The Inclusion of Folic Acid in Weekly Iron-Folic Acid Supplements Confers no Additional Benefit on Anemia Reduction in Nonpregnant Women: A Randomized Controlled Trial in Malaysia.

BACKGROUND: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anemia prevalence is ≥20%; however, it is unknown whether the inclusion of folic acid in weekly IFA supplements reduces anemia. OBJECTIVES: We examined whether the inclusion of folic acid in weekly IFA supplements conferred any benefit on hemoglobin (Hb) concentration, anemia reduction, or iron status [ferritin and soluble transferrin receptor (sTfR)], over iron alone. METHODS: In this secondary analysis of a randomized controlled trial in Malaysia, n = 311 nonpregnant women (18-45 y old) received 60 mg Fe with either 0, 0.4, or 2.8 mg folic acid once-weekly for 16 wk. Fasting blood was collected at baseline and 16 wk. A generalized linear model (normal distribution with identity link) was used to assess Hb concentration at 16 wk (primary outcome). RESULTS: At baseline, 84% of women had low folate status (plasma folate < 14 nmol/L). At 16 wk, marginal mean (95% CI) Hb was 131 (130, 133), 131 (129, 132), and 132 (130, 133) g/L; ferritin was 58.2 (53.9, 62.5), 56.5 (52.2, 60.9), and 58.0 (53.7, 62.3) µg/L; and sTfR was 5.8 (5.5, 6.1), 5.8 (5.5, 6.1), and 5.9 (5.6, 6.2) mg/L in the 0, 0.4, and 2.8 mg/wk groups, respectively, with no differences between groups (P > 0.05). Baseline plasma folate concentration did not modify the effect of treatment on Hb concentration at 16 wk. Among all women, the risks of anemia [risk ratio (RR): 0.65; 95% CI: 0.45, 0.96; P = 0.03] and iron deficiency based on ferritin (RR: 0.30; 95% CI: 0.20, 0.44; P < 0.001) were lower at 16 wk than at baseline. CONCLUSIONS: Despite the low folate status among these nonpregnant Malaysian women, the inclusion of folic acid in weekly IFA supplements did not reduce anemia or improve iron status, over iron alone. However, the benefits of folic acid for neural tube defect prevention still warrant its retention in weekly IFA supplements.This trial was registered at www.anzctr.org.au as ACTRN12619000818134.

Weekly iron-folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia.

INTRODUCTION: Weekly iron-folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk. METHODS: We conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks. RESULTS: At 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group. CONCLUSION: Weekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed. TRAIL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).

Measuring thiamine status in dried blood spots.

BACKGROUND: A reliable and robust method with minimum sample collection requirement for thiamine assay is needed in clinical and research settings. METHODS: A simple and robust assay for three vitamers (thiamine, Th; thiamine monophosphate, TMP; and thiamine diphosphate, TDP) using a 6.35-mm dried blood spot (DBS) disc was developed, validated and applied. RESULTS: We were able to quantify accurately thiamine status covering all major vitamers Th, TMP and TDP with acceptable recovery (90%-114%), limit of quantification (TDP: 3.0 nM, TMP and Th: 1.5 nM), linearity (TDP: LOQ 400 nM, TMP and Th: LOQ 50 nM, all R2 > 0.99), imprecision (coefficient variation < 4.3% for TDP, <10.0% for TMP and < 12.6% for Th) and stability at -20 °C for up to 42 days. By recruiting 20 healthy participants, we cross compared finger capillary DBS with venous whole blood and venous blood pre-spotted on filter papers. The results demonstrated minimum bias between methods. A preliminary dosing study showed the method had excellent sensitivity after a single dose of supplemental thiamine. CONCLUSIONS: We have developed and clinically validated a simple, robust, accurate and sensitive assay for the analysis of thiamine status in DBS, suitable for large-scale population studies.

Effect of enhanced homestead food production on anaemia among Cambodian women and children: A cluster randomized controlled trial.

