Associations of Serum Folate and Holotranscobalamin with Cardiometabolic Risk Factors in Rural and Urban Cameroon

A low intake of fruit and vegetables and a high intake of meat are associated with higher cardiometabolic disease risk; however much prior research has relied on subjective methods for dietary assessment and focused on Western populations. We aimed to investigate the association of blood folate as an objective marker of fruit and vegetable intake and holotranscobalamin (holoTC) as a marker of animal-sourced food intake with cardiometabolic risk factors. We conducted a population-based cross-sectional study on 578 adults (mean ± SD age = 38.2 ± 8.6 years; 64% women). The primary outcome was a continuous metabolic syndrome score. The median serum folate was 12.9 (IQR: 8.6–20.5) nmol/L and the mean holoTC was 75 (SD: 34.3) pmol/L. Rural residents demonstrated higher serum folate concentrations (15.9 (9.8–25.9) nmol/L) than urban residents (11.3 (7.9–15.8) nmol/L), but lower holoTC concentrations (rural: 69.8 (32.9) pmol/L; urban: 79.8 (34.9)) pmol/L, p < 0.001 for both comparisons. There was an inverse association between serum folate and metabolic syndrome score by −0.20 in the z-score (95% CI, −0.38 to −0.02) per 10.8 (1 SD) of folate) in a model adjusted for socio-demographic factors, smoking status, alcohol intake, BMI, and physical activity. HoloTC was positively associated with the metabolic syndrome score in unadjusted analysis (0.33 (95% CI, 0.10 to 0.56)) but became non-significant (0.17 (−0.05 to 0.39)) after adjusting for socio-demographic and behavioural characteristics. In conclusion, serum folate and holoTC were associated with the metabolic syndrome score in opposite directions. The positive association between serum holoTC and the metabolic syndrome score was partly dependent on sociodemographic characteristics. These findings suggest that, based on these biomarkers reflecting dietary intakes, public health approaches promoting a higher intake of fruit and vegetables may lower cardiometabolic risk factors in this population.

Serum folate status among blood donors in south-central China

Folate deficiency has been confirmed to be related to various diseases. Unfortunately, there are few reports on the folate status of Chinese adults. This study aims to evaluate the serum folate status of blood donors in south-central China. In this study, 248 blood donors were included. The information on subjects was collected by a brief questionnaire concerning alcohol consumption habits, smoking habits, fruit and vegetable consumption and physical activity. The serum folate concentration was measured by electrochemiluminescence immunoassay. The geometric mean serum folate concentration was 13.4[Formula: see text]nmol[Formula: see text]l[Formula: see text] (95% CI, 12.7–14.1). The prevalence of serum folate concentrations below 6.8[Formula: see text]nmol[Formula: see text]l[Formula: see text] was 5.2% (95% CI, 2.5–8.0). There were significant differences in serum folate concentrations with respect to sex ([Formula: see text]-values [Formula: see text] 0.05), age ([Formula: see text]-values [Formula: see text] 0.05), fruit and vegetable consumption ([Formula: see text]-values [Formula: see text] 0.05), and alcohol consumption habits ([Formula: see text]-values [Formula: see text] 0.05). The concentration of serum folate increased with age ([Formula: see text]-values [Formula: see text] 0.05) and fruit and vegetable consumption ([Formula: see text]-values [Formula: see text] 0.05). Individuals with an age of 30 years or younger were nearly 3.5 times as likely as those aged over 30 years to have an insufficient level of serum folate (OR = 3.48; 95% CI: 1.01–11.99). An age of 30 years or younger was a risk factor for folate deficiency. Most blood donors had sufficient serum folate concentrations in south-central China. National surveys of folate status should be implemented in China.

Direct and Indirect Effects of Indoor Particulate Matter on Blood Indicators Related to Anemia

Exposure to indoor particulate matter (PM) is a potential risk factor that increases systemic inflammation and affects erythropoiesis. This study investigated the association between exposure to indoor PM and blood indicators related to anemia (BIRA) in housewives. Indoor PM and blood folate status are important factors in the risk of anemia. This was a housewife cohort study; we recruited 284 housewives in Seoul and Ulsan, Republic of Korea. Indoor exposure to PM2.5 and PM10 was measured by gravimetric analysis and sensors. We investigated the BIRA, such as hemoglobin (Hb), hematocrit, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), and mean corpuscular Hb concentration (MCHC). Statistical analysis was performed by multiple linear regression model and mediation analysis. The association between BIRA and PM was assessed by multiple linear regression models fitted by mediation analyses. The increase in the level of indoor PM2.5 was associated with a decrease in MCV (Beta coefficient (B): −0.069, Standard error (SE): 0.022) and MCH (B: −0.019, SE: 0.009) in gravimetric measurements. The increase in the level of indoor PM2.5 was associated with a decrease in Hb (B: −0.024, SE: 0.011), hematocrit (B: −0.059, SE: 0.033), and MCV (B: −0.081, SE: 0.037) and MCH (B: −0.037, SE: 0.012) in sensor measurements (PM2.5-Lag10). Further, we identified a serum folate-mediated PM effect. The indoor PM exposure was significantly associated with decreased Hb, MCV, and MCH in housewives. Taken together, our data show that exposure to indoor PM is a risk factor for anemia in housewives. Blood folate concentration can be a mediating factor in the effect of indoor PM on BIRA. Therefore, folate intake should be recommended to prevent anemia in housewives. Moreover, indoor PM exposure should be managed.

