Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population.

BACKGROUND AND AIMS: Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk. METHODS AND RESULTS: In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed. FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet. CONCLUSIONS: A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD.

Intake of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol in relation to vascular inflammation and endothelial dysfunction in middle age-elderly men and post-menopausal women living in Northern Italy.

BACKGROUND AND AIMS: It has been suggested that lignan intake may decrease the risk for cardiovascular disease (CVD) by modifying traditional risk factors as well as aortic stiffness. However, the role of dietary lignans on the vascular system is largely unknown. The objective was to investigate whether dietary intake of plant lignans in a free-living population was associated with markers of vascular inflammation and function. METHODS AND RESULTS: We performed a cross-sectional study in 242 (151 males) men and post-menopausal women. Anthropometric characteristics and lignan intake were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), insulin, high-sensitive C-reactive protein, glucose, total cholesterol, HDL-cholesterol and triacylglycerols were measured in fasting blood samples. Brachial flow-mediated dilation (FMD) measurements were available for 101 subjects (56 males). Median (interquartile range) daily intake of matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol (LARI), and total lignans was 20.9 microg (17.4), 335.3 microg (289.1), 96.7 microg (91.1), 175.7 microg (135.8), and 665.5 microg (413.7), respectively, as assessed by 3-day weighed food record. Plasma concentrations of sICAM-1 (whole sample) significantly decreased (mean (95%CI) = 358 microg/L (320-401), 276 microg/L (252-303), 298 microg/L (271-326), and 269 microg/L (239-303), P per trend 0.013) and FMD values (FMD sub-group) significantly increased (4.1% (2.2-6.0), 5.7% (4.3-7.2), 6.4% (4.9-7.8), and 8.1% (6.3-10.0), P per trend 0.016) across quartiles of energy-adjusted MAT intake, even after adjustment for relevant clinical and dietary variables. Intake of SECO was also inversely related to plasma sICAM-1 (P per trend 0.018), but not to FMD values. No relationship between intake of PINO, LARI or total lignans and either sICAM-1 or FMD values was observed. CONCLUSIONS: Higher MAT intakes in the context of a typical Northern Italian diet are associated to lower vascular inflammation and endothelial dysfunction, which could have some implications in CVD prevention.

Intervention study with a high or low antioxidant capacity diet: effects on circulating beta-carotene.

BACKGROUND AND OBJECTIVES: A cross-sectional observation suggests that total antioxidant capacity (TAC) of the diet positively affects plasma concentrations of beta-carotene independent of beta-carotene intake. This study was carried out to investigate the effect of two dietary strategies, designed to be comparable in fruits, vegetables, fibre, alcohol and beta-carotene intake but substantially different in their TAC, on changes in antioxidant intake and antioxidant status, and in particular in circulating beta-carotene concentrations. SUBJECTS: A randomized cross-over intervention trial involving 33 healthy participants and consisting of two 14-day dietary periods (high TAC diet, HT; low TAC diet, LT) with a 14-day washout in between was conducted. RESULTS: Energy, macronutrient, dietary fibre, alcohol and beta-carotene intake was not significantly different between LT and HT, whereas intake of other carotenoids and dietary TAC was significantly higher in the HT than in the LT (P<0.001). Circulating carotenoids (with the exception of alpha-carotene, which followed an inverse trend) and alpha-tocopherol decreased significantly during the LT and increased during the HT period. Among these, beta-carotene almost doubled its concentration in plasma after the HT diet. CONCLUSIONS: The increase in circulating beta-carotene along with the increase in dietary TAC suggests that plasma beta-carotene could be a marker of TAC intake rather than of beta-carotene intake itself. This may explain, in part, why beta-carotene supplementation alone has shown no benefit in chronic disease prevention and adds to a putative beneficial role of high dietary TAC diets, which merits further investigation.

ADMA is independently related to flow-mediated vasodilation in subjects at low cardiovascular risk.

