Dietary supplements for obesity.

Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements. Dietary supplements are considered an attractive alternative to traditional therapy due to their low toxicity profile and their accessibility to the general population. Dietary supplements may include one or more dietary ingredients. In this narrative review, we analyze the effects on obesity and obesity-related issues of various natural components. For example, there are a myriad of supplements that have been used as dietary supplements for weight loss such as minerals, vitamins, amino acids, metabolites, herbs, and plant extracts. This narrative review aims to present the benefits and side-effects of several ingredients of dietary supplements for weight loss and treatment of obesity. In particular, the mechanism of action, results of clinical trials, and possible side effects will be presented for the following ingredients: ß-Glucans, bitter orange, calcium, vitamin D, chitosan, chromium, cocoa, coleus forskohlii, conjugate linoleic acid, ephedra sinica, fucoxanthin, garcinia cambogia, glucomannan, green coffee, green tea, guar gum, raspberry, hoodia gordonii, irvingia gabonensis, phenylpropylamine, pyruvate, white kidney bean.

Dietary supplements in retinal diseases, glaucoma, and other ocular conditions.

Environmental pollution, inadequate eating habits and unhealthy lifestyles have led to a tremendous increase in ocular diseases worldwide. Given the costly treatments that are currently available for the most common and threatening eye diseases (such as cataract, dry eye disorder, or diabetic retinopathy), curing these diseases or preventing refractive errors by taking nutraceuticals and natural compounds that are present in our daily diet is a very valuable intervention. The eyes are the most important part of our visual system and require micronutrients such as vitamins, carotenoids, trace metals, and omega-3 fatty acids in order to function properly and to protect themselves against light-induced and age-mediated degenerative disorders. The Mediterranean Diet (MedDiet) has been in the limelight since the 1980s because of the several health benefits it provides, including eye health. MedDiet is characterized by the consumption of small amounts of red meat, while emphasizing the intake of fish, eggs, nuts, legumes, citrus fruits, green vegetables, olives and their derivatives, especially olive oil, and dairy products in a proportionate manner, in order to achieve the maximum health benefits. The antioxidant, anti-inflammatory, and neuroprotective properties of these foods - both when used as an ingredient in the dietary regime or as a source of nutritional supplements - have shown promising results in the management of chronic degenerative ocular diseases, both in animal models and in human subjects. In this chapter, we will focus on the importance of MedDiet and natural compounds for the visual system and its role in slowing down age-related ocular degeneration.

Dietary supplements in lymphedema.

Lymphedema is a chronic inflammatory disorder resulting from ineffective fluid uptake by the lymphatic system, and the effects are principally felt in the lower limbs. The condition is said to be primary when caused by genetic mutations and secondary when caused by injuries, infections, or surgery. Lymphedema, a worldwide pathology, does not have an effective therapy so far. Leukotriene B4 has recently been identified as a key molecule in lymphedema pathogenesis. Surgical, nonsurgical, and pharmacological treatments have been proposed; however, they do not cure the disease and only ameliorate the symptoms. Nutrition and nutritional status are extremely important in lymphedema physiopathology. Obesity is a comorbidity that exacerbates the risk for secondary lymphedema and constitutes a negative prognostic factor. Indeed, anti-inflammatory foods and their effects on the inflammatory state and on oxidative stress are now being investigated for their possible therapeutic role in lymphedema. Although no special diet has so far been proven to be very effective, specific dietary tips could help in alleviating the edematous state of patients with lymphedema. A few supplements have been tested for lymphedema treatment. Among them, GARLIVE® containing hydroxytyrosol, hesperidin, spermidine and vitamin A, exhibited promising effects in the animal model. Hydroxytyrosol, a polyphenol from olives, showed anti-inflammatory effects and reduced leukotriene B4 synthesis, thus holding promise as a potential natural candidate for lymphedema treatment.

