Prevalent vitamin B-12 deficiency in twelve-month-old Guatemalan infants is predicted by maternal B-12 deficiency and infant diet

Approximately one-third of low-income women and children studied in Guatemala are reported to have deficient (<148 pmol/L) or marginal (148-220 pmol/L) plasma vitamin B-12 concentrations. Because vitamin B-12 deficiency can adversely affect infant development and cognitive function, the present study examined predictors of deficient plasma vitamin B-12 concentrations at the age of 12 mo. Analyses were performed on baseline data from a randomized clinical trial in 304 Guatemalan infants, 80% of whom were partially breast-fed, and their mothers. Exclusion criteria for infants included twins, severe stunting or moderate wasting, reported major health problems, severe developmental delay, hemoglobin <95 g/L, maternal age <17 y, and maternal pregnancy >3 mo. Data collected included socio-economic status, infant anthropometry, vitamin B-12 intake from complementary foods, and breast-feeding frequency reported by mothers. A complete blood count and plasma vitamin B-12, folate, ferritin, and C-reactive protein were measured. Deficient or marginal plasma vitamin B-12 concentrations were found in 49% of infants and 68% of mothers. The mean intake of maternal vitamin B-12 was 3.1 microg/d, and infants consumed 2.2 microg/d from complementary foods. In linear regression analysis, infant plasma B-12 concentration was strongly and positively associated with maternal plasma vitamin B-12 and B-12 intake from complementary foods (predominantly powdered cow's milk), and inversely associated with frequency of breast-feeding and larger household size (P < 0.0001). Vitamin B-12 supplementation of lactating women, food fortification, and education to improve infant's vitamin B-12 status are potential interventions that can improve the vitamin B-12 status of mothers and infants in this population.     

Vitamin B-12: low milk concentrations are related to low serum concentrations in vegetarian women and to methylmalonic aciduria in their infants

In a group of 13 strict vegetarian and 6 omnivorous lactating women, relationships were studied among maternal milk and serum vitamin B-12, and milk vitamin B-12 and infant urinary methylmalonic acid (MMA) excretion. Milk vitamin B-12 concentrations were lower in women consuming a strict vegetarian diet compared with an omnivorous diet. Milk vitamin B-12 was inversely related to length of time on a vegetarian diet and positively correlated with maternal serum vitamin B-12 concentrations. Infant urinary MMA excretion was inversely related to milk vitamin B-12 concentrations less than 362 pmol/L. The 1989 recommended dietary allowance for vitamin B-12 of 221 pmol/d for infants is close to the intake below which infant urinary MMA excretion is increased. We conclude that the current RDA for infants provides little margin of safety.     

Pyridoxine supplementation of lactating mothers: relation to maternal nutrition status and vitamin B-6 concentrations in milk

Vitamin B-6 status, assessed by plasma pyridoxal phosphate (PLP) concentrations, and vitamin B-6 concentrations in breast milk were examined in 47 lactating mothers supplemented with different amounts of pyridoxine.HCl (PN.HCl) during pregnancy and the first 6 mo of lactation. PLP concentrations in cord blood and maternal plasma at 2 d postpartum and vitamin B-6 concentration in colostrum were positively correlated with the amount of PN.HCl supplementation prenatally (r = 0.71, p less than 0.001; r = 0.74, p less than 0.001; and r = 0.78, p less than 0.001, respectively). Correlations between the amounts of PN.HCl supplementation postnatally and plasma PLP concentrations increased with the length of supplementation. Plasma PLP concentrations were also correlated with vitamin B-6 concentrations of milk samples, which were obtained on the same day as plasma. PN.HCl supplements between 2.5 and 4.0 mg/d (2.1-3.4 mg PN equivalents) ensured vitamin B-6 adequacy of the mother and maintained relatively saturated concentrations of vitamin B-6 in breast milk.     

