Pharmacokinetics of a Single Dose of Turmeric Curcuminoids Depends on Formulation: Results of a Human Crossover Study.

BACKGROUND: Curcuminoids from turmeric rhizome have significant health benefits but low bioavailability. OBJECTIVES: To assess the pharmacokinetics of a novel natural turmeric dried colloidal suspension compared with 4 other turmeric formulations (including a standardized extract) at their respective recommended dosages. METHODS: Thirty healthy men and women (18 to 45 y old) were enrolled in a randomized, open-labeled, crossover trial, and sequentially consumed single oral doses of standard turmeric extract (1500 mg), liquid micellar preparation (1000 mg), piperine-curcuminoid combination (1515 mg), phytosome formulation (1000 mg), or the dried colloidal suspension (300 mg). Eleven blood samples were obtained over 24 h, plasma was extracted with or without deconjugation with ß-glucuronidase or sulfatase, and ultra-high-pressure liquid chromatography/tandem MS was used to quantify the 3 parent curcuminoids and 12 metabolites. Classical pharmacokinetics parameters were derived. RESULTS: The total AUC values of unconjugated curcuminoids were highly variable within participants, with no significant differences between formulations. However, the AUC values for total curcuminoids (including all metabolites) showed significant product effects. Indeed, the micellar preparation delivered higher levels of total curcuminoids than any other formulation (8540 ng·h/mL), reaching significance when compared with the dried colloidal suspension and standard extract (6520 and 5080 ng·h/mL, respectively). After dose normalization, both micellar and dried colloidal formulations showed significantly higher AUC levels than the standard extract (respectively 136 and 72.9, compared with 3.7 ng·h/mL/mg). Total curcuminoid absorption levels were also significantly higher for the dried colloidal suspension when compared with either piperine or phytosome formulations. Interestingly, no significant differences were observed between the piperine-curcuminoid combination and the standard extract. No serious adverse events were reported. CONCLUSIONS: The administration of a low dose of the novel natural dried colloidal suspension provided high unconjugated and conjugated curcuminoid absorption, with significant beneficial differences when compared with the high dose of standard extract.This trial was registered at clinicaltrials.gov as NCT03621865.

Randomized double blind placebo-controlled trial of Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: improvement in abdominal pain and bloating in those with predominant constipation.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain and/or discomfort. Probiotics have been reported to benefit IBS symptoms but the level of benefit remains quite unclear. OBJECTIVE: This study was designed to assess the benefit of Saccharomyces cerevisiae I-3856 on IBS symptoms. METHODS: A randomized, double blind, placebo-controlled trial has been performed in 379 subjects with diagnosed IBS. Subjects were randomly supplemented with the probiotics (1000 mg) or placebo for 12 weeks. Questionnaires (gastrointestinal symptoms, stools, wellbeing, and quality of life) were completed. Primary endpoint was percentage of responders defined as having a 50% decrease in the weekly average "intestinal pain/discomfort score" for at least 4 out of the last 8 weeks of the study. RESULTS: There was no overall benefit of S. cerevisiae I-3856 on IBS symptoms and wellbeing in the study population. Moreover, S. cerevisiae I-3856 was not statistically significant predictor of the responder status of the subjects (p > 0.05). Planned subgroup analyses showed significant effect in the IBS-C subjects: improvement of gastrointestinal symptoms was significantly higher in active group, compared to placebo, on abdominal pain/discomfort and bloating throughout the study and at the end of the supplementation. CONCLUSIONS: In this study, S. cerevisiae I-3856 at the dose of 1000 mg per day does not improve intestinal pain and discomfort in general IBS patients. However, it seems to have an effect in the subgroup with constipation which needs further studies to confirm (NCT01613456 in ClinicalTrials.gov registry).

Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: a randomized, double-blind placebo-controlled study.

BACKGROUND: Bacillus probiotics health benefits have been until now quite poorly studied in the elderly population. This study aimed to assess the effects of Bacillus subtilis CU1 consumption on immune stimulation and resistance to common infectious disease (CID) episodes in healthy free-living seniors. RESULTS: One hundred subjects aged 60-74 were included in this randomized, double-blind, placebo-controlled, parallel-arms study. Subjects consumed either the placebo or the probiotic (2.10(9) B. subtilis CU1 spores daily) by short periodical courses of 10 days intermittently, alternating 18-day course of break. This scheme was repeated 4 times during the study. Symptoms of gastrointestinal and upper/lower respiratory tract infections were recorded daily by the subjects throughout the study (4 months). Blood, saliva and stool samples were collected in a predefined subset of the first forty-four subjects enrolled in the study. B. subtilis CU1 supplementation did not statistically significantly decrease the mean number of days of reported CID symptoms over the 4-month of study (probiotic group: 5.1 (7.0) d, placebo group: 6.6 (7.3) d, P = 0.2015). However, in the subset of forty-four randomized subjects providing biological samples, we showed that consumption of B. subtilis CU1 significantly increased fecal and salivary secretory IgA concentrations compared to the placebo. A post-hoc analysis on this subset showed a decreased frequency of respiratory infections in the probiotc group compared to the placebo group. CONCLUSION: Taken together, our study provides evidence that B. subtilis CU1 supplementation during the winter period may be a safe effective way to stimulate immune responses in elderly subjects.

