Digestive tolerance of inulin-type fructans: a double-blind, placebo-controlled, cross-over, dose-ranging, randomized study in healthy volunteers

Background Similar to other indigestible carbohydrates or dietary fibres, a consumption of too large quantities of inulin-type fructans may cause some digestive problems. Aim To compare the digestive tolerance of inulin-type fructans, administered during 2 weeks, at different doses. Methods Eighty-four healthy volunteers (aged 18-45 years, mean body mass index 25.1 kg/m(2) and mean total fibre consumption 12 g) were included in a double-blind, placebo-controlled, randomized, cross-over study comparing Fibrulose F97 (5 and 20 g/day), Fibruline Instant (5, 10 and 20 g/day) and Fibruline XL (10 g/day) (degrees of polymerization respectively equal to 2-20, 2-60 with an average of 10, and 2-60 with an average >20) to placebo. The study was decomposed into five 2-week periods: placebo run-in, treatment 1, placebo washout, treatment 2, placebo run-out. The following symptoms were assessed using visual analogue scales: flatulence, rumbling, bloating, abdominal pain, abdominal cramps, nausea, stool frequency and stool consistency. The primary variable was the mean difference between treatment and placebo in terms of tolerance (sum of the eight visual analogue scales). Results The three products tended to increase digestive symptoms whatever the dose but the change was mild (maximum, +19 mm on the 800-mm scale) and significant (P<0.001) for Fibruline Instant at 20 g/day only. At 20 g/day, a statistically significant difference between Fibruline Instant and Fibrulose F97 was demonstrated (P=0.011). There was a dose-effect relationship both for Fibrulose F97 (P>0.05) and Fibruline Instant (P=0.042). All the other tendencies were non-significant. Conclusions The three different inulin-type fructans were very well tolerated.     

Digestive tolerance of inulin-type fructans: a double-blind,placebo-controlled,cross-over,dose-ranging,randomized study in healthy volunteers

Background Similar to other indigestible carbohydrates or dietary fibres, a consumption of too large quantities of inulin-type fructans may cause some digestive problems.

Aim To compare the digestive tolerance of inulin-type fructans, administered during 2 weeks, at different doses.

Methods Eighty-four healthy volunteers (aged 18–45 years, mean body mass index 25.1 kg/m² and mean total fibre consumption 12 g) were included in a double-blind, placebo-controlled, randomized, cross-over study comparing Fibrulose F97 (5 and 20 g/day), Fibruline Instant (5, 10 and 20 g/day) and Fibruline XL (10 g/day) (degrees of polymerization respectively equal to 2–20, 2–60 with an average of 10, and 2–60 with an average >20) to placebo. The study was decomposed into five 2-week periods: placebo run-in, treatment 1, placebo washout, treatment 2, placebo run-out. The following symptoms were assessed using visual analogue scales: flatulence, rumbling, bloating, abdominal pain, abdominal cramps, nausea, stool frequency and stool consistency. The primary variable was the mean difference between treatment and placebo in terms of tolerance (sum of the eight visual analogue scales).

Results The three products tended to increase digestive symptoms whatever the dose but the change was mild (maximum, +19 mm on the 800-mm scale) and significant (P<0.001) for Fibruline Instant at 20 g/day only. At 20 g/day, a statistically significant difference between Fibruline Instant and Fibrulose F97 was demonstrated (P=0.011). There was a dose–effect relationship both for Fibrulose F97 (P>0.05) and Fibruline Instant (P=0.042). All the other tendencies were non-significant.

Conclusions The three different inulin-type fructans were very well tolerated.     

Four-week ingestion of blood orange juice results in measurable anthocyanin urinary levels but does not affect cellular markers related to cardiovascular risk: a randomized cross-over study in healthy volunteers

Purpose

Blood orange juice (OJ) is an important source of anthocyanins (ACN). The latter molecules are endowed with antioxidant activity and might thus modulate different cell function. Our aim was to investigate ACN absorption following a 1-month daily supplementation of blood OJ and their potential effects on cell markers of platelet and leukocyte activation and interaction.

