Milk fat globule membrane and its polar lipids: reviewing preclinical and clinical trials on cognition.

In most parts of the world, life expectancy is increasing thanks to improved healthcare, public health policies, nutrition, and treatment. This increase in lifespan is often not accompanied by an increase in health span, which severely affects people as they age. One notable consequence of this is the increasing prevalence of neurodegenerative diseases such as mild cognitive impairment, dementia, and Alzheimer's disease. Therefore, dietary and pharmaceutical measures must be taken to reduce the burden of such pathologies. Among the different types of nutrients found in the diet, lipids and especially polar lipids are very important for cognition due to their abundance in the brain. Amid the most studied sources of polar lipids, milk fat globule membrane (MFGM) stands out as it is abundant in industrial by-products such as buttermilk. In this narrative review, we discuss the latest, i.e. less than five years old, scientific evidence on the use of MFGM and its polar lipids in cognitive neurodevelopment in early life and their potential effect in preventing neurodegeneration in old age. We conclude that MFGM is an interesting, abundant and exploitable source of relatively inexpensive bioactive molecules that could be properly formulated and utilized in the areas of neurodevelopment and cognitive decline. Sufficiently large randomized controlled trials are required before health-related statements can be made. However, research in this area is progressing rapidly and the evidence gathered points to biological, health-promoting effects.

Fostering wellbeing and healthy lifestyles through conviviality and commensality: Underappreciated benefits of the Mediterranean Diet.

Among the often-neglected features of healthy diets, such as the Mediterranean diet, is the preparation and sharing of food, which is (or was) done in a social environment governed by social rules rather than by time constraints. The act of eating is a daily human practice that is not limited to meeting nutritional and energy needs but also involves a constructed social dimension of sharing meals that is part of the process of human civilization and food cultures around the world. In this narrative review, we outline the importance of conviviality in steering part of the health effects of healthful diets, with special reference to the Mediterranean diet. Based on the available evidence, we suggest that public health initiatives (such as nudging to promote conviviality) to improve people's eating and living styles, reduce loneliness, and promote the sharing of meals could improve health. Interventions aimed at directly increasing/improving people's social relationships, networking, and conviviality can-directly and indirectly-improve both psychological well-being and general health.

Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Background: Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods: A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results: Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s-1; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions: Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.

Correction: Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Correction for 'Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis' by Alicia Saz-Lara et al., Food Funct., 2024, https://doi.org/10.1039/D3FO05061K.

Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model.

SCOPE: Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism. METHODS AND RESULTS: Mice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis. An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl. CONCLUSION: HT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed.

Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs.

Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules in a diet rich in vegetables and fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) are biogenetically and morphologically comparable to mammalian EVs and transport bioactive molecules, including miRNAs. However, the biological functions of PDEVs are not fully understood, and standard isolation protocols are lacking. Here, PDEVs were isolated from four foods with a combination of ultracentrifugation and size exclusion chromatography, and evaluated as vehicles for enhanced transport of synthetic miRNAs. In addition, the role of food-derived EVs as carriers of dietary (poly)phenols and other secondary metabolites was investigated. EVs from broccoli, pomegranate, apple, and orange were efficiently isolated and characterized. In all four sources, 4 miRNA families were present in tissues and EVs. miRNAs present in broccoli and fruit-derived EVs showed a reduced RNase degradation and were ferried inside exposed cells. EVs transfected with a combination of ath-miR159a, ath-miR162a-3p, ath-miR166b-3p, and ath-miR396b-5p showed toxic effects on human cells, as did natural broccoli EVs alone. PDEVs transport trace amounts of phytochemicals, including flavonoids, anthocyanidins, phenolic acids, or glucosinolates. Thus, PDEVs can act as nanocarriers for functional miRNAs that could be used in RNA-based therapy.

Frequency and machine learning predictors of severe depressive symptoms and suicidal ideation among university students.

