Recommendation and intake of dietary supplements periconceptional and during pregnancy: results of a nationwide survey of gynaecologists.

BACKGROUND: Micronutrient supplementation during pregnancy is a controversial issue. For some micronutrients, for example folic acid or iodine, the evidence regarding supplementation is clear, whereas for others, such as zinc or vitamin E, it is not. Studies show that a large number of pregnant women have deficient levels of folic acid and iodine. However, especially with folic acid, starting supplementation during the preconception period is crucial. It is, therefore, important that gynaecologists explain this to their pregnant or preconceptional patients. Our goal was to find out how gynaecologists make their recommendations on this topic, how they assess the compliance of their patients and which micronutrients they consider to be important before/during pregnancy and during breastfeeding. METHOD AND RESULTS: We sent about 12,000 questionnaires to all registered resident gynaecologists in Germany, with a response rate of 12.2%. Regarding which micronutrients gynaecologists  consider to be particularly important during pregnancy, there was a broad agreement for both folic acid and iodine (> 88% answered yes). According to the questionnaire, doctors rate other micronutrients, such as vitamin D and omega-3 fatty acids, as less essential. The controversial evidence level for many micronutrients certainly plays a role here. Overall, the intake rate, especially for preconceptional women, is classified as rather low (< 60%). The most widely valued reason is the high price of dietary supplements. It was also noticeable that doctors consider certain micronutrients to be particularly important but then do not include them in the products they recommend. CONCLUSION: Overall, there seems to be uncertainty about micronutrients in pregnancy and their supplementation. The study situation is often ambiguous and there are no official guidelines, leading to ambiguous recommendations from doctors and therefore low intake rates for pregnant or preconceptional women.

Podcast POEMs (BVS APS): Vitaminas e cognição. Tipos de erros em epidemiologia

Neste episódio 4, vou comentar os resultados de uma revisão sistemática da Cochrane de dezembro de 2018, demonstrando os efeitos do uso de vitaminas e minerais na cognição de pessoas com mais de 40 anos, sem doenças prévias que afetem essa área. Vou falar, também, sobre o acaso, importante ponto a ser conhecido nas avaliações dos resultados de estudos, e sua relação a temas famosos como hipótese nula, hipótese alternativa, erro tipo 1 e erro tipo 2.

Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia.

BACKGROUND: Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases children's risk of developing pneumonia. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited. This is an update of a Cochrane Review first published in 2018. OBJECTIVES: To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries on 28 December 2021. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared vitamin D supplementation with placebo in children (aged one month to five years) hospitalised with acute community-acquired pneumonia, as defined by the World Health Organization (WHO) acute respiratory infection guidelines. For this update, we reappraised eligible trials according to research integrity criteria, excluding RCTs published from April 2018 that were not prospectively registered in a trials registry according to WHO or Clinical Trials Registry - India (CTRI) guidelines (it was not mandatory to register clinical trials in India before April 2018). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. For dichotomous data, we extracted the number of participants experiencing the outcome and the total number of participants in each treatment group. For continuous data, we used the arithmetic mean and standard deviation (SD) for each treatment group together with number of participants in each group. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this update, we included three new trials involving 468 children, bringing the total number of trials to seven, with 1601 children (631 with pneumonia and 970 with severe or very severe pneumonia). We categorised three previously included studies and three new studies as 'awaiting classification' based on the research integrity screen. Five trials used a single bolus dose of vitamin D (300,000 IU in one trial and 100,000 IU in four trials) at the onset of illness or within 24 hours of hospital admission; one used a daily dose of oral vitamin D (1000 IU for children aged up to one year and 2000 IU for children aged over one year) for five days; and one used variable doses (on day 1, 20,000 IU in children younger than six months, 50,000 IU in children aged six to 12 months, and 100,000 IU in children aged 13 to 59 months; followed by 10,000 IU/day for four days or until discharge). Three trials performed microbiological diagnosis of pneumonia, radiological diagnosis of pneumonia, or both. Vitamin D probably has little or no effect on the time to resolution of acute illness (mean difference (MD) -1.28 hours, 95% confidence interval (CI) -5.47 to 2.91; 5 trials, 1188 children; moderate-certainty evidence). We do not know if vitamin D has an effect on the duration of hospitalisation (MD 4.96 hours, 95% CI -8.28 to 18.21; 5 trials, 1023 children; very low-certainty evidence). We do not know if vitamin D has an effect on mortality rate (risk ratio (RR) 0.69, 95% CI 0.44 to 1.07; 3 trials, 584 children; low-certainty evidence). The trials reported no major adverse events. According to GRADE criteria, the evidence was of very low-to-moderate certainty for all outcomes, owing to serious trial limitations, inconsistency, indirectness, and imprecision. Three trials received funding: one from the New Zealand Aid Corporation, one from an institutional grant, and one from multigovernment organisations (Bangladesh, Sweden, and UK). The remaining four trials were unfunded. AUTHORS' CONCLUSIONS: Based on the available evidence, we are uncertain whether vitamin D supplementation has important effects on outcomes of acute pneumonia when used as an adjunct to antibiotics. The trials reported no major adverse events. Uncertainty in the evidence is due to imprecision, risk of bias, inconsistency, and indirectness.