Dietary supplements for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most prevalent female endocrine reproductive disorders, affecting between 4 to 18% of the women in their reproductive age. It is generally characterized by several clinical aspects, among which anovulation, inflammation and infertility. Moreover, PCOS has several health implications, including increased metabolic, reproductive, and psychological risks. Previously, metformin and to some extent thiazolidinediones were considered as drug of choice for PCOS management, but they had several side-effects, and controversial results were obtained about their efficiency, especially in non-insulin-resistant non-obese patients. Thus, alternative treatment options are now being studied for PCOS, including different natural molecules and complementary medicines (CM) for the improvement of their health, wellbeing and fertility. Recently, treatment of PCOS patients with different natural molecules, coming from nutritional supplements and herbal medicines, has attained satisfactory results with the absence of any side effects. In this review, four natural molecules, curcumin, vitamin D, inositol and CoQ10 are discussed for their therapeutic ability. These molecules proved to decrease insulin sensitivity and inflammation, to improve the restoration of ovarian function, and they could restore hormonal balance and regulate the menstrual cycle, all of which are the main features and major concerns for women suffering from PCOS.

Physical activity for health.

Physical activity plays a substantial role in maintaining people's good health and mental wellbeing, but that is not all: not only it positively affects the individuals' mental and physical health, but a lack of physical exercise exerts a negative impact also on the overall economy of a nation. In addition, physical inactivity not only increases the risk of non-communicable diseases (NCD), but also contributes significantly to the increased morbidity and mortality in patients suffering from these diseases. On the contrary, physical activity reduces the risk of NCDs - such as cardiovascular diseases, type 2 diabetes, and cancer - in a dose-dependent manner; regular exercise is also associated with many health benefits and delayed mortality. However, understanding the role of physical activity in modern society and creating an awareness in the general population is one of the most important tasks of health and recreation promoters. Correspondingly, there is a dire need to enhance our knowledge, perception, and awareness of physical activity and its impacts on an individual's health, ultimately contributing to developing a healthy society. The current review will focus on the health benefits of the two most widely studied modifiable lifestyle risk factors, physical activity and diet, focusing particularly on the Mediterranean diet.

Foods of the Mediterranean diet: citrus, cucumber and grape.

Fruit and vegetables are excellent sources of health-promoting bioactive compounds and nutraceuticals. Regular consumption of fruit and vegetables helps prevent the onset and progression of many non-communicable diseases. The Mediterranean diet envisages consumption of healthy vegetables and fruit on a daily basis for maximum health benefits. Traditional use envisages vegetable-based and fruit-based diets, and many studies scientifically proved the beneficial effects of Mediterranean vegetables and fruits. Rich in bioactive phytochemicals, citrus, cucumbers and grapes have antioxidant, anti-inflammatory, antimicrobial, cardioprotective, anti-ageing and anti-cancer properties. Studies indicate that intake of citrus, cucumbers and grapes reduces hypertension, hyperlipidemia, skin problems and infections and improves the health of the cardiovascular and nervous systems. These beneficial effects are mediated by several bioactive molecules present in Mediterranean diet vegetables and fruits, such as citrus, cucumbers and grapes. Indeed, they contains flavones, isoflavones, tannins, polyphenols and many beneficial natural molecules. This review focuses on the bioactive ingredients in citrus fruit, cucumbers and grapes, all components of the Mediterranean diet, and their health effects. A deep understanding of Mediterranean diet's components, as well as clinical trials to test natural molecules beneficial effects, will permit to further explore the therapeutic potential of the Mediterranean diet in several pathological conditions.

Clinical assessment for diet prescription.

