Franca Marangoni

Changes of n − 3 and n − 6 fatty acids in plasma and circulating cells of normal subjects, after prolonged administration of 20:5 (EPA) and 22:6 (DHA) ethyl esters and prolonged washout

Eight normal volunteers (four men and four women) were treated with 3 x 1 g capsules of n-3 fatty acid ethyl esters for a period of 18 weeks, followed by a 24 week washout. Fatty acids of plasma, platelets, monocytes and red blood cells were analyzed at 0, 6, 12 and 18 weeks of treatment and at 4, 14 and 24 weeks of washout. During treatment, accumulation of EPA in plasma and cells was almost maximal at 6 weeks, whereas that of DHA reached a peak at 18 weeks. Arachidonic acid declined somewhat at 12 weeks in plasma and more markedly at 18 weeks in red blood cells and monocytes. During washout, EPA returned rapidly toward pretreatment values in all compartments, but it remained significantly higher in plasma and platelets at the end of washout. DHA declined more slowly, maintaining higher than basal values in plasma and platelets and lower than basal in red blood cells, at the end of washout. Rebound increments of AA occurred in plasma. Finally, the plasma levels of AA, but not those of the n-3 fatty acids, were more markedly modified in males than in females. The presented results suggest interactions between circulating fatty acids in the different compartment after n-3 FA administration, and indicate that very long washouts are necessary for a complete recovery from the induced fatty acid modifications.

Dietary intake of fish vs. formulations leads to higher plasma concentrations of n−3 fatty acids

The n−3 fatty acids from fish appear to be more efficacious, in terms of cardioprotection, than equivalent amounts provided as capsules. Volunteers were given, for 6 wk, either 100 g/d of salmon, providing 383 mg of EPA and 544 mg of DHA, esterified in glycerol lipids, or 1 or 3 capsules of fish oil/d, providing 150 mg of EPA and 106 mg of DHA or 450 mg of EPA and 318 mg of DHA, as ethyl esters. Further, we reevaluated data from a previous study carried out with the same design, i.e., with 3 and 6 capsules/d of fish oil, providing 1290 and 2580 mg/d EPA and 960 and 1920 mg/d DHA. Marked increments in plasma EPA and DHA concentrations (μg/mg total lipid) and percentages of total fatty acids were recorded at the end of treatment with either n−3 capsules or salmon. Net increments of EPA and DHA in plasma lipids were linearly and significantly correlated with the dose after capsule administration. Further, increments in plasma EPA and DHA concentration after salmon intake were significantly higher than after administration of capsules. The same increments would be obtained with at least two- and ninefold higher doses of EPA and DHA, respectively, if administered with capsules rather than salmon. We provide experimental evidence that n−3 fatty acids from fish are more effectively incorporated into plasma lipids than when administered as capsules and that increments in plasma concentrations of EPA and DHA given as capsules are linearly correlated with their intakes.

Moderate alcohol use and health: a consensus document.

AIMS The aim of this consensus paper is to review the available evidence on the association between moderate alcohol use, health and disease and to provide a working document to the scientific and health professional communities. DATA SYNTHESIS In healthy adults and in the elderly, spontaneous consumption of alcoholic beverages within 30 g ethanol/d for men and 15 g/d for women is to be considered acceptable and do not deserve intervention by the primary care physician or the health professional in charge. Patients with increased risk for specific diseases, for example, women with familiar history of breast cancer, or subjects with familiar history of early cardiovascular disease, or cardiovascular patients should discuss with their physician their drinking habits. No abstainer should be advised to drink for health reasons. Alcohol use must be discouraged in specific physiological or personal situations or in selected age classes (children and adolescents, pregnant and lactating women and recovering alcoholics). Moreover, the possible interactions between alcohol and acute or chronic drug use must be discussed with the primary care physician. CONCLUSIONS The choice to consume alcohol should be based on individual considerations, taking into account the influence on health and diet, the risk of alcoholism and abuse, the effect on behaviour and other factors that may vary with age and lifestyle. Moderation in drinking and development of an associated lifestyle culture should be fostered.