Methods

Eighteen healthy subjects (10 men and 8 women) were supplemented for 4?weeks with 1?L/day of either blood OJ or blond OJ (that contains no ACN), following a cross-over design. Blood samples were obtained from fasting participants both at baseline and after each week of treatment to measure plasma ACN concentration. At the same time-intervals, 24-h urinary excretion of these molecules was also measured. At the beginning and the end of each 4-week intervention period, platelet and leukocyte markers and mixed cell conjugates were assessed both in basal condition and upon in vitro collagen/ADP activation.

Results

After 1?week supplementation with blood OJ, 24-h urinary excretion of ACN reached average levels of 11.47?±?5.63?nmol that significantly differed from baseline and remained substantially unchanged until the end of treatment. No plasma accumulation of ACN following blood OJ supplementation was observed. Cellular markers were not significantly affected by either OJ after 4-week supplementation.

Conclusions

Following supplementation of healthy volunteers with 1 L/day of blood OJ for 4?weeks, the ACN plasma levels reached were insufficient to significantly modify cell markers of platelet and leukocyte activation and interaction.     

Postprandial protein metabolism but not a fecal test reveals protein malabsorption in patients with pancreatic exocrine insufficiency

Background & aims

Pancreatic exocrine insufficiency (PEI) impairs fat absorption, but few data are available on protein absorption. We investigated this question in patients with chronic pancreatitis, both in the absence and presence of enzyme therapy, using a stable isotope sensitive method.

Methods

Eleven patients with sustained PEI and regular enzyme substitution were investigated at hospital, after a washout period without enzyme substitution, and later after reintroduction of substitution. The digestibility and postprandial metabolism of dietary protein were characterized after the ingestion of a semi-synthetic single meal containing 20 g ¹⁵N-labeled casein.

Results

At baseline, 20 ± 8% of dietary nitrogen was transferred to the metabolic pools vs. 24.5 ± 7% under enzyme treatment (P = 0.04). After treatment, the transfer of dietary nitrogen tended to increase in plasma amino acids, and increased significantly in plasma proteins and the deamination pool. In contrast, the fecal excretion of dietary nitrogen did not demonstrate any treatment effect. In patients not receiving insulin for diabetes, the treatment stimulated insulin secretion.

Conclusions

Protein malabsorption was mostly undetectable using standard fecal tests. The study of the postprandial fate of dietary protein revealed a moderate increase of its transfer to metabolic pools after enzyme substitution.     

Ginseng does not enhance psychological well-being in healthy, young adults: results of a double-blind, placebo-controlled, randomized clinical trial.

OBJECTIVE: Ginseng is a popular, commercially available dietary supplement that is purported to have a number of psychological benefits. The purpose of this study was to examine these claims, with specific reference to ginseng's effects on affect and mood. DESIGN: Prospective, double-blind, placebo-controlled, randomized clinical trial. PARTICIPANTS/SETTING: Eighty-three adults (40 women, 43 men) participated in this study (mean age = 25.7 year). Participants were recruited from within a university community and at area health clubs. INTERVENTION: Participants were randomly assigned to one of three experimental conditions: placebo (lactose), 200 mg ginseng, or 400 mg ginseng. The ginseng preparation used in this study consisted of the Panax ginseng C A Meyer concentrate G115 in capsular format. Each participant was given a 60-day allotment of their respective supplement along with written instructions about the proper intake and storage of the capsules during the 8-week study period. MAIN OUTCOME MEASURES: Positive affect, negative affect, and total mood disturbance. Measures were obtained pre- and post-intervention. STATISTICAL ANALYSES PERFORMED: Repeated measures multivariate analysis of variance was used. Because there were three dependent variables, and in an effort to minimize the experimentwise-error rate, alpha was adjusted using the Bonferroni technique (i.e., P < .05/3 = P < .016). RESULTS: Ginseng supplementation had no effect on positive affect, negative affect, or total mood disturbance (all P > .016). CONCLUSION: The present findings do not support claims that chronic ginseng supplementation--at either its clinically recommended level or at twice that level--enhances affect or mood in healthy young adults.     

Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study

BACKGROUND: Osteoporosis is a major health problem. It was hypothesized that isoflavone-containing products may be a potential alternative to hormone replacement therapy for preventing bone loss during the menopausal transition. OBJECTIVE: The objective was to investigate whether the consumption of isoflavone-enriched foods for 1 y affects bone mineral density, bone metabolism, and hormonal status in early postmenopausal women. DESIGN: This was a randomized, double-blind, placebo-controlled, parallel, multicenter trial. Two hundred thirty-seven healthy early postmenopausal women [mean (+/-SD) age of 53 +/- 3 y and time since last menses of 33 +/- 15 mo] consumed isoflavone-enriched foods providing a mean daily intake of 110 mg isoflavone aglycones or control products for 1 y while continuing their habitual diet and lifestyle. Outcome measures included bone mineral density of the lumbar spine and total body, markers of bone formation and bone resorption, hormones, isoflavones in plasma and urine, safety variables, and adverse events. RESULTS: Consumption of isoflavone-enriched products did not alter bone mineral density of the lumbar spine and total body or markers of bone formation and bone resorption. Hormone concentrations did not differ between the isoflavone and control groups. Consumption of isoflavone-enriched products resulted in increased isoflavone concentrations in plasma and urine, whereas control products did not. This finding indicated good compliance with treatment. Subgroup analysis did not support an effect of equol phenotype on bone density. The intervention had no effect on a range of safety variables and reported adverse events. CONCLUSION: Consumption of foods containing 110 mg/d of soy isoflavone aglycone equivalents for 1 y did not prevent postmenopausal bone loss and did not affect bone turnover in apparently healthy early postmenopausal white women. This trial was registered at clinicaltrials.gov as NCT00301353.     

Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects

Purpose

Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls.

Methods

Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix (“SMB”, FloraGLO^® Lutein 5 %) or as a cross-linked alginate-matrix beadlet (“AMB”, Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h.

Results

The mean plasma AUC_(0–72h), AUC_(0–672h), and C _max for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T _max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC_(0–72h) and AUC_(0–672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study.

Conclusion

These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.     

Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects--a randomized double-blind placebo-controlled crossover study

BACKGROUND & AIMS: Ingestion of Ginkgo biloba Extract (EGb 761) may increase pancreatic beta-cell function in both healthy subjects with normal glucose tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased insulin production is not due to increased insulin resistance. METHOD: NGT subjects (n = 10; age, 44.2 +/- 13.9 years old), impaired glucose tolerance (IGT) (n = 8; age 51.3 +/- 6.6 years old) and T2DM subjects (n = 8, 51.6 +/- 15.2 years old) completed a randomized, double-blind, placebo-controlled crossover study. After ingesting either EGb 761 (120 mg/day as a single dose) or placebo during each 3-month arm, a 2-step euglycemic insulin clamp was performed. RESULTS: At the low insulin infusion rate (10 mU/m2/min) the glucose metabolic rates (M values) were 3.5 +/- 1.5 vs. 3.0 +/- 0.5 mg/kg (P = 0.16), 3.0 +/- 0.4 vs. 2.8 +/- 0.8 mg/kg (P = 0.19) and 2.6 +/- 0.7 vs. 2.4 +/- 0.5 mg/kg (P = 0.09) for the placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At the high insulin infusion rate (40 mU/m2/min) the M values were 7.3+/-2.3 vs. 8.1 +/- 2.5mg/kg (P = 0.07), 6.2 +/- 1.6 vs. 6.5 +/- 2.1 mg/kg (P = 0.32) and 3.6 +/- 1.6 vs. 3.5 +/- 1.0 mg/kg (P = 0.34) for placebo vs. EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. CONCLUSION: The ingestion of 120 mg of EGb 761 as a single for 3 months did not produce insulin resistance in the non-diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects.     

Antioxidant cocktail following a high-sodium meal does not affect vascular function in young,healthy adult humans: a randomized controlled crossover trial

