This study has been replicated (less elegantly) in many other studies around the world on undernourished populations. A great deal of information also exists on obese individuals placed on hypocaloric diets for weight loss. Even at weights that are above the normal, hypocaloric diets will induce a drop in RMR. This seems to be in proportion to the loss in LBM. In addition, there is an important drop in nonresting energy expenditure.

Cancer
One of the first manifestations of cancer is loss of weight. This has been primarily ascribed to a loss of appetite and decreased food intake. The net effect of such a hypocaloric diet is to lower energy expenditure. Despite the decreased energy expenditure, energy balance is not maintained. As the imbalance continues or exacerbates, severe undernutrition, called cancer cachexia, can result. Some studies have suggested that cancer patients have an increased RMR. These studies have often expressed RMR as kcal/kg of weight and compared the cancer patients with normal weight patients. Clearly, however, as already mentioned above in the Minnesota study, as one loses weight, one loses more fat than LBM. Since the kcal/kg of fat are much lower than the kcal/kg of LBM, losing proportionally greater fat will leave an individual with a higher kcal/kg of total weight. Overall, the available evidence suggests that an increased RMR contributes very little to the loss of weight in cancer patients, whereas decrease in food intake is key.

Infection
Infections are often manifested by fever. Fever is an elevation of body temperature above normal to more than 37.5°C and is a marker of inflammation. The infection may be obvious, with pain, redness, and inflammation at a site, or it may be a fever of unknown origin, such as bacterial endocarditis. In humans, for each temperature increment of 0.6°C (1°F), RMR increases by approximately 10 percent. Thus, a considerable increase of energy expenditure can occur with even a mild elevation of temperature. Cytokines such as tumor necrosis factor, IL-6, and IL-1 have been implicated in this process, probably working through prostaglandins, and re-setting the hypothalamic thermoregulatory center.

AIDS
There have been a number of studies suggesting that RMR is elevated in patients with AIDS, and that this may contribute to their weight loss and eventual demise. The issue is complicated, as with cancer, in that appetite is also decreased. Also, gastrointestinal symptoms are very prominent in many patients. Studies to date have generally observed an increase of about 10 percent in RMR in relation to the LBM, with a great deal of variation. This is probably explained as an infection effect, discussed above. However, studies of total energy expenditure using doubly labeled water suggest that 24-hour energy expenditure is decreased, related to the fact that these patients feel very ill and as a result are very inactive.

Anorexia Nervosa
The weight loss that occurs in anorexia nervosa because of the patients' unwillingness to eat appropriate amounts of calories leads to a decrease in RMR, similar to that which occurs in any other starved individual. However, anorexia nervosa patients are generally overactive, so that their 24-hour energy expenditure tends to be higher than one would predict on the basis of their RMR.

Rheumatoid Arthritis
Rheumatoid arthritis is an inflammatory disease in which cytokine production is increased. A recent study has reported that RMR is 12 percent higher in this disease than would be predicted. This is probably modulated by increased levels of IL-I beta and TNF-alpha. In contrast, TEA is much lower because general activity and certainly exercise is greatly decreased in patients with the disease.