Project description:Objective: This study aimed to investigate the associations between dietary one-carbon metabolism-related nutrients (betaine, choline, methionine, folate, vitamin B6, and vitamin B12) and fluorosis among the Chinese population in an area known for coal-burning fluorosis. Methods: A cross-sectional study was conducted, with 653 fluorosis patients and 241 non-fluorosis participants. Dietary intake was acquired using a validated semi-quantitative 75-item food frequency questionnaire. The risk associations were assessed by unconditional logistical regression. Results: We observed a significant inverse association between dietary betaine, total choline, methionine, folate, vitamin B6, and choline species and fluorosis. The adjusted OR (95% CI) in the highest quartile of consumption compared with the lowest were 0.59 (0.37-0.94) (P-trend = 0.010) for betaine intake, 0.45 (0.28-0.73) (P-trend = 0.001) for total choline intake, 0.45 (0.28-0.72) (P-trend < 0.001) for methionine intake, 0.39 (0.24-0.63) (P-trend < 0.001) for folate intake, 0.38 (0.24-0.62) (P-trend < 0.001) for vitamin B6 intake, and 0.46 (0.28-0.75) (P-trend = 0.001) for total choline plus betaine intake. Dietary intakes of choline-containing compounds, phosphatidylcholine, free choline, glycerophosphocholine, and phosphocholine were also inversely associated with lower fluorosis (all P-trend < 0.05). No significant associations were observed between dietary vitamin B12 or sphingomyelin and fluorosis. Conclusion: The present study suggested that the higher dietary intakes of specific one-carbon metabolism-related nutrients, such as betaine, choline, methionine, folate, and vitamin B6, are associated with lower fluorosis prevalence.
Project description:The preconception period represents an important window for foetal and epigenetic programming. Some micronutrients (B vitamins, choline, betaine, methionine) implicated in one-carbon metabolism (OCM) are essential for major epigenetic processes that take place in early pregnancy. However, few studies have evaluated the implication of the micronutrients in placental DNA methylation. We investigated whether intake of OCM nutrients in the year before pregnancy was associated with placental DNA methylation in the EDEN mother-child cohort. Maternal dietary intake was assessed with a food-frequency questionnaire. Three dietary patterns, 'varied and balanced diet,' 'vegetarian tendency,' and 'bread and starchy food,' were used to characterize maternal OCM dietary intake. The Illumina Infinium HumanMethylation450 BeadChip was used to measure placental DNA methylation of 573 women included in the analyses. We evaluated the association of dietary patterns with global DNA methylation. Then, we conducted an agnostic epigenome-wide association study (EWAS) and investigated differentially methylated regions (DMRs) associated with each dietary pattern. We found no significant association between the three dietary patterns and global DNA methylation or individual CpG sites. DMR analyses highlighted associations between the 'varied and balanced' or 'vegetarian tendency' pattern and DMRs located at genes previously implicated in functions essential for embryonic development, such as neurodevelopment. The 'bread and starchy food' pattern was associated with regions related to genes whose functions involve various metabolic and cell synthesis-related processes. In mainly well-nourished French women without major deficiencies, OCM intake before pregnancy was not associated with major variation in DNA methylation.
Project description:BACKGROUND:Studies disagree as to whether intakes of folate-mediated one-carbon metabolism nutrients are associated with endometrial cancer. METHODS:Using data from the large, prospective NIH-AARP Diet and Health Study, we used Cox proportional hazards models to evaluate endometrial cancer risk associated with calorie-adjusted dietary intake of several B vitamins and methionine. All models accounted for age, race, body mass index (BMI), smoking, oral-contraceptive use, menopausal hormone therapy use and caloric intake. We estimated associations by time from baseline (≤3 or >3 years) and stratified models by BMI (<25 or ≥25 kg/m2). During 16 years of follow-up, we identified 2329 endometrial cancer cases among 114 414 participants. RESULTS:After adjustment for confounding, we observed increased risk for endometrial cancer with greater consumption of dietary total folate, natural folate, B2, B6 and B12 [hazard ratios (HRs) ranging from 1.14 to 1.24 for the highest quintile (Q5) vs the lowest (Q1)]. Higher intakes of total folate, natural folate, B6 and B12 continued to be associated with increased risk when limiting follow-up to >3 years from baseline. We observed risks for the highest intakes of B2 [Q5 vs Q1: HR 1.27 95% confidence interval (CI) 1.07-1.50], B12 (Q5 vs Q1: HR 1.38 CI 1.17-1.63) and methionine (Q5 vs Q1: HR 1.26 CI 1.07-1.48) among women who were overweight/obese, but not among normal/underweight women. CONCLUSIONS:Our findings indicate that one-carbon metabolism plays a role in endometrial carcinogenesis and exploration of this role in tissue and cellular biology studies is warranted.