AIMS: Prospective studies on the mental health of university students highlighted a major concern. Specifically, young adults in academia are affected by markedly worse mental health status than their peers or adults in other vocations. This situation predisposes to exacerbated disability-adjusted life-years. METHODS: We enroled 1,388 students at the baseline, 557 of whom completed follow-up after 6 months, incorporating their demographic information and self-report questionnaires on depressive, anxiety and obsessive-compulsive symptoms. We applied multiple regression modelling to determine associations - at baseline - between demographic factors and self-reported mental health measures and supervised machine learning algorithms to predict the risk of poorer mental health at follow-up, by leveraging the demographic and clinical information collected at baseline. RESULTS: Approximately one out of five students reported severe depressive symptoms and/or suicidal ideation. An association of economic worry with depression was evidenced both at baseline (when high-frequency worry odds ratio = 3.11 [1.88-5.15]) and during follow-up. The random forest algorithm exhibited high accuracy in predicting the students who maintained well-being (balanced accuracy = 0.85) or absence of suicidal ideation but low accuracy for those whose symptoms worsened (balanced accuracy = 0.49). The most important features used for prediction were the cognitive and somatic symptoms of depression. However, while the negative predictive value of worsened symptoms after 6 months of enrolment was 0.89, the positive predictive value is basically null. CONCLUSIONS: Students' severe mental health problems reached worrying levels, and demographic factors were poor predictors of mental health outcomes. Further research including people with lived experience will be crucial to better assess students' mental health needs and improve the predictive outcome for those most at risk of worsening symptoms.

Plant-Based Diets Reduce Blood Pressure: A Systematic Review of Recent Evidence.

PURPOSE OF REVIEW: Accumulating data on the consumption of plant-based diets and their impact on blood pressure indicate a consensus that plant-based diets are linked to reduced blood pressure. The suggested mechanisms of action are manifold, and, in this systematic review, we provide a summary of the most recent findings on plant-based diets and their impact on blood pressure, along with an analysis of the molecules accountable for the observed effects. RECENT FINDINGS: The overwhelming majority of intervention studies demonstrate that plant-based diets result in lower blood pressure readings when compared to diets that are based on animal products. The various mechanisms of action are being clarified. The data discussed in this systematic review allow us to conclude that plant-based diets are associated with lower blood pressure and overall better health outcomes (namely, on the cardiovascular system) when compared to animal-based diets. The mechanisms of action are being actively investigated and involve many macro- and micronutrients plentiful in plants and the dishes prepared with them.

Dietary Fatty Acids and Inflammation: Focus on the n-6 Series.

Among the polyunsaturated fatty acids (PUFAs), those belonging to the n-3 (or ω3) series, i.e., alpha-linolenic (ALA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids have been studied for decades from a pharma-nutritional viewpoint, namely in relation to cardiovascular health. More recent research is focusing on n-6 PUFAs, e.g., linoleic acid (LA), whose levels of consumption are much higher than those of n-3 and that cannot be used "pharmacologically". Perhaps because of this, the biological actions of n-6 PUFAs have not been investigated in details as those of their n-3 counterparts. However, an increasing body of evidence underscores their healthful actions on the cardiovascular system. Among the critiques to n-6 PUFAs and, particularly, LA there is the fact that they are precursors of pro-inflammatory eicosanoids. Hence, the hypothesis posits that we should reduce their intakes precisely to avoid increasing systemic, low-grade inflammation, i.e., one of the major etiological agents in degenerative diseases. In this narrative review, we address the issue of whether n-6 PUFAs are indeed pro-inflammatory, we discuss the most recent evidence of their role(s) in human health and prognosis, and we conclude that adequate intakes of n-6 fatty acids are associated with better cardiovascular health and child development.

Milk fat globule membrane concentrate as a nutritional supplement prevents age-related cognitive decline in old rats: A lipidomic study of synaptosomes.

Aging is associated with a decline in cognitive abilities, mainly in memory and executive functioning. A similar but premature deterioration in cognitive capacities is the hallmark of mild cognitive impairment, Alzeimer's disease and dementia. The biochemical mechanisms that cause these neurodegenerative disorders are poorly understood. However, some evidence suggests that insufficient dietary intakes of some phospholipids could impact on brain function and increase the risk of future cognitive impairment and dementia. We evaluated the cognitive and biochemical effects of supplementation with a milk fat globule membrane (MFGM) concentrate in aged rats. We observed that, compared to control animals, MFGM supplemented rats showed enhanced spatial working memory, but both groups exhibited similar reference spatial learning and emotional memory abilities. No significant differences between BDNF levels in the hippocampus and frontal cortex of treated rats as compared to controls were found. The nootropic effects observed were accompanied by significant changes in the lipid composition of synaptic membranes. MFGM supplementation increased the levels of EPA and DHA acids as well as the plasmalogens content in the synaptosomes isolated from the hippocampus (Synapt-HP) and the frontal cortex (Synapt-FC). In addition enhanced levels of phosphatidyl serine (PS), particularly PS(18:1/18:1), and phosphatidyl inositol (PI) molecular species were observed in Synapt-HP and Synapt-FC of treated animals.Lipidomic analysis also revealed greater concentration of phosphatidyl ethanolamine (PE) molecular species containing very long-chain fatty acids and PE plasmenyls in Synapt-HP as well as an increase of the SM content in Synapt-FC from the MFGM group. Although further studies are needed to confirm the underlying mechanism (individual or synergistic), these results suggest that MFGM supplementation could be employed as a dietary implement to restore the proper cerebral concentration of some bioactive lipids and prevent or slow the progression of age-related cognitive impairment.

