Plasma Folate Levels Research Articles

Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women

ObjectivesRoux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastrointestinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mechanism contributing to its postoperative deficiency. MethodsBiopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. ResultsCompared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations correlated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). ConclusionThe present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcriptomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.

Vitamin B6 Levels and Impaired Folate Status but Not Vitamin B12 Associated with Low Birth Weight: Results from the MAASTHI Birth Cohort in South India.

Vitamins B12 and B6 and folate are known to have implications for pregnancy outcomes. We aimed to describe B6, B12, and folate status in pregnancy and investigate their associations with low birth weight and preterm delivery in mothers recruited from public hospitals in urban Bengaluru. Pregnant women between 18 and 45 years were included in the MAASTHI prospective cohort study. Each participant's age, socioeconomic status, and anthropometry were recorded during baseline and followed up after delivery. Blood samples were collected between the 24th and 32nd weeks of gestation and stored at -80° for analysis. B6, B12, folate, homocysteine, and methylmalonic acid (MMA) levels were analyzed in the stored samples. We found low plasma vitamin B12, folate, and B6 levels in 48.5%, 42.0%, and 10.4% of the women (n = 230), respectively. Elevated MMA and homocysteine were observed among 73.6% and 6.1% of the women, respectively. We found B6 levels were significantly associated with birth weight (β(SE) -0.002(0.0), p = 0.001) after adjusting for age, parity, adiposity, gestational diabetes, and socioeconomic status of the mother. Those with impaired folate deficiency were twice at risk (AOR 1.95 (1.29, 3.07), p = 0.002) of low birth weight. Vitamin B6 levels and impaired folate status were associated with low birth weight in the MAASTHI birth cohort.

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It has been established that peroxidation, inflammatory processes, and organ damage are involved in the pathogenesis of methanol intoxication. Research has shown that using hyperbaric oxygen reduces oxidative stress, inflammation, and tissue damage. In this research, it was investigated how hyperbaric oxygen therapy affected methanol-induced peroxidation and retinal damage in rats. The animals were classified into six categories (n = 8): control group (C), nitrous oxide (N2O) treated group, hyperbaric oxygen (HBO) treated group, methanol (MeOH) treated group, N2O+methanol treated group (N2O+MeOH) and N2O+methanol+hyperbaric oxygen (N2O+MeOH+HBO) treated group. Folate deficiency was started with N2O, four hours before the starting dose (4g/kg) of methanol. The rats were given a methanol maintenance dose (2g/kg, i.p) 24h and 48h after the starting dose. After each methanol administration, rats were given HBO (2 ATA) for 1 hour. Methanol intoxication decreased plasma folic acid levels while increasing formate levels and oxidative stress index and it caused a decrease in the amount of the retinal ganglion cells and thinned the total retinal thickness in folate-deficient mice. HBO treatment reduced the oxidative stress index but did not adequately improve retinal healing. Our findings indicate that the HBO treatment used to treat retinal damage in methanol poisoning was ineffective. However, increasing the duration of HBO therapy may be effective in preventing methanol-induced retinal damage

Methylenetetrahydrofolate reductase polymorphisms and elevated plasma homocysteine levels in small vessel disease.

