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Folic acid (FA) supplementation is recommended in the periconceptional period, for the prevention of neural tube defects. Limited data are available on the folate status of New Zealand (NZ) pregnant women and its association with FA supplementation intake. Objectives were to examine the relationship between plasma folate (PF) and reported FA supplement use at 15 weeks’ gestation and to explore socio-demographic and lifestyle factors associated with PF. We used data and blood samples from NZ participants of the Screening for Pregnancy Endpoints cohort study. Healthy nulliparous women with singleton pregnancy (n 1921) were interviewed and blood samples collected. PF was analysed via microbiological assay. Of the participants, 73 % reported taking an FA supplement at 15 weeks’ gestation – of these, 79 % were taking FA as part of/alongside a multivitamin supplement. Of FA supplement users, 56 % reported consuming a daily dose of ≥800 μg; 39 % reported taking less than 400 µg/d. Mean PF was significantly higher in women reporting FA supplementation (54·6 (se 1·5) nmol/l) v. no FA supplementation (35·1 (se 1·6) nmol/l) (P<0·0001). Reported daily FA supplement dose and PF were significantly positively correlated (r 0·41; P<0·05). Younger maternal age, Pacific and Maori ethnicity and obesity were negatively associated with PF levels; vegetarianism was positively associated with PF. Reported FA supplement dose was significantly associated with PF after adjustment for socio-demographic, lifestyle confounders and multivitamin intake. The relationship observed between FA supplementation and PF demonstrates that self-reported intake is a reliable proxy for FA supplement use in this study population.
The functional effects of folate within C1 metabolism involve interrelationships with vitamin B12, vitamin B6 and riboflavin, and related gene–nutrient interactions. These B vitamins have important roles throughout life, from pregnancy, through childhood, to middle and older age. Achieving optimal nutritional status for preventing folate-related disease is challenging, however, primarily as a result of the poor stability and incomplete bioavailability of folate from natural food sources when compared with the synthetic vitamin form, folic acid. Thus, in European countries, measures to prevent neural tube defects (NTD) have been largely ineffective because of the generally poor compliance of women with folic acid supplementation as recommended before and in early pregnancy. In contrast, countries worldwide with mandatory folic acid fortification policies have experienced marked reductions in NTD. Low vitamin B12 status is associated with increased risk of cognitive dysfunction, CVD and osteoporosis. Achieving optimal B12 status can be problematic for older people, however, primarily owing to food-bound B12 malabsorption which leads to sub-clinical deficiency even with high dietary B12 intakes. Optimising B-vitamin intake may be particularly important for sub-populations with impaired folate metabolism owing to genetic characteristics, most notably the 677C→T variant in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). This common folate polymorphism is linked with several adverse health outcomes, including stroke, however, recent evidence has identified its novel interaction with riboflavin (the MTHFR cofactor) in relation to blood pressure and risk of developing hypertension. This review addresses why and how the optimal status of folate-related B vitamins should be achieved through the lifecycle.
Gestational nutrition is widely recognized to affect an offspring’s future risk of lifestyle-related diseases, suggesting the involvement of epigenetic mechanisms. As folic acid (FA) is a nutrient essential for modulating DNA methylation, we sought to determine how maternal FA intake during early pregnancy might influence tumor sensitivity in an offspring. Dams were maintained on a FA-depleted (FA(−)) or normal (2 mg FA/kg; FA(+)) diet from 2 to 3 days before mating to 7 days post-conception, and their offspring were challenged with chemical tumorigenesis using 7,12-dimethylbenz[a)anthracene and phorbol 12-myristate 13-acetate for skin and 4-nitroquinoline N-oxide for tongue. In both squamous tissues, tumorigenesis was more progressive in the offspring from FA(−) than FA(+) dams. Notably, in the skin of FA(−) offspring, the expression and activity of cylindromatosis (Cyld) were decreased due to the altered DNA methylation status in its promoter region, which contributed to increased tumorigenesis coupled with inflammation in the FA(−) offspring. Thus, we conclude that maternal FA insufficiency during early pregnancy is able to promote neoplasm progression in the offspring through modulating DNA methylation, such as Cyld. Moreover, we propose, for the first time, “innate” utero nutrition as the third cause of tumorigenesis besides the known causes—hereditary predisposition and acquired environmental factors.
