Home parenteral nutrition patients on mixed oil lipid emulsion have a higher rate of hospitalizations compare to those on soybean oil- a prospective 2-year cohort study.

BACKGROUND & AIMS: Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. METHOD: This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value <0.05. RESULTS: A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. CONCLUSION: This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. THE STUDY WAS REGISTERED IN CLINICALTRIALS.GOV: (NCT02299466).

Olive oil-based lipid emulsion is noninferior to soybean oil-based lipid emulsion in the acute care setting: A double-blind randomized controlled trial.

OBJECTIVES: Olive oil (OO)-based intravenous lipid emulsion (IVLE) may have biological advantages for nutrition and inflammation status compared with soybean oil (SO)-based IVLE. We aimed to compare prealbumin levels during infusion of OO- or SO-based IVLE in patients receiving parenteral nutrition in the acute-care setting. METHODS: In this prospective, noninferiority, double blind randomized controlled efficacy trial, patients received either OO-based or SO-based IVLE after providing consent. Biochemical and nutrition parameters were collected at baseline and at 7 to 10 d after initiation of parenteral nutrition. Results are expressed as means (standard deviations). RESULTS: A total of 210 patients completed the study: 102 patients in the SO-based IVLE group and 108 patients in the OO-based IVLE group. Both groups had a significant increase in prealbumin levels from baseline (SO: 0.10 [0.06] versus 0.15 [0.08] g/L; P < 0.0001; OO: 0.11 [0.06] versus 0.16 [0.08] g/L; P < 0.0001), but mean changes between groups were not different (P = 0.53). OO-based IVLE was noninferior to SO-based IVLE in maintaining or increasing serum prealbumin levels, with 20% as the noninferiority margin at follow-up (least square geometric mean ratio [95% CI], 1.10 [0.83,1.47]; P = 0.50). There was a significant improvement in C-reactive protein levels from baseline within each group (SO: 83.24 [69.72] versus 53.4 [59.78] mg/dL; P < 0.0001; OO: 85.13 [68.14] versus 58.75 [60.11] mg/dL; P = 0.004), but mean changes between the groups were not different (P = 0.836). Mortality, length of stay, and infection rates were not different for both groups. CONCLUSIONS: In this study, OO-based IVLE was not inferior to SO-based IVLE in maintaining or increasing the prealbumin level. The improvement of C-reactive protein levels and other clinical outcomes were not different for both groups.

Trends and Novel Research in Hospital Nutrition Care: A Narrative Review of Leading Clinical Nutrition Journals.

Hospital malnutrition is a longstanding problem that continues to be underrecognized and undertreated. The aim of this narrative review is to summarize novel, solution-focused, recent research or commentary to update providers on the prevention of iatrogenic malnutrition as well as the detection and treatment of hospital malnutrition. A narrative review was completed using the top 11 clinically relevant nutrition journals. Of the 13,850 articles and editorials published in these journals between 2013 and 2019, 511 were related to hospital malnutrition. A duplicate review was used to select (n = 108) and extract key findings from articles and editorials. Key criteria for selection were population of interest (adult hospital patients, no specific diagnostic group), solution-focused, and novel perspectives. Articles were categorized (6 classified in >1 category) as Screening and Assessment (n = 17), Standard (n = 25), Advanced (n = 12) and Specialized Nutrition Care (n = 8), Transitions (n = 15), Multicomponent (n = 21), Education and Empowerment (n = 9), Economic Impact (n = 3), and Guidelines (n = 4) for summarizing. Research advances in screening implementation, standard nutrition care, transitions, and multicomponent interventions provide new strategies to consider for malnutrition prevention (iatrogenic), detection, and care. However, several areas requiring further research were identified. Specifically, larger and more rigorous studies that examine health outcomes and economic analyses are urgently needed.

Cancer-related gene expression is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease.

