Supplementation with tocotrienol-rich fraction alters the plasma levels of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor from young and old individuals

Purpose

Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups.

Methods

Subjects were divided into two age groups—32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78 % tocotrienol and 22 % tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.

Results

Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.

Conclusions

TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.     

A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia

Background

Sarcopenia, the age-related loss of muscle mass [defined as appendicular LBM/Height² (aLBM/ht²) below peak value by>1SD], strength and function, is a major contributing factor to frailty in the elderly. MK-0773 is a selective androgen receptor modulator designed to improve muscle function while minimizing effects on other tissues.

Objectives

The primary objective of this study was to demonstrate an improvement in muscle strength and lean body mass (LBM) in sarcopenic frail elderly women treated with MK-0773 relative to placebo.

Design

This was a randomized, double-blind, parallel-arm, placebo-controlled, multicenter, 6-month study. Participants were randomized in a 1:1 ratio to receive either MK-0773 50mg b.i.d. or placebo; all participants received Vitamin D and protein supplementation.

Setting

General community.

Participants

170 Women aged ≥65 with sarcopenia and moderate physical dysfunction.

Measurements

Dual energy X-ray absorptiometry, muscle strength and power, physical performance measures.

Results

Participants receiving MK-0773 showed a statistically significant increase in LBM from baseline at Month 6 vs. placebo (p<0.001). Participants receiving both MK-0773 and placebo showed a statistically significant increase in strength from baseline to Month 6, but the mean difference between the two groups was not significant (p=0.269). Both groups showed significant improvement from baseline at Month 6 in physical performance measures, but there were no statistically significant differences between participants receiving MK-0773 and placebo. A greater number of participants experienced elevated transaminases in the MK-0773 group vs. placebo, which resolved after discontinuation of study therapy. MK-0773 was generally well-tolerated with no evidence of androgenization.

Conclusions

The MK-0773-induced increase in LBM did not translate to improvement in strength or function vs. placebo. The improvement of strength and physical function in the placebo group could be at least partly attributed to protein and vitamin D supplementation.     

The impact of supplemental N-3 long chain polyunsaturated fatty acids and dietary antioxidants on physical performance in postmenopausal women

Objectives

Identify relationships and evaluate effects of long chain polyunsaturated fatty acids (LCPUFA) on frailty and physical performance. Design: Randomized, double blind pilot study.

Setting

University General Clinical Research Center.

Participants

126 postmenopausal women.

Intervention

2 fish oil (1.2g eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) or 2 placebo (olive oil) capsules per day for 6 months. All participants received calcium and vitamin D supplements.

Measurements

Fatty acid levels, frailty assessment, hand grip strength, 8 foot walk, body composition, medical history and co-morbidities, nutrient intake, and inflammatory biomarkers taken at baseline and 6 months.

Results

At baseline, those with greater red blood cell (RBC) DHA and DHA/arachidonic acid (AA) presented with less frailty (r=?0.242, p=0.007 and r=?0.254, p=0.004, respectively). Fish oil supplementation resulted in higher RBC DHA and lower AA compared to baseline and placebo (p<0.001) and an improvement in walking speed compared to placebo (3.0±16 vs. ?3.5±14, p=0.038). A linear regression model included age, antioxidant intake (selenium and vitamin C), osteoarthritis, frailty phenotype, and tumor necrosis factor alpha (TNFα). The model explained 13.6% of the variance in the change in walking speed. Change in DHA/AA (p=0.01) and TNFα (p=0.039), and selenium intake (p=0.031) had the greatest contribution to change in walking speed.

Conclusion

Physical performance, measured by change in walking speed, was significantly affected by fish oil supplementation. Dietary intake of antioxidants (selenium and vitamin C) and changes in TNFα also contributed to change in walking speed suggesting LCPUFA may interact with antioxidants and inflammatory response to impact physical performance.     

Improvement of accommodation with anti-oxidant supplementation in visual display terminal users

Objective

To determine the antioxidant supplementation effect on accommodation among VDT users.

Design

A double blind randomized placebo controlled study. Registered under Clinical Trials.gov Identifier No. NCT00877201.

