Fabio Galvano

Dietary Strategies to Counteract the Effects of Mycotoxins: A Review

We reviewed various dietary strategies to contain the toxic effects of mycotoxins using antioxidant compounds (selenium, vitamins, provitamins), food components (phenolic compounds, coumarin, chlorophyll and its derivatives, fructose, aspartame), medicinal herbs and plant extracts, and mineral and biological binding agents (hydrated sodium calcium aluminosilicate, bentonites, zeolites, activated carbons, bacteria, and yeast). Available data are primarily from in vitro studies and mainly focus on aflatoxin B1, whereas much less information is available about other mycotoxins. Compounds with antioxidant properties are potentially very efficacious because of their ability to act as superoxide anion scavengers. Interesting results have been obtained by food components contained in coffee, strawberries, tea, pepper, grapes, turmeric, Fava tonka, garlic, cabbage, and onions. Additionally, some medicinal herbs and plant extracts could potentially provide protection against aflatoxin B1 and fumonisin B1. Activated carbons, hydrated sodium calcium aluminosilicate, and bacteria seem to effectively act as binders. We conclude that dietary strategies are the most promising approach to the problem, considering their limited or nil interference in the food production process. Nevertheless, a great research effort is necessary to verify the in vivo detoxification ability of the purposed agents, their mode of action, possible long-term drawbacks of these detoxification-decontamination procedures, and their economical and technical feasibility.

Occurrence and Stability of Aflatoxin M1 in Milk and Milk Products: A Worldwide Review

This paper critically reviews data from the literature since 1980 on the occurrence of aflatoxin M1 (AFM1) in human and animal milk, infant formula, dried milk, cheese, and yogurt. Furthermore the influence of storage and processing of milk and milk products on the occurrence and stability of AFM1 is reviewed. It is concluded that (i) efforts in attempting to harmonize already existing regulatory limits for AF in foods and feed should be made; (ii) further investigations should verify the influence of milk storage and processing on AFM1 occurrence to avoid uncertainty in actual practice; (iii) the occurrence of AFM1 in animal milks and milk products is widespread, although, considering the current scientific fund, contamination levels do not seem to be a serious health hazard; however, further studies should provide accurate scientific information concerning the human health hazard related to long-term exposure to subchronic AF levels; (iv) monitoring programs should be more extensive and frequent; and (v) in tropical and subtropical countries, especially in African countries, a particular attention should be used in monitoring milk and milk products other than those from cows, as well as feed. Furthermore, extensive and periodic surveys on the occurrence of AF and their metabolite in human breast milk should be performed, since a serious health hazard to mother, fetus, or infants could occur.

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

Background Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal. Objectives To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies. Methods A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients. Results Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression and healthy subjects. Conclusions The use of omega-3 PUFA is effective in patients with diagnosis of MDD and on depressive patients without diagnosis of MDD.

L -Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis — A Randomized and Controlled Clinical Trial

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabolism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitines supplementation on regression of NASH.METHODS:In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores.RESULTS:At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), γ-glutamyl-transpeptidase (γ-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-α (P=0.000), and histological scores (P=0.000).CONCLUSIONS:L-carnitine supplementation to diet is useful for reducing TNF-α and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH.

Cyanidin-3- O -β-Glucoside and Protocatechuic Acid Exert Insulin-Like Effects by Upregulating PPARγ Activity in Human Omental Adipocytes

OBJECTIVE Insulin resistance (IR) represents an independent risk factor for metabolic, cardiovascular, and neoplastic disorders. Preventing/attenuating IR is a major objective to be reached to preserve population health. Because many insulin-sensitizing drugs have shown unwanted side effects, active harmless compounds are sought after. Dietary anthocyanins have been demonstrated to ameliorate hyperglycemia and insulin sensitivity. This study aimed at investigating whether cyanidin-3-O-β-glucoside (C3G) and its metabolite protocatechuic acid (PCA) might have a role in glucose transport activation in human omental adipocytes and 3T3-L1 cells. RESEARCH DESIGN AND METHODS In cells treated with 50 µmol/L C3G and 100 µmol/L PCA, [3H]-2-deoxyglucose uptake, GLUT4 translocation by immunoblotting, adiponectin secretion, and peroxisome proliferator–activated receptor-γ (PPARγ) activation by enzyme-linked immunosorbent assay kits were evaluated. Parallel experiments were carried out in murine adipocyte 3T3-L1. To define the role of PPARγ in modulating polyphenol effects, small interfering RNA technique and PPARγ antagonist were used to inhibit transcription factor activity. RESULTS C3G and PCA increased adipocyte glucose uptake (P < 0.05) and GLUT4 membrane translocation (P < 0.01). Significant increases (P < 0.05) in nuclear PPARγ activity, as well as in adiponectin and GLUT4 expressions (P < 0.01), were also shown. It is interesting that PPARγ inhibition counteracted the polyphenol-induced adiponectin and GLUT4 upregulations, suggesting a direct involvement of PPARγ in this process. CONCLUSIONS Our study provides evidence that C3G and PCA might exert insulin-like activities by PPARγ activation, evidencing a causal relationship between this transcription factor and adiponectin and GLUT4 upregulation. Dietary polyphenols could be included in the preventive/therapeutic armory against pathological conditions associated with IR.

