Failure of dietary fat intake to promote fat oxidation: a factor favoring the development of obesity.

Seven young men spent three nights and 2 d in a respiration chamber where their rates of energy expenditure and substrate oxidation were continuously measured by indirect calorimetry. During the first 24 h they ingested a mixed maintenance diet containing 35% of calories as fat. An additional amount of 106 +/- 6 g fat/24 h (means +/- SD) was added to this diet during the following 36 h. The fat supplement (987 +/- 55 kcal/d) did not alter 24-h energy expenditure (2783 +/- 232 vs 2820 +/- 284 kcal/d) and failed to promote the use of fat as a metabolic fuel (fat oxidation 1032 +/- 205 vs 1042 +/- 205 kcal/d). The overall energy balance was closely correlated with the fat balance (r = 0.96, p less than 0.001) but not with the carbohydrate balance (r = -0.12, NS). These data indicate that substantial imbalances between intake and oxidation are much more likely for fat than for carbohydrate.

Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis.

Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.

Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group.

New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance- and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, ≥1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults who have acute or chronic diseases need even more dietary protein (ie, 1.2-1.5 g/kg body weight/d). Older people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73m(2)), but who are not on dialysis, are an exception to this rule; these individuals may need to limit protein intake. Protein quality, timing of ingestion, and intake of other nutritional supplements may be relevant, but evidence is not yet sufficient to support specific recommendations. Older people are vulnerable to losses in physical function capacity, and such losses predict loss of independence, falls, and even mortality. Thus, future studies aimed at pinpointing optimal protein intake in specific populations of older people need to include measures of physical function.

Réduction de la consommation de sel: une mesure importante de santé publique en Suisse. [Reducing dietary salt intake: an important public health strategy in Switzerland]

La consommation actuelle de sel (chlorure de sodium) est très supérieure aux besoins physiologiques (1,5 g par jour, soit environ 550 mg par jour de sodium) dans la plupart des pays (> 8 g par jour). Les principales sources de sel sont les pains, les fromages, les produits dérivés de la viande et les plats précuisinés. En moyenne, une consommation élevée de sel est associée à une pression artérielle plus élevée. En Suisse, un adulte sur trois souffre d'hypertension artérielle. La moitié des accidents vasculaires cérébraux et des maladies cardiaques ischémiques sont attribuables à une pression artérielle trop élevée. L'Office fédéral de la santé publique conduit actuellement une stratégie visant à diminuer la consommation de sel dans la population suisse à moins de 5 g par jour sur le long terme (Salz Strategie 2008-2012). [Abstract] Current dietary salt (sodium chloride) intake largely exceeds physiological needs (about 1.5 g salt per day, or 550 mg sodium per day) in most countries (> 8 g salt per day). The main sources of dietar salt intake are breads, cheeses, products derived from meat and ready-to-eat meals. On average, a high-salt diet is associated with higher blood pressure levels. In Switzerland, one out of three adults suffers from arterial hypertension. Half of cerebrovascular events and ischaemic cardiac events are attributable to elevated blood pressure. The Swiss Federal Office of Public Health is currently running a strategy aiming at reducing dietary salt intake in the Swiss population to less than 5 g per day on the long run (Salz Strategie 2008-2012).

Under-reporting of dietary energy intake in five populations of the African diaspora.

