Folate Deficiency Research Articles

Folate Deficiency and/or the Genetic Variant Mthfr677C >T Can Drive Hepatic Fibrosis or Steatosis in Mice, in a Sex-Specific Manner.

Disturbances in one-carbon metabolism contribute to nonalcoholic fatty liver disease (NAFLD) which encompasses steatosis, steatohepatitis, fibrosis, and cirrhosis. The goal is to examine impact of folate deficiency and the Mthfr677C >T variant on NAFLD. This study uses the new Mthfr677C >T mouse model for the human MTHFR677C >T variant. Mthfr677CC and Mthfr677TT mice werefed control diet (CD) or folate-deficient (FD) diets for 4 months. FD and Mthfr677TT alter choline/methyl metabolites in liver and/or plasma (decreased S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio, methyltetrahydrofolate, and betaine; increased homocysteine [Hcy]). FD, with contribution from Mthfr677TT, provokes fibrosis in males. Studies of normal livers reveal alterations in plasma markers and gene expression that suggest an underlying predisposition to fibrosis induced by FD and/or Mthfr677TT in males. These changes are absent or reverse in females, consistent with the sex disparity of fibrosis. Sex-based differences in methylation potential, betaine, sphingomyelin, and trimethylamine-N-oxide (TMAO) levels may prevent fibrogenesis in females. In contrast, Mthfr677TT alters choline metabolism, dysregulates expression of lipid metabolism genes, and promotes steatosis in females. This study suggests that folate deficiency predisposes males to fibrosis, which is exacerbated by Mthfr677TT, whereas Mthfr677TT predisposes females to steatosis, and reveal novel contributory mechanisms for these NAFLD-related disorders.

Stress and Folate Impact Neurodevelopmental Disorders

Autism Spectrum Disorder (ASD) is one of several developmental disabilities that can create significant communication and behavioral challenges in affected individuals. Several studies have found that children with ASD have high levels of Folate Receptor Antibody (FRA), which blocks the transport of folate across the Blood-Brain Barrier (BBB) and leads to Cerebral Folate Deficiency (CFD). Supplementation with folate in its reduced form, such as with folinic acid, has been found to improve communication in autistic children with folate receptor antibodies. Here, we provide an overview of the role of folate in nervous system development, effects of FRA on brain folate levels, and clinical trials that have examined the efficacy of folate supplementation in reducing the symptoms of developmental disabilities. Further, we highlight the importance of prenatal folate supplementation in reducing the risk and severity of developmental disorders and the need for additional research to explore optimal dietary interventions to aid in managing them. The results suggest that supplementing with reduced folate may offer a promising treatment approach for individuals with neurodevelopmental disorders, particularly those with FRA.

Assessing Nutritional Anemia Among University Students in Jazan, Saudi Arabia: A Public Health Perspective.

Nutritional anemia is a significant public health concern worldwide, particularly affecting young adults and children in Saudi Arabia, where inadequate nutrition is considered a primary contributing factor. This study aims to (i) examine the levels of serum iron, folate, and vitamin B12 in young adult students, with a focus on identifying any deficiencies and their association with anemia; (ii) explore the prevalence of mixed-deficiency anemia resulting from deficiencies in serum iron, folate, and vitamin B12 (iii) explore how sociodemographic characteristics and dietary habits influence serum iron, folate, and vitamin B12 levels. This cross-sectional study encompassed 158 young adult students at Jazan University, Saudi Arabia. Blood samples were collected following a comprehensive questionnaire addressing sociodemographic and health characteristics. These samples were analyzed for complete blood count, serum iron, folate, and vitamin B12 levels. The findings of this study revealed a significant decrease in serum iron levels, with 70.6% of males and 88% in females exhibiting reduced level. Additionally, low levels of folate were observed in 4% of the study population, while deficiency in vitamin B12 was found in 2.2% of the study population. However, the simultaneous presence of low serum iron levels along with deficiencies in folate or vitamin B12 was not observed in the study participants. The study indicates that there is a high incidence of low serum iron and ferritin levels among university students in Saudi Arabia, which poses a considerable public health concern. Conversely, the prevalence of folate and vitamin B12 deficiencies among the students was comparatively low, and notably, there were no cases where these deficiencies were observed alongside iron deficiency.

