Human overfeeding experiments: potentials and limitations in obesity research

The maintenance of body weight and body composition depends upon an ef®cient matching between substrate intake and substrate utilization thus insuring an adequate regulation of substrate balance. Perturbation of the human system by overfeeding constitutes a way to enable better understanding of how well the human system is regulated when exposed to a `stressful' nutritional situation. Overfeeding studies are important to carry out in human subjects for several reasons. First, the ingestion of surfeit energy occurs in real life either voluntarily in certain ethnic groups (Pasquet et al. 1992) or spontaneously in many individuals (acute `feasting' or chronic disturbances in food intake behaviour such as binge eating). Second, in order to delineate adaptive mechanisms of metabolic and behavioural natures in response to weight gain, overfeeding studies in human subjects are mandatory. Third, overfeeding studies allow the unravelling of subtle metabolic mechanisms which may be dif®cult to identify under maintenance conditions where a change in the proportion of macronutrient (carbohydrate : fat ratio) has little effect on energy needs (Shah, 1996; Hirsch et al. 1998). Fourth, overfeeding low-protein diets has been also suggested as a tool to unmask metabolic susceptibility to leanness or to fatness in human subjects (Dulloo, 1999). This is because according to a recent review by Stock (1999), proteinde®cient diets seem to be, in overfeeding conditions, a potent stimulus of thermogenesis in man. Taken together, human experimental studies in which a surfeit of energy is imposed constitute an interesting model for our understanding of the control of energy expenditure and its components. The number of studies published since the early 20th century on acute overfeeding in humans is not very large probably due to a number of practical, technical, methodological, ®nancial and ethical dif®culties. In these studies, the typical experimental design has been to deliberately and steadily overfeed at a certain energy level (so that the energy intake is `clamped') for a certain duration, which can range from days to weeks. The effect of the proportion of macronutrient in the food given in excess has been the subject of a very limited number of studies (Horton et al. 1995) so that the study of Lammert et al. (2000) is timely. One issue which has been of concern to some investigators is the extent to which the type of diet deliberately overfed in these experimental studies resembles that which can be realistically eaten in real life under `spontaneous' overfeeding conditions. The dilemma is that, on one hand, the investigator is interested in testing the effect of diets containing a high proportion of a macronutrient of interest (e.g. carbohydrates) in order to activate certain metabolic processes (e.g. de novo lipogenesis) and on the other hand, the type of diet force-fed in experimental studies should be similar to ad libitum feeding in real life. Furthermore, in normal daily living, overfeeding does occur spontaneously at some occasions but passive overconsumption of fat is much easier than of carbohydrate (Blundell et al. 1997, 1999). In contrast to experimental studies, subsequent spontaneous correction of food intake is possible since the diet is taken ad libitum. However, overfeeding studies in freeliving conditions are hampered by the fact that spontaneous food intake is dif®cult to assess accurately over a prolonged period of time (Black et al. 1991; Goldberg et al. 1991). The ®rst overfeeding studies date back to the early 20th century. The term `luxus consumption' was proposed when it was thought by early investigators that the body possesses ef®cient mechanisms to allow dissipation of excess energy into heat and hence can substantially limit weight gain during overfeeding. A subsequent reexamination of these classical studies (based on single subjects i.e. the investigators themselves! ) demonstrated that the conclusions could be challenged (Forbes, 1984). Basically, an increase in energy `disappearance' (or the so called `missing calories') during overfeeding can occur through several mechanisms: decreased energy absorption, decreased energy storage following enhanced obligatory (and regulatory) diet-induced thermogenesis, increased macronutrient turnover and activation of energetically costly processes such as de novo lipogenesis as well as spontaneous increases in the rate of physical activity. In acute experimental overfeeding studies the subjects are investigated in a transition phase (so called dynamic phase) during the initial onset of the metabolic adaptation period. Indeed, according to mathematical empirical models, it takes several years to obtain a steady body weight, during which the energy balance reaches a new equilibrium thanks to a new level of body weight (Weinsier et al. 1993). In an ideal overfeeding study design (somewhat unrealistic in free-living conditions), all the components of macronutrient balance should be assessed together with an independent evaluation of body composition. If one is primarily interested in the effect of overfeeding on body fat storage, two major variables should be measured which should give consistent results: (1) overall fat balance during the entire overfeeding period. This requires measurement of total fat input (i.e. metabolizable fat intake) and total fat output (i.e. total fat utilization); (2) body fat storage by measuring initial body fat minus ®nal body fat using an accurate and precise body composition methodology. In British Journal of Nutrition (2000), 84, 135±137 135