Participants and Controls

Fourty right eyes of 40 healthy VDT users (30 females, 10 males, mean age: 43.8±2.8 years, range: 40?C49 years). 20 subjects (15 females, 5 males; mean age: 44.0±2.7 years, range: 40?C49 years).

Methods

Subjects were required to take an antioxidant supplement, 20 age and sex matched subjects (15 females, 5 males; mean age: 43.6±3.1 years, range: 40?C49 years) were required to take placebo medication for 4 weeks.

Results

The mean of the change in accommodation power was significantly higher in the group receiving antioxidant supplements (0.20±0.50 Diopter(D)) compared to the placebo group (?0.12±0.48(D)) (p<0.05).

Conclusions

Antioxidant supplementation was observed to improve accommodation in Japanese Visual Display Terminal (VDT) Users.     

Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status

Objective

Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians.

Design

Double-blind, placebo controlled, randomised crossover study.

Setting

Community dwelling vegetarians.

Participants

Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. Intervention: Vitamin B-12 (500??g/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41).

Measurement

How-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound.

Results

The mean age of the subjects was 45+9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (??=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028).

Conclusions

Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.     

Supplementation of ascorbic acid and alpha-tocopherol is useful to preventing bone loss linked to oxidative stress in elderly

Objective

To determine the effect of ascorbic acid and alpha-tocopherol on oxidative stress and bone mineral density (BMD) in elderly people.

Design

A double-blind, controlled clinical assay was carried out in a sample of 90 elderly subjects divided into three age-paired random groups with 30 subjects in each group. Group Tx0 received placebo, group Tx1 received 500 mg of ascorbic acid and 400 IU of alpha-tocopherol, whereas group Tx2 received 1,000 mg of ascorbic acid and 400 IU of alpha-tocopherol, for a 12-month period.

Measurements

We measured thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), superoxide dismutase (SOD), and glutation peroxidase (GPx); BMD was obtained on DXA of hip and spine before and after the 12-month treatment period with supplementation of vitamins C and E.

Results

We found a positive correlation between hip-BMD and SOD (r = 0.298, p <0.05) and GPx (r = 0.214, p <0.05). Also, a significantly lower decrease of LPO (p <0.05) was observed as linked with hip bone loss in the Tx2 group than in the Tx0 group.

Conclusions

Our findings suggest that that administration of 1,000 mg of ascorbic acid together with 400 IU of alpha-tocopherol could be useful in preventing or aiding in the treatment of age-related osteoporosis.     

Changes in mineral status are associated with improvements in insulin sensitivity in obese patients following l-arginine supplementation

Purpose

The aim of this study is to evaluate the long-term influence of l-arginine intake on mineral concentration in patients with obesity and to assess the changes in lipid serum levels, fat content, and insulin resistance that result.

Methods

A randomized double-blind placebo-controlled study was conducted. 88 obese patients were randomly assigned to receive either 9 g of l-arginine or placebo daily, for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed and mineral levels were assessed. To assess insulin sensitivity, the gold-standard euglycemic clamp methodology was used.

Results

We found that 6 months of l-arginine supplementation resulted in significant increases in insulin sensitivity (Δ1.1 mg/kg/min, P < 0.01) and zinc levels (Δ1.5 μmol/L, P < 0.001). Moreover, a positive correlation between the change in zinc concentration in serum and the change in insulin sensitivity was observed (R = 0.80, P < 0.01). In the group of patients treated with l-arginine, a negative correlation between the change in zinc concentration in serum and the change in body fat content was noted (R = ?0.38, P < 0.05).

Conclusions

l-Arginine supplementation affects zinc status in obese patients. One beneficial influence is related to the improvements in insulin sensitivity.     

The effect of perinatal fish oil supplementation on neurodevelopment and growth of infants: a randomized controlled trial

Introduction

Long-chain polyunsaturated fatty acids, the most abundant fatty acids in the brain, are essential for the growth and development of the brain and the retina.

Objective

To evaluate the effect of fish oil supplementation on the development (primary outcome) and growth of 4- and 6-month-old infants.

