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.

Effects of exchanging carbohydrate or monounsaturated fat with saturated fat on inflammatory and thrombogenic responses in subjects with abdominal obesity: A randomized controlled trial.

BACKGROUND & AIMS: Modification of the amount and type of dietary fat has diverse effects on cardiovascular risk. METHODS: We recruited 54 abdominally obese subjects to participate in a prospective cross-over design, single-blind trial comparing isocaloric 2000 kcal MUFA or carbohydrate-enriched diet with SFA-enriched diet (control). The control diet consisted of 15E% protein, 53E% carbohydrate and 32E% fat (12E% SFA, 13E% MUFA). A total of ∼7E% of MUFA or refined carbohydrate was exchanged with SFA in the MUFA-rich and carbohydrate-rich diets respectively for 6-weeks. Blood samples were collected at fasting upon trial commencement and at week-5 and 6 of each dietary-intervention phase to measure levels of cytokines (IL-6, IL-1ß), C-reactive protein (CRP), thrombogenic markers (E-selectin, PAI-1, D-dimer) and lipid subfractions. Radial pulse wave analysis and a 6-h postprandial mixed meal challenge were carried out at week-6 of each dietary intervention. Blood samples were collected at fasting, 15 and 30 min and hourly intervals thereafter till 6 h after a mixed meal challenge (muffin and milkshake) with SFA or MUFA (872.5 kcal, 50 g fat, 88 g carbohydrates) or CARB (881.3 kcal, 20 g fat, 158 g carbohydrates)- enrichment corresponding to the background diets. RESULTS: No significant differences in fasting inflammatory and thrombogenic factors were noted between diets (P > 0.05). CARB meal was found to increase plasma IL-6 whereas MUFA meal elevated plasma D-dimer postprandially compared with SAFA meal (P < 0.05). Comparing the 3 meals, there were similar postprandial elevations in IL-6 and D-dimer and postprandial reductions in PAI-1, augmentation index and pressure (time effect: P < 0.05). CARB diet was found to reduce HDL3 by 7.8% and increase small dense HDL (sdHDL) by 8.6% compared with SFA diet (P < 0.05). SFA diet increased large HDL subfractions compared with both CARB and MUFA diets by 4.9% and 6.6% (P < 0.05), respectively. CONCLUSIONS: Overall, the evidence presented in this study suggests that the replacement of SFA with MUFA or refined carbohydrates may not improve inflammatory and thrombogenic markers in abdominally overweight individuals. Indeed increased refined carbohydrates consumption adversely impacts fasting HDL subfractions. This trial was registered under ClinicalTrials.gov. Identifier no. NCT01665482.

Ethnic differences in beta-cell function, dietary intake and expression of the metabolic syndrome among UK adults of South Asian, black African-Caribbean and white-European origin at high risk of metabolic syndrome.

A cross-sectional analysis of ethnic differences in dietary intake, insulin sensitivity and beta-cell function, using the intravenous glucose tolerance test (IVGTT), was conducted on 497 healthy adult participants of the 'Reading, Imperial, Surrey, Cambridge, and Kings' (RISCK) study. Insulin sensitivity (Si) was significantly lower in African-Caribbean (AC) and South Asian (SA) participants [IVGTT-Si; AC: 2.13 vs SA: 2.25 vs white-European (WE): 2.84 (×10(-4) mL µU min)(2), p < 0.001]. AC participants had a higher prevalence of anti-hypertensive therapy (AC: 19.7% vs SA: 7.5%), the most cardioprotective lipid profile [total:high-density lipoprotein (HDL); AC: 3.52 vs SA: 4.08 vs WE: 3.83, p = 0.03] and more pronounced hyperinsulinaemia [IVGTT-acute insulin response (AIR)] [AC: 575 vs SA: 428 vs WE: 344 mL/µU/min)(2), p = 0.002], specifically in female participants. Intake of saturated fat and carbohydrate was lower and higher in AC (10.9% and 50.4%) and SA (11.1% and 52.3%), respectively, compared to WE (13.6% and 43.8%, p < 0.001). Insulin resistance in ACs is characterised by 'normal' lipid profiles but high rates of hypertension and pronounced hyperinsulinaemia.

Application of the BRAFO tiered approach for benefit-risk assessment to case studies on dietary interventions.

