High Folate Intake Research Articles

Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice.

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low-folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual's age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

Association between folate intake and radiographic progression, pain function scores in subjects with radiographic knee osteoarthritis: Data from the osteoarthritis initiative.

Folate has an important role in the functioning of the musculoskeletal system, including modulation of inflammation, immunity, cartilage regeneration, prevention of osteoporosis, and maintenance of muscle strength, but evidence on the association between folate intake and knee pain, functional scores, and radiographic progression in patients with knee osteoarthritis (OA) is still limited. Our population-based cohort was extracted from the osteoarthritis initiative (OAI), focusing on individuals with prevalent radiographic knee OA (with a Kellgren-Lawrence score ≥2). Folate consumption was determined using the food frequency questionnaire. Data regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and radiographic readings were collected over 48 months. We analyzed the compiled data using generalized additive mixed models. Our cohort consisted of 1472 OA patients (626 men and 846 women, mean [SD] age 62.35 [8.92]). At the 48-month follow-up, we observed a significant correlation between higher folate intake and a slower progression of knee pain and functional scores, as evidenced by a statistically significant decrease in the WOMAC total score, WOMAC pain subscale score, and WOMAC function/disability subscale score (p < .05). The fully adjusted models estimated a reduction of -0.028 points per 50 μg/1000 kcal of daily folate intake on the WOMAC pain subscale, -0.117 points on the WOMAC function subscale, and -0.160 points on the total WOMAC scale. Furthermore, our nonparametric fit analysis suggested that a higher intake of folate might decelerate the radiographic progression of OA. Stratified analyses indicated that an increase in folate consumption might particularly benefit men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake. Higher folate intake is correlated with improved knee function and reduced pain in patients with knee OA and might deter the radiographic progression of OA. The benefits appear to be more pronounced in men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake.

Vitamin D, Folate, Vitamin B12, and Iron Status in Pregnant/Postpartum Old Order Anabaptist Women in Southwestern Ontario.

Purpose: To assess vitamin D, folate, vitamin B12, and iron status in Old Order Anabaptist (OOA) pregnant/postpartum women.Methods: Blood was analyzed for plasma 25 hydroxy vitamin D (25(OH)D), red blood cell (RBC) folate, serum vitamin B12, and iron status indicators. Dietary intakes (food and supplements) from 3-day estimated records were compared to Dietary Reference Intakes and Canada's Food Guide (2007).Results: Fifty women participated in this descriptive cross-sectional study. Concentrations of 25(OH)D were low (<50 nmol/L for 20% and < 75 nmol/L for 63%); 42% had total vitamin D intakes < estimated average requirement (EAR). All women had RBC folate above the 1360 mmol/L cut-off. Nineteen percent had folate intakes <EAR; 80% had folic acid supplement intakes >upper limit. One woman had low serum vitamin B12 (<148 pmol/L); serum vitamin B12 was high (>652 pmol/L) for 24%. None had vitamin B12 intakes <EAR; intakes were high compared to the recommended dietary intake. One woman had low hemoglobin; 13% had ferritin <15 μg/L. Thirteen percent had total iron intake <EAR.Conclusions: Overall, dietary intake and serum micronutrient status of OOA pregnant and postpartum women in our study were similar to those reported in previous studies of Canadian women. While some women had low intakes of vitamin D and iron, most had high intakes of folate and vitamin B12. These findings provide guidance to ensure appropriate dietary and supplement intakes in this potentially vulnerable and rarely studied population.

Identification of SIBO Subtypes along with Nutritional Status and Diet as Key Elements of SIBO Therapy.

Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane-dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.

Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing noFA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.

The protective effect of dietary folate intake on gastric cancer is modified by alcohol consumption: A pooled analysis of the StoP Consortium.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 μg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, ORQ4v Q1 = 1.15 (95% CI, 0.85-1.56), and the OR100 μg/day = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect.

