Iron supplementation increases small intestine permeability in primary schoolchildren in Lusaka, Zambia

Elevated intestinal permeability, measured as an increased lactulose:mannitol (L:M) ratio, indicates injury of the small intestinal mucosa. As part of a randomized iron and multi-micronutrient (without iron) supplementation trial (Nchito et al., 2004), we determined intestinal permeability in a subgroup of schoolchildren at 10 months' follow-up to assess the effect of the interventions. Among 153 children (mean age 10.2 years and 53.6% girls) iron supplementation resulted in a higher L:M ratio compared with placebo (0.29 vs. 0.21, P=0.025). There was no effect of multi-micronutrient supplementation, and no interaction between the interventions. The finding could be one of the mechanisms explaining the negative effects of medicinal iron supplementation on morbidity found in some other studies.     

A double-blind, placebo-controlled, glutamine-supplementation trial in growth-faltering Gambian infants

BACKGROUND: Growth faltering during infancy is a characteristic of life in developing countries. Previous studies have shown that small-intestine mucosal enteropathy, accompanied by endotoxemia and a persistent systemic inflammatory response, accounts for up to 64% of the growth faltering in Gambian infants. OBJECTIVE: The objective was to test whether glutamine, with its putative trophic effects on enterocytes, immune cells, and intestinal integrity, can accelerate the repair of the intestine, lower immunostimulation, and reduce growth faltering. DESIGN: Ninety-three infants aged 4-10 mo from the West Kiang region of The Gambia were studied in a double-blind, double-placebo, controlled trial. Glutamine (0.25 mg/kg body wt) or a placebo that contained an isonitrogenous, isoenergetic mix of nonessential amino acids was orally administered twice daily throughout the 5-mo rainy season. Anthropometric measurements were made monthly during the supplementation period and for 6 mo after supplementation. Intestinal permeability was measured monthly (by determining the ratio of lactulose to mannitol), and finger-prick blood samples were collected for the analysis of plasma proteins on 3 occasions. RESULTS: Gambian infants showed a seasonal deterioration in growth and persistently elevated acute phase protein concentrations and intestinal permeability. Oral supplementation with glutamine did not improve growth (x +/- SE: weight gain, 60 +/- 19 and 69 +/- 20 g/mo; length gain, 1.01 +/- 0.05 and 0.95 +/- 0.03 cm/mo) or intestinal permeability [lactulose:mannitol ratio: 0.29 (95% CI: 0.23, 0.35) and 0.26 (95% CI: 0.21, 0.32)] in the glutamine and placebo groups, respectively. It also had no effect on infant morbidity or on plasma concentrations of immunoglobulins or acute phase proteins. CONCLUSION: Glutamine supplementation failed to improve growth or intestinal status in malnourished Gambian infants.     

Effect of Lactobacillus GG on intestinal integrity in Malawian children at risk of tropical enteropathy

BACKGROUND: Tropical enteropathy is an asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity. The histology of tropical enteropathy resembles that seen in small-bowel bacterial overgrowth. OBJECTIVE: This study tested the hypothesis that treatment of 3-5-y-old Malawian children with the probiotic Lactobacillus GG would improve their intestinal function and integrity. DESIGN: Clinically healthy children (n = 164) were enrolled in a placebo-controlled, randomized, double-blind trial. Intestinal function and integrity were measured by using the site-specific sugar-absorption test before and after 30 d of treatment with Lactobacillus GG or placebo. The primary outcomes were the ratios of urinary lactulose to mannitol (L:M) and of urinary sucrose to lactulose (S:L) excretion. RESULTS: Of the 161 children who completed the study, 119 (73%) had tropical enteropathy on enrollment (L:M > 0.10). Children receiving Lactobacillus GG did not differ significantly from the placebo group in the excretion (in % of dose administered) of mannitol (mean +/- SD: 8.9 +/- 4.4 and 8.9 +/- 3.9, respectively), lactulose (0.31 +/- 0.20 and 0.33 +/- 0.23, respectively), or sucrose (0.078 +/- 0.058 and 0.082 +/- 0.075, respectively). L:M and S:L also did not differ significantly between the Lactobacillus and placebo groups (0.19 +/- 0.13 and 0.20 +/- 0.12, respectively, for L:M; 0.58 +/- 0.46 and 0.65 +/- 0.57, respectively, for S:L). CONCLUSION: Administration of Lactobacillus GG for 30 d had no effect on the intestinal integrity of 3-5-y-old Malawian children.     