Folate receptor alpha autoantibodies in the serum of patients with relapsing–remitting multiple sclerosis (RRMS)

Multiple sclerosis (MS) is a potentially progressive, autoimmune neurologic disorder of the central nervous system (CNS), resulting from an autoimmune attack on central nervous system white matter. Folate deficiencies are linked to DNA instability and breakdown of phospholipid membranes and thus might affect myelin integrity. Folic acid exerts its effects through its receptors (FRs). Folate receptor alpha autoantibodies (FRAA) can block folate transport to the brain. Due to important role of folate in the pathogenesis of MS, in this project we aimed to study FRAA serum levels in patients with relapsing remitting multiple sclerosis (RRMS). Fifty-four patients with RRMS and 58 healthy individuals were enrolled in this study. Serum samples were collected from all participants and folate receptor alpha autoantibody (FRAA) serum concentration was measured by Enzyme-linked immunosorbent assay (ELISA). The results showed that FRAA serum levels in patients with RRMS is 67.20±19.79ng/ml as compared to controls which was 37.32±13.26ng/ml. Significant increase in folate receptor autoantibody serum concentration was seen in patients with RRMS when compared to control group (P=0.007). The results showed that a high concentration of folate receptor autoantibody is associated with RRMS. We have also found that 85.18% (46/54) of patients with RRMS were positive for serum FRAA, whereas the prevalence in controls was only 46.55% (27/58). It is concluded that serum FRAA are more prevalent in RRMS patients than controls. The findings also suggest that FRAA might be involved in the pathophysiology of RRMS.

Evaluating the Effect of the Demographic, Trichoscopic and Laboratory Characteristics on The Recurrence of Alopecia Areata.

Alopecia areata (AA) has diverse disease characteristics and multiple factors may interfere with the prognosis of the disease. In this study, the factors affecting the AA recurrence were evaluated. A total of a hundred patients diagnosed with AA between June 2022 and March 2023 were included in this retrospective, cross-sectional study. The patients were divided into two groups according to the presence of outbreaks. Both groups were compared in terms of age, gender, disease duration, number of outbreaks, family history of AA, previous medical treatment history for AA, clinical type, disease severity, presence of accompanying nail findings, and trichoscopic and laboratory characteristics. Among 100 patients, male dominance was found (N = 69). Most of the patients had patchy disease (90/100), mild disease severity (88/100), and a solitary outbreak (65/100). Male gender, longer disease duration, family history, presence of S2 severity of alopecia tool score, trachyonychia, short vellus hairs in trichoscopic examination, hypothyroidism, and folic acid deficiency were factors for AA outbreaks. Male gender and the presence of a family member with AA in the family were defined as the independent prognostic factors for disease recurrence. While demographic, laboratory, and clinical findings are factors for AA outbreaks in the follow-up, male gender and family history should be considered independent predictors.

Intrathecal Methotrexate-Induced Lumbosacral Polyradiculopathy: A Case Report

BACKGROUND: Polyradiculopathy caused by intrathecal methotrexate (IT MTX) is a rare and serious complication of chemotherapy. The pathophysiology involved is likely due to a drug-induced folate deficiency and subsequent local immune reaction in the spinal cord. CASE REPORT: The authors present a 68-year-old woman with stage I breast cancer and stage III diffuse large B-cell lymphoma who developed low back pain after IT MTX treatment. Further workup revealed diffuse rope-like thickening of the cauda equina nerve roots with subtle linear low-level leptomeningeal enhancement on magnetic resonance imaging and severe primary axonal and motor polyneuropathy affecting the upper and lower extremities on electromyography/nerve conduction studies, likely a result of IT MTX toxicity. Treatment should emphasize conservative measures. Alternatively, intravenous immunoglobulin followed by intravenous methylprednisolone can be considered. CONCLUSIONS: Polyradiculopathy caused by IT MTX is a rare finding that can be treated. It would be beneficial to further study the effects of IT MTX and create treatment protocols for its adverse effects. KEY WORDS: Intrathecal methotrexate, polyradiculopathy, cauda equina, cancer, case report

Folate Receptor Alpha Autoantibodies in the Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Population.

