Garlic consumption in relation to colorectal cancer risk and to alterations of blood bacterial DNA.

PURPOSE: Garlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood. METHODS: We conducted a case-control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann-Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence. RESULTS: The OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11-0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus. CONCLUSIONS: The study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.

Cobalamin status is negatively correlated with vascular endothelial-cadherin in vegetarian and vegan women with vitamin B12 deficiency.

Optimal vitamin B12 status is important for vascular health. Vascular endothelial (VE) cadherin is an adherent junction protein involved in the maintenance of a functional endothelium. We hypothesized that vitamin B12 deficiency can negatively affect markers of vascular function, such as VE-cadherin. Within a human intervention study, we explored the possible association between cobalamin status (i.e., vitamin B12, holotranscobalamin, and homocysteine) and VE-cadherin (as marker of vascular health) in vegetarians/vegans (VEG) with B12 deficiency. The associations were evaluated at baseline and after 90-day supplementation with 2000 µg/wk of vitamin B12. On the whole, an inverse association between VE-cadherin and holotranscobalamin (P = .014) and a positive association between VE-cadherin and homocysteine (P = .041) was documented at baseline. VEG women showed higher levels of VE-cadherin compared with VEG men (P = .044), suggesting an increase in endothelial permeability. The intervention with vitamin B12 restored serum vitamin levels and improved the overall cobalamin status, whereas it did not affect VE-cadherin levels. The inverse association between holotranscobalamin and VE-cadherin was also maintained after intervention in women, corroborating the strong correlation between these 2 parameters. The results obtained seem to suggest a possible association between cobalamin status and VE-cadherin even if the intervention with B12 failed to positively affect VE-cadherin levels. Thus, further studies are needed to corroborate these findings and clarify the contribution of a vitamin B12 intervention on VE-cadherin levels in this target population. This trial was registered at ISRCTN registry (ISRCTN75099618).

What Is the Current Direction of the Research on Carotenoids and Human Health? An Overview of Registered Clinical Trials.

Carotenoids have been the object of numerous observational, pre-clinical and interventional studies focused on elucidating their potential impacts on human health. However, the large heterogeneity among the trials, in terms of study duration and characteristics of participants, makes any conclusion difficult to draw. The present study aimed to explore the current carotenoid research trends by analyzing the characteristics of the registered clinical trials. A total of 193 registered trials on ClinicalTrials.gov and ISRCTN were included in the revision. Eighty-three studies were performed with foods, one-hundred-five with food supplements, and five with both. Among the foods tested, tomatoes and tomato-based foods, and eggs were the most studied. Lutein, lycopene, and astaxanthin were the most carotenoids investigated. Regarding the goals, 52 trials were focused on studying carotenoids' bioavailability, and 140 studies investigated the effects of carotenoids on human health. The main topics included eye and cardiovascular health. Recently, the research has focused also on two new topics: cognitive function and carotenoid-gut microbiota interactions. However, the current research on carotenoids is still mostly focused on the bioavailability and metabolism of carotenoids from foods and food supplements. Within this context, the impacts/contributions of food technologies and the development of new carotenoid formulations are discussed. In addition, the research is still corroborating the previous findings on vision and cardiovascular health. Much attention has also been devoted to new research areas, such as the carotenoid-microbiota interactions, which could contribute to explaining the metabolism and the health effects of carotenoids; and the relation between carotenoids and cognitive function. However, for these topics the research is still only beginning, and further studies are need.

Roles and competencies in the nutritional domain for the management of the metabolic diseases and in the hospital setting: A position paper of the Italian College of Academic Nutritionists, MED-49 (ICAN-49).

Epidemiological evidence has confirmed the potential causal relationship between specific dietary factors and non-communicable diseases. However, currently nutrition was shown to be insufficiently integrated into medical education, regardless of the country. Without an adequate nutrition education, it is reasonable to assume that future physicians, as well as other health care professionals, will be not able to provide the highest quality care to patients in preventing and treating non-communicable diseases. Furthermore, the insufficient availability of physicians with specializations in nutrition has posed the basis for the development of non-medical careers in the field of nutrition. The present document was drafting by the Italian College of Academic Nutritionists, MED-49 (ICAN-49), with the aim to provide an overview on the nutritional competency standards covered by several health care professionals (Physicians Clinical Nutrition Specialists, Clinical Dietitians, Professional Clinical Nutrition Specialists, etc) for the prevention of diseases and/or support of pharmacological therapies. The aim of the ICAN 49 is to suggest a major shift in practice opportunities and roles for many nutritionists, especially for the management of the metabolic diseases, and promote a paradigm change: a clinical and educational leadership role for Physician Clinical Nutrition Specialists in the hospital setting.

