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Foods are analysed for their vitamin content to support the verification of regulatory compliance or to generate food composition data. Many international reference methods for the analysis of vitamins in foods originate from the 1990s. Advances in nutrition science and analytical technology and the continuing evolution of statutory regulations necessitate the need of new or supplementary regulatory standards. We have evaluated recent developments in these areas and conclude that most current international reference methods are no longer fit-for-purpose to accurately determine vitamin content in foods and food supplements. We have made recommendations to consider new and/or updated reference methods and regulatory standards for the analysis of vitamins A, D, E, K, B 1 , B 2 , B 3, B 5 , B 6 , B 7 , B 9 , B 12 , C and carotenoids in foods and food supplements. This area of nutrients may benefit from globally harmonised definitions specifying what compounds to include or exclude for analysis, and applicable bioactivity factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: One of the topics that show differences of opinion in the scientific field of nutrition is the recommendation by clinical practice guidelines (CPGs) of an immunomodulatory diet with arginine, nucleotides and omega-3 for individuals diagnosed with cancer undergoing major surgery. The quality of the recommendations is directly related to credibility, transparency and rigour in their development, but also to the quality of the studies published and available for inclusion in the recommendation, such as systematic reviews (SRs) and randomised clinical trials. The aim of this study is to evaluate the methodological quality of the recommendation of perioperative immunomodulatory supplementation for individuals with gastrointestinal and head and neck cancer, the CPGs, and the studies that support the recommendations., Methods and Analysis: We will conduct a systematic search for CPGs. Recommendations for nutritional supplementation with immunomodulatory substrates for individuals undergoing major oncological surgery will be analysed using the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence tool. CPGs will be analysed using the Appraisal of Guidelines Research and Evaluation II tool. The SRs cited in the recommendations will be analysed using the A Measurement Tool to Assess Systematic Reviews II tool and additional questions regarding heterogeneity in reviews. The clinical trials cited in the SRs and in the guideline recommendations (when applicable) will be analysed according to questions regarding heterogeneity in trials. The results will be presented in tables or charts using descriptive analyses., Ethics and Dissemination: The results of this study will be disseminated through relevant conferences and peer-reviewed journals., Protocol Registration Number: 10.17605/OSF.IO/X2GYT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dietary supplements derived from botanicals are commonly consumed and investigated in biomedical studies for their potential health benefits. Accurate identification and quantification of key chemical constituents from botanical ingredients is necessary for consistent product preparations and reproducible research results. Manufacturers need quantitative reference materials of the chemical constituents of interest to verify the content of ingredients and products. The rigor and reproducibility of biomedical research is enhanced through thorough characterization of the interventions used in mechanistic, clinical, and safety investigations. Quantitative reference materials enable reliable product quality assessments and reproducible research results., Objective: Solution-based certified reference material (CRM) mixes were developed as calibrants for phytochemicals in ginger and kava. The kava CRM contained yangonin, desmethoxyyangonin, dihydrokavain, DL-kavain, methysticin, dihydromethysticin, flavokawain A, flavokawain B, and flavokawain C. The ginger CRM contained 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol., Methods: Each phytochemical was sourced as an isolated compound and assigned a purity factor by a mass balance approach accounting for residual impurities. The solution standard mixes were formulated by gravimetric addition of each phytochemical incorporating the purity factor and diluting with acetonitrile to the target concentrations of 500 µg/mL for the gingerols and shogaols, 250 µg/mL for the kavalactones, and 25 µg/mL for the flavokawains., Results: The concentration accuracy of each component in the solution mixes was analytically verified by ultra high performance liquid chromatography with ultraviolet detection (UHPLC-UV) assay comparison to an independently prepared calibration solution. Each component in the ginger and kava CRMs were within 5 and 7% of the target concentrations, respectively., Conclusion: Homogeneous kava and ginger phytochemical solution mixes were produced with accurate constituent concentrations and demonstrated good stability over 2 years. These solution mixes were launched as commercially available CRMs., Highlights: These mixes can be used as accurate concentration stock solutions to prepare calibrators and controls for botanical dietary supplement product testing and standardization., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Vitamin D 3 , an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D 3 in oily drug products using supercritical fluid chromatography-mass spectrometry (SFC-MS). Targeted impurities include two esters of vitamin D 3 and five non-esters including four that are isobaric to vitamin D 3 . Firstly, a screening study highlighted the Torus 1-AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make-up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid-liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC-MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non-ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC-MS as a valuable, versatile, and green tool for routine pharmaceutical QC., (© 2024 John Wiley & Sons Ltd.)

