Serum folate and risk of disabling dementia: a community-based nested case-control study.

PURPOSE: The aim of this study was to examine associations between serum folate levels and risk of disabling dementia that required care under the national insurance (disabling dementia). METHODS: We performed a nested case-control study in a community-based cohort, the Circulatory Risk in Communities Study, involving 13,934 Japanese individuals aged 40-84 years at the baseline period of 1984-2005. Serum folate was measured in 578 cases of incident disabling dementia, and in 1,156 controls whose age (±1 years), sex, area of residence, and baseline year were matched with the cases. The diagnosis of disabling dementia was performed by attending physicians under the National Long-Term Care Insurance System in Japan. Conditional odds ratios of disabling dementia according to quintiles of serum folate were calculated using conditional logistic regression models. RESULTS: After a 20.8-year follow-up, serum folate was inversely associated with risk of disabling dementia. The respective multivariable odds ratios (95% CIs) were 0.71 (0.51-0.99), 0.76 (0.54-1.06), 0.70 (0.49-1.00), and 0.62 (0.43-0.90) for persons with the second, third, fourth, and highest quintiles of serum folate as compared with the lowest quintile (P for trend = 0.03). A similar association was observed for dementia with or without stroke. CONCLUSION: In this nested case-control study with a long follow-up, low serum folate levels were associated with an increased risk of disabling dementia among Japanese individuals.

Folate deficiency may increase the risk for elevated TSH in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and thyroid dysfunction (TD) are two common chronic endocrine disorders that often coexist. Folate deficiency has been reported to be related with the onset and development of T2DM. However, the relationship between folate deficiency and TD remains unclear. This study aims to investigate the association of serum folate with TD in patients with T2DM. METHODS: The study used data on 268 inpatients with T2DM in the Beijing Chao-yang Hospital, Capital Medical University from October 2020 to February 2021. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and serum folate were measured with chemiluminescence immunoassay (CLIA), and folate deficiency was defined as a serum folate concentration < 4.4 ng/mL. Ordinary least squares regression models were used to assess the association of serum folate with TSH concentration. Multivariable logistic regression models were performed to explore the correlation of folate deficiency and the risk for elevated TSH. RESULTS: 15.3% of T2DM patients had TD. Among those patients with TD, 80.5% had elevated TSH. Compared with the normal-TSH and low-TSH groups, the prevalence of folate deficiency was significantly higher in the elevated-TSH group (P < 0.001). Serum folate level was negatively associated with TSH (ß=-0.062, 95%CI: -0.112, -0.012). Folate deficiency was associated with the higher risk for elevated TSH in patients with T2DM (OR = 8.562, 95%CI: 3.108, 23.588). CONCLUSIONS: A low serum folate concentration was significantly associated with a higher risk for elevated TSH among T2DM patients.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

Association of maternal folate and B12 vitamin status with gestational diabetes mellitus: Still an open issue.

OBJECTIVES: There is conflicting evidence about the role of folate and B12in gestational diabetes mellitus (GDM) onset. The association of vitamin status with GDM was therefore revalued, also measuring the B12active form holotranscobalamin. METHODS: 677 women were evaluated at 24-28 weeks of gestation when OGTT was carried out. The 'one-step' strategy was employed for GDM diagnosis. Odds ratio (OR) of having GDM was estimated to quantify the association with vitamin levels. RESULTS: 180 women (26.6%) had GDM. They were older (median, 34.6 vs. 33.3 years, p = 0.019) and had higher body mass index (BMI) (25.8 vs. 24.1 kg/m2, p < 0.001). Multiparous women had lower levels of all evaluated micronutrients, while overweight lowered both folate and total B12, but not holotranscobalamin. Lower total B12(270 vs. 290 ng/L, p = 0.005), but not holotranscobalamin, was observed in GDM, being weakly negatively correlated with fasting glycemia (r = -0.11, p = 0.005) and 1-h OGTT serum insulin (r = -0.09, p = 0.014). At multivariate analysis, age, BMI and multiparity remained the strongest GDM predictors, while total B12(but not holotranscobalamin and folate) showed a slight protective effect (OR = 0.996, p = 0.038). CONCLUSIONS: A weak association between total B12 levels and GDM risk was shown, but it was not confirmed when holotranscobalamin was measured.

