Sophie Hawkesworth

B-Vitamins and Fatty Acids in the Prevention and Treatment of Alzheimer's Disease and Dementia: A Systematic Review

The increasing worldwide prevalence of dementia is a major public health concern. Findings from some epidemiological studies suggest that diet and nutrition may be important modifiable risk factors for development of dementia. In order to evaluate the strength of the available evidence of an association of dietary factors with dementia including Alzheimers disease (AD), we systematically searched relevant publication databases and hand-searched bibliographies up to end July 2007. We included prospective cohort studies which evaluated the association of nutrient levels with the risk of developing dementia and randomized intervention studies examining the treatment effect of nutrient supplementation on cognitive function. One hundred and sixty studies, comprising ninety one prospective cohort studies and sixty nine intervention studies, met the pre-specified inclusion criteria. Of these, thirty-three studies (19 cohort and 14 randomized controlled trials) investigated the effects of folate, B-vitamins, and levels of homocysteine (a biomarker modifiable through B-vitamin supplementation) or fish/fatty acids and are the focus of the present report. Some observational cohort studies indicated that higher dietary intake or elevated serum levels of folate and fish/fatty acids and low serum levels of homocysteine were associated with a reduced risk of incident AD and dementia, while other studies reported no association. The results of intervention studies examining the effects of folic acid or fatty acid supplementation on cognitive function are inconsistent. In summary, the available evidence is insufficient to draw definitive conclusions on the association of B vitamins and fatty acids with cognitive decline or dementia, and further long-term trials are required.

Feeding the world healthily: the challenge of measuring the effects of agriculture on health

Agricultural production, food systems and population health are intimately linked. While there is a strong evidence base to inform our knowledge of what constitutes a healthy human diet, we know little about actual food production or consumption in many populations and how developments in the food and agricultural system will affect dietary intake patterns and health. The paucity of information on food production and consumption is arguably most acute in low- and middle-income countries, where it is most urgently needed to monitor levels of under-nutrition, the health impacts of rapid dietary transition and the increasing ‘double burden’ of nutrition-related disease. Food availability statistics based on food commodity production data are currently widely used as a proxy measure of national-level food consumption, but using data from the UK and Mexico we highlight the potential pitfalls of this approach. Despite limited resources for data collection, better systems of measurement are possible. Important drivers to improve collection systems may include efforts to meet international development goals and partnership with the private sector. A clearer understanding of the links between the agriculture and food system and population health will ensure that health becomes a critical driver of agricultural change.

Use of bioelectrical impedance analysis to assess body composition in rural Gambian children.

Objective:To validate the Tanita BC-418MA Segmental Body Composition Analyser and four-site skinfold measurements for the prediction of total body water (TBW), percentage fat-free mass (%FFM) and percentage body fat (%BF) in a population of rural Gambian children.Subjects/Methods:One hundred and thirty-three healthy Gambian children (65 males and 68 females). FFM estimated by the inbuilt equations supplied with the Tanita system was assessed by comparison with deuterium oxide dilution and novel prediction equations were produced. Deuterium oxide dilution was also used to develop equations for %BF based on four-site skinfolds (biceps, triceps, subscapular and suprailiac).Results:The inbuilt equations underestimated FFM compared to deuterium oxide dilution in all the sex and age categories (P<0.003), with greater accuracy in younger children and in males. The best prediction of %FFM was obtained from the variables height, weight, sex, impedance, age and four skinfold thickness measurements (adjusted R 2=0.84, root mean square error (MSE)=2.07%).Conclusions:These data suggest that the Tanita instrument may be a reliable field assessment technique in African children, when using population and gender-specific equations to convert impedance measurements into estimates of FFM.

Evidence for metabolic endotoxemia in obese and diabetic Gambian women.

Objective:Emerging evidence from animal models suggests that translocation of bacterial debris across a leaky gut may trigger low-grade inflammation, which in turn drives insulin resistance. The current study set out to investigate this phenomenon, termed ‘metabolic endotoxemia’, in Gambian women.Methods:In a cross-sectional study, we recruited 93 age-matched middle-aged urban Gambian women into three groups: lean (body mass index (BMI): 18.5–22.9 kg m−2), obese non-diabetic (BMI: ⩾30.0 kg m−2) and obese diabetic (BMI: ⩾30.0 kg m−2 and attending a diabetic clinic). We measured serum bacterial lipopolysaccharide (LPS) and endotoxin-core IgM and IgG antibodies (EndoCAb) as measures of endotoxin exposure and interleukin-6 (IL-6) as a marker of inflammation.Results:Inflammation (IL-6) was independently and positively associated with both obesity and diabetes (F=12.7, P<0.001). LPS levels were highest in the obese-diabetic group compared with the other two groups (F=4.4, P<0.02). IgM EndoCAb (but not total IgM) was highly significantly reduced in the obese (55% of lean value) and obese diabetic women (30% of lean; F=21.7, P<0.0001 for trend) compared with lean women.Conclusion:These data support the hypothesis that gut-derived inflammatory products are associated with obesity and diabetes. Confirmation of these findings and elucidation of the role of the microbiota, gut damage and the pathways for translocation of bacterial debris, could open new avenues for prevention and treatment of type 2 diabetes.

