Following an application from Unilever PLC, submitted pursuant to Article 19 of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of an application to modify the conditions of use of an Article 14 claim related to plant sterols/stanols and lowering blood LDL-cholesterol authorised by Regulation (EC) No 376/2010 amending Regulation (EC) No 983/2009 and Regulation (EC) No 384/2010. Specifically, the applicant has requested an extension of the conditions of use, i.e. the intake of 1.5 - 3.0 g/d of plant sterols/stanols leads to an LDL-cholesterol lowering effect of 7 – 12 % within one to two weeks. The application included a request for the protection of proprietary data.
The applicant provided a published systematic review and meta-analysis that evaluated the comparative efficacy of plant sterols and plant stanols for lowering blood LDL-cholesterol in healthy and hypercholesterolaemic subjects. Trials were included in the analysis if they were randomised controlled trials directly comparing plant sterols versus plant stanols in healthy or hypercholesterolemic subjects and reported efficacy data suitable for calculation of the change from baseline. Both parallel and cross-over trials were eligible for inclusion. Based on data from 14 studies with 531 subjects, plant sterols and plant stanols at intakes ranging from 1.5 to 3.0 g/d in matrices approved by Regulation (EC) No 376/2010 (yellow fat spreads, dairy products, mayonnaise and salad dressings) were statistically not significantly different in lowering total cholesterol and LDL-cholesterol. In one additional study not included in this meta-analysis no statistically significant differences in LDL-cholesterol lowering efficacy were found between plant sterols and stanols consumed in margarine at an intake of 2.5 g per day over 85 weeks.
Related to the size of the effect, the applicant provided an unpublished meta-analysis on 27 randomised controlled human studies on the LDL-lowering efficacy of ≥ 2.6 to ≤ 3.4 g plant sterols or plant stanols per day in matrices approved by the European Commission. In this analysis the relative pooled LDL-cholesterol lowering effect was 11.3 % (95 % CI: 10.0 - 12.5). The Panel notes some limitations of the applicant’s meta-analysis that contribute to uncertainty of the estimate of the LDL-cholesterol lowering effect, e.g. the study quality not being taken into account, limitations in the description of the random effects model applied by the applicant, and the estimation of relative net changes of LDL-cholesterol levels and variance parameters which were not reported in most of the original publications.
The applicant claimed that the minimum duration required for efficacy was one to two weeks. In three of seven treatment arms, in which the earliest LDL-cholesterol measure was made after one week, the maximum LDL-cholesterol lowering effect was achieved already after one week of intervention, while in four other treatment arms LDL-cholesterol levels continued to decrease until treatment week two, three or four of the intervention. In seven out of seventeen treatment arms in which the earliest LDL-cholesterol measurement was made after two weeks of the intervention the maximum LDL-cholesterol lowering effect was attained after two weeks of intervention, in another six treatment arms most of the reduction was already achieved after two weeks, while in four studies it took longer than two weeks before the maximum reduction was reached. The Panel considers that the minimum duration required to achieve the maximum effect of plant sterols and stanols on LDL-cholesterol lowering is two to three weeks.
The Panel considers that plant sterols and stanol esters at daily intakes ranging from 1.5 to 3.0 g sterols/stanols in matrices approved by Regulation (EC) No 376/2010 (yellow fat spreads, dairy products, mayonnaise and salad dressings) have a similar efficacy on lowering blood LDL-cholesterol.
The Panel concludes that plant sterols and stanol esters at a daily intake of 3 g (range 2.6 - 3.4 g) sterols/stanols in matrices approved by the Regulation (EC) No 376/2010 (yellow fat spreads, dairy products, mayonnaise and salad dressings) lower LDL-cholesterol by 11.3 % (95% CI: 10.0 – 12.5).
The minimum duration required to achieve the maximum effect of plant sterols and stanols on LDL-cholesterol lowering is two to three weeks.
The Panel could have reached these conclusions without considering the unpublished meta-analysis claimed as proprietary by the applicant.