Accurate nutritional assessment based on dietary intake, physical activity, genetic makeup, and metabolites is required to prevent from developing and/or to treat people suffering from malnutrition as well as other nutrition related health issues. Nutritional screening ought to be considered as an essential part of clinical assessment for every patient on admission to healthcare setups, as well as on change in clinical conditions. Therefore, a detailed nutritional assessment must be performed every time nutritional imbalances are observed or suspected. In this review we have explored different techniques used for nutritional and physical activity assessment. Dietary Intake (DI) assessment is a multidimensional and complex process. Traditionally, dietary intake is assessed through self-report techniques, but due to limitations like biases, random errors, misestimations, and nutrient databases-linked errors, questions arise about the adequacy of self-reporting dietary intake procedures. Despite the limitations in assessing dietary intake (DI) and physical activity (PA), new methods and improved technologies such as biomarkers analysis, blood tests, genetic assessments, metabolomic analysis, DEXA (Dual-energy X-ray absorptiometry), MRI (Magnetic resonance imaging), and CT (computed tomography) scanning procedures have made much progress in the improvement of these measures. Genes also plays a crucial role in dietary intake and physical activity. Similarly, metabolites are also involved in different nutritional pathways. This is why integrating knowledge about the genetic and metabolic markers along with the latest technologies for dietary intake (DI) and physical activity (PA) assessment holds the key for accurately assessing one's nutritional status and prevent malnutrition and its related complications.

Gene variants in eating disorders. Focus on anorexia nervosa, bulimia nervosa, and binge-eating disorder.

Eating disorders such as anorexia nervosa, bulimia nervosa and binge-eating disorder, have a deep social impact, concluding with death in cases of severe disease. Eating disorders affect up to 5% of the population in the industrialized countries, but probably the phenomenon is under-detection and under-diagnosis. Eating disorders are multifactorial disorders, resulting from the interaction between environmental triggers, psychological factors, but there is also a strong genetic component. In fact, genetic factors predispose for approximately 33-84% to anorexia nervosa, 28-83% to bulimia nervosa, and 41-57% to binge eating disorder. Twins and family studies have provided an unassailable proof on the heritability of these disorders. Other types of genetic studies, including genome-wide association studies, whole genome sequencing and linkage analysis, allowed to identify the genes and their variants associated with eating disorders and moreover global collaborative efforts have led to delineate the etiology of these disorders. Next Generation Sequencing technologies can be considered as an ideal diagnostic approach to identify not only the common variants, such as single nucleotide polymorphism, but also rare variants. Here we summarize the present knowledge on the molecular etiology and genetic determinants of eating disorders including serotonergic genes, dopaminergic genes, opioid genes, appetite regulation genes, endocannabinoid genes and vitamin D3.

Dietary supplements in neurological diseases and brain aging.

A healthy diet shapes a healthy mind. Diet quality has a strong association with brain health. Diet influences the onset and consequences of neurological diseases, and dietary factors may influence mental health at individual and population level. The link between unhealthy diet, impaired cognitive function and neurodegenerative diseases indicates that adopting a healthy diet would ultimately afford prevention and management of neurological diseases and brain aging. Neurodegenerative diseases are of multifactorial origin and result in progressive loss of neuronal function in the brain, leading to cognitive impairment and motoneuron disorders. The so-called Mediterranean diet (MedDiet) with its healthy ingredients rich in antioxidant, anti-inflammatory, immune, neuroprotective, antidepressant, antistress and senolytic activity plays an essential role in the prevention and management of neurological diseases and inhibits cognitive decline in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The MedDiet also modulates the gut-brain axis by promoting a diversity of gut microbiota. In view of the importance of diet in neurological diseases management, this review focuses on the dietary components, natural compounds and medicinal plants that have proven beneficial in neurological diseases and for brain health. Among them, polyphenols, omega-3 fatty acids, B vitamins and several ayurvedic herbs have promising beneficial effects.

Polyphenols and Lactobacillus reuteri in oral health.

Oral health is one of the necessary preludes to the overall quality of life. Several medical procedures and therapies are available to treat oral diseases in general and periodontal diseases in particular, yet caries, periodontitis, oral cancer, and oral infections remain a global concern. Natural molecules, with their anti-oxidant, anti-inflammatory, and anti-microbic properties, are one of the main sources of oral health and dental health care, and should be supplemented to exploit their beneficial effects. A possible way to improve the intake of these molecules is adhering to a diet that is rich in fruits, vegetables, and probiotics, which has many beneficial properties and can improve overall health and wellbeing. The Mediterranean diet, in particular, provides several beneficial natural molecules, mainly because of the precious nutrients contained in its typical ingredients, mainly plant-based (olives, wine, citrus fruits, and many more). Its beneficial effects on several diseases and in increasing the overall wellbeing of the population are currently being studied by physicians. Among its nutrients, polyphenols (including, among other molecules, lignans, tannins, and flavonoids) seem to be of outmost importance: several studies showed their anticariogenic properties, as well as their effects in decreasing the incidence of non-communicable diseases. Therefore, plant-derived molecules - such as polyphenols - and probiotics - such as Lactobacillus reuteri - have shown a significant potential in treating and curing oral diseases, either alone or in combination, owing to their antioxidant and antimicrobial properties, respectively.