Prediction of Suicidality According to Serum Folate Levels in Depressive Patients Receiving Stepwise Pharmacotherapy

Background: The effects of serum folate levels on suicidal behavior, strongly associated with depression, have not been investigated. Therefore, this study investigated the associations between serum folate levels and suicidal behavior in patients with depressive disorders.Methods: Serum folate levels were measured at baseline in 1,094 patients with depressive disorder, 884 of whom were followed during a 12-month period of stepwise pharmacotherapy. Suicidal behaviors evaluated at baseline were (i) previous suicide attempt and (ii) baseline suicidal severity; behaviors evaluated at follow-up were (iii) increased suicidal severity and iv) fatal/non-fatal suicide attempt. Associations of serum folate levels with four types of suicidal behaviors were analyzed using logistic regression models after adjustment for relevant covariates; they were also examined using area under receiver operating characteristic (AUROC) curve analyses.Results: Reduced serum folate levels (&lt;6.0 ng/mL) were independently associated with all four types of suicidal behaviors. AUROC curve analyses indicated that discriminant or prognostic values of reduced serum folate levels were fair for fatal/non-fatal suicide attempt during follow-up, whereas they were modest for previous suicide attempt, baseline suicidal severity, and increased suicidal severity.Conclusions: Serum folate levels could serve as a biomarker of suicidal behavior in depressive patients. However, it should be used as an adjunct rather than a substitute for prediction of suicidal behavior considering its low prognostic values. Further replication studies are needed for its clinical utilization.

Serum folate concentration and health-related quality of life among the elderly in South Korea

Background The purpose of this study was to investigate the association between serum folate concentration and health-related quality of life (HRQOL) among the elderly in South Korea. Materials and methods The data used in this study were drawn from 1,021 participants over 65 years old in the Korea National Health and Nutrition Examination Survey from 2016–2018. HRQOL was measured by the EQ-5D questionnaire. Participants were divided into tertiles of folate concentration (ranges 1.7–5.6, 5.7–9.4, and 9.5–31.9 ng/mL). We performed multivariable linear regression to examine the relationship between folate and HRQOL, and multivariable logistic regression to examine the relationship between folate and the dimensional problem of HRQOL. Results Higher folate concentrations were significantly associated with higher HRQOL in the elderly. The average HRQOL score of the elderly in the highest tertile of the folate level was 0.0289 higher than that of the lowest tertile (coefficient: 0.0289; 95% CI 0.0016, 0.0563). The HRQOL score increased by 0.0174 points when the folate concentration increased by 100%. When analyzing specific dimensions, a significant association with folate concentration was found only for the self-care dimension of HRQOL (odds ratio for self-care problems: 0.63; 95% CI 0.41, 0.99). Conclusions The elderly with higher serum folate concentration tended to have higher HRQOL. Among HRQOL dimensions, self-care was only significantly associated with folate concentration.

Effectiveness of a fortified drink in improving B vitamin biomarkers in older adults: a controlled intervention trial

Background Older adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in the B vitamin biomarker status. Methods A double-blinded randomised controlled trial was performed in parallel at University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria (i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming > 4 portions of B vitamin-fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease). Recruited participants meeting the inclusion criteria were randomised (by sex and study centre) to receive daily for 16 weeks either B vitamin-fortified or placebo drinks as developed by Smartfish, Norway. Each B vitamin-fortified drink (200 ml) contained 200 µg folic acid, 10 µg vitamin B12, 10 mg vitamin B6 and 5 mg riboflavin, while the placebo was an identical, isocaloric formulation without added B vitamins. Fasting blood samples were collected pre- and post-intervention which were used to measure the primary outcome of change in B vitamin biomarker levels. Results A total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed (37 in the active and 33 in the placebo groups). Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamin biomarkers in the active compared to placebo groups: p < 0.01 for each of serum folate, serum vitamin B12 and plasma pyridoxal 5′-phosphate (vitamin B6) and the functional riboflavin biomarker, erythrocyte glutathione reductase activation coefficient (EGRac). Correspondingly, a significant lowering of serum homocysteine from 11.9 (10.3–15.1) µmol/L to 10.6 (9.4–13.0) µmol/L was observed in response to the active treatment (P < 0.001). Similar results were seen in a per-protocol analysis. Conclusions The results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention option to improve B vitamin status in older adults. Trial registration ISRCTN, ISRCTN61709781—Retrospectively registered, https://www.isrctn.com/ISRCTN61709781

MTHFD1 1958 G>A Genetic Polymorphism (rs2236225) Dichotomy in Schizophrenia: Lower Manifestation Risks, but More Severe Negative Symptoms

