Content of review 1, reviewed on May 13, 2021

This RCT study provides high level evidence for the benefit of olive leaf extract (OLE) in reducing blood pressure and blood lipid profile as well as interleukin-8 in prehypertensive subjects. However the result should be taken into account cautiously since blood pressure lowering effect was statistically significant but not clinically significant and the standard deviation was high. This suggested that OLE has potential effect to be further studied as a complementary medicine in hypertensive subjects along with antihypertensive agents or to be used in prehypertensive subjects along with life style modification. Since this study only included male, the result can only be applied for male population.

Comment on abstract, title and references ● The objective of this study is clearly stated to investigate the effects of a phenolic-rich olive leaf extract (OLE) on blood pressure and a number of associated vascular and metabolic measures. However it is recommended to mention "prehypertensive subjects" in the statement of study objective. ● It is clearly stated in the abstract that OLE significantly reduced blood pressure (day time and 24-hrs systolic and diastolic blood pressure) as well as secondary outcomes (blood lipid profile and interleukin-8 as inflammatory marker). However it is important to point out any finding of harm or adverse effect of intervention in abstract chapter. This is a randomized, controlled, double blind cross over intervention trial, the most vigorous method to confirm the effect of particular intervention in specific population since it can optimally avoid bias and confounding factors.
● The title is concise and quite informative, nevertheless according to consort for herbal intervention it is recommended to state Latin binomial of medicinal product ● All references included were relevant and cited correctly but mostly were not recent (more than 5 years date back). ● Several key studies were included for instance a study by Susalit et al (2011) and previous RCT by Lockyer et al (2015)

Comment on Introduction/background ● Authors mentioned animal and human studies that solidly supported study hypotheses ● The research question was clearly stated in the last sentence of introduction chapter to examine the effect of OLE on 24-h ambulatory blood pressure (BP) and a range of related vascular, lipid and inflammatory markers in 60 pre-hypertensive male volunteers. ● This study was conducted to address the inconsistent existing data regarding the effect of OLE on blood pressure and other cardiovascular markers.

Comment on method ● The subjects were voluntarily recruited and underwent screening for eligibility before randomization. The setting and location where the data were collected as well as time of recruitment were clearly stated. Inclusion and exclusion criteria were clearly defined. However authors didn't restrict salt consumption that may influence blood pressure. All variables defined and measured appropriately ● The study was conducted with a randomized, double blind, controlled, cross over design with allocation concealment, where the influencing factors, including bias and extraneous factors, could be minimized ● Authors provide enough detail to enable replication of method for future studies.

Comment on result ● The table of baseline data didn't present the value of variables of each arm, therefore it is difficult to assess the similarity of baseline data between intervention and control arms. It is recommended that the authors also included weekly food record in this RCT report
● Tables and figures are relevant, clearly presented and narrated in detail ● The author used appropriate units, rounding, and numbering of decimals. However it is recommended to add unit of mg/dl because this unit is widely used in America and many other countries ● Titles, columns, and rows were labelled correctly and clearly ● All tables presented the data categorized from the two arms appropriately ● The text in the results added to the data of baseline characteristics, primary and secondary outcomes ● OLE administration produced statistically significant reduction in day time and ambulatory blood pressure as well as plasma total cholesterol, LDL-C, triglyceride and interleukin-8. ● The findings on blood pressure showed small effect size and was not clinically significant, although it was statistically significant

Comment on discussion and conclusion The results were discussed from several point of views. Authors pointed out the consistency of the result with previous studies. They also added explanation on biological plausibility of OLE regarding its protective effect on blood pressure and other risk factors of cardiovascular disease. They argued that although the reduction of blood pressure was smaller than expected effect size, it was physiolgicaly significant to reduce CHD risk. ● The conclusion can answer the aims of the study ● The conclusions are supported by relevant references and results ● Authors described several potential bias that may cause limitations of the study but were not fatal and . may suggest for future studies.

Source

    © 2021 the Reviewer.

References

    Stacey, L., Ian, R., Edward, S. J. P., Parveen, Y., Welma, S. 2017. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: a randomised controlled trial. European Journal of Nutrition.