Dietary Fat Restriction Research Articles

Reduced or modified dietary fat for preventing cardiovascular disease.

Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched through to June 2010. References of Included studies and reviews were also checked. Trials fulfilled the following criteria: 1) randomised with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I(2) 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis.Few studies compared reduced with modified fat diets, so direct comparison was not possible. The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

Clinical trial: efficacy of a low or modified fat diet for the prevention of gastrointestinal toxicity in patients receiving radiotherapy treatment for pelvic malignancies

Inflammatory responses to pelvic radiotherapy can result in severe changes to normal gastrointestinal function with potentially severe long-term effects. Reduced or modified fat diets may confer benefit. This randomised controlled trial recruited patients with gynaecological, urological or lower gastrointestinal malignancy due to receive radical radiotherapy. Patients were randomised to a low fat (20% total energy from long chain triglycerides), modified fat (20% from long chain triglycerides and 20% from medium chain triglycerides) or normal fat diet (40% total energy from long chain triglycerides). The primary outcome was a difference in change in Inflammatory Bowel Disease Questionnaire--Bowel (IBDQ-B) score, from the start to end of radiotherapy. A total of 117 patients with pelvic tumours (48% urological; 32% gastrointestinal; 20% gynaecological), with mean (SD) age: 65 (11.0) years, male:female ratio: 79:38, were randomised. The mean (SE) fall in paired IBDQ-B score was -7.3 (0.9) points, indicating a worsening toxicity. Differences between groups were not significant: P = 0.914 (low versus modified fat), P = 0.793 (low versus normal fat) and P = 0.890 (modified versus normal fat). The difference in fat intake between low and normal fat groups was 29.5 g [1109 kJ (265 kcal)] amounting to 11% (of total energy intake) compared to the planned 20% differential. Full compliance with fat prescription was only 9% in the normal fat group compared to 93% in the low fat group. A low or modified fat diet during pelvic radiotherapy did not improve gastrointestinal symptom scores compared to a normal fat intake. An inadequate differential in fat intake between the groups may have confounded the results.

Fatty acids in cardiovascular health and disease: A comprehensive update

Research dating back to the 1950s reported an association between the consumption of saturated fatty acids (SFAs) and risk of coronary heart disease. Recent epidemiological evidence, however, challenges these findings. It is well accepted that the consumption of SFAs increases low-density lipoprotein cholesterol (LDL-C), whereas carbohydrates, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) do not. High-density lipoprotein (HDL)-C increases with SFA intake. Among individuals who are insulin resistant, a low-fat, high-carbohydrate diet typically has an adverse effect on lipid profiles (in addition to decreasing HDL-C, it also increases triglyceride and LDL particle concentrations). Consequently, a moderate fat diet in which unsaturated fatty acids replace SFAs and carbohydrates are not augmented is advised to lower LDL-C; compared with a low-fat diet, a moderate-fat diet will lower triglycerides and increase HDL-C. Now, there is some new evidence that is questioning the health benefits of even MUFAs and PUFAs. In addition, in a few recent studies investigators have also failed to demonstrate expected cardiovascular benefits of marine-derived omega-3 fatty acids. To clarify the clinical pros and cons of dietary fats, the National Lipid Association held a fatty acid symposium at the 2011 National Lipid Association Scientific Sessions. During these sessions, the science regarding the effects of different fatty acid classes on coronary heart disease risk was reviewed.

Gut bacteria profiles of Mus musculus at the phylum and family levels are influenced by saturation of dietary fatty acids

BackgroundMammalian gut microbiota have been implicated in a variety of functions including the breakdown of ingested nutrients, the regulation of energy intake and storage, the control of immune system development and activity, and the synthesis of novel chemicals. Previous studies have shown that feeding mammalian hosts a high-fat diet shifts gut bacteria at the phylum level to reduce the ratio of Bacteroidetes-to-Firmicutes, while feeding hosts a fat-restricted diet increases this ratio. However, few studies have investigated the differential effects of fatty acid type on gut bacterial profile. MethodsOver a 14-week period, Mus musculus were fed a diet rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), omega-6 polyunsaturated fatty acids (n-6 PUFAs), or saturated fatty acids (SFAs). Fecal pellets were collected before and after the treatment period from 12 randomly selected mice (4 per treatment group). Bacterial DNA was extracted from the pellets and characterized by analysis of the hypervariable V3 region of the 16S rRNA. Nominal logistic regression models were used to assess shifts in microbial profile at the phylum and family levels in response to diet. ResultsA significant decrease in the proportion of phylum Bacteroidetes species was observed for mice fed any of the three diets over time. However, the SFA-rich diet group showed a significantly greater decrease in Bacteroidetes proportion (−28%) than did either the n-3 PUFA group (−10%) or the n-6 PUFA group (−12%). At the family level, a significant decrease in proportion of Porphyromonadaceae was observed for mice fed the n-6 PUFA-rich diet, and a significant decrease in proportion of Lachnospiraceae was observed for mice fed the SFA-rich diet. There was no significant effect of diet type on body mass change. ConclusionOur results indicate that SFAs have stronger effects than PUFAs in shifting gut microbiota profiles toward those typical of obese individuals, and that dietary fatty acid saturation influences shifts in gut microbiota independently of changes in body mass.

