Cholestyramine:

Protocol for taking cholestyramine for biotoxin illness

•  Take on an empty stomach. Take 4 grams of pure cholestyramine or 9 grams of Questran, or as prescribed.

•  Mix with 6 oz of water or apple juice and drink. Follow with another 6 oz of water or more.

•  Wait 30 minutes and then eat your meal.

•  Take Medications 30 minutes before cholestyramine or 2 hours after.

•  If you forget the cholestyramine and eat, wait for 1 hour before taking the next dose of cholestyramine.

•  Take 4 doses of cholestyramine per day

•  If you have indigestion, reflux, or constipation see information below.

What is Cholestyramine?

Quick answer: Cholestyramine is a medication that has largely been used in the past to lower elevated levels of cholesterol.

Detailed answer: Cholestyramine is a bile acid sequestrant, like colestipol and colesevelam. These molecules are positively charged non-digestible resins that bind to bile acids in the intestine to form an insoluble complex, which is excreted in the feces. They are used mainly for the treatment of high cholesterol levels, in patients not responding to dietary treatment as well as a second line-treatment for pruritus associated with cholestatic disease, in patients with incomplete biliary obstruction. Several data indicate that modulation of bile acid homeostasis has a good clinical effect in managing diabetes mellitus and the diarrhea from bile acid malabsorption.Cholestyramine is an anion binding resin that has a quaternary ammonium side chain that creates a localized, net positive charge.  The functional group of the anion exchange resin is a quaternary ammonium group attached to an inert styrene-divinylbenzene copolymer.

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.

How the enterohepatic circulation is involved in circulating biotoxins.
During normal digestion, bile acids are secreted into the intestines. A major portion of the bile acids are absorbed from the intestinal tract and returned to the liver via the enterohepatic circulation. Biotoxins bound to the bile acids are re-circulated back to the liver with the bile acids. If the bile acid/biotoxin mix is bound by a sequestrant such as Cholestyramine, they are then propelled out of the body as part of the feces. Cholestyramine is not absorbed into the body, so all of it is removed in the feces and anything attached to it (such as biotoxins) is removed with it.

When is Cholestyramine used by Practitioners?
In the past it was used to treat high cholesterol levels. In this regard, Cholestyramine has largely been replaced by statins. It is still used in people who can not take statins.
Additionally, it is used to treat pruitis (itchy skin) that occurs during liver failure or partial biliary obstruction. It is also used to treat diarrhea due to bile acid malabsorption.
One use that is becoming more common-place is its use to adsorb toxins A and B produced by Clostridium difficile biotoxins.
It is used in a “wash out” procedure in patients taking leflunomide or teriflunomide to aid drug elimination when the drug needs to be discontinued due to severe side effects.
The use of Cholestyramine is an “off label” use. This means that it has not been studied  for its use for CIRS. However, the FDA in 1999 did ruyle that there was not reason to expect an increased risk to a person’s health from us of Cholestyramine in patients who have biotoxin illness such as from ciguatera, mold, pfiesteria, or post-lyme syndrome compared to people who do not have these illnesses. Practitioners can prescribe Cholestyrmine under this FDA exemption.

Why use it for Chronic Inflammatory Response Syndrome (CIRS) due to biotoxin damage?
People with CIRS are unable to remove the biotoxins from their body as well as other people. 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 is Cholestyramine used?
To bind biotoxins, 4 grams of Cholestyramine is taken 4 times per day. (Dosing for children or people under 120# needs to be altered accordingly.) Cholestyrmine products on the market usually mix Cholestyramine with other ingredients to make it taste better and mix into water better or look more appealing to the user. These products are often in 9 gram doses (4 grams of cholestyramine and 5 grams of additives.) However, some folks with biotoxin illness are unable to take Cholestyramine with these additives and their practitioner has a compounding pharmacist provide Cholestyramine without these extra ingredients since a pure cholestyramine is unavailable on the open market.
 
