D-allulose enhances postprandial fat oxidation in healthy humans

Tomonori Kimura M.S. Akane Kanasaki M.S. Noriko Hayashi M.S. Takako Yamada M.S. Tetsuo Iida Ph.D. a, Yasuo Nagata Ph.D. Kazuhiro Okuma Ph.D.

Source: ScienceDirect 2017.

Highlights

• d-Allulose, a C-3 epimer of d-fructose, reduces body weight and abdominal fat mass in animals, possibly through increased energy expenditure.
• We examined the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy humans.
• d-Allulose enhanced postprandial fat oxidation and suppressed carbohydrate oxidation.
• To our knowledge, this is the first report showing that d-allulose enhances energy metabolism even at a low dose of 5 g in healthy humans.
• d-Allulose may be a novel sweetener for regulating and maintaining healthy body weight.

Abstract

Objective

d-Allulose, a C-3 epimer of d-fructose, reduces body weight and fat tissue weight in animal studies and is expected to be an effective anti-obesity sweetener.

Our animal study suggests that one of the mechanisms of the anti-obesity function of d-allulose is to increase energy expenditure.

However, only a few studies have examined the underlying mechanism in humans to date.

The objective of this study was to examine the effects of a single ingestion of d-allulose on postprandial energy metabolism in healthy participants.

Method

Thirteen healthy men and women (mean age 35.7 ± 2.1 years and body mass index 20.9 ± 0.7 kg/m2) were investigated.

The study was a randomized, single-blind, crossover design with a 1-week washout period.

Thirty minutes after ingesting 5 g of d-allulose or 10 mg of aspartame without sugar as a control, overnight-fasted participants consumed a standardized meal, and energy metabolism was evaluated by indirect calorimetry.

Blood was collected during the experiment, and biochemical parameters such as plasma glucose levels were analyzed.

Results

The area under the curve for fat oxidation was significantly higher in the d-allulose group than in the control group (10.5 ± 0.4 vs. 9.6 ± 0.3 kJ·4 h·kg −1 body weight [BW]; P < 0.05), whereas that for carbohydrate oxidation was significantly lower (8.1 ± 0.5 vs. 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.

Other parameters such as insulin, total cholesterol, or triacylglycerol were not changed.

Conclusion

d-Allulose enhances postprandial fat oxidation in healthy humans, suggesting that it may serve as a novel sweetener for regulating and maintaining healthy body weight, possibly through enhancing energy metabolism.

Introduction

Obesity is one of the factors that affect most of the prevalent lifestyle-related health complications, such as coronary heart disease, diabetes, and certain types of cancer [1].

Obesity arises from an imbalance between energy intake and energy expenditure [1].

However, it is difficult to reduce energy intake from foods because advanced food technology has brought energy-dense or energy-hidden foods to the market.

Therefore, increasing energy expenditure has become an attractive strategy for managing or preventing obesity.

To this end, food ingredients that burn energy have been investigated.

d-Allulose (previously referred to as d-psicose), a C-3 epimer of d-fructose, is 70% as sweet as sucrose and rarely occurs in nature, thus it is referred to as a rare sugar [2].

d-Allulose is also formed from d-fructose during cooking and is present in very small amounts in various foods such as fruit juices and colas [3].

d-Allulose content ranges from 0.5 to 130.6 mg per 100 g; fruit juice contains 21.5 mg and cola beverage contains 38.3 mg.

Daily intake of d-allulose is ~0.2 g [3].

Approximately 70% of d-allulose is absorbed and then excreted in the urine.

The remaining part is not fermented in the large intestine and excreted in the feces [4].

Furthermore, d-allulose is a calorie-free sweetener [5], and the Food and Drug Administration (FDA) approved it as a generally recognized as safe ingredient in 2014.

Studies have shown that d-allulose is a potential antidiabetic and anti-obesity sweetener;

0.2 g/kg of d-allulose reduces sugar absorption by inhibiting intestinal α-glucosidase in Wistar rats compared with untreated animals [6].

Administration of 0.2 g/kg of d-allulose activates glucokinase translocation from the nucleus to the cytosol of the liver, which promotes glycogen biosynthesis in Wistar and Goto-Kakizaki (type 2 diabetes mellitus [T2DM] model) rats [7].

In healthy humans, a single intake of 5 g of d-allulose improves insulin sensitivity after maltodextrin administration [8].

Feeding with a 5% d-allulose solution enhances insulin sensitivity in obese Otsuka Long-Evans Tokushima T2DM model rats compared with pure water [9].

Furthermore, d-allulose reduces body weight and abdominal fat mass in animal studies [10], [11], [12], [13].

The proposed underlying mechanism for the d-allulose-induced anti-obesity effect is that it inhibits hepatic lipogenic enzymes, such as fatty acid synthase (FAS) and glucose-6-phosphate dehydrogenase activities [10], [12], increases hepatic carnitine palmitoyltransferase activity, which is essential for fatty acid oxidation [13], and increases energy expenditure [12], [13].

However, no studies have been performed to date on whether and how d-allulose modifies energy metabolism in humans.

