Cholestyramine How It Works in CIRS

Why use it for Chronic Inflammatory Response Syndrome (CIRS) due to biotoxin damage?
People with CIRS are unable to remove the mold toxins from their body due to a genetic varient. The immune system of the CIRS patient is unable to remove these toxins and is the instigator of an inflammatory response. Cholestyramine binds to biotoxins that cause CIRS allowing them to be eliminated via the feces. These biotoxins must be removed from the body of the person with CIRS or they will never get well. Once they are removed the inflammatory process that they started then needs to be addressed. The use of Cholestyramine is considered “off-label.” It is legal to give medications off label and most physicians give medications off label. You need to know that your prescription is being used off-label.

How does Cholestyramine work?
Cholestyramine is not absorbed. If it is not taken with food it binds to bile salts, cholesterol and biotoxins in the small intestine. They are not able to be absorbed and are excreted with the cholestyramine in the stool. Overtime the biotoxins are removed from the bodies tissues as long as there is no re-exposure. Cholestyramine only removes the biotoxins from the body. It does not necessarily correct inflammatory problems or other cascading events that those biotoxins created. Additional work usually needs to be done to correct these issues.

Details on How Cholestyramine Works:
It is used as a bile acid sequestrant. Since it is a strong ion exchange resin, it can exchange it’s choloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. It removes bile acids from the body by forming insoluble complexes with the bile acids. The whole thing is then removed in the feces. Usually, the bile and things attached to the bile acids would be picked back up from the intestines as part of the enterohepatic circulation. This is a continual recycling of bile and any biotoxins in the bile. However, when the bile acids are bound to Cholestyramine, the Cholestyramine and the bound bile acids/biotoxins are removed via the feces.

Besides binding the bile acids, cholestyramine has been shown to also bind some free mycotoxins. For instance it binds a significant amount of Ochratoxin A when given as a contaminant to rats in their diet. The cholestyramine showed a greater affinity for the ochratoxin than the bile salts taurodeoxycholate and taurocholate. (Bile salts are bile acids that are conjugated to usually taurine or glycine amino acids.)

How the enterohepatic circulation is involved in circulating biotoxins.
Bile acids are made in the liver cells, from cholesterol. CYP7A1 regulates the rate-limiting step in the bile biosyntheitc pathway. The bile acids are secreted into the gallbladder via the bile acid exporter pump (BSEP)(for storage and concentration). During normal digestion, bile, with the bile acids included is secreted from the liver and gall bladder into the intestines. Most of the bile acids are usually re-absorbed in the part of the intestines called the terminal ileum, via the apical sodium-dependent bile acid transporter (ASBT). They are transported back to the liver in the portal blood to be re-excreted into the bile again. The movement of the bile from the liver into the intestines and its return back to the liver is called the enterohepatic circulation. Biotoxins bound to the bile acids in the bile are re-circulated back to the liver with the bile acids. If the bile acid/biotoxin mix becomes bound by a bile acid sequestrant such as Cholestyramine while still in the intestines, the mix is not able to be reabsorbed by the intestines.

You might wonder why can’t the mycotoxin/bile acid/cholestyramine mix be re-absorbed. Cholestyramine is not able to be absorbed by the intestines, so anything attached to cholestyramine is not going to be absorbed, even if it usually would get re-absorbed. Since Cholestyramine is strongly bound to the the bile acids and they are bound to the mycotoxins, the whole lot is lost in the feces. Remember, additionally some types of toxins will bind directly to the Cholestyramine also.

