Unravelling the health effects of fasting : a long road from obesity treatment to healthy life span increase and improved cognition

In recent years a revival of interest has emerged in the health benefits of intermittent fasting and long-term fasting, as well as of other related nutritional strategies. In addition to meal size and composition a new focus on time and frequency of meals has gained attention. The present review will investigate the effects of the main forms of fasting, activating the metabolic switch from glucose to fat and ketones (G-to-K), starting 12-16 h after cessation or strong reduction of food intake. During fasting the deactivation of mTOR regulated nutrient signalling pathways and activation of the AMP protein kinase trigger cell repair and inhibit anabolic processes. Clinical and animal studies have clearly indicated that modulating diet and meal frequency, as well as application of fasting patterns, e.g. intermittent fasting, periodic fasting, or long-term fasting are part of a new lifestyle approach leading to increased life and health span, enhanced intrinsic defences against oxidative and metabolic stresses, improved cognition, as well as a decrease in cardiovascular risk in both obese and non-obese subjects. Finally, in order to better understand the mechanisms beyond fasting-related changes, human studies as well as non-human models closer to human physiology may offer useful clue

A new noninvasive method for the accurate and precise assessment of varicose vein diameters

The feasibility and reproducibility of a new ultrasonic method for the direct assessment of maximal varicose vein diameter (VVD) were evaluated. A study was also performed to demonstrate the capacity of the method to detect changes in venous diameter induced by a pharmacologic treatment. Patients with varicose vein disease were recruited. A method that allows the precise positioning of patient and transducer and performance of scans in a gel-bath was developed. Maximal VVD was recorded both in the standing and supine positions. The intraassay reproducibility was determined by replicate scans made within 15 minutes in both positions. The interobserver variability was assessed by comparing VVDs measured during the first phase baseline examination with those obtained during baseline examinations in the second phase of the study. The error in reproducibility of VVD determinations was 5.3% when diameters were evaluated in the standing position and 6.4% when assessed in the supine position. The intramethod agreement was high, with a bias between readings of 0.06 ±0.18 mm and of –0.02 ±0.19 mm, respectively, in standing and supine positions. Correlation coefficients were better than 0.99 in both positions. The method appears to be sensitive enough to detect small changes in VVDs induced by treatments. The proposed technique provides a tool of potential valid use in the detection and in vivo monitoring of VVD changes in patients with varicose vein disease. The method offers an innovative approach to obtain a quantitative assessment of varicose vein progression and of treatment effects, thus providing a basis for epidemiologic survey

Lipoprotein(a) Lowering-From Lipoprotein Apheresis to Antisense Oligonucleotide Approach

It is well-known that elevated lipoprotein(a)-Lp(a)-levels are associated with a higher risk of cardiovascular (CV) mortality and all-cause mortality, although a standard pharmacotherapeutic approach is still undefined for patients with high CV risk dependent on hyperlipoproteinemia(a). Combined with high Lp(a) levels, familial hypercholesterolemia (FH) leads to a greater CVD risk. In suspected FH patients, the proportion of cases explained by a rise of Lp(a) levels ranges between 5% and 20%. In the absence of a specific pharmacological approach able to lower Lp(a) to the extent required to achieve CV benefits, the most effective strategy today is lipoprotein apheresis (LA). Although limited, a clear effect on Lp(a) is exerted by PCSK9 antagonists, with apparently different mechanisms when given with statins (raised catabolism) or as monotherapy (reduced production). In the era of RNA-based therapies, a new dawn is represented by the use of antisense oligonucleotides APO(a)Lrx, able to reduce Lp(a) from 35% to over 80%, with generally modest injection site reactions. The improved knowledge of Lp(a) atherogenicity and possible prevention will be of benefit for patients with residual CV risk remaining after the most effective available lipid-lowering agents

Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases

Clear evidence supports a role for circulating and locally-produced osteocalcin (OC) in the pathophysiology of cardiovascular (CV) lesions and CV risk, also in combination with metabolic changes, including type 2 diabetes mellitus (T2DM). Reduced plasma OC levels are associated with greater incidence of pathological CV changes, like arterial and valvular calcification, coronary and carotid atherosclerosis and increased carotid intima-media thickness. The actual relationship between OC levels and incidence of major CV events is, however, still unclear. Moreover, reduced circulating OC levels have been mostly associated with insulin resistance, metabolic syndrome or T2DM, indicating relevant OC actions on pancreatic \u3b2-cells and insulin secretion and activity. Based on these observations, this review article will attempt to summarize the current evidence on the potential usefulness of circulating OC as a biomarker for CV and metabolic risk, also evaluating the currently open issues in this area of research

Effects of Vegetable Proteins on Hypercholesterolemia and Gut Microbiota Modulation

Risk assessment tools, i.e., validated risk prediction algorithms, to estimate the patient\u2019s 10-year risk of developing cardiovascular disease (CVD) should be used to identify high-risk people for primary prevention. Current evidence confirms that appropriate monitoring and control of risk factors either reduces the likelihood of CVD or slows down its progression. It is thus crucial that all health professionals make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and adequate physical activity to the use of functional foods, food supplements, and drugs. The gut microbiota, which encompasses 1 7 1014 resident microorganisms, has been recently recognized as a contributing factor in the development of human disease. This review examines the effect of both some vegetable food components belong to the \u201cprotein food group\u201d and the underexploited protein-rich hempseed on cholesterolemia and gut microbiota composition

Influence of body variables in the development of metabolic syndrome : A long term follow-up study