Critique of Public Health Guidance for Vitamin D and Sun Exposure in the Context of Cancer and COVID-19.

Official public health pronouncements about sun exposure and vitamin D can be summarized as follows: First, there is no such thing as a safe tan. Therefore, avoid exposing the skin to sunshine. Second, in the absence of sunshine, a daily intake of 800 IU/day (20 mcg/d) vitamin D or less is sufficient for the health needs of almost all members of the population. However, exposure of the skin to sunlight induces multiple mechanisms that lower blood pressure, while also initiating production of vitamin D, which is needed to produce a hormone that regulates multiple systems including the cellular biology that affects cancer mortality. Disease-prevention relationships point to a beneficial threshold for serum 25-hydroxyvitamin D [25(OH)D; the index of vitamin D nutrition] that is at least 75 nmol/l (30 ng/ml). To ensure the threshold for all adults, an average per-day minimum total input of vitamin D3 from sunshine/UVB exposure, and/or from food (natural food like fish or fortified food like milk), and/or vitamin supplementation of at least 4,000 IU/d (100 mcg/d) is required. Strong, although not Level-1, evidence indicates that the maintenance of that threshold will lower mortality overall, lower mortality from cancer, and lower the risk of certain other diseases such as respiratory infection and COVID-19.

The diabetogenic effects of chronic supplementation of vitamin C or E in rats: Interplay between liver and adipose tissues transcriptional machinery of lipid metabolism.

AIM: The chronic administration of vitamin C and E can differentially disrupt hepatic insulin molecular pathway in rats. Hence, this study evaluated their effects on lipogenesis in the liver and adipose tissue and investigated the possible involvement of microRNA (miR)-22/29a/27a in the induced impaired glucose tolerance. MAIN METHODS: Wistar rats were orally supplemented with vitamin C (100, 200, and 500 mg/kg) or vitamin E (50, 100, and 200 mg/kg) for eight months. KEY FINDINGS: Vitamin C or E at the highest doses significantly altered liver weight and index, serum and hepatic lipids, adiponectin, and liver enzymes; besides their reported unfavorable effect on glucose homeostasis. Vitamin C and E negatively affected peroxisome proliferator-activated receptor coactivator-1 (PGC-1α), sterol regulatory element-binding protein (SREBP)-1c/-2, miR-22/29a/27a expression, and adipose perilipin 1 to different extents, effects that were supported by the histopathological examination. SIGNIFICANCE: The current study provides a deeper insight into the findings of our previous study and highlights the detrimental effects of chronic vitamins supplementation on lipid metabolism. Overall, these findings emphasize the damage caused by the mindless use of supplements and reinforce the role of strict medical monitoring, particularly during the new COVID-19 era during which numerous commercial supplements are claiming to improve immunity.

Association between Vitamin Intake and Chronic Kidney Disease According to a Variant Located Upstream of the PTGS1 Gene: A Cross-Sectional Analysis of Shika Study.