The ultra-processed foods hypothesis: a product processed well beyond the basic ingredients in the package.

The NOVA classification of food items has become increasingly popular and is being used in several observational studies as well as in nutritional guidelines and recommendations. We propose that there is a need for this classification and its use in the formulation of public health policies to be critically discussed and re-appraised. The terms 'processing' and 'ultra-processing', which are crucial to the NOVA classification, are ill-defined, as no scientific, measurable or precise reference parameters exist for them. Likewise, the theoretical grounds of the NOVA classification are unclear and inaccurate. Overall, the NOVA classification conflicts with the classic, evidence-based evaluation of foods based on composition and portion size because NOVA postulates that the food itself (or how much of it is eaten) is unimportant, but rather that dietary effects are due to how the food is produced. We contend that the NOVA system suffers from a lack of biological plausibility so the assertion that ultra-processed foods are intrinsically unhealthful is largely unproven, and needs further examination and elaboration.

Hydroxytyrosol decreases EDNRA expression through epigenetic modification in colorectal cancer cells.

The Mediterranean diet (MD) is one of the healthiest ones and is associated with a lower incidence of cardiovascular and cerebrovascular diseases as well as cancer. Extra virgin olive oil (EVOO) is probably the most idiosyncratic component of this diet. EVOO has been attributed with many healthful effects, which may be due to its phenolic components, e.g. including hydroxytyrosol (HT). Recent studies suggest that EVOO and HT have molecular targets in human tissues and modulate epigenetic mechanisms. DNA methylation is one of the most studied epigenetic mechanisms and consists of the addition of a methyl group to the cytosines of the DNA chain. Given the purported health effects of EVOO (poly)phenols, we analyzed the changes induced by HT in DNA methylation, in a colorectal cancer cell line. Caco-2 cells were treated with HT for one week or with the demethylating agent 5'-azacytidine for 48 h. Global DNA methylation was assessed by ELISA. DNA bisulfitation was performed and Infinium Methylation EPIC BeadChips were used to analyze the specific methylation of CpG sites. We show an increase in global DNA methylation in Caco-2 cells after HT treatment, with a total of 32,141 differentially methylated (CpGs DMCpGs). Interestingly, our analyses revealed the endothelin receptor type A gene (EDNRA) as a possible molecular target of HT. In summary, we demonstrate that cellular supplementation with HT results in a specific methylome map and propose a potential gene target for HT.

Animal- and Plant-Based Protein Sources: A Scoping Review of Human Health Outcomes and Environmental Impact.

Dietary proteins are indispensable to human nutrition. In addition to their tissue-building function, they affect body composition and regulate various metabolic pathways, as well as satiety and immune system activity. Protein use can be examined from a quantitative or qualitative viewpoint. In this scoping review, we compare animal- and plant-based protein sources in terms of their effects on human health and the environment. We conclude that the consumption of vegetable protein sources is associated with better health outcomes overall (namely, on the cardiovascular system) than animal-based product use. The healthier outcomes of vegetable protein sources dovetail with their lower environmental impact, which must be considered when designing an optimal diet. Indeed, the health of the planet cannot be disjointed from the health of the human being. Future research will clarify the mechanisms of action underlying the health effects of plant-based protein sources when compared with animal sources, fostering better agronomic practices and influencing public health in a direction that will benefit both the planet and its inhabitants.

Science and claims of the arena of food bioactives: comparison of drugs, nutrients, supplements, and nutraceuticals.

