Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial

Objective: Studies have suggested a link between lycopene and insulin-like growth factor-1 ( IGF-1). The aim of this study was to test the effect of lycopene supplementation on IGF-1 and binding protein-3 ( IGFBP-3) status in healthy male volunteers.

Effect of simvastatin on physiological and biological outcomes in patients undergoing esophagectomy: a randomised placebo controlled trial

OBJECTIVE: To test whether simvastatin improves physiological and biological outcomes in patients undergoing esophagectomy.

BACKGROUND: One-lung ventilation during esophagectomy is associated with inflammation, alveolar epithelial and systemic endothelial injury, and the development of acute lung injury (ALI). Statins that modify many of the underlying processes are a potential therapy to prevent ALI.

METHODS: We conducted a randomized double-blind placebo-controlled trial in patients undergoing esophagectomy. Patients received simvastatin 80 mg or placebo enterally for 4 days preoperatively and 7 days postoperatively. The primary end point was pulmonary dead space (Vd/Vt) at 6 hours after esophagectomy or before extubation. Inflammation was assessed by plasma cytokines and intraoperative exhaled breath condensate pH; alveolar type 1 epithelial injury was assessed by plasma receptor for advanced glycation end products and systemic endothelial injury by the urine albumin-creatinine ratio.

RESULTS: Thirty-nine patients were randomized; 8 patients did not undergo surgery and were excluded. Fifteen patients received simvastatin and 16 received placebo. There was no difference in Vd/Vt or other physiological outcomes. Simvastatin resulted in a significant decrease in plasma MCP-1 on day 3 and reduced exhaled breath condensate acidification. Plasma receptor for advanced glycation end products was significantly lower in the simvastatin-treated group, as was the urine albumin-creatinine ratio on day 7 postsurgery. ALI developed in 4 patients in the placebo group and no patients in the simvastatin group although this difference was not statistically significant (P = 0.1).

CONCLUSIONS: In this proof of concept study, pretreatment with simvastatin in esophagectomy decreased biomarkers of inflammation as well as pulmonary epithelial and systemic endothelial injury.

The short-term effect of topical dorzolamide compared with placebo on perimetry testing in normal subjects

Purpose. To study the effect of topical dorzolamide on retinal sensitivity in normal subjects. Methods. 20 normal subjects were prospectively randomized in a two period crossover study. Baseline threshold perimetry (HVF, program 24-2, Statpac analysis) was obtained. The study eye was randomly chosen and then was randomly assigned to receive either dorzolamide 2% or placebo one hour before repeat HVF. After at least two weeks washout the same eye was given the opposite drop one hour prior to repeat HVF. Global indices were compared using a paired T-test. Results. AFTER PLACEBO AFTER DORZOLAMIDE P-VALUE (mean±SD) (mean±SD) MD 0.12±1.4 0.16±1.4 0.82 PSD 1.83±0.6 1.66±0.4 0.04 SF 1.28±0.4 1.24±0.2 0.73 CPSD 1.05±0.9 0.84±0.6 0.35 Conclusion. In this population, topical dorzolamide had little effect on visual function.

The effect of multiple micronutrient supplementation on left ventricular ejection fraction in patients with chronic stable heart failure: a randomized, placebo-controlled trial:A randomized, placebo-controlled trial

Objectives: This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction (LVEF) in patients with heart failure. Background: Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients. However, there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months. The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography. Secondary endpoints were Minnesota Living With Heart Failure Questionnaire score, 6-min walk test distance, blood concentrations of N-terminal prohormone of brain natriuretic peptide, C-reactive protein, tumor necrosis factor alpha, interleukin-6, interleukin-10, and urinary levels of 8-iso-prostaglandin F2 alpha. Results: Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group, indicating excellent compliance with the intervention. There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline (mean difference: 1.6%, 95% confidence interval: -2.6 to 5.8, p = 0.441). There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups. Conclusions: This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement. (Micronutrient Supplementation in Patients With Heart Failure [MINT-HF]; NCT01005303).

Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study

Epidemiological studies have shown an inverse association between dietary intake of whole grains and the risk of chronic disease. This may be related to the ability to mediate a prebiotic modulation of gut microbiota. However, no studies have been conducted on the microbiota modulatory capability of whole-grain (WG) cereals. In the present study, the impact of WG wheat on the human intestinal microbiota compared to wheat bran (WB) was determined. A double-blind, randomised, crossover study was carried out in thirty-one volunteers who were randomised into two groups and consumed daily 48g breakfast cereals, either WG or WB, in two 3-week study periods, separated by a 2-week washout period. Numbers of faecal bifidobacteria and lactobacilli (the target genera for prebiotic intake), were significantly higher upon WG ingestion compared with WB. Ingestion of both breakfast cereals resulted in a significant increase in ferulic acid concentrations in blood but no discernible difference in faeces or urine. No significant differences in faecal SCFA, fasting blood glucose, insulin, total cholesterol (TC), TAG or HDL-cholesterol were observed upon ingestion of WG compared with WB. However, a significant reduction in TC was observed in volunteers in the top quartile of TC concentrations upon ingestion of either cereal. No adverse intestinal symptoms were reported and WB ingestion increased stool frequency. Daily consumption of WG wheat exerted a pronounced prebiotic effect on the human gut microbiota composition. This prebiotic activity may contribute towards the beneficial physiological effects of WG wheat.

A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects

There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides–Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed. There were no adverse gastrointestinal symptoms apart from a significant increase in mild and moderate bloating upon VLCI ingestion. These observations were also confirmed by in vitro gas production measurements. In conclusion, daily consumption of VLCI extracted from globe artichoke exerted a pronounced prebiotic effect on the human faecal microbiota composition and was well tolerated by all volunteers.

The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial

Rationale: There has recently been increasing interest in the potential of flavanols, plant derived compounds found in foods such as fruit and vegetables, to ameliorate age-related cognitive decline. Research suggests that cocoa flavanols improve memory and learning, possibly as a result of their anti-inflammatory and neuroprotective effects. These effects may be mediated by increased cerebral blood flow (CBF), thus stimulating neuronal function. Objectives: The present study employed arterial spin labelling (ASL) functional magnetic resonance imaging (FMRI) to explore the effect of a single acute dose of cocoa flavanols on regional CBF. Methods: CBF was measured pre and post consumption of low (23mg) or high (494mg) 330ml equicaloric flavanol drinks matched for caffeine, theobromine, taste and appearance according to a randomised counterbalanced crossover double-blind design in eight males and ten females, aged 50-65 years. Changes in perfusion from pre to post consumption were calculated as a function of each drink. Results: Significant increases in regional perfusion across the brain were observed following consumption of the high flavanol drink relative to the low flavanol drink, particularly in the anterior cingulate cortex (ACC) and the central opercular cortex of the parietal lobe. Conclusions: Consumption of cocoa flavanol improves regional cerebral perfusion in older adults. This provides evidence for a possible acute mechanism by which cocoa flavanols are associated with benefits for cognitive performance.

Exercise and calcium combined results in a Greater osteogenic effect than either factor alone: a blinded randomized placebo-controlled trial in boys

We examined the combined effects of exercise and calcium on BMC accrual in pre- and early-pubertal boys. Exercise and calcium together resulted in a 2% greater increase in femur BMC than either factor alone and a 3% greater increase in BMC at the tibia–fibula compared with the placebo group. Increasing dietary calcium seems to be important for optimizing the osteogenic effects of exercise.

Introduction: Understanding the relationship between exercise and calcium during growth is important given that the greatest benefits derived from these factors are achieved during the first two decades of life. We conducted a blinded randomized-controlled exercise–calcium intervention in pre- and early-pubertal boys to test the following hypotheses. (1) At the loaded sites (femur and tibia–fibula), exercise and calcium will produce greater skeletal benefits than either exercise or calcium alone. (2) At nonloaded sites (humerus and radius–ulna), there will be an effect of calcium supplementation.

Materials and Methods: Eighty-eight pre- and early-pubertal boys were randomly assigned to one of four study groups: moderate impact exercise with or without calcium (Ca) (Ex + Ca and Ex + placebo, respectively) or low impact exercise with or without Ca (No-Ex + Ca and No-Ex + Placebo, respectively). The intervention involved 20 minutes of either moderate- or low-impact exercise performed three times a week and/or the addition of Ca-fortified foods using milk minerals (392 ± 29 mg/day) or nonfortified foods over 8.5 months. Analysis of covariance was used to determine the main and combined effects of exercise and calcium on BMC after adjusting for baseline BMC.

Results: At baseline, no differences were reported between the groups for height, weight, BMC, or bone length. The increase in femur BMC in the Ex + Ca group was 2% greater than the increase in the Ex + placebo, No-Ex + Ca, or No-Ex + Placebo groups (all p < 0.03). At the tibia–fibula, the increase in BMC in the Ex + Ca group was 3% greater than the No-Ex + placebo group (p < 0.02) and 2% greater than the Ex + Placebo and the No-Ex + Ca groups (not significant). No effect of any group was detected at the humerus, ulna–radius, or lumbar spine for BMC, height, bone area, or volume.

