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Leptin receptors (LepR) are expressed in brain areas controlling food intake homeostasis, such as the hypothalamus, the hippocampus and the prefrontal cortex. In a previous study we reported that long-term intake of saturated and monounsaturated fat alters hypothalamic LepR signalling. The current study aims at investigating the effect of foods high in either saturated (SOLF) or monounsaturated fat (UOLF) on LepR functionality in the hippocampus and the prefrontal cortex. Male mice were placed on SOLF/UOLF (eight weeks), then treated with recombinant murine leptin (1 mg/kg). After 60 min, brain regions were dissected and processed for western blot of phosphorylated STAT3 (pSTAT3), Akt (pAkt) and AMPK (pAMPK). Levels of SOCS3 were also quantified. SOLF itself increased basal levels of pSTAT3, while UOLF impaired leptin-induced phosphorylation of both Akt and AMPK. SOCS3 levels were specifically increased by UOLF within the prefrontal cortex. Our results show that SOLF and UOLF differently affect LepR signalling within the hippocampus and the prefrontal cortex, which points to the complex effect of saturated and unsaturated fat on brain function, particularly in areas regulating food intake., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the therapeutic effect of PEGlated nanoliposome of pistachio unsaturated oils (PEGNLPUOs) and their efficacy to attenuate inflammation in multiple sclerosis (MS). This study was a randomized, double-blind, placebo-controlled clinical trial phase I. The level of docosahexaenoic and eicosapentaenoic acid was significantly increased and the level of matrix metallopeptidase-9 was significantly decreased in MS patients treated with PEGNLPUOs. The level of cytokine showed a Th2-biased response with attenuation of inflammation after treatment with PEGNLPUOs. The number of relapses, disability scores, and T2 lesions was significantly decreased after treatment with PEGNLPUOs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

High-fat diets are linked with obesity and changes in dopamine neurotransmission. Mounting evidence shows that saturated fat impacts dopamine neurons and their terminal fields, but little is known about the effect a diet high in unsaturated fat has on the dopamine system. This study sought to determine whether fat type, saturated vs. unsaturated, differentially affected body weight, blood glucose regulation, locomotor behavior, and control of dopamine release and uptake at dopamine neuron terminals in the nucleus accumbens (NAc). C57BL/6 mice were fed a control diet or a nutrient-matched diet high in saturated fat (SF), unsaturated flaxseed oil (Flax) or a blend of the two fats. After 6-weeks, mice from each high-fat diet group gained significantly more weight than Controls, but the group fed Flax gained less weight than the SF group and had fasting blood glucose levels similar to Controls. Ex-vivo fast scan cyclic voltammetry revealed the SF group also had significantly slower synaptic dopamine clearance and a reduced capacity for phasic dopamine release in the nucleus accumbens (NAc), but the Flax and Blend groups resembled Controls. These data show that different types of dietary fat have substantially different effects on metabolic phenotype and influence how dopamine terminals in the NAc regulate dopamine neurotransmission. Our data also suggests that a diet high in unsaturated fat may preserve normal metabolic and behavioral parameters as well as dopamine signaling in the NAc.

Objective: We recently showed that measurement of the susceptibility of LDL (low-density lipoprotein) to aggregation is an independent predictor of cardiovascular events. We now wished to compare effects of overfeeding different dietary macronutrients on LDL aggregation, proteoglycan-binding of plasma lipoproteins, and on the concentration of oxidized LDL in plasma, 3 in vitro parameters consistent with increased atherogenicity., Approach and Results: The participants (36 subjects; age, 48+/-10 years; body mass index, 30.9+/-6.2 kg/m2) were randomized to consume an extra 1000 kcal/day of either unsaturated fat, saturated fat, or simple sugars (CARB) for 3 weeks. We measured plasma proatherogenic properties (susceptibility of LDL to aggregation, proteoglycan-binding, oxidized LDL) and concentrations and composition of plasma lipoproteins using nuclear magnetic resonance spectroscopy, and in LDL using liquid chromatography mass spectrometry, before and after the overfeeding diets. LDL aggregation increased in the saturated fat but not the other groups. This change was associated with increased sphingolipid and saturated triacylglycerols in LDL and in plasma and reduction of clusterin on LDL particles. Proteoglycan binding of plasma lipoproteins decreased in the unsaturated fat group relative to the baseline diet. Lipoprotein properties remained unchanged in the CARB group., Conclusions: The type of fat during 3 weeks of overfeeding is an important determinant of the characteristics and functional properties of plasma lipoproteins in humans.

Backgrounds & Aims: Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat., Methods: In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000 kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and 1 H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding., Results: The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample Bray-Curtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline., Conclusions: Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website: ClinicalTrials.gov., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background: In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown., Aim: To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals., Setting/ Methods: Twenty-two healthy subjects were given 150 mL of full milk cream (54 g fat) and 59 mL of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood was drawn at fasted before 0 h (h) and at 1 h, 2 h and 4 h after ingestion. Post-ingested values of proneurotensin and plasma triglycerides were compared with fasting levels and post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with that of plasma triglycerides., Results: An immediate rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 h for proneurotensin [mean (95% confidence interval)] of 22 (12-31) pmol/L (P < 0.001) and at 3 h for triglycerides of 0.60 (0.43-0.78) mmol/L (P < 0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 h of 62 (46-78) pmol/L (P < 0.001) and plasma triglycerides at 3 h of 0.32 (0.18-0.45) mmol/L (P < 0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r = 0.49, P = 0.021) and olive oil (r = 0.55, P = 0.008), respectively., Conclusion: Proneurotensin increases after an oral lipid load of both cream and olive oil and the rise of post-ingestion plasma triglycerides is significantly related to the rise of post-ingestion proneurotensin.

