Dietary Flavonoid and Subclass Intakes are not Associated with Markers of Bone Health in U.S. Adults Age 50+ Years.

BACKGROUND: Dietary flavonoid intakes have been associated with improved markers of bone health in Chinese and Scottish cohorts, but little data exist in middle aged to older adults in the United States. OBJECTIVES: The objective of our research was to assess if dietary flavonoid intakes are associated with bone mineral density (BMD), bone mineral content (BMC), and bone area of the lumbar spine and femoral neck in a nationally representative population of middle aged to older U.S. adults. We further sought to investigate if relationships of the main flavonoid subgroups (i.e., anthocyanins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones) exist, as a secondary objective. METHODS: Cross-sectional data from individuals aged 50+ years enrolled in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were used in our analyses (N = 2590). Weighted multivariate logistic regression models were used to investigate the relationship between quartiles of flavonoid intake and BMD, BMC, and bone area of the lumbar spine and femoral neck of participants. RESULTS: Mean age of participants was 63.4 ± 0.52 years and 64.1 ± 0.52 years for men and women, respectively. Average total flavonoid intake was 217 ± 19.4 mg/day and 306 ± 26.9 mg/day for men and women, respectively. Total flavonoid intakes were not significantly associated with BMD, BMC, or bone area of the femoral neck or lumbar spine in male or female participants. Flavonoid subclass intakes were also not consistently associated with improved markers of bone health. CONCLUSION: Although several limitations exist, this cross-sectional analysis of U.S. adults aged 50+ years provides contradictory evidence to the hypothesis that higher flavonoid and flavonoid subclass intakes beneficially impacts markers of bone health. Large prospective cohort investigations that better capture long-term dietary flavonoid intake and ascertain fractures the primary outcome, as well as randomized controlled trials, are needed to fully elucidate the effects flavonoids on bone health.

Association of Egg Intake With Alzheimer's Dementia Risk in Older Adults: The Rush Memory and Aging Project.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with increasing prevalence due to population aging. Eggs provide many nutrients important for brain health, including choline, omega-3 fatty acids, and lutein. Emerging evidence suggests that frequent egg consumption may improve cognitive performance on verbal tests, but whether consumption influences the risk of Alzheimer's dementia and AD is unknown. OBJECTIVES: To examine the association of egg consumption with Alzheimer's dementia risk among the Rush Memory and Aging Project cohort. METHODS: Dietary assessment was collected using a modified Harvard semiquantitative food frequency questionnaire. Participants' first food frequency questionnaire was used as the baseline measure of egg consumption. Multivariable adjusted Cox proportional hazards regression models were used to investigate the associations of baseline egg consumption amount with Alzheimer's dementia risk, adjusting for potential confounding factors. Subgroup analyses using Cox and logistic regression models were performed to investigate the associations with AD pathology in the brain. Mediation analysis was conducted to examine the mediation effect of dietary choline in the relationship between egg intake and incident Alzheimer's dementia. RESULTS: This study included 1024 older adults {mean [±standard deviation (SD)] age = 81.38 ± 7.20 y}. Over a mean (±SD) follow-up of 6.7 ± 4.8 y, 280 participants (27.3%) were clinically diagnosed with Alzheimer's dementia. Weekly consumption of >1 egg/wk (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.34, 0.83) and ≥2 eggs/wk (HR: 0.53; 95% CI: 0.35, 0.81) was associated with a decreased risk of Alzheimer's dementia. Subgroup analysis of brain autopsies from 578 deceased participants showed that intakes of >1 egg/wk (HR: 0.51; 95% CI: 0.35, 0.76) and ≥2 eggs/wk (HR: 0.62; 95% CI: 0.44, 0.90) were associated with a lower risk of AD pathology in the brain. Mediation analysis showed that 39% of the total effect of egg intake on incident Alzheimer's dementia was mediated through dietary choline. CONCLUSIONS: These findings suggest that frequent egg consumption is associated with a lower risk of Alzheimer's dementia and AD pathology, and the association with Alzheimer's dementia is partially mediated through dietary choline.

Pulse Consumption and Health Outcomes: A Scoping Review.