Conclusions: In this group of normally active boys with adequate calcium intakes, additional exercise and calcium supplementation resulted in a 2–3% greater increase in BMC than controls at the loaded sites. These findings strengthen the evidence base for public health campaigns to address both exercise and dietary changes in children for optimizing the attainment of peak BMC.

The effect of topical wheatgrass cream on chronic plantar fasciitis: a randomized, double-blind, placebo-controlled trial

Objectives: To investigate the efficacy of a topical wheatgrass cream for improving pain and function in patients with chronic plantar fasciitis.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Eighty participants with chronic plantar fasciitis were randomly assigned to a treatment group (wheatgrass cream) or a control group (placebo cream). All participants applied a cream twice daily for 6 weeks. Follow up was conducted at 6 and 12 weeks.

Main outcome measures: Visual Analogue Scale (VAS) for daily first-step pain and the Foot Health Status Questionnaire (FHSQ) for overall foot function. Secondary measures of foot posture, calf muscle strength and range of ankle dorsiflexion were also assessed.

Results: No significant differences were found between groups with respect to main outcomes of first-step pain or foot function at any time. Both groups improved significantly from baseline to 6 weeks, and these improvements were maintained at 12 weeks.

Conclusions: The topical application of wheatgrass cream is no more effective than a placebo cream for the treatment of chronic plantar fasciitis.

Effect of deer velvet on sexual function in men and their partners: a double-blind, placebo-controlled study

The use of alternative medicines and herbal remedies is an increasing trend in Western societies. For years, people have taken products made of deer velvet for their alleged beneficial effects on sexual function. There has been no scientific investigation of the effects of deer velvet powder on the sexual functioning of human males. This study investigated sexual function in men during a 12-week double-blind, placebo-controlled trial of deer velvet. Thirty-two volunteer male participants, aged 45–65 years, and their partners, were randomly assigned to either the deer velvet or placebo study group. The males took capsules containing ground deer velvet or placebo everyday for 12 weeks. Two sexual function questionnaires (the International Index of Erectile Function and the Brief Index of Sexual Function for Women) used at pre- and posttreatment assessed changes in sexual functioning in males and their partners. Blood tests at baseline, and end of study, determined levels of sex-related hormones in male participants. There were no significant differences in the sexual behavior of the men taking deer velvet compared with the men taking placebo capsules. There were no significant hormone changes from baseline to the end of the study in either group of men. We conclude that in normal males there was no advantage in taking deer velvet to enhance sexual function. All alternative health products or nutritional supplements should be subjected to randomized placebo-controlled trials to determine efficacy.

Effect of vitamin D supplementation alone on muscle function in postmenopausal women: a randomized, double-blind, placebo-controlled clinical trial

The present study investigates the effects of vitamin D on muscle function in postmenopausal women. It has been shown that vitamin D supplementation in postmenopausal women with hypovitaminosis D provides significant protective factor against sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass. We aimed to evaluate the effect of supplementation of vitamin D (VITD) alone on muscle function in younger postmenopausal women. In this double-blind, placebo-controlled clinical trial, 160 Brazilian postmenopausal women were randomized into two groups: VITD group consisting of patients receiving vitamin D3 1000 IU/day orally (n = 80) or placebo group (n = 80). Women with amenorrhea for more than 12 months and age 50-65 years, with a history of falls (previous 12 months), were included. The intervention time was 9 months, with assessments at two points, start and end. Lean mass was estimated by total-body dual-energy X-ray absorptiometry (DXA) and muscle strength by handgrip strength and chair rising test. The plasma concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance liquid chromatography (HPLC). Statistical analysis was by intention to treat (ITT), using ANOVA, Student's t test, and Tukey's test. After 9 months, average values of 25(OH)D increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/ml (+45.4 %) in the VITD group and decreased from 16.9 ± 6.7 to 13.8 ± 6.0 ng/ml (-18.5 %) in the placebo group (p < 0.001). In the VITD group, there was significant increase in muscle strength (+25.3 %) of the lower limbs by chair rising test (p = 0.036). In women in the placebo group, there was considerable loss (-6.8 %) in the lean mass (p = 0.030). The supplementation of vitamin D alone in postmenopausal women provided significant protective factor against the occurrence of sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass.

Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia

Patients with critical limb ischaemia have a high rate of amputation and mortality. We tested the hypothesis that non-viral 1 fibroblast growth factor (NV1FGF) would improve amputation-free survival.

The effect of naloxone-3-glucuronide on colonic transit time in healthy men after acute morphine administration: a placebo-controlled double-blinded crossover preclinical volunteer study

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.