Obesity Does Not Interfere with the Cholesterol-Lowering Effect of Plant Stanol Ester Consumption (as Part of a Heart-Healthy Diet)

Dietary modifications including plant stanol ester consumption are recommended measures to control serum and low-density lipoprotein (LDL)-cholesterol concentrations, but obesity can affect their responses. We investigated whether body mass index (BMI) affects serum cholesterol levels during plant stanol (mainly sitostanol) ester consumption. This ad hoc analysis was based on earlier results of a cross-over, randomized controlled trial of postmenopausal women consuming rapeseed oil-based margarine without or with plant stanol ester (3 g plant stanols/day) for seven weeks. We classified the subjects as normal-weight (BMI ≤ 25 kg/m2, n = 9, mean 22.6 kg/m2) or overweight/obese (BMI > 25 kg/m2, n = 11, mean 28.4 kg/m2), and recalculated the results, focusing on cholesterol absorption, cholesterol synthesis, and fecal steroid outputs. Serum cholesterol levels were similar in the groups during the control diet. Plant stanol ester reduced serum cholesterol by 0.63 ± 0.19 mmol/L (11%) in normal-weight and by 0.75 ± 0.13 mmol/L (12%) in overweight/obese subjects (p < 0.05 for both), and cholesterol absorption was reduced in both groups. However, relative and dietary cholesterol absorption were more effectively reduced in normal-weight subjects. In conclusion, overweight/obesity did not interfere with the serum cholesterol response to plant stanol ester consumption despite substantial differences in cholesterol metabolism between the groups.

Plant Stanol Esters Reduce LDL (Low-Density Lipoprotein) Aggregation by Altering LDL Surface Lipids

Objective: Plant stanol ester supplementation (2–3 g plant stanols/d) reduces plasma LDL (low-density lipoprotein) cholesterol concentration by 9% to 12% and is, therefore, recommended as part of prevention and treatment of atherosclerotic cardiovascular disease. In addition to plasma LDL-cholesterol concentration, also qualitative properties of LDL particles can influence atherogenesis. However, the effect of plant stanol ester consumption on the proatherogenic properties of LDL has not been studied. Approach and Results: Study subjects (n=90) were randomized to consume either a plant stanol ester-enriched spread (3.0 g plant stanols/d) or the same spread without added plant stanol esters for 6 months. Blood samples were taken at baseline and after the intervention. The aggregation susceptibility of LDL particles was analyzed by inducing aggregation of isolated LDL and following aggregate formation. LDL lipidome was determined by mass spectrometry. Binding of serum lipoproteins to proteoglycans was measured using a microtiter well-based assay. LDL aggregation susceptibility was decreased in the plant stanol ester group, and the median aggregate size after incubation for 2 hours decreased from 1490 to 620 nm, P =0.001. Plant stanol ester-induced decrease in LDL aggregation was more extensive in participants having body mass index<25 kg/m 2 . Decreased LDL aggregation susceptibility was associated with decreased proportion of LDL-sphingomyelins and increased proportion of LDL-triacylglycerols. LDL binding to proteoglycans was decreased in the plant stanol ester group, the decrease depending on decreased serum LDL-cholesterol concentration. Conclusions: Consumption of plant stanol esters decreases the aggregation susceptibility of LDL particles by modifying LDL lipidome. The resulting improvement of LDL quality may be beneficial for cardiovascular health. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01315964.

Lowering Low-Density Lipoprotein Cholesterol Concentration with Plant Stanol Esters to Reduce the Risk of Atherosclerotic Cardiovascular Disease Events at a Population Level: A Critical Discussion

Atherosclerotic cardiovascular diseases (ASCVDs) cause every fifth death worldwide. However, it is possible to prevent the progression of ASCVDs by reducing circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Recent large meta-analyses demonstrated that by reducing the dietary intake of saturated fat and cholesterol, it is possible to reduce the risk of ASCVD events. Plant stanols, as fatty-acid esters, were developed as a dietary adjunct to reduce LDL-C levels as part of a heart-healthy diet. They reduce cholesterol absorption so that less cholesterol is transported to the liver, and the expression of LDL receptors is upregulated. Ultimately, LDL-C concentrations are reduced on average by 9–12% by consuming 2–3 g of plant stanol esters per day. In this review, we discuss recent information regarding the prevention of ASCVDs with a focus on dietary means. We also present new estimates on the effect of plant stanol ester consumption on LDL-C levels and the risk of ASCVD events. Plant stanol esters as part of a heart-healthy diet plausibly offer a means to reduce the risk of ASCVD events at a population level. This approach is not only appropriate for subjects with a high risk of ASCVD, but also for subjects at an apparently lower risk to prevent subclinical atherosclerosis.

Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease

Niemann-Pick type C (NPC)1 disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key factor in the development of atherosclerosis and NASH. In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH, and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring a Npc1-null allele (Npc1nih), creating a dysfunctional NPC1 protein. Npc1nih mice were fed a 2% or 6% plant stanol ester-enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1nih mice fed the plant stanol-enriched diet exhibited lower hepatic cholesterol accumulation, damage, and inflammation than regular chow-fed Npc1nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular toward an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.

Decreasing the Cholesterol Burden in Heterozygous Familial Hypercholesterolemia Children by Dietary Plant Stanol Esters

This review covers the current knowledge about plant stanol esters as a dietary treatment option for heterozygous familial hypercholesterolemia (he-FH) children. The current estimation of the prevalence of he-FH is about one out of 200–250 persons. In this autosomal dominant disease, the concentration of plasma low-density lipoprotein cholesterol (LDL-C) is strongly elevated since birth. Quantitative coronary angiography among he-FH patients has revealed that stenosing atherosclerotic plaques start to develop in he-FH males in their twenties and in he-FH females in their thirties, and that the magnitude of the plaque burden predicts future coronary events. The cumulative exposure of coronary arteries to the lifelong LDL-C elevation can be estimated by calculating the LDL-C burden (LDL-C level × years), and it can also be used to demonstrate the usefulness of dietary stanol ester treatment. Thus, when compared with untreated he-FH patients, the LDL-C burden of using statin from the age of 10 is 15% less, and if he-FH patients starts to use dietary stanol from six years onwards and a combination of statin and dietary stanol from 10 years onwards, the LDL-C burden is 21% less compared to non-treated he-FH patients. We consider dietary stanol treatment of he-FH children as a part of the LDL-C-lowering treatment package as safe and cost-effective, and particularly applicable for the family-centered care of the entire he-FH families.