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

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

Associations between Serum Folate Concentrations and Functional Disability in Older Adults.

Folate may have beneficial effects on physical function through its antioxidant effect. Thus, we investigated the associations between serum folate and functional disability in older adults. Data from the National Health and Nutrition Examination Survey 2011-2018 were used. Serum folate included 5-methyltetrahydrofolate and total folate. Five domains of functional disability, including lower extremity mobility (LEM), instrumental activities of daily living (IADL), activities of daily living (ADL), leisure and social activities (LSA), and general physical activities (GPA), were self-reported. Multivariable-adjusted logistic regression models and restricted cubic splines were employed. 5-Methyltetrahydrofolate was inversely associated with IADL and GPA disability, and the multivariate-adjusted ORs (95% CIs) in the highest versus lowest quartiles were 0.65 (0.46-0.91) and 0.70 (0.50-0.96), respectively. The total folate was also inversely associated with IADL (OR quartile 4vs1 = 0.65, 95% CI: 0.46-0.90) and GPA (OR quartile 3vs1 = 0.66, 95% CI: 0.44-0.99) disability. The dose-response relationships showed a gradual decrease in the risk of IADL and GPA disability as serum folate increased. In the sex, age, BMI, and alcohol consumption subgroup analyses, we saw that the associations were primarily found in females, under 80 years old, normal weight, and non-drinkers. Sensitivity analyses further confirmed the robustness of our results. Our results indicated that serum folate concentrations were negatively associated with IADL and GPA disability, especially in females. In other subgroup analyses, we discovered that these negative associations were primarily prevalent in participants under 80 years old, normal weight, and non-drinkers.

Associations of Serum Folate and Homocysteine Concentrations with All-Cause, Cardiovascular Disease, and Cancer Mortality in Men and Women in Korea: the Cardiovascular Disease Association Study.

BACKGROUND: Evidence on the association of serum folate and homocysteine concentrations with risk of mortality in the general population is unclear. OBJECTIVES: This study aimed to examine the associations of serum folate and homocysteine concentrations with all-cause, CVD, and cancer mortality risk in Korean men and women aged ≥40 y. METHODS: In this population-based prospective cohort study, serum folate and homocysteine concentrations were measured in a subset of participants enrolled between 2005 and 2012. A total of 21,260 participants were linked to mortality data from the survey date to 31 December 2019. Cox proportional hazards models and restricted cubic splines were used to identify the associations of serum folate and homocysteine concentrations with mortality. RESULTS: During a median follow-up of 12.3 y, 2501, 549, and 842 deaths were attributed to all-cause, CVD, and cancer, respectively. The prevalence of folate deficiency and hyperhomocysteinemia were higher in men than in women. In men, a nonlinear inverse association was observed between serum folate concentrations and all-cause mortality. Men in the third quartile of serum folate concentrations exhibited a lower risk of all-cause mortality (HR: 0.85; 95% CI: 0.73, 0.99) than those in the lowest quartile. Serum homocysteine concentration was positively associated with all-cause and CVD mortality. Men and women in the highest compared with those in the lowest serum homocysteine quartile showed a higher risk of CVD mortality (HR: 1.60; 95% CI: 1.07, 2.39; and HR: 1.79; 95% CI: 1.11, 2.89, respectively). Hyperhomocysteinemia combined with folate deficiency was associated with increased all-cause, CVD, and cancer-related mortality rates. CONCLUSIONS: Higher serum homocysteine and lower serum folate concentrations were associated with an increased risk of all-cause, CVD, and cancer-related mortality in Korean adults. The finding of a nonlinear inverse relationship between serum folate concentration and mortality in men warrants further investigation.

The association between serum folate and ultrasound - defined hepatic steatosis.

