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ObjectiveNeural tube defects (NTDs) are a preventable folate deficiency disorder; increasing folic acid intake through food fortification increases serum and red blood cell folate and reduces the risk of an NTD pregnancy. There is controversy over the blood folate level needed to achieve the full preventive effect because of discrepant study conclusions.MethodsResults from two published studies were used to determine the relationship between serum folate and NTD risk which was compared with the observed result in a randomised trial of folic acid that increased serum folate from 5 ng/mL to 44 ng/mL among women who took a 4 mg daily periconceptional folic acid supplement.ResultsBoth studies showed a proportional (logarithmic) relationship between serum folate and NTD risk without evidence of a folate threshold above which there is no further NTD risk reduction. The suggestion of a threshold is due to the incorrect interpretation of the folate-NTD risk association when plotted on arithmetic scales, which conceals the proportional relationship between the two. Also, both studies accurately estimated the observed result from the randomised trial that achieved a median serum folate level of 44 ng/mL and an 83% preventive effect. This is much higher than has been achieved with current levels of folic acid fortification with serum folate between 10 and 16 ng/mL, resulting in an approximate 20% preventive effect.ConclusionTo achieve fully effective fortification, median population serum folate levels need to be about 44 ng/mL, which would globally prevent about 250 000 NTD cases every year.

Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China.

Background: Within Cambodia, micronutrient deficiencies continue to be prevalent in vulnerable groups, such as women and children. Fortification of staple foods such as rice could be a promising strategy for Cambodia to improve micronutrient status. Objective: Our objective was to investigate the impact of multiple-micronutrient fortified rice (MMFR), distributed through a World Food Program school-meals program (WFP-SMP) on serum zinc concentrations and folate status in a double-blind, cluster-randomized, placebo-controlled trial. Methods: Sixteen schools were randomly assigned to receive one of three different types of extruded-fortified rice (UltraRice Original (URO), UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. A total of 1950 schoolchildren (6–16 years old) participated in the study. Serum zinc (all groups) and folate (only in NutriRice and placebo group) concentrations were assessed from morning non-fasting antecubital blood samples and were measured at three time points (baseline and after three and six months). Results: After six months of intervention, serum zinc concentrations were significantly increased in all fortified rice group compared to placebo and baseline (0.98, 0.85 and 1.40 µmol/L for URO, URN and NutriRice, respectively) (interaction effect: p < 0.001 for all). Children in the intervention groups had a risk of zinc deficiencies of around one third (0.35, 039, and 0.28 for URO, URN, and NutriRice, respectively) compared to the placebo (p < 0.001 for all). The children receiving NutriRice had higher serum folate concentrations at endline compared to children receiving normal rice (+2.25 ng/mL, p = 0.007). Conclusions: This study showed that the high prevalence of zinc and folate deficiency in Cambodia can be improved through the provision of MMFR. As rice is the staple diet for Cambodia, MMFR should be considered to be included in the school meal program and possibilities should be explored to introduce MMFR to the general population.

Purpose We investigated whether daily supplementation with low-dose B vitamins in the healthy elderly population improves the Framingham risk score (FRS), a predictor of cardiovascular disease risk. Methods Between 2007 and 2012, a double-blind randomized controlled trial was conducted in a rural area of North China. In all, 390 healthy participants aged 60–74 were randomly allocated to receive daily vitamin C (50 mg; control group) or vitamin C plus B vitamins (400 µg folic acid, 2 mg B 6 , and 10 µg B 12 ; treatment group) for 12 months. FRSs were calculated for all 390 subjects. Results Folate and vitamin B 12 plasma concentrations in the treatment group increased by 253 and 80 %, respectively, after 6 months, stopped increasing with continued supplementation after 12 months and returned to baseline levels 6 months after supplementation cessation. Compared with the control group, there was no significant effect of B vitamin supplementation on FRSs after 6 months (mean difference −0.38; 95 % CI −1.06, 0.31; p  = 0.279), whereas a significant effect of supplementation was evident after 12 months (reduced magnitude 7.6 %; −0.77; 95 % CI −1.47, −0.06; p  = 0.033). However, this reduction disappeared 6 months after supplementation stopped (−0.07; 95 % CI −0.80, 0.66; p  = 0.855). The reduction in FRS 12 months after supplementation was more pronounced in individuals with a folate deficiency (10.4 %; −1.30; 95 % CI −2.54, −0.07; p  = 0.039) than in those without (4.1 %; −0.38; 95 % CI −1.12, 0.36; p  = 0.313). B vitamins increased high-density lipoprotein cholesterol by 3.4 % after 6 months (0.04; 95 % CI −0.02, 0.10; p  = 0.155) and by 9.2 % after 12 months (0.11; 95 % CI 0.04, 0.18; p  = 0.003). Compared with the control group, this change in magnitude decreased to 3.3 % (0.04; 95 % CI −0.02, 0.10; p  = 0.194) 6 months after supplementation cessation. Conclusions Daily supplementation with a low-dose of B vitamins for 12 months reduced FRS, particularly in healthy elderly subjects with a folate deficiency. These reduced effects declined after supplementation cessation, indicating a need for persistent supplementation to maintain the associated benefits.

