Changes in Inflammatory Biomarkers Across Weight Classes in a Representative US Population: A Link Between Obesity and Inflammation

Obesity has been linked with a chronic state of inflammation which may be involved in the development of metabolic syndrome, cardiovascular disease, non-alcoholic steatohepatitis, and even cancer. The objective of this study was to examine the association between obesity class and levels of inflammatory biomarkers from men and women who participated in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Serum concentrations of C-reactive protein (CRP) and fibrinogen were measured among US participants of the 1999–2004 NHANES. We examined biomarker levels across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as BMI of <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, and ≥40.0, respectively. With CRP levels for normal weight individuals as a reference, CRP levels nearly doubled with each increase in weight class: +0.11 mg/dl (95% CI, 0.06–0.16) for overweight, +0.21 mg/dl (95% CI, 0.16–0.27) for obesity class 1, +0.43 mg/dl (95% CI, 0.26–0.61) for obesity class 2, and +0.73 mg/dl (95% CI, 0.55–0.90) for obesity class 3. With normal weight individuals as a reference, fibrinogen levels increase with increasing weight class and were highest for obesity class 3 individuals, +93.5 mg/dl (95% CI, 72.9–114.1). Individuals with hypertension or diabetes have higher levels of CRP and fibrinogen levels compared to individuals without hypertension or diabetes, even when stratified according to BMI. There is a direct association between increasing obesity class and the presence of obesity-related comorbidities such as diabetes and hypertension with high levels of inflammatory biomarkers

Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein. During a 6 h time course after PCT 145 plasma metabolites, 79 proteins and 7 clinical chemistry parameters were quantified. Multiple processes related to metabolism, oxidation and inflammation reacted to the PCT, as demonstrated by changes of 106 metabolites, 31 proteins and 5 clinical chemistry parameters. The PCT was applied in a dietary intervention study to evaluate if the PCT would reveal additional metabolic changes compared to non-perturbed conditions. The study consisted of a 5-week intervention with a supplement mix of anti-inflammatory compounds in a crossover design with 36 overweight subjects. Of the 231 quantified parameters, 31 had different responses over time between treated and control groups, revealing differences in amino acid metabolism, oxidative stress, inflammation and endocrine metabolism. The results showed that the acute, short term metabolic responses to the PCT were different in subjects on the supplement mix compared to the controls. The PCT provided additional metabolic changes related to the dietary intervention not observed in non-perturbed conditions. Thus, a metabolomics based quantification of a standardized perturbation of metabolic homeostasis is more informative on metabolic status and subtle health effects induced by (dietary) interventions than quantification of the homeostatic situation

Pleiotropic Benefit of Monomeric and Oligomeric Flavanols on Vascular Health - A Randomized Controlled Clinical Pilot Study

BACKGROUND: Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded. METHODS: In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets. RESULTS: In the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05). CONCLUSION: Our integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT00742287

Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia

Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Preferably this treatment should involve low optimally tolerable doses of hypolipidemic drugs. Thus, we undertook a study to determine the safety and efficacy of combination therapy with fibrates and small doses of atorvastatin. Twenty-two patients with mixed hyperlipidemia were started on a fibrate regimen (micronised fenofibrate 200 mg/day or ciprofibrate 100 mg/day). Because after 12 weeks of therapy the fibrate failed to normalise the serum lipid profile, small doses of atorvastatin (5 mg/day) were added for a further 12 weeks. The administration of the fibrates resulted in a significant decrease in total and LDL-cholesterol levels, as well as in triglycerides, and an increase in HDL-cholesterol levels. The addition of atorvastatin (5 mg/day) resulted in a further decrease in total and LDL-cholesterol levels. Consequently, the hypolipidemic therapy target was achieved in most of the patients. Combination therapy was well tolerated and no significant increases in serum liver and muscle enzymes were noticed. We conclude that the careful administration of small doses of atorvastatin in patients with mixed dyslipidemia receiving fibrates is associated with a significant amelioration of lipid abnormalities

Assessing the treatment effect in metabolic syndrome without perceptible diabetes (ATTEMPT): A prospective-randomized study in middle aged men and women

Aim: To assess the reduction in estimated cardiovascular disease (e-CVD) risk after multifactorial treatment for 6 months and follow this change during the next 3-years. Patients-Methods: This prospective, randomized, target driven study included 1,123 subjects (512/611 men/women, aged 45-65 years) with metabolic syndrome (MetS) without diabetes or CVD referred to specialist outpatient clinics. Patients were randomized to two treatment groups: group A with low density lipoprotein cholesterol (LDL-C) target of &lt;100 mg/dl and group B with a target of &lt;130 mg/dl. Atorvastatin was used in both groups on top of optimal multifactorial treatment, (quinapril, amlodipine, hydrochlorothiazide for hypertension, metformin for impaired fasting glucose, and orlistat for obesity). The e-CVD risk was calculated using the Framingham, the PROCAM and Reynold&apos;s equations. Results: Reductions in e-CVD risk at 6 months were &gt;50% in all patients, but were superior in group A and in women. Reductions were even greater during the next 3-years and were mainly attributed to changes in lipid profile. Actual CVD events were 1 in group A and 13 in group B; p=0.0012. Conclusions: Attaining the treatment target of LDL-C&lt;100 mg/dl within multifactorial treatment of MetS by expert clinics, is achievable and beneficial even in patients without diabetes or known CVD. This induces a considerable e-CVD risk reduction in MetS patients. Actual CVD events were negligible, suggesting that e-CVD risk overestimates actual CVD risk in MetS, at least in patients achieving LDL-C&lt;100 mg/dl [ClinicalTrials.gov ID: NCT00416741]. © 2011 Bentham Science Publishers