Association of vitamin A and zinc status with altered intestinal permeability: analyses of cohort data from northeastern Brazil

To examine the association of intestinal barrier function with vitamin A deficiency and whether supplementation of micronutrients improves intestinal function and/or linear growth, height-for-age z-score (HAZ), concentrations of serum retinol and zinc, and intestinal permeability were determined in a cross-sectional sample of 75 children in northeastern Brazil. Effects of vitamin A and supplementation of zinc on intestinal permeability and growth were also determined comparing results before and after treatment in 20 children and age-matched controls. Lactulose:mannitol (L/M) permeability ratios inversely correlated with serum retinol concentrations (r = -0.55, p < 0.0005). Increased L/M permeability ratios with reduced concentrations of serum retinol were predominantly attributable to lower absorption of mannitol (r = 0.28, p = 0.02). L/M permeability ratios (p = 0.001) and HAZ scores (p = 0.007) improved with supplementation. It is concluded that impaired intestinal barrier function and linear growth shortfalls improve following supplementation of vitamin A and zinc in this setting.     

Intestinal permeability in runners in the 1996 Chicago marathon

Abdominal cramping, nausea, diarrhea, and GI bleeding are often reported in long-distance runners. This study set out to determine the effects of prolonged (2-4 hrs) exercise and NSAID ingestion on gastric and intestinal permeability during the first 5 hrs following the 1996 Chicago Marathon. Thirty-four healthy volunteers (20 M, 14 F; ages 30-50) completed the race and ingested the test solution (5 g sucrose, 5 g lactulose, 2 g rhamnose, in 40 ml water) within 10-15 min. The urinary excretion ratio of lactulose/rhamnose was used to assess small intestine permeability; sucrose excretion was used to evaluate gastric impairment. There were no significant differences for mean training mileage, postrace rectal temperature, and percent dehydration between runners who ingested NSAIDs and those who did not. In all, 75% of subjects reported aspirin or ibuprofen ingestion before or during the race. Runners who ingested ibuprofen had significant elevations in urinary lactulose excretion and lactulose/rhamnose ratio, whereas those who ingested aspirin or who did not ingest either NSAID had no significant differences in urinary excretion of lactulose, rhamnose, sucrose, or lactulose/rhamnose ratio compared to resting controls. Thirteen of the 26 NSAID users and 4 of the 8 non-users reported GI symptoms. It is concluded that (a) ibuprofen but not aspirin ingestion during prolonged exercise may increase gastrointestinal permeability and lead to GI symptoms, and (b) prolonged exercise alone can produce GI symptoms.     

The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: a randomized controlled trial

BACKGROUND: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as reflected by decreased intestinal permeability. The aim of our study was to investigate whether glutamine-enriched enteral nutrition in VLBW infants enhances the normal decrease in intestinal permeability, as measured by the sugar absorption test (SAT). METHODS: In a double-blind, randomized, placebo-controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1,500 g) received enteral glutamine supplementation (0.3 g/kg/d) or an isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Intestinal permeability, determined from the urinary lactulose/mannitol (L/M) ratio after an oral dose of lactulose and mannitol, was assessed at 4 time points: before the start of the study, and at days 7, 14, and 30 of life. RESULTS: At least 2 SATs were performed in 45/52 (86%) and 45/50 (90%) infants in the glutamine-supplemented and control groups, respectively. Baseline patient and nutrition characteristics were not different between the groups. There was no effect of glutamine-enriched enteral nutrition on the decrease of the L/M ratio between the start and end of the study (p = .78). In both treatment groups, median urinary lactulose concentrations decreased (p < .001), whereas median urinary mannitol concentrations increased (p = .003). CONCLUSIONS: Glutamine-enriched enteral nutrition does not enhance the postnatal decrease in intestinal permeability in VLBW infants. Any beneficial effect of glutamine may involve other aspects of intestinal integrity; for example, modulation of the intestinal inflammatory response.     

