Fish Oil, Plant Polyphenols, and Their Combinations Have No Tumor Growth Promoting Effects on Human Lung and Colon Carcinoma Xenograft Mice.

The goal of this study was to evaluate if combinations of ingredients with known anti-cachexia benefits (Fish oil-FO with either curcumin or Green tea extract-GTE), have adverse effects on tumor growth, using human carcinoma xenograft mice models. FO (EPA/DHA 360 mg/kg bw), GTE (90 mg/kg bw), and curcumin (180 mg/kg bw) were administered orally, alone or in combination, to nude mice bearing either A549 human non-small cell lung carcinoma or SW620 human colon carcinoma tumors. Bodyweight, tumor growth, survival time, and other clinical endpoints were assessed. The ingredients either alone or in combinations were well tolerated in both lung and colon tumor-bearing mice. There were no significant group differences between individual or combination treatments for tumor growth (A549 or SW620) as measured by the median time in days to endpoint of tumor volume (TTE). TTE results indicate that these ingredients (alone or combinations) did not adversely impact tumor growth. No significant differences in body weights or survival were observed between controls and treatment groups indicating no adverse health effects of the ingredients. In conclusion, FO, GTE or curcumin administered as monotherapies and in combination were well tolerated and displayed no adverse effects on tumor growth in mouse xenograft models of lung and colon cancer.

Biomarker Changes in Response to a 12-Week Supplementation of an Oral Nutritional Supplement Enriched with Protein, Vitamin D and HMB in Malnourished Community Dwelling Older Adults with Sarcopenia.

Malnutrition and sarcopenia commonly overlap and contribute to adverse health outcomes. Previously, chronic supplementation with two oral nutritional supplements (ONS), control (CONS) and experimental ONS enriched with protein, vitamin D and ß-hydroxy ß-methylbutyrate (HMB) (EONS), improved muscle strength and quality in malnourished sarcopenic older adults, with EONS demonstrating early strength benefits at 12 weeks. To understand the underlying biological mechanisms contributing to the observed early strength benefits of EONS, we examined serum biomarker changes in response to 12-week supplementation. Serum samples (EONS (n = 90) and CONS (n = 103)) collected at baseline and 12 weeks were analyzed. Biomarkers (n = 243) were measured using multiplexed immunoassay, commercial immunoassays and ELISAs. Sixty markers were excluded with levels below assay detection limits. Sixteen biomarkers significantly changed in response to both interventions including nutritional and metabolic markers. Thirteen biomarkers significantly changed in response to EONS but not CONS. Increases in immunoglobulins, myoglobin, total protein, vitamin E and magnesium were observed with EONS. Inflammation-related ferritin and osteopontin decreased, while soluble receptors for cytokines increased, suggesting decreased inflammation. Sex hormone-binding globulin associated with sarcopenia also decreased with EONS. Biomarkers reflective of multiple biological systems were impacted by nutritional intervention in sarcopenic older adults. Incremental biomarker changes were observed in response to EONS containing HMB that possibly link to improvements in skeletal muscle health.

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.

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.

The Cost-Effectiveness of Oral Nutrition Supplementation for Malnourished Older Hospital Patients.

BACKGROUND: Malnutrition, which is associated with increased medical complications in older hospitalized patients, can be attenuated by providing nutritional supplements. OBJECTIVE: This study evaluates the cost effectiveness of a specialized oral nutritional supplement (ONS) in malnourished older hospitalized patients. METHODS: We conducted an economic evaluation alongside a multicenter, randomized, controlled clinical trial (NOURISH Study). The target population was malnourished older hospitalized patients in the USA. We used 90-day (base case) and lifetime (sensitivity analysis) time horizons. The study compared a nutrient-dense ONS, containing high protein and ß-hydroxy-ß-methylbutyrate to placebo. Outcomes included health-care costs, measured as the product of resource use and per unit cost; quality-adjusted life-years (QALYs) (90-day time horizon); life-years (LYs) saved (lifetime time horizon); and the incremental cost-effectiveness ratio (ICER). All costs were inflated to 2015 US dollars. RESULTS: In the base-case analysis, 90-day treatment group costs averaged US$22,506 per person, compared to US$22,133 for the control group. Treatment group patients gained 0.011 more QALYs than control group subjects, reflecting the treatment group's significantly greater probability of survival through 90 days' follow-up, as reported by the clinical trial. Hence, the 90-day follow-up period ICER was US$33,818/QALY. Assuming a lifetime time horizon, estimated treatment group life expectancy exceeded control group life expectancy by 0.71 years. Hence, the lifetime ICER was US$524/LY. The follow-up period for the trial was relatively short. Some of the patients were lost to follow-up, thus reducing collection of health-care utilization data during the clinical trial. CONCLUSION: Our findings suggest that the investigative ONS cost-effectively extends the lives of malnourished hospitalized patients.

