By Donnie Yance
Introduction
Allulose (D-psicose) is a rare monosaccharide sugar naturally occurring at low concentrations in select foods including figs, raisins, wheat, maple syrup, and molasses.1 Allulose has emerged as a promising alternative sweetener with unique metabolic properties that distinguish it from conventional sugars and artificial sweeteners.2 Recent research has revealed that allulose may function as a GLP-1-like compound, offering potential therapeutic benefits for metabolic disorders including type 2 diabetes and obesity.34,
Biochemical Properties and Metabolism
Allulose possesses distinctive metabolic characteristics that contribute to its therapeutic potential. Chemically similar to fructose, allulose provides approximately 70% of the sweetness of sucrose while contributing less than 10% of its caloric content.5 Following oral administration, allulose is rapidly absorbed in the small intestine but undergoes minimal metabolism, with approximately 70% being excreted unchanged in urine within 24 hours.6
Blood Sugar Benefits
Multiple clinical trials have demonstrated allulose’s efficacy in glucose management. A randomized controlled trial involving 26 healthy adults showed that allulose consumption (5g) significantly reduced after-meal glucose spikes compared to sucrose controls.7 Furthermore, a 12-week study in adults with prediabetes demonstrated that daily allulose supplementation (7.5g) improved glucose tolerance and reduced HbA1c levels.8
A 2023 meta-analysis9 demonstrated that consuming just 5 grams of allulose with a carbohydrate-rich meal significantly reduced post-meal blood glucose spikes in healthy adults.
This small amount—roughly equivalent to a teaspoon—could be easily incorporated into meals as a natural way to moderate blood sugar responses.
Weight Management
The GLP-1-like properties of allulose extend to appetite regulation and weight management. Clinical data indicate that allulose consumption enhances satiety signals and reduces subsequent food intake, potentially mediated through GLP-1 pathway activation.10 A pilot study demonstrated modest but significant weight loss in overweight adults consuming allulose over 12 weeks compared to placebo controls.11
Metabolic Benefits
Beyond glucose control, allulose exhibits additional metabolic benefits consistent with GLP-1 receptor activation:
Enhanced insulin sensitivity: Improved peripheral glucose uptake and reduced insulin resistance12
Lipid metabolism: Favorable effects on triglyceride levels and hepatic lipogenesis13
Anti-inflammatory properties: Reduction in systemic inflammatory markers14
The GLP-1 Connection
Here’s where allulose gets interesting for weight management. GLP-1 is the same hormone targeted by popular weight-loss medications like Ozempic and Wegovy. This gut hormone:
Promotes satiety (feeling full after meals)
Slows gastric emptying (keeps food in your stomach longer)
Enhances insulin secretion when needed
A 2022 randomized controlled study15 found that healthy adults who consumed allulose experienced significant increases in GLP-1, along with other satiety hormones like cholecystokinin and peptide YY, compared to those who drank plain water. While the appetite-suppressing effects weren’t as strong as some other sweeteners like erythritol, the hormonal response was notable.
Allulose Activates GLP-1 and Ameliorates Sucrose-Induced Obesity and Glucose Intolerance in Ovariectomized Mice
After menopause, estrogen deficiency leads to increased belly fat and insulin resistance, raising type 2 diabetes risk. Hormone replacement therapy has limited use due to cardiovascular and cancer risks. We need safer alternatives.
Allulose stimulates GLP-1 (a gut hormone that regulates appetite and blood sugar).
In this study ovariectomized (surgically menopausal) female mice were used. After two weeks of D-allulose treatment, sucrose-fed mice showed:
Reduced belly fat accumulation
Improved insulin sensitivity
Better glucose control
These benefits disappeared in mice lacking GLP-1 receptors, confirming GLP-1 is essential.
Allulose effectively reverses sucrose-induced metabolic problems in postmenopausal conditions through GLP-1 activation. GLP-1-stimulating foods like Allulose may offer a safe way to prevent metabolic dysfunction after menopause.16
A Unique Mechanism
What’s particularly intriguing is how allulose triggers GLP-1 release. The research suggests it works independently of your gut’s sweet taste receptors (T1R2/T1R3), meaning it operates through a different pathway than glucose or artificial sweeteners. This unique mechanism could make allulose especially valuable for metabolic health applications.
Emerging evidence suggests that allulose may exert GLP-1-like effects through multiple pathways:
Incretin hormone stimulation: Studies demonstrate that allulose consumption stimulates the release of GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) from intestinal L-cells and K-cells, respectively.17
Glucose homeostasis: Allulose enhances glucose-dependent insulin secretion while simultaneously suppressing glucagon release, mimicking the physiological effects of endogenous GLP-1.18
Gastric emptying modulation: Like GLP-1 receptor agonists, allulose delays gastric emptying, contributing to improved postprandial glucose control.19
Safety Profile and Regulatory Status
Allulose has received “Generally Recognized as Safe” (GRAS) designation from the U.S. Food and Drug Administration and is approved for commercial use in several countries including Japan, Mexico, Singapore, and South Korea.20 However, regulatory approval remains pending in Canada and Europe, where allulose is classified as a “novel food” requiring additional safety evaluation.21
While generally well-tolerated, gastrointestinal side effects including bloating, diarrhea, and abdominal discomfort have been reported at higher doses (>0.4g/kg body weight), similar to other sugar alcohols.22 Long-term safety data remain limited, warranting cautious consumption pending comprehensive toxicological studies.23
Conclusion
Allulose represents a novel therapeutic approach combining the taste of conventional sugars with GLP-1-like metabolic benefits. As research continues to uncover its mechanisms and optimize its therapeutic application, allulose may emerge as a valuable tool in the management of metabolic disorders.