Использование витаминов группы В в профилактических и лечебных дозах при сахарном диабете 2-го типа

Polyhypovitaminosis is a risk factor for many diseases. Adequate dietary intake of vitamins may help prevent/reduce the risk of progression of several diseases, including type 2 diabetes (T2D). Objective. To analyze the sufficiency of B vitamins and efficacy of their administration in patients with T2D depending on the dose. Vitamin deficiencies typical for patients with T2D worsen the course of the disease and increase the risk of complications. Higher intake of vitamins B1, B2 and folate is associated with a lower risk of T2D, and higher intake of folate and vitamin B6 is associated with a lower risk of cardiovascular diseases in patients with T2D. Higher intake of vitamin B6 by individuals with T2D is associated with a lower incidence of diabetic retinopathy. In T2D patients, low levels of the coenzyme form of vitamin B6 and high serum levels of 4-pyridoxic acid increase the risk of all-cause mortality. Patients with diabetic retinopathy have significantly reduced levels of vitamin B12. The incidence of vitamin B2 deficiency based on serum levels is found in approximately 30–40% of patients with T2D and diabetic nephropathy. Metformin administration worsens vitamin B12 supply and increases the risk of T2D complications. The need to eliminate vitamin deficiencies and improve the sufficiency of B vitamins is undeniable. There are prophylactic and therapeutic doses of vitamins. Continuous intake of multivitamin supplements with a complete set of all B vitamins in prophylactic doses consistent with the recommended daily intake (RDI) will reduce the risk of T2D progression. Administration of B vitamins during 1 month to 5 years in therapeutic doses well above the RDI results in improvement of carbohydrate metabolism, antioxidant and clinical status in patients with T2D, but may lead to undesirable effects. Conclusion. When prescribing B vitamins to T2D patients, it is recommended to distinguish between prophylactic doses of vitamins that meet the body’s needs and can and should be taken continuously, and therapeutic doses, that are close to the upper safe intake level and may cause adverse reactions. Key words: type 2 diabetes, B vitamins, sufficiency, prophylactic and therapeutic doses of vitamins

Folic acid for the primary prevention of stroke: a systematic review and meta-analysis.

Results from studies were inconsistent with regard to the effect of folic acid on the primary prevention of stroke. The aim of this study was to analyze the association between folic acid and the primary prevention of stroke using the data from observational studies and randomized controlled trials (RCTs). Eligible publications published until June 2024 were searched in the database of PubMed, Web of Science and Embase. This study included all observational studies and RCTs of folic acid with first stroke as the reporting endpoints. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled in the random-effects model to assess the effect of folic acid on the primary prevention of stroke. Results from 12 observational publications with 16 research, including 312,320 participants, were combined to explore the association between dietary folic acid intake and the primary prevention of stroke. The results showed that high dietary folic acid intake was associated with a 17% reduction in stroke incidence (RR:0.83; 95% CI: 0.73-0.94), and the effect of dietary folic acid was greater in areas without grain fortification (RR:0.80; 95% CI: 0.67-0.95). The pooled results from 12 RCTs, totaling 75,042 participants, indicated that folic acid supplementation was not associated with the stroke primary prevention (RR:0.92; 95% CI: 0.80-1.05), but folic acid supplementation was effective in areas without grain fortification (RR:0.78; 95% CI: 0.68-0.89). Our meta-analysis demonstrated that dietary folic acid is effective in stroke primary prevention, and folic acid supplementation is effective in stroke primary prevention only in areas without grain fortification. https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024516991.

Association between nutrient intake and female infertility: a study based on NHANES database