PURPOSE: It has been discovered that a folate shortage may raise the risk of hepatic steatosis. We investigated the relationship between serum folate and controlled attenuation parameter (CAP) among 3606 participants over from the National Health and Nutrition Examination Survey (NHANES). MATERIALS AND METHODS: Multivariate logistic regression studies were carried out to calculate the relationship between serum folate and CAP. Additionally, generalized additive models and fitted smoothing curves were carried out. RESULTS: After adjusting for other variables, we discovered that serum folate had a negative correlation with CAP. Males and whites maintained a negative correlation of serum folate with CAP when subgroup analyses were stratified by sex and race/ethnicity. The relationship between blood folate levels and CAP in whites had an U-shaped curve (inflection point: 34 ng/ml). CONCLUSION: According to our study, the majority of Americans, particularly men and whites, had a negative correlation between serum folate and CAP. Among white people, this connection followed an U-shaped pattern. These findings may provide guidance for monitoring serum folate level and controlling oral folate dosage in clinic, so as to prevent liver steatosis more effectively.Key MessagesThe size of the cohort in our study is large, and our findings come from a nationally representative database.Our study revealed a negative relationship between serum folate and CAP among most Americans, especially in male and whites, which may provide evidence for medications to treat hepatic steatosis.In whites, the association of serum folate with CAP was an U-shaped curve (inflection point: 34 ng/ml). This may provide guidance for monitoring serum folate level and controlling oral folate dosage in clinic, so as to prevent liver steatosis more effectively.

Association of serum folate levels during pregnancy and prenatal depression.

OBJECTIVE: To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship. METHODS: This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control's Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range. RESULTS: Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR] = 1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively). CONCLUSION: Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.

Association between serum folate concentrations and blood lead levels in adolescents: A cross-sectional study.

As a heavy metal, lead is a common toxic agent. Its accumulation in the body is harmful to physical health, particularly in children and adolescents. Studies have reported that folate may play a protective role in lead exposure. An association between serum folate concentrations (SFC) and blood lead levels (BLL) has been documented in adults, but studies in adolescents are limited. This study investigated the relationship between SFC and BLL in American adolescents. This cross-sectional study collected relevant data on both SFC and BLL of 5,195 adolescents in the NHANES database from 2007 to 2018. Multivariable linear regressions and smooth curve fittings were adopted to evaluate the correlation between BLL and SFC. After adjusting potential confounders, we found negative relationships between BLL and SFC [ß = -0.0041 (-0.0063, -0.0019)], and the associations were significant in non-Hispanic Whites, Mexican Americans, and other races but not significant in non-Hispanic blacks (P = 0.139). Furthermore, the negative trends were significant in adolescents aged 16-19 years and females aged 12-15 years but insignificant in males aged 12-15 years (P = 0.172). Therefore, these findings provide a basis for future research on the mechanism of folate in regulating blood lead levels.

Serum folate levels in children with epilepsy seen in a tertiary health care facility in north central Nigeria.

Background: Children suffering from epilepsy are maintained on antiepileptic drugs (AED) to ensure a reasonable quality of life. These drugs, however, are not without side effects. Notable among which is interference with the metabolism of folate with its attendant clinical implications such as megaloblastic anemia and bleeding diathesis. Aim: This study was carried out to determine the serum folate levels of children with epilepsy, compare the folate levels of these children with that of controls, the levels in subjects on different AED, and to investigate the possible effect of duration of AED use on serum folate levels. Patients and Methods: It was a comparative cross-sectional study involving children with epilepsy aged 2-14 years attending the paediatric neurology clinic of University of Ilorin Teaching Hospital (UITH), Ilorin. A total of 140 epileptic and 140 age-and-sex-matched nonepileptic children as controls were recruited into the study. Results: Mean serum folate levels in subjects of 6.3 ± 1.6 ng/mL was significantly lower than 7.5 ± 1.5 ng/mL in controls (P = 0.001). The mean serum folate level in subjects on AED was comparable with the value in AED naïve subjects. The mean serum folate level was also comparable among subjects on carbamazepine, phenobarbitone, and valproate as monotherapy. There was no correlation between the duration of AED use and the mean serum folate levels (r = -0.180; P = 0.069). Conclusion: The mean serum folate level in subjects was significantly lower than the value in controls; but was comparable in subjects on carbamazepine, phenobarbitone, and valproate as monotherapy. There was no correlation between the duration of AED use and mean serum folate levels.