Vitamin A supplementation of women postpartum and of their infants at immunization alters breast milk retinol and infant vitamin A status

Vitamin A supplementation of lactating mothers and of infants at the time of diphtheria-pertussis-tetanus (DPT) and oral polio vaccine (OPV) immunizations have both been suggested as measures to prevent deficiency among infants. This multicenter randomized, double-blind, placebo-controlled trial was conducted in Ghana, India and Peru to determine the effect of maternal vitamin A supplementation on breast milk retinol and of maternal and infant supplementation on infant vitamin A status. Mothers in the intervention group received 60 mg vitamin A (as retinol palmitate) at 18-42 d postpartum; their infants were given 7.5 mg three times, i.e., at 6, 10 and 14 wk of age with DPT and OPV immunizations. Mothers and infants in the comparison group received a placebo. Maternal supplementation resulted in higher breast milk retinol at 2 mo postpartum [difference in means 7.1, 95% confidence interval (CI), 3.4, 10.8 nmol/g fat] and lower proportion of mothers with breast milk retinol < or = 28 nmol/g fat (15.2 vs. 26.6%, 95% CI of difference -16.6, -4.1%). At 6 and 9 mo, maternal supplementation did not affect breast milk retinol or the proportion of mothers with low breast milk retinol. Vitamin A supplementation of the mothers and their infants reduced the proportion of infants with serum retinol < or = 0.7 micro mol/L (30.4 vs. 37%, 95% CI of difference -13.7, 0.6%) and that with low vitamin A stores as indicated by the modified relative dose response (MRDR) > 0.06 (44.2 vs. 52.9%, 95% CI of difference -16.6, -0.9%) at 6 mo. Supplementation had no effect at 9 mo. The beneficial effect of supplementation on breast milk retinol and infants' vitamin A status varied by site. It was greatest in India followed by Ghana and Peru. At the doses used, maternal supplementation improved breast milk retinol status at 2 mo (P < 0.001) and maternal and infant supplementation modestly increased (P = 0.03) infant vitamin A status at 6 mo of age. Additional strategies to improve vitamin A status of 6- to 9-mo-old infants must be considered.     

Vitamin B-6 status of breast-fed neonates: influence of pyridoxine supplementation on mothers and neonates.

Vitamin B-6 concentrations in human milk are known to respond rapidly to changes in maternal vitamin B-6 intake. In this study, mothers were supplemented during the first 28 d of lactation with 2 or 27 mg pyridoxine (PN)-HCl/d and a subgroup of breast-fed infants of the 2-mg/d-supplemented mothers were supplemented with 0.4 mg PN-HCl/d. Vitamin B-6 intakes of breast-fed infants reflected the amount of their mother's supplement; intakes were highest for the vitamin-supplemented infants. Vitamin B-6 intake of mothers was a strong indicator of infant vitamin B-6 status. Vitamin intake of infants correlated significantly with five measures of vitamin B-6 status. Plasma pyridoxal-5'-phosphate (PLP) concentrations and birth weight were the strongest predictors of infant growth that were examined. Alkaline phosphatase activity in the mother's milk and infant plasma reflected pyridoxal-PLP ratios in these fluids, suggesting that the enzyme acts in regulating circulating vitamer concentrations.     

Increased urinary methylmalonic acid excretion in breast-fed infants of vegetarian mothers and identification of an acceptable dietary source of vitamin B-12

Increased urinary methylmalonic acid (UMMA) concentrations might indicate vitamin B-12 deficiency. Our study tested the hypothesis that elevated UMMA in breast-fed infants is associated with decreased maternal serum B-12 concentrations. UMMA concentrations were measured in 17 vegetarian mothers and their infants and in six infants of nonvegetarian mothers. Serum vitamin B-12 concentrations were determined in all mothers. Range of UMMA for vegetarian infants (3-924 mcg/mg [2.6-790.9 mumol/mmol] creatinine) was much broader than that for omnivorous infants (2-25 mcg/mg [1.7-21.4 mumol/mmol] creatinine). Maternal UMMA and serum vitamin B-12 were negatively correlated (r = -0.700, p = 0.003). Infant UMMA concentrations correlated positively with maternal UMMA concentrations (r = 0.686, p = 0.003) and inversely with maternal serum vitamin B-12 concentrations (r = -0.681, p less than 0.001). In three infants with high UMMA concentrations, vitamin B-12 treatment (oral B-12, vitamin B-12 injection, or a modification of maternal diet within the vegetarian philosophy) led to an abrupt decrease of UMMA.     

