Showing papers in "Nutrition Research Reviews in 2020"

The biology of ergothioneine, an antioxidant nutraceutical.

Abstract: Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

Therapeutic and preventive properties of honey and its bioactive compounds in cancer: an evidence-based review.

Abstract: Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.

Single components of botanicals and nature-identical compounds as a non-antibiotic strategy to ameliorate health status and improve performance in poultry and pigs.

Abstract: In the current post-antibiotic era, botanicals represent one of the most employed nutritional strategies to sustain antibiotic-free and no-antibiotic-ever production. Botanicals can be classified either as plant extracts, meaning the direct products derived by extraction from the raw plant materials (essential oils (EO) and oleoresins (OR)), or as nature-identical compounds (NIC), such as the chemically synthesised counterparts of the pure bioactive compounds of EO/OR. In the literature, differences between the use of EO/OR or NIC are often unclear, so it is difficult to attribute certain effects to specific bioactive compounds. The aim of the present review was to provide an overview of the effects exerted by botanicals on the health status and growth performance of poultry and pigs, focusing attention on those studies where only NIC were employed or those where the composition of the EO/OR was defined. In particular, phenolic compounds (apigenin, quercetin, curcumin and resveratrol), organosulfur compounds (allicin), terpenes (eugenol, thymol, carvacrol, capsaicin and artemisinin) and aldehydes (cinnamaldehyde and vanillin) were considered. These molecules have different properties such as antimicrobial (including antibacterial, antifungal, antiviral and antiprotozoal), anti-inflammatory, antioxidant, immunomodulatory, as well as the improvement of intestinal morphology and integrity of the intestinal mucosa. The use of NIC allows us to properly combine pure compounds, according to the target to achieve. Thus, they represent a promising non-antibiotic tool to allow better intestinal health and a general health status, thereby leading to improved growth performance.

The role of meat in the European diet: current state of knowledge on dietary recommendations, intakes and contribution to energy and nutrient intakes and status.

Abstract: The role of meat in the diet has come under scrutiny recently due to an increased public emphasis on providing healthy diets from sustainable food systems and due to health concerns relating to the consumption of red and processed meat. The present review aimed to summarise dietary guidelines relating to meat, actual meat intakes and the contribution of meat to energy and nutrient intakes of children, teenagers and adults in Europe. The available literature has shown that food-based dietary guidelines for most countries recommend consuming lean meat in moderation and many recommend limiting red and processed meat consumption. Mean intakes of total meat in Europe range from 40 to 160 g/d in children and teenagers and from 75 to 233 g/d in adults. Meat contributes to important nutrients such as protein, PUFA, B vitamins, vitamin D and essential minerals such as Fe and Zn; however, processed meat contributes to significant proportions of saturated fat and Na across population groups. While few data are available on diaggregated intakes of red and processed meat, where data are available, mean intakes in adults are higher than the upper limits recommended by the UK Scientific Advisory Committee on Nutrition (70 g/d) and the World Cancer Research Fund (500 g/week). While there are no recommendations for red and processed meat consumption in children and teenagers, intakes currently range from 30 to 76 g/d. The present review provides a comprehensive overview of the role of meat in the European diet which may be of use to stakeholders including researchers, policy makers and the agri-food sector.

Dietary Approaches to Stop Hypertension (DASH): potential mechanisms of action against risk factors of the metabolic syndrome

Abstract: The metabolic syndrome is a cluster of disorders dominated by abdominal obesity, hypertriacylglycerolaemia, low HDL-cholesterol, high blood pressure and high fasting glucose. Diet modification is a safe and effective way to treat the metabolic syndrome. Dietary Approaches to Stop Hypertension (DASH) is a dietary pattern rich in fruits, vegetables and low-fat dairy products, and low in meats and sweets. DASH provides good amounts of fibre, K, Ca and Mg, and limited quantities of total fat, saturated fat, cholesterol and Na. Although DASH was initially designed for the prevention or control of hypertension, using a DASH diet has other metabolic benefits. In the present review, the effect of each dietary component of DASH on the risk factors of the metabolic syndrome is discussed. Due to limited fat and high fibre and Ca content, individuals on the DASH diet are less prone to overweight and obesity and possess lower concentrations of total and LDL-cholesterol although changes in TAG and HDL-cholesterol have been less significant and available evidence in this regard is still inconclusive. Moreover, high amounts of fruit and vegetables in DASH provide great quantities of K, Mg and fibre, all of which have been shown to reduce blood pressure. K, Mg, fibre and antioxidants have also been effective in correcting glucose and insulin abnormalities. Evidence is provided from cross-sectional investigations, cohort studies and randomised controlled trials, and, where available, from published meta-analyses. Mechanisms are described according to human studies and, in the case of a lack of evidence, from animal and cell culture investigations.