Intestinal permeability after early postoperative enteral nutrition in patients with upper gastrointestinal malignancy

BACKGROUND: Increased intestinal permeability may lead to sepsis in resected upper gastrointestinal (GI) cancer patients. This study sought to determine whether these patients demonstrated increased intestinal permeability and if early postoperative enteral nutrition would alter this result. METHODS: Nineteen patients undergoing complete resection of upper GI malignancy were randomized into two groups: the nonfed group received IV crystalloid, and the fed group started enteral nutrition by jejunostomy on postoperative day (POD) 1. Six nonoperative volunteers were controls. The lactulose/mannitol test was performed on PODs 1 and 5. Ten grams of lactulose and 5 g of mannitol were given, and urine was collected for 6 hours. RESULTS: All patients (nonfed, 1.895+/-0.34; fed, 0.893+/-0.24) had elevated lactulose/mannitol ratios on POD 1 vs controls (0.262+/-0.1; p < .008 and p = .05). These elevated levels returned toward control levels in both groups by day 5 (nonfed, 0.533+/-0.1, p = .06; fed, 0.606+/-0.12, p = .08). CONCLUSIONS: Major upper GI surgery for malignancy resulted in a significant increase in intestinal permeability on POD 1. With or without enteral nutrition, this measure of intestinal permeability returned to normal on POD 5 in well-nourished patients.     

Differential response of plasma and immune cell's vitamin E levels to physical activity and antioxidant vitamin supplementation

OBJECTIVE: To assess the differential response of plasma, lymphocyte and neutrophil vitamin E levels to high-intensity physical activity and to vitamin C and E supplementation. SUBJECTS: In all, 14 male trained amateur runners (32-36 y old) were randomly divided in two groups (supplemented and placebo), and participated in a half marathon race. The subjects did not take any other supplements than the ones provided for this study. INTERVENTION: Vitamin C (152 mg/day) and E (50 mg/day) supplementation was administrated to athletes for a month, using a new almond-based isotonic and energetic beverage (supplemented group). The usual dietary habits of participants were assessed using a self-reported 7-day 24-h recall before the day of the study. To avoid the beverage influence, nonenriched vitamin C and E almond-based isotonic and energetic beverage was given to the placebo group. After 1 month, subjects participated in a half marathon race (21 km run). Vitamin E concentration was determined in plasma, neutrophils and lymphocytes before and immediately after the race, and 3 h after finishing the race. RESULTS: Daily energy intake and caloric profile of supplemented and placebo group were not different except for vitamin C and E supplementation. Vitamin supplementation and exercise had no effect on vitamins E levels in plasma. The exercise significantly (P<0.05) increased the lymphocyte vitamin E concentration both in the placebo (+119%) and supplemented groups (+128%), and neutrophil vitamin E content in the supplemented group (+88%). These levels remained significantly (P<0.05) high after the short recovery. After exercise, vitamin E levels in lymphocytes and neutrophils of supplemented subjects were practically twice the levels before exercise, whereas neutrophil vitamin E content of the placebo group was close to those in plasma. CONCLUSION: After endurance exercise, lymphocytes increased their vitamin E content in the supplemented and placebo subjects whereas this trend in neutrophils was just observed in the supplemented group. The determination of vitamin E content in lymphocytes and neutrophils after exercise is a useful tool to assess the functional status of vitamin E.     

