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.

Establishing Yourself as an Expert in Nutrition Science: Advice for Young Professionals.

In today's world in which there is a surplus of both scientists and online nutrition "experts," how do young professionals establish themselves? Becoming established as an expert requires selling yourself and your ideas to your colleagues and the general public by using effective communication skills. Helping young professionals develop these skills was the goal of a panel held at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2015. This panel featured a set of distinguished speakers who discussed techniques and strategies to enhance professional reputations centered around effectively leveraging communication platforms and opportunities to engage with colleagues. Early-career nutrition scientists can use the guidance provided by the panelists to improve their visibility and be a champion for themselves in order to establish themselves as experts in the field.

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.

Suboptimal Serum α-Tocopherol Concentrations Observed among Younger Adults and Those Depending Exclusively upon Food Sources, NHANES 2003-20061-3.

Vitamin E is an essential nutrient for human health, with an established function as a lipid-soluble antioxidant that protects cell membranes from free radical damage. Low vitamin E status has been linked to multiple health outcomes, including total mortality. With vitamin E being identified as a 'shortfall nutrient' because >90% of American adults are not consuming recommended amounts of vitamin E, we aimed to determine the prevalence of both clinical vitamin E deficiency (serum α-tocopherol concentration < 12 µmol/L) and failure to meet a criterion of vitamin E adequacy, serum α-tocopherol concentration of 30 µmol/L, based on the Estimated Average Requirement (EAR) and lowest mortality rate in the Alpha-Tocopherol Beta-Carotene (ATBC) study. The most recent nationally-representative cross-sectional data (2003-2006) among non-institutionalized US citizens with available serum concentrations of α-tocopherol from the National Health and Nutrition Examination Survey (NHANES); Centers for Disease Control and Prevention were analyzed. Serum α-tocopherol distributions were compared between those reporting consumption of food without supplement use (FOOD) and food and supplement use (FOOD+DS) by sex, age, and race/ethnicity. Only 1% of the US population is clinically deficient. FOOD consumers have lower average α-tocopherol levels (24.9± 0.2 µmol/L) than FOOD+DS users (33.7 ± 0.3 µmol/L), even when adjusted for total cholesterol. Using a criterion of adequacy of 30 µmol/L, 87% of persons 20-30 y and 43% of those 51+y had inadequate vitamin E status (p<0.01). A significant greater prevalence of FOOD compared to FOOD+DS users did not meet the criterion of adequacy which was based on the EAR and low ATBC mortality rate consistently across age, sex, and race/ethnic groups. The prevalence of inadequate vitamin E levels is significantly higher among non-users of dietary supplements. With declining usage of vitamin E supplements, the population should be monitored for changes in vitamin E status and related health outcomes.

Successful scientist: What's the winning formula?

What does it take to become a successful scientist? This question is usually asked or thought about at some point in a young scientist's career. The early stages of a scientific career are fraught with many hardships, and achieving success can seem impossible and daunting. After encountering many obstacles, it becomes easy to focus on failures and lose sight of career goals. The journey to success can seem so simple when looked upon from the outside, but even the best scientists have endured many hardships, which are often not communicated. This educational symposium featured a diverse panel of 5 accomplished scientists representing different work environments, such as government, industry, and academia. They discussed tips on how to have a successful career journey and the key qualities of a successful scientist. Also, they revealed the secret to what's in the winning formula for success.

ω-3 fatty acid supplementation as a potential therapeutic aid for the recovery from mild traumatic brain injury/concussion.

Sports-related concussions or mild traumatic brain injuries (mTBIs) are becoming increasingly recognized as a major public health concern; however, no effective therapy for these injuries is currently available. ω-3 (n-3) fatty acids, such as docosahexaenoic acid (DHA), have important structural and functional roles in the brain, with established clinical benefits for supporting brain development and cognitive function throughout life. Consistent with these critical roles of DHA in the brain, accumulating evidence suggests that DHA may act as a promising recovery aid, or possibly as a prophylactic nutritional measure, for mTBI. Preclinical investigations demonstrate that dietary consumption of DHA provided either before or after mTBI improves functional outcomes, such as spatial learning and memory. Mechanistic investigations suggest that DHA influences multiple aspects of the pathologic molecular signaling cascade that occurs after mTBI. This review examines the evidence of interactions between DHA and concussion and discusses potential mechanisms by which DHA helps the brain to recover from injury. Additional clinical research in humans is needed to confirm the promising results reported in the preclinical literature.

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.

Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer.

Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3ß), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3ß was elevated in the colonic mucosa of obese mice (P<.02). Moreover, ß-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P<.05), as was the expression of a downstream target gene, c-myc (P<.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer.