Comparison of four different immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry assay for serum folate.

OBJECTIVES: Accurate measurement of serum folate is essential for the diagnosis and management of various disorders. This study aims to investigate the between-method differences of four immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method. METHODS: Roche Cobas (USA), Abbott Alinity i2000 (USA), Beckman Coulter Access (USA), Mindray CL-6000i (China), and the ID-LC-MS/MS method were compared using 46 human serum samples. The results were analysed by Passing-Bablok regressions and Bland-Altman plots. A bias of 13.31% based on biological variation was used as the bias criterion. RESULTS: All the within-run and total coefficients of variation (CVs) met the specification. The folate concentrations determined by all the assays were significantly different (p=0.0028). All assays had correlation coefficients over 0.97 with each other. The 95% confidence intervals (CIs) for the slope seldom contained 1 and few 95% CIs for the intercept contained 0 in the regression equations. Compared to ID-LC-MS/MS, the biases of all assays ranged from -20.91 to 13.56 nmol/L, and the mean relative biases ranged from -9.85 to 40.33%. The predicted mean relative biases at the medical decision levels rarely met the criterion. CONCLUSIONS: Assays for serum folate had good correlations with each other but lacked good agreement. The accuracy and consistency of assays for serum folate should be measured and assessed routinely. Standardization work to improve the accuracy of serum folate assays, such as the extension of traceability to reference methods or materials, calibration standardization efforts, and assay-adjusted cut-offs should be promoted.

Folate intake and incident chronic kidney disease: a 30-year follow-up study from young adulthood to midlife.

BACKGROUND: The relation of long-term dietary folate intake with incident chronic kidney disease (CKD) remains uncertain. OBJECTIVES: We aimed to investigate the association between dietary folate intake and incident CKD in a 30-y follow-up study from young adulthood to midlife. METHODS: A total of 4038 American adults aged 18-30 y and without reduced estimated glomerular filtration rate (eGFR) were enrolled in 1985-1986 and monitored until 2015-2016 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. Diet was assessed by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The primary outcome was incident CKD, defined as an eGFR <60 mL · min-1 · 1.73 m-2 or a urinary albumin to creatinine ratio (ACR) ≥30 mg/g. The secondary outcomes included 1) incident decreased eGFR, defined as an eGFR <60 mL · min-1 · 1.73 m-2, and 2) incident albuminuria, defined as an ACR ≥30 mg/g. RESULTS: During the follow-up, 642 (15.9%) participants developed CKD. Overall, there was a significant L-shaped relation of dietary folate with incident CKD after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted HRs (95% CIs) in quintiles 2-5 for incident CKD were 0.69 (0.56, 0.85), 0.35 (0.27, 0.45), 0.34 (0.26, 0.45), and 0.39 (0.30, 0.51), respectively. Similar results were found for the secondary outcomes. Moreover, the L-shaped association was confirmed in a subset of the cohort (n = 1462) with serum folate measured at baseline, in 1992, and in 2000. CONCLUSIONS: Higher folate intake in young adulthood was longitudinally associated with a lower incidence of CKD later in life. Additional studies are warranted to establish the causal inference.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Maternal micronutrient status and its association with sociodemographic, maternal, and dietary factors in a cross-sectional study.

