BACKGROUND: We compared serum vitamin C (VIC) status of the adult (≥20 y) US population in the National Health and Nutrition Examination Survey (NHANES) 2017-2018 with combined data from 2003-2004 and 2005-2006. METHODS: VIC was measured using HPLC with electrochemical detection. Mean data were stratified by age, sex, race/Hispanic origin, income, body mass index, dietary intake, supplement use, and smoking status. Prevalence of VIC deficiency (<11.4 μmol/L) was calculated. RESULTS: In NHANES 2017-2018, the mean VIC was 8 μmol/L higher in people ≥60 y compared with those 20-59 y of age, 10 μmol/L lower in men vs women, 8 μmol/L lower in low vs high income, 11 μmol/L lower in obese vs healthy weight, and 15 μmol/L lower in smokers vs nonsmokers. Differences in mean VIC across race/Hispanic origin groups ranged from 2 to 7 μmol/L. Mean VIC was 27 μmol/L higher with vitamin C-containing supplement use and positively associated (Spearman ρ = 0.33; P < 0.0001) with increasing dietary intake. The associations between mean VIC and the investigated covariates were generally consistent and the prevalence of deficiency was not significantly different between survey periods (6.8% vs 7.0%; P = 0.83). However, a few subgroups had double the risk. We found no significant survey differences in mean VIC (51.2 vs 54.0 μmol/L; P = 0.09). CONCLUSIONS: Overall VIC status of the US adult population has remained stable since last assessed in the NHANES 2005-2006 survey. Vitamin C deficiency remained high for those with low dietary intake and who smoke.

CDC COVID-19 surveillance systems monitor SARS-CoV-2 antibody prevalence to collect information about asymptomatic, undiagnosed, and unreported disease using national convenience samples of blood donor data from commercial laboratories (1,2). However, nonrandom sampling of data from these systems could affect prevalence estimates (1-3). The National Health and Nutrition Examination Survey (NHANES) collects SARS-CoV-2 serology data among a sample of the general U.S. civilian population (4). In addition, NHANES collects self-reported COVID-19 vaccination and disease history, and its statistical sampling design is not based on health care access or blood donation. Therefore, NHANES data can be used to better quantify asymptomatic SARS-CoV-2 infection prevalence and seropositivity attained through infection without vaccination. Preliminary NHANES 2021-2022 results indicated that 41.6% of adults aged ≥18 years had serology indicative of past infection and that 43.7% of these adults, including 57.1% of non-Hispanic Black or African American (Black) adults, reported never having had COVID-19, possibly representing asymptomatic infection. In addition, 25.5% of adults whose serology indicated past infection reported never having received COVID-19 vaccination. Prevalences of seropositivity in the absence of vaccination were higher among younger adults and Black adults, reflecting the lower observed vaccination rates among these groups (5). These findings raise health equity concerns given the disparities observed in SARS-CoV-2 infection and COVID-19 vaccination. Results from NHANES 2021-2022 can guide ongoing efforts to achieve vaccine equity in COVID-19 primary vaccination series and booster dose coverage.

BACKGROUND: Data from the 2007-2010 NHANES suggested that vitamin D supplements contributed to increased serum concentrations of 25-hydroxyvitamin D [25(OH)D] in the US population. OBJECTIVES: We sought to determine whether 25(OH)D continued to increase during NHANES 2011-2014 and whether associations of 25(OH)D with preselected covariates differed across time periods. METHODS: For this study, 25(OH)D was measured in adults (≥20 y) using LC-MS/MS. Descriptive and regression analyses were stratified by survey period to investigate the effects of age, race-Hispanic origin, sex, season, BMI, dietary vitamin D, and vitamin D-containing supplements. A multiple linear regression model was used to assess 25(OH)D changes between two 4-y survey periods, namely 2007-2010 and 2011-2014. RESULTS: We observed several significant concomitant increases between 2007-2010 and 2011-2014: unadjusted mean 25(OH)D increased by 2.7 nmol/L (95% CI: 0, 5.4 nmol/L; P = 0.048), the percentage of persons taking any vitamin D-containing supplements increased 2.9% (95% CI: 0.03, 5.5%; P = 0.0314), and the percentage of persons taking high-dose (≥1000 IU/d) vitamin D-containing supplements increased 8.6% (95% CI: 6.9, 9.9%; P < 0.0001). With covariate adjustment, the increase in 25(OH)D from 2007-2010 to 2011-2014 was no longer statistically significant [1.4 nmol/L (95% CI: -3.0, 0.23 nmol/L; P = 0.09)]. After adjustments, several large differences in 25(OH)D remained, namely non-Hispanic blacks had 25(OH)D 22 nmol/L lower than that of non-Hispanic whites, and users of vitamin D-containing supplements ≥1000 IU/d had 25(OH)D 31 nmol/L higher than that of nonusers. CONCLUSIONS: After adjusting for vitamin D supplement dose, the overall adjusted increase in 25(OH)D was no longer statistically significant, suggesting that changes in US adults' 25(OH)D concentrations between NHANES periods 2007-2010 and 2011-2014 may primarily be associated with changes in vitamin D supplementation.

