Effectiveness and Safety of Dietetic Supplementation of a New Nutraceutical on Lipid Profile and Serum Inflammation Biomarkers in Hypercholesterolemic Patients.

Background: To assess the effectiveness and safety of a new nutraceutical (NC) on lipid profile, inflammation biomarkers and creatine phosphokinase (CPK) serum levels in hypercholesterolemic patients. Methods: 40 patients underwent hypolipemic treatment with NC. Initial and final (after 12 weeks) screening included medical history, physical examination, and measurement of serum lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides), hepatic (GOT, GPT, γGT), and renal (serum creatinine and urea) functions, CPK level and many inflammation biomarkers (hs-CRP and fibrinogen). At the screening visit, all patients were instructed to follow a normocaloric and hypolipidic diet during the study period. Results: The treatment with supplementation of NC demonstrated a significant reduction of serum total cholesterol (224 ± 11.2 mg/dL vs. 178 ± 10.7; p < 0.001), LDL-cholesterol (141 ± 10.6 vs. 116 + 10.1; p < 0.001), triglycerides (183 ± 13 vs. 159 ± 11.5; p < 0.01), serum inflammatory biomarkers as hs-CRP (2.24 ± 0.83 vs. 1.76 ± 0.61 mg/dL; p < 0.01), fibrinogen (315 ± 43 vs. 199 ± 41 mg/dL; p < 0.01) and a significantly increase of HDL-cholesterol (44 ± 7 vs. 53 ± 7 mg/dL; p < 0.01). Hepatic and renal function and serum CPK were normal. No adverse events was reported. Conclusions: The treatment with NC has demonstrated a significant reduction of LDL-cholesterol (-17.73%), total cholesterol (-20.53%) and triglycerides (-13.1%), with a significant increase of HDL-cholesterol values (+20.45%). The improvement of lipid profile was associated with a significant reduction of serum inflammation biomarkers as hs-PCR (-27%) and fibrinogen (-36.8%) with good tolerability profile.

Anti-obesity activity of the marine carotenoid fucoxanthin.

Nowadays the global tendency towards physical activity reduction and an augmented dietary intake of fats, sugars and calories is leading to a growing propagation of overweight, obesity and lifestyle-related diseases, such diabetes, hypertension, dyslipidemia and metabolic syndrome. In particular, obesity, characterized as a state of low-level inflammation, is a powerful determinant both in the development of insulin resistance and in the progression to type 2 diabetes. A few molecular targets offer hope for anti-obesity therapeutics. One of the keys to success could be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity effects of fucoxanthin, a characteristic carotenoid, exactly belonging to xanthophylls, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups. Fucoxanthin, which can be isolated from edible brown seaweeds, recently displayed its many physiological functions and biological properties. We reviewed recent studies and this article aims to explain essential background of fucoxanthin, focusing on its promising potential anti-obesity effects. In this respect, fucoxanthin can be developed into promising marine drugs and nutritional products, in order to become a helpful functional food.

Marine Carotenoids against Oxidative Stress: Effects on Human Health.

Carotenoids are lipid-soluble pigments that are produced in some plants, algae, fungi, and bacterial species, which accounts for their orange and yellow hues. Carotenoids are powerful antioxidants thanks to their ability to quench singlet oxygen, to be oxidized, to be isomerized, and to scavenge free radicals, which plays a crucial role in the etiology of several diseases. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. In this respect, various novel marine carotenoids have recently been isolated from marine organisms and displayed several utilizations as nutraceuticals and pharmaceuticals. Marine carotenoids (astaxanthin, fucoxanthin, ß-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. This review aims to describe the role of marine carotenoids against oxidative stress and their potential applications in preventing and treating inflammatory diseases.

Resveratrol and anti-atherogenic effects.