B vitamins in breast milk: relative importance of maternal status and intake, and effects on infant status and function

Infants should be exclusively breastfed for the first 6 mo of life. However, maternal deficiency of some micronutrients, conveniently classified as Group I micronutrients during lactation, can result in low concentrations in breast milk and subsequent infant deficiency preventable by improving maternal status. This article uses thiamin, riboflavin, vitamin B-6, vitamin B-12, and choline as examples and reviews the evidence for risk of inadequate intakes by infants in the first 6 mo of life. Folate, a Group II micronutrient, is included for comparison. Information is presented on forms and concentrations in human milk, analytical methods, the basis of current recommended intakes for infants and lactating women, and effects of maternal supplementation. From reports of maternal and/or infant deficiency, concentrations in milk were noted as well as any consequences for infant function. These milk values were used to estimate the percent of recommended daily intake that infants fed by a deficient mother could obtain from her milk. Estimates were 60% for thiamin, 53% for riboflavin, 80% for vitamin B-6, 16% for vitamin B-12, and 56% for choline. Lack of data limits the accuracy and generalizability of these conclusions, but the overall picture that emerges is consistent across nutrients and points to an urgent need to improve the information available on breast milk quality.     

Vitamin B-6 status of Egyptian mothers: relation to infant behavior and maternal-infant interactions

Functional consequences of marginal maternal vitamin B-6 status for behavior of the neonate and for mother-infant interactions at age 3-6 mo were assessed by a double-blind procedure. In 27 of 70 Egyptian village women studied, vitamin B-6 concentration of their milk was considered indicative of poor maternal vitamin B-6 nutriture. Neonatal behavior, quantified by the Brazelton Neonatal Behavioral Assessment Scale, showed that consolability, appropriate build-up to a crying state, and response to aversive stimuli were significantly correlated with maternal vitamin B-6 nutriture. Naturalistic observational procedures, used twice monthly with infants aged 3-6 mo, indicated that mothers assessed as having marginal vitamin B-6 status were less responsive to their infants' vocalizations, showed less effective intervention to infant distress, and were more likely to use older siblings as care-givers than were mothers of better vitamin status. We conclude that vitamin B-6 was a factor influencing both the behavior of the mother and her infant.     

Assessment of vitamin B-12, folate, and vitamin B-6 status and relation to sulfur amino acid metabolism in neonates

BACKGROUND: Total serum homocysteine (tHcy) has been used as an indicator of intracellular vitamin B-12, vitamin B-6, and folate status in adults, but data for neonates and infants are lacking. Vitamin B-12 deficiency may have fatal effects on neurologic development in infants; therefore, early diagnosis is crucial. OBJECTIVE: Our aim was to provide a reference range for tHcy in neonates and to explore the relation of tHcy to 1) serum vitamin concentrations, 2) the product of the transsulfuration pathway (cysteine), and 3) nutritional factors. DESIGN: tHcy, cysteine, folate, vitamin B-12, and vitamin B-6 were measured in 123 healthy, breast-fed neonates. The influence of nutrition (formula or human milk) on these variables was investigated in 60 infants. RESULTS: The mean (+/-SD) tHcy concentration was 7.8 +/- 3.1 micromol/L. tHcy showed a linear association with log vitamin B-12 (r = -0.64, P: < 0. 001), red blood cell folate (r = -0.33, P: < 0.001), and cysteine (r = 0.36, P: < 0.001). The strongest linear association was found between tHcy and the ratio of log cysteine to log vitamin B-12 (r = 0.71, P: < 0.0001). We found more neonates with probable tissue deficiencies of vitamin B-12 and folate on the basis of tHcy measurements than was expected from the analysis of serum vitamin concentrations alone (15.4% compared with 9.7%). Breast-fed infants had significantly lower vitamin B-12 concentrations and significantly higher serum tHcy and cysteine concentrations and ratios of log cysteine to log vitamin B-12 than did formula-fed infants (P: < 0.001). CONCLUSIONS: tHcy can be used as a functional indicator of vitamin B-12 and folate status in neonates. The ratio of cysteine to vitamin B-12 can be used as an additional index of impaired intracellular Hcy metabolism. tHcy and cysteine concentrations in infants are affected by nutritional factors.     

Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study

BACKGROUND: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake. OBJECTIVE: We hypothesized that vitamin B-12 concentrations vary according to intake source. DESIGN: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26-49, 50-64, and 65-83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat. RESULTS: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others. CONCLUSIONS: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability.     

Plasma vitamin B-12 concentrations in an elderly latino population are predicted by serum gastrin concentrations and crystalline vitamin B-12 intake

The prevalence of vitamin B-12 deficiency increases with age, probably resulting from malabsorption of food-bound B-12 secondary to gastric atrophy. On the basis of this assumption, the Institute of Medicine (IOM) recommends those aged >50 y consume crystalline vitamin B-12. There is limited information on the prevalence of gastric atrophy in the elderly and whether the IOM recommendation would be effective. The objective of this study was to assess predictors of vitamin B-12 status and their interactions in free-living elderly. Individuals (n = 57) with deficient plasma vitamin B-12 (p-B12 < 148 pmol/L) were compared with 68 individuals with marginal p-B12 (148-221 pmol/L) and 52 with normal p-B12 (>221 pmol/L) in a cross-sectional sample (n = 1546) of elderly (>60 y) Latinos in California. Associations were examined among p-B12 and serum gastrin, vitamin B-12 intake from food and crystalline sources, and medications that putatively affect vitamin B-12 absorption. Serum gastrin was elevated, indicating gastric atrophy, in 48% of participants with deficient p-B12, 23% with marginal p-B12 and 21% of normal p-B12 participants, and was a significant predictor of deficient p-B12 and high plasma homocysteine (p-tHcy). Median total vitamin B-12 intake exceeded recommendations and was similar among status groups. Crystalline vitamin B-12 intake in the normal p-B12 group was higher than in the deficient p-B12 group (P < 0.01), and tended to be higher than the marginal group (P = 0.07). When serum gastrin was elevated, p-B12 was predicted by crystalline vitamin B-12, but not by intake of vitamin B-12 from food. Elevated serum gastrin was highly prevalent and predicted vitamin B-12 depletion. Crystalline vitamin B-12 intake predicted p-B12 in individuals with elevated serum gastrin, supporting IOM recommendations to increase consumption of crystalline vitamin B-12.     

Effects of different levels of vitamin B-6 supplementation on vitamin B-6 concentrations in human milk and vitamin B-6 intakes of breastfed infants

Vitamin B-6 has been reported to vary in concentration in human milk in response to changes in maternal intake of the vitamin. This study examined the effects of such changes on the breastfed infants' intake of vitamin B-6. Lactating mothers received 0, 2.5, 10.0 or 20.0 mg pyridoxine X HCl (PN X HCl) for 3 consecutive days in addition to dietary sources. Dietary intakes of vitamin B-6 (mean = 1.8 +/- 0.2 mg/day) were similar among the four groups. Vitamin B-6 was determined in milk samples from each feeding and milk intakes of infants were estimated by test-weighing. Nonsupplemented mothers had lower vitamin B-6 in their milk (93 +/- 8 micrograms/L) and vitamin B-6 intake of their infants was lower (0.06 +/- 0.01 mg/day) compared to other groups. Maternal supplementation with 2.5, 10.0 or 20.0 mg PN X HCl was paralleled by vitamin B-6 levels in milk of 192 +/- 16, 247 +/- 25 and 413 +/- 45 micrograms/L, respectively, and by vitamin B-6 intakes of breastfed infants of 0.12 +/- 0.02, 0.22 +/- 0.02 and 0.28 +/- 0.03 mg/day, respectively. When maternal intakes of vitamin B-6 approximated 20.0 mg/day, breastfed infants were unlikely to receive the current RDA of 0.3 mg vitamin B-6/day.     

