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Insufficient daytime sleep may result in reduction of effectiveness and safety during overnight military missions. The usefulness of temazepam and zaleplon to optimize afternoon sleep and their effects on performance and alertness during a subsequent night shift were studied. Method: In a randomized double-blind within-subjects design, 11 subjects took 20 mg of temazepam, 10 mg of zaleplon, or placebo before a 5:30-10:00 p.m. sleep period. Sleep length and quality were measured. Subjects were kept awake throughout the night while alertness, cognitive performance, and muscle power were repeatedly measured. Results: Temazepam provided significantly longer and qualitatively better sleep than zaleplon or placebo. During the night, sleepiness increased and muscle power was impaired in all conditions. Better sleep was correlated with less sleepiness during the night. Conclusion: Temazepam is useful to optimize a 4.5-hour afternoon sleep before overnight missions. Irrespective of hypnotic treatment, sleepiness and fatigue increased during the night shift.

Brain serotonin function has been implicated in the control of sleep and sleep related memory dysfunctions are attributed to deficient brain serotonin activity. Depletion of the serotonin precursor tryptophan reduces brain serotonin function and is found to cause sleep abnormalities and cognitive decline. We hypothesized that enhancing pre-sleep brain tryptophan availability via a dietary increase in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp/LNAA) improves post-sleep memory functioning particularly in subjects with mild sleep complaints. To test whether evening intake of a tryptophan-rich diet increases the plasma Trp/LNAA ratio before sleep and improves early morning behavioral and brain measures of memory function in subjects with mild sleep complaints and controls. Twenty-eight subjects with mild sleep complaints and 28 controls participated in a double-blind placebo-controlled study. They stayed at the laboratory for an overnight sleep to monitor their post-sleep memory performance following either an evening diet containing tryptophan-rich protein or placebo protein. Evening dietary-induced changes in the plasma Trp/LNAA ratio were measured. Besides measuring behavioral changes, also task-related electroencephalographic brain activity (ERP) was measured as an index of cerebral changes in memory function. The tryptophan-rich diet caused a 130% increase in the plasma Trp/LNAA ratio (P = 0.0001) and in all subjects improved behavioral (P=0.001) and ERP (P=0.05) brain measures of memory function. Post-sleep memory function improves after pre-sleep dietary increases in plasma TRP/LNAA probably by improved sleep. Copyright © 2006 by New Century Health Publishers, LLC.

β-carotene has been hypothesised to reduce lung cancer risk. We studied the effect of 14 weeks of β-carotene supplementation (20 mg d-1) on the frequency of micronuclei in sputum in 114 heavy smokers in a double-blind trial. Micronuclei reflect DNA damage in exfoliated cells and may thus provide a marker early-stage carcinogenesis. Pre-treatment blood levels of cotinine, β-carotene, retinol and vitamins C and E were similar in the placebo group (n = 61) and the treatment group (n = 53). Plasma β-carotene levels increased 13-fold in the treatment group during intervention. Initial micronuclei counts (per 3,000 cells) were higher in the treatment group than in the placebo group (5.0 vs 4.0, P < 0.05). During intervention, the treatment group showed a 47% decrease, whereas the placebo group showed a non-significant decrease (16%). After adjustment for the initial levels, the treatment group had 27% lower micronuclei counts than the placebo group at the end of the trial (95% CI: 9-41%). These results indicate that β-carotene may reduce lung cancer risk in man by preventing DNA damage in early-stage carcinogenesis.

The objective of this study was to establish the possible occurrence of eye irritation and subjective symptoms in human volunteers exposed to propylene glycol monomethyl ether (PGME) vapour at concentrations of 0, 100 and 150 ppm. Testing was conducted in 12 healthy male volunteers using a repeated measures design. Each subject was exposed for 2.5 h to each of the three exposure conditions that were spaced 7 days apart. The exposure sequences were counterbalanced and the exposure to the test substance and the effect measurements were conducted in a double-blind fashion. During all exposure sessions, 20 ppm diethyl ether was used as a 'masking agent' for vapour exposure. Measurements of pre- and post exposure eye redness, corneal thickness, tear film break-up time, conjunctival epithelial damage, blinking frequency, and subjective ratings on discomfort were used to evaluate the possible irritating effects of PGME. The results indicated no significant treatment effects for any of the objective parameters. Results of the subjective ratings indicated very slight effects on the eyes in the 150 ppm PGME condition only. No significant effects of treatment were found for the remaining questions concerning the perceived intensity of the smell in the room, the (un)pleasantness of the smell, the perceived effects on the skin, effects on the throat, shivering, muscle aching, and intestinal cramps. In conclusion, the results of the present study indicated minimal subjective eye effects at 150 ppm only, and no impact on the objective measures of eye irritation at either of the two exposure levels. It was concluded that the no adverse effect concentration for eye irritation due to PGME vapour was at least 150 ppm. © 2003 Elsevier Science Ireland Ltd. All rights reserved.

