d-Allulose enhances postprandial fat oxidation in healthy humans

doi:10.1016/j.nut.2017.06.007

Nutrition

Volumes 43–44, November–December 2017, Pages 16-20

https://doi.org/10.1016/j.nut.2017.06.007 Get rights and content

Highlights

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d-Allulose, a C-3 epimer of d-fructose, decreases body weight and abdominal adipose tissue weight in animals probably through enhanced energy expenditure.
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We examined the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy humans.
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d-Allulose enhanced postprandial fat oxidation and decreased carbohydrate oxidation.
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To our knowledge, this is the first report showing that d-allulose enhances energy metabolism in healthy humans at a low dose of 5 g.
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d-Allulose could be a novel sweetener to control and maintain healthy body weight.

Abstract

Objective

d-Allulose, a C-3 epimer of d-fructose, has been reported to decrease body weight and adipose tissue weight in animal studies and is expected to be a potent antiobese sweetener. Our animal study suggested that one of the mechanisms of d-allulose's antiobesity function is an increase in energy expenditure. However, a few studies have thus far explored the underlying mechanism in humans. The aim of this study was to examine the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy participants.

Methods

Thirteen healthy men and women (mean age of 35.7 ± 2.1 y and body mass index 20.9 ± 0.7 kg/m²) were studied. The study was a randomized, single-blind crossover design with a 1-wk washout period. At 30 min after taking 5 g of d-allulose or 10 mg of aspartame without any sugar as a control, overnight-fasted participants ingested a standardized meal, and energy metabolism was evaluated by a breath-by-breath method. During the experiment, blood was collected and biochemical parameters such as plasma glucose were analyzed.

Results

In the d-allulose–treated group, the area under the curve of fat oxidation was significantly higher than in the control group (10.5 ± 0.4 versus 9.6 ± 0.3 kJ·4 h·kg⁻¹ body weight [BW]; P < 0.05), whereas that of carbohydrate oxidation was significantly lower (8.1 ± 0.5 versus 9.2 ± 0.5 kJ·4 h·kg⁻¹ BW; P < 0.05). Furthermore, plasma glucose levels were significantly lower, and free fatty acid levels were significantly higher in the d-allulose group than in the control group. No other parameters such as insulin, total cholesterol, or triacylglycerol were modified.

Conclusion

d-Allulose enhances postprandial fat oxidation in healthy humans, indicating that it could be a novel sweetener to control and maintain healthy body weight, probably through enhanced energy metabolism.

Introduction

Obesity is one of the factors affecting most of the prevalent lifestyle-related health complications such as coronary heart disease, diabetes, and certain types of cancer [1]. Obesity results from an imbalance between energy intake and energy expenditure [1]. However, it is difficult to decrease energy intake from foods because advanced food technology has introduced energy-packed or energy-hidden foods to the market. Therefore, an increase in energy expenditure has emerged as an attractive strategy for treating or preventing obesity. To this end, food ingredients to burn energy have been explored.

d-Allulose (previously referred to as d-psicose), a C-3 epimer of d-fructose, has 70% sweetness of sucrose, is rarely found in nature, and therefore is referred to as a rare sugar [2]. d-Allulose is also formed from d-fructose during cooking and is present in a very small amount in various foods such as fruit juices and cola drinks [3]. The d-allulose content per 100 g ranges from 0.5 to 130.6 mg; fruit juice contains 21.5 mg and cola drink 38.3 mg. The daily intake of d-allulose is ∼0.2 g [3]. About 70% of d-allulose is absorbed and then is excreted via urine. The remaining is not fermented in the large intestine and is excreted into feces [4]. Furthermore, d-allulose is a noncaloric sweetener [5] and has been approved as a Generally Recognized as Safe ingredient by the Food and Drug Administration in 2014.

Studies showed that d-allulose is a potential antidiabetic and antiobese sweetener; 0.2 g/kg of d-allulose decreases absorption of sugar by inhibiting intestinal α-glucosidase in Wistar rats compared with nontreated animals [6]. Intake of 0.2 g/kg of d-allulose activates the translocation of glucokinase from the nucleus to the cytosol in the liver that facilitates glycogen biosynthesis in Wistar and Goto-Kakizaki (type 2 diabetes mellitus [T2DM] model) rats [7]. In healthy humans, a single ingestion of 5 g of d-allulose improves insulin sensitivity after administering maltodextrin [8]. Feeding the 5% d-allulose solution enhances insulin sensitivity in T2DM model Otsuka Long-Evans Tokushima Fatty rats compared with only water [9]. Furthermore, d-allulose decreases body weight and abdominal adipose tissue weight in animal studies [10], [11], [12], [13]. The proposed underlying mechanism of d-allulose–induced antiobese action is that it suppresses the activity of hepatic lipogenic enzymes such as fatty acid synthase (FAS) and glucose-6-phosphate dehydrogenase [10], [12], augments the hepatic carnitine palmitoyltransferase activity essential for fatty acid oxidation [13], and increases energy expenditure [12], [13].