OBJECTIVE: The aim of this study was to determine whether hepatic gene expression related to hepatocellular carcinoma (HCC) is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional study, the associations between hepatic gene expression and liver histology, insulin resistance, anthropometrics, diet, and physical activity were assessed in patients with non-alcoholic steatohepatitis (NASH; n = 19) or simple steatosis (SS; n = 20). In a group of patients with NASH, we then conducted a 1-y, single-arm, pilot study using ω-3 polyunsaturated fatty acid (PUFA) supplementation to determine whether changes in hepatic PUFA content would have a modulating effect on hepatic gene expression and would affect liver histology. RESULTS: In the cross-sectional study, histological features of disease severity correlated with AKR1B10, ANXA2, PEG10, SPP1, STMN2, MT1A, and MT1B in NASH and with EEF1A2, PEG10, and SPP1 in SS. In addition, PEG10, SPP1, ANXA2, and STMN2 expression correlated positively with insulin resistance in NASH. SPP1 and UBD correlated strongly with body mass index in SS. Associations between ENPP2, AKR1B10, SPP1, UBD, and waist circumference depended on sex and diagnosis. Several genes correlated with protein, fat, or carbohydrate intake. PEG10 correlated positively with physical activity in NASH and inversely with plasma vitamin C in both groups. Despite increased erythrocyte and hepatic ω-3 PUFA, supplementation did not alter hepatic gene expression and liver histology. CONCLUSIONS: HCC-related gene expression was associated with liver histology, body mass index, waist circumference, diet, and physical activity but was not affected by ω-3 PUFA supplementation.

Non-Antibiotic Antimicrobial Catheter Lock Solutions in Patients on Home Parenteral Nutrition.

Patients on home parenteral nutrition (HPN) are dependent on central venous access for long-term sustenance, and catheter-related bloodstream infections (CRBSIs) are a major cause of morbidity and mortality in this patient population. As such, there is much interest in finding new methods for preventing CRBSIs in patients on HPN. As it is thought that these infections are preceded by microbial colonization of the catheter, one approach is to use antimicrobial catheter lock solutions. Although antibiotic catheter lock solutions have been present for decades, their use has been mostly limited to the treatment of CRBSIs due to concern for promoting microbial resistance. Recently, however, with the advent of non-antibiotic antimicrobial catheter lock solutions, this approach is gaining popularity as a promising method to decrease rates of CRBSI in HPN patients.

Effect of Discontinuation of Manganese Supplementation From Home Parenteral Nutrition Solutions on Whole-Blood Levels and Magnetic Resonance Imaging of the Brain: A 5-Year Cohort Study.

BACKGROUND: Manganese (Mn) is included in current premixed multiple trace element (TE) additives for home parenteral nutrition (HPN). However, there is a risk of oversupplementation of Mn due to contamination from PN additives. Oversupplementation can produce Mn toxicity with neurologic symptoms and abnormalities on brain magnetic resonance imaging (MRI). In 2009, we reported that whole-blood Mn levels were above the upper limit of normal in 16 HPN patients, with 81% having MRI findings. Subsequently, we removed Mn supplementation from all our HPN patients. We present a 5-year follow-up here. METHODS: This is a prospective cohort study on 11 of the surviving 16 patients on HPN. All patients had Mn removed from PN and had yearly monitoring of blood Mn levels. Eight patients had a repeat MRI to evaluate for resolution of basal ganglia deposits. Patient demography, clinical history, and bloodwork were recorded. RESULTS: Five of 6 patients who initially had elevated Mn levels had normal levels on follow-up. All patients who had Mn levels measured serially had a decrease in levels; the mean percent decrease of Mn was 38.1% (range, 10.1%-53.8%). Two patients had elevated Mn despite the absence of supplementation. Six of 8 patients who had repeat MRIs had complete resolution abnormalities. CONCLUSIONS: Removal of Mn as an additive in HPN solutions resulted in resolution of MRI abnormalities in most patients. Over 5 years, all patients except for 1 maintained normal blood Mn levels. Therefore, Mn levels should be monitored and supplementation be individualized.