Effect of Coffee and Cocoa-Based Confectionery Containing Coffee on Markers of DNA Damage and Lipid Peroxidation Products: Results from a Human Intervention Study.

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2'-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups.

Mechanistic aspects of carotenoid health benefits - where are we now?

Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain-related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms - direct or via transcription factors such as NRF2 and NF-κB - and activation of nuclear hormone receptor pathways such as of RAR, RXR or also PPARs, via carotenoid metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

From carotenoid intake to carotenoid blood and tissue concentrations - implications for dietary intake recommendations.

There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels (including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations <1000 nmol/L have been related to increased chronic disease risk, no dietary reference intakes (DRIs) exist. Although high total plasma/serum carotenoid concentrations of up to 7500 nmol/L are achievable after supplementation, a plateauing effect for higher doses and prolonged intake is apparent. In this review and position paper, the current knowledge on carotenoids in serum/plasma and tissues and their relationship to dietary intake and health status is summarized with the aim of proposing suggestions for a "normal," safe, and desirable range of concentrations that presumably are beneficial for health. Existing recommendations are likewise evaluated and practical dietary suggestions are included.

The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine.

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today's knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal.

Oral Supplementation with Sucrosomial Ferric Pyrophosphate Plus L-Ascorbic Acid to Ameliorate the Martial Status: A Randomized Controlled Trial.

Altered martial indices before orthopedic surgery are associated with higher rates of complications and greatly affect the patient's functional ability. Oral supplements can optimize the preoperative martial status, with clinical efficacy and the patient's tolerability being highly dependent on the pharmaceutical formula. Patients undergoing elective hip/knee arthroplasty were randomized to be supplemented with a 30-day oral therapy of sucrosomial ferric pyrophosphate plus L-ascorbic acid. The tolerability was 2.7% among treated patients. Adjustments for confounding factors, such as iron absorption influencers, showed a relevant response limited to older patients (≥ 65 years old), whose uncharacterized Hb loss was averted upon treatment with iron formula. Older patients with no support lost -2.8 ± 5.1%, while the intervention group gained +0.7 ± 4.6% of circulating hemoglobin from baseline (p = 0.019). Gastrointestinal diseases, medications, and possible dietary factors could affect the efficacy of iron supplements. Future opportunities may consider to couple ferric pyrophosphate with other nutrients, to pay attention in avoiding absorption disruptors, or to implement interventions to obtain an earlier martial status optimization at the population level.

Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation.

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran®). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran® were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran™ Phytosome™, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone was found effective thus confirming the ex-vivo results.

Eight-week hempseed oil intervention improves the fatty acid composition of erythrocyte phospholipids and the omega-3 index, but does not affect the lipid profile in children and adolescents with primary hyperlipidemia.

Children affected by primary hyperlipidemia have a high risk of developing cardiovascular diseases (CVDs) during adulthood. Several studies have reported a positive association between the intake of polyunsaturated fatty acids (PUFAs) and improvements in lipid markers and CVD risk. Dietary supplements may represent a potential strategy in the management of hyperlipidemia. In this context, the effectiveness of hempseed oil (HSO) rich in PUFAs (particularly linoleic acid (LA) and α-linolenic acid (ALA)) in the modulation of hyperlipidemia has been poorly investigated. The present pilot study aimed to explore the impact of HSO supplementation on the serum lipid profile and fatty acid (FA) composition of red blood cells (RBCs) in children and adolescents with primary hyperlipidemia. A randomized, 8 week long, parallel dietary intervention study was performed. Thirty-six hyperlipidemic probands (6-16 years) on diet therapy were randomized into two groups: the HSO group, receiving 3 g of HSO providing 1.4 g of LA and 0.7 g/day of ALA, and the control group. Both groups received specific dietary guidelines. Before and after the intervention, blood samples were collected and the serum lipid profile, FA composition of RBCs and omega-3-index were analyzed. Eight weeks of supplementation with HSO significantly (p < .01) reduced the RBC content of total saturated and monounsaturated FAs (-5.02 ±â€¯7.94% and - 2.12 ±â€¯2.23%, respectively), increased the levels of total n-3 and n-6 PUFAs (+1.57 ±â€¯1.96% and + 5.39 ±â€¯7.18%, respectively) and the omega-3 index (+1.18 ±â€¯1.42%), but failed to affect the serum lipid profile compared to the control group. In conclusion, our findings seem to support the contribution of HSO supplementation in improving the RBC phospholipid composition and omega-3 index, while no effect was observed regarding modulation of the lipid profile. Further controlled studies are necessary to achieve a complete understanding of the effects of HSO in the modulation of hyperlipidemia and CVD risk in this and other target groups.

