Clifford L. Johnson

Body composition estimates from NHANES III bioelectrical impedance data

BACKGROUND: Body composition estimates for the US population are important in order to analyze trends in obesity, sarcopenia and other weight-related health conditions. National body composition estimates have not previously been available.OBJECTIVE: To use transformed bioelectrical impedance analysis (BIA) data in sex-specific, multicomponent model-derived prediction formulae, to estimate total body water (TBW), fat-free mass (FFM), total body fat (TBF), and percentage body fat (%BF) using a nationally representative sample of the US population.DESIGN: Anthropometric and BIA data were from the third National Health and Nutrition Examination Survey (NHANES III; 1988–1994). Sex-specific BIA prediction equations developed for this study were applied to the NHANES data, and mean values for TBW, FFM, TBF and %BF were estimated for selected age, sex and racial-ethnic groups.RESULTS: Among the non-Hispanic white, non-Hispanic black, and Mexican-American participants aged 12–80 y examined in NHANES III, 15 912 had data available for weight, stature and BIA resistance measures. Males had higher mean TBW and FFM than did females, regardless of age or racial-ethnic status. Mean TBW and FFM increased from the adolescent years to mid-adulthood and declined in older adult age groups. Females had higher mean TBF and %BF estimates than males at each age group. Mean TBF also increased with older age groups to approximately 60 y of age after which it decreased.CONCLUSIONS: These mean body composition estimates for TBW, FFM, TBF and %BF based upon NHANES III BIA data provide a descriptive reference for non-Hispanic whites, non-Hispanic blacks and Mexican Americans in the US population.

Serum Total Homocysteine Concentrations in the Third National Health and Nutrition Examination Survey (1991-1994): Population Reference Ranges and Contribution of Vitamin Status to High Serum Concentrations

Homocysteine, a non-protein-forming sulfur amino acid, has attracted attention because elevated concentrations of circulating total homocysteine are associated with an increased risk for vascular disease (1, 2). Homocysteine is also a sensitive functional marker of inadequate cellular folate and vitamin B12 concentrations (3). Inadequate status of these vitamins has important health consequences that may be independent of their role in homocysteine metabolism. Low folate concentrations increase a womans risk for having a baby with a neural tube defect (4, 5), and an inadequate vitamin B12 concentration is known to produce various neurologic and cognitive effects (6, 7). Persons with low circulating folate or vitamin B12 concentrations have higher fasting total homocysteine concentrations (8-10), and elevated fasting total homocysteine concentrations are usually normalized by treatment with folic acid and vitamin B12 (6, 11-14). However, less is known about the importance of these vitamins as risk factors for high homocysteine concentration in the general population. Only three studies have examined the relation between homocysteine concentration and its vitamin determinants in samples that were designed to be representative of U.S. national (8) or regional (9, 10) populations. One of these studies (9) reported that approximately two thirds of all cases of moderately elevated total homocysteine concentrations were potentially attributable to low vitamin concentrations, but estimation of the proportion of cases with high homocysteine concentrations that can be attributed to inadequate vitamin status is complicated by the lack of a standard definition of a high total homocysteine concentration. In the absence of a definition based on increased risk for an adverse health outcome, such as vascular disease, upper reference limits from samples of healthy persons without established risk factors for high homocysteine concentrations have been used to define a high total homocysteine concentration (10, 15-17). We previously described the distribution of total serum homocysteine concentrations in participants 12 years of age or older from the third National Health and Nutrition Examination Survey (NHANES III), a population-based sample of U.S. residents (18). These data present a unique opportunity to develop population reference ranges for serum total homocysteine concentration and to determine the extent to which elevated homocysteine concentrations are associated with low circulating vitamin concentrations in a representative sample of U.S. residents. Methods Participants The NHANES III was developed to obtain nationally representative information on the health and nutritional status of the civilian, noninstitutionalized U.S. population (19, 20). Homocysteine concentrations were measured as part of an NHANES III surplus sera project on serum samples from participants 12 years of age or older who were seen during phase II of this survey (19911994). This project is described in greater detail elsewhere (18). Homocysteine concentrations were measured at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University by using the high-performance liquid chromatography method of Araki and Sako (21). The interassay coefficient of variation for this assay was 6%. Folate and vitamin B12 were determined for phase 2 specimens at the Centers for Disease Control and Prevention central laboratory by using a Quanta Phase II radioassay kit (Bio-Rad Laboratories, Hercules, California), and analyses are described in detail in the NHANES III Laboratory Procedures Manual (22). The coefficients of variation for folate and vitamin B12 were 6% and 7%, respectively. Informed consent was obtained from all respondents. The NHANES III protocol was approved by the National Center for Health Statistics NHANES Institutional Review Board, and measurement of serum homocysteine was approved by the Human Investigations Review Committee at the New England Medical Center. We used the following search strategy, combining Medical Subject Headings (MeSH terms) and text words, to identify all population-based studies relating vitamin status to circulating homocysteine concentrations: ([homocysteine (MeSH] OR homocysteine [Text Word]) AND (vitamins [MeSH] OR vitamin [Text Word]]) AND (epidemiologic studies [MeSH] OR data collection [MeSH] OR survey [Text Word]]. This search identified 137 citations, of which 16 were reviews. We selected original studies that 1) were designed to be representative of national, regional, or local populations and 2) described the relation between circulating homocysteine concentrations and either intake or circulating concentrations of folate or vitamin B12. As of 1 March 1999, 3 articles met our criteria (8-10). Statistical Analysis We used sample weights in analyses to account for unequal probability of selection and nonresponse and to produce estimates of means and percentiles that were representative of the noninstitutionalized, civilian U.S. population. We used SUDAAN statistical software (23) to account for the complex survey design in the variance estimates. Because total homocysteine, folate, and vitamin B12 values were skewed, logarithmic transformations were applied. To show the relations between total homocysteine concentrations and vitamin concentrations, we classified participants into age- and sex-specific vitamin decile categories and estimated the geometric mean of the serum total homocysteine concentration within each decile. Analyses were adjusted for ethnicity and serum creatinine concentration. In addition, the relation between total homocysteine and folate concentrations was adjusted for vitamin B12 concentrations, and the relation between total homocysteine and vitamin B12 was adjusted for folate concentrations. We tested the associations between homocysteine and vitamins for interactions with age, sex, and ethnicity. We tested for trend of total homocysteine concentration across vitamin concentrations by using linear regression with the logarithm of the continuous vitamin concentration as the independent variable, adjusting as described above. We showed the trend by using the SYSTAT LOWESS procedure to fit smoothed curves (24) to the geometric mean total homocysteine concentrations in the vitamin decile categories (25). It has been suggested that population reference ranges for the total homocysteine concentration be established in samples of persons without established risk factors for a high homocysteine concentration (10, 15-17). For our reference sample, we included persons whom we assumed to be folate- and vitamin B12-replete (that is, their serum concentrations of both vitamins were above the 50th percentile) and had normal serum creatinine concentrations (<90 mol/L for women and<110 mol/L for men). Pregnant women were excluded. We used the 5th and the 95th percentiles from the reference sample to estimate population reference ranges. To identify the potential impact of low vitamin concentrations on high total homocysteine concentration, we needed to establish values for high total homocysteine and low vitamin concentrations. We used the sex-specific 95th percentiles in the participants 20 to 39 years of age (the reference sample) to define high total homocysteine concentrations for all age groups. We used this reference sample because homocysteine concentrations changed little with age in this group, unlike in the other age groups (18). We defined low vitamin concentrations as a folate concentration less than 11 nmol/L (26, 27) and a vitamin B12 concentration less than 185 pmol/L (28, 29). We calculated the prevalence of high total homocysteine concentration; the prevalence ratio for high total homocysteine concentration; the attributable risk percentage; and the population attributable risk percentage for persons with low concentrations of folate, vitamin B12, or both compared with persons who had adequate concentrations of both of these vitamins. The attributable risk percentage estimates the excess cases of high homocysteine concentrations among persons with low vitamin concentrations, whereas the population attributable risk percentage takes into account the prevalence of low vitamin concentrations in the population and estimates the excess of high homocysteine concentrations associated with low vitamin concentrations in the entire population. We used the design effect for total homocysteine concentration, which is the ratio of the complex sampling design variance derived by using SUDAAN software (23) to the simple random sample variance calculated by using SAS software (30), to determine the recommended minimum sample size needed to achieve stable estimates of means, proportions, and percentiles according to the National Center for Health Statistics analytic guidelines (19). On the basis of an average design effect of approximately 1.4 for our sample, means and medians derived from fewer than 42 participants, 10th and 90th percentiles derived from fewer than 112 participants, and 5th and 95th percentiles derived from fewer than 224 participants were deemed unstable. Sample size for stable estimates of the proportions varied by the magnitude of the proportion, ranging from 42 for proportions of 0.5 to 224 for proportions of 0.05 or 0.95. We indicate in the text and tables statistics that did not meet the appropriate sample size. We categorized participants into three ethnic groups: non-Hispanic white, non-Hispanic black, and Mexican American. We excluded persons from other ethnic groups (n=436) because their inclusion produced unstable estimates of mean total homocysteine concentration after adjustment for ethnicity. Our analyses are based on 8086 participants with complete data on serum total homocysteine, folate, vitamin B12, and creatinine concentrations. Results Table 1 shows selected characteristics of the sample by sex and ethnic group. On average, non-Hispanic white pa

Characterizing extreme values of body mass index–for-age by using the 2000 Centers for Disease Control and Prevention growth charts

BACKGROUND The 2000 Centers for Disease Control and Prevention (CDC) growth charts included lambda-mu-sigma (LMS) parameters intended to calculate smoothed percentiles from only the 3rd to the 97th percentile. OBJECTIVE The objective was to evaluate different approaches to describing more extreme values of body mass index (BMI)-for-age by using simple functions of the CDC growth charts. DESIGN Empirical data for the 99th and the 1st percentiles of BMI-for-age were calculated from the data set used to construct the growth charts and were compared with estimates extrapolated from the CDC-supplied LMS parameters and to various functions of other smoothed percentiles. A set of reestimated LMS parameters that incorporated a smoothed 99th percentile were also evaluated. RESULTS Extreme percentiles extrapolated from the CDC-supplied LMS parameters did not match well to the empirical data for the 99th percentile. A better fit to the empirical data was obtained by using 120% of the smoothed 95th percentile. The empirical first percentile was reasonably well approximated by extrapolations from the LMS values. The reestimated LMS parameters had several drawbacks and no clear advantages. CONCLUSIONS Several approximations can be used to describe extreme high values of BMI-for-age with the use of the CDC growth charts. Extrapolation from the CDC-supplied LMS parameters does not provide a good fit to the empirical 99th percentile values. Simple approximations to high values as percentages of the existing smoothed percentiles have some practical advantages over imputation of very high percentiles. The expression of high BMI values as a percentage of the 95th percentile can provide a flexible approach to describing and tracking heavier children.

Stature prediction equations for elderly non-Hispanic white, non-Hispanic black, and Mexican-American persons developed from NHANES III data.

OBJECTIVE To develop new, nationally representative equations to predict stature for racial/ethnic groups of the elderly population in the United States. DESIGN Anthropometric data for stature, knee height, and sitting height for adults aged 60 years or older were collected from a sample of persons in the third National Health and Nutrition Examination Survey (1988-1994), a national probability sample of the US population. SUBJECTS A gender- and racial/ethnic-stratified sample of 4,750 persons from the US population (1,369 non-Hispanic white men, 1,472 non-Hispanic white women, 474 non-Hispanic black men, 481 non-Hispanic black women, 497 Mexican-American men, 457 Mexican-American women) aged 60 years or older participated in this study. STATISTICAL ANALYSES Sampling weights were used to adjust the individual data to account for unequal probabilities of selection, nonresponse, and coverage errors so that all individual data used in these analyses represented national probability estimates. Regression analysis was performed to predict stature in each gender and ethnic group, and the results were cross-validated. RESULTS Stature prediction models using knee height and age and sitting height and age were evaluated for each gender and racial/ethnic group. The equations with knee height and age were selected on the basis of root mean square error and pure errors in cross-validation and on the accuracy and validity of measures of knee height over sitting height. Results of these regressions, including regression coefficients, standard errors of the coefficients, multiple correlation coefficients, root mean square error, and the standard error for the individual for the final equations, are presented. CONCLUSIONS New stature prediction equations using knee height and age are presented for non-Hispanic white, non-Hispanic black and Mexican-American elderly persons from current nationally representative data. These equations should be applied when a measure of stature cannot be obtained, for example, for persons with amputations of the leg, or with spinal curvature or who are confined to bed. Predicted stature values are acceptable surrogates in nutritional indexes.

Total energy intake of the US population: the third National Health and Nutrition Examination Survey, 1988-1991.

The third National Health and Nutrition Examination Survey (NHANES III) was conducted to assess the health and nutritional status of the US population. As part of the nutritional status assessment, reliable 24-h dietary recalls were collected for 14,801 examined persons. Mean (+/- SEM) energy intakes are reported for persons aged > or = 2 mo by age, sex, and race-ethnicity. Males had higher mean energy intakes than did females. Energy intakes peaked during late adolescence and young adulthood and declined thereafter. Energy intake patterns were similar among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Underreporting was addressed by computing a ratio of energy intake (EI) to estimated basal metabolic rate (BMRest). This ratio (EI:BMRest) was 1.47 for adult males and 1.26 for nonpregnant adult females. Overweight adults had a lower mean EI:BMRest (1.09 in females and 1.28 in males). Underreporting in food consumption surveys remains problematic among females and overweight persons.

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.

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

NHANES Monitoring of Serum 25-Hydroxyvitamin D: A Roundtable Summary

A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 3) approaches for integrating the recently available standard reference material for vitamin D in human serum (SRM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 4) questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later.

Serum ferritin and death from all causes and cardiovascular disease: the NHANES II mortality study.

Abstract PURPOSE: The purpose of this study was to assess the association between serum ferritin and death from all causes, cardiovascular diseases (CVD), CHD and myocardial infarction (MI). Positive body iron stores have been proposed as a risk factor for coronary heart disease (CHD). While most epidemiologic studies using serum ferritin and other measures of body iron stores have not found an association between iron and heart disease risk, the hypothesis remains controversial. As a result, we examined the relationship of serum ferritin, the principle blood measure of body iron stores, to risk of death in a cohort with a standardized exam and long follow-up. METHODS: The baseline data for this prospective cohort study were collected in 1976–1980 as part of the second National Health and Nutrition Examination Study (NHANES II) with mortality follow-up using the National Death Index (NDI) through December 31, 1992. The analytic sample n = 1604 consisted of 128 black men, 658 white men, 100 black women and 718 white women 45–74 years of age at baseline who, based on self-reported data, were free of coronary heart disease at baseline and had no missing data. The main outcome measures were the relative risk of death for persons with serum ferritin levels: RESULTS: Most of the deaths were among white men n = 254 and women n = 168 . There were relatively few deaths among black men n = 50 and too few in women n = 23 to reliably model. The largest number of CVD n = 119 , CHD n = 82 , and MI n = 49 deaths were in white men while there were 69 CVD, 45 CHD and 13 MI deaths in white women. Black men with a serum ferritin level of RR = 3.1 with 95% confidence limits of 1.5–6.5 . There were no other statistically significant associations for all causes mortality for the other three race/sex groups. Additionally, there were no statistically significant associations between serum ferritin and any of the cardiovascular endpoints for any of the groups. There was an apparent but nonsignificant u-shaped association between serum ferritin and all causes mortality in black men and between serum ferritin and CVD death in white women. However, in both cases very wide confidence limits preclude further interpretation. CONCLUSIONS: Overall, the results do not support the hypothesis that positive body iron stores, as measured by serum ferritin, are associated with an increased risk of CVD, CHD or MI death or between serum ferritin and all causes mortality. Most of the research to date with serum ferritin has been conducted in European men or in European American men. Our results are consistent with the primarily negative results for that race/sex group. More research is needed in women and minority groups, including an explanation of why such an association would exist in these groups but not in white men before an association can be established in them.

Prevalence of severe obesity in adults in the United States

This report presents estimates of the prevalence of severe obesity in the civilian noninstitutionalized population 20 to 74 years of age in the United States by sex and age, based on body measurements obtained from the Health and Nutrition Examination Survey 1971-1974 conducted by the National Center for Health Statistics. The Health and Nutrition Examination Survey (HANES) was designed to measure the nutritional status of the U.S. population as well as certain aspects of the general health status and medical care needs. A nationwide probability sample of 28,043 persons was selected to be examined in 65 primary sampling units visited between April 1971 and June 1974. Findings in this report are based on examinations of 12,900 persons aged 20 to 74 years, from a total group of 20,749 examined persons aged 1 to 74 years. These fmdings are shown as national estimates based on weighted observations, i.e., the data obtained for each examined person are extrapolated to the level of the total population of which the sample was representative. The appropriate weights were used to account for both sampling fractions and survey response results. The HANES nutrition examination included a general medical examination by a physician for indicators of nutritional deficiencies, skin examination by a dermatologist, and dental examination by a dentist. Body measurements were taken by a trained technician; a dietary interview was administered consisting of a 24-hr recall of food consumption and a food-frequency questionnaire. Routine laboratory tests were performed on whole blood, serum, plasma, and urine. A description of the sampling process, HANES operation, has been published previously (1).