Micro but mighty-Micronutrients in the epigenetic regulation of adaptive immune responses.

Micronutrients are essential small molecules required by organisms in minute quantity for survival. For instance, vitamins and minerals, the two major categories of micronutrients, are central for biological processes such as metabolism, cell replication, differentiation, and immune response. Studies estimated that around two billion humans worldwide suffer from micronutrient deficiencies, also known as "hidden hunger," linked to weakened immune responses. While micronutrients affect the immune system at multiple levels, recent studies showed that micronutrients potentially impact the differentiation and function of immune cells as cofactors for epigenetic enzymes, including the 2-oxoglutarate-dependent dioxygenase (2OGDD) family involved in histone and DNA demethylation. Here, we will first provide an overview of the role of DNA methylation in T cells and B cells, followed by the micronutrients ascorbate (vitamin C) and iron, two critical cofactors for 2OGDD. We will discuss the emerging evidence of these micronutrients could regulate adaptive immune response by influencing epigenetic remodeling.

Unraveling the genetics underlying micronutrient signatures of diversity panel present in brown rice through genome-ionome linkages.

Rice (Oryza sativa) is an important staple crop to address the Hidden Hunger problem not only in Asia but also in Africa where rice is fast becoming an important source of calories. The brown rice (whole grain with bran) is known to be more nutritious due to elevated mineral composition. The genetics underlying brown rice ionome (sum total of such mineral composition) remains largely unexplored. Hence, we conducted a comprehensive study to dissect the genetic architecture of the brown rice ionome. We used genome-wide association studies, gene set analysis, and targeted association analysis for 12 micronutrients in the brown rice grains. A diverse panel of 300 resequenced indica accessions, with more than 1.02 million single nucleotide polymorphisms, was used. We identified 109 candidate genes with 5-20% phenotypic variation explained for the 12 micronutrients and identified epistatic interactions with multiple micronutrients. Pooling all candidate genes per micronutrient exhibited phenotypic variation explained values ranging from 11% to almost 40%. The key donor lines with larger concentrations for most of the micronutrients possessed superior alleles, which were absent in the breeding lines. Through gene regulatory networks we identified enriched functional pathways for central regulators that were detected as key candidate genes through genome-wide association studies. This study provided important insights on the ionome variations in rice, on the genetic basis of the genome-ionome relationships and on the molecular mechanisms underlying micronutrient signatures.

The association between several serum micronutrients and benign prostatic hyperplasia: Results from NHANES 2003-2006.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition that affects the quality of life of older men. Specific micronutrients, including retinol, retinyl esters, carotenoids, vitamin E, and vitamin C, have antioxidant and anti-inflammatory properties. However, the correlation between serum concentrations of these micronutrients and BPH is unclear. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES), which included 2067 representative US men. BPH was assessed using the self-reported questionnaire. This association was explored by adjusting for confounders using multivariate logistic regression. RESULTS: After fully adjusting for confounders, for every 0.01 µmol/L increase in serum retinyl esters, the risk of BPH increased by 2% (OR = 1.02; 95% CI: 1.01-1.03; p = 0.006). Based on the Bonferroni-corrected p-value, we found this correlation to be significant. One µmol/L increase in total carotenoids was associated with a 22% increase in BPH risk (OR = 1.22; 95% CI: 1.03-1.46; p = 0.025). By analyzing the correlation between different types of carotenoids and BPH, we also found that ß-carotenoids (OR = 1.43; 95% CI: 1.03-1.99; p = 0.036) was also positively correlated with BPH. The subgroup analysis revealed a positive correlation between serum vitamin E (OR = 1.02; 95% CI: 1.00-1.04; p = 0.018) and BPH in men under 60 years of age. Serum retinyl ester (OR = 1.02; 95% CI: 1.01-1.04; p = 0.008) and carotenoid (OR = 1.52; 95% CI: 1.22-1.87; p < 0.001) concentrations were positively correlated with BPH in men over 60 years of age. CONCLUSION: Our study suggests that excessive serum retinyl esters, total carotenoids, and especially ß-carotenoids are potential risk factors for BPH, and this association should be further investigated.

Genetic biofortification: advancing crop nutrition to tackle hidden hunger.