Despite its public health importance, the causes of small vessel disease (SVD) are not fully understood. The presence of SVD in monogenic twins indicates the involvement of genetic factors in the pathogenesis of this disease. The purpose of this study was to investigate the association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with SVD risk. Patients with SVD and matched controls were recruited from Tianjin Union Medical Center and Tianjin Huanhu Hospital. Clinical and laboratory data were collected. Plasma total homocysteine (tHcy) and folate levels were measured, and MTHFR rs1801133 (C677T) and rs1801131 (A1298C) single-nucleotide polymorphisms were genotyped. We analyzed potential associations among SVD and MTHFR polymorphisms, tHcy, and folate levels. Patients with SVD displayed significantly decreased plasma folate levels (Z=-3.537, p<.001) and increased tHcy levels (Z=4.910, p<.001) compared with controls. Significantly different plasma tHcy levels were associated with rs1801133 (χ2 =6.664, p=.036), and post hoc analysis indicated higher plasma tHcy levels in individuals carrying the TT allele compared with levels in those carrying the TC allele (Z=2.478, p=.013). No significant differences in tHcy levels were observed for rs1801131 alleles. The genotype and allele frequencies of rs1801133 were different between SVD and control groups (χ2 =9.378, p=.009). There was no significant difference in distributions of rs1801131 genotypes between the two groups, and multivariable logistic regression analysis showed that rs1801131 and rs1801133 were not significantly associated with the risk of SVD. Our study indicates that an elevated plasma tHcy level is independently associated with the development of SVD. Although MTHFR rs1801133 is linked to increased plasma homocysteine (Hcy) levels, it is not a risk factor for SVD. rs1801131 is not related to Hcy levels or SVD risk.

Exploiting Underutilised crops

Exploiting Underutilised crops

Homocysteine exchange across skeletal muscle in patients with chronic kidney disease.

Sites and mechanisms regulating the supply of homocysteine (Hcy) to the circulation are unexplored in humans. We studied the exchange of Hcy across the forearm in CKD patients (n=17, eGFR 20 ± 2ml/min), in hemodialysis (HD)-treated patients (n=14) and controls (n=9). Arterial Hcy was ~ 2.5 folds increased in CKD and HD patients (p < 0.05-0.03 vs. controls). Both in controls and in patients Hcy levels in the deep forearm vein were consistently greater (+~7%, p < 0.05-0.01) than the corresponding arterial levels, indicating the occurrence of Hcy release from muscle. The release of Hcy from the forearm was similar among groups. In all groups arterial Hcy varied with its release from muscle (p < 0.03-0.02), suggesting that muscle plays an important role on plasma Hcy levels. Forearm Hcy release was inversely related to folate plasma level in all study groups but neither to vitamin B12 and IL-6 levels nor to muscle protein net balance. These data indicate that the release of Hcy from peripheral tissue metabolism plays a major role in influencing its Hcy plasma levels in humans and patients with CKD, and that folate is a major determinant of Hcy release.

Possible Combined Effects of Plasma Folate Levels, Global DNA Methylation, and Blood Cadmium Concentrations on Renal Cell Carcinoma.

Epigenetic effects of environmental pollutants may be related to carcinogenesis. This study aimed to explore the association between the global DNA methylation marker: 5-methyl-2-deoxycytidine (5mdC) and renal cell carcinoma (RCC), and further investigated whether plasma folate and vitamin B12 levels and 5mdC modified the association between blood cadmium concentrations and RCC. We recruited 174 RCC patients and 673 non-RCC controls. Blood cadmium concentrations, plasma folate and vitamin B12 levels were measured. The amount of 5mdC in the DNA sample was expressed as percentages of the total cytosine content. An increase of 5mdC (%) and plasma folate and vitamin B12 levels were associated with decreasing odds ratio (OR) of RCC. Although plasma folate levels were not directly associated with 5mdC (%), a combined effect was observed with the odds of low plasma folate levels and low 5mdC (%) were greater among RCC patients compared to controls (OR (95% confidence interval, CI) = 11.86 (5.27-26.65)). Additionally, we observed that the odds of low plasma folate and high blood cadmium levels were greater among RCC patients than in controls (OR (95% CI): 8.15 (1.39-7.13)). This study provides suggestive evidence that plasma folate levels may modify the associations between 5mdC (%) or blood cadmium concentrations and RCC.

