A Systematized Review of the Relationship Between Obesity and Vitamin C Requirements.

Obesity rates have increased globally in recent decades. Body weight is used as a modifiable factor in determining vitamin requirements. Accordingly, vitamin C requirements are volumetrically scaled from data for healthy weight males to other age- and sex-based categories. Likewise, it is possible that increases in body weight due to obesity may affect vitamin C needs. A systematized literature review was performed to summarize evidence on whether obesity affects vitamin C intake or status. The literature was also scanned for potential mechanisms for the relationship. Many observational studies showed that vitamin C status is lower in overweight and obese children and adults; this may be explained by lower vitamin C intakes. Nevertheless, a reanalysis of carefully conducted intervention studies has demonstrated a lower vitamin C status in participants who were overweight or obese when given the same dose of vitamin C as subjects of normal weight. Several mechanisms have been proposed to potentially explain why vitamin C status is lower in people with obesity: changes in vitamin C partitioning between lean and adipose tissue, volumetric dilution, metabolic alterations due to obesity, and gut microbial dysbiosis. Depletion-repletion or pharmacokinetic studies that include individuals of diverse body weights and ages would be helpful to further investigate whether obesity increases requirements for vitamin C. The current evidence base supports a lower vitamin C status in people who are overweight or obese; however, the association may be attenuated by lower vitamin C intakes.

Development of a workflow for the selection, identification and optimization of lactic acid bacteria with high γ-aminobutyric acid production.

Lactic acid bacteria produce γ-aminobutyric acid (GABA) as an acid stress response. GABA is a neurotransmitter that may improve sleep and resilience to mental stress. This study focused on the selection, identification and optimization of a bacterial strain with high GABA production, for development as a probiotic supplement. The scientific literature and an industry database were searched for probiotics and potential GABA producers. In silico screening was conducted to identify genes involved in GABA production. Subsequently, 17 candidates were screened for in vitro GABA production using thin layer chromatography, which identified three candidate probiotic strains Levilactobacillus brevis DSM 20054, Lactococcus lactis DS75843and Bifidobacterium adolescentis DSM 24849 as producing GABA. Two biosensors capable of detecting GABA were developed: 1. a transcription factor-based biosensor characterized by the interaction with the transcriptional regulator GabR was developed in Corynebacterium glutamicum; and 2. a growth factor-based biosensor was built in Escherichia coli, which used auxotrophic complementation by expressing 4-aminobutyrate transaminase (GABA-T) that transfers the GABA amino group to pyruvate, hereby forming alanine. Consequently, the feasibility of developing a workflow based on co-culture with producer strains and a biosensor was tested. The three GABA producers were identified and the biosensors were encapsulated in nanoliter reactors (NLRs) as alginate beads in defined gut-like conditions. The E. coli growth factor-based biosensor was able to detect changes in GABA concentrations in liquid culture and under gut-like conditions. L. brevis and L. lactis were successfully encapsulated in the NLRs and showed growth under miniaturized intestinal conditions.

Micronutrient intakes in the Dutch diet: foods, fortified foods and supplements in a cross sectional study.

PURPOSE: This study investigates intakes of risk micronutrients from non-fortified foods, fortified foods and food supplements in different age and gender sub-groups of the Dutch population. METHODS: This is a secondary analysis of the Dutch National Food Consumption Survey (DNFCS 2012-2016, N = 4313, 1-79 years). The proportion of the population with Habitual Intakes below the Estimated Average Requirement (EAR) and above the Upper Level (UL) for calcium, iron, zinc, vitamin A, vitamin B6, folate, vitamin D and vitamin E from non-fortified foods, fortified foods and total intake including food supplements was calculated using Statistical Program to Assess Dietary Exposure (SPADE). RESULTS: More than 50% of the population had an intake below the EAR for calcium, iron, vitamin D and folate. Intakes were inadequate for certain sub-groups for the other vitamins and minerals. Adolescents and women were the population sub-groups most likely to have an intake below the EAR. For zinc, vitamin A and folic acid, more than 1% of toddlers exceeded the UL from the total intake. A negligible proportion exceeded the UL for the other vitamins and minerals. CONCLUSION: Inadequate intakes were found for several micronutrients in various population sub-groups despite an apparently well-nourished population. Intakes of zinc, folic acid and vitamin A from food supplements in toddlers and preschoolers should be investigated further to ensure they do not exceed recommended amounts. These results can be used to inform policy makers and to design nutritional interventions to improve micronutrient intakes in the Netherlands.