There is inconsistent evidence on the efficacy of agriculture programmes at improving women and children's anaemia and nutritional status. The primary aim of this study was to evaluate the impact of a nutrition-sensitive enhanced homestead food production (EHFP) programme on anaemia in women (18-45 years) and children (6-59 months) in rural Cambodia. Secondary outcomes were women's micronutrient status and women and children's anthropometry. In this cluster-randomized controlled trial, 900 households from 90 villages (clusters) were randomized to either (a) home gardens and behaviour change communication (BCC) on nutrition, hygiene, women's empowerment, and marketing (EHFP); (b) home gardens plus fishponds and BCC (EHFP + F); or (c) control (no intervention). Haemoglobin concentration and anthropometry were measured in women and children at baseline and at 22 months. Venous blood samples were collected in a subset of women (n = 450) at baseline and at 22 months. Generalized linear mixed effect models with repeated measures were used to evaluate the difference across groups and the change from baseline to end of study. Ninety clusters, 552 women, and 754 children completed the trial. Compared with control, we found a statistically significant impact on anaemia prevalence in children (-14.0 percentage points; P = 0.02) and retinol binding protein concentrations in women (difference in difference: 0.34; P = 0.02) randomized to EHFP and EHFP + F groups, respectively. No other statistically significant effects on anaemia, nutritional biomarker concentrations, or anthropometry were observed. Future research is needed to examine longer term impacts of EHFP on anthropometry in women and children and into the nutritional causes of anaemia among children in Cambodia.

Concentrations of Water-Soluble Forms of Choline in Human Milk from Lactating Women in Canada and Cambodia.

Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and glycerophosphocholine). It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin. Scarce information exists on milk choline from countries differing in animal-source food availability. In this secondary analysis of samples from previous trials, the concentrations of the water-soluble forms of choline were quantified by liquid chromatography-tandem mass spectrometry in mature milk samples collected from lactating women in Canada (n = 301) and in Cambodia (n = 67). None of the water-soluble forms of choline concentrations in milk differed between Canada and Cambodia. For all milk samples (n = 368), free choline, phosphocholine, glycerophosphocholine, and the sum of water-soluble forms of choline concentrations in milk were (mean (95%CI)) 151 (141, 160, 540 (519, 562), 411 (396, 427), and 1102 (1072, 1133) µmol/L, respectively. Theoretically, only 19% of infants would meet the current Adequate Intake (AI) for choline. Our findings suggest that the concentrations in milk of water-soluble forms of choline are similar in Canada and Cambodia, and that the concentration used to set the infant AI might be inaccurate.

Randomized controlled trial assessing the efficacy of a reusable fish-shaped iron ingot to increase hemoglobin concentration in anemic, rural Cambodian women.

Background: Anemia affects 45% of women of childbearing age in Cambodia. Iron supplementation is recommended in populations in which anemia prevalence is high. However, there are issues of cost, distribution, and adherence. A potential alternative is a reusable fish-shaped iron ingot, which, when added to the cooking pot, leaches iron into the fluid in which it is prepared.Objective: We sought to determine whether there was a difference in hemoglobin concentrations in rural Cambodian anemic women (aged 18-49 y) who cooked with the iron ingot or consumed a daily iron supplement compared with a control after 1 y.Design: In Preah Vihear, 340 women with mild or moderate anemia were randomly assigned to 1) an iron-ingot group, 2) an iron-supplement (18 mg/d) group, or 3) a nonplacebo control group. A venous blood sample was taken at baseline and at 6 and 12 mo. Blood was analyzed for hemoglobin, serum ferritin, and serum transferrin receptor. Hemoglobin electrophoresis was used to detect structural hemoglobin variants.Results: Anemia prevalence was 44% with the use of a portable hemoglobinometer during screening. At baseline, prevalence of iron deficiency was 9% on the basis of a low serum ferritin concentration. There was no significant difference in mean hemoglobin concentrations between the iron-ingot group (115 g/L; 95% CI: 113, 118 g/L; P = 0.850) or iron-supplement group (115 g/L; 95% CI: 113, 117 g/L; P = 0.998) compared with the control group (115 g/L; 95% CI: 113, 117 g/L) at 12 mo. Serum ferritin was significantly higher in the iron-supplement group (73 µg/L; 95% CI: 64, 82 µg/L; P = 0.002) than in the control group at 6 mo; however, this significance was not maintained at 12 mo (73 µg/L; 95% CI: 58, 91 µg/L; P = 0.176).Conclusions: Neither the iron ingot nor iron supplements increased hemoglobin concentrations in this population at 6 or 12 mo. We do not recommend the use of the fish-shaped iron ingot in Cambodia or in countries where the prevalence of iron deficiency is low and genetic hemoglobin disorders are high. This trial was registered at clinicaltrials.gov as NCT02341586.

Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women.

Background: Traditionally, vitamin B1 status is assessed by a functional test measuring erythrocyte transketolase (ETK) activity or direct measurement of erythrocyte thiamine diphosphate (eThDP) concentration. However, such analyses are logistically challenging, and do not allow assessment of vitamin B1 status in plasma/serum samples stored in biobanks. Using a multiplex assay, we evaluated plasma concentrations of thiamine and thiamine monophosphate (TMP), as alternative, convenient measures of vitamin B1 status. Methods: We investigated the relationships between the established biomarker eThDP and plasma concentrations of thiamine and TMP, and compared the response of these thiamine forms to thiamine fortification using samples from 196 healthy Cambodian women (aged 18-45 years.). eThDP was measured by high performance liquid chromatography with fluorescence detection (HPLC-FLD) and plasma thiamine and TMP by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Plasma thiamine and TMP correlated significantly with eThDP at baseline and study-end (p < 0.05). Among the fortification groups, the strongest response was observed for plasma thiamine (increased by 266%), while increases in plasma TMP (60%) and eThDP (53%) were comparable. Conclusions: Plasma thiamine and TMP correlated positively with eThDP, and all thiamine forms responded significantly to thiamine intervention. Measuring plasma concentrations of thiamine forms is advantageous due to convenient sample handling and capacity to develop low volume, high-throughput, multiplex assays.

Improved Sanitation Facilities are Associated with Higher Body Mass Index and Higher Hemoglobin Concentration Among Rural Cambodian Women in the First Trimester of Pregnancy.

Multiple factors contribute to undernutrition in Cambodian women. Our aim was to determine if type of household sanitation facility was associated with body mass index (BMI) and hemoglobin (Hb) concentration among pregnant women. Women (N = 544) from 75 villages in Kampong Chhnang Province had their height, weight, and Hb measured (HemoCue Hb 201+) in the first trimester. Sociodemographic and household characteristics were collected. Multivariable linear and logistic regression models were used for analyses. Approximately 40% (N = 221) of women reported primarily using an 'improved' sanitation facility (closed pit latrine) and ∼60% (N = 323) used 'non-improved' facilities (open defecation). Mean ± standard deviation (SD) BMI was higher among women with improved versus non-improved facilities (19.9 ± 3.0 kg/m2 versus 19.4 ± 2.3 kg/m2; P = 0.01). Mean ± SD Hb concentration was also higher among women with improved versus non-improved facilities (118 ± 12 g/L versus 114 ± 14 g/L; P = 0.001). Anemia prevalence (Hb < 110 g/L) was higher among women with non-improved facilities (34% versus 25%; P = 0.04). An improved sanitation facility was a positive predictor of BMI (ß = 0.57 kg/m2; 95% confidence interval [CI] = 0.10, 1.04) and Hb concentration (ß = 2.94 g/L; 95% CI = 0.53, 5.35), adjusting for age, parity, household size, village, gestation week, source of drinking water, and iron folic acid supplementation. Poor sanitation was associated with lower BMI and Hb concentration among pregnant Cambodian women. This warrants multisectoral approaches involving the health, nutrition, water, and sanitation sectors to effectively improve maternal health in Cambodia.

Perinatal Consumption of Thiamine-Fortified Fish Sauce in Rural Cambodia: A Randomized Clinical Trial.

