Nutritional Treatment in a Cohort of Pediatric Patients with Familial Hypercholesterolaemia: Effect on Lipid Profile.

Background and aims: Familial Hypercholesterolaemia (FH) is characterised by a genetic alteration in the transport and metabolism of cholesterol that leads to elevated levels of total cholesterol (CT) and low-density lipoprotein cholesterol (LDL-C) and early onset of atherosclerosis. According to the current guidelines, diet and promotion of healthy habits are first-line treatments. Little is known about the effectiveness of cholesterol-lowering diet and healthy lifestyle habits on plasma cholesterol and lipid profile in children and adolescents with FH. The aim of the study is to investigate the effect of the nutritional counseling on plasma lipid profile in FH children at the first step of treatment. Methods: 115 FH children (2−17 years) were included in the study; dietary habits were evaluated through a Food Frequency Questionnaire (FFQ) and blood samples for lipid profile were collected at the enrollment (T0) and six months later (T1). Results: the lipid profile at T0 and T1, expressed as mean ± standard deviation in mg/dL, was, respectively: total cholesterol 285.9 ± 51.1 and 276.6 ± 46.8 (paired test difference p value < 0.01), LDL-cholesterol 214.9 ± 47.7 and 206.4 ± 46.6 (p value < 0.01), HDL-cholesterol 52.9 ± 13 and 54.4 ± 11.5 (p value 0.07), triglycerides 87 ± 46.7 and 82.2 ± 38.4 (p value 0.4), non-HDL cholesterol 233 ± 51.4 and 222.2 ± 47.4 (p < 0.01). In the dietary habits (weekly portions) we observed an improvement (p ≤ 001) for fruit and vegetables, fish, pulses, whole foods, and a reduction (p < 0.01) for meat, sausages, cheese, junk foods consumption. Conclusions: In FH children we have highlighted an improvement of the plasma lipid profile and in healthy dietary habits after nutritional counseling.

Una visión genética de la hipercolesterolemia familiar / A genetic view of familial hypercholesterolemia

Objetivo: mostrar información revisada de manera sistemática de estudios publicados relacionados con la hipercolesterolemia familiar (HF), la nutrición y los genes que intervienen en el desarrollo de esta patología. Resultados: el análisis de los resultados de investigación consultados pone de manifiesto que la hipercolesterolemia familiar es un trastorno que se produce debido a mutaciones en genes que codifican el receptor de LDL, que se puede transmitir de forma autosómica dominante o bien autosómica recesiva. La importancia de su diagnóstico radica en que las personas afectas presentan una elevada frecuencia de enfermedad coronaria prematura, reduciéndose de forma importante su expectativa de vida. Conclusiones: no existen criterios clínicos específicos con un valor predictivo absoluto para el diagnóstico de HF; el diagnóstico genético permite demostrar defectos funcionales en el gen del receptor LDL, constituyendo la confirmación definitiva del diagnóstico, de ahí la importancia de presentar una visión genética del desarrollo de esta patología, que puede ser tratada para generaciones futuras de manera adecuada a través de la dietoterapia en la familia afectada (AU)

Objective: to show reviewed information of published studies relating to Familial Hypercholesterolemia (FH), nutrition, and genes involved in the development of this pathology. Results: an analysis showing familial hypercholesterolemia as a disorder occuring due to mutations in gene encoding of the LDL receptor, which can be transmitted as an autosomal dominant or autosomal recessive. It’s diagnosis is important for those with a greater likelihood of premature coronary disease, and can significantly reduce life expectancy. Conclusions: there are no specific clinical criteria with absolute predictive value for the diagnosis of HF, Genetic diagnosis can prove functional defects in the LDL receptor gene, constituting definitive confirmation of the diagnosis, thus the importance of presenting a genetic vision of development of this disease, which can be treated adequately through diet therapy affecting future generations in the family concerned (AU)

Plasma cholesterol-lowering activity of dietary dihydrocholesterol in hypercholesterolemia hamsters.