Studies on the nutritional status of vegetarians in Spain are lacking. Prevention of vitamin B12 deficiency is the main concern, as dietary sources are of animal origin. The present study aimed to evaluate vitamin B12 and folate status of Spanish vegetarians using classical markers and functional markers. Participants were adult and healthy lacto-ovo vegetarians (forty-nine subjects) and vegans (fifty-four subjects) who underwent blood analyses and completed a FFQ. Serum vitamin B12, homocysteine (Hcy), methylmalonic acid (MMA), erythrocyte folate and haematological parameters were determined. The effects of the type of plant-based diet, and the intake of supplements and foods were studied by a FFQ. Mean erythrocyte folate was 1704 (sd 609) nmol/l. Clinical or subclinical vitamin B12 deficiency was detected in 11 % of the subjects (MMA>271 nmol/l) and 33 % of the participants showed hyperhomocysteinaemia (Hcy>15 µmol/l). Regarding plant-based diet type, significantly higher Hcy was observed in lacto-ovo vegetarians compared with vegans (P = 0·019). Moreover, use of vitamin B12 supplements involved an improvement of vitamin B12 status but further increase in erythrocyte folate (P = 0·024). Consumption of yoghurts was weakly associated with serum vitamin B12 adequacy (P = 0·049) and that of eggs with lower Hcy (P = 0·030). In conclusion, Spanish vegetarians present high folate status but vitamin B12 subclinical deficiency was demonstrated using functional markers. The lack of influence of dietary sources on functional markers and the strong effect of vitamin B12 supplement intake emphasise the need of cobalamin supplementation in both lacto-ovo vegetarians and vegans.
Periconceptional folic acid (FA) is known to have a protective effect in the prevention of neural tube defects (NTD), leading to global recommendations for FA supplementation before and in early pregnancy. Maternal folate throughout pregnancy may have other roles in offspring health, including neurodevelopment and cognitive performance in childhood. Folate is essential for C1 metabolism, a network of pathways involved in several biological processes including nucleotide synthesis, DNA repair and methylation reactions. The evidence reviewed here shows a conclusive role for offspring health of maternal folate nutrition in early pregnancy and probable benefits in later pregnancy. Folate-mediated epigenetic changes in genes related to brain development and function offer a plausible biological basis to link maternal folate with effects in offspring brain, albeit this research is in its infancy. Mandatory FA fortification of food has proven to be highly effective in decreasing NTD cases in populations where it has been implemented, but this policy is controversial owing to concerns related to potential adverse effects of over-exposure to FA. In the absence of population-wide fortification, and given the generally poor compliance with current FA recommendations, optimising folate status of mothers in very early pregnancy for protection against NTD remains challenging. Thus, current policy in the UK, Ireland and elsewhere in Europe for the prevention of NTD (based on periconceptional FA supplementation only), has proven to be largely ineffective. This review addresses the evidence and the controversies that surround this area, as well as identifying the challenges in translating policy into practice.
Conotruncal heart defects are considered to be one of the most common types of birth defect worldwide. Genetic disturbances in folate metabolism such as Thymidylate synthase may increase risk for conotruncal heart defects. We evaluated two common Thymidylate synthase polymorphisms, including the 28 bp tandem repeat in the promoter enhancer region of the 5′-untranslated region and the 6 bp deletion in the 3′-untranslated region, as risk factors of conotruncal heart defects including various subtypes of malformations, in a total of 193 mothers with conotruncal heart defect in offspring and 234 healthy controls in the Chinese population. Logistic regression analyses revealed that mothers who were homozygotes with deletion (−/−) had a 1.8-fold (odds ratio: 1.8; 95% confidence interval: 1.0–3.0, p = 0.040) increased risk for conotruncal heart defect in offspring, respectively, when compared with mothers carrying the wild type (+/+) genotype. Consistently, individuals carrying the genotype −/− of the Thymidylate synthase 6 bp deletion also had higher plasma homocysteine levels compared to the mothers carrying the genotype +/+ in the control and conotruncal heart defect groups (p = 0.006 and p = 0.004, respectively). However, our results showed that Thymidylate synthase 28 bp tandem repeat polymorphism was not associated with risk for conotruncal heart defect and plasma homocysteine level. In conclusion, our data suggest that the maternal Thymidylate synthase 6 bp deletion polymorphism might be associated with plasma homocysteine level and risk for conotruncal heart defect in offspring.
