Evaluating the impact of using a wound-specific oral nutritional supplement to support wound healing in a rehabilitation setting.

Chronic wounds adversely affect patient quality of life, increase the risk of mortality, and impose high costs on healthcare systems. Since protein-energy malnutrition or specific nutrient deficiencies can delay wound healing, nutritionally focused care is a key strategy to help prevent or treat the occurrence of non-healing wounds. The objective of our study of inpatients in a rehabilitation hospital was to quantify the effect of daily wound-specific oral nutritional supplementation (WS-ONS) on healing chronic wounds. Using electronic medical records, we conducted a retrospective analysis of patients with chronic wounds. We identified records for (a) a treatment group who received standard wound care + usual hospital diet + daily WS-ONS for ≥14 days, and (b) a control group who received standard wound care + a usual hospital diet. We collected data for demographics, nutritional status, and wound-relevant health characteristics. We examined weekly measurements of wound number and sizes (surface area for superficial wounds or volume for non-superficial wounds). There were 341 patients identified, 114 with 322 wounds in the treatment group and 227 patients with 420 wounds in the control group. We found that rehabilitation inpatients who were given nutritional support had larger wounds and lower functional independence on admission. At discharge, wound area reduction (percent) was nearly two-fold better in patients who were given daily WS-ONS + usual hospital diet compared to those who consumed usual diet only (61.1% vs 34.5%). Overall, weekly wound improvement (lowered wound area or wound volume) was more likely in the WS-ONS group than in the Control group, particularly from the start of care to week 2. Inpatients with largest wounds and lowest functional independence on admission were most likely to be given WS-ONS, an indication that caregivers recognised the need for supplementation. Week-to-week improvement in wound size was more likely in patients who received WS-ONS than in those who did not. Specifically, wound areas and wound volumes were significantly lower at discharge among patients who were given specialised nutritional support. More research in this field is needed to improve care and reduce healthcare costs.

Malnutrition and Pressure Injury Risk in Vulnerable Populations: Application of the 2019 International Clinical Practice Guideline.

ABSTRACT: Nutrition plays a vital role in promoting skin integrity and supporting tissue repair in the presence of chronic wounds such as pressure injuries (PIs). Individuals who are malnourished are at greater risk of polymorbid conditions, adverse clinical outcomes, longer hospital lengths of stay, PI development, and mortality, and incur increased healthcare costs compared with patients who are adequately nourished. In addition, some patient populations tend to be more vulnerable to PI formation, such as neonates, patients with obesity, older adults, and individuals who are critically ill. Accordingly, this article aims to review the latest nutrition care recommendations for the prevention and treatment of PIs, including those recommendations tailored to special populations. A secondary objective is to translate nutrition recommendations into actionable steps for the healthcare professional to implement as part of a patient plan of care.Implementing an evidence-based plan of care built around individualized nutrition interventions is an essential step supporting skin integrity for these populations. The 2019 Prevention and Treatment of Pressure Ulcers/Injuries: Clinical Practice Guideline (CPG) affirms that meeting nutrient requirements is essential for growth, development, maintenance, and repair of body tissues. Many macronutrients and micronutrients work synergistically to heal PIs. Registered dietitian nutritionists play an important role in helping patients identify the most nutrient dense foods, protein supplements, and oral nutrition supplements to meet their unique requirements.

An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat.

The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

Impact of a specialized oral nutritional supplement on quality of life in older adults following hospitalization: Post-hoc analysis of the NOURISH trial.

