Dietary Folate Research Articles

Dose-response association between dietary folate and niacin intakes with diabetes among Chinese adults: a cross-sectional study

BackgroundThe aim of this study was to examine the relationship between dietary intake of folate and niacin and diabetes risk in Chinese adults.MethodsThis is a cross-sectional study. Demographic and anthropometric data along with information on dietary intake of vitamins were collected, and eligible participants were recruited to complete the questionnaire. A binary logistic regression analysis was conducted to examine the association between dietary intake of vitamins and diabetes risk, with adjustment for potential confounders. Non-linear dose-response relationships between dietary intake of folate and niacin and diabetes risk were also evaluated using adjusted restricted cubic splines.ResultsOf the 3106 eligible participants, 15.9% had diabetes. Median folate was significantly higher in diabetic patients than in controls (32.030 vs. 27.600 gμ), while median niacin was significantly lower (7.000 vs. 7.900 mg). After controlling for potential confounders, binary logistic regression analysis showed that each unit increase in folate intake was associated with a 1.002-fold increase in the risk of developing diabetes (odds ratio (OR) = 1.002; 95% confidence interval (CI) 1.000–1.004; P = 0.022), while each unit increase in niacin intake was associated with a 3.5% reduction in diabetes risk (OR = 0.965; 95% CI 0.944–0.986; P = 0.001). The plots of restricted cubic splines presented an atypical inverted U-shaped association between dietary intake of folate and diabetes risk.ConclusionsDiabetic patients had a low intake of vitamins, especially the B vitamins. Dietary intake of folate and niacin tended to be independently associated with the risk of diabetes. Nevertheless, this study is observational and a large-scale randomized controlled trial is yet to be conducted, which will add to the evidence of the study results.

Micronutrient supplement intakes among collegiate and masters athletes: A cross-sectional study.

In our cross-sectional study, we evaluated micronutrient supplementation intake among Collegiate and Masters Athletes. We conducted a cross-sectional study to assess micronutrient supplementation consumption in Collegiate and Masters Athletes, comparing sex and sport classification within each respective group. Micronutrient supplement consumption data were measured using a Food Frequency Questionnaire. A two-way analysis of variance was used to explore the differences among Collegiate and Masters Athletes' supplement intakes of the following vitamins and minerals: vitamins A, B6, B12, C, E, D, and calcium, folate, iron, magnesium niacin, riboflavin, selenium, thiamine, and zinc. When significant differences were found, a Bonferroni post hoc test was performed to identify specific group differences. The significance level was set a priori at p < 0.05. A total of 198 athletes (105 females and 93 males) were included in the study. Participants were 36.16 ± 12.33 years of age. Collegiate male athletes had significantly greater vitamin A [1,090.51 ± 154.72 vs. 473.93 ± 233.18 mg retinol activity equivalents (RAE)/day] (p < 0.036), folate [337.14 ± 44.79 vs. 148.67 ± 67.50 mcg dietary folate equivalents (DFE)/day] (p < 0.027), and magnesium (65.35 ± 8.28 vs. 31.28 ± 12.48 mg/day) (p < 0.031) intakes compared to Collegiate female athletes. Collegiate CrossFit Athletes (940.71 ± 157.54 mg/day) had a significantly greater vitamin C intake compared to Collegiate General Athletes (156.34 ± 67.79 mg/day) (p < 0.005), Collegiate Triathletes (88.57 ± 148.53 mg/day) (p < 0.027), Collegiate Resistance Training Athletes (74.28 ± 143.81 mg/day) (p < 0.020), and Collegiate Powerlifters (175.71 ± 128.63 mg/day) (p < 0.044). Masters females had significantly greater calcium intakes compared to Masters males (494.09 ± 65.73 vs.187.89 ± 77.23 mg/day, respectively) (p < 0.002). Collegiate Runners (41.35 ± 6.53 mg/day) had a significantly greater iron intake compared to Collegiate Powerlifters (4.50 ± 6.53 mg/day) (p < 0.024). Masters Swimmers (61.43 ± 12.10 mg/day) had significantly greater iron intakes compared to Masters General Athletes (13.97 ± 3.56 mg/day) (p < 0.014), Masters Runners (17.74 ± 2.32 mg/day) (p < 0.03), Masters Triathletes (11.95 ± 3.73 mg/day) (p < 0.008), Masters CrossFit Athletes (15.93 ± 5.36 mg/day) (p < 0.043), Masters Rowers (9.10 ± 3.36 mg/day) (p < 0.003), and Masters Cyclists (1.71 ± 9.88 mg/day) (p < 0.011). Masters Powerlifters (47.14 ± 9.65 mg/day) had significantly greater zinc intakes compared to Masters General Athletes (9.57 ± 2.84 mg/day) (p < 0.015), Masters Runners (10.67 ± 1.85 mg/day) (p < 0.017), Masters Triathletes (10.24 ± 2.98 mg/day) (p < 0.020), Masters Rowers (9.33 ± 2.68 mg/day) (p < 0.013), and Masters Cyclists (1.43 ± 7.88 mg/day) (p < 0.019). There were no other significant differences among the other micronutrient supplement intakes between the sexes or among the sport classification. We reported significant differences among female and male Collegiate and Masters Athletes. Additionally, we reported significant differences among Collegiate and Masters Athletes sport classifications. Further research should examine both dietary and micronutrient supplement intake among Collegiate and Masters Athletes to examine the extent that athletes exceed the Recommended Dietary Allowances (RDA), and the potential effects on health and performance.

