Plasma changes in micronutrients following a multivitamin and mineral supplement in healthy adults

OBJECTIVE: To estimate the micronutrient (riboflavin, folate, vitamin C, vitamin B(12), iron, zinc and copper) bioavailability in healthy adults from a multi-micronutrient dietary supplement to assess the possible influence on it by the tablet disintegration properties and by the relative intestinal permeability of subject. METHODS: The bioavailability of seven micronutrients from a single brand of multi-micronutrient dietary supplement was measured on two separate occasions in the presence of a standardized test meal in 15 healthy adult subjects. Each subject visited the Metabolic Research Unit on four separate randomized occasions for an absorption test. One test measured the intestinal permeability. The other three tests measured the postprandial changes in plasma or serum concentrations after consuming a test meal alone (control:placebo effect), or the test meal with either whole or crushed and powdered dietary supplements. 15 healthy Caucasian adult volunteers, aged 42 +/- 14 years. RESULTS: The 12 hour-post-dose AUC for riboflavin, folate and vitamin C (whole and crushed tablet), and that for vitamin B(12) (only for the crushed tablet treatment) and iron (only for the whole tablet treatment) were all significantly (p < 0.001) higher than after a test meal alone. In contrast there was no significant increase in the AUC after supplement intake for zinc and copper. Neither the form of the supplement for all micronutrients tested nor intestinal permeability of the subject for riboflavin, folate, vitamin C, iron, zinc and copper influenced the postdose nutrient AUC. In contrast, for vitamin B(12) the intestinal permeability of the subject influenced significantly the nutrient AUC (p = 0.003). CONCLUSION: Tablet disintegration characteristics of this dietary supplement did not limit absorption of these seven micronutrients. The intestinal permeability of subject was only positively correlated with the B(12) bioavailability. Results are suggestive of using multi-micronutrients dietary supplements as a vehicle to decrease the prevalence of multiple micronutrient deficiencies overall for vitamins in healthy adults.     

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.     

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.     

Daily multi-micronutrient supplementation during tuberculosis treatment increases weight and grip strength among HIV-uninfected but not HIV-infected patients in Mwanza, Tanzania

Undernutrition is common among tuberculosis (TB) patients. The objective of this study was to assess the effect of multi-micronutrient supplementation during TB treatment on weight, body composition, and handgrip strength. A total of 865 patients with smear-positive (PTB+) or -negative (PTB-) pulmonary TB were randomly allocated to receive a daily biscuit with or without multi-micronutrients for 60 d during the intensive phase of TB treatment. Weight, arm fat area, arm muscle area, and handgrip strength were assessed at baseline and after 2 and 5 mo. At 2 mo, the multi-micronutrient supplementation led to a higher handgrip gain (1.22 kg; 95% CI = 0.50, 1.94; P = 0.001) but had no effects on other outcomes. The effects of multi-micronutrient supplementation were modified by HIV infection (P-interaction = 0.002). Among HIV- patients, multi-micronutrient supplementation increased weight gain by 590 g (95% CI = -40, 1210; P = 0.07) and handgrip strength by 1.6 kg (95% CI = 0.78, 2.47; P < 0.001), whereas among HIV+ patients, it reduced weight gain by 1440 g (95% CI = 290, 2590; P = 0.002) and had no effect on handgrip strength (0.07 kg; 95% CI = -1.30, 1.46; P = 0.91). The reduced weight gain among HIV+ patients receiving multi-micronutrient supplementation seemed to be explained by a higher proportion of patients reporting fever. At 5 mo, the effects on weight were sustained, whereas there was no effect on handgrip strength. In conclusion, multi-micronutrient supplementation given as a biscuit is beneficial among HIV- PTB patients and may be recommended to TB programs. More research is needed to develop an effective supplement for HIV+ PTB patients.     