BACKGROUND & AIMS: Both during and after hospitalization, nutritional care with daily intake of oral nutritional supplements (ONS) improves health outcomes and decreases risk of mortality in malnourished older adults. In a post-hoc analysis of data from hospitalized older adults with malnutrition risk, we sought to determine whether consuming a specialized ONS (S-ONS) containing high protein and beta-hydroxy-beta-methylbutyrate (HMB) can also improve Quality of Life (QoL). METHODS: We analyzed data from the NOURISH trial-a randomized, placebo-controlled, multi-center, double-blind study conducted in patients with congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Patients received standard care + S-ONS or placebo beverage (target 2 servings/day) during hospitalization and for 90 days post-discharge. SF-36 and EQ-5D QoL outcomes were assessed at 0-, 30-, 60-, and 90-days post-discharge. To account for the missing QoL observations (27.7%) due to patient dropout, we used multiple imputation. Data represent differences between least squares mean (LSM) values with 95% Confidence Intervals for groups receiving S-ONS or placebo treatments. RESULTS: The study population consisted of 622 patients of mean age ±standard deviation: 77.9 ± 8.4 years and of whom 52.1% were females. Patients consuming placebo had lower (worse) QoL domain scores than did those consuming S-ONS. Specifically for the SF-36 health domain scores, group differences (placebo vs S-ONS) in LSM were significant for the mental component summary at day 90 (-4.23 [-7.75, -0.71]; p = 0.019), the domains of mental health at days 60 (-3.76 [-7.40, -0.12]; p = 0.043) and 90 (-4.88 [-8.41, -1.34]; p = 0.007), vitality at day 90 (-3.33 [-6.65, -0.01]; p = 0.049) and social functioning at day 90 (-4.02 [-7.48,-0.55]; p = 0.023). Compared to placebo, differences in LSM values for the SF-36 general health domain were significant with improvement in the S-ONS group at hospital discharge and beyond: day 0 (-2.72 [-5.33, -0.11]; p = 0.041), day 30 (-3.08 [-6.09, -0.08]; p = 0.044), day 60 (-3.95 [-7.13, -0.76]; p = 0.015), and day 90 (-4.56 [-7.74, -1.38]; p = 0.005). CONCLUSIONS: In hospitalized older adults with cardiopulmonary diseases and evidence of poor nutritional status, daily intake of S-ONS compared to placebo improved post-discharge QoL scores for mental health/cognition, vitality, social functioning, and general health. These QoL benefits complement survival benefits found in the original NOURISH trial analysis. CLINICAL TRIAL REGISTRATION: NCT01626742.

An amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley rats.

The aims of this investigation were to evaluate the effect of an amino acid supplement on the glucose response to an oral glucose challenge (experiment 1) and to evaluate whether differences in blood glucose response were associated with increased skeletal muscle glucose uptake (experimental 2). Experiment 1 rats were gavaged with either glucose (CHO), glucose plus an amino acid mixture (CHO-AA-1), glucose plus an amino acid mixture with increased leucine concentration (CHO-AA-2), or water (PLA). CHO-AA-1 and CHO-AA-2 had reduced blood glucose responses compared with CHO, with no difference in insulin among these treatments. Experiment 2 rats were gavaged with either CHO or CHO-AA-1. Fifteen minutes after gavage, a bolus containing 2-[(3)H]deoxyglucose and [U-(14)C]mannitol was infused via a tail vein. Blood glucose was significantly lower in CHO-AA-1 than in CHO, whereas insulin responses were similar. Muscle glucose uptake was higher in CHO-AA-1 compared with CHO in both fast-twitch red (8.36 ± 1.3 vs. 5.27 ± 0.7 µmol·g(-1)·h(-1)) and white muscle (1.85 ± 0.3 vs. 1.11 ± 0.2 µmol·g(-1)·h(-1)). There was no difference in Akt/PKB phosphorylation between treatment groups; however, the amino acid treatment resulted in increased AS160 phosphorylation in both muscle fiber types. Glycogen synthase phosphorylation was reduced in fast-twitch red muscle of CHO-AA-1 compared with CHO, whereas mTOR phosphorylation was increased. These differences were not noted in fast-twitch white muscle. These findings suggest that amino acid supplementation can improve glucose tolerance by increasing skeletal muscle glucose uptake and intracellular disposal through enhanced intracellular signaling.

Influence of carbon monoxide leaks on the measurement error of total haemoglobin mass.

