Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here, we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, and Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin.

BACKGROUND

The role of one-carbon metabolism nutrients in colorectal carcinogenesis is not fully understood. Associations might be modified by mandated folic acid (FA) fortification or alcohol intake.

OBJECTIVE

We investigated associations between intakes of folate, riboflavin, vitamin B-6, and vitamin B-12 and colorectal cancer (CRC) in the Women's Health Initiative Observational Study, stratified by time exposed to FA fortification and alcohol intake.

METHODS

A total of 88,045 postmenopausal women were recruited during 1993-1998; 1003 incident CRC cases were ascertained as of 2009. Quartiles of dietary intakes were compared; HRs and 95% CIs were estimated by Cox proportional hazards models.

RESULTS

Dietary and total intakes of vitamin B-6 in quartile 4 compared with quartile 1 (HR: 0.80; 95% CI: 0.66, 0.97 and HR: 0.80; 95% CI: 0.66, 0.99, respectively) and total intakes of riboflavin (HR: 0.81; 95% CI: 0.66, 0.99) were associated with reduced risk of CRC overall and of regionally spread disease. In current drinkers who consumed <1 drink (13 g alcohol)/wk, B vitamin intakes were inversely associated with CRC risk (P-interaction < 0.05). Dietary folate intake was positively associated with CRC risk among women who had experienced the initiation of FA fortification for 3 to <9 y (P-interaction < 0.01).

CONCLUSIONS

Vitamin B-6 and riboflavin intakes from diet and supplements were associated with a decreased risk of CRC in postmenopausal women. Associations of B vitamin intake were particularly strong for regional disease and among women drinkers who consumed alcohol infrequently. Our study provides new evidence that the increased folate intake during the early postfortification period may have been associated with a transient increase in CRC risk.

The addition of additives (electrolytes, trace elements, and vitamins) to parenteral nutrition (PN) mixtures can lead to precipitation as a result of physical incompatibilities and can lead to chemical degradation of individual ingredients. The most significant cause of precipitation is excessive concentrations of calcium phosphate. The most significant cause of chemical instability is the oxidation of specific vitamins. The factors influencing calcium phosphate solubility include the commercial amino acid source, the calcium and phosphate salts used, temperature, magnesium concentration, and final volume. Precipitation can be avoided by organic phosphates. Trace element precipitation is most commonly caused by the formation of iron phosphate salts or copper cysteinate in cysteine-containing amino acid infusions. The least stable nutrient is ascorbic acid, which reacts with oxygen, and is catalyzed by copper ions. Oxygen originates from PN ingredients, the filling process, air remaining in the bag after filling, and oxygen permeation through the bag wall. Storage in multilayered bags with reduced gas permeability can protect residual ascorbic acid. Other chemical losses are caused by the reduction of thiamine by metabisulfite, and photodegradation of daylight-sensitive vitamins, especially retinol and riboflavin, during administration.

One of the pathways involved in the acquisition of the essential metal iron by bacteria involves the reduction of insoluble Fe(3+) to soluble Fe(2+), followed by transport of Fe(2+) to the cytoplasm. Flavins have been implicated as electron donors in this poorly understood process. Ferrous iron uptake is essential for intestinal colonization by the important pathogen Campylobacter jejuni and may be of particular importance under low-oxygen conditions. In this study, the links among riboflavin biosynthesis, ferric reduction, and iron acquisition in C. jejuni NCTC11168 have been investigated. A riboflavin auxotroph was generated by inactivation of the ribB riboflavin biosynthesis gene (Cj0572), and the resulting isogenic ribB mutant only grew in the presence of exogenous riboflavin or the riboflavin precursor diacetyl but not in the presence of the downstream products flavin adenine dinucleotide and flavin mononucleotide. Riboflavin uptake was unaffected in the ribB mutant under iron-limited conditions but was lower in both the wild-type strain and the ribB mutant under iron-replete conditions. Mutation of the fur gene, which encodes an iron uptake regulator of C. jejuni, resulted in an increase in riboflavin uptake which was independent of the iron content of the medium, suggesting a role for Fur in the regulation of the as-yet-unknown riboflavin transport system. Finally, ferric reduction activity was independent of iron availability in the growth medium but was lowered in the ribB mutant compared to the wild-type strain and, conversely, increased in the fur mutant. Taken together, the findings confirm close relationships among iron acquisition, riboflavin production, and riboflavin uptake in C. jejuni.

