High Dose EPA/DHA Fish Oil, Cholestyramine, and the Herx

I've been having a difficult time getting started on cholestyramine therapy to start removing the biotoxins from my system. As a part of my treatment plan, I first have to remove myself from sources of biotoxin exposure, primarily mold. Once that is done it's time for toxin removal from the body. Cholestyramine is a bile acid sequestrate intended for use in lowering cholesterol. Coincidentally, cholestyramine's unique structure and positive molecular charge forms strong bonds with negatively charged biotoxins, be it from mold, lyme, or other sources. As such, this makes Cholestyramine an excellent vehicle for binding and removing biotoxins. Cholestyramine has been used by the U.S. Government to treat military personal exposed to neurotoxic agents because it is so effective an has few side effects. Cholestyramine or (CSM) for short, does not leave the digestive tract and does not make it's way into the blood stream. Simply put, CSM binds to biotoxins which have been processed by the liver and, excreted into the bowel via the bile ducts. Once CSM comes in contact with the biotoxic bile, it binds to it tightly and holds on to it until It can be excreted when you have a bowel movement.

So what's the problem with CSM? Shouldn't removing toxins from the body in this way be pretty easy? It should, but it isn't always that easy. CSM causes gastrointestinal symptoms and constipation, not good things to have when your goal is to pass the bound toxins as quickly as possible. But there is a second reason why CSM can make things worse. Biotoxins from Mold and Lyme sources are fat-soluble meaning that they predominately reside in your adipocytes (fat-cells). If you envision CSM as the guy who opens the flood gate and puts a fishing net across the way to catch any fish that come through, you can understand what CSM is doing in your body. Once CSM starts binding to the biotoxins in your enteric system and ushers them out of the body, there is now "new space" for more biotoxins to move on down the line. Think of this process like a bucket that's too full. Once you dump out some of the contents, you have room for more. In a rudimentary way, that is what happens in our bodies. So if we know that the biotoxins are stored in the adipocytes (fat cells) and that they are migrating from those cells into the blood, and then being processed by organs such as the liver into the bile and into the enteric system, the delivery channel becomes clear. Now you see why it is important to have a bile sequestrate ready and waiting for the newest batch of toxic-bile to be delivered, bound, and ushered away.

So far so good, right? In a perfect world perhaps. In people with Lyme toxins another key process can take place. As many of you probably know, CSM has been shown to cause "Herxheimer" reactions in many. After reading through Dr. Ritchie Shoemaker's book Desperation Medicine, I now understand to a small degree what is happening to those of us who get worse once we commence this kind of treatment. If we go back to the elimination channel of biotoxins talked about in the previous paragraph, we can look at a particular process that occurs specifically in those with Lyme toxins. The biochemistry of this process is a bit complex, but it's not impossible to understand. The presence of biotoxins (in this case those from borrelia burgdorferi) bind to the insulin receptor sites on adipocyte cells (fat cells). Once there, a switch is turned on which triggers and alters DNA transcription of mRNA, causing the adipocyte to produce a powerful cytokine called Tumor Necrosis Factor-alpha or (TNF) for short. The role of TNF in autoimmune and inflammatory disease has recently drawn a lot of attention as it should. In the case of innate immune response and biotoxin illness, it is also significant. So what does this mean? Simply, once the biotoxin "parks the car in the adipocyte's garage", the adipocyte's becomes a TNF-producing factory. Envision millions of cells in the body producing this powerful cytokine. In controlled amounts, TNF and other immunoregulatory cytokines such as the IL (Interleukins) IL-1, IL-8, etc. are helpful and a vital part of the immune systems response to infection because they help to induce fever, synthesis of phase proteins by the liver, and activation of T & B lymphocytes. However, in much higher quantities, these cytokines are responsible for many of the pathological symptoms we see in inflammatory conditions. Simply put, too much TNF will make you feel absolutely awful. Such an influx of TNF is often called the "TNF storm". Cytokine storms can be dangerous and in some cases cause damage to various organs. An example of this is the neurotoxic effects of elevated TNF causing damage to the rentromedical hypothalamic (VHM) neurons resulting in hyperphagia, hyperglycemia, hyperinsulinemia, hypertriglycerdemia, and impaired glucose tolerance (IGT). High concentrations of TNF are also correlated with the induced apoptosis of neuronal cells.