Selecting a dietary supplement with appropriate dosing for 6 key nutrients in pregnancy

BackgroundMost pregnant women in the United States (US) are at risk of inadequate intake of key nutrients during pregnancy from foods alone. Current dietary supplement practices reduce risk of inadequacy for only some nutrients and induce excessive intake of other nutrients. ObjectivesOur study aimed to estimate the doses of supplementation needed to help most pregnant women achieve the recommended intake without exceeding upper limits for key prenatal nutrients and to identify US dietary supplements providing these doses. MethodsWe conducted 24-h dietary recalls in 2450 pregnant participants aged 14–50 y from 2007 to 2019. We estimated the usual intake of vitamins A and D, folate, calcium, iron, and ω-3 FAs from foods alone. We calculated the target doses of supplementation needed to shift 90% of participants to consume above the estimated average requirement and keep 90% below the tolerable upper limit. We identified products in the Dietary Supplement Label Database providing these target doses of supplementation. ResultsThe target dose for supplementation was ≥198 mcg retinol activity equivalents of total vitamin A (with ≤2063 mcg preformed retinol); 7–91 mcg vitamin D; 169–720 mcg dietary folate equivalents of folic acid; 383–943 mg calcium; 13–22 mg iron; and ≥59 mg ω-3 FAs. Out of 20,547 dietary supplements (including 421 prenatal products), 69 products (33 prenatal) contained all 6 nutrients; 7 products (2 prenatal) contained target doses for 5 nutrients. Only 1 product (not a prenatal) contained target doses for all 6 nutrients, but it currently costs ∼USD200/mo and requires 7 tablets per daily serving. ConclusionsAlmost no US dietary supplements provide key nutrients in the doses needed for pregnant women. Affordable and convenient products that fill the gap between food-based intake and estimated requirements of pregnancy without inducing excess intake are needed to support pregnant women and their offspring. Am J Clin Nutr 20XX;xx:xx–xx.

Reduced methionine synthase expression results in uracil accumulation in mitochondrial DNA and impaired oxidative capacity.

