We showed that administration of [6S]-5-MTHF is more effective than is folic acid supplementation at improving folate status. In addition, the study indicates that the recommended period for preconceptional folic acid supplementation should be extended to >4 wk for maximal prevention of NTDs based on folate concentrations. [6S]-5-MTHF might be an efficient and safe alternative to folic acid.

Glycine is a precursor of purines, protein, glutathione, and 1-carbon units as 5,10-methylenetetrahydrofolate. Glycine decarboxylation through the glycine cleavage system (GCS) and glycine-serine transformation by serine hydroxymethyltransferase (SHMT) require pyridoxal 5'-phosphate (PLP; active form of vitamin B-6) as a coenzyme. The intake of vitamin B-6 is frequently low in humans. Therefore, we determined the effects of vitamin B-6 restriction on whole-body glycine flux, the rate of glycine decarboxylation, glycine-to-serine conversion, use of glycine carbons in nucleoside synthesis, and other aspects of 1-carbon metabolism. We used a primed, constant infusion of [1,2-(13)C(2)]glycine and [5,5,5-(2)H(3)]leucine to quantify in vivo kinetics in healthy adults (7 males, 6 females; 20-39 y) of normal vitamin B-6 status or marginal vitamin B-6 deficiency. Vitamin B-6 restriction lowered the plasma PLP concentration from 55 +/- 4 nmol/L (mean +/- SEM) to 23 +/- 1 nmol/L (P < 0.0001), which is consistent with marginal deficiency, whereas the plasma glycine concentration increased (P < 0.01). SHMT-mediated conversion of glycine to serine increased from 182 +/- 7 to 205 +/- 9 micromol x kg(-1) x h(-1) (P < 0.05), but serine production using a GCS-derived 1-carbon unit (93 +/- 9 vs. 91 +/- 6 micromol x kg(-1) x h(-1)) and glycine cleavage (163 +/- 11 vs. 151 +/- 8 micromol x kg(-1) x h(-1)) were not changed by vitamin B-6 restriction. The GCS produced 1-carbon units at a rate (approximately 140-170 micromol x kg(-1) x h(-1)) that greatly exceeds the demand for remethylation and transmethylation processes (approximately 4-7 micromol x kg(-1) x h(-1)). We conclude that the in vivo GCS and SHMT reactions are quite resilient to the effects of marginal vitamin B-6 deficiency, presumably through a compensatory effect of increasing substrate concentration.

Folate, an essential nutrient found naturally in foods in a reduced form, is present in dietary supplements and fortified foods in an oxidized synthetic form (folic acid). There is widespread agreement that maintaining adequate folate status is critical to prevent diseases due to folate inadequacy (e.g., anemia, birth defects, and cancer). However, there are concerns of potential adverse effects of excess folic acid intake and/or elevated folate status, with the original concern focused on exacerbation of clinical effects of vitamin B-12 deficiency and its role in neurocognitive health. More recently, animal and observational studies have suggested potential adverse effects on cancer risk, birth outcomes, and other diseases. Observations indicating adverse effects from excess folic acid intake, elevated folate status, and unmetabolized folic acid (UMFA) remain inconclusive; the data do not provide the evidence needed to affect public health recommendations. Moreover, strong biological and mechanistic premises connecting elevated folic acid intake, UMFA, and/or high folate status to adverse health outcomes are lacking. However, the body of evidence on potential adverse health outcomes indicates the need for comprehensive research to clarify these issues and bridge knowledge gaps. Three key research questions encompass the additional research needed to establish whether high folic acid or total folate intake contributes to disease risk. 1) Does UMFA affect biological pathways leading to adverse health effects? 2) Does elevated folate status resulting from any form of folate intake affect vitamin B-12 function and its roles in sustaining health? 3) Does elevated folate intake, regardless of form, affect biological pathways leading to adverse health effects other than those linked to vitamin B-12 function? This article summarizes the proceedings of an August 2019 NIH expert workshop focused on addressing these research areas.

Multiple biomarkers for anemia and iron deficiency were significantly influenced by the presence of hemoglobin disorders, hence reducing their diagnostic sensitivity. Further investigation of the unexpectedly low prevalence of IDA in Cambodian women is warranted.

