alpha-cyclodextrin and Body-Weight

The prevalence of pre-diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre-diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha-cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti-hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12-month randomized controlled trial to investigate the metabolic effects of these two products in people with pre-diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow-up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre-diabetes to help reduce the risk of progression to type 2 diabetes.

Topics: Adult; alpha-Cyclodextrins; Blood Glucose; Body Weight; Cholesterol; Diabetes Mellitus, Type 2; Female; Ginsenosides; Humans; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Triglycerides

α-Cyclodextrin (α-CD), a cyclic polymer of glucose, has been shown to lower plasma cholesterol in animals and humans; however, its effect on atherosclerosis has not been previously described.. apoE-knockout mice were fed either low-fat diet (LFD; 5.2% fat, w/w), or Western high fat diet (21.2% fat) containing either no additions (WD), 1.5% α-CD (WDA); 1.5% β-CD (WDB); or 1.5% oligofructose-enriched inulin (WDI). Although plasma lipids were similar after 11 weeks on the WD vs. WDA diets, aortic atherosclerotic lesions were 65% less in mice on WDA compared to WD (P < 0.05), and similar to mice fed the LFD. No effect on atherosclerosis was observed for the other WD supplemented diets. By RNA-seq analysis of 16S rRNA, addition of α-CD to the WD resulted in significantly decreased cecal bacterial counts in genera Clostridium and Turicibacterium, and significantly increased Dehalobacteriaceae. At family level, Comamonadaceae significantly increased and Peptostreptococcaceae showed a negative trend. Several of these bacterial count changes correlated negatively with % atherosclerotic lesion and were associated with increased cecum weight and decreased plasma cholesterol levels.. Addition of α-CD to the diet of apoE-knockout mice decreases atherosclerosis and is associated with changes in the gut flora.

Topics: alpha-Cyclodextrins; Animals; Aorta; Atherosclerosis; beta-Cyclodextrins; Body Weight; Cecum; Diet, Fat-Restricted; Diet, High-Fat; Dietary Supplements; Female; Gastrointestinal Microbiome; Intestinal Absorption; Lipids; Mice, Knockout, ApoE

High dietary intake of saturated fat and cholesterol, and elevated low-density lipoprotein cholesterol levels are some of the modifiable risk factors for cardiovascular disease. Alpha-cyclodextrin (a-CD) when given orally has been shown in rats to increase fecal saturated fat excretion and to reduce blood total cholesterol levels in obese hypertriglyceridemic subjects with type 2 diabetes mellitus. In this study, the effects of dietary a-CD on lipid metabolism in low-density lipoprotein receptor knockout mice were investigated. Low-density lipoprotein receptor knockout mice were fed a "Western diet" (21% milk fat) with or without 2.1% of a-CD (10% of dietary fat content) for 14 weeks. At sacrifice, there was no difference in body weight; but significant decreases were observed in plasma cholesterol (15.3%), free cholesterol (20%), cholesterol esters (14%), and phospholipid (17.5%) levels in mice treated with alpha-CD compared with control mice. The decrease in total cholesterol was primarily in the proatherogenic apolipoprotein B-containing lipoprotein fractions, with no significant change in the high-density lipoprotein fraction. Furthermore, alpha-CD improved the blood fatty acid profile, reducing the saturated fatty acids (4.5%) and trans-isomers (11%) while increasing (2.5%) unsaturated fatty acids. In summary, the addition of alpha-CD improved the lipid profile by lowering proatherogenic lipoproteins and trans-fatty acids and by decreasing the ratio of saturated and trans-fatty acids to polyunsaturated fatty acids (-5.8%), thus suggesting that it may be useful as a dietary supplement for reducing cardiovascular disease.

Topics: alpha-Cyclodextrins; Animals; Atherosclerosis; Body Weight; Cholesterol Esters; Cholesterol, LDL; Dietary Fats; Eating; Fatty Acids, Nonesterified; Female; Lipid Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Random Allocation; Receptors, LDL; Triglycerides

This study was designed to investigate a new dietary fiber, alpha-cyclodextrin, marketed under the trade name FBCx (Wacker Biochem, Adrian, MI), for beneficial effects on weight reduction and the improvement of certain blood parameters in rats. Male Wistar rats were divided into 4 groups and fed ad libitum for a period of 6 weeks: (1) a normal low-fat diet (LF; 4% fat wt/wt); (2) an LF diet with FBCx added; (3) a high-fat diet (HF, 40% fat wt/wt); and (4) an HF diet with FBCx. The FBCx was added at the rate of 10% (wt/wt) of the fat in the diet. Body weight and food intake were recorded 3 times per week. Plasma constituent levels and liver and fecal lipid contents, as well as body composition were determined at sacrifice. Adding FBCx to the diet significantly reduced weight gain in rats fed with an HF diet relative to rats fed with the HF control diet (P < .05). FBCx also elicited a reduction in plasma triglyceride levels of 30%, total cholesterol of 9%, and increased the fat content of the feces in the rats fed with the HF diet with FBCx. In addition, the serum leptin levels were normalized, and the calculated insulin sensitivity was improved. No adverse effects were observed in the rats consuming FBCx. It would appear that FBCx might be effective in reducing body weight gain and improving metabolic syndrome.

