Plasma Low-density Lipoprotein Cholesterol Concentrations Research Articles

Superiority of Traditional Cooking Process forBugak(Korean Traditional Fried Dish) for Plasma Lipid Reduction

In this study, the efficacy and mode of action of the Korean traditional fried dish bugak for reducing plasma lipids are investigated. Three different studies were performed as follows: lipid-lowering effects of bugak compared with (1) different preparation methods, (2) different batters, and (3) different frying oils. Traditionally, bugak is prepared with fermented glutinous rice batter (FGR) and pan-fried in unroasted sesame oil (USSO; this preparation of bugak is referred to as FGRUSSO). FGR is prepared by placing the glutinous rice and water in a crock for 7 days at room temperature. For the study, wheat flour batter (WF) and soybean oil (SBO) were alternatively used. Low-density lipoprotein receptor knockout (LDLr⁻/⁻) mice (n=24) were fed atherogenic diets with bugak (20 g/100 g of feed) for 10 weeks. Plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) concentration and hepatic lipid accumulations decreased significantly in mice fed FGRUSSO, compared with bugak made with WF and fried in SBO (WFSBO). Protein expression of fatty acid synthesis (FAS) and 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMGCR) in the FGRUSSO group was decreased, although sterol regulatory element-binding proteins (SREBP-1 and -2) were not different. When batter differences were compared, TG concentration of mice fed bugak prepared with FGR and fried in SBO (FGRSBO) was lower than the WFSBO group due to suppression of hepatic FAS expression. In the oil comparison study, TC and LDL-C concentrations in the FGRUSSO group were lower due to attenuated HMGCR activity. In conclusion, bugak prepared by traditional cooking methods was most effective for lowering plasma TG, TC, and LDL-C via suppressing hepatic FAS and HMGCR activity, although transcription factors for regulating lipogenic enzyme expression were not significantly different.

The beneficial effect of soybean (Glycine max (L.) Merr.) leaf extracts in adults with prediabetes: a randomized placebo controlled trial.

The present study investigated the effects of soybean leaf extracts (SLEs) on blood glucose, insulin resistance, body fat and dyslipidemia in prediabetes subjects, and compared them with the effects of banaba extracts (BE) which is known to ameliorate diabetes in several animals and clinical studies. Overweight subjects with mild hyperglycemia (fasting blood glucose level of 100-125 mg dL(-1)) were randomly assigned to three groups and administered four capsules containing starch (2 g per day, Placebo), BE (300 mg per day, 0.3% corosolic acid) or SLE (2 g per day) during regular meals for 12 weeks. The SLE as well as BE significantly decreased the baseline-adjusted final blood glucose, HbA1c, HOMA-IR and transaminase levels compared to the placebo group. The body weight, BMI and WHR were not different between the groups, but the baseline-adjusted final body fat content and waist circumference were lower in the BE and SLE groups than in the placebo group. Furthermore, the baseline-adjusted final plasma triglyceride concentration was lower in the BE and SLE groups compared to the placebo group. There were no significant differences in plasma total cholesterol and LDL-cholesterol concentrations between the groups. However, the SLE, but not the BE, significantly increased the plasma HDL-cholesterol concentration and the ratio of HDL-cholesterol to total cholesterol after 12 weeks of supplementation compared to the placebo group, while the atherogenic index was decreased. Taken together, these data suggest that SLE may play an important role in improving blood glucose, insulin resistance, adiposity, and dyslipidemia in prediabetes subjects consuming their habitual diet, similar to or better than BE.