BACKGROUND: Increased plasma concentrations of asymmetric dimethylarginine (ADMA) contribute to impair endothelial function in patients with established cardiovascular disease (CVD) and/or individuals with clinical syndromes known to increase CVD. However, the impact of ADMA on endothelial function in apparently healthy individuals has not been determined. MATERIALS AND METHODS: To address this issue, we measured endothelial-dependent vasodilatation in response to forearm ischaemia (flow-mediated vasodilatation, FMD) in 111 non-smoking, healthy volunteers with low CVD risk by the Framingham risk equation. Measurements were also made of multiple anthropometric, metabolic, and dynamic variables related to FMD. l-arginine and its methylated derivates (ADMA and SDMA) were quantified by high-liquid pressure chromatography. RESULTS: After adjustment by gender, lower values for FMD were significantly associated with increases in plasma ADMA concentrations (anova linear trend by FMD tertiles, P < 0.05) as well as in brachial artery diameter (partial r = -0.352, P = 0.001), body mass index (-0.337, P = 0.001), fasting insulin (-0.368, P < 0.001) and high-sensitivity C-reactive protein (-0.283, P = 0.007) plasma concentrations, and with decreased HDL cholesterol (0.233, P = 0.026). Multiple linear regression analysis indicated that the only statistically significant predictors of FMD were brachial artery diameter (P < 0.001), ADMA (P < 0.05) and fasting plasma insulin (P < 0.001) concentrations. CONCLUSIONS: In conclusion, a significant relationship between increases in plasma ADMA concentration and lower values of FMD is not limited to patients with clinical syndromes related to CVD, but can also be seen in healthy subjects at low global CVD risk.

The total antioxidant capacity of the diet is an independent predictor of plasma beta-carotene.

OBJECTIVE: To investigate the contribution of the total antioxidant capacity (TAC) of the diet to plasma concentrations of beta-carotene. DESIGN: Cross-sectional study. SETTING: Department of Public Health and Department of Internal Medicine and Biomedical Sciences, University of Parma. SUBJECTS: A total of 247 apparently healthy adult men (n=140) and women (n=107). METHODS: A medical history, a physical exam including height, weight, waist circumference and blood pressure measurements, a fasting blood draw, an oral glucose tolerance test and a 3-day food record. RESULTS: We observe a negative trend across quartiles of plasma beta-carotene for most biological variables clustering in the insulin resistance syndrome, as well as for traditional and new risk factors for type II diabetes and cardiovascular disease (CVD), including C-reactive protein and gamma-glutamyltranspeptidase (P<0.05). Regarding dietary characteristics, energy-adjusted intake of fat, fiber, fruits, vegetables, beta-carotene, vitamin C, vitamin E and dietary TAC significantly increased with increasing plasma beta-carotene (P<0.05), whereas alcohol intake decreased (P=0.013). Adjusted geometric means (95% confidence interval) of plasma beta-carotene significantly increased across quartiles of dietary TAC, even when single dietary antioxidants were considered in the model (QI=0.087 mg/dl (0.073-0.102); QII=0.087 mg/dl (0.075-0.103); QIII=0.114 mg/dl (0.098-0.132) and QIV=0.110 mg/dl (0.093-0.130); P for linear trend=0.026). When the population was divided on the basis of alcohol consumption, this trend was also observed in subjects drinking <20 g alcohol/day (P=0.034), but not in those with higher alcohol intake (P=0.448). CONCLUSIONS: Dietary TAC is an independent predictor of plasma beta-carotene, especially in moderate alcohol drinkers. This may explain, at least in part, the inverse relationship observed between plasma beta-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of beta-carotene supplements alone in reducing such risk.

What is the contribution of differences in three measures of tumor necrosis factor-alpha activity to insulin resistance in healthy volunteers?