Effect of two different sublingual dosages of vitamin B12 on cobalamin nutritional status in vegans and vegetarians with a marginal deficiency: A randomized controlled trial.

BACKGROUND & AIMS: Vegetarians and vegans are more vulnerable to vitamin B12 deficiency with severe risks of megaloblastic anemia, cognitive decline, neuropathy, and depression. An easy and simple method of supplementation consists of taking one weekly dosage of 2000 µg. However, single large oral doses of vitamin B12 are poorly absorbed. The present research evaluates the ability of two different sublingual dosages of vitamin B12 (350 µg/week vs 2000 µg/week) in improving cyanocobalamin (vitamin B12) nutritional status in vegans and vegetarians with a marginal deficiency. METHODS: A 12-week randomized, double-blind, controlled, parallel intervention trial was performed. Forty subjects with marginal vitamin B12 deficiency were enrolled and randomly divided into two groups: test group Ld (low dose, 350 µg/week) and control group Hd (high dose, 2000 µg/week) vitamin B12 supplementation. Blood samples were collected at baseline and after 15, 30, 60, and 90 days from the intervention for the determination of vitamin B12, related metabolic markers, and blood cell counts. RESULTS: Two-way analysis of variance showed a significant effect of time (P < 0.0001) and of time × treatment interaction (P = 0.012) on serum concentration of vitamin B12 that increased after 90-day supplementation (Ld and Hd) compared to baseline. Both the supplements increased (P < 0.0001, time effect) the levels of holotranscobalamin, succinic acid, methionine and wellness parameter, while decreased (P < 0.0001, time effect) the levels of methylmalonic acid, homocysteine and folate compared to baseline. No difference was observed between groups (Ld vs Hd). No effect was detected for vitamin B6 and blood cell count. CONCLUSIONS: In our experimental conditions, both supplements were able to restore adequate serum concentrations of vitamin B12 and to improve the levels of related metabolic blood markers in subjects with a marginal deficiency. The results support the use of a sublingual dosage of 50 µg/day (350 µg/week) of cobalamin, instead of 2000 µg/week (provided as a single dose), to reach a state of nutritional adequacy of vitamin B12 in this target population. This study was registered at www.isrctn.org as ISRCTN75099618.

Effect of hazelnut on serum lipid profile and fatty acid composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia: A randomized controlled trial.

BACKGROUND & AIM: Regular intake of nuts improves lipid profile and thus reduces the cardiovascular (CV) risk associated with hyperlipidemia. The aim of the study was to investigate the effect of a dietary intervention with hazelnuts (HZNs, 15-30 g/day, depending on patient weight) on serum lipid profile, anthropometric parameters and fatty acids (FAs) composition of erythrocyte phospholipids in children and adolescents with primary hyperlipidemia. METHODS: Eight-week randomized, single blind, controlled, three-arm, parallel-group study. Sixty-six subjects were enrolled and randomized in 3 groups receiving: 1) hazelnuts with skin (HZN+S); 2) hazelnuts without skin (HZN-S); 3) dietary advices for hyperlipidemia only (controls). Before and after intervention, clinical parameters were measured and blood samples were collected for the evaluation of serum lipid levels and phospholipid FA composition of erythrocytes. RESULTS: Two-way ANOVA showed a significant effect of time on serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)/LDL-C ratio and non-HDL-C (p ≤ 0.001), but not of treatment and time × treatment interaction. In particular, HZN+S and HZN-S significantly reduced the concentrations of LDL-C and increased HDL-C/LDL-C ratio. HZNs also had a favorable impact on FAs composition of erythrocyte phospholipids, as demonstrated by time × treatment interaction, with a significant increase of monounsaturated fatty acids (MUFAs) (p = 0.008) and MUFAs/saturated fatty acids (SFAs) ratio (p = 0.002) with respect to the control group. CONCLUSIONS: For the first time, we documented a positive effect of HZN consumption on lipid profile and FA composition of erythrocyte phospholipids in children with primary hyperlipidemia. Further studies are encouraged to better define HZN impact on the markers of CV risk in this population. The trial was registered under ISRCTN.com, ID no. ISRCTN12261900.