Cosupplementation with vitamin E and coenzyme Q10 reduces circulating markers of inflammation in baboons

BACKGROUND: Inflammation and oxidative stress are processes that mark early metabolic abnormalities in vascular diseases. OBJECTIVES: We explored the effects of a high-fat, high-cholesterol (HFHC) diet on vascular responses in baboons and the potential response-attenuating effects of vitamin E and coenzyme Q(10) (CoQ(10)) supplementation. DESIGN: We used a longitudinal design by subjecting 21 baboons (Papio hamadryas) to sequential dietary challenges. RESULTS: After being maintained for 3 mo on a baseline diet (low in fat and cholesterol), 21 baboons were challenged with an HFHC diet for 7 wk. The serum C-reactive protein (CRP) concentrations did not change. Subsequent supplementation of the HFHC diet with the antioxidant vitamin E (250, 500, or 1000 IU/kg diet) for 2 wk reduced serum CRP concentrations from 0.91 +/- 0.02 to 0.43 +/- 0.06 mg/dL. Additional supplementation with CoQ(10) (2 g/kg diet) further reduced serum CRP to approximately 30% of baseline (0.28 +/- 0.03 mg/dL; P = 0.036 compared with the HFHC diet). Introduction of the HFHC diet itself significantly decreased serum P-selectin (from 48.8 +/- 7.2 to 32.9 +/- 3.7 ng/dL, P = 0.02) and von Willebrand factor (from 187.0 +/- 10.1 to 161.9 +/- 9.0%, P = 0.02) concentrations. However, neither vitamin E alone nor vitamin E plus CoQ(10) significantly altered the serum concentrations of P-selectin or von Willebrand factor. CONCLUSIONS: Dietary supplementation with vitamin E alone reduces the baseline inflammatory status that is indicated by the CRP concentration in healthy adult baboons. Cosupplementation with CoQ(10), however, significantly enhances this antiinflammatory effect of vitamin E.     

Effects of long-term supplementation with moderate pharmacologic doses of vitamin E are saturable and reversible in patients with type 1 diabetes

BACKGROUND: Vitamin E supplementation has been proposed as adjunctive therapy to counteract the increased LDL oxidation in diabetes and thus prevent or delay cardiovascular complications. OBJECTIVE: The objective of this study was to investigate the effect of a moderate pharmacologic dose of vitamin E for 相似文献   

Antioxidant supplementation enhances neutrophil oxidative burst in trained runners following prolonged exercise

The influence of an antioxidant vitamin supplement on immune cell response to prolonged exercise was determined using a randomized, double-blind, placebo-controlled, cross-over study. Twelve healthy endurance subjects (n = 6 male, n = 6 female; mean +/- SD for age, 30.1 +/- 6.2 yr; height, 1.76 +/- 7 m; body mass, 72.2 +/- 10.2 kg; VO2max, 63.7 +/- 12 ml x kg(-1) x min(-1)) participated in the study. Following a 3-week period during which subjects ingested a multivitamin and -mineral complex sufficient to meet the recommended daily allowance, they took either a placebo or an antioxidant vitamin supplement (containing 18 mg beta-carotene, 900 mg vitamin C, and 90 mg vitamin E) for 7 days prior to a 2-h treadmill run at 65% VO2max. Blood samples were drawn prior to and immediately following exercise. These were analyzed for neutrophil oxidative burst activity, cortisol and glucose concentrations, and white blood cell counts, as well as serum anti-oxidant vitamin concentrations. Plasma vitamin C, vitamin E, and beta-carotene concentrations significantly increased following 7-day supplementation (p < .05). In comparison to the placebo group, neutrophil oxidative burst was significantly higher following exercise (p < .05), but no differences were found in any other parameter following the 7-day supplementation period. Although the impact of exercise on neutrophil function is multifactorial, our data suggest that antioxidant supplementation may be of benefit to endurance athletes for the maintenance of this particular function of the innate immune system following the 7-day supplementation period.     