While probiotics are generally considered safe, concerns persist regarding the accuracy of labels on these supplements and their potential contribution to the spread of antibiotic resistance genes. Given that probiotics are predominantly ingested with a view towards obtaining particular health benefits. The objective of this study is to assess the composition of 50 widely available probiotic supplements in the USA using shotgun metagenome sequencing. The study also determines the potential resistome profile, and the functional characteristics of these products. This study finds that 67% of products does not contain any labeling inaccuracies. Antimicrobial Resistance Genes (ARGs) are identified in several products, particularly Bacillus-based products carrying between 10 and 56 genes. The risk posed by the presence of these ARGs requires further study. Functional analysis reveals differences in metabolic profiles among probiotic supplements, indicating the importance of strain-level selection for personalized probiotics. This study provides updated and comprehensive analysis to evaluate a snapshot of the USA market. The study demonstrates that label inaccuracies occur on approximately one third of popular dietary supplement products sold in the USA, supporting the need for improved approaches to marketing and quality control. Further, the risk of antibiotic resistance, especially in Bacillus-based formulations, should be assessed., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Introduction: The increasing prevalence of nutritional supplement use in the United States, combined with the risk of adverse effects from these largely unregulated products, poses a significant challenge to health care professionals. The purpose of our study is to evaluate the use of nutritional supplements in an active duty military population, particularly those supplements with increased adverse effect profiles, and the sources of information that service members use to make decisions regarding the safety and efficacy of supplements., Materials and Methods: The investigators distributed a voluntary, anonymous, self-report survey to a battalion of active duty service members to collect demographic data and information pertaining to the use of, adverse effects from, and sources of information utilized regarding the safety and efficacy of nutritional supplements. Statistical analysis utilized Fisher's exact test for categorical variables and Kruskal-Wallis test for numeric variables via SAS 9.4 (SAS Institute Inc., Cary, NC, USA). The Henry Ford Health System Institutional Review Board evaluated and approved the study. The battalion commander approved the study protocol before the distribution of the survey., Results: Over 50% of respondents reported using high-risk nutritional supplements. Males were more likely to use high-risk supplements than females (54.3% vs. 28.1%; P = .0017). Non-Commissioned Officers were more likely to use high-risk supplements than Junior Enlisted soldiers (67.2% vs. 40.2%, P = .0037). Only 27% of respondents who used high-risk supplements utilized medical professionals as their source of knowledge regarding the safety and efficacy of supplements. Females were more likely than males to seek supplement information from medical professionals (28.1% vs. 10.6%; P = .0202). Company-Grade Officers were more likely to seek supplement information from medical professionals than Junior Enlisted soldiers (40.9% vs. 8.3%; P = .0018). There was no statistically significant difference found for the rate of high-risk supplement use and obtaining information from a medical professional (P = .6982). About 3% of respondents reported adverse or unintended effects of supplement use., Conclusions: The results of our study suggest that a minority of service members seek advice from medical professionals regarding nutritional supplements, women are more likely to do so than men, men may be more likely to use high-risk supplements than women, and Non-Commissioned Officers use high-risk supplements more often than Junior Enlisted. Limitations of this study include the voluntary self-report survey design, relatively small sample size, and single location. A larger, multicenter study would aid to alleviate these limitations in future studies. Numerous studies investigating nutritional supplement use and associated risks are present in the literature; however, the data comparing supplement use with sources of information regarding safety and efficacy are lacking., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Importance: Dietary supplements for weight loss, among the most popular supplement products on the market, are promoted not only for losing weight and shedding fat, but also for added benefits of energy and performance, all packed into 1 capsule with multiple combinations of ingredients. Fraudulent marketing of weight loss supplements, some with exaggerated claims, some that are potentially dangerous, and some that contain illegal ingredients, is ever present, especially through online sources, where multiple manufacturers target service members by offering military discounts., Objectives: To examine whether select dietary supplements marketed online for weight loss from companies advertising military discounts are accurately labeled according to the Supplement Facts listed ingredients, whether they contain any ingredients prohibited for use in the military, and to qualitatively describe the products' label claims., Design, Setting, and Participants: In this case series, 30 dietary supplement products marketed for weight loss were selected and purchased in June 2023 from 12 online companies advertising military discounts. Data were analyzed from July to August 2023., Main Outcomes and Measures: Liquid chromatography-mass spectrometry was used to verify whether products were accurately labeled according to the Supplement Facts listed ingredients and whether they contained any substances on the DoD Prohibited Dietary Supplement Ingredients List. A separate analysis was conducted to describe product label claims by using the Operation Supplement Safety (OPSS) Risk Assessment Scorecard., Results: Of the 30 products tested, analysis showed that 25 had inaccurate labels. Of these, 24 had ingredients listed on the label that were not detected (misbranded); 7 had hidden components not present on the label, some of which would be considered adulterated; and 10 had substances on the DoD Prohibited Dietary Supplement Ingredients List either on or hidden from the label. All products were rated as risky when applying the OPSS Scorecard., Conclusions and Relevance: In this case series study, the majority of products had inaccurate labels. Some were misbranded, others would be considered adulterated with ingredients not allowed in dietary supplements, and some contained ingredients prohibited for use in the military.

Botanical dietary supplement use is widespread and growing, therefore, ensuring the safety of botanical products is a public health priority. This commentary describes the mission and objectives of the Botanical Safety Consortium (BSC) - a public-private partnership aimed at enhancing the toolkit for conducting the safety evaluation of botanicals. This partnership is the result of a Memorandum of Understanding between the US FDA, the National Institute of Environmental Health Sciences, and the Health and Environmental Sciences Institute. The BSC serves as a global forum for scientists from government, academia, consumer health groups, industry, and non-profit organizations to work collaboratively on adapting and integrating new approach methodologies (NAMs) into routine botanical safety assessments. The objectives of the BSC are to: 1) engage with a group of global stakeholders to leverage scientific safety approaches; 2) establish appropriate levels of chemical characterization for botanicals as complex mixtures; 3) identify pragmatic, fit-for-purpose NAMs to evaluate botanical safety; 4) evaluate the application of these tools via comparison to the currently available safety information on selected botanicals; 5) and integrate these tools into a framework that can facilitate the evaluation of botanicals. Initially, the BSC is focused on oral exposure from dietary supplements, but this scope could be expanded in future phases of work. This commentary provides an overview of the structure, goals, and strategies of this initiative and insights regarding our first objectives, namely the selection and prioritization of botanicals based on putative toxicological properties., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The characterization of folate status in subjects at risk of deficiency and with altered vitamin homeostasis is crucial to endorse preventive intervention health policies, especially in developed countries. Several physiological changes (i.e. pregnancy), clinical situations and diseases have been associated to increased requirement, impaired intake and absorption of folate. However clinical practice guidelines (CPG) endorse folic acid supplementation generally discarding the use of its determination in serum to assess the risk of deficiency and/or its concentration at baseline. Poor confidence on the diagnostic accuracy of serum folate assays still persists in the current CPGs although recent standardization efforts have greatly improved inter-method variability and precision. In this review we critically appraise the methodological issues concerning laboratory folate determination and the evidence on the potential adverse effects of folic acid exposure. The final aim is to build a sound background to promote serum folate-based cost-effective health care policies by optimizing folic acid supplementation in subjects at risk of deficiency and with altered folate homeostasis. Our first result was to adjust in relation to current serum folate assays the thresholds reported by CPGs as index of folate status, defined on the association with metabolic and hematologic indicators. We identify a statistically significant difference between the estimated thresholds and accordingly show that the assessment of folate status actually changes in relation to the assay employed. The use of the method-dependent thresholds here reported may pragmatically endorse the stewardship of folic acid supplementation in clinical practice and increase the cost-effectiveness of health care policies., Competing Interests: Conflict of interest For all authors no conflicts of interest or financial ties to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The novel coronavirus infection is also called COVID-19 (coronavirus disease 2019). The infection has affected millions of people worldwide and caused morbidity as well mortality in patients with pre-existing chronic conditions such as metabolic, respiratory and cardiovascular disorders. The severity of the disease is mostly seen in people with low immunity and chronic sufferers of respiratory, cardiovascular and metabolic disorders. To date, there is no specific treatment available for COVID-19. Precaution and prevention are the most recommended options followed for controlling the spread of infection. Trace elements such as zinc, calcium, iron and magnesium play an important role in boosting the immunity of the host system. These components assist in the development and functioning of lymphocytes, cytokines, free radicals, inflammatory mediators and endothelial functioning. This review summarizes the common dietary supplements that are regularly consumed in Saudi Arabia and are known to contain these vital trace elements. Data available in Google Scholar, NCBI, PUBMED, EMBASE and Web of Science about COVID-19, micronutrients, trace elements and nutritional supplements of Saudi Arabia was collected. By highlighting the traditionally used dietary components containing the essential elements, this review could provide useful knowledge crucial for building immunity in the population.

Introduction: Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and 'at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.