We prospectively studied the relationship between dietary intake at baseline and the development of AIDS over 6 years in a population-based sample of 296 human immunodeficiency virus (HIV)-seropositive men. Nutrient intake was assessed before HIV serostatus was known. Subjects diagnosed with AIDS at baseline or during the 1st year were excluded. After adjustment for baseline CD4 T-lymphocyte count, HIV symptoms, and other risk factors, no nutrients were significantly associated with AIDS. However, when the continuous CD4 count and HIV symptom variables were replaced with a single binary health status variable, the hazard of AIDS decreased as consumption increased for all 11 micronutrients; this relationship was statistically significant for iron, vitamin E, and riboflavin and approached significance for vitamins C, thiamine, and niacin. Higher intake of all 11 micronutrients was associated with higher CD4 counts at baseline, and was significantly so for six of them. Daily multivitamin use was associated with a reduced hazard of AIDS [hazard ratio (HR) = 0.7; 95% confidence interval (CI) = 0.5, 1.0] and a significantly reduced risk for low CD4 counts at baseline (HR = 0.6, 95% CI = 0.4, 0.9). Additional studies are needed to determine whether dietary intake modifies the rate of developing AIDS in those who are HIV seropositive.

OBJECTIVE

To investigate the associations between 4 categories of daily 100% juice consumption (0 fl oz,>> 0 to < or = 6 fl oz;>> 6 to < 12 fl oz; and>> or = 12 fl oz) and nutrient and food group intake and weight in children.

METHODS

Cross-sectional study.

METHODS

Secondary analysis of the 1999-2002 National Health and Nutrition Examination Survey data.

METHODS

Children 2 to 11 years of age (N = 3618).

METHODS

Juice consumption.

METHODS

The association between juice consumption, nutrient intake, food group consumption, and weight status was determined as was the likelihood of overweight with juice consumption.

RESULTS

Mean daily juice consumption was 4.1 fl oz, which contributed a mean intake of 58 kcal (3.3% of total energy intake). Compared with nonconsumers, the overall nutritional profile of those consuming 100% juice had significantly higher intakes of energy, carbohydrates, vitamins C and B(6), potassium, riboflavin, magnesium, iron, and folate and significantly lower intakes of total fat, saturated fatty acids, discretionary fat, and added sugar. Children consuming 100% juice also consumed significantly more servings of total whole fruit than nonconsumers. No significant differences were found in weight status and the amounts of 100% juice consumed. There was no difference in the likelihood of being overweight between juice consumers and nonconsumers.

CONCLUSIONS

On average, children consumed less than the maximum amounts of 100% juice recommended by the American Academy of Pediatrics. One hundred percent juice consumption was associated with better nutrient intake than in the nonconsumption group and was not associated with weight status or the likelihood of being overweight in children 2 to 11 years of age.

A randomized double-blind study was carried out comparing single daily dose phenobarbital plus antipyretic instruction to a placebo plus antipyretic instruction to prevent a recurrent seizure following an initial simple febrile seizure. Parents of 138 consecutive children presenting to an emergency room with a first simple febrile convulsion received verbal and written instructions about fever control. Seventy-nine then agreed to participate in this study. Children were randomized to receive either placebo with riboflavin tracer (n = 40) or phenobarbital 5 mg/kg in a single daily dose with a riboflavin tracer (n = 39) for 12 months or until another seizure occurred. Urine fluorescence for riboflavin was used to monitor compliance in all patients. Serum phenobarbital levels were obtained at each follow-up visit and averaged 1.4 mg/dl throughout the study. The significant difference (P less than 0.02) in the incidence of recurrent seizures between patients receiving phenobarbital (2/39) and those receiving placebo (10/40) suggests that a single daily dose of phenobarbital is more effective than counseling parents about antipyretic therapy in preventing recurrent seizures following an initial febrile seizure.