Chronic kidney disease (CKD) patients have been advised to take vitamins; however, the effects have been controversial. The individual differences in developing CKD might involve genetic variants of inflammation, including variant rs883484 located upstream of the prostaglandin-endoperoxide synthase 1 (PTGS1) gene. We aimed to identify whether the 12 dietary vitamin intake interacts with genotypes of the rs883484 on developing CKD. The population-based, cross-sectional study had 684 Japanese participants (≥40 years old). The study used a validated, brief, self-administered diet history questionnaire to estimate the intake of the dietary vitamins. CKD was defined as estimated glomerular filtration < 60 mL/min/1.73 m2. The study participants had an average age of 62.1 ± 10.8 years with 15.4% minor homozygotes of rs883484, and 114 subjects had CKD. In the fully adjusted model, the higher intake of vitamins, namely niacin (odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.57−0.96, p = 0.024), α-tocopherol (OR = 0.49, 95% CI: 0.26−0.95, p = 0.034), and vitamin C (OR = 0.97, 95% CI: 0.95−1.00, p = 0.037), was independently associated with lower CKD tendency in the minor homozygotes of rs883484. The results suggested the importance of dietary vitamin intake in the prevention of CKD in middle-aged to older-aged Japanese with minor homozygous of rs883484 gene variant.

An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19.

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.

Monthly Increase in Vitamin D Levels upon Supplementation with 2000 IU/Day in Healthy Volunteers: Result from "Integriamoci", a Pilot Pharmacokinetic Study.

Vitamin D (VD) is a calcium- and phosphate-controlling hormone used to treat bone disorders; yet, several other effects are progressively emerging. VD deficiency is highly prevalent worldwide, with suboptimal exposure to sunlight listed among the leading causes: oral supplementation with either cholecalciferol or calcitriol is used. However, there is a scarcity of clinical studies investigating how quickly VD concentrations can increase after supplementation. In this pilot study, the commercial supplement ImmuD3 (by Erboristeria Magentina®) was chosen as the source of VD and 2000 IU/day was administered for one month to 21 healthy volunteers that had not taken any other VD supplements in the previous 30 days. Plasma VD levels were measured through liquid chromatography coupled to tandem mass spectrometry after 7, 14, and 28 days of supplementation. We found that 95% of the participants had insufficient VD levels at baseline (<30 ng/mL; median 23.72 ng/mL; IQR 18.10-26.15), but after 28 days of supplementation, this percentage dropped to 62% (median 28.35 ng/mL; IQR 25.78-35.20). The median increase in VD level was 3.09 ng/mL (IQR 1.60-5.68) after 7 days and 8.85 ng/mL (IQR 2.85-13.97F) after 28 days. This study suggests the need for continuing VD supplementation and for measuring target level attainment.

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

Prevalence and characteristics of multivitamin-multimineral (MVMM) use among Saudi populations in Riyadh, Saudi Arabia: A cross-sectional study.

ABSTRACT: Use of multivitamin multimineral (MVMM) preparations is prevalent and growing worldwide, contributing to major health expenditure. Minimal literature on prevalence and characteristics of MVMM use is available from Saudi Arabia.The study was conducted to determine the prevalence and characteristics of MVMM use among Saudi population in Riyadh, Saudi Arabia.A cross-sectional study was conducted at 6 shopping malls located in the different regions of Riyadh city for 6 months from February 01, 2019, to July 31, 2019. A well-structured English questionnaire was developed, translated into Arabic language, and validated by the experts. A pertinent inclusion and exclusion criteria were established. After having informed consent to be included in the study, the printed copies of the questionnaire were distributed among the participants using a convenient sampling technique. The data were collected and analyzed using SPSS version 24. Descriptive statistics were presented as numbers, percentages, means, and standard deviations. A P value of ≤.05 and 95% confidence intervals were used to report the statistical significance.Out of 1200 surveys distributed, 1105 were returned by the participants (response rate 92%). Prevalence of MVMM supplements use turned out to be 47%. The study revealed statistically significant association between MVMM use and gender, marital status, education, regular exercise, smoking, following special diet, and eating fruits and vegetables (P ≤ .05). Majority of the participants used MVMM on daily basis (57.9%), and hospital prescriptions (57.9%) were the most common reason of MVMM use. Majority of the participants used MVMM for diet supplements (32.2%), health promotion (29.4%), and treatment of disease (16%).The MVMM use is prevalent in Saudi population, warranting sound regulatory policies for their judicial use and increase awareness about the benefits and side effects of dietary supplements.

Impact of cytokine storm on severity of COVID-19 disease in a private hospital in West Jakarta prior to vaccination.

