Fatty acid composition of cholesterol esters reflects dietary fat intake after dietary interventions in a multinational population.

BACKGROUND: The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake. PURPOSE: To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters. METHODS: In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements. RESULTS: Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001). CONCLUSIONS: This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.

Maximizing cardiovascular benefits of fish consumption within the One Health approach: Should current recommendations be revised?

AIMS: Current dietary recommendations on fish consumption for cardiovascular disease (CVD) prevention put somewhat vague emphasis on fatty fish, mainly driven by evidence on the cardioprotective effects of n-3 PUFAs. Recent data on the consumption of different types of fish in relation to hard cardiovascular endpoints suggests that fatty but not lean fish can contribute to CVD prevention. This considered, we aimed at evaluating, by an environmental perspective, fish consumption limited to the fatty type - in appropriate amounts for optimizing CVD prevention - within the European context. DATA SYNTHESIS: Starting from the current average intake of total fish by the European population (i.e., 2 servings/week of fatty plus lean fish), we show that the shift towards the consumption of 2 servings/week of solely fatty fish - appropriate for optimizing CVD prevention - would allow a 32% saving of greenhouse gas (GHG) emissions related to fish consumption. This is due to the lower environmental impact of fatty fish globally considered, compared to lean fish. However, since the carbon footprint of different fatty fish species can vary significantly - with small blue fish (e.g., anchovies, sardines, herrings) in the lowest range, we estimated that GHG emissions due to fish consumption in Europe could be reduced by 82% by focusing on small blue fish consumption. CONCLUSIONS: Consumption of 2 servings/week of small blue fish could represent a feasible and effective choice among the functional dietary strategies available to achieve the maximal benefits for human and environmental health.

Recent Trends in Dietary Habits of the Italian Population: Potential Impact on Health and the Environment.

Population growth, globalization, urbanization, and economic pressures are causing changes in food consumption all over the world. The study's aims are (1) to evaluate trends in food habits in Italy to highlight deviations from the traditional Mediterranean diet, (2) to analyze the features of the present Italian diet that should be modified to meet evidence-based global scientific targets for a healthy and sustainable diet proposed by the EAT-Lancet Commission. Trends in food availability for human consumption during the period 2000-2017 were assessed using the food balance sheets (FBSs). Greenhouse gas (GHG) emission was estimated according to life cycle assessment (LCA) analyses. During the study period, the availability of animal fat and beef meat greatly declined (-58% and -32%, respectively), followed by fruit, potatoes, vegetables, milk, and non-tropical oils (-20%, -15%, -13%, -14%, and -11%, respectively). A substantial increase has occurred for tropical oils, fish, and nuts (+156, +26%, and +21%, respectively). In order to meet the targets of consumption proposed by the EAT-Lancet Commission, the consumption of legumes and nuts should be almost doubled, whereas the consumption of meat, eggs, dairy products, animal fat, tropical oils, and sugars should be reduced by proportions ranging from 60% to 90%. If implemented, these changes would reduce the diet-related greenhouse gas emission by nearly 50%. In conclusion, these data call for nutritional education programs and interventions on the food system aimed at promoting a healthier and more environmentally sustainable diet. To this end, the availability and affordability of products with a better impact on human health and the environment should be promoted.

Dietary Fibre Consensus from the International Carbohydrate Quality Consortium (ICQC).

Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.

Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals.