BACKGROUND: Elevated plasma methylmalonic acid (MMA) and/or total homocysteine (tHcy), as well as low serum vitamin B12 and/or holotranscobalamin (holoTC) are indicative of vitamin B12 deficiency. Combined indicators (cB12), which pool some or all 4 markers into an index, may be a more reliable diagnostic tool to overcome inconclusive diagnoses with individual markers. OBJECTIVES: We aimed to describe different cB12 score combinations and estimate the prevalence of low or transitional vitamin B12 status compared with individual markers. DESIGN: Using cross-sectional data for B12, MMA, and tHcy in persons ≥20 y participating in NHANES 1999-2004 (n = 12,335), we examined raw and covariate-adjusted regression models to assess determinants of 3cB12 (all 3 markers) and combinations of 2cB12 (2 markers). RESULTS: 3cB12 was significantly associated with B12 (Spearman r = 0.75), MMA (r = -0.70), and tHcy (r = -0.59). The 3cB12 reference interval (2.5th to 97.5th percentile) was -0.538 to 1.60. In covariate-adjusted models, we found no association of 3cB12 with age; adult females and users of B12 supplements had higher, while adults with advanced chronic kidney disease had lower 3cB12 levels regardless of race-Hispanic origin group (self-reported). Only 2.7% of adults had low or transitional vitamin B12 status using the proposed cB12 cutoff of ≤-0.5, while the prevalence of low (or low-normal) status depended on the selected individual marker and its cutoff: 2.2% and 13% for B12 < 148 and 148-222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff (250-320 nmol/L); and 8.4% for tHcy > 13 µmol/L. The reference intervals for B12, MMA, and tHcy overlapped from the low (<-2.5) to the transitional (-2.5 to -0.5) and to the adequate (>-0.5) cB12 categories. CONCLUSIONS: Vitamin B12 deficiency may be overestimated among US adults when individual, conventional markers are used. When only 2 markers are available, the combination of B12 and MMA provides results comparable to 3cB12.

BACKGROUND: HIV antibody testing has been included in the National Health and Nutrition Examination Survey, for ages 18-49 since 1999 and for ages 18-59 years since 2009 enabling estimation of trends in HIV prevalence as part of national surveillance in the U.S. household population. Self-reported HIV testing and antiretroviral (ARV) use was also included in the survey since 1999. SETTING: A continuous household-based probability sample of the U.S. population. METHODS: From 1999-2018, 29,020 participants age 18-49 years were tested for HIV antibody and 34,092 participants age 18-59 years were asked about self-report of any previous HIV testing. RESULTS: HIV prevalence was 0.41% among those aged 18-59 in 2009-2018 with a non-significant trend over time among those aged 18-49 years from 1999-2002 to 2015-2018. However, significant declines in prevalence were seen among those aged 18-39 years (0.37% to 0.11%), women (0.22% to 0.06%) and non-Hispanic black persons (2.14% to 0.80%). Participants age aged 18-39 self-reported a decline in HIV testing while those aged 40-49 and 50-59 years, non-Hispanic black persons and women reported an increase in getting a HIV test. Prevalence of infection and self-reported history of HIV testing varied by demographic and risk groups. HIV testing among HIV positive persons was 83.9%. ARV therapy among those HIV positive was under 50%. CONCLUSION: Though total HIV prevalence and previous self-reported HIV testing remained stable for the last 20 years, there were significant declines in age and demographic subgroups. Prevalence for both outcomes varied by demographic and risk variables.

BACKGROUND: Concern has been expressed by some that sodium reduction could lead to increased prevalence of hyponatremia and hyperkalemia for specific population subgroups. Current concentrations of serum sodium and potassium in the US population can help address this concern. METHODS: We used data from the National Health and Nutrition Examination Survey 2009-2016 to examine mean and selected percentiles of serum sodium and potassium by sex and age group among 25 520 US participants aged 12 years or older. Logistic regression models with predicted residuals were used to examine the age-adjusted prevalence of low serum sodium and high serum potassium among adults aged 20 or older by selected sociodemographic characteristics and by health conditions or medication use. RESULTS: The distributions of serum sodium and potassium concentrations were within normal reference intervals overall and across Dietary Reference Intake life-stage groups, with a few exceptions. Overall, 2% of US adults had low serum sodium (<135 mmol/L) and 0.6% had high serum potassium (>5 mmol/L). Prevalence of low serum sodium and high serum potassium was higher among adults aged 71 or older (4.7 and 2.0%, respectively) and among adults with chronic kidney disease (3.4 and 1.9%), diabetes (5.0 and 1.1%), or using certain medications (which varied by condition), adjusted for age; whereas, prevalence was <1% among adults without these conditions or medications. CONCLUSIONS: Most of the US population has normal serum sodium and potassium concentrations; these data describe population subgroups at higher risk of low serum sodium and high serum potassium and can inform clinical care.

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 approximately 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.