Nutraceutical support in heart failure: a position paper of the International Lipid Expert Panel (ILEP).

Abstract: Heart failure (HF) is a complex clinical syndrome that represents a major cause of morbidity and mortality in Western countries. Several nutraceuticals have shown interesting clinical results in HF prevention as well as in the treatment of the early stages of the disease, alone or in combination with pharmacological therapy. The aim of the present expert opinion position paper is to summarise the available clinical evidence on the role of phytochemicals in HF prevention and/or treatment that might be considered in those patients not treated optimally as well as in those with low therapy adherence. The level of evidence and the strength of recommendation of particular HF treatment options were weighed up and graded according to predefined scales. A systematic search strategy was developed to identify trials in PubMed (January 1970 to June 2019). The terms ‘nutraceuticals’, ‘dietary supplements’, ‘herbal drug’ and ‘heart failure’ or ‘left verntricular dysfunction’ were used in the literature search. The experts discussed and agreed on the recommendation levels. Available clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, l-carnitine, d-ribose, carnosine, vitamin D, probiotics, n-3 PUFA and beet nitrates) might be associated with improvements in self-perceived quality of life and/or functional parameters such as left ventricular ejection fraction, stroke volume and cardiac output in HF patients, with minimal or no side effects. Those benefits tended to be greater in earlier HF stages. Available clinical evidence supports the usefulness of supplementation with some nutraceuticals to improve HF management in addition to evidence-based pharmacological therapy.

Expert consensus on low-calorie sweeteners: facts, research gaps and suggested actions.

Abstract: A consensus workshop on low-calorie sweeteners (LCS) was held in November 2018 where seventeen experts (the panel) discussed three themes identified as key to the science and policy of LCS: (1) weight management and glucose control; (2) consumption, safety and perception; (3) nutrition policy. The aims were to identify the reliable facts on LCS, suggest research gaps and propose future actions. The panel agreed that the safety of LCS is demonstrated by a substantial body of evidence reviewed by regulatory experts and current levels of consumption, even for high users, are within agreed safety margins. However, better risk communication is needed. More emphasis is required on the role of LCS in helping individuals reduce their sugar and energy intake, which is a public health priority. Based on reviews of clinical evidence to date, the panel concluded that LCS can be beneficial for weight management when they are used to replace sugar in products consumed in the diet (without energy substitution). The available evidence suggests no grounds for concerns about adverse effects of LCS on sweet preference, appetite or glucose control; indeed, LCS may improve diabetic control and dietary compliance. Regarding effects on the human gut microbiota, data are limited and do not provide adequate evidence that LCS affect gut health at doses relevant to human use. The panel identified research priorities, including collation of the totality of evidence on LCS and body weight control, monitoring and modelling of LCS intakes, impacts on sugar reduction and diet quality and developing effective communication strategies to foster informed choice. There is also a need to reconcile policy discrepancies between organisations and reduce regulatory hurdles that impede low-energy product development and reformulation.

Breast cancer prevention in premenopausal women: role of the Mediterranean diet and its components.

Abstract: Breast cancer (BC) is a growing public health concern in most developed and developing countries. Since an increasing number of patients with BC are diagnosed before the menopause and premenopausal women show a more aggressive phenotype, there is consistent interest in promoting prevention strategies in order to reduce the incidence of BC in the premenopause. The Mediterranean diet (MD) has been reported to have beneficial effect in terms of cancer prevention. This healthy dietary pattern consists primarily of foods having important antioxidant properties along with a favourable fatty acid profile, all associated with a reduced risk of cancer. Due to the large variability in study subject characteristics, the protective role of the MD on BC still remains controversial and studies that have investigated the association between adherence to the MD and risk of BC in premenopausal women are fewer than those in postmenopausal women. In addition, the possibility that the beneficial effects of the MD are due to a single component or might more probably derive from the synergic effects of all components of the MD remains a scantly explored field. Considering the increased risk of recurrence and mortality rate of BC in premenopausal women as compared with postmenopausal women, the aim of the present report is to provide a general overview of the current evidence on the relationship between BC and the MD specifically in premenopausal women, and to emphasise the potential role of the MD as an effective measure to reduce the risk of developing BC in premenopausal women.

Early-life programming of adipose tissue.