Ассоциация полиморфизма генов ферментов фолатного цикла и риска развития осложнений беременности

Polymorphisms in the genes of folate cycle enzymes are considered as the main cause of reduced plasma levels of folate and vitamin B12, impaired homocysteine metabolism, and the development of pregnancy complications. Objective. To study the association of polymorphism in folate cycle enzyme genes, MTHFR-677C&gt;T, MTHFR-1298A&gt;C, MTR‑2756A&gt;G, MTRR-66A&gt;G, with the risk of pregnancy complications. Patients and methods. The study was conducted in outpatient settings and included 96 women aged between 20 and 40 years with a history of 1 to 3 pregnancies who applied for preconception care. Results. When examining the association between the presence of a complicated history in this group of women and folate cycle enzyme gene polymorphisms using the Fisher test, a statistically significant correlation was detected for MTHFR-677C&gt;T, MTHFR-1298A&gt;C, MTR-2756A&gt;G, and MTRR-66A&gt;G. Conclusion. The presence/absence of genetic polymorphisms of folate cycle enzymes should be considered when predicting the risks of pregnancy complications and developing a personalized preconception care program to select individual regimens of folate supplementation. Key words: genes, folate cycle, polymorphism, folates, pregnancy

Vitamin B12 deficiency induces glucose intolerance, delays peak insulin levels and promotes ketogenesis in female rats.

Vitamin B12 (B12) deficiency is common among individuals with diabetes mellitus, but it is unknown if B12 deficiency contributes to impaired glucose homeostasis in this disorder. Female Sprague-Dawley rats were assigned to a control or B12-deficient diet for 4 weeks. Intraperitoneal glucose tolerance tests were performed after 25 days, and blood and liver samples were collected for metabolic profiling. B12 deficiency resulted in a prediabetic-like phenotype characterised by glucose intolerance, a delayed peak in plasma insulin levels following a glucose challenge and increased ketogenesis. We attributed increased ketogenesis to reduced liver anaplerosis, which limited the availability of the TCA cycle intermediates citrate, succinate and succinyl-CoA. This was associated with increased Mut mRNA levels and citrate synthase activity in the liver. One-carbon metabolite levels were altered in plasma and the liver, which was linked to reduced methylation capacity, altered amino acid levels and elevated Slc7a5 mRNA expression. Plasma folate and biotin levels were reduced, as were the majority of B vitamins in the liver. Changes in these B12-dependent processes and reduced B vitamin amounts likely contributed to deficits in glucose handling. Our findings highlight that B12 deficiency may promote the development of metabolic disorders like diabetes mellitus and emphasise the importance of adequate B12 intake for metabolic health.

Maternal folate status and placental vascular malperfusion: Findings from a high-risk US minority birth cohort

IntroductionMaternal folate deficiency was associated with preeclampsia (PE) and PE was associated with placental maternal vascular malperfusion (MVM). However, no study has examined the association of maternal folate status with placental MVM. MethodsWe examined the association of maternal folate status and placental MVM in the Boston Birth Cohort. Primary exposure variables were maternal self-reported multivitamin supplement (<2, 3–5, >5 times/week) per trimester; and plasma folate levels (nmol/L) after birth. Primary outcome was presence/absence of placental MVM defined by the Amsterdam Placental Workshop Group standard classification. Covariates included demographics, chronic hypertension, clinically diagnosed PE, eclampsia and HELLP syndrome, gestational and pre-gestational diabetes, overweight/obesity, maternal cigarette smoking and alcohol use. Associations between folate and placental MVM were evaluated using multivariate logistic regressions. ResultsOf 3001 mothers in this study, 18.8% of mothers had PE, 37.5% had MVM. Mothers with the lowest self-reported frequency of folate intake had the highest risk of MVM (OR 1.45, 95% CI 1.03–2.05), after adjusting for the covariates. Consistently, among a subset of 939 mothers with plasma folate levels, folate insufficiency was associated with increased risk of MVM (OR 1.65, 95% CI 1.03–2.63), after adjusting for the covariables. As expected, mothers with low folate and placental MVM had highest rates of PE compared to those of high folate and no MVM (p < 0.001). DiscussionIn this high-risk birth cohort, low maternal folate status was associated with increased risk of placental MVM. Further investigation should explore the association between folate status, placental findings and the great obstetrical syndrome.