Furthermore, for d-allulose to be widely used in diets, clinical studies are required.

Thus, we investigated the effect of a single ingestion of d-allulose on postprandial energy metabolism in 13 healthy individuals.

We measured short-term (4-h) energy metabolism because d-allulose is rapidly metabolized and excreted from the body after intake [14] and has an immediate effect on lipid metabolism in rats [13].

To our knowledge, the present study was the first to show that d-allulose enhanced fat oxidation and suppressed carbohydrate oxidation in healthy humans.

This finding suggests that d-allulose may help in healthy body weight regulation, partly through enhanced energy metabolism in humans.

Section Details

Participants

Thirteen healthy volunteers (five males and eight females) were recruited for the study.

Participants were excluded if they were diagnosed with diabetes mellitus or metabolic disorders such as cardiovascular disease.

The study included individuals with a mean age of 35.7 ± 2.1 years and a body mass index (BMI) of 20.9 ± 0.7 kg/m2.

The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Matsutani Chemical Industry Co., Ltd. (Hyogo, Japan).

Written Energy Metabolism Parameters

There was no significant difference in REE between the two groups (Fig. 1A).

However, d-allulose ingestion 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 for REE, CEE, and FEE at 4 h postprandial are summarized in Fig. 1E. The AUC for FEE was significantly increased:

* Explanation of Figure 1

Resting Energy Expenditure (REE) values for the two groups are shown as follows:

• D-allulose group:

[\text{REE} = 4.2 \pm 0.2 \text{ kJ·min}^{-1}] (i.e., approx. 4.2 kJ/minute resting energy consumption).

• Control (aspartame) group:

[\text{REE} = 4.1 \pm 0.2 \text{ kJ·min}^{-1}] (i.e., approx. 4.1 kJ/minute).

What does this mean in practice?

The resting energy requirements of the two groups are almost identical, so allulose itself did not significantly increase REE, but rather increased postprandial fat oxidation after eating.

Based on the results, the effect on weight maintenance is more related to the altered oxidation direction (fat vs. carbohydrate) and greater energetic utilization after eating, rather than an increase in basal metabolic rate.

D-allulose significantly increased fat burning (FEE = fat oxidation / Fat Energy Expenditure) after meals, while resting energy consumption (REE) did not change significantly.

What does the study specifically show?

In the allulose group, fat oxidation (FEE) increased significantly in the postprandial period, especially from 90 minutes onwards, and the 4-hour AUC (Area Under the Curve) was also greater than in the control group.

At the same time, carbohydrate oxidation and the respiratory quotient (RQ) decreased, indicating that the body oxidized more fat and less carbohydrate under the effect of allulose.

How can this be summarized?

Allulose contributed to increased energy expenditure not by increasing the resting metabolic rate (REE), but by enhancing postprandial fat burning (FEE); thus, FEE showed a significant increase, but there was no significant difference in REE.

RQ in the study

"Respiratory Quotient", which is the ratio of carbon dioxide produced and oxygen consumed by the body.

In other words, how much carbon dioxide the body produces for a unit of consumed oxygen.

What does its value mean in fat/carbohydrate oxidation?

RQ ≈ 1.0 → the body primarily oxidizes carbohydrates.

RQ ≈ 0.7 → the body primarily oxidizes fat.

RQ ≈ 0.8–0.85 → the body burns both in combination, typical range for resting metabolic rate.

In the d-allulose article, the decreased RQ indicates that after the meal, the body oxidized less carbohydrate and more fat, meaning that fat burning (FEE) increased under the effect of allulose.

The AUC

In a scientific context, it is an abbreviation for "Area Under the Curve": thus, the value of the area under a curve, which summarizes how a given quantity (e.g., fat oxidation, carbohydrate oxidation, hormone concentration) has changed over time.

What is its practical significance?

For example, if you measure fat oxidation (kW or kJ/min) for hours after a meal, the AUC tells you the total amount of energy the body burned from fat during that period (e.g., over 4 hours), not just the instantaneous values.

In SI-like terms, this is most often given in energy-time units, e.g., kJ·h·kg⁻¹ or kJ·4 h·kg⁻¹, thus a measure of a kind of "total exposure" or "total energy consumption."

Discussion

In previous animal studies, d-allulose reduced body weight and abdominal fat mass [10], [11], [12], [13], suggesting that diets containing 3%–5% d-allulose may have anti-obesity effects.

The proposed mechanism for d-allulose-induced anti-obesity effects is that d-allulose inhibits hepatic lipogenesis [10], [12] and enhances hepatic fatty acid oxidation, leading to increased energy expenditure [13].

Partially agreeing with previous animal studies [13], the current study showed that:

Conclusion

At a low dose, d-allulose enhanced postprandial fat oxidation and suppressed carbohydrate oxidation in healthy humans.

This suggests that d-allulose can potentially serve as an anti-obesity sweetener in humans.

Further human studies are needed to confirm these effects, including a large number of individuals with various diseases, such as diabetes and obesity.

Acknowledgements

The authors thank the volunteers who participated in the study.

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