Total haemoglobin mass (Hb(mass)) can be assessed with low measurement error using carbon monoxide (CO) rebreathing. However, variability in measurement error of Hb(mass) has been reported across laboratories and it has previously been suggested that CO leaks contribute to this variability. As a result of employing a standardized leak monitoring procedure using two CO detectors, we were able to retrospectively examine the impact of CO leaks on Hb(mass) values from past test-retest studies in our laboratory using the optimized CO rebreathing method. Test-retest data were collected to determine measurement error, with subjects tested twice within 5 days. Test-retest data were placed into separate categories based on magnitude and duration of CO leak observed during one of the two tests. The No Leak category contained test-retest data in which no leak occurred during either test. The Minor Leak category contained test-retest data in which one of the tests had a CO leak of magnitude less than 30 ppm and less than 5 seconds duration, whereas the Major Leak category included test-retest data in which a leak greater than this magnitude or duration occurred. Measurement error was lowest in the No Leak category (1.9%; 95%CI: 1.6-2.3%; n = 56), approximately doubled in the Minor Leaks category (3.6%; 95%CI: 2.6-6.1%; n = 13), and dramatically increased in the Major Leaks category (9.3%; 95%CI: 6.3-17.6%; n = 10). We recommend careful monitoring of potential CO leaks using multiple detectors. To minimize measurement error, tests in which any CO leak is detected should be excluded.

Specialized oral nutritional supplement (ONS) improves handgrip strength in hospitalized, malnourished older patients with cardiovascular and pulmonary disease: A randomized clinical trial.

BACKGROUND & AIMS: Oral Nutritional Supplements (ONS) are used to treat malnutrition and improve clinical outcomes in malnourished patients. Poor handgrip strength (HGS) is associated with an increased risk of mortality, disability and other adverse health consequences. This analysis examined the effect of a specialized ONS on HGS and its relationship to nutritional status in hospitalized, older adults with malnutrition who were participants in the NOURISH trial. METHODS: We enrolled older (≥65years), malnourished (Subjective Global Assessment [SGA] class B/C) adults hospitalized for cardiovascular and pulmonary events: congestive heart failure, acute myocardial infarction, pneumonia and/or chronic obstructive pulmonary disease exacerbation in a double-blind, randomized, placebo-controlled trial (NOURISH study). During hospitalization and until 90 days after discharge, participants received standard-of-care plus a high protein and beta-hydroxy-beta-methylbutyrate containing ONS (S-ONS; n = 328) or a placebo supplement (n = 324), aimed at 2 servings/day. HGS was evaluated by dynamometer at baseline, hospital discharge, day (d) 30, d60, and d90 post-discharge. RESULTS: Post hoc, repeated measures analysis of data at discharge, d30, d60, and d90 showed significantly higher HGS in the S-ONS vs. the placebo group in the evaluable group (Least Squares Means ± Standard Error: (23.25 ± 0.25 vs. 22.63 ± 0.25, p = 0.043). At d90, there was a significant positive association between HGS and nutritional status (SGA) improvements in the entire cohort: 49% of participants with increased HGS from discharge had improved nutritional status versus 31% with unchanged or decreased HGS (p = 0.003). HGS and the scores on the Katz index of independence in activities of daily living (ADL) were positively associated at all visits including all ITT subjects (Pearson's r range: 0.24 to 0.34, all p < 0.0001). CONCLUSIONS: S-ONS provided during hospitalization and up to 90 days post-discharge improves HGS in malnourished older adults following cardiovascular and pulmonary events and may contribute to improvement in patients' overall recovery. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov NCT01626742.

Reduced mortality risk in malnourished hospitalized older adult patients with COPD treated with a specialized oral nutritional supplement: Sub-group analysis of the NOURISH study.