Fatty acid composition of membrane bilayers: Importance of diet polyunsaturated fat balance

In one of the most extensive analyses to date we show that the balance of diet n−3 and n−6 polyunsaturated fatty acids (PUFA) is the most important determinant of membrane composition in the rat under ‘normal’ conditions. Young adult male Sprague–Dawley rats were fed one of twelve moderate-fat diets (25% of total energy) for 8weeks. Diets differed only in fatty acid (FA) profiles, with saturate (SFA) content ranging 8–88% of total FAs, monounsaturate (MUFA) 6–65%, total PUFA 4–81%, n−6 PUFA 3–70% and n−3 PUFA 1–70%. Diet PUFA included only essential FAs 18:2n−6 and 18:3n−3. Balance between n−3 and n−6 PUFA is defined as the PUFA balance (n−3 PUFA as % of total PUFA) and ranged 1–86% in the diets. FA composition was measured for brain, heart, liver, skeletal muscle, erythrocytes and plasma phospholipids, as well as adipose tissue and plasma triglycerides. The conformer–regulator model was used (slope=1 indicates membrane composition completely conforming to diet). Extensive changes in diet SFA, MUFA and PUFA had minimal effect on membranes (average slopes 0.01, 0.07, 0.07 respectively), but considerable influence on adipose tissue and plasma triglycerides (average slopes 0.27, 0.53, 0.47 respectively). Diet balance between n−3 and n−6 PUFA had a biphasic influence on membrane composition. When n−3 PUFA<10% of total PUFA, membrane composition completely conformed to diet (average slope 0.95), while diet PUFA balance>10% had little influence (average slope 0.19). The modern human diet has an average PUFA balance ~10% and this will likely have significant health implications.

Hepatic and muscular effects of different dietary fat content in VLCAD deficient mice

BackgroundVery long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common long-chain fatty acid oxidation defect presenting with heterogeneous clinical phenotypes. Dietary fat plays a crucial role in disease pathogenesis and fat restriction is a common treatment measure. We here investigate the hepatic and muscular effects of a fat-enriched and a fat-restricted diet. MethodsVLCAD knock-out (KO) and wild-type (WT) mice are subjected to a fat-rich (10.6%), a fat-reduced (2.6%) or a regular mouse diet (5.1%) for 5weeks. Analyses are performed at rest and after one hour exercise on a treadmill. Acylcarnitines in muscle as well as lipid and glycogen content in muscle and liver are quantified. Expression of genes involved in lipogenesis is measured by Real-Time-PCR. ResultsAt rest, VLCAD KO mice develop no clinical phenotype with all three diets, but importantly VLCAD KO mice cannot perform one hour exercise as compared to WT, this is especially apparent in mice with a fat-reduced diet. Moreover, changes in dietary fat content induce a significant increase in muscular long-chain acylcarnitines and hepatic lipid content in VLCAD KO mice after exercise. A fat-reduced diet up-regulates hepatic lipogenesis at rest. At the same time, muscular glycogen is significantly lower than in WT. ConclusionsWe here demonstrate that a fat-reduced and carbohydrate-enriched diet does not prevent the myopathic phenotype in VLCAD KO mice. An increase in dietary fat is safe at rest with respect to the muscle but results in a significant muscular acylcarnitine increase after exercise.