The scientific community and lay press are participating in a heated debate over the usefulness of food bioactives when used as dietary supplements. This debate often ignores hard scientific evidence and the outcomes of proper research in either direction. Some propose that health claims should be awarded based on classic pharmacological parameters of efficacy and safety. Others suggest that a botanical history of their safe use and basic biological evidence in support of their effects should suffice to allow their marketing. The current regulatory impasse does not help solve this conundrum. It is time for scientists, regulators, and legislators to open an epistemological debate on the appropriateness of using classic pharmacological methods for substances that do not share the usual drug profiles and which are, consequently, difficult to study in humans.

Therapeutic potential of broccoli-derived extracellular vesicles as nanocarriers of exogenous miRNAs.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression. The wide-ranging biological activities of microRNAs stimulated research on disease mechanisms and is suggesting appealing therapeutic applications. When unprotected, miRNAs suffer from rapid degradation and appropriate strategies need to be developed to improve their therapeutic potential. Since the first observation of miRNAs being naturally transported by extracellular vesicles (EVs), the latter have been proposed as specific transport means for drug delivery, conferring stability and increasing resistance against RNase degradation. However, a standard, reproducible, and cost-effective protocol for EV isolation is lacking. Here, the use of broccoli-derived EVs as a therapeutic vehicle for extracellular RNA drug delivery was assessed. EVs were isolated from broccoli, combining ultracentrifugation and size exclusion chromatography methodology. Caco-2 cells were exposed to isolated EVs loaded with exogenous miRNAs and cellular viability was tested. The miRNAs were taken up by this intestinal cell line. Our results show that broccoli EVs can be efficiently isolated, characterized, and loaded with exogenous miRNAs, leading to toxicity in caco-2 cells. Because the pharmaceutical industry is searching for novel drug delivery nanovesicles with intrinsic properties such as low immunogenicity, stability to the gastrointestinal tract, ability to overcome biological barriers, large-scale production, cost-effectiveness, etc., broccoli-isolated nanovesicles might be suitable candidates for future pharmacological applications. We propose broccoli as a natural source of EVs, which are capable of transporting exogenous miRNAs with potential therapeutic effects and suggest that appropriate toxicological and randomized controlled trials as well as patent applications are warranted.

Educating health care professionals on the importance of proper diets. An online course on nutrition, health, and sustainability.

The majority of university curricula for health professionals does not incorporate courses on human nutrition and its links with human and planetary health. This primarily applies to medical and pharmacy students, who have important counselling roles and are at the forefront of public health. To address this important issue, EIT Food recently launched an online course on nutrition, health, and sustainability. Learners were able to provide feedback on the course through an end-of-course survey and social interaction on the FutureLearn platform. The course was very well attended worldwide and received positive feedback from learners. A total of 3,858 students enrolled in the program, from >20 countries. Learners reported inadequate training on nutrition in their own curriculum and indicated they would use key insights from the course to inform their own practice. This report provides insights from the course, which could be used as guidance for future initiatives.

Nutri-Epigenetic Effects of Phenolic Compounds from Extra Virgin Olive Oil: A Systematic Review.

Dietary components can induce epigenetic changes through DNA methylation, histone modification, and regulation of microRNAs (miRNAs). Studies of diet-induced epigenetic regulation can inform anticipatory trials and fine-tune public health guidelines. We systematically reviewed data on the effect of extra virgin olive oil (EVOO) and its phenolic compounds (OOPCs) on the epigenetic landscape. We conducted a literature search using PubMed, Scopus, and Web of Science databases and scrutinized published evidence. After applying selection criteria (e.g., inclusion of in vitro, animal, or human studies supplemented with EVOO or its OOPCs), we thoroughly reviewed 51 articles, and the quality assessment was performed using the revised Cochrane risk of bias tool. The results show that both EVOO and its OOPCs can promote epigenetic changes capable of regulating the expression of genes and molecular targets involved in different metabolic processes. For example, oleuropein (OL) may be an epigenetic regulator in cancer, and hydroxytyrosol (HT) modulates the expression of miRNAs involved in the development of cancer, cardiovascular, and neurodegenerative diseases. We conclude that EVOO and its OOPCs can regulate gene expression by modifying epigenetic mechanisms that impact human pathophysiology. A full elucidation of the epigenetic effects of EVOO and its OOPCs may contribute to developing different pharma-nutritional strategies that exploit them as epigenetic agents. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42022320316.