AIMS: Gut microbiota significantly impacts human health and is influenced by dietary changes. We evaluated the effects of diets naturally rich in polyphenols (PP) and/or long-chain n-3 polyunsaturated fatty acids (LCn3) on microbiota composition in an ancillary analysis of a randomized controlled trial in individuals at high cardiometabolic risk. METHODS: Seventy-eight individuals with high waist circumference and at least one additional component of the metabolic syndrome were randomized to an isoenergetic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; or (d) high LCn3 and PP. Microbiota analysis was performed on feces collected before and after the intervention. DGGE analysis of the predominant bacteria, Eubacterium rectale and Blautia coccoides group (Lachnospiraceae, EREC), Clostridium leptum (Ruminococcaceae, CLEPT), Bacteroides spp., Bifidobacteria, and Lactobacillus group was performed. A quantitative real-time PCR was performed for the same group, additionally including Atopobium cluster (Coriobatteriaceae). Before and after the intervention, participants underwent a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid response. RESULTS: Adherence to the four diets was optimal. PP significantly increased microbial diversity (p = 0.006) and CLEPT (p = 0.015), while it reduced EREC (p = 0.044). LCn3 significantly increased the numbers of Bifidobacteria (p = 0.041). Changes in CLEPT numbers correlated with changes in early insulin secretion (r = 0.263, p = 0.030). Changes in Atopobium numbers correlated with postprandial triglycerides in plasma (r = 0.266, p = 0.026) and large VLDL (r = 0.313, p = 0.009), and cholesterol in large VLDL (r = 0.319, p = 0.008). CONCLUSIONS: Diets naturally rich in PP or LCn3 influenced gut microbiota composition in individuals at high cardiometabolic risk. These modifications were associated with changes in glucose/lipid metabolism.

Quality of Life in Women Diagnosed with Breast Cancer after a 12-Month Treatment of Lifestyle Modifications.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p < 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p < 0.001), body image (p < 0.001), future perspective (p < 0.001), well-being (p = 0.001), and reductions in fatigue (p < 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p < 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

Adherence to the traditional Mediterranean diet in a population of South of Italy: factors involved and proposal of an educational field-based survey tool.

We developed and validated a tool assessing the adherence to the Mediterranean diet based on current nutritional recommendations for health promotion (MEDI-Quest). Four-hundred-and-eleven clinically healthy subjects completed both the MEDI-Quest-score and the validated MedDietScore (MDS). A good accordance between MEDI-Quest and MDS was observed (R = 0.638), as well as for the percentage of individuals having similar scores with both methods for each food group. Regarding socio-cultural-factors, higher adherence was observed in people with older-age (OR = 1.030, p < .0001), more qualifier-employment (OR = 1.136, p < .005), higher-income (OR = 1.925, p < .0001), interest in reading-food-labels (OR = 2.057, p < .0001), and having frequent physical activity (OR = 1.608, p < .05). In conclusion, our findings show that (1) the MEDI-Quest score well correlate with MDS, and (2) the adherence to the Mediterranean diet is not particularly high due to less cultural roots. It could be necessary to improve people's knowledge about food and nutrition, taking into consideration believes embedded in their family, tradition and religion.

A nutritional intervention programme at a worksite canteen to promote a healthful lifestyle inspired by the traditional Mediterranean diet.

This study investigates the effectiveness and long-term impact on the composition of the habitual diet of a nutritional intervention programme - undertaken through panels, totems, and table mats or handout leaflets - based on the promotion at a worksite canteen of healthy food-choices resembling the traditional Mediterranean diet. A significantly higher choice of dishes based on wholegrain cereals, legumes, white meat and fish, and a lower choice of dishes based on refined cereals, red and processed meat, eggs and cheese was observed at the end of the intervention and after six months and three years of follow-ups. A significantly better adherence to the nutritional recommendations for saturated-fat, cholesterol, sugars and fibre was observed. This study reveals that a nutritional intervention programme promoting the traditional Mediterranean diet and utilising a minimally intensive approach is feasible and effective to modify in a beneficial way the dietary habits of a working population and keep these changes in the long-term.

Low glycemic index diet, exercise and vitamin D to reduce breast cancer recurrence (DEDiCa): design of a clinical trial.

BACKGROUND: Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. METHODS: Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. DISCUSSION: DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. TRIAL REGISTRATION: May 11, 2016; NCT02786875 . EUDRACT NUMBER: 2015-005147-14.

Polyphenol-rich diets improve glucose metabolism in people at high cardiometabolic risk: a controlled randomised intervention trial.