What else has been used to bind biotoxins?
Welchol: Welchol is only 25% as effective compared to Cholestyramine according to Dr. Ritchie Shoemaker, the pioneer in CIRS treatment. Dr. Shoemaker uses this as an alternative to Cholestyramine if his patients can not tolerate Cholestyramine. However, treatment takes much longer.
Although Dr. Shoemaker claims other agents are not able to provide similar clinical results in his 10,000 patients he has treated for CIRS due to water-damaged buildings, I am listing them here and you can go to their links (soon available) to get additional details on them. Some practitioners use these agents and claim these agents work to bind biotoxins but none of them have the clinical research on these agents as biotoxin sequestrants to compare with Dr. Shoemaker’s research and I have not yet been able to verify any of these agents work nearly as well. I find there is some research invitro as well as some animal studies and I will be providing links to that data in the future.
Charcoal
Bentonite Clay
Chlorella
Celite
Zeolite
Probiotics
Tannins
Water soluble fibers

Research with a cholestyramine product called Coestipol showed if you mixed it 50% (2.5 g of psyllium and 2.5 g colestipol) with Psyllium seed was able to reduce cholesterol more significantly than colestipol alone or psyllium alone. It also reduced gastrointestinal irritation from the cholestyramine.
http://www.ncbi.nlm.nih.gov/pubmed/7661492
This leads me to believe that we might be able to use psyllium or other water soluble fibers to mix 50/50 with cholestyramine for biotoxin removal. However, I do not know how much of this action is due to an increased synthesis of bile acids from cholesterol. What do I mean? Well, here are the mechanisms of action of cholestyramine and how it effects cholesterol:

Mechanism of Action:

Bile acids are synthesized by the liver by oxidation from cholesterol.
These drugs bind to bile acids in the intestinal lumen & prevent their normal reabsorption. The resin itself (cholestryamine) is not absorbed from the GI tract.
The fecal loss of bile acids results in an increased hepatic synthesis of bile acids from cholesterol, resulting in a reduction in hepatic cholesterol content.
The fall in hepatic cholesterol content results in an up-regulation of LDL receptors.
The upregulation of hepatic LDL receptors increases the removal of LDL and intermediate-density lipoprotein cholesterol (IDL) from plasma.

In vitro and in vivo studies to assess the effectiveness of cholestyramine as a binding agent for fumonisins.

Several adsorbent materials were tested at I mg/ml for their in vitro capacity to adsorb fumonisin B1(FB1) from aqueous solutions. Cholestyramine showed the best adsorption capacity (85% from a solution containing 200 microg/ml FB1) followed by activated carbon (62% FB1). Bentonite adsorbed only 12% of the toxin from a solution containing 13 microg/ml FB1, while celite was not effective even at the lowest tested FB1 concentration (3.2 microg/ml). Cholestyramine was tested in vivo to evaluate its capacity to reduce the bioavailability of fumonisins (FBs) in rats fed diet contaminated with toxigenic Fusarium verticillioides culture material. Rats were exposed for one week to FBs-free diet, FBs-contaminated diet containing 6 or 20 microg/g FB1 + FB2 and the same FBs-contaminated diet added of 20 mg/g cholestyramine. The increase of sphinganine/sphingosine (SA/SO) ratio in urine and kidney of treated rats was used as specific and sensitive biomarker of fumonisin exposure. The addition of cholestyramine to the FBs-contaminated diets consistently reduced the effect of FBs by reducing significantly (P < 0.05) both urinary and renal SA/SO ratios.

J Food Prot. 1999 Dec;62(12):1461-5.
Cholestyramine protection against ochratoxin A toxicity: role of ochratoxin A sorption by the resin and bile acid enterohepatic circulation.
Kerkadi A1, Barriault C, Marquardt RR, Frohlich AA, Yousef IM, Zhu XX, Tuchweber B.

