Regan L Bailey

Biomarkers of Nutrition for Development—Folate Review

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folates history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

Total folate and folic acid intake from foods and dietary supplements in the United States: 2003–2006

BACKGROUND The term total folate intake is used to represent folate that occurs naturally in food as well as folic acid from fortified foods and dietary supplements. Folic acid has been referred to as a double-edged sword because of its beneficial role in the prevention of neural tube defects and yet possible deleterious effects on certain cancers and cognitive function. Previous monitoring efforts did not include folic acid from dietary supplements and are therefore not complete. OBJECTIVE Our objective was to combine data on dietary folate (as measured by two 24-h recalls) and folic acid from dietary supplements (collected with a 30-d frequency questionnaire) with the use of the bias-corrected best power method to adjust for within-person variability. DESIGN The National Health and Nutrition Examination Survey (NHANES) is a nationally representative, cross-sectional survey. Linear contrasts were constructed to determine differences in dietary and total folate intake for age and racial-ethnic groups by sex; prevalence of inadequate and excessive intakes is presented. RESULTS In 2003-2006, 53% of the US population used dietary supplements; 34.5% used dietary supplements that contained folic acid. Total folate intake (in dietary folate equivalents) was higher for men (813 +/- 14) than for women (724 +/- 16) and higher for non-Hispanic whites (827 +/- 19) than for Mexican Americans (615 +/- 11) and non-Hispanic blacks (597 +/- 12); 29% of non-Hispanic black women had inadequate intakes. Total folate and folic acid intakes are highest for those aged > or =50 y, and 5% exceed the Tolerable Upper Intake Level. CONCLUSIONS Improved total folate intake is warranted in targeted subgroups, which include women of childbearing age and non-Hispanic black women, whereas other population groups are at risk of excessive intake.

Estimation of Trends in Serum and RBC Folate in the U.S. Population from Pre- to Postfortification Using Assay-Adjusted Data from the NHANES 1988–2010

The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was ≤ 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups. The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and postfortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact.

Dietary supplement use is associated with higher intakes of minerals from food sources

BACKGROUND Dietary supplement use is extensive in US adults. Some reports suggested that supplement users had higher nutrient intakes from the diet than did nonusers, but to our knowledge this finding has not been examined in nationally representative survey data. OBJECTIVE In this analysis, we examined mineral intakes from the diet by supplement-use categories and how these supplements contributed to meeting or exceeding Dietary Reference Intakes for selected minerals. DESIGN Data from adults (≥19 y of age; n = 8860) who participated in NHANES 2003-2006, a nationally representative, cross-sectional survey, were examined. Supplement use was defined as the participants self-reported use of a supplement that contained one or more selected minerals. RESULTS Dietary intakes of minerals from food sources were higher for magnesium, copper, potassium, and selenium in male supplement users than in nonusers. For women, dietary intakes of minerals from food sources were higher for users than for nonusers for each mineral examined except for selenium. In women, users of calcium-containing dietary supplements were much more likely to meet the Estimated Average Requirement (EAR) than were nonusers. Even after consideration of supplement use, >14% of adults had inadequate intakes for calcium and magnesium on the basis of the percentage of adults with usual intakes less than the EAR. The prevalence of adults who exceeded the tolerable upper intake level (UL) for calcium, zinc, iron, and magnesium was higher in users than in nonusers. CONCLUSIONS Individuals who used mineral-containing dietary supplements had higher mineral intakes from food sources in the diet than did nonusers. For all minerals examined, and particularly for calcium and magnesium in men and women and iron in women, supplement use decreased the prevalence of intake inadequacy for each respective mineral; however, supplements contributed to risk of potentially excessive intakes for calcium, iron, zinc, and magnesium.

Examination of Vitamin Intakes among US Adults by Dietary Supplement Use

BACKGROUND More than half of US adults use dietary supplements. Some reports suggest that supplement users have higher vitamin intakes from foods than nonusers, but this observation has not been examined using nationally representative survey data. OBJECTIVE The purpose of this analysis was to examine vitamin intakes from foods by supplement use and how dietary supplements contribute to meeting or exceeding the Dietary Reference Intakes for selected vitamins using data from the National Health and Nutrition Examination Survey among adults (aged ≥19 years) in 2003-2006 (n=8,860). RESULTS Among male users, mean intakes of folate and vitamins A, E, and K from food sources were significantly higher than among nonusers. Among women, mean intakes of folate and vitamins A, C, D, and E from foods were higher among users than nonusers. Total intakes (food and supplements) were higher for every vitamin we examined among users than the dietary vitamin intakes of nonusers. Supplement use helped lower the prevalence of intakes below the Estimated Average Requirement for every vitamin we examined, but for folic acid and vitamins A, B-6, and C, supplement use increased the likelihood of intakes above the Tolerable Upper Intake Level. CONCLUSIONS Supplement use was associated with higher mean intakes of some vitamins from foods among users than nonusers, but it was not associated with the prevalence of intakes less than the Estimated Average Requirement from foods. Those who do not use vitamin supplements had significantly higher prevalence of inadequate vitamin intakes; however, the use of supplements can contribute to excess intake for some vitamins.