Adequate thymidylate [deoxythymidine monophosphate (dTMP) or the "T" base in DNA] levels are essential for stability of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Folate and vitamin B12 (B12) are essential cofactors in folate-mediated one-carbon metabolism (FOCM), a metabolic network which supports synthesis of nucleotides (including dTMP) and methionine. Perturbations in FOCM impair dTMP synthesis, causing misincorporation of uracil (or a "U" base) into DNA. During B12 deficiency, cellular folate accumulates as 5-methyltetrahdryfolate (5-methyl-THF), limiting nucleotide synthesis. The purpose of this study was to determine how reduced levels of the B12-dpendent enzyme methionine synthase (MTR) and dietary folate interact to affect mtDNA integrity and mitochondrial function in mouse liver. Folate accumulation, uracil levels, mtDNA content, and oxidative phosphorylation capacity were measured in male Mtr+/+ and Mtr+/- mice weaned onto either a folate-sufficient control (C) diet (2 mg/kg folic acid) or a folate-deficient (FD) diet (lacking folic acid) for 7 weeks. Mtr heterozygosity led to increased liver 5-methyl-THF levels. Mtr+/- mice consuming the C diet also exhibited a 40-fold increase in uracil in liver mtDNA. Mtr+/- mice consuming the FD diet exhibited less uracil accumulation in liver mtDNA as compared to Mtr+/+ mice consuming the FD diet. Furthermore, Mtr+/- mice exhibited 25% lower liver mtDNA content and a 20% lower maximal oxygen consumption rates. Impairments in mitochondrial FOCM are known to lead to increased uracil in mtDNA. This study demonstrates that impaired cytosolic dTMP synthesis, induced by decreased Mtr expression, also leads to increased uracil in mtDNA.

Long-term dietary folic acid supplementation attenuated aging-induced hippocampus atrophy and promoted glucose uptake in 25-month-old rats with cognitive decline

The brain has high energy demand making it sensitive to changes in energy fuel supply. Aging shrinks brain volume, decreases glucose uptake availability of the brain, and finally, causes cognitive dysfunction. Folic acid supplementation delayed cognitive decline and neurodegeneration. However, whether folic acid affects brain energy metabolism and structural changes is unclear. The study aimed to determine if long-term dietary folic acid supplementation could alleviate age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in Sprague-Dawley (SD) rats. According to folic acid levels in diet, 3-months old male SD rats were randomly divided into four intervention groups for 22 months in equal numbers: folic acid-deficient diet (FA-D) group, folic acid-normal diet (FA-N) group, low folic acid-supplemented diet (FA-L) group, and high folic acid-supplemented diet (FA-H) group. The results showed that serum folate concentrations decreased and serum homocysteine (Hcy) concentrations increased with age, and dietary folic acid supplementation increased serum folate concentrations and decreased Hcy concentrations at 11, 18, and 22 months of intervention. Dietary folic acid supplementation attenuated aging-induced hippocampus atrophy, which was showed by higher fractional anisotropy and lower mean diffusivity in the hippocampus, increased brain 18F-Fluorodeoxyglucose (18F-FDG) uptake, then stimulated neuronal survival, and alleviated age-related cognitive decline in SD rats. In conclusion, long-term dietary folic acid supplementation alleviated age-related cognitive decline by attenuating hippocampus atrophy and promoting brain glucose uptake in SD rats.

Dietary Folate Deficiency Promotes Lactate Metabolic Disorders to Sensitize Lung Cancer Metastasis through MTOR-Signaling-Mediated Druggable Oncotargets

Lactate metabolism plays a pivotal role in cancers but is often overlooked in lung cancer (LC). Folate deficiency has been linked to lung cancer development, but its impact on lactate metabolism and cancer malignancy is unclear. To investigate this, mice were fed either a folate-deficient (FD) or control diet and intrapleurally implanted with lung cancer cells pre-exposed to FD growth medium. Results showed that FD promoted lactate over-production and the formation of tumor oncospheroids (LCSs) with increased metastatic, migration, and invasion potential. Mice implanted with these cells and fed an FD diet developed hyperlactatemia in blood and lungs. This coincided with increased expression of hexokinase 2 (HK2), lactate dehydrogenase (LDH), and decreased expression of pyruvate dehydrogenase (PDH). Pre-treatment of the FD-LCS-implanted mice with the mTORC1 inhibitor, rapamycin, and the anti-metabolic drug metformin abolished FD/LCS-activated mTORC1 and its targets including HIF1α, HK2, LDH, and monocarboxylate transporters (MCT1 and MCT4), which coincided with the reduction in lactate disorders and prevention of LC metastasis. The findings suggest that dietary FD promotes lactate metabolic disorders that sensitize lung cancer metastasis through mTOR-signaling-mediated targets.

