The effect of allulose on blood glucose levels in type 2 diabetes: a meta-analysis of clinical trials

Source: ScienceDirect 2024.

Main features

• Allulose significantly reduces postprandial glucose in patients with type 2 diabetes.
• Allulose reduces time above range (TAR), which improves glycemic control.
• Allulose may potentially improve insulin sensitivity, although more research is needed to confirm this effect.

Objective

This meta-analysis examines the effects of allulose on blood sugar levels in patients with type 2 diabetes (T2DM).

Primary outcomes include postprandial blood glucose, while secondary outcomes include time in range (TIR), time above range (TAR), fasting plasma glucose (FPG), and insulin area under the curve (AUC).

Mode

A systematic search was conducted in PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library databases up to May 20, 2024.

The research also included randomized, controlled trials that examined the effects of allulose on glycemic parameters in patients with type 2 diabetes.

Data were synthesized using a random-effects meta-analysis model, and the quality of studies was assessed using the Cochrane risk of bias tool.

Results

Six studies with 126 participants were examined.

Allulose significantly reduced glucose AUC (SMD: -0.6662, 95% CI [-1.1360, -0.1964], p = 0.0054), with moderate heterogeneity (I2 = 58.3%).

Insulin AUC showed a non-significant decrease (SMD: -0.3648, 95% CI [-0.7783, 0.0488], p = 0.0839).

Fasting blood glucose (FPG) showed a non-significant decrease (MD: -5.8925, 95% CI [-20.4892, 8.7043], p = 0.4288), while TAR decreased significantly (MD: -8.8204, 95% CI [-14.4101, -3.2307], p = 0.0020). No significant change was observed in TIR (MD: 7.1211, 95% CI [-1.6028, 15.8450], p = 0.1096).

Conclusion

Allulose showed significant reductions in postprandial glucose levels and TAR, supporting its role in glycemic control in patients with type 2 diabetes.

The results are sound, although further research is needed to confirm its long-term effects on insulin sensitivity and metabolic health.

The studies

1.) Preechasuk, 2022 Double-blind, randomized, controlled, crossover clinical trial Thailand Participants consumed allulose (7 g) or aspartame twice daily for 12 weeks, with a 2-week washout period between treatments. 12 weeks 16 37.5% 54.2 (10.4) 73.3 (15.0) 28.3 (5.5) 6.6 (0.6) 110 (14)

2.) Noronha, 2018. Double-blind, randomized, controlled, acute nutritional equivalence design with washout periods Canada Participants received fructose or allulose (0 g, 5 g or 10 g) added to a 75 g glucose solution, with blood glucose and insulin levels measured. 7 weeks 22 50% 66 (1.2) 76.2 (3.7) 27.0 (0.9) 6.7 (0.1) 124 (3.6) (transformed)

3.) Fukunaga, 2023. Prospective, randomized, single-blind, crossover comparative study Japan Participants were given a diabetic diet with and without D-allulose (8.5 g per meal) in a crossover design with washout periods. 5 days 20 70% 61.0 (11.9) 65.6 (14.2) 25.6 (4.2) 9.2 (1.8) 148 (39) (transformed)

4.) Tak, 2023 Single-arm, historical-controlled pilot clinical trial South Korea Participants consumed 2 packets of diabetes-specific oral nutritional supplement (ONS) containing allulose (200 kcal/200 ml) instead of breakfast for 8 weeks. 8 weeks 26 53.8% 58.23 (6.19) 67.20 (8.29) 25.59 (1.82) – 104.6 (13.4)

5.) Japan, 2022 Pilot, prospective intervention study Malaysia Participants consumed 8.5 g of D-allulose before iftar for 5 days during Ramadan, with continuous glucose monitoring. 10 days 12 50% 55.2 (6.83) 82.7 (19.8) 32.2 (7.6) 6.7 (0.41) –

6.) Hayashi, 2010. Double-blind, randomized, controlled, crossover clinical trial Japan Participants consumed 5 g of D-psicose three times daily for 12 weeks and had their blood sugar levels measured at multiple time points. 12 weeks 30 50% 55.0 (11.4) 65.3 (13.1) 24.9 (4.4) – 104.6 (13.4)

∗Values ​​for continuous variables are given as mean (SD).

Abbreviations.