The use of blood donor history and state-of-the-art FDA-licensed serological and nucleic acid testing (NAT) assays have greatly reduced the "infectious window" for several transfusion-transmitted pathogens. Currently transmission of human immunodeficiency virus (HIV), Human T-cell Lymphotropic Virus (HTLV), hepatitis viruses and West Nile Virus are rare events. The seroprevalence of cytomegalovirus in the donor population is high and cytomegalovirus infection can cause significant complications for immunocompromised recipients of blood transfusion. Careful use of CMV seronegative blood resources and leukoreduction of blood products are able to prevent most CMV infections in these patients. Currently, bacterial contamination of platelet concentrates is the greatest remaining infectious disease risk in blood transfusion. Specialized donor collection procedures reduce the risk of bacterial contamination of blood products; blood culture and surrogate testing procedures are used to detect potential bacterially contaminated platelet products prior to transfusion. A rapid quantitative immunoassay is now available to test for the presence of lipotechoic acid and lipopolysaccharide bacterial products prior to platelet transfusion. Attention has now turned to emerging infectious diseases including variant Creutzfeldt-Jakob disease, dengue, babesiosis, Chagas' disease and malaria. Challenges are presented to identify and prevent transmission of these agents. Several methods are being used or in development to reduce infectivity of blood products, including solvent-detergent processing of plasma and nucleic acid cross-linking via photochemical reactions with methylene blue, riboflavin, psoralen and alkylating agents. Several opportunities exist to further improve blood safety through advances in infectious disease screening and pathogen inactivation methods.

OBJECTIVE

To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) in patients with painful pseudophakic bullous keratopathy (PBK).

METHODS

University of São Paulo, São Paulo and Sadalla Amin Ghanem Eye Hospital, Joinville, Santa Catarina, Brazil.

METHODS

This prospective study included consecutive eyes with PBK that had CXL. After a 9.0 mm epithelial removal, riboflavin 0.1% with dextran 20% was applied for 30 minutes followed by ultraviolet-A irradiation (370 nm, 3 mW/cm(2)). Therapeutic contact lenses were placed for 1 week. Corneal transparency, central corneal thickness (CCT), and ocular pain were assessed preoperatively and 1 and 6 months postoperatively. Statistical analysis was by paired t tests.

RESULTS

Fourteen patients (14 eyes) with a mean age 71.14 years +/- 11.70 (SD) (range 53 to 89 years) were enrolled. Corneal transparency was better in all eyes 1 month after surgery. At 6 months, corneal transparency was similar to preoperative levels (P = .218). The mean CCT was 747 mum preoperatively and 623 mum at 1 month; the decrease was statistically significant (P<.001). At 6 months, the mean CCT increased to 710 mum, still significantly thinner than preoperatively (P = .006). Pain scores at 6 months were not significantly different than preoperatively (P = .066).

CONCLUSIONS

Corneal CXL significantly improved corneal transparency, corneal thickness, and ocular pain 1 month postoperatively. However, it did not seem to have a long-lasting effect in decreasing pain and maintaining corneal transparency in patients with PBK.

OBJECTIVE

To assess the possible damage to ocular tissues during treatment of keratoconus with UV-A-riboflavin corneal collagen cross-linking (CXL).

METHODS

Single center, prospective, interventional study.

METHODS

Fourteen eyes of 14 patients aged 28.2 ± 5.9 (mean ± SD) years with progressive keratoconus were treated with UV-A-riboflavin CXL. Corneal endothelium was assessed with the endothelial specular microscope. Central retina was assessed with biomicroscopy fundus examination and with optical coherence tomography using macular thickness protocol. Patients were assessed preoperatively, at week 1, month 1, 3, 6, 9, and 12 after treatment.

RESULTS

Comparative preoperative and postoperative results showed stable endothelial cell density (2730 cells/mm, 2793 cells/mm, and 2640 cells/mm, preoperatively, at month 6, and at month 12, respectively) and stable foveal thickness (203, 202, and 205 μm, preoperatively, at month 6, and at month 12, respectively). No morphological abnormalities were noted.

CONCLUSIONS

UV-A-riboflavin CXL seems to be a safe procedure that does not cause damage to the corneal endothelium and central retina.

