100 years since Scott reached the pole: a century of learning about the physiological demands of Antarctica.

The 1910-1913 Terra Nova Expedition to the Antarctic, led by Captain Robert Falcon Scott, was a venture of science and discovery. It is also a well-known story of heroism and tragedy since his quest to reach the South Pole and conduct research en route, while successful was also fateful. Although Scott and his four companions hauled their sledges to the Pole, they died on their return journey either directly or indirectly from the extreme physiological stresses they experienced. One hundred years on, our understanding of such stresses caused by Antarctic extremes and how the body reacts to severe exercise, malnutrition, hypothermia, high altitude, and sleep deprivation has greatly advanced. On the centenary of Scott's expedition to the bottom of the Earth, there is still controversy surrounding whether the deaths of those five men could have, or should have, been avoided. This paper reviews present-day knowledge related to the physiology of sustained man-hauling in Antarctica and contrasts this with the comparative ignorance about these issues around the turn of the 20th century. It closes by considering whether, with modern understanding about the effects of such a scenario on the human condition, Scott could have prepared and managed his team differently and so survived the epic 1,600-mile journey. The conclusion is that by carrying rations with a different composition of macromolecules, enabling greater calorific intake at similar overall weight, Scott might have secured the lives of some of the party, and it is also possible that enhanced levels of vitamin C in his rations, albeit difficult to achieve in 1911, could have significantly improved their survival chances. Nevertheless, even with today's knowledge, a repeat attempt at his expedition would by no means be bound to succeed.

Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease.

BACKGROUND: Crohn disease (CD) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating (peripheral blood) mononuclear cells (PBMCs). Fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters PBMC function. OBJECTIVE: We investigated the effect of fish oil plus antioxidants on cytokine production by PBMCs from patients with CD with raised C-reactive protein concentrations (>/=6.9 mg/L) or erythrocyte sedimentation rates (>/=18 mm/h). DESIGN: A randomized placebo-controlled trial of fish oil (2.7 g EPA and DHA/d; n = 31) or placebo (olive oil; n = 31) for 24 wk was conducted in patients with CD. The fish-oil group additionally received an antioxidant preparation (vitamins A, C, and E and selenium). Exclusion criteria included corticosteroid use. Fatty acid composition was measured by gas chromatography. Production of tumor necrosis factor alpha, interferon gamma (IFN-gamma), and prostaglandin E(2) (PGE(2)) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin (lipopolysaccharide). RESULTS: Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into PBMCs (P < 0.001) and lower arachidonic acid (P = 0.006) and lower production of IFN-gamma by mitogen-stimulated PBMCs (P = 0.012) and of PGE(2) by lipopolysaccharide-stimulated PBMCs (P = 0.047). CONCLUSION: Dietary supplementation with fish oil plus antioxidants is associated with modified PBMC composition and lower production of PGE(2) and IFN-gamma by circulating monocytes or macrophages. The response of extraintestinal manifestations of CD should be investigated in a randomized controlled trial.

Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation.

BACKGROUND: Prostaglandin E(2) (PGE(2)) inhibits lymphocyte proliferation and the production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells, but the effect of PGE(2) on interleukin 4 (IL-4) production is unclear. Fish oil, which contains eicosapentaenoic and docosahexaenoic acids, inhibits production of PGE(2). The effects of fish oil on lymphocyte proliferation and production of IFN-gamma and IL-4 are unclear and may be influenced by the availability of antioxidants. OBJECTIVE: We investigated the effect of dietary fish oil with and without antioxidant cosupplementation on lymphocyte proliferation and the production of PGE(2), IFN-gamma, and IL-4 by peripheral blood mononuclear cells. DESIGN: Sixteen healthy men received dietary fish-oil supplements providing 0.3, 1, and 2 g eicosapentaenoic acid plus docosahexaenoic acid/d for 4 consecutive weeks each (total of 12 wk). All subjects were randomly assigned to daily cosupplementation with either antioxidants (200 microg Se, 3 mg Mn, 30 mg RRR-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 micro g vitamin A) or placebo. RESULTS: Fish-oil supplementation decreased PGE(2) production and increased IFN-gamma production and lymphocyte proliferation from baseline values. Cosupplementation with antioxidants did not affect cytokine production or lymphocyte proliferation. CONCLUSION: Dietary fish oil modulates production of IFN-gamma and lymphocyte proliferation in a manner consistent with decreased production of PGE(2), but this effect is not modified by antioxidant cosupplementation.

Peripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with nutritional deficiencies, altered plasma concentrations of polyunsaturated fatty acids (PUFA) and an anti-inflammatory response to fish oil that contains n-3 PUFA. This suggests that, in CD, immune cells may have altered n-3 PUFA composition with functional consequences. The aim of this study is to investigate n-3 and n-6 PUFA composition and synthetic function of peripheral blood mononuclear cells (PBMC) in the basal state. METHODS: A case control study of 52 adult CD patients and healthy, age- and sex-matched controls. Composition of PBMC and plasma phospholipids were measured by gas chromatography and production of tumour necrosis factor-alpha, prostaglandin E2 (PGE2) and interferon-gamma (IFN-gamma) by PBMC were measured by ELISA. RESULTS: CD was associated with higher concentrations of eicosapentaenoic acid and other n-3 PUFA, and lower arachidonic acid (AA) (n-6 PUFA) in PBMC. This was not explained by differences in dietary fat intake. Lower rates of production of PGE2 and IFN-gamma by PBMC were noted in quiescent and active CD, respectively, compared to controls. CONCLUSIONS: CD is associated with a greater availability, and not a deficiency, of n-3 PUFA in PBMC, but lower concentrations of AA, and lower rates of production of PGE2 and IFN-gamma, compared to healthy controls.