It is taken 30 minutes prior to a meal. Make sure the meal has at least 1 teaspoon oil/fat in it. Could be one egg or a pat of butter/coconut oil etc. This will get the bile going at the correct time to meet up with the Cholestyramine. Take it 30 minutes before breakfast, lunch and dinner and then at bed. Drink a minimum of 12 oz of water with it, but better to drink more if you are able. This helps decrease constipation from the Cholestyramine. For people who are concerned about constipation or having a reaction from pulling out the biotoxins, start slow at 1 gram (1/4 dose) 2 times per day on day one. If no problems increase to 2 grams (1/2 dose) the next day for two times that day, then 3 grams or ¾ dose day 3 for two doses that day and the full dose on day 4 but still only two times. Then on day 5 go to using the full dose of 4 grams Cholestyramine 3 times per day, 30 minutes before meals and on the 6th day 4 times, with the last dose before bed. Four doses each day is best, but for some people due to drug regimens or other reasons they can only take it three times per day.  

If you eat first, wait at least 1 hour before taking your next dose of Cholestyramine.

When Can I take other medications:
Take all medications one hour prior to taking the Cholestyramine or two hours after taking cholestyramine. Do not take any food with them unless necessary for the medicine and then only what is necessary and try to stay away from eating fatty foods if possible.

How Long is it used?
It is usually used until a person’s Visual Contrast Sensitivity test normalizes. (Link to test here. It is generally prescribed for one month. This allows the body to completely dump all the biotoxins out of the body via the bile. Usually, people report feeling better the first week. However, generally they need to use it for the full month to get the full effect. Additionally, if the person is re-exposed to biotoxins again (see list of biotoxins) they will once again need to remove these biotoxins with a bile sequestrant such as Cholestyramine.

Is it Safe?
It has been used for more than forty years and many patients have taken it for  long periods of time. The FDA ruled in 1999 that there was no reason to expect an increased risk from giving Cholestyramine to patients with biotoxin illnesses, such as mold, pot-Lyme, cuguatera, pfiesteria and blue green algae syndromes compared to those who do not have biotoxin illnesses.

Detox Reactions (Also see Contraindications & Adverse Reactions)
Some people report a detox reaction. If the person has a significantly high MMP-9 level this is more likely to happen and can be lessened or negated by using Omega-3-fatty acids and the no-amylose diet for ten days. On day 6 the patient starts the Cholestyramine.

Dr. Ritchie Shoemaker (CIRS due to water-damaged buildings pioneer and leader in field) has noted that reactions to cholestyramine treatment may be specific to CIRS causes and are often associated with various illnesses or lab makers. For instance the person with a significantly elevated MMP-9, a history of ciguatera, Lymes or MARCoNs  may have a worsening of symptoms with taking Cholestyramine. True intensification or worsening of clinical presentation, will result in a fall in VCS scores in row E by day 3 (after Cholestyramine treatment begins) followed by a fall in row D. MMP-9  will rise from baseline. (If this happens Lymes should be ruled out as well as MARCoNs.)

What is thought to be happening when detox reactions occur?
This usually happens around dose 6-10. It is more common in Post Lyme patients than others. It is thought that the reaction is tied to a dissociation constant of toxins to receptors. If the binding is tight, like ciguatera the intensification never occurs. If the toxins are internalized into dendritic cells such as in mold and cyanobacteria toxins, there is no intensification.
When the Cholestyramine binds the toxins and they are removed with it in the stool, this pushes the dissociation to the right to release more toxin from everywhere in the body. Before the newly released toxins go into the bile and are removed by the Cholestyramine they cause an intense release of cytokines in the body. This in turn causes the inflammation that leads to the various detox symptoms.

How long until I feel better?
Generally people notice improvement the first week. Most people feel much better after a month. Treatment is faster for the young and slower for the elderly. The sicker can take longer to get well. Other reasons it may take longer are poor compliance with Cholestyramine, the person may still be exposed to toxins (Did they remove themselves from all water-damaged buildings or remediate their home appropriately?) They also may have a MARCoNs infection.

Digestion reactions that may happen
Common reactions early on in treatment are reflux of stomach acid (heart burn), bloating, belching and general indigestion, constipation. Some people will dissolve the Cholestyramine in apple juice to help reduce the heartburn. This really does help. Some people also find  dissolving it in luke-warm water and then adding ice will help reduce heartburn.

