Risk of Deficiency in Multiple Concurrent Micronutrients in Children and Adults in the United States

Certain population sub-groups in the United States are vulnerable to micronutrient malnutrition. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) describing the biochemical status of vitamins A, B6, B12, C, D, E, folate, and anemia, were aggregated to determine the overall risk of multiple concurrent deficiencies in U.S. children and adults (n = 15,030) aged >9 years. The prevalence of deficiency risk according to socio-demographic, life-stage, dietary supplement use, and dietary adequacy categories was investigated. Thirty-one percent of the U.S. population was at risk of at least one vitamin deficiency or anemia, with 23%, 6.3%, and 1.7% of the U.S. population at risk of deficiency in 1, 2, or 3–5 vitamins or anemia, respectively. A significantly higher deficiency risk was seen in women (37%), non-Hispanic blacks (55%), individuals from low income households (40%), or without a high school diploma (42%), and underweight (42%) or obese individuals (39%). A deficiency risk was most common in women 19–50 years (41%), and pregnant or breastfeeding women (47%). Dietary supplement non-users had the highest risk of any deficiency (40%), compared to users of full-spectrum multivitamin-multimineral supplements (14%) and other dietary supplement users (28%). Individuals consuming an adequate diet based on the Estimated Average Requirement had a lower risk of any deficiency (16%) than those with an inadequate diet (57%). Nearly one-third of the U.S. population is at risk of deficiency in at least one vitamin, or has anemia.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Suboptimal Plasma Long Chain n-3 Concentrations are Common among Adults in the United States, NHANES 2003–2004

Population data on long-chain omega-3 polyunsaturated fatty acid (LCn-3 PUFA) status from biomarkers of dietary intake is lacking. The objectives were to describe plasma LCn-3 PUFA concentrations and compare them to concentrations associated with cardiovascular health and dietary recommendations for two servings of seafood/week. Fasting plasma fatty acids were measured among 1386 subjects ≥20 years from the National Health and Nutrition Examination Survey, 2003–2004. LCn-3 concentrations represent the sum of eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid relative to total fatty acids (expressed as a percentage). Mean LCn-3 PUFA concentration was 2.07% (95% CI 1.95–2.19). Overall, 80.6% of participants had LCn-3 below concentrations recommended for cardiovascular health. Hispanic participants were the most likely to have LCn-3 PUFA below recommended levels. Nearly all participants (95.7%) had LCn-3 below concentrations associated with cardiovascular protection. Older participants (≥60 years) had higher LCn-3 PUFA concentrations than those aged 20–39 years but not aged 40–59 years. LCn-3 PUFA concentrations were lower for Hispanic participants relative to non-Hispanic black participants. Suboptimal LCn-3 concentrations are common among U.S. adults. These findings highlight the need to increase LCn-3 intake among Americans.Medicine, Faculty ofNon UBCPopulation and Public Health (SPPH), School ofReviewedFacult

Maternal B Vitamin Supplementation From Preconception Through Weaning Suppresses Intestinal Tumorigenesis in Apc1638N Mouse Offspring

Objective—Variations in the intake of folate are capable of modulating colorectal tumorigenesis; however, the outcome appears to be dependent on timing. This study sought to determine the effect of altering folate (and related B vitamin) availability during in-utero development and the suckling period on intestinal tumorigenesis. Design—Female wildtype mice were fed diets either mildly deficient, replete or supplemented with vitamins B2, B6, B12 and folate for 4 weeks before mating to Apc1638N males. Females remained on their diet throughout pregnancy and until weaning. After weaning, all Apc1638N offspring were maintained on replete diets for 29 weeks. Results—At 8 months of age tumour incidence was markedly lower among offspring of supplemented mothers (21%) compared with those of replete (59%) and deficient (55%) mothers (p=0.03). Furthermore, tumours in pups born to deficient dams were most likely to be invasive (p=0.03). The expression of Apc, Sfrp1, Wif1 and Wnt5a—all of which are negative regulatory elements of the Wnt signalling cascade—in the normal small intestinal mucosa of pups decreased with decreasing maternal B vitamin intake, and for Sfrp1 this was inversely related to promoter methylation. β-Catenin protein was elevated in offspring of deficient dams. Conclusions—These changes indicate a de-repression of the Wnt pathway in pups of deficient dams and form a plausible mechanism by which maternal B vitamin intake modulates tumorigenesis in offspring. These data indicate that maternal B vitamin supplementation suppresses, while deficiency promotes, intestinal tumorigenesis in Apc1638N offspring

Associations Between Single Nucleotide Polymorphisms in Folate Uptake and Metabolizing Genes with Blood Folate, Homocysteine, and DNA Uracil Concentrations

