Research Progress | Exploring the Relationship Between D-Allulose and Health

On July 2, 2025, the Department of Food Safety Standards, Monitoring, and Evaluation of China’s National Health Commission released the Announcement on D-Allulose and 19 Other “Three New Foods” (Announcement No. 4 of 2025). After a five-year review process, D-Allulose has officially been approved for compliance, becoming the most notable new food ingredient in this announcement.

Research Progress

D-Allulose attenuated metaflammation by calming adipose tissue macrophages, boosting intestinal barrier, and modulating gut microbiota in HFD mice

Abstract: Nutrient overconsumption leads to obesity and metabolic disorders, triggering metabolic inflammation. D-Allulose exhibits anti-obesity and hypoglycemic properties; however, its role in metabolic inflammation remains unclear. In this study, high-fat diet (HFD)-fed mice were supplemented with 300 mg/kg D-Allulose for 60 consecutive days. Inflammatory levels in various tissues, changes in gut barrier function, and gut microbiota composition — as a key biomarker of metabolic inflammation — were analyzed. Results showed that D-Allulose significantly attenuated HFD-induced metabolic inflammation, as evidenced by reduced inflammatory markers and suppressed activation of pro-inflammatory macrophages in adipose tissue. Moreover, D-Allulose effectively restored impaired gut barrier function by upregulating tight junction proteins, replenishing goblet cells, and modulating gut microbiota composition, thus improving intestinal integrity and alleviating metabolic inflammation. These findings highlight the potential of D-Allulose in managing obesity and metabolic inflammation, offering new directions for its future application.

Conclusion: D-Allulose protects against HFD-induced metabolic inflammation through multiple mechanisms:

1. Reducing inflammatory cytokine levels and inhibiting activation of metabolically activated macrophages in adipose tissue.

2. Increasing goblet cell numbers and tight junction protein expression (e.g., ZO-1, OCLN), thereby reducing intestinal permeability and circulating LPS levels.

3. Altering gut microbiota structure to further protect the intestinal barrier.

Reference:

Zhao T T, Zhao G Q, Gao F, et al. D-allulose attenuated metaflammation by calming adipose tissue macrophages, boosting intestinal barrier, and modulating gut microbiota in HFD mice[J]. Journal of Functional Foods, 2024, 121: 106417. DOI:10.1016/j.jff.2024.106417

Camel Milk and D-Allulose synergistically improved camel dairy flavor and alleviated insulin resistance of human HepG2 Cells

Abstract: Camel milk, widely consumed in desert and semi-arid regions, possesses high nutritional value and potential therapeutic properties. However, its unique flavor limits broader acceptance. This study explored camel milk protein components with potential insulin resistance-alleviating effects, as well as the synergistic hypoglycemic effect of camel milk and D-Allulose. Cell viability, glucose consumption, and morphological changes were evaluated in treated HepG2 insulin-resistant cells. Sensory evaluation experiments were conducted to determine a formula that enhances camel milk flavor. The optimal concentration for alleviating insulin resistance was found to be 4 mg/mL of CWP4 protein combined with 1 mg/mL D-Allulose for 12 hours. Adding D-Allulose to camel milk at a 1:36 ratio reduced undesirable odors while preserving most favorable flavor attributes. This work supports the development of camel milk-based functional foods with potential benefits for blood glucose regulation, expanding its consumer market.

Conclusion: The combination of 4 mg/mL CWP4 protein and 1 mg/mL D-Allulose for 12 hours yielded optimal effects on improving insulin resistance in HepG2 cells. Flavor profiling showed that a 1:36 ratio of D-Allulose to camel milk improved sensory properties without compromising overall taste. These findings lay the groundwork for further studies on camel milk’s functional range and mechanisms, promoting its development into functional foods and health products for diabetes management.

Reference:

Aili T, Xu Z X, Liu C, et al. Camel milk and D-allulose synergistically improved camel dairy flavor and alleviated insulin resistance of human HepG2 cells[J]. Heliyon, 2025, 11(2): e41825. DOI:10.1016/j.heliyon.2025.e41825

Improving diabetic wound healing: therapeutic potential of D-Allulose supplement in diabetic skin tissue repair and inflammation modulation

Abstract: With the global rise of type 2 diabetes mellitus (T2DM), impaired wound healing in diabetic skin tissue poses a significant health challenge. Minimizing adverse effects while addressing this condition is critical. D-Allulose has demonstrated lipid-lowering and anti-inflammatory properties by improving insulin resistance and glucose intolerance. However, its potential role in diabetic wound repair remains underexplored. This study demonstrated that oral administration of D-Allulose significantly improved skin wound healing in HFD-fed T2DM rats. The treatment enhanced granulation tissue formation, fibroblast activation, collagen deposition, angiogenesis, and reduced M1 macrophage polarization and tissue inflammation. Furthermore, D-Allulose attenuated high glucose-induced inflammatory responses through regulation of the p38/NLRP3/Caspase-1 pathway and improved cell viability and proliferation partly via mTOR pathway activation.

Conclusion: D-Allulose supplementation partially restored abnormal p38/NLRP3 and mTOR pathway expression in diabetic skin tissue and fibroblasts, alleviating chronic inflammation associated with T2DM and HFD. The treatment also improved cellular senescence and pro-inflammatory responses, supporting its potential as a promising dietary supplement-based strategy for enhancing wound healing and quality of life in diabetic patients.

Reference:

Wang Z, Shi Y H, Zheng P C, et al. Improving diabetic wound healing: the therapeutic potential of allulose supplement in diabetic skin tissue repair and inflammation modulation[J]. Food Bioscience, 2024, 62: 105439. DOI:10.1016/j.fbio.2024.105439

Impact of D-Allulose consumption on Enteric pathogens in human gut Microbiota: A randomized controlled trial study

Abstract: D-Allulose is a GRAS (Generally Recognized as Safe) rare sugar and a potential sucrose substitute. Despite its growing popularity, limited studies have examined its effects on human gut microbiota, including pathogenic species. This 12-week, randomized, double-blind, parallel, placebo-controlled trial evaluated the safety of D-Allulose consumption in humans. Subjects received either 15 g/day D-Allulose or sucralose (placebo). Fecal samples were collected before and after intervention and analyzed using shotgun metagenomics to assess microbial diversity, taxonomic shifts, pathogenic bacteria abundance (C. difficile, H. hepaticus, K. pneumoniae, B. fragilis, S. aureus, S. enterica), and short-chain fatty acid (SCFA) production. No significant differences were observed in microbial diversity, pathogenic bacteria levels, or SCFA production, indicating that D-Allulose consumption is safe and does not adversely affect the gut microbiome or pathogen prevalence.

Conclusion: This study confirms the safety of D-Allulose as a food ingredient, with no negative impact on gut microbiota or SCFA production. These results provide valuable evidence for its continued use and research in nutrition and health sciences. Future work should explore the long-term effects of D-Allulose on gut microbiota and metabolic health across diverse populations and dietary contexts.

Reference:

Park H, Baek J, Park S Y, et al. Impact of D-allulose consumption on Enteric pathogens in human gut Microbiota: a randomized controlled trial study[J]. Journal of Functional Foods, 2024, 122: 106555. DOI:10.1016/j.jff.2024.106555