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New study published

A new study in Clinical Nutrition evaluating the cholesterol metabolism in low versus high cholesterol absorbers concludes that plant stanol ester effectively reduce LDL cholesterol in both high and low cholesterol absorbers (1).

Context

A growing evidence-base suggests that inter-personal differences in cholesterol absorption affect the risk of developing atherosclerotic cardiovascular disease (ASCVD) (2-6). High cholesterol absorption efficiency, which occurs mainly due to genetic variability, has been characterised as increased absorption and decreased excretion of both cholesterol and bile acids resulting in an increased ASCVD risk compared with low cholesterol absorbers (6). High cholesterol absorbers tend to have increased LDL-C and non-HDL cholesterol. Plant stanol ester consumption inhibits cholesterol absorption and effectively lowers LDL cholesterol as shown also in previous published studies. However, the effect of plant stanol ester in high vs. low cholesterol absorbers had not been explored in detail in earlier studies.

Study methodology

The recent publication by Helena Gylling et al. evaluated the effects of dietary plant stanol ester on serum lipids and cholesterol metabolism in a post hoc study of three randomized, double-blind, controlled trials (7-9). Participants in these trials consumed foods with or without added plant stanol ester for 6 to 9 weeks in the absence of other diet/lifestyle changes. The measurements included assessments of cholesterol absorption, whole-body cholesterol synthesis, and faecal steroid (cholesterol and its metabolites and bile acids) outputs.

The participants were classified into low (n=20) and high (n=21) cholesterol absorbers by their cholesterol absorption efficiency (based on the plasma cholesterol absorption marker cholestanol at baseline).

Findings

Daily consumption of plant stanol ester improved the metabolic profiles of cholesterol to less atherogenic in both high and low cholesterol absorbers. Consuming plant stanol esters similarly reduced serum total cholesterol, LDL-cholesterol and non-HDL-cholesterol concentrations in the low- and high absorbers without side effects. It can be deduced that the individual profile of cholesterol metabolism therefore does not interfere with the LDL and non-HDL cholesterol-lowering efficacy of plant stanol ester.

However, the study provide evidence that high and low cholesterol absorbers have different cholesterol metabolism, clearly showing that the cholesterol metabolism of high cholesterol absorbers is more atherogenic due to a lower faecal clearance of cholesterol and its metabolites and bile acids.

Key insight

Both in low and high cholesterol absorbers, consumption of plant stanol esters can lower the circulating concentrations of atherogenic apoB-containing lipoproteins by about 10%, on average, and improve the metabolic profiles of cholesterol.
High cholesterol absorbers have an enhanced risk of developing atherosclerotic cardiovascular disease partly due to a decreased clearance of cholesterol from the body.
Link to article

References

1. Gylling H, Öörni K, Nylund L, Wester I, Simonen P. The profile of cholesterol metabolism does not interfere with the cholesterol-lowering efficacy of phytostanol esters. Clinical Nutrition 2024 https://doi.org/10.1016/j.clnu.2024.01.022

2. J. Yamaguchi, E. Kawada-Watanabe, R. Koyanagi, H. Arashi, H. Sekiguchi, K. Nakao, et al., Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER. Atherosclerosis 274 (2018) 139-145.

3. S. Otto, D. Lütjohann, A. Kerksiek, S. Friedrichs, P.C. Schultze, S. Möbius-Winkler, et al., Increased cholesterol absorption is associated with In-stent-restenosis after stent implantation for stable coronary artery disease. Steroids. 187 (2022) 109079. doi:10.1016/j.steroids.2022.109079.

4. N.R. Matthan, M. Pencina, J.M. LaRocque, P.F. Jacques, R.B. D’Agostino, E.J. Schaefer, et al., Alterations in cholesterol absorption/synthesis markers characterize Framingham Offspring Study participants with CHD, J. Lipid Res. 50 (2009) 1927-1935, https://doi.org/10.1194/jlr.P900039-JLR200.

5. A. Nomura, C.A. Emdin, H.H. Won, G.M. Peloso, P. Natarajan, D. Ardissino, et al., Heterozygous ABCG5 gene deficiency and risk of coronary artery disease, Circ. Genom. Precis. Med. (2020), 13e002871, https://doi.org/10.1161/circgen. 119.002871.

6. P. Simonen, K. Öörni, J. Sinisalo, T.E. Strandberg, I. Wester, H. Gylling, High cholesterol absorption: A risk factor of atherosclerotic cardiovascular diseases? Atherosclerosis 376 (2023) 53-62. doi: 10.1016/j.atherosclerosis.2023.06.003

7. H.T. Vanhanen, J. Kajander, H. Lehtovirta, T.A. Miettinen, Serum levels, absorption efficiency, faecal elimination and synthesis of cholesterol during increasing doses of dietary sitostanol esters inhypercholesterolaemic subjects, Clinical Science 87 (1994) 61-67.

8. H. Gylling, T.A. Miettinen, Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment, Diabetologia 354 37 (1994) 773-780.

9. H. Gylling, R. Radhakrishnan, T.A. Miettinen, Reduction of serum cholesterol in postmenopausal women with previous myocardial infarction and cholesterol malabsorption induced by dietary sitostanol ester margarine. Women and dietary sitostanol, Circulation 96 (1997) 4226-4231.

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