Malnutrition, often termed "hidden hunger," represents a pervasive global issue carrying significant implications for health, development, and socioeconomic conditions. Addressing the challenge of inadequate essential nutrients, despite sufficient caloric intake, is crucial. Biofortification emerges as a promising solution by enhance the presence of vital nutrients like iron, zinc, iodine, and vitamin A in edible parts of different crop plants. Crop biofortification can be attained through either agronomic methods or genetic breeding techniques. Agronomic strategies for biofortification encompass the application of mineral fertilizers through foliar or soil methods, as well as leveraging microbe-mediated mechanisms to enhance nutrient uptake. On the other hand, genetic biofortification involves the strategic crossing of plants to achieve a desired combination of genes, promoting balanced nutrient uptake and bioavailability. Additionally, genetic biofortification encompasses innovative methods such as speed breeding, transgenic approaches, genome editing techniques, and integrated omics approaches. These diverse strategies collectively contribute to enhancing the nutritional profile of crops. This review highlights the above-said genetic biofortification strategies and it also covers the aspect of reduction in antinutritional components in food through genetic biofortification.

Low vitamin B12 blood levels in sickle cell disease: Data from a large cohort study in Tanzania.

Sickle cell disease (SCD) is associated with high rates of undernutrition and stunting. Undernutrition in combination with chronic haemolysis may lead to deficiencies in micronutrients necessary for erythropoiesis. Here we examined selected levels of ferritin, vitamins B2 , B6 , B9 and B12 , and vitamin C that were measured in blood samples from 820 SCD patients from Tanzania with no history of hospital admission, infections or painful episodes in the previous 30 days. We studied children (0-8 years), early adolescents (9-14 years), late adolescents (15-17 years) and adults (≥18 years). Severely low levels of vitamin B12 were observed across the four age groups. Despite the lowered vitamin B12 concentrations, total homocysteine concentrations were normal across both genders in all age groups. We found no significant gender-related differences between the other measured micronutrients. In this large SCD population, spanning the whole life cycle, a low level of vitamin B12 was consistently found across both genders and all age groups. Given the pivotal role of vitamin B12 in cellular metabolism, particularly in erythropoiesis, more studies are required to unravel how to better detect clinically relevant vitamin B12 deficiency among SCD patients, and thus to identify more precisely those who need supplementation of vitamin B12 .

Biofortification of Triticum species: a stepping stone to combat malnutrition.

BACKGROUND: Biofortification represents a promising and sustainable strategy for mitigating global nutrient deficiencies. However, its successful implementation poses significant challenges. Among staple crops, wheat emerges as a prime candidate to address these nutritional gaps. Wheat biofortification offers a robust approach to enhance wheat cultivars by elevating the micronutrient levels in grains, addressing one of the most crucial global concerns in the present era. MAIN TEXT: Biofortification is a promising, but complex avenue, with numerous limitations and challenges to face. Notably, micronutrients such as iron (Fe), zinc (Zn), selenium (Se), and copper (Cu) can significantly impact human health. Improving Fe, Zn, Se, and Cu contents in wheat could be therefore relevant to combat malnutrition. In this review, particular emphasis has been placed on understanding the extent of genetic variability of micronutrients in diverse Triticum species, along with their associated mechanisms of uptake, translocation, accumulation and different classical to advanced approaches for wheat biofortification. CONCLUSIONS: By delving into micronutrient variability in Triticum species and their associated mechanisms, this review underscores the potential for targeted wheat biofortification. By integrating various approaches, from conventional breeding to modern biotechnological interventions, the path is paved towards enhancing the nutritional value of this vital crop, promising a brighter and healthier future for global food security and human well-being.

Arbuscular mycorrhizal fungi increased biomass, nutritional value, and cochineal resistance of Opuntia ficus-indica plants.