In the United States the marketing of dietary supplements, of which the majority are herbal supplements, is currently a multibillion-dollar industry involving use from over half of the adult population. Due to their frequency of use and the lack of regulation of herbal supplements by the Food and Drug Administration (FDA) it is important for the health and safety of consumers to know about consistency of supplements and any possible contamination by harmful products, such as heavy metals or microorganisms. The purpose of the study was to determine consistency and contamination within and between bottles of common herbal supplements. Duplicate bottles of 29 herbal supplements were tested for consistency for antioxidant activity, phenolic concentration and flavonoid concentration under methanolic and water extraction. The supplements were also analyzed for the presence of metals and fungal contaminants. For all of the supplements tested there was high variability around the mean in antioxidant activity, phenolic concentrations and flavonoid concentrations, with coefficients of variation (CV) ranging from 0-120. Zinc was found in almost 90% of the supplements, nickel in about half of the supplements and lead in none of the supplements. Approximately 60% of the supplements contained fungal isolates. Although the majority of the fungi that were found in the supplements are generally not hazardous to human health, many of them could be problematic to sensitive groups, such as immunocompromised individuals. The data, which demonstrates contamination and a lack of consistency, in conjunction with previous studies on supplement contamination, strengthen the case that the FDA should regulate over-the-counter herbal supplements the same way that they regulate food and drugs. Until such time it is crucial that consumers are informed that many of the supplements that they take may lack the standardization that would reduce the chance of contamination and lead to consistency from one pill to the next., Competing Interests: The authors have declared that no competing interests exist.

Garlic ( Allium sativum ), a widely distributed plant with great cultural and medicinal significance, is one of the most popular herbal dietary supplements in Europe and North America. Garlic supplements are consumed for a variety of reasons, including for their purported antihypertensive, antibacterial, and anticarcinogenic effects. The steady increase in the global herbal dietary supplement market paired with a global patchwork of regulatory frameworks makes the development of assays for authentication of these products increasingly important. A DNA mini-barcode assay was developed using the P6 loop of the plastid trnL UAA intron to positively identify A. sativum products. Analysis of 43 commercially available garlic herbal dietary supplements produced mini-barcode sequences for 33 supplements, all of which contained detectable amounts of A. sativum . The trnL UAA P6 mini-barcode can be highly useful for specimen identification, particularly for samples that may contain degraded DNA.

Introduction: Introduction: metabolic syndrome in postmenopausal women can improve with a healthy diet. Objectives: to evaluate whether a dietary intervention with dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids increases selenium plasma levels and improves cardiovascular risk factors in postmenopausal women with metabolic syndrome. Material and methods: a randomized, triple-blind, controlled clinical trial carried out in GP surgeries. Recruitment: April 2018, 46 postmenopausal women with metabolic syndrome who were frequent dairy consumers. Randomization: 23 in control group and 23 in experimental group. Intervention: consumption of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids (milk, yogurt, fresh cheese) for three months. Controls took conventional dairy. Primary endpoint: plasma selenium levels; secondary endpoints: metabolic syndrome criteria. Registration number 2018/256, Galicia Ethics Committee. Results: in all, 23 women in the control group and 21 in the intervention group completed the trial. Selenium increased in the intervention group (7.2 µg/L, 95 % CI, 3.7/10.8) compared to the control group (-4.5 µg/L, 95 % CI, -8/-1) (p < 0.001) and very low-density lipoprotein cholesterol decreased (-2.3 mg/dL, 95 % CI, -5.6/1) compared to the control group (1.9 mg/dL, 95 % CI, -0.7/4.5) (p = 0.043). Waist circumference (p = 0.010), body mass index (p = 0.047) and high-density lipoprotein cholesterol (p < 0.001) in the experimental group improved in comparison to baseline measurements. Conclusions: an intervention with dairy products naturally enriched with selenium and omega-3 in a sample of postmenopausal women with metabolic syndrome can improve plasma selenium levels and very low-density lipoprotein cholesterol.

Introduction: Background: peri- and post-menopausal women exhibit a high tendency towards obesity and visceral fat deposition, which increases cardiometabolic risk. Objective: to evaluate through a prospective nutritional study the effect of carotenoid consumption on cardiometabolic risk biomarkers in peri- and post-menopausal women. Material and methods: twelve peri- and post-menopausal women without previous symptoms of cardiovascular disease, but with some cardiometabolic risk factor, were recruited. Their diet was supplemented during 4 weeks with orange-carrot juice, tomato juice, and boiled spinach, providing 415 mg of total carotenoids/week (carotenes, cryptoxanthin, lycopene, and lutein + zeaxanthin). At the beginning (TI) and at the end (TF) of the intervention period blood samples were drawn to measure biochemical parameters, oxidative stress, inflammation and endothelial function biomarkers, and plasma carotenoid levels. Results: at TF a significant decrease (p < 0.05) in LDL-cholesterol and atherogenic index, and an increase in HDL-cholesterol were observed. Plasma carotenoids increased significantly (p < 0.05) from 0.56 µg/mL at TI to 1.22 µg/mL at TF. Concurrently, a shift in oxidative stress and inflammation biomarkers was detected, with a decrease in plasma C-reactive protein and malonaldehyde levels, and an increase in adiponectin. However, endothelial dysfunction biomarkers (sVCAM and sICAM) and total antioxidant capacity remained unchanged. Conclusions: dietary supplementation with carotenoids leads to an increase in plasma carotenoids, a decrease in atherogenic dyslipidemia, and an improvement in oxidative stress and inflammation biomarkers, which indicates a reduction in cardiometabolic risk.