Nutritional impact of excluding red meat from the Canadian diet

The objective of the study was to examine differences in nutrient intake between consumers and non-consumers of red meat and to assess nutritional adequacy of consumers relative to Recommended Daily Allowance (RDA) in Canada. Matching estimators were used to identify differences in nutrient intake between the two groups. Statistically significant differences were observed in nutrient intake between red meat consumers and non-consumers, including lower daily intake of protein, riboflavin, niacin, vitamin D, and zinc and a higher daily intake of dietary fiber, folate, and magnesium among Canadians who did not consume red meat. Further, red meat consumers and non-consumers had nutrient intakes below RDA for dietary energy, fiber, and calcium. While individuals who did not consume red meat were at increased risk of calcium, vitamin D, energy, and potassium inadequacy, those who consumed red meat were at increased risk of dietary fiber, vitamin A, and magnesium inadequacy.

Folate, vitamin B6, and vitamin B12 intakes are negatively associated with the prevalence of hypertension: A national population-based study

We hypothesized that the prevalence of hypertension is related to B-vitamin intake in the general population, but it has not been sufficiently studied. This study aimed to investigate the intakes of dietary folate, vitamin B6, and vitamin B12 concerning hypertension in US adults. A total of 55 569 adults from National Health and Nutrition Examination Survey III and 1999–2014 were included in this study. Nutrient intake was collected from subjects through one or two 24-hour dietary reviews. Multiple logistic regression models were used to examine the relationship between these nutrient intakes and hypertension. Among male participants, dietary folate, vitamin B6, and vitamin B12 intakes were significantly and negatively associated with the prevalence of hypertension, with multivariate-adjusted odds ratios (ORs) of 0.61 (95% confidence interval [CI], 0.55–0.68), 0.65 (95% CI, 0.59–0.72), and 0.84 (95% CI, 0.75–0.95) for the highest quartile group compared with the lowest group. Results were similar for female participants, with multivariate-adjusted ORs of 0.63 (95% CI, 0.57–0.71), 0.60 (95% CI, 0.53–0.66), and 0.87 (95% CI, 0.77–0.98) for the highest quartile group. Moreover, there was a linear trend (Ptrend < .001) in both men and women that the prevalence of hypertension tended to decrease with increased intake of folate, vitamin B6, and vitamin B12; however, the decreases above the third quartile were negligible. Dietary folate, vitamin B6, and vitamin B12 were significantly associated negatively with hypertension, indicating that these nutrients might have a protective effect against hypertension in United States adults.

Current Consumption of Traditional Cowpea-Based Dishes in South Benin Contributes to at Least 30% of the Recommended Intake of Dietary Fibre, Folate, and Magnesium.

Regular consumption of legumes is recommended worldwide for its environmental and health benefits. Cowpea, the most frequently consumed pulse in West African countries, is rich in nutrients and health-promoting bioactive compounds. A one-week retrospective food frequency questionnaire was used to estimate the contribution of the cowpea-based dishes to the recommended nutrient intake (RNI), based on their consumption frequency, intake, and nutritional composition. Participants were 1217 adults (19-65 years) from three urban or rural areas in southern Benin. Out of all respondents, 98% reported that they usually consumed cowpea-based dishes. The mean consumption frequency was 0.1 to 2.4 times/week, depending on the type of cowpea-based dish. The mean amount consumed was 71 g and 58 g of seeds/adult/day in urban and rural areas respectively. The mean daily contribution of cowpea-based dishes to RNI was 15% for energy, 42% for fibre, 37% for magnesium, 30% for folate, 26% for protein, and just above 15% for zinc and potassium. Thus, such regular cowpea consumption should be maintained.

The associations of dietary folate and serum folate with lipid profiles: findings from the national health and nutrition examination survey 2011–2016