Objective: Post-prandial lipaemia (PL), oxidative stress (OS), and complement component C3 (C3) values are related to the atherosclerosis process. The post-prandial response of C3 after an oral fat load test (OFLT) using unsaturated fat is poorly addressed. The aim of this study was to analyze and compare the post-prandial response of OS markers and C3 values in men and women after an OFLT using unsaturated fat., Methods: The study included a total of 22 healthy subjects with normal lipids and normal blood glucose (11 men and 11 pre-menopausal women). An oral unsaturated fat load test (OFLT: 50g fat per m 2 body surface) was performed using a commercial liquid preparation of long chain triglycerides (Supracal®). OS markers and C3 were measured using standardized methods at fasting state and every 2h up to 8h after the OFLT., Results: Men showed statistically significant higher C3, oxidized glutathione (GSSG), and oxidized-reduced glutathione (GSSG/GSH) ratio values at fasting state compared to that obtained in women. In addition, post-prandial C3 values and GSSG/GSH ratios were significantly higher in men compared to women. The GSSG value and GSSG/GSH ratio significantly decreased in men after the OFLT compared to fasting values. In contrast, the post-prandial OS markers decrease observed in women was not statistically significant., Conclusions: In fasting state, men showed higher statistically significant C3 values and OS markers than women. The post-prandial OS markers (GSSG and GSSG/GSH ratio) significantly decrease after the OFLT with unsaturated fat in men compared to women., (Copyright © 2019 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood., Objectives: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9)., Methods: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis., Results: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets., Conclusions: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. This trial was registered at clinicaltrials.gov as NCT01235832., (Copyright © The Author(s) 2020.)

Purpose: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls., Methods: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina., Results: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity., Conclusions: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state.

Background: Modifying the type of dietary fat consumed may impact appetite, therefore having implications in weight management., Objective: To test the effects of a 5-day, high-fat diet rich in poly-unsaturated fatty acids (PUFAs) and a diet rich in mono-unsaturated fatty acids (MUFAs) on markers of appetite., Methods: Fifteen normal weight men participated in a randomized cross-over design with two controlled feeding trials (3d lead-in diet, pre-diet visit, 5d PUFA- or MUFA-rich diet, post-diet visit). The 5d diets (50% fat) were rich in either PUFA (25% of energy) or MUFA (25% of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA corresponding to the 5-day diet. Fasting and postprandial subjective ratings of appetite were determined and blood draws were performed for 4h after each meal to determine changes in appetite hormones. An ad libitum buffet meal was given at the end of pre- and post-diet visits., Results: Acutely, at the pre-diet visit, the PUFA-rich meal resulted in lower ghrelin (hunger hormone) (iAUC: -350.85 ± 60.70 vs. -233.16 ± 61.42 pg/ml/8h, for PUFA vs. MUFA, respectively; p < 0.05) and higher CCK (satiation hormone) (iAUC: 238.09 ± 46.07 vs. 196.84 ± 33.92 pM/8h, for PUFA vs. MUFA, respectively; p < 0.05). No other acute meal challenge differences were found. The 5d high PUFA diet resulted in lower hunger ratings (iAUC: -172.06 ± 40.59 vs. -274.46 ± 41.47 mm/8h, for pre-to post-diet, respectively; p < 0.05). However, energy intake, ratings of fullness, or PYY did not change from pre-to post-diet for either MUFA or PUFA, and no other changes were observed with the MUFA diet., Conclusions: Acutely, a PUFA-rich meal results in ghrelin suppression and higher CCK. After a 5-day high-fat diet, PUFAs suppressed postprandial hunger while MUFAs did not change any measures of appetite., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: To examine whether a low-carbohydrate, high-unsaturated/low-saturated fat diet (LC) improves glycaemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D)., Methods: A total of 115 adults with T2D (mean [SD]; BMI, 34.6 [4.3] kg/m 2 ; age, 58 [7] years; HbA1c, 7.3 [1.1]%) were randomized to 1 of 2 planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1 hour, 3 days/week) for 2 years: LC: 14% energy as carbohydrate, 28% as protein, 58% as fat (<10% saturated fat); or low-fat, high-carbohydrate, low-glycaemic index diet (HC): 53% as CHO, 17% as protein, 30% as fat (<10% saturated fat). HbA1c, glycaemic variability (GV), anti-glycaemic medication effect score (MES, calculated based on the potency and dosage of diabetes medication), weight, body composition, CVD and renal risk markers were assessed before and after intervention., Results: A total of 61 (LC = 33, HC = 28) participants completed the study (trial registration: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820). Reductions in weight (estimated marginal mean [95% CI]; LC, -6.8 [-8.8,-4.7], HC, -6.6 [-8.8, -4.5] kg), body fat (LC, -4.3 [-6.2, -2.4], HC, -4.6 [-6.6, -2.7] kg), blood pressure (LC, -2.0 [-5.9, 1.8]/ -1.2 [-3.6, 1.2], HC, -3.2 [-7.3, 0.9]/ -2.0 [-4.5, 0.5] mmHg), HbA1c (LC, -0.6 [-0.9, -0.3], HC, -0.9 [-1.2, -0.5] %) and fasting glucose (LC, 0.3 [-0.4, 1.0], HC, -0.4 [-1.1, 0.4] mmol/L) were similar between groups (P ≥ 0.09). Compared to HC, the LC achieved greater reductions in diabetes medication use (MES; LC, -0.5 [-0.6, -0.3], HC, -0.2 [-0.4, -0.02] units; P = 0.03), GV (Continuous Overall Net Glycemic Action calculated every 1 hour (LC, -0.4 [-0.6, -0.3], HC, -0.1 [-0.1, 0.2] mmol/L; P = 0.001), and 4 hours (LC, -0.9 [-1.3, -0.6], HC, -0.2 [-0.6, 0.1] mmol/L; P = 0.02)); triglycerides (LC, -0.1 [-0.3, 0.2], HC, 0.1 [-0.2, 0.3] mmol/L; P = 0.001), and maintained HDL-C levels (LC, 0.02 [-0.05, 0.1], HC, -0.1 [-0.1, 0.01] mmol/L; P = 0.004), but had similar changes in LDL-C (LC, 0.2 [-0.1, 0.5], HC, 0.1 [-0.2, 0.4] mmol/L; P = 0.85), brachial artery flow mediated dilatation (LC, -0.5 [-1.5, 0.5], HC, -0.4 [-1.4, 0.7] %; P = 0.73), eGFR and albuminuria., Conclusions: Both diets achieved comparable weight loss and HbA1c reductions. The LC sustained greater reductions in diabetes medication requirements, and in improvements in diurnal blood glucose stability and blood lipid profile, with no adverse renal effects, suggesting greater optimization of T2D management., (© 2017 John Wiley & Sons Ltd.)

