Study results

TitleAuthor(s)YearResultsFundingReported harmsConclusionsEffect due to factor under investigation?Consistent with other studies?Applicable to guideline population?Notes
Plant stanols do not restore endothelial function in pre- pubertal children with familial hypercholesterolemia despite reduction of low- density lipoprotein cholesterol levelsJakulj L; Vissers MN; Rodenburg J; Wiegman A; Trip MD; Kastelein- John JP;2006VariablesStanolPlaceboMean changeNoneThis study demonstrates that plant stanols reduce LDL-C concentrtions in children with FH without improving endothelial functionThis is a very small study but appears to be concordant with other studies in this field.YesYes
TC6.47+/−1.357.00+/−1.49−0.53(−0.79 to 0.28)
LDL-C4.77+/−1.325.24+/−1.45−0.48(−0.69 to0.27)
HDL-C1.35+/−0.241.38+/−0.27−0.03(−0.13 to 0.06)
TG0.61+/−0.51–0.840.57+/−0.51–0.93−0.05(−0.18 to 0.08)
FMD%)10.5(+/−5.1)10.5(+/−5.1)0.05(−2.40 to 2.51)
Changes in TC and LDL-C were significant compared to placebo p<0.001

Plant sterols were decreased in serum, lipoproteins and red cells by about 25% with stanols and increased from 37–80% with sterols, especially with high statin doses.”
Non-cholesterol sterols in serum, lipoproteins, and red cells in statin-treated FH subjects off and on plant stanol and sterol ester spreadsKetomäki A; Gylling H; Miettinen TA;2005VariablesBaselineStanolsSterolsFinnish Heart Research Foundation, Finnish Medical Society Duodecim, Research Foundation of Orion, Biomedicum Helsinki Foundation, Finnish Cultural Foundation, Ida Montin Foundation, Helsinki University Central HospitalNoneStanols and sterols both reduce LDL-C but sterols increase serum, lipoprotein and red cell plant sterol levels in statin treated FH subjects while all the respective values are decreased with stanols. There is some evidence that elevated serum plant sterols pose an increased coronary risk and the authors therefore state that increases of serum plant sterol levels should be avoided, especially in atherosclerosis prone individuals such as subjects with FH.This is a very small study but apppears to be concordant with other studies in the fieldYesYesNo placebo control in this study
TC6.30+/−0.245.65+/−0.225.71+/−0.21
LDL-C4.50+/−0.213.81+/−0.183.86+/−0.19
HDL-C1.26+/−0.051.32+/−0.041.37+/−0.04
TG1.19+/−0.101.16+/−0.121.05+/−0.09
Changes in TC and LDL-C were significant from baseline p<0.05 Changes in HDL-C and TG were significant from baseline p<0.01

Plant sterols were decreased in serum, lipoproteins and red cells by about 25% with stanols and increased from 37–80% with sterols, especially with high statin doses.”
Phytosterols/stanols lower cholesterol concentrations in familial hypercholesterolemic subjects: a systematic review with meta-analysisMoruisi KG; Oosthuizen W; Opperman AM;2006UnknownThe results of the SR of 6 studies showed LDL-C reduction of 14–15% and TC reduction of 11% in children with the highest dosages of 2.3 g/day plant sterol and 2.8 g/day plant stanol enriched spreads. Intake of 1.6 g/day plant sterol enriched spread by ch ConclKQQ3-9 “The results of the SR of 6 studies showed LDL-C reduction of 14–15% and TC reduction of 11% in children with the highest dosages of 2.3 g/day plant sterol and 2.8 g/day plant stanol enriched spreads. Intake of 1.6 g/day plant sterol enriched spread by children resulted in reductions of 10.2% in LDL-C and 7.4% in TC concentrations. In the adult group, 2.5 g/day plant sterol enriched spread caused a reduction of 10% in LDL-C and 8% in TC concentrations.
The results of the meta analysis of 124 subjects on 2.3 +/− 0.5 g phytosterols/stanols/day for 6.5 +/− 1.9 weeks were as follows: TC reducedby 0.65 mmol/l (95% CI −0.88 to −0.42 mmol/l, p<0.00001) and LDL-C by 0.64 mmol/l (95% CI −0.86 to −0.43 mmol/l, p<0.00001). I squared was 0%.”
This SR included only controlled, randomized, double blind studies with good compliance and sufficient statistical power. Six trials from 1976 to 2004 qualified to be in the review. Four of these were included in the meta analysis.
Comparison of efficacy of plant stanol ester and sterol ester: short- term and longer-term studiesO’Neill FH; Sanders-Tom AB; Thompson GR;2005There was no statistical difference in the response to plant sterols or stanols between FH subjects taking statins and unaffected subjects. Decreases in LDL-C ranged from 4.8% to 6.6%. Changes in total cholesterol ranged from 3% to 7.5%. Decreases in both concentrations were more marked in the plant sterol group at 1 month and in the plant stanol group at 2 months. In the plant sterol group the decrease at 2 months was only half as great as at 1 month and was no longer significantly different from baseline. Changes in HDL-C were slight but there was a tendency for values to decrease by about 3% in each of the groups.

Sterols: Increased serum plant sterols and a significant decrease in 7 alpha-hydroxy-4-cholesten-3-one a marker of bile acid synthesis

Stanols: Lowered significantly both LDL-C and plant sterol levels and had no effect on bile acid synthesis
UnknownNoneThe findings suggest that absorption of dietary plant sterols downregulates bile acid synthesis which attenuates their cholesterol lowering efficacy. The authors conclude that plant stanos are preferable for the long term management of hypercholesterolemiaIt would be interesting to evaluate this effect in a long term studyYesYes
Dietary treatment for familial hypercholesterolaemiaPoustie VJ; Rutherford P;2001Cochrane CollaborationCholesterol lowering diet compared with no dietary intervention:
One trial with 19 participants. NS difference.
Cholesterol-lowering diet compared with all other dietary interventions:
5 trials with 80 participants. NS differences for ischaemic heart disease, death, TC, LDL-C, HDL-C, TG, Apo A and Apo B,
Cholesterol-lowering diet compared with low fat diet:
One trial with 16 participants. NS difference.
Cholesterol lowering diet compared with increase in plant stanols:
One trial of 14 children with NS difference.
Cholesterol lowering diet compared with increase in plant sterols:
Two trials but one (Neil) failed to provide data from FH subgroup and the other found NS difference.
Cholesterol lowering diet compared to high protein diet:
Two trials were combined and NS difference was found on ischaemic heart disease, death, TC, LDL-C, HDL-C, TG. Author’s conclusion: No conclusions can be made about the effectiveness of cholesterol lowering diets or other dietary interventions for FH due to lack of adequate data. An RCT is needed to investigate dietary treatment for FH.”
All seven eligible trials were randomised controlled cross over trials. All were short term trials with each arm of the trial lasting between one and three months.

From: Appendix C, Clinical data extractions and excluded studies

Cover of Identification and Management of Familial Hypercholesterolaemia (FH)
Identification and Management of Familial Hypercholesterolaemia (FH) [Internet].
NICE Clinical Guidelines, No. 71.
National Collaborating Centre for Primary Care (UK).
Copyright © 2008, Royal College of General Practitioners.

All rights reserved. No part of this publication may be reproduced in any form (including photocopying or storing it in any medium by electronic means and whether or not transiently or incidentally to some other use of this publication) without the written permission of the copyright owner. Applications for the copyright owner’s written permission to reproduce any part of this publication should be addressed to the publisher.

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.