Metabolic diseases

CLASS="LinkBox"> Editorial Obesity: definitely a growing concern Time to implement Australia's strategy for preventing overweight and obesity MJA 2001; 174: 553-554 Obesity is increasingly recognised as a health problem by the Australian community, with frequent discussions of obesity-related issues in the media and heavy marketing of weight-loss products. There is abundant evidence to support this view, not least being the 1995 National Nutrition Survey showing that 56% of adult Australians are either overweight or obese.1A casual ...

Louise A Baur

CLASS="LinkBox"> Research Prevalence of overweight and obesity in Australian children and adolescents: reassessment of 1985 and 1995 data against new standard international definitions Anthea M Magarey, Lynne A Daniels and T John C Boulton MJA 2001; 174: 561-564 For editorial comment, see Baur; see also Eckersley Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Paediatrics Abstract Objective: To review the prevalence of overweight and ...

Anthea M Magarey · Lynne A Daniels

Editorial Iron deficiency in children: food for thought Many Australian children are at risk of iron deficiency and long term neurocognitive impairment MJA 2001; 174: 162-163 Iron deficiency is the most common nutritional deficiency worldwide. Iron depletion and deficiency and, less commonly, iron-deficiency anaemia (defined in the Box) are prevalent in all age groups, but particularly in infants, the elderly and women after the onset of menses, and also in socioeconomically deprived populations, such as refugees and recent migrants. Infancy is the critical period for brain growth, and nutrient deficiencies during this time may affect psychomotor development and neurocognition. Iron-deficient infants are often apathetic, listless, irritable and anorexic. These symptoms resolve rapidly with iron supplementation, but less well known is the fact that long term neurocognitive impairment may persist.1,2 Young children with iron-deficiency anaemia have been found to score 12 to 15 points lower on the Bayley infant development scale than their iron-sufficient peers.3 Prolonged iron supplementation improved these scores and other performance parameters, such as fine motor and discriminative skills, but did not produce complete resolution despite an excellent haematological response.4Persisting deficits in a variety of psychometric tests have also been shown both in five-year-olds in Chile and 10-year-olds in Costa Rica who were iron deficient in infancy,1,5 but there are no convincing data on long term outcome in adult life. In older children with iron deficiency (eg, teenage girls), iron supplementation can also improve neurocognitive performance.6 Therefore, although no studies have established a direct causal relationship between iron deficiency and performance, it is prudent to prevent iron depletion and, if present, to treat it until iron status is normal. Australian paediatricians have long been aware that populations who have recently migrated, such as the Vietnamese, as well as refugees from most of the world's troublespots and Indigenous populations, have a high prevalence of iron deficiency. In this issue of the Journal, Karr and colleagues report on the iron status of a group of Sydney children whose mothers were born in an Arabic-speaking country.7 In this group of 403 children aged 12-38 months, prevalence of iron-deficiency anaemia was 6%, iron deficiency without anaemia 9%, and iron depletion 23%. These levels are disturbing. Similar results have been found among children of South East Asian descent in Adelaide, South Australia.8 Although most children with iron depletion will suffer no long term harm, they should be viewed as part of a continuum, with children with iron-deficiency anaemia at greatest risk of not achieving their full intellectual potential. Most of these children have no other nutritional deficiency and, indeed, are often obese. The risk factors for impaired iron status identified by Karr and colleagues were similar to those seen in other countries, and include prematurity, excessive consumption of cows' milk and recent maternal immigration. However, the mechanisms by which these risk factors contribute to iron depletion are explored only superficially by Karr and colleagues, and no convincing strategies to correct iron depletion were espoused other than provision of Arabic interpreters at early childhood health centres. Some of the reasons the identified risk factors contribute to iron depletion are as follows. Prematurity results in inadequate iron accrual. Cows' milk is deficient in iron and in young infants causes occult microscopic blood loss from the colon. Recent maternal immigration may be linked to poverty, and these children may consume excessive amounts of cows' milk because it is cheap and readily available. Recent immigrant mothers may also have inadequate iron stores, resulting in diminished iron stores in their babies. Once children become iron deficient, they become very restricted in the range of foods they will accept. Appetite and tolerance of new or previously discarded foods improves with iron repletion.9 Furthermore, maternal iron deficiency results in large placental size and small babies whose iron stores are insufficient to sustain them through rapid early growth.10 The currently fashionable "Barker hypothesis" states that health outcomes in later life are programmed by intrauterine events. Infants who are small for gestational age tend to have worse adult outcomes and are more likely to develop insulin resistance and hypertension. Maternal iron deficiency may conceivably result in yet to be recognised consequences in adult life. Medical practitioners should try to ensure that children and women of childbearing age are iron replete. Commonsense dictates that, because of the concern over persisting neurocognitive deficits, it is much better to prevent iron deficiency in the community than to treat it case by case. Although it is tempting to view iron depletion as a problem of disadvantage, many other children are at risk. We therefore recommend that: Young children of high-risk ethnic groups, survivors of prematurity and children with excessive cows' milk consumption or prolonged breast-feeding (breast milk is very low in iron) should have a full blood examination and iron studies, including measurement of ferritin levels. Any developmentally delayed child should be screened for iron status. In addition, children with breath holding may be iron deficient, and breath holding may improve substantially following iron supplementation.11 Iron-depleted children should receive full supplementation of elemental iron at a dose of 6 mg/kg per day for about two to three months, when the iron studies should be repeated. Commercial iron preparations are relatively unpalatable, and it is often difficult to enforce prolonged therapy. Iron absorption is enhanced if supplements are administered with a vitamin C source, such as orange juice. Parents should be warned that bowel motions are often black and that this does not denote ill-health. Dietary advice about iron-rich foods should also be offered. Protocol advice for iron deficiency should be incorporated into the early years program currently being promoted by the Commonwealth Department of Health and Aged Care and the Royal Australasian College of Physicians, which concentrates on optimising intellectual and social outcomes with interventions aimed at infants. Some countries, not including Australia, recommend iron supplementation in infancy. The most effective measure on a global scale to prevent iron deficiency has been fortification of infant formula with iron, and currently all breast-milk substitute formulas in Australia are iron fortified. This intervention is most effective in the first year of life, but does not address the problem of infants who are exclusively breastfed and children with a large intake of cows' milk. All infants should have iron-rich foods, particularly red meat, introduced shortly after six months of age. A dietary program aimed at improving iron status in Australian mothers and children would benefit both individuals and society as a whole. The high incidence of iron-deficiency anaemia in this cohort of Australian children of Arabic background and its known association with persisting neurocognitive deficits should provide Australian health planners with food for thought. Richard T L Couper Senior Paediatric Gastroenterologist University of Adelaide, Women's and Children's Hospital, Adelaide, SA Karen N Simmer Associate Professor and Staff Neonatologist Flinders University and Flinders Medical Centre, Adelaide, SA Lozoff B, Jimenez E, Wolf A. Long-term developmental outcome of infants with iron deficiency. N Engl J Med 1991; 325: 687-694. De Andraca I, Walter T, Castillo M, et al. Iron deficiency anaemia and its effects upon psychological development at preschool age: a longitudinal study. Nestlé Foundation Nutritional Annual Report. Lausanne: Nestlé Foundation, 1990; 53-62. Oski FA, Honig AS. The effects of therapy on the developmental scores of iron deficient infants. J Pediatr 1978; 92: 21-25. Lozoff B, Wolf AW, Jimenez E. Iron deficiency anaemia and infant development: effects of extended oral iron therapy. J Pediatr 1996; 129: 382-385. Lozoff B, Jimenez E, Hagen J, et al. Poorer behavioural and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000; 105: ES1. Bruner AB, Joffe A, Duggan AK, et al. Randomized study of cognitive effects of iron supplementation in non-anaemic iron deficient adolescent girls. Lancet 1996; 348: 992-996. Karr MA, Mira M, Alperstein G, et al. Iron deficiency in Australian-born children of Arabic background in central Sydney. Med J Aust 2001; 174: 165-168. Oti-Boateng P, SeshadTi R, Petrick S, Gibson RA, Simmer K. Iron status and dietary iron intake of 6-24 month old children in Adelaide. J Paediatr Child Health 1998; 34: 250-253. Stockman JA. Microcytic anaemias. In: Behram RE, editor. Nelson textbook of paediatrics. 14th ed. Philadelphia: WB Saunders, 1992; 1239-1241. Hindmarsh PC, Geary NIPP, Rodeck CH, et al. Effects of early maternal iron stores on placental weight and structure. Lancet 2000; 356: 719-723. Mocan H, Yildiran A, Orhan F, Erduran E. Breath holding spells in 91 children and response to treatment with iron. Arch Dis Child 1999; 81: 361-362. Definitions of impaired iron statusIron depletion: Low iron stores but no change in haematological parameters. Iron deficiency: Low iron stores and reduced mean cell volume but normal haemoglobin concentration. Iron-deficiency anaemia: Low iron stores, reduced mean cell volume and reduced haemoglobin concentration. Back to text