N-nitrosamine Mitigation with Nitrite Scavengers in Oral Pharmaceutical Drug Products.

N-nitrosamines are likely human carcinogens. After N-nitrosamine contaminants were detected in pharmaceutical products in 2018, regulatory authorities set a framework for the risk assessment, testing and mitigation of N-nitrosamines in drug products. One strategy to inhibit the formation of N-nitrosamines during the manufacture and storage of drug products involves the incorporation of nitrite scavengers in the formulation. Diverse molecules have been tested in screening studies including the antioxidant vitamins ascorbic acid and α-tocopherol, amino acids, and other antioxidants used in foods or drugs, for inclusion into drug products to mitigate N-nitrosamine formation. This review article outlines key considerations for the inclusion of nitrite scavengers in oral drug product formulations.

Contribution of base diet, voluntary fortified foods and supplements to micronutrient intakes in the UK.

The objective of the present study was to evaluate the contribution of voluntary fortified foods and supplements to reducing micronutrient shortfalls in the UK population. A secondary analysis of the UK National Diet and Nutrition Survey was conducted (2012/13-2013/14, N 2546, 1·5-95 years). Micronutrient intakes were derived from food consumption intake data and food composition data and calculated as the proportion below or above the Dietary Reference Values for males and females of different age groups, for those on a base diet only, users of fortified foods but no supplements and users of fortified foods and supplements. Of the population consuming a base diet only, 21-45 % and 5-29 % fell below the Estimated Average Requirement (EAR) for minerals and vitamins, respectively. About 3-13 % fewer consumers of fortified foods fell below the EAR for vitamins and minerals. Supplements barely reduced the prevalence of intakes below the EAR. Among supplement non-users and users, 99 and 96 % failed to meet the reference intakes for vitamin D. More women than men were at risk of inadequacies of micronutrient intakes. The prevalence of inadequacies declined with increasing age. Voluntary fortified foods but not supplements made a meaningful contribution to intakes of vitamin and minerals, without risk of unacceptably high intakes. These insights may help the UK to define approaches to address micronutrients of concern in vulnerable groups.

The effect of long chain omega-3 polyunsaturated fatty acids on muscle mass and function in sarcopenia: A scoping systematic review and meta-analysis.

BACKGROUND & AIMS: Sarcopenia is characterized by the progressive loss of skeletal muscle mass and function, which reduces mobility and quality of life. Risk factors for sarcopenia include advanced age, physical inactivity, obesity, and chronic diseases such as cancer or rheumatoid arthritis. Omega-3 long chain polyunsaturated fatty acids (LC PUFAs) might be associated with a reduction in risk of sarcopenia due to their anti-inflammatory effects. METHODS: We conducted a systematic review and meta-analysis to quantify the effects of omega-3 LC PUFAs on muscle mass, volume and function parameters. The National Library of Medicine's MEDLINE/PubMed database was searched on 9th October 2020 for randomized controlled trials that used omega-3 LC PUFAs as an intervention with muscle-related endpoints. A snowballing search to identify additional studies was completed on 23rd April 2021. The meta-analysis was conducted using meta-essentials worksheet 3. Bias was assessed using the Jadad scale. RESULTS: 123 studies were identified with the systematic searches. Most studies were performed in disease populations, such as cancer or chronic obstructive pulmonary disease (COPD), or in healthy individuals after a fatiguing exercise bout. The endpoints lean body mass, skeletal muscle mass, mid-arm muscle circumference, handgrip strength, quadriceps maximal voluntary capacity (MVC), and 1-repetition maximum chest press were selected for meta-analysis based on the number of available studies; thus 66 studies were included in the quantitative synthesis. Using a random effects model and 2-tailed p-value, there was a significant relationship in favor of omega-3 LC PUFA supplementation for lean body mass (effect size 0.27, 95%CI 0.04 to 0.51), skeletal muscle mass (effect size 0.31, 95%CI 0.01 to 0.60) and quadriceps MVC (effect size 0.47, 95%CI 0.02 to 0.93). CONCLUSION: The results indicate that there is a positive effect of omega-3 LC PUFA supplementation on overall body muscle mass and strength. Small study size and heterogeneity limit the applicability of these findings for sarcopenia prevention. Larger trials in populations at risk of sarcopenia would strengthen the evidence base.