AIM/HYPOTHESIS: Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3) are associated with lower cardiovascular risk. This may relate to their influence on glucose metabolism and diabetes risk. We evaluated the effects of diets naturally rich in polyphenols and/or LCn3 of marine origin on glucose metabolism in people at high cardiometabolic risk. METHODS: According to a 2 × 2 factorial design, individuals with high waist circumference and at least one more component of the metabolic syndrome were recruited at the obesity outpatient clinic. Eighty-six participants were randomly assigned by MINIM software to an isoenergetic diet: (1) control, low in LCn3 and polyphenol (analysed n = 20); (2) rich in LCn3 (n = 19); (3) rich in polyphenols (n = 19); or (4) rich in LCn3 and polyphenols (n = 19). The assigned diets were known for the participants and blinded for people doing measurements. Before and after the 8 week intervention, participants underwent a 3 h OGTT and a test meal with a similar composition as the assigned diet for the evaluation of plasma glucose, insulin and glucagon-like peptide 1 (GLP-1) concentrations, and indices of insulin sensitivity and beta cell function. RESULTS: During OGTT, polyphenols significantly reduced plasma glucose total AUC (p = 0.038) and increased early insulin secretion (p = 0.048), while LCn3 significantly reduced beta cell function (p = 0.031) (two-factor ANOVA). Moreover, polyphenols improved post-challenge oral glucose insulin sensitivity (OGIS; p = 0.05 vs control diet by post hoc ANOVA). At test meal, LCn3 significantly reduced GLP-1 total postprandial AUC (p < 0.001; two-factor ANOVA). CONCLUSION/INTERPRETATION: Diets naturally rich in polyphenols reduce blood glucose response, likely by increasing early insulin secretion and insulin sensitivity. These effects may favourably influence diabetes and cardiovascular risk. The implications of the decrease in insulin secretion and postprandial GLP-1 observed with diets rich in marine LCn3 need further clarification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01154478. FUNDING: The trial was funded by European Community's Seventh Framework Programme FP7/2009-2012 under grant agreement FP7-KBBE-222639, Etherpaths Project and 'Ministero Istruzione Università e Ricerca' PRIN 2010-2011 - 2010JCWWKM.

Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial.

BACKGROUND: The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk. OBJECTIVE: This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress. DESIGN: According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured. RESULTS: Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane. CONCLUSIONS: Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.

Lipoprotein subfractions and dietary intake of n-3 fatty acid: the Genetics of Coronary Artery Disease in Alaska Natives study.

BACKGROUND: Few studies have compared lipoprotein composition with dietary intake. OBJECTIVE: The lipoprotein subfraction profile was evaluated in relation to diet in Alaska Eskimos at high cardiovascular risk but with a low frequency of hyperlipidemia and high intake of n-3 (omega-3) fatty acids. DESIGN: A population-based sample (n = 1214) from the Norton Sound Region of Alaska underwent a physical examination and blood sampling. Analyses were from 977 individuals who did not have diabetes or use lipid-lowering medications and had complete dietary information (food-frequency questionnaire) and a lipoprotein subfraction profile (nuclear magnetic resonance spectroscopy). RESULTS: After adjustment for age, BMI, total energy intake, and percentage of energy from fat, the intake of n-3 fatty acids was significantly associated with fewer large VLDLs (P = 0.022 in women, P = 0.064 in men), a smaller VLDL size (P = 0.018 and P = 0.036), more large HDLs (P = 0.179 and P = 0.021), and a larger HDL size (P = 0.004 and P = 0.001). After adjustment for carbohydrate and sugar intakes, large VLDLs (P = 0.042 and 0.018) and VLDL size (P = 0.011 and 0.025) remained negatively associated with n-3 fatty acid intake in women and men, and large HDLs (P = 0.067 and 0.005) and HDL size (P = 0.001 in both) remained positively associated with n-3 fatty acid intake in women and men. In addition, large LDLs (P = 0.040 and P = 0.025) were positively associated in both sexes, and LDL size (P = 0.006) showed a positive association in women. There were no significant relations with total LDL particles in either model. CONCLUSIONS: Dietary n-3 fatty acids, independent of the reciprocal changes in carbohydrate and sugar intakes, are associated with an overall favorable lipoprotein profile in terms of cardiovascular risk. Because there are no relations with total LDL particles, the benefit may be related to cardiovascular processes other than atherosclerosis.

