Article Text

Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study
  1. Francesco Franchi1,
  2. Dmitry M Yaranov1,
  3. Fabiana Rollini1,
  4. Andrea Rivas1,
  5. Jose Rivas Rios1,
  6. Latonya Been1,
  7. Yuma Tani2,
  8. Masaaki Tokuda3,
  9. Tetsuo Iida2,
  10. Noriko Hayashi2,
  11. Dominick J Angiolillo1,
  12. Arshag D Mooradian1
  1. 1Department of Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA
  2. 2Matsutani Chemical Industry Co. Ltd, Itami, Japan
  3. 3Kagawa University, Takamatsu, Japan
  1. Correspondence to Dr Francesco Franchi; francesco.franchi{at}


Introduction Current dietary guidelines recommend limiting sugar intake for the prevention of diabetes mellitus (DM). Reduction in sugar intake may require sugar substitutes. Among these, D-allulose is a non-calorie rare monosaccharide with 70% sweetness of sucrose, which has shown anti-DM effects in Asian populations. However, there is limited data on the effects of D-allulose in other populations, including Westerners.

Research design and methods This was a prospective, randomized, double-blind, placebo-controlled, crossover study conducted in 30 subjects without DM. Study participants were given a standard oral (50 g) sucrose load and randomized to placebo or escalating doses of D-allulose (2.5, 5.0, 7.5, 10.0 g). Subjects crossed-over to the alternate study treatment after 7–14 days of wash out. Plasma glucose and insulin levels were measured at five time points: before and at 30, 60, 90 and 120 min after ingestion.

Results D-allulose was associated with a dose-dependent reduction of plasma glucose at 30 min compared with placebo. In particular, glucose was significantly lower with the 7.5 g (mean difference: 11; 95% CI 3 to 19; p=0.005) and 10 g (mean difference: 12; 95% CI 4 to 20; p=0.002) doses. Although glucose was not reduced at the other time points, there was a dose-dependent reduction in glucose excursion compared with placebo, which was significant with the 10 g dose (p=0.023). Accordingly, at 30 min D-allulose was associated with a trend towards lower insulin levels compared with placebo, which was significant with the 10 g dose (mean difference: 14; 95% CI 4 to 25; p=0.006). D-allulose did not reduce insulin at any other time point, but there was a significant dose-dependent reduction in insulin excursion compared with placebo (p=0.028), which was significant with the 10 g dose (p=0.002).

Conclusions This is the largest study assessing the effects of D-allulose in Westerners demonstrating an early dose-dependent reduction in plasma glucose and insulin levels as well as decreased postprandial glucose and insulin excursion in subjects without DM. These pilot observations set the basis for large-scale investigations to support the anti-DM effects of D-allulose.

Trial registration number NCT02714413.

  • diabetes mellitus
  • type 2
  • nutrients
  • dietary sugars

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Supplementary materials


  • Contributors FF, DMY, ADM and DJA designed the study protocol and drafted the manuscript. FF designed the statistical analyses and analyzed the data. LB, DMY, FR, AR and JRR were involved in patient recruitment. LB, DMY, FR, AR, JRR YT, MT, TI and NH critically revised the manuscript for important intellectual content. All authors approved the final manuscript.

  • Funding The study was funded by an investigator-initiated grant from Matsutani Chemical Industry Co. Ltd. Matsutani Chemical Industry Co. Ltd. had no role in study design conception, conduct of the study or decision to publish these results.

  • Competing interests FF has received payment as an individual for consulting fee or honorarium from AstraZeneca, Bayer and Sanofi. DJA has received payment as an individual for: (a) consulting fee or honorarium from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi and The Medicines Company; (b) participation in review activities from CeloNova and St. Jude Medical. Institutional payments for grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli-Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co. Ltd., Merck, Novartis, Osprey Medical, Renal Guard Solutions and the Scott R. MacKenzie Foundation. YT, TI and NH are employees of Matsutani Chemical Industry Co. Ltd., which is a manufacturer of D-allulose. All other authors have no conflicts of interest to disclose.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Western Institutional Review Board (protocol number 20160589) and complied with the Declaration of Helsinki. All subjects gave their written informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.