Allulose Vs type 2 diabetes (T2D): The Sweet Solution for Weight Management and Glycemic Control

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The escalating global prevalence of type 2 diabetes (T2D) and obesity represents a significant public health challenge, necessitating the exploration of innovative dietary strategies to mitigate these conditions. The burgeoning epidemic of type 2 diabetes (T2D) and obesity worldwide requires a relentless pursuit of innovative and effective interventions.

Allulose (d-psicose) is a rare natural sugar found naturally in small quantities in certain fruits. Allulose offers the sweetness of fructose yet is metabolically distinct; it is the C-3 epimer of fructose that, unlike fructose, has no effect on glucose or insulin. Furthermore, unlike fructose, allulose is not a substrate for de novo lipogenesis and elicits no inhibitory effect on fatty acid oxidation. Altogether, these reasons make allulose an attractive candidate for the dietary management of metabolic disorders, both by displacing dietary fructose as well as providing putative metabolic benefits itself. Unlike traditional sugars, allulose is largely absorbed by the small intestine and excreted without being fully metabolized, thus providing a low-calorie alternative to sucrose and high-fructose corn syrup, in addition to other low- or zero-calorie sweeteners.

Recent studies in humans have highlighted allulose’s potential benefits, including improved glycemic control and reduced adiposity, without the deleterious metabolic effects associated with conventional sugars. However, while clearly eliciting an increase in endogenous glucagon-like peptide-1 (GLP-1) release, which is heavily exploited with weight loss drugs, the mechanisms underlying these beneficial effects remain to be fully elucidated. Furthermore, while human studies provide critical insights, animal models, particularly rodent models of T2D and obesity, offer valuable opportunities to explore the physiological, metabolic, and molecular responses to allulose in a controlled setting.

This 12-week study aimed to investigate the effects of dietary allulose supplementation in a rat model of diet-induced obesity and T2D. We hypothesized that allulose supplementation would lead to significant improvements in body weight, insulin sensitivity, and glycemic control compared to control animals fed a standard diet without allulose. Additionally, we sought to explore the potential mechanisms by which allulose exerts its effects, including its impact on adipocyte metabolism and adipokine production, liver nutrient handling, and inflammatory markers.

By elucidating the metabolic effects of allulose in a well-established animal model of T2D and obesity, this study seeks to contribute to the growing body of literature supporting the use of allulose as a safe and effective dietary intervention for managing these conditions. The findings from this research could have significant implications for dietary recommendations, food industry practices, and the development of novel therapeutic strategies targeting the etiologies of T2D and obesity. The aim of this study was to confirm previous findings on the effect of allulose in mitigating some of the metabolic effects of a Western diet and add to this by including outcomes specific to adipose physiology and mitochondrial bioenergetics.

The outcomes of this study contribute to our understanding of the metabolic effects of allulose, especially in the context of diet-induced changes in body weight, food consumption, insulin resistance, and tissue-specific metabolic responses. Notably, our findings support previous work finding that supplementation with allulose in a Western diet (WD) mitigates some of the adverse effects commonly associated with high-fat, high-sugar diets, such as increased body weight and insulin resistance, findings that bear obvious significance throughout the world. In addition, this work provides novel insight into the GLP-1 dynamics, as well as insight into adipocyte changes and mitochondrial function.

The initial observations of our work act to confirm those found in prior work. The observation that body weight was significantly increased in both WD+stevia and WD+allulose groups compared to their standard diet (SD) counterparts, albeit to different extents, underscores the complex interplay between dietary sugars and weight regulation. The lesser degree of weight gain in the WD+allulose group suggests a potential protective effect of allulose against diet-induced obesity. This is supported by previous research indicating that allulose has anti-obesity effects in both animal and human studies, primarily through a reduction in visceral fat and the improvement of lipid metabolism.

Furthermore, the blunted increase in food consumption observed in the WD+allulose group compared to the WD+stevia group may indicate an appetite-regulating effect of allulose. This finding aligns with studies suggesting that allulose can influence the satiety cascade and reduce overall caloric intake. The significant increase in active glucagon-like peptide-1 (GLP-1) levels in the allulose groups highlights another mechanism through which allulose may exert its metabolic benefits. GLP-1, a hormone involved in glucose regulation and appetite control, has been shown to be elevated by allulose intake, enhancing glucose tolerance and reducing weight gain. While others have shown increased GLP-1 secretion in response to allulose, we believe our results are the first to report an increased GLP-1 in a state, suggesting that allulose elicits a lingering effect, well past the point of consumption.

