Marc Enslen

Multicenter randomized-control led clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after ileo-caecal resection

Background Seventy percent of Crohns disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo‐caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LA1 on early postoperative endoscopic recurrence of CD. Methods Seventy patients with CD were enrolled prior to elective ileo‐caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestlé (1010 colony‐forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LA1 on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization. Results Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention‐to‐treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 ± 1.32 versus 1.22 ± 1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LA1 and placebo groups, respectively (P = 0.33). Using a per‐protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LA1 versus placebo groups: 1.44 ± 1.31 versus 1.05 ± 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LA1 and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LA1 and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi‐square test, P = 0.91 and log‐rank test: P = 0.79). Conclusion Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo‐caecal resection. (Inflamm Bowel Dis 2007)

Slow release caffeine and prolonged (64‐h) continuous wakefulness: effects on vigilance and cognitive performance

Some long work or shift work schedules necessitate an elevated and prolonged level of vigilance and performance but often result in sleep deprivation (SD), fatigue and sleepiness, which may impair efficiency. This study investigated the effects of a slow‐release caffeine [(SRC) at the daily dose of 600 mg] on vigilance and cognitive performance during a 64 h continuous wakefulness period. Sixteen healthy males volunteered for this double‐blind, randomised, placebo controlled, two‐way crossover study. A total of 300‐mg SRC or placebo (PBO) was given twice a day at 21:00 and 9:00 h during the SD period. Vigilance was objectively assessed with continuous electroencephalogram (EEG), the multiple sleep latency tests (MSLT) and wrist actigraphy. Cognitive functions (information processing and working memory), selective and divided attention were determined with computerised tests from the AGARD‐NATO STRES Battery (Standardised Tests for Research with Environmental Stressors). Attention was also assessed with a symbol cancellation task and a Stroop’s test; alertness was appreciated from visual analogue scales (VAS). Tests were performed at the hypo (02:00–04:00 h, 14:00–16:00 h) and hypervigilance (10:00–12:00 h, 22:00–00:00 h) periods during SD. Central temperature was continuously measured and safety of treatment was assessed from repeated clinical examinations. Compared with PBO, MSLT showed that SRC subjects were more vigilant from the onset (P=0.001) to the end of SD (P < 0.0001) whereas some cognitive functions were improved till the thirty third of SD but others were ameliorated through all the SD period and alertness was better from the thirteenth hour of SD, as shown by Stroop’s test (P=0.048). We showed that 300‐mg SRC given twice daily during a 64‐h SD is able to antagonize the impairment produced on vigilance and cognitive functions.

Measurement of caffeic and ferulic acid equivalents in plasma after coffee consumption: small intestine and colon are key sites for coffee metabolism.

Previous studies on coffee examined absorption of phenolic acids (PA) in the small intestine, but not the contribution of the colon to absorption. Nine healthy volunteers ingested instant soluble coffee ( approximately 335 mg total chlorogenic acids (CGAs)) in water. Blood samples were taken over 12 h, and at 24 h to assess return to baseline. Many previous studies, which used glucuronidase and sulfatase, measured only PA and did not rigorously assess CGAs. To improve this, plasma samples were analyzed after full hydrolysis by chlorogenate esterase, glucuronidase and sulfatase to release aglycone equivalents of PA followed by liquid-liquid extraction and ESI-LC-ESI-MS/MS detection. Ferulic, caffeic and isoferulic acid equivalents appeared rapidly in plasma, peaking at 1-2 h. Dihydrocaffeic and dihydroferulic acids appeared in plasma 6-8 h after ingestion (T(max=)8-12 h). Substantial variability in maximum plasma concentration and T(max) was also observed between individuals. This study confirms that the small intestine is a significant site for absorption of PA, but shows for the first time that the colon/microflora play the major role in absorption and metabolism of CGAs and PA from coffee.

Effects of a new slow release formulation of caffeine on EEG, psychomotor and cognitive functions in sleep-deprived subjects

Caffeine is a widely‐consumed psychoactive substance whose stimulant effects on mood, attention and performance are largely recognised. The central nervous system pharmacodynamic profile of a single oral dose of a new slow release (SR) caffeine formulation (600 mg) was assessed in a randomised, double‐blind, crossover, placebo‐controlled study. Twelve young, health, male, sleep‐deprived (for 36 h) subjects were studied using EEG and various measures of psychomotor and cognitive functions, including critical flicker fusion (CFF), choice reaction task (CRT), tracking, continuous performance task (CPT), Stroop test, body sway and subjective evaluation (Stanford Sleepiness Scale). Caffeine significantly ( < 0/05) antagonised the detrimental effects of sleep‐deprivation on EEG (i.e. produced a significant decrease in delta and theta relative power and a significant increase in alpha and beta (12–40 Hz) relative power) and psychomotor performance (significant increase in speed of reaction on the CRT and Stroop tests, significant decrease in body sway, significant increase in accuracy of the CPT and significant reduction in subjective sedation) compared to placebo. The effect peaked 4 h after dosing and was maintained until the end of sleep deprivation (i.e. 24 h after dosing). In conclusion, the present results demonstrate that a single dose of caffeine SR possesses alerting effects which are able to reverse the deleterious effect of 36 h sleep deprivation for at least 24 h. Copyright