The folate receptor alpha autoantibodies (FRAAs) are associated with cerebral folate deficiency (CFD) and autism spectrum disorder (ASD). Both of these syndromes have overlapping characteristics with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS). Thus, we propose that the FRAAs may contribute to the symptomatology of PANS/PANDAS. To test this hypothesis, 1 mL of serum from 47 patients (age range = 6-18 years old) clinically diagnosed with PANS/PANDAS was sent to Vascular Strategies (Plymouth Meeting, PA, USA) for analysis of FRAAs. Moreover, 63.8% of PANS/PANDAS patients (male = 15; female = 15) were found to have either the blocking and/or blinding FRAAs, with 25 (83.3%; male = 14; female = 11) having binding FRAAs, two (6.7%; all female = 2) having blocking FRAAs, and 3 (10%; male = 1; female = 2) having both binding and blocking. Furthermore, surprisingly, ASD was associated with a 0.76 lower binding titer (p = 0.02), and severe tics were associated with a 0.90 higher binding titer (p = 0.01). A case of a FRAA-positive patient is provided to illustrate that a treatment plan including leucovorin can result in symptom improvement in patients with PANS/PANDAS who are FRAA-positive. These data, for the first time, demonstrate that PANS/PANDAS is associated with FRAAs and suggest folate metabolism abnormalities may contribute to PANS/PANDAS symptomatology. Further studies investigating the therapeutic nature of leucovorin in the treatment of PANS/PANDAS are needed. Such studies may open up an alternative, safe, and well-tolerated treatment for those with the PANS/PANDAS diagnosis.

Folate in the United States Population and its Association with Congestive Heart Failure.

To investigate the relationship between red blood cell (RBC) folate and congestive heart failure (CHF). We extracted the concentrations of RBC folate and collated CHF information from the National Health and Nutrition Examination Survey (NHANES) survey (12820 individuals). Weighted univariate logistic regression, weighted multivariate logistic regression, and restrictive cubic spline (RCS) were used to assess the relationship between RBC folate concentrations and CHF. The unadjusted model showed that the highest tertile group of RBC folate concentration was significantly associated with a higher risk of CHF compared to the lowest tertile group of RBC folate levels (odds ratio [OR] = 3.09; 95% confidence interval [CI], 2.14-4.46). Similar trends were seen in the multivariate-adjusted analysis (OR = 1.98; 95% CI: 1.27-3.09). The OR was 1.0 when the predicted RBC folate exceeded 2757 nmol/L in the RCS model, indicating that the risk of CHF was low and relatively stable up to a predicted RBC folate level of 2757 nmol/L, but began to increase rapidly thereafter (p = 0.001). The risk of CHF may be increased either by high RBC folate concentrations (highest tertile of RBC folate or 2637 nmol/L) or by folate deficiency. Considering the two sides of the association between RBC folate and CHF, there is a need for large-scale clinical research to better investigate if the association between RBC folate and CHF is a cause-effect relationship, what are the underlying pathophysiological basis, as well as to identify optimal dietary folate equivalent (DFE) and RBC folate concentration intervals.