• BMI: Body Mass Index.

• HbA1c: Glycated hemoglobin.

• N: Number of participants.

3.2. Glucose and insulin AUC values

Glucose AUC

Six studies were included in the glucose AUC analysis, with a total of 190 observations (95 in the experimental group and 95 in the control group).

The random effects model showed a significant decrease in glucose AUC with a standardized mean difference (SMD) of -0.6662 (95% CI [-1.1360, -0.1964], p = 0.0054).

Moderate heterogeneity was observed between studies (I2 = 58.3%, τ2 = 0.1912, p = 0.0349), indicating some variability in effect sizes.

The use of Hedges' g resulted in a bias-corrected SMD, and the restricted maximum-likelihood estimator was used to estimate τ2 ( Figure 2 ).

This suggests that allulose may contribute to a clinically significant reduction in glucose AUC, although further studies are needed to confirm the consistency of this effect.

Figure 2. Meta-analysis of the effect of allulose on glucose and insulin area under the curve (AUC).

Panel A: This forest plot shows the change in glucose AUC. Panel B: This forest plot shows the change in insulin AUC.

Abbreviations: AUC: Area under the curve, SMD: Standardized mean difference, CI: Confidence interval.

Insulin AUC

Three studies were included in the analysis of insulin AUC, with a total of 116 observations (58 in the experimental group and 58 in the control group). The random effects model suggested a non-significant reduction in insulin AUC, with a SMD of -0.3648 (95% CI [-0.7783, 0.0488], p = 0.0839). Heterogeneity was low (I2 = 26.7%, τ2 = 0.0232, p = 0.2555), indicating minimal variability between studies ( Figure 2 ).

Although the effect on insulin AUC was not statistically significant, the trend towards a decrease suggests that allulose may play a beneficial role in modulating insulin levels.

3.3. Glucose control parameters

Two studies were included in the analysis of fasting blood glucose levels, with a total of 68 observations.

The random effects model indicated a non-significant reduction in fasting blood glucose, with a pooled mean difference (MD) of -5.8925 (95% CI [-20.4892, 8.7043], p = 0.4288).

Heterogeneity was low (I2 = 28.4%, τ2 = 31.6308, p = 0.2372) ( Figure 3 ).

The wide confidence intervals reflect the uncertainty about the effect, which is likely due to the small sample size and short study duration.

4. Dissertation

The results of this meta-analysis provide a comprehensive assessment of the effects of allulose on various glycemic parameters in individuals with type 2 diabetes mellitus (TIDM).

The significant AUC reduction observed in six studies suggests that allulose is effective in reducing postprandial glucose levels , which is key in the treatment of type 2 diabetes (TIDM) and the prevention of complications.

The observed glucose AUC reduction is statistically significant, making the clinical relevance of this effect noteworthy.

Allulose's ability to lower glucose levels without significantly increasing insulin secretion may help preserve pancreatic β-cell function and improve insulin sensitivity over time, making it particularly beneficial for those with insulin resistance or individuals with preserved pancreatic function.

Allulose likely reduces intestinal glucose absorption by inhibiting glucose transporters and increases hepatic glucokinase activity, which promotes glycogen synthesis [7, 8].

These mechanisms explain the reduction in glucose AUC and suggest broader metabolic benefits, potentially improving overall insulin sensitivity and glycemic control.

Furthermore, the ability of allulose to stabilize blood sugar levels throughout the day, as suggested by a decrease in TAR and an increase in TIR, suggests a role in maintaining better glycemic control over time.

The significant differences in fasting plasma glucose (FPG) and insulin AUC levels, despite the observed trends, suggest that the primary effect of allulose is on postprandial rather than fasting glucose levels.

This is consistent with the different regulatory mechanisms of insulin in the fasting and postprandial states.

Fasting glucose levels are maintained by basal insulin and hepatic glucose production, which are less sensitive to short-term dietary changes, such as allulose intake.

In contrast, postprandial glucose levels are regulated by rapid absorption and insulin-mediated clearance, where allulose may have the greatest effect.

Mechanistically, allulose appears to modulate glucose through multiple pathways. It likely inhibits intestinal glucose absorption through glucose transporter interactions, reducing postprandial glucose spikes.