Nondairy Creamer, but Not Milk, Delays the Appearance of Coffee Phenolic Acid Equivalents in Human Plasma

Chlorogenic acids (CGA) are antioxidants found in coffee. They are becoming of interest for their health-promoting effects, but bioavailability in humans is not well understood. We hypothesized that adding whole milk or sugar and nondairy creamer to instant coffee might modulate the bioavailability of coffee phenolics. Nine healthy participants were asked to randomly drink, in a crossover design, instant coffee (Coffee); instant coffee and 10% whole milk (Milk); or instant coffee, sugar, and nondairy creamer already premixed (Sugar/NDC). All 3 treatments provided the same amount of total CGA (332 mg). Blood was collected for 12 h after ingestion and plasma samples treated using a liquid-liquid extraction method that included a full enzymatic cleavage to hydrolyze all CGA and conjugates into phenolic acid equivalents. Hence, we focused our liquid chromatography-Electrospray ionization-tandem MS detection and quantification on caffeic acid (CA), ferulic acid (FA), and isoferulic acid (iFA) equivalents. Compared with a regular black instant coffee, the addition of milk did not significantly alter the area under the curve (AUC), maximum plasma concentration (C(max)), or the time needed to reach C(max) (T(max)). The C(max) of CA and iFA were significantly lower and the T(max) of FA and iFA significantly longer for the Sugar/NDC group than for the Coffee group. However, the AUC did not significantly differ. As a conclusion, adding whole milk did not alter the overall bioavailability of coffee phenolic acids, whereas sugar and nondairy creamer affected the T(max) and C(max) but not the appearance of coffee phenolics in plasma.

Slow versus fast proteins in the stimulation of beta-cell response and the activation of the entero-insular axis in type 2 diabetes.

We tested whether ingestion of whey protein can induce greater post‐prandial amino acid (AA) levels in the plasma and a higher beta‐cell response than casein ingestion in type 2 diabetes mellitus patients.

Recovery after Prolonged Sleep Deprivation: Residual Effects of Slow-Release Caffeine on Recovery Sleep, Sleepiness and Cognitive Functions

A long work schedule often results in sleep deprivation, sleepiness, impaired performance and fatigue. We investigated the residual effects of slow-release caffeine (SRC) on sleep, sleepiness and cognitive performance during a 42-hour recovery period following a 64-hour continuous wakefulness period in 16 healthy males, according to a double-blind, randomised, placebo-controlled, crossover study. Three hundred milligrams of SRC or placebo was given twice a day at 21:00 and 9:00 during the first 48 h of wakefulness. Recovery sleep was analysed with electroencephalography (EEG) and wrist actigraphy, daytime sleepiness with continuous EEG, sleep latency tests and actigraphy and cognitive functions with computerized tests from the NATO AGARD STRES battery. Both drug groups exhibited almost the same sleep architecture with a rebound of slow-wave sleep during both recovery nights and of REM sleep during the second night. Wakefulness level and cognitive functions were similarly impaired in both groups on the first day of recovery and partially returned to baseline on the second. To conclude, SRC appears to have no unwanted side-effects on recovery sleep, wakefulness and cognitive performance after a long period of sleep deprivation and might therefore be a useful choice over other psychostimulants for a long work schedule.

Acetogenic fibers reduce fasting glucose turnover but not peripheral insulin resistance in metabolic syndrome patients

BACKGROUND & AIMS The acute ingestion of an acetogenic indigestible carbohydrate (lactulose) increased acetate turnover associated with decreased lipolysis (glycerol turnover) in insulin-resistant patients. It is not known whether a decreased lipolysis by chronic ingestion of acetogenic indigestible carbohydrates or fibers improves glucose turnover and insulin sensitivity. METHODS Twenty-one men with metabolic syndrome ingested daily standardized drinks, with or without 28 g acetogenic fibers (acacia gum and pectin), for 5 weeks in a randomized double-blind crossover controlled study design. Euglycaemic-hyperinsulinaemic (EH) clamps coupled with kinetic studies were performed in the fasting state after treatments. RESULTS Flatulence was more frequent with fiber treatment. Body weight, lipids as well as acetate and glycerol turnovers were unchanged. Fasting endogenous glucose turnover was improved after fiber treatment (7.9 ± 1.3 μmol kg(-1) min(-1)) compared with control (8.6 ± 1.6 μmol kg(-1) min(-1), P < 0.05). But insulin sensitivity (glucose infusion rate) during the EH clamp was not different at the end of fiber and control treatments, 3.7 ± 1.8 and 3.8 ± 1.5 mg kg(-1) min(-1), respectively, nor fasting plasma glucose and insulin. CONCLUSIONS The chronic ingestion of acacia gum and pectin fibers did not decrease lipolysis but improved fasting endogenous glucose turnover with no effect on peripheral insulin resistance in metabolic syndrome patients.