Influence of polymeric enteral nutrition supplemented with different doses of glutamine on gut permeability in critically ill patients

OBJECTIVES: To evaluate the effect of glutamine-supplemented polymeric enteral formulas on the recovery of gut-permeability abnormalities in critically ill patients. METHODS: Twenty-three patients were randomized to receive a conventional casein-based enteral formula (ADN), ADN plus glutamine in a dose of 0.15 g x kg(-1) x d(-1) or ADN plus 0.30 g x kg(-1) x d(-1) of glutamine for 8 d. The lactulose mannitol permeability test (L/M) was performed at baseline and at the end of the study. Nineteen healthy volunteers served as controls for the L/M test. RESULTS: An increase in permeability compared with control subjects was observed in patients at baseline (mean +/- standard error of the mean; L/M ratio: 0.11 +/- 0.03 and 0.025 +/- 0.004, respectively; P < 0.02). The L/M ratio improved after the period of enteral nutrition as a whole (initial L/M: 0.11 +/- 0.03, final L/M: 0.061 +/- 0.01; P < 0.03), but no difference was found between groups. CONCLUSIONS: Even though polymeric enteral nutrition was associated with a significant improvement in the L/M ratio, glutamine supplementation did not show a specific influence in improving recovery of gut permeability in critically ill patients.     

Age-related association of small intestinal mucosal enteropathy with nutritional status in rural Gambian children

Small bowel enteropathy (assessed by the lactulose (L) : mannitol (M) permeability test) is a major factor in infant growth faltering and malnutrition in The Gambia. However, little is known about its persistence and nutritional effect beyond 2 years of age. This was addressed by two cross-sectional studies of intestinal permeability and nutritional status in 162 residents, aged 2-60 years, living in three villages in rural Gambia. L:M ratio was found to be highest in the youngest children and although there was a significant improvement with age (P<0.0001), values were always greater than the range found in UK counterparts. M recovery (mean value 5.68 (se 0.12) %) was at all times between one-third and one-half of expected UK values and showed no improvement with age. Gut barrier function, assessed by L uptake, improved with age (P<0.001) and fell within the UK normal range beyond age 10 years. Both the L:M permeability ratio and L recovery were significantly associated with height-for-age z-scores and -0.22 respectively, P<0.001), a relationship that persisted throughout childhood and into adulthood. Change in height-for-age z-score between the two visits was also related to the L:M ratio P=0.018). The close within-subject correlation of permeability variabilities between the two visits suggests a long-term persistence of enteropathy within individuals. It appears that the small bowel enteropathy previously described in Gambian infants persists through to adulthood. Although the lesion improves with age, the relationship between attained height and L:M permeability raises the possibility that enteropathy may continue to limit growth throughout childhood and puberty.     

The effect of early enteral nutrition on hyperthermic intraoperative intraperitoneal chemotherapy-induced mucosal permeability following gastrectomy

Aim: To investigate (1) the effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) on intestinal permeability of patients with advanced gastric cancer and (2) the protective effect of postoperative enteral nutrition (EN) on patients. Methods: >All patients were divided randomly into 3 groups: the EN group, treated with EN during postoperative period; the EN+HIIC group, treated with HIIC and postoperative EN; and the PN+HIIC group, treated with HIIC and postoperative parenteral nutrition. The lactulose/mannitol (L/M) ratio was used to evaluate the permeability of intestinal mucous. Results: Compared with the ratio of L/M on the day before operation (POD‐1), the ratio of L/M on POD+3 increased significantly in all 3 groups (P < .0001) and then decreased gradually. The L/M ratio of the EN and EN+HIIC groups recovered to the baseline on POD+12. In contrast, the PN+HIIC group still had an elevated L/M ratio until POD+12. The ratios of L/M in the EN+HIIC group on POD+7 and POD+12 were significantly different from those of the PN+HIIC group (0.0855 ± 0.0462 vs 0.1298 ± 0.063, P = .007; 0.0336 ± 0.0235 vs 0.0616 ± 0.0430, P = .038, respectively). Conclusion: Gastric cancer radical resection resulted in a significant increase in intestinal permeability. HIIC aggravated the injury of intestinal mucous permeability, which could be reversed by EN.     

Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia

Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies.     

A multi-micronutrient beverage enhances the vitamin A and zinc status of Nigerian primary schoolchildren

Schoolchildren in Nigeria are rarely targeted by micronutrient interventions. We completed a 6-mo, double-blind, placebo-controlled trial to determine the effects of a multi-micronutrient beverage on biochemical and anthropometric indicators of nutritional status among schoolchildren participating in a pilot school feeding program in Nasarawa State, Nigeria. Children received 1 of 2 interventions 5 d/wk during school hours: 1) 250 mL/d of a multi-micronutrient beverage that included vitamin A, iron, and zinc (micronutrient); or 2) an isoenergetic control beverage (control). At baseline, 566 children 5-13 y old were randomized to groups (micronutrient: n = 288; control: n = 278). Height, weight, hemoglobin, and serum concentrations of C-reactive protein, ferritin, retinol, and zinc were measured at baseline and at the end of the study. A total of 270 children in the micronutrient group and 264 children in the control group completed the study. Self-reports of vomiting increased in both groups at 6 mo; however, the prevalence tended to be greater in the micronutrient group (21%) compared to the control group (14%) (P = 0.06). Biochemical changes were greater in the micronutrient group compared to control for serum retinol (0.10 ± 0.02 μmol/L vs. 0.02 ± 0.02 μmol/L; P = 0.016) and zinc (1.0 ± 0.2 μmol/L vs. 0.6 ± 0.2 μmol/L; P = 0.031). The intervention did not significantly affect hemoglobin or serum ferritin concentrations. The cost effectiveness of the intervention needs to be further evaluated, as does the efficacy of the beverage on anemia and indicators of iron status.     

肠内营养对活动期溃疡性结肠炎患者肠道通透性的影响

目的 探讨肠内营养(EN)对活动期溃疡性结肠炎患者肠道通透性的影响。方法 采用随机数字表法将24例轻、中度活动期溃疡性结肠炎患者分为常规组(n=11)和常规+ EN组(n=13),分别给予美沙拉秦+少渣饮食治疗和美沙拉秦+短肽型肠内营养剂治疗14 d。采用高压液相色谱分析法分别检测治疗前后患者尿液中乳果糖及甘露醇的浓度,计算乳果糖/甘露醇排泄率的比值(L/M)。结果 治疗前常规组和常规+ EN组的L/M分别为0.039±0.025和0.072±0.019,两组的差异无统计学意义(P=0.069)。治疗2周后,常规+EN组的L/M为0.038±0.012,明显低于治疗前(P =0.043),常规组的L/M为0.032±0.022,与治疗前的差异无统计学意义(P=0.730)。结论 EN可以降低活动期溃疡性结肠炎患者的肠道通透性。     

The effect of endotoxin and turpentine administration on intestinal permeability in the rat

Intestinal permeability in 4-week-old rats has been assessed by the dual sugar (lactulose/mannitol) permeability test before and for two days after induction of systemic inflammation by various endotoxins and turpentine. Evidence of an inflammatory response to these agents was provided by marked reductions in food consumption and growth rate, hypoalbuminaemia, and a large increase in the plasma concentration of the acute-phase protein alpha-2-macroglobin. Abnormal values for intestinal permeability occurred only in animals which had been injected with E. coli 0111:B4 endotoxin. Neither turpentine nor the other endotoxins produced any detectable effect. Within 2-7h of the first exposure to a low dose, (3mg/kg) of either phenol or trichloroacetic extracts of E. coli 0111:B4 endotoxin, the lactulose:mannitol (L M ) ratio was elevated by 32% and 50% respectively (p < 0.05), but the rise was not sustained despite continued twice-daily injections of endotoxin. Administration of a higher dose, (10 mg/kg twice daily, phenol extract) resulted in diarrhoea, and a greater more persistent increase in the L M ratio; 115% (p < 0.05) 2-7h after the first injection, and 49% above control values, (p < 0.01) 24h later. The increase in L M ratio appeared to be due to a decrease in mannitol excretion. Total urinary lactulose also tended to fall, especially in rats given the high dose of endotoxin. It is concluded that a systemic inflammatory response does not necessarily lead to a change in intestinal permeability as measured by the dual sugar permeability test. The transient permeability changes observed following E. coli 0111:B4 administration may be a specific reaction to this material rather than to a more general systemic stimulus.     