Abstract
We have shown that the addition of cholestyramine (CHA, a resin known to bind bile salts in the gastrointestinal tract) to ochratoxin A (OTA)-contaminated rat diets reduced plasma levels of the toxin and prevented OTA-induced nephrotoxicity. To elucidate the mechanism of action of CHA, we carried out in vitro experiments to determine whether the resin may bind the toxin. For comparative purposes, binding of bile salts to the resin was also examined. Results showed that CHA binds both OTA and bile salts (taurodeoxycholate [TDC] and taurocholate [TCA]). Also, CHA showed greater affinity for OTA and TDC than for TCA. At 1 mM concentration, 96% of OTA and 80% of TDC were bound to the resin, while for TCA binding was only 50%. However, saturation of the resin was reached at higher levels with bile acids compared to OTA (3.67 mmol/g resin for TCA and 3.71 mmol/g resin for TDC versus 2.85 mmol/g resin for OTA). To characterize the nature of the binding of the toxin to CHA, NaCl (0 to 200 mM) was added to a fixed amount of OTA or bile acids. As expected, TCA absorption was decreased by the addition of NaCl (<50 mM), indicating electrostatic binding. However, OTA and TDC sorption was decreased only at high concentrations of NaCl (>150 mM), suggesting a stronger binding to the resin than that shown with TCA. Sequential competitive studies demonstrated that CHA binds more OTA than TCA. The results of the in vivo study show the role of bile salts in OTA absorption. The toxin's plasma levels at 1 and 3 h after a single oral dose of OTA were significantly decreased in bile salt-depleted rats compared to the control. Thus, the alteration of the bile salt biliary pool and OTA enterohepatic circulation may be an additional mechanism of action of the resin against mycotoxin toxicity.
PMID: 10606152 [PubMed - indexed for MEDLINE]

Abstract
The extensive use of adsorbents in the livestock industry has led to the introduction of a wide range of new products on the market, most of them claiming high in vitro mycotoxin adsorption capacity. However, adsorbents that may appear effective in vitro do not necessarily retain their efficacy when tested in vivo. Studies performed in our laboratory during the past few years aiming to evaluate the efficacy of various adsorbent materials in binding Fusarium mycotoxins are reported. Adsorption experiments were performed in in vitro screening tests for Fusarium mycotoxins at different pHs; by in vivo tests using the increase of the sphinganine to sphingosine ratio in rat urine and tissues as a biomarker of fumonisin exposure; and by a dynamic, computer-controlled, gastrointestinal model simulating the gastrointestinal tract of healthy pigs. Most of the commercially available mycotoxin-binders failed in sequestering in vitro Fusarium mycotoxins. Only for a small number of adsorbent materials was the ability to bind more than one mycotoxin demonstrated. Cholestyramine was proven to be an effective binder for fumonisins and zearalenone in vitro, which was confirmed for zearalenone in experiments using a dynamic gastrointestinal model and for fumonisins in in vivo experiments. No adsorbent materials, with the exception of activated carbon, showed relevant ability in binding deoxynivalenol and nivalenol. The in vitro efficacy of activated carbon toward fumonisins was not confirmed in vivo by the biomarker assay. The dynamic gastrointestinal model was a reliable tool to study the effectiveness of adsorbent materials in reducing the bioaccessibility of Fusarium mycotoxins, as an alternative to the more difficult and time-consuming studies with domestic livestock.
PMID: 16019808 [PubMed - indexed for MEDLINE

J Med Microbiol. 1979 Nov;12(4):487-96.
The ability of cholestyramine resin and other adsorbents to bind Escherichia coli enterotoxins.
Mullan NA, Burgess MN, Bywater RJ, Newsome PM.
Several adsorbent materials were evaluated for their ability to bind Escherichia coli enterotoxins. Cholestyramine, a strong anion-exchange resin, bound the heat-labile and the heat-stable types of enterotoxin and reduced significantly their effects ...

Psyllium is a soluble gel-forming fiber that has been shown to bind to the bile acids in the gut and prevent their normal reabsorption, sim

If you found this information helpful, I would appreciate your support in keeping the site going. If you would like to donate to my work, I thank you in advance and send you my deep felt gratitude.