BACKGROUND: Hospitalized, malnourished older adults with chronic obstructive pulmonary disease (COPD) have an elevated risk of readmission and mortality. OBJECTIVE: Post-hoc, sub-group analysis from the NOURISH study cohort examined the effect of a high-protein oral nutritional supplement (ONS) containing HMB (HP-HMB) in malnourished, hospitalized older adults with COPD and to identify predictors of outcomes. METHODS: The NOURISH study (n = 652) was a multicenter, randomized, placebo-controlled, double-blind trial. The COPD subgroup (n = 214) included hospitalized, malnourished (based on Subjective Global Assessment), older adults (≥65 y), with admission diagnosis of COPD who received either standard-of-care plus HP-HMB (n = 109) or standard-of-care and a placebo supplement (n = 105) prescribed 2 servings/day from within 3 days of hospital admission (baseline) and up to 90 days after discharge. The primary study outcome was a composite endpoint of incidence of death or non-elective readmission up to 90-day post-discharge, while secondary endpoints included changes in hand-grip strength, body weight, and nutritional biomarkers over time. Categorical outcomes were analyzed using Cochran-Mantel-Haenszel tests, longitudinal data by repeated measures analysis of covariance; and changes from baseline by analysis of covariance. p-values ≤ 0.05 were considered statistically significant. Multivariate logistic regression was used to model predictors of the primary outcome and components. RESULTS: In patients with COPD, 30, 60, and 90-day hospital readmission rate did not differ, but in contrast, 30, 60, and 90-day mortality risk was approximately 71% lower with HP-HMB supplementation relative to placebo (1.83%, 2.75%, 2.75% vs. 6.67%, 9.52% and 10.48%, p = 0.0395, 0.0193, 0.0113, resp.). In patients with COPD, compared to placebo, intake of HP-HMB resulted in a significant increase in handgrip strength (+1.56 kg vs. -0.34 kg, p = 0.0413) from discharge to day 30; increased body weight from baseline to hospital discharge (0.66 kg vs. -0.01 kg, p < 0.05) and, improvements in blood nutritional biomarker concentrations. The multivariate logistic regression predictors of the death, readmission or composite endpoints in these COPD patients showed that participants who were severely malnourished (p = 0.0191) and had a Glasgow prognostic score (GPS) Score of 1 or 2 had statistically significant odds of readmission or death (p = 0.0227). CONCLUSIONS: Among malnourished, hospitalized patients with COPD, supplementation with HP-HMB was associated with a markedly decreased mortality risk, and improved handgrip strength, body weight, and nutritional biomarkers within a 90-day period after hospital discharge. This post-hoc, subgroup analysis highlights the importance of early identification of nutritional risk and administration of high-protein ONS in older, malnourished patients with COPD after hospital admission and continuing after hospital discharge.

The use of a protein and energy dense eicosapentaenoic acid containing supplement for malignancy-related weight loss in children.

BACKGROUND: The aim of nutritional therapy in cancer patients is to prevent weight loss and to improve functional capacity and quality of life. Clinical studies however, have continued to demonstrate that a reduction in body weight loss is difficult to achieve in cancer cachexia. Several studies have shown that supplementation with eicosapentaenoic acid (EPA), an omega-3 fatty acid, has anti-cachectic effects in adult cancer patients. This study evaluated the clinical effects of a protein and energy dense EPA containing nutritional supplement in a group of pediatric cancer patients receiving active chemotherapy treatment. METHODS: The study was a prospective, randomized, single center, open-label design. Fifty-two patients diagnosed with pediatric malignant disease and receiving intensive chemotherapy were included. Thirty-three patients received a nutritional supplement containing EPA in addition to their regular food intake. Nineteen control patients did not receive supplementation. Patients were examined and their data (body weight, body mass index, and weight percentile) were recorded regularly once a month for 3 months. A subgroup of patients was evaluated for 6 months. RESULTS: At 3 months, there were significantly fewer patients in the treatment group as compared to controls that showed losses in body weight (P = 0.001), BMI (P = 0.002), and a negative deviation in weight percentile (P = 0.021). In addition, remission rate was significantly (P = 0.036) higher in the treatment group as compared to controls. CONCLUSIONS: This study demonstrates a decrease in cancer-induced weight loss in pediatric patients fed a protein and energy dense nutrition supplement containing EPA.

Specialized High-Protein Oral Nutrition Supplement Improves Home Nutrient Intake of Malnourished Older Adults Without Decreasing Usual Food Intake.

