IBD treatment 2008

Inflammation of the bowel responds to the anti-inflammatory diet differently from other inflammatory diseases, such as arthritis or allergies. Special attention must be paid to absorption problems, e.g. B12, methionine, and intestine-specific interactions -- glucosamine and heparin.

There has been a flurry of reports in the last few months on new therapies for inflammatory bowel diseases (IBD). The emphasis has been on delivery directly to the bowel, as opposed to through the blood circulation and a return to earlier observations on the relationship between thrombosis and antiphospholipid disease and IBD. Both of these conditions bring up the use of therapeutic heparin. Clotting is usually associated with heparin, since controlling clotting is the major clinical use of heparin, but heparin is taken completely out of its natural context -- the gut.

Heparin is a fragment of heparan sulfate (HS), a long polysaccharide synthesized sugar by sugar on a protein. Thus all heparin starts as a heparan sulfate proteoglycan (HSPG) and all HSPGs pass through the secretory system of cells, but the proteins are embedded in the inside of the membrane of the secretory vesicles, so instead of being released into the extracellular environment, the HSPGs are displayed on the outside surface of the cells. The cell surface is dominated by a forest of HS chains. Most extracellular proteins, including the inflammatory interleukins, bind to the HS chains. Receptors that are needed to respond to the hormones bind in pairs to pairs of hormone proteins with the HS between them, like two pairs of buns on an HS hot dog. The HS is an integral part of the signaling systems and also many other complex processes such as clotting.

As HS passes through mast cells the HS is enzymatically cleaved into fragments of heparin. The heparin is negatively charged and the histamine and enzymes secreted by the mast cells are positively charged, so they neutralize each other. When a mast cell releases histamine in response to allergens binding to its surface, histamine and heparin are released. Heparin is produced for drug use from scrapings of hog and cattle intestinal mast cells. A major feature of IBD is enhanced activity of intestinal epithelial mast cells.

IBD is frequently associated with other inflammatory conditions, such as thrombosis, the tendency to produce clots, or antiphospholipid antibody production (APA). Both thrombosis and APA are treated with heparin and aspirin. Aspirin might appear obvious to inhibit COX-2, the enzyme that produces inflammatory prostaglandins from omega-6 fatty acids, unfortunately these same prostaglandins are needed for the integrity of the gut. That is why aspirin can cause bleeding of the gut. This is also why aspirin inhibits muscle growth following exercise, since muscle growth requires inflammatory prostaglandins. COX-2 inhibitors also block production of anti-inflammatory prostaglandins from omega-3 fatty acids (fish oil).

Heparin would be a natural treatment for IBD, but it is usually administered by injection or intramuscularly and has a systemwide impact on many signaling systems, including clotting. Since bleeding is already a symptom of IBD, keeping administered heparin out of the blood would be an advantage. The other alternative is oral administration. Bathing the stomach and intestines in heparin on the way to its application in the lower bowel is a problem, because HSPGs are rapidly cycled on the surface of cells and any heparin in contact with a cell is rapidly internalized.

The answer to IBD drug administration is to use a system that delivers the drug to the affected bowel. There are several systems recently reported that encapsulate and selectively release drugs. The drugs of choice seem to be heparin and Mesalazine. Another new approach is the use of glucosamine. Since glucosamine acts directly on the gut to produce systemic anti-inflammation, it is a natural choice. Acupuncture is also highly effective in some cases of IBD and it is particularly useful, because it also produces a very strong placebo effect to which IBD seems to be very sensitive. From my experience in other areas of pain relief and anti-inflammation connected with acupuncture, I would also expect castor oil packs to be very useful for IBD. If you have had experience with these anti-inflammatory approaches, I would enjoy your comments.