BACKGROUND: Opuntia ficus-indica (L.) Miller is dominantly growing on degraded soils in arid and semi-arid areas. The plants might establish a strong association with arbuscular mycorrhizal fungi (AMF) to adapt to nutrient, drought, and herbivore insect stress. The objective of this study was to investigate the effects of AMF inoculations and variable soil water levels (SWA) on the biomass, nutrient concentration, nutritional composition, and nutrient digestibility of the spiny and spineless O. ficus-indica by inducing resistance to cochineal stress. One mother Opuntia ficus-indica cladode was planted in a single pot in each field with 24 kg mixed soil. AMF inoculums were cultured in sorghum plants in a greenhouse and were inoculated in the planted cladodes. The planted cladodes were arranged using a completely randomized design (CRD) with three factors: AMF (present and absent); O. ficus-indica type (spiny and spineless) and four water treatments with 0-25% of plant available soil water (SWA), 25-50% of SWA, 50-75% of SWA, and 75-100% of SWA. RESULTS: Drought stress reduced the below and above-ground biomass, cladode nutrient content, nutritional composition, and in vitro dry matter digestibility (IVDMD) and in vitro organic matter digestibility (IVOMD). AMF colonization significantly increased biomass production with significant changes in the macro and micro-nutrient concentrations of O. ficus-indica. AMF inoculation significantly increased the IVDMD and IVOMD of both O. ficus-indica types by improving the biomass, organic matter (OM), crude protein (CP), and reduced fiber and ash contents. AMF-inoculated cladodes improved the nutrient concentrations of the cladodes. AMF caused an increase in biomass production, increased tolerance to cochineal stress, and improved nutrient concentration, nutritional composition, and nutrient digestibility performance of O. ficus-indica plants. CONCLUSIONS: AMF improved the performance of the O. ficus-indica plant to resist drought and cochineal stress and increased the biomass, nutrient concentration, nutritional composition, and nutrient digestibility. The potential of O. ficus-indica to adapt to cochineal stress is controlled by the macro and micro-nutrient concentration brought by the AMF association.

Italian and Middle Eastern adherence to Mediterranean diet in relation to Body Mass Index and non-communicable diseases: nutritional adequacy of simulated weekly food plans.

BACKGROUND: The Mediterranean diet (MD), known to prevent obesity, overweight and the related non communicable diseases (NCD), is based on typical dishes, foods and on a common cultural milieu. Although MD is the basis of dietary guidelines, the prevalence of obesity, overweight and NCD, is increasing both in Western regions, and even more in Middle Eastern regions (MER). This study aimed to analyze (i) the impact of different levels of adherence to the MD, in Italy and MER, on body mass index (BMI) (ii) the bromatological composition of a simulated 7-days food plan (7-DFP) based on Italian or MER typical meals, following MD criteria and the Italian or MER food base dietary guideline; (iii) the optimization of nutrients impacting on NCD. METHODS: The 7-DFPs were implemented using a dietary software. The association between adherence to MD and BMI was evaluated by pooled estimated ORs (with 95% confidence intervals and p-values). Pooled measures were obtained by the methods appropriate for meta-analysis. The different food-based guidelines have been compared. RESULTS: The pooled ORs of obese status comparing medium vs. high adherence to MD were: 1.19 (95% C.I.: 0.99; 1.42, p-value = 0.062) and 1.12 (95% C.I.: 0.90; 1.38, p-value = 0.311) for MER and Italy respectively. For the comparison of low vs. high adherence, the pooled ORs were 1.05 (95% C.I.: 0.88; 1.24, p-value = 0.598) for MER, and 1.20 (95% C.I.: 1.02; 1.41, p-value = 0.031) for Italy when outliers are removed. High adherence to the MD resulted as potential protective factor against obesity. In MER 7-DFP: total fats is higher (34.5 E%) vs. Italian 7-DFP (29.4 E%); EPA (20 mg) and DHA (40 mg) are lower than recommended (200 mg each); sugars (12.6 E%) are higher than recommended (< 10 E%). Calcium, Zinc, and vitamin D do not reach target values in both 7-DFPs. CONCLUSION: This study highlights that, even when 7-DFPs follow MD and refer to nutrient needs, it is necessary to verify nutrient excesses or deficits impacting on NCD. High MD adherence is protective toward NCDs. MD principles, and energy balance should be communicated according to socioeconomic and educational levels.

Role of transcription factor complex OsbHLH156-OsIRO2 in regulating manganese, copper, and zinc transporters in rice.

Iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) are essential micronutrients that are necessary for plant growth and development, but can be toxic at supra-optimal levels. Plants have evolved a complex homeostasis network that includes uptake, transport, and storage of these metals. It was shown that the transcription factor (TF) complex OsbHLH156-OsIRO2 is activated under Fe deficient conditions and acts as a central regulator on Strategy II Fe acquisition. In this study, the role of the TF complex on Mn, Cu, and Zn uptake was evaluated. While Fe deficiency led to significant increases in shoot Mn, Cu, and Zn concentrations, the increases of these divalent metal concentrations were significantly suppressed in osbhlh156 and osiro2 mutants, suggesting that the TF complex plays roles on Mn, Cu, and Zn uptake and transport. An RNA-sequencing assay showed that the genes associated with Mn, Cu, and Zn uptake and transport were significantly suppressed in the osbhlh156 and osiro2 mutants. Transcriptional activation assays demonstrated that the TF complex could directly bind to the promoters of OsIRT1, OsYSL15, OsNRAMP6, OsHMA2, OsCOPT1/7, and OsZIP5/9/10, and activate their expression. In addition, the TF complex is required to activate the expression of nicotianamine (NA) and 2'-deoxymugineic acid (DMA) synthesis genes, which in turn facilitate the uptake and transport of Mn, Cu, and Zn. Furthermore, OsbHLH156 and OsIRO2 promote Cu accumulation to partially restore the Fe-deficiency symptoms. Taken together, OsbHLH156 and OsIRO2 TF function as core regulators not only in Fe homeostasis, but also in Mn, Cu, and Zn accumulation.

Perspectives on embryo maturation and seed quality in a global climate change scenario.

Global climate change has already brought noticeable alterations to multiple regions of our planet, including increased CO2 concentrations and changes in temperature. Several important steps of plant growth and development, such as embryogenesis, can be affected by such environmental changes; for instance, they affect how stored nutrients are used during early stages of seed germination during the transition from heterotrophic to autotrophic metabolism-a critical period for the seedling's survival. In this article, we briefly describe relevant processes that occur during embryo maturation and account for nutrient accumulation, which are sensitive to environmental change. Most of the nutrients stored in the seed during its development-including carbohydrates, lipids, and proteins, depending on the species-accumulate during the seed maturation stage. It is also known that iron, a key micronutrient for various electron transfer processes in plant cells, accumulates during embryo maturation. The existing literature indicates that climate change can not only affect the quality of the seed, in terms of total nutritional content, but also affect seed production. We discuss the potential effects of temperature and CO2 increases from an embryo-autonomous point of view, in an attempt to separate the effects on the parent plant from those on the embryo.

High-resolution plasma metabolomics and thiamine status in critically Ill adult patients.

INTRODUCTION: Thiamine (Vitamin B1) is an essential micronutrient and is classically considered a co-factor in energy metabolism. The association between thiamine status and whole-body metabolism in critical illness has not been studied. OBJECTIVES: To determine association between whole blood thiamine pyrophosphate (TPP) concentrations and plasma metabolites and connected metabolic pathways using high resolution metabolomics (HRM) in critically ill patients. METHODS: Cross-sectional study performed at Erciyes University Hospital, Kayseri, Turkey and Emory University, Atlanta, GA, USA. Participants were critically ill adults with an expected length of intensive care unit stay longer than 48 h and receiving chronic furosemide therapy. A total of 76 participants were included. Mean age was 69 years (range 33-92 years); 65% were female. Blood for TPP and metabolomics was obtained on the day of ICU admission. Whole blood TPP was measured by HPLC and plasma HRM was performed using liquid chromatography/mass spectrometry. Data was analyzed using regression analysis of TPP levels against all plasma metabolomic features in metabolome-wide association studies (MWAS). MWAS using the highest and lowest TPP concentration tertiles was performed as a secondary analysis. RESULTS: Specific metabolic pathways associated with whole blood TPP levels in regression and tertile analysis included pentose phosphate, fructose and mannose, branched chain amino acid, arginine and proline, linoleate, and butanoate pathways. CONCLUSIONS: Plasma HRM revealed that thiamine status, determined by whole blood TPP concentrations, was significantly associated with metabolites and metabolic pathways related to metabolism of energy, carbohydrates, amino acids, lipids, and the gut microbiome in adult critically ill patients.

Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients.

Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non-communicable diseases-where the pathogen is missing; leading to increased morbidity and mortality as micronutritional uptake and distribution in the body is hindered. Here, we discuss the acute immune response in respect to nutrients, the opposing nutritional demands of regulatory and inflammatory cells and particularly focus on some nutrients linked with inflammation such as iron, vitamins A, Bs, C, and other antioxidants. We propose that while the absorption of certain micronutrients is hindered during inflammation, the dietary lymph path remains available. As such, several clinical trials investigated the role of the lymphatic system during protein absorption, following a ketogenic diet and an increased intake of antioxidants, vitamins, and minerals, in reducing inflammation and ameliorating disease.