To assess the folate status of US women in a study of a folate-fortified oral contraceptive (OC) using the Short Folate Food Frequency Questionnaire and plasma and red blood cell (RBC) folate samples. Sub-analysis from a multi-centre, randomised, double-blind, controlled contraceptive trial with assessments at baseline and 6 months. We calculated dietary folate equivalents (DFE) consumed and the proportion of participants meeting folate adequacy benchmarks. Eight centres in the USA. Healthy women aged 18-40 years requesting contraception with no contraindications for OC use. Overall, 385 participants were randomised to either a novel folate-fortified OC or a marketed OC. The 262 (68 %) participants compliant with the protocol were included in the analysis set. Baseline daily DFE consumption was 529·8 (sd 342·1) μg and similar in both groups. At follow-up, the fortified OC group had higher intake than the conventional OC group (1225·9 (sd 346·2) μg compared with 500·6 (sd 361·2) μg). Mean plasma folate level increased from 44·5 (sd 17·2) to 55·8 (sd 21·1) nmol/l. Mean RBC folate level increased from 996·7 (sd 369·8) to 1311·9 (sd 436·0) nmol/l. The proportion meeting selected folate adequacy benchmarks increased in the fortified OC group (P < 0·001). Lack of adequate folate intake in reproductive-aged women from dietary sources or supplements alone suggests the need for novel approaches. Use of folate-fortified OC ensures adequate folate levels and meeting of folate benchmarks.

Folate (vitamin B9) plays a crucial role in fundamental cellular processes, including nucleic acid biosynthesis, methyl group biogenesis and amino acid metabolism. The detection and correction of folate deficiency prevents megaloblastic anaemia and reduces the risk of neural tube defects. Coexisting deficiencies of folate and vitamin B12 are associated with cognitive decline, depression and neuropathy. Folate deficiency and excess has also been implicated in some cancers. Excessive exposure to folic acid, a synthetic compound used in supplements and fortified foods, has also been linked to adverse health effects. Of at least three distinct laboratory markers of folate status, it is the total abundance of folate in serum/plasma that is used by the majority of laboratories. The analysis of folate in red cells is also commonly performed. Since the folate content of red cells is fixed during erythropoiesis, this marker is indicative of folate status over the preceding ~4 months. Poor stability, variation in polyglutamate chain length and unreliable extraction from red cells are factors that make the analysis of folate challenging. The clinical use of measuring specific folate species has also been explored. 5-Methyltetrahydrofolate, the main form of folate found in blood, is essential for the vitamin B12-dependent methionine synthase mediated remethylation of homocysteine to methionine. As such, homocysteine measurement reflects cellular folate and vitamin B12 use. When interpreting homocysteine results, age, sex and pregnancy, specific reference ranges should be applied. The evaluation of folate status using combined markers of abundance and cellular use has been adopted by some laboratories. In the presence of discordance between laboratory results and strong clinical features of deficiency, treatment should not be delayed. High folate status should be followed up with the assessment of vitamin B12 status, a review of previous results and reassessment of folic acid supplementation regime.