Methods

In this triple-blind randomized controlled trial, 150 pregnant women aged 18–35 years, who were referred to healthcare centres of Tabriz-Iran, were randomly allocated into two groups. One group of women consumed fish oil supplementation (containing 120 mg docosahexaenoic acid and 180 mg eicosapentaenoic acid) daily, while the other consumed a placebo from the 20th week of pregnancy till 30 days after childbirth in a parallel design by a computer-generated block randomization scheme. The neurodevelopment of infants was the primary outcome; it was assessed using the ages and stages questionnaire (ASQ) at 4- and a-6 months of age. The growth of these infants was measured using weight, length and head circumference. The participants, the caregivers, and those assessing the outcomes were blind to the group assignment.

Results

Only one woman in the placebo group discontinued the intervention because of persistent severe nausea. All 75 neonates aged 4- and a-6 months in the fish oil supplementation group, along with 73 and 71 neonates aged 4 and 6 months, respectively in the placebo group, were followed and analysed. Although the mean scores of neurodevelopment at the end of 4 and 6 months were higher in the supplemented group than in the placebo group in each ASQ domain, a statistically significant difference was observed only in the communication domain at the 4th month (adjusted mean difference 2.63; 95% confidence interval 0.36–4.89). There was no significant difference in weight, length, or head circumference between the two groups of infants aged 4 and 6 months (P ≥ 0.05).

Conclusion

Based on the results, perinatal fish oil supplementation is beneficial for the communication domain of neurodevelopment of 4-month-old infants. The study results relating to the supplementation effect on other domains are inconclusive. There ought to be further studies with up-to-date lipidomic analysis to find biochemical correlate compared to an intervention and developmental finding.

     

Coenzyme Q10 supplementation ameliorates inflammatory signaling and oxidative stress associated with strenuous exercise

Background

Exhausting exercise induces muscle damage associated with high production of free radicals and pro-inflammatory mediators.

Aim

The objective of this study was to determine for the first time and simultaneously whether oral coenzyme Q₁₀ (CoQ₁₀) supplementation can prevent over-expression of inflammatory mediators and oxidative stress associated with strenuous exercise.

Methods

The participants were classified in two groups: CoQ₁₀ group (CG) and placebo group (PG). The physical test consisted in a constant run (50?km) that combined several degrees of high effort (mountain run and ultra-endurance), in permanent climbing.

Results

Exercise was associated with an increase in TNF-α, IL-6, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and isoprostane levels, revealing the degree of inflammation and oxidative stress induced. Oral supplementation of CoQ₁₀ during exercise was efficient reducing oxidative stress (decreased membrane hydroperoxides, 8-OHdG and isoprostanes generation, increased catalase, and total antioxidant status), which would lead to the maintenance of the cell integrity. Data obtained also indicate that CoQ₁₀ prevents over-expression of TNF-α after exercise, together with an increase in sTNF-RII that limits the pro-inflammatory actions of TNF. Moreover, CoQ₁₀ supplementation reduced creatinine production.

Conclusions

CoQ₁₀ supplementation before strenuous exercise decreases the oxidative stress and modulates the inflammatory signaling, reducing the subsequent muscle damage.     

Cognitive changes with omega-3 polyunsaturated fatty acids in non-demented older adults with low omega-3 index

Objectives

To investigate the changes in specific domains of cognitive function in older adults reporting subjective memory complaints with a low omega-3 index receiving omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or placebo.

Design

This is a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT) using subjects randomized to the n-3 PUFA supplementation or placebo group.

Setting

French community dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia.

Participants

A subgroup of MAPT subjects in the lowest quartile of omega-3 index distribution with baseline values ≤ 4.83 % (n = 183).

Intervention

The n-3 PUFA supplementation group consumed a daily dose of DHA (800 mg) and EPA (a maximum amount of 225 mg) for 3 years. The placebo group received identical capsules comprising liquid paraffin oil.

Measurements

Linear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in eight cognitive tests over 36 months.

Results

There was less decline on the Controlled Oral Word Association Test (COWAT) in the n-3 PUFA supplementation group compared to placebo (p = 0.009; between group mean difference over 36 months, 2.3; 95% CI, 0.6,4.0). No significant differences for any of the other cognitive tests were found, including other tests of executive functioning, although, numerically all results were in favour of the n-3 PUFA supplementation.