Vitamins, the gut microbiome and gastrointestinal health in humans.

The gut microbiome plays important roles in the maintenance of host health and the pathogenesis of many diseases. Diet is a key modulator of the gut microbiome. There is increasing evidence that nutrients other than fermentable fiber affect the gut microbial composition. In this review, we discuss the effects of vitamins on the gut microbiome, and related gastrointestinal health, based on in vitro, animal and human studies. Some vitamins, when provided in large doses or when delivered to the large intestine, have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals (vitamins A, B2, D, E, and beta-carotene), increasing or maintaining microbial diversity (vitamins A, B2, B3, C, K) and richness (vitamin D), increasing short chain fatty acid production (vitamin C), or increasing the abundance of short chain fatty acid producers (vitamins B2, E). Others, such as vitamins A and D, modulate the gut immune response or barrier function, thus, indirectly influencing gastrointestinal health or the microbiome. Future research is needed to explore these potential effects and to elucidate the underlying mechanisms and host health benefits.

The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins.

Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

Considerations for Secondary Prevention of Nutritional Deficiencies in High-Risk Groups in High-Income Countries.

Surveys in high-income countries show that inadequacies and deficiencies can be common for some nutrients, particularly in vulnerable subgroups of the population. Inadequate intakes, high requirements for rapid growth and development, or age- or disease-related impairments in nutrient intake, digestion, absorption, or increased nutrient losses can lead to micronutrient deficiencies. The consequent subclinical conditions are difficult to recognize if not screened for and often go unnoticed. Nutrient deficiencies can be persistent despite primary nutrition interventions that are aimed at improving dietary intakes. Secondary prevention that targets groups at high risk of inadequacy or deficiency, such as in the primary care setting, can be a useful complementary approach to address persistent nutritional gaps. However, this strategy is often underestimated and overlooked as potentially cost-effective means to prevent future health care costs and to improve the health and quality of life of individuals. In this paper, the authors discuss key appraisal criteria to consider when evaluating the benefits and disadvantages of a secondary prevention of nutrient deficiencies through screening.

Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota.

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N-oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans.

Impact of Biological Feedback and Incentives on Blood Fatty Acid Concentrations, Including Omega-3 Index, in an Employer-Based Wellness Program.

Eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) are important fatty acids for the retina and brain. More than 95% of Americans have suboptimal EPA + DHA blood concentrations. This cross-sectional employer-based study assessed whole blood fatty acid levels of volunteers participating in an onsite wellness biometric screening program and was designed to determine if an incentive, a $5 coupon for a 90-day supply of fish oil supplement typically costing $18-30, stimulated incremental dietary behavior change relative to nutritional status assessment alone to increase EPA + DHA concentrations. Volunteers completed a dietary survey and finger stick blood samples were collected to be analyzed for fatty acid composition. In addition, 636 individuals participated in the initial onsite biometric screening. Three months later, and without prior knowledge, all employees were invited to a second screening. At the second screening, 198 employees volunteered for the first time and 149 employees had a second test (17.9%). At baseline, the average age (n = 834) was 45 year and omega-3 index was 5.0% with 41% female. EPA + DHA concentration, i.e., omega-3 index, was significantly lower in men (4.8%) than women (5.2%), as were DHA and linoleic acid (LA) concentrations (p < 0.05). Baseline omega-3 index was positively and linearly associated with omega-3 intake. Only 4% of volunteers had an omega-3 index >8% on initial screening. Among the 149 individuals with two measurements, omega-3 intake from supplements, but not food, increased significantly from 258 to 445 mg/d (p < 0.01) at the second test as did the omega-3 index (+0.21, p < 0.02). In this employed population, only 1% redeemed a coupon for an omega-3 supplement.

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.

How to Achieve Transparency in Public-Private Partnerships Engaged in Hunger and Malnutrition Reduction.