ASUHAN KEBIDANAN PEMBERIAN SARI KURMA UNTUK MENINGKATKAN KADAR HEMOGLOBIN IBU HAMIL DENGAN ANEMIA DI PUSKESMAS TANJUNG BALAI KARIMUN

According to WHO, the global prevalence of anemia in pregnant women worldwide is 41.8%. The main cause of anemia in pregnancy is iron deficiency, followed by folate deficiency. One way to overcome anemia in pregnancy is by consuming iron foodstuffs, including dates. The purpose of this study was to provide integrated midwifery care for pregnant women with mild anemia by giving date juice to increase hemoglobin levels. Midwifery care uses a midwifery management approach. This type of research uses case study qualitative data. Midwifery care was carried out at the Tanjung Balai Health Center with subjects pregnant women at 32 weeks of gestation with mild anemia. The research instrument uses a case study format and observation sheets. Data collection techniques use primary data through anamnesis, physical examination, interviews and observation. Evaluation of the care provided related to giving date palm juice 3 times a day can help increase HB levels. For health workers, it is hoped that they can improve the quality of midwifery services through a management approach to midwifery care for the prevention of mild anemia with date juice.

Evaluation the Impact of Folic Acid Deficiency During Pregnancy and Preterm Birth

Evaluation the Impact of Folic Acid Deficiency During Pregnancy and Preterm Birth

Homocysteine, hyperhomocysteinemia, and H-type hypertension.

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 μmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH.

Role of folic acid in regulating gut microbiota and short-chain fatty acids based on an in vitro fermentation model.

Folic acid deficiency is common worldwide and is linked to an imbalance in gut microbiota. However, based on model animals used to study the utilization of folic acid by gut microbes, there are challenges of reproducibility and individual differences. In this study, an in vitro fecal slurry culture model of folic acid deficiency was established to investigate the effects of supplementation with 5-methyltetrahydrofolate (MTHF) and non-reduced folic acid (FA) on the modulation of gut microbiota. 16S rRNA sequencing results revealed that both FA (29.7%) and MTHF (27.9%) supplementation significantly reduced the relative abundance of Bacteroidetes compared with control case (34.3%). MTHF supplementation significantly improved the relative abundance of Firmicutes by 4.49%. Notably, compared with the control case, FA and MTHF supplementation promoted an increase in fecal levels of Lactobacillus, Bifidobacterium, and Pediococcus. Short-chain fatty acid (SCFA) analysis showed that folic acid supplementation decreased acetate levels and increased fermentative production of isobutyric acid. The in vitro fecal slurry culture model developed in this study can be utilized as a model of folic acid deficiency in humans to study the gut microbiota and demonstrate that exogenous folic acid affects the composition of the gut microbiota and the level of SCFAs. KEY POINTS: •Establishment of folic acid deficiency in an in vitro culture model. •Folic acid supplementation regulates intestinal microbes and SCFAs. •Connections between microbes and SCFAs after adding folic acid are built.

Nutritional support during pregnancy

Aim: to summarize new data regarding the effectiveness of nutritional support during pregnancy.Materials and Methods. A search for publications was carried out in the PubMed/MEDLINE, Scopus, Web of Science, RSCI databases by retrieving queries for the following keywords: nutritional support, pregnancy, micronutrients, vitamins, macronutrients, without language restrictions. 71 sources with full text access were selected for analysis.Results. Nutritional status during pregnancy markedly impacts on mother's and neonate’s health. During pregnancy, requirements for macro- and micronutrients increase to maintain maternal homeostasis and support fetal growth. Increasing calorie intake in general female population demonstrates modest effects on pregnancy and fetal outcomes, whereas for pregnant women in poor income countries it results in no long-term benefits for children by assessing their anthropometric parameters and neurocognitive development. Despite the lack of conclusive evidence, in many countries sensible calorie restriction during pregnancy is recommended. Some micronutrients are vital for mother and fetus, because their deficiency is accompanied by increased risk of adverse pregnancy outcomes. For instance, folic acid deficiency is associated with the risk of developing fetal neural tube defects, iodine deficiency is coupled to the risk of emerging pediatric intellectual development disorders associated with congenital hypothyroidism, and calcium deficiency is related to a high risk of maternal hypertensive disorders. Therefore, micronutrient supplementation represents a technology with good potential in fighting for maternal and child health. Nonetheless, despite some advances in understanding nutritional support in pregnant women, many studies provide controversial data substantiating a need to conduct further investigations.Conclusion. Overall, recent year research confirms that the supplementation of micro- and macronutrients during pregnancy is an effective tool for “fetal programming” allowing to impact on maternal and fetal health. At the same time, an analysis of the literature showed a significant lack of research in the field of creating individual nutrition programs and nutritional support for pregnant women belonging to different segments of the population, living in different geographical regions, etc.

