Reallocating sitting time to standing or stepping through isotemporal analysis: associations with markers of chronic low-grade inflammation.

Although high levels of sitting time are adversely related to health, it is unclear whether moving from sitting to standing provides a sufficient stimulus to elicit benefits upon markers of chronic low-grade inflammation in a population at high risk of type 2 diabetes (T2DM). Three hundred and seventy two participants (age = 66.8 ± 7.5years; body mass index (BMI) = 31.7 ± 5.5kg/m2; Male = 61%) were included. Sitting, standing and stepping was determined using the activPAL3TM device. Linear regression modelling employing an isotemporal substitution approach was used to quantify the association of theoretically substituting 60 minutes of sitting per day for standing or stepping on interleukin-6 (IL-6), C-reactive protein (CRP) and leptin. Reallocating 60 minutes of sitting time per day for standing was associated with a -4% (95% CI -7%, -1%) reduction in IL-6 (p = 0.048). Reallocating 60 minutes of sitting time for light stepping was also associated with lower IL-6 levels (-28% (-46%, -4%; p = 0.025)). Substituting sitting for moderate-to-vigorous (MVPA) stepping was associated with lower CRP (-41% (-75%, -8%; p = 0.032)), leptin (-24% (-34%, -12%; p ≤ 0.001)) and IL-6 (-16% (-28%, 10%; p = 0.036). Theoretically replacing 60 minutes of sitting per day with an equal amount of either standing or stepping yields beneficial associations upon markers of chronic-low grade inflammation.

Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

Reactive oxygen species production and mitochondrial dysfunction in white blood cells are not valid biomarkers of ageing in the very old.

Reliable and valid biomarkers of ageing (BoA) are needed to understand mechanisms, test interventions and predict the timing of adverse health events associated with ageing. Since increased reactive oxygen species (ROS) production and mitochondrial dysfunction are consequences of cellular senescence and may contribute causally to the ageing of organisms, we focused on these parameters as candidate BoA. Superoxide levels, mitochondrial mass and mitochondrial membrane potential in human peripheral blood mononuclear cells (PBMCs) and subpopulations (lymphocytes and monocytes) were measured in participants from the Newcastle 85+ study, a population-based study of the very old (aged 85 years and older). The intra- and inter-assay precision expressed as coefficient of variation (CV) for all parameters was acceptable (3% to 12% and 5 to 22% respectively). All parameters were stable in the short-term (1 week interval) in a sample of control individuals in the PBMCs and lymphocyte subpopulation, however they were unstable in the monocyte subpopulation; this rendered monocytes unreliable for further analysis. There was a significant association between superoxide levels and mitochondrial mass (positive in lymphocytes, p = 0.01) and between superoxide levels and mitochondrial membrane potential (negative in PBMCs, p = 0.01; positive in lymphocytes, p = 0.05). There were also significant associations between superoxide levels and mitochondrial parameters with other markers of oxidative stress-induced cellular senescence (p≤0.04), however some were in the opposite direction to expected. No associations were found between the measured parameters and age-related outcomes, including cognitive impairment, disability, co-morbidity and survival - questioning the validity of these parameters as candidate BoA in the very old.

Effect of short-term reduced physical activity on cardiovascular risk factors in active lean and overweight middle-aged men.

OBJECTIVES: An experimental reduction in physical activity is a useful tool for exploring the health benefits of physical activity. This study investigated whether similarly-active overweight men show a more pronounced response to reduced physical activity than their lean counterparts because of their atherogenic phenotype (i.e., greater abdominal adiposity). METHODS: From 115 active men aged 45-64years, we recruited nine active lean (waist circumference <84cm) and nine active central overweight men (waist circumference >94cm). Fasting blood samples and responses to an oral glucose tolerance test (OGTT) were measured at baseline and following one week of reduced physical activity to simulate sedentary levels (removal of structured exercise and reduced habitual physical activity). RESULTS: Glucose and insulin areas under the curve (AUC), CRP, ALT, TAG were all higher in the overweight group and remained so throughout (P<0.05). Insulin and glucose AUC responses to an OGTT, as well as fasting triglyceride (TAG) concentrations, increased in both groups as a result of the intervention (P<0.05). There was no change in interleukin-6, C-reactive protein (CRP), Tumour Necrosis Factor-α, soluble intracellular adhesion molecule 1, or alanine transaminase (ALT). CONCLUSION: One-week of reduced activity similarly-impaired glucose control and increased fasting TAG in both lean and overweight men. Importantly, in spite of very similar (high) levels of habitual physical activity, central overweight men displayed a poorer profile for various inflammatory and metabolic outcomes (CRP, ALT, TAG, glucose AUC and insulin AUC).

An investigation into the relationship between sleep-disordered breathing, the metabolic syndrome, cardiovascular risk profiles, and inflammation between South Asians and Caucasians residing in the United Kingdom.