Introduction: Long-chain polyunsaturated fatty acids (LC-PUFAs) are critical for infant growth and development, particularly arachidonic acid (ARA, C20:4n-6) and docosahexaenoic acid (DHA, C22:6n-3). ARA and DHA are components of cell membrane phospholipids and play an important role in cell division, differentiation, and signaling; and DHA is the n-3 fatty acid predominant in the developing brain and retina. During the third trimester of pregnancy, LC-PUFAs increase substantially in fetal circulation, and a "biomagnification" process in the fetal brain is observed. Moreover, LC-PUFAs are precursors of eicosanoids and metabolites, which modulate the intensity and duration of the immune response. LC-PUFA synthesis implies complex desaturation and elongation processes on their principal precursors, linoleic acid (LA) (18:3 n-6) (series n-6) and α-linolenic acid (LNA) (20:3 n-3) (series n-3), where fatty acid desaturases (FADS) and elongases (ELOVL) are competing. It is important to notice that during the first months of life, as a consequence of low enzymatic activity, LC-PUFA synthesis from LA and LNA is reduced, especially in those infants carrying variations in the FADS and ELOVL genes, which are involved in LC-PUFA synthesis, and so they are unable to supply their own DHA and ARA needs. Homozygote infants for FADS haplotype A (97 % of the Latinoamerican population) show low levels of ARA (only 43 %) and DHA (only 24 %) when compared to those carrying haplotype D (more prevalent in Europe, Africa and Asia). Human milk is the only source of LA, LNA, ARA, and DHA for the neonate and infant till complementary feeding (CF) is introduced. Infants fed with infant formulas must receive enough amounts of LA, LNA, ARA, and DHA to cover their nutritional requirements. The new guidelines by the European Food Safety Authority (EFSA) (2016) recommend that infant formulas and follow-on formulas must contain 20-50 mg of DHA/100 kcal (0.5-1 % of total fatty acids, which is higher than in human milk and the majority of infant formulas in the market), and it is not necessary to add ARA. This new regulation, which is already applicable since February 2020, has resulted in profound controversy because there is no scientific evidence about its appropriateness and safety for healthy children. Then, different international expert groups have revised the research already published about the effects of ARA and DHA addition to infant formulas, and discussed different emerging questions from this European directive. The expert group led from the University of Granada (Spain) recommends the addition of ARA in similar or higher concentrations than those of DHA, at least equal to those present in human milk (0.3 % of total fatty acids), although preferably 0.5 % and up to around 0.64 % of total fatty acids, since new studies confirm the optimal intake of ARA and DHA during the different developmental stages. This recommendation could be of particular importance for infants carrying the haplotype A of FADS.

This review, with handy tables, summarizes which vitamins offer proven benefits-and which don't.

Introduction: The human body, particularly the brain, requires energy, stored in the form of adenosine triphosphate. Energy metabolism during cellular respiration is dependent on the presence of multiple micronutrients, which act as essential components, coenzymes, or precursors at every stage. An adequate supply of multiple micronutrients is vital for efficient energy production. However, micronutrient intakes below the recommended dietary allowance are common, even in industrialized countries. Intakes of vitamins A, D, E, folate, iron, zinc, and selenium are suboptimal across all age groups. Suboptimal micronutrient levels have been shown to contribute to low energy levels, physical and mental fatigue, and impaired cognitive performance and wellbeing - symptoms frequently present in the general population. When supplemented in combination in well-conducted trials, multiple micronutrients ± coenzyme Q10 reduced oxidative stress in chronic fatigue syndrome; in healthy people they increased cerebral blood-flow hemodynamic response, energy expenditure, and fat oxidation; reduced mental and physical fatigue; improved the speed and accuracy of cognitive function during demanding tasks; and reduced stress. The results from these clinical trials suggest that even in industrialized countries, where adults might be assumed to have a healthy, balanced diet, there is a rationale to supplement with multiple micronutrients, including coenzyme Q10, to improve nutritional status, support energy metabolism, and improve subjective wellbeing.

Background: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes., Results: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers., Conclusions: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 ., (© 2021. The Author(s).)

Background: Coronary heart disease (CHD) is one of the most common causes of death and disease burden in the world. Current fish oil aiming to prevent and treat CHD have shown a large variety of effects with low levels of evidence., Objective: To evaluate the efficacy of fish oil for protection against CHD, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of fish oil for protection against CHD., Methods: We retrieved relevant articles published from January 1966 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. RCTs of fish oil in preventing CHD were selected. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. The first selection involved 360 citations. After screening and evaluation of suitability, 19 RCTs adjusted for clustering were included in the meta-analysis. All selected manuscripts considered that fish oil was effective in preventing CHD, secondary outcome measures included angina, sepsis and death., Results: Compared with the control group, fish oil may confer significant protection against CHD (odds ratio = 0.84; 95% confidence interval: 0.72-0.98). There was no significant difference in the incidence of secondary outcomes between the observation group and the control group (P > .05)., Conclusion: The above results show that fish oil plays an important role in reducing CHD and cardiovascular events. However, because of the suboptimal quality of the studies included into the meta-analysis, these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients., Registration Details: CRD42020183719., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The appropriate strategies to minimize skeletal deterioration following bariatric surgeries are inconclusive. This randomized controlled trial evaluated the effect of preoperative vitamin supplementation on bone mineral density (BMD) and biochemical parameters in females post-sleeve gastrectomy (SG)., Methods: Participants were randomized to a 2-month preoperative treatment with a multivitamin and vitamin D 4000 IU/d (intervention arm) or 1200 IU/d (control arm). Preoperative and 12-month postoperative follow-up evaluations included anthropometrics, biochemical parameters, and dual energy X-ray absorptiometry (DEXA)., Results: Sixty-two females (median age 29.7 years and median BMI 43.4 kg/m 2 ) were recruited, 87% completed the 12-month follow-up. For the intervention and control arms, significant and similar reductions at 12-months post-surgery were observed in BMD of the hip (-6.8 ± 3.7% vs. -6.0 ± 3.6%; P = 0.646) and of the femoral neck (-7.1 ± 5.8% vs. -7.2 ± 5.5%; P = 0.973). For the intervention compared to the control arm, the 25 hydroxyvitamin D (25(OH)D) increment was greater after 2 months treatment, and vitamin D deficiency rates were lower at 3 and 6-months follow-up (P < 0.016). However, at 12-months postoperative, 25(OH)D values and vitamin D deficiency were comparable between the arms (P > 0.339). Predictors for BMD decline in the total hip were the percentage of excess weight-loss, age>50 years, and lower initial BMI (P ≤ 0.003)., Conclusions: SG was associated with a significant decline in BMD of the hip and femoral neck in young and middle-aged women, and was unaffected by preoperative vitamin D supplementation. Females who are peri-menopausal or with greater postoperative weight-loss should be particularly followed for BMD decline., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Preterm infants are at increased risk for vitamin D deficiency (VDD). We aimed to assess the adequacy of standardized vitamin D supplementation protocol in very low birth weight (VLBW) infants. Additionally, vitamin D status of mother/infant couples and the associations between vitamin D status at birth and morbidities of the infants were investigated., Methods: In this single-center, prospective cohort study blood samples were collected from 55 mothers just before delivery and from their infants at birth and on the 30th day of life (DOL) for 25 hydroxy vitamin D (25OHD) measurements. Vitamin D was initiated in dose of 160 IU/kg by parenteral nutrition on the first DOL and oral vitamin D supplementation (400 IU/day) was administered when enteral feedings reached 50% of total intake or on the 15th DOL., Results: The median 25OHD levels of the infants were 16.12 (9.14-20.50) in cord blood and 36.32 (31.10-44.44) in venous blood on the 30th DOL (p<0.01). In 98% of the VLBW infants 25OHD reached sufficient levels on the 30th DOL. None of the mothers had sufficient vitamin D levels (25OHD >30 ng/mL). Maternal 25OHD levels were correlated with the 25OHD levels of the infants in cord blood (r=0.665, p<0.001). There was a significant difference in mean cord 25OHD levels between winter (13.65 ± 5.69 ng/mL) and summer seasons (19.58 ± 11.67 ng/mL) (p=0.021). No association was found between neonatal morbidity and vitamin D status., Conclusions: The results clearly show that by utilizing the current supplementation protocol, the majority of VLBW infants with deficient/insufficient serum 25OHD levels reached sufficient levels on the 30th DOL. Furthermore, vitamin D levels in mother/infant couples were found to be highly correlated., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