Factors associated with nutritional decline in hospitalised medical and surgical patients admitted for 7 d or more: a prospective cohort study.

This prospective cohort study was conducted in eighteen Canadian hospitals with the aim of examining factors associated with nutritional decline in medical and surgical patients. Nutritional decline was defined based on subjective global assessment (SGA) performed at admission and discharge. Data were collected on demographics, medical information, food intake and patients' satisfaction with nutrition care and meals during hospitalisation; 424 long-stay (≥7 d) patients were included; 38% of them had surgery; 51% were malnourished at admission (SGA B or C); 37% had in-hospital changes in SGA; 19·6% deteriorated (14·6% from SGA A to B/C and 5% from SGA B to C); 17·4% improved (10·6% from SGA B to A, 6·8% from SGA C to B/A); and 63·0 % patients were stable (34·4% were SGA A, 21·3% SGA B, 7·3% SGA C). One SGA C patient had weight loss ≥5%, likely due to fluid loss and was designated as stable. A subset of 364 patients with admission SGA A and B was included in the multiple logistic regression models to determine factors associated with nutritional decline. After controlling for SGA at admission and the presence of a surgical procedure, lower admission BMI, cancer, two or more diagnostic categories, new in-hospital infection, reduced food intake, dissatisfaction with food quality and illness affecting food intake were factors significantly associated with nutritional decline in medical patients. For surgical patients, only male sex was associated with nutritional decline. Factors associated with nutritional decline are different in medical and surgical patients. Identifying these factors may assist nutritional care.

Altered hepatic gene expression in nonalcoholic fatty liver disease is associated with lower hepatic n-3 and n-6 polyunsaturated fatty acids.

UNLABELLED: In nonalcoholic fatty liver disease, hepatic gene expression and fatty acid (FA) composition have been reported independently, but a comprehensive gene expression profiling in relation to FA composition is lacking. The aim was to assess this relationship. In a cross-sectional study, hepatic gene expression (Illumina Microarray) was first compared among 20 patients with simple steatosis (SS), 19 with nonalcoholic steatohepatitis (NASH), and 24 healthy controls. The FA composition in hepatic total lipids was compared between SS and NASH, and associations between gene expression and FAs were examined. Gene expression differed mainly between healthy controls and patients (SS and NASH), including genes related to unsaturated FA metabolism. Twenty-two genes were differentially expressed between NASH and SS; most of them correlated with disease severity and related more to cancer progression than to lipid metabolism. Biologically active long-chain polyunsaturated FAs (PUFAs; eicosapentaenoic acid + docosahexaenoic acid, arachidonic acid) in hepatic total lipids were lower in NASH than in SS. This may be related to overexpression of FADS1, FADS2, and PNPLA3. The degree and direction of correlations between PUFAs and gene expression were different among SS and NASH, which may suggest that low PUFA content in NASH modulates gene expression in a different way compared with SS or, alternatively, that gene expression influences PUFA content differently depending on disease severity (SS versus NASH). CONCLUSION: Well-defined subjects with either healthy liver, SS, or NASH showed distinct hepatic gene expression profiles including genes involved in unsaturated FA metabolism. In patients with NASH, hepatic PUFAs were lower and associations with gene expression were different compared to SS.

The role of n - 6 and n - 3 polyunsaturated fatty acids in the manifestation of the metabolic syndrome in cardiovascular disease and non-alcoholic fatty liver disease.

Cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD) are manifestations of the metabolic syndrome. CVD remains the number one cause of mortality in the West, while NAFLD is the most common liver disease. Growing evidence suggests that polyunsaturated fatty acids (PUFA) influence risk factors including circulating lipids and inflammation on the development of CVD and NAFLD. N - 6 and n - 3 PUFA are comprised of distinct family members, which are increasingly recognized for their individual effects. Therefore, this review examines what is currently known about the specific effects of the major n - 3 and n - 6 PUFA on CVD and NAFLD. Overall, this review supports a beneficial effect of n - 3 PUFA and highlights distinctive effects between alpha-linolenic acid found in plant oils relative to marine derived eicosapentaenoic acid and docosahexaenoic acid. This review also highlights contrasting health effects between the n - 6 PUFA, linoleic and arachidonic acid.

The role of nutrients in the development, progression, and treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in adults and children and is currently the third most common indication for liver transplantation in North America. Its pathogenesis is thought to be secondary to multiple "hits" derived from the dietary components, adipose tissue, immune system, and intestinal microbiota. Lack of physical activity may contribute as well. Nutrients may exert their effect directly or through alteration of the intestinal microbiota. Research focusing on specific dietary components predisposing to NAFLD has shown conflicting results. Total energy intake, and macronutrients, has been linked to the development of NAFLD. Fructose not only contributes to hepatic steatosis but may trigger inflammatory signals as well. Polyunsaturated fatty acids are thought to exert anti-inflammatory effects. The role of vitamins as well as minerals in this field is actively being investigated. In this review, we discuss the evidence-linking macronutrients (such as carbohydrates and fat in general and fructose, fiber, short chain fatty acids, polyunsaturated fatty, and choline specifically) and micronutrients (such as vitamin E and C and minerals) with the development and treatment of NAFLD. We also discuss the literature on physical activity and NAFLD.

The Canadian Home Total Parenteral Nutrition (HTPN) Registry: vitamin K supplementation and bone mineral density.

BACKGROUND: Vitamin K supplementation improves bone health, and its absence might be associated with low bone mineral density (BMD). The authors aim to assess vitamin K supplementation practices in Canadian home parenteral nutrition (HPN) programs and their relationship with BMD. METHODS: This is a cross-sectional study of 189 patients from the Canadian HPN registry. RESULTS: All 189 patients studied received M.V.I.-12, which does not contain vitamin K. Of those, 41.3% were supplemented with 10 mg of intravenous vitamin K (VK+) weekly, whereas the others did not receive vitamin K except via lipid emulsion (VK-). Short bowel syndrome accounted for 69% of VK+ and 46% of VK- patients. On univariate analysis, VK+ patients had substantially lower body mass index (BMI) and received lower bisphosphonate infusion than did VK-patients. There were no statistically significant differences in HPN calcium or lipid content, liver function test results, age, sex, or reason for HPN between the 2 groups. Patients who were VK+ had higher lumbar spine T scores and hip T scores than did VK-patients. General linear modeling analysis, adjusted for BMI, age, PN magnesium, PN phosphate, PN calcium, and bisphosphonate as possible predictors of BMD, showed a trend toward better hip T scores (P = .063) for VK+ patients compared with VK- patients. CONCLUSION: In HPN patients supplemented with vitamin K, the trend toward a better hip BMD compared with no supplementation suggests a role for vitamin K in preserving BMD. This requires further study.

In patients with HIV-infection, chromium supplementation improves insulin resistance and other metabolic abnormalities: a randomized, double-blind, placebo controlled trial.