Project description:BackgroundNutrients involved in one-carbon metabolism are hypothesized to protect against pancreatic cancer development.MethodsThe Singapore Chinese Health Study database was used to prospectively examine the association between intake of one-carbon metabolism-related nutrients and pancreatic cancer risk. Between 1993 and 1998, 63,257 men and women ages 45 to 74 years were enrolled into the cohort. The daily intakes of the following one-carbon metabolism-related nutrients were assessed at enrollment using a 165-item food frequency questionnaire: betaine, choline, folate, and vitamins B2, B6, and B12. Multivariable HRs and 95% confidence intervals (CI) for pancreatic cancer risk associated with dietary intakes of one-carbon metabolism-related nutrients were calculated.ResultsAs of December 2013, 271 incident pancreatic cancer cases were identified during an average of 16.3 years of follow-up. Higher intakes of vitamin B6 and choline were associated with statistically significant decreases in the risk of developing pancreatic cancer. Compared with the lowest quartile, HRs (95% CIs) for the highest quartiles of vitamin B6 and choline were 0.52 (0.36-0.74; P trend = 0.001) and 0.67 (0.48-0.93; P trend = 0.04), respectively. There were no clear associations between the other one-carbon metabolism-related nutrients and pancreatic cancer risk.ConclusionOur study suggests that higher intake of vitamin B6 and choline may lower the risk of pancreatic cancer.ImpactOur prospective findings are consistent with the in vivo evidence for protective roles of vitamin B6 and choline on pancreatic cancer development.
Project description:Few studies have evaluated the role of methylation-pathway nutrients involved in fetal growth (B vitamins, choline, betaine, and methionine). These one-carbon metabolism (OCM) nutrients are essential for DNA methylation in the periconception period. We aimed to characterize dietary patterns of 1638 women from the EDEN mother-child cohort in the year before pregnancy according to the contribution of OCM nutrients and to study the association of such patterns with anthropometric measurements at birth. Dietary intake before pregnancy was assessed by using a semi-quantitative food frequency questionnaire. We used the reduced-rank regression (RRR) method to identify dietary patterns using OCM nutrients as intermediate variables. We ran linear regressions models to study the association between dietary patterns scores and birth weight, length, head circumference, gestational age, and sex-specific z-scores, adjusting for maternal characteristics and vitamin supplementation before and during pregnancy. Three patterns, "varied and balanced", "vegetarian tendency", and "bread and starchy food" were identified, explaining 58% of the variability in OCM nutrient intake. Higher scores on the "varied and balanced" pattern tended to be associated with higher birth length and weight. In mainly well-nourished young French women, we did not find evidence that variability in OCM nutrient intake has major effects on fetal growth.
Project description:Diabetes mellitus (DM) affects about 9.3% of the population globally. Hyperhomocysteinemia (HHcy) has been implicated in the pathogenesis of DM, owing to its promotion of oxidative stress, β-cell dysfunction, and insulin resistance. HHcy can result from low status of one-carbon metabolism (OCM) nutrients (e.g., folate, choline, betaine, vitamin B6, B12), which work together to degrade homocysteine by methylation. The etiology of HHcy may also involve genetic variation encoding key enzymes in OCM. This review aimed to provide an overview of the existing literature assessing the link between OCM nutrients status, related genetic factors, and incident DM. We also discussed possible mechanisms underlying the role of OCM in DM development and provided recommendations for future research and practice. Even though the available evidence remains inconsistent, some studies support the potential beneficial effects of intakes or blood levels of OCM nutrients on DM development. Moreover, certain variants in OCM-related genes may influence metabolic handling of methyl-donors and presumably incidental DM. Future studies are warranted to establish the causal inference between OCM and DM and examine the interaction of OCM nutrients and genetic factors with DM development, which will inform the personalized recommendations for OCM nutrients intakes on DM prevention.
Project description:Background and aimsThere are limited studies describing the association between dietary intake of one-carbon metabolism nutrients and hyperglycemia. The present study aimed to investigate the association of habitual dietary intake of one-carbon metabolism nutrients with hyperglycemia in a fluorosis area in China, and explored the interaction between these nutrients and fluorosis related to hyperglycemia.MethodIn a cross-sectional study, we recruited 901 villagers, ages ranging from 18-75, in Guizhou Province. Dietary data and other covariate data were obtained through an interviewer-administered questionnaire. We collected venous blood samples from participants who had fasted for one night to obtain fasting blood glucose levels and we categorized dietary intake of betaine, total choline, methionine, folate, vitamins B6 and B12, and choline subclasses into quartiles (Q1-Q4). The lowest quartile (Q1) served as the reference group. An unconditional logistic regression model was used to evaluate the protective effects of a dietary intake of one-carbon nutrients against hyperglycemia. We calculated Odds Ratios (ORs) with 95% confidence intervals (CIs). A presence or absence of fluorosis subgroup analysis was performed to determine the potential effect of fluorosis on hyperglycemia.ResultAfter adjusting for potential confounding factors, we found that a greater intake of dietary vitamin B6, total choline and methyl-donor index was inversely associated with the occurrence of hyperglycemia (P-trend <0.05). However, there were no significant associations between hyperglycemia and the dietary intake of folate, vitamin B12, methionine, and betaine. As for the choline subgroups, it showed that the dietary intake of free choline, phosphatidylcholine, and glycerol phosphatidylcholine was negatively correlated with the occurrence of hyperglycemia (P < 0.05). In contrast, there was no statistical association between dietary phosphatidylcholine and sphingomyelin and hyperglycemia (all P > 0.05). The results of subgroup analysis showed that dietary intake of folate, vitamin B6, total choline, free choline, glycerol phosphorylcholine, and phosphocholine had a protective effect against the occurrence of hyperglycemia in the non-fluorosis subgroup, although no effects were observed in the fluorosis subgroup. There were significant interactions between these nutrients and fluorosis (P = 0.010-0.048).ConclusionThe study demonstrated that higher dietary intake of vitamin B6, total choline, methyl-donor index, free choline, glycerol phosphorylcholine, and phosphocholine in choline compounds were associated with a lower incidence of hyperglycemia. Moreover, the associations were modified by the presence or absence of fluorosis. Further investigation is needed to test the association in large-scale follow-up studies.