It can also stimulate the release of GLP-1 , which increases insulin sensitivity and reduces glucagon levels, promoting stable glucose levels without significant insulin secretion [27].

Additionally, allulose may increase glucokinase activity in liver cells, promoting glycogen storage versus glucose release, thereby improving postprandial control.

Together, these mechanisms highlight the targeted effects of allulose on postprandial glucose regulation.

Longer-term studies are recommended to further assess the gradual effects on fasting glucose and insulin levels.

While specific dosing recommendations for allulose are still being developed, our results suggest that individuals with type 2 diabetes may benefit from allulose as a supplemental dietary intervention to stabilize postprandial glucose levels.

Future studies should focus on determining optimal dosing among different patient demographics to improve clinical applicability.

Although each trial is randomized, we acknowledge that factors such as dietary habits and physical activity levels may be confounding factors, and controlling for these in future studies may refine our understanding of the effects of allulose.

The manuscript now notes that although allulose occurs naturally in some fruits, human safety data remain limited; no adverse effects were reported in the studies presented here, but further research is needed in different populations to ensure safe use.

Furthermore, we emphasize that clinicians should assess each patient's individual needs and closely monitor blood glucose levels when using allulose in therapy to ensure personalized, safe care.

Clinicians should consider each patient's unique health profile when recommending allulose, with careful monitoring of blood glucose changes to ensure safe and effective use.

Individualized dosing and monitoring can help optimize benefits and mitigate unexpected reactions.

Allulose has key differences when compared to other sweeteners, such as sucralose and stevia.

Sucralose, while effective in maintaining glucose levels in healthy individuals, has been shown to increase insulin AUC in obese people, potentially affecting insulin sensitivity [28].

In contrast, allulose reduces glucose AUC without significantly affecting insulin AUC, thus offering a more favorable option for managing postprandial glucose levels without overstimulating insulin secretion [23].

Stevia reduces both glucose and insulin AUC [29], but available data suggest that allulose tends to decrease insulin AUC, although the effect was not statistically significant.

This trend indicates that allulose may help reduce insulin secretion without overstimulating the pancreas, which may support better long-term metabolic control in individuals with type 2 diabetes.

However, further studies are needed to confirm the findings regarding the AUC of allulose insulin.

From a broader clinical perspective, the effects of allulose may complement other common interventions for type 2 diabetes (T2DM) , such as dietary modification, physical activity, and drug treatments.

While medications such as metformin or glucagon-like peptide-1 (GLP-1) receptor agonists are effective in reducing postprandial glucose levels, allulose offers an additional dietary approach that may further improve glycemic control.

Allulose may work particularly well in conjunction with GLP-1 receptor agonists, given their complementary mechanisms of action.

GLP-1 receptor agonists improve glycemic control by enhancing insulin secretion and slowing gastric emptying, while allulose reduces glucose absorption and minimizes postprandial peaks .

Together, these interventions may provide a more comprehensive approach to managing postprandial glucose levels without overly burdening insulin secretion.

However, more research is needed to fully understand the long-term effects of using allulose in combination with GLP-1 receptor agonists, especially with regard to insulin sensitivity and overall metabolic health.

Several limitations should be considered when interpreting these results. The small sample size and short duration of many studies may limit the generalizability of the results.

Additionally, variability in study design, allulose doses, and administration forms likely contributed to the heterogeneity observed in some of the results.

The limited number of studies on the insulin AUC of allulose further limits the ability to draw strong conclusions in this area. Future studies should focus on assessing the long-term effects of allulose on insulin sensitivity and glycemic control in different populations.

Looking ahead, future research should focus on conducting larger, long-term studies to confirm the sustained effects of allulose on glycemic control and explore its effects on other metabolic parameters, such as lipid profiles and body weight.

Standardizing the doses and forms of allulose used in clinical trials will improve comparability and provide clearer guidelines for clinical practice.

Additionally, investigating the potential effects of allulose on the gut microbiota will provide deeper insight into its role in overall metabolic health.

In conclusion , this meta-analysis supports the efficacy of allulose in reducing postprandial glucose levels in individuals with type 2 diabetes, highlighting its valuable potential as a dietary intervention.

By addressing current limitations with larger, long-term studies, we can better understand its full potential and incorporate allulose into clinical guidelines for the treatment of type 2 diabetes .

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