Resistant Maltodextrin Suppresses Intestinal Phenols Production by Modifying the Intestinal Environment.

Protein is an essential nutrient that plays several roles in the maintenance of the human body. A high-protein diet is also known to play an important role in weight management in obese individuals and in maintaining muscle strength in the elderly. However, over-consumption of protein can have negative effects on health, including deterioration of the intestinal environment by the production of amino acid metabolites such as phenols. Interest in the regulation of the intestinal environment to maintain health has gained attention recently. Resistant maltodextrin (RMD) is a prebiotic dietary fiber. Therefore, we investigated whether RMD suppressed the production of amino acid metabolites through intestinal regulation in rats. Wistar rats were fed either an AIN-93G diet or a modified AIN-93G diet containing 5% tyrosine. RMD (2.5% or 5.0%) was provided with drinking water. The rats were fed these diets and water ad libitum for 3 wk. Urine was collected overnight, after which serum, liver, kidneys, and the whole cecum were collected from rats under anesthesia with isoflurane for analysis of phenols and microbiota. RMD decreased the cecal, serum, and urinary levels of phenols, especially phenol. Moreover, the relative abundance of intestinal Romboutsia ilealis showed a significant correlation with the cecal phenols levels, and RMD decreased the abundance of this species. Thus, RMD may suppress phenols production and decrease serum phenols levels by altering the intestinal environment in rats.

Long-term D-Allose Administration Favorably Alters the Intestinal Environment in Aged Male Mice.

D-Allose, a C3 epimer of D-glucose, has potential to improve human health as a functional food. However, its effect on the intestinal environment remains unknown. Aged humans progressively express changes in the gut, some of which deleteriously affect gastrointestinal health. In this study, we profiled the intestinal microbiome in aged mice and analyzed organic acids produced by bacteria in cecum contents after long-term ingestion of D-allose. D-Allose did not significantly change organic acid concentration. However, long-term ingestion did significantly increase the relative abundance of Actinobacteria and reduce the relative abundance of Proteobacteria. These results suggest that oral D-allose improves the proportion of favorable intestinal flora in aged mice. D-Allose significantly decreased the relative abundance of Lachnospiraceae bacteria, but increased the relative abundance of Bacteroides acidifaciens and Akkermansia muciniphila. Thus, D-allose might serve as a nutraceutical capable of improving the balance of gut microbiome during aging.

d-allulose protects against diabetic nephropathy progression in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes.

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.

Effect of D-allulose feeding on the hepatic metabolomics profile in male Wistar rats.

The rare sugar d-allulose is a C-3 epimer of d-fructose and is known to have several health benefits such as anti-obesity and anti-diabetic effects through the alteration of enzymatic and genetic expressions in each organ. Most of the ingested d-allulose is absorbed in the small intestine and then rapidly excreted in the urine. As d-allulose was reported to be present in the liver before it is excreted, d-allulose may modulate some hepatic metabolites including glucose and lipid metabolism. Therefore, we investigated the hepatic metabolomics profile in rats after feeding d-allulose to study the overall alteration of hepatic metabolism. Wistar rats were fed an AIN-93G diet with/without 3% d-allulose for 4 weeks. Their liver samples were then collected and subjected to metabolomics analysis using CE-TOFMS and LC-TOFMS. The results showed that d-allulose induced significant increases in 42 metabolites and significant decreases in 21 metabolites. In particular, we found at the substance levels that d-allulose regulated metabolites involved in the metabolic pathways of fatty acid ß-oxidation, cholesterol, and bile acid. In addition, this study newly showed the possibility that d-allulose alters glucuronic acid/xylulose pathways. In the future, we need more detailed research on the metabolomics profile of other organs related to these pathways for a comprehensive understanding of d-allulose functions.

D-Allulose enhances uptake of HDL-cholesterol into rat's primary hepatocyte via SR-B1.