Bone mineral density is a complex trait regulated by an interaction between genetic and environmental factors. Recent studies have identified a functional polymorphism affecting codon 677 of the methylenetetrahydrofolate reductase (MTHFR) gene that is associated with reduced bone mineral density (BMD) in Japanese and Danish postmenopausal women and increased risk of fracture in elderly Danish women. Since dietary B vitamins can influence circulating homocysteine (tHcy) levels, we examined the relationship among MTHFR genotype, B complex vitamins (folate, vitamin B12, vitamin B6 and riboflavin), BMD, and rate of change in BMD in a longitudinal study of 1241 Scottish women aged 45-54 years, at the time of initial study, who were followed up for a mean (SD) of 6.6 (0.7) years. There was no significant association between BMD and either MTHFR genotype or B complex vitamins when examined separately. However, we detected a significant interaction among quartile of energy-adjusted riboflavin intake, MTHFR 'TT' genotype, and BMD (P = 0.01 for baseline FN BMD, P = 0.02 for follow-up FN BMD). Increasing dietary riboflavin intake correlated with LS BMD and FN BMD in homozygotes for the MTHFR 'T' allele, which remained significant for FN after adjustment for confounders (r = 0.192, P = 0.036 for baseline; r = 0.186, P = 0.043 at follow-up) but not in the other genotypes. This raises the possibility that riboflavin intake and MTHFR genotype might interact to regulate BMD. Further work is required to determine if this association holds true for other populations and ethnic groups.

The NAD(P)H:flavin oxidoreductase from Escherichia coli, Fre, is a monomer of 26.2 kDa that catalyzes the reduction of free flavins by NADPh or NADH. Overexpression in E. coli now allows the preparation of large amounts of pure protein. Structural requirements for recognition of flavins as substrates and not as cofactors were studied by steady-state kinetics with a variety of flavin analogs. The entire isoalloxazine ring was found to be the essential part of the flavin molecule for interaction with the polypeptide chain. Methyl groups at C-7 and C-8 of the isoalloxazine ring and the N-3 of riboflavin also play an important role in that interaction, whereas the ribityl chain of the riboflavin is not required for binding to the protein. On the other hand, the presence of the 2'-OH of the ribityl chain stimulates the NADPH-dependent reaction significantly. Moreover, a study of competitive inhibitors for both substrates demonstrated that Fre follows a sequential ordered mechanism in which NADPH binds first followed by riboflavin. Lumichrome, a very good inhibitor of Fre, may be used to inhibit flavin reductase in E. coli growing cells. As a consequence, it can enhance the antiproliferative effect of hydroxyurea, a cell-specific ribonucleotide reductase inactivator.

The bifunctional enzyme, FAD synthetase (FS), from Corynebacterium ammoniagenes was overproduced in Escherichia coli and purified, and its steady-state kinetic properties were investigated. Although FMN is an intermediate product in the conversion of riboflavin to FAD, FMN must be released after formation, and then rebind for adenylylation. It was shown that adenylylation of FMN is reversible; FAD and pyrophosphate can be converted to FMN and ATP by the enzyme. In contrast, under the conditions studied, phosphorylation of riboflavin is irreversible. A method is described for analysis of two catalytic cycles, occurring on one enzyme, which have a substrate and/or product in common. The binding order for the phosphorylation cycle of FS was established as riboflavin(in), ATP(in), ADP(out), and FMN(out). The order for the adenylylation cycle was ATP(in), FMN(in), pyrophosphate(out), and FAD(out). A set of steady-state constants was determined, and without additional optimization, these constants were sufficient to describe experimental progress curves for conversion of riboflavin to FAD. In independent studies, it was demonstrated that FMN binds to apo-FS with a dissociation constant of 6-7 microM, which is 2 orders of magnitude higher than the KD value for riboflavin. For the steady-state kinetic analysis, this represents reversible binding of FMN(out) in the phosphorylation cycle (cycle I), which effectively inhibits catalysis in the adenylylation cycle (cycle II).

OBJECTIVE

To evaluate the effectiveness and safety of transepithelial corneal collagen crosslinking (CXL) in children with keratoconus and the refractive changes induced by this treatment.

METHODS

Ophthalmology Department, Ain-Shams University Hospitals, Cairo, Egypt.

