Glutathione: in sickness and in health.

There is increasing evidence that free radical damage may be an important cause of some of the adverse effects of disease and advancing age. Much of the clinical evidence to support this hypothesis is based on the protective effect sometimes observed in those on diets high in antioxidants and those given antioxidants therapeutically. Further support would be obtained if plasma markers for oxidative damage such as lipid peroxidation products (lipid hydroperoxide [LHP]) were raised and antioxidants such as glutathione were low in the old and the sick, particularly in those who are acutely and severely ill. We have therefore measured plasma glutathione and LHP in healthy young individuals, healthy older individuals, and two groups of elderly patients, one with chronic ill-health attending outpatients and one acutely ill and in hospital. We studied 66 young healthy volunteers (mean 24· 5 [SD 4· 7] years) and 58 community-based healthy elderly individuals (70· 7 [4· 8] years). Health was defined as an absence of major medical or surgical illness in the previous 5 years, no hospital admissions, no current medication, and a subjective perception of good health. We also studied 49 patients attending general medical clinics (75· 7 [8· 3] years) with a variety of chronic illnesses including ischaemic heart disease, arthritis, diabetes, and hypertension. Finally, 47 hospitalised elderly patients (77· 2 [8· 6] years) were studied during the course of an acute illness within the first week of admission. Non-fasting venous blood was sampled into standard edetic acid (glutathione) and lithium heparin (LHP) tubes. Samples were all taken by one person (SN) and care was taken to minimise haemolysis. They were centrifuged immediately at 3500 rpm, 4oC for 15 min, and plasma stored at -80oC until analysis. Plasma for glutathione was pre-treated with 30% perchloric acid to stabilise thiol groups. Total plasma glutathione was determined by enzyme-rate assay and plasma LHP by ferrous oxidation of xylenol orange. A sample size of at least 47 in each group was needed to detect a 20% change in plasma glutathione with 80% power at the 95% confidence limit. Statistical difference between groups was determined by ANOVA and the level of significance taken as p<0· 05. The results are presented in the figure. The plasma glutathione in young healthy adults was 0· 54 (SE 0· 02) μmol/L. In the healthy elderly glutathione was significantly lower (0· 29 [0· 01] μmol/L, p<0· 0001). The age-adjusted values for elderly outpatients were significantly lower than in the healthy elderly (0· 24 [0· 01] μmol/L, p<0· 0001) and values for elderly inpatients were lower than for elderly outpatients (0· 17 [0· 01] μmol/L, p<0· 01). The marker for oxidative damage, LHP, was low in the healthy young adults (2· 14 [0· 17] μmol/L) and higher in the healthy elderly (3· 14 [0· 20] μmol/L, p<0· 01). It was higher in the sick elderly (8· 51 [0· 66] and 8· 84 [0· 63] μmol/L in outpatients and inpatients, respectively [p<0· 0001 compared with healthy elderly]).