Cholestyramine to Treat CIRS & How it Works
This page contains educational material about Cholestyramine. This information is for educational purposes only. Nothing in this text is intended to serve as medical advice. All medical decisions should be made only with the guidance of your own personal medical authority. I am doing my best to get this data up quickly and correctly. If you find errors in this data, please let me know. The cholestyramine pages on this site: Cholestyramine: What is It Cholestyramine: Why is it used in CIRS & How It Works Cholestyramine: How to Take It/Safety Cholestyramine: Alternatives - Research on Biotoxin Binders
Why use it for Chronic Inflammatory Response Syndrome (CIRS) due to biotoxin damage? People with CIRS are unable to remove the mold toxins from their body due to a genetic varient. The immune system of the CIRS patient is unable to remove these toxins and is the instigator of an inflammatory response. Cholestyramine binds to biotoxins that cause CIRS allowing them to be eliminated via the feces. These biotoxins must be removed from the body of the person with CIRS or they will never get well. Once they are removed the inflammatory process that they started then needs to be addressed. The use of Cholestyramine is considered “off-label.” It is legal to give medications off label and most physicians give medications off label. You need to know that your prescription is being used off-label. How does Cholestyramine work? Cholestyramine is not absorbed. If it is not taken with food it binds to bile salts, cholesterol and biotoxins in the small intestine. They are not able to be absorbed and are excreted with the cholestyramine in the stool. Overtime the biotoxins are removed from the bodies tissues as long as there is no re-exposure. Cholestyramine only removes the biotoxins from the body. It does not necessarily correct inflammatory problems or other cascading events that those biotoxins created. Additional work usually needs to be done to correct these issues. Details on How Cholestyramine Works: It is used as a bile acid sequestrant. Since it is a strong ion exchange resin, it can exchange it’s choloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. It removes bile acids from the body by forming insoluble complexes with the bile acids. The whole thing is then removed in the feces. Usually, the bile and things attached to the bile acids would be picked back up from the intestines as part of the enterohepatic circulation. This is a continual recycling of bile and any biotoxins in the bile. However, when the bile acids are bound to Cholestyramine, the Cholestyramine and the bound bile acids/biotoxins are removed via the feces. Besides binding the bile acids, cholestyramine has been shown to also bind some free mycotoxins. For instance it binds a significant amount of Ochratoxin A when given as a contaminant to rats in their diet. The cholestyramine showed a greater affinity for the ochratoxin than the bile salts taurodeoxycholate and taurocholate. (Bile salts are bile acids that are conjugated to usually taurine or glycine amino acids.) How the enterohepatic circulation is involved in circulating biotoxins. Bile acids are made in the liver cells, from cholesterol. CYP7A1 regulates the rate-limiting step in the bile biosyntheitc pathway. The bile acids are secreted into the gallbladder via the bile acid exporter pump (BSEP)(for storage and concentration). During normal digestion, bile, with the bile acids included is secreted from the liver and gall bladder into the intestines. Most of the bile acids are usually re-absorbed in the part of the intestines called the terminal ileum, via the apical sodium-dependent bile acid transporter (ASBT). They are transported back to the liver in the portal blood to be re-excreted into the bile again. The movement of the bile from the liver into the intestines and its return back to the liver is called the enterohepatic circulation. Biotoxins bound to the bile acids in the bile are re-circulated back to the liver with the bile acids. If the bile acid/biotoxin mix becomes bound by a bile acid sequestrant such as Cholestyramine while still in the intestines, the mix is not able to be reabsorbed by the intestines. You might wonder why can’t the mycotoxin/bile acid/cholestyramine mix be re-absorbed. Cholestyramine is not able to be absorbed by the intestines, so anything attached to cholestyramine is not going to be absorbed, even if it usually would get re-absorbed. Since Cholestyramine is strongly bound to the the bile acids and they are