BACKGROUND AND AIM: Coronavirus Disease 2019 (COVID-19) has become a worldwide pandemic and is a threat to global health. Patients who experienced cytokine storms tend to have a high mortality rate. However, to date, no study has investigated the impact of cytokine storms. MATERIALS AND METHODS: This retrospective cohort study included only COVID-19 positive patients hospitalized in a Private Hospital in West Jakarta between March and September 2020. All patients were not vaccinated during this period and treatment was based on the guidelines by the Ministry of Health Indonesia. A convenience sampling method was used and all patients who met the inclusion criteria were enrolled. RESULTS: The clinical outcome of COVID-19 patients following medical therapy was either cured (85.7%) or died (14.3%), with 14.3% patients reported to have cytokine storm, from which 23.1% led to fatalities. A plasma immunoglobulin (Gammaraas®) and/or tocilizumab (interleukin-6 receptor antagonist; Actemra®) injection was utilised to treat the cytokine storm while remdesivir and oseltamivir were administered to ameliorate COVID-19. Most (61.5%) patients who experienced the cytokine storm were male; mean age 60 years. Interestingly, all patients who experienced the cytokine storm had hypertension or/ and diabetes complication (100%). Fever, cough and shortness of breath were also the common symptoms (100.0%). Almost all (92.3%) patients with cytokine storm had to be treated in the intensive care unit (ICU). Most (76.9%) patients who had cytokine storm received hydroxychloroquine and all had antibiotics [1) azithromycin + levofloxacin or 2) meropenam for critically ill patients] and vitamins such as vitamins C and B-complex as well as mineral. Unfortunately, from this group, 23.1% patients died while the remaining 70% of patients recovered. A significant (p<0.05) correlation was established between cytokine storms and age, the presence of comorbidity, diabetes, hypertension, fever, shortness of breath, having oxygen saturation (SPO2) less than 93%, cold, fatigue, ward of admission, the severity of COVID-19 disease, duration of treatment as well as the use of remdesivir, Actemra® and Gammaraas®. Most patients recovered after receiving a combination treatment (oseltamivir + remdesivir + Antibiotics + Vitamin/Mineral) for approximately 11 days with a 90% survival rate. On the contrary, patients who received oseltamivir + hydroxychloroquine + Gammaraas® + antibiotics +Vitamin/Mineral, had a 83% survival rate after being admitted to the hospital for about ten days. CONCLUSION: Factors influencing the development of a cytokine storm include age, duration of treatment, comorbidity, symptoms, type of admission ward and severity of infection. Most patients (76.92%) with cytokine storm who received Gammaraas®/Actemra®, survived although they were in the severe and critical levels (87.17%). Overall, based on the treatment duration and survival rate, the most effective therapy was a combination of oseltamivir + favipiravir + hydroxychloroquine + antibiotics + vitamins/minerals.

Nutritional Behaviors, Vitamin Supplementation and Physical Activity among Polish Adults during the COVID-19 Pandemic.

The COVID-19 pandemic and its consequences, including social isolation, movement restrictions and work instability have altered many people's nutritional behaviors and daily lifestyle. The aim of the study was to evaluate the influence of the COVID-19 pandemic on selected eating habits, physical activity and daily lifestyle changes of Polish adults (n = 145). The self-designed and anonymous questionnaire was available online from the 1 May 2021 to the 15 May 2021. In general, 60% of respondents declared that the COVID-19 pandemic did not affect their dietary habits, whereas 26% of surveyed individuals answered in the affirmative. The effect of the COVID-19 pandemic on changing dietary habits was differentiated by age (Pearson's χ2 = 12.604; p = 0.0134). The number of meals consumed by respondents per day differed across gender groups (Pearson's χ2 = 9.653; df = 4; p = 0.0466). An increase in body weight during the COVID-19 pandemic was reported by 43% of women and 7.6% of surveyed men. Additionally, hybrid working women declared most often an increase in body mass independent of age, education level and living place. Moreover, the majority of respondents who reported the effect of the pandemic on changing dietary habits also declared more frequent sweets consumption. The study revealed that respondents who stated more frequent sweets consumption during the COVID-19 pandemic were more likely associated with an increase in body mass (OR = 6.75, 95% CI, 6.75-91.25). No increase in the consumption of vitamin D, C and Mg supplements and pickled products was found.