BackgroundFolate is considered to be related to lipid metabolism. With the increasing numbers of folic acid fortification nations, the associations of dietary folate and serum folate with lipid profiles deserve more attention and are worth further study.MethodsUS adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) were evaluated. Participants taking folic acid supplements were excluded. The multivariate linear regression model and smooth curve fitting were applied to assess the associations. The segmented regression model was employed to examine the threshold effect of nonlinear relationships.ResultsOur cross-sectional study included 3706 participants in total. There was a negative relationship between serum folate (log transformed) and triglycerides (β = –0.223, 95% CI: –0.337, –0.110) and low-density lipoprotein cholesterol (LDL-C) (β = –0.152, 95% CI: –0.296, –0.007) and a positive relationship between serum folate (log transformed) and high-density lipoprotein cholesterol (HDL-C) (β = 0.090, 95% CI: 0.033,0.146). There was a negative association between dietary folate (log transformed) and total cholesterol (TC) (β = –0.299, 95% CI: –0.465, –0.134) and LDL-C (β = –0.266, 95% CI: –0.409, –0.123). A nonlinear relationship was found between dietary folate (log transformed) and HDL-C. Threshold effect analysis showed that the inflection point was 377.57 ug. Within the inflection point, the β-coefficient of HDL-C was 0.105 (95% CI: 0.018, 0.192); beyond the inflection point, there was no relationship (β = –0.067, 95% CI: –0.162, 0.028).ConclusionsOptimal dietary folate and high serum folate were associated with favorable lipid profiles. Dietary folate, in the recommended 300–400 ug/d, had a beneficial effect on improving lipid profiles.

Controlled Dietary Folate Affects Folate Status in Nonpregnant Women

In a study designed to estimate the requirement for dietary folate in nonpregnant women, 17 women (21–27 y) consumed 200, 300, or 400 µg/d of total folate for 70 d which was provided by low folate conventional foods (30 µg) plus supplemental folic acid. Group means for initial serum and erythrocyte folate and plasma homocysteine concentrations were not significantly different. Serum and erythrocyte folate decreased relative to the initial value in the 200 µg/d group (43.4 ± 12.1%, 13.6 ± 16.6%, respectively; mean ± SD), in contrast to an increase in the 400 µg/d group (16.8 ± 52.0%, 10.2 ± 18.5%, respectively). The final serum folate in the 200 and 300 µg/d groups (6.4 ± 0.8 nmol/L, 7.3 ± 1.1 nmol/L, respectively) was significantly lower than that of the 400 µg/d group (14.3 ± 2.0 nmol/L), with evidence in the 200 µg/d and 300 µg/d groups of low (<6.8 nmol/L) serum folate concentrations. Differences in final erythrocyte folate did not reach statistical significance, although low values (<362 nmol/L) were frequent in subjects with 200 µg/d intake. In the 200 µg/d group, plasma homocysteine was negatively correlated with serum and erythrocyte folate, and final mean plasma homocysteine (12.6 ± 1.7 µmol/L) was significantly higher than that of the 300 or 400 µg/d groups. Elevated plasma homocysteine levels (>16 µmol/L) were observed in the 200 µg/d group only. Data from this study indicate that 200 µg/d of folate was not sufficient to maintain folate status of these women and suggest that the current RDA of 180 µg/d may not be adequate to meet the dietary folate intake needs of nonpregnant women.

Associations between Folate and Alcohol Consumption with Colorectal Tumor Ki67 Expression in the Southern Community Cohort Study

Folate is hypothesized to accelerate cell proliferation in colorectal cancer (CRC) by supporting DNA synthesis, while alcohol is also linked to gastrointestinal epithelial proliferation, despite biological antagonism of folate. We report associations between folate and alcohol consumption with the proliferation marker Ki67 in CRC tumors from the Southern Community Cohort Study. Tumor samples were obtained from formalin-fixed paraffin-embedded tissue blocks. The percentage of cells expressing Ki67 was measured immunohistochemically. Exposures were assessed via questionnaire pre-diagnosis. Associations were assessed via linear regression. In 248 cases (40–78 years), neither dietary folate, folic acid supplements, nor total folate intake were associated with Ki67. Folic acid supplement use was associated with Ki67 in distal/rectal tumors (β [95% confidence interval]: 7.5 [1.2-13.8], p = .02) but not proximal tumors (-1.4 [-7.1-4.3], p=.62). A positive trend for total folate was observed for distal/rectal tumors (1.6 [0.0-3.3] per 200 μcg, p-trend=.05). Heavy drinking (women: ≥1 drink/day, men: ≥2 drinks/day) was associated with higher Ki67 (6.4 [1.0-11.9], vs. nondrinkers, p=.02), especially for distal/rectal tumors (10.4 [1.6-19.1], p=.02). Negative interaction between alcohol, total folate was observed for distal/rectal tumors (p-interaction=.06). Modest associations between folate, alcohol consumption and distal/rectal tumor Ki67 expression suggest accelerated proliferation, consistent with folate’s role in DNA synthesis.

