John Garrow

Thermogenic response to temperature, exercise and food stimuli in lean and obese women, studied by 24 h direct calorimetry

1. Total heat loss was measured by 24 h direct calorimetry in five obese and five lean women who were maintained throughout the study on a diet supplying 3·3 MJ/d. Each subject was measured five times to assess the effect of temperature, exercise and food on energy expenditure. Within each weight group a Latin-square design was used to balance sequence effects on the thermogenic responses to temperature, exercise and food. 2. Compared with the control day, on which no thermogenic stimulus was given, the increase in 24 h heat production by the lean and obese women caused by 30 min exercise on a bicycle ergometer against a load of 20 N was 10·1 and 10·3 W for obese and lean groups respectively. There was no evidence in either group of a measurable long-term increase in metabolism which would increase the energy cost of the exercise above that predicted from indirect calorimetry during the exercise. 3. The increase in heat production associated with ingesting an extra 4·4 MJ (obese group) or 4·0 MJ (lean group) was 3·4 and 3·0 W respectively. This response was similar to that predicted from indirect calorimetry for a few hours after the meal. 4. The obese and lean groups differed in metabolic response to calorimetry at the upper or lower limits of the thermal comfort zone, which was determined individually for each subject. The difference from control values in the obese group was an increase of 3·8 W on the ‘warm’ run, and a decrease of 2·0 W on the ‘cool’ run. Among subjects the change was an increase of 0·4 W on the ‘warm’ run, and an increase of 4·8 W on the ‘cool’ run. The differences between the groups did not achieve statistical significance. The lower and upper temperature limits were similar in the two groups: 23·2–26·4° for the obese group, and 23·3–26·2° for the lean group. 5. The most striking difference between lean and obese subjects in the present study was the much higher resting metabolic rate, and total energy expenditure, of the obese group. During the control run the obese group had a mean energy expenditure of 96·1 W, compared with 61·7 W in the lean group. There was no overlap: the lowest energy expenditure for an obese subject was 81·4 W and the highest for a lean subject was 76·1 W. In comparison to this large difference in baseline the magnitude of the thermogenic responses was small. 6. Under the conditions of this study there was nothing to support the view that a failure of thermogenic response is an important factor in the causation of human obesity. To support that view it would be necessary to show differences in thermogenesis in lean and obese subjects which were at least an order of magnitude greater than those which we have observed.

Randomised controlled trial of novel, simple, and well supervised weight reducing diets in outpatients.

Abstract Objectives: To investigate the contribution of novelty and simplicity to compliance with a low energy diet among obese outpatients. Design: Three arm randomised trial for 16 weeks. Setting: NHS hospital obesity clinic. Subjects: 45 patients aged over 17 years with a body mass index >27 who were not diabetic, pregnant, or lactating. Interventions: Conventional 3.4 MJ diet (control), isoenergetic novel diet of milk only, or milk plus one designated food daily. Follow up visit every 4 weeks. Main outcome measure: Weight loss. Results: Mean weight loss (kg) after 16 weeks on control, milk only, and milk plus diets was 1.7 (95% confidence interval −0.3 to 3.7), 9.4 (5.9 to 12.9), and 7.0 (2.7 to 11.3) respectively. Weight loss on the novel diets was significantly greater than on the control diet. Conclusions: Dietary treatment can achieve as much weight loss in obese outpatients over 16 weeks as has been reported for the most successful drug treatment, but compliance with the prescribed diet is poor unless the diet is novel and simple.