METHODS

Prospective comparative case series.

METHODS

Patients younger than 18 years with bilateral keratoconus had transepithelial CXL with the use of transepithelial riboflavin. The other eye was used as a control and was treated conservatively. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and corneal tomography at 12 months were the main outcome measures.

RESULTS

The mean age of the 22 patients (22 eyes) was 15.7 years ± 2.1 (SD). After transepithelial CXL, the improvement in the mean UDVA was statistically significant (from 0.95 ± 0.34 logMAR to 0.68 ± 0.45 logMAR) (P<.05). No eye lost lines of preoperative UDVA; 1 eye lost 1 line of preoperative CDVA. There was no improvement in the control group in UDVA or CDVA (P>.05). The mean simulated keratometry (K) decreased by a mean of 2.03 diopters (D), with mean flattening of the apical K by 2.20 D; both results were statistically significant (P<.05). In the control group, the simulated K increased by a mean of 0.59 D (P>.05), with mean steepening of the apical K by 2.9 D (P<.05). No significant changes occurred in the endothelial cell count in either group.

CONCLUSIONS

Preliminary results of transepithelial CXL in children with keratoconus were encouraging, with no evidence of progression of keratoconus over 12 months.

Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), we assessed the effects of an antioxidant micronutrient combination (800 mg dl-alpha-tocopherol acetate, 24 mg beta-carotene, 1.0 g vitamin C, 200 microg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (P = 0.002), and CySS decreased by 19% (P = 0.03); however, interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status.

Riboflavin and ubiquinone (Coenzyme Q(10), CoQ(10)) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults. Riboflavin (vitamin B(2))-derived cofactors are essential for the function of numerous dehydrogenases. Genetic defects of the riboflavin transport have been detected in Brown-Vialetto-Van Laere and Fazio-Londe syndromes (C20orf54), and haploinsufficiency of GPR172B has been proposed in one patient to cause persistent riboflavin deficiency. Mutations in the electron tranferring fravoprotein genes (ETFA/ETFB) and its dehydrogenase (ETFDH) are causative for multiple acyl-CoA dehydrogenase deficiency. Mutations in ACAD9, encoding the acyl-CoA dehydrogenase 9 protein were recently reported in mitochondrial disease with respiratory chain complex I deficiency. All these conditions may respond to riboflavin therapy. CoQ(10) is a lipid-soluble component of the cell membranes, where it functions as a mobile electron and proton carrier, but also participates in other cellular processes as a potent antioxidant, and by influencing pyrimidine metabolism. The increasing number of molecular defects in enzymes of the CoQ(10) biosynthetic pathways (PDSS1, PDSS2, COQ2, COQ6, COQ9, CABC1/ADCK3) underlies the importance of these conditions. The clinical heterogeneity may reflect blocks at different levels in the complex biosynthetic pathway. Despite the identification of several primary CoQ(10) deficiency genes, the number of reported patients is still low, and no true genotype-phenotype correlations are known which makes the genetic diagnosis still difficult. Additionally to primary CoQ(10) deficiencies, where the mutation impairs a protein directly involved in CoQ(10) biosynthesis, we can differentiate secondary deficiencies. CoQ(10) supplementation may be beneficial in both primary and secondary deficiencies and therefore the early recognition of these diseases is of utmost importance.

BACKGROUND

Significant subgroups in most European populations have intakes below nationally recommended levels for several vitamins, minerals and trace elements, placing individuals at risk of suboptimal intake of important vitamins and minerals. The voluntary addition of micronutrients to the appropriate foods may help address the risks associated with low micronutrient intakes. However, concerns need to be addressed regarding the potential for unacceptably high intakes, particularly for those people consuming very large amounts of food.

OBJECTIVE

To develop a model to estimate the level of each micronutrient that can be added safely to foods.

METHODS

A theoretical model was developed based on the critical factors which determine the risk of unacceptably high intake for each micronutrient at high levels of food/energy intakes. These included 1) Tolerable Upper Intake Levels (UL), 2) high micronutrient intakes in Europe at the 95(th) percentile intake for each nutrient, 3) the proportion of fortified foods in the diets of individuals at the 95(th) percentile for energy intakes, 4) the proportion of foods to which micronutrients could practically be added, and 5) a range of estimates for the fractions of foods which might be actually fortified for each nutrient. A maximum level was set up for each micronutrient per typical serving or 100 kcal portion. The outputs of the model were then compared against a recent model developed by AFSSA, based on the food intake data in France.