So what can we do to reduce or stop a TNF storm if we have lyme toxins in our bodies and have to start removing them with CSM, Welchol, or other bile sequestrates? Thanks to doctor Shoemaker's research we have an answer. As I said before, the biotoxin, in this case from Lyme, binds to the insulin receptor site on the adipocyte in much the same way as insulin itself would do. If we can block the insulin receptor site, we can block not only insulin binding, but also biotoxin binding as well. That is exactly what happens when one takes the pharmaceutical drug, Pioglitazone (Actos). So Actos can be used to significantly blunt or mitigate the symptoms of a TNF storm resulting from stirring up latent biotoxins in the bodies fat stores. With this information at hand, we can see why pretreating with Pioglitazone prior to CSM commencement is important. So are there problems with taking Pioglitazone? In my case there seems to be. Because the function of Pioglitazone is to help normalize insulin in type 2 diabetics, those with insulin related problems and low-leptin as a result of biotoxin illness can have adverse reactions to the drug. In patients with low-leptin (as myself) and those who are very slim (as myself), Pioglitazone can cause blood sugar levels to drop too low.

What other options are there for people who need to pre-treat before starting CSM or sequestrate therapies? High doses of omega3's Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) can help. In keratinocytes (predominant cell type in skin) and fibroblasts (think collagen), AA, EPA/DHA reduced basal secretion of IL-8 (Interleukin-8, a pro inflammatory chemokine produced by macrophages) by 66% and 63% respectively. http://www.ncbi.nlm.nih.gov/pubmed/15654981 It becomes obvious that EPA/DHA plays a key role in reducing inmmunoregulatory cytokines including IL-10, TNFalpha, and INFgamma. These oils also have strong regulatory effects on B-Lymphocyte gene transcription. Macrophages (white blood cells in the tissue produced by the division of monocytes), and monocytes themselves are also responsible for producing key cytokines, TNF, IL-1 and IL-6. High doses of omega3's have been shown to reduce capacity of monocytes to synthesize IL-1 mRNA. Basically, EPA/DHA does what Actos does, but also has direct affects on the immune cells which regulate and release these inflammatory cytokines. Pharmacological drugs like cortocosteroids and cyclosporin are traditionally used as inflammatory controllers in this case, albeit they have side effects. That being said, EPA/DHA in high concentrations can achieve similar results, with little risk of side-effects, and have many other benefits for the body especially for the circulatory system. Bottom line, high dose omega3's EPA/DHA and those from Flax Seed have high potential for reducing cytokine progression. EPA/DHA has an amazing ability to suppress platelet activating factor (PAF) which is a potent platelet aggregator and leukocyte activator with links to RA, arthritis, asthma, endotoxic shock, and acute renal transplant rejection. http://www.ncbi.nlm.nih.gov/pubmed/15654981

So enough with the nitty-gritty, where am I at? Like I said, I started CSM therapy and got much much sicker. My inclination is that this was due to some sort of TNF-storm as a result of mobilizing latent biotoxins from my fat cells. I've since stopped CSM and was instructed to take high dose EPA/DHA to pre-treat before starting a new bile sequestrate, Welchol. Welchol is about 25% as effective as CSM, but is gentler on the body. Nordic Naturals is a good quality fish oil that I'm using right now to start. The doses may be different depending on multiple factors such as weight, etc, so I cannot say with certainty that my prescribed daily dose is right for anyone else. That being said, I need to try to get up to 2.4g EPA and 1.8g DHA daily for 8 days prior to commencing Welchol therapy. This works out to roughly 8 capsules per day. I am assuming that at this high dose, the fish oil can really start to suppress inflammatory cytokines, increase low VEGF (vascular endothelial growth factor), and mitigate increased TNF symptoms. As for now, I'm having trouble working my dose of the fish oils up as they seem to make me feel worse. I suspect that the high fat concentration of the EPA/DHA capsules is stimulating bile flow (full of toxins) in my body and that could be making me feel worse after taking them. I've also read that high dose EPA/DHA and Chlorella functions similarly to Actos and CSM. Perhaps there is some factor unbeknownst to me allowing the EPA/DHA to cause further detox? That would be a bit contradictory however. So, I will wait and see. Slowly work my doses up until I can tolerate the 8 capsules per day. Wish me luck!