A review of the epidemiological evidence for the 'antioxidant hypothesis'.

OBJECTIVE: The British Nutrition Foundation was recently commissioned by the Food Standards Agency to conduct a review of the government's research programme on Antioxidants in Food. Part of this work involved an independent review of the scientific literature on the role of antioxidants in chronic disease prevention, which is presented in this paper. BACKGROUND: There is consistent evidence that diets rich in fruit and vegetables and other plant foods are associated with moderately lower overall mortality rates and lower death rates from cardiovascular disease and some types of cancer. The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids and other antioxidant nutrients afford protection against chronic diseases by decreasing oxidative damage. RESULTS: Although scientific rationale and observational studies have been convincing, randomised primary and secondary intervention trials have failed to show any consistent benefit from the use of antioxidant supplements on cardiovascular disease or cancer risk, with some trials even suggesting possible harm in certain subgroups. These trials have usually involved the administration of single antioxidant nutrients given at relatively high doses. The results of trials investigating the effect of a balanced combination of antioxidants at levels achievable by diet are awaited. CONCLUSION: The suggestion that antioxidant supplements can prevent chronic diseases has not been proved or consistently supported by the findings of published intervention trials. Further evidence regarding the efficacy, safety and appropriate dosage of antioxidants in relation to chronic disease is needed. The most prudent public health advice remains to increase the consumption of plant foods, as such dietary patterns are associated with reduced risk of chronic disease.

Diet and cardiovascular disease in the UK: are the messages getting across?

Cardiovascular disease (CVD) is a leading cause of premature death in the UK and a major cause of ill health and disability. Whilst death rates from CVD have been falling since the late 1970s in the UK, levels of morbidity (such as angina) do not seem to be falling and may even be rising in some age-groups, especially as the population ages. There is broad consensus that lifestyle factors, including physical activity and diet, are fundamental determinants of heart disease risk. Current recommendations to reduce cardiovascular risk include maintaining a healthy body weight, eating five or more portions of fruit and vegetables each day, reducing intake of fat (particularly saturated fatty acids), reducing salt intake and eating one portion of oily fish per week. Although some improvements have been made in recent years (e.g. a reduction in total fat intake), national studies suggest that more effective campaigns are required to increase awareness of the benefits of these dietary changes. The present paper will discuss how the dietary messages relating to CVD are best communicated to the general public and will identify some of the main barriers to their implementation.

Fetal programming and the Leningrad Siege study.

The Leningrad Siege Study investigated the relationship between decreased maternal food intake and risk factors for coronary heart disease in adult life. The study screened 169 subjects exposed to intrauterine starvation during the Siege of Leningrad (now St. Petersburg) 1941-4, 192 subjects born in Leningrad before the siege and 188 subjects born concurrently with these two groups but outside the area of the siege. No difference was found between the subjects exposed to starvation in utero and during infancy in glucose tolerance [in utero: 5.2 mmol/l (95% confidence interval 5.1 to 5.3; infancy: 5.3 (5.1 to 5.5), p = 0.94], insulin concentration, blood pressure, lipid concentration or coagulation factors. The intrauterine exposed group had evidence of endothelial dysfunction by higher concentrations of von Willebrand factor and a stronger interaction between adult obesity and blood pressure. Non-systematic differences in subscapular to triceps skinfold ratio, diastolic blood pressure and clotting factors were demonstrated compared to the non-exposed groups. In conclusion, this study did not find an association between intrauterine starvation and glucose intolerance, dyslipidaemia, hypertension or cardiovascular disease in adult life. These findings differ from studies of subjects exposed to maternal starvation during the Dutch Hunger Winter. However, the dissimilar effects of exposure to the two famines may contribute to our understanding of the mechanisms of the thrifty phenotype and support the importance of catch-up growth during early childhood, a situation that occurred in the Netherlands by not in Leningrad.

Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study.

OBJECTIVE: To investigate the relation between decreased maternal food intake and risk factors for coronary heart disease in adult life. DESIGN: Cross sectional study. SUBJECTS: 169 subjects exposed to malnutrition in utero (intrauterine group) during the siege of Leningrad (now St Petersburg) in 1941-4; 192 subjects born in Leningrad just before rationing began, before the siege (infant group); and 188 subjects born concurrently with the first two groups but outside the area of the siege (unexposed group). SETTING: Ott Institute of Obstetrics and Gynaecology, St Petersburg. MAIN OUTCOME MEASURES: Development of risk factors for coronary heart disease and diabetes mellitus-obesity, blood pressure, glucose tolerance, insulin concentrations, lipids, albumin excretion rate, and clotting factors. RESULTS: There was no difference between the subjects exposed to starvation in utero and those starved during infant life in: (a) glucose tolerance (mean fasting glucose: intrauterine group 5.2 (95% confidence interval 5.1 to 5.3), infant group 5.3 (5.1 to 5.5), P = 0.94; mean 2 hour glucose: intrauterine group 6.1 (5.8 to 6.4), infant group 6.0 (5.7 to 6.3), P = 0.99); (b) insulin concentration; (c) blood pressure; (d) lipid concentration; or (e) coagulation factors. Concentrations of von Willebrand factor were raised in the intrauterine group (156.5 (79.1 to 309.5)) compared with the infant group (127.6 (63.9 to 254.8); P < 0.001), and female subjects in the intrauterine group had a stronger interaction between obesity and both systolic (P = 0.01) and diastolic (P = 0.04) blood pressure than in the infant group. Short adult stature was associated with raised concentrations of glucose and insulin 2 hours after a glucose load-independently of siege exposure. Subjects in the unexposed group had non-systematic differences in subscapular to triceps skinfold ratio, diastolic blood pressure, and clotting factors compared with the exposed groups. CONCLUSIONS: Intrauterine malnutrition was not associated with glucose intolerance, dyslipidaemia, hypertension, or cardiovascular disease in adulthood. Subjects exposed to malnutrition showed evidence of endothelial dysfunction and a stronger influence of obesity on blood pressure.