Background. Low back pain (LBP) and neck pain (NP) are a major public health problem with considerable costs for individuals, companies and society. Therefore, prevention is imperative. The Stay@Work study investigates the (cost-)effectiveness of Participatory Ergonomics (PE) to prevent LBP and NP among workers. Methods. In a randomised controlled trial (RCT), a total of 5,759 workers working at 36 departments of four companies is expected to participate in the study at baseline. The departments consisting of about 150 workers are pre-stratified and randomised. The control departments receive usual practice and the intervention departments receive PE. Within each intervention department a working group is formed including eight workers, a representative of the management, and an occupational health and safety coordinator. During a one day meeting, the working group follows the steps of PE in which the most important risk factors for LBP and NP, and the most adequate ergonomic measures are identified on the basis of group consensus. The implementation of ergonomic measures at the department is performed by the working group. To improve the implementation process, so-called 'ergocoaches' are trained. The primary outcome measure is an episode of LBP and NP. Secondary outcome measures are actual use of ergonomic measures, physical workload, psychosocial workload, intensity of pain, general health status, sick leave, and work productivity. The cost-effectiveness analysis is performed from the societal and company perspective. Outcome measures are assessed using questionnaires at baseline and after 6 and 12 months. Data on the primary outcome as well as on intensity of pain, sick leave, work productivity, and health care costs are collected every 3 months. Discussion. Prevention of LBP and NP is beneficial for workers, employers, and society. If the intervention is proven (cost-)effective, the intervention can have a major impact on LBP and NP prevention and, thereby, on work disability prevention. Results are expected in 2010. Trial registration. ISRCTN27472278. © 2008 Driessen et al; licensee BioMed Central Ltd.

Background: Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. Objective: This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and umami) on food intake, hunger and fullness, gastrointestinal symptoms, and gastrointestinal peptide release. Design: Fifteen healthy volunteers [6 male; mean ± SEM age: 23.9 ± 2.0 y; mean ± SEM body mass index (in kg/m2): 22.4 ± 0.3] received 5 treatments in a double-blind, randomized, placebo-controlled crossover design. Test days started with the insertion of a nasoduodenal catheter followed by a standardized liquid breakfast. Participants received an intraduodenal infusion 150 min after breakfast, containing quinine (bitter), rebaudioside A (sweet), monosodium glutamate (umami), a combination of the 3 tastants, or placebo (tap water) over a period of 60 min. Food intake was measured during an ad libitum meal, and visual analog scales were used to monitor gastrointestinal complaints and hunger and fullness scores. Blood samples were drawn at regular intervals for cholecystokinin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) analysis. Results: Infusion of the combination of tastants substantially decreased food intake (422 ± 97 kcal vs. 486 ± 104 kcal for placebo, P < 0.05), whereas both a combination of tastants and umami decreased hunger scores compared with placebo. No change in cholecystokinin, GLP-1, or PYY concentrations was observed during the infusions. Intraduodenal infusions of the tastants did not result in gastrointestinal symptoms. Conclusions: Intraduodenal infusion of umami and a combination of tastants inhibits feelings of hunger, but only the latter also reduces food intake. However, these alterations were not accompanied by changes in the plasma concentrations of the gut-derived peptides cholecystokinin, GLP-1, or PYY. This trial was registered at clinicaltrials.gov as NCT01956838.

