Vitamin D Fortification of Consumption Cow's Milk: Health, Nutritional and Technological Aspects. A Multidisciplinary Lecture of the Recent Scientific Evidence.

Vitamin D is essential in assuring bone health at all stages of life, but its non-skeletal effects are also essential: This vitamin impacts the physiology of the immune system, skeletal muscles and adipose tissue, glucose metabolism, skin, cardiovascular and reproductive systems, neuro-cognitive functions and cell division. The incidence of vitamin D deficiency is widespread worldwide, at any age, in young and healthy subjects, as well as in pregnant women and the elderly population, due to several factors, including inadequate sunlight exposure, skin pigmentation and coverage, adiposity, lifestyle and low dietary intakes. To overcome this problem, the fortification of foods that are consumed on a daily basis, such as milk, is strongly advisable. This opinion paper aims to discuss, in a multidisciplinary way, the current evidence supporting the importance of vitamin D in health and disease and the role of milk as an optimal carrier of this vitamin, to promote adequate intakes, highlighting its unique physico-chemical characteristics linked to both fat globule membrane and casein micelle structure. Moreover, it addresses the impact of industrial processing and storage of consumption milk on the stability of these structures, thus in determining vitamin D bioavailability and the achievement of adequate intakes.

Phytosterols, Cholesterol Control, and Cardiovascular Disease.

The use of phytosterols (or plant sterols) for the control of plasma cholesterol concentrations has recently gained traction because their efficacy is acknowledged by scientific authorities and leading guidelines. Phytosterols, marketed as supplements or functional foods, are formally classified as food in the European Union, are freely available for purchase, and are frequently used without any health professional advice; therefore, they are often self-prescribed, either inappropriately or in situations in which no significant advantage can be obtained. For this reason, a panel of experts with diverse medical and scientific backgrounds was convened by NFI-Nutrition Foundation of Italy-to critically evaluate and summarize the literature available on the topic, with the goal of providing medical doctors and all health professionals useful information to actively govern the use of phytosterols in the context of plasma cholesterol control. Some practical indications to help professionals identify subjects who will most likely benefit from the use of these products, optimizing the therapeutic outcomes, are also provided. The panel concluded that the use of phytosterols as supplements or functional foods to control Low Density Lipoprotein (LDL) cholesterol levels should be preceded by the assessment of some relevant individual characteristics: cardiovascular risk, lipid profile, correct understanding of how to use these products, and willingness to pay for the treatment.

Nutraceuticals and functional foods for the control of plasma cholesterol levels. An intersociety position paper.

Current evidence shows that cholesterol management either reduces the likelihood of cardiovascular disease (CVD) or slows down its progression. Hence, it is important that all health professionals make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and positive lifestyle changes to the use of functional foods, food supplements, and drugs. This review examines the effect of the most frequently occurring cholesterol-lowering substances in functional foods or in supplements across Europe, namely plant sterols and stanols, monacolin K found in red yeast rice, berberine and beta-glucans. We conclude that currently available supplements and functional foods can effectively reduce plasma LDL cholesterol levels by about 5 to 25%, either alone or in combination. Suitable candidates for these products are mainly individuals at low absolute cardiovascular risk at a young age or according to classic algorithms. Of note, despite being freely available for purchase, these products should be used following shared agreement between the physician and the patient ("concordance").

The polyunsaturated fatty acid balance in kidney health and disease: A review.

Epidemiological studies show that circulating polyunsaturated fatty acids contribute to preserve renal function. In renal disease states there is generally a lack of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) as measured in biological samples, but despite intense research for more than 30 years, it is still unclear how and to what extent their supplementation would benefit kidney disorders. Studies evaluating the n-6 series and the kidney are less frequent. The last compilation of clinical trials with n-3 LCPUFA supplements focusing on renal function and damage dates back to 2012. We here discuss n-3 and n-6 fatty acids in relation to the kidney summarizing single- and double blind randomized controlled trials performed between 2012 and 2016. Nine were sub-studies/post-hoc analyses of previous parent trials. Twelve out of the twenty trials reported on fatty acid profile or fatty acid species. Factors that may explain inconsistent results obtained after supplementation with the n-3 LCPUFA EPA and DHA in kidney disease are discussed such as baseline levels determining response, drug interaction. The need of evaluating fatty acid status before and after intervention is emphasized, to match changes in outcome measure with changes of any fatty acid potentially involved.

Fatty Acids in Nephrotic Syndrome and Chronic Kidney Disease.