OBJECTIVE: Cholesterol analogs have been used to treat hypercholesterolemia. The present study was to examine the effect of dihydrocholesterol (DC) on plasma total cholesterol (TC) compared with that of ß-sitosterol (SI) in hamsters fed a high cholesterol diet. METHODS AND RESULTS: Forty-five male hamsters were randomly divided into 6 groups, fed either a non-cholesterol diet (NCD) or one of five high-cholesterol diets without addition of DC and SI (HCD) or with addition of 0.2% DC (DA), 0.3% DC (DB), 0.2% SI (SA), and 0.3% SI (SB), respectively, for 6 weeks. Results showed that DC added into diet at a dose of 0.2% could reduce plasma TC by 21%, comparable to that of SI (19%). At a higher dose of 0.3%, DC reduced plasma TC by 15%, less effective than SI (32%). Both DC and SI could increase the excretion of fecal sterols, however, DC was more effective in increasing the excretion of neutral sterols but it was less effective in increasing the excretion of acidic sterols compared with SI. Results on the incorporation of sterols in micellar solutions clearly demonstrated both DC and SI could displace the cholesterol from micelles with the former being more effective than the latter. CONCLUSION: DC was equally effective in reducing plasma cholesterol as SI at a low dose. Plasma TC-lowering activity of DC was mediated by inhibiting the cholesterol absorption and increasing the fecal sterol excretion.

Effect of a low-fat diet enriched either with rapeseed oil or sunflower oil on plasma lipoproteins in children and adolescents with familial hypercholesterolaemia. Results of a pilot study.

BACKGROUND/OBJECTIVES: There is convincing evidence that unsaturated fatty acids exert favourable effects on plasma cholesterol levels. However, it is not clear which type of oil has the most pronounced effect, especially not in paediatric patients. The aim was to compare two low-fat diet regimes enriched with either monounsaturated fatty acids by rapeseed oil (RO) or polyunsaturated fatty acids by sunflower oil (SO) in children affected with familial hypercholesterolaemia (FH). SUBJECTS/METHODS: Twenty-one children aged 6-18 years affected with FH were enrolled in this randomized and double-blind pilot trial. The subjects and their families were trained to adhere to a low-fat/low-cholesterol diet. All visible fats were to be replaced by either RO or SO (14-27 g/day) for 13 weeks. Dietary adherence was controlled by repeated 4-day dietary records; plasma lipids, lipoproteins and risk markers were assessed at baseline and post-intervention. Out of 21 subjects, 16 could be followed-up after 6 months. RESULTS: Both fat-modified diets resulted in significant reduction in total cholesterol concentrations of 9.4% (RO P<0.005 vs SO P<0.05) and low-density lipoprotein (LDL) cholesterol concentrations of 12.7% (P<0.005) for RO and 11.3% (P<0.05) for SO. The reduction of the LDL/high-density lipoprotein (HDL) cholesterol ratio (RO 9% vs SO 3.5%) and high-sensitivity C-reactive protein (RO 16.8% vs SO 1.7%) were not statistically significant, respectively. In most participating families, a change in eating habits could be observed. CONCLUSIONS: A fat-modified diet enriched with RO seems to have very similar effects on cholesterol levels as with SO. However, our study suggests that RO has possibly more favourable effects concerning cardiovascular risk profile. Both diets appear to be feasible and were well accepted among our subjects. Although these results are promising, larger trials will be required to validate our findings.

Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia.

BACKGROUND: A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolaemia (FH). However, a consensus has yet to be reached on the most appropriate dietary treatment. Plant sterols are commonly used in FH although patients may know them by other names like phytosterols or stanols. OBJECTIVES: To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register, which is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated with each new issue of The Cochrane Library), quarterly searches of MEDLINE and the prospective handsearching of one journal - Journal of Inherited Metabolic Disease. Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 22 August 2013. We also searched PubMed to 05 February 2012. SELECTION CRITERIA: Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial eligibility and risk of bias and one extracted the data, with independent verification of data extraction by a colleague. MAIN RESULTS: In the 2014 update of the review, 15 trials have been included, with a total of 453 participants across seven comparison groups. The included trials had either a low or unclear risk of bias for most of the parameters used for risk assessment. Only short-term outcomes could be assessed due to the short duration of follow up in the included trials. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included trials. No significant differences were noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found for the following comparisons and outcomes: for the comparison between plant sterols and cholesterol-lowering diet (in favour of plant sterols), total cholesterol levels, mean difference 0.30 mmol/l (95% confidence interval 0.12 to 0.48); decreased serum LDL cholesterol, mean difference -0.60 mmol/l (95% CI -0.89 to -0.31). Fasting serum HDL cholesterol levels were elevated, mean difference -0.04 mmol/l (95% CI -0.11 to 0.03) and serum triglyceride concentration was reduced, mean difference -0.03 mmol/l (95% CI -0.15 to -0.09), although these changes were not statistically significant. Similarly, guar gum when given as an add on therapy to bezafibrate reduced total cholesterol and LDL levels as compared to bezafibrate alone. AUTHORS' CONCLUSIONS: No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, for the primary outcomes: evidence and incidence of ischaemic heart disease, number of deaths and age at death,due to the lack of data on these. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein, dietary fibers to a cholesterol-lowering diet.