Karen N Simmer

Research Iron deficiency in Australian-born children of Arabic background in central Sydney Margaret A Karr, Michael Mira, Garth Alperstein, Samia Labib Boyd H Webster, Ahti T Lammi and Patricia Beal MJA 2001; 174: 165-168 For editorial comment, see Couper and Simmer Abstract - Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Public and environmental health Abstract Objectives: To determine the prevalence of iron depletion and deficiency, and iron-deficiency anaemia, along with risk factors for iron depletion, in Australian-born children aged 12-36 months of Arabic-speaking background. Design: Community-based survey. Setting: Central Sydney Area Health Service (CSAHS), NSW, April to August, 1997. Participants: All children born at five Sydney hospitals between 1 May 1994 and 30 April 1996, whose mothers gave an Arabic-speaking country of birth and resided in the area served by the CSAHS. Main outcome measures: Full blood count (haemoglobin, mean corpuscular haemoglobin, mean corpuscular volume), plasma ferritin concentration, haemoglobin electrophoresis, potential risk factors for iron depletion. Results: Families of 641 of the 1161 eligible children were able to be contacted, and 403 agreed to testing (response rate, 62.9% among those contacted). Overall, 6% of children had iron-deficiency anaemia, another 9% were iron deficient without anaemia, and 23% were iron depleted. Multiple logistic regression analysis showed three significant independent risk factors for iron depletion: < 37 weeks' gestation (odds ratio [OR], 5.88, P = 0.001); mother resident in Australia for less than the median time of 8.5 years (OR, 1.96, P = 0.016); and daily intake of > 600 mL cows' milk (OR, 3.89, P = < 0.001). Conclusion: Impaired iron status is common among children of Arabic background, and targeted screening is recommended for this group. Numerous studies have documented the adverse health effects of iron deficiency in infants and preschool children, including growth retardation,1,2 gastrointestinal changes,3 impaired immune function,4 impaired behavioural and mental development5,6 and decline in psychomotor development.7,8 In 1992-1994, a study of Sydney children aged 9-62 months found that 1.1% had iron-deficiency anaemia, while 2.8% were iron deficient without anaemia and another 10.5% were iron depleted.9 The prevalence of iron-deficiency anaemia appeared to be higher among children of Arabic-speaking background, but the small number of these children prevented firm conclusions, and the reasons for any difference were not clear. The most important determinants of iron status in infants are growth rate relative to iron endowment at birth, dietary iron content and bioavailability and gastrointestinal blood loss.10 Risk factors for iron deficiency in infancy and childhood include prematurity, low birth weight,11,12 exclusive breastfeeding beyond six months of age,13 introduction of whole cows' milk before 12 months of age,14 and high intake of cows' milk.15 We examined the prevalence of impaired iron status in a large group of Australian-born children of Arabic-speaking background and evaluated their risk factors for iron depletion. Methods The study was a community-based survey undertaken between April and August 1997. Participants Children were identified from the medical records of five Sydney hospitals, which, according to the Midwives Data Base, account for 92% of deliveries to mothers born in an Arabic-speaking country and residing in the area served by the Central Sydney Area Health Service (CSAHS).16 Eligibility criteria were: birthdate between 1 May 1994 and 30 April 1996; mother gave an Arabic-speaking country of birth on admission; postcode of mother's place of residence was in the area served by the CSAHS. Hospitals were asked to exclude stillbirths and neonatal deaths. Contact details were obtained from the medical records. Survey Parents of all eligible children were sent a letter about the study in both Arabic and English. Five days later, they were telephoned to discuss queries and to invite their child's participation. If they agreed, an appointment was made at a convenient early childhood health centre, or a home visit was arranged. Parents were asked to bring the child's Personal Health Record for assessment of birth weight and gestation. Demographic data were obtained using a structured questionnaire administered by an Arabic-speaking research assistant (S L). Questions were also asked about the child's feeding habits since birth and whether the child had had a fever in the two weeks before the blood test, as fever can elevate plasma ferritin concentration.17 Investigations About 0.75 mL of blood was collected by fingerprick and tested at the Royal Alexandra Hospital for Children (RAHC), Sydney, NSW. Haematological investigations (using a Coulter S+IV, Fullerton, Cal, USA) included measurement of haemoglobin and red cell indices. Plasma ferritin concentration was measured by immunoradiometric assay (Biorad, Hercules, Cal, USA). Haemoglobin electrophoresis was performed on all samples to detect haemoglobinopathies. Definitions of impaired iron status are shown in Box 1. All parents were notified of their children's results. Children with poor iron status or haemoglobinopathy were referred to their general practitioners (GPs). A copy of the laboratory report was sent to the GP and to the parents, if they so requested. Statistical analyses Children found to have a haemoglobinopathy were excluded from the analyses, which were performed using Stata (version 5).21 Statistical tests were performed after adjustment for possible cluster effects both within hospitals and within families (as some families contributed more than one child to the study). Confidence intervals were similarly adjusted. Adjusted χ2 tests were used to examine relationships between iron depletion and demographic and risk factors. Variables found to be significantly associated with iron depletion were then entered into a multivariate logistic regression model. Prevalence of impaired iron status was compared with prevalence in children from the general population of central Sydney assessed in 1992-1994.9 Data from that study were re-examined for children aged 12-38 months, using a ferritin level < 10 µg/L to define iron depletion. To test the representativeness of our sample group, demographic characteristics of the mothers were compared with those of all women who in the 1996 census gave an Arabic-speaking country of birth, resided in the area served by the CSAHS, were aged 15-45 years and had children aged 12-38 months. These data were obtained from the Australian Bureau of Statistics. Ethical approval for all components of this study was obtained from the CSAHS Ethics Review Committee. All participating parents gave informed written consent. Results We were able to contact families of 641 of the 1161 eligible children and tested 403 of these children (63% response rate among those able to be contacted). Haematological testing identified a haemoglobinopathy in 21 children, who were therefore excluded from analysis, although two had other haematological parameters consistent with iron depletion. This left 382 children with a plasma ferritin result, and 315 with complete haematological results (blood volume was insufficient for a complete examination in the other 67). Median age of the 382 children at the time of data collection was 25 months (range, 12-38 months). Age distribution was 12-23 months (149 children), 24-35 months (204), and 36-38 months (29). Just over half the children (53%) were male. Prevalence of impaired iron status Prevalence of impaired iron status is shown in Box 2. Overall, 38% of children with an Arabic background had impaired iron status, comprising 6% with iron-deficiency anaemia, a further 9% with iron deficiency without anaemia and a further 23% with iron depletion. The Box also shows prevalences found in 1992-1994 among children the same age in the general population of central Sydney.9 The proportion of children with impaired iron status was substantially higher among Australian-born children of Arabic-speaking background in 1997 than among children of the same age in the general community in 1992-1994. Among the children of Arabic background, those who were reported as having a fever in the two weeks before the blood test were statistically less likely to fulfil the criteria for iron depletion (19/122 versus 68/260; F1,339 = 5.07; P = 0.025). However, they did not differ significantly in rates of iron deficiency (11/108 versus 16/207; F1,282 = 0.49; P = 0.48) or iron-deficiency anaemia (8/108 versus 12/207; F1,282 = 0.31; P = 0.58). The rate of iron depletion among the 260 children reported not to have had a fever in the two weeks before the blood test was 26% (95% CI, 21%-32%). There were no significant differences in iron status between the sexes or between age groups. Risk-factor analysis Potential risk factors among the 382 children are shown in Box 3. Univariate analysis revealed that prematurity, mother resident in Australia less than the median time of 8.5 years, mother born in a country other than Lebanon, and daily intake of more than 600 mL of cows' milk were significantly associated with iron depletion (Box 4). None of the other variables tested, including age of introduction of cows' milk, were significantly associated with iron depletion. Multivariate logistic regression analysis determined that prematurity, mother resident in Australia less than the median time of 8.5 years, and daily intake of more than 600 mL of cows' milk, but not mother born in a country other than Lebanon, were independently associated with iron depletion (Box 4). Children who had been born prematurely were almost six times more likely to be iron depleted, while those who drank more than 600 mL cows' milk per day were almost four times as likely and those whose mothers had been in Australia less than the median time (8.5 years) were almost twice as likely. Representativeness of sample We compared post-secondary education and time in Australia between the sample group and all women who in the 1996 census gave an Arabic-speaking country of birth, resided in the area served by the CSAHS, were aged 15-45 years and had children aged 12-38 months. In the sample group, 29% (116/403) had post-secondary qualifications (95% CI, 24%-33%), compared with 30.2% in the census group (421/1392). Similarly, 30% (121/401) of our sample had been in Australia for six to 10 years (95% CI, 26%-35%), while the corresponding figure for the census group was 26.4% (368/1392). The 238 parents who declined a blood test for their child were questioned by telephone about the age and sex of the child and the volume of cows' milk consumed daily; 180 parents (76%) responded. There were no significant differences between their children and those who had blood tests in age (P = 0.7), sex (P = 0.6) or reported volume of cows' milk consumed daily (P = 0.17). Among the 382 children tested for iron depletion, 67 had moved place of residence since birth and 315 had not moved. The proportion with iron depletion did not differ between these two groups (OR, 1.31; 95% CI, 0.73-2.36). Nor did it differ between the 67 children who had only ferritin level estimated and the 315 who gave sufficient blood for a full haematological examination (OR, 1.03; 95% CI, 0.53-2.01). Discussion These results indicate a public health problem in Australian-born children of Arabic-speaking background in central Sydney that could indicate a nationwide problem. More than a third of these children had impaired iron status, including 6% with iron-deficiency anaemia and another 9% with iron deficiency without anaemia. These prevalences are higher than those found in children the same age in the general population of central Sydney in 1992-1994.9There are several potential sources of bias in this study. The first was the use of retrospective records and consequent failure to contact about 45% of mothers. This is a common problem in such retrospective studies.22,23 However, the mothers of the children studied did not differ significantly from all women in the 1996 census who were aged 15-45 years with children in the target age range, gave an Arabic-speaking country of birth and resided in the CSAHS, while prevalence of iron depletion did not differ between children who had moved residence since birth and those who had not. It is unlikely that our sample differed substantially from the total study population. A second potential source of bias was non-response. However, children whose parents refused a blood test did not differ significantly from those who had a blood test in age, sex and proportion who drank more than 600 mL cows' milk daily. Finally, children whose blood samples were insufficient for full haematological assessment did not differ significantly in prevalence of iron depletion from those who had a full assessment. In the group of children reported to have had a fever in the two weeks before the blood test, a significantly lower proportion fulfilled the criteria for iron depletion. Therefore, the rate of iron depletion reported may be an underestimate. The definition of iron deficiency used in this study was particularly stringent, requiring abnormal values for three laboratory indicators of iron status. Criteria used by the United States Third National Health and Nutrition Examination Survey were less stringent: individuals were diagnosed as iron-deficient if they had abnormal values for two of three laboratory indicators (serum ferritin, free erythrocyte protoporphyrin or transferrin saturation).18 Nevertheless, that survey found rates of iron deficiency and iron-deficiency anaemia among children aged one to two years less than half the rates found in our study (3% versus 6% in our study). The US rate was similar to the rate found in children in the general population of central Sydney in 1992-1994. Risk of iron depletion in our study was greater in children whose mothers had been in Australia for less than the median time of 8.5 years. About 79% of these mothers spoke Arabic, or mainly Arabic, in the home. Early childhood health centres in central Sydney have specific days on which an Arabic interpreter is present, but anecdotal reports suggest that many mothers do not avail themselves of this service. Newly arrived mothers should be targeted in hospital, immediately postpartum, and given information as to which days an Arabic interpreter will be at their local centre and strongly encouraged to attend on a regular basis. Prematurity is well documented as a risk factor for iron deficiency, and this should be kept in mind by GPs and other healthcare providers. Of particular interest is the risk associated with the volume of cows' milk consumed daily. The National Health and Medical Research Council recommends that children aged under 12 months should not receive cows' milk as the main source of milk, while those aged over 12 months should not receive more than 600 mL per day.24 In the multiple logistic regression model, children who consumed more than 600 mL per day were almost four times as likely to have iron depletion, and targeted screening is strongly indicated based on this dietary history. Cows' milk is a poor source of iron, displaces foods with greater available iron and may also increase gastrointestinal occult blood loss. GPs should be aware of the importance of a dietary history for children of Arabic-speaking background and should enquire particularly about the volume of cows' milk consumed per day after 12 months of age. Acknowledgements We wish to thank the parents and children who participated in this study, the haematology laboratory staff at the Royal Alexandra Hospital for Children, Sydney, and the nurses of the participating Early Childhood Health Centres. The blood collection skills of Mrs Rhonda Dryden were invaluable to this study. The study was funded by the National Health and Medical Research Council Public Health Research Development Committee, Grant No: 97-417-7. References Aukett MA, Parks YA, Scott PH, Wharton BA. Treatment with iron increases weight gain and psychomotor development. Arch Dis Child 1986; 61: 849-857. Prasad AN, Prasad C. Iron deficiency; non-hematological manifestations. Prog Food Nutr Sci 1991; 15: 255-283. Berant M, Khourie M, Menzies IS. Effect of iron deficiency on small intestinal permeability in infants and young children. J Pediatr Gastroenterol Nutr 1992; 14: 17-20. Thibault H, Galtn P, Selz F, et al. The immune response in iron-deficient young children: effect of iron supplementation on cell-mediated immunity. Eur J Pediatr 1993; 152: 120-124. Oski FA, Honig AS, Helu B, Howanitz P. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 1983; 71: 877-880. Lozoff B, Jiminez E, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med 1991; 325: 687-694. Williams J, Wolff A, Daly A, et al. Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study. BMJ 1999; 318: 693-697. Walter T, De Andraca I, Chadud P, Perales CG. Iron deficiency anemia: adverse effects on infant psychomotor development. Pediatrics 1989; 84: 7-17. Karr M, Alperstein G, Causer J, et al. Iron status and anaemia in preschool children in Sydney. Aust N Z J Public Health 1996; 20: 618-622. Dallman PR, Siimes MA, Stekel A. Iron deficiency in infancy and childhood [review]. Am J Clin Nutr 1980; 33: 86-118. Gorten MK, Cross ER. Iron metabolism in premature infants: 2. Prevention of iron deficiency. J Pediatr 1964; 64: 509-520. Friel JK, Andrews WL, Matthew JD, et al. Iron status of very-low-birth-weight infants during the first 15 months of infancy. CMAJ 1990; 143: 733-737. Calvo EB, Galindo AC, Aspres NB. Iron status in exclusively breast-fed infants. Pediatrics 1992; 90: 375-379. Penrod JC, Anderson K, Acosta PB. Impact on iron status of introducing cow's milk in the second six months of life. J Pediatr Gastroenterol Nutr 1990; 10: 462-467. Mills AF. Surveillance for anaemia: risk factors in patterns of milk intake. Arch Dis Child 1990; 65: 428-431. NSW Department of Health, NSW Midwives Data Collection, 1994. Sydney: NSW Department of Health, 1995. Elin RJ, Wolff SM, Finch CA. Effect of induced fever on serum iron and ferritin concentrations in man. Blood 1977; 49: 147-153. Looker AC, Dallman PR, Carroll MD, et al. Prevalence of iron deficiency in the United States. JAMA 1997; 277: 973-976. Dallman PR, Siimes MA. Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr 1979; 94: 26-31. Dallman PR, Looker AC, Johnson CL, Carroll M. Influence of age on laboratory criteria for the diagnosis of iron deficiency anaemia and iron deficiency in infants and children. In: Hallberg L, Asp N-G, editors. Iron nutrition in health and disease. London: J Libbey, 1996: 64-74. Stata statistical software release 5.0 [computer program]. College Station, Texas: Stata Corporation, 1997. McBride WG, Black BP, English BJ. Blood lead levels and behaviour of 400 preschool children. Med J Aust 1982; 2: 26-29. Ranmuthugala G, Karr M, Mira M, et al. Opportunistic sampling from early childhood centres: a substitute for random sampling to determine lead and iron status of pre-school children? Aust N Z J Public Health 1998; 22: 512-514. National Health and Medical Research Council. Dietary guidelines for children and adolescents. Canberra: AGPS, 1995. (Received 2 Mar, accepted 1 Sep, 2000) Authors' details Central Sydney Area Health Service, Sydney, NSW. Margaret A Karr, MPH, MSc(Med), Senior Research Officer, Division of General Practice; Michael Mira, MB BS, PhD, Clinical Professor, Department of General Practice, University of Sydney; Garth Alperstein, FRACP, Paediatrician and Clinical Senior Lecturer, University of Sydney, and Conjoint Senior Lecturer, University of New South Wales, Sydney, NSW; Samia Labib, BA, MEd(Health), Senior Interpreter, Health Interpreter Service. Department of Haematology, Royal Alexandra Hospital for Children, Sydney, NSW. Boyd H Webster, FRCPA, Senior Staff Specialist; Ahti T Lammi, FRACP, FRCPA, Senior Staff Specialist; Patricia Beal, MSc, Senior Hospital Scientist. Reprints will not be available from the authors. Correspondence: Professor M Mira, General Practice Casualty, Balmain Hospital, Booth Street, Balmain, NSW 2041. michaelmira_auATyahoo.co.uk 1: Definitions of impaired iron status used in the survey of children of Arabic background Iron depletion18 Plasma ferritin level Iron deficiency19 Iron depletion plus Mean corpuscular volume plus Mean corpuscular haemoglobin Iron-deficiency anaemia20 Iron deficiency plus Haemoglobin level Back to text 2: Prevalence of impaired iron status among children aged 12-38 months of Arabic background in central Sydney in 1997 Arabic background General population9 Iron status* Number % (95% CI) Number % (95% CI) Iron depletion Iron deficiency Iron-deficiency anaemia 87/382 27/315 20/315 23% (19%-27%) 9% (5%-12%) 6% (4%-9%) 36/381 14/329 5/329 9% (7%-12%) 4% (2%-7%) 2% (0-3%) *Definitions of iron status in children of Arabic background are shown in Box 1. The same definitions were used for children in the general population, except that iron deficiency was defined as iron depletion plus mean corpuscular volume < 70fL (age, 12-23 months) or < 73fL (age, 24-38 months), or red cell zinc protoporphyrin level > 80µmol/mol haem. Back to text 3: Potential risk factors for iron depletion among 382 children aged 12-38 months of Arabic background in central Sydney, 1997 Children with Children without Potential risk factors iron depletion iron depletion P* Born before 37 weeks' gestation 12/87 (14%) 10/295 (3%) 0.001 Birth weight 7/86 (8%) 8/293 (3%) 0.05 Breastfed initially 70/87 (81%) 245/295 (83%) 0.59 Breastfed at time of data collection 4/87 (5%) 9/295 (3%) 0.49 Cows' milk introduced before age of 12 months 32/87 (37%) 76/295 (26%) 0.06 Cows' milk introduced before age of 9 months 15/87 (17%) 36/295 (12%) 0.20 Consume >600mL cows' milk per day 54/83 (65%) 109/287 (38%) Consume ≥1L cows' milk per day 23/83 (28%) 30/287 (11%) Iron-fortified cereal as first solid 38/87 (44%) 149/295 (51%) 0.27 Consume meat 42/87 (48%) 122/295 (41%) 0.26 Receiving vitamin supplement 3/87 (3%) 11/295 (4%) 0.90 Receiving iron-containing supplement 1/87 (1%) 4/295 (1%) 0.88 Mother not born in Lebanon 26/87 (30%) 49/295 (17%) 0.01 Arabic or mainly Arabic spoken at home 58/87 (67%) 180/293 (61%) 0.39 Mother resident in Australia less than median time (8.5 years) 53/86 (62%) 137/294 (47%) 0.02 *By adjusted χ2 test. Back to text 4: Risk factors significantly associated with iron depletion among children aged 12-38 months of Arabic background in central Sydney, 1997 Univariate analysis Multivariate analysis Risk factor Odds ratio (95% CI) P Odds ratio (95% CI) P Gestation ≥37 weeks 1.00 1.00 4.55 (1.70-12.50) 0.003 5.88 (2.22-20.0) 0.001 Years mother in Australia ≥8.5 years 1.00 1.00 1.82 (1.10-3.03) 0.02 1.96 (1.36-3.33) 0.016 Cows' milk consumed daily ≤600mL 1.00 1.00 >600mL 3.04 (1.80-5.13) 3.89 (2.22-6.80) Country of birth Lebanon 1.00 Country other than Lebanon 2.14 (1.18-3.88) 0.01 NS NS=Not significant. Back to text

Margaret A Karr · Michael Mira · Garth Alperstein · Samia Labib · Boyd H Webster · Ahti T Lammi · Patricia Beal

EBM in Action Does drinking carrot juice affect cancer of the prostate? MJA 2001; 174: 197 Clinical question - Search question - Search - Summary of findings - Outcome - References - - More articles on Men's health Clinical question "Does drinking carrot juice have any effect on prostate cancer?" A general practitioner asked this question after her patient, a 77-year-old man who had been diagnosed with invasive prostate cancer, commenced drinking four glasses of carrot juice a day. Information about the exact staging of the cancer was not available. Search question The search question was refined to "What effect does the consumption of beta-carotene have on prostate cancer? Are there any adverse effects, and if so, at what quantity of consumption do they occur?". Ideally, a randomised controlled trial of men recently diagnosed with prostate cancer, comparing a high intake of beta-carotene with no beta-carotene intake, would be the appropriate clinical study design to answer this question. The outcomes assessed would be the appearance of metastases, patient morbidity and mortality, and any adverse effects of the beta-carotene. Search The search terms "beta-carotene", "prostate" and "cancer" were combined to identify appropriate trials. We searched databases including Cochrane Library and SUMSearch (<http://sumsearch.uthscsa.edu/searchform4.htm>), which searches for systematic reviews and original research, and links to PubMed Clinical Queries. Our search yielded five relevant studies. Summary of findings The best evidence identified was a large randomised controlled trial of 29 133 healthy men who were cigarette smokers.1 The men receiving beta-carotene (20 mg) daily had an increased incidence of prostate cancer compared with those receiving placebo (138 v 112 men with prostate cancer). Further analysis of the results showed prostate cancer incidence to be 23% higher (95% CI, -4% to 59%) and mortality 15% higher (95% CI, -30% to 89%) in men who received beta-carotene compared with those who did not, but this trend was not significant.2 A prospective cohort study found no evidence of either protection or harm associated with dietary beta-carotene.3 Two case-control studies, one involving beta-carotene supplements and the other dietary beta-carotene, found a protective effect of high levels of beta-carotene intake.4,5 One of these studies reported a significant protective effect of high levels of dietary beta-carotene (relative risk of prostate cancer [RR], 0.60; 95% CI, 0.37 to 0.99), particularly in men younger than 68 years (RR, 0.30; 95% CI, 0.13 to 0.66).5We were unable to find any studies evaluating the influence of beta-carotene in patients with established prostate cancer. Outcome Although two observational studies suggested that high levels of beta-carotene intake reduced the risk of prostate cancer, the best evidence found that beta-carotene increased the incidence of prostate cancer. The GP discussed this information with her patient, who nevertheless elected to continue to drink lots of carrot juice! Christopher B Del Mar Professor Paul P Glasziou Associate Professor Anneliese B Spinks Research Officer Sharon L Sanders Research Officer Centre for General Practice Medical School, University of Queensland, Herston, QLD c.delmarATcgp.uq.edu.au References Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 1995; 62 (6 Suppl): 1427S-1430S. Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998; 90: 440-446. Daviglus ML, Dyer AR, Persky V, et al. Dietary beta-carotene, vitamin C, and risk of prostate cancer: results from the Western Electric Study. Epidemiology 1996; 7: 472-477. Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 1999; 59: 1225-1230. Mettlin C, Selenskas S, Natarajan N, Huben R. Beta-carotene and animal fats and their relationship to prostate cancer risks. A case-control study. Cancer 1989; 64: 605-612.