Abstract: Worldwide obesity is increasing at an alarming rate in children and adolescents, with the consequent emergence of co-morbidities. Moreover, the maternal environment during pregnancy plays an important role in obesity, contributing to transgenerational transmission of the same and metabolic dysfunction. White adipose tissue represents a prime target of metabolic programming induced by maternal milieu. In this article, we review adipose tissue physiology and development, as well as maternal influences during the perinatal period that may lead to obesity in early postnatal life and adulthood. First, we describe the adipose tissue cell composition, distribution and hormonal action, together with the evidence of hormonal factors participating in fetal/postnatal programming. Subsequently, we describe the critical periods of adipose tissue development and the relationship of gestational and early postnatal life with healthy fetal adipose tissue expansion. Furthermore, we discuss the evidence showing that adipose tissue is an important target for nutritional, hormonal and epigenetic signals to modulate fetal growth. Finally, we describe nutritional, hormonal, epigenetic and microbiome changes observed in maternal obesity, and whether their disruption alters fetal growth and adiposity. The presented evidence supports the developmental origins of health and disease concept, which proposes that the homeostatic system is affected during gestational and postnatal development, impeding the ability to regulate body weight after birth, thereby resulting in adult obesity. Consequently, we anticipate that promoting a healthy early-life programming of adipose tissue and increasing the knowledge of the mechanisms by which maternal factors affect the health of future generations may offer novel strategies for explaining and addressing worldwide health problems such as obesity.

Formation of advanced glycation endproducts in foods during cooking process and underlying mechanisms: a comprehensive review of experimental studies.

Abstract: Advanced glycation endproducts (AGE) are a group of complex and heterogeneous molecules, sharing some common characteristics such as covalent cross-link formation among proteins, the effect of transforming the colour of food products into yellow-brown colours and fluorescence formation. AGE are linked to many diseases including diabetes, renal diseases, CVD, liver diseases, neuro-degenerative and eye disorders, female reproductive dysfunction, and even cancer. AGE are formed endogenously but are also provided from exogenous sources including diet and tobacco. Western diet, rich in processed and/or heat-treated foods, fat and sugar, increases the exposure to AGE. The foods that contain high levels of fat and protein are generally rich in terms of AGE, and are also prone to AGE formation during cooking compared with carbohydrate-rich foods such as vegetables, fruits, legumes and whole grains. The present article aimed to review the literature about the effects of different cooking methods and conditions on the AGE content of food and AGE formation mechanisms using a comprehensive approach.

Metabotyping and its role in nutrition research.

Abstract: Personalised nutrition is at its simplest form the delivery of dietary advice at an individual level. Incorporating response to different diets has resulted in the concept of precision nutrition. Harnessing the metabolic phenotype to identify subgroups of individuals that respond differentially to dietary interventions is becoming a reality. More specifically, the classification of individuals in subgroups according to their metabolic profile is defined as metabotyping and this approach has been employed to successfully identify differential response to dietary interventions. Furthermore, the approach has been expanded to develop a framework for the delivery of targeted nutrition. The present review examines the application of the metabotype approach in nutrition research with a focus on developing personalised nutrition. Application of metabotyping in longitudinal studies demonstrates that metabotypes can be associated with cardiometabolic risk factors and diet-related diseases while application in interventions can identify metabotypes with differential responses. In general, there is strong evidence that metabolic phenotyping is a promising strategy to identify groups at risk and to potentially improve health promotion at a population level. Future work should verify if targeted nutrition can change behaviours and have an impact on health outcomes.

Effects of obesity on cholesterol metabolism and its implications for healthy ageing.

Abstract: The last few decades have witnessed a global rise in the number of older individuals. Despite this demographic shift, morbidity within this population group is high. Many factors influence healthspan; however, an obesity pandemic is emerging as a significant determinant of older people’s health. It is well established that obesity adversely affects several metabolic systems. However, due to its close association with overall cardiometabolic health, the impact that obesity has on cholesterol metabolism needs to be recognised. The aim of the present review is to critically discuss the effects that obesity has on cholesterol metabolism and to reveal its significance for healthy ageing.

Protein intake adequacy among Nigerian infants, children, adolescents and women and protein quality of commonly consumed foods.