The global market of food supplements is growing rapidly with a large turnover. Fish oil supplements represent a significant part of this turnover as they are believed to have important health benefits. Conversely, there are few papers in the literature about the quality control of fish oil capsules. As prior studies illustrate, a perfect agreement with the label is rarely found, and in some isolated cases, large amounts of soybean oil are also detected, indicating a true adulteration rather than a non-compliance with the label. None of the available studies refer to the Italian market, which ranks first in Europe in the consumption of food supplements. In this present communication, a quality control of fish-oil-based supplements from the Italian market was carried out for the first time. With minor deviations, all results showed substantial agreement with the label. However, the most important conclusion from this research is that compliance with the label is not enough to judge a product of good quality. The analysis of the overall fatty acid composition showed that some supplements have a high level of saturated fatty acids, and therefore they did not undergo a proper purification process. This may represent a safety issue since the purification process also allows the removal of toxic contaminants.

The implementation of REGULATION (EC) No 1924/2006 has led to the formation of a list of health claims that can be used in food supplements (EU 432/2012). However, such supplements are often composed of plant preparations with claims omitted from this list. The peculiarity of plants is related to their long history of use, that could allow claims based on traditionally recognized health effects. In addition, the scientific literature has been enriched over the years through clinical studies that have assessed the bioavailability and efficacy of bioactive components, and investigated their mechanisms of action. Based on existing recognized models which aim to classify research according to the level of scientific evidence, Synadiet developed a three-grade model (A, B or C) for assessing plants health claims. In this paper, the applicability of the model is illustrated through an example for which a Grade B health claim attesting the possible contribution of red clover isoflavones to the improvement of blood lipid levels in postmenopausal women has been attributed. The model appears able to be easily extrapolated to claims pertaining to other plants. If adopted by consensus at European level, this model could initiate the implementation of a positive list of health claims on plant preparations.

Multi-ingredient pre-workout supplements (MIPS) contain Citrus aurantium as a source of bioactive amines such as p-synephrine, but concerns regarding the authenticity of ingredients in some supplements as well as adverse effects from consumption have been raised. R-(-)-Synephrine is the predominant enantiomer in Citrus aurantium extracts while synthetic preparations are often racemic. The aims of this study were to develop a screening method to determine the ratio of synephrine enantiomers in pre-workout supplements listing Citrus aurantium and to assess the ingredient authenticity by directly comparing their ratios to that found in Citrus aurantium standardised reference materials (SRMs). Quantification of enantiomers in the supplements and SRMs was achieved using a validated, high-performance liquid chromatography-single quadrupole mass spectrometry (HPLC-UV-QDa) direct enantioseparation method with a cellobiohydrolase (CBH) column (100 × 4.0 mm, 5 μM) and UV detection at 225 nm. Citrus aurantium SRMs were found to have an average enantiomeric ratio of 94:6 (R:S) with total synephrine ranging from 5.7 to 90.2 mg/g. Within the pilot sample of pre-workout supplements tested, only 42% (5/12) had enantiomeric ratios consistent with the SRMs with total synephrine ranging from 0.03 to 91.2 mg/g. For the remaining supplements, four had racemic ratios of synephrine (0.14 to 5.4 mg/g), two lacked any detectable levels of synephrine, and one had solely the S-(+)-enantiomer (0.15 mg/g). These results bring the authenticity of labelling of some pre-workout supplements into question and highlight the need for more stringent labelling regulations and testing for dietary supplements., (© 2021 John Wiley & Sons, Ltd.)

Introduction: Omega-3 long-chain, polyunsaturated fatty acids are essential, so they must be provided through the diet, as their biological synthesis is limited, making it essential to meet their requirements during physiological stages such as pregnancy and lactation. A narrative review was conducted on the effects of omega-3 supplementation during pregnancy and lactation on the fatty acid composition of breast milk in the first months of life. Eight randomized clinical studies were analyzed, showing a significant increase in docosahexaenoic acid (DHA) concentration in breast milk (BM) post-supplementation, compared to control groups. One study evaluated the dose needed to achieve 8 % DHA in erythrocytes and 1 % DHA in BM, reaching these levels with a supplementation close to 1 g of docosahexaenoic acid + eicosapentaenoic acid (EPA). Finally, a trial was found that used supplementation with small lipid contributions (0,59 g α-linolenic acid (ALA)), without generating significant changes in the DHA composition of LM, but in the ALA content. Therefore, it is inferred that omega-3 supplementation beneficially modifies DHA and EPA levels in the composition of BM in pregnant women and during the lactation stage, although further studies are needed to identify doses, times, beneficial effects on development, and more efficient forms of delivery of omega-3 supplementation.

Introduction: The use of nutritional supplements (NSs) is a widespread practice in both professional and amateur athletes. Their choice must be based on criteria of safety, legality, and effectiveness. There are several risks that some of these products can trigger, this being a reason for fraud to the consumer. By way of example, the presence of a legal substance in doses higher than its recommendation may cause unwanted side effects; on the other hand, its presence in quantities lower than necessary (effective threshold) may not have the effect expected or announced by the product. Therefore, the objective of this review was to describe the existence of fraud in relation to nutritional labeling and/or to the content of NSs intended for athletes. A narrative review was conducted through PubMed in which 16 studies met the inclusion criteria. The results show that nutritional labeling differs from the actual amounts of ingredients. This type of fraud has been found in protein powder supplements, pre-workout mixtures, creatine, and beverages containing vitamins and minerals, among others. Fraud due to errors in the labeling by omission of substances present in the product or by errors in the analysis or declaration of quantities, is high. This lack of transparency in the actual composition of labels can contribute to sports performance and/or health problems in the athlete. Therefore, an improvement of the legislation on NS is necessary to ensure their safety, effectiveness, and legality.

USPSTF findings would support screening selective populations at risk for deficiency. But the value of supplements for prevention is nil or still unknown.