Lowering LDL cholesterol with margarine containing plant stanol/sterol esters: is it still relevant in 2011?

Recommendations about the use of plant stanol/sterol esters have not been updated since 2001. There have been many developments in medicines for lipid-lowering since 2001. In this review, the use of margarines containing stanol or sterol esters, to lower LDL cholesterol is considered in the 2011 setting. Firstly, there is a brief overview of the effects of the stanols/sterols on LDL cholesterol, which shows that these agents have a modest ability to lower LDL cholesterol, and are not effective in all conditions. Secondly, the relevance of the stanols/sterols in 2010/1 is questioned, given they have not been shown to reduce clinical endpoints, and have no effects on HDL cholesterol or triglyceride levels. Finally, there is a section comparing the stanols/sterols with the present day prescription lipid lowering medicines. Prescription drugs (statins, ezetimibe, and niacin) have a much greater ability to lower LDL cholesterol than the stanol/sterol esters, and also increase levels of HDL cholesterol and decrease levels of triglycerides. The statins and niacin have been shown to reduce cardiovascular clinical endpoints. Except in borderline normo/hypercholesterolemia, prescription drugs should be preferred to stanol/sterol esters for lowering LDL cholesterol in 2011.

A fish-oil-rich diet reduces vascular oxidative stress in apoE(-/-) mice.

Oxidative stress contributes to lipid peroxidation and decreases nitric oxide (NO) bioavailability in atherosclerosis. While long-chain (n-3) polyunsaturated fatty acids (PUFA) are easily oxidized in vitro, they improve endothelial function. Hence, this study postulates that long-chain (n-3) PUFA decrease atherogenic oxidative stress in vivo. To test this, apoE(-/-) mice were fed a corn oil- or a fish oil (FO)-rich diet for 8, 14 or 20 weeks and parameters related to NO and superoxide (O(2)(.-)) plus markers of lipid peroxidation and protein oxidative damage in the aortic root were evaluated. The FO-rich diet increased NO production and endothelial NO synthase (NOS) expression and lowered inducible NOS, p22(phox) expression and O(2)(.-)production after 14 and 20 weeks of diet. Protein lipoxidative damage (including 4-hydroxynonenal) was decreased after a long-term FO-diet. This supports the hypothesis that a FO-rich diet could counteract atherogenic oxidative stress, showing beneficial effects of long-chain (n-3) PUFA.

Dietary treatment for familial hypercholesterolaemia.

BACKGROUND: A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolemia. However, a consensus has yet to be reached on the most appropriate dietary treatment. OBJECTIVES: To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register.Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 09 October 2009.We also searched PubMed till 01 June 2008. SELECTION CRITERIA: Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial eligibility and methodological quality and one extracted the data, with independent verification of data extraction by a colleague. MAIN RESULTS: In the present update, four new trials have been added making eleven trials with a total of 331 participants eligible for inclusion. Only short-term outcomes could be assessed due to the short duration of follow up in the included studies. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included studies. No significant difference was noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found only for the following comparison and outcome: total cholesterol levels for the comparison between plant sterols and cholesterol-lowering diet, mean difference 0.70 (95% confidence interval 0.19 to 1.21). AUTHORS' CONCLUSIONS: No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, due to the lack of adequate data. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein to a cholesterol-lowering diet.