Paul P Glasziou · Anneliese B Spinks · Sharon L Sanders

Indigenous Health Research Increase in prevalence of obesity and diabetes and decrease in plasma cholesterol in a central Australian Aboriginal community Robyn McDermott, Kevin G Rowley, Amanda J Lee, Sabina Knight and Kerin O'Dea MJA 2000; 172: 480-484 Abstract - Subject and Methods - Results - Discussion - Acknowledgements - References - Authors' details - - More articles on Aboriginal health Abstract Objective: To document change in prevalence of obesity, diabetes and other cardiovascular diease (CVD) risk factors, and trends in dietary macronutrient intake, over an eight-year period in a rural Aboriginal community in central Australia. Design: Sequential cross-sectional community surveys in 1987, 1991 and 1995. Subjects: All adults (15 years and over) in the community were invited to participate. In 1987, 1991 and 1995, 335 (87% of eligible adults), 331 (76%) and 304 (68%), respectively, were surveyed. Main outcome measures: Body mass index and waist : hip ratio; blood glucose level and glucose tolerance; fasting total and high density lipoprotein (HDL) cholesterol and triglyceride levels; and apparent dietary intake (estimated by the store turnover method). Intervention: A community-based nutrition awareness and healthy lifestyle program, 1988-1990. Results: At the eight-year follow-up, the odds ratios (95% CIs) for CVD risk factors relative to baseline were obesity, 1.84 (1.28-2.66); diabetes, 1.83 (1.11-3.03); hypercholesterolaemia, 0.29 (0.20-0.42); and dyslipidaemia (high triglyceride plus low HDL cholesterol level), 4.54 (2.84-7.29). In younger women (15-24 years), there was a trebling in obesity prevalence and a four- to fivefold increase in diabetes prevalence. Store turnover data suggested a relative reduction in the consumption of refined carbohydrates and saturated fats. Conclusion: Interventions targeting nutritional factors alone are unlikely to greatly alter trends towards increasing prevalences of obesity and diabetes. In communities where healthy food choices are limited, the role of regular physical activity in improving metabolic fitness may also need to be emphasised. The high rates of obesity, diabetes and other cardiovascular disease (CVD) risk factors in Australian Aboriginal communities1-4 lead to high rates of diabetic complications and excess mortality in relatively young people.5-7 With often poor access to appropriate, good quality secondary prevention services,8,9 some communities have sought to emphasise primary prevention of diabetes in community-based health programs aimed at improving individual food choices and the quality of the food supply.10,11In the community described here, a community-based nutrition awareness and healthy lifestyle program was commenced in 1988, after a 1987 survey showed high rates of obesity, diabetes and other CVD risk factors. The program continued for two years and culminated in a risk factor survey and store turnover study in 1991, followed by a series of family-based workshops to provide feedback on the results. A third survey was carried out in 1995. We describe the trends in CVD risk factors (anthropometry, lipid levels, and glucose intolerance) and apparent dietary intake over this eight-year period. Subjects and methods Cross-sectional surveys were carried out in June 1987, May 1991 and April 1995 at a rural Aboriginal community. The surveys were approved by the Alice Springs Institutional Ethics Committee (which, in 1995, had an Aboriginal subcommittee), and by the Deakin University Ethics Committee, after consultation with the community council and health council. All adult members of the community (those 15 years and over) were invited to participate and volunteers gave written informed consent. Pregnant or non-Indigenous community members were excluded. Results were returned to individual participants and summary reports presented to the community council. The resident population at the time of each survey (excluding visitors from other communities) was determined by household census. Blood tests: Twelve millilitres of blood was taken after an overnight fast and a second blood sample collected two hours after a 75 g glucose drink. Blood samples were kept cold until centrifugation and the plasma frozen immediately thereafter until analysis. Levels of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol (after precipitation of other lipoproteins with 15% w/v PEG 6000) and triglycerides were measured by standard enzymatic techniques using commercial kits (Boehringer-Mannheim, Mannheim, Germany). Glucose tolerance was classified according to WHO criteria.12 Hypercholesterolaemia was defined as a plasma cholesterol concentration ≥ 5.5 mmol/L; and Dyslipidaemia was defined as the combination of a low HDL cholesterol level ( ≤ 0.9 mmol/L) plus hypertriglyceridaemia (a fasting plasma triglyceride level ≥ 2.0 mmol/L). Anthropometry: Measurements were made by trained staff using standard techniques.13 Body weight was measured to 0.1 kg, with the subject in light clothing, using digital electronic scales; height was measured to 0.1 cm using a stadiometer; and waist and hip circumferences were measured to 0.1 cm. Obesity was defined as a body mass index (BMI) > 30 kg/m2. Smoking status: Current smoking status was ascertained in 1991 and 1995 using a yes/no questionnaire. Dietary intake: Apparent dietary intake was measured using the store turnover method14 for the three months before each of the surveys. This method estimates general trends in food consumption, as the local store is the main source of food for the community. Expressing data as nutrient density (ie, as a proportion of total energy intake) avoids estimating per capita intake and gives a valid measure of dietary quality for the community.10,14 Intervention: A community-based nutrition awareness and healthy lifestyle program was conducted from 1988 to 1990. The program, which included a resident non-Aboriginal project officer and Aboriginal coworker, concentrated mainly on raising awareness of diabetes in the community, promoting healthy food-buying habits and improving the quality of food purchased by the community store. Some details of the intervention are given in Scrimgeour et al.15 Statistical analyses: Although some community members were screened on more than one occasion (Box 1), analyses were performed assuming purely cross-sectional data. Trends in continuous variables were tested by linear regression using SPSS.16 Separate analyses were performed for men and women. Regression models included year of survey, age group and an interaction term of year of survey with age group. Also included was a dummy variable indicating whether that individual was screened once only or on more than one occasion, the interaction terms of this dummy variable with year of survey and age group, and a three-way interaction term. The latter two variables were excluded from the final model if found to be non-significant. For categorical data, trends in prevalence were tested by a χ2 test for linear association. Confidence intervals for prevalence data were calculated assuming a binomial distribution and adjusted using the finite sampling factor: (N-n)/(N-1), where N is the population size and n is the sample size. Mantel-Haenszel age-weighted odds ratios and exact 95% confidence intervals for risk factors were calculated using EpiInfo software.17 Sensitivity analyses were performed to test for selection bias in the 1991 and 1995 survey samples. Results Response rates Survey participation rates were 87% of the adults normally resident and present at the time of the survey in 1987, 76% in 1991 and 68% in 1995 (Box 1). Participation rates by younger people were progressively lower with each survey. Anthropometry There was no statistically significant change in mean BMI among men (Box 2A; the regression analysis had sufficient statistical power to detect a difference in BMI over time of 0.15 kg/m2). Although mean BMI rose in the two older age groups, this was because men returning for repeat screenings tended to have a higher mean BMI than those screened only once (P = 0.062). Similarly, there was no significant change in waist circumference or waist : hip ratio among men (Box 2). Among women, there was a significant increase in mean BMI, particularly in those aged 15-24 years (Box 2A). The increase in mean BMI (equivalent to about 10 kg in body weight) among women aged 15-24 years was accompanied by an increase in mean waist circumference, but no significant change in waist : hip ratio. Among women 35 years and older, mean BMI remained very high over the eight-year period. For the community as a whole, the prevalence of obesity increased significantly over the survey period: 1987 -- 22.8% (95% CI, 22.2%-23.5%); 1991 -- 32.0% (95% CI, 30.6%-33.3%); 1995 -- 37.0% (95% CI, 35.1%-38.8%); χ2 = 15.5, df = 1, P < 0.001. There was a trebling in prevalence of obesity among women in the age group 15-24 years over the eight-year period (χ2 = 14.4, df = 1, P < 0.001), but no change among men of the same age group (χ2 = 0.2, df = 1, P = 0.636; Box 3). For the older age groups, there was already a high prevalence of obesity among women in 1987, which remained high (Box 3). The prevalence of obesity increased significantly among men aged 25-34 years during the follow-up period (χ2 = 5.2, df = 1, P = 0.022; Box 3). The increase among men aged 35 years and older was not statistically significant (χ2 = 2.0, df = 1, P = 0.155). The statistical power of analyses of prevalence changes in age and sex subgroups was somewhat low because of sparse data and, in some cases, low prevalence. Glucose tolerance For the community as a whole, there was a trend to an increasing prevalence of diabetes:1987 -- 11.6% (95% CI, 11.1%-12.0%); 1991 -- 18.6% (95% CI, 17.4%-19.7%); 1995 -- 20.7% (95% CI, 17.7%-22.2%); χ2= 9.9, df = 1, P = 0.002; with significant increases in prevalence among men aged 25-34 years (χ2 = 4.8, df = 1, P = 0.029) and women aged 35 years and older (χ2 = 3.9, df = 1, P = 0.048; Box 3). However, the prevalence of impaired glucose tolerance (IGT) did not change significantly: 1987 -- 8.4% (95% CI, 8.0%-8.8%); 1991 -- 9.4% (95% CI, 8.6%-10.3%); 1995 -- 7.5% (95% CI, 5.6%-8.5%). χ2= 0.13, df = 1, P = 0.721. Plasma lipids There was a highly significant decrease in mean levels of plasma cholesterol between 1987 and 1991 (Box 2B). This decrease occurred across all ages and in both sexes. This fall in total cholesterol level was partly due to decreases in HDL cholesterol levels, which also occurred in all age- and sex-specific categories, with the largest decrease among women aged 15-24 years (Box 2B). Conversely, among both men and women, there was an increase of similar magnitude in mean fasting plasma triglyceride level in all age groups (Box 2B). After excluding subjects with diabetes from the analysis, these trends to lower total and HDL cholesterol and higher triglyceride levels were still apparent (data not shown). Changes in CVD risk factor profile Box 4 shows the changing prevalence of cardiovascular risk factors as odds ratios compared with baseline. By 1995, community members were more likely to be obese, diabetic and dyslipidaemic (high plasma triglyceride and low plasma HDL cholesterol levels), whereas the risk of hypercholesterolaemia declined. Apparent dietary macronutrient intake Box 5 summarises changes in apparent community intake of sugar, total fat and saturated fat. As a proportion of total energy intake, there was a decline in total and saturated fat and sugar intake. Complex carbohydrate intake was 22%, 21% and 30% of total energy in 1987, 1991 and 1995, respectively. Store turnover data also suggested that, compared with 1987, there were decreases in the approximate per capita daily intake of sugar, fruit and vegetables and increases in flour and bread consumption (data not shown). Representativeness of the survey samples The sensitivity analyses performed assumed that the non-responders in 1991 and 1995 were all non-diabetic and non-obese. With this assumption, the linear trend to an increase in prevalence remained for obesity (χ2 = 5.0, df = 1, P = 0.025) but not for diabetes (χ2 = 1.0, df = 1, P = 0.320). A more realistic, but still conservative, assumption is that the non-responders in the 1991 and 1995 surveys had the same prevalence of obesity and diabetes as in the first survey sample. With this assumption, there were significant increases in estimated prevalences of obesity (23%, 30% and 32% in 1987, 1991 and 1995, respectively; χ2 = 9.4; df = 1; P = 0.002) and diabetes (12%, 17% and 18%; χ2 = 6.1; df = 1; P = 0.014). Among men, regression analysis indicated that those who were screened on more than one occasion had a greater increase in waist : hip ratio with time (P = 0.014) and lower HDL cholesterol levels (P = 0.004) compared with men screened only once. Among women, those who were screened on more than one occasion had higher BMI (P = 0.020) compared with women screened only once. There were no other significant differences apparent between these groups, nor were there any other significant interactions with time. Furthermore, a comparison of baseline data for subjects screened in 1987 and again at either or both of the subsequent surveys with those who were not rescreened revealed no significant differences in mean age, BMI, cholesterol and triglyceride levels or glucose tolerance among either men or women. Together, these observations make it unlikely that the observed trends in obesity, diabetes and plasma lipids are artifacts due to sampling bias. Discussion The community store intervention and education campaign in this central Australian Aboriginal community was associated with a decrease in apparent dietary