Digestive absorption of silicon, supplemented as orthosilicic acid-vanillin complex.

SCOPE: Silicon (Si) is an abundant element on earth. It is found naturally in water in the form of orthosilicic acid (OSA), however this form is not stable under certain conditions such as in highly concentrated and non-neutral pH solutions, which lead to its polymerization and reduced bioavailability. This study aimed to assess the bioavailability of Si from OSA stabilized by vanillin (OSA-VC). METHODS AND RESULTS: This was a single-center, double-blind, cross-over randomized controlled trial. Fourteen healthy subjects were recruited and consumed either OSA-VC or a placebo on two separate occasions. Blood and urine samples were collected during 6 h following ingestion and analyzed to determine Si absorption and excretion. Plasma Si area under the curve (0-6 h) was significantly higher after OSA-VC ingestion compared to placebo ingestion (p = 0.0002). Significantly higher urinary Si excretion was also reported over the 6-h period after OSA-VC ingestion compared to placebo (p<0.0001). Approximately 21% of ingested Si was excreted in urine during this period. CONCLUSION: Although many studies have investigated the metabolism and bioavailability of Si supplemented in foods or as a food ingredient, this was the first to investigate and demonstrate the digestibility of OSA administered in a complex form with vanillin.

A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial.

OBJECTIVE: To investigate the effect of a natural cholesterol-lowering supplement (NCLS) containing red yeast rice, policosanols and artichoke leaf extracts on blood lipid concentrations as well as on safety parameters when given over 16 weeks in 100 volunteers with untreated moderate hypercholesterolemia, in a randomized, double-blind, placebo-controlled trial. RESULTS: Reduction of primary outcome low-density lipoprotein cholesterol [-0.22 g/L (95% confidence interval, CI: -0.31 to -0.12) corresponding to -14.3% from baseline (95% CI: -21.5 to -7.2) compared to placebo], as well as total cholesterol, apolipoprotein B100 and apolipoprotein B100/apolipoprotein A-I ratio, were observed after 16 weeks of supplementation with NCLS. These effects were already observed at Week 4 and 10 of supplementation. No significant changes were observed in high-density lipoprotein, triacylglycerol, creatine kinase, lactate dehydrogenase and coenzyme Q10 levels, as well as in markers of liver and renal function. CONCLUSIONS: The NCLS was effective in reducing low-density lipoprotein cholesterol and apolipoprotein B100 in subjects with moderate hypercholesterolemia, without modifying safety parameters.

Effect on LDL-cholesterol of a large dose of a dietary supplement with plant extracts in subjects with untreated moderate hypercholesterolaemia: a randomised, double-blind, placebo-controlled study.

PURPOSE: To determine the effect of 4 weeks of supplementation, then, withdrawal of a dietary supplement (DS) containing red yeast rice extract, policosanol and artichoke leaf extract at twice the recommended daily dose (6 tablets, 6-TAB) compared to the usual dose (3-TAB) or to a placebo (PLA), on blood lipid profiles and safety biomarkers. METHODS: Forty-five healthy subjects (15 per group), with untreated hypercholesterolaemia, were included in this randomised, double-blind, placebo-controlled clinical trial. RESULTS: After 4 weeks of supplementation, LDL-C was significantly lower in 6-TAB (-0.21 g/l; 95 % CI -0.38 to -0.03 g/l; p = 0.0217) and 3-TAB (-0.25 g/l; 95 % CI -0.42 to -0.07 g/l; p = 0.0071) compared to PLA, although no difference in LDL-cholesterol was observed between the two groups, while no effect was seen on triacylglycerol and HDL-cholesterol. Four weeks after the end of supplementation, no difference in LDL-C was seen between the PLA group and the DS-treated groups. The muscle breakdown biomarkers, as well as biomarkers of liver and renal function, were altered by neither dose of the DS. Acute application of the DS on permeabilised skeletal muscle fibres of rats did not induce deleterious effects on mitochondrial function. CONCLUSIONS: Supplementation with twice the recommended dose of the DS was effective in reducing LDL-cholesterol and appeared safe, but according to the present results, no additional benefit could be achieved compared to the recommended dose.