What can be done about the constipation?
The simplest thing is that patients are helped by drinking more water. 16 oz with each dose is best. 12 oz is necessary at minimum. Drinking more water thru the day is also necessary. Fruits such as plums and cherries are helpful. Some people use water soluble fiber such as psyllium seed. Research has shown psyllium mixed with cholestyramine works better to lower cholesterol than cholestyramine by itself. It may be that it will work similar with biotoxins although there is not research on it. If using the water soluble fiber,  drink plenty of water with it. Some patients find using vitamin C to bowel tolerance can be helpful, while others use magnesium for constipation.  Those using Vitamin C, usually take it 1 hour prior to taking their Cholestyramine dose or they take it with their meals. Most patients are taking 1 -2 grams 4 times per day. They back off the dose if they get loose bowels. Magnesium is taken with meals usually in 100 mg doses per meal. While magnesium glycinate is a good form to absorb, magnesium citrate is a better form if you want to induce bowel evacuation. The vitamin C and magnesium is only used as a solution to constipation if water, fruit and water soluble fiber is not helping enough.
5- Hydroxytryptophan (5-HTP), a supplement that people take at night to help them sleep, also helps move the intestines to promote evacuation of bowel contents. People sometimes take this at night before bed to help them sleep and have a bowl movement in the AM. Vitamin C, magnesium and 5-HTP should not be substituted for drinking lots of water.

Diarrhea
Some patients with chronic biotoxin illness have diarrhea or softer, frequent stools. For these people the cholestyramine is usually beneficial as it helps to solidify their stool.

What are the contraindications & Adverse Reactions for Cholestyramine?
Research has shown that Choleystyramine is not absorbed, but entirely removed in the feces. Problems that arise therefore are usually related to its action in the gut.
It is not given to kids under 3 years old.
It is not indicated for oral consumption if there is complete biliary obstruction where bile is not secreted into the intestine. It is also not indicated in individuals who have shown hypersensitivity to it or any of it’s components.
Choleystramine binds bile acids, so it may therefore interfere with normal fat digestion and absorption and thus may prevent absorption of fat-soluble vitamins such as A,D,E and K. When Cholestyramine is given for long periods of time, concomitant supplementation with water-miscible or parenteral(shots) forms of fat-soluble vitamins should be considered.
The adverse reactions are largely due to Cholestyramine binding bile acids and causing fat soluble vitamin deficiencies or binding of drugs. The most common adverse reaction is constipation.
Please go to this link for an extensive list of less common adverse reactions: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=63274

Where do I get Cholestyramine?
You will need a prescription in the United States.
If you want pure Cholestyramine without additives you need to get it from a compounding pharmacist.
In the United States we have a couple products that are common on the market. The following list of ingredients in them is from this link: http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=63274

QUESTRAN® (Cholestyramine for Oral Suspension, USP), the chloride salt of a basic anion exchange resin, a cholesterol lowering agent, is intended for oral administration. Cholestyramine resin is quite hydrophilic, but insoluble in water. The cholestyramine resin in QUESTRAN is not absorbed from the digestive tract. Four grams of anhydrous cholestyramine resin is contained in 9 grams of QUESTRAN POWDER. QUESTRAN POWDER contains the following inactive ingredients: acacia, citric acid, D&C Yellow No. 10, FD&C Yellow No. 6, flavor (natural and artificial), polysorbate 80, propylene glycol alginate, and sucrose (421 mg/g powder).

QUESTRAN LIGHT.
Four grams of anhydrous cholestyramine resin is contained in 6.4 grams of QUESTRAN LIGHT. QUESTRAN LIGHT (Orange Vanilla) contains the following inactive ingredients: aspartame, citric acid USP anhydrous, D&C Yellow No. 10, FD&C Yellow No. 6, flavors (natural and artificial Orange, natural and artificial Vanilla Cream), maltodextrin, magnesium sulfate USP heptahydrate, propylene glycol alginate, colloidal silicon dioxide, and xanthan gum.   

If you do not want these additives in your Cholestyramine, you will need to have your practitioner order it from a compounding pharmacist.                                                                                      
Please note that Questran Light contains aspartame which should never be consumed by people with the genetic condition knows as phenylketonuria or PKU.
Additionally, there are other people who react to aspartame too.

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

Currently the research I have is thrown on this page here. I will organize it better ASAP.

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:

1. Mechanism of Action:
1. Bile acids are synthesized by the liver by oxidation from cholesterol.
2. 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.
3. 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.
4. The fall in hepatic cholesterol content results in an up-regulation of LDL receptors.
5. The upregulation of hepatic LDL receptors increases the removal of LDL and intermediate-density lipoprotein cholesterol (IDL) from plasma.

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, similar to the bile acid sequestrant drugs. http://www.ncbi.nlm.nih.gov/pubmed/17438377