intake of total and saturated fats and refined carbohydrates and a corresponding increase in complex carbohydrate intake. Associated with the change in dietary fat intake, there were reductions in plasma cholesterol levels in all age groups and both sexes. However, there were increases in the prevalence of obesity (60% increase) and diabetes (80% increase) over the survey period. While the study design does not allow us to ascribe cause-and-effect relationships between the intervention process and the trends in outcomes, the data imply that an attempt to modify diet alone is insufficient to reverse trends to increasing prevalence of obesity and diabetes. Although the biochemical assays at baseline were performed on a different instrument to that used in the two follow-up surveys, the apparent changes in lipid profiles between the first and subsequent surveys are unlikely to be due to methodological differences as the same enzymatic methods were used for all three surveys and the kits purchased from the same source; quality control samples were routinely run and did not vary significantly over the study period; and the changes observed are entirely consistent with the changes in dietary fat intake. Our results are similar to those reported after five years of a non-communicable disease intervention program in Mauritius:18 a major improvement in circulating cholesterol levels, but rapidly increasing prevalence of obesity and diabetes. The increase in prevalence of diabetes that we found approaches the highest recorded.19 The trebling in the prevalence of obesity among women aged 15-24 years was associated with a four- to fivefold increase in prevalence of diabetes. In contrast, there was no change in mean BMI for men in this age range. Thus, weight gain and onset of diabetes in women was apparently accelerated. Anecdotal evidence suggests this sex difference in secular trends in body weight may be due to high participation by young men in vigorous sporting activities such as football, whereas regular exercise by young women is limited in this community. Exercise has been shown to have protective effects against the incidence of diabetes,20 even independently of dietary change. Hence, community-directed interventions aimed at increasing physical activity may improve health outcomes. The prevalence of diabetes in older age groups was extremely high in both men and women. Prior to 1991, diabetes was absent in men under 25 years and relatively uncommon among young women. By 1995, cases of type 2 diabetes were beginning to appear even at this young age. The decreasing age of onset of diabetes in this community has major public health implications with respect to diabetic complications, hyperglycaemia in pregnancy, and the subsequent intergenerational amplification of diabetes risk.21 We have previously reported that body fat distribution, as indicated by waist : hip ratio, among women in this community was unusual for an Aboriginal population, with the central deposition of body fat being less apparent than in other Aboriginal groups.2 Consistent with this, there were no major changes in mean waist : hip ratio for women in the subsequent surveys, even in the young women who had a large increase in waist circumference. Despite these adverse trends in obesity and diabetes, the community has achieved significant improvements in dietary quality, as indicated by the changes in the food supply at the store, and in plasma cholesterol levels. However, a healthy diet consistent with National Health and Medical Research Council (NHMRC) guidelines22 has not been achieved. This problem goes beyond the realm of individual choice and reflects endemic poverty, high prices coupled with low incomes, often poor quality of fruit and vegetables in community stores, household economies which discourage the consumption of fresh foods, lack of domestic refrigeration, and unavailability of many nutritious foods.23 Reversal of obesity is difficult even in the absence of such major environmental and social barriers.24 Hence, early intervention to prevent or delay the onset of excessive weight gain is likely to be more effective in reducing diabetes and cardiovascular risk in such communities.25 In conclusion, our results suggest that a focus on nutrition and dietary habits alone may be insufficient to prevent excessive weight gain and diabetes among adults in Aboriginal communities. Further systematic studies of intervention processes, impacts and associated outcomes are required to address this issue. Acknowledgements This work was supported by grants from the NHMRC (No. 954605) and the Commonwealth Department of Health and Family Services. Special thanks to Fiona McLachlan, Sunil Piers, Nick Williams, Kathy Abbott and the health workers and nursing staff of Territory Health Services in Central Australia. We gratefully acknowledge the expert technical assistance of Connie Karschimkus and Olga Strommer and statistical advice of Elmer Villanueva. References O'Dea K, Guest CS. Diabetes in Aborigines and other Australian populations. Aust J Public Health 1992; 16: 340-349. O'Dea K, Patel M, Kubisch R, et al. Obesity, diabetes and hyperlipidemia in a central Australian Aboriginal community with a long history of acculturation. Diabetes Care 1993; 16: 1004-1010. Gault A, O'Dea K, Rowley KG, et al. Abnormal glucose tolerance and other coronary heart disease risk factors in an isolated Aboriginal community in central Australia. Diabetes Care 1996; 19: 1269-1273. O'Dea K. Westernization and non-insulin-dependent diabetes in Australian Aborigines. Ethnicity Dis 1991; 1: 171-187. Phillips CB, Patel MS, Weeramanthri TS. High mortality from renal disease and infection in Aboriginal central Australians with diabetes. Aust J Public Health 1995; 19: 482-486. Veroni M, Gracey M, Rouse I. Patterns of mortality in Western Australian Aboriginals, 1983-1989. Int J Epidemiol 1994; 23: 73-81. Thomson NJ. Recent trends in Aboriginal mortality. Med J Aust 1991; 154: 235-239. Phillips CB, Patel MS, Carbaron Y. Utilisation of health services by Aboriginal Australians with diabetes. Diab Res Clin Practice 1993; 20: 231-239. Deeble J, Mathers C, Smith L, et al. Expenditure on health services for Aboriginal and Torres Strait Islander People. Canberra: Australian Institute of Health and Welfare, 1998. (Catalogue No. HWE 6.) Lee AJ, Bonson APV, Yarmirr D, et al. Sustainability of a successful health and nutrition program in a remote Aboriginal community. Med J Aust 1995; 162: 633-635. Spinks M, White G. Looma, Western Australia: Diabetes Program. In: Bear-Wingfield R, editor. Sharing good tucker stories. A guide for Aboriginal and Torres Strait Islander communities. Canberra: Commonwealth Department of Health and Family Services, 1996: 63-69. World Health Organization: Diabetes Mellitus: Report of a WHO Study Group. World Health Organ Tech Rep Ser 1985; No. 727. Callaway CW, Chumlea WC, Bouchard C, et al. Circumferences. In: Lohman TG, Roche AF, Masturell R, editors. Anthropometric standardisation reference manual. Champaign, Ill: Human Kinetics Books, 1988: 39-54. Lee AJ, O'Dea K, Mathews JD. Apparent dietary intake in remote Aboriginal communities. Aust J Public Health 1994; 18: 190-197. Scrimgeour D, Rowse T, Knight S. Food purchasing behaviour in an Aboriginal community. 2. Evaluation of an intervention aimed at children. Aust J Public Health 1994; 18: 67-70. SPSS [computer program], version 9.0. Chicago Ill: SPSS Inc, 1998. EpiInfo [computer program], version 6. Atlanta, Ga: Centers for Disease Control and Prevention, 1993. Dowse GK, Gareeboo H, Alberti KGMM, et al, for the Mauritius Non-communicable Disease Study Group. Changes in population cholesterol concentrations and other cardiovascular risk factor levels after five years of the non-communicable disease intervention programme in Mauritius. BMJ 1995; 311: 1255-1259. Dowse GK, Spark RA, Mavo B, et al. Extraordinary prevalence of non-insulin-dependent diabetes mellitus and bimodal plasma glucose distribution in the Wanigela people of Papua New Guinea. Med J Aust 1994; 16: 767-774. Pan X-R, Li G-W, Hu Y-H, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and diabetes study. Diabetes Care 1997; 20: 537-544. Pettit DJ, Nelson RG, Saad MF, et al. Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care 1993; 16: 310-314. National Health and Medical Research Council. Dietary guidelines for Australians. Canberra: NHMRC/AGPS, 1992. Leonard D, Beilin R, Moran M. Whichway kaikai blo umi? Food and nutrition in the Torres Strait. Aust J Public Health 1995; 19: 589-595. World Health Organization. Obesity: preventing and managing the global epidemic. Geneva: WHO, 1998: 107-158. Macaulay AC, Paradis G, Potvin L, et al. The Kahnawake Schools Diabetes Prevention Project: intervention, evaluation and baseline results of a diabetes primary prevention program with a native community in Canada. Prev Med 1997; 26: 779-790. (Received 11 Oct 1999, accepted 20 Mar 2000) Authors' details Health Surveillance, Queensland Health, Tropical Public Health Unit, Cairns, QLD. Robyn McDermott, MPH, FAFPHM, Director. Monash University, Centre for Population Health and Nutrition, Monash Medical Centre, Melbourne, VIC. Kevin G Rowley, BAppSci, PhD, Research Fellow; currently, Research Fellow, Department of Medicine, St Vincent's Hospital, Melbourne. Kerin O'Dea, BSc, PhD, Head. Menzies School of Health Research, Darwin, NT. Amanda J Lee, GradDipDiet, PhD, Public Health Nutrition Consultant. Territory Health Services, Alice Springs, NT. Sabina Knight, RN, MTH, Staff Development Officer (Remote). Reprints will not be available from the authors. Correspondence: Dr K G Rowley, Department of Medicine, Clinical Sciences Building, St Vincent's Hospital, Fitzroy, VIC 3065. rowleykATmail.medstv.unimelb.edu.au Make a comment 1: Age- and sex-specific response rates for the three cross-sectional surveys in a rural Aboriginal community Men Women 15-24 y25-34 y35 y +15-24 y25-34 y35 y +1987Population, N Sample, n Response rate % Of sample rescreened90 71 79% 56% 54 42 78% 41%58 48 83% 58% 87 81 93% 69%47 45 96% 49% 68 61 90% 56%1991Population, N Sample, n Response rate % Of sample rescreened 87 51 59% 37% 61 35 57% 60%63 54 86% 46% 95 72 76% 46%57 50 88% 54% 72 69 96% 67%1995Population, N Sample, n Response rate % Of sample rescreened81 48 59% 40% 72 38 53% 61%63 43 68% 74% 94 49 52% 33%58 56 97% 73% 81 71 88% 62%Back to text 2: Trends in anthropometric variables and plasma lipid levels, stratified by age and sex 15-24 years25-34 years35 years and overP*P†A: Anthropometric variables Body mass index (BMI), kg/m2Men 1987 1991 199524.5 (23.4-25.6) 24.1 (22.9-25.4) 24.8 (23.3-26.3)26.3 (24.7-28.0) 27.0 (25.0-29.0) 28.7 (27.2-30.2)26.0 (24.7-27.3) 27.8 (26.2-29.5) 28.2 (26.6-29.9) 0.514 0.992 Women 1987 1991 199524.5 (23.2-25.7) 24.6 (23.1-26.1) 29.1 (27.3-31.0)27.8 (26.0-29.7) 28.8 (26.9-30.7) 29.7 (27.7-31.8)30.2 (28.3-32.1) 31.8 (30.0-33.6) 30.4 (28.7-32.1) <0.001 0.004 Waist circumference, cmMen 1987 1991 199586.2 (83.0-89.4) 85.3 (82.0-88.7) 84.8 (81.2-88.4)91.0 (87.3-94.6) 93.9 (89.4-98.4) 95.1 (91.1-99.2)97.9 (93.4-102.5) 99.0 (95.2-102.8) 98.2 (93.1-103.3) 0.834 0.340 Women 1987 1991 199581.5 (78.7-84.4) 82.3 (79.3-85.4) 90.0 (86.7-93.4)92.0 (87.8-96.2) 95.4 (90.5-100.2) 92.2 (88.2-96.3)98.3 (94.1-102.4) 99.9 (96.3-103.5) 94.0 (90.9-97.2) <0.001 <0.001 Waist:hip ratioMen 1987 1991 19950.87 (0.85-0.88) 0.87 (0.86-0.89) 0.88 (0.87-0.90)0.92 (0.90-0.94) 0.94 (0.92-0.96) 0.94 (0.93-0.96)0.97 (0.96-0.98) 0.99 (0.97-1.01) 1.00 (0.98-1.02) 0.293 0.160 Women 1987 1991 1995 0.82 (0.80-0.83) 0.85 (0.82-0.87) 0.85 (0.83-0.88)0.85 (0.83-0.87) 0.89 (0.85-0.92) 0.85 (0.84-0.87)0.85 (0.84-0.87) 0.89 (0.87-0.91) 0.86 (0.84-0.88) 0.134 0.095 Data are means (95% confidence interval). *P-value for change over time. †P-value for interaction of change over time with age group. Back to textB: Plasma lipids Total cholesterol, mmol/LMen 1987 1991 19955.3 (5.0-5.6) 4.5 (4.3-4.8) 4.5 (4.3-4.8)6.0 (5.7-6.3) 4.8 (4.6-5.1) 5.3 (5.0-5.6)6.2 (5.7-6.6) 5.5 (5.1-5.9) 5.5 (5.2-5.8) 0.034 0.571 Women 1987 1991 19955.2 (4.9-5.4) 4.3 (4.1-4.5) 4.5 (4.3-4.8)5.7 (5.3-6.1) 4.8 (4.5-5.0) 4.8 (4.5-5.1)5.5 (5.3-5.8) 5.0 (4.7-5.3) 5.0 (4.8-5.3) 0.001 0.317 HDL cholesterol, mmol/LMen 1987 1991 19951.17 (1.10-1.24) 0.88 (0.82-0.94) 0.83 (0.76-0.90)1.23 (1.10-1.36) 0.84 (0.77-0.91) 0.79 (0.73-0.85)1.05 (0.96-1.14) 0.78 (0.72-0.84) 0.76 (0.70-0.81) <0.001 0.180 Women 1987 1991 19951.45 (1.33-1.57) 0.98 (0.91-1.05) 0.88 (0.81-0.95)1.25 (1.12-1.38) 0.81 (0.75-0.87) 0.86 (0.81-0.92)1.18 (1.10-1.27) 0.84 (0.79-0.89) 0.82 (0.78-0.86) <0.001 0.011 Triglycerides, mmol/LMen 1987 1991 19951.1 (1.0-1.3) 1.6 (1.4-1.9) 1.7 (1.5-1.9)1.6 (1.3-2.0) 2.3 (1.9-2.7) 2.1 (1.8-2.5)2.1 (1.8-2.5) 3.0 (2.5-3.6) 2.9 (2.4-3.6) 0.004 0.419 Women 1987 1991 19951.0 (0.9-1.1) 1.2 (1.1-1.4) 1.6 (1.4-1.8)1.3 (1.2-1.6) 1.8 (1.6-2.1) 1.8 (1.5-2.0)1.6 (1.4-1.8) 2.2 (2.0-2.5) 2.2 (2.0-2.4) <0.001 0.248 Data are means (95% confidence interval), except triglycerides, which are geometric means (95% CI). *P-value for change over time. †P-value for interaction of change over time with age group. Back to text Back to text 4: Risk ratios for cardiovascular risk factors in the follow-up surveys (1991 and 1995) compared with baseline (odds ratios and 95% CIs)* 198719911995Obesity Impaired glucose tolerance (IGT) Diabetes Hypercholesterolaemia Dyslipidaemia Smoking1.00 1.00 1.00 1.00 1.00 - 1.50 (1.03-2.17) 1.04 (0.58-1.87) 1.63 (0.98-2.69) 0.24 (0.17-0.35) 4.73 (3.06-7.61) 1.001.84 (1.28-2.66) 0.76 (0.41-1.41) 1.83 (1.11-3.03) 0.29 (0.20-0.42) 4.54 (2.84-7.29) 0.73 (0.52-1.03) *Compared with 1987 (or 1991 for smoking), Mantel-Haenszel-weighted (for age) odds ratios and exact 95% confidence intervals. Back to text Back to text