Long-term pharmacologic doses of vitamin E only moderately affect the erythrocytes of patients with type 1 diabetes mellitus

In erythrocytes from diabetic patients, increased membrane lipid peroxidation might lead to abnormalities in composition and function. To study this relationship, we investigated the effects of a moderate pharmacologic dose of vitamin E for 1 y on erythrocyte membrane peroxidation in vitro and on its fatty acid composition, antioxidant capacity and rheological function. In a random and double-blind manner, type 1 diabetic patients (n = 44) were assigned to the following two groups: Group S received 250 IU (168 mg) d-alpha tocopherol 3 times daily for 1 y. Group P received placebo for 6 mo followed by d-alpha-tocopherol for an additional 6 mo. Variables were monitored every 3 mo. After 3 mo of supplementation, serum vitamin E doubled (P < 0.0005), thiobarbituric acid reactive substances in erythrocyte membranes incubated with tert-butyl hydroperoxide decreased by 25% (P = 0.006) and the lagtime of fluorescence increased from 28 +/- 16 to 41 +/- 28 min (P = 0.028). Patients who did not respond to supplementation (13 of 44) had lower serum lipids (P = 0.017) and body mass index (P = 0.024). We did not detect any significant effects of vitamin E supplementation on membrane lipid composition, antioxidant capacity or blood viscosity. Continuing supplementation for up to 1 y did not further affect serum vitamin E or membrane peroxidation. Stopping supplementation was followed by a return to inclusion values. These results show that the decrease in erythrocyte membrane peroxidation after vitamin E supplementation is moderate, saturable, reversible, restricted to some individuals and has no detectable effect on erythrocyte composition and function.     

The impact of vitamins and/or mineral supplementation on blood pressure in type 2 diabetes

OBJECTIVE: The present study designed to assess the effect of Mg+Zn, vitamin C+E, and combination of these micronutrients on blood pressure in type 2 diabetic patients. MATERIALS AND METHODS: In a randomized, double-blind, placebo controlled clinical trial, 69 type 2 diabetic patients were randomly divided into four groups, each group receiving one of the following daily supplement for three months; group M: 200 mg Mg and 30 mg Zn (n = 16), group V: 200 mg vitamin C and 150 mg vitamin E (n = 18), group MV: minerals plus vitamins (n = 17), group P: placebo (n = 18). Blood pressure was measured at the beginning and at the end of the trial. Treatment effects were analyzed by general linear modeling. RESULTS: Results indicate that after three months of supplementation levels of systolic, diastolic and mean blood pressure decreased significantly in the MV group by 8 mmHg (122 +/- 16 vs. 130 +/- 19 mmHg), 6 mmHg (77 +/- 9 vs. 83 +/- 11 mmHg), and 7 mmHg (92 +/- 9 vs. 99 +/- 13 mmHg), respectively (p < 0.05). Also combination of vitamin and mineral supplementation had significantly effects in increasing serum potassium (p < 0.05) and in decreasing serum malondialdehyde (p < 0.05). There was no significant change in the levels of these parameters in the other three groups. CONCLUSION: The results of the present study indicated that in type 2 diabetic patients a combination of vitamins and minerals, rather than vitamin C and E or Mg and Zn, might decrease blood pressure.     

Poor intestinal permeability in mildly stunted Nepali children: associations with weaning practices and Giardia lamblia infection

