Abstract & Commentary
Synopsis: Being overweight is associated with symptoms of gastroesophageal reflux (GERD) in a dose-dependent way. This association is stronger for women than for men, particularly for premenopausal women and for those taking hormone replacement therapy (HRT). Weight loss reduces the risk of GERD.
Source: Nilsson M, et al. JAMA. 2003;290:66-72.
This report comes from 2 population-based, cross-sectional case-control studies conducted in Norway. Data were collected from a total of 47,556 people in 2 separate surveys conducted about 10 years apart (1984-1986 for Helseunder-sokelsen I Nord-Trondelag 1 or HUNT 1, and 1995-1997 for HUNT 2). Written questionnaires distributed at health centers collected data on 813 variables. For this report, Nilsson and colleagues have focused on 58,596 individuals in the HUNT 2 survey who responded to a question about experiencing heartburn or regurgitation within the preceding 12 months. Because of the extensiveness of the questionnaire, Nilsson et al were able to control for every known relevant variable, and they used other "nonspecific gastrointestinal symptoms" (nausea, constipation, diarrhea) as control symptoms in the logistic regression model. After exclusion of pregnant women and those with incomplete data, 20,369 men and 22,994 women were included in the final analysis; 3113 (about 5%) reported severe heartburn and were considered "cases." The mean age of the group was 52 years and their mean body mass index (BMI) was 28.1 kg/m2.
There was a moderate dose-dependent relationship between increasing BMI (above 25) and symptoms of GERD. This dose-dependent relationship was stronger in women than in men; the most obese men (BMI > 35) had about a 3.3-fold increased risk, but the most obese women had a 6.3-fold increased risk. This risk was less for postmenopausal women than premenopausal women (odds ratio, 4.2 vs 6.8). However, normal weight postmenopausal women who had ever taken estrogen-only HRT had more than twice the risk of GERD symptoms as did those normal-weight women who did not take reflux. The greatest risk of reflux symptoms was seen in women who had ever taken estrogen-only HRT and who had a BMI > 35; the likelihood of symptoms in these individuals was increased more than 33-fold compared with normal-weight people who had not taken HRT.
Nilsson et al also used data from the HUNT 1 study to assess the effect of weight change on the 72.8% of subjects who had participated in both studies. The risk of reflux was dose-dependently greater with increasing net BMI gain, controlling for all other variables. Further, a loss of more than 3.5 BMI units was associated with striking reduction in the risk of reflux symptoms.
Comment by Barbara A. Phillips, MD, MSPH
This is the first study to convincingly demonstrate a strong dose-dependent relationship between increasing weight and increasing symptoms of gastroesophageal reflux. Further, it documents reduced risk of symptoms with weight loss and increased risk with weight gain. There have been 3 prior population-based studies that addressed the relationship between obesity and GERD, including a previous one by the same authors.1 They assert (and I agree) that in one of their previous studies,2 they simply did not include enough obese people to show a relationship. The current epidemic of obesity is a relatively new thing. As we grow fatter, we will likely continue to discover new associations (none of them good) between being overweight and health outcomes. The other prior studies1,3 did find a weak relationship between BMI and reflux but did not do separate analyses between men and women. They hypothesize that estrogen is a significant culprit in causing GERD symptoms and point out that obese women have greater synthesis of estrone in fatty tissue as well as greater circulating levels of unbound estradiol.
There are 2 bits of good news here: Weight loss appears to be associated with a reduced risk of GERD, and menopause without hormones may be associated with less heartburn.
Dr. Phillips, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.
1. Locke GR, et al. Am J Med. 1999;106:642-649.
2. Lagergren J, et al. Gut. 2000;47:26-29.
3. Ruhl CE, Everhart JE. Ann Epidemiol. 1999;9:424-435.