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

OBJECTIVE: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. DESIGN: A randomized crossover dietary intervention. SUBJECTS AND INTERVENTIONS: In all, 15 healthy volunteers (age 23+/-1.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time=-24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t=-9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t=-1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t=0, a permeability test was performed. RESULTS: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio=0.036; 0.014-0.092, P<0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P=0.3). CONCLUSION: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. SPONSORSHIP: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.     

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.     

谷氨酰胺对多器官功能障碍综合征病人营养代谢及肠道屏障的影响

目的:评价谷氨酰胺(Gln)对多器官功能障碍综合征(MODS)病人营养状态及肠道黏膜通透性的影响.方法:将20例MODS病人随机分为对照组和Gln组,比较两组病人血清清蛋白、转铁蛋白、血糖、氮平衡以及尿乳果糖/甘露醇比值(L/M)的变化,并观察病人肝、肾功能及不良反应.结果:Gln组治疗后清蛋白、前清蛋白和转铁蛋白均较治疗前明显升高,与对照组相比差异有显著性意义(P＜0.05);Gln组负氮平衡于第4天、对照组于第8天转化为正氮平衡,两组比较差异有显著性意义(P＜0.05);Gln组尿L/M降低,与对照组相比差异有显著性意义(P＜0.05);病人肝、肾功能和血糖等均无变化.结论:Gln可促进MODS病人蛋白质合成,改善负氮平衡,降低肠黏膜通透性,无不良反应发生.     

Effects on haemoglobin of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomized,controlled trial in Kenyan school children

OBJECTIVE: To assess the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on haemoglobin concentration (Hb), using schools as a health delivery system. STUDY AREA AND POPULATION: Nine hundred seventy-seven children between 9 and 18 y of age from 19 primary schools in Bondo District, western Kenya, were included in the trial. The 746 (76.4%) children on whom baseline Hb was available were included in this study. DESIGN: The study was a randomized, placebo-controlled, double-blind, two-by-two factorial trial of the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on Hb after 8 months. INTERVENTION: Single treatment of infected children with albendazole (600 mg) for geohelminths and praziquantel (40 mg/kg) for Schistosoma mansoni and daily supplementation with 13 micronutrients. RESULTS:: Multi-micronutrient supplementation (3.5 g/l, 95% CI 1.7, 5.3; P=0.0002) and anthelminthic treatment (2.0 g/l, 95% CI 0.2, 3.9; P=0.03) increased Hb independently (interaction, P=0.33). The effects were also independent of baseline Hb and general nutritional status. The treatment effect was due to reductions in S. mansoni and hookworm intensities of infection, in that Hb increased by 0.4 and 0.2 g/l, respectively, per 100 epg reductions in egg output. Interestingly, among S. mansoni-infected children, the effect of treatment seemed stronger in those with compared to those without co-existing malaria parasitaemia (interaction, P=0.09). CONCLUSION: Multi-micronutrient supplementation and multi-helminth chemotherapy increased Hb among school children, irrespective of initial Hb and nutritional status.     