The role of inflammation and oxidative stress in atherosclerosis development has been increasingly well recognized over the past decade. Inflammation has a significant role at all stages of atherosclerosis, including initiation, progression and plaque formation. Resveratrol is a naturally occurring polyphenolic compound found in grape products, berry fruits and red wine. Its ability to behave therapeutically as a component of red wine has attracted wide attention. Accumulating evidence suggests that it is a highly pleiotropic molecule that modulates numerous targets and molecular functions. Epidemiological studies indicate that the Mediterranean diet, rich in resveratrol, is associated with a reduced risk of atherosclerosis. Resveratrol is believed to decrease circulating low-density lipoprotein cholesterol levels, reduce cardiovascular disease risk; it reduces lipid peroxidation, platelet aggregation and oxidative stress. Resveratrol is considered a safe compound, since no significant toxic effects have been demonstrated after administration of a broad range of concentrations, and an effective anti-atherogenic agent.

Mediterranean diet and cardiovascular risk factors: a systematic review.

The aim of this paper was to systematically review and analyze the epidemiological evidence on the role of Mediterranean diet (MD) in the prevention of cardiovascular diseases (CVD). Fifty-eight studies exploring the relation between MD and lipoprotein concentration, antioxidative capacity and inflammatory markers, hypertension, obesity, diabetes, and metabolic syndrome, were identified and selected. These included 33 cross-sectional, 9 cohort, and 16 intervention studies. Most of the studies showed favorable effects of MD on CVD, although a certain degree of controversy remains in the respect of some issues, as obesity. Important methodological differences and limitations in the studies make difficult to compare results, thus further studies, particularly randomized clinical trials, are needed to finally substantiate the benefits of MD and to shed some lights on mechanisms.

Role of dietary and endogenous antioxidants in diabetes.

Diabetes affects different people of all ages, race, and sex. This is a condition characterized by a state of chronic hyperglycaemia that leads to an increase of intracellular oxidative stress linked to the overproduction of free radicals. In the present review, we focus our attention on the molecular mechanisms leading to oxidative stress-mediates complications with particular regard to central nervous system (CNS). Furthermore, the present review reports the effects of different kind of antioxidants with enzymatic and nonenzymatic action that may significantly decrease the intracellular free radicals' overproduction and prevents the hyperglycaemia-mediated complications.

Peripheral biomarkers of oxidative stress and their limited potential in evaluation of clinical features of Huntington's patients.

CONTEXT: Peripheral oxidative biomarkers could be useful for monitoring clinical features of Huntington's disease (HD). MATERIALS AND METHODS: Cu/Zn-superoxide dismutase (Cu/Zn-SOD), neuron-specific enolase (NSE) and 8-hydroxy-2'-deoxyguanosine (8-oxoGua) serum levels were analysed in 18 HD patients and 10 controls. Clinical measures were recorded from each HD patients. RESULTS: Cu/Zn-SOD, NSE and 8-oxoGua values were higher in HD patients than in controls. Cu/Zn-SOD and NSE correlated positively. No correlation was observed between the biomarkers analysed and the clinical measures assessed. DISCUSSION AND CONCLUSION: Serum oxidative biomarkers could express the neuronal oxidative processes going on in HD patients but are inadequate to evaluate clinical features of the disease.

Marine bioactives and potential application in sports.

An enriched diet with antioxidants, such as vitamin E, vitamin C, ß-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values and site-specific association.

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p<0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p<0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects.

Weight loss in obese prepubertal children: the influence of insulin resistance.

BACKGROUND: Insulin resistance (IR), a link of paramount importance between obesity and cardiovascular/metabolic complications, seems to be implicated in weight changes. OBJECTIVE: To determine whether IR could influence weight status during a 1-year intervention program in obese prepubertal children. METHODS: Forty-four children with IR (IR group) and 42 children without IR (NIR group) were enrolled. Body mass index standard deviation score (BMI-SDS), waist circumference (WC), and homeostasis model assessment (HOMA-IR) were evaluated. RESULTS: NIR children showed a significant reduction of BMI-SDS and WC at final assessment (p = 0.009 and p = 0.001, respectively), whereas IR children presented unchanged values. HOMA-IR decreased after intervention in the NIR group (p = 0.0008), but was exacerbated in IR children (p = 0.004). A positive and significant association between HOMA-IR at baseline and BMI at follow-up was found (B ± SE = 0.87 ± 0.24, p = 0.001). HOMA-IR at baseline was also significantly associated with WC at follow-up (B ± SE = 2.12 ± 0.69, p = 0.003). CONCLUSIONS: IR seems to influence adiposity changes in obese prepubertal children. Further longitudinal studies are needed to verify the relationship between IR and weight loss during childhood.

