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. 2024 Jun 10;16(12):1821.
doi: 10.3390/nu16121821.

The Metabolic and Endocrine Effects of a 12-Week Allulose-Rich Diet

Kevin B Cayabyab  1 , Marley J Shin  1 , Micah S Heimuli  1 , Iris J Kim  1 , Dominic P D'Agostino  2 , Richard J Johnson  3 , Andrew P Koutnik  4 , Nick Bellissimo  5 , David M Diamond  6 , Nicholas G Norwitz  7 , Juan A Arroyo  1 , Paul R Reynolds  1 , Benjamin T Bikman  1
Affiliations

The Metabolic and Endocrine Effects of a 12-Week Allulose-Rich Diet

Kevin B Cayabyab et al. Nutrients. .

Abstract

The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess.

Keywords: allulose; diabetes; insulin resistance; mitochondria; obesity.

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Conflict of interest statement

B.T.B. receives royalties from the sale of a book about insulin resistance and is an advisor for Unicity International and Nutrishus Brands. A.P.K. is an inventor of patents related to ketone bodies (US11452704B2; US11596616B2) and is on the Scientific Advisory Board for Simply Good Foods and Nutrishus Brands. D.P.D. is co-owner of Ketone Technologies LLC, Ketonutrition.org and an advisor to Nutrishus Brands. N.G.N. has a ketogenic cookbook, profits from which are all donated to charity or promoting open science, and is an advisor to Nutrishus Brands. P.R.R., N.B., D.M.D., and R.J.J. are advisers to Nutrishus Brands.

Figures

Figure 1
Figure 1
Body weight, food consumption, and endocrine changes in 12 weeks of allulose consumption. Throughout the 12 wk trial, rats manifested several significant changes. Firstly, allulose consumption blunted weight gain with a Western diet ((A); n = 10), reflected in a reduced overall food consumption ((B); n = 10). Insulin (C) and glucose (D) levels, used to compute the HOMA-IR (E), while increased significantly in the WD+stevia group, were normal in the WD+allulose group (n = 8). GLP-1 was significantly elevated throughout the trial in both groups consuming allulose ((F); n = 8). * p < 0.05; ** p < 0.005; *** p < 0.0005.
Figure 2
Figure 2
Glucose, insulin, and pyruvate tolerance tests in allulose-fed rats. At the end of the 12 wks trial, animals underwent tolerance tests to glucose ((A); 2 g/kg BW), insulin ((B); 0.75 IU/kg BW), and pyruvate ((C); 0.75 IU/kg BW) (n = 6). Based on the area under the curve (AUC), rats on WD+stevia had the most dramatic response to each stimulus, with a blunted response seen in the WD+allulose in glucose (A) and insulin (B) tolerance tests, and a normal response to pyruvate (C). * p < 0.05; ** p < 0.005; *** p < 0.0005 vs. SD+stevia; # p < 0.05 vs. WD+stevia.
Figure 3
Figure 3
Liver analysis following 12 wks of allulose consumption. Liver mass was measured (A) prior to the analysis of glycogen (B) and triglycerides (C) following 12 wks of a Western diet (WD) and standard diet (SD) with stevia or allulose in the drinking water. Mitochondrial respiration (see Section 2) was measured to determine any direct impact of diet on function (D). The liver enzymes alanine (ALT) and aspartate aminotransferase (AST) were quantified (E) in the plasma as a marker of liver health. N = 8. * p < 0.05; ** p < 0.005; *** p < 0.0005 vs. SD+stevia.
Figure 4
Figure 4
Adipose mitochondrial function analysis following 12 wks of allulose consumption. Mitochondrial respiration ((A); see Section 2) was measured in subcutaneous adipose tissue in rats following 12 wks of a Western diet (WD) and standard diet (SD) with stevia or allulose in the drinking water. ATP was also determined (B) and a combination of variables was used to determine the degree to which tissue produced ATP based on respiration rates (C). N = 7. * p < 0.05 vs. SD+stevia.
Figure 5
Figure 5
Kidney analysis following 12 wks of allulose consumption. Kidney mass was measured (A) prior to analysis of glycogen (B) following 12 wks of a Western diet (WD) and standard diet (SD) with stevia or allulose in the drinking water. N = 10. * p < 0.05 vs. SD+stevia.
Figure 6
Figure 6
Hormone levels in allulose-fed rats. At the end of the 12 wk trial, plasma was collected from rodents on a Western diet (WD) and standard diet (SD) with stevia or allulose in the drinking water. Analytes included c-reactive protein (CRP), adiponectin, and leptin (A). Adiponectin and leptin were further used to create a ratio that is reflective of adipocyte size (B). N = 6. * p < 0.05; ** p < 0.005; *** p < 0.0005 vs. SD+stevia.
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References

    1. Hossain A., Yamaguchi F., Matsuo T., Tsukamoto I., Toyoda Y., Ogawa M., Nagata Y., Tokuda M. Rare sugar D-allulose: Potential role and therapeutic monitoring in maintaining obesity and type 2 diabetes mellitus. Pharmacol. Ther. 2015;155:49–59. doi: 10.1016/j.pharmthera.2015.08.004. - DOI - PubMed
    1. Lanaspa M.A., Sanchez-Lozada L.G., Choi Y.J., Cicerchi C., Kanbay M., Roncal-Jimenez C.A., Ishimoto T., Li N., Marek G., Duranay M., et al. Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: Potential role in fructose-dependent and -independent fatty liver. J. Biol. Chem. 2012;287:40732–40744. doi: 10.1074/jbc.M112.399899. - DOI - PMC - PubMed
    1. Preechasuk L., Luksameejaroenchai C., Tangjittipokin W., Kunavisarut T. 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. 2023;62:2939–2948. doi: 10.1007/s00394-023-03205-w. - DOI - PubMed
    1. Niibo M., Kanasaki A., Iida T., Ohnishi K., Ozaki T., Akimitsu K., Minamino T. d-allulose protects against diabetic nephropathy progression in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes. PLoS ONE. 2022;17:e0263300. doi: 10.1371/journal.pone.0263300. - DOI - PMC - PubMed
    1. Iida T., Hayashi N., Yamada T., Yoshikawa Y., Miyazato S., Kishimoto Y., Okuma K., Tokuda M., Izumori K. Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans. Metab. Clin. Exp. 2010;59:206–214. doi: 10.1016/j.metabol.2009.07.018. - DOI - PubMed