder how many threads need to be pulled, until the "emperor's sweater" is lying in a pile at his hairy feet.]
However, liver transplantation remains the only cure for this disease, [don'cha love that kinda med-speak?] and the best postoperative survival is seen in patients whose serum bilirubin does not exceed 180 micromol/L at the time of liver transplantation [10.5 mg/dL]. Recurrence takes place but is rarely symptomatic and does not deter from the benefits of transplantation.
[Think we'll see black-market organ-traffickers hiring blog-trolls to squelch the VA-truth movement at some point?, or will big pharma beat them to it, ha. What if all it took to avoid these expensive and dangerous consequences was some simple, effective, short-term clearance of VA a couple of times a year? Cheap insurance for sure. We could teach it in grade-school.]
Added a few things at the end of the 5:07am post and a link to a paper with contraindications re: cholestyramine.
Here's one that says cholestyramine was approved for use in the United States in 1973.
https://www.ncbi.nlm.nih.gov/books/NBK548431/
Is it a coincidence that it is used to this day for sweeping over-dosed drugs out of the system? The 1965 paper, cited at the top of this thread, reported how it did the same thing for a mega-dose of Vitamin A, given to "normal" men in the study. Interesting timing, since VA fortification of foods began in 1973, if I recall that year correctly from one of Grant's books covering the subject. Could the authorities have been anticipating a potential mistake in the process of adding VA to milk? Every process has critical control points, and hazard analysis was in use. Did they figure they needed an antidote waiting on the shelf, and being produced in quantity, in the event something really bad happened; like a big overdose of VA added to a large batch of milk? That might have put the kibosh on things if it ever occurred. Any ideas for a good fiction title?
https://www.survivingmold.com/docs/ESSAY_on_CIRS_Treatment_Whitcomb_V2.pdf
Here's a biotoxin-removal trained M.D. in Wisconsin who gives a very detailed review of the protocol.
His statements starting on page 49 are very interesting. Here's a snip:
Adequate standards of remediation are another problem many patients frequently encounter. The real estate market will adjust and drive stricter controls. The current method of most so-called mold experts is to sample for spores and do a cursory walk through. Anyone with more than 6 months of CIRS experience will find dismayed clients who have engaged such experts and now are confronted with abnormal lab tests, continued illness and an ERMI score of 12. A home with such a score will soon be unsellable, once the SAIIE program has been implemented a few times in the courts and shown to be repeatedly valid.
comment: ERMI is a test where you swab surfaces and vacuum a bit of carpeting and send the kit back to the lab for genetic testing that shows the worst 36 types of mold/fungus/bacteria found in Water Damaged Buildings, and it quantifies each, and gives a final score on how bad the overall situation is in the home or building. It only costs $125 last I looked. I'm ordering a kit next week to use at my MIL's care facility. They did a quick air sample and said everything's fine, but six crews are working every day tearing out walls, people are being relocated, the vacuum truck is out back, so, there's no doubt they're stirring up literally quintillions of spore fragments carrying mycotoxins. That's why so many of her fellow residents are getting so sick. She's probably among the 76% who only get watery eyes and sniffles and coughs from exposure, which is fortunate.
People with copper toxicity use cholestyramine because copper is excreted through the gallbladder. Some people have to remove the gallbladder on copper detox. Copper accumulates in the bile and damages the function of the gallbladder. I saved my gallbladder with two coffee enemas daily for three years. I have read about cholesteramine a few years ago but is a prescription drug.
Why eating beans on low VA diet may be so useful?
The soluble fiber in beans binds the bile and carries out forcing the liver to produce new, clean bile. This will eventually decongest the gallbladder and liver. Enteropathic circulation is interrupted.
It's not a study but the article is interesting:
http://www.karenhurd.com/why-beans-dont-cause-gas.html
"Beans are a bile magnet. Bile and beans have an incredible affinity or liking for one another. They make a sort of chemical bond that is almost impossible to break. Most of the other foods with which bile binds in the intestinal tract are foods with which the bile makes temporary bonds. But when the bean enters, the bile leaves all other foods behind and rushes to make a permanent bond with the bean.
Now you must know something else about bile. This digestive fluid that the liver makes is released into the duodenum (the first part of the small intestine). It travels to the last part of the small intestine, doing its digestive work, and when it reaches the terminal part of the ileum, bile is reabsorbed and returns to the liver! How much bile returns? Ninety to ninety-five percent!
Please understand that bile is the trash truck for the liver. The liver cleans the blood stream of fat soluble waste and deposits it in the bile. Hopefully the bile will make it past the terminal part of the ileum, get into the large intestine and make its way on out into the toilet. However, that is not what is happening in the normal American's digestive tract. The bile returns to the liver with its garbage in tow!
Unless the bile meets up with the mighty bean.
