(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an in vitro model. METHODS: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles. RESULTS: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways. CONCLUSION: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.

Resveratrol and vascular health: evidence from clinical studies and mechanisms of actions related to its metabolites produced by gut microbiota.

Cardiovascular diseases are among the leading causes of mortality worldwide, with dietary factors being the main risk contributors. Diets rich in bioactive compounds, such as (poly)phenols, have been shown to potentially exert positive effects on vascular health. Among them, resveratrol has gained particular attention due to its potential antioxidant and anti-inflammatory action. Nevertheless, the results in humans are conflicting possibly due to interindividual different responses. The gut microbiota, a complex microbial community that inhabits the gastrointestinal tract, has been called out as potentially responsible for modulating the biological activities of phenolic metabolites in humans. The present review aims to summarize the main findings from clinical trials on the effects of resveratrol interventions on endothelial and vascular outcomes and review potential mechanisms interesting the role of gut microbiota on the metabolism of this molecule and its cardioprotective metabolites. The findings from randomized controlled trials show contrasting results on the effects of resveratrol supplementation and vascular biomarkers without dose-dependent effect. In particular, studies in which resveratrol was integrated using food sources, i.e., red wine, reported significant effects although the resveratrol content was, on average, much lower compared to tablet supplementation, while other studies with often extreme resveratrol supplementation resulted in null findings. The results from experimental studies suggest that resveratrol exerts cardioprotective effects through the modulation of various antioxidant, anti-inflammatory, and anti-hypertensive pathways, and microbiota composition. Recent studies on resveratrol-derived metabolites, such as piceatannol, have demonstrated its effects on biomarkers of vascular health. Moreover, resveratrol itself has been shown to improve the gut microbiota composition toward an anti-inflammatory profile. Considering the contrasting findings from clinical studies, future research exploring the bidirectional link between resveratrol metabolism and gut microbiota as well as the mediating effect of gut microbiota in resveratrol effect on cardiovascular health is warranted.

Isoflavones Effects on Vascular and Endothelial Outcomes: How Is the Gut Microbiota Involved?

Isoflavones are a group of (poly)phenols, also defined as phytoestrogens, with chemical structures comparable with estrogen, that exert weak estrogenic effects. These phytochemical compounds have been targeted for their proven antioxidant and protective effects. Recognizing the increasing prevalence of cardiovascular diseases (CVD), there is a growing interest in understanding the potential cardiovascular benefits associated with these phytochemical compounds. Gut microbiota may play a key role in mediating the effects of isoflavones on vascular and endothelial functions, as it is directly implicated in isoflavones metabolism. The findings from randomized clinical trials indicate that isoflavone supplementation may exert putative effects on vascular biomarkers among healthy individuals, but not among patients affected by cardiometabolic disorders. These results might be explained by the enzymatic transformation to which isoflavones are subjected by the gut microbiota, suggesting that a diverse composition of the microbiota may determine the diverse bioavailability of these compounds. Specifically, the conversion of isoflavones in equol-a microbiota-derived metabolite-seems to differ between individuals. Further studies are needed to clarify the intricate molecular mechanisms behind these contrasting results.

Dietary (Poly)phenols and Cognitive Decline: A Systematic Review and Meta-Analysis of Observational Studies.

SCOPE: This study aims to systematically review observational studies investigating the relation between dietary (poly)phenol consumption and various cognitive outcomes. METHODS AND RESULTS: Embase and PubMed databases are searched from inception to April 2023 for observational studies investigating the relation between dietary (poly)phenol intake and cognitive outcomes. For quantitative analyses, random effects models, subgroup analyses, and dose-response analyses are performed. A total of 37 studies are included in the systematic review. Among (poly)phenols, a higher intake of flavonoids is associated with better cognitive function and lower odds of cognitive decline (although with some exceptions). A quantitative meta-analysis shows an overall inverse association with cognitive impairment and reduced association with the incidence of dementia or related disorders for total flavonoids (relative risk (RR) = 0.83, 95% confidence interval (CI): 0.76, 0.89), anthocyanins (RR = 0.73, 95% CI: 0.60, 0.89), flavones (RR = 0.77, 95% CI: 0.63, 0.94), flavan-3-ols (RR = 0.86, 95% CI: 0.82, 0.91), and flavonols (RR = 0.88, 95% CI: 0.80, 0.96). Data on other (poly)phenolic compounds (i.e., phenolic acids) are promising but too preliminary. CONCLUSION: Habitual inclusion of flavonoids in the diet may play a preventive role against cognitive disorders.

