Folate Concentrations Research Articles

Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400µg or 800µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age.

A mixture of (6S)-5-methyltetrahydrofolate-calcium salt ((6S)-5-MTHF-Ca) and folic acid (FA) from multimicronutrient supplements may show a dose-dependent effect on serum folate concentrations. The study compares fasting concentrations of serum folate spices after 8 weeks of either 400 or 800µgday-1 of 1:1 folate mixture in 172 nonpregnant women. Serum (6S)-5-MTHF concentrations raise from a mean (SD) of 19.1 (13.4) to 73.9 (19.6) nmolL-1 in the 800µg group and from 17.5 (9.4) to 54.5 (21.1) nmolL-1 in the 400µg group (p < 0.001 within-group changes). The raise in serum (6S)-5-MTHF is stronger in the 800µg compared to the 400µg group (p < 0.001 between-group). The prevalence of FA concentrations ≥0.20nmolL-1 increases between baseline and week 8 in both groups, but is not different between the groups (p = 0.116). The mean percentage of (6S)-5-MTHF of total serum folate increases in both intervention groups, but is not different between the groups at 8 weeks (95.5 (4.1)% versus 94.4 (5.7)%, p = 0.309). Supplementation of multimicronutrients with 800µg folate mix for 8 weeks causes higher serum (6S)-5-MTHF concentrations, but not a higher prevalence of detectable FA compares to 400µg folate.

Synergizing Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus with folic acid for enhanced drought resistance in wheat by metabolites and antioxidants

Drought stress imposes a serious challenge to cultivate wheat, restricting its growth. Drought reduces the capability of plant to uptake essential nutrients. This causes stunted growth, development and yield. Traditional ways to increase wheat growth under drought stress have shortcomings. Using plant-growth-promoting rhizobacteria (PGPR) has proved feasible and eco-friendly way to enhance wheat growth even under the drought stress. Combining PGPR in consortiums further boosts up their effects. In this study, we have checked the efficacy of drought-tolerant Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus in combination. These strains were allowed to grow on PEG 6000 with concentrations (-0.15, -0.49, -0.73 and − 1.2) Mega Pascal (MPa) alone and in combination. Furthermore, Fourier transmission infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used. Their biochemical traits such as solubilization of K, P and Zn and the synthesis of siderophore, indole acetic acid (IAA), protease, amylase, hydrogen cyanide (HCN) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase were done. In addition to this, we investigated the optimum folic acid concentration i.e 150 ppm for wheat against drought stress. We conducted a pot experiment to check the growth-enhancing and drought-mitigating effects of consortium and folic acid alone and in combination. As a result, we found a significantly increased wheat biomass, relative water content (RWC), chlorophyll content, antioxidants including glutathione reductase and total soluble sugars and protein content under all treatments. However, the combined treatment of bacterial consortium and folic acid showed maximum potential to boost wheat growth and survival even under drought. We also investigated the minerals uptake by wheat after the treatments and found maximum nutrient uptake under the co-effect of folic acid and bacterial consortium We believe this is the first study that has investigated the optimal dose of folic acid for wheat. Our research is also novel in that we seek to investigate the effects of folic acid along with a bacterial consortium comprising Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus on wheat grown under the drought stress.

Improvement of serum folate status in the US women of reproductive age with fortified iodised salt with folic acid (FISFA study).

Mandatory folic acid fortification of enriched grains has reduced neural tube defect prevalence in several countries. We examined salt as an additional vehicle for folic acid fortification. The primary objective was to examine the change in serum folate concentration after 1 month of consumption of fortified iodised salt with folic acid (FISFA) among women of reproductive age. The secondary objectives were to examine (1) the feasibility of implementing FISFA intervention and (2) the acceptability of FISFA. We conducted a pre–post intervention study (January–April 2023). Participants received a FISFA saltshaker with the study salt (1 g of sodium chloride salt fortified with 100 mcg of folic acid) to use instead of regular table salt for 1 month. Serum folate was measured using the Elecsys Folate-III immunoassay method at baseline and 1-month endpoint. Change in serum folate was assessed using a two-tailed Wilcoxon signed rank test for paired samples. Metropolitan city, Southern USA. Non-pregnant, 18–40-year-old women who lived alone/with a partner. Thirty-two eligible women consented to participate, including eleven non-Hispanic-White, eleven non-Hispanic-Black and ten Hispanic. Post-intervention, there was a significant increase in median serum folate concentration of 1·40 nmol/l (IQR 0·74–2·05; P < 0·001) from 24·08 nmol/l to 25·96 nmol/l in an analytical sample of n 29. An increase was seen in 28/29 (93 %) participants. Feasibility: 100 % study consent and compliance. FISFA acceptability: 25 d average use; 1·28 g average daily intake; 96·7 % and 90 % reported taste and colour of FISFA as highly acceptable, respectively. FISFA is an effective approach to increasing serum folate concentrations among women of reproductive age. Findings should be replicated in a larger study.