Abstract: Protein is important for growth, maintenance and protection of the body. Both adequacy of protein quantity and protein quality in the diet are important to guarantee obtaining all the essential amino acids. Protein-energy malnutrition is widely present in developing countries such as Nigeria and might result in stunting and wasting. Needs for protein differ depending on age and physiological status and are higher during growth, pregnancy and lactation. The present review assessed protein quantity and quality in diets of Nigerian infants, children, adolescents, and pregnant and lactating women. Literature reviews and calculations were performed to assess adequacy of Nigerian protein intake and to examine the Nigerian diet. The digestible indispensable amino acid score was used to calculate protein quality of nine Nigerian staple foods and of a mixture of foods. The Nigerian population had mostly adequate protein intake when compared with the most recent protein recommendations by the FAO (2013) and WHO/FAO/UNU (2007). An important exception was the protein intake of adolescent girls and pregnant and lactating women. Most of the assessed Nigerian plant-based staple foods were of low protein quality and predominantly lacked the amino acid lysine. The addition of animal-source foods can bridge the protein quality gap created by predominance of plant-based foods in the Nigerian diet. The methodology of this review can be applied to other low- and middle-income countries where diets are often plant-based and lack variety, which might influence protein intake adequacy.

Copper physiology in ruminants: trafficking of systemic copper, adaptations to variation in nutritional supply and thiomolybdate challenge.

Abstract: Ruminants are recognised to suffer from Cu-responsive disorders. Present understanding of Cu transport and metabolism is limited and inconsistent across vets and veterinary professionals. There has been much progress from the studies of the 1980s and early 1990s in cellular Cu transport and liver metabolism which has not been translated into agricultural practice. Cu metabolism operates in regulated pathways of Cu trafficking rather than in pools of Cu lability. Cu in the cell is chaperoned to enzyme production, retention within metallothionein or excretion via the Golgi into the blood. The hepatocyte differs in that Cu-containing caeruloplasmin can be synthesised to provide systemic Cu supply and excess Cu is excreted via bile. The aim of the present review is to improve understanding and highlight the relevant progress in relation to ruminants through the translation of newer findings from medicine and non-ruminant animal models into ruminants.

Amino acid transportation, sensing and signal transduction in the mammary gland: key molecular signalling pathways in the regulation of milk synthesis.

Abstract: The mammary gland, a unique exocrine organ, is responsible for milk synthesis in mammals. Neonatal growth and health are predominantly determined by quality and quantity of milk production. Amino acids are crucial maternal nutrients that are the building blocks for milk protein and are potential energy sources for neonates. Recent advances made regarding the mammary gland further demonstrate that some functional amino acids also regulate milk protein and fat synthesis through distinct intracellular and extracellular pathways. In the present study, we discuss recent advances in the role of amino acids (especially branched-chain amino acids, methionine, arginine and lysine) in the regulation of milk synthesis. The present review also addresses the crucial questions of how amino acids are transported, sensed and transduced in the mammary gland.

The potential role of dietary advanced glycation endproducts in the development of chronic non-infectious diseases: a narrative review.

Abstract: Increasing clinical and experimental evidence accumulated during the past few decades supports an important role for dietary advanced glycation endproducts (AGE) in the pathogenesis of many chronic non-infectious diseases, such as type 2 diabetes, CVD and others, that are reaching epidemic proportions in the Western world. Although AGE are compounds widely recognised as generated in excess in the body in diabetic patients, the potential importance of exogenous AGE, mostly of dietary origin, has been largely ignored in the general nutrition audience. In the present review we aim to describe dietary AGE, their mechanisms of formation and absorption into the body as well as their main mechanisms of action. We will present in detail current evidence of their potential role in the development of several chronic non-infectious clinical conditions, some general suggestions on how to restrict them in the diet and evidence regarding the potential benefits of lowering their consumption.

Biomarkers of appetite: is there a potential role for metabolomics?

Abstract: Knowing the biological signals associated with appetite control is crucial for understanding the regulation of food intake. Biomarkers of appetite have been defined as physiological measures that relate to subjective appetite ratings, measured food intake, or both. Several metabolites including amino acids, lipids and glucose were proposed as key molecules associated with appetite control over 60 years ago, and along with bile acids are all among possible appetite biomarker candidates. Additional metabolites that have been associated with appetite include endocannabinoids, lactate, cortisol and β-hydroxybutyrate. However, although appetite is a complex integrative process, studies often investigated a limited number of markers in isolation. Metabolomics involves the study of small molecules or metabolites present in biological samples such as urine or blood, and may present a powerful approach to further the understanding of appetite control. Using multiple analytical techniques allows the characterisation of molecules, such as carbohydrates, lipids, amino acids, bile acids and fatty acids. Metabolomics has proven successful in identifying markers of consumption of certain foods and biomarkers implicated in several diseases. However, it has been underexploited in appetite control or obesity. The aim of the present narrative review is to: (1) provide an overview of existing metabolites that have been identified in human biofluids and associated with appetite control; and (2) discuss the potential of metabolomics to deepen understanding of appetite control in humans.