The soluble fiber in a bean binds tightly with the bile. Interestingly, soluble fiber has a very unique characteristic. It cannot cross the intestinal barrier anywhere. Period.
So if the bile is bound to the soluble fiber in a bond that cannot be broken, when the bile tries to reabsorb and return to the liver, it will find that it cannot, because the soluble fiber will not allow that passage. Therefore, the bile with all of its toxic liver trash will be tossed into the toilet in the form of a bowel movement.
What if the bile is not tossed into the toilet? What happens then? When it returns to the liver, full of trash, the liver is waiting with more trash. The liver is constantly filtering the blood stream. Just because the bile is running around in the gastro-intestinal tract doesn’t mean the liver stops filtering blood. So the returning bile is loaded down with more toxic waste as it passes through the liver again. So the cycle goes, until the recycling bile is so loaded down with garbage that it can no longer do an efficient job in digesting the foods in the intestinal tract. Instead of digesting the foods, the bile ferments the foods. Fermentation always causes gas. Now we have a problem with flatulence.
The answer is to get rid of the nasty bile. If we had new, fresh clean bile then the foods would not be fermented but digested properly, and no gas would form. How can we get rid of the nasty bile? Eat beans!"
https://www.sciencedirect.com/science/article/pii/S0308814602001929
Considering cholestyramine as 100 bound, the relative in vitro bile acid bindings for the soy protein, pinto beans, black beans and wheat gluten, on equal protein basis, were 17, 23, 30 and 12%, respectively. - black beans with 30% are the best.
https://www.ncbi.nlm.nih.gov/pubmed/9215540
"These data suggest that legume consumption lower LDL cholesterol by partially interrupting the enterohepatic circulation of bile acids and increases cholesterol saturation of bile by increasing hepatic secretion of cholesterol."
https://www.healthline.com/nutrition/foods-high-in-soluble-fiber
Black beans and lima beans contain the highest amount of soluble fiber.
Clearing of metabolic waste via enterohepatic recirculation:
http://www.karenhurd.com/uploads/1/0/8/8/108872535/enterohepaticrecirculation.pdf
https://experiencelife.com/article/fiber-why-it-matters-more-than-you-think/
“Estrogen is made from fats. It’s an example of a fat-soluble waste that is cleared by the liver,” Hurd explains. “But if you don’t ➺ properly eliminate polluted bile, that estrogen goes back into your bloodstream, and the estrogen levels in your bloodstream mount,” she continues. “Then those estrogens can stimulate the growth of abnormal cells, which can lead to the growth of cancerous cells. And, then we have estrogen-type cancers, such as breast cancer, uterine cancer, fallopian tube cancer, ovarian cancer and vaginal cancer. Why are these cancers being stimulated? Because estrogen is stimulating their growth. Why do we have so much estrogen? Because we never threw it away via elimination when we had the chance.”
The encouraging news, says Hurd, is that one of the most promising ways to help end this vicious cycle — and to eliminate many painful and frustrating conditions whose symptoms are commonly treated with drugs or surgery — is simply to eat an ample supply of fiber-rich foods."
"Moreover, Hurd explains, the trashier and sludgier your bile becomes, the more acidic and irritating it becomes to your tissues. This can lead to a host of problems, including swelling and inflammation in your colon, duodenum and all the way up in your esophagus.
"If we don’t eat enough soluble fiber, our bile, instead of being ushered out of the body and then replaced with fresh bile produced by the liver, is repeatedly recirculated in our system. In the process, it becomes more concentrated with toxins, which, in turn, can lead to all sorts of inflammatory diseases such as gallbladder disease, intestinal inflammation, and even skin conditions like acne, eczema and psoriasis."
“Inflammation in the esophagus includes all kinds of things like Barrett’s esophagus, where you have this thickening of the opening, so things feel like they get stuck in your throat,” says Hurd.
Sludgy bile causes not only various diseases of the gallbladder, explains Hurd, but also tertiary skin conditions, such as acne, eczema and psoriasis, which depend upon a properly functioning gallbladder to help bile break down into little pieces, or emulsify, the fats. The results, says Hurd, are predictable: “If you don’t have the right types of fats in your skin, you’ll have skin problems.”
Worse, if the fats are not successfully emulsified via the bile, the body falls back on a second, less desirable chemical process capable of breaking these long-chain fatty acids into usable short-chain fatty acids. That process is called oxidation, and it can lead both to premature aging and to inflammatory diseases of all kinds, including heart disease."
Therefore, coffee enemas are so successful:
https://drjaydavidson.com/coffee-enema-missing-links/
"Bile: A green or yellow fluid produced in the liver and stored in the gallbladder, which helps your body emulsify and digest fats. Bile also helps you safely remove the waste in your body. Inside bile is cholesterol, electrolytes, toxins, bile salts, and more. During a coffee enema, old bile is flushed out, causing your body to produce new, clean bile."