Skip to main content
SpringerLink
Log in

Short-term effects of allulose consumption on glucose homeostasis, metabolic parameters, incretin levels, and inflammatory markers in patients with type 2 diabetes: a double-blind, randomized, controlled crossover clinical trial

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Allulose is a rare monosaccharide with almost zero calories. There is no study of short-term allulose consumption in patients with type 2 diabetes (T2D). Thus, we aimed to study the effect of allulose consumption for 12 weeks on glucose homeostasis, lipid profile, body composition, incretin levels, and inflammatory markers in patients with T2D.

Methods

A double-blind, randomized, controlled crossover study was conducted on sixteen patients with T2D. Patients were randomly assigned to allulose 7 g twice daily or aspartame 0.03 g twice daily for 12 weeks. After a 2-week washout, patients were crossed over to the other sweetener for an additional 12 weeks. Oral glucose tolerance tests, laboratory measurements, and dual-energy X-ray absorptiometry were conducted before and after each phase.

Results

This study revealed that short-term allulose consumption exerted no significant effect on glucose homeostasis, incretin levels, or body composition but significantly increased MCP-1 levels (259 ± 101 pg/ml at baseline vs. 297 ± 108 pg/mL after 12 weeks of allulose, p = 0.002). High-density lipoprotein cholesterol (HDL-C) significantly decreased from 51 ± 13 mg/dl at baseline to 41 ± 12 mg/dL after 12 weeks of allulose, p < 0.001.

Conclusion

Twelve weeks of allulose consumption had a neutral effect on glucose homeostasis, body composition, and incretin levels. Additionally, it decreased HDL-C levels and increased MCP-1 levels.

Trial registration

This trial was retrospectively registered on the Thai Clinical Trials Registry (TCTR20220516006) on December 5, 2022.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Availability of data and materials

The dataset used and/or analyzed during the current study is available from the corresponding author on reasonable request.

Abbreviations

75-g OGTT:

75-gram oral glucose tolerance test

AUC:

Area under the receiver operating characteristic curve

ABCA1:

ATP-binding cassette A1

ABCG1:

ATP-binding cassette G1

BIA:

Bioelectrical impedance analysis

BMI:

Body mass index

CHD:

Coronary heart disease

DBP:

Diastolic blood pressure

DEXA:

Dual-energy X-ray absorptiometry

eGFR:

Estimated glomerular filtration rate

FPG:

Fasting plasma glucose

GIP:

Gastric inhibitory polypeptide

GLP-1:

Glucagon-like peptide 1

HbA1c:

Glycated hemoglobin

HDL-C:

High-density lipoprotein cholesterol

HOMA-B:

Homeostatic model assessment of beta cell function

HOMA-IR:

Homeostatic model assessment of insulin resistance

IL-6:

Interleukin-6

LDL-C:

Low-density lipoprotein cholesterol

MCP-1:

Monocyte chemoattractant protein-1

OLETF rat:

Otsuka Long-Evans Tokushima Fatty rat

SR-B1:

Scavenger receptor class B type 1

T2D:

Type 2 diabetes mellitus

SBP:

Systolic blood pressure

TNF alpha:

Tumor necrosis factor-alpha

References

  1. Hruby A, Hu FB (2015) The epidemiology of obesity: a big picture. Pharmacoeconomics 33(7):673–689. https://doi.org/10.1007/s40273-014-0243-x

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, Pavkov ME, Ramachandaran A, Wild SH, James S, Herman WH, Zhang P, Bommer C, Kuo S, Boyko EJ, Magliano DJ (2021) IDF diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Practice. https://doi.org/10.1016/j.diabres.2021.109119

    Article  Google Scholar 

  3. American Diabetes Association Professional Practice C (2021) 5. Facilitating behavior change and Well-being to improve health outcomes: standards of medical care in diabetes—2022. Diabetes Care 45(Supplement_1):S60-S82. https://doi.org/10.2337/dc22-S005