Chronic high sodium intake is a risk factor for cardiovascular disease as it impairs vascular function through an increase in oxidative stress. The objective of this study was to investigate the acute effects of a high-sodium meal (HSM) and antioxidant (AO) cocktail on vascular function. We hypothesized that a HSM would impair endothelial function, and increase arterial stiffness and wave reflection, while ingestion of the AO cocktail would mitigate this response. Healthy adults ingested either an AO cocktail (vitamin C, E, alpha-lipoic acid) or placebo (PLA) followed by a HSM (1500 mg) in a randomized crossover blinded design. Blood pressure (BP), endothelial function (flow-mediated dilation; FMD) and measures of arterial stiffness (pulse wave velocity; PWV) and wave reflection (augmentation index; AIx) were made at baseline and 30, 60, 90, and 120 min after meal consumption. Forty-one participants (20M/21W; 24 ± 1 years; BMI 23.4 ± 0.4 kg/m²) completed the study. Mean BP increased at 120 min relative to 60 min (60 min: 79 ± 1; 120 min: 81 ± 1 mmHg; time effect P = .01) but was not different between treatments (treatment × time interaction P = .32). AIx decreased from baseline (time effect P < .001) but was not different between treatments (treatment × time interaction P = .31). PWV (treatment × time interaction, P = .91) and FMD (treatment × time interaction P = .65) were also not different between treatments. In conclusion, a HSM does not acutely impair vascular function suggesting young healthy adults can withstand the acute impact of sodium on the vasculature and therefore, the AO cocktail is not necessary to mitigate the response.     

胰岛素对短肠综合征大鼠蛋白质代谢及肠功能代偿的影响

目的:采用短肠综合征(SBS)大鼠的TEN模型,研究胰岛素(INS)对蛋白质代谢的影响及其残存肠管的代偿作用. 方法: 将30只大鼠随机分为三组,每组10只.假手术(Sham)组、短肠(SBS)组和短肠 胰岛素(SBS-INS)组.Sham组大鼠仅切断吻合小肠;SBS组切除85%小肠;SBS-INS组切除85%以上小肠并皮内注射速效胰岛素制剂.各组大鼠术后均行TEN支持.观察大鼠术后的一般情况、营养状况、氮平衡、残存肠黏膜DNA和蛋白质含量、肠绒毛高度、肠隐窝深度和隐窝细胞的增殖指数. 结果:SBS-INS组大鼠术后第12～14天体质量显著高于SBS组,术后第5～14天,氮平衡亦显著优于SBS组;SBS-INS组大鼠的营养指标、肠黏膜DNA和蛋白质含量、肠绒毛高度、肠隐窝深度和隐窝细胞的增殖指数,显著高于SBS组. 结论:胰岛素能促进EN支持的SBS大鼠蛋白质合成及残存肠管的代偿,从而增加肠道的吸收面积,改善营养状况.     

Safety,tolerability and immunogenicity of GS-4774, a hepatitis B virus-specific therapeutic vaccine,in healthy subjects: A randomized study

Background

GS-4774 is a recombinant, heat-killed, yeast-based immunotherapy engineered to express hepatitis B virus (HBV)-specific antigens. GS-4774 is being developed as a therapeutic vaccine for chronic HBV infection. The aim of this study was to assess the safety, tolerability and immunogenicity of GS-4774 in healthy subjects.

Design

This was a randomized, open-label, dose-ascending study. Subjects were allocated to one of three dose groups (n = 20 per group) to receive 10, 40 or 80 yeast units (YU; 1 YU = 10⁷ yeast) of GS-4774 in two immunization regimens (five subcutaneous injections at weekly intervals with one monthly booster or three subcutaneous injections at monthly intervals). T-cell-mediated responses were determined by interferon (IFN)-γ enzyme-linked immunospot (ELISpot) assay and lymphocyte-proliferation assay (LPA).

Results

Adverse events were reported by 39 of 60 (65%) subjects; all were mild or moderate and none was serious. Adverse events occurred most frequently in the highest dose group, 80 YU, and the number of individual events was higher after weekly immunization than monthly. The most common adverse events were injection-site reactions. Most (88%) subjects responded to GS-4774 by at least one of the T-cell assays. Following immunization with GS-4774, IFN-γ-producing T-cells specific for HBV antigens were detectable in 30 (51%) subjects. The ELISpot response was observed at all doses, with the highest frequency of responders occurring at the highest dose (10 YU: 45%; 40 YU: 35%; 80 YU: 74%). Proliferative responses to HBV recombinant antigens were observed in 90% subjects; responses were mainly independent of GS-4774 dose and immunization regimen.

