The role of plant stanols in the primary prevention of hypercholesterolemia in patients with arterial hypertension

Aim. To assess the efficacy and safety of plant stanols in patients with arterial hypertension (AH) and disorders of lipid metabolism, without clinical manifestations of atherosclerosis.Material and methods. The study included 40 patients — men at the age of 50-55 years, with AH (stage 1) and cholesterol above 5,0 mmol/l and LDL cholesterol above 3,0 mmol/l with low and medium risk (SCORE — 1-4%). Patients with coronary artery disease and other clinical manifestations of atherosclerosis, secondary hypertension, liver diseases, diabetes mellitus, secondary dyslipoproteinemia, cardiovascular diseases requiring constant therapy, bronchial asthma were excluded from the study. Patients were randomized into 2 groups of 20 people. In the study group of patients within 3 months received plant stanols (2 tab./day), in the control group — only healthy diet. In addition, patients with high blood pressure received antihypertensive therapy. Assessment of lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) was performed at baseline and after 3 months. At the beginning of the study, after 3 months of the study patients underwent a full medical examination. Safety control of plant stanols was carried out by determination of liver enzymes (aspartic transaminase (AST), alanine transaminase (ALT)), before and after the completion of the study.Results. Patients of two groups were comparable in baseline characteristics (lipid parameters, blood pressure level). After 3 months of research beginning patients from study group have statistically significant decrease of total cholesterol and LDL cholesterol. The average level of total cholesterol before treatment was 5,8±0,32 mmol/l, and after treatment — 5,3±0,32 mmol/l, p<0,001. The average level of LDL cholesterol before treatment was 3,6±0,26 mmol/l, and after treatment — 3,3±0,25 mmol/l, p<0,001. According to other lipid parameters (HDL cholesterol, triglycerides) significant differences are not obtained. As a result, there was a significant reduction in the total risk from 4% to 3,1%. As for the control group, the dynamics of lipid parameters were practically not observed. For example, the average level of total cholesterol before treatment was 5,7±0,39 mmol/l, and after treatment — 5,6±0,42 mmol/l. The average level of LDL cholesterol before treatment was 3,6±0,21 mmol/l, and after treatment — 3,6±0,21 mmol/l. The differences between the study and control groups in the reduction of total and LDL cholesterol were highly significant (p<0,001). The study did not reveal the dynamics of liver enzymes. The level of AST before treatment in the study group was 28,4±6,54, and after treatment — 29,5±5,56. ALT levels were 32,3±7,38 and 33,9±5,65, before and after the study, respectively.Conclusion. The study shows the high efficacy and safety of plant stanols. We found a significant decrease of the two most important parameters of lipid metabolism — total cholesterol and LDL cholesterol.

Double-Blind Randomized Placebo Controlled Trial Demonstrating Serum Cholesterol Lowering Efficacy of a Smoothie Drink with Added Plant Stanol Esters in an Indonesian Population

Indonesians have a high intake of saturated fats, a key contributing dietary factor to elevated blood cholesterol concentrations. We investigated the cholesterol lowering efficacy of a smoothie drink with 2 grams of plant stanols as esters to lower serum total and LDL-cholesterol concentrations in hypercholesterolemic Indonesian adults. The double-blind randomized placebo controlled parallel design study involved 99 subjects. Fifty subjects received control drink and dietary advice, and 49 subjects received intervention drink (Nutrive Benecol®) and dietary advice. Baseline, midline (week 2), and endline (week 4) assessments were undertaken for clinical, anthropometric, and biochemical variables. Compared to control, the smoothie drink with plant stanols reduced serum LDL-cholesterol concentration by 7.6% (p<0.05) and 9.0% (p<0.05) in two and four weeks, respectively. Serum total cholesterol was reduced by 5.7% (p<0.05 compared to control) in two weeks, and no further reduction was detected after four weeks (5.6%). Compared to baseline habitual diet, LDL-cholesterol was reduced by 9.3% (p<0.05) and 9.8% (p<0.05) in the plant stanol ester group in two and four weeks, respectively. We conclude that consumption of smoothie drink with added plant stanol esters effectively reduces serum total and LDL-cholesterol of hypercholesterolemic Indonesian subjects already in two weeks. Trial is registered as NCT02316808.