Background This study was designed to investigate the association between nutrients and female infertility. Methods A cross-sectional study on 18–45 years of age reproductive-age women was conducted using the data from the National Health and Nutrition Examination Surveys (NHANES) for the periods 2013–2014 and 2015–2016. Multivariate logistic regression analysis was performed to evaluate the association between nutrients and female infertility. Subgroup analysis was applied to the body mass index (BMI). Results were summarised using an odds ratio (OR) with a 95% confidence interval (CI). Results Of the total 1713 women, 204 women (11.91%) were infertile. The result demonstrated that higher intake of carbohydrate (OR: 0.46, 95% CI: 0.24–0.86, p = 0.018), vitamin A (OR: 0.44, 95% CI: 0.24–0.80, p = 0.009), vitamin C (OR: 0.48, 95% CI: 0.26–0.88, p = 0.020), magnesium (OR: 0.36, 95% CI: 0.17–0.76, p = 0.009), iron (OR: 0.43, 95% CI: 0.23–0.82, p = 0.012), lycopene (OR: 0.55, 95% CI: 0.33–0.91, p = 0.022), and total folate (OR: 0.38, 95% CI: 0.20–0.70, p = 0.003) were associated with a lower risk of female infertility. The subgroup analysis also reported that intakes of vitamin A, vitamin C, and lycopene were related to a lower risk of female infertility among women with a BMI being 18.5–24.9 kg/m2. Among women with BMI > 24.9 kg/m2, high intakes of magnesium, iron and total folate were associated with a decreased risk of female infertility. Conclusions The intake of several nutrients is associated with a decreased risk of female infertility. These findings provide insight into potentially modifiable lifestyle factors associated with female infertility.

The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer.

Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HRT3-T1) = 0.42, 95%CI, 0.25-0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1: 0.83, 95%CI, 0.49-1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.

Perinatal folate levels do not influence tumor latency or multiplicity in a model of NF1 associated plexiform-like neurofibromas

ObjectiveIn epidemiological and experimental research, high folic acid intake has been demonstrated to accelerate tumor development among populations with genetic and/or molecular susceptibility to cancer. Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder predisposing affected individuals to tumorigenesis, including benign plexiform neurofibromas; however, understanding of factors associated with tumor risk in NF1 patients is limited. Therefore, we investigated whether pregestational folic acid intake modified plexiform-like peripheral nerve sheath tumor risk in a transgenic NF1 murine model.ResultsWe observed no significant differences in overall survival according to folate group. Relative to controls (180 days), median survival did not statistically differ in deficient (174 days, P = 0.56) or supplemented (177 days, P = 0.13) folate groups. Dietary folate intake was positively associated with RBC folate levels at weaning, (P = 0.023, 0.0096, and 0.0006 for deficient vs. control, control vs. supplemented, and deficient vs. supplemented groups, respectively). Dorsal root ganglia (DRG), brachial plexi, and sciatic nerves were assessed according to folate group. Mice in the folate deficient group had significantly more enlarged DRG relative to controls (P = 0.044), but no other groups statistically differed. No significant differences for brachial plexi or sciatic nerve enlargement were observed according to folate status.

Maternal high intake of vitamin B12 and folate reduces the risk of adverse birth outcomes among HIV negative pregnant women in Dar es Salaam, Tanzania

AbstractPoor dietary intake of vitamin B12 and folate before and during pregnancy has been associated with adverse birth outcomes. This relationship has not been rigorously evaluated in Tanzania. We performed secondary analyses of data collected during the perinatal study, a double‐blind trial that investigated the effect of vitamin supplements on perinatal outcomes in Tanzania between 2001 and 2004. In this analysis, we used log‐binomial models to investigate the adequacy of vitamin B12 and folate intake among 7633 mothers and the association of vitamin B12 and folate intake during pregnancy with low birth weight, preterm birth (PTB), small for gestational age and foetal death. Sixty‐seven percent of women had vitamin B12 intake below the recommended dietary allowances (RDAs) of 2.6 mcg for pregnant women, and 98% of women had folate intake below the RDA of 600 mcg for pregnant women. Compared with women in the lowest tertile of vitamin B12 intake women in the highest tertile were 26% less likely to have PTB (relative risk [RR] = 0.74, 95% confidence interval [CI]: 0.65, 0.84) and 36% less likely to have severe PTB (RR = 0.64, 95% CI: 0.50, 0.83). Compared with women in the lowest tertile of folate intake women in the highest tertile were 21% less likely to have PTB (RR = 0.79, 95% CI: 0.69, 0.89) and 21% less likely to have severe PTB (RR = 0.79, 95% CI: 0.69, 0.89). The provision of an adequate supply of these nutrients before and during pregnancy would improve pregnancy outcomes in Tanzania.