Conclusions

We found some evidence that n-3 PUFAs might be beneficial for the maintenance of executive functioning in older adults at risk of dementia with low omega-3 index, but this exploratory finding requires further confirmation. A larger specifically designed randomised controlled trial could be merited.

     

Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction

Background

The strength of aging bone depends on the balance between the resorption and formation phases of the remodeling process. The purpose of this study was to examine the interaction of two factors with the potential to exert opposing influences on bone turnover, resistance exercise training and high dietary protein intake. It was hypothesized that resistance training by young, healthy, untrained women with protein intakes near recommended levels (0.8 g·kg^-1·d^-1) would promote bone formation and/or inhibit bone resorption, and that subsequent supplementation to provide 2.4 g protein·kg^-1·d^-1 would reverse these effects.

Methods

Bone formation was assessed with serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and bone resorption with urinary calcium and deoxypyridinoline (DPD). Biochemical, strength, anthropometric, dietary, and physical activity data were obtained from 24 healthy, untrained, eumenorrheic women (18–29y) at baseline, after eight weeks of resistance training (3 d·wk^-1, ~1 hr·d^-1; 3 sets, 6–10 repetitions, 13 exercises, 75–85% maximum voluntary contraction), and after 12 weeks of resistance training and 10 days of protein/placebo supplementation. Subjects were randomized (double-blind) to either a high protein (HP) or training control (TC) group and, during the final 10 days, consumed either enough purified whey protein to bring daily protein intake to 2.4 g·kg^-1·d^-1, or an equivalent dose of isoenergetic, carbohydrate placebo.

Results

Strength, lean tissue mass, and DPD increased significantly in both groups over time, while percent body fat and BAP decreased (repeated measures ANOVA, p ≤ 0.05, Bonferroni correction). No significant changes were observed for serum OC or urinary calcium, and no significant group (TC, HP) × time (baseline, week 8, week 12) interactions emerged for any of the biochemical measures.

Conclusion

(1) Twelve weeks of high-intensity resistance training did not appear to enhance bone formation or inhibit bone resorption in young adult women, as assessed by biochemical markers of bone metabolism. (2) Subsequent maintenance of a high protein intake for 10 days in these regularly-training, calcium-replete women also showed no effects on bone metabolism.     

Antioxidant effect of zinc supplementation on both plasma and cellular red-ox status markers in a group of elderly Italian population

Objectives

The aim of this work was to evaluate the effect of long term supplementation with two moderate dose of Zn on plasma and cellular red-ox status markers in elderly volunteers.

Design, setting and subjects

In a double blind study 108 healthy volunteers, aged 70–85 years, were enrolled. They were randomly divided in 3 groups of treatment, receiving placebo, 15 mg/day and 30 mg/day of Zn for 6 months. Red-ox status markers were assessed at baseline and after 6 months evaluating carotenoids, vitamin A and E in plasma; glutathione (GSH), thiol groups (RSH), malondialdehyde (MDA), percentage of haemolysis and methemoglobin in erythrocytes.

Results

Zn supplementation had no significant effects on red-ox status markers except for vitamin A levels (from 1.94±0.44 to 2.18±0.48 μM in volunteers receiving 15 mg of Zn and from 1.95±0.46 to 2.26±0.56 μM in volunteers receiving 30 mg of Zn), which increased proportionally to zinc dose.

Conclusions

It appears that, differently from unhealthy populations, long-term supplementation with two moderate doses of Zn in a healthy elderly population, with an adequate Zn nutritive status and macro and micronutrients intakes in the range of normality, is an inefficient way to increase antioxidant defences.     

Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

Background

Resting and postprandial oxidative stress is elevated in those with metabolic disorders such as diabetes. Antioxidant supplementation may attenuate the rise in oxidative stress following feeding. Therefore we sought to determine the effects of acetyl L-carnitine arginate (ALCA) on resting and postprandial biomarkers of glucose and lipid metabolism, as well as oxidative stress.