Robyn McDermott · Kevin G Rowley · Amanda J Lee · Sabina Knight · Kerin O'Dea

Medicine and the Community Who's overweight? Comparison of the medical definition and community views Susan M Donath MJA 2000; 172: 375-377 Abstract - Methods - Results - Discussion - References - Authors' details - - More articles on Public and environmental health Abstract Objective: To investigate the extent to which people who are medically defined as overweight perceive themselves to be overweight. Design: Secondary data analysis of the National Health Survey and the National Nutrition Survey conducted by the Australian Bureau of Statistics in 1995. Participants: 10 652 people aged 18 years and over (5076 men, 5576 women) in a multistage cluster sample of households throughout Australia. Main outcome measures: Body mass index (BMI) based on measured height and weight; self-reported perception of body weight (underweight, acceptable weight, or overweight) Results: Among people with a measured BMI ≥ 25, 49.3% of men (95% CI, 48.1%-50.5%) and 72.0% of women (95% CI, 70.8%-73.1%) considered themselves overweight. Among those with a measured BMI < 25, 3.4% of men (95% CI, 2.8%-4.1%) and 12.4% of women (95% CI, 11.4%-13.3%) considered themselves overweight. Older women were less likely to perceive themselves as overweight than younger women. The lowest BMI at which at least half the respondents considered themselves overweight was 26 to < 27 for women aged 18-59 years, and 28 to < 29 for older women and men. Conclusion: For many people, particularly men and older women, the meaning of "overweight" differs from the medical definition. Clinical and public health weight reduction programs which do not take this into account are unlikely to be successful. Overweight and obesity are key preventable risk factors for many diseases, particularly hypertension, cardiovascular disease and non-insulin-dependent diabetes.1 In Australia in 1995, the National Nutrition Survey found that 64% of men and 49% of women aged 18 and over were overweight or obese (using the standard definitions of the National Health and Medical Research Council [NHMRC]).2Despite this, the NHMRC expert report on prevention of obesity and overweight1 found few population-based data on Australians' weight-control behaviours. As the report noted, to understand weight-control behaviours, it is first necessary to answer the question: "Who perceives themselves as overweight?".1 To date, no national Australian studies have addressed this question. Most Australian studies of weight-control attitudes and behaviours have used small and unrepresentative samples and have focused on women, particularly younger women.3 Although two studies used larger, representative samples of adults in Adelaide and Melbourne to investigate the relationship between body mass index (BMI) and perceptions of overweight,4,5 both calculated BMI from self-reported height and weight. Self-reported measures are known to lead to underestimates of BMI.6-8 The 1995 National Health Survey9 and National Nutrition Survey10 provided a unique opportunity to investigate the relationship between Australian adults' subjective perceptions of their weight and their measured BMIs. I used data from these surveys to investigate: to what extent Australian adults with different BMIs perceive themselves to be overweight; and the BMI at which adults perceive themselves to be overweight. Methods The study was a secondary analysis of data from the National Health Survey9 and the National Nutrition Survey10 conducted by the Australian Bureau of Statistics in 1995. Data sources The 1995 National Health Survey was conducted on a multistage, cluster sample of households in all States and Territories of Australia. Information was obtained by personal interview. This study analyses responses to the question: "Do you consider yourself to be acceptable weight, underweight, or overweight?". The 1995 National Nutrition Survey was conducted on a random subsample of the households interviewed for the National Health Survey. Participants in the National Nutrition Survey answered detailed questions about their current food consumption and had their heights and weights measured by specially trained interviewers two to three weeks after the National Health Survey interview.10 Response rates were 97% for the National Health Survey9 and 61% for the National Nutrition Survey.10 Non-responders were more likely to be characterised by one or more of the following: high income, older than 59, unmarried, or unemployed. The current study was based on a sample of 5076 men and 5576 women aged 18 and over for whom height and weight measurements were obtained by the National Nutrition Survey. The sample represents 98.4% of respondents (excluding pregnant women). Data analysis Unit record data, containing detailed information on each person in the sample, were analysed using SPSS11 and Excel.12 The BMI of each person was calculated from measured height and weight (where BMI = ratio of body weight in kilograms to height in metres squared). Overweight was defined as a BMI of 25 or over and obesity as a BMI over 30.1,13 These cutoff points were derived from evidence of the association between BMI and mortality.14Population percentages were estimated from sample percentages using the weighting factors and methods of the Australian Bureau of Statistics (ABS),15 which adjust for the sampling method (multistage, cluster sampling). This ensured that the percentages represented as far as possible the adult Australian population. For percentages close to or equal to zero, exact confidence intervals were calculated using the binomial distribution.16 All other confidence intervals were estimated using the relative standard errors provided by the ABS.2 Results An estimated 64.5% of men and 49.2% of women had a BMI ≥ 25.2 Estimated percentages in each age group are shown in Box 1; percentages increased with age in both sexes until the ages of 50-54 years (men) and 55-59 years (women), and then remained stable or declined slightly. Significantly more men than women had a BMI ≥ 25 in almost all age groups, although the difference was smaller in the age groups over 55 years. Among people with a BMI ≥ 25, an estimated 49.3% of men and 72.0% of women considered themselves overweight (95% CIs, 48.1%-50.5% and 70.8%-73.1%, respectively). Estimated percentages of those who considered themselves overweight are shown in Box 2 by age group. At all ages, women were more likely to consider themselves overweight than men; the difference was significant for all except those aged 70 years and over. Women in this age group were less likely to consider themselves overweight than younger women, while men in their 20s or those 80 years and over were less likely to consider themselves overweight than men of other ages. Among people with a BMI < 25, an estimated 3.4% of men and 12.4% of women considered themselves overweight (95% CIs, 2.8%-4.1% and 11.4%-13.3%, respectively). For men, there was little variation with age (Box 2), and, although there were statistically significant differences between some age groups for women, these differences were small. The estimated percentage of people who considered themselves overweight at each measured BMI is shown in Box 3. Data for men and women in different age groups were analysed separately. For men, there were no significant differences between age groups (not shown). For women, the only significant difference was between women aged under 60 and older women. The percentages of both sexes who considered themselves overweight increased with BMI; the lowest BMI at which at least half the respondents considered themselves overweight was 26 to < 27 for women aged 18-59 years, and 28 to < 29 for older women and men. Discussion This study found that relatively few Australian adults with a BMI less than 25 considered themselves overweight, but that a large proportion of people who were overweight or obese considered their weight to be acceptable. This applied to half of the overweight men and a quarter of the overweight women. A potential limitation of the study was the response rate to the National Nutrition Survey, which was low by ABS standards for household surveys. However, adjustment of results to represent the total population would be expected to minimise the effect of response bias. The results of this study contrast with those of two other Australian studies.4,5 These found that around 25% of men and 45% of women of acceptable weight considered themselves overweight, while only about 15% of overweight men and 5% of overweight women considered their weight to be acceptable. Both earlier studies estimated BMI from self-reported height and weight, which are known to underestimate BMI.6-8 For example, based on self-reported height and weight, 36% of women and 52% of men aged 18 and over were overweight or obese in Australia in 1995,14 considerably fewer than the 49% of women and 64% of men found to be overweight or obese by measurement in the National Nutrition Survey.2 Therefore, in the earlier studies, some people classified as having acceptable weight would have been overweight, and those classified as overweight would mostly have had BMIs well in excess of 25. In addition, when respondents in the earlier studies were asked to assess their weight, they were given the choice of "slightly overweight",4,5 "very overweight"4,5 or "extremely overweight"4 (rather than the single option of "overweight" used in the current study). The option "slightly overweight" was chosen by nearly all who considered themselves overweight but were actually of acceptable weight, and by well over half those who considered themselves overweight and were actually overweight or obese. Thus, another possible explanation for the difference in my results is that, when given the choice of classifying oneself as "acceptable weight" or "overweight", those who consider themselves slightly overweight generally opt for "acceptable weight". The results of this study suggest that, for men and for women aged 60 and over, the meaning of "overweight" differs considerably from the medical definition. For men, "overweight" appears to mean a BMI greater than 28. Only a minority of men consider themselves overweight at lower BMIs, while 30% of men with a BMI of 30-31 consider their weight acceptable. This is consistent with the findings of a recent study of weight-control practices of adults in an Australian rural community; when asked about their weight goals in the next year, only one in five overweight men wished to attain a BMI below 25.17 Some highly muscular men may have a BMI above 25 and not be overweight, but, given the increase in BMI with age, this group is likely to be small. Men's perceptions may be influenced by the high proportion who are overweight; it is so common that being moderately overweight may be seen as normal. For women aged 60 and over, the meaning of "overweight" appears similar to that for men, but for younger women, the meaning is closer to the medical definition. However, for many of these younger women, a BMI in the upper part of the acceptable range constitutes being "overweight". A factor influencing these women's attitudes may be the mass media focus on images of very thin (young) women. The difference in attitudes between women of different ages may reflect a change in attitude with age; as a substantial proportion of older women are overweight, older women may consider it normal. There may also be a generational difference in women's attitudes, possibly related to changes in media images of the ideal female form. For most people, achieving and maintaining weight loss involves considerable lifestyle change, which is unlikely to be achieved unless people consider the reasons are compelling. My study suggests that, for clinical and public health weight reduction programs to be successful, they must first convince many overweight people that their weight is an issue which needs addressing. References National Health and Medical Research Council. Acting on Australia's weight: A strategic plan for prevention of overweight and obesity. Canberra: AGPS, 1997. Australian Bureau of Statistics. National Nutrition Survey: selected highlights, Australia, 1995. Canberra: AGPS, 1995. (Catalogue No. 4802.0.) Crawford D, Owen N. The behavioural epidemiology of weight control. Aust J Public Health 1994; 18: 143-148. Crawford D, Worsley A. Present and desired body weights of Australian adults: a cause for concern? Community Health Stud 1987; 11: 62-67. Paxton S, Sculthorpe A. Weight-loss strategies and beliefs in high and low socioeconomic areas of Melbourne. Aust J Public Health 1994; 18: 412-417. Hill A, Roberts J. Body mass index: a comparison between self-reported and measured height and weight. J Public Health Med 1998; 20: 206-210. Kuskowska Wolk A, Bergstrom R, Bostrom G. Relationship between questionnaire data and medical records of height, weight and body mass index. Int J Obes Relat Metab Disord 1992; 16: 1-9. Nieto Garcia FJ, Bush TL, Keyl PM. Body mass definitions of obesity: sensitivity and specificity using self-reported weight and height. Epidemiology 1990; 1: 146-152. Australian Bureau of Statistics. National Health Survey: users' guide. Canberra: AGPS, 1995. (Catalogue No. 4363.0.) Australian Bureau of Statistics. National Nutrition Survey: users' guide. Canberra: AGPS, 1995. (Catalogue No. 4801.0.) SPSS Inc. SPSS. Release 9.0.1. Chicago, Ill: SPSS Inc, 1999. Microsoft. Excel 97 SR-1. Microsoft, 1997. National Health and Medical Research Council. Reports of the 98th and 100th sessions. Canberra: AGPS, 1984 and 1985. Australian Bureau of Statistics. How Australians measure up. Canberra: AGPS, 1998. (Catalogue No. 4359.0.) Australian Bureau of Statistics. National Nutrition Survey: technical paper for confidentialised unit record file. Canberra: AGPS, 1995. (Catalogue No. 4807.0.) Armitage P, Berry G. Statistical methods in medical research. Oxford: Blackwell, 1994. Crawford D, Owen N, Broom D, et al. Weight control practices of adults in a rural community. Aust N Z J Public Health 1998; 22: 73-79. (Received 9 Sep 1999, accepted 16 Feb 2000) Authors' details Key Centre for Women's Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, VIC. Susan M Donath, BSc, MA, Lecturer. Reprints will not be available from the author. Correspondence: Ms S M Donath, Key Centre for Women's Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3052. s.donathATkcwh.unimelb.edu.au Make a comment Back to text Back to text Back to text

Susan M Donath

Editorial Genetically modified food: consternation, confusion, and crack-up The controversy over genetically modified food exposes larger issues about public trust in science and the role of science in policymaking MJA 2000; 172: 148-149 "The great pioneers of our subject were tormented by crises of belief and uncertainty, which we need to understand in facing our own problems today. It is only today, after 70 years, that such understanding is coming within our reach -- and may soon slip out of our reach."1 Did this desperate plea come recently from a scientist in defensive retreat? A scientist, perhaps, embroiled in the debate about genetically modified food, who flinched on reading that Stanley Ewen and Arpad Pusztai had found an "unexpected proliferative effect" of genetically modified potatoes on rat gut?2Not, thankfully, on this occasion. These were the opening remarks of a respected senior botanist, C D Darlington, in an issue of the Philosophical Transactions of the Royal Society of London devoted entirely to the manipulation of genetic systems in plant breeding. He was writing over 20 years ago. Interference with our systems of food production has always aroused public alarm, occasionally with justification. From soaking crops with pesticides to taking short cuts in the feeding of cattle (bovine revenge being wreaked on Britain with variant Creutzfeldt-Jakob disease), food is a lightning-rod for public fears about scientists' allegedly reckless indifference to safety. But, even by these high standards of public sensitivity, the debate surrounding genetically modified organisms became the scientific controversy of 1999,3 a debate that is summarised in this issue of the Journal, with restrained good temper, by Huppatz and Fitzgerald on one side 4 and Leeder on the other.5 Four larger issues have been exposed by these kinds of exchange in the last months of the 20th century, and the arguments they incite threaten the fragile remnant of trust that remains between the public and scientists. First, how can two (reasonably) well-regarded organisations peer review the same work -- Ewen and Pusztai's research on the effects of feeding genetically modified potatoes to rats -- and yet come to such radically opposite conclusions about its validity, as did the Royal Society and The Lancet? All six Royal Society reviewers pronounced the research "flawed", while five out of six of The Lancet's reviewers judged that Ewen and Pusztai's work should be published.6 Peer review as a reliable technique for assessing the validity of scientific data is surely discredited. The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability -- not the validity -- of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong. A recent editorial in Nature was right to conclude that an over-reliance on peer-reviewed publication "has disadvantages that should be countered by adequate provision of time and resources for independent assessment and, in the midst of controversies, publicly funded agencies providing comprehensive, reliable and prompt complementary information".7 Second, given each outrageously overblown claim and counterclaim about the safety of genetically modified foods, how can the public ever begin to reach a balanced opinion about this important new technology? British -- but hopefully not Australian -- doctors, scientists, politicians, and even journalists, treat the public with little more than patronising contempt when a compelling scientific issue surfaces. According to research published by the United Kingdom's Economic and Science Research Council,8 "the public are not stupid and ignorant about their approach to [genetically modified food] risks but have a sophisticated grasp of the main issues". In the United States, the culture is, as so often, entirely different. Faced with growing public anxiety about genetically modified foods, the Food and Drug Administration (FDA) called three open meetings to discuss the widespread concerns. The FDA plans to channel this public point of view into its own food-labelling and safety policies. Here is a model that other countries might adopt to their advantage. Third, after the latest storm has calmed, how much more do we really know about the safety of genetically modified foods? Regrettably, very little. Considered opinions have been traded,9,10 but few new insights have been gained. The insipid but correct conclusion is that more research -- notably to confirm or refute Ewen and Pusztai's preliminary findings -- is needed. But perhaps the terms of the debate could be refined. Mark Tester, for example, has argued against discussing genetically modified plants as a homogeneous group. Instead, he proposes a classification of such foods based on the type of gene transfer used -- between kingdoms, between plant species, or between genes in a single type of plant genome.11 Each category of transfer carries a diminishing theoretical risk. Careful thinking, and not brutish restatements of old positions, is now required. Finally, this and other recent public health scares have focused attention on the validity of the precautionary principle. This principle states that, where there are significant risks of damage to the public health, we should be prepared to take action to limit those risks, even when scientific knowledge is not conclusive, if the balance of likely costs and benefits justifies it. I have argued that the precautionary principle "offers one useful means to inform decision making".12 By contrast, Aaron Klug, President of the Royal Society, noted in his 1999 anniversary address that the precautionary principle "is no way to deal with uncertainty -- it is a recipe for [scientific] stagnation".13 Therefore, the question remains unresolved: how do policymakers make policy on controversial matters of public health when the scientific evidence is inconclusive? In some ways, this bitter debate is spurious. Huppatz and Fitzgerald repeat a familiar argument -- namely, that "gene technology offers enormous potential for world agriculture". The Royal Society went further, claiming that "we cannot assume that current practices will feed the population of 8 billion expected by 2020";7 hence, genetically modified food offers one solution to a projected global famine. Is this the problem we are trying to solve with genetic modification? If not, then what is? And if so, we may be missing a simpler, but far more profound, answer. The little research that has been conducted about the origins of famine reveals that the solution of "more food" may be no solution at all. There is no direct relation, Amartya Sen concludes in his study of poverty and famine,14 between food availability and starvation. Access to food depends far more on a complex mix of economic, social and political factors -- eg, without an income and a stable environment to exchange money for food, a person may starve in the face of plenty. If Sen's argument is correct, and the evidence he cites is persuasive, seeking a technological food fix for world hunger may be not only the biggest scientific controversy of 1999, but also the most commercially malevolent wild goose chase of the new century. Richard Horton Editor, The Lancet London, UK Reprints: Dr R Horton, The Lancet, 84 Theobald's Road, London, WCIX 8RR, UK. Darlington CD. Genetics and plant breeding, 1910-80. Philos Trans R Soc Lond 1981; B 292: 401-405. Ewen SWB, Pusztai A. Effects of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. Lancet 1999; 354: 1353-1354. Controversy of the year: GM foods under attack. Science 1999; 280: 2243. Huppatz JL, Fitzgerald PA. Genetically modified foods -- safety and regulatory issues. Med J Aust 2000; 172: 170-173. Leeder SR. Genetically modified food -- food for thought. Med J Aust 2000; 172: 173-174. Horton R. Genetically modified foods: "absurd" concern or welcome dialogue? Lancet 1999; 354: 1314-1315. Dangers of over-dependence on peer-reviewed publication [editorial]. Nature 1999; 401: 727. The politics of GM food: risk, science, and public trust. London: Economic and Science Research Council, 1999. The Royal Society Statement, 1998. Genetically modified plants for food use. London: The Royal Society, 1998. Millstone E, Brunner E, Mayer S. Beyond "substantial equivalence". Nature 1999; 401: 525-526. Tester M. Seeking clarity in the debate over the safety of GM foods. Nature 1999; 402: 575. Horton R. The new new public health of risk and radical engagement. Lancet 1998; 352: 251-252. Klug A. Anniversary address 1999. London: The Royal Society, 1999. Sen A. Poverty and famines. Oxford: Oxford University Press, 1981. Make a comment

