Obesity is commonly associated with a high incidence and prevalence of dyslipidaemia, cardiovascular disease and Type II diabetes. Interestingly, studies have also reported decreased antioxidant levels in obese subjects. This may constitute an independent risk factor in the pathogenesis of coronary artery disease as obese subjects would have a decreased capacity to prevent the oxidative modification of low-density lipoproteins, which is a mechanism suggested as central to the development of atherogenesis. As part of a study to investigate responses to weight loss, we have assessed the effects on GSH status of a decrease in body mass of 5%, either after 6 days of complete starvation or 11 days of a very low calorie diet (2.55MJ/day). There were significant differences between the two groups in the synthesis rate of erythrocyte GSH in response to weight loss. Both the fractional and the erythrocyte synthesis rate of GSH decreased significantly ( P <0.01) in the starvation group by 22% and 16% respectively. In contrast, no change in synthesis rates was observed in the very low calorie diet group ( P >0.05). Total erythrocyte concentration of GSH was unaffected by the weight loss within both groups. These results suggest that erythrocyte GSH synthesis is depressed in response to a very rapid weight loss induced by fasting. An acute reduction in GSH synthesis in response to a rapid weight loss may constitute a risk factor during periods of increased GSH demands.

Chronic infection is often accompanied by a wasting process, the metabolic basis of which is not fully understood. The aims of the present study were to measure protein and energy metabolism in patients with melioidosis (a serious and antibiotic-refractory Gram-negative bacterial infection which is endemic in South-East Asia) in order to define the metabolic abnormalities that might contribute to wasting. Whole-body protein turnover was measured using the [ 13 C]leucine technique, both in the fasted state and while consuming a high-energy meal. Resting energy expenditure was measured by indirect calorimetry, and total energy expenditure by the bicarbonate/urea method. Results were normalized for fat-free mass, as estimated from skinfold thickness. Protein turnover was increased in melioidosis patients compared with healthy controls during fasting (170.9 compared with 124.1 µ mol·kg -1 ·h -1 ; P = 0.04), but the net rate of catabolism (22.2 compared with 20.5 µ mol·kg -1 ·h -1 ; P = 0.77) and the anabolic response to feeding were similar in the two groups. Resting energy expenditure was higher in melioidosis patients compared with controls (191.4 and 157.3 kJ·kg -1 ·day -1 respectively; P = 0.04), but total energy expenditure (measured in a separate group of eight patients with melioidosis) was low (192.1 kJ·kg -1 ·day -1 ). In conclusion, this study found no evidence of metabolic causative factors, such as accelerated net protein catabolism during fasting, a blunted anabolic response to feeding or increased daily energy expenditure, and therefore suggests that reduced energy intake is the prime cause of wasting. The observed normal response to feeding should encourage nutritional approaches to prevent wasting.

1. Differing patterns of protein metabolism are seen in wasting due to undernutrition and wasting due to chronic infection. 2. We investigated whole body energy and protein metabolism in nine subjects with pulmonary tuberculosis, six undernourished subjects (body mass index < 18.5 kg/m 2 ) and seven control subjects from an Indian population. Fasting subjects were infused with l-[1- 13 C] leucine (2.3 μmol · h −1 · kg −1 ) for 8 h, 4 h fasted then 4 h fed. Leucine kinetics were derived from 13 C-enrichment of leucine and α-ketoisocaproic acid in plasma and CO 2 in breath. 3. Undernourished subjects, but not tuberculosis subjects, had higher rates of whole body protein turnover per unit lean body mass than controls [163.1 ± 9.4 and 148.6 ± 14.6 μmol compared with 142.8 ± 14.7 μmol leucine/h per kg, based on α-ketoisocaproic acid enrichment ( P = 0.039)]. 4. In response to feeding, protein oxidation increased in all groups. Tuberculosis subjects had the highest fed rates of oxidation (47.0 ± 10.5 compared with 37.1 ± 5.4 μmol · h −1 · kg −1 in controls), resulting in a less positive net protein balance in the fed phase (controls, 39.7 ± 6.2; undernourished subjects, 29.2 ± 10.6; tuberculosis subjects, 24.5 ± 93; P = 0.010). Thus fed-phase tuberculosis subjects oxidized a greater proportion of leucine flux (33.2%) than either of the other groups (controls, 24.0%; undernourished subjects, 24.0%; P = 0.017). 5. Tuberculosis did not increase fasting whole body protein turnover but impaired the anabolic response to feeding compared with control and undernourished subjects. Such ‘anabolic block’ may contribute to wasting in tuberculosis and may represent the mechanism by which some inflammatory states remain refractory to nutrition support.