scholarly journals Demographic, Physiologic, and Lifestyle Characteristics Observed with Serum Total Folate Differ Among Folate Forms: Cross-Sectional Data from Fasting Samples in the NHANES 2011–2016

2019 ◽  
Vol 150 (4) ◽  
pp. 851-860 ◽  
Author(s):  
Zia Fazili ◽  
Maya R Sternberg ◽  
Nancy Potischman ◽  
Chia-Yih Wang ◽  
Renee J Storandt ◽  
...  

ABSTRACT Background Serum folate forms were measured in the US population during recent NHANES to assess folate status. Objective We describe post-folic acid–fortification concentrations of serum folate forms in the fasting US population ≥1 y from the NHANES 2011–2016. Methods We measured 5 biologically active folates and 1 oxidation product (MeFox) of 5-methyltetrahydrofolate (5-methyl-THF). We calculated geometric means of 5-methyl-THF, unmetabolized folic acid (UMFA), nonmethyl folate (sum of tetrahydrofolate, 5-formyltetrahydrofolate, and 5,10-methenyltetrahydrofolate), total folate (sum of above biomarkers), and MeFox by demographic, physiologic, and lifestyle variables; estimated the magnitude of variables on biomarker concentrations after covariate adjustment; and determined the prevalence of UMFA >2 nmol/L. Results After demographic adjustment, age, sex, and race-Hispanic origin were significantly associated with most folate forms. MeFox increased with age, while 5-methyl-THF, UMFA, and nonmethyl folate displayed U-shaped age patterns. Compared with non-Hispanic whites, non-Hispanic blacks had 23% lower predicted 5-methyl-THF but comparable UMFA; non-Hispanic Asians had comparable 5-methyl-THF but 28% lower UMFA; Hispanics, non-Hispanic Asians, and non-Hispanic blacks had ∼20% lower MeFox. After additional physiologic and lifestyle adjustment, predicted UMFA and MeFox concentrations were 43% and 112% higher, respectively, in adults with chronic kidney disease and 17% and 15% lower, respectively, in adults consuming daily 1–<2 alcoholic beverages; 5-methyl-THF concentrations were 20% lower in adult smokers. The prevalence of UMFA >2 nmol/L was highest in persons aged ≥70 y (9.01%) and lowest in those aged 12–19 y (1.14%). During 2011–2014, the prevalence was 10.6% in users and 2.22% in nonusers of folic acid–containing supplements. Conclusions In fasting persons ≥1 y, the demographic, physiologic, and lifestyle characteristics observed with serum total folate differed among folate forms, suggesting biological and/or genetic influences on folate metabolism. High UMFA was mostly observed in supplement users and older persons.

2020 ◽  
Vol 16 (4) ◽  
pp. 543-553
Author(s):  
Luciana Y. Tomita ◽  
Andréia C. da Costa ◽  
Solange Andreoni ◽  
Luiza K.M. Oyafuso ◽  
Vânia D’Almeida ◽  
...  

Background: Folic acid fortification program has been established to prevent tube defects. However, concern has been raised among patients using anti-folate drug, i.e. psoriatic patients, a common, chronic, autoimmune inflammatory skin disease associated with obesity and smoking. Objective: To investigate dietary and circulating folate, vitamin B12 (B12) and homocysteine (hcy) in psoriatic subjects exposed to the national mandatory folic acid fortification program. Methods: Cross-sectional study using the Food Frequency Questionnaire, plasma folate, B12, hcy and psoriasis severity using the Psoriasis Area and Severity Index score. Median, interquartile ranges (IQRs) and linear regression models were conducted to investigate factors associated with plasma folate, B12 and hcy. Results: 82 (73%) mild psoriasis, 18 (16%) moderate and 12 (11%) severe psoriasis. 58% female, 61% non-white, 31% former smokers, and 20% current smokers. Median (IQRs) were 51 (40, 60) years. Only 32% reached the Estimated Average Requirement of folate intake. Folate and B12 deficiencies were observed in 9% and 6% of the blood sample respectively, but hyperhomocysteinaemia in 21%. Severity of psoriasis was negatively correlated with folate and B12 concentrations. In a multiple linear regression model, folate intake contributed positively to 14% of serum folate, and negative predictors were psoriasis severity, smoking habits and saturated fatty acid explaining 29% of circulating folate. Conclusion: Only one third reached dietary intake of folate, but deficiencies of folate and B12 were low. Psoriasis severity was negatively correlated with circulating folate and B12. Stopping smoking and a folate rich diet may be important targets for managing psoriasis.