Project description:PurposeFolate, vitamins B6 and B12, methionine, choline, and betaine are nutrients related to one-carbon metabolism and have been hypothesized to decrease cancer risk. Few studies have evaluated dietary intakes of these nutrients in relation to renal cell cancer (RCC).MethodsWe conducted prospective follow-up studies of women in the Nurses' Health Study and men in the Health Professionals Follow-up Study. Diet was assessed repeatedly using a validated semi-quantitative food-frequency questionnaire in both studies.ResultsDuring follow-up of 24 years among 77,208 women (918,891 person-years) and 22 years among 47,886 men (1,731,752 person-years), we accrued 436 cases of RCC (225 women and 211 men). Intakes of folate, vitamins B6 and B12, methionine, and betaine were not found to be related to RCC risk. Higher intake of free choline, but not other forms of choline, was associated with reduced RCC risk. The results were similar in men and women.ConclusionsWe found little evidence that higher intakes of nutrients related to one-carbon metabolism lower RCC risk. One-carbon metabolism may have little influence on renal carcinogenesis.
Project description:BackgroundNutrients involved in one-carbon metabolism - folate, vitamins B6 and B12, methionine, choline, and betaine - have been inversely associated with multiple cancer sites and may be related to skin cancer. However, there is a lack of research on the association between intake of these nutrients and cutaneous melanoma risk. The aim of this study was to examine the associations between intake of one-carbon metabolism nutrients and cutaneous melanoma risk in two large prospective cohorts.MethodsThe cohorts included 75,311 white women and 48,523 white men. Nutrient intake was assessed repeatedly by food frequency questionnaires and self-reported supplement use. We used Cox proportional hazards regression to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and then pooled HRs using a random-effects model.ResultsOver 24-26 years of follow-up, we documented 1328 melanoma cases (648 men and 680 women). Higher intake of folate from food only, but not total folate, was associated with increased melanoma risk (pooled HR for top versus bottom quintile: 1.36; 95% CI: 1.13-1.64; P for trend = 0.001). The association was significant in men, but attenuated in women. Higher intake of vitamins B6 and B12, choline, betaine, and methionine were not associated with melanoma risk, although there was modest increasing trend of risk for vitamin B6 from food only (pooled HR for top versus bottom quintile: 1.18; 95% CI: 0.99-1.41; P for trend = 0.03).ConclusionsWe found some evidence that higher intake of folate from food only was associated with a modest increased risk of cutaneous melanoma. However, since other factors related to dietary folate intake may account for the observed association, our findings warrant further investigation.
Project description:Many enzymes in one-carbon metabolism (OCM) are up- or down-regulated by the sex hormones which vary diurnally and throughout the menstrual cycle. During pregnancy, estradiol and progesterone levels increase tremendously to modulate physiological changes in the reproductive system. In this work, we extend and improve an existing mathematical model of hepatic OCM to understand the dynamic metabolic changes that happen during the menstrual cycle and pregnancy due to estradiol variation. In particular, we add the polyamine drain on S-adenosyl methionine and the direct effects of estradiol on the enzymes cystathionine β-synthase (CBS), thymidylate synthase (TS), and dihydrofolate reductase (DHFR). We show that the homocysteine concentration varies inversely with estradiol concentration, discuss the fluctuations in 14 other one-carbon metabolites and velocities throughout the menstrual cycle, and draw comparisons with the literature. We then use the model to study the effects of vitamin B12, vitamin B6, and folate deficiencies and explain why homocysteine is not a good biomarker for vitamin deficiencies. Additionally, we compute homocysteine throughout pregnancy, and compare the results with experimental data. Our mathematical model explains how numerous homeostatic mechanisms in OCM function and provides new insights into how homocysteine and its deleterious effects are influenced by estradiol. The mathematical model can be used by others for further in silico experiments on changes in one-carbon metabolism during the menstrual cycle and pregnancy.