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Effect of mulberry fruit extract on glucose fluxes after a wheat porridge meal: a dual isotope study in healthy human subjects

Abstract

Background

Previous research has shown the efficacy of mulberry extracts for lowering post-prandial glucose (PPG) responses. The postulated mechanism is slowing of glucose absorption, but effects on glucose disposal or endogenous production are also possible. This research assessed the effect of a specified mulberry fruit extract (MFE) on these three glucose flux parameters.

Methods

The study used a double-blind, randomized, controlled, full cross-over design. In 3 counter-balanced treatments, 12 healthy adult male subjects, mean (SD) age 24.9 (2.50) years and body mass index 22.5 (1.57) kg/m2, consumed porridge prepared from 13C-labelled wheat, with or without addition of 0.75 g MFE, or a solution of 13C-glucose in water. A co-administered 2H-glucose venous infusion allowed for assessment of glucose disposal. Glucose flux parameters, cumulative absorption (time to 50% absorption, T50%abs), and PPG positive incremental area under the curve from 0 to 120 min (+iAUC0–120) were determined from total and isotopically labelled glucose in plasma. As this exploratory study was not powered for formal inferential statistical tests, results are reported as the mean percent difference (or minutes for T50%abs) between treatments with 95% CI.

Results

MFE increased mean T50%abs by 10.2 min, (95% CI 3.9–16.5 min), and reduced mean 2 h post-meal rate of glucose appearance by 8.4% (95% CI −14.9 to −1.4%) and PPG + iAUC0-120 by 11% (95% CI −26.3 to −7.3%), with no significant changes in glucose disposal or endogenous production.

Conclusions

The PPG-lowering effect of MFE is primarily mediated by a reduced rate of glucose uptake.

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Fig. 1: Cumulative glucose appearance.
Fig. 2: Plasma glucose response.

Data availability

The datasets generated during the current study are not publicly available as the participants did not give express consent for this, but are available on reasonable request, noting that some caveats may apply.

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Acknowledgements

Jeroen Sterken and Anton Porcu are kindly acknowledged for product handling and logistical support for samples, data and meals. Duncan Talbot is acknowledged for executing the analysis of GLP-1, GIP and glucagon.

Funding

This study was funded entirely by Unilever, and Unilever employees collaborated with the academic authors in the study hypothesis/design, execution, analysis and interpretation. The trial was carried out at an independent contract research organization. Unilever employees had no part in the study execution, participant contact or data collection, and were blind to treatment codes which were only revealed when the data were unlocked. The authors confirm that: •Industry funding was transparent, acknowledged, and appropriately recognized throughout all stages of design, implementation, and reporting. •The project design, implementation, analysis, and interpretation was performed with efforts to maximize academic independence in each of these areas. •There was full academic independence to report and publish all the findings. •The raw data can be made available to interested scientists if requested, with the understanding that there could be reasonable caveats for such requests. The test materials are commercially accessible, and the methods provide sufficient detail for independent replication.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study design and protocol development, data interpretation, and writing and reviewing of the manuscript. A-RH managed the interface between the sponsor and study site, and monitoring of data collection. HH was primarily responsible for the statistical design and analyses, which were agreed with all authors in advance of study recruitment. All authors have seen and approved the manuscript, and agreed that any questions related to the accuracy or integrity of any part of the work are appropriately investigated, resolved and documented.

Corresponding authors

Correspondence to Hanny M. Boers or David J. Mela.

Ethics declarations

Competing interests

HMB and A-RH are employees of Unilever, the sponsor of the study and a manufacturer of carbohydrate-containing foods. GSD, HH and DJM were employees of Unilever at the time the research was designed and conducted, but have no current affiliation with the company, and no other competing interests in the topic of this research.

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki, and the protocol approved by the Medical Ethics Review Committee Brabant (Medische Ethische ToetsingsCommissie Brabant, Tilburg, The Netherlands) on 1 December 2015. All participants provided written informed consent. The protocol was registered at www.clinicaltrials.gov (number NCT02662738) prior to undertaking any procedures.

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Boers, H.M., van Dijk, T.H., Duchateau, G.S. et al. Effect of mulberry fruit extract on glucose fluxes after a wheat porridge meal: a dual isotope study in healthy human subjects. Eur J Clin Nutr 77, 741–747 (2023). https://doi.org/10.1038/s41430-023-01282-y

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