To simulate effects of different scenarios of folic acid fortification of food on dietary folate equivalents (DFE) intake in an ethnically diverse sample of pregnant women.
A forty-four-item FFQ was used to evaluate dietary intake of the population. DFE intakes were estimated for different scenarios of food fortification with folic acid: (i) voluntary fortification; (ii) increased voluntary fortification; (iii) simulated bread mandatory fortification; and (iv) simulated grains-and-rice mandatory fortification.
Ethnically and socio-economically diverse cohort of pregnant women in New Zealand.
Pregnant women (n 5664) whose children were born in 2009–2010.
Participants identified their ethnicity as European (56·0 %), Asian (14·2 %), Māori (13·2 %), Pacific (12·8 %) or Others (3·8 %). Bread, breakfast cereals and yeast spread were main food sources of DFE in the two voluntary fortification scenarios. However, for Asian women, green leafy vegetables, bread and breakfast cereals were main contributors of DFE in these scenarios. In descending order, proportions of different ethnic groups in the lowest tertile of DFE intake for the four fortification scenarios were: Asian (39–60 %), Others (41–44 %), European (31–37 %), Pacific (23–26 %) and Māori (23–27 %). In comparisons within each ethnic group across scenarios of food fortification with folic acid, differences were observed only with DFE intake higher in the simulated grains-and-rice mandatory fortification v. other scenarios.
If grain and rice fortification with folic acid was mandatory in New Zealand, DFE intakes would be more evenly distributed among pregnant women of different ethnicities, potentially reducing ethnic group differences in risk of lower folate intakes.
Public health authorities recommend all fertile women to increase their folate intake to 400 µg/d by eating folate-rich foods or by taking a folic acid supplement to protect against neural tube defects. In a previous study it was shown that folate-rich foods improved folate blood status as effectively as folic acid supplementation. The aim of the present study was to investigate, using NMR metabolomics, the effects of an intervention with a synthetic folic acid supplement v. native food folate on the profile of plasma metabolites. Healthy women with normal folate status received, in parallel, 500 µg/d synthetic folic acid from a supplement (n 18), 250 µg/d folate from intervention foods (n 19), or no additional folate (0 µg/d) through a portion of apple juice (n 20). The metabolic profile of plasma was measured using 1H-NMR in fasted blood drawn at baseline and after 12 weeks of intervention. Metabolic differences between the groups at baseline and after intervention were assessed using a univariate statistical approach (P ≤ 0·001, Bonferroni-adjusted significance level). At baseline, the groups showed no significant differences in measured metabolite concentrations. After intervention, eight metabolites, of which six (glycine, choline, betaine, formate, histidine and threonine) are related to one-carbon metabolism, were identified as discriminative metabolites. The present study suggests that different folate forms (synthetic v. natural) may affect related one-carbon metabolites differently.
We aimed to evaluate clinical note documentation of valproate prescribing and establish the level of knowledge among women of child-bearing potential regarding valproate-associated adverse effects, including teratogenesis, in a regional Irish mental health service.
Of the 42 women prescribed sodium valproate, 21.4% (n = 9) had some documentation in relation to associated risks and 33.3% (n = 14) described an awareness of these risks from consultation with their treating mental health team. On clinical interview, 9.5% (n = 4) of individuals with clear documentation of the risks of teratogenesis described no such awareness. Augmentation with lithium was associated with greater awareness of the teratogenic risks of valproate (P = 0.011).
A clear description of the teratogenic risks of valproate and potential management strategies, including advice regarding contraception and supplementation with folic acid, should be clearly documented and provided repeatedly and in context to all women of child-bearing age who are prescribed valproate.
