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UCLA Division of Cancer Prevention and Control, PO Box 956900, Los Angeles, CA 90095-6900, E-mail: wmccarth{at}ucla.edu
Dear Sir:
The welcome article by Hill et al (1) appears at first blush to be merely one small step removed from the still conventional notion that restricting energy intake well below that needed for satiety will yield long-term weight control. After all, Hill et al used fairly severe energy restriction (4180 kJ/d below estimated energy requirements) throughout the 6-mo lead-in period. Closer examination of the study, however, shows that it may actually represent 2 conceptual leaps that promise to advance the field of weight control.
The first advance is the use of a clinical strategy that honors the growing literature on the role of the gut in satiety. Recent empirical findings suggest that satiety is influenced by the nature of the energy ingested (2) and by the form in which the energy is found (3). Such evidence suggests that much of the variance in satiety can be explained by activities in the gut rather than in the brain. Hill et al showed that the use of a lipase inhibitor to reduce fat absorption to 19–22% of absorbed energy results in a daily energy deficit of 544–774 kJ/d (130–185 kcal/d) compared with placebo. The consistently lower weight regain associated with continued orlistat use suggests that the brain was unable to compensate fully for the 30% of fat energy not absorbed during the 1 y of orlistat use.
Although impressive conceptually, this new gut-level pharmacologic strategy appears to yield a modest practical benefit (only 1.3 kg more sustained weight loss than placebo), possibly obtained at some risk of long-term harm and at relatively great cost. The full power of potential nonpharmacologic, alternative approaches to weight control has yet to be evaluated experimentally. Retrospective results of the observational study, the National Weight Control Registry (NWCR) (which Hill originated with Rena Wing), however, showed that a 30-kg weight loss could be maintained for 5 y by including not only a fat intake 30% lower than that of the average American (24% of energy from fat) but also a diet substantially higher in nutrient density (4). Shick et al (5) inferred from the increased nutrient density that the NWCR weight-loss maintenance diet was relatively high in fruit, vegetables, and fiber. A concurrent finding from this same study suggested that long-term maintenance of weight loss requires unusually high levels of physical activity (equivalent to walking 45 km/wk). But proportional reductions in these recommended lifestyle choices still produce measurable long-term weightcontrol benefits in less-selected US adults: eating a lower-fat diet somewhat higher in fruit, vegetables, and fiber and engaging in as little as 4 h of moderate physical activity per week (6).
The second conceptual advance is the illustration that effective, short-term, temporary shaping of qualitative food choices can influence long-term behavioral success at reducing excess energy intake. Hill et al observed that patients taking orlistat early in the trial quickly learned not to exceed the recommended fat intake if they wanted to avoid unpleasant gastrointestinal events. Nearly all (95%) patients assigned to the orlistat condition reported unpleasant gastrointestinal events early in the trial but quickly learned how to avoid such events. Hill et al's Figure 3 appears to show that the orlistat group decreased their dietary fat intake 5-fold more than did the placebo group, from week 2 of orlistat therapy to 1 y of follow-up. Is this sharper decline significant? If so, might it not be reasonably conjectured that orlistat serves as a behavioral analogue to antabuse by making dietary relapses back to high-fat meals unpleasant? This inadvertent aversive therapy effect could help to explain why, in the European orlistat trial (7), taking patients off orlistat during the second year did not impair the weight-control advantage obtained while receiving orlistat during year 1. This result suggests that orlistat therapy could be withdrawn after 1 y with only a partial return of the fat absorption level observed at baseline.
These important conceptual advances, if confirmed, should stimulate increased behavioral research on how qualitative differences in foods relate to variations in satiety and how best to motivate the eating of high-satiety foods. When obtained in minimally processed, natural foods, the constituents water and fiber hold particular promise for contributing to satiety (8). Such issues as meal frequency and starch resistance (9) have been examined with respect to their effect on blood glucose but have yet to be investigated thoroughly with respect to long-term weight control. Finally, there has been remarkably little research on the potential for daily physical activity to influence adherence to a diet of high-satiety foods, especially fruit and vegetables, despite some cross-sectional evidence of dose-response relations (10).
While these theoretical issues are being sorted out by the researchers, the clinician would do well to recommend a sustainable version of the nutrient-rich, high-activity NWCR weight-control strategy before considering the use of orlistat. Not only does the NWCR strategy yield maintenance of far greater excess weight loss long-term than was shown so far for orlistat, but it also yields salubrious increases in micronutrients. The use of orlistat, by contrast, is associated with significant, unavoidable losses of fat-soluble micronutrients, with unknown long-term consequences for health.
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