Conclusions

GS-4774 was safe and well-tolerated in healthy subjects with injection-site reactions being the most frequently reported adverse events. With both weekly and monthly regimens, GS-4774 provided HBV-specific immune responses at all doses evaluated. Further evaluation of GS-4774 is ongoing in patients with chronic HBV infection.Clinical trial registry: Clinicaltrials.gov (NCT01779505)     

Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study

BACKGROUND: In a recent pilot study, the intake of elderberry juice resulted in a significant decrease in serum cholesterol concentrations and an increase in low-density lipoprotein (LDL) stability. This study was designed to verify the preliminary results. OBJECTIVE: We investigated the impact of elderberry juice on cholesterol and triglyceride concentrations as well as antioxidant status in a cohort of young volunteers. DESIGN: Study A: The randomized, placebo-controlled trial for studying the effect of anthocyanes on lipid and antioxidant status, 34 subjects took capsules with 400 mg spray-dried powder containing 10% anthocyanes t.i.d. equivalent to 5 ml elderberry juice for 2 weeks. A subgroup of 14 subjects continued for an additional week to test for resistance to oxidation of LDL. Study B: To investigate the short-term effects on serum lipid concentrations, six subjects took a single dose of 50 ml of elderberry juice (equivalent to 10 capsules) along with a high-fat breakfast. RESULTS: In the placebo-controlled study, there was only a small, statistically not significant change in cholesterol concentrations in the elderberry group (from 199 to 190 mg/dl) compared to the placebo group (from 192 to 196 mg/dl). The resistance to copper-induced oxidation of LDL did not change within 3 weeks. In the single-dose experiment increases in postprandial triglyceride concentrations were not significantly different when the six subjects were investigated with and without elderberry juice. CONCLUSIONS: Elderberry spray-dried extract at a low dose exerts a minor effect on serum lipids and antioxidative capacity. Higher, but nutritionally relevant doses might significantly reduce postprandial serum lipids.     

健康生活方式与糖尿病前期人群糖尿病发病关系的前瞻性研究

目的 探讨健康生活方式对糖尿病前期人群糖尿病发病风险的影响,为糖尿病前期人群的生活方式干预提供参考依据。方法 数据来源于贵州省自然人群队列研究。组合分析9种健康生活方式对糖尿病发病的影响,采用SPSS 26.0对数据进行χ2检验、单因素方差分析、Cox风险回归模型分析及分位数回归模型分析。结果 单种健康生活方式与糖尿病发病关联分析显示,烹调油摄入≤30 g/d、18.5≤BMI＜24 kg/m2能有效降低糖尿病发病风险,HR分别为0.500（95%CI:0.335～0.747）、0.420（95%CI:0.290～0.610）,未发现其他生活方式与糖尿病的发病相关。多种健康生活方式组合分析显示与0～3种相比,保持6种、7种及以上健康生活方式的人群发生糖尿病的风险分别为HR = 0.478（95%CI:0.239～0.956）、HR = 0.282（95%CI:0.108～0.737）。分位数回归结果显示,与0～3种健康生活方式相比,健康生活方式为4/5种以上,能降低0.9分位点的空腹血糖/OGTT 2 h血糖值;当健康生活方式达7种以上,能降低0.3～0.9分位点的血糖值,且分位水平越高,降低的血糖值越多。结论 健康生活方式能有效降低糖尿病前期人群血糖水平,且健康生活方式种类越多,糖尿病发病的风险越小。     

Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers

In humans caffeine stimulates thermogenesis by unknown mechanisms and its effect on body weight has not been studies. The effect of placebo and 100, 200, and 400 mg oral caffeine on energy expenditure, plasma concentrations of substrates and hormones, blood pressure, and heart rate was investigated in a double-blind study in healthy subjects who had a moderate habitual caffeine consumption. Caffeine increased energy expenditure dose dependently and the thermogenic response was positively correlated with the response in plasma caffeine (r = 0.52; p less than 0.018), plasma lactate (r = 0.79; p less than 0.000001), and plasma triglyceride (r = 0.53; p less than 0.02). Stepwise regression analysis with the thermogenic response as the dependent variable excluded plasma caffeine and yielded the following equation: thermic effect (kcal/3 h) = -0.00459 X heart rate + 0.30315 X (triglyceride) + 0.53114 X (lactate) + 15.34 (r = 0.86; p = 0.0001). The results suggest that lactate and triglyceride production and increased vascular smooth muscle tone may be responsible for the major part of the thermogenic effect of caffeine.     

Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study

Background

This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women.

Study Design

On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra®, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing®, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry.

Results

In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values.

Conclusion

Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.