RESULTS

Three categories of micronutrients were identified, in which micronutrients could be added safely to foods at levels (per serving, e. g., 100 kcal) 1) greater than 1 European Commission Recommended Daily Intake (EC RDA): vitamin B12, vitamin C, vitamin E, riboflavin, panthothenic acid, niacin and thiamine; 2) between 50 and 100 % of the EC RDA: vitamin B6, vitamin D, folic acid, biotin, copper, iodine and selenium; 3) between 10 and 40 % of the EC RDA: iron, zinc, calcium, phosphorus and magnesium. A fourth category consisting of retinol, for which high end intake levels are close to UL for some population subgroups in Europe and thus requires further consideration.

CONCLUSIONS

A wide range of vitamins and minerals can be added safely to foods at nutritionally important levels in the current diets of Europeans.

OBJECTIVE

To report a case of endothelial decompensation after a collagen cross-linking (CXL) procedure for keratoconus.

METHODS

An 18-year-old boy had CXL for keratoconus in the right eye. He developed keratouveitis with generalized corneal edema seen 3 weeks after the procedure. Polymerase chain reaction for aqueous humor Herpes simplex virus was negative. The patient was treated with topical steroids. Specular microscopy revealed mildly reduced density of endothelial cells. On follow-up to 6 months, corneal edema increased with the formation of epithelial bullae. Penetrating keratoplasty was performed. Possible causes for this complication are discussed.

RESULTS

Clinical and histopathological analyses revealed generalized loss of endothelial cells along with signs of inflammation.

CONCLUSIONS

Although it is considered very safe, collagen CXL can cause severe keratouveitis and endothelial failure.

Effects of 10 weeks of physical training on free radical scavenging enzyme systems in erythrocytes were investigated in 7 sedentary healthy male students. The training consisted of running over 5 km, 6 times/week. Their maximum oxygen uptake and 12 min walk-run performance increased significantly after training. Of the antioxidant enzyme systems examined in the erythrocytes, both catalase activity and concentration and total glutathione reductase (GR) activity also showed significant increases following the training. The erythrocyte GR activity coefficient also increased significantly. These results suggest that chronic aerobic exercise increases riboflavin requirements and has some positive effects on antioxidative processes.

BACKGROUND

Linear growth retardation and wasting are common in children born to HIV-infected women. Inexpensive interventions that could improve the postnatal growth pattern of such children are needed.

OBJECTIVE

The objective was to examine the effect of supplementing HIV-infected women with multivitamins or vitamin A and beta-carotene, during and after pregnancy, on the growth of their children during the first 2 y of life.

METHODS

We conducted a randomized placebo-controlled trial in 886 mother-infant pairs in Tanzania. At the first prenatal visit, HIV-infected women were randomly assigned to 1 of 4 daily oral regimens in a 2 x 2 factorial fashion: multivitamins (MV: thiamine, riboflavin, vitamin B-6, niacin, vitamin B-12, vitamin C, vitamin E, and folic acid), preformed vitamin A + beta-carotene (VA/BC), MV including VA/BC, or placebo. Supplementation continued during the first 2 y postpartum and thereafter. Children were weighed and measured monthly, and all received vitamin A supplements after 6 mo of age per the standard of care.

RESULTS

Multivitamins had a significant positive effect on attained weight (459 g; 95% CI: 35, 882; P = 0.03) and on weight-for-age (0.42; 95% CI: 0.07, 0.77; P = 0.02) and weight-for-length (0.38; 95% CI: 0.07, 0.68; P = 0.01) z scores at 24 mo. VA/BC seemed to reduce the benefits of MV on these outcomes. No significant effects were observed on length, midupper arm circumference, or head circumference.

CONCLUSIONS

Supplementation of HIV-infected women with multivitamins (vitamin B complex, vitamin C, and vitamin E) during pregnancy and lactation is an effective intervention for improving ponderal growth in children.