Effect of 3-month treatment of children and adolescents with familial and polygenic hypercholesterolaemia with a soya-substituted diet.

Soya protein has well-documented beneficial effects on serum lipid levels in adults, the potential beneficial effect of a prolonged soya protein-substituted diet in children and adolescents with familial (FH) and polygenic hypercholesterolaemia (PH) being unknown. To assess the effect of 3 months' treatment of children and adolescents with FH and PH with a soya-substituted diet on serum lipids and lipoproteins, twenty-three children and adolescents were initially assigned to a standard phase 1 diet for 3 months, after which they were instructed to include soya protein (0.25-0.5 g/kg body weight) into their diet for 3 months. Sixteen patients (ten males and six females, thirteen with FH (eight males and five females), three with PH (two males and one female); mean age 8.8 (sd 4.2) years (range 4-18 years); mean BMI 16.7 (sd 2.6) kg/m2)) completed both phases. The phase 1 diet resulted in a significant reduction of total cholesterol (TC), LDL-cholesterol and apo B by 12.3, 11.8 and 10.6 %, respectively, HDL-cholesterol, TAG, apo A1 and lipoprotein(a) not being different. Dietary intake of soya protein during phase 2 resulted in a significant decrease of TC, LDL-cholesterol and apo B by 7.7, 6.4, and 12.6 %, respectively. TAG, HDL-cholesterol, apo A1, and lipoprotein(a) did not change significantly. Substitution of soya protein for animal protein in a low-fat, fat-modified diet is of additional benefit in many, but not all, children and adolescents with FH and PH when aiming at lowering serum TC, LDL and apo B. It seems to be a feasible long-term dietary lifestyle intervention and may grant additive benefit in the prevention of early vascular disease.

Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing.

Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.

OBJECTIVE: The primary objective of this study was to determine whether the National Cholesterol Education Program Step II (NCEP-II) diet or supplementation with docosahexaenoic acid (DHA) with the diet, affects endothelial function in children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). As secondary endpoints, the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, were all evaluated. METHODS: In a double-blind, placebo-controlled, randomized, crossover study design, 20 children (ages 9-19 years) with FH (n = 12) and FCH (n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II (NCEP-II) and food guide pyramid dietary guidelines for 6 weeks. They were then randomly assigned to supplementation with docosahexaenoic acid (DHA 1.2 g/d) or placebo for 6 weeks, followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound. Plasma levels of total cholesterol, triglycerides and lipoprotein classes (LDL, HDL, VLDL) were measured by ultracentrifugation and enzymatic methods, plasma F2 isoprostanes by gas chromatography/mass spectrometry, urinary 8-OH-2' deoxyguanosine by liquid chromatography, high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography. RESULTS: FMD increased significantly after DHA supplementation compared to baseline (p < 0.001), diet alone (p < 0.002), placebo (p < 0.012) and washout (p < 0.001) phases of the study without affecting biomarkers for oxidative stress, inflammation or ADMA. DHA supplementation was associated with increased levels of total cholesterol (p < 0.01), LDL- and HDL cholesterol concentrations (p < 0.001) compared to the NCEP-II diet. CONCLUSION: This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children. The endothelium may thus be a therapeutic target for DHA. This is consistent with a hypothesis of increasing NO bioavailability, with the potential for preventing the progression of early coronary heart disease in high-risk children.

Prickly pear induces upregulation of liver LDL binding in familial heterozygous hypercholesterolemia.

BACKGROUND: The hypoglycemic effect of prickly pear is well known by native local Indian population since a long time. Beside the beneficial effects on lipid metabolism, oxidation injury and platelet function has been claimed in experimental animals. We recently found an upregulation of apo-B/E receptor. MATERIAL AND METHODS: We therefore examined 10 patients with isolated heterozygous familial hypercholesterolemia (FH) being enrolled in a dietary run-in phase of 6 weeks after dietary counselling and a further 6 weeks of prickly pear addition. Uptake of autologous (123)I-radiolabeled LDL was determined at entry as well as after 6 weeks of daily prickly pear ingestion. RESULTS: We found a significant (p < 0.0001) increase in LDL-uptake by the liver (24.5 +/- 4.9 vs. 31.1 +/- 5.2%) and an enhanced decay in circulating blood. Total (298.0 --> 268.0 mg/dl; p < 0.0001) and LDL-cholesterol (210.5 --> 176.4 mg/dl; p = 0.0001) were significantly affected, while HDL (p = 0.0629) and triglycerides were not. CONCLUSIONS: These findings demonstrate a significant upregulation of (123)I-LDL binding by prickly pear in FH-patients invivo and indicate that prickly pear exerts a significant hypolipidemic action via receptor upregulation.