In vitro assessment of the ability of probiotics, blueberry and food carbohydrates to prevent S. pyogenes adhesion on pharyngeal epithelium and modulate immune responses.

Group A streptococci (GAS) cause 20-30% of pediatric pharyngitis episodes, which are a major cause of ambulatory care visits. Therefore, a strategy to prevent GAS dissemination in children could significantly benefit public healthcare. Contextually, we assessed the possibility of employing alternative food-grade strategies to be used with the oral probiotic L. helveticus MIMLh5 for the prevention of pharyngeal infections. First, we demonstrated through an antagonism-by-exclusion assay that guaran may potentially prevent S. pyogenes adhesion on pharyngeal cells. Subsequently, we showed that an anthocyanin-rich fraction extracted from wild blueberry (BbE) exerts anti-inflammatory effects on the human macrophage cell line U937. Finally, we showed that BbE reduces interferon-ß expression in MIMLh5-stimulated murine dendritic cells, resulting in a reduction in the pro-inflammatory cytokines IL-12 and TNF-α. In conclusion, this proof-of-concept study indicates that different food-grade strategies may be concomitantly adopted to potentially prevent GAS colonization and modulate local immune defences.

Coffee Consumption and Oxidative Stress: A Review of Human Intervention Studies.

Research on the potential protective effects of coffee and its bioactives (caffeine, chlorogenic acids and diterpenes) against oxidative stress and related chronic disease risk has been increasing in the last years. The present review summarizes the main findings on the effect of coffee consumption on protection against lipid, protein and DNA damage, as well as on the modulation of antioxidant capacity and antioxidant enzymes in human studies. Twenty-six dietary intervention studies (involving acute and chronic coffee intake) have been considered. Overall, the results suggest that coffee consumption can increase glutathione levels and improve protection against DNA damage, especially following regular/repeated intake. On the contrary, the effects of coffee on plasma antioxidant capacity and antioxidant enzymes, as well as on protein and lipid damage, are unclear following both acute and chronic exposure. The high heterogeneity in terms of type of coffee, doses and duration of the studies, the lack of information on coffee and/or brew bioactive composition, as well as the choice of biomarkers and the methods used for their evaluation, may partially explain the variability observed among findings. More robust and well-controlled intervention studies are necessary for a thorough understanding of the effect of coffee on oxidative stress markers in humans.

Nutritional therapy for nonalcoholic fatty liver disease.

Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of liver disease in western countries. NAFLD is the hepatic manifestation of metabolic syndrome and may progress to cirrhosis and hepatocellular carcinoma. To date, there are no approved drugs for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification, including increase of physical activity and the adoption of a healthy eating behavior. In this regard, studies aimed to elucidate the effect of dietary interventions and the mechanisms of action of specific food bioactives are urgently needed. The present review tries to summarize the most recent data evidencing the effects of nutrients and dietary bioactive compounds intake (i.e., long-chain PUFA, Vitamin E, Vitamin D, minerals and polyphenols) on the modulation of molecular mechanisms leading to fat accumulation, oxidative stress, inflammation and liver fibrosis in NAFLD patients.

Anthocyanins and phenolic acids from a wild blueberry (Vaccinium angustifolium) powder counteract lipid accumulation in THP-1-derived macrophages.

PURPOSE: Blueberries are a rich source of anthocyanins (ACNs) and phenolic acids (PA), which are hypothesized to protect against development of atherosclerosis. The present study examined the effect of an ACN- and PA-rich fractions, obtained from a wild blueberry powder, on the capacity to counteract lipid accumulation in macrophages derived from monocytic THP-1 cells. In addition, we tested the capacity of pure ACNs and their metabolites to alter lipid accumulation. METHODS: THP-1-derived macrophages were incubated with fatty acids (500 µM oleic/palmitic acid, 2:1 ratio) and different concentrations (from 0.05 to 10 µg mL(-1)) of ACN- and PA-rich fractions, pure ACN standards (malvidin, delphinidin and cyanidin 3-glucoside), and metabolites (syringic, gallic and protocatechuic acids). Lipid accumulation was quantified with the fluorescent dye Nile red. RESULTS: Lipid accumulation was reduced at all concentrations of the ACN-rich fraction tested with a maximum reduction at 10 µg mL(-1) (-27.4%; p < 0.0001). The PA-rich fraction significantly reduced the lipid accumulation only at the low concentrations from 0.05 µg mL(-1) to 0.3 µg mL(-1), with respect to the control with fatty acids. Supplementation with pure ACN compounds (malvidin and delphinidin-3-glucoside and its metabolic products (syringic and gallic acid)) reduced lipid accumulation especially at the low concentrations, while no significant effect was observed after cyanidin-3-glucoside and protocatechuic acid supplementation. CONCLUSIONS: The results demonstrated a potential role of both the ACN- and PA-rich fractions and single compounds in the lipid accumulation also at concentrations close to that achievable in vivo.

