Serum folate levels and urinary arsenic methylation profiles in the US population: NHANES, 2003–2012

Introduction: Serum folate (SF), vitamin B12 (B12), and iron deficiency (def) are common causes of nutritional anemias (NA). These deficiencies are usually multifactorial, with nutritional and non-nutritional causes playing a role. SF, B12, and iron levels are usually ordered in the setting of anemia, and malnutrition with or without neurologic symptoms. Clinical evidence suggests that these def have a strong dietary component and socioeconomic status (SES). The relationship of NA and area-based SES in the US has not been studied. We aimed to determine the relationship of SES with the prevalence of NA. Methods: We performed a cross-sectional analysis of adult patients with SF, B12 and iron levels at Mayo Clinic Arizona and Florida between 2010 and 2018. Race was classified using the NIH criteria. Normal laboratory values were determined according to our lab reference and the US NHANES III. SF levels (mcg/Lt) were defined as deficient <4, normal ≥4.0, and excess ≥20. B12 levels (ng/L) as deficient <150, borderline 150-400, normal >400-900, and excess ≥900. Iron def was determined by ferritin levels (mcg/L) as low <24, normal 24-336, elevated >336 for men, low <11, normal 11-307, elevated >307 for women. Area-Level SES indicators: Median Household income (MHI), unemployment rate (UR), median gross rent month (MGRM), % uninsured, median house value (MHV), % high school; were geocoded by zip code using the 2014 American Community Survey. Demographics and clinical variables were compared between groups by chi-square test for frequency data or Kruskal Wallis rank-sum test for continuous variables. Results: 202,046 samples from 128,084 patients were analyzed. In the sample-level analysis, there were statistically significant associations between SES and SF def; all SES indicators except UR for B12 def; and no differences for iron def, except % uninsured (Table 1). There was no statistically significant interaction between race and SES for SF def and iron def. Race was a statistically significant modifier between B12 def and MHI (p<0.001), % uninsured (p=0.002), and MHV (p=0.007). Asian and Other race had an increase in odds of B12 def with increasing MHI (Asian OR=1.11 , Other OR=1.18); white race had a decrease in odds of B12 def with increasing MHI (OR=0.95 for a $10,000 increase in MHI). Conclusions: We show significant relationships between SES and NA in the US. Differences were observed between SF def and all the SES indicators without race interactions. There were significant interactions between B12 def, race and SES for pts of White, Asian and Other race. There were no differences between SES and race for iron def. These relationships confirm that NA are related to area-level SES and other social determinants of health. Research regarding the causes of these disparities on a population level are needed. Disclosures No relevant conflicts of interest to declare.

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Folate status in the US population 20 y after the introduction of folic acid fortification

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz184 ◽

2019 ◽

Vol 110 (5) ◽

pp. 1088-1097 ◽

Cited By ~ 12

Author(s):

Christine M Pfeiffer ◽

Maya R Sternberg ◽

Mindy Zhang ◽

Zia Fazili ◽

Renee J Storandt ◽

...

Keyword(s):