Genome-Wide Association Study Identifies Genetic Polymorphisms for Folate-Related Biomarkers in Chinese Preconception Women

BackgroundSingle-nucleotide polymorphism (SNP) allele frequencies, dietary habits, and folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females. ObjectivesWe aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine concentrations in Chinese female preconception population. MethodsA genome-wide association study was conducted on 1000 randomly selected preconception Chinese women from the Shanghai Preconception Cohort. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10−7. ResultsThe MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate, and homocysteine concentrations (P = 2.28 × 10−16; P = 8.85 × 10−8, and P = 2.46 × 10−13, repsectively). It is associated with increased RBC folate (β: 0.154 per additional risk allele after log transform), decreased serum folate (β: −0.951 per additional risk allele), and increased serum homocysteine concentrations (β: 1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P = 2.55 × 10−8), although that associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P = 4.91 × 10−17). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P = 1.59 × 10−10). The numbers of signals with a P value of <10−7 for RBC folate, serum folate, vitamin B-12, and homocysteine were 12, 18, 8, and 614, respectively. ConclusionsThis study represents the first genome-wide association study focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker are partly different from other populations. The rs1801133 (C677T) in MTHFR is the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and noncoding rs77025184 are the predominant SNPs for serum folate and homocysteine, respectively.

Betaine and B12 intake, glutathione concentration, and MTHFR, PEMT, and MTHFD1 genotypes are associated with diabetes-related parameters in Polish adults

BackgroundThere is a growing body of evidence on associations between one-carbon metabolism (OCM) and diabetes-related parameters. For this reason, we aimed to examine the associations of plasma choline, betaine, trimethylamine N-oxide (TMAO), glutathione (GSH), serum folate, vitamin B12, DHFR (rs70991108) genotype, MTHFR (rs180113) genotype, MTHFD1 (rs2236225) genotype, PEMT (rs7946 and rs12325817) genotype with fasting glucose level insulin level, and diabetes related indices. MethodsThe study group consisted of 421 Polish adults aged 20–40 years old. Food intake was assessed using a three-day food diary. Plasma concentrations of choline, betaine, and TMAO were determined using ultra-high-performance liquid chromatography electrospray ionization mass spectrometry. Total plasma GSH level was measured using high-performance liquid chromatography. Insulin, folate and vitamin B12 concentrations were estimated using an enzyme-linked immunosorbent assay method. Genotyping was performed using TaqMan probes. ResultsGSH level was negatively associated with insulin (β = -0.11, p < 0.05) and gamma-glutamyltransferase (β = -0.12, p < 0.05), and positively associated with fasting glucose (β = 0.11, p < 0.05). Betaine intake was negatively associated with serum insulin concentration (β = -0.13, p < 0.05) and HOMA-IR (β = -0.12, p < 0.05). Choline intake was negatively associated with insulin (β = -0.17, p < 0.01). Serum folate level was negatively associated with GGTP (β = -0.11; p < 0.05). The MTHFR CC genotype was associated with higher serum insulin level (β = 0.15; p < 0.01) and higher HOMA-IR (β = 0.15, p < 0.01), while the MTHFD1 AA genotype was negatively associated with QUICKI (β = -0.11, p < 0.05). ConclusionsOur findings suggest that higher GSHl higher intake of betaine, B12, and choline; as well as TT genotype of MTHFR and AA genotype of MTHFD1 are associated with lower diabetes-related parameters among adults.

Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.

Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between -transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. Third-trimester BLLs were associated with increased SRS-2 scores [; 95% confidence interval (CI): 1.1, 5.5] among participants with low ( percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (; 95% CI: , 0.5) among those in the middle category ( and percentiles) (p-interaction ). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP (; 95% CI: , 3.1) than those without the T allele (; 95% CI: , 0.7), but the difference was not statistically significant (). Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479.