  4. Sylvetsky AC, Rother KI (2016) Trends in the consumption of low-calorie sweeteners. Physiol Behav 164(Pt B):446–450. https://doi.org/10.1016/j.physbeh.2016.03.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ahmed A, Khan TA, Dan Ramdath D, Kendall CWC, Sievenpiper JL (2022) Rare sugars and their health effects in humans: a systematic review and narrative synthesis of the evidence from human trials. Nutr Rev 80(2):255–270. https://doi.org/10.1093/nutrit/nuab012

    Article  PubMed  Google Scholar 

  6. Iida T, Hayashi N, Yamada T, Yoshikawa Y, Miyazato S, Kishimoto Y, Okuma K, Tokuda M, Izumori K (2010) Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans. Metab Clin Exp 59(2):206–214. https://doi.org/10.1016/j.metabol.2009.07.018

    Article  CAS  PubMed  Google Scholar 

  7. Hossain A, Yamaguchi F, Matsuo T, Tsukamoto I, Toyoda Y, Ogawa M, Nagata Y, Tokuda M (2015) Rare sugar D-allulose: potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus. Pharmacol Ther 155:49–59. https://doi.org/10.1016/j.pharmthera.2015.08.004

    Article  CAS  PubMed  Google Scholar 

  8. Pongkan W, Jinawong K, Pratchayasakul W, Jaiwongkam T, Kerdphoo S, Tokuda M, Chattipakorn SC, Chattipakorn N (2021) d-allulose provides cardioprotective effect by attenuating cardiac mitochondrial dysfunction in obesity-induced insulin-resistant rats. Eur J Nutr 60(4):2047–2061. https://doi.org/10.1007/s00394-020-02394-y

    Article  CAS  PubMed  Google Scholar 

  9. Noronha JC, Braunstein CR, Glenn AJ, Khan TA, Viguiliouk E, Noseworthy R, Blanco Mejia S, Kendall CWC, Wolever TMS, Leiter LA, Sievenpiper JL (2018) The effect of small doses of fructose and allulose on postprandial glucose metabolism in type 2 diabetes: a double-blind, randomized, controlled, acute feeding, equivalence trial. Diabetes Obes Metab 20(10):2361–2370. https://doi.org/10.1111/dom.13374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Han Y, Kwon E-Y, Yu MK, Lee SJ, Kim H-J, Kim S-B, Kim YH, Choi M-S (2018) A preliminary study for evaluating the dose-dependent effect of d-allulose for fat mass reduction in adult humans: a randomized, double-blind, placebo-controlled trial. Nutrients 10(2):160. https://doi.org/10.3390/nu10020160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Organization WH (1985) Diabetes mellitus: report of a WHO study group [meeting held in Geneva from 11 to 16 February 1985]. World Health Organization

    Google Scholar 

  12. Hayashi N, Iida T, Yamada T, Okuma K, Takehara I, Yamamoto T, Yamada K, Tokuda M (2010) Study on the postprandial blood glucose suppression effect of d-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects. Biosci Biotechnol Biochem 74(3):510–519. https://doi.org/10.1271/bbb.90707

    Article  CAS  PubMed  Google Scholar 

  13. Hossain MA, Kitagaki S, Nakano D, Nishiyama A, Funamoto Y, Matsunaga T, Tsukamoto I, Yamaguchi F, Kamitori K, Dong Y, Hirata Y, Murao K, Toyoda Y, Tokuda M (2011) Rare sugar d-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biochem Biophys Res Commun 405(1):7–12. https://doi.org/10.1016/j.bbrc.2010.12.091

    Article  CAS  PubMed  Google Scholar 

  14. Hossain A, Yamaguchi F, Hirose K, Matsunaga T, Sui L, Hirata Y, Noguchi C, Katagi A, Kamitori K, Dong Y (2015) Rare sugar d-psicose prevents progression and development of diabetes in T2DM model Otsuka Long-Evans Tokushima Fatty rats. Drug Des Dev Ther 9:525