Studies on the role of diet in the development of chronic diseases often rely on self-report surveys of dietary intake. Unfortunately, many validity studies have demonstrated that self-reported dietary intake is subject to systematic under-reporting, although the vast majority of such studies have been conducted in industrialised countries. The aim of the present study was to investigate whether or not systematic reporting error exists among the individuals of African ancestry (n 324) in five countries distributed across the Human Development Index (HDI) scale, a UN statistic devised to rank countries on non-income factors plus economic indicators. Using two 24 h dietary recalls to assess energy intake and the doubly labelled water method to assess total energy expenditure, we calculated the difference between these two values ((self-report - expenditure/expenditure) × 100) to identify under-reporting of habitual energy intake in selected communities in Ghana, South Africa, Seychelles, Jamaica and the USA. Under-reporting of habitual energy intake was observed in all the five countries. The South African cohort exhibited the highest mean under-reporting ( - 52·1% of energy) compared with the cohorts of Ghana ( - 22·5%), Jamaica ( - 17·9%), Seychelles ( - 25·0%) and the USA ( - 18·5%). BMI was the most consistent predictor of under-reporting compared with other predictors. In conclusion, there is substantial under-reporting of dietary energy intake in populations across the whole range of the HDI, and this systematic reporting error increases according to the BMI of an individual.

Compliance with the Swiss Society for Nutrition's dietary recommendations in the population of Geneva, Switzerland: a 10-year trend study (1999-2009).

The trends in compliance with the dietary recommendations of the Swiss Society for Nutrition in the Geneva population were assessed for the period from 1999 to 2009 using 10 cross-sectional, population-based surveys (Bus Santé study) with a total of 9,320 participants aged 35 to 75 years (50% women). Dietary intake was assessed using a self-administered, validated, semi-quantitative food frequency questionnaire. Trends were assessed by logistic regression adjusting for age, smoking status, education, and nationality using survey year as the independent variable. After excluding participants with extreme intakes, the percentage of participants with a cholesterol intake of <300 mg/day increased from 40.8% in 1999 to 43.6% in 2009 for men (multivariate-adjusted P for trend=0.04) and from 57.8% to 61.4% in women (multivariate-adjusted P for trend=0.06). Calcium intake >1 g/day decreased from 53.3% to 46% in men and from 47.6% to 40.7% in women (multivariate-adjusted P for trend<0.001). Adequate iron intake decreased from 68.3% to 65.3% in men and from 13.3% to 8.4% in women (multivariate-adjusted P for trend<0.001). Conversely, no significant changes were observed for carbohydrates, protein, total fat (including saturated, monounsaturated, and polyunsaturated fatty acids), fiber, and vitamins D and A. We conclude that the quality of the Swiss diet did not improve between 1999 and 2009 and that intakes deviate substantially from expert recommendations for health promotion and chronic disease risk reduction.

FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

Swiss survey on salt intake: main results

[Contents] 1. Executive summary. 2. Introduction. 3. Methods. 4. Main results. 4.1. Participants. 4.2. Estimation of dietary salt intake using 24-hour urine collection. 4.3. Blood pressure and hypertension. 4.4. Anthropometric data (Body weight, height and body mass index BMI; prevalence of overweight and obesity; waist circumference;...). 4.5. Knowledge and behaviors towards salt. 5. Discussion.

Influence of sodium intake on circulating levels of neuropeptide Y.

Neuropeptide Y (NPY) is present in the adrenal medulla, in sympathetic neurons as well as in the circulation. This peptide not only exerts a direct vasoconstrictor effect, but also potentiates the vasoconstriction evoked by norepinephrine and sympathetic nerve stimulation. The vasoconstrictor effect of norepinephrine is also enhanced by salt loading and reduced by salt depletion. The purpose of this study was therefore to assess whether there exists a relationship between dietary sodium intake and the levels of circulating NPY. Uninephrectomized normotensive rats were maintained for 3 weeks either on a low, a regular or a high sodium intake. On the day of the experiment, plasma levels of NPY and catecholamines were measured in the unanesthetized animals. There was no significant difference in plasma norepinephrine and epinephrine levels between the 3 groups of rats. Plasma NPY levels were the lowest (65.4 +/- 8.8 fmol/ml, n-10, Mean +/- SEM) in salt-restricted and the highest (151.2 +/- 25 fmol/ml, n-14, p less than 0.02) in salt-loaded animals. Intermediate values were obtained in rats kept on a regular sodium intake (117.6 +/- 20.1 fmol/ml). These findings are therefore compatible with the hypothesis that sodium balance might to some extent influence blood pressure regulation via changes in circulating NPY levels which in turn modify blood pressure responsiveness.