Folic Acid ◽

White Women ◽

Geometric Mean ◽

Age Groups ◽

The United States ◽

Reproductive Age ◽

Serum Folate ◽

Folate Status ◽

Cereal Grain ◽

The Us

ABSTRACT Background Enriched cereal-grain products have been fortified in the United States for >20 y to improve folate status in women of reproductive age and reduce the risk of folic acid–responsive neural tube birth defects (NTDs). Objectives Our objectives were to assess postfortification changes in folate status in the overall US population and in women aged 12–49 y and to characterize recent folate status by demographic group and use of folic acid–containing supplements. Methods We examined cross-sectional serum and RBC folate data from the NHANES 1999–2016. Results Serum folate geometric means increased from 2007–2010 to 2011–2016 in persons aged ≥1 y (38.7 compared with 40.6 nmol/L) and in women (35.3 compared with 37.0 nmol/L), whereas RBC folate showed no significant change. Younger age groups, men, and Hispanic persons showed increased serum and RBC folate concentrations, whereas non-Hispanic black persons and supplement nonusers showed increased serum folate concentrations. The folate insufficiency prevalence (RBC folate <748 nmol/L; NTD risk) in women decreased from 2007–2010 (23.2%) to 2011–2016 (18.6%) overall and in some subgroups (e.g., women aged 20–39 y, Hispanic and non-Hispanic black women, and supplement nonusers). After covariate adjustment, RBC folate was significantly lower in all age groups (by ∼10–20%) compared with persons aged ≥60 y and in Hispanic (by 8.2%), non-Hispanic Asian (by 12.1%), and non-Hispanic black (by 20.5%) compared with non-Hispanic white women (2011–2016). The 90th percentile for serum (∼70 nmol/L) and RBC (∼1800 nmol/L) folate in supplement nonusers aged ≥60 y was similar to the geometric mean in users (2011–2014). Conclusions Blood folate concentrations in the US population overall and in women have not decreased recently, and folate insufficiency rates are ∼20%. Continued monitoring of all age groups is advisable given the high folate status particularly in older supplement users.

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Changes in Urinary Arsenic Methylation Profiles in a 15-Year Interval after Cessation of Arsenic Ingestion in Southwest Taiwan

Environmental Health Perspectives ◽

10.1289/ehp.0900560 ◽

2009 ◽

Vol 117 (12) ◽

pp. 1860-1866 ◽

Cited By ~ 17

Author(s):

Yung-Kai Huang ◽

Ya-Li Huang ◽

Yu-Mei Hsueh ◽

Jimmy Tse-Jen Wang ◽

Mo-Hsiung Yang ◽

...

Keyword(s):

Arsenic Methylation ◽

Urinary Arsenic ◽

Arsenic Ingestion

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Folate Deficiency in an Urban Safety Net Population

Blood ◽

10.1182/blood-2020-138971 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 46-46

Author(s):

Lindsey A Hildebrand ◽

Brett Dumas ◽

Charles Milrod ◽

James Hudspeth

Keyword(s):