Anthocyanin Effects on Vascular and Endothelial Health: Evidence from Clinical Trials and Role of Gut Microbiota Metabolites.

Hypertension and derived cardiovascular disease (CVD) are among the leading causes of death worldwide. Increased oxidative stress and inflammatory state are involved in different alterations in endothelial functions that contribute to the onset of CVD. Polyphenols, and in particular anthocyanins, have aroused great interest for their antioxidant effects and their cardioprotective role. However, anthocyanins are rarely detected in blood serum because they are primarily metabolized by the gut microbiota. This review presents studies published to date that report the main results from clinical studies on the cardioprotective effects of anthocyanins and the role of the gut microbiota in the metabolism and bioavailability of anthocyanins and their influence on the composition of the microbiota. Even if it seems that anthocyanins have a significant effect on vascular health, more studies are required to better clarify which molecules and doses show vascular benefits without forgetting the crucial role of the microbiota.

Fish and human health: an umbrella review of observational studies.

Fish represents one of the most important dietary sources of omega-3 polyunsaturated fatty acids, which are known to be associated with various health benefits. This study aimed to systematically review existing meta-analyses of observational studies exploring the association between fish intake and various health outcomes. A systematic search of electronic databases was conducted to retrieve a total of 63 studies. Evidence was deemed as possible for the association between higher fish intake and decreased risk of the acute coronary syndrome, liver cancer, and depression, and limited for other outcomes (including age-related macular degeneration, Alzheimer's disease, heart failure, all-cause and coronary heart disease mortality, total and ischaemic stroke) due to heterogeneity between results and potential otherwise inexplicable confounding factors. In conclusion, results from epidemiological studies support the mechanistic effects associated with omega-3 fatty acids from high fish consumption, but evidence needs to be further corroborated with more reliable results.

The Effect of Dietary Polyphenols on Vascular Health and Hypertension: Current Evidence and Mechanisms of Action.

The aim of this review was to explore existing evidence from studies conducted on humans and summarize the mechanisms of action of dietary polyphenols on vascular health, blood pressure and hypertension. There is evidence that some polyphenol-rich foods, including berry fruits rich in anthocyanins, cocoa and green tea rich in flavan-3-ols, almonds and pistachios rich in hydroxycinnamic acids, and soy products rich in isoflavones, are able to improve blood pressure levels. A variety of mechanisms can elucidate the observed effects. Some limitations of the evidence, including variability of polyphenol content in plant-derived foods and human absorption, difficulty disentangling the effects of polyphenols from other dietary compounds, and discrepancy of doses between animal and human studies should be taken into account. While no single food counteracts hypertension, adopting a plant-based dietary pattern including a variety of polyphenol-rich foods is an advisable practice to improve blood pressure.

Total, red and processed meat consumption and human health: an umbrella review of observational studies.

Meat consumption has represented an important evolutionary step for humans. However, modern patterns of consumption, including excess intake, type of meat and cooking method have been the focus of attention as a potential cause of rise in non-communicable diseases. The aim of this study was to investigate the association between total, red and processed meat with health outcomes and to assess the level of evidence by performing a systematic search of meta-analyses of prospective cohort studies. Convincing evidence of the association between increased risk of (i) colorectal adenoma, lung cancer, CHD and stroke, (ii) colorectal adenoma, ovarian, prostate, renal and stomach cancers, CHD and stroke and (iii) colon and bladder cancer was found for excess intake of total, red and processed meat, respectively. Possible negative associations with other health outcomes have been reported. Excess meat consumption may be detrimental to health, with a major impact on cardiometabolic and cancer risk.

Polyphenols and neuroprotection: Therapeutic implications for cognitive decline.