The updated 2015 Dietary Guidelines for Americans, published in January 2016, have stirred much controversy since the advisory report first appeared. Several important changes have been made, with some recommendations having greater scientific evidence for their support than others. The focus of this review is to discuss specific recommendations from the 2015 Dietary Guidelines for Americans that lack sound scientific evidence; these include: 1) Allowing approximately half of all grains to be refined; 2) The continued recommendations for fat-free or low-fat dairy and limitation of saturated fat intake to <10% of calories; 3) Sodium intake < 2,300 mg/day; and 4) Consumption of up to 27 g/day of “oils” (high in polyunsaturated fat or monounsaturated fat). Based on our review, the aforementioned recommendations found in the updated 2015 Dietary Guidelines for Americans may increase the incidence of cardiometabolic disease, diabetes, obesity, dyslipidemia, cardiovascular disease and possibly cancer.

The implication of lipid peroxidation in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) derive from high abundance of peroxidation-prone polyunsaturated fatty acids in central nervous system and its relatively low antioxidant content. In the present work, we evaluated the effect of dietary changes aimed to modify fatty acid tissular composition in survival, disease onset, protein, and DNA oxidative modifications in the hSODG93A transgenic mice, a model of this motor neuron disease. Both survival and clinical evolution is dependent on dietary fatty acid unsaturation and gender, with high unsaturated diet, leading to loss of the disease-sparing effect of feminine gender. This was associated with significant increases in protein carbonyl and glycoxidative modifications as well as non-nuclear 8-oxo-dG, a marker of mitochondrial DNA oxidation. Comparison of these data with γH2AX immunostaining, a marker of DNA damage response, suggests that the highly unsaturated diet-blunted mitochondrial-nuclear free radical dependent crosstalk, since increased 8-oxo-dG was not correlated with increased DNA damage response. Paradoxically, the highly unsaturated diet led to lower peroxidizability but higher anti-inflammatory indexes. To sum up, our results demonstrate that high polyunsaturated fatty acid content in diets may accelerate the disease in this model. Further, these results reinforce the need for adequately defining gender as a relevant factor in ALS models, as well as to use structurally characterized markers for oxidative damage assessment in neurodegeneration.

In Denmark death from cardiovascular disease (CVD) has decreased, mainly due to a 72% reduction since 1990 in death from ischaemic heart disease from reduced smoking, elimination of industrial trans fatty acids in the diet, and more effective medical treatment. Replacement of saturated fat by carbohydrate and/or n-6 polyunsaturated fat may increase CVD, but it is reduced by substitution with n-3 fats, monounsaturated fat, or low glycaemic index carbohydrates. Despite a high saturated fat content dark chocolate and cheese may reduce CVD and diabetes risk and eggs may be neutral, and less restrictive dietary recommendations are indicated.

Objective: Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat-rich diet (UNSAT; predominantly monounsaturated)., Research Design and Methods: This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2-4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations., Results: At baseline, mean (SD) BMI was 30.2 (6.1) kg/m(2), and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB., Conclusions: A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.

Background: 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., Objectives: 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., Search Methods: 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., Selection Criteria: 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., Data Collection and Analysis: 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., Main Results: 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., Authors' Conclusions: 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.

The dietary intake of saturated fatty acids (SAFA) is associated with a modest increase in serum total cholesterol, but not with cardiovascular disease (CVD). Replacing dietary SAFA with carbohydrates (CHO), notably those with a high glycaemic index, is associated with an increase in CVD risk in observational cohorts, while replacing SAFA with polyunsaturated fatty acids (PUFA) is associated with reduced CVD risk. However, replacing a combination of SAFA and trans-fatty acids with n-6 PUFA (notably linoleic acid) in controlled trials showed no indication of benefit and a signal toward increased coronary heart disease risk, suggesting that n-3 PUFA may be responsible for the protective association between total PUFA and CVD. High CHO intakes stimulate hepatic SAFA synthesis and conservation of dietary SAFA . Hepatic de novo lipogenesis from CHO is also stimulated during eucaloric dietary substitution of SAFA by CHO with high glycaemic index in normo-insulinaemic subjects and during hypocaloric high-CHO/low-fat diets in subjects with the metabolic syndrome. The accumulation of SAFA stimulates chronic systemic low-grade inflammation through its mimicking of bacterial lipopolysaccharides and÷or the induction of other pro-inflammatory stimuli. The resulting systemic low-grade inflammation promotes insulin resistance, reallocation of energy-rich substrates and atherogenic dyslipidaemia that concertedly give rise to increased CVD risk. We conclude that avoidance of SAFA accumulation by reducing the intake of CHO with high glycaemic index is more effective in the prevention of CVD than reducing SAFA intake per se.

Background: Epidemiologic studies have produced conflicting results with respect to an association of dietary fat with breast cancer., Objective: We aimed to investigate the association between fat consumption and breast cancer., Design: We prospectively investigated fat consumption in a large (n = 319,826), geographically and culturally heterogeneous cohort of European women enrolled in the European Prospective Investigation into Cancer and Nutrition who completed a dietary questionnaire. After a mean of 8.8 y of follow-up, 7119 women developed breast cancer. Cox proportional hazard models, stratified by age and center and adjusted for energy intake and confounders, were used to estimate hazard ratios (HRs) for breast cancer., Results: An association between high saturated fat intake and greater breast cancer risk was found [HR = 1.13 (95% CI: 1.00, 1.27; P for trend = 0.038) for the highest quintile of saturated fat intake compared with the lowest quintile: 1.02 (1.00, 1.04) for a 20% increase in saturated fat consumption (continuous variable)]. No significant association of breast cancer with total, monounsaturated, or polyunsaturated fat was found, although trends were for a direct association of risk with monounsaturated fat and an inverse association with polyunsaturated fat. In menopausal women, the positive association with saturated fat was confined to nonusers of hormone therapy at baseline [1.21 (0.99, 1.48) for the highest quintile compared with the lowest quintile; P for trend = 0.044; and 1.03 (1.00, 1.07) for a 20% increase in saturated fat as a continuous variable]., Conclusions: Evidence indicates a weak positive association between saturated fat intake and breast cancer risk. This association was more pronounced for postmenopausal women who never used hormone therapy.