2008 ◽  
Vol 100 (5) ◽  
pp. 1054-1059 ◽  
Author(s):  
Robert Clarke ◽  
Paul Sherliker ◽  
Harold Hin ◽  
Anne M. Molloy ◽  
Ebba Nexo ◽  
...  

Concerns about risks for older people with vitamin B12deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15·8 (sd14·7) nmol/l in 1995 to 31·1 (sd26·2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12status was unaffected by highv.low folate status (>30 nmol/l) (OR 1·50 (95 % CI 0·91, 2·46)v.1·45 (95 % CI 1·19, 1·76)), respectively. The associations of cognitive impairment with low B12status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2·46; 95 % CI 0·90, 6·71)v.(1·56; 95 % CI 1·30, 1·88)). There was no evidence of modification by high folate status of the associations of low B12with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1834-1834
Author(s):  
Nancy Potischman ◽  
Lichen Yang ◽  
Ling Hao ◽  
Martha Linet

Abstract Objectives To evaluate the presence and amounts of folate forms by strata of total folate in a population without fortification or supplementation. Methods The Chinese Families and Children Cohort feasibility study evaluated the potential for follow-up of mothers and offspring who participated in the Community Intervention Program, a folate intervention program conducted in China during 1993–1996. The feasibility study was carried out during 2012. Subjects completed an 8-day protocol that included multiple questionnaires (on diet, physical activity, ultraviolet radiation exposure and other factors) and provided fasting blood samples that were processed in local hospitals. The samples were then shipped frozen to the US. CDC's Nutritional Biomarkers Branch laboratory, which analyzed the 183 serum samples by LC-MS/MS for 6 folate forms; total folate was the sum of 5 biologically active folate forms (excluding MeFox). Results Median total folate concentration (nmol/L) in the 183 Chinese subjects (15.3 nmol/L) was comparable to US data prior to folic acid fortification (NHANES 1988–1994 = 18.4, NHANES 2005–2010 = 40.7). The mean total folate in the lowest quintile was 6.5 nmol/L suggesting folate insufficiency among those individuals with levels below 7 nmol/L. Forty-two of the 183 subjects had detectable levels of unmetabolized folic acid (UMFA) with the measurements of the remaining samples being below the detection limit (0.28 nmol/L). While most of the samples with detectable UMFA were in the top 2 quintiles of total folate (&gt;18.6 nmol/L), all samples measured had fairly low UMFA concentrations (0.28–0.78 nmol/L). Of the 42 subjects with detectable UMFA, 36 lived in an urban center near Shanghai and may have had access to imported foods fortified with folic acid. None of the participants reported dietary supplement usage that contained folic acid. All folate forms also showed lower concentrations than the levels in the US post-fortification, with the distributions generally matching the lower half of the US distributions. Conclusions These data suggest that low levels of UMFA are likely not a marker of excessive folic acid intakes and more likely a marker of limited dihydrofolate reductase enzyme activity. Funding Sources Division of Cancer Control and Population Studies and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Miguel Gonzalez Velez ◽  
Carolyn Mead-Harvey ◽  
Heidi E. Kosiorek ◽  
Yael Kusne ◽  
Leyla Bojanini ◽  
...  

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 &lt;4, normal ≥4.0, and excess ≥20. B12 levels (ng/L) as deficient &lt;150, borderline 150-400, normal &gt;400-900, and excess ≥900. Iron def was determined by ferritin levels (mcg/L) as low &lt;24, normal 24-336, elevated &gt;336 for men, low &lt;11, normal 11-307, elevated &gt;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&lt;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.


1999 ◽  
Vol 17 (No. 1) ◽  
pp. 35-39
Author(s):  
R. Uherova ◽  
M. Horkulicova ◽  
M. Mikusova

Folic acid and its biologically  active derivates  (folacin  or folates)  rank among  the B-group  vitamins  due to their  hydrophilic character. This acid occurs in nature either in the free form or it is bound to proteins or polysaccharides. Folic acid belongs to the group of vitamins which, in the past were not considered important because the relevance of the acid in biological  processes of the living cell has been discovered  by the scientific  research only in recent years. Folates play an important role as co-enzymes in the synthesis of RNA, DNA, proteins and of some essential amino acids. Therefore they are inevitable for the haematopoiesis, growth and reproduction  of cells. In this sense a widely oriented  research  named "Maternal Folate Status" is proceeding  in the U.S.A., Australia and France.