Independent and combined effect of serum copper and folate on depression: cross-sectional data from the NHANES 2011-2016.

Depression is a widespread mental health condition that can impact both mental and physical well-being. Prior research has shown that high levels of copper in the blood and low levels of folate are linked to depression. This study aimed to explore whether serum folate levels, independently or in combination with serum copper levels, associated with the risk of depression. Data from participants aged 18-80 years in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016 were analyzed to examine the role of trace elements. Depression was assessed using the nine-item Patient Health Questionnaire (PHQ-9). Logistic regression analyses were employed to evaluate the main effect of serum copper and folate levels on depression. Three indices, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze the interaction effect. Among the 4,847 participants selected for this study, 429 (8.9%) had PHQ-9 scores above 10, which we defined as having depressive symptoms. After adjusting for all confounding factors, higher serum copper levels [≥15.5 vs. <15.5 μmol/L, odds ratio (OR): 1.54; 95% confidence intervals (CI): 1.18-2.11] and folate deficiency (folate ≥53.7 vs. <53.7 μmol/L, OR: 1.44; 95% CI: 1.21-2.10) were associated with an increased risk of depression. Patients with both higher serum copper levels and folate deficiency (OR: 2.11; 95% CI: 1.43-3.14) had the highest risk of depression than other levels. High copper levels and low folate levels are associated with the occurrence of depression symptoms, and there may be a synergistic effect between them (SI: 1.65; 95% CI: 1.49-4.76), with this interaction accounting for 19% of depression cases (API: 0.19; 95% CI: 0.01-0.54). There may be a synergistic interaction between high copper levels and low folate levels associated with increasing risk of depression. Further population-based interventional studies are needed to confirm whether folic acid supplementation is effective in preventing depression in individuals with high blood copper levels.

Micronutrient status in patients with diabetic foot ulcers: A cross-sectional study in Saudi Arabia.

Patients with diabetes are at risk for developing diabetic foot ulcers (DFUs). It is recognized that type 2 diabetes (T2D) is distinguished by the loss of vitally important micronutrients because of the metabolic nature of this disease and its associated complexities. This study was performed to determine the level of micronutrients in patients with DFUs in Saudi Arabia. From February to May 2022, this descriptive study was conducted, adopting the cross-sectional design and a group of 88 patients with T2D. Applying the convenience sampling method, this study was conducted at a tertiary hospital in Riyadh, Saudi Arabia. Data collection was conducted through a standard questionnaire, and details regarding the demographic variables and micronutrient deficiency were collected. Among the nutritional deficiencies identified, the one with the highest frequency was vitamin D, observed in 43.2% of the patient population; after vitamin D, in order of descent, were low ferritin levels (29.5%), B12 (13.6%), and the folic acid deficiency (12.5%). Folic acid showed a statistically significant difference among patients with cardiovascular disease (CVD) (P = 0.041). Moreover, vitamin B12 showed a significant association among patients who have charcot foot (P = 019) and previous amputation (P = 0.029). Vitamin B12 deficiency is significantly associated with patients who had an amputation; having charcot foot and folic acid revealed a vital relationship among patients with DFUs having CVD. Comprehensive research is a pressing need to enable deeper awareness of micronutrient deficiencies in patients with diabetes.