Survey of the occurrence of aflatoxin M1 in dairy products marketed in Italy: second year of observation

During 1996, 161 samples of milk, 92 samples of dry milk for infant formula and 120 samples of yoghurt, were randomly collected in supermarkets and drug stores in four big Italian cities, and checked for aflatoxin M1 (AFM1) by immunoaffinity column extraction and HPLC. AFM1 was detected in 125 (78%) of milk samples (ranging from < 1 ng/l to 23.5 ng/l; mean level: 6.28 ng/l), in 49 (53%) of dry milk samples (ranging from < 1 ng/l to 79.6 ng/kg; mean level: 32.2 ng/kg) and in 73 (61%) of yoghurt samples (ranging from < 1 ng/kg to 32.1 ng/kg; mean level: 9.06 ng/kg). Altogether, only four samples of dry milk were over the legal limits established by the EC in 1999. It is concluded that during 1996, despite the widespread occurrence of AFM1, mean contamination levels in dairy products sold in Italy were not a serious human health hazard.

DETOXIFICATION METHODS OF AFLATOXINS. A REVIEW.

Detoxification of aflatoxin contaminated foods and feeds is a current problem, as aflatoxins are highly carcinogenic and capable of passing unaltered through metabolic processes and accumulating in the tissues (seriously jeopardizing human and animal health). Although numerous detoxification methods have been tested, none seems able to fulfill the efficacy, safety, safeguarding of nutritional elements and costs requisites of a detoxification process. This paper critically reviews the main chemical detoxification methods and the latest approach to the problem using added sorbents capable of adsorbing aflatoxins.

Cyanidin and cyanidin 3-O-β-D-glucoside as DNA cleavage protectors and antioxidants

Anthocyanins, colored flavonoids, are water-soluble pigments present in the plant kingdom; in fact they are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. Present in beans, fruits, vegetables and red wines, considerable amounts of anthocyanins are ingested as constituents of the human diet (180–215 mg daily). There is now increasing interest in thein vivo protective function of natural antioxidants contained in dietary plants against oxidative damage caused by free radical species. Recently, the antioxidant activity of phenolic phytochemicals, has been investigated. Since the antioxidant mechanism of anthocyanin pigments is still controversial, in the present study we evaluated the effects of cyanidin and cyanidin 3-O-β-D-glucoside on DNA cleavage, on their free radical scavenging capacity and on xanthine oxidase activity. Cyanidin and cyanidin 3-O-β-D-glucoside showed a protective effect on DNA cleavage, a dose-dependent free radical scavenging activity and significant inhibition of XO activity. These effects suggest that anthocyanins exhibit interesting antioxidant properties, and could therefore represent a promising class of compounds useful in the treatment of pathologies where free radical production plays a key role.

Nut consumption on all-cause, cardiovascular, and cancer mortality risk: a systematic review and meta-analysis of epidemiologic studies

BACKGROUND Recent pooled analyses supported a beneficial impact of nut consumption on health, but to our knowledge, whether nuts are associated with overall decreased mortality has not been previously reviewed. OBJECTIVES We aimed to systematically review prospective studies that explored the effects of nut consumption on all-cause, cardiovascular disease (CVD), and cancer mortality and quantify the size effect through a meta-analysis. We also reviewed confounding factors associated with nut consumption to assess potential clustering with other covariates. DESIGN We searched PubMed and EMBASE for studies published up to June 2014. Study characteristics, HRs, and 95% CIs were generated on the basis of quantitative analyses. A dose-response analysis was performed when data were available. RESULTS Seven studies for all-cause mortality, 6 studies for CVD mortality, and 2 studies for cancer mortality were included in the meta-analysis with a total of 354,933 participants, 44,636 cumulative incident deaths, and 3,746,534 cumulative person-years. Nut consumption was associated with some baseline characteristics such as lower body mass index and smoking status as well as increased intakes of fruit, vegetables, and alcohol. One-serving of nuts per week and per day resulted in 4% (RR: 0.96; 95% CI: 0.93, 0.98) and 27% (RR: 0.73; 95% CI: 0.60, 0.88) decreased risk of all-cause mortality, respectively, and decreased risk of CVD mortality [RR: 0.93 (95% CI: 0.88, 0.99) and 0.61 (95% CI: 0.42, 0.91), respectively]. Effects were primarily driven by decreased coronary artery disease deaths rather than stroke deaths. Nut consumption was also associated with decreased risk of cancer deaths when highest compared with lowest categories of intake were compared (RR: 0.86; 95% CI: 0.75, 0.98), but no dose-effect was shown. CONCLUSION Nut consumption is associated with lower risk of all-cause, CVD, and cancer mortality, but the presence of confounding factors should be taken into account when considering such findings.

Protocatechuic Acid and Human Disease Prevention: Biological Activities and Molecular Mechanisms

Epidemiological evidence has shown that a high dietary intake of vegetables and fruit rich in polyphenols is associated with a reduction of cancer incidence and mortality from coronary heart disease. The healthy effects associated with polyphenol consumption have made the study of the mechanisms of action a matter of great importance. In particular, the hydroxybenzoic acid protocatechuic acid (PCA) has been eliciting a growing interest for several reasons. Firstly, PCA is one of the main metabolites of complex polyphenols such as anthocyanins and procyanidins that are normally found at high concentrations in vegetables and fruit, and are absorbed by animals and humans. Since the daily intake of anthocyanins has been estimated to be much higher than that of other polyphenols, the nutritional value of PCA is increasingly recognized. Secondly, a growing body of evidence supports the concept that PCA can exert a variety of biological effects by acting on different molecular targets. It has been shown that PCA possesses antioxidant, anti-inflammatory as well as antihyperglycemic and neuroprotective activities. Furthermore, PCA seems to have chemopreventive potential because it inhibits the in vitro chemical carcinogenesis and exerts pro-apoptotic and anti-proliferative effects in different tissues. This review is aimed at providing an up-dated and comprehensive report on PCA giving a special emphasis on its biological activities and the molecular mechanisms of action most likely responsible for a beneficial role in human disease prevention.