Background: Brain serotonin function is thought to promote sleep regulation and cognitive processes, whereas sleep abnormalities and subsequent behavioral decline are often attributed to deficient brain serotonin activity. Brain uptake of the serotonin precursor tryptophan is dependent on nutrients that influence the availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp:LNAA). Objective: We tested whether evening consumption of α-lactalbumin protein with an enriched tryptophan content of 4.8 g/100 g increases plasma Trp:LNAA and improves alertness and performance on the morning after sleep, particularly in subjects with sleep complaints. Design: Healthy subjects with (n = 14) or without (n = 14) mild sleep complaints participated in a double-blind, placebo-controlled study. The subjects slept at the laboratory for 2 separate nights so that morning performance could be evaluated after an evening diet containing either tryptophan-rich α-lactalbumin or tryptophan-low placebo protein. Evening dietary changes in plasma Trp:LNAA were measured. Behavioral (reaction time and errors) and brain measures of attention were recorded during a continuous performance task. Results: Evening α-lactalbumin intake caused a 130% increase in Trp:LNAA before bedtime (P = 0.0001) and modestly but significantly reduced sleepiness (P = 0.013) and improved brain-sustained attention processes (P = 0.002) the following morning. Only in poor sleepers was this accompanied by improved behavioral performance (P = 0.05). Conclusion: Evening dietary increases in plasma tryptophan availability for uptake into the brain enhance sustained alertness early in the morning after an overnight sleep, most likely because of improved sleep. © 2005 American Society for Clinical Nutrition.

A proof-of-concept study to assess the safety and efficacy of a traditional Chinese medicine formula as treatment for primary dysmenorrhea showed no statistically significant benefit over placebo. However, some efficacy parameters suggested possible superiority of the active treatment and so a larger study needs to be performed to determine whether this remedy has a role in the treatment of dysmenorrhea. © 2006 American Society for Reproductive Medicine.

D-Tagatose is partly absorbed in the stomach and small intestine. Most of it is fermented by the large intestinal microbiota. The effect of D-tagatose on the composition of the microbiota and production of short chain fatty acids (SCFAs) was studied in vivo and in vitro. Gastrointestinal (GI) complaints were also studied. The in vivo study was performed according to a randomized, placebo-controlled, double-blind, five-way cross-over design in healthy subjects (12 men and 18 women). All subjects consumed 30 g raspberry jam containing 7.5 or 12.5 g D-tagatose, 7.8 g fructo-oligosaccharides (positive reference), 7.6 g D-tagatose plus 7.5 g fructo-oligosaccharides, or 15.1 g sucrose (negative reference) at breakfast for 2 weeks in different orders. At the end of each treatment period lipids and safety parameters in blood and GI complaints were evaluated by questionnaires, and faecal microbiota and SCFAs were measured. Furthermore, test-tube incubations of faecal slurries with D-tagatose, fructo-oligosaccharides and sucrose were performed. An in vitro model simulating the large intestine was used to assess the mechanistic effect of D-tagatose on microbiota composition and SCFA production. The high-tagatose treatment resulted in increased numbers of faecal lactobacilli in men, but not in women. Also in vitro, lactobacilli increased. Both the test-tube incubations of fresh faeces from the in vivo study with D-tagatose and the study in the in vitro model showed increased butyrate production after all treatments with D-tagatose. High-tagatose, but not low-tagatose, resulted in a slightly increased defecation frequency and stools of thinner consistency. Only a few GI complaints were reported. The data indicate that daily consumption of 7.5 or 12.5 g D-tagatose may lead to increased production of butyrate and to an increase of lactobacilli, without serious GI complaints. In view of the health-promoting effects of butyrate and lactobacilli, D-tagatose may be considered a prebiotic substrate. © 2005 Taylor & Francis Group Ltd.

Background: In rats, nondigestible oligosaccharides stimulate calcium absorption. Recently, this effect was also found in human subjects. Objective: The objective of the study was to investigate whether consumption of 15 g oligofructose/d stimulates calcium absorption in male adolescents. Design: Twelve healthy, male adolescents aged 14-16 y received, for 9 d, 15 g oligofructose or sucrose (control treatment) daily over 3 main meals. The treatments were given according to a randomized, double-blind, crossover design, separated by a 19-d washout period. On the 8th day of each treatment period, 44Ca was given orally with a standard breakfast containing ≃200 mg Ca. Within half an hour after administration of 44Ca, 48Ca was administered intravenously. Fractional calcium absorption was computed from the enrichment of 44Ca:43Ca and 48Ca:43Ca in 36-h urine samples, which was measured by inductively coupled plasma mass spectrometry. Results: An increase in true fractional calcium absorption (%) was found after consumption of oligofructose (mean difference ± SE of difference: 10.8 ± 5.6; P < 0.05, one sided). The results are discussed in relation to the methods used. Conclusion: Fifteen grams of oligofructose per day stimulates fractional calcium absorption in male adolescents.

Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p < 0.05) and 24.3% (p < 0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p < 0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p < 0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p < 0.001) and 10.5% (p < 0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p < 0.001) and 28.2% (p < 0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen. Copyright © 1997 Schattauer Verlag

BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive vs. standard dose atorvastatin on hemostatic cardiovascular risk factors in patients with Type 2 diabetes mellitus. Patients and methods: The effect of 30 weeks of treatment with atorvastatin 10 and 80 mg on hemostatic cardiovascular risk factors was assessed in a randomized double-blind placebo-controlled trial on 217 patients with Type 2 diabetes mellitus and dyslipidemia. RESULTS AND CONCLUSIONS: Atorvastatin 10 and 80 mg dose-dependently reduced d-dimer (7.4% and 8.5%, respectively, P for trend = 0.004) and PAI-1 antigen levels (9.0% and 18%, respectively, P for trend = 0.021). Levels of fibrinogen, VWF, tissue-type plasminogen activator and FVIIa were not influenced by atorvastatin. In conclusion, in patients with Type 2 diabetes mellitus, atorvastatin dose-dependently improved the levels of the hemostatic risk variables d-dimer and PAI-1. Chemicals/CAS: atorvastatin, 134523-00-5, 134523-03-8; fibrinogen, 9001-32-5; tissue plasminogen activator, 105913-11-9; von Willebrand factor, 109319-16-6; atorvastatin, 110862-48-1; Factor VIIIa, 72175-66-7; Fibrinogen, 9001-32-5; Hemostatics; Heptanoic Acids; Placebos; Pyrroles; Tissue Plasminogen Activator, EC 3.4.21.68; von Willebrand Factor

The aim of this study was to investigate whether a product rich in transgalactooligosaccharides (TOS, Elix'or) stimulates true Ca absorption in postmenopausal women. The study was a double-blind, randomized crossover study, consisting of two 9-d treatment periods separated by a 19-d washout period. During the treatment periods, 12 subjects drank 200 mL yogurt drink twice (at breakfast and lunch) containing either TOS (20 g/d) or the reference substance, sucrose. On d 8 of each treatment period, 44Ca and 48Ca were administered orally and intravenously, respectively. Before and during the 36 h after isotope administration, urine was collected and the ratios of isotopes present were measured by inductively coupled plasma mass spectrometry (ICP-MS). From the isotope enrichments, true calcium absorption was calculated. TOS increased true calcium absorption 16%, from (mean ± SD) 20.6 ± 7.0% during the reference treatment to 23.9 ± 6.9% during the TOS treatment (P = 0.04, one-sided). In conclusion, in this study in postmenopausal women, greater Ca absorption was observed after consumption of a product rich in TOS (Elix'or) compared with the reference treatment. This increase in Ca absorption was likely due solely to TOS. The increased Ca absorption was not accompanied by increased urinary Ca excretion, meaning that TOS also may indirectly increase the uptake of Ca by bones and/or inhibit bone resorption.

Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz. the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen β-gene. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the BclI polymorphism of the fibrinogen β-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immune assay (EIA). In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student t-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen β-gene polymorphisms. Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen β-gene polymorphisms. Chemicals/CAS: Antigens; C-Reactive Protein, 9007-41-4; Fibrinogen, 9001-32-5; Platelet Aggregation Inhibitors; Ticlopidine, 55142-85-3