Recurrent Aphthous Stomatitis: A Review of Hematinic Deficiency Factor

Background: Recurrent aphthous stomatitis (RAS) is a common disease of the oral mucosa, with a prevalence of 5-25% in some population in the world. The etiology of RAS is uncertain, but there are several predisposing factors including nutritional factors due to hematinic deficiency, substances that help in the process of erythropoiesis such as vitamin B12, folic acid, and iron. Aims: This literature study aims to present the role of hematinic deficiency in the pathogenesis RAS. Method of review: This article was created by searching the PubMed and Scopus databases. Results: five studies with the majority using a cross-sectional method and using a sample of 186 to 705 subjects indicate that hematinic deficiency is one of the factors associated with RAS. Three studies state that the RAS group with hematinic deficiency is also associated with anemia, such as microcytic anemia, normocytic anemia, macrocytic anemia, pernicious anemia, and iron deficiency anemia. All studies state that iron deficiency is more common than vitamin B12 and folic acid deficiencies in patients with RAS. Hematinic deficiency causes a decrease capacity of blood to transport oxygen to the oral mucosa, resulting in epithelial atrophy, and this condition is highly susceptible to developing RAS. Conclusion: Hematinic deficiency plays a role in the pathogenesis of RAS.

Nutrition optimisation of young tuberculosis patient with poor oral intake

ABSTRACT A 19-year-old female teenager, Chinese, admitted to medical ward on 30 April 2023 with the reason of admission of recurrent disseminated pulmonary tuberculosis (TB) and presented with fever (2/12), cough (3/7), loose stool (1/12), shortness of breath (6/12), lethargy (2/52) and poor oral intake. She had underlying diseases of hypochromic microcytic anemia anaemia 2° iron-deficiency anaemia and folate deficiency, severe hypoalbuminaemia, hospital-acquired pneumonia due to Pseudomonas infection and persistent fever despite being on anti-TB medication. In this case, the patient had already been referred to a dietitian, but a follow-up was needed as she had a loss of appetite and inadequate oral nutrition for a few days. Her calculated body mass index is 16.1 kg/m2 (underweight) and Subjective Global Assessment (SGA) was rated with Grade B (mild-moderate malnutrition) with a history of severe weight loss for the past 1 month. The biochemical data showed abnormal readings of renal profile, albumin and haemoglobin levels.

Factors Related to the Occurrence of Anemia in Pre-Dialysis Chronic Kidney Disease Patients at Prof. Dr. I Goesti Ngoerah Gede Ngoerah Hospital, 2020-2022

Background: Patients with chronic kidney disease (CKD) are most commonly found to develop complications such as anemia. This complication is caused by deficiencies of erythropoietin, iron, folic acid, and vitamin B12. The prevalence of anemia is associated with patient's glomerular filtration rate (GFR), age, gender, and erythrocyte index. Aims: The aim of this study is to report prevalence of anemia in CKD pre-dialysis patients and factors related to the incidence of anemia in CKD pre-dialysis patients at Prof. Dr. I Goesti Ngoerah Gede Ngoerah Hospital in 2020-2022. Methods: This research is descriptive analytical with a cross-sectional approach by using medical record data of pre-dialysis CKD patients from the Prof. Dr. I Goesti Ngoerah Gede Ngoerah Hospital which obtained a sample of 712 patients. Results: It was found that cases of anemia in pre-dialysis CKD patients were mostly found in women (75%), age group ≥65 years (73.6%), and stage IV (88.2%) and V (94.1%). Pre-dialysis CKD patients stage ≥III (stage III-V) were 1.6 times more likely to develop anemia compared to patients with stages I and II (OR 1.641, 95% CI: 1.175-2.293; p=0.004), as well as female gender 1,6 times more likely to suffer from anemia compared to male patients (OR 1.610, 95% CI: 1.138-2.277; p=0.007). Conclusion: The overview of anemia cases in CKD pre-dialysis patients were dominated by men, age group ≥65 years, and stage V. Prevalence of anemia increases when the patient is stage ≥III (stage III-V) and female. Keywords: Chronic Kidney Disease, anemia, pre-dialysis, age, gender, stage

Awareness of Periconceptional use of Folic Acid to Prevent Neural Tube Defects in Young Females of Dakshina Kannada Region, India: A Cross-sectional Study