Background Breast milk is the sole source of nutrition for exclusively breastfed infants in the first 6 mo of life, yet few studies have measured micronutrient concentrations in breast milk in light of maternal diet and subsequent infant micronutrient intakes. Objectives We evaluated the adequacy of micronutrient intakes of exclusively breastfed Indonesian infants by measuring milk volume and micronutrient concentrations and assessed maternal micronutrient intakes and their relationship with milk concentrations. Methods Mother–infant (2–5.3 mo) dyads (n = 113) were recruited for this cross-sectional study. Volume of breast-milk intake via the deuterium dose-to-mother technique over 14 d and analyzed micronutrient concentrations were used to calculate micronutrient intakes of exclusively breastfed infants. Maternal 3-d weighed food records were collected to assess median (IQR) micronutrient intakes. Multivariate regression analyses examined the association of usual maternal micronutrient intakes with milk micronutrient concentrations after adjustment for confounding variables. Results Mean ± SD intake of breast-milk volume was 787 ± 148 mL/d. Median daily infant intakes of iron, zinc, selenium, magnesium, sodium, and B-vitamins (thiamin, riboflavin, niacin, pantothenic acid, B-6, and B-12) were below their respective Adequate Intakes. Inadequacies in maternal intakes (as % < estimated average requirements) were >40% for calcium, niacin, and vitamins A, B-6, and B-12. Significant positive associations existed between maternal usual intakes of vitamin A, niacin and riboflavin and milk retinol, nicotinamide, and free riboflavin concentrations in both unadjusted and adjusted (for infant age, milk volume, and parity) analyses (all P < 0.05). Conclusions The majority of micronutrient intakes for these exclusively breastfed infants and their mothers fell below recommendations, with associations between maternal intakes and breast-milk concentrations for 3 nutrients. Data on nutrient requirements of exclusively breastfed infants are limited, and a better understanding of the influence of maternal nutritional status on milk nutrient concentrations and its impact on the breastfed infant is needed.

[6S]-5-MTHF was shown to be an adequate alternative to folic acid in reducing tHcy concentrations. Supplementation with 416 micro g [6S]-5-MTHF was no more effective than that with 208 micro g [6S]-5-MTHF.

ObjectivesPeople of South Asian ethnicity are under-represented in health research studies. The objectives of this scoping review were to examine the barriers and facilitators to recruitment of South Asians to health research studies and to describe strategies for improving recruitment.DesignScoping reviewMethodsUsing the Arksey and O’Malley framework for scoping reviews, we comprehensively searched electronic databases (MEDLINE via PubMed, Cochrane Library, CINAHL and PsycINFO). Studies that identified barriers and facilitators to recruitment, or recruitment strategies for South Asian populations were included. Recruitment barriers, facilitators and strategies were grouped thematically and summarised narratively.SynthesisOf 1846 potentially relevant articles, 15 met the inclusion criteria and were included in the thematic synthesis. Multiple facilitators and barriers to enrolment of South Asians in health research studies were identified; these most commonly related to logistical challenges, language and cultural barriers, concerns about adverse consequences of participating and mistrust of research. Several actionable strategies were discussed, the most common being engagement of South Asian communities, demonstration of cultural competency, provision of incentives and benefits, language sensitivity through the use of translators and translated materials and the development of trust and personal relationships.ConclusionThere is a growing awareness of the barriers and facilitators to recruitment of South Asian participants to health research studies. Knowledge of effective recruitment strategies and implementation during the grant funding stages may reduce the risk of poor recruitment and representation of South Asians.

Background: A maternal red blood cell (RBC) folate concentration 906 nmol/L is thought to be optimal for lowering the risk of neural tube defects (NTDs) in pregnancy. Whereas the appearance of folate in RBCs has been followed during folic acid supplementation, data on elimination kinetics are not yet available. Objective: The aim of our investigation was to estimate the steady state conditions and elimination kinetics of folate in RBCs. Design: Data from 2 randomized, placebo-controlled, double-blind intervention trials were used for kinetic modeling. These studies were performed to investigate the appearance of folate in RBCs in healthy women of childbearing age after different supplementation strategies (study 1: n ҃ 69; 400 g folic acid/d and 416 g [6S]-5-methyltetrahydrofolate/d for 24 wk; study 2: n ҃ 21; 800 g folic acid/d for 16 wk). Results: For RBC folate concentrations, steady state conditions were not reached after 24 (study 1) and 16 (study 2) wk of folate supplementation. However, with the use of these data, we calculated the biological half-life (t 1/2 ) of RBC folate to be Ȃ8 wk. With the application of pharmacokinetic principles, steady state conditions for RBC folate should be reached after 40 wk (t 1/2 ҂ 5). Conclusion: With the use of pharmacokinetic principles, the appearance and elimination kinetics of RBC folate can be calculated on the basis of this t 1/2 value.Am J Clin Nutr 2007;86:1414 -9.