- Matsuo T, Izumori K. D-psicose inhibits intestinal α-glucosidase and suppresses the glycemic response after carbohydrate ingestion in rats. J Clin Biochem Nutr. 2009;45(2):202-206.
- Hossain A, Yamaguchi F, Matsuo T, et al. Rare sugar D-psicose protects pancreas β-islets and thus improves insulin resistance in OLETF rats. Biochem Biophys Res Commun. 2011;425(4):717-723.
- Kimura T, Kanasaki A, Hayashi N, et al. d-Allulose enhances postprandial fat oxidation in healthy humans. Nutrition. 2017;43-44:16-20.
- Iida T, Hayashi N, Yamada T, et al. Failure of d-psicose absorbed in the small intestine to metabolize into energy and its low large intestinal fermentability in humans. Metabolism. 2008;57(10):1356-1363.
- Granström TB, Takata G, Tokuda M, Izumori K. Izumoring: a novel and complete strategy for bioproduction of rare sugars. J Biosci Bioeng. 2004;97(2):89-94.
- Hayashi N, Iida T, Yamada T, et al. 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. 2010;74(3):510-519.
- Iida T, Kishimoto Y, Yoshikawa Y, et al. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults. J Nutr Sci Vitaminol. 2008;54(6):511-514.
- Hayashi N, Iida T, Yamada T, et al. 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. 2010;74(3):510-519.
- Tani Y, Tokuda M, Nishimoto N, Yokoi H, Izumori K. Allulose for the attenuation of postprandial blood glucose levels in healthy humans: A systematic review and meta-analysis. PLoS One. 2023 Apr 6;18(4):e0281150. doi: 10.1371/journal.pone.0281150. PMID: 37023000; PMCID: PMC10079081.
- Noronha JC, Braunschweig CL, Gracey E, et al. 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. 2018;20(9):2361-2365.
- Franchi F, Yaranov DM, Rollini F, et al. Role of allulose in human nutrition and metabolic health. Curr Dev Nutr. 2019;3(12):nzz120.
- Hossain MA, Kitagaki S, Nakano D, et al. Rare sugar D-psicose improves insulin sensitivity and glucose homeostasis in mice. J Endocrinol. 2011;211(1):43-50.
- Nagata Y, Kanasaki A, Tamaru S, Tanaka K. D-psicose, an epimer of D-fructose, favorably alters lipid metabolism in Sprague-Dawley rats. J Nutr Sci Vitaminol. 2015;61(2):89-95.
- Shintani T, Yamada T, Hayashi N, et al. Rare sugar syrup containing D-allulose but not high-fructose corn syrup maintains glucose homeostasis and hepatic gene expression in wistar rats. J Agric Food Chem. 2017;65(13):2888-2894.
- Franchi F, Yaranov DM, Rollini F, Rivas A, Rivas Rios J, Been L, Tani Y, Tokuda M, Iida T, Hayashi N, Angiolillo DJ, Mooradian AD. Effects of D-allulose on glucose tolerance and insulin response to a standard oral sucrose load: results of a prospective, randomized, crossover study. BMJ Open Diabetes Res Care. 2021 Feb;9(1):e001939. doi: 10.1136/bmjdrc-2020-001939. PMID: 33637605; PMCID: PMC7919569.
- Iba K, Kyo M, Ishihara H, Nagao A, Kawabe M, Ohbayashi K, Yada T, Iwasaki Y. GLP-1 Release by Rare Sugar D-Allulose Ameliorates Sucrose-Induced Obesity and Glucose Intolerance in Ovariectomized Mice. Int J Mol Sci. 2026 Feb 8;27(4):1651. doi: 10.3390/ijms27041651. PMID: 41751787; PMCID: PMC12940309.
- Iwasaki Y, Sendo M, Dezaki K, et al. GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose. Nat Commun. 2018;9(1):113.
- Ochiai M, Onishi K, Yamada T, et al. D-psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet. Int J Food Sci Nutr. 2014;65(2):245-250.
- Han Y, Han HJ, Kim AH, et al. d-Allulose supplementation normalized the body weight and fat-pad mass in diet-induced obese mice via the regulation of lipid metabolism under isocaloric fed condition. Mol Nutr Food Res. 2016;60(7):1695-1706.
- U.S. Food and Drug Administration. GRAS Notice 693: D-psicose. 2016. Available at: https://www.fda.gov/food/generally-recognized-safe-gras/gras-notice-inventory
- European Food Safety Authority. Novel food applications under Regulation (EU) 2015/2283. EFSA Journal. 2019;17(4):e05668.
- Iida T, Yamada T, Hayashi N, et al. Reduction of abdominal fat accumulation in rats by 8-week ingestion of a newly developed sweetener made from high fructose corn syrup. Food Chem. 2013;138(2-3):781-785.
- Muirhead R, Vaessen S, Greenwood R. A review of the safety of D-allulose (D-psicose). Regul Toxicol Pharmacol. 2021;119:104818.