AIM: Maternal serum micronutrient status can have a significant impact on short- and long-term outcomes for mother and offspring. The aim of this study was to examine the associations of maternal serum folate, ferritin, and vitamin B12 status with maternal and dietary factors. METHODS: This observational cross-sectional study was carried out with 165 healthy pregnant women at least 18 years of age with a singleton pregnancy. Maternal nutrient intake was determined by 24-hour dietary recall method and supplement records. Multivariable analyses using stepwise linear regression models were performed to associations of dietary intakes and maternal serum status. RESULTS: There was a difference between the lowest and highest quartile of maternal serum folate, ferritin, and vitamin B12 status and maternal characteristics and dietary, and total intakes of nutrients (p < 0.05). Multivariable stepwise linear regression analysis showed the predictors of serum folate status were dietary folate equivalent, dietary folate, total vitamin B6 and iron intake. Primer predictors of serum ferritin and vitamin B12 status were dietary protein intake (p < 0.05). CONCLUSION: Our findings support existing recommendations that folic acid supplementation should be prescribed to achieve optimal serum folate status during pregnancy. However, dietary protein intake is important to provide optimal maternal serum vitamin B12 and ferritin status.

Associations of Serum and Red Blood Cell Folate With All-Cause and Cardiovascular Mortality Among Hypertensive Patients With Elevated Homocysteine.

Objectives: This study aims to explore the associations between serum and red blood cell (RBC) folate as indicators of short- and long-term folate status, respectively, and all-cause as well as CVD mortality among hypertensive patients with elevated homocysteine. Methods: A prospective cohort study of the National Health and Nutrition Examination Survey (1999-2006) and 2015 Linked Mortality File was performed. All-cause and CVD mortality risk estimated using Cox proportional hazards models with adjusting for multiple potential covariates. Results: A total of 1,753 hypertensive patients with elevated homocysteine [mean (SD) age, 68.5 (13.1)] were included in the analysis. During a median follow-up of 10.0 years, a total of 899 all-cause and 257 CVD deaths occurred. Compared the highest with the lowest quartile of RBC folate, the multivariable adjusted hazard ratios and 95% confidence intervals for all-cause and CVD death were 1.13 (0.92-1.39) and 1.47 (1.01-2.16) respectively. There was a significant and positive trend between RBC folate and the risk of CVD death (p for trend = 0.0196). No significant association was found between serum folate and mortality risk among the study sample. Conclusions: High level of RBC folate is associated with an increased risk of cardiovascular mortality among hypertensive patients with elevated homocysteine while serum folate has no such effects.

Association between serum folate levels and blood concentrations of cadmium and lead in US adults.

BACKGROUND: Folate may be involved in the detoxification of heavy metals. This has been demonstrated in animal studies, in in vivo and in vitro studies, and clinical evaluations. However, knowledge regarding the associations between serum folate and blood concentrations of cadmium and lead is limited. OBJECTIVE: We aimed to investigate the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults. METHODS: Data on 15,501 adults were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and used for the analysis. Information on serum folate concentrations and blood levels of lead and cadmium was derived from laboratory measurements in the NHANES. Multivariable linear regression was used to examine the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults, controlling for confounders. RESULTS: The serum folate concentration was negatively correlated with blood levels of cadmium and lead (P-trends <0.01). When stratified by sex (male and female) and estimated glomerular filtration rate (eGFR ≤60 and >60 mL/min/1.73 m2), the association between serum folate concentrations and blood levels of cadmium and lead was found to be more stable in adults with eGFR > 60 mL/min/1.73 m2, both in males and females. SIGNIFICANCE: These findings warrant future studies to explore the mechanisms responsible for the beneficial role of folate in regulating cadmium and lead concentrations in the blood.

The relationship between serum folate and grip strength in American adults.