Chromium is an essential micronutrient; chromium deficiency has been reported to cause insulin resistance, hyperglycemia and hyperlipidemia. The aim was to investigate the effect of chromium supplementation on insulin-resistance, other metabolic abnormalities, and body composition in people living with HIV. This was a randomized, double-blind, placebo-controlled trial. Fifty-two HIV-positive subjects with elevated glucose, lipids, or evidence of body fat redistribution, and who had insulin-resistance based on the calculation of homeostasis model of assessment (HOMA-IR > or = 2.5) were assessed. Subjects who were on insulin or hypoglycemic medications were excluded. Subjects were randomized to receive either 400 microg/day chromium-nicotinate or placebo for 16 weeks. Forty-six subjects, 23 in each group, completed the study. Fasting blood insulin, glucose, lipid profile and body composition were measured before and after intervention. Chromium was tolerated without side effects and resulted in a significant decrease in HOMA-IR (median (IQR) (pre:4.09 (3.02-8.79); post: 3.66 (2.40-5.46), p=0.004), insulin (pre: 102 (85-226); post: 99 (59-131) pmol/L, p=0.003), triglycerides, total body fat mass (mean+/-SEM) (pre: 17.3+/-1.7; post: 16.3+/-1.7 kg; p=0.002) and trunk fat mass (pre: 23.8+/-1.9; post: 22.7+/-2.0 %; p=0.008). Blood glucose, C-peptide, total, HDL and LDL cholesterol, and hemoglobin A1c remained unchanged. Biochemical parameters did not change in the placebo group except for LDL cholesterol which increased significantly. Body weight and medication profile remained stable throughout the study for both groups. In summary, chromium improved insulin resistance, metabolic abnormalities, and body composition in HIV+ patients. This suggests that chromium supplements alleviate some of the antiretroviral-associated metabolic abnormalities.

A survey on the usage of supplements in canadian patients living with HIV.

To assess the usage, knowledge and attitudes of Patients Living with HIV with respect to supplements. A questionnaire was mailed to people living with HIV via HIV/AIDS organizations in Ontario and distributed to those attending the HIV-clinic of the University Health Network. The survey was completed by 312 subjects (95 female, 207 male). Self-rated health status was considered fair/good in 77.5% and excellent in 15.4% of participants. Vitamin/mineral supplement was used by 75.6%. Main reasons to take supplements were to: prolong life (56.1%); treat HIV-related conditions (19.9%); increase energy level (42.6%) and to boost immunity (36.5%). Among participants, 54.2% were somewhat familiar with supplements, 44.7% trusted the information on the labels and 28.2% felt that if a supplement is available for sale, it is safe. Supplements were mostly purchased at pharmacies (45.5%) and health food stores (30.1%). Only 25.9% and 27.9% of participants discussed their use of supplements with their HIV or family doctor respectively. Supplements are frequently used by people living with HIV without consulting their doctors. Current research has not shown a clear benefit from micronutrient supplementation and with the possible potential drug interactions, people living with HIV will need nutrition education regarding supplement usage and should report their use to their physicians.

Adequacy of nutritional intake in a Canadian population of patients with Crohn's disease.

Crohn's disease is frequently associated with nutritional deficiencies, often a result of disease activity and poor oral intake. This study investigated the adequacy of dietary intake, based on the Canadian Dietary Reference Intake, in ambulatory patients with Crohn's disease and a normal body mass index (BMI; calculated as kg/m(2)). This was a cross-sectional study of 74 patients with mean age of 35.7+/-1.4 years and BMI of 23.05+/-0.45. All patients completed a 7-day food record and a diary for the Crohn's Disease Activity Index. Mean Crohn's Disease Activity Index was 138.99+/-11.38. Energy and protein intakes were within the recommended levels of intake, but total carbohydrates, fat, and saturated fat intake exceeded the recommended levels of <55%, <35%, and <10% in 39.2%, 27%, and 59.5% of the patients, respectively. Micronutrient intakes were suboptimal most notably for folate, vitamins C, E, and calcium. There were no substantial differences between patients with active and inactive disease in terms of failure to meet the Dietary Reference Intake. In conclusion, in this population sample, a large number of ambulatory patients with Crohn's disease have suboptimal dietary patterns despite a normal BMI and inactive disease. Dietary counseling and supplementation may be warranted in this patient population.

Dietary intake of elderly living in Toronto long-term care facilities: comparison to the dietary reference intake.