Early exposure to toxic metals has a limited effect on blood pressure or kidney function in later childhood, rural Bangladesh

Background Chronic exposure to toxic metals such as arsenic and cadmium has been implicated in the development of kidney and cardiovascular diseases but few studies have directly measured exposure during inutero and early child development. Methods We investigated the impact of exposure to arsenic (mainly in drinking water) and cadmium (mainly in rice) during pregnancy on blood pressure and kidney function at 4.5 years of age in rural Bangladesh. The effect of arsenic exposure in infancy was also assessed. Results Within a cohort of 1887 children recruited into the MINIMat study, exposure to arsenic (maternal urinary arsenic, U-As), but not cadmium, during in utero development was associated with a minimal increase in blood pressure at 4.5 years. Each 1 mg/l increase in pregnancy U-As was associated with 3.69 mmHg (95% CI: 0.74, 6.63; P: 0.01) increase in child systolic and a 2.91 mmHg (95% CI: 0.41, 5.42; P: 0.02) increase in child diastolic blood pressure. Similarly, a 1 mg/l increase in child U-As at 18 months of age was associated with a 8.25 mmHg (95% CI: 1.37, 15.1; P: 0.02) increase in systolic blood pressure at 4.5 years. There was also a marginal inverse association between infancy U-As and glomerular filtration rate at 4.5 years (−33.4 ml/min/1.72 m2; 95% CI: −70.2, 3.34; P: 0.08). No association was observed between early arsenic or cadmium exposure and kidney volume at 4.5 years assessed by ultrasound. Conclusions These modest effect sizes provide some evidence that arsenic exposure in early life has long-term consequences for blood pressure and maybe kidney function.

Maternal protein-energy supplementation does not affect adolescent blood pressure in The Gambia

Background Birthweight, and by inference maternal nutrition during pregnancy, is thought to be an important determinant of offspring blood pressure but the evidence base for this in humans is lacking data from randomized controlled trials. Methods The offspring from a maternal prenatal protein-energy supplementation trial were enrolled into a follow-up study of chronic disease risk factors including blood pressure. Subjects were 11–17 years of age and blood pressure was measured in triplicate using an automated monitor (Omron 705IT). One-thousand two-hundred sixty seven individuals (71% of potential participants) were included in the analysis. Results There was no difference in blood pressure between those whose mothers had consumed protein-energy biscuits during pregnancy and those whose mothers had consumed the same supplement post-partum. For systolic blood pressure the intention-to-treat regression coefficient was 0.46 (95% CI: –1.12, 2.04). Mean systolic blood pressure for control children was 110.2 (SD ± 9.3) mmHg and for intervention children was 110.8 (SD ± 8.8) mmHg. Mean diastolic blood pressure for control children was 64.7 (SD ± 7.7) mmHg and for intervention children was 64.6 (SD ± 7.6) mmHg. Conclusions We have found no association between maternal prenatal protein-energy supplementation and offspring blood pressure in adolescence amongst rural Gambians. We found some evidence to suggest that offspring body composition may interact with the effect of maternal supplementation on blood pressure.

Nutritional supplementation during pregnancy and offspring cardiovascular disease risk in The Gambia.

BACKGROUND Maternal nutritional intake during pregnancy may have important consequences for long-term health in offspring. OBJECTIVE The objective was to follow up the offspring in 2 randomized trials of nutrient supplementation during pregnancy to investigate the effect on cardiovascular disease (CVD) risk in offspring. DESIGN We recruited offspring born during 2 trials in The Gambia, West Africa. One trial provided protein-energy-dense food supplements (1015 kcal and 22 g protein/d) to pregnant (intervention, from 20 wk gestation until delivery) or lactating (control, for 20 wk from birth) women and was randomized at the village level. The second was a double-blind, individually randomized, placebo-controlled trial of calcium supplementation (1.5 g/d), which was also provided from 20 wk gestation until delivery. RESULTS Sixty-two percent (n = 1267) of children (aged 11-17 y) born during the protein-energy trial were recruited and included in the analysis, and 64% (n = 350) of children (aged 5-10 y) born during the calcium trial were recruited and included in the analysis. Fasted plasma glucose was marginally lower in children born to mothers receiving protein-energy supplements during pregnancy than in those children of the lactating group (adjusted mean difference: -0.05 mmol/L; 95% CI: -0.10, -0.001 mmol/L). There were no other differences in CVD risk factors, including blood pressure, body composition, and cholesterol, between children born to intervention and control women from the protein-energy trial. Maternal calcium supplementation during pregnancy was unrelated to offspring blood pressure. CONCLUSION These data suggest that providing supplements to pregnant women in the second half of pregnancy may have little effect on the CVD risk of their offspring, at least in this setting and at the ages studied here. This trial was registered at www.controlled-trials.com as ISRCTN96502494.