The role of fatty acids (FAs) in inflammation and in the related chronic diseases has been demonstrated. However, there is a lack of consistent and agreed knowledge about the role of FA profile and renal physiology and pathology, most articles focusing on the effect of polyunsaturated FAs supplementation, without considering the impact of basal FA metabolism on the efficacy of the supplementation. Here, we have summarized the specific literature concerning the assessment of circulating FA in 2 renal diseases, namely nephrotic syndrome and chronic kidney disease, also under hemodialytic treatment, and have received the most significant contributions in the last years. The effects of changes of FA profile and metabolism and the possible involvement of polyunsaturated FA metabolites in raising and modulating inflammation are discussed.

Palm oil and human health. Meeting report of NFI: Nutrition Foundation of Italy symposium.

The use of palm oil by the food industry is increasingly criticized, especially in Italy, for its purported negative effects on human health and environment. This paper summarizes the conclusions of a Symposium on this topic, gathered by the Nutrition Foundation of Italy, among experts representing a number of Italian Medical and Nutritional Scientific Societies. Toxicological and environmental issues were not considered. Participants agreed that: no evidence does exist on the specific health effects of palm oil consumption as compared to other saturated fatty acids-rich fats; the stereospecific distribution of saturated fatty acids in the triacylglycerol molecule of palm oil limits their absorption rate and metabolic effects; in agreement with International guidelines, saturated fatty acids intake should be kept <10% of total energy, within a balanced diet; within these limits, no effect of palm oil consumption on human health (and specifically on CVD or cancer risk) can be foreseen.

Omega-6 and omega-3 polyunsaturated fatty acid levels are reduced in whole blood of Italian patients with a recent myocardial infarction: the AGE-IM study.

OBJECTIVE: The relationship between whole blood fatty acids and myocardial infarction (MI) risk has not been analyzed in detail, especially in Mediterranean countries. The AGE-IM (Acidi Grassi Essenziali e Infarto Miocardico) study was planned to examine the relationships between MI, whole blood fatty acids and the diet in an Italian cohort. METHODS: 119 Patients with a recent MI and 103 control subjects were enrolled in the study. The whole blood fatty acid composition was determined; information on anthropometrics, biochemical parameters and blood pressure values were also obtained. Diet composition was assessed using a validated food frequency questionnaire from 86 cases and 72 controls. RESULTS: Total PUFA, omega-6 and omega-3 PUFA (as percentage of whole blood fatty acids) were significantly lower in MI patients than in matched controls, whereas saturated and monounsaturated fatty acids were higher in cases. MI infarction risk significantly and steadily decreased with increasing levels of total PUFA (OR: 0.14) and of total omega-6 and omega-3 (OR: 0.15 and 0.37, respectively). No correlation was identified between dietary fats and MI risk or between whole blood fatty acid levels and dietary nutrients and fats. CONCLUSION: Percentage levels of total PUFA, total omega-3 PUFA and total omega-6 PUFA are lower in MI patients than in matched control subjects in the AGE-IM cohort. These data support a favorable association not only of whole blood percentage levels of total omega-3, but also of total omega-6, with cardiovascular risk.

Membrane composition and cellular responses to fatty acid intakes and factors explaining the variation in response.

The lipid membrane bilayer undergoes continuous changes, and its lipid composition is both adaptive and highly varied, with substantial molecular variety. The balance of dietary fats, namely saturated versus unsaturated, and polyunsaturated fatty acids (PUFA) of the n-6 series versus those of the n-3 series, may change membrane composition thus affecting membrane order, intracellular signaling processes, and gene expression. As a consequence, changes in the production of both lipid and peptide mediators influencing the individual adaptive responses take place. More than that of all the other fatty acids, the n-3 PUFA composition of cell membranes depends on their dietary intake. n-3 PUFA levels in cell membranes are related to both inflammatory and immune diseases, possibly by downregulating the expression of genes involved in their synthesis and maybe the pathogenesis of processes associated with the disease itself. The interindividual variability of DNA sequences involved in the synthesis of long-chain PUFA may explain differences in responses to their dietary contribution in regulating the risk of disease. Lifestyle factors (such as smoking and alcohol consumption) may in turn negatively impact PUFA metabolism. Accordingly, different amounts of dietary PUFA may be necessary to meet the requirements for these nutrients in development and disease prevention on an individual basis.

n-3 fatty acids: functional differences between food intake, oral supplementation and drug treatments.