Long-term calcium supplementation does not affect the iron status of 12-14-y-old girls

BACKGROUND: Single-meal studies have established that calcium has an acute inhibitory effect on the absorption of iron. However, there is growing evidence that high calcium intakes do not compromise iron status. OBJECTIVE: We evaluated whether long-term calcium supplementation taken with the main meal affected biomarkers of iron status in adolescent girls with high requirements of both iron and calcium. DESIGN: The study was a randomized, double-blind, placebo-controlled trial of supplementation with 500 mg Ca/d for 1 y among 113 adolescent girls aged 13.2 +/- 0.4 y at enrollment. Participants were advised to take the supplement with their evening meal, which usually contributes the majority of dietary iron. Iron status was assessed at baseline and after 1 y of supplementation by measuring hemoglobin and serum concentrations of ferritin and transferrin receptors (TfRs). RESULTS: The mean (+/-SD) hemoglobin at enrollment was 134 +/- 9 g/L, geometric mean serum ferritin was 26.3 microg/L (interquartile range: 18.6-39.4 microg/L), and serum TfR was 4.19 mg/L (3.52-5.10 mg/L). Daily calcium supplementation had no effect on the least-squares mean concentrations of iron-status markers adjusted for their baseline values (hemoglobin: 136 and 134 g/L, P = 0.31; ferritin: 25.4 and 26.1 microg/L, P = 0.73; TfR: 4.1 and 4.4 mg/L, P = 0.12; and the ratio of TfR to ferritin: 160 and 161 in the calcium and placebo groups, respectively; P = 0.97). CONCLUSION: Although it remains to be shown in iron-deficient persons, long-term iron status does not seem to be compromised by high calcium intakes.     

Effects on serum retinol of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomised,controlled trial in Kenyan school children

OBJECTIVE: To assess the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on serum retinol concentration, using schools as a health delivery system. STUDY AREA AND POPULATION: From 19 primary schools in Bondo District, western Kenya, 977 children between 9 and 18 y were included in the trial. The 644 (65.9%) children on whom baseline serum retinol was available were included in this study. DESIGN: A randomised, placebo-controlled, double-blind, two-by-two factorial trial on the effects of multi-micronutrient supplementation and multi-helminth chemotherapy on serum retinol after 8 months. INTERVENTION: Single treatment with albendazole (600 mg) and praziquantel (40 mg/kg of body weight) and daily multi-micronutrient supplementation with tablet containing 1000 microg vitamin A. RESULTS: Micronutrient supplementation (0.08 micromol/l, 95% CI 0.01, 0.14; P=0.025), but not treatment (0.03 micromol/l, 95% CI -0.04, 0.10; P=0.38), increased serum retinol. However, treatment did increase serum retinol in S. mansoni-infected (0.09, 95% CI 0.02, 0.16; P=0.009), but not in uninfected children (-0.07, 95% CI -0.18, 0.03; P=0.18; interaction, P=0.01). Similarly, reduction in egg output of S. mansoni, but none of the geohelminth, was a predictor, corresponding to a 0.008 micromol/l (95% CI 0.00002, 0.02; P=0.049) increase in serum retinol per 100 epg reduction. Interestingly, interactions were found between age and sex (P=0.046), and malaria parasitaemia and sickle cell phenotype (P=0.04). CONCLUSION: Multi-micronutrient supplementation and reduction in S. mansoni egg output increased serum retinol, irrespective of initial serum retinol. SPONSORSHIP: The Danish International Development Assistance.     

Iron supplementation during infancy--effects on expression of iron transporters, iron absorption, and iron utilization in rat pups