However, no studies thus far have been done to see if and how d-allulose modifies energy metabolism in humans. Furthermore, to apply d-allulose to a broad range of diet regimens, clinical studies are imperative. We thus investigated the effects of a single ingestion of d-allulose on postprandial energy metabolism in 13 healthy individuals. We measured short-term (4-h) energy metabolism as d-allulose is metabolized and excreted from the body quickly after ingestion [14] and has an immediate effect on lipid metabolism in rats [13]. To our knowledge, the present study showed for the first time that d-allulose increased fat oxidation and decreased carbohydrate oxidation in healthy humans. This result suggests the possibility that d-allulose may help control healthy body weight, partially via enhanced energy metabolism in humans.

Section snippets

Participants

Thirteen healthy volunteers (five men and eight women) were recruited. Participants were excluded if they were diagnosed with diabetes or metabolic disorders such as cardiovascular diseases. Individuals with a mean age of 35.7 ± 2.1 y and body mass index (BMI) of 20.9 ± 0.7 kg/m² participated in the study. This study was conducted according to the principles of the Declaration of Helsinki and approved by the Ethics Committee of Matsutani Chemical Industry Co., Ltd. (Hyogo, Japan). Written

Energy metabolic parameters

No significant difference in REE between the two groups was demonstrated (Fig. 1A). However, ingesting d-allulose caused a significant increase in FEE at 90 min compared with the control group (Fig. 1C). CEE and RQ were significantly lower in the d-allulose group than in the control group; CEE at 90, 210, and 240 min (Fig. 1B), and RQ at 240 min (Fig. 1D) were lower. The AUC of REE, CEE, and FEE for 4 h after a meal are summarized in Figure 1E. The AUC of FEE was significantly increased

Discussion

In previous animal studies, d-allulose decreased body weight and abdominal adipose tissue weight [10], [11], [12], [13], suggesting that the 3% to 5% d-allulose diets may have antiobese action. The proposed mechanism of d-allulose–induced antiobese action is that d-allulose suppresses hepatic lipogenesis [10], [12] and augments hepatic fatty acid oxidation, resulting in enhanced energy expenditure [13]. In partial agreement with previous animal studies [13], the present study demonstrated that

Conclusion

At a low dose, d-allulose enhanced postprandial fat oxidation and decreased carbohydrate oxidation in healthy humans. This indicates that d-allulose has the potential to be an antiobese sweetener in humans. Further studies in humans are needed to confirm these effects using a large number of individuals with various diseases such as diabetes and obesity and feeding d-allulose over a long-term period.

Acknowledgments

The authors acknowledge the volunteers who participated in this study.

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Excessive consumption of added sugars has been associated with psychiatric disorders such as stress, anxiety, and depression, especially in women. The aim of this study was to evaluate the effect of natural sweeteners on stress, anxiety, and depression behaviors and physiological effects in C57BL/6 female mice (n = 72). Agave syrup (AS), monk fruit (MF), glycyrrhizin (GLY), xylitol (XYL), and allulose (AL) were administered in the drinking water for 20 weeks. The intake of food and drink, and body weight of the mice was evaluated weekly. Moreover, forced swimming, tail suspension, elevated maze tests, morphometric analyses, organ weight/body weight index estimation, leukocyte count and granulocytes/leukocytes (G/L), and plasma glucose levels were performed at the end of the experimental trial. According to the results, all sweeteners increased weight gain (p < 0.01) but not food and drink intakes or glucose levels. The consumption of AS, MF, XYL, and AL decreased the symptoms of depression, while the consumption of AS, GLY, XYL, and AL increased the signs of anxiety (p < 0.001). In leukocyte count, all sweeteners caused changes compared to the control group (CON) (p < 0.0001). Organ weights, lengths, and G/L ratio showed significant reductions for all sweeteners except GLY. In conclusion, the consumption of natural sweeteners in female mice triggers alterations in behavioral disorders and other physiological responses.
Novel multienzyme cascade for efficient synthesis of D-allulose from inexpensive sucrose
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d-Allulose is one of the most common rare sugars with low calorie and is extensively applied in the food, cosmetic, and pharmaceutical fields. Here, a novel in vitro multienzyme cascade route (MCAS) was designed to produce d-allulose from sucrose. The MCAS route comprised three modules (sucrose phosphorolysis, phosphorylation–dephosphorylation, and ATP regeneration), including five enzymes (sucrose phosphorylase, fructokinase, d-allulose 6-phosphate 3-epimerase, d-allulose 6-phosphatephosphatase, and polyphosphate kinase). As a rate-limiting enzyme, d-allulose 6-phosphate 3-epimerase from Pantoea sp. was semi-rationally engineered, and variant Y143F led to 88.8% yield of d-allulose from 10 mM sucrose using one-pot strategy. ATP consumption was reduced to 5% of the sucrose concentration after introducing ATP-regeneration system. At elevated sucrose concentration of 100 mM by two-step strategy, a d-allulose yield of 70.4% was achieved with a space-time yield of 1.06 g L⁻¹·h⁻¹. This study provides an efficient and cost-effective approach for producing d-allulose from sucrose.
An improved gravimetric method with anti-solvent addition to measure the solubility of D-allulose in water
2023, Journal of Food Engineering
Anti-solvent assisted gravimetric (AAG) method as a novel approach was proposed to accelerate solubility measurement. The new method was to add the anti-solvent into the saturated solution to drive a fast crystallization, and then to evaporate the filtered solution in order to collect the residual solid particles that were added with dried filter cake particles to constitute the total mass of solute in the initial saturated solution. The solubility of d-allulose, as a model compound, was measured by AAG method at temperature of 283.15–353.15 K. Moreover, the measurement by AAG method had a higher processing efficiency and more convenient operation than the traditional gravimetric method, which perform better in the solubility measurement of most viscous systems.
Comparison of postprandial glycemic and insulinemic response of allulose when consumed alone or when added to sucrose: A randomized controlled trial
2023, Journal of Functional Foods
Allulose is a naturally occurring monosaccharide with ∼70% sweetness of sucrose which may blunt postprandial glucose when consumed with a carbohydrate-containing meal. Whether a higher allulose to carbohydrate ratio further inhibits both glycemic and insulinemic responses remains unclear. In an acute, double-blind, randomized design, 14 individuals without diabetes (age:51 ± 15 years, BMI:27.2 ± 4.1 kg/m²) were studied over 120 min on three separate occasions after consuming beverages containing 15 g allulose, 15 g allulose plus 30 g sucrose, or 30 g sucrose. After allulose, allulose + sucrose, and sucrose beverages, respectively, glucose iAUC (mean ± SEM; 0.6 ± 0.2, 86.0 ± 9.5, and 118.1 ± 11.3 mmol × min/L), and peak rise (0.05 ± 0.02, 1.69 ± 0.13, and 3.15 ± 0.23 mmol/L) all differed significantly (p < 0.05). Similarly, insulin iAUC and peak rise were significantly different between all beverages. This study demonstrated that allulose added to sucrose attenuated both postprandial glucose and insulin responses. Thus, dietary substitution of sucrose with allulose may be advantageous, but longer-term studies are needed to confirm long term benefits.
Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis
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Citation Excerpt :
The remaining 37 reports were retrieved in full, of which 23 were excluded. The final analysis consisted of 14 reports [68–81], including a total of 40 trial comparisons in 400 participants. No trials were identified assessing the effect of small doses of sorbose.
To synthesize the evidence of the effect of small doses (≤30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added ≤30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE.
Forty trial comparisons (n = 400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P < 0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P < 0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P = 0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose.
Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements.
Intestinal absorption of D -fructose isomers, D -allulose, D -sorbose and D -tagatose, via glucose transporter type 5 (GLUT5) but not sodium-dependent glucose cotransporter 1 (SGLT1) in rats
2023, British Journal of Nutrition

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: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare and have nothing to disclose.

View full text

Applied nutritional investigationd-Allulose enhances postprandial fat oxidation in healthy humans

Highlights

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Participants

Energy metabolic parameters

Discussion

Conclusion

Acknowledgments

Pharmacol Ther

Metabolism

Am J Clin Nutr

J Lipid Res

Diabetes Metab

Cell Metab

Cell Metab

Am J Clin Nutr

Obesity therapy: altering the energy intake-and-expenditure balance sheet

Nat Rev Drug Discov

Psicose contents in various food products and its origin

Food Sci Technol Res

D-psicose is a rare sugar that provides no energy to growing rats

J Nutr Sci Vitaminol

D-psicose inhibits intestinal α-glucosidase and suppresses glycemic response after carbohydrate ingestion in rats

Tech Bull Fac Agr Kagawa Univ

Suppression of blood glucose levels by D-psicose in glucose tolerance test in diabetic rats

Jpn Pharmacol Ther

Applied nutritional investigation
d-Allulose enhances postprandial fat oxidation in healthy humans