Dietary folic acid addition reduces abdominal fat deposition mediated by alterations in gut microbiota and SCFA production in broilers

Intensive selective breeding for high growth rate and body weight cause excess abdominal fat in broilers. Gut microbiota and folic acid were reported to regulate lipid metabolism. A total of 210 one-day-old broilers were divided into the control (folic acid at 1.3mg/kg) and folic acid groups (folic acid at 13mg/kg) to illustrate the effects of folic acid on growth performance, abdominal fat deposition, and gut microbiota, and the experiment lasted 28d. Results revealed that dietary folic acid addition decreased abdominal fat percentage (P<0.05) and down-regulated genes expression related to cell proliferation and differentiation in abdominal fat including IGF1, EGF, C/EBPα, PPARγ, PLIN1, FABP4 and PCNA (P<0.05). Folic acid addition decreased caecal Firmicutes-to-Bacteroidetes ratio (P<0.01) and increased the proportions of Alistipes, Oscillospira, Ruminococcus, Clostridium, Dehalobacterium and Parabacteroides (P<0.05). Caecal acetic acid, and propionic acid contents were found to be higher under folic acid treatment (P<0.05), which were negatively related to genes expression associated with adipocyte proliferation and differentiation (P<0.05). Ruminococcus was positively correlated with caecal acetic acid content, and the same phenomenon was detected between propionic acid and Oscillospira and Ruminococcus (P<0.05). Acetic acid and Oscillospira were identified to be negatively associated with abdominal fat percentage (P<0.05). In conclusion, our data demonstrated that dietary supplementation of folic acid reduced fat deposition in broilers by inhibiting abdominal adipocyte proliferation and differentiation, which might be mediated by changes in gut microbiota and short chain fatty acid production.

Infant blood concentrations of folate markers and catabolites are modified by 5,10-methylenetetrahydrofolate reductase C677T genotype and dietary folate source

BackgroundFolate intake and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene may affect folate metabolism in infants. ObjectivesWe investigated the association between infant’s MTHFR C677T genotype, the dietary folate source, and concentrations of folate markers in the blood. MethodsWe studied 110 breastfed infants (reference) and 182 infants who were randomly assigned to receive infant formulas enriched with either 78 μg folic acid or 81 μg (6S)-5-methyltetrahydrofolate (5-MTHF) per 100 g milk powder for 12 wk. The blood samples were available at the ages of <1 mo (baseline) and 16 wk. MTHFR genotype and concentrations of folate markers and catabolites [i.e., para-aminobenzoylglutamate (pABG)] were analyzed. ResultsAt baseline, carriers of the TT genotype (vs. CC) had lower mean (SD) concentrations (all in nmol/L) of red blood cell (RBC) folate [1194 (507) vs. 1440 (521), P = 0.033) and plasma pABG [5.7 (4.9) vs. 12.5 (8.1), P < 0.001] but higher plasma 5-MTHF [33.9 (16.8) vs. 24.0 (12.6), P < 0.001]. Irrespective of the genotype, infant formula with 5-MTHF (vs. folic acid) caused a significant increase in RBC folate concentration [1278 (466) vs. 947 (552), P < 0.001]. In breastfed infants, plasma concentrations of 5-MTHF and pABG increased significantly by 7.7 (20.5) and 6.4 (10.5), respectively, from baseline to 16 wk. Infant formula that complies with the present EU legislation for folate intake increased RBC folate and plasma pABG concentrations at 16 wk (P < 0.001) than formula-fed infants. At 16 wk, plasma pABG concentrations remained ∼50% lower in carriers of the TT (vs. the CC) genotype among all feeding groups. ConclusionsFolate intake from infant formula according to the present EU legislation increased RBC folate and plasma pABG concentrations in infants to a greater extent than breastfeeding, particularly in carriers of the TT genotype. However, this intake did not completely abolish the between-genotype differences in pABG. Whether these differences have any clinical relevance, however, remains unclear. This trial was registered at clinicaltrials.gov as NCT02437721.