In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes.

EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-α (TNF-α) and proteolysis-inducing factor (PIF). EPA (50 µM) or curcumin (10 µg ml(-1)) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 µg ml(-1)). In response to TNF-α (25 ng ml(-1))-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-α, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-α, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-α and PIF significantly reduced myotube diameter from 17 to 13 µm for TNF-α (23.5%) and 15 µm (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass.

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.

A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition.

OBJECTIVE: Parenteral nutrition has been associated with metabolic and infectious complications in intensive care unit patients. The underlying mechanism for the high risk of complications is not known but may relate to the proinflammatory effects of soybean oil-based lipid emulsions, the only Food and Drug Administration-approved lipid formulation for clinical use. DESIGN: Prospective, double-blind, randomized, controlled trial. SETTING: Medical-surgical intensive care units from a major urban teaching hospital and a tertiary referral university hospital. PATIENTS: Adult medical-surgical intensive care unit patients. INTERVENTION: Parenteral nutrition containing soybean oil-based (Intralipid) or olive oil-based (ClinOleic) lipid emulsions. MEASUREMENTS: Differences in hospital clinical outcomes (nosocomial infections and noninfectious complications), hospital length of stay, glycemic control, inflammatory and oxidative stress markers, and granulocyte and monocyte functions between study groups. RESULTS: A total of 100 patients were randomized to either soybean oil-based parenteral nutrition or olive oil-based parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil-based parenteral nutrition (age 51 ± 15 yrs, body mass index 27 ± 6 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.5 ± 7 [±SD]), and a total of 51 patients received olive oil-based lipid emulsion in parenteral nutrition (age 46 ± 19 yrs, body mass index 27 ± 8 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.1 ± 6 [±SD]) for a mean duration of 12.9 ± 8 days. The mean hospital blood glucose concentration during parenteral nutrition was 129 ± 14 mg/dL, without differences between groups. Patients treated with soybean oil-based and olive oil-based parenteral nutrition had a similar length of stay (47 ± 47 days and 41 ± 36 days, p = .49), mortality (16.3% and 9.8%, p = .38), nosocomial infections (43% vs. 57%, p = .16), and acute renal failure (26% vs. 18%, p = .34). In addition, there were no differences in inflammatory and oxidative stress markers or in granulocyte and monocyte functions between groups. CONCLUSION: The administration of parenteral nutrition containing soybean oil-based and olive oil-based lipid emulsion resulted in similar rates of infectious and noninfectious complications and no differences in glycemic control, inflammatory and oxidative stress markers, and immune function in critically ill adults.

Prospective analysis of serum carotenoids, vitamin A, and tocopherols in adults with short bowel syndrome undergoing intestinal rehabilitation.

OBJECTIVE: Carotenoids, vitamin A, and tocopherols serve important roles in many key body functions. However, availability of these compounds may be decreased in patients with short bowel syndrome (SBS) due to decreased oral intake of fruits and vegetables and/or decreased intestinal absorption. Little information is available on serum concentrations of carotenoids, vitamin A, and tocopherols during chronic parenteral nutrition (PN) or during PN weaning. The aim of this study was to prospectively examine serum concentrations of a wide variety of carotenoids, vitamin A, and tocopherols in patients with SBS undergoing an intensive 12-wk intestinal rehabilitation program. METHODS: Twenty-one PN-dependent adult patients with SBS were enrolled in a 12-wk intestinal rehabilitation program, which included individualized dietary modification, multivitamin supplementation, and randomization to receive subcutaneous placebo (n = 9) or human growth hormone (0.1 mg . kg(-1) . d(-1); n = 12). PN weaning was initiated after week 4 and advanced as tolerated. Serum concentrations of carotenoids, vitamin A, and tocopherols were determined at baseline and at weeks 4 and 12. RESULTS: A significant percentage of subjects exhibited low serum concentrations for carotenoids and alpha-tocopherol at study entry, and a few subjects had low concentrations of retinol (5%). Carotenoid and vitamin A valves did not improve over time, while alpha-tocopherol levels rose. Serum alpha-tocopherol concentration was negatively associated with PN lipid dose (r = -0.34, P < 0.008). CONCLUSION: Patients with SBS are depleted in diet-derived carotenoids despite oral and intravenous multivitamin supplementation and dietary adjustment during intestinal rehabilitation and PN weaning. Reduction of PN lipid infusion may improve serum alpha-tocopherol concentrations.

Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients.

BACKGROUND: Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. METHODS: This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. RESULTS: Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). CONCLUSIONS: Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Nutrient intake from habitual oral diet in patients with severe short bowel syndrome living in the southeastern United States.

OBJECTIVES: Little data are published on the habitual home oral diet of patients with short bowel syndrome (SBS). METHODS: We assessed nutrient intake from oral food and beverages in 19 stable patients with severe SBS who live in the southeastern United States. Intestinal absorption of energy, fat, nitrogen (N), and carbohydrate (CHO) was determined in a metabolic ward. RESULTS: We studied 12 women and 7 men, age 48 +/- 3 y of age (mean +/- SE) receiving parenteral nutrition for 31 +/- 8 mo following massive small bowel resection (118 +/- 25 cm residual small bowel). The patients demonstrated severe malabsorption of energy (59 +/- 3% of oral intake), fat (41 +/- 5%), N (42 +/- 5%) and CHO (76 +/- 3%). Oral energy intake was 2656 +/- 242 kcal/d (39 +/- 3 kcal/kg/d) and oral protein intake was 1.4 +/- 0.1 g/kg/d. Food/beverage intake constituted 49 +/- 4% of total (enteral plus parenteral) daily fluid intake, 66 +/- 4% of total daily kcal and 58 +/- 5% of total daily N intake. Oral fat intake averaged 92 +/- 11 g/day ( approximately 35% of total oral energy). Oral fluid intake averaged 2712 +/- 240 ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars comprised 42 +/- 3% of oral CHO intake. Usual dietary intake of multiple micronutrients were below the Recommended Dietary Allowances (RDA) in a large percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%), vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%). Only seven patients (37%) were taking oral multivitamin-mineral supplements and only six subjects (32%) were taking oral iron and calcium supplements, respectively. CONCLUSION: In these SBS patients, an oral diet provided a significant proportion of daily nutrient intake. The types of foods and fluids consumed are likely to worsen malabsorption and thus increase PN requirements. Oral intake of essential micronutrients was very low in a significant proportion of these individuals.

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study.

BACKGROUND: Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. OBJECTIVES: We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. METHODS: In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8. RESULTS: Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. CONCLUSIONS: This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Depletion of plasma antioxidants in surgical intensive care unit patients requiring parenteral feeding: effects of parenteral nutrition with or without alanyl-glutamine dipeptide supplementation.

OBJECTIVES: Antioxidant depletion is common in critically ill patients. This study was designed to determine the effects of parenteral nutrition (PN), with or without glutamine (Gln) supplementation, on systemic antioxidant status in adult patients after major surgery who required PN in the surgical intensive care unit (SICU) setting. METHODS: Fifty-nine patients in the SICU who required PN after pancreatic surgery or cardiac, vascular, or colonic (non-pancreatic) surgery were randomized in a double-blinded study to receive standard PN (Gln-free) or Gln-supplemented PN (Gln-PN) in which Gln was provided as alanyl-Gln dipeptide. Conventional PN vitamin and mineral doses were administered to all subjects. Plasma concentrations of the antioxidant glutathione (GSH) and the antioxidant nutrients alpha-tocopherol, vitamin C, and zinc were determined at baseline (initiation of study PN) and again after 7 d of study PN. Data were analyzed for the total study cohort and within the pancreatic surgery and non-pancreatic (cardiac, vascular, and colonic) surgery patient subgroups. RESULTS: Mean plasma antioxidant concentrations were within or slightly below the normal ranges at baseline. However, a larger percentage of patients demonstrated below-normal baseline plasma concentrations of GSH (59%), vitamin C (59%), and zinc (68%), respectively. A smaller percentage of patients exhibited below-normal plasma alpha-tocopherol levels (21%). Study PN significantly improved plasma zinc levels in the entire study group and in each surgical subgroup. Gln-PN significantly improved the change in plasma levels of reduced GSH from baseline to day 7 in the non-pancreatic surgery patients (PN -0.27 microM versus Gln-PN +0.26 microM, P < 0.03). CONCLUSION: Low plasma levels of key antioxidants were common in this group of patients in the SICU despite administration of PN containing conventional micronutrients. Compared with standard PN, Gln-supplemented PN improved plasma GSH levels in patients in the SICU after cardiac, vascular, or colonic operations.

Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series.

BACKGROUND: Cystic fibrosis (CF) and short bowel syndrome (SBS) patients are unable to absorb vitamin D from the diet and thus are frequently found to be severely vitamin D deficient. We evaluated whether a commercial portable ultraviolet (UV) indoor tanning lamp that has a spectral output that mimics natural sunlight could raise circulating 25-hydroxyvitamin D [25(OH)D] levels in subjects with CF and SBS. METHODS: In initial pilot studies, two SBS subjects came to the outpatient clinic twice weekly for 8 weeks for UV light sessions of 6 min each. In a follow-up study, five CF subjects exposed their lower backs in a seated position to the sunlamp at a distance of 14 cm for 5-10 min depending on the skin type five times a week for 8 weeks. Blood samples for 25(OH)D and parathyroid hormone (PTH) measurements were performed at baseline and at the end of the study. RESULTS: In our study, with two SBS subjects, the indoor lamp increased or maintained circulating 25(OH)D levels during the winter months. We increased the UV lamp frequency and found an improved response in the CF patients. Serum 25(OH)D levels in CF subjects at baseline were 21 +/- 3 ng/ml, which increased to 27 +/- 4 ng/ml at the end of 8 weeks (P=0.05). PTH concentration remained largely unchanged in both population groups. CONCLUSION: A UV lamp that emits ultraviolet radiation similar to sunlight and thus produces vitamin D(3) in the skin is an excellent alternative for CF, and SBS patients who suffer from vitamin D deficiency due to fat malabsorption, especially during the winter months when natural sunlight is unable to produce vitamin D3 in the skin. This UV lamp is widely available for commercial home use and could potentially be prescribed to patients with CF or SBS.

Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation.

BACKGROUND: Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. METHODS: Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. RESULTS: The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. CONCLUSIONS: hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.

Parenteral glutamine increases serum heat shock protein 70 in critically ill patients.

OBJECTIVE: Heat shock protein 70 (HSP-70) is protective against cellular and tissue injury. Increased serum HSP-70 levels are associated with decreased mortality in trauma patients. Glutamine (Gln) administration increases serum and tissue HSP-70 expression in experimental models of sepsis. Gln has been safely administered to critically ill patients and can improve clinical outcomes, but the effect of Gln administration on HSP-70 expression in humans is unknown. We examined whether Gln-supplemented parenteral nutrition (PN) increases serum HSP-70 levels in critically ill patients. DESIGN AND SETTING: Randomized, controlled, double-blind study in surgical intensive care units (SICU) in a university hospital. PATIENTS: 29 patients admitted to the SICU and requiring PN for more than 7 days. INTERVENTIONS: Patients received either Gln-PN (containing alanyl-glutamine dipeptide; 0.5 g/kg per day; n=15) or standard Gln-free PN (control-PN) that was iso-nitrogenous to Gln-PN (n=14). Serum HSP-70 concentrations were measured at enrollment and at 7 days. Clinical outcome measures were also determined. RESULTS: HSP-70 concentrations were unchanged in control-PN subjects from baseline to day 7. In marked contrast, Gln-PN subjects demonstrated significantly higher (3.7-fold) serum HSP-70 concentrations than control subjects. In Gln-PN patients there was a significant correlation between increases in HSP-70 levels over baseline and decrease in ICU length of stay. CONCLUSIONS: Gln-PN significantly increases serum HSP-70 in critically ill patients. The magnitude of HSP-70 enhancement in Gln-treated patients was correlated with improved clinical outcomes. These data indicate the need for larger, randomized trials of the Gln effect on serum and tissue HSP-70 expression in critical illness and relationship to clinical outcomes.