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Lancet: Glutathione in Sickness and in Health


Senior Member
Interesting study showed the sickest had the lowest levels of glutathione, and vice versa:

Clinical Pharmacology Section, Department of Medicine, Queen Elizabeth Hospital,
Edgbaston, Birmingham B15 2TH, UK (S L Nuttall); and Academic Department of Geriatric Medicine, University of Birmingham, Birmingham

The Lancet Volume 351, Number 9103 28 February 1998

Glutathione: in sickness and in health

S L Nuttall, U Martin, A J Sinclair, M J Kendall

There is increasing evidence that free radical damage may be an important cause of some of the adverse effects of disease and advancing age.1-3 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, 4C for 15 min, and plasma stored at -80C until analysis. Plasma for glutathione was pre-treated with 30% perchloric acid to stabilise thiol groups. Total plasma glutathione was determined by enzyme-rate assay4 and plasma LHP by ferrous oxidation of xylenol orange.5 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) ?mol/L. In the healthy elderly glutathione was significantly lower (0 29 [0 01] ?mol/L, p<0 0001). The age-adjusted values for elderly outpatients were significantly lower than in the healthy elderly (0 24 [0 01] ?mol/L, p<0 0001) and values for elderly inpatients were lower than for elderly outpatients (0 17 [0 01] ?mol/L, p<0 01).

The marker for oxidative damage, LHP, was low in the healthy young adults (2 14 [0 17] ?mol/L) and higher in the healthy elderly (3 14 [0 20] ?mol/L, p<0 01). It was higher in the sick elderly (8 51 [0 66] and 8 84 [0 63] ?mol/L in outpatients and inpatients, respectively [p<0 0001 compared with healthy elderly]).

Ageing is therefore associated with a decrease in plasma antioxidants and an increase in evidence of oxidative damage even in those who are apparently healthy. Disease, particularly acute severe disease requiring hospital admission, is associated with greater changes in antioxidants and evidence of oxidative damage. These early observations support the hypothesis that oxidative stress may have an important aetiological role and antioxidants a potential therapeutic role. Further studies are needed to confirm these observations but also to determine which disease processes are most closely associated with oxidative damage.

1 Lang CA, Naryshkin S, Schneider DL, et al. Low blood glutathione in healthy aging adults. J
Lab Clin Med 1992; 120: 720-25. [PubMed]
2 Julius M, Lang CA, Gleiberman L, et al. Glutathione and morbidity in a community-based
sample of elderly. J Clin Epidemiol 1994; 47: 1021-26. [PubMed]
3 Fletcher RH, Fletcher SW. Glutathione and ageing: ideas and evidence.
Lancet 1994; 344: 1379-80. [PubMed]
4 Beutler E, Gelbart T. Plasma glutathione in health and in patients with malignant disease. J
Lab Clin Med 1985; 105: 581-84. [PubMed]
5 Nourooz-Zadeh J, Tajaddinni-Sarmadi J, Wolff SP. Measurement of plasma hydroperoxide concentrations by the ferrous oxidation-xylenol orange assay in conjunction with triphenylphosphine. Anal Biochem 1994; 220: 403-09. [PubMed]


Senior Member
Hi, Dan.

Thanks for posting this. These authors certainly found a big difference in plasma glutathione between the healthy and ill patients, which we also see in ME/CFS. Glutathione depletion is certainly not limited to ME/CFS. I think its combination with the methylation partial block is characteristic of ME/CFS and autism. It may also be present in some of the adult neurological diseases, but limited to certain parts of the brain, rather than being bodywide. Their absolute values of plasma glutathione are quite a lot lower than those measured by Health Diagnostics. I think the reason is that Health Diagnostics uses a proprietary combination of enzyme inhibitors in their blood sampling vials to prevent the glutathione from oxidizing. The authors of this paper attempted to prevent this also, but I don't think their method was as effective. Glutathione starts oxidizing as soon as it is removed from the body, unless the enzymes are blocked.

Best regards,