Objectives. The body variable associated with the diagnosis of Metabolic Syndrome (MetS) is an elevated waist circumference (WC), although a number of other variables have been suggested. Among these, an elevated waist-to-height ratio (WHtR), ie a value higher than 0.5, that may identify abnormality, independently from height. An elevated WHtR provided the best correlation with MetS in a prior study in a large Italian population. In order to assess the validity of this conclusion, a long-term follow-up study re-examined this population, also in order to detect possible associations with cardiovascular (CV) risk. Methods and Results. 1,071 subjects with a complete follow-up of over 6 years were evaluated with a comparative assessment of the three anthropometric variables, namely WHtR, WC and body mass index (BMI). WHtR 65 0.5 had the highest sensitivity for the identification of MetS, both in males and females (94.1% and 86.7% respectively). WHtR was of reduced specificity, occurring, yet less frequently (17.7% in males and 30% in females), in patients without MetS. By contrast, enlarged WC occurred with a lower frequency in male patients who developed MetS (30.2%) whereas in females, frequency was higher than in males (69.3%). Finally, a BMI 65 25 kg/m2 had intermediate sensitivity and specificity regardless of gender. WC showed the highest odds ratio (2.62, 95%CI: 1.18-5.78) for the prediction of CV occurrence. Conclusion. The present study confirms WHtR as an excellent screening tool in identifying MetS carriers, but, different from reports in other countries, it shows a lower specificity in our population

Chronic use of light or heavy cigarettes and carotid IMT

Studies supporting the nicotine regulation model of smoking, suggested that smokers compensate the low amount of nicotine from low-nicotine cigarette by changing smoking frequency or other aspects of smoking behaviour. Aim of this study was to evaluate the effect of chronic use of light or heavy cigarettes on carotid artery intima media thickness (IMT): 96 current-, 150 former- and 418 never-smokers were recruited. 161 were light-smokers (pack-years<30) and 85 heavy-smokers (pack-years 6530); 63 subjects were users of cigarettes with low-nicotine (<0.7mg), 183 with high-nicotine ( 650.7mg), 35 with low-tar (<7mg) and 211 with high-tar ( 657mg). IMT in former- (1.05\ub10.33 mm) and current-smokers (1.16\ub10.27 mm) was significantly greater than in never-smokers (0.95\ub10.29 mm) (both p<0.002). The difference between former and current smokers was significant (p=0.015). IMT of light- (1.05\ub10.29 mm) and heavy-smokers (1.17\ub10.34 mm) was higher than in never-smokers (both p<0.001). The difference between heavy- and light-smokers was also significant (p<0.01). On average, IMT of low- (1.09\ub10.25 mm) and high-nicotine (1.08\ub10.33 mm) cigarette consumers was greater than in never-smokers (both p<0.002). No difference in IMT was observed when low- and high-nicotine cigarette consumers were compared. IMT in patients who smoked low-tar (1.083\ub10.29 mm) or high-tar (1.085\ub10.31 mm) cigarettes was greater than in never-smokers (p=0.03 and 0.0001, respectively). No differences were observed between low- and high-tar cigarette smokers. In conclusion light and heavy cigarettes have the same proatherogenic effect

Evidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy

AbstractX-linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of peroxisomal metabolism biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in different tissues and in biological fluids. The disease is clinically characterized by central and peripheral demyelination and adrenal insufficiency, which is closely related to the increased concentrations of these fatty acids. However, the mechanisms underlying the brain damage in X-ALD are poorly known. Considering that free radical generation is involved in various neurodegererative disorders, like Parkinson disease, multiple sclerosis and Alzheimer's disease, in the present study we evaluated various oxidative stress parameters, namely chemiluminescence, thiobarbituric acid reactive species (TBA-RS), total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR) in plasma of X-ALD patients, as well as the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes and fibroblasts from these patients. It was verified a significant increase of plasma chemiluminescence and TBA-RS, reflecting induction of lipid peroxidation, as well as a decrease of plasma TAR, indicating a deficient capacity to rapidly handle an increase of reactive species. We also observed a significant increase of erythrocytes GPx activity and of catalase and SOD activities in fibroblasts from the patients studied. It is therefore proposed that oxidative stress may be involved in pathophysiology of X-ALD

Proteins of white lupin seed, a naturally isoflavone-poor legume, reduce cholesterolemia in rats and increase LDL receptor activity in HepG2 cells

White lupin (Lupinus albus, L.), a widely cultivated crop that has been consumed for many years in Western Europe, may provide a useful alternative for individuals wishing to substitute animal with plant proteins for cardiovascular disease prevention. Lupin seeds have a very low content of isoflavones, and lupin protein isolates are essentially isoflavone free. In rats fed a casein-based cholesterol + cholic acid diet, a relatively low daily intake (50 mg/d by gavage for 2 wk) of total lupin protein extract reduced plasma total and VLDL + LDL cholesterol concentrations by 21 and 30%, respectively (both P<0.001). In an attempt to elucidate the lipid-lowering mechanism, LDL receptor activity was evaluated in a human hepatoma cell line (HepG2). In this model, the lupin total protein extract was essentially inactive, whereas one purified minor protein component, conglutin gamma, had a remarkable upregulatory effect, with maximal increases of 53 and 21% (both P<0.05) for LDL uptake and degradation, respectively. This initial study indicates that lupin, although isoflavone free, has hypocholesterolemic activity similar to that of other leguminous proteins in an established animal model. Further, the cholesterol reduction appears to be associated with stimulation of LDL receptors by a well-defined protein component of the lupin seeds as demonstrated by in vitro studies