Mandatory fortification of staple grains with folic acid and/or vitamin B12 (B12) is under debate in many countries including Ireland, which has a liberal, but voluntary, fortification policy. Older adults can be at risk of both deficiency and high folate status, although little is known on the actual prevalence and the major predictors. Population prevalence estimates from older adults (n 5290 ≥50 years) from the Irish Longitudinal Study on Ageing (TILDA) (Wave 1) are presented here. Measures included plasma total vitamin B12 and folate, whereas predictors included detailed demographic, socio-economic, geographic, seasonal and health/lifestyle data. The prevalence of deficient or low B12 status (<185 pmol/l) was 12 %, whereas the prevalence of deficient/low folate status was 15 %. High folate status (>45 nmol/l) was observed in 8·9 %, whereas high B12 status was observed in 3·1 % (>601 pmol/l). The largest positive predictor of B12 concentration was self-reported B12 injection and/or supplement use (coefficient 51·5 pmol/; 95 % CI 9·4, 93·6; P=0·016) followed by sex and geographic location. The largest negative predictor was metformin use (−33·6; 95 % CI −51·9, −15·4; P<0·0001). The largest positive predictor of folate concentration was folic acid supplement use (6·0; 95 % CI 3·0, 9·0 nmol/l; P<0·001) followed by being female and statin medications. The largest negative predictor was geographic location (−5·7; 95 % CI −6·7, −4·6; P<0·0001) followed by seasonality and smoking. B-vitamin status in older adults is affected by health and lifestyle, medication, sampling period and geographic location. We observed a high prevalence of low B12 and folate status, indicating that the current policy of voluntary fortification is ineffective for older adults.
The aim of this study is to analyse the efficacy rate of folate for the treatment of hyperhomocysteinaemia (HHcy) and to explore how folate metabolism-related gene polymorphisms change its efficacy. This study also explored the effects of gene–gene and gene–environment interactions on the efficacy of folate. A prospective cohort study enrolling HHcy patients was performed. The subjects were treated with oral folate (5 mg/d) for 90 d. We analysed the efficacy rate of folate for the treatment of HHcy by measuring homocysteine (Hcy) levels after treatment. Unconditioned logistic regression was conducted to analyse the association between SNP and the efficacy of folic acid therapy for HHcy. The efficacy rate of folate therapy for HHcy was 56·41 %. The MTHFR rs1801133 CT genotype, TT genotype and T allele; the MTHFR rs1801131 AC genotype, CC genotype and C allele; the MTRR rs1801394 GA genotype, GG genotype and G allele; and the MTRR rs162036 AG genotype and AG+GG genotypes were associated with the efficacy of folic acid therapy for HHcy (P<0·05). No association was seen between other SNP and the efficacy of folic acid. The optimal model of gene–gene interactions was a two-factor interaction model including rs1801133 and rs1801394. The optimal model of gene–environment interaction was a three-factor interaction model including history of hypertension, history of CHD and rs1801133. Folate supplementation can effectively decrease Hcy level. However, almost half of HHcy patients failed to reach the normal range. The efficacy of folate therapy may be genetically regulated.
The prevalence of a sub-clinical vitamin B12 deficiency in the vegetarians is high. Total serum vitamin B12 concentration alone does not reliably reflect vitamin B12 status. Holotranscobalamin (holo-TC) II is a bioactive B12 fraction promoting specific uptake of B12 by cells and the circulating concentration reflects the intake of B12, whereas total homocysteine (tHcy) indicates the metabolic ability. In this study, we investigated the diagnostic value of circulating holo-TC, B12, folate and homocysteine in vegetarians who were at risk of B12 deficiency. B12-related biomarkers were measured in 119 young, healthy graduate vegetarians. None was folate deficient. As per reported definition, half were B12 deficient; 70 % of males and 50 % of females had low plasma holo-TC concentrations; and 92 % of males and half of females had hyperhomocysteinaemia. None had any clinical signs of B12 deficiency. Receiver operating characteristic curve analysis demonstrated similar AUC at the B12 concentration of 100 and 150 pmol/l when holo-TC (0·777 and 0·784) and homocysteine (0·924 and 0·928) were used as variables. Cut-off value of 100 pmol/l resulted in the highest sensitivity of 77·78 % and specificity of 71·05 % with a predictive value of 19·6 pmol/l for holo-TC and a sensitivity of 82·72 % and specificity of 89·7 % with a predictive value of 21·7 µmol/l for homocysteine. The combination of B12, holo-TC and tHcy improves the diagnostic accuracy at these cut-offs, and we suggest that for the young Indian vegetarians the cut-off for plasma B12 and holotrancobalamin is 100 pmol/l and 19·6 pmol/l, respectively, and for homocysteine it is 17·6 (females) and 27 µmol/l (males) for identifying B12 deficiency.