Objective: The primary aim was to assess, the association of the quantity and quality of dietary fat intake from 6 to 12 months of age and serum lipids at 12 months., Subjects/methods: Three hundred healthy term Swedish infants were recruited in a longitudinal prospective study at the age of 6 months; 276 remained in the study at 12 months. Food records and anthropometric data were collected monthly from 6 to 12 months; serum lipids were analysed at 6 and 12 months., Results: Swedish infants had a total fat intake within the Nordic recommendations, but intake of polyunsaturated fatty acids (PUFA) was low (5.6 percent of total energy (E%)) and intake of saturated fatty acids (SAFA) was high (15.1 E%). Higher PUFA intake was associated with lower total serum cholesterol (TC, B=-0.13, P=0.003), lower low-density-lipoprotein cholesterol (LDL-C, B=-0.12, P=0.004) and apolipoprotein B (B=-0.03) (P=0.034) in girls but not in boys. When data from the present study were compared to data from similar studies in Finland and Iceland, it appears that the quality of the dietary fat has greater impact on serum lipid levels than the quantity of fat in the diet., Conclusions: Higher PUFA and lower SAFA intakes may reduce TC and LDL-C early in life, particularly in girls. Further, with respect to lowering serum lipid concentrations in early childhood it seems appropriate to set focus on fat quality rather than the quantity., Sponsorships: Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas), Swedish Research Council, Medicine, Stiftelsen Oskar Foundation, Sven Jerring Foundation, Samariten Foundation, Stiftelsen Goljes minne and Semper AB.

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a critical regulator of adipogenesis. PPAR gamma+/- mice are resistant to high-fat diet-induced obesity and thus PPAR gamma may mediate physiological responses to dietary fat in other mammals. The aim of this study was to determine whether the human PPAR gamma proline to alanine substitution polymorphism (Pro12Ala) modifies the association between dietary fat and adiposity and plasma lipids. Subjects (n=2141) were controls selected for three case-control studies nested within the Nurses' Health Study, a large ongoing prospective cohort study. Associations between intake of total fat, fat subtypes and BMI were different in PPAR gamma 12Ala variant allele-carriers compared with non-carriers. Among homozygous wild-type Pro/Pro individuals, those in the highest quintile of total fat intake, had significantly higher mean body mass index (BMI) compared with those in the lowest quintile (27.3 versus 25.4 kg/m2, respectively; P-trend<0.0001) whereas among 12Ala variant allele-carriers there was no significant trend observed between dietary fat intake and BMI (P-trend=0.99; P-interaction=0.003). In contrast, intake of monounsaturated fat was not associated with BMI among homozygous wild-type women but was inversely associated with BMI among 12Ala variant allele-carriers (mean in lowest quintile=27.6 versus mean in highest quintile=25.5 kg/m2; P-trend=0.006; P-interaction=0.003). The relationship between dietary fat intake and plasma lipid concentrations also differed according to PPAR gamma genotype. These data suggest that PPAR gamma genotype is an important factor in physiological responses to dietary fat in humans.

Single-cell oils are currently included in human infant formula as sources of the long-chain polyunsaturates (LCP) docosahexaenoic acid (DHA) and arachidonic acid (AA) in many countries, but have not yet been approved for use in the USA. We prepared four bovine-milk-based formulas with AA/DHA=0, 34/17, 68/34 and 170/85 (mg per 100 kcal formula) provided by two commercial single-cell oils. These levels correspond approximately to 0, 1, 2 and 5 times the concentrations used in infant formulas and, due to greater consumption of formula per unit body weight, resulted in daily consumption of approximately 0, 3, 6 and 16 times those anticipated for human infants. All other dietary fat (47% of calories) was provided by a vegetable oil blend used in commercial human infant formulas. Domestic piglets were allowed to nurse with the sow for 24 h after parturition, then removed to individual cages and maintained on one of the four diets. At 30 days of age the piglets were sacrificed, and serum collected and organs weighed. With litters treated as a blocked variable, no significant differences among groups were found by analysis of variance for the following serum assays: alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, albumin, glucose, cholesterol, triglycerides, and total protein. No significant differences were found for hematocrit or body weight. No significant differences were found among groups for weights of liver, brain, heart, lung, spleen, kidneys or lung, analyzed as absolute weight and as a fraction of body weight. Hematoxylin/eosin liver sections examined by light microscopy showed no abnormalities as evaluated by an independent pathologist. DHA content in liver and heart and AA content in heart showed significant dose-related accumulation (P<0.05) and confirmed enhanced tissue accretion of DHA and AA from both oils. We conclude that single-cell oils in formula consumed for 1 month in amounts up to 16-fold greater than proposed for human infants in the USA did not result in clinical chemistry or histopathologic indications of toxic effects in neonatal pigs.

The lymphatic transport and the portal absorption of the lipophilic drug halofantrine were investigated in a conscious rat model. The rats were dosed with 0.1 g with triolein, trilinolein or trilinolenin containing 2 mg halofantrine. Following oral administration of the triglycerides, the mesenteric lymph and plasma samples were collected. The lymphatic transport for halofantrine was 11.1+/-1.2 after administration of trilinolein, 9.0+/-3.5 for trilinolenin and 8.6+/-2.2 for triolein and the total amount of halofantrine transported in the lymph was linear proportional with the amount of triglyceride in the lymph. The absorption of halofantrine directly into the blood showed a trend towards a higher AUC for trilinolien and trilinolenin compared to triolein, but no statistical difference could be found. The statistically analysis of the mean total bioavailability therefore shows that the absorption of halofantrine was largely independent on triglyceride unsaturation.