Richard Horton

Gene technology is a new form of biotechnology with much greater potential applications. Biotechnology is nothing new. In fact, humanity has been using biotechnology for the preparation and manufacture of food for hundreds of years -- using yeast for making beer and bread, and selecting and breeding plants and animals for higher productivity and nutritive value. Recombinant-DNA (gene) technology is an aspect of modern biotechnology that represents a quantum leap in potential applications. It allows new genes to be introduced into plants and animals -- genes can therefore be moved from one species to another (eg, from bacteria to plants or from non-crop to crop plants), a feat impossible through conventional plant breeding. (For a description of the science behind gene technology and its applications in agriculture, see references 1 and 2.) Gene technology offers enormous potential benefits for world agriculture, including the possibility of producing higher yields of more nutritious food in more environmentally sustainable ways. It offers a powerful new tool to assist plant breeders to introduce resistance to insects and diseases, as well as traits for higher quality and nutritive value. Moreover, the next generation of genetically modified (GM) crop plants promises a significant impact on human health (eg, rice has been engineered with enhanced levels of vitamin A and iron to correct nutrient deficiencies common in the developing world, although more research is needed for a practical outcome). The first commercial applications of gene technology in crop plants have involved modifying the plant for greater disease or insect resistance or a more efficient production system. Introduction of these GM crops has been extremely rapid, particularly in the United States. In 1996, transgenic crops covered 1.7 million hectares worldwide. By 1998, that area had increased 15-fold to almost 28 million hectares.3 In that year, the most common transgenic crops in the world were soybean and corn, with significant areas of cotton, canola and potato. There are now over 50 individual transgenic products, involving 13 separate crops. It has been predicted that, within 20 years, gene technology will touch every type of agricultural crop in the world, although this will depend on a high level of consumer acceptance. In Australia, only one GM crop is currently grown commercially -- insect-resistant (INGARD) cotton. This is now entering its fourth commercial year and currently accounts for 30% of the Australian cotton crop. In the past three years, GM cotton has been sprayed with less than 50% of the insecticides used on the conventional crop -- a reduction of 1.5 million litres of spray per year.4 Although cotton is the only GM crop in Australia, the ready acceptance of GM crops by farmers in the US has resulted in about 50% of the soybean crop and 30% of the corn crop being genetically modified. This has relevance for Australia, as significant quantities of soybean are imported and used in processed food. Food safety The safety issues surrounding foods derived from GM plants are central to their acceptance into the food chain. Consumers seek reassurance about the safety of the food they eat, in terms of both its immediate and long-term health effects. Rigorous scientific assessment of GM food safety is therefore essential to provide a sound scientific basis for future regulation. In dealing with the issue of safety of food and food products from GM plants, regulatory authorities in many parts of the world have relied on the principle of substantial equivalence. Substantial equivalence is established if food products are essentially the same in composition, nutritive value, functional characteristics and organoleptic properties (taste, smell, mouthfeel). When it has been established that the food derived from a GM plant is substantially equivalent to that produced by the conventional crop, then the focus of testing becomes the introduced genes and their specific products. Alternatively, if a food derived from a GM plant differs from that produced by the conventional crop, then it must be assessed for food safety on a case-by-case basis. For example, transgenic rice with enhanced vitamin A would be considered a "new" food and assessed for safety accordingly. The safety implications of new characteristics introduced into GM plants have been evaluated in much the same way as new food additive or agrochemical products such as pesticides (eg, in-vitro and animal-feeding trials). The company or institution applying for registration for use must provide a dossier describing safety tests performed in compliance with the protocols set by regulatory authorities. These data are rigorously assessed before regulatory approval is given. Examples include antibiotic-resistance genes, used as selectable "markers" during the development of the GM plant (Box 1). Herbicide-resistance genes can also be used as markers and give the plant an agronomic advantage. Both these introduced traits have caused considerable controversy, albeit for different reasons, and illustrate the type of assessment undertaken to establish confidence in their safety. Safety implications of antibiotic resistance Among the common types of selectable marker, antibiotic resistance has created most controversy, mainly because of the fear of transfer to the bacterial microflora of humans or animals. By far the most commonly used antibiotic resistance marker is the NPTII gene, which codes for the enzyme neomycin phosphotransferase NPTII, which inactivates neomycin and related antibiotics, including kanamycin. Numerous studies have suggested that the presence of this antibiotic-resistance gene in any crop or crop products will have negligible impact on food safety.5 A concern about use of antibiotic resistance as a selectable marker is its potential to compromise the therapeutic use of antibiotics in humans and animals. The presence of the gene product in food or feed has been considered, as has the possible transfer of this resistance to gut and potentially hazardous microorganisms. Dröge et al clearly demonstrated that such transfer occurs, if at all, at extremely low frequency.6 Most, if not all, of the NPTII gene ingested will be degraded in the human stomach and small intestine. Moreover, the probability of gut microorganisms integrating this exogenous DNA and producing the NPTII protein is extremely low, particularly as the latter would require the bacterial DNA to be rearranged, with replacement of the plant promoter (the DNA sequence that allows RNA polymerase to bind) by a bacterial promoter. Even if the NPTII protein was produced, it would be expected to rapidly degrade, as shown by experiments under simulated gastric conditions.7-9 Therefore, Kärenlampi, in his 1996 report to the Nordic Council (responsible for directing food policy issues in the five Nordic countries), concluded that the overall risk is effectively zero, and that the therapeutic use of antibiotics in humans or animals will not be affected by commercialisation of transgenic crops containing antibiotic-resistance selectable marker genes.5 Nevertheless, the Royal Society's report on GM plants, while conceding that risks were minimal, recommended that antibiotic-resistance marker genes no longer be used in GM food crops.10 Alternative systems to select for genetic modification are now available, and it is possible to delete the marker gene altogether in regeneration of some crops. Safety implications of herbicide resistance The introduction of herbicide-resistance genes into specific target crops is a major objective of plant biotechnology programs, with some 50% of commercial transgenic crops being herbicide resistant. Herbicide-resistant crops can significantly increase production efficiency. In addition, as they increase farmers' options for weed management (eg, by eliminating the need for pre-planting herbicides and allowing flexible timing of herbicide application for maximum efficacy), herbicide-resistant crops can decrease overall herbicide use and lead to the use of more environmentally acceptable herbicides. By far the largest area is planted to crops tolerant of the herbicide glyphosate (Roundup; Monsanto, St Louis, Mo), which is relatively non-toxic and readily deactivated and degraded in the soil. These crops contain a version of the herbicide target enzyme that was derived from bacteria and is naturally tolerant of the herbicide (Box 2). The target enzyme is present in all plant, microbial and fungal food sources and is therefore not novel to the food supply. A comprehensive series of scientific evaluations showed that the genetically modified version of the enzyme behaves like other versions and has no adverse safety effects.4,11 Detailed analysis of nutrients and antinutrients, including fatty acids, amino acids, protein and micronutrients, in glyphosate-tolerant GM soybeans confirmed that they are substantially equivalent to conventional soybeans currently in commercial use.11 Extensive testing of the bacteria-derived enzyme from GM soybeans established that, in simulated gastric and intestinal fluids, it is not toxic or allergenic and is rapidly digested.4,12 Recent developments Of great concern in late 1998 were reports of experiments by Pusztai at the Rowett Research Institute in the United Kingdom. The results were initally published through the media rather than through peer-reviewed scientific journals and caused considerable controversy and public concern, as they suggested that serious health effects could arise from a genetic modification itself rather than from the particular gene that had been inserted. Pusztai's experiments set out to investigate whether GM potatoes that contained a gene encoding snowdrop lectin (a plant protein with potential to increase insect and nematode resistance) affected the health and growth of rats to which they were fed. He concluded that the GM potatoes significantly affected the immune system of the rats, as a result of the genetic modification itself rather than of the particular gene that had been inserted. These claims were so serious and caused such public concern that the Royal Society set up a review of their implications for food safety. After examining all available information on the experiments, six independent reviewers with expertise in statistics, clinical trials, physiology, nutrition, quantitative genetics, growth and development, and immunology, prepared a report.13 This found that the Pusztai experiments were flawed in many aspects of design, execution and analysis, and that no conclusions could be drawn from them. The expert review group found no credible evidence of adverse effects from GM potatoes. Recently, despite the objections of several referees,14 The Lancet published some of Pusztai and colleagues' experiments.15 While The Lancet undoubtedly felt this was justified to promote critical discussion of the data, no definitive conclusion can reasonably be drawn from the published results. Perhaps because of the unfortunate circumstances surrounding the Pusztai experiments, doubts continue to be raised about the longer-term safety of GM foods. As pointed out above, the principle of substantial equivalence relies on comprehensive testing of the introduced new trait in terms of the gene construct and its product -- not testing the whole food which contains that product. As a general rule, food is not tested for safety, other than for contaminants. For example, a new wheat variety containing new genes for disease resistance produced by conventional breeding is considered identical -- substantially equivalent -- to its parent cultivars. Providing the flour produced from this new wheat variety is acceptable to millers and bakers and similar to flour produced from other wheat, it is accepted into the food chain without further food safety evaluation. Therefore, the products of GM crop plants currently in the food chain have been tested far more thoroughly than any conventional food. Regulation in Australia Australia has been well served by the Genetic Manipulation Advisory Committee (GMAC), which has provided a clear, comprehensive, transparent framework for the conduct of research into GM organisms in the laboratory, in glasshouses, and in the field. The protocols developed and used within the GMAC framework in regulating research into GM organisms in Australia have become the model for similar research in other countries, including Malaysia, Thailand and Singapore. While the present protocol through GMAC provides a satisfactory avenue for planned release of GM organisms to the "proof of concept" (precommercialisation) stage, the pathway to commercialisation is far less clear. To correct this deficiency, the Australian government recently allocated funding for the establishment of an Office of the Gene Technology Regulator (OGTR) to ensure an effective, enforceable system of regulation for the biotechnology industry. This office, currently known as the Interim OGTR, will develop an appropriate regulatory regime to cover the development, clearance and labelling of foods and food products derived from the new gene technologies. As such, it needs to meet the dual imperatives of providing consumers with confidence in the safety and regulation of gene technology products and of fostering an environment conducive to industry innovation and commercialisation. The Interim OGTR is currently seeking community views and comment on the Draft Gene Technology Bill 2000 (dated December 1999), which covers the regulation of all aspects of the research, development and use of GM organisms and their products, where no other body has responsibility. The Government has also established a Senior Ministerial Council to manage biotechnology issues across the relevant portfolios of Health, Industry, Environment, Education and Agriculture, as well as a Commonwealth agency within the Department of Industry, Science and Resources, to be known as Biotechnology Australia, to coordinate the Commonwealth's activities in biotechnology. It is clear that the new regulatory system must provide consumers with confidence that the necessary checks and balances are in place to ensure food derived from the new technology is safe and beneficial. Consumer education will remain a major factor in determining the acceptance of the new technology, and it is important that balanced information on the science of the risk and safety assessment of food derived from gene technology is made freely available to the community. Disclosure statement The authors are employed by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), a publicly funded Australian research organisation. CSIRO Plant Industry undertakes research in the plant sciences, including the use of plant molecular biology to develop new and improved crop plants for the benefit and sustainability of Australian agricultural industries. References Larkin P, editor. Genes at work: biotechnology. Canberra: CSIRO, 1994. Commonwealth Scientific and Industrial Research Organisation. <http://genetech.csiro.au> James C. Global review of commercialised transgenic crops. ISAAA Brief No 8. Ithaca, NY: ISAAA, 1998. Fitt GP, Wilson LJ. Genetic engineering in integrated pest management: case study -- Bt plants. In: Emerging technologies in integrated pest management. Sutton T, Kennedy GG, editors. St Paul, Minn: American Phytopathological Society Press. In press. Kärenlampi S. Health effects of marker genes in genetically engineered food plants. Report to the Nordic Council Copenhagen: TemaNord, 1996: 530. Dröge M, Pühler A, Selbitschka W. Horizontal gene transfer as a biosafety issue: A natural phenomenon of public concern. J Biotechnol 1998; 64: 75-90. Redenbaugh K, Hialt W, Martineau B, et al. Aminoglycoside 3'-phosphotransferase II (APH (39) II or NPTII): Review of its safety and use in the production of gentically engineered plants. Food Biotechnol 1994; 8: 137-165. Nap JP, Bijvoet J, Strikena WJ. Biosafety of kanamycin-resistant transgenic plants: an overview. Transgenic Crops 1992; 1: 239-249. Fuchs RL, Ream JE, Hammond BG, et al. Safety assessment of the neomycin phosphotransferase II (NPTII) protein. Bio/Technology 1993; 11: 1543-1547. The Royal Society. Statement 1998: genetically modified plants for food use. London: The Royal Society, 1998. Padgette SR, Taylor NB, Nida DL, et al. The composition of glyphosate-tolerant soybean seeds is equivalent to conventional soybeans. J Nutr 1996; 126: 702-716. Fuchs RL, Re DB, Rogers SG, et al. Safety evaluation of glyphosate-tolerant soybeans. In: Food safety evaluation. Paris: OECD, 1996: 61-70. The Royal Society. Statement 1999: review of data on possible toxicity of GM potatoes. London: The Royal Society, 1999. Horton R. Genetically modified foods: "absurd" concern or welcome dialogue [editorial]? Lancet 1999; 354: 1314-1315. Ewen SWB, Pusztai A. Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine. Lancet 1999; 354: 1353-1354. Authors' Details CSIRO Plant Industry, Canberra, ACT. John L Huppatz, PhD, Deputy Chief. Paula A Fitzgerald, BA (Comm), Public Affairs Manager. Reprints will not be available from the authors. Correspondence: Ms P A Fitzgerald, CSIRO Plant Industry, GPO Box 1600, Canberra, ACT 2601.

John L Huppatz PhD · Paula A Fitzgerald BA (Comm)

We would be wise to hold off until we know more about the health, ecological and economic effects of genetically modified food. Advocates of genetically modified (GM) foods often assert that the processes of laboratory genetic engineering are really no different from those of plant and animal husbandry. This argument is not as convincing as they expect. Those who express concern about the safety of GM food claim that genetic engineering allows humans to do what nature will not -- they worry that scientists cut and paste genes and can now transfer genes between species. This gene transfer raises new safety questions, making the production and marketing of GM foods a matter for consideration by public health authorities. Food safety is a public health issue. Most food is provided by private enterprise, and consumers understand that food advertising, while commercially justifiable, exhibits the qualities of advertising in general: truth is spun and packaged to make the product attractive. Regulatory mechanisms, including surveillance, have been put in place in many countries over many years to ensure food safety and to balance commercial profit with the public good. Increasingly, food manufacturers and retailers understand the critical importance of safety as well as the healthiness of their product for market share. Can we rely on the food industry regulating itself? Not in all times or all places has the public found commercial interest, even in food production, to be trustworthy. When outbreaks of food poisoning occur, long-held public suspicions erupt as rage. Furthermore, a contributing factor to the outbreak of mad cow disease (bovine spongiform encephalopathy, or BSE) in the United Kingdom was a change in the processing of animal feed. Altered rendering practices, introduced in the late 1970s and early 1980s when the feed industry was deregulated, allowed scrapie-like agents to survive.1 This finding shocked the community and shattered trust in commercially driven food enterprises. The change in rendering practices paralleled adoption of the political view that the food industry needed self-regulation only, and the winding back of the public health food surveillance system. Thus, the attitude of some of the UK public to GM food was formed by their experience with BSE. GM technologies, which are profit driven (for manufacturers of GM strains and the farmers who use them), did not impress a community that felt it had been falsely reassured that food safety could be left to the producers. Although GM food safety is clearly a public health issue, in Australia at present the Genetic Manipulation Advisory Committee (GMAC) and the Interim Office of the Gene Technology Regulator (OGTR) comprise individuals who, although highly skilled, can opine only about the laboratory or clinical safety of products. The federal Minister for Health and Human Services, Michael Wooldridge, has agreed to consider appointing to these bodies a professional with extensive skill and experience in public health. Public health concerns about GM food include potential direct ill-effects from consuming the food, or imported allergens in the food, as well as their ecological impact. The histories of medicine and public health contain many examples of substances initially assumed to be safe and later found otherwise. These range from specific drugs, such as the class IC antiarrhythmic agents (eg, flecainide), which turned out to be proarrhythmic in certain circumstances,2 to more general environmental conditions, such as low level air pollution, once thought harmless but now correlated with mortality rates.3 These histories alone should deter GM food manufacturers from prejudicial paternalism in dealing with public concerns. The forms of testing outlined in this issue of the Journal by Huppatz and Fitzgerald, based on establishing substantial equivalence, are necessary but not sufficient to establish public health safety.4 Even here uncertainties remain, because of the lack of adequate benchmarks for cellular safety of non-GM foods. Most public health safety is established only by intervention followed by careful monitoring. The equivalent approach to GM foods would involve developing suitable surveillance systems for adverse events in those eating GM foods and for ecological impact. Thus, there is some justification for the introduction of these foods under surveyed conditions. Advantage could be taken of natural experiments. For example, the production and consumption of GM foods is greater in the United States than in Europe. Observational studies on the health of the two populations and their agricultural environments may at least provide clues to the long-term consequences of GM foods. This would not be easy, and the effects, as with BSE, might not be apparent for years or even decades if the latency were long between the impact of the food and its expression as illness. What are the concerns with GM food? In the UK and elsewhere in Europe, media coverage of GM foods has been intense and often sensational. In Australia, media concern has been obvious, and, while claims of irresponsible sensationalism have been made, in my opinion the quality of much of the reporting and journalistic comment has been fair to good. An investigative series on GM foods by Mark Ragg, health writer for the Sydney Morning Herald, fuelled the debate in Australia.5 Much that has been written has focused on human safety and the arguments for and against GM food labelling, while relatively less has been concerned as yet with environmental impact. In recent issues of the British Medical Journal strenuous efforts have been made by editorial writers, scientific writers and freelance consultants to dampen the European "bioangst" about wayward genes in GM foods.6-8 However, as far as population and ecological safety are concerned, I believe we are at the scientific starting line: we simply don't know whether GM foods are safe, what their environmental impact will be, or how the gains will trade with the losses. In that case, says the British Medical Association, we should wait until we have evidence that GM foods are safe before proceeding. Science has yet to do its work in establishing the safety of these products.9 In a statement earlier this year, the UK's Chief Scientific Adviser, Robert May, concluded: "There can be questions of health and safety associated with some GM foods, particularly if we introduce genes coding for production of toxins against certain kinds of pests."10 May, together with the Chief Medical Officer, Liam Donaldson, also wrote that, although "there is no current evidence to suggest that the GM technologies used to produce food are inherently harmful . . . nothing can be absolutely certain in a field of rapid scientific and technological development".11 Donaldson and May urged the UK government to study the potential effects of GM food technology on health and to develop a research strategy into the technology.12 Antibiotic resistance: A further worry about GM food arises from the practice of using antibiotic resistance, which is easily established, as a marker to measure the success of a genetic modification. Antibiotic resistance is tagged onto the genetic modification, so that cells that contain the new gene are also antibiotic resistant. Were this resistance to spread to pathogenic bacteria via the GM food, it could cause great harm.9 Ecological and economic effects: Doubt about GM food does not stop at the medical boundary. Many scientists sleep easily about the safety of GM foods for human consumption after proper testing and regulation, while having nightmares about the environmental impact of these foods. For example, genes that code for resistance to chemical herbicides could be transferred from GM plants to weeds. Cultivation of GM crops on a large scale may have implications for biodiversity, the balance of nature and wildlife. Third World countries may have the most to benefit from the potentially greater productivity of GM crops, but, if the price is increasing debt to the multinationals that produce GM seed, it will simply increase the north-south wealth disparity which lies at the heart of so much appalling public ill-health.9 As Jeffrey Sachs, Director of the Centre for International Development and Professor of International Trade at Harvard University, wrote in The Economist: Just as knowledge is becoming the undisputed centrepiece of global prosperity (and lack of it, the core of human impoverishment), the global regime on intellectual property rights requires a new look . . . now transnational corporations and rich-country institutions are patenting everything from the human genome to rainforest biodiversity. The poor will be ripped off unless some sense and equity are introduced into this runaway process.13 Concerns about the terminator gene, which prevents plants being propagated and requires farmers to repurchase fertile stock seed from the manufacturer at each planting, have drawn widespread criticism for much the same reason. This especially unpleasant commercial ploy has major implications for Third World countries. Monsanto has recently been forced to rethink its GM food strategy, with company head Bob Shapiro conceding: We have irritated and antagonised more people than we have persuaded. Our confidence in biotechnology has been widely seen as arrogance and condescension because we thought it was our job to persuade. But too often we forgot to listen.14 In the meantime, a healthy scepticism about the massive commercial interests in GM food is warranted. The moratorium called by the British Medical Association has much to commend it, especially for those who believe that human progress is best served when we listen to the guidance of science -- even when it says "I don't know".9 Disclosure statement No conflicts of interest. References Department of Health, MAFF. Report of the Working Party on Bovine Spongiform Encephalopathy (the "Southwood report"). London: DOH, 1989. Echt DS, Liebson PR, Mitchell B, et al. Mortality and morbidity in patients receiving encainide, flecainide, or placebo: the Cardiac Arrhythmia Suppression Trial. N Engl J Med 1991; 324: 781-788. Dockery DW, Pope CA III, Xu X, et al. An association between air pollution and mortality in six US cities. N Engl J Med 1993; 329: 1753-1759. Huppatz JL, Fitzgerald PA. Genetically modified foods -- safety and regulatory issues. Med J Aust 2000; 172: 170-173. Ragg M. Genetic food: you're eating it. Sydney Morning Herald 1999 Jul 24; 1 (col 1), 10. Dixon B. The paradoxes of genetically modified foods. BMJ 1999; 318: 547-548. Berger A. Hot potato. BMJ 1999; 318: 611. Jones L. Genetically modified foods. BMJ 1999; 318: 581-584. Leeder S. Frankenstein and the hot potato. Aust N Z J Public Health 1999; 23: 227-228. May R. Genetically modified foods: facts, worries, policies, and public confidence. London: Office of Science and Technology, 1999. Donaldson L, May R. Health implications of genetically modified foods. London: Department of Health, 1999. Horton R. Genetically modified foods: "absurd" concern or welcome dialogue? Lancet 1999; 354: 1314. Sachs J. Helping the world's poorest. The Economist 1999 Aug 14: 17-20. Vidal J. GM company chief takes blame for public relations failures and pledges to answer safety concerns. Guardian 1999 Oct 7. Authors' Details Faculty of Medicine, University of Sydney, Sydney, NSW. Stephen R Leeder, FRACP, FAFPHM, FFPHM, Dean. Reprints will not be available from the author. Correspondence: Professor S R Leeder, Faculty of Medicine, University of Sydney, NSW 2006. steveATmedicine.usyd.edu.au