Dietary polyphenols have been the focus of major interest for their potential benefits on human health. Several preclinical studies have been conducted to provide a rationale for their potential use as therapeutic agents in preventing or ameliorating cognitive decline. However, results from human studies are scarce and poorly documented. The aim of this review was to discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes. The evidence published so far is encouraging but contrasting findings are to be taken into account. Most studies on anthocyanins showed a consistent positive effect on various cognitive aspects related to aging or early stages of cognitive impairment. Studies on cocoa flavanols, resveratrol, and isoflavones provided substantial contrasting results and further research is needed to clarify the therapeutic potential of these compounds. Results from other studies on quercetin, green tea flavanols, hydroxycinnamic acids (such as chlorogenic acid), curcumin, and olive oil tyrosol and derivatives are rather promising but still too few to provide any real conclusions. Future translational studies are needed to address issues related to dosage, optimal formulations to improve bioavailability, as well as better control for the overall diet, and correct target population.

Dietary Phenolic Acids and Their Major Food Sources Are Associated with Cognitive Status in Older Italian Adults.

BACKGROUND: Life expectancy is increasing along with the rising prevalence of cognitive disorders. Among the factors that may contribute to their prevalence, modifiable risk factors such as diet may be of primary importance. Unarguably, plant-based diets rich in bioactive compounds, such as polyphenols, showed their potential in decreasing risk of neurodegenerative disorders. Therefore, the aim of the present study is to investigate whether exposure to components of plant-based diets, namely phenolic acids, may affect cognitive status in older Italian adults. METHODS: The demographic, lifestyle and dietary habits of a sample of individuals living in southern Italy were analyzed. Dietary intake was assessed through food frequency questionnaires (FFQs). Data on the phenolic acids content in foods were estimated using the Phenol-Explorer database. Cognitive status was evaluated using The Short Portable Mental Status Questionnaire. Multivariate logistic regression analyses were used to assess the associations. RESULTS: The mean intake of phenolic acids was 346.6 mg/d. After adjustment for potential confounding factors, individuals in the highest quartile of total phenolic acid intake were less likely to have impaired cognitive status (OR = 0.36 (95% CI: 0.14, 0.92)); similarly, the analysis for subclasses of phenolic acids showed the beneficial effect toward cognitive status of greater intake of hydroxycinnamic acids (OR = 0.35 (95% CI: 0.13, 0.91)). Among individual compounds, only higher intake of caffeic acid was inversely associated with impaired cognitive status (OR = 0.32 (95% CI: 0.11, 0.93)); notably, the association with ferulic acid intake was significant only when adjusting for background characteristics, and not for adherence to the Mediterranean diet. CONCLUSIONS: This study revealed that greater intakes of dietary phenolic acids were significantly inversely associated with impaired cognition, emphasizing the possible role of phenolic acids in the prevention of cognitive disorders.

Total Nut, Tree Nut, and Peanut Consumption and Metabolic Status in Southern Italian Adults.

BACKGROUND: Nut consumption has been associated with cardio-metabolic health benefits. However, studies conducted in the Southern Italian population, where adherence to the Mediterranean diet has been reported being relatively high, are rather scarce. The aim of this study was to test the association between consumption of total and specific types of nuts and metabolic status among adults living in Sicily, Southern Italy. METHODS: Demographic and dietary characteristics of 2044 adults living in Southern Italy were analyzed. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between nut consumption and metabolic status adjusting for potential confounding factors. RESULTS: The energy-adjusted model revealed that higher nut intake was inversely associated with occurrence of hypertension, type-2 diabetes, and dyslipidemia. However, the association did not remain significant for the latter after adjusting for the main background characteristics, while an inverse association was stably confirmed for hypertension (OR = 0.61, 95% CI: 0.46-0.80 and OR = 0.44, 95% CI: 0.26-0.74, respectively) even after adjusting for adherence to the Mediterranean diet. Among individual nut types, most of the associations were null except for higher almond intake, which was inversely associated with occurrence of hypertension (OR = 0.70, 95% CI: 0.49-0.99). CONCLUSIONS: Higher nut consumption is associated with overall better metabolic status in individuals living in the Mediterranean area.

Nut and legume consumption and human health: an umbrella review of observational studies.

