Blood Folate Levels: The Latest NHANES Results
NCHS Data Brief ¡ No. 6 ¡ May 2008Click here for data tables for figures 1-5Blood Folate Levels: The Latest NHANES ResultsMargaret A. McDowell, M.P.H., R.D.; David A. Lacher, M.D.; Christine M. Pfeiffer, Ph.D.; Joseph Mulinare,M.D., M.S.P.H.; Mary Frances Picciano, Ph.D.; Jeanne I. Rader, Ph.D.; Elizabeth A. Yetley, Ph.D.; JocelynKennedy-Stephenson, M.S.; and Clifford L. Johnson, M.S.P.H.Key findingsData from the NationalHealth and NutritionExamination Surveys Very large increases inblood folate levels of the U.S.population occurred between1988–1994 and 1999–2000.Small fluctuations in bloodfolate levels occurred over thetime period 1999–2006. The median red blood cell(RBC) folate level of the U.S.population 4 years of ageand older was 266 ng/mL in2005–2006. The median serum folatelevel of the U.S. population4 years of age and older was12.2 ng/mL in 2005–2006.Folate is an essential vitamin for good health. Women of childbearing age areamong the population subgroups that have been shown previously to havelow blood folate levels (1,2). Low blood folate levels are associated withan increased risk of neural tube birth defects. Beginning in 1998, the Foodand Drug Administration (FDA) required the addition of folic acid (a formof folate) to all enriched breads, cereals, flours, corn meal, pasta products,rice, and other cereal grain products sold in the United States (3). Bloodfolate data from the National Health and Nutrition Examination Surveys(NHANES) have documented improvements in the folate status of the U.S.population after folate fortification was implemented (4). Red blood cell(RBC) folate measures long-term folate intake and low levels are associatedwith adverse health effects. Serum folate reflects recent folate intake and lowlevels are an early indicator of inadequate folate status. Pre- and postfortification blood folate levels of the U.S. population 4 years of age and older andprevalence of low blood folate among women of childbearing age (15–45years) are reported.Keywords: folic acid fortification, prevalence, red blood cell folate, serumfolate, survey, trends, National Health and Nutrition Examination SurveysFigure 1. Median RBC folate levels (ng/mL) of the U.S. population, 1988–2006 In 2005–2006, the prevalence of low RBC folate (lessthan 140 ng/mL) among U.S.women of childbearing age(15–45 years) was 4.5%.Persons 4 years of age and older In 2005–2006, the prevalence of low serum folate (lessthan 3 ng/mL) among U.S.women of childbearing agewas 0.3%.Median RBC folate(ng/mL)300250Females 15–45 years of 022003–20042005–2006NOTES: Statistically significant difference between 1988–1994 and 1999–2000 for both groups. Statisticallysignificant difference between 2001–2002 and 2003–2004 for both groups. Statistically significantdifference between 2003–2004 and 2005–2006 for both groups. RBC is red blood cell.SOURCE: CDC/NCHS, National Health and Nutrition Examination Surveys.U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICESCenters for Disease Control and PreventionNational Center for Health Statistics
NCHS Data Brief ¡ No. 6 ¡ May 2008Have levels of RBC folate, a measure of long-term body stores changedsince NHANES III (1988–1994)?Median RBC folate levels increased between 1988 and 1994 (prefortification) and 1999 and 2000(postfortification) followed by small fluctuations between 1999–2000 and 2005–2006.Median RBC folate levels of persons 4 years of age and older increased nearly 60%, from 174 ng/mL to 276 ng/mL between 1988–1994 and 1999–2000. The NHANES 2005–2006 value is 266ng/mL.Median RBC folate levels of women of childbearing age increased 65%, from 160 ng/mL to 264ng/mL between 1988–1994 and 1999–2000. The NHANES 2005–2006 value is 257 ng/mL.Has the prevalence of low RBC folate (less than 140 ng/mL) improved sinceNHANES III (1988–1994)?The prevalence of low RBC folate in the U.S. population 4 years of age and older declined from30.4% in 1988–1994 to 2.8% in 1999–2000 and rates have remained low since that time.Low RBC folate is of particular concern for women of childbearing age. The prevalence of lowRBC folate among U.S. women of childbearing age declined from 37.6% in 1988–1994 to 5.1%in 1999–2000. The 2005–2006 value was 4.5%.Figure 2. Prevalence of RBC folate less than 140 ng/mL by racial and ethnic group: Females 15–45 yearsof age, United States, 1988–2006Total70Non-Hispanic whiteNon-Hispanic blackMexican American59.6160Percent504037.634.538.730201005.1 4.51988–199416.0113.9112.111.61999–20004.0 2.79.41, 22.82001–20025.8 3.64.92003–20044.5 3.72.72005–2006YearSignificantly different from non-Hispanic white persons and Mexican-American persons.2Significantly different from 2003–2004.NOTES: 1988–1994 rates significantly different from those of the 1999–2006 survey periods. RBC is red blood cell.SOURCE: CDC/NCHS, National Health and Nutrition Examination Surveys.1The prevalence of low RBC folate was consistently higher among non-Hispanic black womencompared with non-Hispanic white and Mexican-American women. Significant improvementshave been made in the RBC folate status of all race and ethnicity groups. Among non-Hispanic 2