Despite a large amount of data on the association of folate metabolism disturbances with different aspects of schizophrenia, the role of the MTHFD1 1958 G&gt;A polymorphism in this disorder is barely studied. The aim of this study was to assess the distribution of alleles and genotypes frequencies of MTHFD1 1958 G&gt;A in patients with schizophrenia and healthy controls and to study the association of allele/genotype carriage of this SNP with biochemical markers of one-carbon metabolism and with the severity of schizophrenia symptoms. Methods: In 57 patients with schizophrenia and 37 healthy volunteers the carriage of alleles/genotypes of the MTHFD1 1958 G&gt;A and biochemical markers of folate metabolism disturbances were evaluated. Clinical symptoms of schizophrenia and the severity of extrapyramidal side effects of therapy were assessed in patients. Results: an association of the wild GG genotype with schizophrenia was shown (GG versus AG / AA: &chi;2 = 7.31; p = 0.007). The serum folate level in carriers of the wild genotype GG is lower (in all participants p = 0.024, in patients p = 0.10), and the level of cobalamin in this subgroup is higher (in all participants p = 0.047, in patients p = 0.091) than in carriers of other genotypes. Patients carrying the G allele had less severe negative symptoms (p = 0.0041) and extrapyramidal side effects of antipsychotics (p = 0.054), than patients with AA genotype. The age of psychosis manifestation is the later, the more wild alleles G are present in the genotype (p = 0.00195).

Myelopathy associated with intrathecal methotrexate

A 21-year-old man developed progressive and bilateral lower limb numbness, gait impairment and urinary incontinence over 10 days. He had received intrathecal methotrexate 20 days previously for acute lymphoblastic B-cell leukaemia, following 7 months of systemic chemotherapy. MR scan of the spinal cord showed bilateral symmetric and extensive T2/fluid attenuated inversion recovery (FLAIR) increased signal involving the dorsal columns in the thoracic cord. His serum folate concentration was at the lower end of the normal range. We stopped the intrathecal chemotherapy and gave folate; after a few days, he progressively improved. Myelopathy is an important adverse effect of intrathecal methotrexate, which may cause clinical and imaging features resembling subacute combined degeneration of the spinal cord. CNS infiltration must be excluded, intrathecal chemotherapy stopped and deficiency of folate or vitamin B12 treated as appropriate.

A Retrospective Cross-Sectional Cohort Trial Assessing the Prevalence of MTHFR Polymorphisms and the Influence of Diet on Platinum Resistance in Ovarian Cancer Patients

Ovarian cancer has the lowest survival rate in gynaecologic malignancies with a 5-year survival rate of 43%. Platinum resistance is one of the main drivers of ovarian cancer mortality, of which aberrant methylation has been cited as a significant contributor. Understanding the essential role of the methylenetetrahydrofolate reductase enzyme (MTHFR) on DNA synthesis and repair, and how nutrient status can vastly affect its performance, led to the investigation of MTHFR status and dietary influence on platinum response in epithelial ovarian cancer (EOC) patients. Twenty-five adult female patients who completed first-line platinum-based chemotherapy for primary ovarian cancer were selected from Icon Cancer Centres in Australia. Participants were grouped based on platinum response. A full medical and family history, food frequency questionnaire and single blood test were completed, testing for MTHFR polymorphisms, serum folate, serum and active B12 and homocysteine levels. Nineteen of twenty-five participants had an MTHFR polymorphism. Of those, 20% were compound heterozygous, 12% were heterozygous C677T (CT), 4% homozygous C677T, 12% homozygous A1298C and 28% were heterozygous A1298C (AC). Statistically significant associations were found between dietary zinc (p = 0.0086; 0.0030; 0.0189) and B12 intakes in CT genotypes (p = 0.0157; 0.0030; 0.0068) indicating that zinc or vitamin B12 intakes below RDI were associated with this genotype. There were strong associations of vitamin B6 intakes in AC genotypes (p = 0.0597; 0.0547; 0.0610), and dietary folate in compound heterozygotes with sensitive and partially sensitive disease (p = 0.0627; 0.0510). There were also significant associations between serum folate (p = 0.0478) and dietary B12 (p = 0.0350) intakes above RDI and platinum sensitivity in wild-types as well as strong associations with homocysteine levels (p = 0.0886) and zinc intake (p = 0.0514). Associations with dietary B12 (p = 0.0514) and zinc intakes (p = 0.0731) were also strong in resistant wild types. Results indicate that dietary zinc, B12 and B6 intakes may be associated with platinum sensitivity dependent on MTHFR genotype. These results require further research to clarify the dosages necessary to elicit a response; however, they provide a novel foundation for acknowledging the role of diet on treatment response in EOC.

Association of MTHFR C677T variant genotype with serum folate and Vit B12 in Iranian patients with colorectal cancer or adenomatous polyps

Background The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC. The present study aimed to investigate the clinical significance of C677T polymorphism within the MTHFR gene and its correlation with the serum folate and Vit B12 in the Iranian population suffering from CRC. Methods Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk was analyzed. Results In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT, and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with an increased risk of CRC by 3.68, 1.42, and 3.74-fold in codominant, dominant, and recessive models respectively (p value < 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups (p value > 0.05). Conclusions This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT + C677T genotypes of MTHFR compared with 677CC carriers among CRC patients.