Consumption of nuts and legumes has been associated with several health benefits. The aim of this study was to systematically review existing meta-analyses of observational studies on nut and legume intake and non-communicable diseases, and assess the level of evidence. Out of the six meta-analyses focussed on legume and 15 on nut intake, a possible association with decreased risk of colorectal adenoma and coronary heart disease was found for higher legume consumption, and a decreased risk of cardiovascular and cancer mortality, colon cancer, hypertension and ischaemic stroke for higher nut consumption. The association between legume consumption and cardiovascular diseases (CVDs), as well as nut consumption and risk of cancer, CVD incidence and all-cause mortality, was deemed as "limited" due to heterogeneity between results and/or potential confounding factors. General benefit towards better health can be observed for nut and legume consumption. Further studies are needed to better elucidate potential confounding factors.

Polyphenol-Rich and Alcoholic Beverages and Metabolic Status in Adults Living in Sicily, Southern Italy.

Polyphenol-rich beverage consumption is not univocally accepted as a risk modulator for cardio-metabolic risk factors, despite mechanistic and epidemiological evidence suggesting otherwise. The aim of this study was to assess whether an association between polyphenol-rich beverage consumption and metabolic status could be observed in a Mediterranean cohort with relatively low intake of tea, coffee, red and white wine, beer, and fresh citrus juice. Demographic and dietary characteristics of 2044 adults living in southern Italy were analyzed. Multivariate logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between polyphenol-rich and alcoholic beverage consumption and metabolic status adjusted for potential confounding factors. Specific polyphenol-rich beverages were associated, to a various extent, with metabolic outcomes. Individuals with a higher total polyphenol-rich beverages had higher polyphenols intake and were less likely to have hypertension, type-2 diabetes, and dyslipidemia (OR = 0.57, 95% CI: 0.44-0.73; OR = 0.41, 95% CI: 0.26-0.66; and OR = 0.41, 95% CI: 0.29-0.57, respectively). However, when adjusted for potential confounding factors, only the association with hypertension remained significant (OR = 0.69, 95% CI: 0.50-0.94). Current scientific evidence suggests that such beverages may play a role on cardio-metabolic risk factors, especially when consumed within the context of a dietary pattern characterized by an intake of a plurality of them. However, these associations might be mediated by an overall healthier lifestyle.

Dietary phytoestrogens and biomarkers of their intake in relation to cancer survival and recurrence: a comprehensive systematic review with meta-analysis.

CONTEXT: Recent studies have outlined the potential role of dietary factors in patients who have survived cancer. OBJECTIVE: The aim of this study was to summarize the evidence of the relation between dietary intake of phytoestrogens and their blood biomarkers and, overall, cancer-specific mortality and recurrence in patients with cancer. DATA SOURCES: A systematic search of PubMed, EMBASE, and Web of Science databases of studies published up to September 2019 was performed. Databases were searched for prospective and retrospective cohort studies reporting on dietary phytoestrogen intake and/or blood biomarkers and the outcomes investigated. DATA EXTRACTION: Data were extracted from each identified study using a standardized form. DATA ANALYSIS: Twenty-eight articles on breast, lung, prostate, and colorectal cancer, and glioma were included for systematic review. Given the availability of studies, a quantitative meta-analysis was performed solely for breast cancer outcomes. A significant inverse association among higher dietary isoflavone intake, higher serum/plasma enterolactone concentrations, and overall mortality and cancer recurrence was found. Among other cancer types, 2 studies reported that higher serum enterolactone and higher intake of lignans were associated with cancer-specific survival for colorectal cancer and glioma, respectively. CONCLUSIONS: Dietary phytoestrogens may play a role in survival from breast cancer ; evidence regarding other cancers is too limited to draw any conclusions.

A Call to Action: Now Is the Time to Screen Elderly and Treat Osteosarcopenia, a Position Paper of the Italian College of Academic Nutritionists MED/49 (ICAN-49).

Aging is a risk factor for the development of multiple chronic diseases, including cardiovascular disease, cancer and dementia. Life expectancy has increased in certain countries but this phenomenon is associated with a reduction of years of healthy life. Aging is associated with a number of physical and functional changes, especially sarcopenia. Sarcopenia is a clinical condition associated with a decrease in skeletal muscle and muscle strength, however, sarcopenia is a reversible condition. On the basis of the current scientific literature, sarcopenia could more appropriately capture an individual's vulnerability to negative health-related outcomes since it represents an early form of the chronic diseases. Recognition of this clinical condition can improve the management of older individuals in many different clinical settings. Despite the limitations of the indirect methods used to study body composition, the Italian College of the Academic Nutritionists ME/49 recommends that health authorities and health professionals around the world should make a greater effort to diagnose sarcopenia earlier and to manage it more effectively. In line with the development of cancer screening, the use of two diagnostic tools for sarcopenia (BIA and DXA) should be implemented.