Association of Folic Acid Supplementation, Dietary Folate Intake and Serum Folate Levels with Risk of Gestational Diabetes Mellitus: A Matched Case-Control Study.

Periconceptional folate supplementation is prevalent, raising concerns about possible side effects. The aim of this study was to investigate the associations of folic acid supplementation, dietary folate, serum folate with gestational diabetes mellitus (GDM) risk. In this matched case-control study, 81 pregnant women with GDM (cases) and 81 pregnant women with non-GDM (controls) were identified through age difference (≤3 y) and parity (Both primipara or multipara women) matching, and serum folate levels were measured during the GDM screening (24-28 gestational wk). Folic acid supplementation and dietary folate intake from three months prepregnancy through midpregnancy were assessed using a self-reported questionnaire and food frequency questionnaire. Multivariate binary logistic regression models were used to evaluate the association between folate and GDM. After adjusting for confounding factors, we observed that compared with folic acid supplementation dose ≤400 μg/d, pregnancies without folic acid supplementation and supplemental dose >800 μg/d were associated with GDM risk (adjusted odds ratio=7.25, 95% confidence interval: 1.34-39.36; adjusted odds ratio=4.20, 95% confidence interval: 1.03-17.22), while no significant association with a 400-800 μg/d dose of folic acid supplementation and GDM. Compared with folic acid supplementation dose ≤24 wk, pregnancies without folic acid supplementation were associated with GDM risk (adjusted odds ratio=6.70, 95% confidence interval: 1.22-36.77), while no significant association with folic acid supplementation dose >24 wk and GDM. No significant association of dietary folate and serum folate with GDM was found. No or a higher dose of folic acid supplementation would increase GDM risk and a dose of <800 μg/d is the safe dose.

In Vivo Methylation Capacity Is Not Impaired in Healthy Men during Short-Term Dietary Folate and Methyl Group Restriction

Ten healthy adult men were fed a diet low in folate and exogenous methyl groups to study the effects on in vivo methylation capability. The men were housed in a metabolic unit for the entire 108 d of the study. After a 9-d baseline period (Period 1), the men were fed a soy-product-amino acid defined diet for 45 d, which provided 25 µg/d of folate for 30 d (Period 2) and, with a folate supplement, 99 µg/d for 15 d (Period 3). During Period 2 and Period 3, the low methionine and choline diet was supplemented with methionine for half the subjects to vary the dietary methyl group intake. The periods were then repeated over the next 54 d (Periods 4–6), with a crossover of methionine intakes in Period 5 and Period 6. A 1-g oral dose of nicotinamide was given at the end of each period and methylated urine metabolites determined. Other measures related to in vivo methylation capability included urine creatinine, and plasma and urine carnitine. Even with moderate folate depletion, none of these measures was decreased by low methionine and choline intakes. Plasma methionine concentrations were unchanged throughout. Limiting exogenous methyl group intake by restricting dietary methionine and choline did not impair in vivo methylation capabilities for the variables tested, even at low folate intake.

Association between folate and non-alcoholic fatty liver disease among US adults: a nationwide cross-sectional analysis.

Association between folate and non-alcoholic fatty liver disease among US adults: a nationwide cross-sectional analysis.

Transgenerational impact of grand-paternal lifetime exposures to both folic acid deficiency and supplementation on genome-wide DNA methylation in male germ cells.