IMPORTANCE: Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, remains a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine concentrations, placing breastfed infants at risk of beriberi. OBJECTIVE: To determine if consumption of thiamine-fortified fish sauce yields higher erythrocyte thiamine diphosphate concentrations (eTDP) among lactating women and newborn infants and higher breast milk thiamine concentrations compared with a control sauce. DESIGN, SETTING, AND PARTICIPANTS: In this double-blind randomized clinical trial, 90 pregnant women were recruited in the Prey Veng province, Cambodia. The study took place between October 2014 and April 2015. INTERVENTIONS: Women were randomized to 1 of 3 groups (n = 30) for ad libitum fish sauce consumption for 6 months: control (no thiamine), low-concentration (2 g/L), or high-concentration (8 g/L) fish sauce. MAIN OUTCOMES AND MEASURES: Maternal eTDP was assessed at baseline (October 2014) and endline (April 2015). Secondary outcomes, breast milk thiamine concentration and infant eTDP, were measured at endline. RESULTS: Women's mean (SD) age and gestational stage were 26 (5) years and 23 (7) weeks, respectively. April 2015 eTDP was measured among 28 women (93%), 29 women (97%), and 23 women (77%) in the control, low-concentration, and high-concentration groups, respectively. In modified intent-to-treat analysis, mean baseline-adjusted endline eTDP was higher among women in the low-concentration (282nM; 95% CI, 235nM to 310nM) and high-concentration (254nM; 95% CI, 225nM to 284nM) groups compared with the control group (193nM; 95% CI, 164nM to 222M; P < .05); low-concentration and high-concentration groups did not differ (P = .19). Breast milk total thiamine concentrations were 14.4 µg/dL for the control group (95% CI, 12.3 µg/dL to 16.5 µg/dL) (to convert to nanomoles per liter, multiply by 29.6); 20.7 µg/dL for the low-concentration group (95% CI, 18.6 µg/dL to 22.7 µg/dL ); and 17.7 µg/dL for the high-concentration group (95% CI, 15.6 µg/dL to 19.9 µg/dL). Mean (SD) infant age at endline was 16 (8) weeks for the control group, 17 (7) weeks for the low-concentration group, and 14 (8) for the high-concentration group. Infant eTDP was higher among those in the high-concentration group (257nM; 95% CI, 222nM to 291nM; P < .05) compared with the low-concentration (212nM; 95% CI, 181nM to 244nM) and control (187nM; 95% CI, 155nM to 218nM) groups. CONCLUSIONS AND RELEVANCE: Compared with women in the control group, women who consumed thiamine-fortified fish sauce through pregnancy and early lactation had higher eTDP and breast milk thiamine concentrations and their infants had higher eTDP, which was more pronounced in the high group. Thiamine-fortified fish sauce has the potential to prevent infantile beriberi in this population. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02221063.

Serum Zinc Is a Major Predictor of Anemia and Mediates the Effect of Selenium on Hemoglobin in School-Aged Children in a Nationally Representative Survey in New Zealand.

BACKGROUND: Zinc, selenium, and vitamin D status of New Zealand (NZ) school-aged children was examined in a national survey in 2002. To our knowledge, however, the role of these micronutrients as predictors of hemoglobin has not been explored despite plausible mechanisms for such relations. OBJECTIVE: We examined the relations of iron, zinc, selenium, and vitamin D status with hemoglobin and anemia in children of New Zealand European and other (NZEO) ethnicity enrolled in the 2002 Children's Nutrition Survey and explored whether zinc mediated the relation between selenium and hemoglobin. METHODS: Multivariate regression was performed to examine the relations of serum micronutrient biomarkers, acute inflammation, socioeconomic status, and body mass index (BMI) with hemoglobin and anemia of NZEO children aged 5-15 y (n = 503). A mediation analysis also investigated direct and indirect (through zinc) relations between selenium and hemoglobin. RESULTS: In total, 4.6% of the children were anemic, 3.2% had depleted iron stores, and none had iron deficiency anemia. The prevalence of low serum zinc (<8.7-10.1 µmol/L depending on age and sex), selenium (<0.82 µmol/L), and 25-hydroxyvitamin D (<50 nmol/L) was 14.1%, 22.9%, and 48.5%, respectively. Major predictors of hemoglobin were serum zinc, age, and BMI-for-age z score (P < 0.001); log ferritin and being female were also statistically significant (P < 0.05). Selenium had an indirect effect that was mediated by zinc, with a significant effect of selenium on zinc (P = 0.002) and zinc on hemoglobin (P < 0.001). Zinc was the only variable associated with anemia risk (OR: 5.49; 95% CI: 1.95, 15.46). CONCLUSIONS: Low serum zinc was an independent risk factor for anemia in NZEO school-aged children and mediated the effect of low selenium on hemoglobin. These findings emphasize the importance of considering multiple micronutrient deficiencies in addition to iron when interpreting anemia and of appreciating the mechanistic interactions that underlie these associations.