Effect of Treatment with Cyanidin-3-O-ß-D-Glucoside on Rat Ischemic/Reperfusion Brain Damage.

This study investigated the effect of cyanidin-3-O-ß-glucoside on an experimental model of partial/transient cerebral ischemia in the rats in order to verify the effectiveness of both pre- and posttreatments. Cyanidin-3-O-ß-glucoside-pretreated rats were injected with 10 mg/Kg i.p. 1 h before the induction of cerebral ischemia; in posttreated rats, the same dosage was injected during reperfusion (30 min after restoring blood flow). Cerebral ischemia was induced by bilateral clamping of common carotid arteries for 20 min. Ischemic rats were sacrificed immediately after 20 min ischemia; postischemic reperfused animals were sacrificed after 3 or 24 h of restoring blood flow. Results showed that treatment with cyanidin increased the levels of nonproteic thiol groups after 24 h of postischemic reperfusion, significantly reduced the lipid hydroperoxides, and increased the expression of heme oxygenase and γ-glutamyl cysteine synthase; a significant reduction in the expression of neuronal and inducible nitric oxide synthases and the equally significant increase in the endothelial isoform were observed. Significant modifications were also detected in enzymes involved in metabolism of endogenous inhibitors of nitric oxide. Most of the effects were observed with both pre- and posttreatments with cyanidin-3-O-ß-glucoside suggesting a role of anthocyanin in both prevention and treatment of postischemic reperfusion brain damage.

Fucoxantin: a treasure from the sea.

The World Health Organization (WHO) estimates that 2.3 billion people will be overweight and 700 million obese in 2015. The reasons for this disastrous trend are attributed to the global tendency toward the reduced magnitude of exercise and physical activity and the increased dietary intake of fats, sugars and calories with reduced amount of vitamins and minerals. To prevent life-style-related diseases, like Metabolic Syndrome (MS), researchers' attention is increasingly focusing on some of the so called "functional foods" which may be useful for their prevention and treatment. One of these functional ingredients is fucoxanthin (FX), a characteristic carotenoid present in edible brown seaweeds, such as Undaria pinnatifida (Wakame), Hijikia fusiformis (Hijiki), Laminaria japonica (Ma-Kombu) and Sargassum fulvellum. The increasing popularity of this molecule is certainly due to its anti-obesity effect, primarily detected by murine studies. These works revealed FX mediated induction of uncoupling protein-1 (UCP-1) in abdominal white adipose tissue (WAT) mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Beyond this important role, in recent studies FX has shown a great antioxidant activity, anti-cancer, anti-diabetic and anti-photoaging properties. The aim of this review is to highlight the main effects of FX on human health.

Marine bioactives: pharmacological properties and potential applications against inflammatory diseases.

Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, allergies, asthma, even cancer and many others. Over the past few decades, it was realized that the process of inflammation is virtually the same in different disorders, and a better understanding of inflammation may lead to better treatments for numerous diseases. Inflammation is the activation of the immune system in response to infection, irritation, or injury, with an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved. Although the pathophysiological basis of these conditions is not yet fully understood, reactive oxygen species (ROS) have often been implicated in their pathogenesis. In fact, in inflammatory diseases the antioxidant defense system is compromised, as evidenced by increased markers of oxidative stress, and decreased levels of protective antioxidant enzymes in patients with rheumatoid arthritis (RA). An enriched diet containing antioxidants, such as vitamin E, vitamin C, ß-carotene and phenolic substances, has been suggested to improve symptoms by reducing disease-related oxidative stress. In this respect, the marine world represents a largely untapped reserve of bioactive ingredients, and considerable potential exists for exploitation of these bioactives as functional food ingredients. Substances such as n-3 oils, carotenoids, vitamins, minerals and peptides provide a myriad of health benefits, including reduction of cardiovascular diseases, anticarcinogenic and anti-inflammatory activities. New marine bioactives are recently gaining attention, since they could be helpful in combating chronic inflammatory degenerative conditions. The aim of this review is to examine the published studies concerning the potential pharmacological properties and application of many marine bioactives against inflammatory diseases.