Substance Use ◽

Folic Acid ◽

Social Determinants Of Health ◽

Social Determinants ◽

Folate Deficiency ◽

Safety Net ◽

Serum Folate ◽

Safety Net Hospital ◽

The Us ◽

Urban Safety

Introduction: Folate deficiency is a known cause of megaloblastic anemia. Serum folate level is therefore a common component of the workup for megaloblastic and other anemias. Following mandatory fortification of grain products with folic acid in the US in 1998, folate deficiency has become relatively rare in both the general population and in hospitalized patients. Some authors have suggested that serum folate levels should be tested rarely if at all in countries with mandatory folic acid fortification given low rates of deficiency, high cost per diagnosis of deficiency, and low rates of supplementation for those found to be deficient. However, given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these conclusions may not apply to all populations. In this study, we examine the rate at which serum folate testing detected folate deficiency in an urban safety net hospital and the characteristics of patients found to be folate deficient. Methods: All serum folate tests performed on inpatients and emergency department patients in 2018 at a large safety net hospital in Boston were reviewed. Serum folate levels under 4 ng/mL were considered deficient per WHO criteria. We reviewed the charts of all patients found to be folate deficient, collecting demographic data; data concerning social determinants of health; and clinical data such as hematologic lab data, stated reason for testing, and pertinent disease states such as malnutrition and substance use. We also noted whether the medical team acted upon the folate deficiency. Finally, we performed a cost analysis. Results: Out of 1368 patients whose serum folate was tested, 76 patients (5.5%) met criteria for folate deficiency. Of those patients, chart review found that hematologic abnormality was a documented cause of testing for 63%. Overall, 79% of folate deficient patients were anemic, but only 20% had a macrocytic anemia. 42% had a documented diagnosis of malnutrition. Common social determinants in patients found to be folate deficient include birth outside of the US (25%), homelessness (12%), and alcohol use disorder (29%). Of those found to be folate deficient, 93% were either started on folic acid supplementation or had already been prescribed supplementation prior to testing (5%). Given that our institution charges $71 per folate test, the expected charges per deficient test would total $1278. Discussion: While the decreased incidence of folate deficiency after fortification has led many to conclude that serum folate tests have limited utility, our data show that this conclusion may not apply to all populations. The 5.5% rate with which testing detects folate deficiency at our institution, with 46% of 2018 income from Medicaid, was markedly higher than the 0.4% rate reported in a similar study done at nearby hospital that derived 14% of 2018 income from Medicaid (Theisen-Toupal et al. J Hosp. Med. 2013). Comparisons to other studies are limited, as the cutoff for folate deficiency varies significantly between institutions. However, the markedly higher frequency with which folate deficiency was detected at our institution as compared to others suggests that folate testing may still have a role within safety net and many public hospital systems. In addition, serum folate testing may be more cost effective at such hospitals. At our hospital, the charge per deficient folate test was $1278, while previously published data from the nearby hospital described above showed a charge of over $35,000 per result under 4 ng/mL (Theisen-Toupal et al. J Hosp Med 2013). In addition, our results showed that deficient folate results usually prompted change in management. At our hospital, over 90% of folate deficient patients were prescribed a folic acid supplement at discharge, while prior studies reported rates of supplementation in the range of 0-65% (e.g. Ashraf et al. J Gen Intern Med 2008). This may reflect greater cognizance among our providers of nutritional deficiencies associated with social determinants of health common to our patient population. As our results indicated high rates of anemia, malnutrition, immigrant status, and substance use disorders among folate deficient patients, future research may include comparisons between patients found to have normal vs low folate levels. Identifying correlations between folate deficiency and other patient characteristics may help to target testing towards those most likely to benefit. Disclosures No relevant conflicts of interest to declare.

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Determinants of arsenic methylation efficiency and urinary arsenic level in pregnant women in Bangladesh

Environmental Health ◽

10.1186/s12940-019-0530-2 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Shangzhi Gao ◽

Pi-I Lin ◽

Golam Mostofa ◽

Quazi Quamruzzaman ◽

Mahmudur Rahman ◽

...

Keyword(s):

Pregnant Women ◽

Energy Intake ◽

Protein Intake ◽

Arsenic Concentration ◽

Arsenic Species ◽

Exposure Level ◽

Arsenic Level ◽

Arsenic Metabolism ◽

Arsenic Methylation ◽

Urinary Arsenic

Abstract Background Prenatal inorganic arsenic (iAs) exposure is associated with pregnancy outcomes. Maternal capabilities of arsenic biotransformation and elimination may influence the susceptibility of arsenic toxicity. Therefore, we examined the determinants of arsenic metabolism of pregnant women in Bangladesh who are exposed to high levels of arsenic. Methods In a prospective birth cohort, we followed 1613 pregnant women in Bangladesh and collected urine samples at two prenatal visits: one at 4–16 weeks, and the second at 21–37 weeks of pregnancy. We measured major arsenic species in urine, including iAs (iAs%) and methylated forms. The proportions of each species over the sum of all arsenic species were used as biomarkers of arsenic methylation efficiency. We examined the difference in arsenic methylation using a paired t-test between first and second visits. Using linear regression, we examined determinants of arsenic metabolism, including age, BMI at enrollment, education, financial provider income, arsenic exposure level, and dietary folate and protein intake, adjusted for daily energy intake. Results Comparing visit 2 to visit 1, iAs% decreased 1.1% (p < 0.01), and creatinine-adjusted urinary arsenic level (U-As) increased 21% (95% CI: 15, 26%; p < 0.01). Drinking water arsenic concentration was positively associated with iAs% at both visits. When restricted to participants with higher adjusted urinary arsenic levels (adjusted U-As > 50 μg/g-creatinine) gestational age at measurement was strongly associated with DMA% (β = 0.38, p < 0.01) only at visit 1. Additionally, DMA% was negatively associated with daily protein intake (β = − 0.02, p < 0.01) at visit 1, adjusting for total energy intake and other covariates. Conclusions Our findings indicate that arsenic metabolism and adjusted U-As level increase during pregnancy. We have identified determinants of arsenic methylation efficiency at visit 1.

