Endogenous Estrogens Lower Plasma PCSK9 and LDL Cholesterol But Not Lp(a) or Bile Acid Synthesis in Women

Consumption of plant sterol- or stanol-enriched margarines by statin users results in an additional LDL-cholesterol reduction of approximately 10 %, which may be larger than the average decrease of 3–7 % achieved by doubling the statin dose. However, whether this effect persists in the long term is not known. Therefore, we examined in patients already on stable statin treatment the effects of 85 weeks of plant sterol and stanol ester consumption on the serum lipoprotein profile, cholesterol metabolism, and bile acid synthesis. For this, a double-blind randomised trial was designed in which fifty-four patients consumed a control margarine with no added plant sterols or stanols for 5 weeks (run-in period). For the next 85 weeks, seventeen subjects continued with the control margarine and the other two groups with either a plant sterol (n18) or plant stanol (n19) (2·5 g/d each) ester-enriched margarine. Blood was sampled at the end of the run-in period and every 20 weeks during the intervention period. Compared with the control group, plant sterol and stanol ester consumption reduced LDL-cholesterol by 0·28 mmol/l (or 8·7 %;P = 0·08) and 0·42 mmol/l (13·1 %;P = 0·006) respectively after 85 weeks. No effects were found on plasma concentrations of oxysterols or 7α-hydroxy-4-cholesten-3-one, a bile acid synthesis marker. We conclude that long-term consumption of both plant sterol and stanol esters effectively lowered LDL-cholesterol concentrations in statin users.

Download Full-text

The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0705286104 ◽

2007 ◽

Vol 105 (2) ◽

pp. 663-667 ◽

Cited By ~ 133

Author(s):

A. Berkenstam ◽

J. Kristensen ◽

K. Mellstrom ◽

B. Carlsson ◽

J. Malm ◽

...

Keyword(s):

Bile Acid ◽

Thyroid Hormone ◽

Ldl Cholesterol ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Cardiac Effects ◽

Mimetic Compound

Download Full-text

Common polymorphisms in the CYP7A1 gene do not contribute to variation in rates of bile acid synthesis and plasma LDL cholesterol concentration

Atherosclerosis ◽

10.1016/j.atherosclerosis.2005.01.032 ◽

2005 ◽

Vol 182 (1) ◽

pp. 37-45 ◽

Cited By ~ 13

Author(s):

Anna Abrahamsson ◽

Sergey Krapivner ◽

Ulf Gustafsson ◽

Olle Muhrbeck ◽

Gösta Eggertsen ◽

...

Keyword(s):

Bile Acid ◽

Ldl Cholesterol ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Cholesterol Concentration

Download Full-text

Effect of long term simvastatin administration as an adjunct to ursodeoxycholic acid: evidence for a synergistic effect on biliary bile acid composition but not on serum lipids in humans

Gut ◽

10.1136/gut.44.4.552 ◽

1999 ◽

Vol 44 (4) ◽

pp. 552-556 ◽

Cited By ~ 8

Author(s):

F Lanzarotto ◽

B Panarotto ◽

R Sorbara ◽

M Panteghini ◽

F Pagani ◽

...

Keyword(s):

Bile Acid ◽

Synergistic Effect ◽

Ursodeoxycholic Acid ◽

Acid Composition ◽

Ldl Cholesterol ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Cholesterol Concentration ◽

Biliary Cholesterol ◽

Biliary Bile Acid

BACKGROUNDStimulated bile acid synthesis preferentially utilises newly synthesised cholesterol, raising the posssiblity that combination of simvastatin (an inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator of bile acid synthesis) may result in reduced bile acid synthesis and greater enrichment of the pool with UDCA than that achieved with UDCA treatment alone.AIMSTo investigate the effect of simvastatin and UDCA given alone and in combination on serum and biliary lipid and biliary bile acid composition.METHODSEighteen patients with primary non-familial hypercholesterolaemia were studied during treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a combination of the two drugs. Each regimen was given in random order for three months following a three month lead in period.RESULTSSimvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol but biliary cholesterol concentration remained unchanged. Combination of the two drugs had no synergistic effect on serum cholesterol concentration, but significantly increased the proportion of UDCA in the bile acid pool from 35% during UDCA to 48% during combination treatment (p<0.04).CONCLUSIONSResults showed that: (1) simvastatin reduces serum LDL cholesterol but has no effect on biliary cholesterol concentration, supporting the concept that newly synthesised cholesterol is not the preferential source for biliary cholesterol; and (2) combination of simvastatin with UDCA has the predicted effect of enhancing the proportion of UDCA in the pool. This effect may be of benefit in the treatment of cholestatic liver diseases.

Download Full-text

The age-related increase in LDL cholesterol is not a result of reduced bile acid synthesis

Atherosclerosis ◽

10.1016/0021-9150(95)96548-7 ◽

1995 ◽

Vol 115 ◽

pp. S78

Author(s):

C. Hahn ◽

A. Hofmann ◽

K. von Bergmann

Keyword(s):

Bile Acid ◽

Ldl Cholesterol ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Age Related ◽

Related Increase

Download Full-text

Abstract 5521: Activation of Farnesoid X Receptor (FXR) Reduces Atherosclerosis in LDLRKO and apoEKO Mice

Circulation ◽

10.1161/circ.118.suppl_18.s_566-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Helen B Hartman ◽

Douglas C Harnish ◽

Mark J Evans

Keyword(s):

Bile Acid ◽

Ldl Cholesterol ◽

Atherosclerotic Lesion ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Western Diet ◽