Milk minerals modify the effect of fat intake on serum lipid profile: results from an animal and a human short-term study

Despite a high content of saturated fat, evidence from observational studies indicates that the consumption of dairy products may have a neutral effect or may be inversely associated with the risk of CVD. We aimed to examine whether milk minerals modify the effect of saturated fat on serum lipid profile. We present data from two studies. Study I had a randomised, blinded, parallel design (n 24 pigs) with a 10 d adaptation period during which a high-fat diet was fed to the pigs and a 14 d intervention period during which the same diet either enriched with milk minerals (MM group) or placebo (control group) was fed to the pigs. Study II had a randomised cross-over design (n 9 men) where the subjects were fed either a high-fat diet enriched with milk minerals (MM period) or a regular diet (control period). In both the studies, blood variables were measured before and after the intervention and faecal and urine samples were collected at the end of the dietary periods. The increase in plasma total cholesterol and LDL-cholesterol concentrations but not in HDL-cholesterol concentration was markedly lowered by milk minerals in both the studies. In the animal study, baseline adjusted total cholesterol and LDL-cholesterol concentrations in the MM group were 11% (P = 0.004) and 13% (P = 0.03) lower compared with those in the control group after the intervention. Similarly in the human study, baseline adjusted total cholesterol and LDL-cholesterol concentrations were 6% (P = 0.002) and 9% (P = 0.03) lower after the MM period compared with those in the control period. HDL-cholesterol concentration was not lowered by milk minerals. These short-term studies indicate that the addition of milk minerals to a high-fat diet to some extent attenuates the increase in total cholesterol and LDL-cholesterol concentrations, without affecting HDL-cholesterol concentration.

마라소스 주원료인 고추 및 산초 에탄올추출물의 항산화 및 항비만 효과

본 연구에서는 in vitro에서 중국 사천지역 고추와 산초 에탄올추출물의 항산화 효능 확인 후, 고지방식이에 의해 유도된 비만 마우스를 이용하여 중국 사천지역 고추, 산초, 고추와 산초복합물 투여 후 체중, 간과 복부 피하지방 무게, 혈중지질 함량을 측정하여 항비만 기능성 소재로서의 가능성 여부를 조사하였다. 실험군은 일반식이군, 고지방식이군, 고지방식이에 고추 및 산초, 고추와 산초복합물, HCA(hydroxyl citric acid)를 경구투여한 군의 6군으로 분류하여 8주간 사육 후, 체중, 간, 피하지방, 혈중지질 함량을 측정한 결과는 다음과 같다. 고지방식이만을 섭취한 군은 일반식이군과 비교하여 체중, 간, 복부 피하지방, 혈장지질 농도가 현저하게 증가하였다. 고지방식이에 고추와 산초 에탄올추출물을 경구투여한 군에서 8주 후 고지방군에 비해 유의적으로 체중을 감소시켰고, 복부 피하지방 양은 고지방군 3.77 g, 고추군, 산초군, 고추와 산초복합군은 각각 0.88 g, 0.9 g, 0.97 g으로 농도 의존적으로 복부 피하지방 양을 감소시켰다(P<0.05). 혈중 중성지질, 총콜레스테롤을 농도 의존적으로 감소시켜 혈액 내 지방의 축적을 저해하였고, HDL 콜레스테롤 농도가 고지방군에 비해 고추, 산초 및 고추와 산초복합군이 농도 의존적으로 증가하여(P<0.05) 조직 중의 콜레스테롤을 간으로 운반하여 콜레스테롤의 분해 및 배설을 촉진하여 조직 중의 콜레스테롤량을 감소시켜, 고추 및 산초에탄올추출물 투여가 마우스의 비만을 억제함을 확인할 수 있었다.

Saturated fatty acids activate ERK signaling to downregulate hepatic sortilin 1 in obese and diabetic mice

Hepatic VLDL overproduction is a characteristic feature of diabetes and an important contributor to diabetic dyslipidemia. Hepatic sortilin 1 (Sort1), a cellular trafficking receptor, is a novel regulator of plasma lipid metabolism and reduces plasma cholesterol and triglycerides by inhibiting hepatic apolipoprotein B production. Elevated circulating free fatty acids play key roles in hepatic VLDL overproduction and the development of dyslipidemia. This study investigated the regulation of hepatic Sort1 in obesity and diabetes and the potential implications in diabetic dyslipidemia. Results showed that hepatic Sort1 protein was markedly decreased in mouse models of type I and type II diabetes and in human individuals with obesity and liver steatosis, whereas increasing hepatic Sort1 expression reduced plasma cholesterol and triglycerides in mice. Mechanistic studies showed that the saturated fatty acid palmitate activated extracellular signal-regulated kinase (ERK) and inhibited Sort1 protein by mechanisms involving Sort1 protein ubiquitination and degradation. Consistently, hepatic ERK signaling was activated in diabetic mice, whereas blocking ERK signaling by an ERK inhibitor increased hepatic Sort1 protein in mice. These results suggest that increased saturated fatty acids downregulate liver Sort1 protein, which may contribute to the development of dyslipidemia in obesity and diabetes.