Background: Environmental exposures may alter DNA methylation patterns of T helper cells. As T helper cells are instrumental for allergy development, changes in methylation patterns may constitute a mechanism of action for allergy preventive interventions. While epigenetic effects of separate perinatal probiotic or ω-3 fatty acid supplementation have been studied previously, the combined treatment has not been assessed. We aimed to investigate epigenome-wide DNA methylation patterns from a sub-group of children in an on-going randomised double-blind placebo-controlled allergy prevention trial using pre- and postnatal combined Lactobacillus reuteri and ω-3 fatty acid treatment. To this end, > 866000 CpG sites (MethylationEPIC 850K array) in cord blood CD4+ T cells were examined in samples from all four study arms (double-treatment: n = 18, single treatments: probiotics n = 16, ω-3 n = 15, and double placebo: n = 14). Statistical and bioinformatic analyses identified treatment-associated differentially methylated CpGs and genes, which were used to identify putatively treatment-induced network modules. Pathway analyses inferred biological relevance, and comparisons were made to an independent allergy data set., Results: Comparing the active treatments to the double placebo group, most differentially methylated CpGs and genes were hypermethylated, possibly suggesting induction of transcriptional inhibition. The double-treated group showed the largest number of differentially methylated CpGs, of which many were unique, suggesting synergy between interventions. Clusters within the double-treated network module consisted of immune-related pathways, including T cell receptor signalling, and antigen processing and presentation, with similar pathways revealed for the single-treatment modules. CpGs derived from differential methylation and network module analyses were enriched in an independent allergy data set, particularly in the double-treatment group, proposing treatment-induced DNA methylation changes as relevant for allergy development., Conclusion: Prenatal L. reuteri and/or ω-3 fatty acid treatment results in hypermethylation and affects immune- and allergy-related pathways in neonatal T helper cells, with potentially synergistic effects between the interventions and relevance for allergic disease. Further studies need to address these findings on a transcriptional level, and whether the results associate to allergy development in the children. Understanding the role of DNA methylation in regulating effects of perinatal probiotic and ω-3 interventions may provide essential knowledge in the development of efficacious allergy preventive strategies. Trial registration ClinicalTrials.gov, ClinicalTrials.gov-ID: NCT01542970. Registered 27th of February 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01542970 .

Despite the widespread use of artichoke-based food supplements for obesity control (FSOC), studies on evaluation of the quality/authenticity of these commercial products are scarce. To that aim, a new multi-analytical strategy, based on the use of gas chromatography coupled to mass spectrometry (GC-MS) and high performance liquid chromatography coupled to ultraviolet and mass spectrometry detection (HPLC-UV-MS), in combination with chemometrics, has been developed. Twenty-one artichoke FSOC and different bract and leaf extracts (used as reference samples) were analysed. Sugars, inositols, caffeoylquinic acids, dicaffeoylquinic acids, flavonoids and their glycosides were detected in reference samples and in most artichoke FSOC. Low concentrations of bioactives, and the presence of other compounds probably related to heat treatment during manufacturing (difructosyl anhydrides, 3-deoxyglucosone), or to the addition of caloric additives (maltose, maltotriose) or non-declared plants (e.g. pinitol, disaccharides, silybin derivatives) were also detected in some FSOC by either GC-MS or HPLC-UV-MS. Application of Principal Component Analysis to the combined GC-MS + HPLC-UV data matrix, proved that this multi-analytical strategy provides advantages over single analytical techniques for the detection of the wide variety of fraudulent practices affecting authenticity of artichoke FSOC and for assessment of their quality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Background: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available., Objectives: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment., Design: Forty healthy volunteers between 25 and 40 years of age were recruited. Menaquinone-7 (MK-7) was administrated at 90 μg for 30 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration., Results: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30 days of MK-7 supplementation., Conclusions: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy., Methods: Pregnant women at 6-14 weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they had vitamin D or vitamin B12 deficiency. The control arm received prescribed dietary instruction only. An additional observational arm for those mothers at booking with normal vitamin D and vitamin B12 level was also recruited. All groups received standard care during pregnancy., Results: The primary endpoint of either vitamin D or B12 at term was not met. At baseline 25% participants in both the interventional and control arms had severe D deficiency (<30 nmol/l), reducing to under 3.4% in both groups. No maternal differences in vitamin D or B12 levels were found at delivery between the intervention, control, or observational groups. No significant difference in any of the pregnancy or birth outcomes was observed between three groups., Conclusions: In this study, oral supplementation of high dose intermittent vitamin D or low dose vitamin B12 regime failed to correct the relevant nutritional deficiencies in Bangladeshi pregnant women as per protocol. Both dietary supplementation and high dose vitamin D corrected severe vitamin deficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

The current study was performed to investigate whether dietary β -hydroxy- β -methylbutyrate (HMB) could regulate liver injury in a lipopolysaccharide- (LPS-) challenged piglet model and to determine the mechanisms involved. Thirty piglets (21 ± 2 days old, 5.86 ± 0.18 kg body weight) were randomly divided into the control (a basal diet, saline injection), LPS (a basal diet), or LPS+HMB (a basal diet + 0.60% HMB-Ca) group. After 15 d of treatment with LPS and/or HMB, blood and liver samples were obtained. The results showed that in LPS-injected piglets, HMB supplementation ameliorated liver histomorphological abnormalities induced by LPS challenge. Compared to the control group, the activities of serum aspartate aminotransferase and alkaline phosphatase were increased in the LPS-injected piglets ( P < 0.05). The LPS challenge also downregulated the mRNA expression of L-PFK, ACO, L-CPT-1, ICDH β , and AMPK α 1/2 and upregulated the mRNA expression of PCNA, caspase 3, TNF- α , TLR4, MyD88, NOD1, and NF- κ B p65 ( P < 0.05). However, these adverse effects of the LPS challenge were reversed by HMB supplementation ( P < 0.05). These results indicate that HMB may exert protective effects against LPS-induced liver injury, and the underlying mechanisms might involve the improvement of hepatic energy metabolism via regulating AMPK signaling pathway and the reduction of liver inflammation via modulating TLR4 and NOD signaling pathways., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Yehui Duan et al.)

Introduction: Alpha-galactosidase (α-Gal) is an enzyme responsible for the hydrolyzation of glycolipids and glycoprotein commonly found in dietary sources. More than 20% of the general population suffers from abdominal pain or discomfort caused by intestinal gas and by indigested or partially digested food residuals. Therefore, α-Gal is used in dietary supplements to reduce intestinal gases and help complex food digestion. Marketed enzyme-containing dietary supplements must be produced in accordance with the Food and Drug Administration (FDA) regulations for Current Good Manufacturing Practice (cGMPs)., Aim: in this work we illustrated the process used to develop and validate a spectrophotometric enzymatic assay for α-Gal activity quantification in dietary supplements., Methods: The validation workflow included an initial statistical-phase optimization of materials, reagents, and conditions, and subsequently a comparative study with another fluorimetric assay. A final validation of method performance in terms of specificity, linearity, accuracy, intermediate-precision repeatability, and system precision was then executed., Results and Conclusions: The proven method achieved good performance in the quantitative determination of α-Gal activity in commercial food supplements in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals (ICH) guidelines and is suitable as a rapid in-house quality control test.