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Arsenic exposure and the seroprevalence of total hepatitis A antibodies in the US population: NHANES, 2003–2012

Epidemiology and Infection ◽

10.1017/s0950268815003088 ◽

2016 ◽

Vol 144 (8) ◽

pp. 1641-1651 ◽

Cited By ~ 8

Author(s):

A. CARDENAS ◽

E. SMIT ◽

J. W. BETHEL ◽

E. A. HOUSEMAN ◽

M. L. KILE

Keyword(s):

Regression Models ◽

Hepatitis A ◽

Arsenic Exposure ◽

Effect Modification ◽

Multivariate Logistic Regression ◽

Logistic Regression Models ◽

Immunization Status ◽

Urinary Arsenic ◽

Health And Nutrition ◽

The Us

SUMMARYWe evaluated the association between urinary arsenic and the seroprevalence of total hepatitis A antibodies (total anti-HAV: IgG and IgM) in 11 092 participants aged ⩾6 years using information collected in the US National Health and Nutrition Examination Survey (2003–2012). Multivariate logistic regression models evaluated associations between total anti-HAV and total urinary arsenic defined as the sum of arsenite, arsenate, monomethylarsonate and dimethylarsinate (TUA1). Effect modification by self-reported HAV immunization status was evaluated. Total anti-HAV seroprevalence was 35·1% [95% confidence interval (CI) 33·3–36·9]. Seropositive status was associated with higher arsenic levels and this association was modified by immunization status (P= 0·03). For participants that received ⩾2 vaccine doses or did not know if they had received any doses, a positive dose-response association was observed between increasing TUA1 and odds of total anti-HAV [odds ratio (OR) 1·42, 95% CI 1·11–1·81; and OR 1·75, 95% CI 1·22–2·52], respectively. A positive but not statistically significant association was observed in those who received <2 doses (OR 1·46, 95% CI 0·83–2·59) or no dose (OR 1·12, 95% CI 0·98–1·30). Our analysis indicates that prevalent arsenic exposure was associated with positive total anti-HAV seroprevalence. Further studies are needed to determine if arsenic increases the risk for incident hepatitis A infection or HAV seroconversion.

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Racial Differences in Nutritional Anemias: Analysis of Folate, Vitamin B12, and Iron Deficiencies

Blood ◽

10.1182/blood-2019-123791 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3387-3387

Author(s):

Miguel Gonzalez Velez ◽

Carolyn Mead-Harvey ◽

Heidi E. Kosiorek ◽

Yael Kusne ◽

Leslie Padrnos

Keyword(s):