Vitamin B-6 content of breast milk and neonatal behavioral functioning

OBJECTIVE: To determine if vitamin B-6 intakes of mothers influence the B-6 vitamer content of transition milk and if correlations exist between the vitamin B-6 content of the milk and the infants' neurobehavioral functioning. DESIGN: Transition milk samples were collected from mothers 8 to 11 days after delivery for B-6 vitamer analysis. Neurobehavioral functioning of the neonates was determined at that time. A 24-hour recall was used in estimating vitamin B-6 intakes of the mothers. SUBJECTS: A convenience sample of low-income, lactating women (n = 25) who had normal pregnancies. MAIN OUTCOME MEASURES: B-6 vitamers were measured in the mothers' transition milk samples. Neurobehavioral functioning was assessed using the Brazelton Neonatal Behavioral Assessment Scale (NBAS), and the Center for Epidemiologic Studies Depression Scale was used to evaluate maternal depression. STATISTICAL ANALYSES PERFORMED: Pearson correlation coefficients were used to assess if statistically significant relationships existed between variables. The Mann-Whitney test was used to determine if median group values were significantly different. RESULTS: The major B-6 vitamer in transition milk was pyridoxal. Mothers with vitamin B-6 intake greater than the median value had a significantly higher median pyridoxal level in their breast milk than did the mothers with intakes below the median value. All except one mother had a dietary vitamin B-6 intake that exceeded the Recommended Dietary Allowance. Infant scores on habituation (r = .94, P < .05) and autonomic stability (r = .34, P < .05) subscales of the NBAS were positively correlated with milk pyridoxal values. APPLICATIONS/CONCLUSIONS: Vitamin B-6 is important for normal behavioral functioning of infants. The mothers' vitamin B-6 intake affects vitamin B-6 levels of breast milk and the need for consuming recommended levels of vitamin B-6 should be emphasized to all pregnant and lactating mothers.     

Impact of Maternal Daily Oral Low-Dose Vitamin A Supplementation on the Mother-Infant Pair: A Randomised Placebo-Controlled Trial in China

Background: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. Methods: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D₂), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. Results: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. Conclusions: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.     

Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods

The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous study identified a high prevalence of inadequate vitamin B-12 intakes, this study examined whether plasma vitamin B-12 concentrations were associated with dietary sources of the vitamin at baseline and could be increased by supplementation with animal source foods (ASF). The 4 experimental groups in 503 school children were: 1) control (no food provided); 2) githeri (a maize and bean staple with added oil); 3) githeri + meat (githeri + minced beef); or 4) githeri + milk (githeri + milk). Feedings were isocaloric. Dietary data were collected at baseline, and biochemical data at baseline and after 1 and 2 y of feeding. Baseline plasma vitamin B-12 concentration was 193.6 +/- 105.3 pmol/L and correlated with % energy from ASF (r = 0.308, P < 0.001). The odds ratio for low plasma vitamin B-12 (<148 pmol/L), which occurred in 40% of children, was 6.28 [95% CI: 3.07-12.82] for the lowest vs. highest ASF intake tertile (P < 0.001). Feeding ASF (meat or milk) greatly reduced the prevalence of low plasma vitamin B-12 (P < 0.001). The high prevalence of low plasma vitamin B-12 concentrations in these children is predicted by a low intake of ASF, and supplemental ASF improves vitamin B-12 status.     