n-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for mammalian cells that are not able to synthesise de novo their precursor, α-linolenic acid, and may only partially convert it to eicosapentaenoic acid (EPA) and to a very small extent to docosahexaenoic acid (DHA). For this reason, nutritional guidelines for cardiovascular prevention recommend regular fish consumption (approximately two portions per week) in order to increase the intake of the n-3 PUFAs EPA and DHA, mainly referring to fatty fish, living in cold waters, usually very rich in these fatty acids. However, the indication to consume fish regularly is unlikely to be sufficient to ensure that patients with documented coronary heart diseases receive the daily amount of EPA+DHA (ca. 1g) necessary for effective secondary prevention of the disease. This has prompted the development of pharmaceutical formulations both for dietary supplementation and for therapeutic administration, based on several dietary sources, containing greatly variable amounts of EPA and DHA, often with different availabilities. Critical knowledge of these characteristics allows the selection of the best approach in order to optimise the n-3 PUFA supply in various individuals.

Clinical pharmacology of n-3 polyunsaturated fatty acids: non-lipidic metabolic and hemodynamic effects in human patients.

A high dietary intake of n-3 long chain polyunsaturated fatty acids (PUFA), eicosapentaenoic and docosahexaenoic acids, is associated with a reduced incidence of coronary events. Supplementation with pharmacological doses of the same may improve survival in patients with previous myocardial infarction and established heart failure. Such protective effects may be explained by the action of n-3 PUFA on systemic inflammation, hypertension, endothelial dysfunction, thrombosis, cardiac arrhythmias, heart rate variability and atherosclerotic plaque instability, which are involved in the pathogenesis of these clinical conditions. In this short paper we will review the evidence in support of these pleiotropic effects of n-3 fatty acids.

Fatty acid profiles of blood lipids in a population group in Tibet: correlations with diet and environmental conditions.

The aim of this study was to compare blood fatty acid profiles of two population groups: Italian and Tibetan, differing with regard to ethnic, life style and environmental aspects. Additionally the collection of two staple foods provided the opportunity to analyze typical Tibetan dishes. A new, simple, rapid, and substantially non invasive method for fatty acid (FA) analysis of blood lipids was applied to healthy Italian (n=14) and Tibetan (n=13) subjects. Blood drops obtained from the ear lobe of Tibetans or the fingertip of Italians were adsorbed by a special strip of paper and processed for fatty acid analysis. The fatty acid profiles of the two groups are different, and environmental factors, such as dietary fats and altitudes of Milan, Italy (a low altitude site), and Lhasa, Tibet (a high altitude site) appear to contribute to these differences. More specifically, in Ti-betans higher levels of monounsaturated fatty acids, including the 22 and 24 carbon molecules, were found. This appears to be derived mainly from locally consumed fats (mustard seed oil), and are associated with lower levels of total polyunsaturated fatty acids and higher levels of selected omega 3 fatty acids, when compared to the Italians. These relatively higher levels of monounsaturated fatty acids may also indicate means of adaptation to local prooxidant conditions. The observed differences in blood fatty acid profiles in Tibetans vs. Italians appear to result both from dietary factors and adaptation to local environmental conditions such as the high altitude of the Tibetan location.

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.

Double-blind, placebo-controlled trial comparing effects of supplementation of two micronutrient sprinkles on fatty acid status in Cambodian infants.

BACKGROUND: Infants in developing countries require early dietary interventions to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To what extent these interventions may affect the fatty acid (FA) status is still unknown. OBJECTIVES: To examine and compare the effects of 2 micronutrient "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3, mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian infants. METHODS: A total of 204 infants age 6 mo and living in Kompong Chhnang Province, Cambodia, were randomly assigned to receive daily supplementation of MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in powder form as sprinkles. At the end of the intervention period, FAs in the range of 16 to 24 C were determined in blood drops absorbed on a strip collected from 182 subjects, and values among the 3 intervention subgroups and those of 21 Italian 18-mo-old, normal-growing infants as the reference group were compared. RESULTS: At the end of the supplementation trial, higher levels of the 2 essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3) were found in the MMN group. No differences occurred for the major longer chain derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid approached those of Italian infants, and in addition their alpha-linolenic acid levels were improved. Cambodian infants, mostly still breast-fed through the second year of life, showed significantly higher levels of long-chain derivatives of both the n-6 and the n-3 series compared with Italians. CONCLUSIONS: Supplementation with iron, folic acid, zinc and vitamins was associated with an increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants versus placebo, without significant changes in the concentrations of their longer chain derivatives, resulting in a FA status closer to Italian counterparts for the essential polyunsaturated FA levels. The iron/folate-treated infants showed no differences compared with the other 2 groups. Studies are needed to differentiate the potential effects of the supplemented micronutrients on the FA status.

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 (microg/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.