Neutering in dogs and cats: current scientific evidence and importance of adequate nutritional management.

Abstract: Neutering or spaying is a commonly recommended veterinary procedure. However, veterinarians are often confronted with conflicting findings and differences in concepts regarding practice and proper nutritional management after the procedure. The objective of the present review was to bring to light the most recent literature, summarise it and discuss the findings focusing on the risks and benefits of neutering in dogs and cats, and to determine the appropriate nutritional management for these animals.

Application of nutrient essentiality criteria to dietary carbohydrates.

Abstract: The purpose of the present review is to describe how human physiology at very low carbohydrate intakes relates to the criteria for nutritional essentiality. Although we did not limit ourselves to one particular type or function of carbohydrates, we did primarily focus on glucose utilisation as that function was used to determine the recommended daily allowance. In the general population, the human body is able to endogenously synthesise carbohydrates, and does not show signs of deficiency in the absence of dietary carbohydrates. However, in certain genetic defects, such as glycogen storage disease type I, absence of dietary carbohydrates causes abnormalities that are resolved with dietary supplementation of carbohydrates. Therefore, dietary carbohydrates may be defined as conditionally essential nutrients because they are nutrients that are not required in the diet for the general population but are required for specific subpopulations. Ketosis may be considered a physiological normal state due to its occurrence in infants in addition to at very low carbohydrate intakes. Although sources of dietary carbohydrates can provide beneficial micronutrients, no signs of micronutrient deficiencies have been reported in clinical trials of low-carbohydrate ketogenic diets. Nonetheless, more research is needed on how micronutrient requirements can change depending on the dietary and metabolic context. More research is also needed on the role of dietary fibre during a low-carbohydrate ketogenic diet as the beneficial effects of dietary fibre were determined on a standard diet and several studies have shown beneficial effects of decreasing non-digestible carbohydrates.

Fructose and irritable bowel syndrome.

Abstract: Irritable bowel syndrome (IBS) is a chronic disorder characterised by recurrent abdominal pain or discomfort and transit disturbances with heterogeneous pathophysiological mechanisms. The link between food and gastrointestinal (GI) symptoms is often reported by patients with IBS and the role of fructose has recently been highlighted. Fructose malabsorption can easily be assessed by hydrogen and/or methane breath test in response to 25 g fructose; and its prevalence is about 22 % in patients with IBS. The mechanism of fructose-related symptoms is incompletely understood. Osmotic load, fermentation and visceral hypersensitivity are likely to participate in GI symptoms in the IBS population and may be triggered or worsened by fructose. A low-fructose diet could be integrated in the overall treatment strategy, but its role and implication in the improvement of IBS symptoms should be evaluated. In the present review, we discuss fructose malabsorption in adult patients with IBS and the interest of a low-fructose diet in order to underline the important role of fructose in IBS.

Crosstalk between mitochondrial metabolism and oxidoreductive homeostasis: a new perspective for understanding the effects of bioactive dietary compounds.

Abstract: Mitochondria play an important role in a number of fundamental cellular processes, including energy production, biosynthetic pathways and cellular oxidoreductive homeostasis (redox status), and their dysfunction can lead to numerous pathophysiological consequences. As the biochemical mechanisms orchestrating mitochondrial metabolism and redox homeostasis are functionally linked, mitochondria have been identified as a potential therapeutic target. Consequently, considerable effort has been made to evaluate the efficacy of natural compounds that modulate mitochondrial function. Molecules produced by plants (for example, polyphenols and isothiocyanates) have been shown to modulate mitochondrial metabolism/biogenesis and redox status; however, despite the existence of a functional link, few studies have considered the combined efficacy of these mitochondrial functions. The present review provides a complete overview of the molecular pathways involved in modulating mitochondrial metabolism/biogenesis and redox status. Crosstalk between these critical mechanisms is also discussed, whilst major data from the literature regarding their antioxidant abilities are described and critically analysed. We also provide a summary of recent evidence regarding the ability of several plant-derived compounds to target these mitochondrial functions. An in-depth understanding of the functional link between mitochondrial metabolism/biogenesis and redox status could facilitate the analysis of the biological effects of natural compounds as well as the development of new therapeutic approaches.

Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial.

Abstract: While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48-96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.