Genome-wide interaction analysis of folate for colorectal cancer risk

BackgroundEpidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate’s role in CRC. ObjectivesOur aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. MethodsWe applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). ResultsInverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. ConclusionsVariation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case-Control Study from the Ovarian Cancer Association Consortium.

Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown. We conducted a pooled analysis of six case-control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01-1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

Elevated Maternal Folate Status and Changes in Maternal Prolactin, Placental Lactogen and Placental Growth Hormone Following Folic Acid Food Fortification: Evidence from Two Prospective Pregnancy Cohorts.

Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.

Long-Term Intake of Folate, Vitamin B6, and Vitamin B12 and the Incidence of Parkinson's Disease in a Sample of U.S. Women and Men.

Folate and vitamins B6 and B12 have been proposed as protective against the development of Parkinson's disease (PD). Two prior longitudinal studies were inconclusive. The aim was to examine the association of long-term intake of folate, vitamin B6, and vitamin B12 with the incidence of PD. The study population comprised 80,965 women (Nurses' Health Study, 1984-2016) and 48,837 men (Health Professionals Follow-up Study, 1986-2016) followed prospectively for the development of PD. Intake of B vitamins was measured at baseline and every 4 years thereafter using food frequency questionnaires. We estimated the hazard ratio (HR) and 95% confidence interval (CI) of PD based on quintiles of cumulative average intake adjusting for potential confounders. Secondary analyses considered different lagged exposure periods as well as baseline and recent intakes. In separate analyses of cumulative average intake, total folate, B6, and B12 were not associated with the risk of PD. Results from 8-, 12-, and 16-year lag analyses were consistent with these findings. Results for baseline intake of folate and B6 also pointed toward a null association. In contrast, a lower PD risk was observed among individuals with higher baseline total intake of B12 (pooled HR top vs. bottom quintile: 0.80; 95% CI: 0.67-0.95; P-trend=0.01); results from 20-year lag analyses were consistent with this finding. Our results do not support the hypothesis that a higher intake of folate or vitamin B6 would reduce PD risk in this population. Our results provide moderate support for a possible protective effect of vitamin B12 on the development of PD. © 2023 International Parkinson and Movement Disorder Society.

Metabolic Interaction Between Folate, Vitamin B12, and Polyunsaturated Fatty Acids in Pregnancy.

Fetal growth and development are influenced by maternal nutrition and gestational weight gain. Adequate intake of nutrients such as folate, vitamin B12, and docosahexaenoic acid (DHA) is essential for healthy fetal and placental development. Many countries havea national flour fortification program with folic acid (FA), together with pre-pregnancy supplementation of FA (400μg/day) during the first trimester of pregnancy. The latter has been recommended by the WHO and adapted to local requirements by perinatal guidelines. On the other hand, in population studies, many women of childbearing age have vitamin B12 deficiency (<148pmol/L), which can be additionally masked by high FA intake and maternal pregestational obesity. Under these conditions, these patients could be having pregnancies in a folate/vitamin B12 imbalance, which is associated with higher adiposity, insulin resistance, altered lipid metabolism, and low DHA levels in their offspring. However, if these neonatal consequences of maternal pregestational obesityand folate/vitamin B12 imbalance can be reverted by DHA supplementation during pregnancy has not been addressed. This chapter reviews the literature and exposes the current gaps in knowledge and challenges in maternal nutrition with a life-course perspective.

Riboflavin Intake Inversely Associated with Cardiovascular-Disease Mortality and Interacting with Folate Intake: Findings from the National Health and Nutrition Examination Survey (NHANES) 2005-2016.