BACKGROUND: Reduced nutrient intake is common in patients after hospitalization, contributing to increased risk for readmission and mortality. Oral nutrition supplements can improve nutrition status and clinical outcomes, but intake of food is prioritized by clinicians. This study examines the impact of a high-protein oral nutrition supplement (S-ONS) on nutrient intake post discharge. METHODS: In a subset of patients (14 S-ONS and 16 placebo) from the NOURISH (Nutrition effect On Unplanned ReadmIssions and Survival in Hospitalized patients) trial, 24-hour dietary recalls were conducted on 3 randomly selected days during the weeks of 30, 60, and 90 days post discharge. Nutrient intake was estimated using Nutrition Data System for Research software. Adequate energy and protein intake were defined as 30 kcal/kg/d and 1.2 g/kg/d, respectively. Dietary Reference Intakes (DRIs) were used for other nutrients. RESULTS: Less than half of patients met the requirements for energy, protein, and 12 micronutrients from food intake alone during the study. Energy and protein intakes from food were not diminished relative to placebo. Considering nutrient intake from both food and S-ONS, 50% and 71% of patients receiving S-ONSs met energy and protein goals respectively at 90 days (compared with 29% and 36%, in the placebo group), and 100% met the DRI for total carbohydrate, iron, phosphorus, copper, selenium, thiamin, and riboflavin at all time points, all of which were consumed at higher amounts vs placebo. CONCLUSION: Three months of S-ONS consumption increases intake of numerous nutrients without decreasing nutrient intake from food in older malnourished adults post discharge.

Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial.

BACKGROUND: Hospitalized, malnourished older adults have a high risk of readmission and mortality. OBJECTIVE: Evaluation of a high-protein oral nutritional supplement (HP-HMB) containing beta-hydroxy-beta-methylbutyrate on postdischarge outcomes of nonelective readmission and mortality in malnourished, hospitalized older adults. DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial. SETTING: Inpatient and posthospital discharge. PATIENTS: Older (≥65 years), malnourished (Subjective Global Assessment [SGA] class B or C) adults hospitalized for congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. INTERVENTIONS: Standard-of-care plus HP-HMB (n = 328) or a placebo supplement (n = 324), 2 servings/day. MEASUREMENTS: Primary composite endpoint was 90-day postdischarge incidence of death or nonelective readmission. Other endpoints included 30- and 60-day postdischarge incidence of death or readmission, length of stay (LOS), SGA class, body weight, and activities of daily living (ADL). RESULTS: The primary composite endpoint was similar between HP-HMB (26.8%) and placebo (31.1%). No between-group differences were observed for 90-day readmission rate, but 90-day mortality was significantly lower with HP-HMB relative to placebo (4.8% vs. 9.7%; relative risk 0.49, 95% confidence interval [CI], 0.27 to 0.90; p = 0.018). The number-needed-to-treat to prevent 1 death was 20.3 (95% CI: 10.9, 121.4). Compared with placebo, HP-HMB resulted in improved odds of better nutritional status (SGA class, OR, 2.04, 95% CI: 1.28, 3.25, p = 0.009) at day 90, and an increase in body weight at day 30 (p = 0.035). LOS and ADL were similar between treatments. LIMITATIONS: Limited generalizability; patients represent a selected hospitalized population. CONCLUSIONS: Although no effects were observed for the primary composite endpoint, compared with placebo HP-HMB decreased mortality and improved indices of nutritional status during the 90-day observation period. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.govNCT01626742.

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants on antioxidant status in patients with acute respiratory distress syndrome.