BACKGROUND: Studies conducted in human infants suggest developmental changes in the regulation of iron absorption; however, little is known about the molecular mechanisms regulating iron absorption during infancy. Two intestinal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), were recently identified. OBJECTIVE: The objective was to investigate at a molecular level the regulation of iron absorption during infancy in a rat pup model. We examined the developmental expression of DMT1 and FPN1 and the effects of iron supplementation on their expression and on iron absorption and utilization during infancy. DESIGN: Rat pups were given daily oral doses of 0, 30, or 150 microg Fe from day 2 to day 20 after birth. On days 10 and 20 after birth, (59)Fe absorption, tissue minerals, and intestinal DMT1, FPN1, and ferritin expression were examined. To assess developmental expression, DMT1 and FPN1 were examined in control rats from days 1 to 50 after birth. RESULTS: Intestinal DMT1 and FPN1 were significantly affected by age; expression increased dramatically by day 40. On day 10, no significant effect of iron supplementation on DMT1 and FPN1 gene expression or on iron absorption was observed. By day 20, DMT1 and FPN1 expression and iron absorption had decreased significantly with iron supplementation. CONCLUSIONS: During early infancy, rat pups are unable to down-regulate intestinal iron transporters or iron absorption in response to iron supplementation, whereas down-regulation occurs during late infancy. The current findings provide evidence of the developmental regulation of iron absorption, which emphasizes the need for caution when giving iron supplements to infants at an early age.     

Positive association between dietary iron intake and iron status in HIV-infected children in Johannesburg,South Africa

Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy. In this prospective study, the difference between dietary intakes of iron-deficient children (soluble transferrin receptor >9.4 mg/L) and iron-sufficient children after 18 months on highly active antiretroviral therapy was examined. The association between iron intake and hemoglobin (Hb) concentration was also assessed. Longitudinal data collected for 18 months from 58 HIV-infected African children were assessed by generalized estimation equations, with adjustment for demographic information, dietary intakes, growth parameters, and CD4%. After adjustment for covariates, the longitudinal association between dietary iron intake and Hb concentration remained significant. This association shows that for every 1-mg increase in iron intake per day, Hb increases by 1.1 g/L (P < .001). Mean Hb increased significantly after 18 months of follow-up (106 ± 14 to 129 ± 14 g/L, P < .01), but soluble transferrin receptor also increased (7.7 ± 2.7 to 8.9 ± 3.0 mg/L, P < .01). The incidence of ID increased from 15.2% at baseline to 37.2% after 18 months. Children with animal protein intakes greater than >20 g/d had significantly lower odds for ID at 18 months than did children with lower intakes (odds ratio, 0.40; 95% confidence interval, 0.21-0.77). Dietary iron intake was insufficient to protect against ID, pointing to a need for low-dose iron supplementation for iron-deficient HIV-infected children and interventions to increase the consumption of animal protein.     

A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: interactions between iron and zinc

BACKGROUND: Combined supplementation with iron and zinc during infancy may be effective in preventing deficiencies of these micronutrients, but knowledge of their potential interactions when given together is insufficient. OBJECTIVE: The goal was to compare the effect in infants of combined supplementation with iron and zinc and of supplementation with single micronutrients on iron and zinc status. DESIGN: Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe + 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Venous blood samples were collected at the start and end of the study. Five hundred forty-nine infants completed the supplementation and had both baseline and follow-up blood samples available for analysis. RESULTS: Baseline prevalences of anemia, iron deficiency anemia (anemia and low serum ferritin), and low serum zinc (< 10.7 micromol/L) were 41%, 8%, and 78%, respectively. After supplementation, the Fe group had higher hemoglobin (119.4 compared with 115.3 g/L; P < 0.05) and serum ferritin (46.5 compared with 32.3 microg/L; P < 0.05) values than did the Fe+Zn group, indicating an effect of zinc on iron absorption. The Zn group had higher serum zinc (11.58 compared with 9.06 micromol/L; P < 0.05) than did the placebo group. There was a dose effect on serum ferritin in the Fe and Fe+Zn groups, but at different levels. There was a significant dose effect on serum zinc in the Zn group, whereas no dose effect was found in the Fe+Zn group beyond 7 mg Zn/d. CONCLUSION: Supplementation with iron and zinc was less efficacious than were single supplements in improving iron and zinc status, with evidence of an interaction between iron and zinc when the combined supplement was given.