Expression patterns of folate metabolism-related enzymes in the bovine oviduct: estrous cycle-dependent modulation and responsiveness to folic acid

Folate metabolism is required for important biochemical processes that regulate cell functioning, but its role in female reproductive physiology in cattle during peri- and post-conceptional periods has not been thoroughly explored. Previous studies have shown the presence of folate in bovine oviductal fluid, as well as finely regulated gene expression of folate receptors and transporters in bovine oviduct epithelial cells (BOECs). Additionally, extracellular folic acid (FA) affects the transcriptional levels of genes important for the functioning of BOECs. However, it remains unknown whether the anatomical and cyclic features inherent to the oviduct affect regulation of folate metabolism. The present study aimed to characterize the gene expression pattern of folate cycle enzymes in BOECs from different anatomical regions during the estrous cycle and to determine the transcriptional response of these genes to increasing concentrations of exogenous FA. A first PCR screening showed the presence of transcripts encoding dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MTR) in bovine reproductive tissues (ovary, oviduct and uterus), with expression levels in oviductal tissues comparable to, or even higher than, those detected in ovarian and uterine tissues. Moreover, expression analysis through RT-qPCR in BOECs from the ampulla and isthmus during different stages of the estrous cycle demonstrated that folate metabolism-related enzymes exhibited cycle-dependent variations. In both anatomical regions, DHFR was upregulated during the preovulatory stage, while MTHFR and MTR exhibited increased expression levels during the postovulatory stage. Under in vitro culture conditions, ampullary and isthmic cells were cultured in the presence of 10, 50, and 100 μM FA for 24 h. Under these conditions, isthmus epithelial cells exhibited a unique transcriptional response to exogenous FA, showing a pronounced increase in MTR expression levels. Our results suggest that the expression of folate metabolism-related genes in BOECs is differentially regulated during the estrous cycle and may respond to exogenous levels of folate. This offers a new perspective on the transcriptional regulation of genes associated with the folate cycle in oviductal cells and provides groundwork for future studies on their functional and epigenetic implications within the oviductal microenvironment.

Major evidence of nutritional and metabolic management in the context of bariatric surgery: a systematic review

Introduction: Approximately $315 billion is spent annually on the medical cost of obesity in adult patients in the United States alone. According to the American Society for Metabolic and Bariatric Surgery (ASMBS), the rate of bariatric surgery (BS) increased from 158,000 in 2011 to 196,000 in 2015. This increase in invasive techniques does not eliminate unhealthy habits, therefore, lifestyle modifications, such as healthy eating and correct physical activity programs, can improve surgical results. Objective: To establish the main nutritional and metabolic management strategies in the context of bariatric surgery, to modulate and reduce the problems caused by nutrient deficit. Methods: The systematic review rules of the PRISMA Platform were followed. The search was conducted from May to June 2024 in the Web of Science, Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 135 articles were found. 42 articles were fully evaluated and 18 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 22 studies with a high risk of bias and 24 that did not meet GRADE and AMSTAR-2. Most studies presented homogeneity in their results, with X2=79.7%&gt;50%. It was concluded that the recommendations were gathered to assist in individualized clinical practice in the nutritional management of patients with obesity. In general, patients with obesity have significantly lower concentrations of serum iron, folic acid, vitamins A, B6, B12, C, 25-hydroxyvitamin D, and lipid-standardized vitamin E. Before bariatric surgery, nutritional status should be analyzed and preoperative weight loss can be attempted. Very low-calorie diets and very low-calorie ketogenic diets are prescribed in the last months before surgery. It was noted that the recommendations were gathered to assist in individualized clinical practice in the nutritional management of patients with obesity, including nutritional management. Iron status may be affected by adipose tissue inflammation and increased expression of the systemic iron regulatory protein hepcidin. The postoperative recommendation for vitamin B12 (cobalamin) should be 350-500 micrograms/1000 micrograms monthly, and for folate (folic acid) in the postoperative period should be 1000 micrograms per day.

The use of propionic and lactic acid bacteria to produce cobalamin and folate in injera, an Ethiopian cereal-based fermented food