Prenatal Folate and Choline Levels and Brain and Cognitive Development in Children: A Critical Narrative Review.

Women's nutritional status during pregnancy can have long-term effects on children's brains and cognitive development. Folate and choline are methyl-donor nutrients and are important for closure of the neural tube during fetal development. They have also been associated with brain and cognitive development in children. Animal studies have observed that prenatal folate and choline supplementation is associated with better cognitive outcomes in offspring and that these nutrients may have interactive effects on brain development. Although some human studies have reported associations between maternal folate and choline levels and child cognitive outcomes, results are not consistent, and no human studies have investigated the potential interactive effects of folate and choline. This lack of consistency could be due to differences in the methods used to assess folate and choline levels, the gestational trimester at which they were measured, and lack of consideration of potential confounding variables. This narrative review discusses and critically reviews current research examining the associations between maternal levels of folate and choline during pregnancy and brain and cognitive development in children. Directions for future research that will increase our understanding of the effects of these nutrients on children's neurodevelopment are discussed.

Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review.

Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.

A Skin-Interfaced, Miniaturized Microfluidic Analysis and Delivery System for Colorimetric Measurements of Nutrients in Sweat and Supply of Vitamins Through the Skin.

Nutrients play critical roles in maintaining core physiological functions and in preventing diseases. Technologies for delivering these nutrients and for monitoring their concentrations can help to ensure proper nutritional balance. Eccrine sweat is a potentially attractive class of biofluid for monitoring purposes due to the ability to capture sweat easily and noninvasively from nearly any region of the body using skin-integrated microfluidic technologies. Here, a miniaturized system of this type is presented that allows simple, rapid colorimetric assessments of the concentrations of multiple essential nutrients in sweat, simultaneously and without any supporting electronics - vitamin C, calcium, zinc, and iron. A transdermal patch integrated directly with the microfluidics supports passive, sustained delivery of these species to the body throughout a period of wear. Comparisons of measurement results to those from traditional lab analysis methods demonstrate the accuracy and reliability of this platform. On-body tests with human subjects reveal correlations between the time dynamics of concentrations of these nutrients in sweat and those of the corresponding concentrations in blood. Studies conducted before and after consuming certain foods and beverages highlight practical capabilities in monitoring nutritional balance, with strong potential to serve as a basis for guiding personalized dietary choices.

Do Multivitamin/Mineral Dietary Supplements for Young Children Fill Critical Nutrient Gaps?

BACKGROUND: Nearly a third of young US children take multivitamin/mineral (MVM) dietary supplements, yet it is unclear how formulations compare with requirements. OBJECTIVE: Describe the number and amounts of micronutrients contained in MVMs for young children and compare suggested amounts on product labels to micronutrient requirements. DESIGN: Cross-sectional. SETTING: All 288 MVMs on the market in the United States in the National Institutes of Health's Dietary Supplement Label Database in 2018 labeled for children 1 to <4 years old. MAIN OUTCOME MEASURES: Number of MVM products and amounts per day of micronutrients in each product suggested on labels compared with requirements represented by age-appropriate Daily Values (DV). Micronutrients of public health concern identified by the Dietary Guidelines for Americans (DGA) 2015-2020 (DGA 2015) and DGA 2020-2025 (DGA 2020) or those of concern for exceeding the upper tolerable intake levels. STATISTICAL ANALYSES: Number of products and percent DV per day provided by each micronutrient in each product. RESULTS: The 288 MVMs contained a mean of 10.1 ± 2.27 vitamins and 4.59 ± 2.27 minerals. The most common were, in rank order, vitamins C, A, D, E, B6, B12; zinc, biotin, pantothenic acid, iodine, and folic acid. For micronutrients denoted by the DGA 2015 and DGA 2020 of public health concern, 56% of the 281 products containing vitamin D, 4% of the 144 with calcium, and none of the 60 containing potassium provided at least half of the DV. The upper tolerable intake level was exceeded by 49% of 197 products with folic acid, 17% of 283 with vitamin A, and 14% of 264 with zinc. Most MVMs contained many of 16 other vitamins and minerals identified in national surveys as already abundant in children's diets. CONCLUSIONS: A reexamination of the amounts and types of micronutrients in MVMs might consider formulations that better fill critical gaps in intakes and avoid excess.