To address the potential role that tumor necrosis factor-alpha (TNF-alpha) might play in modulation of insulin resistance in healthy, nondiabetic individuals, we compared plasma TNF-alpha and soluble TNF-alpha receptor 2 (sTNF-R2) concentrations, as well as TNF-alpha polymorphisms, in 94 healthy individuals, stratified into insulin-resistant (IR) and insulin-sensitive (IS) groups based on their plasma insulin concentrations 120 minutes after oral glucose on 2 occasions (1993 and 2000). The IR group (n = 50; 29 men and 21 women) was in the upper quartile and the IS group (n = 44; 24 men and 20 women) in the lowest quartile of the distribution of post-glucose challenge insulin concentrations in a large unselected population (>50 v <23 microU/mL). The IR group had significantly higher values for body mass index, waist-to-hip girth, fasting and post-glucose challenge insulin concentrations, and fasting triglyceride concentrations, and lower high-density lipoprotein cholesterol concentrations as compared to the IS group. Despite the fact that they were relatively more obese, and insulin-resistant, plasma concentrations of TNF-alpha were similar in the IR (1.6 +/- 0.6 pg/mL) and IS (1.7 +/- 0.6 pg/mL) groups, as were the concentrations (5.4 +/- 1.4 v 5.8 +/- 2.0 pg/mL) of sTNF-R2. Furthermore, TNF-alpha polymorphisms (detected by polymerase chain reaction [PCR]) were similar in the 2 groups, with essentially identical allelic frequencies of the 238 (10.3% v 9.4%) and 308 polymorphisms (17.9% v 18.7%). In conclusion, plasma TNF-alpha and sTNF-R2 concentrations, as well as TNF-alpha gene polymorphisms, were not different in healthy volunteers stratified into IR and IS groups on the basis of their plasma insulin response to an oral glucose challenge. Given these data, it does not appear that differences in TNF-alpha activity contribute to the marked variations in insulin action that occur in healthy individuals.

Bone resorption in anorexia nervosa and rehabilitated patients.

OBJECTIVE: To assess the impact of anorexia nervosa and that of nutritional rehabilitation on bone resorption. DESIGN: Cross-sectional, observational study. SETTING: Rome, Italy SUBJECTS: Twenty-eight female patients affected by anorexia nervosa (AN, BMIor=18.5 kg/m(2)) and 34 age- and sex-matched healthy controls (CO, BMI >or=18.5 kg/m(2)). Among AN patients, 16 were affected by the 'restrictive' (ANr) and 12 by the 'purging' type (ANp) of anorexia nervosa. METHOD: Body weight, height and skeletal diameters were measured on each individual. The skeletal mass (SKM) was predicted from the skeletal diameters of the elbow, wrist, knee and ankle, using the equation of Martin. Twenty-four-hour urinary excretion of pyridinium crosslinks of collagen (pyridinoline (Pyd) and deoxypyridinoline (Dpd)) and creatinine was assessed by reversed-phase HPLC with fluorimetric detection after solid-phase extraction and by the Jaffé-method with deproteinization, respectively. RESULTS: Twenty-four-hour urinary output of Pyd and Dpd was not significantly different between AN and CO when expressed in absolute values, but AN showed higher bone resorption than CO when Pyd and Dpd excretion was adjusted by either creatinine (P<0.0000) or the SKM (P<0.05). Within the AN group, urinary excretion of both cross-links was significantly and consistently higher in ANp compared with ANr (P<0.05). However, these differences disappeared when crosslink output was adjusted either by urinary creatinine or SKM. RE subjects showed no differences in bone resorption with the AN group despite weight gain, being crosslink excretion consistently elevated compared to controls (Pyd: P<0.01 by creatinine and P<0.05 by SKM; Dpd: P<0.01 by creatinine and P<0.05 by SKM). CONCLUSION: Bone resorption is elevated in anorexia nervosa and different strategies for low-weight maintenance do not seem to have a differential impact. Increased bone resorption persists in subjects with past diagnosis of anorexia nervosa despite rehabilitation lasting more than 6 months. This finding indicates that bone mass and turnover should be monitored in anorexia nervosa patients and ex-patients well beyond recovery of normal body mass. Further investigation is warranted to examine the long-term effect of such prolonged increase in bone turnover at a young age.

Urinary excretion of pyridinium crosslinks in short children treated with growth hormone.