Carotenoids and vitamins C and E in the prevention of cardiovascular disease.

Atherosclerotic cardiovascular diseases (CVD) are a major source of mortality and morbidity in the general population. Oxidative modification of low-density lipoprotein cholesterol (LDL-C) represents the most important determinant factor in the development and progression of atherosclerotic lesions. Oxidative damage and the production of free radicals (FRs) in the endothelium are some of the main factors involved in the pathogenesis of the atherosclerotic process that causes CVD. Appropriate nutritional practices are of central importance in managing risk and treatment of CVD; in fact, many current guidelines for a healthy general population contain nutritional recommendations to reduce the risk of these diseases. Observational studies of vitamins C and E, the most prevalent natural antioxidant vitamins, suggest that supplemental use of these vitamins may lower the risk for coronary events. Despite these data, several large, randomized controlled trials have failed to confirm the benefits of vitamin C and E in cardiovascular prevention. The aim of this review is to examine the published studies regarding the effect of vitamins (C and E) and beta-carotene supplementation in the prevention of CVD due to atherosclerosis.

Dietary fibers and cardiometabolic diseases.

The high prevalence of cardiovascular disease (CVD) is largely attributable to the contemporary lifestyle that is often sedentary and includes a diet high in saturated fats and sugars and low ingestion of polyunsaturated fatty acids (PUFAs), fruit, vegetables, and fiber. Experimental data from both animals and humans suggest an association between increased dietary fiber (DF) intakes and improved plasma lipid profiles, including reduced low density lipoprotein cholesterol (LDL-C) concentrations. These observations underline that the intake of DF may protect against heart disease and stroke.

The biological effect of pharmacological treatment on dimethylaminohydrolases (DDAH-1) and cationic amino acid transporter-1 (CAT-1) expression in patients with acute congestive heart failure.

AIM: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) which plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The aim of this study was to investigate the effect of pharmacological treatment on symmetric dimethylarginine (SDMA), ADMA and arginine plasma concentrations in patients with acute congestive heart failure (ACHF) through the evaluation of type-1 system cationic amino acid transporter-1/type 1 dimethylarginine dimethylaminohydrolases-1 (CAT-1/DDAH-1). METHODS AND RESULTS: 25 hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction<35%) were included in the study. ADMA, SDMA, and arginine plasma concentrations were assessed before and after pharmacological treatment by high performance liquid chromatography. All patients received an adequate pharmacological treatment for ACHF. ADMA and SDMA plasma levels were significantly higher after pharmacological treatment respect to baseline values (pre-treatment) (0.75 vs 0.48; 1.31 vs 1.03; p<0.01). Arginine plasma concentration was significantly lower after therapy respect to baseline values (0.78 vs 0.99; p<0.01). This is associated more with the modulation of DDAH-1 protein than with of CAT-1 system transport. CONCLUSIONS: In patients with ACHF, acute renal impairment function and the modulation of metabolism and extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA levels after therapy for acute congestive heart failure.

Marine carotenoids and cardiovascular risk markers.

Marine carotenoids are important bioactive compounds with physiological activities related to prevention of degenerative diseases found principally in plants, with potential antioxidant biological properties deriving from their chemical structure and interaction with biological membranes. They are substances with very special and remarkable properties that no other groups of substances possess and that form the basis of their many, varied functions and actions in all kinds of living organisms. The potential beneficial effects of marine carotenoids have been studied particularly in astaxanthin and fucoxanthin as they are the major marine carotenoids. Both these two carotenoids show strong antioxidant activity attributed to quenching singlet oxygen and scavenging free radicals. The potential role of these carotenoids as dietary anti-oxidants has been suggested to be one of the main mechanisms for their preventive effects against cancer and inflammatory diseases. The aim of this short review is to examine the published studies concerning the use of the two marine carotenoids, astaxanthin and fucoxanthin, in the prevention of cardiovascular diseases.