Studies in the Gambia, using the lactulose-mannitol dual-sugar intestinal permeability test (lactulose:mannitol ratio) as a non-invasive way of investigating mucosal damage, have shown that food malabsorption is significantly associated with early growth retardation. In this cross-sectional study, 210 poor urban Nepali children, 0-60 months old, were recruited and measured for height or length and weight, 167 were examined for intestinal permeability and 173 for parasite infection. Weaning and morbidity data were collected from 172 caretakers. Children were mildly stunted (mean height-for-age z-score -1.45) and underweight (mean weight-for-age z-score -1.62). The lactulose:mannitol ratio (0.26) was poorer than that of UK children (0.12), but similar to that found in Bengali children of the same age (0.24). Two stages of weaning, the onset supplementary feeding (6 months) and the cessation of breast-feeding (23 months), were shown to have differential impact. In children currently breast-feeding, the duration of supplementation was negatively related to lactose (P<0.001) and lactose:lactulose values (P<0.0001), indicating lactose maldigestion. In children who had ceased breast-feeding, a longer period of lactation was associated with poorer intestinal permeability (P=0.031), and poorer height-for-age (P=0.024), which was an unexpected result. No significant relationships were found between intestinal permeability and growth, or with morbidity and helminth infection, except in children with Giardia lamblia who had worse lactulose:mannitol ratios than those without (0.43 v. 0.25 respectively, P=0.014). It is likely that insults to the gut (e.g. Giardia) and challenges to the immune system (weaning) have a different impact in early and late infancy.     

The effect of vitamin E and vitamin C supplementation on LDL oxidizability and neutrophil respiratory burst in young smokers

OBJECTIVE: The purpose of this study was to determine the effect of vitamin E and/or vitamin C supplementation on low-density lipoprotein (LDL) oxidizability and neutrophil (PMN) superoxide anion production in young smokers. METHODS: Thirty smokers with a <5 pack-year history were randomly assigned to take placebo; vitamin C (1 g/day); vitamin E (400 IU/day), or both vitamins in a double-blind fashion. Subjects took the supplements for 8 weeks. At weeks 0 and 8, blood was collected for isolation of LDL and PMN, and for antioxidant vitamin analysis. LDL was oxidized with a copper (Cu) catalyst, and oxidation was measured by formation of conjugated dienes over a 5-hour time course. Lag times and maximum oxidation rates were calculated from the time course data. PMN superoxide anion release was assessed by respiratory burst after stimulation with phorbol ester and opsonized zymosan, and their ability to oxidize autologous LDL following treatment with the above stimuli was measured with the conjugated diene assay. RESULTS: Subjects who received vitamin E alone had a significant increase in the lag phase of Cu-catalyzed LDL oxidation (week 0, 118+/-31 min vs. week 8, 193+/-80 min, mean +/- SD, p < 0.05), whereas the vitamin C and placebo groups had no changes in LDL oxidation kinetics. The group receiving both vitamins E and C had a significant reduction in oxidation rate (week 0. 7.4+/-2.3 vs. week 8, 5.1+/-2.1, p < 0.05). There were no significant changes for any group in PMN superoxide anion production or PMN LDL oxidation after stimulation with either phorbol ester or opsonized zymosan. Plasma and LDL vitamin E concentrations were significantly increased in both groups that received vitamin E. The subjects who received vitamin C alone had no significant change in plasma vitamin C concentrations; however, when data were pooled from both groups who received vitamin C, the increases were significant. CONCLUSION: Vitamin E supplementation of young smokers was effective in reducing Cu-catalyzed LDL oxidizability; however, vitamin E and/or C supplementation showed few significant effects on the more physiologically relevant PMN function. This casts doubt on the ability of antioxidant supplementation to reduce oxidative stress in smokers in vivo. Therefore, smoking cessation remains the only means by which young smokers can prevent premature coronary heart disease.     

Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative stress in human skin

BACKGROUND: Ultraviolet radiation (UVR) generates reactive oxygen species in skin that can play a role in skin damage, but reports about the photoprotective properties of oral antioxidant supplements are conflicting. OBJECTIVE: We examined the ability of 2 lipid-soluble antioxidants, vitamin E and beta-carotene, to reduce markers of oxidative stress and erythema in human skin exposed to UVR. DESIGN: Sixteen healthy subjects took either alpha-tocopherol (n = 8; 400 IU/d) or beta-carotene (n = 8; 15 mg/d) for 8 wk. Biopsy samples before and after supplementation were taken from unexposed skin and skin 6 h after 120 mJ/cm(2) UVR. The effects of supplements on markers of oxidative stress in skin and the minimal erythema dose to UVR were assessed. RESULTS: Supplementary vitamin E was bioavailable, the plasma concentration increased from 14.0 +/- 0.66 (x +/- SEM) to 18.2 +/- 0.64 mug/mL (P < 0.01), and the skin concentration increased from 0.55 +/- 0.09 to 1.6 +/- 0.19 ng/mg protein (P < 0.01). Supplementary beta-carotene increased plasma concentrations from 1 +/- 0.3 to 2.25 +/- 0.3 mug/mL (P < 0.05), but skin concentrations were undetectable. Before vitamin E supplementation, UVR increased the skin malondialdehyde concentration from 0.42 +/- 0.07 to 1.24 +/- 0.16 nmol/mg protein (P < 0.01), whereas oxidized or total glutathione increased from 9.98 +/- 0.4% to 12.0 +/- 1.0% (P < 0.05). Vitamin E supplementation significantly decreased the skin malondialdehyde concentration, but neither vitamin E nor beta-carotene significantly influenced other measures of oxidation in basal or UVR-exposed skin. CONCLUSIONS: Vitamin E or beta-carotene supplementation had no effect on skin sensitivity to UVR. Although vitamin E supplements significantly reduced the skin malondialdehyde concentration, neither supplement affected other measures of UVR-induced oxidative stress in human skin, which suggested no photoprotection of supplementation.     

Intestinal permeability, vitamin A absorption and serum alpha-tocopherol in gastrointestinal stromal tumor patients treated with imatinib

Administration of imatinib is the therapy of choice in patients with advanced (inoperable) or metastatic gastrointestinal stromal tumors (GIST). Gastrointestinal toxicity is one of the most common side effects of anticancer therapy, including imatinib. Measurement of intestinal permeability represents a method of noninvasive laboratory assessment of gastrointestinal toxicity. We have measured intestinal permeability (by determining absorption of lactulose, mannitol and xylose), vitamin A absorption and serum alpha-tocopherol in 16 patients with advanced/metastatic GIST treated with imatinib. Lactulose/mannitol and lactulose/xylose ratios as well as parameters of vitamin A absorption did not change significantly during the treatment, but a significant decrease of alpha-tocopherol was observed. We conclude that, in contrast to most other anticancer agents studied so far, imatinib does not have an effect on intestinal permeability. No effect on vitamin A absorption was observed, but serum alpha-tocopherol decreased significantly during the treatment.     

Effect of modest vitamin E supplementation on blood glycated hemoglobin and triglyceride levels and red cell indices in type I diabetic patients.

The glycation of proteins and elevated triglyceride (TG) levels are two of the major risk factors in the development of complications of diabetes. Previous studies have found some beneficial effects of supplementation of pharmacological doses (900-2000 IU/day) of vitamin E in Type II diabetic patients. This study examined whether supplementation with a modest dose of vitamin E (100 IU/day) had any effect on blood glucose, glycated hemoglobin (GHb), TG or red cell counts in Type I diabetic patients.

35 diabetic patients were supplemented with either DL-alpha-tocopherol (vitamin E) capsules (orally, 100 IU/day) or a placebo for 3 months in a double-blind clinical trial. Fasting blood was collected from each diabetic patient before and after vitamin E or placebo supplementation. Data were analyzed using paired “t” tests and the Wilcoxon Signed Rank Test.

Levels of GHb (mean +/? SEM) were 11.5 +/? 0.4 and 12.8 +/? 0.9% (p < 0.05); glucose, 8.8 +/? 1.2 and 11.6 +/? 1.3 mM; and TG, 2.2 +/? 0.2 and 2.9 +/? 0.3 mM (p < 0.03) after vitamin E supplementation versus before supplementation. There were no differences in these parameters after supplementation with the placebo. There was no effect on blood RBC, hematocrit, and hemoglobin levels after supplementation of vitamin E or the placebo. There were no differences in ages and duration of diabetes between placebo and vitamin E-supplemented groups.

