Gallstone Disease in Men Built on Weight Cycling

LEXINGTON, Ky., Nov. 27 -- Yo-yo weight loss may increase the risk of gallstone disease in men, according to researchers here.

Repeated loss-gain cycles was associated with increased gallstone risk later in life by as much as 50% among men who lost more than 20 pounds at an episode, the investigators reported in the Nov. 27 issue of the Archives of Internal Medicine. The original body mass index seemed irrelevant.

Although approximately 30% of adult U.S. men are trying to lose weight, intentional weight loss is an independent predictor of subsequent weight gain. However, the effect of weight cycling on the risk for gallstones in men has been unclear, said Chung-Jyi Tsai, M.D., Sc.D., of the University of Kentucky here and colleagues at Harvard and the National Cancer Institute.

In an analysis of 51,529 U.S. men in the Health Professionals Follow-up Study, 17, 286 weight cyclers were men who had intentional weight loss followed by regain. There were 7,443 weight maintainers, men who had no intentional weight loss and whose net weight remained stable at 5 lb.

The men, ages 40 to 75 and free of gallstones at the 1986 baseline, returned a mailed questionnaire reporting weight status over four years and were then followed from 1992 to 2002.

During 264,760 person-years of follow-up, there were 1,222 cases of symptomatic gallstones. Maintenance of stable weight was relatively uncommon, the researchers reported.

In the 10-year follow-up period beginning in 1992, the risk of symptomatic gallstone disease increased by approximately 40% in men who had one or more loss-gain cycles of more than 20 pounds, the researchers reported

More loss-gain cycles also increased the risk: Two or more weight cycles increased the risk by approximately 30% among men who had cycles of 10 to 19 pounds, and by half as much among men who had cycles of more than 20 pounds. This effect was independent of BMI and other known or suspected risk factors for gallstones, the researchers wrote.

Weight loss categories were five to nine pounds, 10 to 19 pounds, 20 to 49 pounds, and more than 50 pounds. Weight cyclers were divided into three categories: light cyclers (n=10,027; maximum intentional weight loss per episode, five pounds to nine pounds), moderate cyclers (n=5185; maximum intentional weight loss per episode, 10 pounds to 19 pounds), and severe cyclers (n=2,074; maximum intentional weight loss per episode, 20 pounds or more).

After adjusting for potential confounding variables, including BMI, the multivariate relative risk of weight cyclers, compared with weight maintainers was: 1.11 (95% confidence interval [CI], 0.94-1.31) in light cyclers (58%), 1.18 (CI, 0.97-1.43) in moderate cyclers (30%), 1.42 (CI, 1.11-1.81) in severe cyclers (12%); (P value for trend .002).

Analysis of the effect of the number of cycling episodes found that among cyclers, the relative risk of having more than one weight cycle, compared with weight maintainers, was 1.10 (CI, 0.88-1.37) in light cyclers, 1.28 (CI, 1.03-1.59) in moderate cyclers, and 1.51 (CI, 1.13-2.02) in severe cyclers.

At baseline, severe cyclers, compared with light cyclers, tended to be heavier, sedentary, and heavy smokers, and to consume more saturated and monounsaturated fats and caffeine but less alcohol, the researchers found.

Many factors have been associated with the risk of cholesterol gallstones, but supersaturation of bile with cholesterol,

which is closely related to total body fat, is significant, the researchers said.

The potential mechanisms contributing to the association between weight cycling and gallstone formation are likely to be multiple, they said. However, they added that in another follow-up study in which weight regain returned men to their pre-entry body weight, the weight regained was almost exclusively accounted for by an increase in body fat.

Studies have shown, Dr.Tsai's team said, that large swings of body weight, especially during the phase of weight recovery, are particularly sensitive to the accumulation of body fat and to the development of metabolic abnormalities later in life, including insulin resistance, all of which facilitate gallstone formation.

Discussing the study's limitations. The researchers noted that that the effect of weight recycling might not represent the entire effect of recycling in earlier years.

Furthermore, they said, the homogenous nature of the study with respect to race and socioeconomic status, and the fact that the results focused on clinically relevant gallstone disease in men, may mean that the study cannot be generalized to the entire population.

Because it was not possible to do diagnostic screening for the presence of gallstones in this large group and because most gallstones are generally silent in men, it is likely that there was "considerable under-ascertainment" of gallstones in this study, the researchers said. However, they concluded, those results were not likely biased owing to silent gallstones.

They also noted that "although we assessed and adjusted for a number of potential confounders, we cannot exclude the possibility of residual confounding as in any observational studies."