Review: Obesity and COVID-19: A Detrimental Intersection.

Obesity has been recognized as an independent risk factor for critical illness and major severity in subjects with coronavirus disease 2019 (COVID-19). The role of fat distribution, particularly visceral fat (often linked to metabolic abnormalities), is still unclear. The adipose tissue represents a direct source of cytokines responsible for the pathological modifications occurring within adipose tissue in obese subjects. Adipokines are a crucial connection between metabolism and immune system: their dysregulation in obesity contributes to chronic low-grade systemic inflammation and metabolic comorbidities. Therefore the increased amount of visceral fat can lead to a proinflammatory phenotypic shift. This review analyzes the interrelation between obesity and COVID-19 severity, as well as the cellular key players and molecular mechanisms implicated in adipose inflammation, investigating if adipose tissue can constitute a reservoir for viral spread, and contribute to immune activation and cytokines storm. Targeting the underlying molecular mechanisms might have therapeutic potential in the management of obesity-related complications in COVID-19 patients.

COVID-19 and Obesity: Overlapping of Two Pandemics.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has recently led to worldwide research efforts to identify subjects at greater risk of developing more severe illness: overall obesity displayed a strong correlation with critical illness and major severity of COVID-19 manifestations. SUMMARY: Obesity and metabolic disorders are closely linked to chronic systemic inflammation. The adipose tissue constitutes a source of cytokines, which configure a low-grade inflammation and a hypercoagulation status; in addition, diagnosis and care of obese patients are often complicated by excess weight and ventilation difficulties. Key Messages: This review aims to examine the intersection between obesity and adverse outcomes of COVID-19, in order to investigate its preventive and/or therapeutic potential in the management of obesity-related COVID-19 complications.

Effect of Third-Generation Beta Blockers on Weight Loss in a Population of Overweight-Obese Subjects in a Controlled Dietary Regimen.

BACKGROUND: Overweight and obesity often develop in individuals with genetic susceptibility and concomitant risk factors; however, medications can represent precipitating factors in some cases: evidence suggests that some antihypertensive drugs can adversely affect energy homeostasis and metabolism. AIM: The primary aim of this study was to investigate whether long-term therapy with a beta blocker impairs weight loss during a period of appropriate personalized hypocaloric diet and standardized physical activity in overweight and obese hypertensive patients in monotherapy and without comorbidities, compared to other antihypertensive drugs and to a control group not taking antihypertensive therapy. Subjects and Methods. We enrolled overweight and obese patients taking antihypertensive drugs; subjects were divided into 3 groups: those taking traditional beta blockers (bB group), those taking third-generation beta blockers (bB-3 group), and those taking other antihypertensive drugs (non-bB group). We also enrolled subjects receiving neither antihypertensive therapy nor other chronic medication in the prior 12 months as controls. All subjects underwent personalized hypocaloric diets for a period of 24 months with monthly follow-up. Anthropometric parameters were measured at enrollment and then monthly after diet prescription. Glucose and lipid values were assessed at baseline and at 12 and 24 months during dietary regimen. RESULTS: We enrolled a total of 120 overweight and obese patients aged 50.30 ± 1.13 years (mean ± standard deviation) with a mean BMI of 31.79 ± 0.65 kg/m2; 90 were taking antihypertensive drugs (no comorbidity and no polytherapy), while 30 subjects receiving neither antihypertensive therapy nor other chronic medication in the prior 12 months were considered as controls. After 6 months, the percent total weight loss (TWL%) was lower in the bB group (3.62 ± 1.96 versus 5.27 ± 1.76 in the bB-3 group, versus 5.15 ± 1.30 in the non-bB group, and versus 4.70 ± 0.87 in the control group), as well as their BMI. After 24 months, we kept finding the worst result in the bB group (TWL% = 9.22 ± 2.19 versus 12.79 ± 1.72 in the non-bB group and 12.28 ± 1.97 in the control group) with the best trend in the bB-3 group (TWL% = 16.19 ± 2.67).