The extended abnormalities in lipoprotein metabolism in familial hypercholesterolemia: Developing a new framework for future therapies

Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by marked elevation of plasma low-density lipoprotein (LDL) cholesterol concentrations and premature coronary artery disease (CHD). In addition to impaired LDL receptor-mediated clearance of LDL particles, in vitro and in vivo studies suggest that hepatic oversecretion of apolipoprotein (apo) B may contribute to the hypercholesterolemia in FH. This may be due to an effect of the expanded hepatic pool of cholesterol (a consequence of increased receptor-independent uptake of LDL) and/or a direct effect of the LDL receptor on apoB secretion. Hepatic oversecretion of apoB may depend on the type and severity of the genetic mutation causing FH. FH can also increase plasma Lp(a) concentration by an undefined mechanism that may not directly involve the LDL receptor pathway. Decreased catabolism of triglyceride-rich lipoproteins could also be due to deficient LDL receptor function, accounting for postprandial dyslipidemia in FH. The metabolism of high-density lipoprotein (HDL) in FH is poorly understood, but preliminary data suggest abnormal HDL composition and functionality, as well as altered transport of apoA-I. Beyond effects related to specific genetic defects in the LDL pathway, co-existing secondary causes, particularly obesity and insulin resistance, and other genetic variants may also perturb lipoprotein metabolism in individuals with FH. Furthermore, residual risk remains high in statin-treated FH. Knowledge of an extended metabolic framework will, therefore, provide the basis for judiciously selecting new pharmacotherapies to treat FH, including apoB antisense oligonucleotides, microsomal transfer protein (MTP) inhibitors and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

산약 추출물의 리포좀 처리가 Streptozotocin으로 유발된 당뇨 마우스의 혈당 강하 효과와 혈장 인슐린 및 지질에 미치는 영향

Abstract To investigate the effects of coated liposome from Discorea rhizoma extract (DRE) in streptozotocin (STZ)-induced, we evaluated changes in body weight, fasting blood glucose, blood insulin and blood lipid concentrations in mice. Mice were divided into four groups: (DC), diabetic DRE at 10 ㎎/㎏ (DRE-1), diabetic DRE at 50 ㎎/㎏ (DRE-2), and diabetic DRE at 250 ㎎/㎏ (DRE-3). Mice had free access to water and diet (10 weeks). The DC group showed higher blood cholesterol than the DRE-1, DRE-2, DRE-3 groups. In glucose tolerance test, the DRE-1, DRE-2, and DRE-3 groups increased after 30 minutes in decremental glycemic response area under the curve. Fasting blood glucose levels in the DRE groups significantly decreased through 4 weeks. Plasma total cholesterol, triglyceride and LDL-cholesterol concentrations were also lower in the DRE groups. On the other hand, the DRE-1, DRE-2 and DRE-3 groups showed higher HDL-cholesterol and insulin levels than the DC group. Moreover, blood glucose and lipid levels significantly decreased in streptozotocin (STZ)-induced diabetic mice treated with DRE. These results indicate that DRE may reduce elevated blood glucose levels and serum lipid concentrations in hypoglycemic and diabetic mice, suggesting its usefulness as a functional food.Key words: Discorea rhizoma extract, coated liposome, diabetic mice, blood insulin, blood lipid, hypoglycemic

Altered Hepatic Gene Expression Profiles Associated with Improved Fatty Liver, Insulin Resistance, and Intestinal Permeability after Hydroxypropyl Methylcellulose (HPMC) Supplementation in Diet-Induced Obese Mice