Polyunsaturated fatty acid concentrations in human hindmilk are stable throughout 12-months of lactation and provide a sustained intake to the infant during exclusive breastfeeding: an Italian study

While a wealth of data on the fatty acid composition of mature human milk has been published, limited information is available on the quantities of individual fatty acids supplied to the suckling infant with maternal milk, through the whole first year of life. Our aim was to qualitatively and quantitatively evaluate the fatty acid composition of human milk from Italian mothers, throughout extended lactation with particular emphasis on the long-chain polyunsaturated fatty acids. We have thus measured the total fat content and the concentrations of major fatty acids by quantitative GLC in pooled breast hindmilk collected from all feedings over 24 h at colostrum, 1, 3, 6, 9 and 12 months in ten mothers recruited after delivery of full-term infants. Total saturated fatty acids progressively increase and total monounsaturated progressively decrease as percentage levels, while among long-chain polyunsaturated fatty acids, percentages of arachidonic acid and docosahexaenoic acid decrease from colostrum up to the third month. Hindmilk total lipids (mg/dl) rise more than twofold up to 3 months, and then remain stable. The amounts (mg/dl) of linoleic acid and alpha-linolenic acid progressively increase, following the trend of total fat, while arachidonic and docosahexaenoic concentrations (mg/dl) remain stable throughout the whole nursing period. Assessment of the intakes per kg body weight shows different trends for the individual major long-chain polyunsaturated fatty acids supplied to the infant from hindmilk during exclusive breast-feeding (3 months). This information may be useful for the evaluation of infant intakes during extended lactation.

Non-pharmacological control of plasma cholesterol levels

The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Earlier smoking habits are associated with higher serum lipids and lower milk fat and polyunsaturated fatty acid content in the first 6 months of lactation

Objective: To investigate the relation between maternal smoking habits, plasma lipids and milk fatty acid (FA) content and composition.Design: Breastfeeding mothers who gave birth to healthy, full-term infants were recruited. Mothers were interviewed on smoking habits, being defined smokers (S) when usually smoking at least five cigarettes per day before pregnancy.Setting: Department of Pediatrics, San Paolo Hospital, Milan, Italy.Subjects: In total, 92 mothers: 61 non-S (NS) and 31 S.Interventions: Pooled hindmilk was collected at the first raise of milk (colostrum stage), 1, 3 and 6 months, and total lipid (TL) content and fatty acid (FA) composition were evaluated. Maternal dietary habits were assessed by a food-frequency questionnaire. Two subsamples (16 NS, 6 S) were investigated after delivery and at 3 months for serum lipids and FA status. At 6 months after delivery, the number of mothers still breastfeeding decreased to 30. Variables were compared using nonparametric tests.Results: In smoking mothers serum levels of triglycerides, cholesterol and low-density lipoproteins were higher, while those of high-density lipoproteins were lower. TL content in breast milk was similar in the two groups just after delivery but higher in milk from NS at 1 month. TL content and FA absolute amounts of linoleic, arachidonic, α-linolenic and docosahexaenoic (DHA) acid in breast milk were lower in S vs NS 1 month after delivery. Also 3 months after delivery, the breast milk of smoking mothers contained less DHA than the breast milk of nonsmoking mothers.Conclusions: Maternal cigarette smoking in early pregnancy is associated with higher plasma lipid levels and lower milk TL and DHA content in the first months of lactation.

n-3 fatty acid ethyl ester administration to healthy subjects and to hypertriglyceridemic patients reduces tissue factor activity in adherent monocytes.

n-3 Fatty acids are known to influence several functions of monocytes, including adhesion, cytokine synthesis, and superoxide generation. Monocytes express tissue factor, a membrane-bound glycoprotein, that acts as a catalyst in the coagulation cascade. In this study we evaluated the effects of administration of n-3 fatty acid ethyl esters to healthy volunteers and to hypertriglyceridemic patients on tissue factor activity (TF activity) in adherent monocytes. n-3 Fatty acids containing 75% eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (ratio of EPA to DHA, 1.34) were administered (3 g/d) to normal volunteers for 18 weeks. In addition, the effects of this treatment were evaluated in 30 hypertriglyceridemic patients for 24 weeks by using a double-blind, placebo-controlled study. TF activity in adherent monocytes was evaluated with a one-stage clotting assay. Plasma and monocyte fatty acid compositions were determined by gas-liquid chromatography. In healthy volunteers, n-3 fatty acids significantly reduced TF activity in adherent monocytes either in the unstimulated condition or after exposure to endotoxin. The inhibitory effect was observed after 12 weeks of treatment and was more pronounced after 18 weeks (> 70%, P < .001 versus baseline). Concomitantly, levels of EPA and DHA increased in plasma and monocyte lipids. Interestingly, after stopping treatment, monocyte TF activity remained inhibited for at least 14 weeks. Treatment with n-3 fatty acids for 24 weeks also resulted in a significant reduction of TF activity in adherent monocytes from hypertriglyceridemic patients (-31% and -40% in unstimulated and endotoxin-stimulated cells; P < .05 versus baseline).(ABSTRACT TRUNCATED AT 250 WORDS)

myc-immortalized microglial cells express a functional platelet-activating factor receptor.