BACKGROUND: We previously showed that enteral feeding of a diet containing eicosapentaenoic acid, gamma-linolenic acid, and elevated antioxidants improved clinical outcomes compared with a control diet in acute respiratory distress syndrome (ARDS) patients. It has been suggested that oxidative stress may overwhelm endogenous antioxidant levels and allow free radicals to further damage lung tissue. Therefore, we determined whether these ARDS patients were under oxidative stress and whether the experimental diet could improve antioxidant status. METHODS: Ninety-eight ARDS patients received either the experimental or control diet (minimum of 75% of basal energy expenditure x 1.3) for at least 4 to 7 days. Total radical antioxidant potential (TRAP), lipid peroxide levels (LPO), and plasma antioxidant concentrations were determined at baseline and study days 4 and 7. Sixty-two normal individuals were assessed for reference values. RESULTS: At baseline, ARDS patients had significantly lower plasma beta-carotene, retinol, and alpha-tocopherol, lower TRAP, and higher LPO values compared with normals. After 4 days of feeding, beta-carotene and alpha-tocopherol levels were normalized and significantly increased in the experimental group compared with controls. TRAP and LPO were not significantly different between groups and study day 4 and 7 values were not different from baseline values. Retinol levels increased equally in both groups. CONCLUSIONS: Before treatment, ARDS patients were found to be in a state of oxidative stress and had reduced levels of antioxidants. Although enteral nutrition with the experimental diet for at least 4 to 7 days did not reduce oxidative stress as measured, it did restore plasma levels of beta-carotene and alpha-tocopherol to normal or higher levels and appeared to protect ARDS patients from further lipid peroxidation.

Amino acid mixture acutely improves the glucose tolerance of healthy overweight adults.

Certain amino acids have been reported to influence carbohydrate metabolism and blood glucose clearance, as well as improve the glucose tolerance in animal models. We hypothesized that an amino acid mixture consisting of isoleucine and 4 additional amino acids would improve the glucose response of healthy overweight men and women to an oral glucose tolerance test (OGTT). Twenty-two overweight healthy subjects completed 2 OGTTs after consuming 2 different test beverages. The amino acid mixture beverage (CHO/AA) consisted of 0.088 g cystine 2HCl, 0.043 g methionine, 0.086 g valine, 12.094 g isoleucine, 0.084 g leucine, and 100 g dextrose. The control beverage (CHO) consisted of 100 g dextrose only. Venous blood samples were drawn 10 minutes before the start of ingesting the drinks and 15, 30, 60, 120, and 180 minutes after the completion of the drinks. During the OGTT, the plasma glucose response for the CHO/AA treatment was significantly lower than that of the CHO treatment (P < .01), as was the plasma glucose area under the curve (CHO/AA 806 ± 31 mmol/L·3 hours vs CHO 942 ± 40 mmol/L·3 hours). Differences in plasma glucose between treatments occurred at 30, 60, 120, and 180 minutes after supplement ingestion. Plasma glucagon during the CHO/AA treatment was significantly higher than during the CHO treatment. However, there were no significant differences in plasma insulin or C-peptide responses between treatments. These results suggest that the amino acid mixture lowers the glucose response to an OGTT in healthy overweight subjects in an insulin-independent manner.

An amino acid mixture is essential to optimize insulin-stimulated glucose uptake and GLUT4 translocation in perfused rodent hindlimb muscle.

The purpose of this study was to investigate whether an amino acid mixture increases glucose uptake across perfused rodent hindlimb muscle in the presence and absence of a submaximal insulin concentration, and if the increase in glucose uptake is related to an increase in GLUT4 plasma membrane density. Sprague-Dawley rats were separated into one of four treatment groups: basal, amino acid mixture, submaximal insulin, or amino acid mixture with submaximal insulin. Glucose uptake was greater for both insulin-stimulated treatments compared with the non-insulin-stimulated treatment groups but amino acids only increased glucose uptake in the presence of insulin. Phosphatidylinositol 3-kinase (PI 3-kinase) activity was greater for both insulin-stimulated treatments with amino acids having no additional impact. Akt substrate of 160 kDa (AS160) phosphorylation, however, was increased by the amino acids in the presence of insulin, but not in the absence of insulin. AMPK was unaffected by insulin or amino acids. Plasma membrane GLUT4 protein concentration was greater in the rats treated with insulin compared with no insulin in the perfusate. In the presence of insulin, amino acids increased GLUT4 density in the plasma membrane but had no effect in the absence of insulin. AS160 phosphorylation and plasma membrane GLUT4 density accounted for 76% of the variability in muscle glucose uptake. Collectively, these findings suggest that the beneficial effects of an amino acid mixture on skeletal muscle glucose uptake, in the presence of a submaximal insulin concentration, are due to an increase in AS160 phosphorylation and plasma membrane-associated GLUT4, but independent of PI 3-kinase and AMPK activation.