A new method for measuring the body density of obese adults

1. A new apparatus is described with which it is possible to measure the volume (and hence density) of obese patients without requiring them to immerse totally in water. Replicate measurements of subjects with 6, 23 and 38 kg body fat had a standard deviation not greater than 0.3 kg fat. 2. In nineteen obese women body fat was measured by density, total body water, and total body potassium at the beginning, and again at the end, of a period of 3--4 weeks on a reducing diet, during which they lost 5.43 (SD 1.83) kg in weight. The composition of weight loss was also estimated both by energy balance and nitrogen balance during the interval between the two measurements of body composition. 3. The estimates of fat content of the ninetten women at the start of the balance period were 45.63 (SD 14.50) kg by density, 48.07 (SD 13.88) kg by K and 47.09 (SD 13.85) kg by water. The correlation coefficient between the density and K estimate was 0.949, and for the density and water estimate it was 0.971. 4. It is concluded that measurement of density by the new method provides a convenient method for estimating body fatness, and change in fat content, which compares favourably with estimates based on total body water or total body K. However, these methods cannot be used to provide an accurate estimate of the composition of a small weight loss in an individual since deviations up to 4 kg fat occur between fat loss based on change in density and those based on the more reliable (but more tedious) energy balance method.

The short-term prognosis of severe primary infantile malnutrition.

I . Among a series of 343 children with severe primary malnutrition there were 248 for whom, on admission, there were reliable records of age, weight, height, liver size, severity of oedema, skin lesions and angular stomatitis, and concentration of total serum protein, haemoglobin and sodium. For eighty-four of these children the serum bilirubin concentration was also known. 2. The correlations of these characteristics of the children on admission, with mortality, and with the rate of recovery were investigated. 3. Age, weight, oedema and haemoglobin concentration were not significantly related to mortality or to rate of recovery. A multiple regression analysis showed that an increased serum bilirubin concentration and a decreased serum sodium concentration indicated a bad prognosis, and these two factors contributed almost the whole of the multiple correlation coefficient of 0.63 with respect to mortality and 0.59 with respect to speed of rccovery. 4. We conclude that in our series of children death was more closely associated with liver failure or overhydration than with protein depletion, and suggest that the administration of ton much protein or water to an acutely ill malnourished child may precipitate death. 5 . This analysis shows that the mortality observed in our series cannot be adequately explained by any combination of the characteristics considered above ; there must, therefore, be other factors of importance for which we do not have suitable measurements.

Increased energy expenditure in growing adolescents with Crohn's disease

Undernutrition is considered to have a central role in the pathogenesis of growth retardation in Crohns disease. This may occur as a consequence of inadequate food intake, increased energy expenditure, or both. Ten growing adolescents with inactive Crohns disease were assessed with respect to anthropometric parameters and resting energy expenditure, measured by indirect calorimetry during remission, repeated in relapse (N=5), and compared to that predicted from the Harris-Benedict formula. Mean energy intake was assessed with seven-day diaries in five patients and compared to recommended intake for age, sex, weight, and physical activity. Ten healthy, growing, age- and sex-matched adolescents served as controls. Nine patients with inactive Crohns disease, who had ceased growing, were matched for disease site and duration and acted as disease controls. Patients and disease controls had lower body mass index (19.2±0.6; 20.9±0.7) than healthy controls (23.7±0.6;P<0.001). Percent body fat was lower in patients (13.2±1.9%) compared to healthy controls (20.5±2.4%;P<0.05) but not to disease controls (17.0±2.6%). Patients had higher resting energy expenditure per kilogram of fat-free mass than disease or healthy controls (36.9±5.1; 32.9±2.6; 30.9±2.1 kcal;P<0.02). Measured resting energy expenditure in patients, but not in disease or healthy controls, was higher than the predicted (measured: predicted 1.15, 1.03, 0.9, respectively;P<0.03). Energy intake in patients was 97% of recommended intake but the measured ratio of energy intake/resting energy expenditure was lower than the predicted ratio (1.49 vs 1.71;P<0.05). During subsequent relapse in five patients resting energy expenditure was unchanged. In growing adolescents with inactive Crohns disease, there is increased energy expenditure that is not accompanied by an increase in energy intake. Relapse of disease does not appear to increase resting energy expenditure further but may “divert” energy from growth to disease activity. This suggests that nutritional therapy should be directed towards increasing caloric intake to maximize growth potential.

Factors influencing the composition of the weight lost by obese patients on a reducing diet.