This study suggests that modest vitamin E supplementation (100 IU/day) can significantly lower blood GHb and TG levels and does not have any effect on red cell indices in Type I diabetic patients.     

Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation

OBJECTIVE: We previously reported in an open-label pilot trial that a 24-ingredient multivitamin formula favorably influenced homocysteine concentration and LDL-C oxidation indices following 24 weeks of supplementation. Our current aim was to more thoroughly examine this same formula in a randomized, placebo-controlled, clinical study. METHODS: We examined 182 participants for selected plasma vitamin concentrations and clinically relevant variables including homocysteine, lipids and LDL-C oxidation indices at baseline and six months. RESULTS: We found no significant differences between groups for any parameter at baseline. Following six months of vitamin supplementation, we observed elevations in plasma concentrations of vitamin B6 (as pyridoxal 5'-phosphate; PLP), vitamin B12, folate, vitamin C, vitamin E and beta-carotene (p < 0.0001), all of which were significantly greater than respective placebo group changes (p < 0.0001). Homocysteine decreased in the treatment (8.38 +/- 2.9 vs. 6.93 +/- 2.5 micro mol/L; p < 0.0001) and placebo group (8.17 +/- 3.0 vs. 7.42 +/- 2.2 micro mol/L; p < 0.0001) from baseline to six months, respectively, with reductions in the treatment group being greater than placebo (p < 0.008). LDL-C oxidation indices were also improved as LDL-C oxidation rate was decreased (-0.39 micro mol/min/g protein; p < 0.0003) and LDL-C lag time increased (11.3 min; p < 0.003) in supplemented participants. Further analysis also showed that LDL-C oxidation rate was lower (p < 0.0007) and LDL-C lag time longer (p < 0.0001) for the vitamin group than placebo treatment after six months. CONCLUSION: We conclude that a multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL-C oxidation indices.     

Vitamin A supplementation reduces the monocyte chemoattractant protein-1 intestinal immune response of Mexican children

The impact of vitamin A supplementation on childhood diarrhea may be determined by the regulatory effect supplementation has on the mucosal immune response in the gut. Previous studies have not addressed the impact of vitamin A supplementation on the production of monocyte chemoattractant protein 1 (MCP-1), an essential chemokine involved in pathogen-specific mucosal immune response. Fecal MCP-1 concentrations, determined by an enzyme-linked immuno absorption assay, were compared among 127 Mexican children 5-15 mo of age randomized to receive a vitamin A supplement (<12 mo of age, 20,000 IU of retinol; > or =12 mo, 45,000 iu) every 2 mo or a placebo as part of a larger vitamin A supplementation trial. Stools collected during the summer months were screened for MCP-1 and gastrointestinal pathogens. Values of MCP-1 were categorized into 3 levels (nondetectable, or =median). Multinomial logistic regression models were used to determine whether vitamin A-supplemented children had different categorical values of MCP-1 compared with children in the placebo group. Differences in categorical values were also analyzed stratified by gastrointestinal pathogen infections and by diarrheal symptoms. Overall, children who received the vitamin A supplement had reduced fecal concentrations of MCP-1 compared with children in the placebo group (median pg/mg protein +/- interquartile range: 284.88 +/- 885.35 vs. 403.39 +/- 913.16; odds ratio 0.64, 95% CI 0.42-97, P = 0.03). Vitamin A supplemented children infected with enteropathogenic Escherichia coli (EPEC) had reduced MCP-1 levels (odds ratio = 0.38, 95% CI 0.18-0.80) compared with children in the placebo group. Among children not infected with Ascaris lumbricoides vitamin A supplemented children had reduced MCP-1 levels (OR = 0.62, 95% CI 0.41-0.94). These findings suggest that vitamin A has an anti-inflammatory effect in the gastrointestinal tract by reducing MCP-1 concentrations.