Dietary folates and cancer risk in a network of case-control studies.

Background Folate deficiency leads to DNA damage and inadequate repair, caused by a decreased synthesis of thymidylate and purines. We analyzed the relationship between dietary folate intake and the risk of several cancers. Patients and methods The study is based on a network of case-control studies conducted in Italy and Switzerland in 1991-2009. The odds ratios (ORs) for dietary folate intake were estimated by multiple logistic regression models, adjusted for major identified confounding factors. Results For a few cancer sites, we found a significant inverse relation, with ORs for an increment of 100 μg/day of dietary folate of 0.65 for oropharyngeal (1467 cases), 0.58 for esophageal (505 cases), 0.83 for colorectal (2390 cases), 0.72 for pancreatic (326 cases), 0.67 for laryngeal (851 cases) and 0.87 for breast (3034 cases) cancers. The risk estimates were below unity, although not significantly, for cancers of the endometrium (OR = 0.87, 454 cases), ovary (OR = 0.86, 1031 cases), prostate (OR = 0.91, 1468 cases) and kidney (OR = 0.88, 767 cases), and was 1.00 for stomach cancer (230 cases). No material heterogeneity was found in strata of sex, age, smoking and alcohol drinking. Conclusions Our data support a real inverse association of dietary folate intake with the risk of several common cancers.

Alimentation et hypertension artérielle: au-delà du sel de table [Nutrition and hypertension: more than table salt].

The role of dietary sodium intake in the development, and its impact on the treatment, of hypertension are well recognized. However, many other nutritional compounds have been shown, or are believed, to influence blood pressure. Some compounds, such as caffeine and fructose, may raise arterial blood pressure, whereas others might lower arterial blood pressure, for example garlic, dark chocolate, fibers and potassium. In this article, we review several alimentary compounds and their (hypothesized) mechanisms of action, as well as the available evidence supporting a role of these compounds in the "non pharmacological" treatment and prevention of hypertension.