Stephen R Leeder FRACP, FAFPHM, FFPHM

The Weight Debate What should we do about overweight and obesity? The goals of treatment should not necessarily be to normalise weight, but to optimise health MJA 1999; 171: 599-600 Introduction - Why are we getting obese? - Why have we not been effective in treating obesity? - What should we do about obesity? - What has been ignored is our environment - - More articles on Nutrition

Ian D Caterson

The Weight Debate Obesity and virtue. Is staying lean a matter of ethics? Self-control of one's own weight might be described as a form of bioethics John N Burry MJA 1999; 171: 609-610 Article - References - Authors' details - - More articles on Ethics

John N Burry

For Debate The 100-year conflict: salt intake and cardiovascular disease MJA 1998; 169: 174-180 The health effects of dietary salt have long been debated. As early as the beginning of the 20th century, salt restriction was used as a therapeutic measure, first for oedema and then for hypertension, particularly in France.1 Later, in the United States, the benefits of low salt diets for patients with hypertension and renal disease were championed by Allen in the 1920s and 30s and by Kempner in the late 1930s and 40s.1 However, not all investigators were convinced of the value of these diets, and the hazards of overzealous and prolonged salt restriction were also appreciated.1 By the 1960s and 70s, studies linking an increase in blood pressure of indigenous populations with the introduction of salty Western diets persuaded government bodies to recommend reduced salt as part of healthy dietary guidelines. One of the eight Dietary Goals for Australia, announced in 1979 by the then Commonwealth Department of Health, was "Decrease consumption of salt".2 There are, however, many researchers who maintain that there is insufficient evidence of benefit to recommend universal salt restriction. A summary of this controversy, described as "a philosophical clash between the requirements of public health policy and the requirements of good science", appeared in Science last year.3 In the MJA the salt controversy is alive and well. A study by Beard et al published in 1997 showing a low level of conformity with the year 2000 dietary salt target for Australians (<100mmol/day)4 brought an immediate response from Kincaid-Smith, reminding readers of the possible dangers of low salt intake.5 Then, in March 1998, a study by Alderman et al in the Lancet, claiming to have found an inverse association between dietary salt intake and all-cause and cardiovascular disease mortality,6 revived the international controversy, to which the Lancet's letters columns attest.7-10 Here, we present our own salt debate, with three views of the value (or otherwise) of salt restriction as part of a healthy diet. Universal recommendations for sodium intake should be avoided Restriction of salt intake is needed too ameliorate the cardiovascular disease epidemic The salt dilemma: some answers, many questions Link to salt debate references Dr Derek Denton showed unequivocally that increased salt intake causes a substantial rise in blood pressure in chimpanzees.11 Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Editorial Oily fish and asthma - a fishy story? Further studies are required before claims can be made of a beneficial effect of oily fish consumption on asthma Interest in the possible health benefits of dietary fish lipids followed observations that populations with a high dietary intake of fish, such as Greenland Inuit and the Japanese, had low incidences of atherosclerotic disorders and of inflammatory conditions such as rheumatoid arthritis. Our recent understanding of asthma as a chronic inflammatory airway disease has led to speculation that a diet rich in fish oil may also ameliorate asthma. The potential anti-inflammatory effect of fish oil stems from its active ingredient, eicosapentaenoic acid (EPA), which is a competitive substrate with arachidonic acid for the generation of inflammatory mediators. The derivatives of arachidonic acid (an n-6 fatty acid) are leukotriene B4 (LTB4), a potent neutrophil chemoattractant and pro- inflammatory mediator, and the cysteinyl series of leukotrienes (LTC4, LTD4 and LTE4), which produce potent smooth muscle contraction and bronchoconstriction. In contrast, EPA (an n-3 fatty acid), as well as inhibiting arachidonic acid metabolism, is a substrate for the less active prostanoids (e.g., thromboxane A3) and leukotrienes (e.g., LTB5), and so has the potential to reduce airway inflammation and reverse bronchoconstriction. As the most profound anti-inflammatory actions of fish oil are on neutrophil function and mediator generation, it is not surprising that clinical trials of dietary fish oil have been beneficial in diseases where there is a neutrophilic inflammation, such as rheumatoid arthritis, psoriasis, cystic fibrosis and inflammatory bowel disease. However, in asthma the role of neutrophils is much less certain. Eosinophils and mast cells are thought to be the predominant effector cells in asthma (through the release of mediators), with T lymphocytes, macrophages and, possibly, mast cells having initiating and immunomodulatory roles through cytokine secretion. Placebo-controlled interventional studies of high dose fish oil supplementation in patients with asthma have been disappointing. Early short term trials (eight weeks) of up to 4 g/day of EPA in severe asthmatics showed no clinical benefit, despite demonstrating profound suppression of neutrophil chemotaxis and mediator generation.1 In a study in aspirin-intolerant subjects asthma control worsened after six weeks of 3 g/day of EPA, 2 consistent with the known aspirin-like effect of cyclooxygenase inhibition by EPA. Further studies in milder asthmatics with 3.2 g/day for 10 weeks showed no benefit in either clinical symptoms or bronchial hyperresponsiveness,3 despite demonstrating attenuation of allergen-induced late-phase bronchoconstriction induced in the laboratory.4 A more prolonged trial for six months with 3.2 g/day of EPA also showed no clinical benefit in patients with pollen-induced asthma and seasonal hayfever.5 These disappointing results are consistent with in-vitro evidence that EPA does not inhibit eosinophils and mast cells. In contrast to its dampening effect on neutrophils, EPA incubated with cultured murine mast cells produced a marked increase in production of platelet-activating factor, without an effect on histamine release.6 Similarly, stimulated human eosinophils incubated with EPA generated significantly greater amounts of leukotrienes than those incubated with arachidonic acid.7 Furthermore, in asthma there is a complex interaction between cells, cytokines, nerves and lipid and other mediators. Although of the lipid mediators leukotrienes may have the most influential role in asthma, modulating any one group of inflammatory mediators alone may not be sufficient to produce clinical improvement. The only interventional study which has shown positive results was a small placebo-controlled trial of low-dose EPA (1 g/day) for 12 months in 12 adult asthmatic subjects (six taking fish oil and six taking placebo). After nine months a small but significant improvement was found in forced expiratory volume at one second (FEV1).8 However, no details were given of concurrent medication use or assessment of compliance with therapy by leukocyte membrane phospholipid analysis, and there have been no follow-up data since 1991. The question of fish diet and respiratory health has also been investigated from an epidemiological perspective in recent American studies. In a survey of 2526 adult subjects aged 30-70 years, the first National Health and Nutrition Survey found eating fish more than once a week, compared with less than once a week, was associated with a higher level of lung function. However, only 2.9% of subjects in this survey were asthmatic, so no conclusion could be drawn about the effect of fish consumption on asthma.9 The Atherosclerosis Risk in Communities (ARIC) study surveyed 8960 adult current and former smokers10 and reported that a high dietary intake of n-3 fatty acids was inversely related to the risk of chronic obstructive pulmonary disease (COPD). This apparent protective effect is biologically plausible as neutrophilic inflammation is a feature of COPD. The Nurses' Health Study, possibly the largest prospective study of its type, reporting the incidence of adult-onset asthma in 77 866 women aged 34-68 years, found no relationship between dietary intake of fatty acids and the incidence of doctor-diagnosed asthma over a 10-year period.11 With this background, what interpretation can be put on the study by Hodge et al. in this issue of the Journal (page 137)? The novel aspects of this epidemiological survey are that the study population consisted of Australian children aged 8-11, and that the diagnosis of asthma was based both on symptoms and measurement of bronchial hyperresponsiveness. The investigators found an inverse relationship between weekly oily fish intake and prevalence of asthma in 574 schoolchildren. A number of salient points may be made. Firstly, the investigators previously reported an inverse relationship between weekly total fish intake and asthma, which is not evident in this study. This may reflect the inherent variability of food frequency questionnaire data or the different sample sizes of the two studies, but it does raise doubts about the primary hypothesis being tested. Secondly, the estimated mean intake of EPA from a weekly serve of fish10 is about 0.2-0.8 g, which is much lower than the amount that would be expected to have anti-inflammatory effects on leukocyte mediator and cytokine generation. It is possible that it is not the oil in the fish per se but some other dietary or social component associated with families who eat fish which is responsible for these results. Thirdly, a much larger prospective study in adults did not find a similar relationship between dietary fish intake and asthma prevalence.11 Can this discrepancy be explained by subtle effects of low-dose fish oil on the immunological development of asthma in childhood, which are no longer relevant in adulthood? There is currently insufficient understanding of the mechanisms involved to put forward a biologically plausible hypothesis. Finally, the study of Hodge et al. is a cross-sectional study, and thus cannot establish a temporal relationship between oily fish intake and asthma. Nevertheless, these are very interesting data but they need to be confirmed in larger studies. Placebo-controlled prospective intervention studies with dietary manipulation for prolonged periods in childhood are also required before any claim can be substantiated. Until then, unwarranted speculation about the relationship between dietary fats and asthma12 should be avoided as this may have a negative impact on other health outcomes, cause even more confusion about diet and health in the general population and undermine an evidence-based approach to public health initiatives. Francis C K Thien Senior Lecturer Rosalie K Woods Research Fellow E Haydn WaltersProfessor/Director Department of Respiratory Medicine, Alfred Healthcare Group Melbourne, VIC (©MJA 1996; 164: 135-136) Kirsch CM, Payan DG, Wong MYS, et al. Effect of eicosapentaenoic acid in asthma. Clin Allergy 1988; 18: 177-187. Picado C, Castillo JA, Schinca N, et al. Effects of a fish oil enriched diet on aspirin intolerant asthmatic patients: a pilot study. Thorax 1988; 43: 93-97. Arm JP, Horton CE, Mencia-Huerta J-M, et al. Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax 1988; 43: 84-92. Arm JP, Horton CE, Spur BW, et al. The effects of dietary supplementation with fish oil lipids on the airways response to inhaled allergen in bronchial asthma. Am Rev Respir Dis 1989; 139: 1395-1400. Thien FCK, Mencia-Huerta J-M, Lee TH. Dietary fish oil effects on seasonal hay fever and asthma in pollen-sensitive subjects. Am Rev Respir Dis 1993; 147: 1138-1143. Triggiani M, Connell TR, Chilton FH. Evidence that increasing the cellular content of eicosapentaenoic acid does not reduce the biosynthesis of platelet-activating factor. J Immunol 1990; 145: 2241-2248. Thien FCK, Hallsworth MP, Soh C, Lee TH. Effects of exogenous eicosapentaenoic acid on generation of leukotriene C4 and leukotriene C5 by calcium ionophore-activated human eosinophils in vitro. J Immunol 1993; 150: 3546-3552. Dry J, Vincent D. Effect of a fish oil diet on asthma: results of a 1-year double-blind study. Int Arch Allergy Appl Immunol 1991; 95: 156-157. Schwartz J, Weiss ST. The relationship of dietary fish intake to level of pulmonary function in the first National Health and Nutrition Survey (NHANES I). Eur Resp J 1994; 7: 1821-1824. Shahar E, Folsom AR, Melnick SL, et al. Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. N Engl J Med 1994; 331: 228-233. Troisi RJ, Willett WC, Weiss ST, et al. A prospective study of diet and adult-onset asthma. Am J Respir Crit Care Med 1995; 151: 1401-1408. Hodge L, Peat JK, Salome C. Increased consumption of polyunsaturated oils may be a cause of increased prevalence of childhood asthma. Aust N Z J Med 1994; 24: 727. (©MJA 1996; 164: 135-136)