Daily prickly pear consumption improves platelet function.

Prickly pear is traditionally used by Pima Indians as a dietary nutrient against diabetes mellitus. We examined the effect of daily consumption of 250 g in 8 healthy volunteers and 8 patients with mild familial heterozygous hypercholesterolemia on various parameters of platelet function. Beside its action on lipids and lipoproteins, prickly pear consumption significantly reduced the platelet proteins (platelet factor 4 and beta-thromboglobulin), ADP-induced platelet aggregation and improved platelet sensitivity (against PGI2 and PGE1) in volunteers as well as in patients. Also plasma 11-DH-TXB2 and the WU-test showed a significant improvement in both patients and volunteers. In contrast, collagen-induced platelet aggregation and the number of circulating endothelial cells showed a significant response in patients only. No influence of prickly pear ingestion on peripheral platelet count was monitored. The dietary run-in period did not influence any of the parameters of haemostasis examined. No sex difference was seen. Prickly pear may induce at least part of its beneficial actions on the cardiovascular system via decreasing platelet activity and thereby improving haemostatic balance.

Effect of a rapeseed oil substituting diet on serum lipids and lipoproteins in children and adolescents with familial hypercholesterolemia.

OBJECTIVE: Familial hypercholesterolemia (FH) is a predominantly inherited disorder, which contributes to a defect of the LDL-cholesterol receptor. For adults with familial hypercholesterolemia (FH), it is known that a supplementary diet of monounsaturated fatty acids reduces elevated levels of total cholesterol and LDL-cholesterol and may further increase HDL-cholesterol. In particular the reduced intake of dietary fat reduces total serum cholesterol and LDL-cholesterol in the range of 10% to 15% and inhibits LDL-oxidation. Once the diagnosis of familial hypercholesterolemia is made in early childhood a supplementary diet with rapeseed oil should be started as early as possible to prevent development of atherosclerosis and subsequent complications. So far there are no reports of a lipid lowering diet enriched with rapeseed oil in children and adolescents. METHODS: Seventeen children and young adolescents (male = 6, female = 11, ages 4 to 19 years) diagnosed with FH were enrolled in this study. They received dietary training and a classical low fat/low cholesterol diet enriched with rapeseed oil over five months. In the first two months they received orally mean 15 g/day (8-23 g/day), for the remaining three months mean 22 g/day (15-30 g/day) rapeseed oil. The calculation of the three-days dietary protocols showed the following characteristics: 29.5% calories from fat, 14.3% calories from protein and 54.6% calories from carbohydrates. The subjects had six sessions of dietary counseling, and serum lipids levels and lipoprotein(a) were estimated; each month's diet adherence was controlled by a dietitian and discussed with the patients and their families during this five-month study. RESULTS: During five months of rapeseed oil diet serum triglycerides decreased by 29% (119.2+/-62.8 mg/dL vs. 84.9 mean +/- 39.7 mg/dL), VLDL-cholesterol by 27% (23+/-12 mg/dL vs. 17+/-8 mg/dL), total cholesterol by 10% (233+/-35 mg/dL vs. 213+/-36 mg/dL), LDL-cholesterol by 7% (151+/-31 mg/dL vs. 142+/-31 mg/dL). HDL-cholesterol (59+/-15 mg/dL vs. 57+/-11 mg/dL) and Lp(a) (29.8+/-36.3 mg/dL vs. 32.6+/-40.7 mg/dL) were not changed significantly. The diet was well accepted; in most families a sustained change was reported. CONCLUSIONS: Our results indicate that in children and adolescents with FH a lipid-lowering diet with rapeseed oil has a similar effect on total serum cholesterol and LDL-cholesterol compared to classical cholesterol reduction diets (step I). However, an additional pronounced effect on lowering of triglycerides and VLDL-cholesterol can be observed.

Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread.

Plant sterols may be a useful additive therapy in the treatment of hypercholesterolaemic patients. The purpose of this study was to determine the effect of a fat spread enriched with vegetable oil sterols on plasma lipid, lipoprotein and apolipoprotein concentrations. A randomised double blind placebo-controlled crossover trial with two consecutive periods of 8 weeks was conducted. 30 patients with heterozygous familial hypercholesterolaemia treated concurrently with an HMG-CoA reductase inhibitor (statin) and 32 patients with type IIa primary hypercholesterolaemia with a total cholesterol concentration >6.5 mmol/l not taking lipid-lowering drug therapy were recruited from a hospital lipid clinic. The active treatment was a fortified fat spread (25 g/day) providing 2.5 g of plant sterols. The control spread was indistinguishable in taste and appearance. Comparison at the end of the two 8-week trial periods showed a statistically significant reduction in total and LDL-cholesterol with use of the fortified spread but the results were confounded by a carry-over effect, which was partly explained by changes in the background diet. Because a carry-over effect was present, further analyses were restricted to the parallel arms of the first treatment period and were conducted on an intention to treat basis. After 4 weeks, LDL-cholesterol had decreased by 0.04 mmol/l ([0.8%] 95% confidence interval -0.44-0.37 NS) in the placebo group and decreased by -0.76 mmol/l ([15.0%] 95% CI -1.03--0.48, P<0.0001) in the active treatment group. After 8 weeks, the corresponding results were 0.0 mmol/l ([0.0%] 95% CI -0.26-0.24 NS) and -0.51 mmol/l ([10.0%] 95% CI -0.73--0.29 P<0.0001). There were no significant changes in apolipoprotein AI or B concentrations in the placebo group, but there was a small but statistically significant increase in apolipoprotein AI and a decrease in apolipoprotein B in the active treatment group. HDL cholesterol and triglyceride concentrations were unchanged. There was no difference in response between patients with statin-treated familial hypercholesterolaemia and patients with type IIa hyperlipoproteinaemia. We conclude that a fortified fat spread enriched with vegetable oil sterols reduces LDL-cholesterol by 10-15% with no difference in response between hypercholesterolaemic patients prescribed statins and those not taking lipid-lowering drug therapy.

Effects of fish oil supplementation on platelet survival and ex vivo platelet function in hypercholesterolemic patients.

Little is known about the effects of dietary supplementation on platelet survival with low doses of n-3 and n-6 fatty acids in patients with hypercholesterolemia. The effects of a 6-week intervention with fish oil capsules (daily intake: 216 mg eicosapentaenoic acid, 140 mg docosahexaenoic acid, 390 mg gamma-linolenic acid, and 3480 mg linoleic acid) on in vivo platelet survival (111 In-oxine labeled platelets) and on ex vivo markers of platelet activation were investigated in a placebo-controlled, double-blind study with 26 hypercholesterolemic patients. In vivo platelet survival increased in the fish oil group (T) from a mean of 159+/-14 hours to a mean of 164+/-12 hours (p=0.025), whereas it remained unchanged in the placebo (P) group (T vs. P; p=0.055). Ex vivo, thromboxane B2 decreased from a mean of 225+/-16 to 212+/-21 ng/mL (p=0.003) in T but did not change in P (T vs. P: p=0.002). Malondialdehyde formation was lowered significantly by fish oil supplementation from a mean of 5.49+/-1.3 to 5.12+/-1.05 nM/10(9) platelets, p=0.005, as compared with P (T vs. P; p=0.018). The trendwise decrease in 11-DH-thromboxane B2 plasma levels was not significant nor was the increase in platelet sensitivity to prostaglandin I2 by fish oil. Baseline platelet survival in patients with hyperlipoproteinemia type IIa was not different from those with hyperlipoproteinemia IIb and response to treatment in terms of platelet activation markers was not either. The changes in platelet activation parameters in T were associated with significant reductions in cholesterol (-2.9%), low density lipoprotein cholesterol (-3.5%), and triglycerides (-12.4%). Both ex vivo and in vivo platelet activation parameters exhibited signs of decreased activation by a 6-week diet supplemented with n-3 and n-6 fatty acids, which might be beneficial in reducing atherothrombotic risk, in patients with hyperlipoproteinemia type IIa and IIb.