DNA methylation (DNAme) erasure and reacquisition occur during prenatal male germ cell development; some further remodeling takes place after birth during spermatogenesis. Environmental insults during germline epigenetic reprogramming may affect DNAme, presenting a potential mechanism for transmission of environmental exposures across multiple generations. We investigated how germ cell DNAme is impacted by lifetime exposures to diets containing either low or high, clinically relevant, levels of the methyl donor folic acid and whether resulting DNAme alterations were inherited in germ cells of male offspring of subsequent generations. Female mice were placed on a control (FCD), 7-fold folic acid deficient (7FD) or10-to20-fold supplemented (10FS and 20FS) diet before and during pregnancy. Resulting F1 litters were weaned on the respective diets. F2 and F3 males received control diets. Genome-wide DNAme at cytosines (within CpG sites) was assessed in F1 spermatogonia, and in F1, F2 and F3 sperm. In F1 germ cells, a greater number of differentially methylated cytosines (DMCs) were observed in spermatogonia as compared with F1 sperm for all folic acid diets. DMCs were lower in number in F2 versus F1 sperm, while an unexpected increase was found in F3 sperm. DMCs were predominantly hypomethylated, with genes in neurodevelopmental pathways commonly affected in F1, F2 and F3 male germ cells. While no DMCs were found to be significantly inherited inter- or transgenerationally, we observed over-representation of repetitive elements, particularly young longinterspersednuclearelements(LINEs). These results suggest that the prenatal window is the time most susceptible to folate-induced alterations in sperm DNAme in male germ cells. Altered methylation of specific sites in F1 germ cells was not present in later generations. However, the presence of DNAme perturbations in the sperm of males of the F2 and F3 generations suggests that epigenetic inheritance mechanisms other than DNAme may have been impacted by the folate diet exposure of F1 germ cells.

Assessing the nutritional content and adequacy of food parcels among vulnerable Lebanese during a double crisis: COVID-19 pandemic and an economic meltdown.

This study aimed to explore the nutritional content and quality of food parcels distributed in Lebanon and assess their adherence to dietary guidelines during the COVID-19 pandemic and an unprecedented economic crisis. Cross-sectional study (June-July 2020); phone survey (thirty items). Lebanon. Food parcel providers (FPP; n 72) involved in food parcel distribution (FPD), mainly to Lebanese households. FPP included international non-governmental organizations (INGO) (n 3), local non-governmental organizations (n 45) and personal initiatives (n 24). Overall, low adherence to the World Food Programme (WFP) food parcel guidelines were observed among FPP for specific food items, including vegetables, fish, legumes and cereals, whereas salt content significantly surpassed the guidelines (all P-values <0·001). On average, a food parcel provided 608·4 ± 55 kcal/d/person. The greatest contributors to total energy intake (TE) in the food parcel were carbohydrates (46·4 %) and fats (46·8 %), while protein contributed to 7 %TE. In addition, %TE from fats and sugars significantly surpassed the dietary reference intakes (DRI) for a single person per d (134-234 % and 185 % of DRI, respectively, P-values <0·001). Only 10-15 % of daily needs for key micronutrients, including Fe, Zn, thiamin, riboflavin and dietary folate, were met through the food parcels. Adequate food safety and hygiene practices were reported among FPP, yet dramatic changes in food costs due to overlapping crises affected the quality and quantity of food in parcels. Findings highlight the need to improve the nutritional content of food parcels and adherence to dietary guidelines to alleviate food and nutrition insecurity while preventing diet-related diseases among vulnerable beneficiaries in Lebanon.

Association between dietary folate intake and cognitive impairment in older US adults: National Health and Nutrition Examination Survey

ObjectiveTo determine the association between dietary folate intake and low cognitive performance in older adults. MethodsIn this cross-sectional observational study, 2011-2014 data from the 2010 National Health and Nutrition Examination Survey, including 2,524 adults aged 60 years and older, included 24-hour dietary intakes. Total folic acid intake was calculated as the sum of folic acid supplements and dietary folic acid. Cognitive function was assessed using three tests. The association between folate intake and cognitive function was assessed using a multivariate conditional logistic regression model. Results2524 participants from two survey cycles (2011–2014) in the NHANES aged 60 years and over. In the multivariate logistic regression, the OR of developing folate was 0.96 (95% CI: 0.94∼0.98) in participants with Z test. Folate intake was negatively associated with cognitive function. Compared with Q1, Q4(≥ 616.3mg/day) in the AFT and DSST tests reduced the risk of cognitive impairment by 31% (OR = 0.69, 95% CI: 0.52-0.93) and 44% (OR = 0.56). 95% confidence interval: 0.44-0.7). In the comprehensive evaluation of IR and AFT scores, the association between dietary folate intake and low cognitive performance in US adults is linear. We also found a significant interaction between gender and cognitive ability (P value for the interaction was 0.021). ConclusionsDietary intake of folic acid may be inversely associated with cognitive impairment. The DSST study found an L-shaped association between dietary folate intake and cognitive decline in US adults, with an inflection point of approximately 510,383 mg/day.