Another Way Men and Women Differ

At least until menopause, women face a lower risk than men do of artery-clogging heart disease. Michigan scientists now turn up one potential reason: before menopause, one of the avenues for clearing meal-derived fats from the blood operates better in women than in men of the same age. This makes the fat less available to the plaque-forming cells in women’s arterial walls.

Jeffrey F. Horowitz and Nicolas D. Knuth of the University of Michigan in Ann Arbor decided to track how men’s and women’s bodies handle dietary fat in the first 6 to 12 hours after a meal. Although fat can be packaged in several different forms, the vast majority occurs as triglycerides—three fatty acids bound to an alcohol molecule known as glycerol. Overall, the higher the triglyceride concentration in blood after a meal, the greater the heart-disease risk an individual faces.

Although physicians typically make a single measurement of triglycerides in blood, Horowitz and Knuth realized that the several particles that ferry triglycerides around the bloodstream can differ greatly in their capacity to foster atherosclerosis. These triglyceride carriers are commonly known as lipoproteins, and the Michigan scientists wanted to know which lipoproteins the bloodborne triglycerides were part of, for how long, and whether this pattern differed by gender. And indeed it does, the scientists report in the June Journal of Nutrition.

Initially, the body packages dietary fat passing through the intestinal wall into chylomicrons. The least-dense member of the lipoprotein family, these molecules tend to contain almost no cholesterol. In the new study, men kept their triglycerides in those chylomicrons far longer after a meal than did women, a sign of potentially worse fat handling in the men.

A breakfast of whipping cream

The new finding emerged from a small feeding trial involving 10 lean and healthy volunteers—half men, half women. At 6 p.m. on the first day, each participant was admitted for an overnight stay at the university’s metabolic-research center. Dieticians carefully tailored a dinner and a late-evening snack to maintain each recruit’s body weight.

Upon rising the following morning, each volunteer received baseline blood tests followed by an unusual breakfast—liquid whipping cream sweetened with a sugar substitute. It tasted a little like melted ice cream, Horowitz says.

The goal, he explains, was to provide a meal with enough fat to be easily tracked as it moved through biochemical processes in the body. To facilitate that tracking, the researchers added a tracer isotope—carbon-13—to the cream so that the triglycerides it passed on to the volunteers’ bodies could be distinguished from other fats circulating in their blood.

Among the women, triglycerides peaked in blood 2 hours after the creamy breakfast, and the fat’s blood concentration was back to prebreakfast readings within 6 hours of eating. In men, however, the triglyceride rise took roughly twice as long to peak and didn’t return to each man’s baseline concentration until 9 hours after the meal.

Moreover, the scientists report, tests showed that this difference wasn’t because the women broke down the fat more efficiently or just packaged more of it into other lipoproteins. Instead, for reasons that remain unknown, the men simply hung on to their chylomicron triglycerides longer than the women did.

A risk of remnants

That’s potentially bad news for men, Horowitz says. Ordinarily, as the blood circulates chylomicrons through the liver, these lipoproteins give up their triglycerides, and the liver repackages the fats into other lipoproteins, which are eventually used or stored by body tissues. This appears to be what happened in the women.

However, research by others has shown that chylomicrons can undergo degradation before their triglycerides are repackaged in the liver. The problem with this, Horowitz explains, is that remnants of chylomicrons are “more prone to induce formation of foam cells and development of atherosclerotic plaque” than intact chylomicrons are. Foam cells are fatty, bloated blood cells that can be early signs of artery disease.

The concern, he says, is that the longer a chylomicron circulates in the bloodstream, “the greater its potential to develop into a remnant.” His team hasn’t assayed remnant concentrations in men or women, Horowitz says, but expects to do so in a later trial.

In that trial, the team intends to offer volunteers a more normal breakfast than whipping cream. It will have carbohydrates—sugars or starches—and the researchers will measure how those components alter insulin production by the body. Why? Insulin has potent effects on the production of an enzyme that breaks down triglycerides and moves fat into muscles and stores of body fat.

But women, don’t get smug. The seeming female advantage observed in the recent study wanes with age, Horowitz notes. When people have measured overall triglyceride responses to a meal in postmenopausal women and age-matched men, rates of [fat]-clearance from the blood “tend to overlap,” he points out. Horowitz and other researchers suspect that something about estrogen or other hormones causes healthier fat metabolism in women of childbearing age.