bound to the mycotoxins, the whole lot is lost in the feces. Remember, additionally some types of toxins will bind directly to the Cholestyramine also. What else has been used to bind biotoxins? Welchol: Welchol is only 25% as effective compared to Cholestyramine according to Dr. Ritchie Shoemaker, the pioneer in CIRS treatment. Dr. Shoemaker uses this as an alternative to Cholestyramine if his patients can not tolerate Cholestyramine. However, treatment takes much longer. Although Dr. Shoemaker claims other agents are not able to provide similar clinical results in his 10,000 patients he has treated for CIRS due to water-damaged buildings, I am listing them here and you can go to their links (soon available) to get additional details on them. Some practitioners use these agents and claim these agents work to bind biotoxins but none of them have the clinical research on these agents as biotoxin sequestrants to compare with Dr. Shoemaker’s research and I have not yet been able to verify any of these agents work nearly as well. I find there is some research invitro as well as some animal studies and I will be providing links to that data in the future. Charcoal Bentonite Clay Chlorella Celite Zeolite Probiotics Tannins Water soluble fibers I suggest you take a look at the biotoxin removers link. I do want to point out one interesting research article: Research with a cholestyramine product called Coestipol showed if you mixed it 50% (2.5 g of psyllium and 2.5 g colestipol) with Psyllium seed was able to reduce cholesterol more significantly than colestipol alone or psyllium alone. It also reduced gastrointestinal irritation from the cholestyramine. http://www.ncbi.nlm.nih.gov/pubmed/7661492 This leads me to believe that we might be able to use psyllium or other water soluble fibers to mix 50/50 with cholestyramine for biotoxin removal. However, I do not know how much of this action is due to an increased synthesis of bile acids from cholesterol. What do I mean? Well, here are the mechanisms of action of cholestyramine and how it effects cholesterol: Mechanism of Action: Bile acids are synthesized by the liver by oxidation from cholesterol. These drugs bind to bile acids in the intestinal lumen & prevent their normal reabsorption. The resin itself (cholestryamine) is not absorbed from the GI tract. The fecal loss of bile acids results in an increased hepatic synthesis of bile acids from cholesterol, resulting in a reduction in hepatic cholesterol content. The fall in hepatic cholesterol content results in an up-regulation of LDL receptors. The upregulation of hepatic LDL receptors increases the removal of LDL and intermediate-density lipoprotein cholesterol (IDL) from plasma. Some Research on Use of Cholestyramine as bile sequestrant Mycopathologia. 2001;151(3):147-53. In vitro and in vivo studies to assess the effectiveness of cholestyramine as a binding agent for fumonisins. Solfrizzo M, Visconti A, Avantaggiato G, Torres A, Chulze S. Several adsorbent materials were tested at I mg/ml for their in vitro capacity to adsorb fumonisin B1(FB1) from aqueous solutions. Cholestyramine showed the best adsorption capacity (85% from a solution containing 200 microg/ml FB1) followed by activated carbon (62% FB1). Bentonite adsorbed only 12% of the toxin from a solution containing 13 microg/ml FB1, while celite was not effective even at the lowest tested FB1 concentration (3.2 microg/ml). Cholestyramine was tested in vivo to evaluate its capacity to reduce the bioavailability of fumonisins (FBs) in rats fed diet contaminated with toxigenic Fusarium verticillioides culture material. Rats were exposed for one week to FBs-free diet, FBs-contaminated diet containing 6 or 20 microg/g FB1 + FB2 and the same FBs-contaminated diet added of 20 mg/g cholestyramine. The increase of sphinganine/sphingosine (SA/SO) ratio in urine and kidney of treated rats was used as specific and sensitive biomarker of fumonisin exposure. The addition of cholestyramine to the FBs-contaminated diets consistently reduced the effect of FBs by reducing significantly (P < 0.05) both urinary and renal SA/SO ratios. J Food Prot. 1999 Dec;62(12):1461-5. Cholestyramine protection against ochratoxin A toxicity: role of ochratoxin A sorption by the resin and bile acid enterohepatic circulation. Kerkadi A1, Barriault C, Marquardt RR, Frohlich AA, Yousef IM, Zhu XX, Tuchweber B. Abstract We have shown that the addition of cholestyramine (CHA, a resin known to bind bile salts in the gastrointestinal tract) to ochratoxin A (OTA)-contaminated rat diets reduced plasma