Dietary supplementation is a widely adapted strategy to maintain nutritional balance for improving health and preventing chronic diseases. Conflicting results in studies of similar design, however, suggest that there is substantial heterogenicity in individuals' responses to nutrients, and personalized nutrition is required to achieve the maximum benefit of dietary supplementation. In recent years, nutrigenomics studies have been increasingly utilized to characterize the detailed genomic response to a specific nutrient, but it remains a daunting task to define the signatures responsible for interindividual variations to dietary supplements for tissues with limited accessibility. In this work, we used the hepatic response to omega-3 fatty acids as an example to probe such signatures. Through comprehensive analysis of nutrigenomic response to eicosapentaneoid acid (EPA) and/or docosahexaenoic acid (DHA) including both protein coding and long noncoding RNA (lncRNA) genes in human hepatocytes, we defined the EPA- and/or DHA-specific signature genes in hepatocytes. By analyzing gene expression variations in livers of healthy and relevant disease populations, we identified a set of protein coding and lncRNA signature genes whose responses to omega-3 fatty acid exhibit very high interindividual variabilities. The large variabilities of individual responses to omega-3 fatty acids were further validated in human hepatocytes from ten different donors. Finally, we profiled RNAs in exosomes isolated from the circulation of a liver-specific humanized mouse model, in which the humanized liver is the sole source of human RNAs, and confirmed the in vivo detectability of some signature genes, supporting their potential as biomarkers for nutrient response. Taken together, we have developed an efficient and practical procedure to identify nutrient-responsive gene signatures as well as accessible biomarkers for interindividual variations.

Hovenia dulcis Thunberg is an herbal plant, belonging to the Rhamnaceae family, widespread in west Asia, USA, Australia and New Zealand, but still almost unknown in Western countries. H. dulcis has been described to possess several pharmacological properties, such as antidiabetic, anticancer, antioxidant, anti-inflammatory and hepatoprotective, especially in the hangover treatment, validating its use as an herbal remedy in the Chinese Traditional Medicine. These biological properties are related to a variety of secondary metabolites synthesized by the different plant parts. Root, bark and leaves are rich of dammarane-type triterpene saponins; dihydrokaempferol, quercetin, 3,3',5',5,7-pentahydroflavone and dihydromyricetin are flavonoids isolated from the seeds; fruits contain mainly dihydroflavonols, such as dihydromyricetin (or ampelopsin) and hovenodulinol, and flavonols such as myricetin and gallocatechin; alkaloids were found in root, barks (frangulanin) and seeds (perlolyrin), and organic acids (vanillic and ferulic) in hot water extract from seeds. Finally, peduncles have plenty of polysaccharides which justify the use as a food supplement. The aim of this work is to review the whole scientific production, with special focus on the last decade, in order to update phytochemistry, biological activities, nutritional properties, toxicological aspect and regulatory classification of H. dulcis extracts for its use in the European Union.

Objective: To determine sources of key nutrients contributing towards nutritional adequacy during pregnancy (fibre, calcium, iron, zinc and folate) in a cohort of women carrying an Indigenous child., Design: Analysis of cross-sectional data from a prospective longitudinal cohort study that followed Indigenous women through pregnancy., Setting: Women recruited via antenatal clinics in regional and remote locations in NSW, Australia as part of the Gomeroi gaaynggal project., Participants: One hundred and fifty-two pregnant Australian women who identified as Indigenous or carrying an Indigenous child., Measurements and Findings: Measurement outcomes included demographic information, smoking status, anthropometrics (weight and height,), self-reported pre-pregnancy weight, health conditions and dietary information (24-hour food recall). Findings indicate the inadequate intake of key pregnancy nutrients in this cohort. Supplements contributed to the nutrient adequacy of the cohort with 53% reporting use. As expected, predominant sources of fibre were from core food groups, whereas calcium was attained from a range of sources including food and beverages, with small amounts from supplementation. Importantly, supplements contributed significant amounts of iron, zinc and folate., Key Conclusions: There is limited literature on Indigenous Australian maternal nutrition. This study highlights the key dietary contributors of nutritional adequacy during pregnancy for the cohort and that supplementation may be considered a viable source of nutrients during pregnancy for these women. Few women met national nutrient recommendations. The findings present an opportunity to optimise nutrient intakes of Indigenous pregnant women., Implications for Practice: Culturally appropriate targeted interventions to optimise dietary intakes of Indigenous Australian pregnant women is required. Collaborative support of health workers, Indigenous Australian communities, dietitians, and researchers to raise awareness of nutrition during pregnancy is imperative to achieving nutrient targets and optimising pregnancy outcomes. Targeted interventions provide positive opportunities to achieve improvements., Competing Interests: Declaration of Competing Interst None., (Copyright © 2020. Published by Elsevier Ltd.)

According to this study: A study of adults age 70 or older without major comorbidities showed that treatment with vitamin D3, omega-3 fatty acids, or a strength training exercise program didn't result in clinically significant changes in blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Association to early mortality and sedentarism was already demonstrated in the literature; nevertheless, some possible biochemical mechanisms around physical inactivity still need answers. The use of an invertebrate model, such as Drosophila melanogaster , can reproduce reliable responses in inducing an exercise protocol with exogenous antioxidant supplementation. This study main evaluates the effect of exercise (EXE) associated with γ-oryzanol (ORY) supplementation to improve locomotor behavior, antioxidant defenses, and survival in Drosophila melanogaster . Two-day old flies were submitted to a protocol for seven days, divided into five groups: Control, Movement-Limited Flies (MLF), EXE, ORY [25   µM], and EXE + ORY [25   µM]. The survival rate was evaluated, followed by open field and negative geotaxis. Flies were euthanized and subjected to analysis for acetylcholinesterase (AChE) and antioxidant enzymes activity, glycidic and lipid parameters, body weight, reactive species (RS), and lipid peroxidation. EXE and EXE + ORY flies showed increased survival and locomotor activity, improved glycidic and lipid parameters, with a lower RS production, and increased antioxidant defenses compared to Control, and EXE + ORY when compared to the EXE group, obtained an increase in the ratio of protein levels/body weight, decreased ratio of triglyceride levels/body weight and decreased lipid peroxidation. However, MLF showed less survival and decreased locomotor activity, possibly due to increased AChE activity and reduced antioxidant defenses. The EXE and EXE + ORY demonstrate effective results in maintaining endogenous defenses, with increased locomotor activity, supporting evidence on EXE benefits, and supplementation with antioxidant compounds face of health paradigms.HighlightsNew protocol system of exercise on Drosophila melanogaster model.ORY demonstrates synergistic effect with EXE.Exercise with ORY supplementation increases locomotor behavior.Exercise with ORY supplementation decrease oxidative damages on flies.