The effect of lactose intolerance on plasma glucose levels and related biochemical parameters

Aim: To determine the effect of lactose intolerance on serum glucose levels and related biochemical parameters in the adult population who refrain from consuming milk and milk products.&#x0D; Material and Method: This retrospective, observational study was conducted in a tertiary care hospital between January 2016 and December 2019 with 296 participants. Plasma glucose, calcium, 25-hydroxyvitamin D3, folate, vitamin B12, thyroid-stimulating hormone (TSH), and ferritin levels were controlled. Patients with positive lactose intolerance test results were accepted as the study group and negative results were accepted as the control group, and data of two groups were compared.&#x0D; Results: Of the total 296 participants 212 (71.7%) were found to have lactose intolerance and 84 (28.3%) were found to be normal. In the lactose intolerant group, blood glucose levels were significantly lower than the control group (5.14±0.53 mmol/L versus 5.47±0.54 mmol/L, p

Evaluation of feeding ruminal-protected folate and cobalt pectinate on growth performance, carcass characteristics and plasma vitamin B12 and folate status in finishing beef steers.

A large pen feedlot study was conducted to evaluate the response of yearling steers fed novel sources of rumen-protected folate (RPFA) and cobalt (cobalt pectinate; Co-PECT) on plasma levels of vitamin B12 and folate, growth performance, and carcass characteristics. A total of 2,100 steers (initial BW = 381 ± 45.2 kg.) were enrolled in the study at the time of randomization with 2,091 steers started on treatment diets following the transition to the finishing diet. A generalized randomized block design with sampling error (GRBD) with two treatments and 15 pen replications per treatment (5 blocks × 6 pens/block; 30 pens total with 70 steers/pen) were evaluated with pen serving as the experimental unit. A control (CON) treatment consisted of the standard finishing diet while the test diet consisted of the standard finishing diet providing 3.0 mg ∙ kg−1 DM of RPFA and 1.0 mg ∙ kg−1 DM total supplemental cobalt with approximately half coming from Co-PECT (TEST). Blood samples were collected from 60 randomly selected steers at study initiation and prior to shipping for plasma B12 and folate measurement. Data were analyzed with the model including fixed effects of treatment, block, and treatment within block interaction. Live growth performance was not affected by treatment; however, carcass-adjusted performance and hot carcass weight were numerically improved by TEST in 3 of the 5 blocks (treatment × within block interaction, P ≤ 0.03) of cattle. Plasma levels for both folic acid and vitamin B12 were extremely low at study initiation and increased over the course of the feeding period. Feeding TEST increased (P < 0.01) plasma B12 levels compared to CON by the completion of the trial; however, mean levels would still be considered marginal. Plasma folate was lower (P < 0.05) in TEST steers at the beginning of the study, with no difference between treatments by the time cattle were shipped. Results suggested that cattle coming into the feedlot may be of low or marginal status in both plasma folate and vitamin B12. While the status of folate and B12 improved in both CON and TEST with days on feed, providing RPFA and Co-PECT further helped improve vitamin B12 status; although, overall levels remained low, which may have affected the overall response to RPFA. Additional research is required to better understand the role of B vitamin supplementation for growing-finishing feedlots and develop methods for assessing the status and improving potential responses.

5-Methyltetrahydrofolate Attenuates Oxidative Stress and Improves Kidney Function in Acute Kidney Injury through Activation of Nrf2 and Antioxidant Defense.

Oxidative stress is a major mediator of adverse outcomes in acute kidney injury (AKI). Deficiency of micronutrients, such as folate, is common in AKI. Our previous study reported that AKI impaired kidney reabsorption of folate and decreased plasma folate level in rats. The present study investigated the effect of 5-methyltetrahydrofolate (5-MTHF), a biologically active form of folate/folic acid, on AKI-impaired kidney function and oxidative stress. Sprague-Dawley rats developed AKI after kidney ischemia (45 min) and reperfusion (24 h). Injection of 5-MTHF (3 µg/kg body weight) improved kidney function and attenuated oxidative stress with a restoration of glutathione and a reduction of lipid peroxidation in the kidney. Injection of 5-MTHF activated transcription factor Nrf2 and increased the expression of glutathione synthesizing enzymes, superoxide dismutase-1 and heme oxygenase-1 in the kidney. Simulated ischemia-reperfusion through hypoxia-reoxygenation increased oxidative stress in proximal tubular cells. Incubation of cells with 5-MTHF alleviated cell injury and increased antioxidant enzyme expression and intracellular glutathione levels. Inhibition of Nrf2 expression through siRNA transfection abolished the effect of 5-MTHF against oxidative stress. These results suggest that low-dose folic acid can improve kidney function through activation of Nrf2 and restoration of antioxidant defence. Micronutrient supplements may improve clinical outcomes in AKI.

Association and mediation analyses among multiple metals exposure, plasma folate, and community-based impaired estimated glomerular filtration rate in central Taiwan

BackgroundChronic kidney disease (CKD) is increasing, with heavy metal exposure an important risk factor. Additionally, the antioxidant folic acid has been studied for reducing blood arsenic levels and related tissue damage. Therefore, we explored the association and mediation effects among various heavy metal levels in blood, plasma folate, other CKD risk factors, and impaired estimated glomerular filtration rate (eGFR).MethodsWe constructed a community-based cross-sectional study from the Human Biomonitoring and Environmental Health Program in central Taiwan. A total of 1643 participants had lived locally for > 5 years, > 40 years old, and completely received health examinations and biospecimen collections. Impaired eGFR was defined as one single eGFR < 60 mL/min/1.73 m2. Plasma folate and metal levels in blood were determined, as well as urinary 8-hydroxy-2′-deoxyguanosine as an oxidative stress marker. Generalized weighted quantile sum (WQS) regression analysis was used to calculate a WQS score, reflecting overall body-burden of multiple metals (arsenic, cadmium, chromium, nickel, and lead) in blood.ResultsImpaired eGFR was identified in 225 participants. Participants with high WQS scores had increased risk of impaired eGFR (odds ratio = 1.67; 95% confidence interval [CI]: 1.34, 2.07). Of five metals, arsenic, lead, and cadmium were weighted highly in impaired eGFR. Participants with high WQS and folate insufficiency (< 6 ng/mL) had 2.38-fold risk of impaired eGFR compared to those with low WQS and high folate (≥6 ng/mL) (95% CI: 1.55, 5.17). Similar increased 4.16-fold risk of impaired eGFR was shown in participants with high WQS and uric acid levels (95% CI: 2.63, 6.58). However, there were no significant WQS–folate (p = 0.87) or WQS–uric acid (p = 0.38) interactions on impaired eGFR risk. As a mediator, uric acid contributed 24% of the association between WQS score and impaired eGFR risk (p < 0.0001). However, no mediation effect of plasma folate was observed.ConclusionWQS analysis could be applied to evaluate the joint effects of multiple metals exposure. High WQS scores may influence impaired eGFR risk through increased uric acid levels. A large-scale and prospective cohort study is necessary to validate these results and demonstrate any causal relationship.

Plasma folate levels in relation to cognitive impairment: a community-based cohort of older adults in China.

Lower plasma level of folate has been associated with an increased risk of age-related cognitive impairment. However, studies that examined this relation have yielded mixed results. We aimed to examine the prospective association of plasma folate level with risk of cognitive impairment in a community-based prospective cohort of older adults in China. This study included 615 participants (mean age: 76.3years) without baseline cognitive impairment from the Rugao Longevity and Ageing Study (RuLAS). We used logistic regression to examine the prospective association between baseline plasma folate and risk of cognitive impairment in the next two years. Fasting blood samples were collected and assayed for plasma folate level at baseline. Cognitive impairment was defined as Hasegawa Dementia Scale (HDS) score ≤ 21.5 points. During two years' follow-up, 20.7% of the participants developed cognitive impairment. After controlled for age, gender, and plasma homocysteine, ahigher level ofplasma folate was associated with lower odds of cognitive impairment. The corresponding odds ratio (OR) with 95% confidence interval was 0.41 (0.19-0.89) comparing participants atextreme quintiles of plasma folate (median level 17.2 vs. 6.3nmol/L). The associations were similar after further adjustment for major demographic and lifestyle factors (OR = 0.42, 0.18-0.98). Moreover, the inverse association was particularlystronger among males (OR = 0.12, 0.03-0.52) but was non-significant among females. Our findings support a potential beneficial role of higher plasma folate levels in cognitive function in older Chinese adults, particularly among males. Future studies with larger sample size and longer follow-up are warranted to confirm these findings and to identify the optimal plasma folate level for cognitive function.

Associations between Plasma Folate and Vitamin B12, Blood Lead, and Bone Mineral Density among Adults and Elderly Who Received a Health Examination.

This study hypothesized that plasma folate and vitamin B12 levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B12, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B12 levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B12 group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Association of plasma folic acid levels with parameters of glutathione metabolism in hypertensive patients with comorbid diseases

Objective. Hypertension (HTN) is characterized by a high incidence of comorbidity. An individual approach to the management of such patientsrequires new markers for differential diagnosis. The pathophysiology of most comorbidities is closely related to endothelial dysfunction triggered by an imbalance in redox processes.The aim of this work is to assess the relationship between plasma level of folic acid (FA) and the state of the redox system of erythrocyte glutathione in patients with HTN and concomitant target organ damage in cardiovascular diseases (HTN + CVD), chronic kidney disease (HTN + CKD) and discirculatory encephalopathy (HTN + DE).Design and methods. We enrolled 93 patients with HTN admitted to the clinics of the Pavlov University, and 30 donors of the reference group. We assessed plasma concentration of folic acid, the content of reduced glutathione (GSH) and the activity of glutathione reductase (GR) in erythrocytes.Results. In HTN patients with the deficiency of FA, a lower content of GSH and activity of GR in erythrocytes were found compared to the HTN patients without deficiency and the reference group. In the groups HTN + CVD and HTN + DE, the GSH level and GR activity correlated with the plasma concentration of FA and were lower in the subgroups with FA deficiency. In subgroups with normal FA content, these parameters did not differ from the reference indicators.Conclusions. The parameters of GSH and GR in patients with HTN + CVD and HTN + DE, but not HTN + CKD, can be considered as potential markers of functional FA deficiency.

DNA methylation signatures in cord blood associated with birthweight are enriched for dmCpGs previously associated with maternal hypertension or pre-eclampsia, smoking and folic acid intake

ABSTRACT Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women’s Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10−8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: −241, −149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10−255), maternal smoking (7.71%, p = 1.50 x 10−57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.

Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4-year longitudinal study.

This was a longitudinal study utilising the Irish Longitudinal Study on Ageing (n 3849 aged ≥ 50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). A score ≥ 9 on the Center for Epidemiological Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. B12 status profiles (pmol/l) were defined as < 185, deficient low; 185 to < 258, low normal; > 258-601, normal and > 601 high. Folate status profiles (nmol/l) were defined as ≤ 10·0, deficient low; > 10-23·0, low normal; > 23·0-45·0, normal; >45·0, high. Logistic regression models were used to analyse the longitudinal associations. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms v. non-depressed (folate: 21·4 v. 25·1 nmol/l; P = 0·0003; B12:315·7 v. 335·9 pmol/l; P = 0·0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression 4 years later (OR 1·51, 95 % CI 1·01, 2·27, P = 0·043). This finding remained robust after controlling for relevant covariates. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51 % increased likelihood of developing depressive symptoms over 4 years. The findings highlight the need to further explore the low-cost benefits of optimising vitamin B12 status for depression in older adults.