Dietary Sources of Vitamin B-12 and Their Association with Vitamin B-12 Status Markers in Healthy Older Adults in the B-PROOF Study

Low vitamin B-12 concentrations are frequently observed among older adults. Malabsorption is hypothesized to be an important cause of vitamin B-12 inadequacy, but serum vitamin B-12 may also be differently affected by vitamin B-12 intake depending on food source. We examined associations between dietary sources of vitamin B-12 (meat, fish and shellfish, eggs, dairy) and serum vitamin B-12, using cross-sectional data of 600 Dutch community-dwelling adults (≥65 years). Dietary intake was assessed with a validated food frequency questionnaire. Vitamin B-12 concentrations were measured in serum. Associations were studied over tertiles of vitamin B-12 intake using P for trend, by calculating prevalence ratios (PRs), and splines. Whereas men had significantly higher vitamin B-12 intakes than women (median (25th–75th percentile): 4.18 (3.29–5.38) versus 3.47 (2.64–4.40) μg/day), serum vitamin B-12 did not differ between the two sexes (mean ± standard deviation (SD): 275 ± 104 pmol/L versus 290 ± 113 pmol/L). Higher intakes of dairy, meat, and fish and shellfish were significantly associated with higher serum vitamin B-12 concentrations, where meat and dairy—predominantly milk were the most potent sources. Egg intake did not significantly contribute to higher serum vitamin B-12 concentrations. Thus, dairy and meat were the most important contributors to serum vitamin B-12, followed by fish and shellfish.     

Low vitamin B-12 intake and status are more prevalent in Hispanic older adults of Caribbean origin than in neighborhood-matched non-Hispanic whites

Vitamin B-12 deficiency is a recognized problem among older adults, although vitamin B-12 status among differing ethnic groups remains unclear. We examined vitamin B-12 intake and status in a representative sample of elderly Hispanics of Caribbean origin (Puerto Rican and Dominican) and non-Hispanic whites. Dietary intake and plasma values were available for 347 Puerto Ricans, 102 Dominicans and 154 non-Hispanic whites (60-93 y). Relative to non-Hispanic whites, Hispanics had significantly lower vitamin B-12 intake and plasma concentrations; 17% of Hispanics and 10% of non-Hispanic whites had concentrations < 185 pmol/L (P < 0.05). Among Hispanics, log transformed vitamin B-12 intake was significantly associated with plasma concentration (beta = 60 pmol/L per log unit vitamin B-12 intake, P < 0.002 for supplement users and beta = 74 pmol/L per log unit vitamin B-12 intake, P < 0.01 for nonsupplement users). Intake and plasma concentrations were significantly associated among non-Hispanic whites only when supplement users were included (beta = 95 pmol/L per log unit vitamin B-12 intake, P < 0.0001). Hispanic supplement users (18%) had higher plasma concentrations than did nonsupplement users (364 +/- 17 and 297 +/- 8 pmol/L, respectively, P < 0.001). For Hispanics, consumption of breakfast cereal > 4 times/wk compared to no cereal was protective against lower plasma concentrations (8 vs. 24% < 185 pmol/L, P < 0.01). Approximately 40% of both groups with plasma vitamin B-12 < 185 pmol/L had homocysteine > 14 micromol/L, relative to < 17% of those with B-12 > 185 pmol/L. The high prevalence of low vitamin B-12 status in elderly Hispanics appears largely attributed to inadequate intake. As in other populations, sources of unbound vitamin B-12 such as supplements and fortified cereal appear to be protective. Dietary intervention programs targeted to the Hispanic population should promote these vitamin B-12 sources.     

Maternal vitamin A or beta-carotene supplementation in lactating bangladeshi women benefits mothers and infants but does not prevent subclinical deficiency

The effects of maternal postpartum vitamin A or beta-carotene supplementation on maternal and infant serum retinol concentrations, modified relative dose-response (MRDR) ratios and breast milk vitamin A concentrations were assessed during a community-based trial in Matlab, Bangladesh. At 1-3 wk postpartum, women were randomly assigned to receive either (1) a single dose of 200,000 international units [60,000 retinol equivalents (RE)] vitamin A followed by daily placebos (n = 74), (2) daily doses of beta-carotene [7.8 mg (1300 RE)] (n = 73) or (3) daily placebos (n = 73) until 9 mo postpartum. Compared to placebos, vitamin A supplementation resulted in lower maternal MRDR ratios (i.e., increased liver stores) and higher milk vitamin A concentrations at 3 mo, but these improvements were not sustained. The beta-carotene supplementation acted more slowly, resulting in milk vitamin A concentrations higher than the placebo group only at 9 mo. Irrespective of treatment group, over 50% of women produced milk with low vitamin A concentrations (/=0. 06. We conclude that while both interventions were beneficial, neither was sufficient to correct the underlying subclinical vitamin A deficiency in these women nor to bring their infants into adequate vitamin A status.     