Association Between Dietary Flavonoids Intake and Cognitive Function in an Italian Cohort.

BACKGROUND: Diet is one of the leading factors contributing to the prevalence of non-communicable diseases, including neurodegenerative disorders. Dietary polyphenols, antioxidant components and anti-inflammatory agents of plant-based foods rich diets have been shown to modulate neuro-inflammation, adult neurogenesis and brain signaling, all of which are linked to cognitive function. As epidemiological evidence is limited and the results are contradictory, the aim of this study is to explore the association between dietary flavonoid intake and cognitive health among the adult population living in the Mediterranean area. METHODS: The demographic and dietary habits of 808 adults living in southern Italy were analyzed. Food frequency questionnaires (FFQs) were used to assess dietary intake. Data on the polyphenol content in foods were estimated using the Phenol-Explorer database. The Short Portable Mental Status Questionnaire was used as a screening tool for cognitive status. Multivariate logistic regression analyses were used to assess the associations. RESULTS: A significant inverse association between higher dietary intake of total flavonoids (Q4 vs. Q1: OR = 0.39, 95% CI: 0.15, 1.00) and impaired cognitive status was found. Among individual subclasses of flavonoids, flavan-3-ols (Q3 vs. Q1: OR = 0.30, 95% CI: 0.11, 0.76), catechins (Q4 vs. Q1: OR = 0.24, 95% CI: 0.08, 0.72), anthocyanins (Q4 vs. Q1: OR = 0.38, 95% CI: 0.14, 1.00) and flavonols (Q3 vs. Q1: OR = 0.30, 95% CI: 0.11, 0.76) were associated with cognitive health. Among individual polyphenols, only quercetin was associated with cognitive health (Q4 vs. Q1: OR = 0.30, 95% CI: 0.10, 0.91). CONCLUSIONS: The results of this study suggest that higher dietary intake of flavonoids may be associated with better cognitive health among adult individuals.

Tea Consumption and Risk of Cancer: An Umbrella Review and Meta-Analysis of Observational Studies.

Tea is one of the most widely consumed beverages, but its association with cancer risk remains controversial and unclear. We performed an umbrella review to clarify and determine the associations between tea consumption and various types of cancer by summarizing and recalculating the existing meta-analyses. Meta-analyses of observational studies reporting associations between tea consumption and cancer risk were searched on PubMed and Embase. Associations found to be statistically significant were further classified into levels of evidence (convincing, suggestive, or weak), based on P value, between-study heterogeneity, prediction intervals, and small study effects. Sixty-four observational studies (case-control or cohort) corresponding to 154 effect sizes on the incidence of 25 types of cancer were included. Forty-three (27.9%) results in 15 different types of cancer were statistically significant. When combining all studies on the same type of cancer, 19 results in 11 different types of cancer showed significant associations with lower risk of gastrointestinal tract organ cancer (oral, gastric, colorectal, biliary tract, and liver cancer), breast cancer, and gynecological cancer (endometrial and ovarian cancer) as well as leukemia, lung cancer, and thyroid cancer. Only the reduced risk of oral cancer in tea-consuming populations (OR = 0.62; 95% CI: 0.55, 0.72; P value < 10-6) was supported by convincing evidence. Suggestive evidence was found for 6 results on biliary tract, breast, endometrial, liver, and oral cancer. To summarize, tea consumption was shown to have protective effects on some types of cancer, particularly oral cancer. More well-designed prospective studies are needed with consideration of other factors that can cause biases.

Specific Dietary (Poly)phenols Are Associated with Sleep Quality in a Cohort of Italian Adults.