Validating methods for testing natural molecules on molecular pathways of interest in silico and in vitro.

Differentially expressed genes can serve as drug targets and are used to predict drug response and disease progression. In silico drug analysis based on the expression of these genetic biomarkers allows the detection of putative therapeutic agents, which could be used to reverse a pathological gene expression signature. Indeed, a set of bioinformatics tools can increase the accuracy of drug discovery, helping in biomarker identification. Once a drug target is identified, in vitro cell line models of disease are used to evaluate and validate the therapeutic potential of putative drugs and novel natural molecules. This study describes the development of efficacious PCR primers that can be used to identify gene expression of specific genetic pathways, which can lead to the identification of natural molecules as therapeutic agents in specific molecular pathways. For this study, genes involved in health conditions and processes were considered. In particular, the expression of genes involved in obesity, xenobiotics metabolism, endocannabinoid pathway, leukotriene B4 metabolism and signaling, inflammation, endocytosis, hypoxia, lifespan, and neurotrophins were evaluated. Exploiting the expression of specific genes in different cell lines can be useful in in vitro to evaluate the therapeutic effects of small natural molecules.

Main nutritional deficiencies.

Nutrition is the source of energy that is required to carry out all the processes of human body. A balanced diet is a combination of both macro- and micronutrients. "Nutritional inadequacy" involves an intake of nutrients that is lower than the estimated average requirement, whereas "nutritional deficiency" consists of severely reduced levels of one or more nutrients, making the body unable to normally perform its functions and thus leading to an increased risk of several diseases like cancer, diabetes, and heart disease. Malnutrition could be caused by environmental factors, like food scarcity, as well as disease conditions, like anorexia nervosa, fasting, swallowing inability, persistent vomiting, impaired digestion, intestinal malabsorption, or other chronic diseases. Nutritional biomarkers - like serum or plasma levels of nutrients such as folate, vitamin C, B vitamins, vitamin D, selenium, copper, zinc - could be used for the evaluation of nutrient intake and dietary exposure. Macronutrients deficiencies could cause kwashiorkor, marasmus, ketosis, growth retardation, wound healing, and increased infection susceptibility, whereas micronutrient - like iron, folate, zinc, iodine, and vitamin A - deficiencies lead to intellectual impairment, poor growth, perinatal complications, degenerative diseases associated with aging and higher morbidity and mortality. Preventing macro- and micronutrient deficiency is crucial and this could be achieved through supplementation and food-based approaches.

Foods of the Mediterranean diet: tomato, olives, chili pepper, wheat flour and wheat germ.

Mediterranean people, which follows a diet rich in minimally-processed plant-based foods, are believed to live longer and healthier lives than many other populations in the Western world. Epidemiological and clinical data suggest that the Mediterranean diet has beneficial effects for several chronic diseases, such as cardiovascular diseases, obesity, cancer and diabetes. Although the mechanisms of action of the Mediterranean diet are not completely clear, the synergistic effects of a number of its components and their bioactive phytochemicals exert antioxidant, anti-inflammatory, anti-microbial and anti-cancer effects. The Mediterranean diet includes daily consumption of whole cereals, fruit, vegetables and legumes in moderate proportions, weekly consumption of white meat in low to moderate proportions and occasionally sweets and chocolates in small amounts. Since olive oil is the main lipids source, it has special significance for health. Healthy fruit and vegetables, rich in phytochemicals, are a major proportion of this diet and contribute to the overall nutritional value and bioactivity of its components. Here we review the nutritional and health benefits of wheat germ, tomatoes, olives and chili pepper, items at the base of Mediterranean diet food pyramid that provides beneficial molecules, such as polyphenols, vitamins and flavonoids, and exert anti-inflammatory, anti-microbial and anti-oxidative actions.