METABOLIC EFFECTS OF DIETARY PROTEINS

SUMMARY :Non-alcoholic fatty liver disease (NAFLD) is characterized by an elevated intra- hepatocellular lipid (IHCL) concentration (> 5%). The incidence of NAFLD is frequently increased in obese patients, and is considered to be the hepatic component of the metabolic syndrome. The metabolic syndrome, also characterized by visceral obesity, altered glucose homeostasis, insulin resistance, dyslipidemia, and high blood pressure, represents actually a major public health burden. Both dietary factors and low physical activity are involved in the development of the metabolic syndrome. ln animals and healthy humans, high-fat or high-fructose diets lead to the development of several features of the metabolic syndrome including increased intrahepatic lipids and insulin resistance. ln contrast the effects of dietary protein are less well known, but an increase in protein intake has been suggested to exert beneficial effects by promoting weight loss and improving glucose homeostasis in insulin-resistant patients. Increased postprandial thermogenesis and enhanced satiety after protein ingestion may be both involved. The effects of dietary protein on hepatic lipids have been poorly investigated in humans, but preliminary studies in rodents have shown a reduction of hepatic lipids in carbohydrate fed rats and in obese rats. ln this context this work aimed at investigating the metabolic effects of dietary protein intake on hepatic lipid metabolism and glucose homeostasis in humans. The modulation by dietary proteins of exogenous lipid oxidation, net lipid oxidation, hepatic beta-oxidation, triglycerides concentrations, whole-body energy expenditure and glucose tolerance was assessed in the fasting state and in postprandial states. Measurements of IHCL were performed to quantify the amount of triglycerides in the liver. ln an attempt to cover all these metabolic aspects under different point of views, these questions were addressed by three protocols involving various feeding conditions. Study I addressed the effects of a 4-day hypercaloric high-fat high-protein diet on the accumulation of fat in the liver (IHCL) and on insulin sensitivity. Our findings indicated that a high protein intake significantly prevents intrahepatic fat deposition induced by a short- term hypercaloric high-fat diet, adverse effects of which are presumably modulated at the liver level.These encouraging results led us to conduct the second study (Study ll), as we were also interested in a more clinical approach to protein administration and especially if increased protein intakes might be of benefit for obese patients. Therefore the effects of one-month whey protein supplementation on IHCL, insulin sensitivity, lipid metabolism, glucose tolerance and renal function were assessed in obese women. Results showed that whey protein supplementation reduces hepatic steatosis and improves the plasma lipid profile in obese patients, without adverse effects on glucose tolerance or creatinine clearance. However since patients were fed ud-libitum, it remains possible that spontaneous carbohydrate and fat intakes were reduced due to the satiating effects of protein. The third study (Study lll) was designed in an attempt to deepen our comprehension about the mechanisms involved in the modulation of IHCL. We hypothesized that protein improved lipid metabolism and, therefore, we evaluated the effects of a high protein meal on postprandial lipid metabolism and glucose homeostasis after 4-day on a control or a protein diet. Our results did not sustain the hypothesis of an increased postprandial net lipid oxidation, hepatic beta oxidation and exogenous lipid oxidation. Four days on a high-protein diet rather decreased exogenous fat oxidation and enhanced postprandial triglyceride concentrations, by impairing probably chylomicron-TG clearance. Altogether the results of these three studies suggest a beneficial effect of protein intake on the reduction in lHCL, and clearly show that supplementation of proteins do not reduce IHCL by stimulating lipid metabolism, e.g. whole body fat oxidation, hepatic beta oxidation, or exogenous fat oxidation. The question of the effects of high-protein intakes on hepatic lipid metabolism is still open and will need further investigation to be elucidated. The effects of protein on increased postprandial lipemia and lipoproteins kinetics have been little investigated so far and might therefore be an interesting research question, considering the tight relationship between an elevation of plasmatic TG concentrations and the increased incidence of cardiovascular diseases.Résumé :La stéatose hépatique non alcoolique se caractérise par un taux de lipides intra-hépatiques élevé, supérieur à 5%. L'incidence de la stéatose hépatique est fortement augmentée chez les personnes obèses, ce qui mène à la définir comme étant la composante hépatique du syndrome métabolique. Ce syndrome se définit aussi par d'autres critères tels qu'obésité viscérale, altération de l'homéostasie du glucose, résistance à l'insuline, dyslipidémie et pression artérielle élevée. Le syndrome métabolique est actuellement un problème de santé publique majeur.Tant une alimentation trop riche et déséquilibrée, qu'une faible activité physique, semblent être des causes pouvant expliquer le développement de ce