Type 1 Hyperlipoproteinemia and Recurrent Acute Pancreatitis due to Lipoprotein Lipase Antibody in a Young Girl with Sjögren's Syndrome

Type 1 hyperlipoproteinemia (T1HLP) in childhood is most often due to genetic deficiency of lipoprotein lipase (LPL) or other related proteins. The aim was to report a case of marked hypertriglyceridemia and recurrent acute pancreatitis due to the presence of LPL autoantibody in a young girl who was subsequently diagnosed with Sjögren's syndrome. A 9-yr-old African-American girl presented with acute pancreatitis and serum triglycerides of 4784 mg/dl. Strict restriction of dietary fat reduced serum triglycerides, but she continued to experience recurrent pancreatitis. Approximately 18 months thereafter, she developed transient pauciarticular arthritis with elevated serum antinuclear antibody (>1:1280). Minor salivary gland biopsy revealed chronic sialadenitis with a dense periductal lymphocytic aggregate suggestive of Sjögren's syndrome. Genomic DNA was analyzed for LPL, GPIHBP1, APOA5, APOC2, and LMF1. Immunoblotting was performed to detect serum LPL autoantibody. The patient had no disease-causing variants in LPL, GPIHBP1, APOA5, APOC2, or LMF1. Immunoblotting revealed serum LPL antibody. The patient responded to immunosuppressive therapy for Sjögren's syndrome with resolution of hypertriglyceridemia. Unexplained T1HLP in childhood could be secondary to LPL deficiency induced by autoantibodies. Therefore, diagnosis of autoimmune T1HLP should be entertained if clinical features are suggestive of an autoimmune process.

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

Reduced or modified dietary fat for preventing cardiovascular disease.

Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched through to June 2010. References of Included studies and reviews were also checked. Trials fulfilled the following criteria: 1) randomised with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I(2) 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis.Few studies compared reduced with modified fat diets, so direct comparison was not possible. The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

Variability in the clinical management of fatty acid oxidation disorders: results of a survey of Canadian metabolic physicians

There is little robust empirical evidence on which to base treatment recommendations for fatty acid oxidation disorders. While consensus guidelines are important, understanding areas where there is a lack of consensus is also critical to inform priorities for future evaluative research. We surveyed Canadian metabolic physicians on the treatment of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and mitochondrial trifunctional protein (MTP) deficiency. We ascertained physicians' opinions on the use of different interventions for the long-term management of patients as well as for the management of acute illness, focusing on identifying interventions characterized by high variability in opinions. We also investigated factors influencing treatment decisions. We received 18 responses (response rate 45%). Participants focused on avoidance of fasting and increased meal frequency as interventions for the management of MCAD deficiency. For the long-chain disorders, avoidance of fasting remained the most consistently endorsed intervention, with additional highly endorsed treatments differing for VLCAD versus LCHAD/MTP deficiency. L-carnitine supplementation and restriction of dietary fat were characterized by high variability in physicians' opinions, as were several interventions specific to long-chain disorders. Social factors and patient characteristics were important influences on treatment decisions. Based on our findings we suggest that high priority treatments for rigorous effectiveness studies could include L-carnitine supplementation (MCAD and LCHAD/MTP deficiencies), restriction of dietary fat, and, for the long-chain disorders, feeding practices for breastfed infants and the use of various supplements (essential fatty acids, carbohydrates, cornstarch, multivitamins).

The effect of one avocado per day on established and emerging cardiovascular disease (CVD) risk factors: study design

Clinical studies have demonstrated consistently that diets high in monounsaturated (MUFA) and low in saturated fatty acids (SFA) lower total cholesterol and low density lipoprotein cholesterol (LDL‐C) as effectively as lower‐fat, low SFA diets. Avocados are a good source of MUFA and also are rich in vitamins, minerals and phytosterols which could beneficially affect CVD risk. A randomized, 3‐period cross‐over, controlled feeding study was designed to evaluate the effects of avocados on established and emerging risk factors for CVD. Overweight and obese (BMI 25–35 kg/m2) men and women with moderately elevated LDL‐C (25 – 90th) will consume 3 treatment diets with a 2 week run‐in Western diet. Treatment diets are matched for SFA (&lt;7% energy) and include a low‐fat diet (LF: 24% fat, 12% MUFA), a moderate fat diet (MF: 34% fat, 18% MUFA), and a moderate fat diet providing 1 avocado per day (AV: 34% fat, 18% MUFA) with the equivalent fatty acid profile of the MF diet. We hypothesize that the inclusion of 1 avocado per day in a cholesterol‐lowering moderate fat diet will improve CVD risk factors including lipids, lipoproteins, markers of oxidative stress and inflammation, and improve reverse cholesterol transport compared to a heart‐healthy low fat diet and a moderate fat diet without avocado.This study is supported by the Hass Avocado Board of California. ClincalTrials.gov identifier: NCT0123582

