Do β-Blockers Put on Weight?
To the Editor:
Sharma et al1 recently published in this journal a hypothesis about a possible association between the use of β-blockers and weight gain. In fact, Julius et al2 reported a similar finding earlier, postulating that both the blood pressure elevation and the weight gain could reflect a primary increase in sympathetic activity. The use of β-blockers as antihypertensive agents hence could inevitably cause these patients to gain weight. Theoretically, the reasoning seemed to make sense. As a clinician, however, one might wonder if this is true in practice.
We carried out a nationwide survey in Finland in 1997 on the treatment of hypertensive patients in primary health care. Altogether, 1782 hypertensive patients participated in the study, 706 (39.6%) of them males. The patients’ mean age was 63.5 years. As many as 87% of the patients reported regular use of antihypertensive medication. The most frequently used drugs were β-blockers (54%), ACE inhibitors (38%), diuretics (36%), and calcium channel blockers (33%). Half of the patients had had hypertension for >10 years. All of the patients underwent a careful physical examination, including determination of the body mass index (BMI), calculation of the waist-to-hip ratio, and an inquiry about possible changes of body weight during the past 12 months.
Altogether, 829 patients were using a β-blocker as an antihypertensive agent. Most patients had 1 of the following selective β-blockers: metoprolol (271), atenolol (153), bisoprolol (l82), and betaksol (47). The most commonly used nonselective β-blockers were sotalol (59), pindolol (35), timolol (18), and propranolol (15).
The mean BMI of the whole group of β-blocker users was 29.7 kg/m2 (SD, 4.8); that of the nonselective β-blocker group, 29.9 kg/m2 (SD, 4.8); and that of the whole drug-treated group, 29.6 kg/m2 (SD, 4.8). The users of diuretics were fattest, with a mean BMI of 30.4 kg/m2 (SD, 5.2), followed by the ACE inhibitor group at 29.9 kg/m2 (SD, 4.8); the least-fat test group was those on calcium channel blockers at 29.5 kg/m2 (SD, 5.0).
Of the drug-treated hypertensives, 26% had gained weight (mean, 4.2 kg) during the past 12 months, whereas 27% had lost weight (mean, 5.1 kg), and the rest had retained their body weight unchanged. Of the β-blocker users, 26% had gained weight, 24% had lost weight, and 50% had remained unchanged. Of the 127 patients who were using nonselective β-blockers, 23% had gained weight, 23% had lost weight, and 54% had remained unchanged. The β-blocker users did not, however, succeed in slimming as equally often as the nonusers (24.0% versus 30.3%). This difference was statistically significant (P=0.008) and evident among both males and females.
In 1995, we carried out a nationwide study on the status of antihypertensive treatment and the side effects of antihypertensive drugs.3–5 Altogether, 4405 hypertensive patients participated in the study, and 3638 (85%) of them were using antihypertensive drugs. Of the patients, 1748 (48%) were on monotherapy, and 602 patients (35%) were using β-blockers. The most common side effects of β-blockers were fatigue and reluctance to start new tasks (33%), cold hands/feet (32%), impotence (21% of males), muscle cramps/ache (20%), feelings of infirmity (18%), depression (14%), and bradycardia (8%). These reported side effects could explain the difficulties experienced by the patients attempting to lose weight. As clinicians, we often encounter β-blocker-treated hypertensive patients who complain of difficulties in physical exercise because of shortness of breath and numb feet.
In summary, our studies seem to suggest that the use of β-blockers does not seem to cause people to put on weight but rather hinders the attempts of hypertensive patients to lose weight.
Kumpusalo and Takala wonder whether β-blockers cause weight gain in clinical practice. They present data from a nationwide Finnish survey, indicating that body weight in hypertensive patients on β-blockers is not different from that of patients on other antihypertensive medications. Nevertheless, patients on β-blockers were significantly less likely to lose weight.
The interpretation of such cross-sectional data is difficult. First, as indicated by our analysis, the weight gain associated with β-blockers is seen during the first few months of instituting β-blocker therapy.1 Half the patients in the Finnish survey had had hypertension for >10 years, so any initial weight gain may well have been masked by the usual weight-gain associated with aging. Second, weight gain is generally mentioned as an “adverse effect” on the package insert of β-blockers. Indeed, I have observed remarkable increases in weight shortly after instituting β-blockers in several patients. Patients who complain of weight gain (and/or impotence) with β-blockers often ask me to change their medication. In most cases, I concede with this request for the sake of long-term compliance. I wonder how often patients actually complain of weight gain in general practice, and how this might confound the cross-sectional data presented by Kumpusalo and Takala. Third, as discussed in our paper, weight gain with β-blockers may be more evident in younger patients, in whom metabolic rate is more dependent on sympathetic activity than in older patients.2 It may be of interest to note that the average age of the patients in the Finnish survey was 63.5 years.
I am very much intrigued by the observation that 33% of patients on β-blockers complained of fatigue and reluctance to start new tasks. As discussed in our paper, I also think it worthwhile to examine the effect of β-blockers on spontaneous physical activity or nonexercise activity thermogenesis (NEAT), an important determinant of body defense against a hypercaloric diet.3
It will undoubtedly be of interest to examine the incidence and magnitude of β-blocker-induced changes in body weight in the setting of a randomized controlled trial. Furthermore, the capacity to lose weight in patients on β-blockers warrants further investigation. Whether selective, nonselective, and atypical β-blockers differ in their propensity to cause weight gain or prevent weight loss also remains to be resolved.
Sharma AM, Pischon T, Hardt S, Kunz I, Luft FC. β-Adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension. 2001; 37: 250–254.
Levine JA, Eberhardt NL, Jensen MD. Role of nonexercise activity thermogenesis in resistance to fat gain in humans. Science. 1999; 283: 212–214.