Like in many developing countries, the traditional Ethiopian diet relies mainly on starchy staple foods and often lacks sufficient animal-sourced foods which are crucial for cobalamin intake. Furthermore, the concentration of folate in traditionally prepared injera, an Ethiopian cereal-based fermented staple food, is highly variable and injera contains biologically inactive corrinoids. This study aimed to improve the cobalamin and folate content of injera by using cobalamin-producing Propionibacterium freudenreichii and folate-producing Lactiplantibacillus plantarum strains, both individually and combined. Since injera is fermented using backslopping, we also assessed the ability of these strains to produce cobalamin and folate consistently across successive fermentation batches. Changes in the microbial ecosystem were monitored using real-time PCR. The theoretical contribution of the injera prepared using the selected strains to the cobalamin and folate intake of children and women of reproductive age was also calculated. Results showed that using the selected bacterial strains individually increased cobalamin (up to 19.2 μg/100 g of dry matter) and folate (up to 180.2 μg/100 g of dry matter) levels in the injera dough over several backslopping fermentation batches. Regular consumption of the injera with enhanced vitamin content produced using each strain alone would be capable of fulfilling the entire recommended nutrient intake for cobalamin and up to 29 % of the recommended intake for folate for children and women of reproductive age. However, when the strains were used together, the production of both vitamins was reduced. The presence of certain common endogenous bacterial species and genera exhibited significant variability, highlighting the complex response of the native microbiota to the different inoculation strategies employed. Future experiments should consider selecting a microbial consortium comprising non-competing microorganisms to ensure the simultaneous production of cobalamin and folate in fermented foods.

Serum folate levels and risk of metabolic dysfunction-associated steatotic liver disease: results from a cross-sectional study and Mendelian randomization analysis.

Evidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting. This study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis. To investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1,117 participants from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model. In addition, we conducted a two-sample MR study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37,465 individuals) and MASLD (primary analysis: 8,434 cases/770,180 controls; Secondary analysis:1,483 cases/17,781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis. The results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantly lower risk (OR = 0.58, 95% CI: 0.38-0.88, p = 0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after complete adjustments. However, in the IVW of MR analysis, there was no causal relationship between serum folate level and MASLD risk in the primary analysis (OR = 0.75, 95% CI: 0.55-1.02, p = 0.065) and secondary analysis (OR = 0.83, 95% CI: 0.39-1.74, p = 0.618). In observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of p < 0.05, suggesting that our MR study does not support a causal relationship between serum folate levels and MASLD risk. Additional research involving a larger number of cases would contribute to enhancing the confirmation of our preliminary findings.

Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension

BackgroundIn China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. ObjectiveThis study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension. MethodsThis study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. ResultsOur findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT). ConclusionsAdequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy.This trial was registered at clinicaltrials.gov as ChiCTR2100051983.

Power-to-Vitamins: producing folate (vitamin B9) from renewable electric power and CO2 with a microbial protein system

We recently proposed a two-stage Power-to-Protein technology to produce microbial protein from renewable electric power and CO2. Two stages were operated in series: Clostridium ljungdahlii in Stage A to reduce CO2 with H2 into acetate, and Saccharomyces cerevisiae in Stage B to utilize O2 and produce microbial protein from acetate. Renewable energy can be used to power water electrolysis to produce H2 and O2. A drawback of Stage A was the need for continuous vitamin supplementation. In this study, by using the more robust thermophilic acetogen Thermoanaerobacter kivui instead of C. ljungdahlii, vitamin supplementation was no longer needed. Additionally, S. cerevisiae produced folate when grown with acetate as a sole carbon source, achieving a total folate concentration of 6.7 mg per 100 g biomass with an average biomass concentration of 3 g l-1. The developed Power-to-Vitamin system enables folate production from renewable power and CO2 with zero or negative net-carbon emissions.

Excess Folic Acid Exposure Increases Uracil Misincorporation into DNA in a Tissue-Specific Manner in a Mouse Model of Reduced Methionine Synthase Expression

BackgroundFolate and vitamin B12 (B12) are cofactors in folate-mediated 1-carbon metabolism (FOCM), a metabolic network that supports synthesis of nucleotides (including thymidylate [dTMP]) and methionine. FOCM impairments such as a deficiency or imbalance of cofactors can perturb dTMP synthesis, causing uracil misincorporation into DNA. ObjectiveThe purpose of this study was to determine how reduced expression of the B12-dependent enzyme methionine synthase (MTR) and excess dietary folic acid interact to affect folate distribution and markers of genome stability in mouse tissues. MethodsHeterozygous Mtr knockout mice (Mtr+/–) model the FOCM-specific effects of B12 deficiency. Folate accumulation and vitamer distribution, genomic uracil concentrations, and phosphorylated histone H2AX (γH2AX) immunostaining were measured in male Mtr+/+ and Mtr+/− mice weaned to either a folate-sufficient control (C) diet (2 mg/kg folic acid) or a high folic acid (HFA) diet (20 mg/kg folic acid) for 7 wk. ResultsExposure to the HFA diet led to tissue-specific patterns of folate accumulation, with plasma, colon, kidney, and skeletal muscle exhibiting increased folate concentrations compared with control. Liver total folate did not differ. Although unmetabolized folic acid (UMFA) increased 10-fold in mouse plasma with HFA diet, UMFA accounted for <0.2% of total folate in liver and colon tissue. Exposure to HFA diet resulted in a shift in folate distribution in colon tissue with higher 5-methyl-THF and lower formyl-THF than in control mice. Mtr heterozygosity did not impact folate accumulation or distribution in any tissue. Mice on HFA diet exhibited higher uracil in genomic DNA and γH2AX foci in colon. Similar differences were not seen in liver. ConclusionsThis study demonstrates that folic acid, even when consumed at high doses, does not meaningfully accumulate in mouse tissues, although high-dose folic acid shifts folate distribution and increases uracil accumulation in genomic DNA in colon tissue.