Evaluation of serum retinol, the modified-relative-dose-response ratio, and breast-milk vitamin A as indicators of response to postpartum maternal vitamin A supplementation

BACKGROUND: Conflicting results have been reported regarding the relative performance of serum retinol, the modified-relative-dose-response (MRDR) ratio, and breast-milk vitamin A concentrations in detecting changes in maternal vitamin A status. OBJECTIVE: We used receiver operating characteristic analyses and standardized differences to compare the ability of these indicators to detect a response to postpartum vitamin A supplementation in lactating Bangladeshi women. DESIGN: At 2 wk postpartum, women were randomly assigned to receive either a single dose of vitamin A [200000 IU (60000 retinol equivalents); n = 74] or placebo (n = 73). Data from maternal serum and breast milk collected 3 mo postpartum and from infant serum collected 6 mo postpartum were used to examine the ability of serum retinol, the MRDR ratio, and breast-milk vitamin A to discriminate between individuals in the supplemented and unsupplemented groups. Breast milk was collected by expressing the entire contents of one breast that had not been used to feed an infant for > or =2 h (full samples) or without controlling the time since the last breast-feeding episode (casual samples). RESULTS: Casual breast-milk samples performed better than full breast-milk samples in detecting a response to maternal supplementation. The MRDR ratio performed better than serum retinol in both the women and their infants. Overall, the most responsive indicator was the measurement of breast-milk vitamin A per gram of fat in casual breast-milk samples. CONCLUSIONS: Breast-milk vitamin A and the MRDR ratio are responsive indicators of vitamin A status, especially in women with mild vitamin A deficiency.     

Bread cofortified with folic acid and vitamin B-12 improves the folate and vitamin B-12 status of healthy older people: a randomized controlled trial

BACKGROUND: Mandatory fortification of flour with folic acid has reduced the number of neural tube defects in North America. Concerns that high intakes of folic acid might mask vitamin B-12 deficiency in older persons have delayed the introduction of fortification in many European countries. Cofortification of flour with folic acid and vitamin B-12 could simultaneously improve folate and vitamin B-12 status. OBJECTIVE: The objective was to estimate the effect of the consumption of bread fortified with modest amounts of folic acid and vitamin B-12 on folate and vitamin B-12 status in healthy older persons living in the Netherlands, where folic acid fortification is not taking place. DESIGN: Men and women aged 50-75 y were randomly assigned in this 12-wk double-blind, placebo-controlled trial to consume bread fortified with 138 mug folic acid and 9.6 mug vitamin B-12 daily (n = 72) or unfortified bread (n = 70). RESULTS: The consumption of fortified bread increased serum folate concentrations by 45% (mean: 6.3 nmol/L; 95% CI: 4.5, 8.1 nmol/L) and serum vitamin B-12 concentrations by 49% (mean: 102 pmol/L; 95% CI: 82, 122 pmol/L) relative to the placebo group. Fortified bread increased erythrocyte folate concentrations by 22% and holotranscobalamin concentrations by 35%; it decreased homocysteine concentrations by 13% and methylmalonic acid concentrations by 10%. Consumption of fortified bread decreased the proportion of individuals with marginal serum vitamin B-12 concentrations (<133 pmol/L) from 8% at enrollment to 0% after 12 wk. CONCLUSION: Bread fortified with modest amounts of folic acid and vitamin B-12 will improve folate and vitamin B-12 status and a considerable proportion of vitamin B-12 deficiency in older people. This trial was registered at clinicaltrials.gov as NCT00353353.