Lucy M. Browning

Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women

Background:Obesity, inflammation, insulin resistance and cardiovascular disease (CVD) risk are inter-related. Both weight-loss and long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) are independently known to reduce metabolic risk, but the combined effects are unclear.Objective:This study examines whether addition of LC n-3 PUFA to a low fat/high carbohydrate weight-loss programme results in greater improvements in inflammation, insulin sensitivity and CVD risk, than weight-loss alone.Design:One hundred and sixteen overweight insulin-resistant women entered a 24-week randomised intervention study. Thirty-nine women were randomised to a weight-loss programme, with LC n-3 PUFA (WLFO), 38 to a weight-loss programme with placebo oil (WLPO), and 39 to receive placebo oil, with no weight-loss programme (control).Results:Ninety-three women completed the study (35 WLFO, 32 WLPO and 26 control), with significant weight-loss in WLFO (10.8±1.0%) and WLPO (12.4±1.0%) compared to the control group (P<0.0001). The WLFO, but not WLPO or control group, showed significant increases in adipose tissue LC n-3 PUFA (0.34±0.20 vs 0.17±0.10 and 0.16±0.10 %DHA, P<0.0001). Weight-loss showed significant improvements in insulin sensitivity (P<0.001), lipid profile (triglycerides P<0.05) and inflammation (sialic acid P<0.05). Time*group effects showed significant decreases in triglycerides (P<0.05) and increases in adiponectin (P<0.01) with LC n-3 PUFA, in the WLFO vs WLPO groups.Conclusions:Weight-loss improved risk factors associated with CVD, with some additional benefits of LC n-3 PUFA on triglycerides and adiponectin. Given the current low dietary intake of LC n-3 PUFA, greater attention should be given to increase these fatty acids in the treatment of obesity.

Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish

Background: Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake. Objective: We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage. Design: This was a double-blind, randomized, controlled intervention trial in 204 men and women that lasted 12 mo. EPA and DHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHA were assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids). Results: A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue). Conclusions: Plasma phosphatidylcholine EPA plus DHA was identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHA were the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN48398526.

The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype.

Background:  Inflammation is strongly related to obesity and the risk of cardiovascular disease (CVD). The metabolic benefits of long chain (LC) n‐3 polyunsaturated fatty acid (PUFA) may be attributable to its anti‐inflammatory properties.

n-3 polyunsaturated fatty acids, inflammation and obesity-related disease

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor alpha and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.

Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI

Abdominal fat, and in particular, visceral adipose tissue (VAT), is the critical fat depot associated with metabolic aberrations. At present, VAT can only be accurately measured by computed tomography or magnetic resonance imaging (MRI). This study was designed to compare a new abdominal bioelectrical impedance (BIA) device against total abdominal adipose tissue (TAAT) and VAT area measurements made from an abdominal MRI scan, and to assess its reliability and accuracy. One‐hundred twenty participants were recruited, stratified by gender and BMI. Participants had triplicate measures of abdominal fat and waist circumference (WC) with the AB‐140 (Tanita, Tokyo, Japan) and WC measurements using a manual tape measure. A single abdominal MRI scan was performed as the reference method. Triplicate measures with the AB‐140 showed excellent precision for “visceral fat level,” trunk fat %, and WC. AB‐140 “visceral fat level” showed significantly stronger correlations with MRI TAAT area than with MRI VAT area (r = 0.94 vs. 0.65 in men and 0.92 vs. 0.64 in women). AB‐140 WC showed good correlation with manual WC measurements (r = 0.95 in men and 0.90 in women). AB‐140 and manual WCs showed comparable correlations with MRI TAAT area (r = 0.92 and 0.96 in men and 0.88 and 0.88 in women). AB‐140 is a simple, quick, and precise technique to measure abdominal fat and WC in healthy adults. It provides a useful proxy for TAAT measured by MRI, comparable to the correlation obtained with manual WC measurements. Neither the AB‐140 abdominal fat measures nor WC measurement appear to provide a useful proxy measure of VAT.

Circulating Markers of Inflammation and Their Link to Indices of Adiposity

Background: Adipose tissue produces a number of inflammatory mediators. Circulating concentrations of these inflammatory markers are increasingly used as markers of local or systemic inflammation. This study compares results for 3 inflammatory adipokines measured using 2 techniques, (multiplex and ELISA), and determines the relationships with C-reactive protein (CRP), obesity, and the impact of moderate weight loss. Subjects and Methods: Fasting blood samples were collected at baseline and after a 24-week weight loss intervention. Interleukin 6 (IL-6), tumour necrosis factor α(TNF-α), and monocyte chemoattractant protein 1 (MCP-1) were measured using a standard ELISA technique or a new multiplex technique. A total of 54 women with complete data were included in this analysis. Results: Multiplex showed poor correlation with ELISA results, and were not significantly correlated with CRP. Using ELISA data, IL-6 and CRP were significantly correlated with body mass index (BMI) (r = 0.42 and r = 0.55), but MCP-1 and TNF-αwere not (r = – 0.07 and r = 0.06). Changes in MCP-1, TNF-α, and IL-6 were not significantly different between control and weight loss groups. CRP was significantly reduced in weight loss vs. control group (p < 0.05), and change in CRP correlated with change in BMI (r = 0.31). Conclusion: Circulating IL-6 and CRP, but not MCP-1 and TNF-α, are significantly associated with indices of adiposity in obese women. This study suggests that circulating IL-6 and CRP, but not MCP-1 and TNF-α, are useful markers of obesity-related inflammation.

Measuring Abdominal Adipose Tissue: Comparison of Simpler Methods with MRI

Objective: This cross-sectional study compares the relationship of visceral and total abdominal adipose tissue (VAT and TAAT) measurements obtained with magnetic resonance imaging (MRI) and a range of ‘simpler’ techniques suitable for field or bedside use: BMI, waist circumference (WC), bioelectrical impedance (BIA) devices and dual X-ray absorptiometry (DXA). Method: 120 participants were recruited, stratified by gender and BMI (20 men and 20 women within each group: lean, overweight and obese). Measurements included height, weight, WC (at midpoint), DXA L2-L4 fat, and BIA (two whole-body and one abdominal device). MRI was used as the reference. Results: MRI data showed that men have more VAT than women, (mean 147 vs. 93 cm2) despite less TAAT (362 vs. 405 cm2). Correlations of simpler abdominal fat measures showed significantly higher correlations with TAAT than with VAT in men and women. Similarly, trunk and whole-body fat measures were significantly more strongly correlated with TAAT than with VAT. Conclusion: None of the simpler techniques show strong correlations with VAT measured by MRI, but WC, abdominal BIA ‘visceral fat level’ and DXA L2-L4 fat all show similar and strong correlations with TAAT and may be useful in large scale surveys.

Elevated sialic acid, but not CRP, predicts features of the metabolic syndrome independently of BMI in women

AIMS: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome.SUBJECTS: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m2 (geometric mean 33.1±5.8kg/m2) and aged 19–71 y (mean 45.6±12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy.RESULTS: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant (P<0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P<0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 (P<0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P<0.0001).CONCLUSIONS: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.

The pattern of fatty acids displaced by EPA and DHA following 12 Months supplementation varies between blood cell and plasma fractions

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are increased in plasma lipids and blood cell membranes in response to supplementation. Whilst arachidonic acid (AA) is correspondingly decreased, the effect on other fatty acids (FA) is less well described and there may be site-specific differences. In response to 12 months EPA + DHA supplementation in doses equivalent to 0–4 portions of oily fish/week (1 portion: 3.27 g EPA+DHA) multinomial regression analysis was used to identify important FA changes for plasma phosphatidylcholine (PC), cholesteryl ester (CE) and triglyceride (TAG) and for blood mononuclear cells (MNC), red blood cells (RBC) and platelets (PLAT). Dose-dependent increases in EPA + DHA were matched by decreases in several n-6 polyunsaturated fatty acids (PUFA) in PC, CE, RBC and PLAT, but were predominantly compensated for by oleic acid in TAG. Changes were observed for all FA classes in MNC. Consequently the n-6:n-3 PUFA ratio was reduced in a dose-dependent manner in all pools after 12 months (37%–64% of placebo in the four portions group). We conclude that the profile of the FA decreased in exchange for the increase in EPA + DHA following supplementation differs by FA pool with implications for understanding the impact of n-3 PUFA on blood lipid and blood cell biology.

Erythrocyte and plasma fatty acid profiles in patients with epilepsy: Does carbamazepine affect omega-3 fatty acid concentrations?

Fatty acids (FAs) determine membrane properties and may affect cardiac and neuronal function. In this study, FA profiles were determined in 56 patients with epilepsy who participated in a 12-week double-blind randomized trial of omega-3 FA supplementation (1 g eicosapentaenoic acid and 0.7 g docosahexaenoic acid daily). At baseline, subjects on carbamazepine (CBZ) had lower docosahexaenoic acid levels, lower levels of long-chain omega-3 FAs, and a lower Omega-3 Index (a risk factor for coronary heart disease mortality), whereas those on oxcarbazepine had higher total polyunsaturated FAs and a higher Omega-3 Index. Following omega-3 FA supplementation, the Omega-3 Index, eicosapentaenoic acid, and docosahexaenoic acid concentrations significantly increased. Patients on CBZ exhibited a less favorable FA profile, associated with a greater risk of coronary heart disease mortality. As arrhythmias are thought to be an important mechanism in coronary heart disease mortality and sudden unexplained death in epilepsy (SUDEP), the effect of CBZ effect in reducing omega-3 FAs might potentially explain some cases of SUDEP among patients prescribed CBZ.