APOE4 Genotype Exerts Greater Benefit in Lowering Plasma Cholesterol and Apolipoprotein B than Wild Type (E3/E3), after Replacement of Dietary Saturated Fats with Low Glycaemic Index Carbohydrates.

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial ('RISCK' study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC -0.28 mmol/L p = 0.03; apo B -0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

Treatment of childhood anxiety disorder in the context of maternal anxiety disorder: a randomised controlled trial and economic analysis.

BACKGROUND: Cognitive-behavioural therapy (CBT) for childhood anxiety disorders is associated with modest outcomes in the context of parental anxiety disorder. OBJECTIVES: This study evaluated whether or not the outcome of CBT for children with anxiety disorders in the context of maternal anxiety disorders is improved by the addition of (i) treatment of maternal anxiety disorders, or (ii) treatment focused on maternal responses. The incremental cost-effectiveness of the additional treatments was also evaluated. DESIGN: Participants were randomised to receive (i) child cognitive-behavioural therapy (CCBT); (ii) CCBT with CBT to target maternal anxiety disorders [CCBT + maternal cognitive-behavioural therapy (MCBT)]; or (iii) CCBT with an intervention to target mother-child interactions (MCIs) (CCBT + MCI). SETTING: A NHS university clinic in Berkshire, UK. PARTICIPANTS: Two hundred and eleven children with a primary anxiety disorder, whose mothers also had an anxiety disorder. INTERVENTIONS: All families received eight sessions of individual CCBT. Mothers in the CCBT + MCBT arm also received eight sessions of CBT targeting their own anxiety disorders. Mothers in the MCI arm received 10 sessions targeting maternal parenting cognitions and behaviours. Non-specific interventions were delivered to balance groups for therapist contact. MAIN OUTCOME MEASURES: Primary clinical outcomes were the child's primary anxiety disorder status and degree of improvement at the end of treatment. Follow-up assessments were conducted at 6 and 12 months. Outcomes in the economic analyses were identified and measured using estimated quality-adjusted life-years (QALYs). QALYS were combined with treatment, health and social care costs and presented within an incremental cost-utility analysis framework with associated uncertainty. RESULTS: MCBT was associated with significant short-term improvement in maternal anxiety; however, after children had received CCBT, group differences were no longer apparent. CCBT + MCI was associated with a reduction in maternal overinvolvement and more confident expectations of the child. However, neither CCBT + MCBT nor CCBT + MCI conferred a significant post-treatment benefit over CCBT in terms of child anxiety disorder diagnoses [adjusted risk ratio (RR) 1.18, 95% confidence interval (CI) 0.87 to 1.62, p = 0.29; adjusted RR CCBT + MCI vs. control: adjusted RR 1.22, 95% CI 0.90 to 1.67, p = 0.20, respectively] or global improvement ratings (adjusted RR 1.25, 95% CI 1.00 to 1.59, p = 0.05; adjusted RR 1.20, 95% CI 0.95 to 1.53, p = 0.13). CCBT + MCI outperformed CCBT on some secondary outcome measures. Furthermore, primary economic analyses suggested that, at commonly accepted thresholds of cost-effectiveness, the probability that CCBT + MCI will be cost-effective in comparison with CCBT (plus non-specific interventions) is about 75%. CONCLUSIONS: Good outcomes were achieved for children and their mothers across treatment conditions. There was no evidence of a benefit to child outcome of supplementing CCBT with either intervention focusing on maternal anxiety disorder or maternal cognitions and behaviours. However, supplementing CCBT with treatment that targeted maternal cognitions and behaviours represented a cost-effective use of resources, although the high percentage of missing data on some economic variables is a shortcoming. Future work should consider whether or not effects of the adjunct interventions are enhanced in particular contexts. The economic findings highlight the utility of considering the use of a broad range of services when evaluating interventions with this client group. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19762288. FUNDING: This trial was funded by the Medical Research Council (MRC) and Berkshire Healthcare Foundation Trust and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership (09/800/17) and will be published in full in Health Technology Assessment; Vol. 19, No. 38.

Successful manipulation of the quality and quantity of fat and carbohydrate consumed by free-living individuals using a food exchange model.

Our objective in this study was to develop and implement an effective intervention strategy to manipulate the amount and composition of dietary fat and carbohydrate (CHO) in free-living individuals in the RISCK study. The study was a randomized, controlled dietary intervention study that was conducted in 720 participants identified as higher risk for or with metabolic syndrome. All followed a 4-wk run-in reference diet [high saturated fatty acids (SF)/high glycemic index (GI)]. Volunteers were randomized to continue this diet for a further 24 wk or to 1 of 4 isoenergetic prescriptions [high monounsaturated fatty acids (MUFA)/high GI; high MUFA/low GI; low fat (LF)/high GI; and LF/low GI]. We developed a food exchange model to implement each diet. Dietary records and plasma phospholipid fatty acids were used to assess the effectiveness of the intervention strategy. Reported fat intake from the LF diets was significantly reduced to 28% of energy (%E) compared with 38%E from the HM and LF diets. SF intake was successfully decreased in the HM and LF diets to < or =10%E compared with 17%E in the reference diet (P = 0.001). Dietary MUFA in the HM diets was approximately 17%E, significantly higher than in the reference (12%E) and LF diets (10%E) (P = 0.001). Changes in plasma phospholipid fatty acids provided further evidence for the successful manipulation of fat intake. The GI of the HGI and LGI arms differed by approximately 9 points (P = 0.001). The food exchange model provided an effective dietary strategy for the design and implementation across multiple sites of 5 experimental diets with specific targets for the proportion of fat and CHO.

Nutrigenetics and CVD: what does the future hold?

CVD is a common killer in both the Western world and the developing world. It is a multifactorial disease that is influenced by many environmental and genetic factors. Although public health advice to date has been principally in the form of prescribed population-based recommendations, this approach has been surprisingly unsuccessful in reducing CVD risk. This outcome may be explained, in part, by the extreme variability in response to dietary manipulations between individuals and interactions between diet and an individual's genetic background, which are defined by the term 'nutrigenetics'. The shift towards personalised nutritional advice is a very attractive proposition. In principle an individual could be genotyped and given dietary advice specifically tailored to their genetic make-up. Evidence-based research into interactions between fixed genetic variants, nutrient intake and biomarkers of CVD risk is increasing, but still limited. The present paper will review the evidence for interactions between dietary fat and three common polymorphisms in the apoE, apoAI and PPARgamma genes. Increased knowledge of how these and other genes influence dietary response should increase the understanding of personalised nutrition. While targeted dietary advice may have considerable potential for reducing CVD risk, the ethical issues associated with its routine use need careful consideration.

Effect of multiple micronutrient supplementation during pregnancy on inflammatory markers in Nepalese women.

BACKGROUND: Multiple micronutrient supplementation of Nepalese women during pregnancy is associated with a significant increase in birth weight. OBJECTIVE: We tested the hypothesis that improved birth weight in infants of mothers supplemented with micronutrients is associated with a decrease in inflammatory responses and an increase in the production of T helper 1 cells and T helper 2 cells. DESIGN: The study was embedded in a randomized controlled trial of 15 micronutrients, compared with iron-folate supplementation (control), given during pregnancy with the aim of increasing birth weight. Blood samples were collected at 32 wk of gestation, 12-20 wk after supplementation began, for the measurement of inflammatory markers. Breast-milk samples were collected 1 mo after delivery for the measurement of the ratio of milk sodium to potassium (milk Na:K). In an opportunistically selected subgroup of 70 women, mitogen-stimulated cytokine production was measured ex vivo in whole blood. RESULTS: Blood eosinophils; plasma concentrations of the acute phase reactants C-reactive protein, alpha(1)-acid glycoprotein (AGP), neopterin, and ferritin; milk Na:K; and the production of interleukin (IL) 10, IL-4, interferon gamma, and tumor necrosis factor alpha in whole blood did not differ significantly between the supplemented and control groups. Plasma C-reactive protein and AGP were higher in women who had a preterm delivery, and AGP was higher in women who delivered a low-birth-weight term infant than in women who delivered a normal-birth-weight term infant. CONCLUSIONS: The results indicate an association between systemic inflammation in late pregnancy and compromised delivery outcome in Nepalese women but do not support the hypothesis that multiple micronutrient supplementation changes cytokine production or inflammatory markers.

Risk factors for subclinical mastitis among HIV-infected and uninfected women in Lusaka, Zambia.

Subclinical mastitis, defined as raised milk sodium/potassium (Na/K) ratio, is associated with poor infant growth and, among HIV-infected women, with increased milk HIV viral load. We conducted a longitudinal cohort study in Lusaka, Zambia, in order to investigate the relative importance of several potential causes of subclinical mastitis: maternal infection, micronutrient deficiencies and poor lactation practice. Women (198 HIV-infected, 189 HIV-uninfected) were recruited at 34 weeks' gestation and followed up to 16 weeks postpartum for collection of information on their health, their infant's health, infant growth and infant feeding practices. Milk samples were collected from each breast at 11 postpartum visits and blood at recruitment and 6 weeks postpartum. The geometric mean milk Na/K ratio and the proportion of women with Na/K ratio > 1.0 in one or both breasts were significantly higher among HIV-infected than among uninfected women. Other factors associated with the higher mean Na/K ratio in univariable analyses were primiparity, high maternal alpha(1)-acid glycoprotein (AGP) at 6 weeks, maternal overall morbidity and specific breast symptoms, preterm delivery, low infant weight or length, infant thrush and non-exclusive breast feeding. In multivariable analyses, primiparity, preterm delivery, breast symptoms, HIV status and raised AGP were associated with the raised Na/K ratio. Thus the main factors associated with subclinical mastitis that are amenable to intervention are poor maternal overall health and breast health. The impact of improved postpartum health care, especially management of maternal infections and especially in primiparous women, on the prevalence of subclinical mastitis and its consequences requires investigation.