Pulses-comprising the dry, edible seeds of leguminous plants-have long been lauded for their culinary flexibility and substantial nutritional advantages. This scoping review aimed to map the evidence on how pulses contribute to overall human health. Four electronic databases were searched for clinical and observational studies in English. We identified 30 articles (3 cross-sectional studies, 1 federated meta-analysis, 8 prospective cohort studies, 1 before-and-after study, and 17 randomized controlled trials) that met our inclusion criteria. Predominant among the pulses studied were lentils, chickpeas, common bean varieties (e.g., pinto, black, navy, red, kidney), black-eyed peas, cowpeas, and split peas. Consumption modalities varied; most studies examined mixed pulses, while five isolated individual types. In intervention studies, pulses were incorporated into diets by allotting a fixed pulse serving on top of a regular diet or by substituting red meat with pulses, offering a comparative analysis of dietary effects. The health outcomes evaluated were multifaceted, ranging from lipid profiles to blood pressure, cardiovascular disease risk and mortality, type 2 diabetes and glycemic control, metabolic syndrome indicators, inflammatory markers, oxidative stress biomarkers, and hormonal profiles. The most frequently assessed study outcomes included changes in low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, fasting blood sugar, hemoglobin A1c, waist circumference, and C-reactive protein or high-sensitivity C-reactive protein. This review should serve as a call to action for the scientific community to build upon the existing evidence, enriching our understanding of the nutritional and health-promoting attributes of pulses.

Dietary Supplement Use in Transmasculine People: Results of an Online Survey of Volunteer Adults.

INTRODUCTION: Health inequities and disparities in nutrition research exist among transmasculine people. A dearth of evidence on dietary supplement use and motivations exist, partially due to constrained collection of sex and gender identity in national surveys. OBJECTIVE: We sought to investigate common motivations and use of dietary supplements in a voluntary survey of transmasculine people. METHODS: A total of 48 participants completed an online survey detailing dietary supplement use, motivations, and demographic information. RESULTS: 64.5 and 90.0% of participants reported use of 1+ dietary supplement within the past 30-days and during some point in their lifetime, respectively. Top reported product types used included multivitamins (52%), melatonin (52%), vitamin D (46%), vitamin C (35%), fish oil (33%), B-vitamins or B-complex (31%), iron (29%), green tea (29%), biotin (25%), cranberry (23%), zinc (23%), protein powder (23%), probiotics (23%), and calcium (21%). There was no relationship between the number of supplements reported and participant age, BMI, income, or mastectomy status (p > 0.05). Participants reported top motivations being for "improving my overall health" (60.4%), "maintaining health" (54.2%), to "supplement my diet due to not getting enough from food"(41.7%), "mental health" (39.6%), and to "prevent colds, boost immune system" (33.3%). CONCLUSION: Transmasculine people in our study reported a high use of dietary supplements. Differences in the types of products and number of products used, as well as specific motivations for use likely exist within this subpopulation, however, future nationally-representative longitudinal studies are needed to fully elucidate these patterns and for informing evidence-based nutrition guidance.

Defining "low-carb" in the scientific literature: A scoping review of clinical studies.

There remains a lack of scientific consensus on what level of carbohydrate intake constitutes low-carbohydrate diets. We conducted a scoping review to understand how low-carbohydrate diets were defined in the peer-reviewed literature. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Three electronic databases were searched for clinical studies in English. We identified 508 articles (317 randomized controlled, 99 cross-over, 33 before-and-after, 12 non-randomized, and 47 other clinical trials). Most examined effects of low-carbohydrate diets in healthy adults (62.4%), 40 to 59 years old (55.5%), with obesity or overweight (66.1%). The majority reported effects on weight or body composition (29.9%), diabetes (18.7%), or cardiovascular risk factors (12.9%) as primary outcomes. Most articles (56.9%) reported percent of energy from carbohydrates, and of those, 60.3% defined low-carbohydrate diets as being ≤30% of energy from carbohydrates. Some articles (22.9%) reported grams of carbohydrates per day, and of those, most defined low-carbohydrate diets as being under ∼100 grams of carbohydrates per day. Systematic reviews and dose-response meta-regressions utilizing patient-level data on carbohydrate intake, status markers (e.g., RQ/ketones), and health outcomes would be useful in informing consensus around a standardized definition.

Chewing Gum Is Associated with Better Diet Quality but Not Oral Health Measures in U.S. Adults.