BACKGROUND: The aim of this study was to determine the prevalence of sleep-disordered breathing (SDB) in a South Asian and a Caucasian population and to compare the cardiovascular risk factors in those with SDB within these ethnic groups and determine if SDB is independently associated with the metabolic syndrome and markers of inflammation. METHODS: A total of 1,598 participants within a U.K. multiethnic population underwent an oral glucose tolerance test, completed the Berlin Sleep Questionnaire, and provided anthropometric data and fasting bloods. Metabolic syndrome was classified according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The prevalence of SDB was 28.3% and did not differ between the two ethnic groups. South Asians with SDB had a higher body fat percentage (38.4±10% vs. 35.6±9%, P=0.016), glycosylated hemoglobin (5.6±0.5% vs. 5.6±0.5%, P=0.001) and lower high-density lipoprotein cholesterol (1.21±0.23 mmol/L vs. 1.29±0.34 mmol/L, P=0.002) compared to Caucasians with SDB, who were older (59.6±8.6 years vs. 50.4±10.3 years, P<0.001) and had higher systolic blood pressure (139.8±18.5 mmHg vs. 131.7±18.6 mmHg, P<0.001). SDB was associated with metabolic syndrome after adjustment for age, gender, ethnicity, and waist circumference (odds ratio=1.54, 95% confidence interval 1.12-2.09, P=0.01). There was no independent association between SDB and markers of inflammation. CONCLUSION: The relationship between SDB and metabolic syndrome is not driven via the inflammatory pathway. The prevalence of SDB is significantly higher in those with metabolic syndrome although these South Asians had a greater cardiovascular disease (CVD) risk profile the relationship is independent of ethnicity. Routine screening for SDB within primary/secondary care may have a role in the prevention of CVD and type 2 diabetes mellitus.

Active middle-aged men have lower fasting inflammatory markers but the postprandial inflammatory response is minimal and unaffected by physical activity status.

Physical activity modifies some postprandial responses such as glycemic control, although it is unclear whether this translates into lower postprandial inflammation. Our objective in this study was to determine whether postprandial inflammatory markers are lower in active compared with sedentary middle-aged men. Thirteen active and twelve sedentary middle-aged men consumed a mixed meal on one occasion. Blood was taken via a cannula before and up to 8 h after the meal and with a single-use needle before and 8 h after the meal. Active men had lower fasted IL-6 (0.6 +/- 0.2 vs. 1.2 +/- 0.3 pg/ml; P = 0.004) and C-reactive protein (1.3 +/- 0.3 vs. 2.9 +/- 0.6 mg/l; P = 0.04) concentrations than sedentary men. Cannula blood IL-6 concentrations increased by 3.49 pg/ml in the 8 h following the meal (P < 0.001); however, this increase was minimal (0.36 pg/ml) in blood taken via a single-use needle from the contralateral arm (P = 0.013). The sedentary group had larger glucose (P = 0.034), insulin (P = 0.013), and triacylglycerol (P = 0.057) responses to the meal. These results provide further evidence that physical activity is associated with lower inflammatory marker concentrations in a fasted state and a lower postprandial metabolic response to a meal. However, this does not translate into lower postprandial inflammatory markers since the only evidence of postprandial inflammation (a large increase in serum IL-6) was actually due to the cannula used for blood sampling.

Low-dose docosahexaenoic acid lowers diastolic blood pressure in middle-aged men and women.

The intake of (n-3) long-chain PUFA is associated with a decreased risk of fatal myocardial infarction. Whether this effect is attributable to the effects of docosahexaenoic acid [22:6(n-3) (DHA)] on vascular function, particularly at intakes <1 g/d, is unknown. We report a randomized, double-blind, crossover, placebo controlled trial of 0.7 g DHA/d as a purified algal derived triacylglycerol (1.5 g/d) vs. placebo (1.5 g olive oil/d) on vascular function and biochemical indices of endothelial dysfunction in 38 healthy men and women, aged 40-65 y. Each treatment phase lasted 3 mo, separated by a 4 mo washout period. Supplementation increased the proportion of DHA in erythrocytes lipids by 58%, compared with placebo. Arterial compliance and endothelium independent and dependent responses, plasma concentrations of C-reactive protein, soluble thrombomodulin, E-selectin, von Willebrand factor antigen, and urinary microalbumin and isoprostane excretion were unaffected by treatment. Diastolic blood pressure decreased by 3.3 mm Hg (95% CI -6.1 to -0.6; P = 0.01). Heart rate tended to be 2.1 beats/min lower after DHA treatment than after the placebo period (P = 0.15). The results indicate that a moderate increase in the daily intake of DHA to approximately 0.7 g DHA lowers diastolic BP but does not influence indices of endothelial function or arterial stiffness in the short term.

Monoclonal antibody-based time-resolved fluorescence immunoassays for daidzein, genistein, and equol in blood and urine: application to the Isoheart intervention study.

BACKGROUND: Time-resolved fluorescence immunoassays (TR-FIAs) for phytoestrogens in biological samples are an alternative to mass spectrometric methods. These immunoassays were used to test urine and plasma samples from individuals in a dietary intervention trial aimed at determining the efficacy of dietary isoflavones in reducing the risk of coronary heart disease in postmenopausal women. METHODS: We established murine monoclonal TR-FIA methods for daidzein, genistein, and equol. These assays could be performed manually or adapted to an automated analyzer for high throughput and increased accuracy. Analysis of urine was conducted on nonextracted samples. Blood analysis was performed on nonextracted samples for daidzein, whereas genistein and equol required diethyl-ether extraction. RESULTS: Comparison of monoclonal TR-FIA, commercial polyclonal antibody-based TR-FIA, and gas chromatography-mass spectrometry showed correlations (r, 0.911-0.994) across the concentration range observed in the Isoheart study (50 mg/day isoflavones). The concentrations of urinary daidzein and genistein observed during intervention demonstrated good compliance, and a corresponding increase in serum daidzein and genistein confirmed bioavailability of the isoflavone-rich foods; 33 of the 117 volunteers (28.2%) were classified as equol producers on the basis of their urinary equol concentration (>936 nmol/L), and significant differences in the numbers of equol producers were observed between Berlin and the 3 other European cohorts studied. CONCLUSIONS: The validated monoclonal TR-FIA methods are applicable for use in large-scale human phytoestrogen intervention studies and can be used to monitor compliance, demonstrate bioavailability, and assess equol producer status.