BACKGROUND: Diet has been the major focus of attention as a leading risk factor for non-communicable diseases, including mental health disorders. A large body of literature supports the hypothesis that there is a bidirectional association between sleep and diet quality, possibly via the modulation of neuro-inflammation, adult neurogenesis and synaptic and neuronal plasticity. In the present study, the association between dietary total, subclasses of and individual (poly)phenols and sleep quality was explored in a cohort of Italian adults. METHODS: The demographic and dietary characteristics of 1936 adults living in southern Italy were analyzed. Food frequency questionnaires (FFQs) were used to assess dietary intake. Data on the (poly)phenol content in foods were retrieved from the Phenol-Explorer database. The Pittsburg Sleep Quality Index was used to measure sleep quality. Multivariate logistic regression analyses were used to test the associations. RESULTS: A significant inverse association between a higher dietary intake of lignans and inadequate sleep quality was found. Additionally, individuals with the highest quartile of hydroxycinnamic acid intake were less likely to have inadequate sleep quality. When individual compounds were taken into consideration, an association with sleep quality was observed for naringenin and apigenin among flavonoids, and for matairesinol among lignans. A secondary analysis was conducted, stratifying the population into normal weight and overweight/obese individuals. The findings in normal weight individuals showed a stronger association between certain classes of, subclasses of and individual compounds and sleep quality. Notably, nearly all individual compounds belonging to the lignan class were inversely associated with inadequate sleep quality. In the overweight/obese individuals, there were no associations between any dietary (poly)phenol class and sleep quality. CONCLUSIONS: The results of this study suggest that a higher dietary intake of certain (poly)phenols may be associated with better sleep quality among adult individuals.

Diet and Mental Health: Review of the Recent Updates on Molecular Mechanisms.

Over the last decades, there has been a substantial increase in the prevalence of mental health disorders, including an increased prevalence of depression, anxiety, cognitive, and sleep disorders. Diet and its bioactive components have been recognized among the modifiable risk factors, possibly influencing their pathogenesis. This review aimed to summarize molecular mechanisms underlying the putative beneficial effects toward brain health of different dietary factors, such as micro- and macronutrient intake and habits, such as feeding time and circadian rhythm. The role of hormonal homeostasis in the context of glucose metabolism and adiponectin regulation and its impact on systemic and neuro-inflammation has also been considered and deepened. In addition, the effect of individual bioactive molecules exerting antioxidant activities and acting as anti-inflammatory agents, such as omega-3 fatty acids and polyphenols, considered beneficial for the central nervous system via modulation of adult neurogenesis, synaptic and neuronal plasticity, and microglia activation has been summarized. An overview of the regulation of the gut-brain axis and its effect on the modulation of systemic inflammation and oxidative stress has been provided. Finally, the impact of bioactive molecules on inflammation and oxidative stress and its association with brain health has been summarized.

Serum Irisin Concentrations in Severely Inflamed Patients.

Irisin is a recently discovered exercise-induced myokine that has been attributed the role of favoring white-to-brown adipose tissue trans-differentiation. We confirmed in a population-based cohort that irisin serum concentrations are independently correlated with the habitual level of physical activity, but we also observed an independent correlation with serum concentrations of high-sensitivity C-reactive protein (hs-CRP), thus suggesting that inflammation may influence irisin production. In order to investigate the association between irisin and inflammation, we measured serum irisin concentrations in a group of inflamed inpatients. We hypothesized that if an association between irisin and inflammation exists, severely inflamed patients, even though physically inactive, might also exhibit high serum irisin levels. We recruited 40 consecutive markedly inflamed inpatients on the basis of serum CRP levels. Their irisin serum concentrations (Phoenix Europe, Germany) were compared with those obtained in the population-based cohort of the ABCD_2 study (Alimentazione, Benessere Cardiovascolare e Diabete) (ISRCTN15840340). The inflamed patients exhibited higher serum irisin concentrations (median: 6.77 ng/ml; 95% CI for the median: 5.97-7.23) than those observed in the ABCD cohort (median: 5.21 ng/ml; 95% CI for the median: 5.08-5.30; p <0.001). Irisin concentrations were significantly correlated with age (r=-0.44; p <0.001), creatinine (r=-0.35; p <0.05), and fibrinogen (r=0.40; p <0.05) concentrations. No association was observed between irisin, interleukine-6 and tumor necrosis factor alpha. This study confirms the association between inflammation and irisin concentrations. Further studies are needed to understand the mechanisms underlying this association and its possible clinical implications.