OBJECTIVE: Chewing gum (especially sugar-free gum) has been linked to improved oral health, however there is an absence of observational research using nationally-representative data in the United States. We sought to examine the factors associated with chewing gum and its relationship with the oral health status of U.S. adults. METHODS: Cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2013-2018 cycles were used in these analyses. Primary outcomes were the odds of having gum disease, treatment for gum disease, ever being told of bone loss around teeth, root caries, caries, and restoration. Unadjusted and multivariate logistic regression models were used to investigate the relationship of chewing gum use with demographic/lifestyle factors and the oral health status of participants. RESULTS: 2.40% (n = 365) of adults were users of chewing gum and the average among users was 5.20 ± 0.40 g/d. Users of chewing gum were more likely to be female, younger in age, and non-Hispanic Black or Hispanic. Self-reported chewing gum use did not affect the oral health status of U.S. adults (OR: 1.10, 95% CI: 0.42-2.88 for gum disease; OR: 1.34, 95% CI: 0.64-2.81 for treatment for gum disease; OR: 0.56, 95% CI: 0.27-1.17 for bone loss around teeth; OR: 1.01, 95% CI: 0.32-3.12 for root caries; OR: 0.96, 95% CI: 0.54-1.69 for caries), except for restoration (OR: 3.54, 95% CI: 1.78-7.06), but was associated with improved diet quality (OR: 1.86, 95% CI: 1.11-3.12 for a healthy eating index (HEI) of 51-59; OR: 1.96, 95% CI: 1.08-3.56 for HEI of 60-93); and decreased intakes of snacks (OR: 1.64, 1.01-2.69), and added sugars. CONCLUSION: Future observational studies that more accurately capture chewing gum usage are needed, as these analyses have several limitations.

The Relationship of Circulating Choline and Choline-Related Metabolite Levels with Health Outcomes: A Scoping Review of Genome-Wide Association Studies and Mendelian Randomization Studies.

Choline is essential for proper liver, muscle, brain, lipid metabolism, cellular membrane composition, and repair. Understanding genetic determinants of circulating choline metabolites can help identify new determinants of choline metabolism, requirements, and their link to disease endpoints. We conducted a scoping review to identify studies assessing the association of genetic polymorphisms on circulating choline and choline-related metabolite concentrations and subsequent associations with health outcomes. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement scoping review extension. Literature was searched to September 28, 2022, in 4 databases: Embase, MEDLINE, Web of Science, and the Biological Science Index. Studies of any duration in humans were considered. Any genome-wide association study (GWAS) investigating genetic variant associations with circulating choline and/or choline-related metabolites and any Mendelian randomization (MR) study investigating the association of genetically predicted circulating choline and/or choline-related metabolites with any health outcome were considered. Qualitative evidence is presented in summary tables. From 1248 total reviewed articles, 53 were included (GWAS = 27; MR = 26). Forty-two circulating choline-related metabolites were tested in association with genetic variants in GWAS studies, primarily trimethylamine N-oxide, betaine, sphingomyelins, lysophosphatidylcholines, and phosphatidylcholines. MR studies investigated associations between 52 total unique choline metabolites and 66 unique health outcomes. Of these, 47 significant associations were reported between 16 metabolites (primarily choline, lysophosphatidylcholines, phosphatidylcholines, betaine, and sphingomyelins) and 27 health outcomes including cancer, cardiovascular, metabolic, bone, and brain-related outcomes. Some articles reported significant associations between multiple choline types and the same health outcome. Genetically predicted circulating choline and choline-related metabolite concentrations are associated with a wide variety of health outcomes. Further research is needed to assess how genetic variability influences choline metabolism and whether individuals with lower genetically predicted circulating choline and choline-related metabolite concentrations would benefit from a dietary intervention or supplementation.

Comparison of the nutrient composition of eggs produced in the Guatemalan highlands during the wet and dry seasons.