'Malnutrition Universal Screening Tool' predicts mortality and length of hospital stay in acutely ill elderly.

Malnutrition and its impact on clinical outcome may be underestimated in hospitalised elderly as many screening procedures require measurements of weight and height that cannot often be undertaken in sick elderly patients. The 'Malnutrition Universal Screening Tool' ('MUST') has been developed to screen all adults, even if weight and/or height cannot be measured, enabling more complete information on malnutrition prevalence and its impact on clinical outcome to be obtained. In the present study, 150 consecutively admitted elderly patients (age 85 (sd 5.5) years) were recruited prospectively, screened with 'MUST' and clinical outcome recorded. Although only 56 % of patients could be weighed, all (n 150) could be screened with 'MUST'; 58 % were at malnutrition risk and these individuals had greater mortality (in-hospital and post-discharge, P<0.01) and longer hospital stays (P=0.02) than those at low risk. Both 'MUST' categorisation and component scores (BMI, weight loss, acute disease) were significantly related to mortality (P<0.03). Those patients with no measured or recalled weight ('MUST' subjective criteria used) had a greater risk of malnutrition (P=0.01) and a poorer clinical outcome (P<0.002) than those who could be weighed and, within both groups, clinical outcome was worse in those at risk of malnutrition. The present study suggests that 'MUST' predicts clinical outcome in hospitalised elderly, in whom malnutrition is common (58 %). In those who cannot be weighed, a higher prevalence of malnutrition and associated poorer clinical outcome supports the importance of routine screening with a tool, like 'MUST', that can be used to screen all patients.

High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial.

Crohn's disease is associated with altered bone turnover that may be influenced by nutritional status, the systemic inflammatory response, cytokine production by circulating (peripheral blood) mononuclear cells (PBMC) and antioxidant micronutrient intake. High-dose fish oil is associated with reductions in disease relapse and inflammatory markers, and modulates PBMC function. The effect of fish oil plus antioxidants on bone turnover and PBMC function (the production of interferon-gamma and prostaglandin E2) in Crohn's disease was investigated in a randomised-controlled trial. Patients with currently or recently raised biochemical markers of inflammation (C-reactive protein > or = 6.9 mg/l or erythrocyte sedimentation rate > or =18 mm/h) received fish oil (providing 2.7 g/d EPA and DHA) and antioxidants (vitamins A, C and E, and Se) (n 31) or placebo (n 30) for 24 weeks. Bone turnover was assessed by measuring the concentrations of urinary deoxypyridinoline (bone resorption) and serum osteocalcin (bone formation). Fish oil plus antioxidants were associated with increases in EPA, DHA Se in plasma (all P < 0.01), and with a reduction in interferon-gamma production by mitogen-stimulated PBMC, which demonstrated a negative correlation with deoxypyridinoline/creatinine:osteocalcin ratio (r - 0.33, P = 0.009). There were no differences between the groups at 24 weeks in the response of deoxypyridinoline or osteocalcin or their ratio, or in nutritional status. Dietary supplementation in Crohn's disease with high intakes of EPA and DHA, as fish oil, plus antioxidants was associated with a modulated production of interferon-gamma by PBMC but not altered indices of bone turnover.

Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation.

Increased dietary consumption of the n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (20 : 5n-3; EPA) and docosahexaenoic acid (22 : 6n-6; DHA) is associated with their incorporation into circulating phospholipid and increased production of lipid peroxide metabolites. The relationship between peripheral blood mononuclear cell (PBMC) function, n-3 PUFA intake and antioxidant co-supplementation is poorly defined. We therefore investigated tumour necrosis factor (TNF)-alpha and interleukin (IL) 6 production by PBMC and phospholipid fatty acid composition in plasma and erythrocytes of healthy male subjects (n 16) receiving supplemental intakes of 0.3, 1.0 and 2.0 g EPA+DHA/d, as consecutive 4-week courses. All subjects were randomised in a double-blind manner to receive a concurrent antioxidant supplement (200 microg Se, 3 mg Mn, 30 mg D-alpha-tocopheryl succinate, 90 mg ascorbic acid, 450 microg vitamin A (beta-carotene and retinol)) or placebo. There was a positive dose-dependent relationship between dietary n-3 PUFA intake and EPA and DHA incorporation into plasma phosphatidylcholine and erythrocyte phosphatidylethanolamine, with a tendency towards a plateau at higher levels of intake. Production of TNF-alpha and IL-6 by PBMC decreased with increasing n-3 PUFA intake but tended towards a 'U-shaped' dose response. Both responses appeared to be augmented by antioxidant co-supplementation at intermediate supplementary n-3 PUFA intakes. Thus, increased dietary n-3 PUFA consumption resulted in defined but contrasting patterns of modulation of phospholipid fatty acid composition and PBMC function, which were further influenced by antioxidant intake.