The Impact of Delayed Processing of Chilled Whole Blood Specimens on the Measurement of Nutritional Biomarkers in the United Kingdom National Diet and Nutrition Survey Rolling Programme.

BACKGROUND: The logistics of timely processing of blood specimens remains a barrier in population health studies to the generation of micronutrient status data. OBJECTIVES: To test a blood specimen processing protocol that includes overnight postage with cooling and its effect on nutritional biomarker concentrations. METHODS: This study was embedded within the United Kingdom National Diet and Nutrition Survey. Paired specimens were collected from 64 participants (16 y+). One set of specimens were processed within 2 h of collection ["field"] and paired samples were mailed in an insulated box with cold packs using an overnight postal service to a central laboratory ["postal"]. Specimen processing protocols were aligned across field sites and the central laboratory. Specimens were frozen and later analyzed using established methods for vitamins, minerals, lipids, ferritin, and C-reactive protein (CRP). Percent difference was calculated between protocols and compared with quality specifications determined from intra- and interindividual variation. RESULTS: In the postal protocol, ferritin [geometric mean percent difference (95% confidence interval)] [6% (3, 8)] (P = 0.002) and zinc [4% (1, 6)] (P = 0.004) were higher compared with the field protocol. Retinol [-3% (-4, -1)] (P < 0.0001) and selenium [-3% (-5, -1)] (P = 0.003) concentrations were lower in the postal protocol, whereas total [2% (1, 3)] and HDL [4% (2, 5)] cholesterol were higher (P < 0.0001) than in the field protocol. Percent differences were within the optimum quality specification for the majority of biomarkers, but ferritin, zinc, and selenium fell outside of the optimum limits. Higher ferritin concentration in the postal protocol led to a decrease in the proportion of specimens with ferritin concentration <15 µg/L from 13% to 9%. CONCLUSIONS: The majority of micronutrient biomarkers, serum lipids, and CRP were minimally affected by delayed processing when cooled. The study suggests acceptable stability of nutritional biomarkers within the described protocol, which can provide accurate data for nutritional biomarkers commonly measured in studies and surveys.

Vitamin B12 Is Associated with Higher Serum Testosterone Concentrations and Improved Androgenic Profiles Among Men with Infertility.

BACKGROUND: Infertility impacts 16% of North American couples, with male factor infertility contributing to ∼30% of cases. Reproductive hormones, especially testosterone, are essential for spermatogenesis. An age-independent population-level decline in testosterone concentrations over the past few decades has been proposed to be a consequence of diet and lifestyle changes. Vitamin B12 is present in the testes and has been suggested as an adjuvant nutritional therapy for male infertility due to its potential to improve sperm parameters. However, evidence examining the relationship between vitamin B12 and reproductive hormones is limited. OBJECTIVES: The objective was to cross-sectionally examine the relationship between serum vitamin B12 and male reproductive hormones (luteinizing hormone, follicular stimulating hormone, total testosterone, estradiol, and prolactin). METHODS: Men with infertility (n = 303) were recruited from Mount Sinai Hospital in Toronto, Canada. Serum was analyzed for vitamin B12 and reproductive hormones. Statistical analyses included nonparametric Spearman's rank correlation coefficient, linear regression, logistic regression, and effect modification by age and BMI linear regressions. RESULTS: An independent monotonic relationship between serum vitamin B12 and total testosterone (ρ = 0.19, P = 0.001) was observed. Serum vitamin B12 was linearly associated with total testosterone (unadjusted ß = 0.0007, P = 0.008 and adjusted ß = 0.0005, P = 0.03). Compared to individuals in the lowest tertile of serum vitamin B12, those in the middle tertile (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI]: 0.25, 0.93, P = 0.03) and the highest tertile (unadjusted OR = 0.41; 95% CI: 0.22, 0.77, P = 0.005 and adjusted OR = 0.44; 95% CI: 0.22, 0.87, P = 0.02) had reduced odds of testosterone deficiency. CONCLUSIONS: These findings suggest that among men with infertility, low serum vitamin B12 is associated with a higher risk of testosterone deficiency and impaired androgenic hormonal profiles that impact spermatogenesis and consequently, fertility.