Effect of Diets Differing in Fat Content on Chronic Diarrhea in Cats

Fat-restricted diets have been advocated for dogs with diarrhea for many years. Recommendations for cats with diarrhea have varied between low-fat and high-fat diets, but there have been no published studies to support either recommendation. The objective of this study was to compare the clinical responses of cats with chronic diarrhea to dietary management using either a high fat or a low fat, highly digestible diet. Sixty pet cats with chronic diarrhea were recruited; 55 cats completed the study. Randomized, double-blinded, controlled clinical trial. Upon completion of baseline measures, cats were fed 1 of 2 diets for 6 weeks, during which the owners recorded fecal scores daily using an illustrated fecal score chart ranging from 0 (very watery) to 100 (firm and dry). After 6 weeks, cats were reevaluated by the attending veterinarians. Fecal scores improved significantly, with 78.2% of cats improving by at least 25 points on the 100-point scale or having a final fecal score of at least 66. Over one third of the cats developed normal stools. There were no differences in clinical responses between the diets. Clinical improvement was noted within the 1st week, and maximized within 3 weeks. These results show that dietary management can be helpful in cats with chronic diarrhea, but dietary fat content does not appear to affect the outcome. Cats that do not respond within 3 weeks should be evaluated further.

Anderson's disease/chylomicron retention disease in a Japanese patient with uniparental disomy 7 and a normal SAR1B gene protein coding sequence

BackgroundAnderson's Disease (AD)/Chylomicron Retention Disease (CMRD) is a rare hereditary hypocholesterolemic disorder characterized by a malabsorption syndrome with steatorrhea, failure to thrive and the absence of chylomicrons and apolipoprotein B48 post-prandially. All patients studied to date exhibit a mutation in the SAR1B gene, which codes for an essential component of the vesicular coat protein complex II (COPII) necessary for endoplasmic reticulum to Golgi transport. We describe here a patient with AD/CMRD, a normal SAR1B gene protein coding sequence and maternal uniparental disomy of chromosome 7 (matUPD7).Methods and ResultsThe patient, one of two siblings of a Japanese family, had diarrhea and steatorrhea beginning at five months of age. There was a white duodenal mucosa upon endoscopy. Light and electron microscopy showed that the intestinal villi were normal but that they had lipid laden enterocytes containing accumulations of lipid droplets in the cytoplasm and lipoprotein-size particles in membrane bound structures. Although there were decreased amounts in plasma of total- and low-density lipoprotein cholesterol, apolipoproteins AI and B and vitamin E levels, the triglycerides were normal, typical of AD/CMRD. The presence of low density lipoproteins and apolipoprotein B in the plasma, although in decreased amounts, ruled out abetalipoproteinemia. The parents were asymptomatic with normal plasma cholesterol levels suggesting a recessive disorder and ruling out familial hypobetalipoproteinemia. Sequencing of genomic DNA showed that the 8 exons of the SAR1B gene were normal. Whole genome SNP analysis and karyotyping revealed matUPD7 with a normal karyotype. In contrast to other cases of AD/CMRD which have shown catch-up growth following vitamin supplementation and a fat restricted diet, our patient exhibits continued growth delay and other aspects of the matUPD7 and Silver-Russell Syndrome phenotypes.ConclusionsThis patient with AD/CMRD has a normal SAR1B gene protein coding sequence which suggests that factors other than the SAR1B protein may be crucial for chylomicron secretion. Further, this patient exhibits matUPD7 with regions of homozygosity which might be useful for elucidating the molecular basis of the defect(s) in this individual. The results provide novel insights into the relation between phenotype and genotype in these diseases and for the mechanisms of secretion in the intestine.

Changes in Body Weight and Metabolic Indexes in Overweight Breast Cancer Survivors Enrolled in a Randomized Trial of Low-Fat vs. Reduced Carbohydrate Diets

Overweight status is common among women breast cancer survivors and places them at greater risk for metabolic disorders, cardiovascular morbidity, and breast cancer recurrence than nonoverweight survivors. Efforts to promote weight control in this population are needed. The objective of this research was to evaluate the effect of low-fat or low-carbohydrate diet counseling on weight loss, body composition, and changes in metabolic indexes in overweight postmenopausal breast cancer survivors. Survivors (n = 40) were randomized to receive dietitian counseling for a low-fat or a reduced carbohydrate diet for 6 mo. Weight and metabolic measures, including glucose, insulin, HbA1c, HOMA, lipids, hsCRP, as well as blood pressure were measured at baseline, 6, 12 and 24 wk. Dietary intake of fat and carbohydrate was reduced by 24 and 76 g/day, respectively. Weight loss averaged 6.1 (± 4.8 kg) at 24 wk and was not significantly different by diet group; loss of lean mass was also demonstrated. All subjects demonstrated improvements in total/HDL cholesterol ratio, and significant reductions in HbA1c, insulin, and HOMA. Triglycerides levels were significantly reduced only in the low-carbohydrate diet group (−31.1 ± 36.6; P = 0.01). Significant improvements in weight and metabolic indexes can be demonstrated among overweight breast cancer survivors adherent to either a carbohydrate- or fat-restricted diet.