    Article  CAS  Google Scholar 

  15. Schroeder M, Zagoory-Sharon O, Shbiro L, Marco A, Hyun J, Moran TH, Bi S, Weller A (2009) Development of obesity in the Otsuka Long-Evans Tokushima Fatty rat. Am J Physiol-Regulat Integrative Comparat Physiol 297(6):R1749–R1760. https://doi.org/10.1152/ajpregu.00461.2009

    Article  CAS  Google Scholar 

  16. Kanasaki A, Iida T, Murao K, Shirouchi B, Sato M (2020) D-Allulose enhances uptake of HDL-cholesterol into rat’s primary hepatocyte via SR-B1. Cytotechnology 72(2):295–301. https://doi.org/10.1007/s10616-020-00378-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ouimet M, Barrett TJ, Fisher EA (2019) HDL and reverse cholesterol transport. Circ Res 124(10):1505–1518. https://doi.org/10.1161/circresaha.119.312617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ma B, Jia J, Wang X, Zhang R, Niu S, Ni L, Di X, Liu C (2020) Differential roles of Scavenger receptor class B type I: a protective molecule and a facilitator of atherosclerosis (Review). Mol Med Rep 22(4):2599–2604. https://doi.org/10.3892/mmr.2020.11383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kozarsky KF, Donahee MH, Glick JM, Krieger M, Rader DJ (2000) Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 20(3):721–727. https://doi.org/10.1161/01.atv.20.3.721

    Article  CAS  PubMed  Google Scholar 

  20. Kozarsky KF, Donahee MH, Rigotti A, Iqbal SN, Edelman ER, Krieger M (1997) Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 387(6631):414–417. https://doi.org/10.1038/387414a0

    Article  CAS  PubMed  Google Scholar 

  21. Ueda Y, Gong E, Royer L, Cooper PN, Francone OL, Rubin EM (2000) Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics. J Biol Chem 275(27):20368–20373. https://doi.org/10.1074/jbc.M000730200

    Article  CAS  PubMed  Google Scholar 

  22. Ji Y, Wang N, Ramakrishnan R, Sehayek E, Huszar D, Breslow JL, Tall AR (1999) Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile. J Biol Chem 274(47):33398–33402. https://doi.org/10.1074/jbc.274.47.33398

    Article  CAS  PubMed  Google Scholar 

  23. Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder A, Alam DS, Di Angelantonio E, Abecasis G, Chowdhury R, Erdmann J, Nordestgaard BG, Nielsen SF, Tybjærg-Hansen A, Schmidt RF, Kuulasmaa K, Liu DJ, Perola M, Blankenberg S, Salomaa V, Männistö S, Amouyel P, Arveiler D, Ferrieres J, Müller-Nurasyid M, Ferrario M, Kee F, Willer CJ, Samani N, Schunkert H, Butterworth AS, Howson JM, Peloso GM, Stitziel NO, Danesh J, Kathiresan S, Rader DJ (2016) Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science (New York, NY) 351(6278):1166–1171. https://doi.org/10.1126/science.aad3517

    Article  CAS  Google Scholar 

  24. Oteng AB, Kersten S (2020) Mechanisms of action of trans fatty acids. Adv Nutr (Bethesda, MD) 11(3):697–708. https://doi.org/10.1093/advances/nmz125

    Article  Google Scholar 

  25. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen M-R, Tokgozoglu L, Wiklund O, Group ESCSD (2020) 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J 41(1):111–188. https://doi.org/10.1093/eurheartj/ehz455

    Article  PubMed  Google Scholar 

  26. Singh S, Anshita D, Ravichandiran V (2021) MCP-1: function, regulation, and involvement in disease. Int Immunopharmacol 101:107598. https://doi.org/10.1016/j.intimp.2021.107598