Abstract: The autacoid platelet‐activating factor (PAF) takes part in a complex network of interactions regarding the cellular components of nervous tissues. Efforts aimed at characterizing the effects of PAF in the brain have been recently focalized on neurons because PAF exerts pleiotropic effects on these cells. Less attention has instead been paid to the glial component of the brain. We have used microglial cell lines immortalized from 13‐day‐old mouse embryo brains by a myc‐transducing retrovirus. When exposed to physiological doses of PAF, immortalized microglial cells showed increases in intracellular free calcium concentrations due to release of calcium from internal stores, as well as to extracellular calcium influxes. These profiles of reactivity were independent from the immortalizing process, being observable in primary microglial cultures and in immortalized clones showing different proliferative rates. PAF was also able to induce transient expression of the c‐fos protooncogene in serum‐starved cultures and induced a strong chemotactic response in microglial cells. In contrast with control macrophage cultures, PAF did not promote prostaglandin or leukotriene synthesis in immortalized cells. This was most likely due to the low amount of total arachidonic acid found in immortal microglia, with respect to that observed in freshly isolated cells. Our data suggest that several of the effects observed after PAF stimulation might be independent from PAF‐induced arachidonic acid metabolism. The availability of an in vitro microglial model might now help in studying the proinflammatory effects of PAF, both direct or microglia mediated, in the neural environment.

Recent advances in the biology of n-6 fatty acids

The intensive research carried out in the last 10 years on the unique biological functions of n-3 fatty acids (FA), has promoted comparative investigations on various aspects (metabolic, functional) of the biology of n-6 FA. The involvement of peroxisomes in fatty acid metabolism, initially described for the n-3 acids, has now been shown also for the n-6 FA (formation of 22 carbon delta 4 unsaturated FA, formation of newly identified products of beta-oxidation of arachidonic acid, AA). Additional pathways of AA conversion, beyond the classical eicosanoids, give rise to a series of biologically active products, such as the epoxides, involved in the modulation of vascular functions, through the cytochrome p450 system, and to the AA-ethanolamide, anandamide, an endogenous ligand of the cannabinoid receptors, through a phospholipase-mediated process. Finally, nonenzymatic oxidation products of AA, the isoprostanes, isomers of prostaglandins, also endowed of potent biological activities, are generated both in in vitro-induced lipid oxidation and in vivo, being considered as reliable markers of in vivo oxidative stress. As to the nutritional aspects of the n-6 FA, attention is now paid to the intake of preformed long-chain polyunsaturated FA (PUFA) in the n-6 series, mainly AA, through the diet, in analogy with the intake of the long-chain n-3 FA, in fish-eating populations. The importance of the dietary intake of preformed AA is now recognized in newborns, through maternal milk. The ranges of the intakes of AA in population groups, not currently adequately estimated, appear to be wider than generally assumed, and the elevated intakes in some population groups, in the order of several hundred milligrams per day, may be partly responsible of yet unexplored population-based differences in physiologic variables. Recent research on the functional effects of n-6 FA has confirmed their lipid-lowering effects, which can be observed also in neonates, and has shown that, in cooperation with the n-3, they directly and indirectly contribute to modulate functional parameters at the cellular level, such as receptor function, ion channels, and gene expression. From a nutritional point of view, it is clear that PUFA represent the biologically most active component of dietary fat, and the n-6 are quantitatively the most relevant fraction in our diet. In the light of the diversified activities of n-6 and n-3 PUFA, a correct balance between the various fatty acids is recommended.

The glycemic index of bread and biscuits is markedly reduced by the addition of a proprietary fiber mixture to the ingredients.

BACKGROUND AND AIM Low glycemic index (GI) foods are associated with improved prevention and control of metabolic and cardiovascular diseases (e.g. diabetes and myocardial infarction), even if the impact of their consumption within mixed meals is difficult to predict. Since the availability of wheat based products maintaining taste and texture of traditional ones, but with a low GI, is of relevant nutritional interest, the aim of this study was to assess the effects of a specific proprietary fiber mix, added to the wheat flour used for biscuits and bread preparation, on their GI. METHODS AND RESULTS Fifteen healthy non-diabetic volunteers ate on different days a portion equivalent to 75 g of available carbohydrates, of fiber enriched bread, traditional bread, fiber enriched biscuits and traditional biscuits, or a solution of 75 g of glucose in water. The glycemic index of each product was calculated by relating the area under their glycemic curve to that of glucose. The areas under the glycemic curves of fiber enriched bread and biscuits were lower than those obtained with the equivalent control food. Consequently, a marked reduction of their GI of 21% and 41% for bread and biscuits, respectively, was observed. CONCLUSION The fiber mix added to the flour used in the preparation of biscuits and bread markedly reduces their GI. A similar effect could be expected in other oven-baked foods produced using the same fiber supplementation.