Dietary supplements for lipedema.

Lipedema is a chronic disease that mostly manifests in females as the abnormal distribution of subcutaneous adipose connective tissue, usually coupled with bruising, pain, and edema. Lipedema molecular pathophysiology is currently not clear, but several studies suggest that genetics and hormonal imbalance participate in lipedema pathogenesis. Women with lipedema present in some cases with elevated body mass index, and the appearance of obesity in addition to lipedema, where the obesity can cause serious health issues as in lipedema-free individuals with obesity, such as diabetes and cardiovascular disorders. Unlike obesity, lipedema tissue does not respond well to diet or physical exercise alone. Therefore, in this review we discuss the effect of various dietary supplements that, along with diet and physical exercise, cause fat burning and weight loss, and which could potentially be important in the treatment of lipedema. Indeed, an effective fat burner should convert stored fats into energy, mobilize and break down triglycerides in adipocytes, boost metabolism and inhibit lipogenesis. Common ingredients of fat burning supplements are green tea, caffeine, chromium, carnitine, and conjugated linoleic acid. The use of fat burners could act synergistically with a healthy diet and physical exercise for decreasing adipose tissue deposition in patients with lipedema and resolve related health issues. The effects of fat burners in human studies are sometimes contradictory, and further studies should test their effectiveness in treating lipedema.

Next-Generation Sequencing of a Large Gene Panel for Outcome Prediction of Bariatric Surgery in Patients with Severe Obesity.

Obesity is a chronic disease in which abnormal deposition of fat threatens health, leading to diabetes, cardiovascular diseases, cancer, and other chronic illnesses. According to the WHO, 19.8% of the adult population in Italy is obese, and the prevalence is higher among men. It is important to know the predisposition of an individual to become obese and to respond to bariatric surgery, the most up-to-date treatment for severe obesity. To this purpose, we developed an NGS gene panel, comprising 72 diagnostic genes and 244 candidate genes, and we sequenced 247 adult obese Italian patients. Eleven deleterious variants in 9 diagnostic genes and 17 deleterious variants in 11 candidate genes were identified. Interestingly, mutations were found in several genes correlated to the Bardet-Biedl syndrome. Then, 25 patients were clinically followed to evaluate their response to bariatric surgery. After a 12-month follow-up, the patients that carried deleterious variants in diagnostic or candidate genes had a reduced weight loss, as compared to the other patients. The NGS-based panel, including diagnostic and candidate genes used in this study, could play a role in evaluating, diagnosing, and managing obese individuals, and may help in predicting the outcome of bariatric surgery.

A next generation sequencing gene panel for use in the diagnosis of anorexia nervosa.

PURPOSE: The aim of this study was to increase knowledge of genes associated with anorexia nervosa (AN) and their diagnostic offer, using a next generation sequencing (NGS) panel for the identification of genetic variants. The rationale underlying this test is that we first analyze the genes associated with syndromic forms of AN, then genes that were found to carry rare variants in AN patients who had undergone segregation analysis, and finally candidate genes intervening in the same molecular pathways or identified by GWAS or in mouse models. METHODS: We developed an NGS gene panel and used it to screen 68 Italian AN patients (63 females, 5 males). The panel included 162 genes. Family segregation study was conducted on available relatives of probands who reported significant genetic variants. RESULTS: In our analysis, we found potentially deleterious variants in 2 genes (PDE11A and SLC25A13) associated with syndromic forms of anorexia and predicted deleterious variants in the following 12 genes: CD36, CACNA1C, DRD4, EPHX2, ESR1, GRIN2A, GRIN3B, LRP2, NPY4R, PTGS2, PTPN22 and SGPP2. Furthermore, by Sanger sequencing of the promoter region of NNAT, we confirmed the involvement of this gene in the pathogenesis of AN. Family segregation studies further strengthened the possible causative role of CACNA1C, DRD4, GRIN2A, PTGS2, SGPP2, SLC25A13 and NNAT genes in AN etiology. CONCLUSION: The major finding of our study is the confirmation of the involvement of the NNAT gene in the pathogenesis of AN; furthermore, this study suggests that NGS-based testing can play an important role in the diagnostic evaluation of AN, excluding syndromic forms and increasing knowledge of the genetic etiology of AN. LEVEL OF EVIDENCE: Level I, experimental study.