Background: It has been reported that walnuts reduce serum cholesterol levels in normal young men., Objective: To assess the acceptability of walnuts and their effects on serum lipid levels and low-density lipoprotein (LDL) oxidizability in free-living hypercholesterolemic persons., Design: Randomized, crossover feeding trial., Setting: Lipid clinic at a university hospital., Patients: 55 men and women (mean age, 56 years) with polygenic hypercholesterolemia., Intervention: A cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced approximately 35% of the energy obtained from monounsaturated fat. Patients followed each diet for 6 weeks., Measurements: Low-density lipoprotein fatty acids (to assess compliance), serum lipid levels, lipoprotein(a) levels, and LDL resistance to in vitro oxidative stress., Results: 49 persons completed the trial. The walnut diet was well tolerated. Planned and observed diets were closely matched. Compared with the Mediterranean diet, the walnut diet produced mean changes of -4.1% in total cholesterol level, -5.9% in LDL cholesterol level, and -6.2% in lipoprotein(a) level. The mean differences in the changes in serum lipid levels were -0.28 mmol/L (95% CI, -0.43 to -0.12 mmol/L) (-10.8 mg/dL [-16.8 to -4.8 mg/dL]) (P<0.001) for total cholesterol level, -0.29 mmol/L (CI, -0.41 to -0.15 mmol/L) (-11.2 mg/dL [-16.3 to -6.1 mg/dL]) (P<0.001) for LDL cholesterol level, and -0.021 g/L (CI, -0.042 to -0.001 g/L) (P = 0.042) for lipoprotein(a) level. Lipid changes were similar in men and women except for lipoprotein(a) levels, which decreased only in men. Low-density lipoprotein particles were enriched with polyunsaturated fatty acids from walnuts, but their resistance to oxidation was preserved., Conclusion: Substituting walnuts for part of the mono-unsaturated fat in a cholesterol-lowering Mediterranean diet further reduced total and LDL cholesterol levels in men and women with hypercholesterolemia.

Objective: To evaluate the effect of dietary low-saturated fat, low-cholesterol intervention on fat intake and fatty acid compositions in serum cholesterol ester (CE), phospholipid (PL) and triglyceride (TG) fractions in five-year-old children., Design and Subjects: The STRIP project is a prospective, randomised intervention project in which 1062 seven-month-old infants were recruited from the well-baby clinics. 764 children participated in the 5-year follow-up; 202 of them were randomly selected for this study. Diet was assessed with 4-d dietary records. Serum CE, PL and TG fatty acid compositions were analysed with gas-liquid chromatography., Results: Saturated fat intake of intervention children (mean (confidence interval)) (girls 11.9 (11.2-12.6) % of energy intake (E%); boys 12.5 (11.9-13.1)) was lower than that of the control children (girls 14.4 (13.7-15.2) E%; boys 15.0 (14.3-15. 8) E%) (P=0.0001 for the difference between intervention and control groups). The intake of unsaturated fat differed only slightly. Dietary ratios of polyunsaturated to saturated fatty acids (PS ratios) of the intervention and control diets were 0.44 and 0.33, respectively (P=0.0001). Furthermore, serum cholesterol concentrations of the intervention and control children differed (4. 28 (4.13-4.43) mmol/L vs 4.49 (4.35-4.63) mmol/L; P=0.04). Relative proportion of saturated fatty acids in serum TG was lower (34.9% vs 36.3%; P=0.04) and that of n-6 polyunsaturated fatty acids higher (13.9% vs 12.4%; P=0.0004) in the intervention than in the control children, whereas serum CE and PL fatty acid compositions of intervention and control groups were closely similar. However, intake of linoleic acid correlated better with serum linoleic acid relative content in the CE fraction (r=0.36; P=0.0001) than in the PL (r=0.27; P=0.0002) or in the TG (r=0.23; P=0.0016) fraction., Conclusions: Intervention resulted in decreased intake of saturated fatty acids and lowered serum total and LDL cholesterol concentrations. Of serum lipid fractions, TG fatty acid composition was the most sensitive and parallelled the findings in dietary food records.

Purpose: The National Cholesterol Education Program (1991) recommended that children 2 years of age or more derive less than 30% of their daily energy intake from total fat, less than 10% from saturated fat, up to 10% from polyunsaturated fat, and 10% to 15% from monounsaturated fat, and that they consume less than 300 mg/day of cholesterol. The purpose of this study was to assess whether preadolescent children were following these dietary guidelines in 1994 and to determine the relationship of diet to obesity., Methods: This cross-sectional study was performed in elementary schools in southeast Baltimore, Maryland. The subjects were 468 children, grades 2 through 5 (mean age, 8.9 +/- 0.8 years). The main outcome measures were a 24-hour diet record, body mass index, and skinfold thickness., Results: Mean percentage of total daily energy (TDE) from fat was 31.1%; saturated fat, 11.0%; monounsaturated fat, 10%; and polyunsaturated fat, 4.9%. Mean dietary cholesterol was 199.1 mg/day. Although the means for total and saturated fat are at recommended levels, the distribution of the dietary responses indicates that 50% of the children exceeded these targets. Twenty-five percent exceeded 35% of TDE derived from fat, and 25% exceeded 13% TDE derived from saturated fat. Fifty percent of children consumed below the desired level of monounsaturated fat, and almost no children consumed the desired 10% of polyunsaturated fat. Although mean dietary cholesterol was at a desired level, 16% of the children consumed more than 300 mg/day and 10% more than 377 mg/day. The negative correlation for sum of skinfold measurements with TDE (r = -0.14; P < 0.05), suggesting that fatter children consume fewer calories than thinner children, was the only correlate among dietary components and obesity., Conclusion: A substantial percentage of children in the United States are still not meeting recommended levels for dietary intake of fat and cholesterol. The trend for fatter children to consume fewer daily calories suggests that obesity is not entirely a result of overconsumption.

Blood lipids and apo B levels were measured on 101 Coronary Heart Disease patients and 100 controls. The results showed that the apo B levels of patients were higher than that of controls. The average values were (877 +/- 129) mg/L and (800 +/- 95) mg/L respectively. It was found that there was close association among body mass index(BMI), ratio of waist circumference to hip circumference(WHR) and apo B levels. Besides, the results showed that dietary habit of "eating fat meat" might result in the increase of apo B concentration while the VC intake was negatively associated with serum apo B levels.

The present study examines whether the consumption of a moderately altered olive oil influenced body weight gain and food efficiency ratio of pregnant rats as well as placental and fetal development. Olive oil used for frying 15 times undergoes a relatively slight alteration involving a statistically significant increase in polar content (9.0+/-0.1 mg/100 mg oil vs 2.0+/-0.1 mg/100 mg oil; p < 0.001). The methyl ester content also increased (5.1+/-0.8 mg/100 mg oil vs 1.8+/-0.5 mg/100 mg oil; p < 0.02), while the linoleic acid and oleic acid contents decreased significantly (6.2+/-0.6% oil vs 7.2+/-0.2% oil and 75.8+/-0.6% vs 78.9+/-0.2%, respectively, both p < 0.05). Wistar rats were divided into four groups, two of which included pregnant rats (P1 and P2) and the other two, non-pregnant rats (NP1 and NP2). Groups NP1 and P1 received a diet containing 15% of fat as unused olive oil, while groups NP2 and P2 were fed a diet with a fat content of 15% as the olive oil used in 15 fryings. Pregnancy increased food intake, body weight, weight gain and food efficiency ratio (P1 vs NP1, and P2 vs NP1), while consumption of the used olive oil diet with respect to the unused oil diet did not alter food intake, body weight, weight gain and food efficiency ratio, placental weight, fetal weight and the number of fetuses in P2 rats with respect to P1 ones. These results suggest that in pregnant rats consumption of olive oil with a moderate level of alteration, as the only dietary fat source, exerts no detrimental effects on the mother weight gain or conceptus development.