1. Weight loss, resting metabolic rate and nitrogen loss were measured in forty obese inpatients on reducing diets. 2. Five subjects ate 3.55 MJ/d for 6 weeks (Expt 1). Twenty-one subjects ate 4.2 MJ/d for the first week, 2.0 MJ/d for the second week and 4.2 MJ/d for the third week (Expt 2). Fourteen subjects ate 3.4 MJ/d for the first week and then 0.87 MJ protein or carbohydrate for the second or third weeks, using a cross-over design for alternate patients (Expt 3). 3. Patients in Expt 1 had highest weight loss and N loss in the first 2 weeks, but adapated to the energy restriction over the remaining weeks. On average subjects were in N balance at the end of the study. 4. In Expt 2 patients eating 2.0 MJ/d in week 2 showed increased weight loss compared with week 1. N loss was not raised but it failed to decrease as it had in Expt 1. Weight loss and N loss were reduced on return to 4.2 MJ/d for a third week. 5. In Expt 3 patients eating 0.87 MJ protein showed significantly more weight loss and less N loss than patients eating 0.87 MJ carbohydrate. 6. Resting metabolic rate decreased with time on the low-energy diet, but the manipulations of energy or protein content did not significantly affect the pattern of decrease. 7. Both weight loss and N loss were greater the lower the energy intake, and both decreased with time. Diets with a high protein:energy value give a favourable value for N:weight loss at each level of energy intake.

Predisposition to obesity.

65 women whose build ranged from normal to grossly obese were investigated to test the hypothesis that obese people, especially those with a genetic predisposition to obesity (manifest by early onset and family history of obesity), have a low energy expenditure. For the group as a whole, resting metabolic rate was related to obesity index, but the age of onset and family history of obesity had no effect on this relationship. The findings suggest that a familial predisposition to obesity is more likely to relate to energy intake than to energy expenditure.

EFFECTS ON WEIGHT AND METABOLIC RATE OF OBESE WOMEN OF A 3·4 MJ (800 kcal) DIET

103 obese women (mean [SD] Quetelets index [weight/height2] 38 [8] kg/m2) were admitted to a metabolic ward and were kept strictly to a diet providing 3.4 MJ (800 kcal) daily for 3 weeks. Body weight was measured daily and fasting resting metabolic rate (RMR) on days 1, 7, and 21. Both weight and RMR fell more rapidly in the first week than later. The thermic effect of feeding fell immediately on the lower energy intake, and there was an adaptive reduction of about 6% in RMR in week 1. After 3 weeks, the average weight loss was 4.9 (1.2) kg (about 5% of initial weight) and the average fall in RMR 8.8%. If after substantial weight loss a woman eats just enough to maintain energy balance the adaptive reduction in metabolic rate is restored to normal, and the thermic effect of feeding is restored in proportion to the new energy intake, but total energy requirements remain less than in the obese state to the extent that fat-free mass has been reduced. Thus, an obese woman who reduces weight by 30% over a year will thereafter have requirements for weight maintenance which are reduced by about 15%.

THE RELATIONSHIP OF THE SIZE AND COMPOSITION OF THE HUMAN PLACENTA TO ITS FUNCTIONAL CAPACITY

An analysis was made of placentae from 500 consecutive deliveries of live singleton babies in the Royal Free Hospital, and of a further series of “high risk” patients, so as to bring the combined series to 700 cases.

Flushing away the fat. Weight loss during trials of orlistat was significant, but over half was due to diet.

News p 835 Obesity (body mass index >30 kg/m2) is a serious disease which predisposes to heart disease, hypertension, stroke, diabetes, osteoathritis, obstructive sleep apnoea, gallstones, and some cancers sensitive to sex hormones. It accounts for 2-7% of total healthcare costs and a substantial proportion of disability pensions. Obesity is out of control in most affluent countries of the world, and its prevalence is increasing rapidly in developing countries. The World Health Organisation describes it as a global epidemic.1 This week, with the launch of orlistat, hopes have been raised that there is a new, effective weapon against the rising prevalence of obesity. In 1976 in the United Kingdom an expert committee sounded a warning that obesity was “one of the most important medical and public health problems of our time.”2 In 1980 a survey showed that 6% of men and 8% of women were obese,3 and in 1992 the government set a target that the prevalence of obesity (then 8% of men and …