Objectives: To evaluate vitamin B-12 status of U.S. adults. High serum methylmalonic acid (MMA) is a specific functional indicator of low vitamin B-12 status, but it is not sensitive because concentrations also increase with impaired renal function. Our goal was to describe the distribution of serum vitamin B-12 and MMA in U.S. adults, and estimate age-specific reference intervals for serum MMA in a subpopulation with replete vitamin B-12 status and normal renal function. Methods: We examined cross-sectional data for serum vitamin B-12 and MMA in U.S. adults participating in the National Health and Nutrition Examination Survey from 2011–2014. Vitamin B-12 was assessed by electrochemiluminescence assay and MMA by isotope-dilution LC-MS/MS. Results: In both bivariate and multivariate analysis age, race/Hispanic origin, and vitamin B-12 supplementation were generally significantly associated with serum vitamin B-12 and MMA concentrations before and after controlling for additional covariates. We observed higher serum vitamin B-12 and MMA concentrations in persons ≥60 y compared with younger age groups. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations compared with non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were wider for persons ≥60 y compared with younger age groups. Compared with the overall population, the central 95% reference interval for serum MMA concentrations was considerably narrower for a vitamin B-12 replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, while serum MMA showed notable increases with impaired renal function. Conclusions: The higher serum MMA concentrations throughout the entire distribution in older persons who are vitamin B-12 replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret the vitamin B-12 status in clinical and epidemiologic research. Funding Sources: This work was supported by direct appropriations from U.S. Congress.

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 approximately 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 ( approximately 70 nmol/L) and RBC ( approximately 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 approximately 20%. Continued monitoring of all age groups is advisable given the high folate status particularly in older supplement users.

BACKGROUND: Serum vitamin B-12 is measured to evaluate vitamin B-12 status. Serum methylmalonic acid (MMA) is a specific functional indicator of vitamin B-12 status; however, concentrations increase with impaired renal function. OBJECTIVE: The aim of this study was to describe the distribution of serum vitamin B-12 and MMA in US adults, and estimate age-specific reference intervals for serum MMA in a healthy subpopulation with replete vitamin B-12 status and normal renal function. METHODS: We examined cross-sectional data for serum vitamin B-12 and MMA in adults participating in the NHANES from 2011 to 2014. Vitamin B-12 was measured by electrochemiluminescence assay and MMA by isotope-dilution liquid chromatography-tandem mass spectrometry. RESULTS: In both bivariate and multivariate analyses, age, race/Hispanic origin, and vitamin B-12 supplement use were generally significantly associated with serum vitamin B-12 and MMA concentrations. Serum MMA concentrations increased with age, particularly in persons aged >/=70 y. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations than non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were widest for persons aged >/=70 y compared with younger age groups. Compared with the overall population, the central 95% reference intervals for serum MMA concentrations were considerably narrower for a vitamin B-12-replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, whereas serum MMA showed notable, increases with impaired renal function. CONCLUSIONS: The higher serum MMA concentrations throughout the entire distribution in older persons (especially persons aged >/=70 y) who are vitamin B-12-replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret vitamin B-12 status in epidemiologic research.

BACKGROUND: Vitamin D is important for bone health; in 2014 it was the fifth most commonly ordered laboratory test among Medicare Part B payments. OBJECTIVES: The aim of this study was to describe vitamin D status in the US population in 2011-2014 and trends from 2003 to 2014. METHODS: We used serum 25-hydroxyvitamin D data from NHANES 2011-2014 (n = 16,180), and estimated the prevalence at risk of deficiency (<30 nmol/L) or prevalence at risk of inadequacy (30-49 nmol/L) by age, sex, race and Hispanic origin, and dietary intake of vitamin D. We also present trends between 2003 and 2014. RESULTS: In 2011-2014, the percentage aged >/=1 y at risk of vitamin D deficiency or inadequacy was 5.0% (95% CI: 4.1%, 6.2%) and 18.3% (95% CI: 16.2%, 20.6%). The prevalence of at risk of deficiency was lowest among children aged 1-5 y (0.5%; 95% CI: 0.3%, 1.1%), peaked among adults aged 20-39 y (7.6%; 95% CI: 6.0%, 9.6%), and fell to 2.9% (95% CI: 2.0%, 4.0%) among adults aged >/=60 y; the prevalence of at risk of inadequacy was similar. The prevalence of at risk of deficiency was higher among non-Hispanic black (17.5%; 95% CI: 15.2%, 20.0%) than among non-Hispanic Asian (7.6%; 95% CI: 5.9%, 9.9%), non-Hispanic white (2.1%; 95% CI: 1.5%, 2.7%), and Hispanic (5.9%; 95% CI: 4.4%, 7.8%) persons; the prevalence of at risk of inadequacy was similar. Persons with higher vitamin D dietary intake or who used supplements had lower prevalences of at risk of deficiency or inadequacy. From 2003 to 2014 there was no change in the risk of vitamin D deficiency; the risk of inadequacy declined from 21.0% (95% CI: 17.9%, 24.5%) to 17.7% (95% CI: 16.0%, 19.7%). CONCLUSION: The prevalence of at risk of vitamin D deficiency in the United States remained stable from 2003 to 2014; at risk of inadequacy declined. Differences in vitamin D status by race and Hispanic origin warrant additional investigation.