Background: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer., Methods: We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs)., Results: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer., Conclusions: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

Study Objective: The aim was to examine the hypothesis that hydrogenated fats, particularly those obtained from marine oils, may present a health hazard., Design: Storage fat specimens obtained at necropsy were collected from several areas in England and Wales during 1975-1978. Cases (n = 136 samples) consisted of males dying of ischaemic heart disease, male deaths from unrelated causes acting as controls (n = 95 samples). The fatty acid compositions of the specimens were determined, and analysis included those acids--16:1 trans and "higher" C-20 plus C-22 (H)--highly characteristic of partially hydrogenated marine oils., Measurements and Main Results: The case samples, which had been shown to be the richer in 16:1 trans (p less than 0.005), were now found to have a significantly higher value of the ratio 16:1 trans to H (p less than 0.002), arising from consumption of differing hydrogenated marine oil types., Conclusions: It is concluded that the cases had consumed a greater amount (p less than 0.001) of hydrogenated marine oils of a certain type, ie, that manufactured from certain highly unsaturated raw oils. The process of partial hydrogenation results in conversion to a product containing large amounts of polyunsaturated acids (PUFA) which are no longer in the natural all-cis methylene interrupted configuration. Such isomeric PUFA may obstruct or compete with utilisation of natural PUFA. It is further concluded that the case excess did not rise from medical advice favouring margarine or from any difference in social class status, but rather from fortuitous selection of margarine brand.

The effects of polyunsaturated, monounsaturated and saturated dietary fat on total and hepatic cholesterol synthesis were studied in the guinea-pig. Male Hartley guinea-pigs were fed semi-synthetic diets containing 7.5% (w/w) of either corn oil (CO), olive oil (OL) or lard for a period of 5 weeks and rates of endogenous cholesterol synthesis were determined from the incorporation of [3H]water into digitonin-precipitable sterols (DPS) and by measurement of sterol balance. In addition, total and expressed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities were determined in hepatic microsomes. Rates of whole body cholesterol synthesis determined by incorporation of [3H]water into DPS were significantly lower for guinea-pigs on the CO diet with values of 18.7 +/- 1.8 mumol/h (n = 4) vs. 26.7 +/- 4.8 and 24.6 +/- 1.8 mumol/h for animals on the OL (n = 4) and lard (n = 3) diets (P less than 0.001), respectively. Hepatic cholesterol synthesis rates were significantly decreased in animals on the OL diet, whether determined from incorporation of [3H]water into DPS or by analysis of HMG-CoA reductase activity. Hepatic total and free cholesterol levels were not different for animals on the three dietary fats; however, cholesteryl ester levels were 35% lower in guinea-pigs fed the lard diet (P less than 0.02). Sterol balance measurements indicated that whole body cholesterol synthesis rates were not affected by dietary fat quality (51.9 +/- 12.2, 42.8 +/- 7.6 and 51.2 +/- 20.2 mg/kg per day for animals on the CO, OL and lard diets, respectively). This is in striking contrast to the observed reduction in cholesterol synthesis rates for animals on the polyunsaturated CO diet as determined by incorporation of [3H]water into DPS. One possible explanation for the discrepancy between the sterol balance and [3H]water incorporation data is a polyunsaturated fat-mediated effect on energy utilization, which affects the equilibration of NADPH with the body water pool such that the [3H]NADPH has a lower specific activity than body [3H]water.

The specificity of a statistical association increases the likelihood that it represents a causal relationship. In exploring the relationship between dietary fat and cancer, specificity applies both to cancer sites (outcome) and to component fats (exposure). In this study, Armstrong-Doll criteria were used to select female cancer incidence data for breast, cervix, lung, and colon, and male incidence data for lung, colon, and prostate for 1973-1977 from 20 countries with reliable registry data. Truncated age-standardized rates were correlated with estimates of per capita disappearance of total fat and of saturated, monounsaturated, and polyunsaturated (total, fish omega-3, omega-6) fats in 1975-1977. Multiple regression analyses were standardized for estimated total calorie intakes and used to assess the association between each fat and incidence at each cancer site. Estimates of per capita dietary and crude fiber intakes were also included in the analysis. Total calorie intake was not associated with cancer at any site when controlled for total fat intake, whereas total fat intake was strongly associated with cancers of the breast, colon, and prostate even after adjustment for total calorie intake. Cancers of the lung and cervix were not correlated with dietary fat intake. Monounsaturated fat had no positive association with cancer at any site. Saturated fat was positively associated with incidence of cancers of the breast, colon, and prostate and polyunsaturated fat was associated with incidence of breast and prostate cancers but not colon cancer. Fiber intake, when included in the analysis, affected the magnitude of the fat-cancer correlations, particularly between total fat and colon cancer. Fish omega-3 polyunsaturated fat had a nonsignificant negative association with the cancer sites studied. The findings supported hypotheses based on the results of animal experiments showing that different kinds of fatty acids have different tumor-promoting capabilities.

Early weaning of piglets induces a rapid decrease in the concentration of all plasma lipoproteins within 2 d. The decline was more progressive when 20% saturated fatty acid (lard) (SF) was added to the diet; saturated fatty acid was more effective than unsaturated fatty acid (sunflower oil) (UF). Medium-chain triglycerides had no protective effect. Intestinal synthesis of apoprotein AI was twofold higher in preweaning piglets than in adults (12.9% of total synthesis vs 5.9%, p less than 0.01) when measured in intestinal mucosa. On day 4 of weaning, synthesis was still at the preweaning level in all groups but on day 7 was maintained only by the SF diet (11.7%). We conclude that long-chain lipids, particularly saturated fatty acids, prevent a decrease in lipoproteins at weaning, mainly by maintaining intestinal apo AI synthesis at a high level.