The respective examples, described in this paper, illustrate how the BRAFO-tiered approach, on benefit-risk assessment, can be tested on a wide range of case studies. Various results were provided, ranging from a quick stop as the result of non-genuine benefit-risk questions to continuation through the tiers into deterministic/probabilistic calculations. The paper illustrates the assessment of benefits and risks associated with dietary interventions. The BRAFO tiered approach is tested with five case studies. In each instance, the benefit-risk approach is tested on the basis of existing evaluations for the individual effects done by others; no new risk or benefit evaluations were made. The following case studies were thoroughly analysed: an example of food fortification, folic acid fortification of flour, macronutrient replacement/food substitution; the isocaloric replacement of saturated fatty acids with carbohydrates; the replacement of saturated fatty acids with monounsaturated fatty acids; the replacement of sugar-sweetened beverages containing mono- and disaccharides with low calorie sweeteners and an example of addition of specific ingredients to food: chlorination of drinking water.

UK Food Standards Agency Workshop Report: carbohydrate and cardiovascular risk.

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 14 October 2008 to discuss current FSA-funded research on carbohydrates and cardiovascular health. The objective of this workshop was to discuss the results of recent research and to identify any areas which could inform future FSA research calls. This workshop highlighted that the FSA is currently funding some of the largest, well-powered intervention trials investigating the type of fat and carbohydrate, whole grains and fruit and vegetables, on various CVD risk factors. Results of these trials will make a substantive contribution to the evidence on diet and cardiovascular risk.

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.

A prospective study of micronutrient status in adolescent pregnancy.

BACKGROUND: Adolescents are more likely than adults to consume energy-dense, micronutrient-poor diets and to experience adverse pregnancy outcomes. OBJECTIVES: The objectives were to assess micronutrient intake and blood biomarkers prospectively in pregnant adolescents recruited to the About Teenage Eating (ATE) Study and to determine associations with pregnancy outcome. DESIGN: Pregnant adolescents (n = 500) were recruited from 2 UK inner city populations. Dietary intake was assessed with three 24-h dietary recalls, and micronutrient status was assessed by measurement of third trimester blood biomarkers. Pregnancy outcomes included small-for-gestational age (SGA) birth and preterm delivery. RESULTS: Median iron and folate intakes were lower than UK and US recommended amounts. Folate and vitamin B-12 status were lower in smokers, despite no differences in dietary intake. Serum folate was <7.0 nmol/L in 12% of subjects, and serum total homocysteine (tHcy) was elevated (>10 micromol/L) in 20% of subjects. Fifty-two percent of the subjects had iron deficiency anemia, and 30% had serum 25-hydroxyvitamin D concentrations <25 nmol/L. The incidence of SGA birth was higher in subjects with poorer folate status (red blood cell folate, P = 0.003; serum folate, P = 0.02; tHcy, P = 0.01; simple regression) and those with low folate intakes, regardless of the inclusion (P = 0.021) or exclusion (P = 0.049) of intake from supplements (simple regression). Adjustment for confounding variables confirmed the independence of these associations. The risk of SGA birth was also higher in subjects with low food iron intake (P = 0.049), but not when intake included iron from supplements (P = 0.21). The risk of SGA birth was lower in subjects with iron deficiency anemia (P = 0.002). CONCLUSION: Poor micronutrient intake and status increase the risk of SGA births in pregnant adolescents.

UK Food Standards Agency Workshop Report: the effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health.

This report summarises a workshop convened by the UK Food Standards Agency (FSA) on 11 September 2006 to review the results of three FSA-funded studies and other recent research on effects of the dietary n-6:n-3 fatty acid ratio on cardiovascular health. The objective of this workshop was to reach a clear conclusion on whether or not it was worth funding any further research in this area. On the basis of this review of the experimental evidence and on theoretical grounds, it was concluded that the n-6:n-3 fatty acid ratio is not a useful concept and that it distracts attention away from increasing absolute intakes of long-chain n-3 fatty acids which have been shown to have beneficial effects on cardiovascular health. Other markers of fatty acid intake, that more closely relate to physiological function, may be more useful.

Effect of vitamin B12 treatment on haptocorrin.

BACKGROUND: Haptocorrin (HC) carries the major part of circulating cobalamin, but whether HC is altered on treatment with vitamin B12 remains unknown. METHODS: Our study included 3 populations: a population of vegan men (n = 174; vegan population), of whom 63 were treated daily with 5 mg of oral vitamin B12 for 3 months; a group of patients with a previous methylmalonic acid (MMA) concentration >0.4 micromol/L (n = 140; population with suspected deficiency), of which 69 were treated with weekly vitamin B12 injections (1 mg) for 4 weeks; and a subgroup of participants in a vitamin B intervention study (n = 88; nondeficient population), of whom 45 were treated daily with 0.4 mg of oral vitamin B12 for 3 months. Total HC and holoHC were measured by ELISA. Cobalamin was measured by an intrinsic factor (IF)-based assay. Samples were collected at baseline and 3 months after start of treatment. RESULTS: Compared with baseline results for the 3 study populations, total HC and holoHC increased 30 pmol/L for every 100 pmol/L increase in cobalamin. After treatment with vitamin B12, holoHC (P <0.0001) and total HC (P <0.0001) increased significantly in the vegan population. Only holoHC increased in the population with suspected deficiency (P <0.0001), whereas no alteration was observed in the nondeficient population. CONCLUSIONS: The HC concentration is decreased in severely cobalamin-deficient individuals and increases on treatment. The concentration of cobalamin also relates significantly to the HC concentration in nondeficient individuals.