Serum molecules of the folate-driven one-carbon cycle as indicators of depressive tendencies in the elderly

AimsThe folate-driven one-carbon (1C) cycle plays a significant role in the occurrence and development of depression. This study aimed to examine the potential of important molecules of the folate-driven 1C cycle as biomarkers for depressive tendency. MethodsNinety-five serum samples from older adults (age >60 years) were collected for this study. We quantified the concentrations of key metabolites and coenzymes of the folate-driven 1C cycle using Ultra-Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (UPLC-MS/MS) and familiar clinical liver and kidney indicators in serum. Based on the differences in Hamilton Depression Rating Scale (HAMD)-17 scores, we compared the concentrations of measured molecules between elderly individuals with low and high levels of depression defined as HAMD-17 scores of 0–7 and 8–24, respectively. We also analyzed the concentration ranges of these molecules reflecting the level of depressive tendencies in the cohort. ResultsOur results showed significant variations in serum folate concentrations, SAM (S-adenosylmethionine), TBA (total bile acid), and SAM/SAH (S-enosylhomocysteine) ratios in elderly individuals with different HAMD-17 scores. Serum folate concentrations below 15.5 nmol/L and SAM/SAH ratios below 13.0 exhibited elevated levels of depressive tendency experienced among the participants. ConclusionsThe concentrations of serum folate, SAM, TBA, and SAM/SAH ratios might be used as indicators of depressive tendencies in the elderly population. A serum folate concentration of 15.5 nmol/L and a SAM/SAH ratio of 13.0 might be critical thresholds for indicating depressive tendencies in the Chinese elderly population.

Association of serum folate concentrations with the mortality of cancer: a prospective cohort study.

The association between serum folate concentrations and the mortality of cancer remains unclear. We aim to investigate the association of serum folate concentrations with all-cause and cause-specific mortality among American adults with cancer. This cohort study included 4535 patients with cancer from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Cox proportional hazards model and two-piecewise Cox proportional hazards model were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. During a median follow-up of 37,792 person-years, there were 1998 all-cause deaths and 616 cancer deaths. Non-linear and L-shaped associations were observed between serum folate concentrations and the risk of all-cause and cancer mortality among patients with cancer. Notably, the mortality rates reached a plateau at 23.7ng/mL for all-cause mortality and 23.57ng/mL for cancer mortality. When folate levels fell below these thresholds, the risk of all-cause and cancer mortality decreased by approximately 2.1% (HR 0.979; 95% CI 0.969-0.989) and 3.6% (HR 0.964; 95% CI 0.948-0.981), respectively, with each unit increase in the folate concentration up to the thresholds. Our study reveals that low serum folate concentrations are linked to an elevated risk of cancer mortality among individuals with cancer within a certain range and supplementation of folate in cancer patients to achieve specific serum folate level threshold (23.7ng/mL) might reduce the risk of cancer mortality.

Dietary folic acid intake, 13 genetic variants and other factors with red blood cell folate concentration in pregnancy-preparing population

PurposeThis study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population.Methods519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable.ResultsThe median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178–0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273.ConclusionIn pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level.