Cholesterol Lowering Effect of Plant Stanol Ester Yoghurt Drinks with Added Camelina Oil

The aim of this study was to investigate the effects of yoghurt minidrinks containing two doses of plant stanol ester either with or without added camelina oil on the serum cholesterol levels in moderately hypercholesterolemic subjects. In this randomised, double-blind, parallel group study, 143 subjects consumed a 65 mL minidrink together with a meal daily for four weeks. The minidrink contained 1.6 or 2.0 grams of plant stanols with or without 2 grams of alpha-linolenic acid-rich camelina oil. The placebo minidrink did not contain plant stanols or camelina oil. All plant stanol treated groups showed statistically significant total, LDL, and non-HDL cholesterol lowering relative to baseline and relative to placebo. Compared to placebo, LDL cholesterol was lowered by 9.4% (p<0.01) and 8.1% (p<0.01) with 1.6 g and 2 g plant stanols, respectively. With addition of Camelina oil, 1.6 g plant stanols resulted in 11.0% (p<0.01) and 2 g plant stanols in 8.4% (p<0.01) reduction in LDL cholesterol compared to placebo. In conclusion, yoghurt minidrinks with plant stanol ester reduced serum LDL cholesterol significantly and addition of a small amount of camelina oil did not significantly enhance the cholesterol lowering effect. This trial was registered with ClinicalTrials.gov NCT02628990.

Use of Animal Models in Plant Sterol and Stanol Research

Cholesterol-lowering properties of plant sterols were reported approximately six decades ago. However, over the past couple of decades we have learnt more about other cardiovascular benefits of regular consumption of plant sterols and/or plant stanols. In particular a series of animal studies has consistently reported that dietary plant sterols and/or plant stanols or their fatty acid esters can reduce atherogenesis to a different extent in different animal models. Such effects may be mediated not only through reductions in LDL cholesterol levels, but also through other mechanisms including anti-inflammatory effects. In this manuscript, various animal models including mice, rabbits, hamsters, and others which have been used to establish cardiovascular benefits of plant sterols are discussed.

Serum Cholesterol Reduction Efficacy of Biscuits with Added Plant Stanol Ester

This study’s aim was to test the low-density lipoprotein cholesterol- (LDL-c-) lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded to 3.4 g of plant stanol esters. The biscuit is a new food format that can be consumed as a snack. In a double-blind, placebo-controlled parallel design study, 119 mildly to moderately hypercholesterolemic volunteers were randomized to plant stanol or control groups. Subjects were comparable in age, gender, lipid profiles, and body mass index. They consumed a control biscuit once a day for a two-week period, followed by a four-week intervention period that either had a plant stanol ester biscuit or a control. During the habitual diet, one biscuit per day was consumed at any time that subjects wished. Serum lipid profiles were measured at the first day of run-in, at baseline, and at the study’s end. Compared to the control, the total cholesterol (TC), LDL-c, and the LDL-to-high-density lipoprotein (LDL/HDL) ratio had serum reductions of 4.9%, 6.1%, and 4.3%, respectively, and were observed after 4 weeks of biscuit consumption with added plant stanols (P < 0.05). A significantly higher reduction in LDL-c (8.9%) and LDL/HDL ratio (11.4%) was measured in those taking a plant stanol biscuit with a meal compared to those who consumed a plant stanol biscuit without other food. In conclusion, incorporating plant stanols into a biscuit is an attractive, convenient, and acceptable way to modestly lower elevated cholesterol concentrations. For optimal efficacy, biscuits should be consumed with a meal as part of a healthy diet.

Abstract 15438: Serum Proprotein Convertase Subtilisin/Kexin Type 9 Levels Are Not Increased by Plant Stanol Ester Consumption

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating cholesterol metabolism mainly by binding to LDL receptors targeting them for degradation. Statins, inhibitors of cholesterol synthesis, increase the serum PCSK9 concentration limiting the potential of statins to reduce LDL cholesterol (C) concentration, whereas ezetimibe, an inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols lower LDL-C by inhibiting cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Hypothesis: We assessed the hypothesis that consumption of plant stanol esters lowers LDL-C without increasing circulating PCSK9 levels. Methods: Ninety-two normo- and mildly hypercholesterolemic subjects, 35 men and 57 women (mean age 50.8±1.0 (SE) years) were randomly divided into plant stanol ester (STANOL) (n=46) and control (n=46) groups. They consumed spread enriched with (STANOL group) and without (control group) plant stanol (3g /d) ester in a double-blind intervention for six months. Serum lipids and lipoproteins were analysed enzymatically and serum PCSK9 concentration was quantitated with Quantikine Elisa Immunoassay at baseline and after the intervention. Results: At baseline, serum PCSK9 levels correlated positively with LDL-C in the whole study population. Serum total, LDL-C and non-HDL-C concentrations, similar between the study groups at baseline, declined by 7%,10%, and 11% at the end of the intervention in the STANOL group compared with the control group (p< 0.001, for all). The baseline serum PCSK9 concentrations were similar between the groups (STANOL 284±16 ng/ml, controls 273±16 ng/ml, ns). At the end of the intervention, serum PCSK9 concentrations were unchanged from baseline in both groups and did not differ between the groups (STANOL 293 ±15 ng/ml, controls 309±16 ng/ml, ns). Conclusion: In conclusion, plant stanol ester consumption does not affect the circulating PCSK9 concentration. Thus, plant stanols provide an efficient dietary means to lower LDL-C concentration without interfering with the LDL receptor-mediated cellular cholesterol uptake and removal.