Cholesterol Homeostasis ◽

Farnesoid X Receptor ◽

Protective Mechanism ◽

Lesion Development

The nuclear hormone receptors farnesoid X Receptor (FXR) and small heterodimer partner (SHP) regulate bile acid synthesis and cholesterol homeostasis in a complex fashion. In regard to atherosclerosis, FXR repression of bile acid synthesis has been proposed to be either detrimental due to reduced elimination of cholesterol or beneficial due to decreased cholesterol absorption. FXRKO mice have failed to resolved this question, with atherosclerotic lesions in FXRKO mice either enhanced (apoE, FXRdKO mice) or reduced (LDLR, FXRdKO mice). Here we demonstrate that the synthetic ligand FXR-450 blocked Western diet-mediated increases in VLDL and LDL cholesterol in both male or female LDLRKO and male or female apoEKO mice. Correspondingly, FXR-450 strongly reduced lesion development in female and male ApoEKO mice fed a Western diet. To determine if FXR-450 reduction of lipids and atherosclerotic lesion size is solely mediated by induction of SHP and repression of bile acid synthesis, LDLRKO/SHPKO and ApoEKO/SHPKO were similarly analyzed. In female LDLRKO/SHPKO or female apoEKO/SHPKO, FXR-450 no longer reduced VLDL or LDL cholesterol. Surprisingly, FXR-450 still reduced VLDL and LDL cholesterol in male LDLRKO/SHPKO and male apoEKO/SHPKO. Further FXR-450 significantly reduced lesion development in male apoEKO/SHPKO mice. These results demonstrate activation of FXR has highly beneficial effects on plasma lipids and lesion formation in multiple mouse atherosclerosis models. Further, while induction of SHP appears to be the predominant protective mechanism of FXR activation in female mice, additional mechanisms may play a role, particularly in male mice.

Download Full-text

Influence of Chitosan Treatment on Surrogate Serum Markers of Cholesterol Metabolism in Obese Subjects

10.20944/preprints201801.0046.v2 ◽

2018 ◽

Author(s):

Dieter Lütjohann ◽

Milka Marinova ◽

Karsten Wolter ◽

Winfried Willinek ◽

Norman Bitterlich ◽

...

Keyword(s):

Bile Acid ◽

Ldl Cholesterol ◽

Cholesterol Metabolism ◽

Cholesterol Absorption ◽

Acid Synthesis ◽

Placebo Treatment ◽

Bile Acid Synthesis ◽

Cholesterol Concentration ◽

Surrogate Markers ◽

Obese Subjects

Chitosan treatment results in significantly lower serum LDL cholesterol concentrations. To assess the working mechanism of chitosan, we measured serum surrogate markers of cholesterol absorption (campesterol, sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and degradation to bile acids (7α-hydroxy-cholesterol, 27-hydroxy-cholesterol) corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m2) were studied under chitosan (n=61) and placebo treatment (n=55). The participants were briefly educated regarding improvement of nutrition quality and energy expenditure. Daily chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased significantly more (P=0.0252) under chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with the expected greater decreases in markers of cholesterol absorption under chitosan treatment. Also, increase in markers of cholesterol synthesis and bile acid synthesis under chitosan treatment was not any greater than under placebo treatment. In conclusion, a significant selective reduction of serum LDL cholesterol under chitosan treatment is neither associated with a reduction of serum surrogate markers of cholesterol absorption nor with an increases of markers for cholesterol and bile acid synthesis.

Download Full-text

Influence of Chitosan Treatment in Obese Subjects on Surrogate Plasma Markers of Cholesterol Metabolism

10.20944/preprints201801.0046.v1 ◽

2018 ◽

Author(s):

Dieter Lütjohann ◽

Milka Marinova ◽

Karsten Wolter ◽

Winfried Willinek ◽

Norman Bitterlich ◽

...

Keyword(s):

Bile Acid ◽

Ldl Cholesterol ◽

Cholesterol Metabolism ◽

Cholesterol Absorption ◽

Acid Synthesis ◽

Placebo Treatment ◽

Bile Acid Synthesis ◽

Cholesterol Concentration ◽

Surrogate Markers ◽

Obese Subjects

Chitosan treatment results in significantly lower plasma LDL-cholesterol concentrations. To test the working mechanism of Chitosan, we measured plasma surrogate markers of cholesterol absorption, synthesis, and degradation to bile acids corrected for cholesterol concentration (R_sterols). One hundred sixteen obese subjects (BMI 31.7, range 28.1 – 38.9 kg/m2) were studied under Chitosan treatment (n=61) and placebo treatment (n=55) during 12 weeks. The participants underwent a short nutrition education on how to improve quality of nutrition and energy expenditure. Daily Chitosan intake was 3200 mg. RESULTS. Plasma LDL-cholesterol concentration decreased significantly stronger (P=0.0252) under Chitosan (-8.67 ± 18.18 mg/dl, 5.6%) than under placebo treatment (-1.00 ± 24.22 mg/dl, 0.9%). This reduction was not associated with corresponding decreases of markers of cholesterol absorption under Chitosan treatment. As a marker for cholesterol synthesis R_lathosterol showed a trend towards a stronger decrease under Chitosan treatment (P=0.0759). Regarding markers of bile acid synthesis, R_7α-hydroxy-cholesterol decreased significantly only under Chitosan treatment, but not stronger than under placebo treatment. In conclusion, a significant selective reduction of plasma LDL-cholesterol under Chitosan treatment is neither associated with an expected reduction of plasma surrogate markers of cholesterol absorption nor with expected increases of markers for cholesterol and bile acid synthesis.

Download Full-text