syndrome. Chez l'animal et le volontaire sain, des alimentations enrichies en graisses ou en sucres (fructose) favorisent le développement de facteurs associés au syndrome métabolique, notamment en augmentant le taux de lipides intra-hépatiques et en induisant le développement d'une résistance à l'insuline. Par ailleurs, les effets des protéines alimentaires sont nettement moins bien connus, mais il semblerait qu'une augmentation de l'apport en protéines soit bénéfique, favorisant la perte de poids et l'homéostasie du glucose chez des patients insulino-résistants. Une augmentation de la thermogenese postprandiale ainsi que du sentiment de satiété pourraient en être à l'origine.Les effets des protéines sur les lipides intra-hépatiques chez l'homme demeurent inconnus à ce jour, cependant des études préliminaires chez les rongeurs tendent à démontrer une diminution des lipides intra hépatiques chez des rats nourris avec une alimentation riche en sucres ou chez des rats obèses.Dans un tel contexte de recherche, ce travail s'est intéressé à l'étude des effets métaboliques des protéines alimentaires sur le métabolisme lipidique du foie et sur l'homéostasie du glucose. Ce travail propose d'évaluer l'effet des protéines alimentaires sur différentes voies métaboliques impliquant graisses et sucres, en ciblant d'une part les voies de l'oxydation des graisses exogènes, de la beta-oxydation hépatique et de l'oxydation nette des lipides, et d'autre part la dépense énergétique globale et l'évolution des concentrations sanguines des triglycérides, à jeun et en régime postprandial. Des mesures des lipides intra-hépatiques ont aussi été effectuées pour permettre la quantification des graisses déposées dans le foie.Dans le but de couvrir l'ensemble de ces aspects métaboliques sous différents angles de recherche, trois protocoles, impliquant des conditions alimentaires différentes, ont été entrepris pour tenter de répondre à ces questions. La première étude (Etude I) s'est intéressée aux effets d'u.ne suralimentation de 4 jours enrichie en graisses et protéines sur la sensibilité à l'insuline et sur l'accumulation de graisses intra-hépatiques. Les résultats ont démontré que l'apport en protéines prévient l'accumulation de graisses intra-hépatiques induite par une suralimentation riche en graisses de courte durée ainsi que ses effets délétères probablement par le biais de mécanismes agissant au niveau du foie. Ces résultats encourageants nous ont conduits à entreprendre une seconde étude (Etude ll) qui s'intéressait à l'implication clinique et aux bénéfices que pouvait avoir une supplémentation en protéines sur les graisses hépatiques de patients obèses. Ainsi nous avons évalué pendant un mois de supplémentation l'effet de protéines de lactosérum sur le taux de graisses intrahépatiques, la sensibilité à l'insuline, la tolérance au glucose, le métabolisme des graisses et la fonction rénale chez des femmes obèses. Les résultats ont été encourageants; la supplémentation en lactosérum améliore la stéatose hépatique, le profil lipidique des patientes obèses sans pour autant altérer la tolérance au glucose ou la clairance de la créatinine. L'effet satiétogene des protéines pourrait aussi avoir contribué à renforcer ces effets. La troisième étude s'est intéressée aux mécanismes qui sous-tendent les effets bénéfiques des protéines observés dans les 2 études précédentes. Nous avons supposé que les protéines devaient favoriser le métabolisme des graisses. Par conséquent, nous avons cherché a évaluer les effets d'un repas riche en protéines sur la lipémie postprandiale et l'homéostasie glucidique après 4 jours d'alimentation contrôlée soit isocalorique et équilibrée, soit hypercalorique enrichie en protéines. Les résultats obtenus n'ont pas vérifié l'hypothèse initiale ; ni une augmentation de l'oxydation nette des lipides, ni celle d'une augmentation de la béta-oxydation hépatique ou de l'oxydation d'un apport exogène de graisses n'a pu étre observée. A contrario, il semblerait même plutôt que 4 jours d'a]irnentation hyperprotéinée inhibent le métabolisme des graisses et augmente les concentrations sanguines de triglycérides, probablement par le biais d'une clairance de chylornicrons altérée. Globalement, les résultats de ces trois études nous permettent d'attester que les protéines exercent un effet bénéfique en prévenant le dépot de graisses intra-hépatiques et montrent que cet effet ne peut être attribué à une stimulation du métabolisme des lipides via l'augmentation des oxydations des graisses soit totales, hépatiques, ou exogènes. La question demeure en suspens à ce jour et nécessite de diriger la recherche vers d'autres voies d'exploration. Les effets des protéines sur la lipémie postprandiale et sur le cinétique des lipoprotéines n'a que peu été traitée à ce jour. Cette question me paraît néanmoins importante, sachant que des concentrations sanguines élevées de triglycérides sont étroitement corrélées à une incidence augmentée de facteurs de risque cardiovasculaire.

Opposite impacts of dietary versus supplemental calcium on cardiovascular health.

Commentary on: Li K, Kaaks R, Linseisen J, et al . Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European prospective investigation into cancer and nutrition study (EPIC-Heidelberg). Heart 2012; 98 :920 - 5

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.