Observational studies and treatment trials investigating nutrition and cognitive function, with a focus on folate and soya and dementia, were reviewed. Data suggested that effects of folic acid based interventions may only be shown before cognitive decline is evident and/or if people are folate deficient. In older people in Indonesia, Hawai'i and China, tofu, which can contain high levels of phytoestrogens, was found to increase dementia risk. This association was not mediated by a vegetarian diet, socioeconomic status, formaldehyde, thyroid function, or loss of teeth. On the other hand, human observational and animal treatment studies suggested that tempe, a fermented soya product containing phytoestrogens and folate, reduced dementia risk and improved memory. High oestrogen levels were found to increase dementia risk in older women. However, in women with adequate serum folate, high oestrogen levels did not confer additional dementia risk and may protect ageing neurons. In conclusion, reviews seem to suggest that folic acid interventions are only effective on cognitive outcomes in people who are folate deficient and do not have cognitive impairment. Frequent consumption of tofu may have detrimental effects on memory and increase dementia risk in older East Asian people, while tempe may reduce these risks. Possibly folate in tempe offsets the potential negative effects of oestrogenic compounds on ageing neurons.
To investigate the associations of organic food consumption with maternal pre-pregnancy BMI, hypertension and diabetes in pregnancy, and several blood biomarkers of pregnant women.
Prospective cohort study.
Pregnant women were recruited at midwives’ practices and through channels related to consumption of food from organic origin.
Pregnant women who filled in FFQ and donated a blood sample (n 1339). Participant groups were defined based on the share of consumed organic products; to discriminate between effects of food origin and food patterns, healthy diet indicators were considered in some statistical models.
Consumption of organic food was associated with a more favourable pre-pregnancy BMI and lower prevalence of gestational diabetes. Compared with participants consuming no organic food (reference group), a marker of dairy products intake (pentadecanoic acid) and trans-fatty acids from natural origin (vaccenic and rumenic acids) were higher among participants consuming organic food (organic groups), whereas elaidic acid, a marker of the intake of trans-fatty acids found in industrially hydrogenated fats, was lower. Plasma levels of homocysteine and 25-hydroxyvitamin D were lower in the organic groups than in the reference group. Differences in pentadecanoic acid, vaccenic acid and vitamin D retained statistical significance when correcting for indicators of the healthy diet pattern associated with the consumption of organic food.
Consumption of organic food during pregnancy is associated with several health-related characteristics and blood biomarkers. Part of the observed associations is explained by food patterns accompanying the consumption of organic food.
To examine the prevalence of folate inadequacy and toxicity based on usual intakes from food and supplements, as well as biomarkers of folate, secondary data analyses were performed using cross-sectional, nationally representative data from the Canadian Community Health Survey, Cycle 2.2 (n 32 776), as well as biomarker data from the Canadian Health Measures Survey, Cycles 1, 2 and 3 (n 15 754). On the basis of unfortified food sources, Canadians would struggle to consume adequate amounts of folate. When folate intakes from all food sources were considered, the overall prevalence of folate inadequacy was low across all age/sex groups, with the exception of females >70 years. However, >10 % of supplement users were above the tolerable upper intake level, increasing to almost 18 % when overage factors were accounted for. In addition, between 20 and 52 % of supplement users had elevated erythrocyte folate concentrations, depending on the cut-off used. Results from this study suggest that insufficient dietary intakes of folate in Canadians have been ameliorated because of the fortification policy, although folate inadequacy still exists across all age groups. However, supplement users appear to be at an increased risk of folic acid (FA) overconsumption as well as elevated erythrocyte folate. As such, the general population should be informed of the potential risks of FA overconsumption resulting from supplement use. This study suggests a need for more careful assessment of the risks and benefits of food fortification, particularly fortification above mandated levels, and FA supplement use in the general population.
To examine overall micronutrient intake periconceptionally and throughout pregnancy in a population-based cohort of Australian women.
In a prospective cohort study, micronutrient dosages were extracted from self-reported maternal supplement use, recorded pre-conception, and for each trimester of pregnancy. A food frequency scale (DQESv2) captured usual maternal diet for gestational weeks 14–26. The influence of sociodemographic and lifestyle factors associated with supplement use was examined using logistic regression, and changes in micronutrient intakes prior to and throughout pregnancy were assessed using repeated-measures ANOVA analyses.