Effects of baked products enriched with n-3 fatty acids, folates, ß-glucans, and tocopherol in patients with mild mixed hyperlipidemia.

OBJECTIVE: To assess whether a diet containing foods enriched with ß-glucans (3.6 g/d), folic acid (1600 µg/d), long-chain (800 mg/d) and short-chain (400 mg/d) n-3 fatty acids, and tocopherols (120 mg/d) is able to modulate positively the cardiovascular risk profile in people at slightly increased cardiovascular risk. METHODS: Sixteen subjects with mild plasma lipid abnormalities were studied according to a randomized crossover design. After a 2-week run-in period, they followed a diet containing baked products enriched with active nutrients (active diet) or a diet containing the same products but without active nutrients (control diet) for 1 month and then crossed over to the other diet. At the end of each period, a test meal of the same composition as the corresponding diet was administered, and plasma samples were obtained before and for 6 hours after the meal. Hunger and satiety were evaluated by the visual analog scale at fasting and after the meal. RESULTS: Fasting plasma triglycerides were significantly lower after the active versus the control diet (1.56 ± 0.18 vs 1.74 ± 0.16 mmol/l, p < 0.05), as was the postprandial level of chylomicron triglycerides and the insulin peak (p < 0.05). The active diet also reduced fasting homocysteine (8 ± 0.6 vs 10 ± 0.8 µmol/l, p < 0.05) and the feeling of hunger at the fifth and sixth hour (p < 0.05). CONCLUSIONS: Baked functional products enriched with n-3 fatty acids, folates, ß-glucans, and tocopherols within the context of a balanced diet lower fasting and postprandial plasma triglycerides, fasting homocysteinemia, and the postprandial insulin peak. They induce a greater feeling of satiety with possible beneficial implications on energy intake.

ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).

Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies' Task forces on CVD prevention in clinical practice.2 ­ 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat.

Non-pharmacological control of plasma cholesterol levels.

The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study.

BACKGROUND AND AIMS: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. METHODS AND RESULTS: Altogether 151 healthy subjects (age 49+/-8 years, BMI 26.5+/-3.0kg/m(2)) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration (P=0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes (P=0.007 among three genotypes). The rare -250A allele was related to low HL activity (P<0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. CONCLUSION: The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.

Fish oil, insulin sensitivity, insulin secretion and glucose tolerance in healthy people: is there any effect of fish oil supplementation in relation to the type of background diet and habitual dietary intake of n-6 and n-3 fatty acids?

AIM: To evaluate whether a moderate supplementation of long-chain n-3 fatty acids is able to modulate insulin sensitivity, insulin secretion, beta-cell function and glucose tolerance in healthy individuals consuming a diet rich in either saturated or monounsaturated fat, also in relation to their habitual dietary intake of n-6 and n-3 fatty acid. METHODS AND RESULTS: One hundred and sixty-two healthy individuals were randomly assigned to follow either one of two isoenergetic diets for 3 months, one rich in monounsaturated fats and the other rich in saturated fats. Within each group there was a second randomisation to fish oil (n-3 fatty acids 3.6 g/day) or placebo. At the beginning and at the end of the treatment periods insulin sensitivity (SI), first phase insulin response (FPIR) and glucose tolerance (K(G)-value) were evaluated by the intravenous glucose tolerance test (IVGTT). Fish oil did not have any effect on SI, FPIR, K(G)-value and disposition index in either diet. Even after dividing subjects according to the median value of n-6/n-3 ratio of serum phospholipids at baseline, there was no change in SI (Delta SI 0.42+/-0.34 on fish oil vs 0.14+/-0.23 on placebo for those with n-6/n-3 <4.85; -1.03+/-0.47 on fish oil vs -0.27+/-0.32 on placebo for those with n-6/n-3 >4.85) (M+/-SE), FPIR (Delta FPIR 135.9+/-78.9 vs 157.2+/-157.5 pmol/L; 38.8+/-181.7 vs 357.1+/-181.7 pmol/L), K(G)-value (Delta K(G) 0.14+/-0.15 vs 0.12+/-0.11; -0.32+/-0.16 vs 0.15+/-0.15) or disposition index (Delta disposition index 1465.4+/-830.4 vs 953.8+/-690.0; -1641.6+/-1034.3 vs 446.6+/-905.1). Considering the 75th percentile of n-6/n-3 ratio (5.82) the results on insulin sensitivity, insulin secretion and disposition index were confirmed, while, in this more extreme situation, n-3 fatty acid supplementation induced a significant deterioration of K(G)-value (p=0.02). CONCLUSIONS: In healthy individuals a moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, beta-cell function or glucose tolerance. The same is true even when the habitual dietary intake of n-6 and n-3 fatty acids is taken into account.