The potential of chicken eggs as a nutritionally complete protein and source of key micronutrients during the first 1000 days post-conception has been progressively recognized across the globe, particularly in resource-poor settings. Fluctuation of egg nutrient content by season is relatively unknown, which may influence international food composition databases and outcomes in intervention studies using egg supplementation. To better interpret the findings of The Saqmolo' Project, we conducted comprehensive nutrient analyses on eggs produced during the wet and dry seasons in the highlands of central Guatemala. We randomly collected 36 shell eggs from a local farm during both seasons, hard-boiled, and prepared them for transport to the United States, where they were pooled and assessed for their nutrient composition. Methods of the Association of Official Analytical Chemists, the American Oil Chemists Society, and the American Association of Cereal Chemists were utilized to determine total energy, moisture, ash, total protein, total fat, fatty acids, total carbohydrates, 12 vitamins, 11 minerals, and carotenoids, by season, in some instances with modifications. Differences in nutrient composition between de-shelled hard-boiled eggs collected between seasons were assessed using an analysis of variance (ANOVA) and Tukey's family error rate comparison test. Most nutrients in eggs produced in the highlands of central Guatemala differed negligibly (but statistically significantly) based on seasonality. Only vitamins A and E, folate, choline, and calcium fluctuated at clinically significant levels relative to the AI/RDA for infants 7-12 months. Total energy, protein, trans fatty acids, moisture, and vitamin D3 levels did not differ between seasons (p > .05). Further multi-year sampling is needed to examine how seasonal variation affects the nutrient composition of eggs. These data may be used to supplement existing national and regional food composition databases.

Association of Pork Intake with Cognitive Performance in Older Adults Enrolled in the National Health and Nutrition Examination Survey (NHANES), 2011-2014 Data Cycles.

BACKGROUND: Pork provides higher levels of several nutrients important for cognitive maintenance in older adults. A pilot clinical study suggests the addition of moderate amounts of pork to a Mediterranean-style diet improves cognition in older adults. There is an absence of observational research that isolates effects of pork from other red meats. OBJECTIVE: To examine the relationship of pork intake on cognitive performance in older adults. METHODS: Cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2011-2014 cycles were used in these analyses. Pork intake was assessed using data from two non-consecutive 24-h dietary recalls. Cognitive function was assessed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning, CERAD Delayed Recall, Animal Fluency, and Digital Substitution tests. Statistical analyses were adjusted for sample weighting and survey design variables to account for the complex design. Student t-tests (continuous variables) and Pearson chi-squared tests (categorical variables) were employed to compare participant characteristics between the low and normal cognitive performance groups. Logistic regression was used to determine the relationship of pork intake (low, medium, and high) with prevalence of low cognitive performance, with the non-consumer group as the referent category. RESULTS: Pork intake was not beneficially or detrimentally associated performance on the any of the cognitive tests in both the crude and multivariate models (p > 0.05). CONCLUSIONS: Prospective cohort investigations and larger/longer-term clinical trials are needed to fully elucidate effects of pork intake on cognition in older adults.

Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.

BACKGROUND: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.

Consumption Patterns and the Nutritional Contribution of Total, Processed, Fresh, and Fresh-Lean Pork to the U.S. Diet.

Pork has the potential to provide several macro and micronutrients to the diet, as it is a commonly consumed protein in the United States and across many cultures worldwide. There is an absence of clinical and observational studies that isolate the nutritional contribution of various types of pork intake from that of other red and/or processed meats. The objective of this study was to assess consumption patterns and the nutritional contribution of total, processed, fresh, and fresh-lean pork to the diets of participants aged 2+ years enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 data cycles. The recent National Cancer Institute method was used to disaggregate fresh and processed pork intake from the USDA Food Patterns Equivalents Database. The mean intake of total pork among consumers was estimated to be 79.5 ± 0.82, 54.2 ± 0.69, 54.6 ± 0.93, and 45.9 ± 0.73, g/d for men, women, boys, and girls, respectively. Total pork consumption subtly increased intakes of total energy and several macro and micronutrients, decreased diet quality (HEI-2015) scores (adults only), and consumption of other "healthful" food groups. Only subtle but clinically insignificant effects of pork intake on biomarkers of nutritional status were shown. These trends were largely driven by processed pork consumption and the co-consumption of foods such as condiments. Increasing the availability and education around fresh-lean cuts may help to increase intake of protein and other key nutrients across certain subpopulations, without adversely affecting diet quality and biomarkers of health status.

Relationship between short-term self-reported dietary magnesium intake and whole blood ionized magnesium (iMg2+) or serum magnesium (s-Mg) concentrations.