2019 ◽  
Vol 110 (5) ◽  
pp. 1088-1097 ◽  
Author(s):  
Christine M Pfeiffer ◽  
Maya R Sternberg ◽  
Mindy Zhang ◽  
Zia Fazili ◽  
Renee J Storandt ◽  
...  

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.


2012 ◽  
Vol 15 (10) ◽  
pp. 1818-1826 ◽  
Author(s):  
Daniel A Enquobahrie ◽  
Henry A Feldman ◽  
Deanna H Hoelscher ◽  
Lyn M Steffen ◽  
Larry S Webber ◽  
...  

AbstractObjectiveWe assessed serum homocysteine (tHcy) and folate concentrations among US adolescents before and after fortification of cereal-grain products with folic acid, and associations with demographic, behavioural and physiological factors.DesignObservational study conducted among participants of a randomized trial.SettingThe Child and Adolescent Trial for Cardiovascular Health (CATCH) study.SubjectsAdolescents (n2445) in grades 8 (pre-fortification, mean age 14 years) and 12 (post-fortification, mean age 18 years).ResultsAverage serum concentrations of tHcy, folate and vitamin B6increased by 17 %, 16 % and 14 %, respectively, while serum concentrations of vitamin B12decreased by 11 % post-fortification. Folic acid fortification provided, on average, an additional intake of 118 μg folate/d. Male sex (P< 0·0001) and white race (P= 0·0008) were associated with significantly greater increases in tHcy concentration, while increases in BMI (P= 0·006) and serum folate concentration (P< 0·0001) were associated with significant decreases in tHcy concentration. Female sex (P< 0·0001), non-smoking (P< 0·0001), use of multivitamins (P< 0·0001) and higher dietary intake of folate (P= 0·001) were associated with significantly greater increases in serum folate concentrations. From grade 8 to grade 12, the upward age trend in serum tHcy concentration was uninterrupted in its course (P> 0·50); whereas serum folic acid concentration showed a downward trend that incurred a discrete jump upward (17 % higher;P< 0·0001) with fortification. These trends differed significantly for malesv. females (P< 0·001 for interaction).ConclusionsFortification had a significant impact on improving folate status but not serum tHcy concentrations among US adolescents.


2014 ◽  
Vol 84 (5-6) ◽  
pp. 286-294 ◽  
Author(s):  
Hrishikesh Chakraborty ◽  
Kwame A. Nyarko ◽  
Norman Goco ◽  
Janet Moore ◽  
Danilo Moretti-Ferreira ◽  
...  

Abstract. Background: Several countries have implemented mandatory folic acid fortification of wheat flour and selected grain products to increase the folate intake of reproductive-aged women. Brazil implemented a folic acid fortification program in 2004. No previous studies have examined folate differences among Brazilian women following the mandate. Objective: We evaluate differences in serum and red blood cell (RBC) folate concentrations between two samples of women of childbearing age from selective communities in Brazil, one tested before (N = 116) and the other after the mandate (N = 240). Methods: We compared the baseline folate levels of women enrolled in a prevention study shortly before the fortification mandate was implemented, to baseline levels of women from the same communities enrolled in the same study shortly after fortification began. The participants were women enrolled in a folate supplementation clinical trial, at a hospital specializing in treating craniofacial anomalies in the city of Bauru from January 29, 2004 to April 27, 2005. We only compared baseline folate levels before the women received oral cleft prevention program (OCPP) folic acid supplements. Results: Women enrolled after the fortification mandate had higher means of serum folate (20.3 versus 11.2 nmol/L; p < 0.001) and RBC folate (368.3 versus 177.6 nmol/L; p < 0.001) than women enrolled before the mandate. Differences in folate levels between the two groups remained after adjusting for several co-variables. Conclusions: The results suggest that serum and RBC folate levels among women of childbearing age increased after implementing the folic acid fortification mandate in Brazil.


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