The objective of this study was to analyze labeling practices and compliance with regulatory standards for shark cartilage supplements sold in the United States. The product labels of 29 commercial shark cartilage supplements were assessed for compliance with U.S. regulations. Claims, including nutrient content, prohibited disease, and nutritional support statements, were examined for compliance and substantiation. Overall, 48.3% of the samples had at least one instance of noncompliance with labeling regulations. The most common labeling violations observed were: missing a domestic address/phone number, non-compliant nutrient content claim, missing/incomplete disclaimer, missing statement of identity, prohibited disease claims, and incomplete "Supplement Facts" label. The use of prohibited disease claims and nutritional support statements without the required disclaimer is concerning from a public health standpoint because consumers may delay seeking professional treatment for a disease. The results of this study indicate a need for improved labeling compliance among shark cartilage supplements.

Background: Botanical ingredients based on plants, algae, fungi or lichens have become widely available on the European Union market offering numerous preparations with considerable differences in classification. They are under the categories of food supplements, herbal medicinal products, cosmetics or medical devices., Purpose: The aim of the present work is to highlight how the European regulations concerning the different categories of botanicals can lead to different commercial choices such as time/cost for product development, application for a marketing authorisation, permitted indication (medical or health claim), and as a consequence, the same botanical products are sold in European Union as herbal medicinal products, food supplements, cosmetics or medical devices. Five different widely used botanicals, namely St. John's wort, valerian, ginkgo, ginseng, and green tea were selected to better explain the failure of harmonization through European Union., Methods: A search of PubMed, ScienceDirect, European Medicines Agency and European commission web sites for medical devices and cosmetics, and European Food Safety Authority websites were conducted and the available information on regulation of herbal medicinal products, food supplements, medical devices and cosmetics in the European Union was collected. In addition, a market survey of all the sold botanical products in Europe was analysed by consultation of the medicines, medical devices, cosmetic and food agencies websites of the European countries., Results: The current European legislation needs implementation and follow up because in the different countries the legal positions of the botanical products varied and it is possible to find the same product classified in the different categories, namely registered medicinal product including prescription only medicine, traditional herbal medicinal product, well established herbal medicinal products or food supplement, or medical device, or homoeopathic/anthroposophical medical product, cosmetic., Conclusions: There is an urgent need of harmonization, together with the implementation of interoperable vigilance databases, to avoid borderline options., (Copyright © 2020. Published by Elsevier GmbH.)

&lt;b&gt;Background and Objective:&lt;/b&gt; Vitamin A Deficiency (VAD) is a critical public health problem that affects the health of kids worldwide and may induce anemia and oxidative stress. The current study aimed to pre-clinically assess the effect of a cupcake, prepared to be served for primary school children, on vitamin A deficiency and related anemia and oxidative stress in rats. &lt;b&gt;Materials and Methods:&lt;/b&gt; Flour of flash orange sweet potatoes, as a rich source of pro-vitamin A, was used to prepare the cupcake. The chemical composition, amino acids and sensory evaluation of the cupcake were done. The biological evaluation was carried out using 18 weaning rats in three groups (control group, vitamin A-deficient group and vitamin A-deficient group fed on a diet fortified with 20% of the prepared cupcake for two months). &lt;b&gt;Results:&lt;/b&gt; The results indicated the high value of vitamin A in the prepared cupcake. Excellent sensory characteristics were noticed. Feeding on the VDA diet fortified with the prepared cupcake suppressed the reduction in Retinol-Binding Protein (RBP), hemoglobin and iron. Total Iron Binding Capacity (TIBC) increased in the VAD group. Also, feeding on the prepared cupcake suppressed the reduction in Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) and the elevation of Malondialdehyde (MDA). &lt;b&gt;Conclusion:&lt;/b&gt; It can be suggested that the prepared cupcake is promising in preventing of vitamin A deficiency and related anemia and oxidative stress. Thus, the prepared cupcake may be efficient for children to prevent vitamin A deficiency.

The notion of probiotics as microbes that confer health benefits has its origins in the speculative ideas that are more than a century old, yet remain largely unsubstantiated by scientific evidence. The recent advances in microbiome science have highlighted the importance of intestinal microbes in human physiology and disease pathogenesis. These developments have provided a boost to the probiotics industry, which continues to experience exponential growth driven mainly by creative marketing. Consumers, patients, and most health care providers are not able to discern the underlying science or differentiate the permitted claims that promise vague health benefits from disease-specific claims reserved for drugs. No probiotic product has been able to satisfy the regulatory requirements to be categorized as a drug, a substance intended to cure, mitigate, or prevent disease. However, patients take probiotic products in the belief that they will help to treat their intestinal or systemic diseases. Thus far, the regulators have failed to create policies that would assist to inform the public in this area. In fact, the existing regulatory regime actually creates formidable barriers to research that could provide evidence for clinical efficacy of probiotic products. We propose a potential solution to this vexing problem, where a committee created through a partnership of academia, professional organizations, and industry, but free of potential conflicts of interest, would be charged with rigorous evaluation of specific probiotic products and the evidence in support of their different claims. Companies that would submit to this process would earn the trust of consumers and healthcare providers, as well as a distinction in the marketplace., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: To critically examine the research on novel supplements and strategies designed to enhance carbohydrate delivery and/or availability., Methods: Narrative review., Results: Available data would suggest that there are varying levels of effectiveness based on the supplement/supplementation strategy in question and mechanism of action. Novel carbohydrate supplements including multiple transportable carbohydrate (MTC), modified carbohydrate (MC), and hydrogels (HGEL) have been generally effective at modifying gastric emptying and/or intestinal absorption. Moreover, these effects often correlate with altered fuel utilization patterns and/or glycogen storage. Nevertheless, performance effects differ widely based on supplement and study design. MTC consistently enhances performance, but the magnitude of the effect is yet to be fully elucidated. MC and HGEL seem unlikely to be beneficial when compared to supplementation strategies that align with current sport nutrition recommendations. Combining carbohydrate with other ergogenic substances may, in some cases, result in additive or synergistic effects on metabolism and/or performance; however, data are often lacking and results vary based on the quantity, timing, and inter-individual responses to different treatments. Altering dietary carbohydrate intake likely influences absorption, oxidation, and and/or storage of acutely ingested carbohydrate, but how this affects the ergogenicity of carbohydrate is still mostly unknown., Conclusions: In conclusion, novel carbohydrate supplements and strategies alter carbohydrate delivery through various mechanisms. However, more research is needed to determine if/when interventions are ergogenic based on different contexts, populations, and applications.