The effect of hydroxypropyl methylcellulose (HPMC) on hepatic gene expression was analyzed by exon microarray and real-time PCR from livers of diet-induced obese (DIO) mice fed a high-fat (HF) diet supplemented with either 6% HPMC or 6% microcrystalline cellulose (MCC). HPMC-fed mice exhibited significantly reduced body weight gain (55% lower compared to MCC), liver weight (13%), plasma LDL-cholesterol concentration (45%), and HF diet-increased intestinal permeability (48%). HPMC significantly reduced areas under the curve for 2 h insulin and glucose responses, indicating enhanced insulin sensitivity and glucose metabolism. HPMC up-regulated hepatic genes related to fatty acid oxidation, cholesterol and bile acid synthesis, and cellular activation of glucocorticoid (bile acid recycling) and down-regulated genes related to oxidative stress, triglyceride synthesis, and polyunsaturated fatty acid elongation. In conclusion, HPMC consumption ameliorates the effects of a HF diet on intestinal permeability, insulin resistance, hepatic lipid accumulation, glucocorticoid-related bile acid recycling, oxidative stress, and weight gain in DIO mice.

Pharmacogenomics of Lipid-Lowering Therapies

Statins are the most widely used group of lipid-lowering drugs and they have been shown to be effective in the prevention of cardiovascular disease, primarily by reducing plasma low-density lipoprotein cholesterol concentrations and possibly through other pleiotropic effects. However, there are large variations in lipid responses to statins and some patients have intolerable muscle adverse drug reactions, which may in part be related to genetic factors. In the last decade, pharmacogenetic studies on statins ranging from the candidate gene approach to the more recent genome-wide association studies have provided evidence that genetic variations play an important role in determining statin responses. This review summarizes the current understanding on the pharmacogenomics of statins and other lipid-lowering drugs in current use.

Beyond LDL Cholesterol in Assessing Cardiovascular Risk: apo B or LDL-P?

Plasma concentrations of LDL cholesterol (LDL-C)4 are positively associated with increased risk of atherosclerotic cardiovascular disease. There is a variety of robust evidence indicating that this association is causal in nature. First, rare and common genetic variants that specifically influence LDL-C concentrations are also strongly associated with cardiovascular risk (1). Second, interventions that reduce LDL-C, especially but not exclusively statin therapy, reproducibly reduce cardiovascular events (2). In fact, the data with statins are so strong that they are often used in patients whose LDL-C concentrations are not particularly increased, a setting in which statins have still been shown to reduce cardiovascular risk. Thus there is substantial interest in lipoprotein-related biomarkers that provide information about future cardiovascular risk above and beyond LDL-C itself. LDL contains a core of hydrophobic lipid, mostly cholesteryl ester, a shell of phospholipids, and single molecule of the large protein apolipoprotein B-100 (apo B). It has long been appreciated that LDL particles vary in size and density, which is largely due to variation in the amount of cholesteryl ester in the particle (3). Because the LDL-C measurement is a measure of the amount of cholesterol being carried in LDL, it is not a reliable measure of LDL particle concentration: small, dense LDL particles have much less cholesterol than large, buoyant LDL particles. Interestingly, however, there is evidence that small, dense LDL may be more atherogenic, which has led to the concept that the overall number of LDL particles may be more predictive of cardiovascular risk than the LDL-C concentration itself (3). Several methods have emerged that allow a more direct quantification of the number of LDL particles. Because an LDL particle contains a single molecule of apo B, it is possible to directly estimate the number of particles through a simple measurement of apo B …

Plasma and hepatic cholesterol-lowering effects of tomato pomace, tomato seed oil and defatted tomato seed in hamsters fed with high-fat diets

The cholesterol-lowering effects of tomato pomace (TP), tomato seed oil (TSO) and defatted tomato seed (DTS) were determined in male Golden Syrian hamsters. Hamsters fed high-fat diets containing 10% TSO or 18% DTS were compared to a diet containing 10% corn oil and 10% microcrystalline cellulose (control 1), 42% TP were compared to 25% microcrystalline cellulose (control 2). TP, TSO and DTS reduced hepatic total cholesterol (TC) content. DTS also lowered plasma TC and low-density lipoprotein cholesterol (LDL-C) concentrations. Fecal excretion of lipid, bile acid and cholesterol increased in the DTS group compared to control 1. DTS-fed hamsters had higher levels of hepatic CYP7A1, CYP51, ABCB11, and ABCG5 gene expression than control, suggesting both hepatic bile acid and cholesterol synthesis increased due to increased fecal excretion of bile acid and cholesterol. The results suggest that protein, dietary fibre or phenolic compounds in DTS may be responsible for plasma cholesterol decrease.

Atherogenic dyslipidemia and combination pharmacotherapy in diabetes: recent clinical trials.

Patients with type 2 diabetes (T2D) are at a markedly increased risk of cardiovascular disease (CVD). Dyslipidemia is a common risk factor and a strong predictor of CVD in T2D patients. Although statins decrease the incidence of CVD in T2D, residual cardiovascular risk remains high despite the achievement of optimal or near-optimal plasma low-density lipoprotein (LDL) cholesterol concentrations. This may, in part, be due to uncorrected atherogenic dyslipidemia. Hypertriglyceridemia, the driving force behind diabetic dyslipidemia, results from hepatic overproduction and/or delayed clearance of triglyceride-rich lipoproteins. In patients treated with a statin to LDL-cholesterol goals, the addition of ezetimibe, fenofibrate, niacin, or n-3 fatty acid ethyl esters may be required to correct the persistent atherogenic dyslipidemia. Clinical trial evidence describing best practice is limited, but recent data supports the strategy of adding fenofibrate to a statin, and suggests specific benefits in dyslipidemic patients and in the improvement of diabetic retinopathy. However, based on results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled LDL-cholesterol. Further evidence is required to support the role of ezetimibe and n-3 fatty acids in treating residual CVD risk in statin-treated T2D patients.

Gender May Affect the Dose-Dependent Action of Capsaicinoids on Plasma and Hepatic Cholesterol Levels of Rats

Sex differences on the effect of dose-dependent capsaicinoids on lipid metabolism were studied in rats. 24 rats of each sex were administered orally 0 mg/kg, 2.5 mg/kg, 5 mg/kg or 7.5 mg/kg capsaicinoids daily for 28 days. In male rats, body weight gained, and the levels of total lipids, total cholesterol and triglycerides in the liver were significantly decreased as the dose of capsaicinoids increased. On the other hand, plasma total cholesterol (TC), triglycerides (TG), HDL- and LDL-cholesterol concentration and liver weight were not affected by capsaicinoids. While in female rats, plasma TC, TG, HDL-C and LDL-C concentration, liver total lipids, TC and TG concentration were significantly decreased as the dose of capsaicinoids increased. The mRNA level of hepatic TRPV1, ileac ASBT and IBABP were increased as the dose of capsaicinoids increased in all rats groups. The mRNA level of hepatic HMG-CoA reductase, CYP7A1 and FXR were significantly decreased in female rats groups. These results show that the hypocholesterolemic effect of capsaicinoids in dose-dependent manner in rats was mediated by inhibited synthesis of endogenous cholesterol, female rats were more sensitive than male rats on hypolipidemic effect of capsaicinoids.

Associations Between Polymorphisms in the Glucocorticoid-Receptor Gene and Cardiovascular Risk Factors in a Chinese Population

BackgroundGlucocorticoid is an important regulator of energy homeostasis. Glucocorticoid receptor (GR) gene polymorphisms that contribute to variability in glucocorticoid sensitivity have been identified. We explored the associations of single-nucleotide polymorphisms (SNPs) of the GR gene with traditional cardiovascular risk factors in the Chinese Han population.MethodsWe recruited 762 consecutive adults who underwent a regular physical examination at Beijing Xuanwu Hospital. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), body mass index (BMI), and waist-to-hip ratio were measured. Fourteen tag SNPs and 5 functional SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Differences between genotypes/alleles for each SNP were adjusted for sex and age and tested using a general linear model procedure. Various models of inheritance, including additive, dominant, and recessive, were tested.ResultsAmong the 19 SNPs examined, 5 markers were associated with cardiovascular risk factors. The rs41423247 GG genotype and the rs7701443 AA genotype were associated with higher BMI and systolic blood pressure (P < 0.0004), and the rs17209251 GG genotype was associated with higher systolic blood pressure (P < 0.0004). Lower systolic blood pressure, total cholesterol, and LDL cholesterol were observed among rs10052957 A allele carriers (P < 0.0004), and lower plasma glucose and LDL-cholesterol concentrations were observed among rs2963156 TT carriers (P < 0.0004).ConclusionsPolymorphism of the GR gene was associated with cardiovascular risk factors and may contribute to susceptibility to cardiovascular disease.