Maternal Iron and Vitamin D Status during the Second Trimester Is Associated with Third Trimester Depression Symptoms among Pregnant Participants in the APrON Cohort.

BACKGROUND: The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed. OBJECTIVES: This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals. METHODS: The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained. RESULTS: Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (ß: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (ß: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (ß: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 µg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (ß: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 µg/L) and vitamin D (25(OH)D <75 nmol/L) (ß: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients. CONCLUSIONS: A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy.

Dietary supplement intake in women with breast cancer before and after diagnosis: results from the SUCCESS C trial.

BACKGROUND: There is little evidence that dietary supplements are beneficial for patients with breast cancer; therefore, they are usually not recommended by treatment guidelines. The aim of the present analysis was to assess the prevalence of dietary supplement (DS) intake among women before and after a breast cancer diagnosis. METHODS: Participants in the SUCCESS C lifestyle intervention study, a randomized controlled trial in women with newly diagnosed intermediate- to high-risk breast cancer, completed two questionnaires on dietary supplement intake 24 months (QS1) and 48 months (QS2) after beginning the lifestyle intervention. The study was registered on 12.17.2008 under the EU Clinical Trials Register https://www.clinicaltrialsregister.eu/ , trial registration number: 2008-005453-38. The questionnaires collected data on DS intake during the 5-year period prediagnosis (QS1) and in the period postdiagnosis (QS2). Multivariate logistic regression models were fitted to examine differences in DS intake between the two intervention groups. The groups were then pooled to examine differences in DS use between the prediagnostic and postdiagnostic period. RESULTS: A total of 320 questionnaires from 58.5% of intervention group completers and 416 questionnaires from 46.6% of low-level intervention group completers were included in the analysis. Overall, 20.2% of all respondents reported taking DS prior to their diagnosis. After a cancer diagnosis, the percentage of women taking DS significantly increased to 56.4% (p for time effect < 0.0001). No differences in DS intake between the intervention groups were observed. Single or combined preparations of vitamins and minerals/trace elements were the most frequently reported supplements. Notably, a 9-fold increase in vitamin D intake was reported postdiagnosis, where the proportion of women increased from 3.8 to 34.5%. CONCLUSION: A 3-fold increase in the reported intake of dietary supplements was seen in women after a breast cancer diagnosis. These observations underscore the need to incorporate patient education surrounding the use of dietary supplements in a treatment care plan, particularly addressing the negligible benefits as well as the potential risks and treatment interactions.

Serum Zinc Concentrations by Inflammation Status, Time of Day, and Fasting Status for Estimating Zinc Deficiency in 6-59-Mo-Old Children: Results from the Brazilian National Survey on Child Nutrition (ENANI-2019).

BACKGROUND: Serum zinc concentration (SZC) is considered the best biomarker of zinc status in population-level evaluations. However, zinc deficiency (ZD) estimations can be biased if they do not consider blood collection timing, inflammation, and fasting status. OBJECTIVES: The objectives of this study were to determine SZC without and with adjustment for inflammation, according to blood collection timing and fasting status, estimate ZD prevalence, and evaluate the associated factors with ZD in a representative sample of Brazilian children aged <5 y. METHODS: Population-based study with 7597 children aged 6-59 mo surveyed by the Brazilian National Survey on Child Nutrition. SZC was adjusted for inflammation using the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia regression correction approach, with high-sensitive C-reactive protein, assessed according to blood collection timing (morning/afternoon) and fasting status (<8 and ≥8 h). SZC <65 µg/dL (morning collection) or SZC <57 µg/dL (afternoon collection) were classified as ZD. The analysis between associated factors and ZD used the adjusted prevalence ratio (PR). RESULTS: After adjusting for inflammation, SZC was higher in all percentiles and varied according to collection timing and fasting status. Children who had blood collected in the morning without fasting or in the afternoon had lower SZC than those assessed in the morning with fasting. The differences in adjusted SZC according to the timing of collection and fasting status were greater in the higher percentiles of the distribution, with the greatest absolute difference observed when comparing the 95th percentile of morning fasting compared with nonfasting (20.3 µg/dL). The prevalence of ZD estimated without and with adjusting SZC for inflammation was 17.8% and 13.8%, respectively. The occurrence of diarrhea, fever, or respiratory symptoms in the 15 d before blood collection was associated with a higher prevalence of ZD (PR: 1.42; 95% confidence interval: 1.04, 1.94). CONCLUSIONS: Adjusting SZC for inflammation and considering fasting status is important to avoid overestimating the prevalence of ZD.