The aim of this study was to evaluate the effect of growth hormone (GH) treatment on bone resorption in children with GH deficiency and those with idiopathic short stature. The study population included seven children with subnormal spontaneous GH secretion and 13 children with idiopathic short stature, all of them pre-pubertal. Anthropometric measurements, free, protein-bound and total urinary pyridinoline (Pyd) and deoxypyridinoline (Dpd), serum GH, and serum immunoreactive PTH were measured at baseline and months 1, 3, 6 and 12 of GH treatment. The urinary excretion of total Pyd and Dpd, standardized by the cube of height (m3) in overnight, 24-hour urine collections was not different from age-matched healthy controls at baseline in either group of patients. During treatment with human recombinant GH, both pyridinium crosslinks increased above normal values, reaching a peak after one month in children with GH deficiency and later (after 3-6 months) in children with short stature. Free and total crosslink forms were correlated, and GH treatment did not affect the proportion of free to bound crosslinks. Serum concentrations of iPTH showed a moderate but not statistically significant increase. This study provides no evidence of reduced bone resorption in untreated GH deficiency or in idiopathic short stature. GH treatment induced a marked, but temporary, increase of bone resorption in both groups of patients.

Calcium, physical activity and bone health--building bones for a stronger future.

Adequate provision of nutrients composing the bone matrix and regulating bone metabolism should be provided from birth in order to achieve maximal bone mass, compatible with individual genetic background, and to prevent osteoporosis later in life. Low calcium intake (<250 mg day(-1)) in children is associated with both a reduced bone mineral content and hyperparathyroidism. Optimal calcium intake is, however, still a matter of controversy. The minimisation of fracture risk would be the ideal functional outcome on which to evaluate lifetime calcium intakes, but proxy indicators, such as bone mass measurements or maximal calcium retention, are used instead. Calcium recommendations in Europe and the United States are based on different concepts as to requirements, leading to somewhat different interpretations of dietary adequacy. Minerals and trace elements other than calcium are involved in skeletal growth, some of them as matrix constituents, such as magnesium and fluoride, others as components of enzymatic systems involved in matrix turnover, such as zinc, copper and manganese. Vitamins also play a role in calcium metabolism (e.g. vitamin D) or as co-factors of key enzymes for skeletal metabolism (e.g. vitamins C and K). Physical activity has different effects on bone depending on its intensity, frequency, duration and the age at which it is started. The anabolic effect on bone is greater in adolescence and as a result of weight-bearing exercise. Adequate intakes of calcium appear necessary for exercise to have its bone stimulating action.

In vivo elemental partition analysis using fast neutrons. A tool for testing the efficacy of new clinical interventions.

The nutritional status of patients can be evaluated by monitoring changes in body composition, including depletion of protein and muscle; distribution of adipose tissue; and changes in hydration status, and bone or cell mass. Fast neutron activation (for N and P) and neutron inelastic scattering (for C and O) are used to assess in vivo elements characteristic of specific body compartments. Nonbone phosphorus for muscle is measured by the 31P(n,alpha)28Al reaction, and nitrogen for protein via the (n,2n) fast neutron reaction. The carbon-to-oxygen (C/O) ratio is used to measure distribution of fat and lean tissue in the body and to monitor small changes in lean mass and its quality. In addition to evaluating the efficacy of new treatments, the method is used to study the mechanisms of depletion of lean tissue with aging.

Neutron activation analysis determination of body composition.

The nutritional status of patients can be evaluated by monitoring changes in body composition, including the depletion of protein and muscle, adipose tissue distribution and changes in hydration status, bone or cell mass. Neutron activation analysis is a unique reference tool for the in-vivo determination of body composition. In this review we describe the recent changes in the field that followed the advent of new portable generators of fast neutrons, capable of performing elemental analysis in the clinical environment. New models were developed based on the partition of the measurable elements of the body. The recent developments help evaluate new treatments for wasting and obesity, in which change in body composition is the main outcome.

The respiratory quotient as a prognostic factor in weight-loss rebound.