Multi-stakeholder partnerships are important facilitators of improving nutrition in developing countries to achieve the United Nations' Sustainable Development Goals. Often, the role of industry is challenged and questions are raised as to the ethics of involving for-profit companies in humanitarian projects. The Second International Conference on Nutrition placed great emphasis on the role of the private sector, including industry, in multi-stakeholder partnerships to reduce hunger and malnutrition. Governments have to establish regulatory frameworks and institutions to guarantee fair competition and invest in infrastructure that makes investments for private companies attractive, eventually leading to economic growth. Civil society organizations can contribute by delivering nutrition interventions and behavioral change-related communication to consumers, providing capacity, and holding governments and private sector organizations accountable. Industry provides technical support, innovation, and access to markets and the supply chain. The greatest progress and impact can be achieved if all stakeholders cooperate in multi-stakeholder partnerships aimed at improving nutrition, thereby strengthening local economies and reducing poverty and inequality. Successful examples of public-private partnerships exist, as well as examples in which these partnerships did not achieve mutually agreed objectives. The key requirements for productive alliances between industry and civil society organizations are the establishment of rules of engagement, transparency and mutual accountability. The Global Social Observatory performed a consultation on conflicts of interest related to the Scaling Up Nutrition movement and provided recommendations to prevent, identify, manage and monitor potential conflicts of interest. Multi-stakeholder partnerships can be successful models in improving nutrition if they meet societal demand with transparent decision-making and execution. Solutions to the issue of malnutrition are available. We have the resources and knowledge, and we must act as a global community in the immediate future. Transparency about the roles and contributions of each partner may be a key factor for successful cooperation in multi-stakeholder partnerships.

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.

Nutritional status as assessed by nutrient intakes and biomarkers among women of childbearing age--is the burden of nutrient inadequacies growing in America?

OBJECTIVE: Understanding nutrient intakes among women of childbearing age within the USA is important given the accumulating evidence that maternal body weight gain and nutrient intakes prior to pregnancy may influence the health and well-being of the offspring. The objective of the present study was to evaluate nutritional status in women of childbearing age and to ascertain the influence of ethnicity and income on nutrient intakes. DESIGN: Nutritional status was assessed using data on nutrient intakes through foods and supplements from the National Health and Nutrition Examination Survey. Biomarker data from the Centers for Disease Control and Prevention were used to assess nutritional status for selected nutrients. Poverty-income ratio was used to assess family income. SUBJECTS: White (n 1560), African-American (n 889) and Mexican-American (n 761) women aged 19-30 and 31-50 years were included. SETTING: A nationally representative sample of non-pregnant women of childbearing age resident in the USA. RESULTS: African-American women had the lowest intakes of fibre, folate, riboflavin, P, K, Ca and Mg. Women (31-50 years) with a poverty-income ratio of ≤ 1.85 had significantly lower intakes of almost all nutrients analysed. Irrespective of ethnicity and income, a significant percentage of women were not consuming the estimated recommended amounts (Estimated Average Requirement) of several key nutrients: vitamin A (~80%), vitamin D (~78%) and fibre (~92%). Nutrient biomarker data were generally reflective of nutrient intake patterns among the different ethnic groups. CONCLUSIONS: Women of childbearing age in the USA are not meeting nutrient intake guidelines, with differences between ethnic groups and socio-economic strata. These factors should be considered when establishing nutrition science advocacy and policy.

Obesity is associated with increased red blood cell folate despite lower dietary intakes and serum concentrations.

BACKGROUND: Folates are essential cofactors in metabolic pathways that facilitate biological methylation and nucleotide synthesis, and therefore have widespread effects on health and diseases. Although obesity is prevalent worldwide, few studies have investigated how obesity interacts with folate status. OBJECTIVE: Based on data from the NHANES, this study aims to examine the association between body mass index (BMI) and obesity-related metabolic factors with blood folate status. METHODS: A nationally representative sample of 3767 adults from the NHANES (2003-2006) was used as the study population. Regression analyses, with and without adjustment for demographic factors and dietary intakes, were performed to examine associations between BMI and metabolic factors with serum and RBC folate. RESULTS: The results indicate serum folate concentrations were lower in obese groups compared to the desirable BMI and overweight categories, paralleling lower intakes in this group. In contrast, RBC folate increased incrementally with BMI. Regression analyses demonstrated an inverse relation between BMI and serum folate but a positive relation for RBC folate (P < 0.01). Waist circumference, serum triglycerides, and fasting plasma glucose each displayed significant positive relations with RBC folate (P < 0.01), although relations with serum folate were not significant and consistent. CONCLUSIONS: In summary, obesity is associated with decreased serum folate, which parallels decreased folate intakes. In contrast, obesity is positively associated with RBC folate. Therefore, RBC folate, in addition to serum folate, should also be considered as a critical biomarker for folate status, especially in the obese population. Future research is needed to understand how obesity differentially alters serum and RBC folate status because they are associated with a variety of medical complications.