Methods

Twenty-nine pre-diabetic men and women were randomly assigned to either 3 g·day^-1 of ALCA (n = 14; 31 ± 3 yrs) or placebo (n = 15; 35 ± 3 yrs) in a double-blind design, to consume for eight weeks. Fasting blood samples were taken from subjects both pre and post intervention. After each fasting sample was obtained, subjects consumed a high fat, high carbohydrate meal and additional blood samples were taken at 1, 2, 4, and 6 hours post meal. Samples were analyzed for a variety of metabolic variables (e.g., glucose, HbA1c, lipid panel, C-reactive protein, nitrate/nitrite, and several markers of oxidative stress). Area under the curve (AUC) was calculated for each variable measured post meal, both pre and post intervention.

Results

ALCA, but not placebo, resulted in an increase in nitrate/nitrite (25.4 ± 1.9 to 30.1 ± 2.8 μmol·L^-1) from pre to post intervention, with post intervention values greater compared to placebo (p = 0.01). No other changes of statistical significance were noted (p > 0.05), although ALCA resulted in slight improvements in glucose (109 ± 5 to 103 ± 5 mg·dL^-1), HbA1c (6.6 ± 1.1 to 6.2 ± 1.2%), and HOMA-IR (3.3 ± 1.3 to 2.9 ± 1.2). AUC postprandial data were not statistically different between ALCA and placebo for any variable (p > 0.05). However, nitrate/nitrite demonstrated a moderate effect size (r = 0.35) for increase from pre (139.50 ± 18.35 μmol·L^-1·6 hr^-1) to post (172.40 ± 21.75 μmol·L^-1·6 hr^-1) intervention with ALCA, and the magnitude of decrease following feeding was not as pronounced as with placebo.

Conclusion

Supplementation with ALCA results in an increase in resting nitrate/nitrite in pre-diabetics, without any statistically significant change in other metabolic or oxidative stress variables measured at rest or post meal.     

Effect of vitamin K on vascular health and physical function in older people with vascular disease–a randomised controlled trial

Background and Aims

Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease.

Methods and results

A double blind, randomised, placebo-controlled trial. Participants aged ≤ 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform.

Results

80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs ?6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (?130 [SD 117] pmol/L vs +13 [SD 180] pmol/L, p<0.001). No change was seen in endothelial function (between group difference ?0.3% [95%CI ?1.3 to 0.8], p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (?0.8m/s [95%CI ?1.8 to 0.3], p=0.15) while all other vascular and physical function outcomes unchanged.

Conclusions

Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease.

     

Sustainability of a physical activity and nutrition program for seniors

Objective

This prospective cohort study aimed to determine the impact of a low cost, home-based physical activity and nutrition program for older adults at 6 months follow-up.

Design

A follow-up survey was conducted 6 months after program completion via computer-assisted telephone interviewing. The International Physical Activity Questionnaire and the Fat and Fibre Barometer were used to measure physical activity levels and dietary behaviours, respectively. Self-reported height, weight, waist and hip circumferences were obtained. Changes over three time points of data collection (baseline, post-program, follow-up) and differences between the intervention and control groups were assessed. The use of program materials was also evaluated.

Setting

Community and home-based.

Participants

Insufficiently active 60 to 70 year olds (n = 176, intervention and n = 198, control) residing in suburbs within the Perth metropolitan area.

Results

A sustained improvement was observed for the intervention group in terms of fat avoidance behaviours (p interaction =.007). Significant improvements were found for strength exercises, fibre intake, body mass index and waist-to-hip ratio at either post-program or follow-up, however the overall effect was not significant. At post-program, the intervention group increased time spent participating in moderate activity by 50 minutes (p >.05), which was followed by a significant decline at follow-up (p <.05). Among intervention group participants, males and females differed with respect to strength exercises and moderate physical activity.

Conclusion

This low-cost physical activity and nutrition intervention resulted in a sustained improvement in fat avoidance behaviours and overall short-term gains in physical activity. Future studies for older adults are recommended to investigate gender-specific behavioural barriers as well as booster interventions which focus on physical activity.     

Short-term creatine supplementation does not reduce increased homocysteine concentration induced by acute exercise in humans

Purpose

The purpose of the study is to evaluate the effects of creatine supplementation on homocysteine (Hcy) plasma levels after acute exercise in humans.