OBJECTIVE: Since we and others have shown that supplemental magnesium raises whole blood ionized magnesium (iMg2+) we investigated the relationships between self-reported dietary magnesium intake and concentrations of whole blood iMg2+ and serum magnesium (s-Mg). METHODS: We obtained whole blood iMg2+ concentrations, as well as s-Mg concentrations, from a pilot, three-arm, randomized, controlled, crossover bioavailability study of magnesium supplements (n = 23; 105 measures). Dietary magnesium intake was assessed using three-day food records and the Nutrition Data System for Research (NDSR, University of Minnesota, MN, USA). Whole blood iMg2+ was measured with an electrode analyser (NOVA Biochemical, Waltham, MA, USA), whereas s-Mg was measured using atomic absorption spectroscopy. A linear mixed-effects model was employed with dietary magnesium as the outcome variable and iMg2+, s-Mg, study treatment and study visit as fixed effects. We adjusted age, gender, race and body mass index covariates. RESULTS: Values for dietary magnesium, iMg2+ and s-Mg were 303.8 ± 118.9 mg/day, 1.3 ± 0.1 mg/dL and 2.2 ± 4.1 mg/dL, respectively. No association was found between dietary magnesium intake and iMg2+ -125 ± 176.95 (p = .49) or s-Mg -9.33 ± 5.04 (p = .08). CONCLUSIONS: Whole blood iMg2+ and s-Mg concentrations do not reflect short-term self-reported dietary intake in adults. Further research is needed to determine whether blood biomarkers of magnesium may reflect dietary magnesium intake.Key messagesDietary intake of magnesium, a shortfall nutrient, may be objectively measured using blood biomarkers of magnesium.Serum magnesium and whole blood iMg2+ were not associated with short-term dietary intake of magnesium.

Lactoferrin for Mental Health: Neuro-Redox Regulation and Neuroprotective Effects across the Blood-Brain Barrier with Special Reference to Neuro-COVID-19.

Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons. As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, dementia, depression, and multiple sclerosis. As an endogenous iron-chelator, lactoferrin prevents iron accumulation and dopamine depletion in Parkinson's disease patients. Oral lactoferrin supplementation could modulate the p-Akt/PTEN pathway, reduce Aß deposition, and ameliorate cognitive decline in Alzheimer's disease. Novel lactoferrin-based nano-therapeutics have emerged as effective drug-delivery systems for clinical management of neurodegenerative disorders. Recent emergence of the Coronavirus disease-2019 (COVID-19) pandemic, initially considered a respiratory illness, demonstrated a broader virulence spectrum with the ability to cross the blood-brain barrier and inflict a plethora of neuropathological manifestations in the brain - the Neuro-COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are widely reported in Parkinson's disease, Alzheimer's disease, dementia, and multiple sclerosis patients with aggravated clinical outcomes. Lactoferrin, credited with several neuroprotective benefits in the brain could serve as a potential adjuvant in the clinical management of Neuro-COVID-19.

Label compliance for ingredient verification: regulations, approaches, and trends for testing botanical products marketed for "immune health" in the United States.

During the COVID-19 pandemic, the botanical product market saw a consumer interest increase in immune health supplements. While data are currently insufficient to support public health guidance for using foods and dietary supplements to prevent or treat COVID-19 and other immune disorders, consumer surveys indicate that immune support is the second-most cited reason for supplement use in the United States. Meanwhile, consumers showed increased attention to dietary supplement ingredient labels, especially concerning authenticity and ingredient claims. Top-selling botanical ingredients such as elderberry, turmeric, and functional mushrooms have been increasingly marketed toward consumers to promote immune health, but these popular products succumb to adulteration with inaccurate labeling due to the intentional or unintentional addition of lower grade ingredients, non-target plants, and synthetic compounds, partially due to pandemic-related supply chain issues. This review highlights the regulatory requirements and recommendations for analytical approaches, including chromatography, spectroscopy, and DNA approaches for ingredient claim verification. Demonstrating elderberry, turmeric, and functional mushrooms as examples, this review aims to provide industrial professionals and scientists an overview of current United States regulations, testing approaches, and trends for label compliance verification to ensure the safety of botanical products marketed for "immune health."

Recommendation on an updated standardization of serum magnesium reference ranges.