We used data from NHANES to explore the associations between serum folate and grip strength, and found that high levels of serum folate were associated with increased grip strength among females rather than males. It is recommended to maintain a proper level of serum folate, especially in women. PURPOSE: Associations and dose-response relationships between serum total folate, 5-methyltetrahydrofolate, and grip strength in general adults were unknown. Thus, we conducted this analysis for further exploration. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) database of 2011-2014 cycle were used. The independent variables including serum total folate, combined total folate (total folate plus Mefox), and 5-methyltetrahydrofolate. The dependent variable was BMI-corrected grip strength. Linear regression and the restricted cubic splines were used in our analyses. RESULTS: A total of 9079 adults aged over 20 years were included. In multivariate-adjusted model 2, compared with quartile (Q) 1, grip strength increased in Q3 of combined total folate and total folate, and the weighted ß values with 95% confidence intervals (CIs) of grip strength were 0.06 (0.01, 0.12) and 0.06 (0.00, 0.10) for combined total folate and total folate, respectively. In the stratified analysis by gender, positive relationships between combined total folate, total folate, and 5-methyltetrahydrofolate and grip strength were found only in females, with ß (95% CIs) of 0.07 (0.02, 0.12), 0.07 (0.03, 0.12), and 0.09 (0.05, 0.13) for combined total folate, total folate, and 5-methyltetrahydrofolate in Q4, respectively. Non-linear positive dose-response relationships between serum folate and grip strength were also found only in females, not in males. CONCLUSION: Our study suggested a positive association between serum folate and grip strength, while this positive association was only found in females; besides, the dose-response relationships were in a non-linear trend. Thus, it is recommended to maintain a proper serum folate level to keep better muscle strength, especially for women.

Serum Folate and All-Cause Mortality is of Non-Linear Relationship Among Population with Chronic Kidney Disease: A Retrospective Cohort Study.

AIM: A transition toward high serum folate concentrations has been noticed following the mandatory folate fortification. To explore this further, we studied the relationship between folate and health outcomes in population with chronic kidney disease (CKD). METHODS: We retrospectively explored the relationships between serum folate and risk of all-cause death in this population. We analyzed data of 2142 subjects with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Vital status was followed through December 31, 2006. RESULTS: Cox regression was used to estimate hazard ratios (HRs) of mortality for individuals with serum folate in rest quintiles compared with individuals with the fourth quintile. After an average follow-up of 57.4 months with 157 deaths recorded, a reversed J-shaped association was revealed after conducting multivariable adjustment. The mortality rate in population with lower and higher folate levels were 8.29% and 12.67%, respectively, and the corresponding adjusted HRs were 2.41 (95% confidence interval, CI=1.32-4.40) and 2.10 (1.20-3.70). Kaplan-Meier curve showed survival benefits for the fourth quintile of serum folate as compared to the first and fifth quintile. CONCLUSION: Serum folate concentrations may influence all-cause mortality in a non-linear pattern in the CKD population. It is reasonable to recommend periodic surveillance in the CKD population to maintain the serum folate concentration in an appropriate level.

Interactions Between Handgrip Strength and Serum Folate and Homocysteine Levels on Cognitive Function in the Elderly Chinese Population.

BACKGROUND: Handgrip strength (HGS) and serum folate and homocysteine (Hcy) levels were associated with cognitive function. However, little was known whether there were interactions between HGS and serum folate and Hcy levels on cognitive function. OBJECTIVE: To examine the interactions between HGS and serum folate and Hcy levels on cognitive function. METHODS: This study analyzed the baseline data of the Tianjin Elderly Nutrition and Cognition Cohort study. All participants aged ≥60 years were potential eligible. HGS was measured using a grip strength dynamometer. Serum folate and Hcy levels were assayed using standard laboratory protocol. A Mini-Mental State Examination was used to assess cognitive function. Linear regressions were employed to examine the interactions between HGS and serum folate and Hcy levels on cognitive function. RESULTS: 4,484 participants were included in this study. There were interactions between HGS and serum folate and Hcy levels on cognitive function. Furthermore, subjects with strong HGS and sufficient folate level had the best cognitive function (ß= 2.018), sequentially followed by those with strong HGS and insufficient folate level (ß= 1.698) and with poor HGS and sufficient folate level (ß= 0.873). Similarly, cognitive function was ranked in the descending order of subjects with strong HGS and normal Hcy level (ß= 1.971), strong HGS and high Hcy level (ß= 1.467), and poor HGS and normal Hcy level (ß= 0.657). CONCLUSION: There were interactions between HGS and serum folate and Hcy levels on cognitive function. However, the temporal associations cannot be examined in a cross-sectional study. Further cohort study should be conducted to confirm these associations in the future.