Regional specific effect of saturated vs unsaturated fat on leptin receptor signalling in mice brain areas regulating feeding.

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.

The therapeutic effect of PEGlated nanoliposome of pistachio unsaturated oils and its efficacy to attenuate inflammation in multiple sclerosis: A randomized, double-blind, placebo-controlled clinical trial phase I.

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.

Replacing Saturated Fats with Unsaturated Fats from Walnuts or Vegetable Oils Lowers Atherogenic Lipoprotein Classes Without Increasing Lipoprotein(a).

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.

Dietary lipid unsaturation influences survival and oxidative modifications of an amyotrophic lateral sclerosis model in a gender-specific manner.

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.

Saturated fat, carbohydrates and cardiovascular disease.

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.

Dietary fat in infancy should be more focused on quality than on quantity.

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.

Effect of low-saturated fat, low-cholesterol dietary intervention on fatty acid compositions in serum lipid fractions in 5-year-old children. The STRIP project.

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.

Maternal body weight gain and fetus development of rats fed a moderately altered olive oil.

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.

Whole body and hepatic cholesterol synthesis rates in the guinea-pig: effect of dietary fat quality.

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.

Types of dietary fat and the incidence of cancer at five sites.

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.

Influence of dietary lipids on serum apoproteins AI and B and on intestinal synthesis of apo AI in the early weaning of piglets: comparison of saturated, unsaturated, and medium-chain triglycerides.

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.

Dietary recommendations to prevent coronary heart disease.

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)

Influence of caffeine consumption on 7,12-dimethylbenz(a)anthracene-induced mammary gland tumorigenesis in female rats fed a chemically defined diet containing standard and high levels of unsaturated fat.

The effect of caffeine (430-500 mg/liter of drinking water) on the initiation and promotion phases of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland tumorigenesis in female Sprague-Dawley rats fed a chemically defined diet containing standard (5%) or high (20%) levels of fat (corn oil) was examined. In the initiation studies, caffeine and the standard or high fat diet treatments were provided for 34 days, from 24-29 days of age to 58-63 days of age. Three days prior to termination of caffeine-fat diet treatments, each rat received a single dose of DMBA. In the promotion studies, caffeine and the standard or high fat diets were provided commencing 3 days after a single dose of DMBA (at 56-61 days of age) and until termination of the study. Caffeine consumption, during the initiation phase significantly (P less than 0.05) reduced mammary carcinoma multiplicity (number of tumors/rat), in rats fed either a standard or high fat diet. In the promotion studies, prolonged consumption of caffeine in rats fed either a standard or high fat diet did not significantly effect mammary carcinoma multiplicity. In the early stages of promotion, an apparent increase in mammary carcinoma multiplicity was observed; this increase in mammary carcinoma multiplicity did not, however, reach the 5% level of statistical probability. When caffeine was administered during both the initiation and promotion phases, no significant effect on mammary carcinoma multiplicity was observed. Treatment of rats during the initiation or promotion phases with caffeinated coffee (via drinking water) mimicked the mammary tumor modulating activities of caffeine. Decaffeinated coffee consumption did not effect either the initiation or promotion phases of this tumorigenic process. In both the initiation and promotion studies, caffeine and/or coffee consumption did not significantly affect the incidence of mammary carcinomas (percentage of rats bearing mammary carcinomas) or the mean latency period of mammary tumor appearance. Thus, in female rats fed a chemically defined standard or high fat diet, caffeine consumption can significantly influence chemical carcinogenesis of the mammary gland; an effect that is dependent upon the duration and time-span of caffeine administration.

Serum triglycerides and HDL cholesterol from SHR after evening primrose oil and other polyunsaturated fats.

Spontaneously hypertensive rats (SHR) were fed diets enriched with evening primrose (EPO), sunflower (SO) and linseed oils (LO) as well as palm kernel fat (PKF), the latter being deficient in polyunsarated fatty acids (PUFA). In SHR fed EPO serum triglycerides were lowest and HDL1 cholesterol was highest as compared to the other groups of animals. Total cholesterol was not different. The data suggest that - as with blood pressure - serum lipids and lipoproteins might be influenced most effectively by EPO in comparison to other polyunsaturated fats.

Effects of low fat diets varying in P/S ratio on nutrient intakes, fecal excretion, blood chemistry profiles, and fatty acids of adult men.

Twenty-three apparently healthy volunteers aged 35 to 60 years consumed closely monitored self-selected (SS) diets for five weeks followed by two low fat controlled diets (25% energy) for two six-week periods followed by another five-week SS diet. The two low fat diets, fed in a crossover design to one-half of the subjects per controlled diet period, had a polyunsaturated/saturated (P/S) fat ratio of either 0.3 or 1.0. Results are reported for bi-weekly measurements of energy and nutrients; blood profiles and plasma fatty acids; and for end-of-period values for stool characteristics. Blood chemistry profiles differed in the two groups. The low P/S diet produced significant increases not only in cholesterol, but in 16:0, 16:1, and percent saturated fatty acids and decreases in 18:2 and omega 6 fatty acids. The reverse was seen with the high P/S diet. The essential fatty acid (EFA) linoleic acid returned in the poststudy period to prestudy levels (all subjects), but arachidonic acid did not. The explanation for negative correlation between magnesium intake or excretion and percent plasma linoleic acid must await further research.

Increased cholesteryl ester content in liver of mice fed lipid emulsion diets high in polyunsaturated fats.

Mice were fed a liquid diet containing different fat sources for 6 days and several biochemical parameters in the liver were examined. Mice fed diets containing Nutralipid or Liposyn as 45% of total calories had 30.5 +/- 2.5 and 25.8 +/- 3.7 nmol cholesteryl esters per milligram liver protein, respectively, as compared with 13.14 +/- 2.4 for those fed regular mouse food and 13.7 +/- 2.45 for those fed an emulsion containing mostly triolein as fat source. A similar increase in liver cholesteryl esters resulting from estrogen treatment has been proposed as the basis for changes resulting in decreased bile flow in the rat. It is suggested that the high content of polyunsaturated fatty acids in nutrient emulsions might be responsible for cholestasis sometimes observed in patients receiving these preparations. This is further supported by the observation that, as in the case of estrogen treatment, the cholesteryl ester level returned to normal when mice were treated with the detergent Triton WR-1339.

Concentration and composition of serum lipoproteins during a low-fat diet at two levels of polyunsaturated fat.

A 12-week dietary intervention was carried out among 40 families from North Karelia, a county in Finland with an exceptionally high rate of coronary heart disease and high serum cholesterol values. The proportion of dietary energy derived from fat was reduced during the 12-week intervention period from about 39% to 23% in all families. The families were randomly allocated into two groups. Twenty families consumed a diet with a polyunsaturated to saturated fat (P/S) ratio of 0.9 (group I), while the other 20 families had a diet with a P/S ratio of 0.4 (group II). Total serum cholesterol decreased by 16% and 9% in men of groups I and II, respectively, and by 16% in women of both groups. These changes were due to a decrease in both low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. LDL cholesterol and phospholipid reached minimum values after 6 weeks on both intervention diets, but LDL protein responded more slowly. Thus, after 6 weeks LDL had an altered composition containing less cholesterol and phospholipids and more protein and triglycerides than during the baseline diet. During the intervention, the linoleic acid content in the serum cholesteryl ester fraction increased, and the magnitude of this change correlated negatively with the changes in total and LDL cholesterol. The decrease in HDL cholesterol during the two intervention diets was due to a fall in the HDL2 cholesterol (29% and 24% in men, and 26% and 25% in women in groups I and II, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of polyunsaturated isocaloric fat diets on plasma lipids, apolipoproteins and fatty acids.

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.

Similar serum lipoprotein reductions by lipid-lowering diets with different polyunsaturated:saturated fat values.

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.