You may have read news reports that the Food and Drug Administration approved the first ever officially sanction weight-loss drug for over-the-counter sales. The drug, Alli (generic name: orlistat), has been sold for the last eight years as the prescription drug Xenical. The difference between the OTC version and the prescription version is in the dosage. Alli will be sold as a 60 mg version whereas Xenecal has been sold as a 120 mg version. All consumers need to do to get the prescription dose of the drug is to take a double dose. But according to the manufacturer, even the lower dose is effective.
Glaxo studies have shown that the 60-milligram dose provides 85 percent of the weight loss of the higher dose. One capsule is supposed to be taken at mealtime.
Alli is not the drug you want to take if you’re following a low-carb diet.
MD and I have had extensive experience with this drug. Back in the early 1990s our clinic in Little Rock was one of the largest clinics participating in one of the stages of the orlistat study. In fact, our clinic was the largest in terms of number of patients in the orlistat maintenance study.
Since MD and I were the only physicians at our clinic, we both had a lot of hands-on experience dealing with patients taking orlistat. Or oily stat as we called it. Why oily stat? Well, because of the side effects.
The top three side effects of oily stat are: fecal incontinence, oil spotting, and my all time favorite, flatus with discharge. Any of these side effects can lead to a most unpleasant social situation.
These side effects are a function of how the drug works. Orlistat is a lipase inhibitor. Lipase is an enzyme in the small intestine that breaks fats down into their component fatty acids so that these fatty acids can be absorbed. When lipase enzymes are inhibited, the fats don’t break down, and, consequently, don’t absorb. When fats aren’t absorbed into the small intestine, they make their way down to the colon. Under normal situations the colon never has to deal with fat because it’s usually absorbed way upstream, so the colon isn’t prepared to deal with fat. The fat slides down the colon and makes its way out at the bottom end. If all goes well, it sees the light of day when you want it to. But often the colon gets rid of this fat on its own schedule, whether convenient for you or not.
Our patients used to complain bitterly about these unwanted and untimely discharges of fat that would ruin their clothing and sometimes even their furniture. We had one lady who termed the discharges themselves as cosmic pizza grease because that’s what they looked like. Soon, all of the patients were using this phrase to describe them.
Orlistat basically puts those who take it on a drug-induced low-fat diet. Consequently, those taking it suffer the same consequences as those on long-term low-fat diets: depression (we had many patients who had to be removed from the study due to depression), low-levels of vitamin K and other fat soluble vitamins, and gall bladder disease.
Let’s digress just for a moment to discuss gall bladder disease because many people don’t understand how a low-fat diet can cause gall bladder disease. The pancreas produces the lipase enzymes that break down fat, but these enzymes are helped by the bile salts produced by the liver. The liver makes these bile salts and stores them in the gall bladder, a little sack that sits underneath the liver. When a load of fat enters the small intestine, the gall bladder squirts a stream of bile salts into the load of fat going through to begin the breakdown process. The slurry of fat and bile salts are acted on by the lipase enzymes to complete the fat breakdown to individual fatty acids that can then be fully absorbed by the small intestine.
When people have problems producing bile salts, they have the same side effects as with orlistat. The mass of fat can’t be broken down completely for absorption by the lipase enzymes alone, so fat reaches the colon and causes problems.
As the bile salts finish their work with the fat, the liver plucks them out and recycles them, sending them back to the gall bladder. If very little fat enters the small intestine as a consequence of a low-fat diet, the gall bladder doesn’t get the signal to squirt out the bile acids. The bile acids in the gall bladder sit there and tend to concentrate over time. Since a major component of the bile salts is cholesterol, the cholesterol tends to supersaturate and can precipitate out as small cholesterol stones. (One family of cholesterol-lowering drugs work by preventing the re-absorption of cholesterol in the bile salts by the liver, allowing them to leave the GI tract through the stool.) These stones can cause real problems because they can work their way down the tiny ducts through which the gall bladder squirts its contents into the small intestine. What usually happens is that a person follows a low-fat diet for an extended period of time allowing stasis of the bile in the gall bladder and small stone formation. Then this person has a hankering for a big, greasy cheeseburger or other fat-filled meal and chows down on it. As the fat enters the small intestine it sends the normal signal to the gall bladder to release some bile salts. The gall bladder constricts to squirt the bile salts into the intestine and pushes one of these small stones into the duct. When that happens, the opposite of fun begins. As anyone can tell you who has had this happen, the pain is excruciating. Most people who have this happen blame the fatty food, but it isn’t the fatty food that causes the underlying problem. The underlying problem is set up by the low-fat diet.
In our clinical study we did gall bladder ultrasounds on all patients as they started. We eliminated from the study anyone who had gall stones. After six months on a low-fat diet, we redid the gall bladder ultrasounds of all the patients and found that about 10 percent of them had developed gall stones.
Orlistat works in theory by putting people on a drug-induced low-fat diet. In reality it works by putting people on an actual low-fat diet. Since orlistat prevents the absorption of about 25 percent of the fat coming down the GI tract, the more fat that is eaten, the greater the amount this 25 percent represents. There is a point at which the 25 percent that hits the colon causes the side effects. Patients on the drug quickly learned how much fat they could eat before they had problems, and kept their fat intake below this limit. The orlistat ended up acting like Antabuse for fat. (Antabuse is the drug that alcoholics take to prevent their drinking. If they take Antibuse and consume alcohol, they become seriously ill. So they avoid drinking.)
(Interestingly, when the representatives of the drug company that developed orlistat came and talked to us, they gave us a little history of the development of the drug. Like many drugs, orlistat was kind of a lab mistake. When the researchers realized that it was a lipase inhibitor that would decrease the absorption of fat, the first thing that popped into their minds was that they had a cholesterol-lowering drug on their hands. Makes sense, since ‘everyone’ knows that dietary fat makes cholesterol levels go up. Turns out that orlistat didn’t reduce cholesterol levels–if anything, it made them worse. So they scratched the idea of using it as a cholesterol-lowering drug and punted. They decided to use it as a weight-loss drug because ‘everyone’ knows that dietary fat causes obesity.)
How does all this apply to a low-carb diet? Well, by definition, a low-carb diet is in most cases a high-fat diet. If one takes orlistat while following a high-fat diet, very bad things happen. Very socially-embarrassing bad things. Cosmic pizza grease cubed. And at random times. Unbidden and unwanted. And unforgettable.
If you’re following a low-fat diet and you want to make sure you stick with it, give Alli a try.
The manufacturer, GlaxoSmithKline, said it planned to sell the medication for $1 to $2 for a day’s dose. The company has predicted that five million to six million people a year will use the drug.
If you’re on a low-carb diet, don’t be one of them.