NCHS Data Brief ¡ No. 6 ¡ May 2008black women, the prevalence of low RBC folate declined from 59.6% in 1988–1994 to 12.1% in1999–2000. During the same time period, the prevalence of low RBC folate declined from 34.5%to 4.5% among non-Hispanic white women and from 38.7% to 1.6% among Mexican-Americanwomen.In 2005–2006, the prevalence of low RBC folate was 9.4% for non-Hispanic black, 3.7% for nonHispanic white, and 2.7% for Mexican-American women.Did NHANES 2005–2006 RBC folate levels differ by sex and age?Median RBC folate levels varied by sex and age.RBC folate levels were lowest among adolescents 12–19 years of age and highest among adults60 years of age and older.Females 60 years of age and older had higher median RBC folate levels (347 ng/mL) comparedwith males 60 years of age and older (304 ng/mL).Figure 3. Median RBC folate levels by sex and age: United States, 2005–20064–11 years12–19 years20–59 years60 years of age and olderMedian RBC folate 2542652712371200150100500Total sampleMaleFemaleSignificantly different from persons 4–11, 20–59, and 60 years of age and older.Significantly different from persons 4–11, 12–19, and 20–59 years.Significantly different from males 60 years of age and older.NOTE: RBC is red blood cell.SOURCE: CDC/NCHS, National Health and Nutrition Examination Surveys.123Were there race and ethnicity differences in median RBC folate levels ofwomen of childbearing age in 2005–2006?Median RBC folate levels of women of childbearing age varied by race and ethnicity.The median RBC folate level of non-Hispanic black women (210 ng/mL) was significantly lowercompared with non-Hispanic white and Mexican-American women, whereas the median levels ofnon-Hispanic white (272 ng/mL) and Mexican-American (252 ng/mL) women were similar. 3
NCHS Data Brief ¡ No. 6 ¡ May 2008Have median serum folate levels, a measure of recent folate intake,changed since NHANES III (1988–1994)?Median serum folate levels nearly tripled for the U.S. population 4 years of age and older from5.5 ng/mL in 1988–1994 (prefortification) to 14.2 ng/mL in 1999–2000 (postfortification).After a modest decline in median serum folate levels from 1999–2000 through 2003–2004, the2005–2006 estimate of 12.2 ng/mL shows no change since the previous 2-year period.Median serum folate levels of women of childbearing age (15–45 years) increased from 4.8 ng/mL in 1988–1994 to 13.0 ng/mL in 1999–2000. The NHANES 2005–2006 value is 11.4 ng/mL.Figure 4. Median serum folate levels (ng/mL) of the U.S. population, 1988–2006Median serum folate(ng/mL)16Persons 4 years ofage and older141210Females 15–45 years of 042005–2006YearNOTE: Statistically significant differences between 1988–1994 and 1999–2000 and between 1999–2000 and2001–2002 for both groups. Statistically significant difference between 2001–2002 and 2003–2004 for persons 4years of age and older.SOURCE: CDC/NCHS, National Health and Nutrition Examination Surveys.Has the prevalence of low serum folate (less than 3 ng/mL) improved since1988–1994?The prevalence of low serum folate in the U.S. population 4 years of age and older declined from15.5% in 1988–1994 to 0.5% in 1999–2000 and rates have remained below 1% since that time.The prevalence of low serum folate among women of childbearing age declined from 20.6% in1988–1994 to 0.8% in 1999–2000. The prevalence of low serum folate has remained low andstable among women of childbearing age between 1999–2000 and 2005–2006.There were no race and ethnicity differences in the prevalence of low serum folate among womenof childbearing age in 2005–2006. The prevalence of low serum folate was 0.3% overall and therates were 0.4% for Mexican-American women, 0.0% for non-Hispanic black women, and 0.4%for non-Hispanic white women. 4