The objective of our study was to determine the prevalence of anaemia among 14-19 years school going girls, risk factors for it and profile of micronutrient status among rural girls from western state of India. Using a cross-sectional design, we obtained information on socio-demography, menstruation, dietary habits, knowledge and daily consumption of the government recommended iron and folic acid (IFA) tablets, and anthropometry. Blood was collected to assess Hb, red blood cell indices, serumFe, folate and vitamin B levels. Nagpur district, Maharashtra, India. A total of 221 girls aged 14-19 years studying in twenty-four government institutes included. 57 % girls were anaemic, 84 % had deficiency of one or more micronutrients and 60 % were malnourished based on body mass index (BMI). The prevalence of Fe, vitamin B and folate deficiency was 37·7 %, 69·8 % and 1·4 %, respectively. Among anaemic girls, Fe and vitamin B deficiency was observed in 45·5 % and 67·5 %, respectively, . among non-anaemic girls it was 27 % and 73 %, respectively. Fe deficiency was a predictor of anaemia and its severity. Girls residing in non-nuclear family were more likely to have anaemia. The consumption of daily non-vegetarian food and green leafy vegetables was 3 % and 3·6 %, respectively. Only 9 % consumed IFA tablets in the past 2 weeks. Anaemia is common in adolescent girls, particularly associated with Fe and vitamin B deficiency. There is need to reconsider the approach to prevention of anaemia in adolescent girls, particularly before they become pregnant.

Objectives : To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for ‘high’ metabolite concentrations and (3) the estimated prevalence of vitamin B 12 /folate deficiency on the basis of different decision limits. Design : Double-blind placebo-controlled intervention study. Setting : Outpatient clinic. Subjects : A total of 209 community-dwelling subjects, median age 76 y (range 70–93) y. Interventions : Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B 6 . Results : High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B 12 deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys ( P <0.001) and S-MMA ( P =0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B 12 and age. Conclusions : Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA. Sponsorship : Support—Recip AB.

To conduct a systematic review of the published peer-reviewed articles on the biochemical assessment of nutritional status of South African infants, children and adolescents in 1997-2022. Online databases (Pubmed, CINAHL, EbscoHost and SAePublications) were used to identify thirty-nine papers. South Africa, 1997-2022. Infants, children and adolescents. Vitamin A deficiency prevalence was 35-67 % before 2001 and mostly below 16 % after 2008. Anaemia ranged from 5·4 to 75·0 %, with 36-54 % of infants below 1 year being anaemic. Among 0- to 6-year-olds, iron deficiency (ID) was 7·2-39·4 % in rural and 16-41·9 % in urban areas. Zn deficiency remained high, especially among 0- to 6-year-olds, at 39-48 %. Iodine insufficiency (UIC < 100 µg/l) was between 0 and 28·8 %, with excessive levels in two areas. Vitamin D deficiency was 5 % for 11- to 17-year-olds in one urban study but 33-87 % in under 10-week-old infants. The 2005 national survey reported sufficient folate status among 0- to 6-year-olds, and vitamin B deficiency was 0-21 %. Low-grade inflammation was between 5 % and 42 % depending on the biomarker and cut-offs. Vitamin A status may have improved meaningfully during the last 25 years in South Africa to below 16 %, and iodine and folate deficiency appears to be low particularly among 0- to 6-year-olds. However, confirmation is needed by a national survey. Anaemia, Fe and Zn deficiencies still pose severe problems, especially among 0- to 6-year-olds. Sufficient data on vitamin D and B status are lacking.

Plant-based diets may increase the risk of vitamin B 12 deficiency due to limited intake of animal-source foods, while dietary folate increases when adhering to plant-based diets. In this cross-sectional study, we evaluated the B 12 and folate status of Norwegian vegans and vegetarians using dietary B 12 intake, B 12 and folic acid supplement use, and biomarkers (serum B 12 (B 12 ), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA) and serum folate). Vegans ( n 115) and vegetarians ( n 90) completed a 24-h dietary recall and a FFQ and provided a non-fasting blood sample. cB 12 , a combined indicator for evaluation of B 12 status, was calculated. B 12 status was adequate in both vegans and vegetarians according to the cB 12 indicator; however 4 % had elevated B 12 . Serum B 12 , tHcy, MMA concentrations and the cB 12 indicator (overall median: 357 pmol/l, 9·0 µmol/l, 0·18 µmol/l, 1·30 (cB 12 )) did not differ between vegans and vegetarians, unlike for folate (vegans: 25·8 nmol/l, vegetarians: 21·6 nmol/l, P = 0·027). Serum B 12 concentration < 221 pmol/l was found in 14 % of all participants. Vegetarians revealed the highest proportion of participants below the recommended daily intake of 2 µg/d including supplements (40 v . 18 %, P < 0·001). Predictors of higher serum B 12 concentrations were average daily supplement use and older age. Folate deficiency (< 10 nmol/l) was uncommon overall (< 2·5 %). The combined indicator cB 12 suggested that none of the participants was B 12 -depleted; however, low serum B 12 concentration was found in 14 % of the participants. Folate concentrations were adequate, indicating adequate folate intake in Norwegian vegans and vegetarians.