Lean body mass gain in patients with head and neck squamous cell cancer treated perioperatively with a protein- and energy-dense nutritional supplement containing eicosapentaenoic acid.

BACKGROUND: Cancer-associated weight loss may be mediated by an inflammatory response to cancer. Eicosapentaenoic acid (EPA) may suppress this response. METHODS: Beginning no later than 2 weeks before surgery, patients with head and neck cancer and with weight loss, who were undergoing major resection with curative intent consumed a protein- and energy-dense nutritional supplement containing EPA from fish oil, in addition to usual diet or tube feed. RESULTS: Thirty-one subjects consumed an average of 1.8 containers/day before surgery and 1.5/day during hospitalization (per container: 300 kilocalories, 16 grams (g) protein, 1.08 g EPA). Seventy percent of subjects maintained or gained weight before hospital admission. Mean weight gain was 0.71 kg at admission and 0.66 kg at discharge. At discharge lean body mass increased by 3.20 kg (p < .001) and fat decreased by 3.19 kg (p < .001). CONCLUSIONS: An EPA-containing protein- and energy-dense nutritional supplement may help increase perioperative lean body mass in patients with head and neck cancer-related weight loss.

An amino acid mixture enhances insulin-stimulated glucose uptake in isolated rat epitrochlearis muscle.

Protein and certain amino acids (AA) have been found to lower blood glucose. Although these glucose-lowering AA are important modulators of skeletal muscle metabolism, their impact on muscle glucose uptake remains unclear. We therefore examined how an AA mixture consisting of 2 mM isoleucine, 0.012 mM cysteine, 0.006 mM methionine, 0.0016 mM valine, and 0.014 mM leucine impacts skeletal muscle glucose uptake in the absence or presence of a submaximal (sINS) or maximal insulin (mINS) concentration. The AA mixture, sINS, and mINS significantly increased 2-[(3)H]deoxyglucose (2-DG) uptake by 63, 79, and 298% above basal, respectively. When the AA mixture was combined with sINS and mINS, 2-DG uptake was further increased significantly by 26% (P = 0.028) and 14% (P = 0.032), respectively. Western blotting analysis revealed that the AA mixture increased basal and sINS Akt substrate of 160 kDa (AS160) phosphorylation, while AA mixture did not change phosphorylation of Akt or mammalian target of rapamycin (mTOR) under these conditions. Interestingly, addition of the AA mixture to mINS increased phosphorylation of mTOR, Akt as well as AS160, compared with mINS alone. These data suggest that certain AA increase glucose uptake in the absence of insulin and augment insulin-stimulated glucose uptake in an additive manner. Furthermore, these effects appear to be mediated via a pathway that is independent from the canonical insulin cascade and therefore may prove effective as an alternative therapeutic treatment for insulin resistance.

Diffuse cerebral vasoconstriction (Call-Fleming syndrome) and stroke associated with antidepressants.

Call-Fleming syndrome is a reversible segmental vasoconstriction of cerebral arteries manifested by a "thunderclap" headache and focal neurologic symptoms. Although of unknown etiology, it has been reported in association with vasoactive sympathomimetic drugs. The authors report Call-Fleming syndrome in two patients with history of antidepressant use. Although the association is hypothetical, the authors suggest consideration of Call-Fleming syndrome in patients presenting with headache, focal deficits, and evidence of cerebral ischemia during antidepressant use.

Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome.

OBJECTIVE: Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation. DESIGN: Prospective, randomized, double-blind, controlled clinical trial. SETTING: Intensive Care Unit of the Ohio State University Medical Center. PATIENTS: A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome. INTERVENTIONS: A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4. CONCLUSIONS: This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.