The aim of the study was to investigate the bioavailability of tryptophan (Trp) from a Trp-enriched peptide mixture in healthy men. A second objective was to investigate the effect of this Trp-enriched protein hydrolysate on potential parameters of serotonergic activity. serum serotonim melatonin and prolactin and urinary 5-hydroxyindol-acetic acid and 6-sulfatoxymelatonin. Glucose and insulin were measured as the placebo consisted of orange juice with added glucose. The study was a randomised, double blind, placebo-controlled, four-way crossover trial in eight healthy male subjects. Treatments consisted of a single oral load of a Trp-enriched protein hydrolysate containing 500 mg L-Trp, 500 mg L-Trp plus addition of a mixture of amino acids having the same composition as in the hydrolysate, 500 mg L-Trp, and placebo. Before and after ingestion blood and urine were collected during a period of 4 hours. The Trp-enriched protein hydrolysate increased the plasma Trp/LNAA ratio by about 70% at 60 to 90 min after ingestion. AM three Trp treatments induced a comparable plasma Trp-response demonstrating that Trp is readily available for the body independent of whether it was peptide-bonded or in free amino acid form. None of the Trp treatments affected serum serotonim prolactin, melatonin and insulin concentrations, as well as urinary 5-hydroxyindol-acetic acid and 64-sulfatoxymelatonin concentrations during the 4-hour measurement period in the morning. Copyright © 2004 by New Century Health Publishers, LLC.

Objective: To evaluate the scientific evidence for purported intolerance to dietary biogenic amines. Data Sources: MEDLINE was searched for articles in the English language published between January 1966 and August 2001. The keyword biogenic amin* was combined with hypersens*, allerg*, intoler*, and adverse. Additionally, the keywords histamine, tyramine, and phenylethylamine were combined with headache, migraine, urticaria, oral challenge, and oral provocation. Articles were also selected from references in relevant literature. Study Selection: Only oral challenge studies in susceptible patients were considered. Studies with positive results (ie, studies in which an effect was reported) were only eligible when a randomized, double-blind, placebo-controlled design was used. Eligible positive result studies were further evaluated according to a number of scientific criteria. Studies with negative results (ie, studies in which no effect was reported) were examined for factors in their design or methods that could be responsible for a false-negative outcome. Results of methodologically weak or flawed studies were considered inconclusive. Results: A total of 13 oral challenge studies (5 with positive results and 8 with negative results) were found. Three of them (all with positive results) were considered ineligible. By further evaluation of the 10 eligible studies, 6 were considered inconclusive. The 4 conclusive studies all reported negative results. One conclusive study showed no relation between biogenic amines in red wine and wine intolerance. Two conclusive studies found no effect of tyramine on migraine. One conclusive study demonstrated no relation between the amount of phenylethylamine in chocolate and headache attacks in individuals with headache. Conclusions: The current scientific literature shows no relation between the oral ingestion of biogenic amines and food intolerance reactions. There is therefore no scientific basis for dietary recommendations concerning biogenic amines in such patients.

Epidemiological studies have shown that hormone therapy (HT) increases the risk of venous thromboembolism in post menopausal women. The mechanism of this increased risk is unknown; however, activation of the haemostatic system is known to contribute to the pathogenesis of venous thromboembolism. In post-menopausal women the estrogen /progestogen composition of the HT can influence the level of haemostatic activation. It was the objective of this study to compare changes in inhibitors and activation markers of the haemostatic system in healthy post-menopausal women taking estradiol (2 mg) combined with dydrogesterone or a new progestin, trimegestone. A multicentre study of 186 women randomised to six months therapy with either estradiol (2 mg) +trimegestone (0.5 mg) or estradiol (2 mg) +dydrogesterone (10 mg) was performed. Antithrombin and protein S activity was decreased and activated protein C (APC) resistance, D-dimer and prothrombin fragment 1.2, were increased in both groups on treatment. Protein C activity was decreased and plasmin-antiplasmin complex was increased in the trimegestone group only. The increase in plasmin-antiplasmin complex and D-dimer was greater after six cycles of treatment in the trimegestone group compared with the dydrogesterone group. In conclusion, decreased levels of inhibitors of blood coagulation and increased thrombin production were found in both groups however a greater increase in the levels of plasmin-antiplasmin complex and D-dimer was found in the trimegestone group. This suggests an enhanced fibrinolytic response in this group. Further studies are required to determine the significance of this finding with respect to venous thrombosis risk. © 2008 Schattauer GmbH.