OBJECTIVE: To compare the dietary intake of elderly living in 11 long-term care facilities (LTCFs) to the Estimated Average Requirement set as part of the Dietary Reference Intake for older adults. DESIGN: A cross-sectional assessment of dietary intake using a 3 days food record among 407 elderly with mean age of 85.2 +/- 7.7 years and BMI of 23.8 +/- 5.7 kg/m(2). This population sample was similar to the one living in LTCFs in the province of Ontario. RESULTS: The daily energy intake was 1513 +/- 363 kcal (6330.4 +/- 1518.8 kJ). Percentage of energy from fat, saturated fat, polyunsaturated fat, protein, and carbohydrate were 30%, 11%, 5.2%, 15%, and 56%, respectively. Although these values were close to the recommendations, 29.5% had protein intake below the recommended 0.8 g/kg; and 38.3% of subjects had cholesterol intake more than the recommended 300 mg/d. More than 50% of the subjects had suboptimal intake of calcium, magnesium, zinc and vitamins E, B(6), and folate. In addition, greater than 15% had suboptimal intakes of other micronutrients such as vitamins A, C, niacin, and copper. CONCLUSIONS: Elderly subjects living in LTCFs in Toronto despite having a normal body mass index (BMI), do not meet the recommended levels of intake for protein and many of the micronutrients. LTCFs staff should monitor dietary intake. Menu modification and micronutrient supplementation may be required in order to meet the daily requirements of these elderly.

Effect of multivitamin and mineral supplementation on episodes of infection in nursing home residents: a randomized, placebo-controlled study.

OBJECTIVES: To evaluate the effect of vitamin and mineral supplementation on infections in an elderly institutionalized population. DESIGN: Eighteen-month, randomized, placebo-controlled trial. SETTING: Twenty-one long-term care facilities. PARTICIPANTS: Seven hundred sixty-three subjects from 21 long-term care facilities. INTERVENTION: Participants were randomized to receive one multivitamin and mineral supplementation daily or placebo. MEASUREMENTS: The primary outcome was number of infections per subject. Secondary outcomes were antibiotic use and hospitalization rates. Infection control surveillance was conducted over 18 months using standardized criteria. RESULTS: Outcome data from 748 subjects, mean age 85, were included in the intention-to-treat analysis. Using univariate analyses, there was no difference in infectious episodes between the supplemented and placebo groups (3.5 infections per 1,000 resident-days vs 3.8 infections per 1,000 resident-days, odds ratio (OR)=0.92, 95% confidence interval (CI)=0.82-1.03, P=.12). There was a reduction in antibiotic usage in the supplementation group, but this was not significant in the multivariate model. There was no difference in the number of hospital visits. In the multivariate analysis, the effect of multivitamin use on total number of infections was not significant (OR=0.77, 95% CI=0.54-1.1). Subjects without dementia had a greater rate of infections than those with dementia (OR=1.44, 95% CI=1.19-1.76). In post hoc subgroup analysis, subjects without dementia who received supplementation had a significantly lower rate of infections than those who received placebo (relative risk=0.81, 95% CI=0.66-0.99). CONCLUSION: Overall, multivitamin and mineral supplementation does not have a significant effect on the incidence of infections in institutionalized seniors, although the subgroup of residents in long-term care without dementia may benefit from supplementation. Further research is needed to determine its effect in high-risk subgroups within the nursing home population.

Exacerbation of dextran sulfate sodium-induced colitis by dietary iron supplementation: role of NF-kappaB.