Dietary screening tool identifies nutritional risk in older adults

BACKGROUND No rapid methods exist for screening overall dietary intakes in older adults. OBJECTIVE The purpose of this study was to develop and evaluate a scoring system for a diet screening tool to identify nutritional risk in community-dwelling older adults. DESIGN This cross-sectional study in older adults (n = 204) who reside in rural areas examined nutrition status by using an in-person interview, biochemical measures, and four 24-h recalls that included the use of dietary supplements. RESULTS The dietary screening tool was able to characterize 3 levels of nutritional risk: at risk, possible risk, and not at risk. Individuals classified as at nutritional risk had significantly lower indicators of diet quality (Healthy Eating Index and Mean Adequacy Ratio) and intakes of protein, most micronutrients, dietary fiber, fruit, and vegetables. The at-risk group had higher intakes of fats and oils and refined grains. The at-risk group also had the lowest serum vitamin B-12, folate, beta-cryptoxanthin, lutein, and zeaxanthin concentrations. The not-at-nutritional-risk group had significantly higher lycopene and beta-carotene and lower homocysteine and methylmalonic acid concentrations. CONCLUSION The dietary screening tool is a simple and practical tool that can help to detect nutritional risk in older adults.

Prevalence and predictors of children's dietary supplement use: the 2007 National Health Interview Survey

BACKGROUND Little is known about the characteristics of US children who are dietary supplement users. OBJECTIVE We described the prevalence and predictors of and reasons for giving children dietary supplements. DESIGN The study included children <18 y of age who participated in the Complementary and Alternative Medicine supplement of the National Health Interview Survey of 2007 whose proxies provided complete information on child dietary supplement use. RESULTS A total of 37% of subjects used dietary supplements, 31% of subjects used multivitamin mineral (MVM) products exclusively, 4% of subjects used single vitamins or minerals solely or in combination with MVMs, and 2% of subjects used nonvitamin, nonmineral products either solely or in combination with other supplements. Users were more likely than nonusers to be Asian, white, or non-Hispanic; belong to families with higher parental education and income levels; reside in areas other than the South; be in good, very good, or excellent health; have private health insurance; and have a usual place at which they received conventional medical care. Children (3%) with the most disease burden and health care were more likely to use supplements than were healthier children. Supplements were given for the prevention or treatment of many illnesses and conditions. Neither the caregivers reasons nor specific supplements used were consistently associated with particular conditions. CONCLUSIONS The 37% of US children who used any type of dietary supplements differed from nonusers in family socioeconomic status and many other health-related characteristics. Users were given supplements to prevent or treat many illnesses and conditions for which there is only limited evidence of their efficacy.

Fortified foods are major contributors to nutrient intakes in diets of US children and adolescents.

BACKGROUND Even in an era of obesity and dietary excess, numerous shortfall micronutrients have been identified in the diets of US children and adolescents. To help tailor strategies for meeting recommendations, it is important to know what foods contribute greatly to micronutrient intakes. Data are lacking on specific contributions made by added nutrients. OBJECTIVE Our aims were to examine the impact of fortification on nutrient adequacy and excess among US children and adolescents and to rank food sources of added nutrient intake and compare rankings with those based on total nutrient intake from foods. DESIGN AND STATISTICAL ANALYSES Data were from 7,250 respondents 2 to 18 years old in the National Health and Nutrition Examination Survey 2003-2006. Datasets were developed that distinguished nutrient sources: intrinsic nutrients in foods; added nutrients in foods; foods (intrinsic plus added nutrients); and total diet (foods plus supplements). The National Cancer Institute method was used to determine usual intakes of micronutrients by source. The impact of fortification on the percentages of children having intakes less than the Estimated Average Requirement and more than the Upper Tolerable Intake Level was assessed by comparing intakes from intrinsic nutrients to intakes from intrinsic plus added nutrients. Specific food sources of micronutrients were determined as sample-weighted mean intakes of total and added nutrients contributed from 56 food groupings. The percentage of intake from each grouping was determined separately for total and added nutrients. RESULTS Without added nutrients, a high percentage of all children/adolescents had inadequate intakes of numerous micronutrients, with the greatest inadequacy among older girls. Fortification reduced the percentage less than the Estimated Average Requirement for many, although not all, micronutrients without resulting in excessive intakes. Data demonstrated the powerful influence of fortification on food-source rankings. CONCLUSIONS Knowledge about nutrient intakes and sources can help put dietary advice into a practical context. Continued monitoring of top food sources of nutrients and nutrient contributions from fortification will be important.

Why US children use dietary supplements

Background:Dietary supplements are used by one-third of children. We examined motivations for supplement use in children, the types of products used by motivations, and the role of physicians and health care practitioners in guiding choices about supplements.Methods:We examined motivations for dietary supplement use reported for children (from birth to 19 y of age; n = 8,245) using the National Health and Nutrition Examination Survey 2007–2010.Results:Dietary supplements were used by 31% of children; many different reasons were given as follows: to “improve overall health” (41%), to “maintain health” (37%), for “supplementing the diet” (23%), to “prevent health problems” (20%), and to “boost immunity” (14%). Most children (~90%) who use dietary supplements use a multivitamin–mineral or multivitamin product. Supplement users tend to be non-Hispanic white, have higher family incomes, report more physical activity, and have health insurance. Only a small group of supplements used by children (15%) were based on the recommendation of a physician or other health care provider.Conclusion:Most supplements used by children are not under the recommendation of a health care provider. The most common reasons for use of supplements in children are for health promotion, yet little scientific data support this notion in nutrient-replete children.

Unmetabolized Folic Acid Is Detected in Nearly All Serum Samples from US Children, Adolescents, and Adults

BACKGROUND Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements. OBJECTIVES We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L. METHODS Serum samples from the cross-sectional NHANES 2007-2008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLC-tandem mass spectrometry. RESULTS In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (≥8 h) adults (≥20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L. CONCLUSIONS UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ≥1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements.