Carbohydrates and gallstones

A persuasive article in the June issue of Gut, a British gastroenterology journal, presenting data on the relation of excess carbohydrate intake in men to the development of gall stone disease.
Before we get to the article, let me give a brief review of gall stone disease.
The job of the digestive tract is to break down the food we eat and prepare it for absorption, then to carry out the absorption. Fat entering the small intestine is mixed with bile acids – made in the liver – that emulsify the fat, making it better able to be further broken down with lipases, enzymes that break it apart into its component fatty acids. The bile acids-fatty acid emulsified combo forms into micelles, molecules that allow the fat to be absorbed into the cells lining the small intestine. The bile acids then break off and recirculate back to the liver.
The liver produces bile, which is composed of bile acids, cholesterol, and a few other substances. This bile travels from the liver to the gall bladder – a little sack tucked beneath the liver – through a small tube called the hepatic duct. The gall bladder stores the bile and waits for a fatty meal to enter the small intestine. When the fatty meal arrives, the gall bladder squeezes the bile out through the bile duct (another small tube) that joins with the hepatic duct to form the common duct and empties into the upper end of the small intestine. So when the fatty meal arrives, the gall bladder douses it with the bile it has been storing for just this occasion. The bile then mixes with the fat and breaks it down for absorption as described above.
If very few fatty meals come down the tract – for example, if the owner of the GI tract is following the Ornish or other low-fat diet – the bile sits around in the gall bladder, unsquirted. The liver continues to make bile, but slows down a little in its production. The cholesterol component of the bile tends to become more concentrated with time and can ultimately become supersaturated and precipitate as a small cholesterol gallstone (cholesterol accounts for 80-90% of gallstones). If the stone stays in the gall bladder, it typically doesn’t pose a problem. The problem arises when the stone makes its way into and occludes the bile duct, or, even worse, if it travels further and blocks the common duct. In either case, terrible, colicky pain ensues ending up with a trip to the surgeon.
If one eats fatty foods often, then the gall bladder constantly empties itself and generally stays free from gall stones. If a one doesn’t eat much fat because one is following a low-fat diet or one is on one of the modified fasting programs (Optifast, Medifast, etc.), then one’s gall bladder doesn’t empty and the bile sits around supersaturating. Then if one blows it out, so to speak, on a big steak dinner, or a giant cheeseburger, or any kind of fatty meal, the gall bladder squeezes this sludgy gunk that may contain a few small stones into the bile duct, and, bingo!, one has a serious problem all of a sudden. One of the big problems people have with the fasting programs and with low-fat diets is a high incidence of gall bladder disease. We did a large maintenance study a few years ago in our clinic for the weight-loss drug Orlistat (now Xenical) during which we had to put patients on a low-fat weight-loss diet for six months, then they were randomized onto on of a number of doses of Orlistat or placebo. Before they started the six month low-fat diet, the subjects all underwent a gall bladder ultrasound looking for stones. Anyone found with stones couldn’t participate in the study. Those without stones started the diet and had another ultrasound at the end of the six months on the low-fat diet, but before starting the medication. I can’t remember how exactly many patients developed gall stones during that six month period without going back through the data, which is stored 1000 miles away right now, but I do remember that it was a considerable number, something like 10-20% it seems.
Interestingly, I just pulled out my most recent Internal Medicine textbook, the 2004 edition of Lange’s Current Medical Diagnosis and Treatment, to see if it listed any kind of frequency of gallstones as a function of diet (it didn’t) and found the following sentence in the section on gallstone disease:

A low-carbohydrate diet and physical activity may help prevent gallstones, and consumption of caffeinated coffee appears to protect against gallstones in women.

I’m surprised they were so enlightened; I’ll bet the part about low-carb diets didn’t appear in the 1994 edition.
On to the study.
The authors lay out the premise for their study:

Epidemiological studies of carbohydrate consumption and gall stone disease have shown mixed results. Although the available evidence indicates that insulin resistance, chronic hyperglycaemia, and associated disorders of lipid metabolism are important predictors of gall stone disease, the relationship between dietary glycaemic load and glycaemic index and the risk of gall stone disease have not been examined.

The study subjects:

The Health Professionals Follow up Study is a prospective investigation of 51 529 US male health professionals, aged 40-75 years in 1986.

The researchers divided the subjects into quintiles (5 groups each containing 1/5 of the subjects) based on carbohydrate consumption, with the highest quintile being that one containing the subjects who consumed the most carbs, the lowest quintile, the opposite. The researchers then followed this group for 12 years and looked at the dietary intake of those who developed symptomatic gallstones as a function of total carbohydrate intake, glycemic index, and glycemic load (the glycemic index times the number of carbs providing this glycemic index).
The findings:
Glycemic load

The relative risk for the highest compared with the lowest quintile of glycaemic load was 1.46 (95% CI 1.14, 1.87; p for trend = 0.007).

Glycemic index

In a multivariate analysis that included the same covariates as those for glycaemic load, the relative risk for the highest compared with the lowest quintile of dietary glycaemic index was 1.18 (95% CI 1.01, 1.39; p for trend = 0.04).

Total carbohydrate intake

Intake of total carbohydrate was significantly associated with an increased risk. In the multivariate model, the relative risk for the highest compared with the lowest quintile of dietary carbohydrate was 1.59 (95% CI 1.25, 2.02; p for trend = 0.002).

As you can see based on the different relative risks above, the factor that shows the greatest relative risk is not the glycemic index – which was weak – nor even the glycemic load, but was just the plain old non-sexy total carbohydrate intake.
In an interesting twist, the researchers massaged the data a little to get even a better handle on what was going on. They figured that a lot of gallstones turned up during routine checkups on these older gentlemen that wouldn’t have been otherwise discovered. The researcher’s thinking (which I believe was valid) is that these findings as part of a physical exam would make the data biased in the direction of the more health conscious subjects, i.e., those who get regular physical exams.
Let me digress a little here. One of the great things about this study is that it lists alcohol and caffeine intake and whether or not subjects are smokers. This data provides what I call the alcohol, caffeine, tobacco index of perceived health. I say perceived health because most people think that smoking, booze, and coffee are bad for them. We who know better understand that smoking is definitely bad, but that alcohol in moderation and coffee are actually healthful. But the average Joe doesn’t really know that. So, when you see a listing of how much a group of people smoke, drink, and consume coffee, you can tell a lot about the health consciousness of the group. In the case of the study quintiles under consideration, it’s interesting to note that the highest quintile of carbohydrate consumption smoked, drank and consumed coffee at much, much lower rates than did the group who consumed the least amount of carbohydrate, which tells me a lot. We all know that during the course of this study (1986-1998) a high-carb, low-fat diet was (and in the minds of the great unwashed masses, to a certain extent still is) synonymous with a “healthy” diet, so it stands to reason that health conscious people would both consume more carbs, less fat, and have more routine checkups. These ideas occurred to the researchers, too, because when they saw the data showing that those who ate more carbs, i.e., those who were perceived to be healthier, got more gallstone disease, they wondered if it was really more gallstone disease or if maybe it was just more gallstone disease detected during routine visits that wouldn’t have otherwise been found skewing the data in a way showing that carb intake is related to gallstone formation. So, they eliminated those subjects who had had regular checkups during the early period of the study and recalculated the data.
In their words:

To evaluate the potential for detection bias due to increased medical surveillance among men with greater carbohydrate intake, we additionally excluded men with a routine medical check up between 1986 and 1988. Compared with men in the lowest quintile of carbohydrate intake, men in the highest quintile of carbohydrate had a multivariate relative risk of 1.97 (95% CI 1.39, 2.78; p for trend = 0.001).

The data showed an even greater relative risk for gallstone formation as a function of carbohydrate intake: 1.97 (almost double) verses 1.56.
The authors of this study actually listed the absolute number of grams of carbohydrate, fat, and protein these subjects consumed instead of idiotically listing them as percentage of energy, which gives a much more accurate picture of what’s really going on. But just for grins, in a burst of reverse idiocy, I recalculated the macronutrients as percentages to see how they stacked up. The highest quintile of carb intake got 58% of their calories as carbs and 25% as fat, while the lowest quintile consumed 44% of calories as carb and 36% as fat. What’s amazing to me, and what goes a long way toward explaining the huge rise in obesity and diabetes over the last two decades, is that these lowest quintile guys who smoked, and boozed, and, god forbid, drank coffee consumed only 36% of their calories as fat. In the mid seventies and for all the decades before as far back as data was collected and recorded the average fat consumption – not the fat consumption of the least health conscious segment of the population, but the average fat consumption – of Americans was about 46%. When fat consumption falls from 46% to 36% and the carb consumption goes up by a commensurate amount and everyone gets fat, then you hear people say that fat makes you fat: you’ve just got to wonder.
One last issue. Although this study looked at gallstone disease as a function of carbohydrate intake, there is really no way to determine if the high carbohydrate intake caused the gallstones or if the higher fat diet prevented them. As carb intake goes up, fat goes down, and vice verse. All nutritional macronutrient studies have four components that are all interconnected: fat, carbohydrate, protein, and calories. If researchers keep the calories the same and add carbs and subtract fat, then the findings can be caused either by more carbs or less fat – it’s difficult to tell which. If the carbs are kept the same and the researchers add fat, then the calories go up. If changes take place it’s impossible to tell if they were caused by the added fat or the added calories. This macronutrient-calorie interdependence is what makes nutritional studies so difficult.
In this case, the authors conclude:

Our findings suggest that a high intake of carbohydrate, glycaemic load, and glycaemic index increases the risk of symptomatic gall stone disease among men. These results add to the concern that low fat, high carbohydrate diets may not be an optimal dietary recommendation. [My italics.]

Amen.