Metropolitan hospital sites in Melbourne, Australia.
Women with a viable singleton pregnancy were recruited at less than 19 weeks’ gestation (n 2146).
Compared with non-users, women using supplements during pregnancy were more likely to have planned their pregnancy, be >25 years old, primiparous, Caucasian, non-smokers, have a tertiary education and be consuming a folate-rich diet. Intakes of folate, Fe and Zn were significantly lower in the periconceptional period, compared with other periods (P<0·001). Intakes below Recommended Daily Intake levels were common both periconceptionally and throughout pregnancy, with 19–46 % of women not meeting the Recommended Daily Intake for folate, 68–82 % for Fe and 17–36 % for Zn. Conversely, 15–19 % of women consumed beyond the recommended Upper Limit for folate and 11–24 % for Fe.
The study highlights the need for improved public health education on nutritional needs during pregnancy, especially among women with lower educational achievements and income.
To estimate the folate status of New Zealand women of childbearing age following the introduction, in 2010, of a new voluntary folic acid fortification of bread programme.
The 2011 Folate and Women’s Health Survey was a cross-sectional survey of women aged 18–44 years carried out in 2011. The survey used a stratified random sampling technique with the Electoral Roll as the sampling frame. Women were asked about consumption of folic-acid-fortified breads and breakfast cereals in a telephone interview. During a clinic visit, blood was collected for serum and erythrocyte folate measurement by microbiological assay.
A North Island (Wellington) and South Island (Dunedin) city centre in New Zealand.
Two hundred and eighty-eight women, of whom 278 completed a clinic visit.
Geometric mean serum and erythrocyte folate concentrations were 30 nmol/l and 996 nmol/l, respectively. Folate status was 30–40 % higher compared with women of childbearing age sampled as part of a national survey in 2008/09, prior to the introduction of the voluntary folic acid bread fortification programme. In the 2011 Folate and Women’s Health Survey, reported consumption of fortified bread and fortified breakfast cereal in the past week was associated with 25 % (P=0·01) and 15 % (P=0·04) higher serum folate concentrations, respectively.
Serum and erythrocyte folate concentrations have increased in New Zealand women of childbearing age since the number of folic-acid-fortified breads was increased voluntarily in 2010. Consumption of fortified breads and breakfast cereals was associated with a higher folate status.
To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women.
A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual.
The Ottawa Hospital and Kingston General Hospital, Ontario, Canada.
Pregnant women recruited between 12 and 20 weeks of gestation.
A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited.
BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.
The importance of folate during pregnancy was established more than 80 years ago by Lucy Wills’ ground-breaking studies of tropical macrocytic anaemia. More recently, it has become apparent that the adverse consequences of inadequate nutrient supply during early developmental may be exacerbated by over-nutrition postnatally. The present paper aims to review recent evidence that maternal methyl donor (notably folate) supply peri-conceptually and during pregnancy has long-term effects on offspring (metabolic) health. In addition, we propose the hypothesis that epigenetic mechanisms, especially DNA methylation, may mediate the effects of these early life nutritional insults. We discuss evidence from a natural experiment in human subjects which provides proof of principle for the hypothesis. We describe an attempt to test this hypothesis using a mouse model in which female C57Bl/6 mice were randomised to low or normal folate diets prior to, and during, pregnancy and lactation. Low maternal folate supply resulted in offspring that were more susceptible to detrimental metabolic effects of a high-fat diet fed from weaning, manifested as increased circulating TAG concentration. Interestingly, this metabolic phenotype in adult offspring occurred without any detectable change in adiposity, suggesting a different aetiological origin from the more commonly reported observation that maternal undernutrition leads to increased offspring adiposity and to symptoms of the Metabolic Syndrome. The widespread prevalence of overweight and obesity and of folate deficiency among women of child-bearing age highlights the possibility that this double nutritional insult may exacerbate the risk of metabolic disease in their offspring.
Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2–4 (v. 1) were 0·66 (95 % CI 0·48, 0·91), 0·52 (95 % CI 0·37, 0·74) and 0·34 (95 % CI 0·23, 0·50) (Ptrend<0·001) for folate and 0·72 (95 % CI 0·52, 1·00), 0·55 (95 % CI 0·39, 0·78) and 0·44 (95 % CI 0·30, 0·63) (Ptrend<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (Pinteraction=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population.