Prenatal supplementation with Corn Soya Blend Plus reduces the risk of maternal anemia in late gestation and lowers the rate of preterm birth but does not significantly improve maternal weight gain and birth anthropometric measurements in rural Cambodian women: a randomized trial.

BACKGROUND: Corn Soya Blend (CSB) Plus is a fortified dietary supplement used to help Cambodian women meet their nutritional requirements in pregnancy, although little is known about its ability to improve pregnancy outcomes. OBJECTIVE: This study assessed the effect of prenatal CSB Plus supplementation on birth weight and secondary outcomes of low birth weight (<2500 g), small for gestational age, birth length and head circumference, preterm birth (<37 wk), maternal weight gain, and anemia at 24-28 wk, 30-32 wk, and 36-38 wk of gestation among rural Cambodian women. DESIGN: A cluster-randomized trial was conducted in 75 villages in Kampong Chhnang Province, in which 547 women received CSB Plus (treatment) during the first trimester until delivery or continued their normal diet (control) based on their village residence. All women received routine daily iron folic acid tablets and were treated with additional iron folic acid if they were anemic (hemoglobin <11 g/dL). Cluster-adjusted linear mixed-effect and logistic regression models were used to examine group differences. RESULTS: There was no significant difference in birth weight between the CSB Plus and control group (46 g; 95% CI: -31, 123 g; P = 0.24). Significant reductions were observed in preterm birth (OR = 0.33; 95% CI: 0.12, 0.89) and anemia at 36-38 wk (OR = 0.51; 95% CI: 0.34, 0.77). There were no significant differences in low birth weight, small for gestational age, birth length, head circumference, or maternal weight gain. A higher rate of fetal loss was observed in the treatment group (10.2% compared with 3.7%; P < 0.01). CONCLUSIONS: In Cambodian women, CSB Plus consumed during pregnancy did not significantly increase maternal weight gain or improve birth size but did reduce maternal anemia in late gestation and preterm birth in comparison with women consuming a normal diet. The unexpectedly higher rate of fetal loss in the treatment group is concerning and warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01413776.

Factors affecting the acceptability and consumption of Corn Soya Blend Plus as a prenatal dietary supplement among pregnant women in rural Cambodia.

OBJECTIVE: Undernutrition is prevalent among pregnant women in Cambodia. The provision of fortified dietary supplements is one strategy to help pregnant women meet their nutritional needs. Corn Soya Blend Plus (CSBP) is a widely used prenatal dietary supplement in areas with high rates of undernutrition and food insecurity. However, little is known about its acceptability during pregnancy. The present study aimed to identify factors that affected the acceptability and consumption of CSBP supplements among pregnant women. DESIGN: Women completed a structured interview designed to provide information on facilitators of and barriers to utilization. In addition, six focus groups were conducted with a subset of women (n 70) to further explore attitudes, perceptions and experiences related to CSBP use. SETTING: Two districts in Kampong Chhnang Province, Cambodia. SUBJECTS: Pregnant women (n 288) participating in a cluster-randomized trial of CSBP. RESULTS: The acceptability of CSBP was influenced by sensory attributes, family support, peer influences, and attitudes related to diet, nutritional status and weight gain in pregnancy. Attaining adequate nutrition was considered less important than other concerns during pregnancy, particularly anxiety related to the costs of delivery and postpartum care. Acceptance was lower among new mothers due to fears of weight gain. Health benefits were common reasons for continued use and minor side-effects, such as nausea, were not major barriers to consumption. CONCLUSIONS: CSBP was generally well accepted in this population. However, organoleptic factors and perceptions regarding nutrition and weight gain in pregnancy, particularly for first-time mothers, were barriers to increasing acceptance among Cambodian women.