Objective: To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI). Design: Randomised placebo-controlled trial. Setting: General community. Participants: Community-dwelling adults aged 70-80 with MCI. Interventions : The 152 participants were randomly assigned to two interventions: (1) a twice-weekly, group-based, moderate-intensity walking programme (WP, n = 77) or a low-intensity placebo activity programme (n = 75) for one year; and (2) daily vitamin pill containing 5 mg folic acid, 0.4 mg vitamin B-12, 50 mg vitamin B-6 (FA/B12/B6, n = 78) or placebo pill (n = 74) for one year. Outcome measures: Cognitive function, measured with neuropsychological tests at baseline and after six and 12 months. Results: Median session attendance at the exercise programmes (25th-75th percentile) was 63% (2%-81%) and median compliance with taking pills (25th-75th percentile) was 100% (99%-100%). Gender was an effect modifier. Intention-to-treat analysis revealed no main intervention effect for either intervention. In women in the WP, attention (Stroop combination task) improved by 0.3 seconds (p = 0.04) and memory (auditory verbal learning test) by 0.04 words (p = 0.06) with each percentage increase in session attendance. In men attending at least 75% of the sessions, the WP improved memory (β 1.5 (95% CI: 0.1 to 3.0) words). Conclusion: The walking programme and/or FA/B12/B6 supplementation were not effective in improving cognition within one year. The walking programme, however, was efficacious in improving memory in men and memory and attention in women with better adherence. Trial registration: International Standard Randomised Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/. Chemicals / CAS: Folic Acid, 59-30-3; Vitamin B 12, 68-19-9; Vitamin B 6, 8059-24-3

Objective: To determine the effect of folic acid, vitamin B6 and B12 fortified spreads on the blood concentrations of these vitamins and homocysteine. Design and setting: A 6-week randomized, double-blinded, placebo-controlled, parallel trial carried out in a clinical research center. Subjects: One hundred and fifty healthy volunteers (50% males). Interventions: For 6 weeks, the subjects consumed the test spreads (20 g/day): containing per 20 g (1) 200μ g folic acid, 2μ g vitamin B12 and 1 mg vitamin B6, or (2) 400μ g folic acid, 2μ g vitamin B12 and 1 mg vitamin B6 or (3) no B-vitamins (control spread). Results: The B-vitamin status increased on using the test spreads, with the largest effect on the serum folate concentration: 48% in men and 58% in women on spread 1 and 92 and 146%, respectively, on spread 2 (P-values all <0.05). The plasma homocysteine decreased in the groups treated with the fortified spreads as compared to the control group. Average decreases were for males: 0.7±1.5±μmol/l (6.8%) on spread 1 and 1.7 ± 1.7 μmol/l (17.6%) on spread 2 and for females: 1.4 ± 1.2 μmol/l (14.2%) and 2.4 ± 2.0 μmol/l (23.3%), respectively (P-values all <0.05). Conclusions: Consumption of a spread fortified with folic acid, vitamin B6 and vitamin B12 for 6 weeks significantly increases the blood concentrations of these vitamins and significantly decreases the plasma concentration of homocysteine. Fortified staple foods like spreads can contribute to the lowering of homocysteine concentrations.

Ginkgo biloba extract has been advocated for the improvement of blood circulation in circulatory disorders. This study investigated the effect of the Gingko biloba extract EGb 761 on skin blood flow in healthy volunteers and accompanying changes in urinary metabolites. Twenty-seven healthy middle-aged subjects participated in a randomized, double-blind, placebo-controlled, crossover study. Subjects received 240 mg/d EGb 761 or placebo for periods of 3 weeks. Skin blood flow was measured on the forefoot using laser Doppler flowmetry and changes in urinary metabolites were identified by a combination of nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis (MVDA). These measurements were performed on 24-h urine samples collected at the end of the intervention periods. Following EGb 761 treatment, overall mean skin blood flow was significantly reduced as compared with placebo. Remarkably, the change of skin blood flow after EGb 761 intervention was proportionally related to blood flow after placebo treatment: subjects showed either an increased, decreased or unaltered skin blood flow. NMR/MDVA analyses showed that urinary metabolic patterns differed depending on the change in baseline blood flow after treatment with EGb 761. The present findings substantiate that EGb 761 has a multi-directional modulating action on blood flow in healthy subjects and support findings of a vasoregulatory role of this extract. Moreover, the results indicate that metabolic fingerprinting provides a powerful means to identify biochemical markers that are associated with functional changes.