levels of the toxin and prevented OTA-induced nephrotoxicity. To elucidate the mechanism of action of CHA, we carried out in vitro experiments to determine whether the resin may bind the toxin. For comparative purposes, binding of bile salts to the resin was also examined. Results showed that CHA binds both OTA and bile salts (taurodeoxycholate [TDC] and taurocholate [TCA]). Also, CHA showed greater affinity for OTA and TDC than for TCA. At 1 mM concentration, 96% of OTA and 80% of TDC were bound to the resin, while for TCA binding was only 50%. However, saturation of the resin was reached at higher levels with bile acids compared to OTA (3.67 mmol/g resin for TCA and 3.71 mmol/g resin for TDC versus 2.85 mmol/g resin for OTA). To characterize the nature of the binding of the toxin to CHA, NaCl (0 to 200 mM) was added to a fixed amount of OTA or bile acids. As expected, TCA absorption was decreased by the addition of NaCl (<50 mM), indicating electrostatic binding. However, OTA and TDC sorption was decreased only at high concentrations of NaCl (>150 mM), suggesting a stronger binding to the resin than that shown with TCA. Sequential competitive studies demonstrated that CHA binds more OTA than TCA. The results of the in vivo study show the role of bile salts in OTA absorption. The toxin's plasma levels at 1 and 3 h after a single oral dose of OTA were significantly decreased in bile salt-depleted rats compared to the control. Thus, the alteration of the bile salt biliary pool and OTA enterohepatic circulation may be an additional mechanism of action of the resin against mycotoxin toxicity. PMID: 10606152 [PubMed - indexed for MEDLINE] Food Addit Contam. 2005 Apr;22(4):379-88. Recent advances on the use of adsorbent materials for detoxification of Fusarium mycotoxins. Avantaggiato G1, Solfrizzo M, Visconti A. Abstract The extensive use of adsorbents in the livestock industry has led to the introduction of a wide range of new products on the market, most of them claiming high in vitro mycotoxin adsorption capacity. However, adsorbents that may appear effective in vitro do not necessarily retain their efficacy when tested in vivo. Studies performed in our laboratory during the past few years aiming to evaluate the efficacy of various adsorbent materials in binding Fusarium mycotoxins are reported. Adsorption experiments were performed in in vitro screening tests for Fusarium mycotoxins at different pHs; by in vivo tests using the increase of the sphinganine to sphingosine ratio in rat urine and tissues as a biomarker of fumonisin exposure; and by a dynamic, computer-controlled, gastrointestinal model simulating the gastrointestinal tract of healthy pigs. Most of the commercially available mycotoxin-binders failed in sequestering in vitro Fusarium mycotoxins. Only for a small number of adsorbent materials was the ability to bind more than one mycotoxin demonstrated. Cholestyramine was proven to be an effective binder for fumonisins and zearalenone in vitro, which was confirmed for zearalenone in experiments using a dynamic gastrointestinal model and for fumonisins in in vivo experiments. No adsorbent materials, with the exception of activated carbon, showed relevant ability in binding deoxynivalenol and nivalenol. The in vitro efficacy of activated carbon toward fumonisins was not confirmed in vivo by the biomarker assay. The dynamic gastrointestinal model was a reliable tool to study the effectiveness of adsorbent materials in reducing the bioaccessibility of Fusarium mycotoxins, as an alternative to the more difficult and time-consuming studies with domestic livestock. PMID: 16019808 [PubMed - indexed for MEDLINE J Med Microbiol. 1979 Nov;12(4):487-96. The ability of cholestyramine resin and other adsorbents to bind Escherichia coli enterotoxins. Mullan NA, Burgess MN, Bywater RJ, Newsome PM. Several adsorbent materials were evaluated for their ability to bind Escherichia coli enterotoxins. Cholestyramine, a strong anion-exchange resin, bound the heat-labile and the heat-stable types of enterotoxin and reduced significantly their effects ... Psyllium is a soluble gel-forming fiber that has been shown to bind to the bile acids in the gut and prevent their normal reabsorption, sim ilar to the bile acid sequestrant drugs. http://www.ncbi.nlm.nih.gov/pubmed/17438377 If you found this information helpful, I would appreciate your support in keeping the site going. If you would like to donate to my work, I thank you in advance and send you my deep felt gratitude.
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