PURPOSE: Serum magnesium is the most frequently used laboratory test for evaluating clinical magnesium status. Hypomagnesemia (low magnesium status), which is associated with many chronic diseases, is diagnosed using the serum magnesium reference range. Currently, no international consensus for a magnesemia normal range exists. Two independent groups designated 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L) as the low cut-off point defining hypomagnesemia. MaGNet discussions revealed differences in serum magnesium reference ranges used by members' hospitals and laboratories, presenting an urgent need for standardization. METHODS: We gathered and compared serum magnesium reference range values from our institutions, hospitals, and colleagues worldwide. RESULTS: Serum magnesium levels designating "hypomagnesemia" differ widely. Of 43 collected values, only 2 met 0.85 mmol/L as the low cut-off point to define hypomagnesemia. The remainder had lower cut-off values, which may underestimate hypomagnesemia diagnosis in hospital, clinical, and research assessments. Current serum magnesium reference ranges stem from "normal" populations, which unknowingly include persons with chronic latent magnesium deficit (CLMD). Serum magnesium levels of patients with CLMD fall within widely used "normal" ranges, but their magnesium status is too low for long-term health. The lower serum magnesium reference (0.85 mmol/L) proposed specifically prevents the inclusion of patients with CLMD. CONCLUSIONS: Widely varying serum magnesium reference ranges render our use of this important medical tool imprecise, minimizing impacts of low magnesium status or hypomagnesemia as a marker of disease risk. To appropriately diagnose, increase awareness of, and manage magnesium status, it is critical to standardize lower reference values for serum magnesium at 0.85 mmol/L (2.07 mg/dL; 1.7 mEq/L).

Association of Total, Added, and Natural Phosphorus Intakes with Biomarkers of Health Status and Mortality in Healthy Adults in the United States.

The Western diet is high in dietary phosphorus, partially due to added phosphorus, (i.e., phosphates) predominantly present in processed food products. Elevated serum phosphate levels, otherwise known as hyperphosphatemia, have been associated with changes in health status, of note detrimental effects on cardiovascular and renal health. However, the extent to which highly absorbed added phosphorus contributes to these changes is relatively unknown, due to its poor characterization among food composition databases. Industry-provided data on phosphorus source ingredients and ranges of added phosphorus present in food categories to enable a more accurate estimation of the total, added, and natural phosphorus intakes in the U.S. population. Using regression analyses, we then assessed relationships between estimated total, added, and natural phosphorus intakes on biomarkers of health status and mortality in individuals enrolled in the National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 2001-2016 datasets. Total, added, and natural phosphorus intakes were associated with several biomarkers of health status. Added phosphorus intake was consistently inversely associated with HDL cholesterol in both men and women, whereas naturally occurring phosphorus intake was inversely correlated with the risk of elevated blood pressure. However, in most cases, the predicted impact of increases in phosphorus intake would result in small percentage changes in biomarkers. No meaningful associations between phosphorus and mortality were found, but indications of a correlation between mortality with quintiles of naturally occurring phosphorus were present, depending on covariate sets used. The disparate results for natural and added phosphorus intakes within the current study provide increased support for updating current food composition databases to more accurately account for dietary phosphorus intake as total, naturally occurring, and added phosphorus.

Effects of 100% Orange Juice on Markers of Inflammation and Oxidation in Healthy and At-Risk Adult Populations: A Scoping Review, Systematic Review, and Meta-analysis.

One hundred percent orange juice (OJ) has no added sugar, naturally contains flavonoids and ascorbic acid, and can modulate the body's oxidative and inflammatory systems. This scoping review, systematic review, and meta-analysis investigated associations between 100% OJ and markers of inflammation or oxidation in healthy adults and those at risk for chronic diseases. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and scoping review extension. Literature in English was searched to July 2021 in Embase and 4 Ovid platform databases. Clinical and observational studies of any duration were eligible. Cochrane Collaboration tools were used to assess the risk of bias in controlled trials. Strength of evidence was determined using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The scoping review presents a qualitative synthesis of evidence in summary and results tables. Twenty-one interventional studies (16 controlled trials and 5 before-after studies) conducted in 307 healthy and 327 at-risk participants were included. Six common markers [C-reactive protein (CRP) or high-sensitivity CRP (hs-CRP), IL-6, TNF-α, malondialdehyde (MDA), oxidized LDL (oxLDL), and antioxidant capacity] measured across 16 studies were systematically reviewed, and results were synthesized narratively. Random-effects model meta-analyses were conducted on 10 studies reporting hs-CRP, IL-6, and/or MDA. After consuming 100% OJ, healthy and at-risk participants showed significantly lower IL-6 concentrations (pooled net difference: -1.51 pg/mL; 95% CI: -2.31, -0.70) and lower, but nonsignificant, hs-CRP (pooled net change: -0.58 mg/L; 95% CI: -1.22, 0.05) and MDA (crossover trials pooled net difference: -0.06 µmol/L; 95% CI: -0.19, 0.08). Findings suggest that 100% OJ may reduce inflammation, but results should be interpreted with caution due to moderate risk of bias, very low strength of evidence, and the low number of subjects. This study was registered on PROSPERO (https://www.crd.york.ac.uk/prospero/) as CRD42021235438.