High fat diet subverts hepatocellular iron uptake determining dysmetabolic iron overload.

Increased serum ferritin associated with mild hepatic iron accumulation, despite preserved upregulation of the iron hormone hepcidin, is frequently observed in patients with dysmetabolic overload syndrome (DIOS). Genetic factors and Western diet represent predisposing conditions, but the mechanisms favoring iron accumulation in DIOS are still unclear. Aims of this study were to assess the effect a high-fat diet (HFD) on hepatic iron metabolism in an experimental model in rats, to further characterize the effect of free fatty acids on iron metabolism in HepG2 hepatocytes in vitro, and to assess the translational relevance in patients with fatty liver with and without iron accumulation. Despite decreased uptake of dietary iron, rats fed HFD accumulated more hepatic iron than those fed regular diet, which was associated with steatosis development. Hepatic iron accumulation was paralleled by induction of ferritin, in the presence of preserved upregulation of hepcidin, recapitulating the features of DIOS. HFD was associated with increased expression of the major iron uptake protein Transferrin receptor-1 (TfR-1), consistently with upregulation of the intracellular iron sensor Iron regulated protein-1 (IRP1). Supplementation with fatty acids induced TfR-1 and IRP1 in HepG2 hepatocytes, favoring intracellular iron accumulation following exposure to iron salts. IRP1 silencing completely abrogated TfR-1 induction and the facilitation of intracellular iron accumulation induced by fatty acids. Hepatic TfR-1 mRNA levels were upregulated in patients with fatty liver and DIOS, whereas they were not associated with liver fat nor with inflammation. In conclusion, increased exposure to fatty acids subverts hepatic iron metabolism, favoring the induction of an iron uptake program despite hepatocellular iron accumulation.

Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human Caco-2 intestinal cells.

Intestinal inflammation is a natural process crucial for the maintenance of gut functioning. However, abnormal or prolonged inflammatory responses may lead to the onset of chronic degenerative diseases, typically treated by means of pharmacological interventions. Dietary strategies for the prevention of inflammation are a safer alternative to pharmacotherapy. Anthocyanins and other polyphenols have been documented to display anti-inflammatory activity. In the present study, three bioactive fractions (anthocyanin, phenolic, and water-soluble fractions) were extracted from a wild blueberry powder. The Caco-2 intestinal model was used to test the immunomodulatory effect of the above fractions. Only the anthocyanin-rich fraction reduced the activation of NF-κB, induced by IL-1ß in intestinal epithelial Caco-2 cells. Specifically, concentrations of 50 and 100 µg mL(-1) decreased NF-κB activation by 68.9 and 85.2%, respectively (p ≤ 0.05). These preliminary results provide further support for the role of food bioactives as potential dietary anti-inflammatory agents.

Modulation of plasma antioxidant levels, glutathione S-transferase activity and DNA damage in smokers following a single portion of broccoli: a pilot study.

BACKGROUND: Broccoli is a rich source of bioactive compounds (i.e. glucosinolates, carotenoids, vitamin C and folate) that may exert an antioxidant effect and reduce oxidative damage. The objective of this pilot study was to investigate the effect of broccoli consumption on carotenoids, vitamin C and folate absorption, glutathione S-transferase (GST) activity, and oxidatively induced DNA damage in male smokers. METHODS: Ten healthy subjects consumed a single portion of steamed broccoli (250 g) with cooked pasta. Blood was drawn at baseline and at 3, 6 and 24 h from consumption. RESULTS: Broccoli significantly (P ≤ 0.01) increased plasma level of vitamin C and folate (+35% and 70%, respectively) at 3 h, and ß-carotene (+8%) at 6 h. A modulation of GST activity occurred in plasma 6 h after broccoli consumption. A significant (P ≤ 0.01) reduction of the levels of H2O2-induced DNA damage (-18%) was observed in blood mononuclear cells 24 h after broccoli intake in GSTM1 positive, but not in GSTM1 null subjects. CONCLUSION: One portion of broccoli increased plasma antioxidant levels, modulated plasma GST activity and improved cell resistance against H2O2-induced DNA damage in healthy smokers. These results support the importance of consuming fruit and vegetable regularly.