NCHS Data Brief ¡ No. 6 ¡ May 2008Did median serum folate levels differ by sex and age in 2005–2006?Serum folate levels were highest in young children and older adults; median serum folate wassignificantly higher in children 4–11 years of age and adults 60 years of age and older comparedwith adolescents 12–19 years of age and adults 20–59 years of age.Females 60 years of age and older had the highest median serum folate level (17.1 ng/mL) andtheir serum folate level was significantly higher compared with their male counterparts (14.1 ng/mL).Figure 5. Median serum folate levels by sex and age: United States, 2005–20064–11 yearsMedian serum folate (ng/mL)1816141216.412–19 years15.820–59 years60 years of age and older17.1216.616.114.111.6111.2111.61111.6 11.9110.511086420Total sampleMaleFemaleSignificantly different from persons 4–11 and 60 years of age and older.Significantly different from males 60 years of age and older.SOURCE: CDC/NCHS, National Health and Nutrition Examination Surveys.12Did median serum folate levels of women of childbearing age (15–45 years)vary by race and ethnicity group in 2005–2006?Non-Hispanic white women had significantly higher median serum folate (11.8 ng/mL) comparedwith non-Hispanic black (9.8 ng/mL) and Mexican-American women (10.4 ng/mL).SummaryThe NHANES data demonstrate that measures of folate status that reflect both short-term andlong-term folate intake have improved. The median serum and RBC folate levels of the U.S.population 4 years of age and older and of women of childbearing age have increased significantly over the time period from 1988 to 2006. The large increases in blood folate levels that occurredbetween 1988–1994 and 1999–2000 were followed by small fluctuations from 1999 to 2006.In addition to the overall trends in blood folate, the most recent NHANES data also showed thatthe prevalence of low blood folate has improved among women of childbearing age. The prevalence of low serum folate among women of childbearing age was very low in all racial and ethnicgroups and significant reductions in the prevalence of low RBC folate have also occurred in all 5
NCHS Data Brief ¡ No. 6 ¡ May 2008racial and ethnic subgroups. Government agencies, health care organizations, and health careproviders are continuing to work together to educate consumers, particularly minority women ofchildbearing age, to consume adequate amounts of folate.DefinitionsFolate: a water-soluble B vitamin that is found in many foods.Folic acid: Folic acid is the synthetic form of folate that is found in dietary supplements andadded to enriched flour and grain products such as breads, pasta, rice, and cereals.Median value: The 50th percentile value of the distribution. One-half of the sample (or population) is above the median value and one-half is below the value.Neural tube defect: A group of birth defects that are caused by incomplete development of thebrain, spinal cord, or their protective coverings. Spina bifida is one of the most common types ofneural tube defects.Data source and methodsThe National Health and Nutrition Examination Survey (NHANES) data (5) were used for allof the analyses presented in this data brief. NHANES is conducted by the Centers for DiseaseControl and Prevention’s (CDC), National Center for Health Statistics, to monitor the health andnutritional status of the U.S. population. The annual NHANES samples are composed of thecivilian, noninstitutionalized U.S. household population. The annual samples are selected usinga complex, multistage sampling method that includes the selection of primary sampling units(counties), household segments within the counties, and sample persons from selected households. Prior to 1999, NHANES data were collected periodically. NHANES became a continuousannual survey in 1999.Every year approximately 5,000 infants, children, and adults from the United States are selectedto participate in NHANES. The NHANES sample design includes oversampling in order toproduce reliable estimates of health and nutritional measures for population subgroups. In1999–2006, the oversampled groups included black and Mexican-American persons, persons withlow income, adolescents 12–19 years of age, and adults 60 years of age and older.Survey participants are asked to complete the household interview and health examination components of the survey. The laboratory component of the health examination includes an extensivearray of laboratory tests that are performed on blood, urine, and other types of specimens. CDC’sNational Center for Environmental Health Laboratory in Atlanta, Ga., performed the serum andRBC folate analyses for NHANES III and NHANES 1999–2006. The folate analysis methodology and quality assurance provisions are described in the NHANES Laboratory ProceduresManuals for each of the 2-year survey cycles (6–9). An earlier report examined U.S. blood folatetrends and methodological considerations for their interpretation (4). 6