Genetic analysis of genes associated with Mendelian dementia.

BACKGROUND AND AIM: Dementia is a disease associated with cognitive and/or behavioral changes that interfere with the ability to perform daily activities. Alzheimer's disease is the most common type of dementia. The aim of this mini-review is to summarize all the syndromes characterized by dementia and for which the associated gene is known. METHODS: We searched those syndromes in PubMed and OMIM database. RESULTS: Two forms of dementia exist: the multifactorial dementia results from the interaction of different genetic and environmental factors, the hereditary dementia associated with a single gene. Individuals with a family history of dementia and early onset of the disease are more likely to have a hereditary form of dementia. Dementias are mainly autosomal dominant, but they can also be autosomal recessive or X-linked. CONCLUSIONS: Since dementia has high clinical and genetic heterogeneity, the use in diagnostics of a large panel of genes may greatly help to speed up the determination of the molecular diagnosis and/or establish a risk of recurrence in family members for the purpose of planning appropriate preventive and/or therapeutic measures.

Genetic test for the personalization of sport training.

Genetic variants may contribute to confer elite athlete status. However, this does not mean that a person with favourable genetic traits would become a champion because multiple genetic interactions and epigenetic contributions coupled with confounding environmental factors shape the overall phenotype. This opens up a new area in sports genetics with respect to commercial genetic testing. The analysis of genetic polymorphisms linked to sport performance would provide insights into the potential of becoming an elite endurance or power performer. This mini-review aims to highlight genetic interactions that are associated with performance phenotypes and their potentials to be used as markers for talent identification and trainability.

Bacteriophages presence in nature and their role in the natural selection of bacterial populations.

Phages are the obligate parasite of bacteria and have complex interactions with their hosts. Phages can live in, modify, and shape bacterial communities by bringing about changes in their abundance, diversity, physiology, and virulence. In addition, phages mediate lateral gene transfer, modify host metabolism and reallocate bacterially-derived biochemical compounds through cell lysis, thus playing an important role in ecosystem. Phages coexist and coevolve with bacteria and have developed several antidefense mechanisms in response to bacterial defense strategies against them. Phages owe their existence to their bacterial hosts, therefore they bring about alterations in their host genomes by transferring resistance genes and genes encoding toxins in order to improve the fitness of the hosts. Application of phages in biotechnology, environment, agriculture and medicines demands a deep insight into the myriad of phage-bacteria interactions. However, to understand their complex interactions, we need to know how unique phages are to their bacterial hosts and how they exert a selective pressure on the microbial communities in nature. Consequently, the present review focuses on phage biology with respect to natural selection of bacterial populations.

Natural compounds as inhibitors of SARS-CoV-2 endocytosis: A promising approach against COVID-19.

BACKGROUND AND AIM: The recent COVID-19 pandemic caused by SARS-CoV-2 affected more than six million people and caused thousands of deaths. The lack of effective drugs or vaccines against SARS-CoV-2 further worsened the situation. This review is focused on the identification of molecules that may inhibit viral entry into host cells by endocytosis. METHODS: We performed the literature search for these natural compounds in the articles indexed in PubMed. RESULTS: Natural products against viral infections have been gaining importance in recent years. Specific natural compounds like phytosterols, polyphenols, flavonoids, citrus, galangal, curcuma and hydroxytyrosol are being analyzed to understand whether they could inhibit SARS-CoV-2. CONCLUSIONS: We reviewed natural compounds with potential antiviral activity against SARS-CoV-2 that could be used as a treatment for COVID-19.