200 The effect of carbohydrate- and fat-restricted diet on B16F10 melanoma model in C57BL6 mice: focus on tumor growth inhibition and its underlying molecular target signaling pathways

Swiss, C57BL6 and CBA males were given 0.1 ml of 40% ethanol per mouse per day for three consecutive days intraperitoneally. These males were mated with untreated virgin Swiss females employing a 4-day mating schedule and three consecutive matings were carried out. In other study, C57BL6 males were given an ascending gradient of 5% to 40% ethanol in drinking water for a total period of 11 weeks. These males were mated with C57BL6 females for 2 weeks. Females were dissected at mid-term pregnancy for the examination of uterine contents including total, live and dead implants. All the investigations comprised at least two or three independent experiments which were evaluated independently as well as after pooling the data. Swiss, C57BL6 and CBA males given 0.1 ml of 40% ethanol, intraperitoneally, gave no evidence of any significant increase in post-implication lethality in the postmeiotic phase of spermatogenesis attributable to ethanol treatment. A moderate but significant reduction in mean total implants indicating pre-implantation losses was seen in Swiss but not in CBA mice. Prolonged feeding of ethanol up to 40% in drinking water failed to provide any evidence of dominant lethal mutations in C57BL6 males at the pre-implantation level and the post-implantation lethals were also not significantly higher than in controls. In Swiss mice, however, the mutagenic index based on both pre- and post-implantation lethality was consistently positive.

Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome—LIPGENE: a European randomized dietary intervention study

Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. A free-living, single-blinded dietary intervention study. MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men. There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations

Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

PP8 CHANGES OF EXCESS BODY WEIGHT IN CHILDREN WITH DYSLIPIDEMIAS ON LIPID-LOWERING DIETARY THERAPY DURING A TWO-YEAR FOLLOW-UP

Cardiovascular disease (CVD) is the first cause of morbility and mortality among adults. The relationship between dyslipidemias, childhood overweight and high risk of premature CVD is well known. Current guidelines about management of dyslipidemias in children and adolescents, recommended a prudent diet which maintained adequate nutrients and calories and ideal body weight, while reducing the proportion of intake from total fat, saturated fat and cholesterol intake. Because of its presumed safety, lipid-lowering dietary therapy has been considered as the miliarstone of management. The safety about nutritional status of the fat and cholesterol restricted diet was investigated in various clinical trials. Childhood overweight is defined by a value of BMI from 85th to 95th percentile, while a value of BMI > 95th percentile is used to define obesity. Excess Body Weight (EBW%) is considered as the percentage of weight exceeding 50th centile and is used to estimate the degree of overweight. Objective: To evaluate the relationship between EBW and dyslipidemia in a cohort of dislipidemic children. Materials and methods: During a period of twenty-eight months, from January 2008 to April 2010, 382 outpatients (188 m and 194 f), aged from 1 to 18 yrs, were recruited at our Paediatric Lipid Unit. 246/382 were affected by familial hypercholesterolemia (FH), 9/382 by secondary hypercholesterolemia (SH), 3/382 by primary hypertrygliceridemia (PHT), 8/382 by secondary hypertrygliceridemia (SHT) and 116/382 hadn’t yet received a defined diagnosis. During this period of follow-up we estimated the EBW of our patients at the first visit, when children were in free diet. After they started a dietary program was evaluated the trend of weight at each control through analysis of EBW. Results: The mean value of EBW decreases from 111% (at the first visit) to 101,33% (at the last control) in patients with FH, from 126% to 111% in patients with SH, from 105,46% to 95,1% in patients with PHT, from 158,53% to 130,8% in patients with SHT while eraised from 112,98% to 129,21% in patients without a defined diagnosis. The graph below shows the trend of EBW for each group of patients.

Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38% energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28%E) with (LFHCC n-3) or without (LFHCC) 1·24g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P=0·83; 15-keto-dihydro-PGF2α, P=0·45; and CRP, P=0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.

Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure

Section 6: Nonpharmacologic Management and Health Care Maintenance in Patients With Chronic Heart Failure