Topics: alpha-Cyclodextrins; Animals; Blood Glucose; Body Composition; Body Weight; Cholesterol; Dietary Fats; Dietary Fiber; Eating; Feces; Insulin; Leptin; Liver; Male; Obesity; Rats; Rats, Wistar; Triglycerides

The toxicity of alpha-cyclodextrin (alpha-CD), a cyclic polymer of six alpha-1,4-linked glucopyranosyl units with potential applications as a food ingredient, more specifically a water-soluble dietary fiber, was examined in a 4-week range finding study and a 13-week oral toxicity study in rats. In the 4-week study, the test substance was administered to groups of Bor:WISW(SPF;Cpb) rats at dietary levels of 0, 1, 5, and 15% (5 rats/sex/group). An additional group received a diet with 5% beta-CD. In the 13-week study, groups of Crl:(WI)WU Br rats received diets with 0, 1.5, 5, or 20% alpha-CD. An additional group received a diet with 20% lactose (20 rats/sex/group). Satellite groups of 10 rats/sex were attached to the control, 20% alpha-CD and 20% lactose group. Following the 13-week treatment period, these satellite groups were kept on a standard, cereal-based rodent diet for a 4-week recovery period. Parameters measured during the two studies included clinical signs, body weights, food and water intake, hematological and clinicochemical parameters, and organ weights as well as gross and histopathological observations at necropsy. In the 13-week study, ophthalmoscopic examinations as well as urine and feces analyses were also conducted. There were no treatment-related mortalities in either study. In the 4-week study, persistent diarrhea was the most prominent, treatment-related effect observed in the animals of the 15% alpha-CD group especially in the male animals. In association with this effect, food consumption and food conversion efficiency were decreased. In line with observations from studies with other low-digestible, yet fermentable carbohydrates, the weight of the full and empty cecum was increased significantly in the 5% alpha-CD, 5% beta-CD, and 15% alpha-CD group. The reduced relative liver weights (in males and females) and the significantly increased relative testes weight which were observed in the 15% alpha-CD group, were attributed to the impaired nutritional condition (due to diarrhea) and the reduced body weight of the animals of this group, respectively. Microscopic examination of the main organs did not reveal pathological alterations that could be attributed to the alpha-CD treatment. In the 13-week study, soft stool and infrequent mild diarrhea were observed only during the first 2-3 weeks in the 20% alpha-CD and 20% lactose group (mainly male animals). Accordingly, body weights were reduced in males of the 20% lactose group througho

Topics: Administration, Oral; alpha-Cyclodextrins; Animals; Body Weight; Cyclodextrins; Diarrhea; Female; Male; Organ Size; Rats; Rats, Wistar; Toxicity Tests, Chronic

The application of alpha-cyclodextrin (alpha-CD) as an alternative vehicle for water insoluble and volatile chemicals was investigated in toxicity studies of p-chloro-alpha, alpha, alpha-trifluorotoluene (CTFT). Groups of F344 rats and B6C3F1 mice of each sex were administered CTFT (97% pure) by gavage in either corn oil or alpha-CD aqueous formulations daily for 14 consecutive days. The dose levels used were 10 (mice only), 50, 400, and 1000 mg/kg for corn oil vehicle and 10, 50, and 400 mg/kg (maximum achievable dose at gavage volume of 5 ml/kg) for alpha-CD vehicle. With both vehicles CTFT and alpha 2u-globulin were found to accumulate in the male rat kidney after 14 days of exposure and a dose-related toxic nephropathy was observed at dose of 50 mg/kg or higher. The hepatocellular hypertrophy and cytoplasmic vacuolation of the adrenal cortex which appeared in dosed male and female rats were also found to be independent of vehicle. Clinical pathology findings suggested a mild anemia and cholestasis in rats. With both vehicles no tissue bioaccumulation of CTFT was found in male or female mice. Vehicle-independent hepatocellular hypertrophy and cholestasis were also observed in mice at doses of 400 and 1000 mg/kg. In conclusion, the alpha-CD vehicle does not affect the toxic responses of CTFT in both sexes of both species. The results of the studies suggest that alpha-CD may be an appropriate alternative vehicle for toxicity studies.

Topics: alpha-Cyclodextrins; Alpha-Globulins; Animals; Blood Cell Count; Body Weight; Capsules; Corn Oil; Cyclodextrins; Female; Humans; Infant, Newborn; Kidney; Liver; Male; Mice; Mice, Inbred Strains; Organ Size; Pharmaceutical Vehicles; Proteins; Rats; Rats, Inbred F344; Species Specificity; Toluene

Digestibility of alpha- and beta-cyclodextrin (CD) and nutritional consequences of alpha-CD and a CD mixture (n-dextrin, alpha-, beta-and gamma-CDs = 50, 30, 15 and 5% by weight) were investigated in rats. In contrast with beta-CD, alpha-CD was revealed to be indigestible. Growing rats were fed on diets supplemented with the CD mixture at 19.5, 39, 58.5 and 78% levels for 110 days, resulting in smaller weight gain and body fat deposition when they were fed on a higher CD diet. Rates of weight loss during the restricted feeding were faster in rats fed on a higher CD diet. These were due to food efficiency lowered by CD. Reduced serum and liver triacylglycerol (TG) levels were noted during a 110-day period of feeding of the CD diets, and the former was revealed due to a reduced hepatic-intestinal TG secretion rate. Rats fed on a 78% CD diet, which contained alpha-CD at the 24% level, showed abnormal symptoms such as poor appetite and constipation with gas accumulation in the large intestine, and some of them died during the first 2-week feeding period. However, the surviving animals showed adaptation to the diet in the later period of the 110-day feeding. These results suggest that alpha-CD may be classified as dietary fiber which can modulate lipid metabolism in rats. Furthermore, the CD mixture may be available as a calorie substitute for weight control, which may owe mostly to alpha-CD.

Topics: alpha-Cyclodextrins; Animals; Body Weight; Cyclodextrins; Dextrins; Diet; Digestion; Feces; Intestinal Mucosa; Lipids; Lipoproteins, VLDL; Liver; Oligosaccharides; Rats; Rats, Inbred Strains; Starch; Triglycerides