The association between intakes of riboflavin and mortality has not been examined intensively in general populations. In this study, 10,480 adults in the 2005-2016 National Health and Nutrition Examination Survey (NHANES) were followed-up until 2019 for their vital status. Riboflavin and folate were assessed by two-day 24 h recall. The date and cause of death were obtained from the US Mortality Registry. The risks of all-cause mortality and cardiovascular disease (CVD) mortality were investigated using a Cox regression analysis. During a mean of 8.5 years follow-up, there were 1214 deaths registered (including 373 deaths from CVD and 302 from cancer). Compared to low level (quartile 1, Q1) of riboflavin intake, the hazard ratios (HRs) (95% confidence interval (CI)) for high level (quartile 4, Q4) were 0.53 (0.31-0.90) for CVD mortality and 0.62 (0.48-0.81) for all-cause mortality. The inverse association between riboflavin intake and CVD mortality was only significant among those with a high intake of folate (p for interaction 0.045). Those with a high folate intake (Q4) and low intake of riboflavin (Q1) had the highest risk of CVD mortality (HR 4.38, 95% CI 1.79-10.72), as compared with a high intake of both riboflavin and folate. In conclusion, riboflavin intake was inversely associated with all-cause mortality and CVD mortality, and the association was modified by folate intake.

High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults.

Mandatory fortification of food with synthetic folic acid (FA) was instituted in 1998 to reduce the incidence of neural tube defects. Adequate folate status is correlated with numerous health benefits. However, elevated consumption of FA is controversially associated with deleterious effects on health. We previously reported that excess FA mimicked folate depletion in a lymphoblastoid cell line. To explore the impact of FA intake from fortified food, we conducted an observational human study on 33 healthy participants aged 18–40 not taking any supplements. Food intake, anthropomorphic measurements, and blood samples were collected and analyzed. Our results show that individuals belonging to the highest tertile of folic acid intake, as well as ones with the highest folic acid to total folate intake ratio (FAR), display a significantly greater incidence of lymphocyte genomic damage. A decrease in global DNA methylation is observed in the highest tertile of FAR compared to the lowest (p = 0.055). A downward trend in the overall gene expression of select DNA repair and one carbon cycle genes (MGMT, MLH1, UNG, MTHFR, MTR) is noted with increased folate status and FA intake. These results provide supporting evidence that high consumption of FA from fortified foods can precipitate genomic instability in peripheral lymphocyte in vivo.

Prenatal exposure to tobacco and adverse birth outcomes: effect modification by folate intake during pregnancy

BackgroundFetal exposure to tobacco increases the risk for many adverse birth outcomes, but whether diet mitigates these risks has yet to be explored. Here, we examined whether maternal folate intake (from foods and supplements) during pregnancy modified the association between prenatal exposure to tobacco and with preterm delivery, small-for-gestational age (SGA) births, or neonatal adiposity.MethodsMother–child pairs (n = 701) from Healthy Start were included in this analysis. Urinary cotinine was measured at ~ 27 weeks gestation. Diet was assessed using repeated 24-h dietary recalls. Neonatal adiposity (fat mass percentage) was measured via air displacement plethysmography. Interaction was assessed by including a product term between cotinine (< / ≥ limit of detection [LOD]) and folate (< / ≥ 25th percentile [1077 µg/day]) in separate logistic or linear regression models, adjusting for maternal age, race, ethnicity, education, pre-pregnancy body mass index, and infant sex.ResultsApproximately 26% of women had detectable levels of cotinine. Folate intake was significantly lower among women with cotinine ≥ LOD as compared to those with cotinine < LOD (1293 µg/day vs. 1418 µg/day; p = 0.01). Folate modified the association between fetal exposure to tobacco with neonatal adiposity (p for interaction = 0.07) and SGA (p for interaction = 0.07). Among those with lower folate intake, fetal exposure to tobacco was associated with lower neonatal adiposity (mean difference: -2.09%; 95% CI: -3.44, -0.74) and increased SGA risk (OR: 4.99; 95% CI: 1.55, 16.14). Conversely, among those with higher folate intake, there was no difference in neonatal adiposity (mean difference: -0.17%; 95% CI: -1.13, 0.79) or SGA risk (OR: 1.15; 95% CI: 0.57, 2.31).ConclusionsIncreased folate intake during pregnancy (from foods and/or supplements) may mitigate the risk of fetal growth restriction among those who are unable to quit smoking or cannot avoid secondhand smoke during pregnancy.