BACKGROUND: In colitis, iron therapy may be given to treat anemia, but it may also be detrimental based on our previous studies using a rat model with colitis where iron supplementation increased disease activity and oxidative stress. This effect was partially reduced by an antioxidant. AIMS: The aim of this study was to further evaluate, in rats with dextran sulfate sodium (DSS)-induced colitis, the effect of iron on neutrophilic infiltration, cytokines and nuclear factor kappa-B (NF-kappaB)-associated inflammation and to determine whether the addition of vitamin E would be beneficial. METHODS: Colitis was induced with DSS at 50 g/l in drinking water for 7 days. DSS rats were randomized to the following: DSS, receiving a control, non-purified diet (iron, 270 mg and DL-alpha-tocopherol acetate, 49 mg/kg); DSS+iron (diet+iron, 3,000 mg/kg); DSS+vitamin E (diet+DL-alpha-tocopherol acetate, 2,000 mg/kg); or the DSS+iron+vitamin E. Colonic inflammation, myeloperoxidase activity (MPO), lipid peroxides (LPO), proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6] and NF-kappaB binding activity were measured. RESULTS: The DSS+iron group showed a significant increase in inflammatory scores, MPO, TNF-alpha, IL-1, LPO and NF-kappaB activity compared to DSS or DSS+vitamin E. The addition of vitamin E to iron (DSS+iron+vitamin E group) significantly reduced the inflammatory scores, TNF-alpha and IL-6. None of the other parameters were affected. CONCLUSION: Iron increases disease activity in colitis, and this is associated with oxidative stress, neutrophilic infiltration, increased cytokines and activation of NF-kappaB. This detrimental effect was partially reduced by vitamin E.

Antioxidant vitamin supplementation in Crohn's disease decreases oxidative stress. a randomized controlled trial.

OBJECTIVE: We showed previously that patients with Crohn's disease (CD) had increased oxidative stress and lower antioxidant vitamins compared with healthy controls. This is despite inactive or mildly active disease and maintenance therapy. The aim of this study was to evaluate in these patients the effects of antioxidant vitamin supplementation on oxidative stress. METHODS: This is a randomized controlled trial where stable but oxidatively stressed CD subjects (n = 57) were supplemented with vitamins E (800 IU) and C (1000 mg) or their placebo for 4 wk. Oxidative stress measured by breath pentane and ethane output, plasma lipid peroxides, and F2-isoprostane was assessed at baseline and at 4 wk. Disease activity was also monitored by measuring CD activity index and plasma orosomucoid. RESULTS: During supplementation, plasma vitamin C and alpha-tocopherol increased and all indices of oxidative stress decreased significantly. Disease activity remained stable. CONCLUSIONS: In this population, vitamin E and C supplementation resulted in a significant reduction in oxidative stress. This suggests that patients with inactive or mildly active CD can be oxidatively stressed and have increased requirement in antioxidant vitamins.

Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulfate sodium-induced colitis.

Inflammatory bowel disease is often associated with iron deficiency anemia and oral iron supplementation may be required. However, iron may increase oxidative stress through the Fenton reaction and thus exacerbate the disease. This study was designed to determine in rats with dextran sulfate sodium (DSS)-induced colitis whether oral iron supplementation increases intestinal inflammation and oxidative stress and whether the addition of an antioxidant, vitamin E, would reduce this detrimental effect. Four groups of rats that consumed 50 g/L DSS in drinking water were studied for 7 d and were fed: a control, nonpurified diet (iron, 270 mg, and dl-alpha-tocopherol acetate, 49 mg/kg); diet + iron (iron, 3000 mg/kg); diet + vitamin E (dl-alpha-tocopherol acetate, 2000 mg/kg) and the diet + both iron and vitamin E, each at the same concentrations as above. Body weight change, rectal bleeding, histological scores, plasma and colonic lipid peroxides (LPO), plasma 8-isoprostane, colonic glutathione peroxidase (GPx) and plasma vitamin E were measured. Iron supplementation increased disease activity as demonstrated by higher histological scores and heavier rectal bleeding. This was associated with an increase in colonic and plasma LPO and plasma 8-isoprostane as well as a decrease in colonic GPx. Vitamin E supplementation decreased colonic inflammation and rectal bleeding but did not affect oxidative stress, suggesting another mechanism for reducing inflammation. In conclusion, oral iron supplementation resulted in an increase in disease activity in this model of colitis. This detrimental effect on disease activity was reduced by vitamin E. Therefore, the addition of vitamin E to oral iron supplementation may be beneficial.