Homozygous familial hypercholesterolemia: development and a case illustration

Familial hypercholesterolemia (FH) is a genetic disease caused by a mutation of the gene encoding for the low density lipoproteins (LDL) membrane receptor. The mutation is transmitted in an autosomal dominant mode and is manifested by permanent elevation of the plasma LDL-cholesterol concentration; such elevation is responsible for the early onset of cardiovascular complications. The other clinical manifestation is the existence of extravascular cholesterol deposits: xanthomas and corneal arcus. There are two forms of familial hypercholesterolemia: homozygous FH and heterozygous FH which is generally less severe biologically and clinically. We report in this work, a case of FH diagnosed at the laboratory of clinical chemistry of Rabat children's hospital. The lipid profile revealed a dramatic LDL-cholesterol elevation (24 mmol/L) with normal triglycerides concentration (0.84 mmol/L). The physical examination revealed cutaneous xanthomas. The diagnosis of homozygous FH was strongly suggested by family study.

Into the future: diversifying lipid management

Raised plasma LDL-cholesterol (LDL-C) concentration is a key risk factor for atherosclerosis, and statins are the most important preventive treatment. The Cholesterol Treatment Trialists' Collaboration showed a 10% reduction in all-cause mortality per 1·0 mmol/L reduction in LDL-C concentration in landmark statin trials, largely because of a reduction in coronary heart disease deaths.1 The yearly rate of myocardial infarction, coronary revascularisation, and ischaemic stroke was reduced by just over 20% per 1·0 mmol/L reduction in LDL-C concentration.

Effects of Cationic Hydroxyethyl Cellulose on Dyslipidemia in Hamsters

Cationic hydroxyethyl cellulose (cHEC) was supplemented in a high-fat diet to determine if this new soluble fiber had an effect on hypercholesterolemia and dyslipidemia associated with cardiovascular disease using Golden Syrian hamster as an animal model. Supplementation of 3-5% cHEC in a high-fat diet for 4 weeks led to significant weight gain reduction in hamsters. In addition, significant decreases in adipose and liver weights, concentrations of plasma total, VLDL, and LDL cholesterol, and hepatic lipids were shown. No significant improvements in glucose and insulin levels were observed with cHEC; however, a significant increase in plasma adiponectin and a decrease in leptin were observed. As compared with controls, 8% cHEC-fed hamsters had greater levels of mRNA for CYP7A1 (cytochrome P450 7A1; 2-fold of control; P < 0.05), CYP51 (lanosterol 14α-demethylase; 6-fold of control; P < 0.05), and LDLR (LDL receptor; 1.5-fold of control) in the liver. These findings suggest the possibility of the use of cHEC for cholesterol reduction and beneficial effects on the cardiovascular risk factors.

Marginal Vitamin B-6 Deficiency Decreases Plasma (n-3) and (n-6) PUFA Concentrations in Healthy Men and Women1–3