Nutrient Status and Supplement Use During Pregnancy Following Metabolic Bariatric Surgery: A Multicenter Observational Cohort Study

IntroductionPregnant women with a history of metabolic bariatric surgery (MBS) are at high risk of developing nutrient deficiencies, leading to greater challenges to reach nutritional requirements. This study compared nutrient status of women using specialized “weight loss surgery” multivitamin supplementation (WLS-MVS) to those using standard supplementation (sMVS) during pregnancy following MBS.MethodsMulticenter observational cohort study including 119 pregnant women at 41.0 (18.5–70.0) months after Roux-en-Y gastric bypass (RYGB, n = 80) or sleeve gastrectomy (SG, n = 39). Routine blood samples were analyzed every trimester (T1, T2, T3), and micronutrient serum levels were compared between WLS-MVS and sMVS users.ResultsDuring pregnancy after RYGB, WLS-MVS users demonstrated higher serum concentrations of hemoglobin (7.4 [7.2, 7.5] vs. 7.0 [6.8, 7.3] mmol/L), ferritin (23.2 [15.0, 35.7] vs. 13.7 [8.4, 22.4] µg/L), and folic acid (31.4 [28.7, 34.2] vs. 25.4 [21.3, 29.4] nmol/L) and lower serum vitamin B6 levels (T1: 90.6 [82.0, 99.8] vs. 132.1 [114.6, 152.4] nmol/L) compared to sMVS users. Iron deficiencies and elevated serum vitamin B6 levels were less prevalent in the WLS-MVS group. During pregnancy after SG, WLS-MVS users showed higher serum vitamin D concentrations (89.7 [77.6, 101.8] vs. 65.4 [53.3, 77.4] nmol/L) and lower serum vitamin B1 concentrations (T2: 137.4 [124.2, 150.6] vs. 161.6 [149.0, 174.1] nmol/L, T3: 133.9 [120.1, 147.7] vs. 154.7 [141.9, 167.5] nmol/L) compared to sMVS users.ConclusionLow maternal concentrations of micronutrients are highly prevalent during pregnancy after MBS. The use of specialized multivitamin supplementation generally resulted in higher serum levels during pregnancy compared to standard supplementation. Future research is needed to investigate how supplementation strategies can be optimized for this high-risk population.Graphical

Association of serum homocysteine with vitamin B12 and folate levels in women with pre-eclampsia in a tertiary health care center in Nepal

BackgroundPre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia.MethodAn observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman’s rank correlation test. A p-value < 0.05 was considered statistically significant.ResultsThis study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L).ConclusionHomocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia.

Association between folate level and cervical intraepithelial neoplasia risk: a systematic review and meta-analysis.

There were several studies about the association between folate level and the risk of cervical intraepithelial neoplasia (CIN). This meta-analysis was conducted to evaluate whether folate deficiency is related to a high risk of CIN and cervical cancer. Odds ratios (ORs)/relative risks and 95% confidence intervals (CIs) were summarized regarding the association between folate level and risk of CIN or cervical cancer. The meta-analysis indicated that higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with a lower risk of CIN, as demonstrated by a random-effects model (OR = 0.42, 95% CI: 0.28-0.62). Conversely, no significant association was found between erythrocyte folate levels and the risk of CIN, as indicated by a random-effects model (OR = 0.69, 95% CI: 0.43-1.12). In addition, random-effects models demonstrated that higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with lower risks of CIN grade 1 and CIN grades 2 or 3, compared with the lowest quartile of serum folate (CIN grade 1: OR = 0.52, 95% CI: 0.29-0.93; CIN grades 2 or 3: OR = 0.33, 95% CI: 0.19-0.58). Higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with a lower risk of cervical cancer, compared with the lowest quartile of serum folate (OR = 0.53, 95% CI: 0.36-0.79). Serum low folate levels could increase the risk of CIN and cervical cancer, while erythrocyte folate concentration was not associated with the risk of CIN.

Folic acid as a green inhibitor for corrosion protection of Q235 carbon steel in 3.5 wt% NaCl solution

AbstractThis study combines experimental and theoretical explorations. The corrosion inhibition performance of different concentrations (50, 100, 250, and 500 ppm) of folic acid in 3.5 wt% NaCl solution on Q235 steel was tested by weight loss and electrochemical test. The corrosion inhibition efficiency increased with the gradual increase of folic acid concentration and reached a maximum of 87% at 500 ppm folic acid. The experimental results for electrochemistry and weight loss are in good agreement with the simulation calculations. The adsorption of folic acid on the steel surface obeyed the Langmuir isotherm, and the adsorption process was a combination of chemisorption and physisorption. The contact angle test also yielded the maximum increase in hydrophobicity of the specimen surface at the added folic acid concentration of 500 ppm. The corrosion morphology after the addition of corrosion inhibitor was relatively flat. The adsorption orientation of folic acid molecules on the steel surface in an aqueous environment was investigated using density functional theory (DFT)/molecular dynamics (MD) simulations. The microscopic mechanism of action of folic acid corrosion inhibitors is clarified.