The differential responses in insulin and glucose levels between the groups, with the WD+stevia group exhibiting a gradual increase while the WD+allulose group did not, further emphasizes the beneficial role of allulose in modulating glucose homeostasis and insulin sensitivity. These data are consistent with the notion that allulose could improve glycemic control through both glucose deposition and production, improving insulin sensitivity to augment deposition into muscle and reducing production from glycogenosis, as well as positionally decreasing enteral absorption through substrate competition.

Our analysis of liver and adipose tissue further elucidates the tissue-specific metabolic effects of allulose, including novel findings of changes in mitochondrial function. While liver triglycerides were only elevated in the WD+stevia group, suggesting that allulose may prevent liver fat accumulation, the significant glycogen accumulation across all intervention groups, particularly in the allulose groups, could reflect a shift in nutrient utilization or storage mechanisms. This finding may partly explain those observed by Liu et al., where they reported an improvement in exercise capacity in allulose-fed rodents.

Given our and others’ findings of protection against obesity with the inclusion of allulose, we sought to leverage our previous experience with analyzing adipose mitochondrial bioenergetics to determine the relevance of allulose in this. We observed greater mitochondrial uncoupling in adipose tissue of both allulose groups, suggesting a novel effect of allulose in this process. This mechanism may help explain the observed weight regulation effects. Due to tissue limitations, we were unable to directly measure uncoupling protein levels in adipose tissue to confirm a protein-level change.

This study includes some limitations. One limitation of this study is the use of stevia as a control. We sought to use a control sweetener that is both common and mostly inert. Because of their widely varied natures, it is impossible to be certain that the doses of allulose and stevia used are “equal”. Accordingly, we used doses of both that have been used previously. Importantly, while stevia has been shown to stimulate GLP-1 secretion in cell culture, we know of no such evidence in rodents or humans. This suggests that some of the advantages seen with allulose in this study could be specific to GLP-1 release. Furthermore, stevia is an ideal control in this study given previous evidence suggesting that stevia has no effect, compared with water, on metrics of weight gain. However, the lack of a water-only group should be noted. A second limitation is the lack of histological data on the liver and kidney. While our findings suggest a benign effect of allulose supplementation based on kidney and liver nutrient storage and, in the case of liver, enzymes, histological comparisons would have allowed greater insight into the state of these tissues.

The quest for food components that can mitigate adverse metabolic conditions without compromising dietary satisfaction is paramount. By both providing novel data and supporting previous work, our study demonstrates that allulose supplementation in a WD context can modulate body weight, food consumption, and metabolic parameters in a manner that favors improved metabolic health.

The importance of dietary interventions in managing and potentially reversing metabolic disorders cannot be overstated. As the global burden of T2D and obesity continues to rise, finding effective, safe, and acceptable dietary components is crucial. Allulose, with its unique metabolic profile and beneficial effects on glycemic control and weight management, emerges as a promising candidate in this regard. The potential mechanisms through which allulose exerts these effects, including modulation of GLP-1 levels, appetite regulation, and alterations in adipocyte metabolism and mitochondrial function, provide a comprehensive framework for understanding its role in metabolic health.

Further research is essential to fully elucidate the mechanisms underlying allulose’s beneficial effects and to translate these findings into practical dietary recommendations. Long-term human studies are needed to confirm the safety and efficacy of allulose supplementation in diverse populations and to determine the optimal dosing and duration for maximum benefit. Additionally, exploring the potential synergistic effects of allulose with other dietary interventions or pharmacological treatments could open new avenues for comprehensive management of T2D and obesity.

In conclusion, this study adds to the growing body of evidence supporting the use of allulose as a dietary intervention for improving metabolic health. By highlighting its effects on body weight, glycemic control, and metabolic parameters, and by providing insights into its mechanisms of action, this research underscores the potential of allulose to contribute to the management of T2D and obesity. Continued exploration of this promising compound, both in experimental and clinical settings, will be crucial in harnessing its full potential for public health benefit.


reference link : https://www.mdpi.com/2072-6643/16/12/1821

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