The Evolution of Science and Regulation of Dietary Supplements: Past, Present, and Future.

Dietary supplement use in the United States is widespread and increasing, especially among certain population groups, such as older Americans. The science surrounding dietary supplements has evolved substantially over the last few decades since their formal regulation in 1994. Much has been learned about the mechanisms of action of many dietary supplement ingredients, but the evidence on their health effects is still building. As is true of much nutrition research, there are many studies that point to health effects, but not all are at the level of scientific evidence (e.g., randomized controlled interventions), rigor, or quality needed for definitive statements of efficacy regarding clinical end points. New technologies and approaches are being applied to the science of dietary supplements, including nutrigenomics and microbiome analysis, data science, artificial intelligence (AI), and machine learning-all of which can elevate the science behind dietary supplements. Products can contain an array of bioactive compounds derived from foods as well as from medicinal plants, which creates enormous challenges in data collection and management. Clinical applications, particularly those aimed at providing personalized nutrition options for patients, have become more sophisticated as dietary supplements are incorporated increasingly into clinical practice and self-care. The goals of this article are to provide historical context for the regulation and science of dietary supplements, identify research resources, and suggest some future directions for science in this field.

Zinc status or supplementation and its relation to soil-transmitted helminthiasis in children: A systematic review.

Soil-transmitted helminths (STHs) parasitic infection is known as one of the most common infections around the world affecting more than a quarter of the world's population. The relationship between STH infections and micronutrient deficiencies are closely related and often coexist among the affected population. The study, therefore, aimed to summarise the available literature focusing on the effect of zinc status/deficiency or supplementation on STH infection or reinfection in children. For this purpose, we adopted a systematic approach and searched the existing literature on PubMed, Scopus, and Cochrane Library databases. A search term was entered to retrieve the available data. A total of 12 articles were included in this review after applying the inclusion/exclusion criteria. Most of the included studies reported a lower zinc status in children affected with any parasitic infection. Regarding the effect of zinc status and supplementation on parasitic infection in children, we found only a few studies (n = 4) with inconsistent result findings. This review reported that children infected with STH have lower zinc levels; however, a limited number of studies showed the effect of zinc supplements on the risk of STH warrants the need for further studies in this regard.

Supplementation with (6S)-5-methyltetrahydrofolic acid appears as effective as folic acid in maintaining maternal folate status while reducing unmetabolised folic acid in maternal plasma: a randomised trial of pregnant women in Canada.

Folic acid supplementation is recommended during pregnancy to support healthy fetal development; (6S)-5-methyltetrahydrofolic acid ((6S)-5-MTHF) is available in some commercial prenatal vitamins as an alternative to folic acid, but its effect on blood folate status during pregnancy is unknown. To address this, we randomised sixty pregnant individuals at 8-21 weeks' gestation to 0·6 mg/d folic acid or (6S)-5-MTHF × 16 weeks. Fasting blood specimens were collected at baseline and after 16 weeks (endline). Erythrocyte and serum folate were quantified via microbiological assay (as globally recommended) and plasma unmetabolised folic acid (UMFA) via LC-MS/MS. Differences in biochemical folate markers between groups were explored using multivariable linear/quantile regression, adjusting for baseline concentrations, dietary folate intake and gestational weeks. At endline (n 54), the mean values and standard deviations (or median, inter-quartile range) of erythrocyte folate, serum folate and plasma UMFA (nmol/l) in those supplemented with (6S)-5-MTHF v. folic acid, respectively, were 1826 (sd 471) and 1998 (sd 421); 70 (sd 13) and 78 (sd 17); 0·5 (0·4, 0·8) and 1·3 (0·9, 2·1). In regression analyses, erythrocyte and serum folate did not differ by treatment group; however, concentrations of plasma UMFA in pregnancy were 0·6 nmol/l higher (95 % CI 0·2, 1·1) in those supplementing with folic acid as compared with (6S)-5-MTHF. In conclusion, supplementation with (6S)-5-MTHF may reduce plasma UMFA by ∼50 % as compared with supplementation with folic acid, the biological relevance of which is unclear. As folate is currently available for purchase in both forms, the impact of circulating maternal UMFA on perinatal outcomes needs to be determined.