Previous animal studies showed that severe vitamin B-6 deficiency altered fatty acid profiles of tissue lipids, often with an increase of linoleic acid and a decrease of arachidonic acid. However, little is known about the extent to which vitamin B-6 deficiency affects human fatty acid profiles. The aim of this study was to determine the effects of marginal vitamin B-6 deficiency on fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy adults fed a 28-d, low-vitamin B-6 diet. Healthy participants (n = 23) received a 2-d, controlled, vitamin B-6–adequate diet followed by a 28-d, vitamin B-6–restricted diet to induce a marginal deficiency. Plasma HDL and LDL cholesterol concentrations, FFA concentrations, and erythrocyte and PBMC membrane fatty acid compositions did not significantly change from baseline after the 28-d restriction. Plasma total arachidonic acid, EPA, and DHA concentrations decreased from (mean ± SD) 548 ± 96 to 490 ± 94 μmol/L, 37 ± 13 to 32 ± 13 μmol/L, and 121 ± 28 to 109 ± 28 μmol/L [positive false discovery rate (pFDR) adjustedP < 0.05], respectively. The total (n-6):(n-3) PUFA ratio in plasma exhibited a minor increase from 15.4 ± 2.8 to 16.6 ± 3.1 (pFDR adjustedP < 0.05). These data indicate that short-term vitamin B-6 restriction decreases plasma (n-3) and (n-6) PUFA concentrations and tends to increase the plasma (n-6):(n-3) PUFA ratio. Such changes in blood lipids may be associated with the elevated risk of cardiovascular disease in vitamin B-6 insufficiency.

Decreased Plasma Cholesterol Concentrations After PUFA‐Rich Diets are not Due to Reduced Cholesterol Absorption/Synthesis

Plasma cholesterol concentrations increase with consumption of high saturated fatty acid (SFA) and decrease with high polyunsaturated fatty acid (PUFA) diets, leading to shifts in lipid levels consistent with reduction in heart disease risk. Direct measurements of cholesterol absorption, one of the key regulators of plasma cholesterol levels, have not been performed in humans after consumption of high PUFA diets. Thus, cholesterol absorption and fractional synthesis rates (FSRs) were measured in 16 healthy adults (8 males and 9 females) using a randomized cross-over study with a diet containing high (PUFA/SFA) P/S ratio (2:1) and a low P/S ratio (0.5:1). Cholesterol absorption and fractional cholesterol synthetic rates were measured using stable isotopes after 20 days of dietary intervention. Diet did not affect cholesterol absorption or synthesis. There was a significant decrease in plasma cholesterol concentrations (P < 0.02), specifically LDL-cholesterol (P < 0.02), without a change in HDL-cholesterol or triacylglycerol concentrations. Intraluminal cholesterol solubilization and plasma sterol (cholesterol biosynthetic intermediates and plant sterols) levels were not affected by diet. Thus, consumption of diets with a high P/S ratio reduces plasma total and LDL-cholesterol concentrations independent of shifts in cholesterol absorption or synthesis.

Milk phospholipid and plant sterol-dependent modulation of plasma lipids in healthy volunteers

Hypolipidemic and/or hypocholesterolemic effects are presumed for dietary milk phospholipid (PL) as well as plant sterol (PSt) supplementation. The aim was to induce changes in plasma lipid profile by giving different doses of milk PL and a combination of milk PL with PSt to healthy volunteers. In an open-label intervention study, 14 women received dairy products enriched with moderate (3 g PL/day) or high (6 g PL/day) dose of milk PL or a high dose of milk PL combined with PSt (6 g PL/day + 2 g PSt/day) during 3 periods each lasting 10 days. Total cholesterol concentration and HDL cholesterol concentration were reduced following supplementation with 3 g PL/day. No significant change in LDL cholesterol concentration was found compared with baseline. High PL dose resulted in an increase of LDL cholesterol and unchanged HDL cholesterol compared with moderate PL dose. The LDL/HDL ratio and triglyceride concentration remained constant within the study. Except for increased phosphatidyl ethanolamine concentrations, plasma PL concentrations were not altered during exclusive PL supplementations. A combined high-dose PL and PSt supplementation led to decreased plasma LDL cholesterol concentration, decreased PL excretion, increased plasma sphingomyelin/phosphatidyl choline ratio, and significant changes in plasma fatty acid distribution compared with exclusive high-dose PL supplementation. Milk PL supplementations influence plasma cholesterol concentrations, but without changes of LDL/HDL ratio. A combined high-dose milk PL and PSt supplementation decreases plasma LDL cholesterol concentration, but it probably enforces absorption of fatty acids or fatty acid-containing hydrolysis products that originated during lipid digestion.