Methods

Twenty-three young (under-20) soccer players were divided into 2 groups: creatine (Cr)- and placebo (Pla)-supplemented groups. The supplementation was performed in double-blind controlled manner using creatine or placebo tablets with 0.3 g/kg during 7 days. Before and after 7 days of supplementation, the athletes performed an acute high-intensity sprint exercise (two consecutive running-based anaerobic sprint test protocol consisted in 6 × 35 m sprint with 10 s between them). Blood samples were collected before and after 7 days of supplementation as well as 0 and 1 h after exercise protocol.

Results

Homocysteine concentration significant increased (P < 0.05) 1 h after acute exercise (18 %). Acute exercise also decreased red blood cell S-adenosylmethionine (SAM) 30 % with no changes in SAM/SAH ratio. Seven days of creatine supplementation were able to increase (P < 0.05) plasma creatine concentration (Pla 130.1 ± 21.7 vs Cr 1,557.2 ± 220.3 μmol/L) as well as decrease (P < 0.05) plasma guanidinoacetic acid (33 %). Controversially, creatine supplementation did not change Hcy plasma level after 7-day supplementation (Pla 6.9 ± 0.2 vs Cr 7.2 ± 0.2 μmol/L) or after acute exercise (Pla 8.2 ± 0.3 vs Cr 8.4 ± 0.3 μmol/L). No changes in plasma vitamin B12 and folate as well as cysteine and methionine were found.

Conclusions

Seven days of creatine supplementation does not avoid increased plasma Hcy induced by acute sprint exercise in humans.     

Cost analysis of amlodipine versus enalapril in patients with coronary artery disease and normal blood pressure

Objectives

To analyse 2-year hospitalization and cost data collected during a prospective, double-blind, randomized, controlled trial comparing amlodi-pine, enalapril and placebo in normotensive patients with coronary artery disease (CAD).

Methods

All patients who were enrolled in the CAMELOT study were included in this economic substudy. Patients with CAD and normal blood pressure were randomized to amlodipine, enalapril or placebo, and followed up for 24 months (between 1999 and 2004). Data on hospitalizations and medication use were obtained from the clinical trial. Costs were assigned from secondary sources. Total costs ($US, year 2004 values) were estimated as the sum of costs associated with cardiovascular hospitalizations, study medications and concomitant cardiovascular medications. Costs and resource use were analysed by treatment arm overall and for selected patient subgroups. Cost differences were evaluated using nonparametric bootstrap techniques.

Results

Of 1991 patients enrolled, 663 were treated with amlodipine, 673 were treated with enalapril and 655 were treated with placebo. Significantly fewer patients were hospitalized for cardiovascular reasons in the amlodipine group (16.4%) than in the placebo group (22.7%;p < 0.01), but not compared with the enalapril group (20.1%;p = 0.09). The amlodipine group also had numerically fewer days in hospital per patient (1.1) than the enalapril (1.3) and placebo (1.5) groups. Mean 2-year per-patient costs in the amlodipine group were estimated to be $US609 and $US717 lower than for the placebo and enalapril groups, respectively.

Conclusions

These results suggest that use of amlodipine may reduce costs of care among CAD patients with normal blood pressure.     

Effect of the dietary supplement Meltdown on catecholamine secretion, markers of lipolysis, and metabolic rate in men and women: a randomized, placebo controlled, cross-over study

Background

We have recently reported that the dietary supplement Meltdown^® increases plasma norepinephrine (NE), epinephrine (EPI), glycerol, free fatty acids (FFA), and metabolic rate in men. However, in that investigation measurements ceased at 90 minutes post ingestion, with values for blood borne variables peaking at this time. It was the purpose of the present investigation to extend the time course of measurement to 6 hours, and to include women within the design to determine if sex differences to treatment exist.

Methods

Ten men (24 ± 4 yrs) and 10 women (22 ± 2 yrs) ingested Meltdown^® or a placebo, using a randomized, cross-over design with one week separating conditions. Blood samples were collected immediately before supplementation and at one hour intervals through 6 hours post ingestion. A standard meal was provided after the hour 3 collection. Samples were assayed for EPI, NE, glycerol, and FFA. Five minute breath samples were collected at each time for measurement of metabolic rate and substrate utilization. Area under the curve (AUC) was calculated. Heart rate and blood pressure were recorded at all times. Data were also analyzed using a 2 (sex) × 2 (condition) × 7 (time) repeated measures analysis of variance, with Tukey post hoc testing.