Comparison of efficacy of plant stanol ester and sterol ester: short-term and longer-term studies.

Published data suggest that the cholesterol-lowering effect of dietary plant sterol esters is less marked in longer-term than in short-term studies, whereas plant stanol esters maintain their efficacy. To investigate this further, healthy subjects and patients with familial hypercholesterolemia (FH) receiving statins were randomized to receive plant sterol ester 1.6 g/day or plant stanol ester 1.6 g/day or 2.6 g/day for 2 months. There was no difference among the 3 groups in the pooled low-density lipoprotein (LDL)-lowering response of FH patients and healthy subjects, but the effect of plant sterol diminished at 2 months and was not significantly different from baseline. This was accompanied by increases in serum plant sterols and a significant decrease in 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, especially in FH patients not taking bile acid sequestrants. In contrast, plant stanol esters lowered significantly both LDL cholesterol and plant sterols at 2 months and had no effect on bile acid synthesis. Slight decreases in serum lipid-soluble antioxidants occurred with both plant sterol and stanol esters. Our findings suggest that absorption of dietary plant sterols downregulates bile acid synthesis, which attenuates their cholesterol-lowering efficacy. We conclude that plant stanol esters are preferable for the long-term management of hypercholesterolemia.

Dietary fat and postprandial lipids.

Impaired clearance of chylomicron remnants is associated with increased risk of atherosclerosis and cardiovascular disease. An intake of 40 to 50 g of fat in a meal results in significant lipemia in healthy adults, with consecutive fat-containing meals enhancing the lipemia. This would suggest that limiting fat intake to approximately 30 g on each eating occasion would minimize postprandial lipemia. Sedentary behavior and obesity independently impair the postprandial metabolism of lipids. Postprandial lipemia causes endothelial dysfunction and results in a transient increase in factor VII activated (FVIIa) concentration. Plasminogen activator inhibitor type-1 activity is associated with fasting plasma triacylglycerol concentration, but is not influenced by postprandial lipemia. Trans-18:1 acid appears to increase cholesterol ester transfer activity acutely compared with oleate. Randomized stearic acid-rich fats result in less postprandial lipemia and a lower postprandial increase in FVIIa, whereas unrandomized cocoa butter results in similar postprandial lipemia and increases in FVIIa compared with oleate. A background diet containing in excess of 3 g/d of long-chain omega-3 fatty acids decreases postprandial lipemia by stimulating lipoprotein lipase expression and decreasing very low-density lipoprotein synthesis, but a diet enriched in alpha-linolenic acid (up to 9.5 g/d) does not show these effects. Future research on diet and postprandial lipids needs to exploit newly gained knowledge on the regulation of adipocyte metabolism by adipokines and nuclear hormone receptors, particularly with regard to fat patterning and reverse cholesterol transport.

High- versus low-fat diets in human diseases.

PURPOSE OF REVIEW: To evaluate the evidence with regard to high-versus low-fat diets in the context of the prevention and management of obesity, type 2 diabetes and coronary heart disease. RECENT FINDINGS: Despite the increasing prevalence of obesity, there is no evidence to support the view that this is caused by an increased intake of fat. Fat sensors play an important role in regulating energy balance and lipid metabolism, and hypoenergetic diets containing 30-35% energy from fat promote weight loss. High intakes of carbohydrates with a high glycaemic index can result in insulin resistance, but this effect can be modulated by increased physical activity. SUMMARY: Although arguments to decrease the intake of trans and saturated fatty acids are cogent, the scientific basis for a reduction in the proportion of energy from fat below 30% energy is not supported by experimental evidence. A modest reduction in fat intake to 30-35% energy, with the bulk of carbohydrates being derived from complex carbohydrates from unrefined sources, would appear to be the best option for the prevention of obesity and cardiovascular disease. Increased physical activity appears to be particularly important in modulating the adverse effects associated with high-carbohydrate low-fat diets.