[Comparative study on the effect of antiatherosclerotic diet enriched with polyunsaturated omega-3 fatty acids of plant and animal origin on the level of natural antibodies against catecholamines in patients with cardiovascular diseases]. / Sravnitel'nyi analiz vliianiia protivoateroskleroticheskikh diet, obogashchennykh PNZhK omega-3 pastitel'nogo i zhivotnogo proiskhozhdeniia na uroven' estestvennykh antitel k katekholaminam u bol'hykh serdechno-sosudistymi zabolevaniiami.

The levels of natural antibodies against catecholamines in 138 patients with cardiovascular diseases was studied and the comparative analysis of influence of antiatherosclerotic diets with different origin of PUFA omega-3 on dynamic of these parameters was made. For the first time discovered universal action of diets with PUFA omega-3 vegetable and animal origin on parameters of humoral immunity: in case of primary excess of norm of the contents of natural antibodies to adrenaline, noradrenaline and dopamine as a result of treatment these parameters were reduced or did not change; and at is primary a low their level--parameters increased in most cases. The greatest immunocorrection effect was rendered by diet, enriched PUFA omega-3 of freshwater fishes fat.

[Study of metabolic and clinical effects of polyunsaturated fatty acids omega-3 from "Eicovit" in patients with ischemic heart disease and familial hyperlipoproteinemia]. / Izuchenie kliniko-metabolicheskikh éffektov PNZhK omega-3, soderzhashchikhsia v "Eikovite", u bol'nikh ishemicheskoi bolezn'iu serdtsa i semeinymi giperlipoproteidemiiami.

The influence of antiatherosclerotic diet with including 15 g preparation "Eikovit" containing fat of freshwater fish on fat acid composition of erythrocytes membrane was studied in 399 patients with ishemic heart disease and hyperlipidemia. Against a background of positive influence on clinical symptoms of diseases, lipids of blood serum, homeostasis expressed influence of PUFA omega-3 in "Eikovit" on biomembrane fat acid composition was noted. It was shown sharp increasing a quota an eicosapentaenic acid by simultaneous reducing PUFA omega-6 level.

Effect of dietary fish supplementation on lipoprotein levels in patients with hyperlipoproteinemia.

Effect of dietary fish was investigated in 51 study group patients and 50 age- and sex-matched control group patients, all with type II-b hyperlipoproteinemia. In the study and control group, 21 and 22 patients, respectively, had well regulated non-insulin dependent diabetes mellitus. Neither the study group nor control group patients smoked or consumed alcohol beverages. Blood pressure was within normal limits (16/11-20/12 kPa) in both groups. During a six-month study period, the study group took 0.5-1 kg breaded pilchard per week, whereas the control group patients were on their standard hypolipoproteinemic diet. The following parameters were determined in both study and control group patients before the study, every 3 months during the study, and 3 months after the completion of the study, total cholesterol, HDL cholesterol (HDL2 and HDL3), LDL cholesterol, VLDL cholesterol, triglycerides, blood glucose and uric acid. Fish intake was found to statistically significantly decrease the levels of total cholesterol (-10.7%), LDL cholesterol (-11.7%), VLDL cholesterol (-14.8%) and triglycerides (-12.3%) (p < 0.05), whereas a statistically significant increase was observed in the levels of HDL cholesterol (+5.3%) and HDL3 (+7.4%) (p < 0.05). Three months after the completion of the study, when the study group patients had resumed their standard hypolipoproteinemic diet without extra fish intake, the levels of lipoprotein fractions returned to those recorded before the study. There were no statistically significant changes in the levels of blood glucose, uric acid and HDL2. In the control group, no statistically significant changes in lipoprotein fractions were recorded. Our findings suggested that dietary intake of 0.5-1 kg fish containing a small amount of omega-3 fatty acids, along with the standard hypolipoproteinemic diet, may decrease the level of atherogenic lipoprotein fractions, and increase the level of lipoprotein protective fractions, thus reducing or at least delaying the development of atherosclerosis.