Results

No sex × condition interactions were noted for AUC for any variable (p > 0.05). Hence, AUC data are collapsed across men and women. AUC was greater for Meltdown^® compared to placebo for EPI (367 ± 58 pg·mL^-1·6 hr^-1 vs. 183 ± 27 pg·mL^-1·6 hr^-1; p = 0.01), NE (2345 ± 205 pg·mL^-1·6 hr^-1 vs. 1659 ± 184 pg·mL^-1·6 hr^-1; p = 0.02), glycerol (79 ± 8 μg·mL^-1·6 hr^-1 vs. 59 ± 6 μg·mL^-1·6 hr^-1; p = 0.03), FFA (2.46 ± 0.64 mmol·L^-1·6 hr^-1 vs. 1.57 ± 0.42 mmol·L^-1·6 hr^-1; p = 0.05), and kilocalorie expenditure (439 ± 26 kcal·6 hrs^-1 vs. 380 ± 14 kcal·6 hrs^-1; p = 0.02). No effect was noted for substrate utilization (p = 0.39). Both systolic and diastolic blood pressure (p < 0.0001; 1–16 mmHg), as well as heart rate (p = 0.01; 1–9 bpm) were higher for Meltdown^®. No sex × condition × time interactions were noted for any variable (p > 0.05).

Conclusion

Ingestion of Meltdown^® results in an increase in catecholamine secretion, lipolysis, and metabolic rate in young men and women, with a similar response for both sexes. Meltdown^® may prove to be an effective intervention strategy for fat loss, assuming individuals are normotensive and their treatment is monitored by a qualified health care professional.     

Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality

Background

Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans.

Purpose

The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality.

Methods

In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7?days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48?h were collected and urinary 6-sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period. Trial differences were determined using a repeated measures ANOVA.

Results

Total melatonin content was significantly elevated (P?<?0.05) in the cherry juice group, whilst no differences were shown between baseline and placebo trials. There were significant increases in time in bed, total sleep time and sleep efficiency total (P?<?0.05) with cherry juice supplementation. Although there was no difference in timing of the melatonin circardian rhythm, there was a trend to a higher mesor and amplitude.

Conclusions

These data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep.     

Effects of ACE-inhibition on IGF-1 and IGFBP-3 concentrations in older adults with high cardiovascular risk profile

Objectives

The present study evaluates the effects of a 6-month treatment with an ACE-inhibitor (ie, fosinopril) on serum concentrations of total IGF-1 and IGF binding protein (IGFBP)-3 in older adults at high risk for cardiovascular disease.

Design

Data are from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study, a double-blind, crossover, randomized, placebo-controlled trial.

Setting

Participants were recruited from the communities of Winston Salem, NC, and Greensboro, NC.

Participants

Subjects ≥55 years old with high cardiovascular disease risk profile.

Intervention

The intervention consisted of 6-month administration of fosinopril vs. placebo.

Measurements

Serum concentrations of total IGF-1 and IGFBP-3 were measured in 100 participants of the TRAIN study at baseline, 6-month and 12-month follow-up visits. Differences in total IGF-1 and IGFBP-3 concentrations were assessed using two-sided paired t-tests.

Results

The mean age of participants (47% women) was 66.5 (standard deviation 7.2) years. Serum concentrations of total IGF-1 were significantly higher after 6-month treatment with fosinopril compared to placebo (203.73 ng/mL vs 194.24 ng/mL; p=0.02): After ACE-inhibitor intervention, significantly higher serum IGFBP-3 concentrations compared to controls (4308.81 ng/mL vs 4086.93 ng/mL; p=0.03) were also reported.

Conclusions

A six-month treatment with fosinopril increases systemic levels of total IGF-1 and IGFBP-3 in older adults with high cardiovascular risk profile. This may represent a potential biological explanation to the beneficial effects of ACE-inhibition on stroke, ischemic heart disease and insulin resistance.