OBJECTIVE: To investigate the possible metabolic factors predisposing to weight gain subsequent to the cessation of a rapid-weight-loss diet. DESIGN: Prospective, longitudinal, intervention study of a 2 MJ diet daily for 28 d in a metabolic ward followed by a 12-month outpatient follow-up under a conventional, hypocaloric diet. SUBJECTS: Thirty-five females and one male, all with morbid obesity defined by a body mass index > or = 35 kg/m2. MEASUREMENTS: VO2 and VCO2 measured by 30 min indirect calorimetry to calculate resting energy expenditure and resting respiratory quotient at the beginning and end of very-low-calorie diet; body composition assessed by hydrostatic weighing on day 1; weight recorded on days 1 and 28 and at follow-up of 3, 6 and 12 months. RESULTS: From among all the variables considered, the resting respiratory quotient measured on day 28, even adjusted for weight loss during hospitalisation, was the only one that correlated significantly with the weight changes recorded during follow-up. CONCLUSION: Subjects who showed a respiratory quotient on day 28 in the lower range (< 0.72) were more able to maintain the weight-loss achieved with the very-low-calorie diet while those in the higher range (> 0.75) were less able to do so over the follow-up period. Thus, an appropriately measured respiratory quotient could prove useful in clinical practice as a prognostic marker of the long-term effectiveness of low- and very-low-calorie diets used to induce rapid weight loss.

A study of the prognostic respiratory markers of sustained weight loss in obese subjects after 28 days on VLCD.

OBJECTIVE: To investigate parameters of energy metabolism during a 28 d VLCD to identify possible prognostic markers of weight change observed, subsequently, when the subjects were on a six-month hypocaloric diet. DESIGN: Longitudinal, clinical intervention study of a 2 MJ diet daily for 28 d and six month follow-up under a conventional, hypocaloric diet. SUBJECTS: Seven pre-menopausal women and one male all morbidly obese but otherwise healthy (age: 16-47 y, BMI 38.9-50.5 kg/m2). MEASUREMENTS: Body weight, resting energy expenditure (REE), resting respiratory quotient (RQ) and the 5 h thermic effect of food (TEF) were assessed by indirect calorimetry at the beginning and at the end of a 28 d VLCD treatment. Body composition was measured on day 1 by hydrodensitometry and tetrapolar bioelectrical impedance (TBIA), on day 28 by TBIA and nitrogen balance (NB) and by TBIA on follow-up. RESULTS: The individual weight loss during VLCD (mean 9.9 +/- 2.4 kg) was significant (P < 0.01) and correlated significantly with energy deficit (r = 0.83, P = 0.01). REE/FFM decreased 6.2% (FFMTBIA) and 8.9% (FFMNB), respectively. TEF28 was unchanged from TEF1 while fasting RQ declined during the intervention period but was back to baseline already within one month of follow-up even though the mean weight loss at six months had increased to 14.0 +/- 5.6 kg. There was a significant (P < 0.05) positive correlation between RQ28 and body-weight changes after one, three and six months of follow-up. The RQ28 explained 60-72% of the inter-individual variation in weight change. CONCLUSION: The resting RQ measurement is recommended as a simple and inexpensive assessment at the end of a strict weight-loss regimen in order to identify those individuals who may need greater assistance in maintaining a weight-loss when placed on a subsequent, free-living hypocaloric diet.

Changes in body composition and resting energy expenditure after rapid weight loss: is there an energy-metabolism adaptation in obese patients?

The aim of this study was to assess changes in resting energy expenditure (REE) related to changes in fat free mass (FFM) in nine morbid obese (BMI 43 +/- 5.1 kg/m2) hospitalised females on VLCD. REE was measured by 30 min indirect calorimetry before and after 28 days of hospitalisation. Changes in FFM were assessed by bioelectrical impedance analysis (BIA), hydrostatic weighing (HW) and nitrogen balance (N). REE decreased 11.5% from 7.8 +/- 1.0 to 6.9 +/- 0.8 MJ/d. Total weight loss was 8.4 +/- 1.9 kg or 7.4% with an estimated FFM loss of 3.4 +/- 1.8 (BIA), 2.9 +/- 1.9 (HW) and 1.8 +/- 1.0 (N). As the fall in REE was larger than the loss of FFM, it is concluded that morbid obese patients develop an energy saving adaptation during rapid weight loss.