The evidence that limiting dietary saturated fat and cholesterol will lower LDL cholesterol and contribute to the reduction in risk of cardiovascular disease is adequate for sound dietary recommendations to patients and to the public at large. Reduction of intake of all saturated fats to less than 10% of calories is a practical and achievable goal for Western man. Further reduction to less than 7% of calories is possible with a motivated and well instructed patient. The mechanism by which saturated fatty acids, particularly palmitate and laurate raise LDL cholesterol need detailed biochemical and physiologic study. Dietary cholesterol is unnecessary and clearly contributes to vascular disease in Western man. This vascular effect appears to be only partially explained by its effect on LDL cholesterol. Reduction to less than 300 mg per day for men of average size is achievable. Women and those eating fewer calories should strive for even less. Monounsaturated fats (oleic acid) can be consumed at levels of 20% of calories without significant concern if total calories are within limits to maintain desirable weight. Omega-6 polyunsaturated fats do not offer a significant health concern and need not be limited below the current intake of 7% of calories in the United States. Populations eating higher levels should be monitored to determine if such intakes are associated with either improved health or long-term ill effects since this level of intake has not been a long-standing tradition in any known culture. Omega-3 fatty acids might be increased to 2 or 3% of calories with potential benefit. Eating fish and marine animals is the most clearly documented safe method for achieving this. Larger intakes and particularly the use of fish oil supplements is unproven therapy for vascular disease prevention and needs much further study as a medical treatment for a variety of disorders. Protein intake is more than adequate in the USA and further increases could have negative effects on the prevalence of renal disease and osteoporosis. Although these issues are of hypothetical interest at the moment, they are worthy of considerable investigation. Complex carbohydrates consumed as components of vegetables, fruits and grains should be considered proven safe and healthful. Increasing calories from these sources at the expense of saturated fats and simple sugars should prove highly beneficial to Western populations. Fiber from these sources may have beneficial effects on blood cholesterol and intestinal function. Soluble fiber is documented to lower LDL cholesterol but the mechanism of this effect is not established and is worthy of considerable study.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma lipids, blood glucose, and urinary glucose excretion were measured in 270 juvenile diabetic children upon admission to and throughout periods of summer camping during which the effect of a usual and a modified diabetic diet was assessed. The usual diabetic diet contained 700-1,500 mg. cholesterol daily with a polyunsaturated/saturated (P/S) ratio of 0.1, while the modified diet limited cholesterol to 300 mg. daily with a P/S ratio of 1.0. Both diets maintained calories with 40 per cent as fat, 40 per cent as carbohydrate, and 20 per cent as protein. Analysis of fasting blood glucose, qualitative and quantitative glucose excretion, and body weight indicated that groups were comparable except for the diet used. Elevated mean levels of cholesterol and triglycerides were approximately equally distributed in diabetic children of both sexes upon admission to camp, with 24 per cent demonstrating hyperlipoproteinemia. Eleven per cent had type II, 10 per cent type IV, and 3 per cent type V hyperlipoproteinemia upon admission. After following the usual diet, 21 per cent were type II, 1 per cent type IV, and none type V, with no reduction in the over-all incidence of hyperlipoproteinemia despite lower triglyceride and glucose levels. After consumption of the modified diet, hyperlipoproteinemia was reduced to 5 per cent, with 4 per cent type II and 1 per cent type IV. Results of this study indicated that plasma lipids in juvenile diabetics were elevated when first observed and that the control of blood sugar levels along with a diabetic diet with lower cholesterol and increased polyunsaturated fat significantly reduced the incidence of hyperlipoproteinemia more effectively than control of blood sugar levels alone.

Three controlled dietary intervention studies were carried out in 1981-1983 in North Karelia, Finland, to asses the impact of dietary fat intake modification on blood pressure (BP). All these studies involved middle-aged men and women in rural or semirural areas and comprised a baseline period, a six week (or 12 weeks in the third study) intervention period and a four to six week return to baseline. During the intervention period the total fat intake was reduced from 39% to 24% of energy and the polyunsaturated/saturated (P/S) ratio increased from 0.2 to 0.4-1.2. In all groups energy intake was kept constant. For the present report data from the three studies were pooled for a series of stepwise regression analyses to predict changes in BP with different dietary changes. For both systolic (SBP) and diastolic (DBP) blood pressure, change in polyunsaturated fatty acid intake was the strongest dietary predictor of BP change. Changes in body weight, total fat intake, urinary sodium and potassium did not have significant predictive power in any of the analyses. The findings support the hypothesis that modification of dietary fat intake is a significant predictor of change in BP.

Two experiments with male turkeys were designed to study the effects of eating cooked ground beef on plasma lipid and lipoprotein levels. In both experiments, cooked ground beef from forage-finished cattle (F-Bf) and grain-finished cattle (G-Bf) were added at an average of 28.1 and 34.5 g of beef per 100 g of ration in order to provide 40% of the protein requirement. The experimental diets formulated to be isocaloric and isonitrogenous were: 1) basal diet (negative control) in which soybean meal and corn oil served as protein and fat sources, respectively; 2) basal plus crystalline cholesterol (positive control) incorporated at 1 and 2% of the diet in trials 1 and 2, respectively; 3) basal plus F-Bf; 4) basal plus G-Bf. The polyunsaturated to saturated fat ratio averaged 3.45 for diets 1 and 2 and 0.17 for diets 3 and 4, respectively. At 16 weeks, consumption of diets 3 and 4 elevated (P less than 0.05) plasma triglyceride levels and phospholipid levels (trial 1). In trial 2, only diet 4 elevated (P less than 0.05) plasma phospholipid levels. In both trials, the beef diets did not significantly elevate plasma cholesterol and high density lipoprotein (HDL) cholesterol levels above the basal diet. However, the major apoprotein in the HDL fraction, apolipoprotein A-I (apoA-I), was increased (P less than 0.05) in the plasma of male turkeys fed the G-Bf diet in both trials and F-Bf diet in trial 1. Plasma apolipoprotein B (apoB), primarily found in low density lipoproteins (LDL), was increased (P less than 0.05) in one of the two trials by the inclusion of beef in the diet. There were no significant differences in plasma cholesterol, HDL-cholesterol, apoA-I and apoB levels between the types of beef (F-Bf vs. G-Bf).