Perspective: Estrogen and the Risk of Cognitive Decline: A Missing Choline(rgic) Link?

Factors that influence the risk of neurocognitive decline and Alzheimer's disease (AD) may provide insight into therapies for both disease treatment and prevention. Although age is the most striking risk factor for AD, it is notable that the prevalence of AD is higher in women, representing two-thirds of cases. To explore potential underlying biological underpinnings of this observation, the intent of this article is to explore the interplay between cognitive aging and sex hormones, the cholinergic system, and novel hypotheses related to the essential nutrient choline. Mechanistic evidence points toward estrogen's neuroprotective effects being strongly dependent on its interactions with the cholinergic system, a modulator of attentional functioning, learning, and memory. Estrogen has been shown to attenuate anticholinergic-induced impairments in verbal memory and normalize patterns of frontal and occipital cortex activation, resulting in a more "young adult" phenotype. However, similar to estrogen replacement's effect in cardiovascular diseases, its putative protective effects may be restricted to early postmenopausal women only, a finding supportive of the "critical window hypothesis." Estrogen's impact on the cholinergic system may act both locally in the brain but also through peripheral tissues. Estrogen is critical for inducing endogenous choline synthesis via the phosphatidylethanolamine N-methyltransferase (PEMT) gene-mediated pathway of phosphatidylcholine (PC) synthesis. PEMT is dramatically induced in response to estrogen, producing not only a PC molecule and source of choline for the brain but also a key source of the long-chain ω-3 fatty acid, DHA. Herein, we highlight novel hypotheses related to hormone replacement therapy and nutrient metabolism aimed at directing future preclinical and clinical investigation.

Academy of Nutrition and Dietetics Nutrition Research Network: The Saqmolo' Project Rationale and Study Protocol for a Randomized Controlled Trial Examining the Influence of Daily Complementary Feeding of Eggs on Infant Development and Growth in Guatemala.

Adequate nutrition during the complementary feeding period is critical for optimal child growth and development and for promoting long-term educational attainment and economic potential. To prioritize limited public health resources, there is a need for studies that rigorously assess the influence of multicomponent integrated nutrition interventions in children younger than age 2 years in different contexts. This study aimed to describe the rationale and protocol for the Saqmolo' Project using the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. The Saqmolo' (ie, "egg" in the Mayan language, Kaqchiquel) Project is an individually randomized, partially blinded, controlled comparative effectiveness trial to evaluate the influence of adding delivery of a single whole egg per day to local standard nutrition care (ie, growth monitoring, medical care, deworming medication, multiple micronutrient powders for point-of-use food fortification [chispitas], and individualized complementary and responsive feeding education for caregivers) for 6 months, compared with the local standard nutrition care package alone, on child development, growth, and diet quality measures in rural indigenous Mayan infants aged 6 to 9 months at baseline (N = 1,200). The study is being executed in partnership with the Wuqu' Kawoq/Maya Health Alliance, a primary health care organization located in central Guatemala. Primary outcomes for this study are changes in global development scores, assessed using the Guide for Monitoring Global Development and the Caregiver Reported Child Development Instruments. Secondary outcomes include changes in infant hemoglobin, anthropometric measures (including z scores for weight for age, length for age, weight for length, and head circumference for age), and diet quality as measured using the World Health Organization's infant and young child feeding indicators. The results of the Saqmolo' Project may help to inform public health decision making regarding resource allocation for effective nutrition interventions during the complementary feeding period.