Maternal one-carbon nutrient intake and cancer risk in offspring.

Dietary intake of one-carbon nutrients, particularly folate, vitamin B(2) (riboflavin), vitamin B(6) , vitamin B(12) , and choline have been linked to the risk of cancers of the colon and breast in both human and animal studies. More recently, experimental and epidemiological data have emerged to suggest that maternal intake of these nutrients during gestation may also have an impact on the risk of cancer in offspring later in life. Given the plasticity of DNA methylation in the developing embryo and the established role of one-carbon metabolism in supporting biological methylation reactions, it is plausible that alterations in maternal one-carbon nutrient availability might induce subtle epigenetic changes in the developing embryo and fetus that persist into later life, altering the risk of tumorigenesis throughout the lifespan. This review summarizes the current literature on maternal one-carbon nutrient intake and offspring cancer risk, with an emphasis on cancers of the colon and breast, and discusses specific epigenetic modifications that may play a role in their pathogenesis.

Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT-LacZxApc1638N mice.

The Wnt pathway is a pivotal signaling cascade in colorectal carcinogenesis. The purpose of this work is to determine whether depletion of folate and other metabolically related B vitamins induces in vivo activation of intestinal Wnt signaling and whether this occurs in parallel with increased tumorigenesis. A hybrid mouse was created by crossing a Wnt-reporter animal (BAT-LacZ) with a model of colorectal cancer (Apc1638N). A mild depletion of folate and vitamins B2, B6, and B12 was induced over 16 wk, and the control animals in each instance were pair fed a diet containing the basal requirement of these nutrients. The multiplicity of macroscopic tumors and aberrant crypt foci both increased by ~50% in the hybrid mice fed the depletion diet (P<0.05). A 4-fold elevation in Wnt signaling was produced by the depletion diet (P<0.05) and was accompanied by significant changes in the expression of a number of Wnt-related genes in a pattern consistent with its activation. Proliferation and apoptosis of the colonic mucosa both changed in a protransformational direction (P<0.05). In summary, mild depletion of multiple B vitamins produces in vivo activation of colonic Wnt signaling, implicating it as a key pathway by which B-vitamin inadequacies enhance intestinal tumorigenesis.

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 B(2), B(6), B(12) and folate for 4 weeks before mating to Apc(1638N) males. Females remained on their diet throughout pregnancy and until weaning. After weaning, all Apc(1638N) 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. ß-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 Apc(1638N) offspring.

Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are associated with altered DNA uracil concentrations in an urban Puerto Rican population.

BACKGROUND: Five genes--UNG, SMUG1, MBD4, TDG, and DUT--are involved in the repair or prevention of uracil misincorporation into DNA, an anomaly that can cause mutagenic events that lead to cancer. Little is known about the determinants of uracil misincorporation, including the effects of single nucleotide polymorphisms (SNPs) in the abovementioned genes. Because of their metabolic function, folate and other one-carbon micronutrients may be important factors in the control of uracil misincorporation. OBJECTIVES: We sought to identify polymorphisms in uracil-processing genes that are determinants of DNA uracil concentration and to establish whether one-carbon nutrient status can further modify their effects. DESIGN: We examined the relations between 23 selected variants in the 5 uracil-processing genes, uracil concentrations in whole-blood DNA, and one-carbon nutrient (folate, vitamins B-6 and B-12, and riboflavin) status in 431 participants of the Boston Puerto Rican Health Study. RESULTS: Four SNPs in DUT, UNG, and SMUG1 showed a significant association with DNA uracil concentration. The SNPs in SMUG1 (rs2029166 and rs7296239) and UNG (rs34259) were associated with increased uracil concentrations in the variant genotypes (P = 0.011, 0.022, and 0.045, respectively), whereas the DUT SNP (rs4775748) was associated with a decrease (P = 0.023). In this population, one-carbon nutrient status was not associated with DNA uracil concentration, and it did not modify the effect of these 4 identified SNPs. CONCLUSION: Because elevated uracil misincorporation may induce mutagenic lesions, possibly leading to cancer, we propose that the 4 characterized SNPs in DUT, UNG, and SMUG1 may influence cancer risk and therefore deserve further investigation.

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), gamma-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>C and RFC1 intron 5A>G polymorphisms were associated with significantly altered plasma homocysteine concentrations. The FOLH1 1561C>T SNP was associated with altered plasma folate concentrations. The MTHFR 677TT genotype was associated with a approximately 34% lower DNA uracil content (P = 0.045), whereas the G allele of the GGH -124T>G 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>G SNP may modulate the risk of carcinogenesis and therefore warrants further attention.