Introduction: Neural Tube Defects (NTDs) are one of the common congenital anomalies leading to miscarriages and serious disabilities in newborns. NTDs are the second most common type of birth defects. Even though the aetiology of NTDs is multifactorial, Folic Acid (FA) deficiency is the most common cause. There are limited Indian studies on awareness of FA usage in the general public. Aim: To assess the awareness and usage of FA to prevent NTDs in young ladies of Mangaluru, Dakshina Kannada (DK) district, Karnataka, India. Materials and Methods: It was a community-based crosssectional study conducted at Father Muller Medical College in Dakshina Kannada district, Mangaluru, Dakshina Kannada (DK) district, Karnataka, India from August 2023 to October 2023. A total of 300 young Indian females aged 18-35 years, residing in the study district, were randomly chosen as participants. Data were collected by an interviewer using a semistructured questionnaire with two components. Part 1 focused on sociodemographic details, while Part 2 gathered information on the awareness of FA supplements, dietary sources of FA, the best time, and dosage of FA supplements to prevent NTDs. Descriptive analysis of the data was done. Results: The study included 90 married and 210 unmarried females. The average age of the participants was 23.7±5.7 years. The study results observed that only 103 (34%) of the participants had heard about FA supplements. A total of 240 (80%) of them said they were not aware of the preferred time for FA. Only 9 (3%) females could mention the correct dose of FA. Conclusion: The study results indicate a gross lack of awareness about FA supplements to prevent NTDs in the general population of the region.

Tryptophan Metabolism in Obesity: The Indoleamine 2,3-Dioxygenase-1 Activity and Therapeutic Options.

Obesity activates both innate and adaptive immune responses in adipose tissue. Adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-γ)-producing cluster of differentiation (CD)4+ T cells in adipose tissue of obese subjects. The increased formation of neopterin and degradation of tryptophan may result in decreased T-cell responsiveness and lead to immunodeficiency. The activity of inducible indoleamine 2,3-dioxygenase-1 (IDO1) plays a major role in pro-inflammatory, IFN-γ-dominated settings. The expression of several kynurenine pathway enzyme genes is significantly increased in obesity. IDO1 in obesity shifts tryptophan metabolism from serotonin and melatonin synthesis to the formation of kynurenines and increases the ratio of kynurenine to tryptophan as well as with neopterin production. Reduction in serotonin (5-hydroxytryptamine; 5-HT) production provokes satiety dysregulation that leads to increased caloric uptake and obesity. According to the monoamine-deficiency hypothesis, a deficiency of cerebral serotonin is involved in neuropsychiatric symptomatology of depression, mania, and psychosis. Indeed, bipolar disorder (BD) and related cognitive deficits are accompanied by a higher prevalence of overweight and obesity. Furthermore, the accumulation of amyloid-β in Alzheimer's disease brains has several toxic effects as well as IDO induction. Hence, abdominal obesity is associated with vascular endothelial dysfunction. kynurenines and their ratios are prognostic parameters in coronary artery disease. Increased kynurenine/tryptophan ratio correlates with increased intima-media thickness and represents advanced atherosclerosis. However, after bariatric surgery, weight reduction does not lead to the normalization of IDO1 activity and atherosclerosis. IDO1 is involved in the mechanisms of immune tolerance and in the concept of tumor immuno-editing process in cancer development. Serum IDO1 activity is still used as a parameter in cancer development and growth. IDO-producing tumors show a high total IDO immunostaining score, and thus, using IDO inhibitors, such as Epacadostat, Navoximod, and L isomer of 1-methyl-tryptophan, seems an important modality for cancer treatment. There is an inverse correlation between serum folate concentration and body mass index, thus folate deficiency leads to hyperhomocysteinemia-induced oxidative stress. Immune checkpoint blockade targeting cytotoxic T-lymphocyte-associated protein-4 synergizes with imatinib, which is an inhibitor of mitochondrial folate-mediated one-carbon (1C) metabolism. Antitumor effects of imatinib are enhanced by increasing T-cell effector function in the presence of IDO inhibition. Combining IDO targeting with chemotherapy, radiotherapy and/or immunotherapy, may be an effective tool against a wide range of malignancies. However, there are some controversial results regarding the efficacy of IDO1 inhibitors in cancer treatment.