NCHS Data Brief ¡ No. 6 ¡ May 2008The NHANES examination sample weights were used for all of the data analyses reported. Thesurvey sample weights account for the differential probabilities of selection, nonresponse, andnoncoverage. The standard errors of the percentages were estimated using Taylor series linearization, a method that incorporates the sample weights and sample design (10). Differences betweengroups were evaluated using a univariate t-statistic. Trend tests were performed to evaluatechanges in blood folate levels over time. Trends were examined using log-transformed data because the blood folate distributions were skewed. All significance tests were two-sided using p 0.05 as the level of statistical significance. All data analyses were performed using the statisticalpackages SAS version 9.1 (SAS Institute, Cary, N.C.) and SUDAAN version 9.0 (RTI, ResearchTriangle Park, N.C.).About the authorsMargaret A. McDowell, David A. Lacher, and Clifford L. Johnson are with the Centers for Disease Control and Prevention’s (CDC) National Center for Health Statistics, Division of Healthand Nutrition Examination Surveys; Christine M. Pfeiffer is with CDC’s National Center forEnvironmental Health, Division of Laboratory Sciences; Joseph Mulinare is with CDC’s National Center for Birth Defects and Developmental Disabilities, Division of Birth Defects andDevelopmental Disabilities; Mary Frances Picciano and Elizabeth A. Yetley are with the NationalInstitutes of Health, Office of Dietary Supplements; Jeanne I. Rader is with the Food and DrugAdministration, Division of Bioanalytical Chemistry, Center for Food Safety and Applied Nutrition; and Jocelyn Kennedy-Stephenson is with the Northrop Grumman Corporation under contract to CDC’s National Center for Health Statistics.References1. Senti FR, Pich SM. Analysis of folate data from the second National Health and NutritionExamination Survey (NHANES II). J Nutr 115:1398–402. 1985.2. Wright JD, Bialostosky K, Gunter EW, et al. Blood folate and vitamin B12: United States,1988–1994. National Center for Health Statistics. Vital Health Stat 11 (243):1–78. 1998.3. Food and Drug Administration. Food standards: Amendment of standards of identity for enriched grain products to require addition of folic acid. Final Rule. Federal Register 61(44):8781–97. 1996.4. Pfeiffer CM, Johnson CL, Jain RB, Yetley EA, Picciano MF, Rader JI, et al. Trends inblood folate and vitamin B-12 concentrations in the United States, 1988–2004. Am J Clin Nutr.86(3):718–27. 2007.5. Centers for Disease Control and Prevention, National Center for Health Statistics. Datasets andRelated Documentation. Available from: k.htm [Accessed January 29, 2008.] 7
NCHS Data Brief ¡ No. 6 ¡ May 20086. Centers for Disease Control and Prevention, National Center for HealthStatistics. Laboratory Manuals and Procedures for NHANES 1999–2000.Available from: http://www.cdc.gov/nchs/about/major/nhanes/lab99 00.htm[Accessed January 29, 2008].7. Centers for Disease Control and Prevention, National Center for HealthStatistics. Laboratory Manuals and Procedures for NHANES 2001–2002.Available from: 001–2002/lab01 02.htm [Accessed January 29, 2008].8. Centers for Disease Control and Prevention, National Center for HealthStatistics. Laboratory Manuals and Procedures for NHANES 2003–2004.Available from: 003–2004/lab03 04.htm [Accessed January 29, 2008].9. Centers for Disease Control and Prevention, National Center for HealthStatistics. Laboratory Manuals and Procedures for NHANES 2005–2006.Available from: 005–2006/lab05 06.htm [Accessed January 29, 2008].10. National Center for Health Statistics. The National Health and Nutrition Examination Surveys (NHANES) Analytic and Reporting Guidelines.Updated September 2006. Available from: 003–2004/analytical guidelines.htm [Accessed January29, 2008].U.S. DEPARTMENT OFHEALTH & HUMAN SERVICESCenters for Disease Control and PreventionNational Center for Health Statistics3311 Toledo RoadHyattsville, MD 20782OFFICIAL BUSINESSPENALTY FOR PRIVATE USE, 300ISSN 1941-4927 (Print ed.)ISSN 1941-4935 (Online ed.)CS118968T31372 (05/08)DHHS Publication No. (PHS) 2008–1209Suggested citationMcDowell MA, Lacher DA, Pfeiffer CM,Mulinare J, Picciano MF, Rader JI, et al.Blood folate levels: The latest NHANESresults. NCHS data briefs, no 6. Hyattsville,MD: National Center for Health Statistics.2008.Copyright informationAll material appearing in this report is in thepublic domain and may be reproduced or copied without permission; citation as to source,however, is appreciated.National Center for HealthStatisticsDirectorEdward J. Sondik, Ph.D.Acting Co-Deputy DirectorsJennifer H. Madans, Ph.D.Michael H. SadagurskyFIRST CLASS MAILPOSTAGE & FEES PAIDCDC/NCHSPERMIT NO. G-284
Females 60 years of age and older had the highest median serum folate level (17.1 ng/mL) and . their serum folate level was significantly higher compared with their male counterparts (14.1 ng/ mL). Did median serum folate levels of women of childbearing age
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