Impact of the Pro12Ala polymorphism of the PPAR-gamma2 gene on serum triacylglycerol response to n-3 fatty acid supplementation.

Serum lipid responses to dietary modification are partly determined by genetic factors. The objective of the present study was to investigate the influence of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene on serum lipid and lipoprotein responses to n-3 fatty acid supplementation. A total of 76 men and 74 women (age 49+/-8 years, body mass index 26.5+/-3.0 kg/m(2)) participated in a controlled multi-center study. Subjects were randomly assigned to consume either fish oil supplements (3.6g n-3 fatty acids/day containing 2.4 g of EPA and DHA) or placebo capsules containing olive oil for 3 months. At baseline, the Pro12Ala polymorphism was not associated with serum total and lipoprotein lipid concentrations or lipoprotein lipase activity in the fasting state. After the 3-month study period, carriers of the Ala12 allele presented a greater decrease in serum triacylglycerol concentration in response to n-3 fatty acid supplementation than did subjects with the Pro12Pro genotype when the total dietary fat intake was below 37 E% (p=0.003) or the intake of saturated fatty acids was below 10 E% (p=0.006). Changes in serum total cholesterol, serum LDL cholesterol and HDL cholesterol concentrations were similar among the genotypes in the n-3 fatty acid supplementation group and in the placebo group. In conclusion, the Pro12Ala polymorphism of the PPAR-gamma2 gene may modify the inter-individual variability in serum triacylglycerol response to n-3 fatty acid supplementation.

Effects of dietary saturated, monounsaturated and n-3 fatty acids on fasting lipoproteins, LDL size and post-prandial lipid metabolism in healthy subjects.

BACKGROUND: The influence of the quality of dietary fat on some aspects of lipid metabolism-i.e. lipoprotein concentrations, post-prandial lipids and LDL size-is not completely understood, especially in healthy individuals. OBJECTIVES: Aim of this study was to evaluate the effects of different types of dietary fat (monounsaturated vs. saturated fatty acids, and n-3 or placebo supplementation) on fasting lipoproteins, LDL size and post-prandial lipids in healthy people. DESIGN: One hundred and sixty-two individuals were randomly assigned to follow two isoenergetic diets, one rich in saturated fatty acids (SFA diet) and the other in monounsaturated fatty acids (MUFA diet). Each group was further randomised to receive supplementation with fish oil (3.6 g/day) or placebo. RESULTS: The type of diet significantly affected LDL cholesterol and triacylglycerol content, which was higher with the SFA diet and lower with the MUFA diet. The changes between the two diets were statistically significant for cholesterol (P<0.01) and triacylglycerol (P<0.03). VLDL cholesterol and triacylglycerol were significantly reduced and LDL cholesterol significantly increased by fish oil supplementation. Plasma triacylglycerol was significantly lower in those taking n-3 fatty acids, also 1 and 3 h after a test-meal. Neither type of diet nor n-3 supplementation affected LDL size. CONCLUSIONS: A moderate substitution of saturated fatty acids with monounsaturated fatty acids has beneficial effects on lipid metabolism also in healthy individuals. A moderate supplementation of long-chain n-3 fatty acids in healthy individuals reduces both fasting and post-prandial triacylglycerol concentrations but increases LDL cholesterol, irrespective of the type of diet.