Effectiveness and safety of a high-dose weekly vitamin D (20,000 IU) protocol in older adults living in residential care.

OBJECTIVES: To report 25 hydroxyvitamin D (25OHD) concentrations, an indicator of vitamin D status, in older adults living in residential care 1 year after a protocol of weekly 20,000 IU of vitamin D was started. DESIGN: Cross-sectional. SETTING: Five residential care facilities in British Columbia, Canada. PARTICIPANTS: Residents aged 65 and older from five facilities (N=236). MEASUREMENTS: Participants provided a blood sample. Demographic and health information was obtained from the medical record. RESULTS: Mean 25OHD was 102 nmol/L (95% confidence interval (CI)=98-106 nmol/L). Three percent of residents had a 25OHD concentration of less than 40 nmol/L, 6% <50 nmol/L, and 19% <75 nmol/L. In those who received 20,000 IU/wk or more for 6 months or longer (n=147), mean 25OHD was 112 nmol/L (95% CI=108-117 nmol/L), and none had a 25OHD level of less than 50 nmol/L. Hypercalcemia (>2.6 mmol/L), a potential consequence of too much vitamin D, was present in 14%, although 25OHD levels did not differ in those with and without hypercalcemia (108 vs 101 nmol/L; P=.17). CONCLUSION: Twelve months after implementation of a 20,000-IU/wk vitamin D protocol for older adults in residential care, mean 25OHD concentrations were high, and there was no evidence of poor vitamin D status. Given the absence of demonstrated benefit of high 25OHD concentrations to the residential care population, dosages less than 20,000 IU/wk of vitamin D are recommended.

25-Hydroxyvitamin D concentrations in children with Crohn's disease supplemented with either 2000 or 400 IU daily for 6 months: a randomized controlled study.

OBJECTIVES: To assess vitamin D status of pediatric patients with Crohn's disease (CD) and to compare their serum 25-hydroxyvitamin D (s-25OHD) with established cutoffs and assess whether 6 months of supplementation with 2000 IU/d, vs 400 IU/d, would reduce the group prevalence of vitamin D below these cutoffs. STUDY DESIGN: Subjects 8-18 years (n = 83) with quiescent CD were randomized to either 400 or 2000 IU vitamin D3/d for 6 months. RESULTS: Baseline mean ± SD s-25OHD was 24 ± 8 ng/mL; 13 subjects (16%) had an s-25OHD <16 ng/mL, 27 (33%) < 20 ng/mL, and 65 (79%) < 30 ng/mL. There was no significant difference between groups in achieving the cutoffs of 16 ng/mL or 20 ng/mL at 6 months; however, only 35% of the 400 IU group achieved the greater cutoff of 30 ng/mL compared with 74% in the 2000 IU group (P < .001). Baseline adjusted mean s-25OHD concentrations at 6 months were 9.6 ng/mL (95% CI 6.0-13.2, P < .001) greater in the 2000 IU than the 400 IU group. Disease activity was not affected by supplement dose. Few subjects exceeded safety marker cutoffs, and this did not differ by dose. CONCLUSIONS: At baseline, a high proportion of patients had a mean s-25OHD >20 ng/mL. 2000 IU vitamin D3/d is more effective in raising s-25OHD concentrations to > 30 ng/mL in children with CD than 400 IU/d, but both treatments were equally effective at achieving 16 or 20 ng/mL.

Wheat rolls fortified with microencapsulated L-5-methyltetrahydrofolic acid or equimolar folic acid increase blood folate concentrations to a similar extent in healthy men and women.

Mandatory folic acid fortification of grains such as wheat flour has been introduced in several countries to reduce the incidence of neural tube defects. There are concerns, however, that folic acid could mask the hematologic signs of vitamin B-12 deficiency and lead to other adverse health outcomes in the population. Calcium L-5-methyltetrahydrofolic acid (L-5-MTHF), a synthetic form of reduced folate, should not mask vitamin B-12 deficiency and may be safer than folic acid. Unfortunately, L-5-MTHF is not stable in most food matrices such as bread. Microencapsulation of L-5-MTHF with sodium ascorbate and a modified starch is effective at preventing loss of the vitamin during baking and storage. Our aim was to assess the efficacy of wheat rolls fortified with microencapsulated L-5-MTHF or equimolar folic acid compared with wheat rolls containing no added folate (placebo) at increasing blood folate concentrations during 16 wk. Healthy men and women aged 18-45 y (n = 45) were randomly assigned to consume wheat rolls that contained L-5-MTHF (452 µg/d), the molar equivalent of folic acid (400 µg/d), or placebo. At 16 wk, the mean (95% CI) erythrocyte folate was 0.48 (0.27, 0.71) and 0.37 (0.17, 0.57) µmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P = 0.001) groups, respectively, than in the placebo group. Likewise, the mean plasma folate was 23 (12, 34) and 23 (12, 34) nmol/L higher in the L-5-MTHF (P < 0.001) and folic acid wheat roll (P < 0.001) groups, respectively, than in the placebo group. There were no significant differences in blood folate concentrations between the L-5-MTHF and folic acid wheat roll groups. Both microencapsulated L-5-MTHF and folic acid-fortified wheat rolls increased blood folate concentrations compared with placebo.

Differences in erythrocyte folate concentrations in older adults reached steady-state within one year in a two-year, controlled, 1 mg/d folate supplementation trial.

Daily supplementation with folate increases erythrocyte folate concentrations; however, the time to reach steady-state concentrations has not been empirically demonstrated. Previous predictions of time to steady state or time to 90% steady-state concentration, based on modeling changes in erythrocyte folate during short-term trials, range widely from 40 to 86 wk. We sought to determine the time to steady-state erythrocyte folate concentrations following the initiation of daily folate supplementation using data collected from a 2-y, double-blind, placebo-controlled, randomized trial involving 276 participants aged 65 y or older. The daily supplement contained 1 mg of folate. Erythrocyte folate concentrations were measured, using a microbiological assay, at baseline and at 6, 12, 18, and 24 mo. The mean plasma and erythrocyte folate concentrations in the folate-supplemented group were higher than in the placebo group at 6, 12, 18, and 24 mo (P < 0.001). Adjusted for baseline differences, the difference in erythrocyte folate concentrations between the folate and placebo group at 6 mo was 1.78 µmol/L (95% CI: 1.62-1.95 µmol/L). The difference increased significantly to 2.02 µmol/L (95% CI: 1.85-2.18 µmol/L) at 12 mo. This difference (between the folate and placebo groups) did not significantly change after a further year of folate supplementation; at 18 mo, it was 2.09 µmol/L (95% CI: 1.92-2.27 µmol/L) and at 24 mo it was 1.98 µmol/L (95% CI: 1.18-2.15 µmol/L). Twelve months of daily folate supplementation with 1 mg is sufficient time to cause erythrocyte folate concentrations to reach a new steady state.

Suboptimal vitamin D levels in pregnant women despite supplement use.

OBJECTIVE: Obtaining adequate vitamin D during pregnancy is important for the health of mother and child. Low circulating 25-hydroxyvitamin D (25OHD) concentrations, a measure of vitamin D status, have been reported in pregnant women in several countries; yet, there are few studies of pregnant Canadian women. We measured 25OHD concentrations in a multi-ethnic group of pregnant women living in Vancouver (49 degrees N) and explored the determinants of 25OHD. METHODS: 336 pregnant women (16-47 y) between 20 and 35 weeks gestation provided a blood sample and completed questionnaires. RESULTS: Mean 25OHD was 67 (95% CI 64-69) nmol/L. Only 1% of women had a 25OHD concentration indicative of severe deficiency (<25 nmol/L). However, 24% and 65% of women were vitamin D insufficient based on cut-offs of 50 and 75 nmol/L, respectively. In multivariate analysis, mean 25OHD concentrations were 12 nmol/L higher in the summer compared to in winter. Women of European (White) ethnicity had a 9-13 nmol/L higher mean 25OHD concentration than women from other ethnic groups. Almost 80% of women took vitamin D-containing supplements containing > or = 400 IU/d. However, 24% and 65% of these women had 25OHD <50 and <75 nmol/L, respectively. CONCLUSION: Vitamin D insufficiency was not uncommon in this group of pregnant women. Season and ethnicity were determinants of 25OHD but the magnitude of their effect was not large. Most women took vitamin D-containing supplements but this did not provide much protection against insufficiency. Consideration should be given to increasing the amount of vitamin D in prenatal supplements.