The effects of two low fat diets with differing ratios of polyunsaturated to saturated fatty acids (P/S) on blood lipids, lipoproteins (LP), and apolipoproteins (Apo) were studied in 23 adult men, 30-60 years old, using a crossover design. Both test diets had 25% fat calories with either a P/S of 0.3 (Diet 1) or a P/S of 1.0 (Diet 2) and equivalent amounts of cholesterol. The study consisted of four periods: a 5-week prestudy on self-selected diet (SS), two 6-week test diet periods followed by a second 5-week post-study period on the SS diet. When compared with the SS diet, Diet 2 lowered the mean plasma total cholesterol (TC) by about 20% (P less than 0.01). Low density lipoprotein (LDL) cholesterol was also decreased by about 18% by Diet 2 (P less than 0.01). The high P/S diet did not cause a change in total cholesterol in the high density lipoprotein (HDL) subclass2 (HDL2) when compared to the SS diet. Levels of triglycerides (TG) were slightly reduced in HDL2 but showed a greater reduction in HDL3 in both diets. Phospholipids (PL) were significantly reduced in HDL2 and in HDL3, but the reduction in HDL3 PL was not statistically significant. Apo A-I levels were not changed by either diet when compared with the SS diet, but Apo A-II levels of HDL2 and HDL3 were significantly decreased by the low fat diets, and there was no P/S effect. No other consistent changes in apoprotein levels occurred. Our data suggest that, in men with normal lipid levels, practical dietary changes involving a moderate increase in P/S from 0.3 to 1.0 in a low fat, low cholesterol diet do influence lipoprotein composition and apoprotein distribution in a short time. The reduction in cholesterol in total lipid composition and in LDL lipids which accompanied the reduction of dietary fat and cholesterol are considered to be beneficial.

Lipid-lowering diets enriched in polyunsaturated fat decrease the serum cholesterol in hyperlipoproteinaemia, usually by reducing both the low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol concentrations. The aim of the present study was to investigate whether the effects on LDL could be maintained but those on HDL cholesterol be diminished by reducing the ratio, polyunsaturated:saturated fat (P:S) of the diet. Twenty hyperlipoproteinaemic patients (six with type IIa, eight with type IIb and six with type IV) in a metabolic ward were given two fat-modified diets during two consecutive 3-week periods in a randomized order. The diets were identical with regard to nutrient composition but differed with regard to the P:S values, which were 2.0 and 1.3 respectively. The lipoprotein-lipid composition and serum apolipoprotein concentrations were similar at the end of the two dietary periods in type IIa and type IV patients but in type IIb patients a more pronounced reduction of the LDL-cholesterol concentration by 9% (P less than 0.05) was achieved on the diet with the higher P:S value. The HDL-cholesterol did not differ significantly. The results indicate that increasing the P:S value of lipid-lowering diets from 1.3 to 2.0 does not offer a great advantage with regard to the lipoprotein-lipid reductions achieved in moderate hyperlipoproteinaemia.

The Minnesota Coronary Survey was a 4.5-year, open enrollment, single end-time double-blind, randomized clinical trial that was conducted in six Minnesota state mental hospitals and one nursing home. It involved 4393 institutionalized men and 4664 institutionalized women. The trial compared the effects of a 39% fat control diet (18% saturated fat, 5% polyunsaturated fat, 16% monounsaturated fat, 446 mg dietary cholesterol per day) with a 38% fat treatment diet (9% saturated fat, 15% polyunsaturated fat, 14% monounsaturated fat, 166 mg dietary cholesterol per day) on serum cholesterol levels and the incidence of myocardial infarctions, sudden deaths, and all-cause mortality. The mean duration of time on the diets was 384 days, with 1568 subjects consuming the diet for over 2 years. The mean serum cholesterol level in the pre-admission period was 207 mg/dl, falling to 175 mg/dl in the treatment group and 203 mg/dl in the control group. For the entire study population, no differences between the treatment and control groups were observed for cardiovascular events, cardiovascular deaths, or total mortality. A favorable trend for all these end-points occurred in some younger age groups.

The effect of an increased polyunsaturated fatty acid concentration in the diet on the plasma lipoproteins from a normal group of healthy persons and from a group of hypercholesterolemic patients, consuming an isoenergetic and an isocholesterolemic diet, was examined and the changes in the plasma phospholipids were measured. Nine normal and 10 hypercholesterolemic patients were treated with a polyunsaturated diet for 1 month. Controls and hypercholesterolemic patients were screened on their lipid and lipoprotein profiles and their P/S ratio in the diet was calculated and increased with a factor 4. In the control group the P/S ratio was increased from 0.35 to 1.38 and in the hypercholesterolemic group from 0.46 to 1.59. They received the diet for at least 4 weeks before a second analysis of lipids and lipoproteins. The most important results are a decrease of plasma cholesterol, followed by a significant increase of HDL cholesterol. The cholesterol-lowering effect results largely from the plasma LDL decrease, especially in the patient group. Apo A-I is decreased accompanied by a significant increase of the ratio HDL-C/apo A-I. The observed changes are most pronounced in the hypercholesterolemic group. There is no change in apo B but a significant change in the linoleic acid concentration especially in the HDL cholesterol esters. The major phospholipids in plasma are identical in both groups and there is an identical change under the PUFA diet, sphingomyelin is increased and phosphatidylcholine is decreased, which may be related to an increase of the HDL2/HDL3 ratio.

Studies were carried out to examine the effects of dietary fat and cholesterol on cholesterol homeostasis in man. 75 12-wk studies were carried out during intake of 35% of calories as either saturated or polyunsaturated fat, first low and then high in dietary cholesterol. Dietary fat and cholesterol intakes, plasma lipid and lipoprotein levels, cholesterol absorption and sterol synthesis in isolated blood mononuclear leukocytes were measured during each diet period. In 69% of the studies the subjects compensated for the increased cholesterol intake by decreasing cholesterol fractional absorption and/or endogenous cholesterol synthesis. When an increase in plasma cholesterol levels was observed there was a failure to suppress endogenous cholesterol synthesis. Plasma cholesterol levels were more sensitive to dietary fat quality than to cholesterol quantity. The results demonstrate that the responses to dietary cholesterol and fat are highly individualized and that most individuals have effective feedback control mechanisms.