We all know that in the wonderful world of dietary supplements, there are many ingredients and products which boast the end-all claim – fat blocking. Most of these products are quite similar, they contain fiber-derived products which claim to either bind to the fat or contain lipophilic properties which allow fat to be dissolved and then excreted. The problem is that some of these products have been shown in trials not to be as effective as we would have hoped, and many companies use illegitimate extracts or sources to produce products which have very few beneficial effects to begin with. Rather then wasting money, and even worse, time, it seems as if most bodybuilders and fitness enthusiasts have derailed this idea of using a ‘fat-blocker’ and have stuck to the tried and proven supplements.

Luckily the good folks at Roche Pharmaceuticals have developed a product to treat obesity called Xenical®. Xenical® (orlistat) is a prescription weight loss medication which has shown in studies to be quite effective when it comes to blocking fat out of the diet. The new gets better, the FDA has just recently approved for orlistat to be sold over the counter by GlaskoSmithKline under the trade name Alli™. Alli™ should be available in stores nation wide summer 2007 as part of a weight loss package. This is good news for us! We now have a pharmaceutical grade FDA approved fat blocker in which we don’t need to go through the shady little bald guy in the corner of the gym to get for us. In this article I am going to discuss the pharmacology, dosing and side effects of orlistat, so you can make up your own mind if you want to use this product or not in your weight loss needs.

Pharmacology

In order to properly understand the mechanism behind orlistat, we need to understand how the enzyme lipase works and its effects on fat absorption. Lipase is an enzyme which is secreted from the pancreas and is necessary for the absorption and digestion of fatty acids which are ingested from the diet. While different forms of lipase do exist, i.e. hepatic lipase and pharyngeal lipase, orlistat’s mechanism of action focuses solely on pancreatic lipase. Triglycerides which are taken in through the diet cannot be directly absorbed in the intestinal mucosa. Instead, when inside the lumen the triglyceride chains are coated with bile salts which allows for them to be broken down more easily. Sufficient amounts of pancreatic lipase are then released into the lumen in the form of pancreatic juice, allowing the hydrolysis of the triglycerides. The net result leaves us with monomers in the form of 2-monogylceride and free fatty acids which are then moved into the small intestine and absorbed through the lymphatic system via the lacteal vessel.

Ninety-percent of dietary fat comes in the form of triglycerides. Of this 90%, 95% of the fat is actually broken down and absorbed in the small intestine after being broken down by lipase. Orlistat works as a reversible inhibitor of lipase. It forms a covalent bond with the lipase enzyme occupying the same site which triglycerides normally would. Due to the fact that orlistat possesses a structural similarity to triglycerides, it can keep the lipase enzyme bound for a significant amount of time allowing 30% of the fat which was taken in from the diet to pass through the intestine without being absorbed.

The above diagram gives us an easy to follow outline of how orlistat’s mechanism takes place inside the intestinal tract. On the left hand side we can see what normally happens when triglycerides are taken in through the diet. They interact with bile acids and the lipase enzyme to systematically breakdown and cleave the fatty acid into its counter parts. The fatty acids and the monoglycerides are then taken up through the mucosal cell. On the right side of the diagram, we can see how Xenical® binds to the lipase enzyme thereby occupying the enzyme’s activity allowing the triglycerides to pass through the intestine unchanged.