Vitamin B12 ◽

Racial Differences ◽

The United States ◽

Racial Group ◽

Serum Folate ◽

Nutritional Deficiencies ◽

Racial Groups ◽

The Us ◽

Level Analysis ◽

Prevalence Of Anemia

Background: Serum folate (SF), vitamin B12 (B12), and iron deficiencies (def) are common causes of nutritional anemias. These deficiencies are usually multifactorial, with nutritional and non-nutritional factors playing a role. SF, B12, and iron levels are usually ordered in the setting of anemia, and malnutrition with or without neurologic symptoms. Since folic acid fortification, the prevalence of SF def in the United States (US) is <1% in the general population. B12 def and iron def range between 6-12%, and 1-11% respectively depending on the population studied. The prevalence of nutritional anemias secondary to SF, B12, and/or iron def by racial groups in the US is poorly studied, and most data available focuses on non-Hispanic whites (NHW). We aimed to determine the prevalence of anemia secondary to nutritional deficiencies by racial groups in the US. Methods: We performed a retrospective analysis of patients with SF, B12 and iron levels at Mayo Clinic Arizona between 01/2010 and 10/2018. Race was classified according to the NIH criteria. Normal laboratory values were determined according to our lab reference and the US National Health and Nutrition Examination Survey (NHANES) III. SF levels (mcg/Lt) were defined as deficient <4, normal ≥4.0, and excess ≥20. B12 levels (ng/L) as deficient <150, borderline 150-400, normal >400-900, and excess ≥900. Iron def was determined by ferritin levels (mcg/L) as low <24, normal 24-336, elevated ≥336 for men, low <11, normal 11-307, elevated ≥307 for women. Demographics and clinical variables were compared between groups by chi-square test for frequency data or Kruskal Wallis rank-sum test for continuous variables. Multivariable logistic regression was used for a sample-level analysis adjusting for age and gender and using NHW as a reference group. Results: A total of 79,926 SF, 107,731 B12, and 39,827 ferritin samples from 67,683 patients were analyzed. Demographics and sample analysis are presented in Table 1. In the sample-level analysis, 23,008 (25%) had anemia with higher prevalence in the American Indian/Alaskan Native (AI/AN) 49% and African Americans (AA) 43% (p<0.001). The prevalence of SF def was 446/79,926 (0.6%), B12 def 1,548/107,731 (1.4%), and iron def 5,212/39,827 (13.1%). 23 had concomitant SF and B12 deficiency, 25 SF and iron def, and 144 B12 and iron def. The SF def prevalence by racial groups was: AI/AN 11 (1.9%), AA 19 (1.1%), NHW 378 (0.6%), Hispanic 28 (0.5%), Asian 4 (0.2%). The B12 def prevalence by racial groups was: Asian 89 (3.4%), NHW 1,274 (1.4%), Hispanic 87 (1.3%), AA 30 (1.3%), AI/AN 10 (1.3%). Iron def prevalence by racial groups: AI/AN 71 (20.5%), Asian 198 (17.6%), AA 180 (16.9%), Hispanic 432 (15.6%), NHW 4,161 (12.4%). In the multivariate sample-level analysis, the presence of anemia was higher in the AI/AN (OR: 4.51, 95%CI: 3.70-5.49, p<0.0001), AA (OR 3.34, 95%CI: 2.99-3.74, p<0.0001), Asian (OR 1.52, 95%CI: 1.35-1.73, p<0.0001) and Hispanic racial group (OR 1.41, 95%CI: 1.30-1.52, p<0.0001). SF def was more common in the AI/AN (OR: 2.94, 95%CI: 1.60-5.39, p<0.001) and AA (OR 1.71, 95%CI: 1.08-1.53, p=0.02). B12 def was more common in the Asian racial group (OR: 2.535, 95%CI: 20.03-3.16, p<0.0001). Iron def was more common in the AI/AN (OR: 1.62, 95%CI: 1.21-2.17, p<0.001), Asian (OR 1.31, 95%CI: 1.0-1.57, p=0.003), and AA racial group (OR 1.26, 95%CI: 1.05-1.52, p=0.001). Conclusions: In our cohort, we show that despite the low prevalence of nutritional anemias in the US, racial disparities exist. Major differences were observed in the prevalence of anemia, SF def and iron def especially among AI/AN and AA. These differences may be linked to medical causes, nutritional practices and other social determinants of health. More research regarding the causes of these disparities and its clinical implications on a population level are needed. Targeted strategies to improve folate, B12 and iron intake in at higher risk populations could decrease adverse outcomes and decrease healthcare disparities caused by nutritional anemias. T able 1. Sample-level comparison by race Disclosures No relevant conflicts of interest to declare.

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