Rosalie K Woods

Research Consumption of oily fish and childhood asthma risk Linda Hodge, Cheryl M Salome, Jennifer K Peat, Michelle M Haby, Wei Xuan and Ann J Woolcock For editorial comment, see Thien et al. Abstract - Authors' details - Introduction - Methods - Results - Discussion - Appendix - Acknowledgements - References - Box 1 - Box 2 - Box 3 - Figure - © MJA 1996 - Abstract Objective: To investigate the association between diet and airway disease in children in the light of epidemiological studies suggesting that consumption of fish more than once a week reduces the risk of developing airway hyperresponsiveness (AHR). Design: Diet was assessed by a detailed food frequency questionnaire and airway disease by respiratory symptoms or airway responsiveness to exercise. Methods: A questionnaire, containing questions about the frequency of eating more than 200 foods, was sent to the parents of 574 children in whom we had measured recent wheeze (by questionnaire), AHR (by exercise) and atopy (by skin prick tests) six months before this study. We defined current asthma as the presence of both recent wheeze and AHR. Results: Response rate to the questionnaire was 81.5% (n = 468). After adjusting for confounders such as sex, ethnicity, country of birth, atopy, respiratory infection in the first two years of life and a parental history of asthma or smoking, children who ate fresh, oily fish (> 2% fat) had a significantly reduced risk of current asthma (odds ratio, 0.26; 95% confidence interval, 0.09-0.72; P < 0.01). No other food groups or nutrients were significantly associated with either an increased or reduced risk of current asthma. Conclusion: These data suggest that consumption of oily fish may protect against asthma in childhood. MJA 1996; 164: 137-140 Introduction The substantial increase in the prevalence of childhood asthma in the past 20 years has affected both rural and urban communities of westernised countries,1,2 suggesting that local environmental factors, such as exposure to allergens or industrial air pollutants, are not the cause. However, the widespread changes in diet may be responsible. Seaton et al.3 have postulated that increases in the prevalence of asthma may be due to a reduced intake of antioxidant vitamins (beta-carotene, vitamins A, C and E) and mineral cofactors essential for antioxidant defence mechanisms (selenium, zinc and copper) as a result of reduced consumption of meat, fresh fish, fruit and vegetables in Western diets. Reduced consumption of magnesium4 and increased consumption of salt5 have been implicated as risk factors for airway hyperresponsiveness (AHR). Our own epidemiological studies of Australian schoolchildren have shown that children who eat fish more than once a week have a third the risk of AHR of children who do not eat fish regularly.6 However, these studies did not include other dietary questions, so that fish consumption may have been a marker for another dietary characteristic. Here, we investigate the association between diet, as assessed by a detailed dietary questionnaire, and airway disease, assessed by respiratory symptoms or airway responsiveness to exercise. Methods Subjects In June 1993, a cross-section of 808 children aged 8-11 years from schools randomly selected from all schools within a 10 km radius of Sydney General Post Office had airway responsiveness to exercise, respiratory symptoms and atopy measured and frequency of fish consumption assessed.7 In October 1993, 584 children were selected from this group in a stratified case-control design and their parents were asked to complete a detailed food frequency questionnaire about their child's eating habits. The selection criteria included all children with AHR, all children who had had wheeze in the last 12 months (recent wheeze) and a three-in-five sample of children with normal airways (no AHR or recent wheeze), who were chosen by excluding two children after every three from numerically ordered lists of children identified by number. The study coordinator who collected the food frequency questionnaires was blind to the respiratory symptom and AHR status of the subjects. Ethical approval for the study was obtained from the Ethics Review Committee of the University of Sydney. Permission to approach schools was obtained from the New South Wales Department of School Education and the Catholic Education Office. Respiratory questionnaire In June 1993 the parents or guardians of the children completed a standard respiratory questionnaire, with questions on age, sex, ethnicity, country of birth, history of asthma or wheeze in the last 12 months, medication use, and also parents' occupations, history of asthma and smoking. The questionnaire included the question used in previous studies about the dietary consumption of fish - "How often does your child eat a meal that contains fish?" - with the options of replying "never or rarely", "once a week", or "more than once a week". Dietary questionnaire In October 1993, a food frequency questionnaire (adapted from that developed and validated by the Commonwealth Scientific and Industrial Research Organisation [CSIRO], Division of Human Nutrition, South Australia8,9) was distributed to the selected children, whose parents were asked to complete this for their child's usual eating habits over the last year. The questionnaire identified consumption patterns (daily, weekly, monthly, rarely or never) of more than two hundred foods commonly consumed in Australia. Additional questions on the type of fresh fish consumed and regular consumption of vitamin, mineral or herbal supplements were included. Estimates of sodium intake included naturally occurring sodium in foods, salt added in cooking, at the table and from processed foods. If questionnaires were not returned after one month the parents were contacted by telephone and offers were made to replace the questionnaires, or to provide assistance. In 11 cases, where neither parent spoke fluent English, an interpreter was commissioned to complete the questionnaire with the parents over the telephone. Returned dietary questionnaires were checked for missing or obviously erroneous information. Parents were contacted by telephone to complete omitted sections or to clarify erroneous information. Each food in the dietary questionnaire was allocated to one of 23 different food groups (see Appendix). Diets were analysed for energy, fibre and 39 nutrients (see Appendix). Definitions of respiratory categories, atopy, and categories of fish, plus a list of fish with more than 2% fat, are given in Box 1. Statistical analyses The questionnaires were analysed by the Division of Human Nutrition, CSIRO, South Australia, using Australian tables of nutrient composition12 for energy, protein, fat, carbohydrates, vitamins and minerals. The total quantity of food in each food group for every child was converted to a common base of weekly serves with Clinical Reporting Systems software.13 Data were analysed with the statistical package SAS.14The association between fish, food or nutrient intake and respiratory category was analysed categorically using chi-squared tests, and continuously using Student's t tests and analysis of variance. Some values obtained from the nutrient analysis were well outside what could reasonably be expected in children of this age group. These outliers were excluded from the statistical analysis. The number of exclusions never exceeded nine subjects in any analysis and were not significantly associated with any of the respiratory groups. Logistic regression was used to adjust estimates for the effects of known confounders for the effect of fish consumption on AHR and symptoms of asthma (e.g., sex, race, country of birth, atopy, early respiratory infection, parental smoking and parental asthma). Only those confounding factors found to be significant or approaching significance (P < 0.1) (atopy, parental asthma, early respiratory infection, country of birth) were included in the model. Results Of the 584 children selected 574 received the dietary questionnaire and 468 completed questionnaires were returned (81.5%). Non-responders were not significantly different from responders in the prevalence of AHR (26.0% v. 27.1%) or fish consumption (46.2% v. 52.1%). Box 2 shows details of the children studied. Children with current asthma did not differ significantly from children with normal airways in the consumption of any nutrient or food group. (Tables showing mean weekly intake in standard serves of food groups and mean daily intake [SD] of nutrients for children with normal airways and children with current asthma are available from the authors.) Children with wheeze only had a significantly higher intake of red meat (P < 0.05), offal meat (P < 0.001) and vitamin B12 (P < 0.03) and a significantly lower intake of mixed vegetables (P < 0.05) than children with normal airways. Children with AHR only consumed significantly more offal meat (P = 0.001) and high fat/high sugar foods (P < 0.001) than children with normal airways. They also had higher intakes of nitrogen, protein, total sugar, cholesterol, potassium nicotinamide, total nicotinamide, calcium, copper, zinc, vitamin B12 (P < 0.05) and refined sugar (P < 0.01). Total fish intake per week did not differ significantly between children with normal airways (1.2 serves per week; 95% confidence interval [CI], 1.0-1.3), AHR only (1.2 serves; CI, 0.9-1.5), wheeze only (1.2 serves; CI, 0.8-1.5) and current asthma (1.0 serve; CI, 0.8-1.2). Fresh fish was eaten by 84% (CI, 79.6%-88.4%) of children with normal airways, and by 72% (CI, 61.6%-82.4%) of children with current asthma. When fresh fish was divided into oily and non-oily types, significantly fewer children with current asthma (15.5%; CI, 7.1%-23.9%) included oily fish in their diet than did children with normal airways (30.8%; CI, 25.2%-36.4%; P < 0.05). There were no significant differences in the proportions of children with current asthma (56.3%; CI, 44.8%-67.8%) and normal children (52.9%; CI, 46.9%-58.9%) who ate exclusively non-oily fish. Neither fresh fish consumption nor respiratory disease was significantly associated with socioeconomic status, as defined by the father's occupation, or with the consumption of vitamin, mineral or other dietary supplements (including fish oil). The unadjusted risk (odds ratio) for children having current asthma was significantly lower in those who consumed any fresh fish or oily fresh fish (Box 3). Current asthma was found in only 8.8% (CI, 3.8%-13.8%) of children who ate oily fish, but in 15.6% (CI, 11.2%-20.0%) of those who ate non-oily fish only and 23% (CI, 14.2%-31.8%) of those who never ate fresh fish (Figure). When the results were adjusted for the effects of other known risk factors such as atopy, parental asthma, parental smoking, ethnicity, country of birth, early respiratory illness and sex, only children who ate oily fresh fish had a significantly reduced risk of current asthma. In these children, the risk was almost a quarter that of children who did not eat oily fish (odds ratio, 0.26; CI, 0.09-0.72) (Box 3). Consumption of any fresh fish, whether or not it was separated into oily fresh fish and non-oily fresh fish, did not significantly reduce the risk of AHR only or wheeze only either before or after adjustment for other risk factors. Discussion Our study shows that regular consumption of fresh, oily fish is associated with a reduced risk of current asthma. This reduced risk remained significant after adjustment for other known risk factors for asthma, including sex, atopy, parental asthma, parental smoking, early respiratory infection, ethnicity and place of birth. The subjects were selected from a random cross-sectional sample of children which was stratified (on the basis of recent respiratory symptoms and AHR to exercise) to increase the proportion of cases in the study group. The response rate was high (81.5%) and non-responders were not different from responders with respect to AHR or fish consumption. Socioeconomic status was not a confounder for either respiratory illness or fish consumption. Current asthma was defined as recent wheeze plus AHR to exercise. We have shown previously that current asthma, defined as recent wheeze plus AHR to histamine, identifies a group with severe, ongoing respiratory impairment, while those with AHR only and wheeze only have a milder condition which differs only slightly from the normal group.15 The diets of children with current asthma differed from those of the normal group only in the consumption of fresh, oily fish. In our previous study, more than one serve of fish per week was associated with a reduced risk of asthma,6 but in that study it was not possible to distinguish the effects of oily and non-oily fish. In the study reported here we were unable to detect differences in total fish consumption, possibly because of the smaller sample size. There were no significant differences between respiratory groups in the consumption of non-oily fish, suggesting that parents had not selectively withheld fish from the diets of asthmatic children. It is unclear why consumption of canned and processed fish was not associated with reduced risk of asthma. Processing may alter the integrity or activity of the fatty acids in fish oils. Several foods and nutrients in the diets of children with AHR only and wheeze only differed significantly from those of the normal group. However, none of these factors differed between the asthmatic and normal groups, suggesting that they are unlikely to have an aetiological role. Intake of offal meats was higher in both the AHR-only and wheeze-only groups, but, as offal meats are eaten by very few children, this may be a type I error. Vitamin B12 intake was also higher in both the AHR-only and wheeze-only groups, but the mechanism by which this could affect respiratory symptoms or AHR is unclear. There were no significant differences between any of the respiratory groups in consumption of sodium, vitamin C, vitamin E, selenium or magnesium. These findings do not support previous evidence that these dietary factors are important in the aetiology of asthma.4,5,16 Reduced risk of current asthma was associated with the consumption of oily fish, but not with non-oily fish. Fish oil contains the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory effects.17 Theoretically, EPA could either prevent the development of asthma or reduce its severity by altering two of the cardinal features of asthma, namely airway inflammation and AHR. Supplementation with EPA reduces production of leukotriene B4,18 a chemical mediator responsible for the recruitment of inflammatory cells, such as neutrophils, into the airways. It also reduces production of the cytokine tumour necrosis factor (TNF),19 which increases airway responsiveness.20 Fish oil supplements given over 6-10 weeks cause a substantial uptake of EPA in neutrophil membrane phospholipids.18,21 In asthmatics, this may reduce the allergen-induced late asthmatic response,22 but does not change severity of asthma.21,22 However, a recent study suggests that a longer period of supplementation may be required to reduce asthma severity.23 Data of recent fish consumption (during the last 12 months) were used in our study, but may also reflect lifetime dietary habits. In conclusion, we have shown that consumption of oily fish is associated with a reduced risk of asthma in childhood. Although further studies are required to confirm these benefits, public health interventions to increase the consumption of oily fish may reduce the morbidity and prevalence of asthma in children. Appendix The 23 food groups were: cereals; dairy products; eggs; red, white, preserved meat and offal; seafood, fried, steamed, canned fish and fish fingers; red, green, white, mixed and other vegetables; legumes; high and low vitamin C fruit and other fruit; high sugar or fat content; and other. The 39 nutrients were: nitrogen; protein; starch; refined, natural and total sugar; total carbohydrate; saturated, monounsaturated, polyunsaturated and total fat; cholesterol; carotene; retinol; vitamin A; thiamine; riboflavin; potassium nicotinic acid and total nicotinic acid; niacin; vitamins B6 and B12; pantothenic acid; biotin; free and total folate; vitamins C, D, E; calcium; copper; iron; magnesium; manganese; phosphorus; potassium; selenium; sodium; and zinc. Acknowledgements This study was supported by the Fisheries Research and Development Corporation, Australia. The authors thank Dr Katrine Baghurst for allowing us to use the dietary questionnaire, Sally Record and Kay Pender for their help with the nutritional analyses, Elena Belooussova for data organisation and Suzanne Gray for her assistance with collecting the questionnaires. We are grateful for the support of the New South Wales Department of School Education, the Catholic Education Office and the Principals and teachers of all the schools involved. We are especially grateful to the parents and the children who participated in the survey. (©MJA 1996; 164: 137-140) References Robertson CF, Bishop J, Sennhauser FH, Mallol J. International comparison of asthma prevalence in children: Australia, Switzerland, Chile. Pediatr Pulmonol 1993; 16: 219-226. Burney P, Chinn S, Rona RJ. Has the prevalence of asthma increased in children? Evidence from the national study of health and growth 1973-86. BMJ 1990; 300: 1306-1310. Seaton A, Godden DJ, Brown K. Increase in asthma: a more toxic environment or a more susceptible population? Thorax 1994; 49: 171-174. Britton J, Pavord I, Richards K, et al. Dietary magnesium, lung function, wheezing, and airway hyperreactivity in a random adult population sample. Lancet 1994; 344: 357-362. Burney PG, Neild JE, Twort CHC, et al. Effect of changing dietary sodium on the airway response to histamine. Thorax 1989; 44: 36-41. Peat JK, Salome CM, Woolcock AJ. Factors associated with bronchial hyperresponsiveness in Australian adults and children. Eur Respir J 1992; 5: 921-929. Haby MM, Peat JK, Mellis CM, et al. An exercise challenge for epidemiological studies of childhood asthma: validity and repeatability. Eur Respir J 1995; 8: 729-736. Baghurst KI, Record SJ. Intake and sources in selected Australian subpopulations of dietary constituents implicated in the etiology of chronic diseases. J Food Nutr 1983; 40: 1-15. Rohan TE, Record SJ, Cook MG. Repeatability of estimates of nutrient and energy intake: the quantitative food frequency approach. Nutr Res 1987; 7: 125-137. Analyses of NSW fish and shellfish. Sydney: Australian Government Analytical Laboratory, 1989. Sinclair A, Dunstan GA, Naughton JM, et al. The lipid content and fatty acid composition of commercial marine and freshwater fish and molluscs from temperate Australian waters. Aust J Nutr Diet 1992; 49: 77-83. English R, Lewis J. Composition of foods Australia. 1st ed. Vols 1-5. Canberra: AGPS, 1989-1990. Clinical Reporting Systems [computer program], version 3.0. Sydney: Clinical Reporting Systems Pty Ltd. 1992. SAS [computer program], version 5. Cary, NC: SAS Institute, 1984. Toelle BG, Peat JK, Salome CM, et al. Toward a definition of asthma for epidemiology. Am Rev Respir Dis 1992; 146: 633-637. Stone J, Hinks LJ, Beasley R, et al. Reduced selenium status of patients with asthma. Clin Sci 1989; 77: 495-500. Kremer JM, Jubiz W, Michalek A, et al. Fish-oil fatty acid supplementation in active rheumatoid arthritis. Ann Intern Med 1987; 106: 497-503. Lee TH, Hoover RL, Williams JD, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985; 312: 1217-1224. Endres S, Ghorbani R, Kelley VE, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989; 320: 265-271. Thomas PS, Yates DH, Barnes PJ. Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects. Am J Respir Crit Care Med 1995; 152: 76-80. Arm JP, Horton CE, Mencia-Huerta J-M, et al. Effect of dietary supplementation with fish oil lipids on mild asthma. Thorax 1988; 43: 84-92. Arm JP, Horton CE, Spur BW, et al. The effects of dietary supplementation with fish oil lipids on the airways response to inhaled allergen in bronchial asthma. Am Rev Respir Dis 1989; 139: 1395-1400. Dry J, Vincent D. Effects of fish oil diet on asthma: results of a 1-year double blind study. Int Arch Appl Immunol 1991; 95: 156-157. (Received 31 May, accepted 28 Nov 1995) Authors' details Institute of Respiratory Medicine, Royal Prince Alfred Hospital, Sydney, NSW. Linda Hodge, MSc(Med), GradDipNutr&Diet, Dietitian. Department of Medicine, University of Sydney, Sydney, NSW. Cheryl M Salome, BSc, Senior Research Officer. Jennifer K Peat, PhD, Senior Research Officer. Michelle M Haby, MSc, Research Assistant. Wei Xuan, MSc, MApplStat, Statistician. Ann J Woolcock, MD, FRACP, Professor in Respiratory Medicine. Reprints: Professor A J Woolcock, Institute of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, NSW 2050. (©MJA 1996; 164: 137-140)

Linda Hodge · Cheryl M Salome · Jennifer K Peat · Michelle M Haby · Wei Xuan · Ann J Woolcock