Dietary Supplementation of Rural Gambian Women during Pregnancy Does Not Affect Body Composition in Offspring at 11–17 Years of Age

Fetal nutrition is thought to be an important determinant of later disease risk, although evidence from randomized-controlled trials in humans is lacking. We followed children born during a protein-energy supplementation trial to investigate to what extent this maternal supplement, which improved birth weight, influenced offspring body composition in adolescence. Subjects were 1270 Gambian children (659 boys, 611 girls) aged 11-17 y whose mothers had participated in the original cluster-randomized trial and had received the supplement during pregnancy (intervention) or postpartum (control). Basic anthropometry was measured using standard techniques and fatness was assessed by bioelectrical impedance analysis and population-specific prediction equations. For boys, mean body fat was 12.6% for both intervention and control groups. Mean trunk fat was 11.9% in the intervention group and 12.0% in the control. Intervention girls had a mean body fat of 19.5% and trunk fat of 15.2%; for control girls, it was 19.3 and 14.8%, respectively. BMI, body fat, trunk fat, fat mass index, and fat-free mass index did not differ for either sex when analyzed with generalized estimating equations adjusted for age, maternal height, maternal parity, location, season of birth, and menarche in females. Neither infant-attained size nor the onset of menarche were affected by maternal supplementation. These findings suggest that protein-energy supplements to pregnant women, compared with lactating women, do not affect offspring body composition during adolescence.

Effect of maternal calcium supplementation on offspring blood pressure in 5- to 10-y-old rural Gambian children.

Background: Evidence suggests that increased maternal calcium intake during pregnancy may result in lower offspring blood pressure, prompting calls for more robust data in this field, particularly in settings of habitually low calcium intake. Objective: The objective was to investigate the effect of maternal calcium supplementation on blood pressure in offspring by recruiting children born after a randomized, double-blind, placebo-controlled trial of calcium supplementation during pregnancy. Design: Children (n = 389) from a rural area of The Gambia (mean age: 7.4 ± 1.2 y; range: 5–10 y), whose mothers received a calcium supplement (1500 mg Ca/d from 20 wk of gestation until delivery) or placebo, were followed up in West Africa. Blood pressure was assessed under standardized conditions with use of the Omron 705IT automated oscillometric device (Morton Medical Ltd, London, United Kingdom), and anthropometric and body composition (bioelectrical impedance) measurements were also made. Results: The analysis was restricted to 350 children born at term, which represented 64% of original trial births. There was no difference in systolic (adjusted mean difference: −0.04 mm Hg; 95% CI: −1.78, 1.69 mm Hg) or diastolic (adjusted mean difference: 0.25 mm Hg; 95% CI: −1.27, 1.77 mm Hg) blood pressure between children whose mothers had received calcium and those who received placebo. No interaction between childhood body mass index (in kg/m2; mean: 14.0) and maternal calcium supplementation was observed in this study. Conclusion: Calcium supplementation in the second half of pregnancy in Gambian women with very low habitual calcium intakes may not result in lower offspring blood pressure at 5–10 y of age.

Combined Food and Micronutrient Supplements during Pregnancy Have Limited Impact on Child Blood Pressure and Kidney Function in Rural Bangladesh

Observational evidence suggests nutritional exposures during in utero development may have long-lasting consequences for health; data from interventions are scarce. Here, we present a trial follow-up study to assess the association between prenatal food and micronutrient supplementation and childhood blood pressure and kidney function. During the MINIMat Trial in rural Bangladesh, women were randomly assigned early in pregnancy to receive an early or later invitation to attend a food supplementation program and additionally to receive either iron and folate or multiple micronutrient tablets daily. The 3267 singleton birth individuals with measured anthropometry born during the trial were eligible for a follow-up study at 4.5 y old. A total of 77% of eligible individuals were recruited and blood pressure, kidney size by ultrasound, and glomerular filtration rate (GFR; calculated from plasma cystatin c) were assessed. In adjusted analysis, early invitation to food supplementation was associated with a 0.72-mm Hg [(95% CI: 0.16, 1.28); P = 0.01] lower childhood diastolic blood pressure and maternal MMS supplementation was associated with a marginally higher [0.87 mm Hg (95% CI: 0.18, 1.56); P = 0.01] childhood diastolic blood pressure. There was also some evidence that a supplement higher in iron was associated with a higher offspring GFR. No other effects of the food or micronutrient interventions were observed and there was no interaction between the interventions on the outcomes studied. These marginal associations and small effect sizes suggest limited public health importance in early childhood.