Reliable change indices for the ruff 2 and 7 selective attention test in older adults.

The assessment of suspected dementia often involves the analysis of change scores from neuropsychological tests administered on two occasions. Frequently, no information is available to allow the significance of a change to be evaluated. Our aim was to prepare data useful for estimating the statistical significance of retest changes for persons older than the age of 65 on the Ruff 2 and 7 Selective Attention Test, one of the few paper-and-pencil tests of attention available to the clinician. The sample tested was composed of 234 healthy adults taking part in a randomized double-blind trial of the effect on cognitive performance of lowering homocysteine using dietary supplements, during which no treatment effects were detected. The test was found to be sensitive to the effects of aging and was well tolerated by our sample of older adults. Retest reliability for the speed of visual search for digit targets (2 and 7) under both the same category (other digits) and different category (letter) distracter conditions was high, and the practice effects during a 12-month period were substantial. Test-retest data with a 1-year interval were used to estimate reliability coefficients and to calculate Reliable Change indices useful for evaluating persons with suspected dementia. The rate of decline in search speed as a function of age was the same for both distraction conditions, suggesting that older persons used a controlled serial search process for targets in both conditions of this test.

The majority of older British Columbians take vitamin D-containing supplements.

OBJECTIVES: Health Canada recommends vitamin D supplements (10 microg/d) for Canadians aged > or = 50 years, but no data are available on adoption of this recommendation. Accordingly, this study was conducted to determine the current use of vitamin D supplements among British Columbian adults 50 years and over, and to explore relationships among vitamin D supplement use, socio-demographic variables, and knowledge, attitudes and beliefs about vitamin supplementation. METHODS: A population-representative stratified sample, recruited by random-digit dialling, completed a telephone-administered survey in late fall of 2008. Respondents provided details on supplements used in the past month (dosage, frequency, etc.) and demographic data, and responded to statements reflecting health beliefs about supplements, from which a Supplement Health Belief score was calculated. Eligible non-respondents indicated their age, sex, and whether they had used a supplement within the past month. RESULTS: Similar proportions of participants (n = 969) and non-respondents (n = 1,027) reported any supplement use in the past month. Among participants, 60% had used a vitamin D supplement (median intake among supplement users was 10 microg/d) and 3% exceeded the Tolerable Upper Intake Level of 50 microg/d. In multivariate analysis, vitamin D supplementation was significantly associated with female sex, not smoking, higher educational attainment, having a health care professional recommend supplement use, and a higher Supplement Health Belief score. CONCLUSION: Although most older adults used a vitamin D supplement, further dissemination of this recommendation is needed.

Despite mandatory fortification of staple foods, vitamin D intakes of Canadian children and adults are inadequate.

Vitamin D is largely obtained through sun-induced skin synthesis and less from dietary sources, but during Canadian winters, skin synthesis is non-existent. The objective of this study was to estimate vitamin D intakes in Canadians from food sources. Data used in this study included food intakes of Canadians reported in the 2004 Canadian Community Health Survey Cycle 2.2 (CCHS 2.2), a nationally representative sample of 34,789 persons over the age of 1 year. The mean+/-SD dietary intake of vitamin D from food of Canadians was 5.8+/-0.1 microg/day, with males 9-18 years having the highest mean intakes (7.5+/-0.2 microg/day) and females 51-70 years having the lowest intakes (5.2+/-0.3 microg/day). Males in all age groups had higher intakes than females and White Canadians had higher vitamin D intakes than Non-Whites in most age sex groups. Milk products contributed 49% of dietary vitamin D followed by meat and meat-alternatives (31.1%). The majority of Canadians consume less than current recommended intake of vitamin D from food. Consideration should be given to strategies to improve vitamin D intake of Canadians by increasing both the amount of vitamin D added to foods and range of foods eligible for fortification.