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Georgakis MK, Malik R, Björkbacka H, Pana TA, Demissie S, Ayers C, Elhadad MA, Fornage M, Beiser AS, Benjamin EJ, Boekholdt SM, Engström G, Herder C, Hoogeveen RC, Koenig W, Melander O, Orho-Melander M, Schiopu A, Söderholm M, Wareham N, Ballantyne CM, Peters A, Seshadri S, Myint PK, Nilsson J, de Lemos JA, Dichgans M (2019) Circulating monocyte chemoattractant protein-1 and risk of stroke. Circ Res 125(8):773–782. https://doi.org/10.1161/CIRCRESAHA.119.315380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li J, Zhang Y, Guo X, Wu Y, Huang R, Han X (2021) Circulating level of monocyte chemoattractant protein-1 and risk of coronary artery disease: a case-control and Mendelian randomization study. Pharmacogenom Personalized Med 14:553–559. https://doi.org/10.2147/pgpm.S303362

    Article  Google Scholar 

  29. Murao K, Yu X, Cao WM, Imachi H, Chen K, Muraoka T, Kitanaka N, Li J, Ahmed RA, Matsumoto K, Nishiuchi T, Tokuda M, Ishida T (2007) D-Psicose inhibits the expression of MCP-1 induced by high-glucose stimulation in HUVECs. Life Sci 81(7):592–599. https://doi.org/10.1016/j.lfs.2007.06.019

    Article  CAS  PubMed  Google Scholar 

  30. Karabacak M, Kahraman F, Sert M, Celik E, Adali MK, Varol E (2015) Increased plasma monocyte chemoattractant protein-1 levels in patients with isolated low high-density lipoprotein cholesterol. Scand J Clin Lab Invest 75(4):327–332. https://doi.org/10.3109/00365513.2014.1003595

    Article  CAS  PubMed  Google Scholar 

  31. Tölle M, Pawlak A, Schuchardt M, Kawamura A, Tietge UJ, Lorkowski S, Keul P, Assmann G, Chun J, Levkau B, van der Giet M, Nofer J-R (2008) HDL-associated lysosphingolipids inhibit NAD(P)H oxidase-dependent monocyte chemoattractant protein-1 production. Arterioscler Thromb Vasc Biol 28(8):1542–1548. https://doi.org/10.1161/ATVBAHA.107.161042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the patients who generously agreed to participate in this study; the Siriraj Institute of Clinical Research (SICRES) for assisting with the investigation process; and Khemajira Karaketklang for her assistance with statistical analysis.

Funding

This study was funded by grants from the Innovation and Technology Assistance Program (ITAP) of the National Science and Technology Development Agency (NSTDA) (Pathum Thani, Thailand) and from the Rajburi Sugar Co., Ltd. (Bangkok, Thailand). The funders had no role in the study’s design; in the collection, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Author information

Authors and Affiliations

  1. Siriraj Diabetes Center of Excellence, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Lukana Preechasuk, Chanoknan Luksameejaroenchai & Tada Kunavisarut

  2. Siriraj Center of Research Excellence for Diabetes, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Watip Tangjittipokin

  3. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Watip Tangjittipokin

  4. Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand

    Tada Kunavisarut

Authors
  1. Lukana Preechasuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chanoknan Luksameejaroenchai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Watip Tangjittipokin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tada Kunavisarut
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LP and TK designed the study. CL generated a random allocation sequence and assigned participants to the intervention. LP, CL, WT and TK conducted the experiments. LP and CL analyzed the data. LP and CL wrote the first draft. LP and TK had primary responsibility for reviewing and editing the final content. All authors read and approved the final version of the paper.

Corresponding author

Correspondence to Tada Kunavisarut.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval and consent to participate

The study protocol was approved by the Siriraj Institutional Review Board (CoA no. Si 301/2020) and complied with all of the principles set forth in the 1964 Declaration of Helsinki and its subsequent amendments. All enrolled patients provided written informed consent to participate.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Preechasuk, L., Luksameejaroenchai, C., Tangjittipokin, W. et al. Short-term effects of allulose consumption on glucose homeostasis, metabolic parameters, incretin levels, and inflammatory markers in patients with type 2 diabetes: a double-blind, randomized, controlled crossover clinical trial. Eur J Nutr 62, 2939–2948 (2023). https://doi.org/10.1007/s00394-023-03205-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-023-03205-w

Keywords

Search

Navigation