Background—Folate is an essential nutrient that supports nucleotide synthesis and biological methylation reactions. Diminished folate status results in chromosome breakage and is associated with several diseases, including colorectal cancer. Folate status is also inversely related to plasma homocysteine concentrations—a risk factor for cardiovascular disease. Objective—We sought to gain further understanding of the genetic determinants of plasma folate and homocysteine concentrations. Because folate is required for the synthesis of thymidine from uracil, the latter accumulating and being misincorporated into DNA during folate depletion, the DNA uracil content was also measured. Design—Thirteen single nucleotide polymorphisms (SNPs) in genes involved in folate uptake and metabolism, including folate hydrolase (FOLH1), folate polyglutamate synthase (FPGS), γ-glutamyl hydrolase (GGH), methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MTR), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC1), were studied in a cohort of 991 individuals. Results—The MTHFR 677TT genotype was associated with increased plasma homocysteine and decreased plasma folate. MTHFR 1298A\u3eC and RFC1 intron 5A\u3eG polymorphisms were associated with significantly altered plasma homocysteine concentrations. The FOLH1 1561C\u3eT SNP was associated with altered plasma folate concentrations. The MTHFR 677TT genotype was associated with a ≈34% lower DNA uracil content (P = 0.045), whereas the G allele of the GGH – 124T\u3eG SNP was associated with a stepwise increase in DNA uracil content (P = 0.022). Conclusion—Because the accumulation of uracil in DNA induces chromosome breaks, mutagenic lesions, we suggest that, as for MTHFR C677T, the GGH – 124 T\u3eG SNP may modulate the risk of carcinogenesis and therefore warrants further attention

Metabolomics reveals a role for the chromatin-binding protein HMGN5 in glutathione metabolism.

High mobility group nucleosome-binding protein 5 (HMGN5) is a chromatin architectural protein that binds specifically to nucleosomes and reduces the compaction of the chromatin fiber. The protein is present in most vertebrate tissues however the physiological function of this protein is unknown. To examine the function of HMGN5 in vivo, mice lacking the nucleosome-binding domain of HMGN5 were generated and characterized. Serological analysis revealed that compared to wild-type littermates (Hmgn5(+/Y)), mice with a targeted mutation in the HMGN5 gene (Hmgn5(tm1/Y)), had elevated serum albumin, non-HDL cholesterol, triglycerides, and alanine transaminase, suggesting mild hepatic abnormalities. Metabolomics analysis of liver extracts and urine revealed clear differences in metabolites between Hmgn5(tm1/Y) and their Hmgn5(+/Y) littermates. Hmgn5(tm1/Y) mice had a significant increase in hepatic glutathione levels and decreased urinary concentrations of betaine, phenylacetylglycine, and creatine, all of which are metabolically related to the glutathione precursor glycine. Microarray and qPCR analysis revealed that expression of two genes affecting glutathione metabolism, glutathione peroxidase 6 (Gpx6) and hexokinase 1 (Hk1), was significantly decreased in Hmgn5(tm1/Y) mouse liver tissue. Analysis of chromatin structure by DNase I digestion revealed alterations in the chromatin structure of these genes in the livers of Hmgn5(tm1/Y) mice. Thus, functional loss of HMGN5 leads to changes in transcription of Gpx6 and Hk1 that alter glutathione metabolism

Distribution of serum α-tocopherol concentrations among individuals ≥20y, excluding pregnant or lactating women, stratified by race-ethicity and supplement.

<p>A. Non-Hispanic White. B. Non-Hispanic Black. C. Mexican American. D. Other. Lines represent density (as a percentage) through non-parametric kernel density estimation.</p

Distribution of serum α-tocopherol concentrations among individuals ≥20y, excluding pregnant or lactating women, stratified by supplement use.

<p>Lines represent density (as a percentage) through non-parametric kernel density estimation.</p

Distribution of serum α-tocopherol concentrations among individuals ≥20y, excluding pregnant or lactating women, stratified by sex and supplement use.

<p>A. Males. B. Females. Lines represent density (as a percentage) through non-parametric kernel density estimation.</p

Prevalences of cholesterol-adjusted serum α-tocopherol concentrations below cut-off (5.8 μmol/mmoL) among individuals in the United States (NHANES 2003–2006) (TOTAL), stratified by reported food use (FOOD), food and supplement use (FOOD+DS) and demographic characteristics (%).

<p>^a Serum α-tocopherol (μmol/L) divided by total cholesterol (mmol/L). Cut-off value (5.8 μmol/mmol) based on American Heart Association recommendation of desirable total cholesterol level (<200 mg/dL).</p><p>^b Sample size (n = 7,920) excludes individuals: <20 years; who were pregnant or lactating; with α-tocopherol concentrations >99 percentile; or unavailable data for α-tocopherol concentration, age, sex, race/ethnicity, total cholesterol. To account for complex survey design, SAS survey procedures (surveymeans) as well as cluster, strata, and sampling weights (proportionally scaled to included sample) were used.</p><p>^c Includes multi-racial and any other Hispanic individuals</p><p>^d Based on Rao-Scott chi-square p-value</p><p>Prevalences of cholesterol-adjusted serum α-tocopherol concentrations below cut-off (5.8 μmol/mmoL) among individuals in the United States (NHANES 2003–2006) (TOTAL), stratified by reported food use (FOOD), food and supplement use (FOOD+DS) and demographic characteristics (%).</p

Proportion (%) of adults ≥20y at or below the serum α-tocopherol concentration shown on the Y-axis, excluding pregnant or lactating women, for the total population and by supplement use.

<p>The dotted horizontal line represents a criterion of adequacy set at 30 μmol/L.</p