D-Allulose, a C-3 epimer of D-fructose, is a rare sugar and a non-caloric sweetener. D-Allulose is reported to have several health benefits, such as suppressing a rise in postprandial glucose levels and preventing fat accumulation in rodents and humans. Additionally, low HDL-cholesterol levels post-D-allulose feeding were observed in humans but it is unclear how D-allulose decreased HDL-cholesterol levels. It is necessary to research the mechanism of HDL-cholesterol reduction by D-allulose ingestion because low HDL-cholesterol levels are known to associate with increased atherosclerosis risk. We therefore investigated the mechanism by which D-allulose lowers HDL-cholesterol using rat's primary hepatocytes. Sprague Dawley rats were fed an AIN-93G based diet containing 3% D-allulose for 2 weeks. Thereafter, primary hepatocytes were isolated by perfusion of collagenase. We measured the ability of HDL-cholesterol uptake in hepatocytes and the protein levels of scavenger receptor class B type 1 (SR-B1) as a HDL-cholesterol receptor. D-Allulose enhanced hepatocyte uptake of HDL-cholesterol, with a concurrent increase in hepatic SR-B1 protein levels. The results suggest that D-allulose enhances HDL-cholesterol uptake into the liver by increasing SR-B1 expression. It is estimated that HDL-cholesterol levels decreased accordingly. Since SR-B1 overexpression would decrease HDL-cholesterol levels, reportedly preventing atherosclerosis development, D-allulose could be a useful sweetener for atherosclerosis prevention.

Rare sugars, d-allulose, d-tagatose and d-sorbose, differently modulate lipid metabolism in rats.

BACKGROUND: Rare sugars including d-allulose, d-tagatose, and d-sorbose are present in limited quantities in nature; some of these rare sugars are now commercially produced using microbial enzymes. Apart from the anti-obesity and anti-hyperglycaemic activities of d-allulose, effects of these sugars on lipid metabolism have not been investigated. Therefore, we aimed to determine if and how d-tagatose and d-sorbose modulate lipid metabolism in rats. After feeding these rare sugars to rats, parameters on lipid metabolism were determined. RESULTS: No diet-related effects were observed on body weight and food intake. Hepatic lipogenic enzyme activity was lowered by d-allulose and d-sorbose but increased by d-tagatose. Faecal fatty acid excretion was non-significantly decreased by d-allulose, but significantly increased by d-sorbose without affecting faecal steroid excretion. A trend toward reduced adipose tissue weight was observed in groups fed rare sugars. Serum adiponectin levels were decreased by d-sorbose relative to the control. Gene expression of cholesterol metabolism-related liver proteins tended to be down-regulated by d-allulose and d-sorbose but not by d-tagatose. In the small intestine, SR-B1 mRNA expression was suppressed by d-sorbose. CONCLUSION: Lipid metabolism in rats varies with rare sugars. Application of rare sugars to functional foods for healthy body weight maintenance requires further studies. © 2017 Society of Chemical Industry.

d-Allulose enhances postprandial fat oxidation in healthy humans.

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.

D-psicose, an epimer of D-fructose, favorably alters lipid metabolism in Sprague-Dawley rats.

D-Psicose, a C3 epimer of D-fructose, is known to lower body weight and adipose tissue weight and affect lipid metabolism. The precise mechanism remains unknown. It has been reported that D-psicose has a short half-life and is not metabolized in the body. To determine how D-psicose modifies lipid metabolism, rats were fed diets with or without 3% D-psicose for 4 weeks. Rats were decapitated without fasting every 6 h over a period of 24 h. Changes in serum and liver lipid levels, liver enzyme activity, and gene expression were quantified in experiment 1. Rats fed D-psicose had significantly lower serum insulin and leptin levels. Liver enzyme activities involved in lipogenesis were significantly lowered by the D-psicose diet, whereas gene expression of a transcriptional modulator of fatty acid oxidation was enhanced. In experiment 2, feeding the D-psicose diet gave significantly lower body weight (389 ± 3 vs 426 ± 6 g, p < 0.05) and food intake (23.8 ± 0.2 vs 25.7 ± 0.4 g/day, p < 0.05) compared to the control diet. Rats fed the D-psicose diet gave significantly higher energy expenditure in the light period and fat oxidation in the dark period compared to rats fed the control diet, whereas carbohydrate oxidation was lower. In summary, these results indicate that the D-psicose diet decreases lipogenesis, increases fatty acid oxidation, and enhances 24 h energy expenditure, leading to d-psicose's potential for weight management.