Vitamin therapy in sepsis.

Vitamins are essential micronutrients with key roles in many biological pathways relevant to sepsis. Some of these relevant biological mechanisms include antioxidant and anti-inflammatory effects, protein and hormone synthesis, energy generation, and regulation of gene transcription. Moreover, relative vitamin deficiencies in plasma are common during sepsis and vitamin therapy has been associated with improved outcomes in some adult and pediatric studies. High-dose intravenous vitamin C has been the vitamin therapy most extensively studied in adult patients with sepsis and septic shock. This includes three randomized control trials (RCTs) as monotherapy with a total of 219 patients showing significant reduction in organ dysfunction and lower mortality when compared to placebo, and five RCTs as a combination therapy with thiamine and hydrocortisone with a total of 1134 patients showing no difference in clinical outcomes. Likewise, the evidence for the role of other vitamins in sepsis remains mixed. In this narrative review, we present the preclinical, clinical, and safety evidence of the most studied vitamins in sepsis, including vitamin C, thiamine (i.e., vitamin B1), and vitamin D. We also present the relevant evidence of the other vitamins that have been studied in sepsis and critical illness in both children and adults, including vitamins A, B2, B6, B12, and E. IMPACT: Vitamins are key effectors in many biological processes relevant to sepsis. We present the preclinical, clinical, and safety evidence of the most studied vitamins in pediatric sepsis. Designing response-adaptive platform trials may help fill in knowledge gaps regarding vitamin use for critical illness and association with clinical outcomes.

Vitamin C and scar strength: analysis of a historical trial and implications for collagen-related pathologies.

A double-blind controlled trial initiated in 1944 has led to the common narrative that a 10-mg daily vitamin C intake is adequate to prevent and treat impaired wound healing, and by inference, other collagen-related diseases such as heart disease or stroke. The WHO relies on this narrative to set the recommended nutrient intake for vitamin C. This narrative, however, is based on what is known as the eyeball method of data assessment. The 1944 trial published individual participant data on scar strength providing an opportunity to statistically probe the validity of the 10-mg narrative, something which has not yet been done. The findings show that a vitamin C intake that averages to 10 mg/d over a mean follow-up of 11.5 mo was associated with a 42% weakened scar strength when compared with 80 mg vitamin C intake/d (P < 0.001). The observed dose-response curve between scar strength and vitamin C intake suggests that the daily vitamin C intake needed to prevent collagen-related pathologies is in the range recommended by the National Academy of Medicine and the European Food Safety Authority (75 to 110 mg/d), not the WHO recommendation (45 mg/d). The findings also show that a vitamin C intake that averages to 65 mg/d over a mean follow-up of 6.5 mo failed to restore the normal wound-healing capacity of vitamin C-depleted tissues; such tissues had a 49% weaker scar strength when compared with nondepleted tissues (P < 0.05). Thus, average daily vitamin C intakes ∼50% higher than the WHO recommends may fail to treat existing collagen-related pathologies. It is concluded that the prior lack of statistical analyses of a landmark trial may have led to a misleading narrative on the vitamin C needs for the prevention and treatment of collagen-related pathologies.

The effects of dietary vitamin D supplementation and in vitro 1,25 dihydroxyvitamin D3 treatment on autophagy in bone marrow-derived dendritic cells from high-fat diet-induced obese mice.

Obesity is associated with the dysregulation of vitamin D metabolism and altered immune responses in bone marrow-derived dendritic cells (BMDCs). Vitamin D can affect the differentiation, maturation, and activation of dendritic cells (DCs) and regulate autophagy via vitamin D receptor signaling. Autophagy was shown to be involved in the functions of DCs. We investigated the effects of dietary vitamin D supplementation and in vitro 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on autophagy in BMDCs from control diet (CON)-fed lean and high-fat diet (HFD)-induced obese mice. C57BL/6 male mice were fed CON or HFD with 10% or 45% kcal fat, respectively, supplemented with 1,000 or 10,000 IU vitamin D/kg diet (vDC or vDS) for 12 weeks. BMDCs were generated by culturing bone marrow cells from the mice with 20 ng/mL rmGM-CSF and treated with 1 nM 1,25(OH)2D3. