Ellie Duly

Exercise-Induced Lipid Peroxidation: Implications for Deoxyribonucleic Acid Damage and Systemic Free Radical Generation

Exercise‐induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high‐intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO2max: 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO2max) of aerobic exercise with a 15‐min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid‐soluble antioxidants. Lipid‐derived oxygen‐centered free radicals (hyperfine coupling constants aNitrogen = 13.7 Gauss (G) and aβHydrogen = 1.8 G) increased as a result of acute moderate and high‐intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid‐soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid‐derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis. Environ. Mol. Mutagen. 52:35–42, 2011.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

AIMS To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients. METHODS AND RESULTS A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission. CONCLUSION Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST. CLINICAL TRIAL REGISTRATION http://www.controlled-trials.com/ISRCTN52480460.

Exercise and postprandial lipaemia: effects on peripheral vascular function, oxidative stress and gastrointestinal transit

Postprandial lipaemia may lead to an increase in oxidative stress, inducing endothelial dysfunction. Exercise can slow gastric emptying rates, moderating postprandial lipaemia. The purpose of this study was to determine if moderate exercise, prior to fat ingestion, influences gastrointestinal transit, lipaemia, oxidative stress and arterial wall function. Eight apparently healthy males (age 23.6 ± 2.8 yrs; height 181.4 ± 8.1 cm; weight 83.4 ± 16.2 kg; all data mean ± SD) participated in the randomised, crossover design, where (i) subjects ingested a high-fat meal alone (control), and (ii) ingested a high-fat meal, preceded by 1 h of moderate exercise. Pulse Wave Velocity (PWV) was examined at baseline, post-exercise, and in the postprandial period. Gastric emptying was measured using the 13C-octanoic acid breath test. Measures of venous blood were obtained prior to and following exercise and at 2, 4 and 6 hours post-ingestion. PWV increased (6.5 ± 1.9 m/sec) at 2 (8.9 ± 1.7 m/sec) and 4 hrs (9.0 ± 1.6 m/sec) post-ingestion in the control group (time × group interaction, P < 0.05). PWV was increased at 2 hrs post-ingestion in the control compared to the exercise trial; 8.9 ± 1.7 vs. 6.2 ± 1.5 m/sec (time × group interaction, P < 0.05). Lipid hydroperoxides increased over time (pooled exercise and control data, P < 0.05). Serum triacylglycerols were elevated postprandially (pooled exercise and control data, P < 0.05). There were no changes in gastric emptying, cholesterol, or C-reactive protein levels. These data suggest that acute exercise prior to the consumption of a high-fat meal has the potential to reduce vascular impairments.

Physical activity, lipids, apolipoproteins, and Lp(a) in the Northern Ireland Health and Activity Survey

In a cross-sectional study using a two-stage probability sample (N = 1,600) of the population of Northern Ireland, there was an inverse association between the highest recorded recent activity and total cholesterol (P < or = 0.01), LDL (P < or = 0.01), triglyceride (P < or = 0.05) and Chol:HDL ratio (P < or = 0.001) in males, and total cholesterol (P < or = 0.001), LDL (P < or = 0.001), and triglyceride (P < or = 0.01) in females; between habitual activity and HDL (P < or = 0.05) in males and total cholesterol (P < or = 0.05) and triglyceride (P < or = 0.01) in females. There was a relationship between the highest recorded activity and apoAI (P < or = 0.01) and apoB (P < or = 0.01) in males and with apoB (P < or = 0.001) in females; between habitual activity and apoAI (P < or = 0.01) and apoAII (P < or = 0.05) in males and apoB (P < or = 0.01) in females; between past activity and Lp(a) in females (P < or = 0.05). After adjustment for possible confounding factors, total cholesterol (P < or = 0.05) and LDL (P < or = 0.05) were unexpectedly higher in males who were active throughout life. Total cholesterol (P < or = 0.05) and LDL (P < or = 0.001) were higher in females with highest recorded activity and triglycerides lower (P < or = 0.05) in those habitually active. An association between highest recorded activity and apoAI (P < or = 0.01), and past activity and apoAI:apoB ratio (P < or = 0.05) was shown in males and in females, after adjustment, and between apoB (P < or = 0.05) and highest recorded activity.

Increased serum apolipoprotein(a) in patients with chronic renal failure treated with continuous ambulatory peritoneal dialysis

Patients with end-stage renal failure (ESRF) on renal replacement therapy are at significantly increased risk of cardiovascular disease. To determine whether altered concentrations of apolipoprotein(a) (apo(a)), the plasminogen-like protein moiety of the atherogenic particle lipoprotein(a), contributed to this increased risk, apo(a) concentrations were measured in 48 non-diabetic patients with ESRF treated by continuous ambulatory peritoneal dialysis (CAPD) therapy and compared with 65 controls. Apo(a) concentration was increased in CAPD patients compared to controls (geometric mean 419 units/l versus 137 units/l; ratio of means 3.06 (95% CI 1.95-4.80). We conclude that CAPD patients have increased apo(a) concentrations which may contribute to their increased risk of cardiovascular disease.

Acute effects of walking on inflammatory and cardiovascular risk in sedentary post-menopausal women.

Abstract Biochemical markers of inflammation are emerging as new predictors of risk of cardiovascular disease (CVD) and may alter acutely with exercise. Few studies have been conducted on the effects of walking on these markers or whether different walking intensities elicit varied effects. As there is growing interest in modifiable lifestyle factors such as walking to reduce CVD risk, these inflammatory responses warrant investigation. The aim of this study was to compare the effects of walking at 50% versus 70% of predicted maximal heart rate on C-reactive protein (CRP), plasma fibrinogen, and trigylcerides in sedentary post-menopausal women. Twelve post-menopausal women (mean age 58 years, s ± 6; stature 1.62 m, s ± 0.06; body mass 66.8 kg, s ± 6.2) completed two 30-min treadmill walks in a randomized cross-over design. Fasted blood samples were taken (for the determination of plasma fibrinogen, CRP, and lipids) before, immediately after, and 1 and 24 h after exercise. Triglyceride concentrations decreased from pre-exercise to 24 h post exercise at both walking intensities (time×group interaction, P < 0.05). No significant effects were observed for plasma fibrinogen, CRP, total cholesterol, low-density or high-density lipoprotein cholesterol (time x group interaction, P > 0.05). The results of this study suggest that fasting plasma triglycerides are decreased on the morning after 30 min of brisk walking at either 50% or 70% of maximal heart rate (moderate and vigorous intensity).

Gastrointestinal transit, post-prandial lipaemia and satiety following 3 days high-fat diet in men

Background/Objectives:High-fat (HF) diets of 2 weeks have been shown to accelerate gastric emptying (GE). To date, no studies have shown any alteration in GE following shorter HF diets. The aim of this study was to assess if an HF, high-energy diet of 3 days can adapt gastrointestinal (GI) transit, blood lipids and satiety.Subjects/Methods:Eleven male volunteers participated in a study consisting of three, 3-day interventions each separated by a test day. During the first intervention, volunteers recorded their diet. In the second and third interventions, volunteers repeated their food diary plus either a low-fat yogurt or HF yogurt supplement in randomized order. Test days involved measurement of GE using the 13C octanoic-acid breath-test, mouth-to-caecum transit time (MCTT) using the inulin H2 breath test and satiety using visual analogue scales. Blood samples for measurement of lipaemia were taken using a venous cannula.Results:MCTT was different between the three test days (P=0.038), with the shortest MCTT following the HF intervention. GE was shortest following the HF intervention. There were no differences in satiety between the interventions. The HF intervention reduced triglycerides, total cholesterol and low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol.Conclusion:This study shows that changes in GI transit owing to an HF diet can occur in a time period as short as 3 days.

Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia, glycemia, and appetite responses to high-fat breakfast

BackgroundCinnamon has been shown to delay gastric emptying of a high-carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it is dietary fat which is implicated in the etiology and is associated with obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and glycemic responses, oxidative stress, arterial stiffness, as well as appetite sensations and subsequent food intake following a high-fat meal.MethodsA single-blind randomized crossover study assessed nine healthy, young subjects. GE rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined using the 13C octanoic acid breath test. Breath, blood samples and subjective appetite ratings were collected in the fasted and during the 360 min postprandial period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty acid intake relationships were also examined.ResultsCinnamon did not change gastric emptying parameters, postprandial triacylglycerol or glucose concentrations, oxidative stress, arterial function or appetite (p < 0.05). Strong relationships were evident (p < 0.05) between GE Thalf and 1-day palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3 intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial stiffness and oxidative stress following a HF meal.Conclusions3 g cinnamon did not alter the postprandial response to a high-fat test meal. We find no evidence to support the use of 3 g cinnamon supplementation for the prevention or treatment of metabolic disease. Dietary fatty acid intake requires consideration in future gastrointestinal studies.Trial registrationTrial registration number: at http://www.clinicaltrial.gov: NCT01350284

Exercise training and impaired glucose tolerance in obese humans

Abstract Individuals with impaired glucose tolerance (IGT) are at greater risk of developing diabetes than in normoglycaemia. The aim of this study was to examine the effects of 12-weeks exercise training in obese humans with IGT. Eleven participants (6 males and 5 females; 49±9 years; mean Body Mass Index (BMI) 32.4 kg · m−2), completed a 12-week brisk walking intervention (30 min per day, five days a week (d · wk−1), at 65% of age-predicted maximal heart rate (HRmax). Anthropometric measurements, dietary intake, pulse wave velocity (PWV, to determine arterial stiffness) and blood pressure (BP) were examined at baseline and post intervention. Fasting blood glucose, glycosylated haemoglobin, insulin, blood lipids, indices of oxidative stress and inflammation (lipid hydroperoxides; superoxide dismutase; multimeric adiponectin concentration and high-sensitivity C-reactive protein) were also determined. Post intervention, PWV (9.08±1.27 m · s−1 vs. 8.39±1.21 m · s−1), systolic BP (145.4±14.5 vs. 135.8±14.9 mmHg), triglycerides (1.52±0.53 mmol . L−1 vs. 1.31±0.54 mmol . L−1), lipid hydroperoxides (1.20±0.47 μM · L−1 vs. 0.79±0.32 μM · L−1) and anthropometric measures decreased significantly (P < 0.05). Moderate intensity exercise training improves upper limb vascular function in obese humans with IGT, possibly by improving triglyceride metabolism, which may subsequently reduce oxidative stress. These changes were independent of multimeric adiponectin modification and alterations in other blood biomarkers.

Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance

Obese subjects with impaired glucose tolerance (IGT) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease. This randomised controlled investigation was designed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT. All data were collected from 24 obese (BMI ≥ 30 kg/m2) IGT patients. Following participant randomisation into two groups, fasting venous blood samples were obtained at baseline, and before and following intervention. The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65% HRmax for 30 minutes a day, 5 days per week, while ingesting 1 gram per day of α-lipoic acid for 12 weeks. The second group consisted of 12 participants who completed the same 12 week control phase, but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only (no exercise). The main findings show a comparatively greater rate of low density lipoprotein (LDL) oxidation in the group consisting of α-lipoic acid only (p < 0.05 vs. pre intervention), although total oxidant status was lower post intervention (p < 0.05 vs. baseline) in this group. However, exercise and α-lipoic acid in combination attenuates LDL oxidation. Furthermore, in the α-lipoic acid supplement plus exercise training group, total antioxidant capacity was significantly increased (p < 0.05 vs. baseline and pre intervention). Body fat percentage and waist and hip circumference decreased following exercise training (p < 0.05 vs. post intervention). There were no selective treatment differences for a range of other clinical outcomes including glycaemic regulation (p > 0.05). These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise, suggesting that in IGT the use of this antioxidant treatment does not ameliorate metabolic disturbances, but instead may detrimentally contribute to the pathogenesis of atherosclerosis and development of CVD. However, when α-lipoic acid is combined with exercise, this atherogenic effect is abolished.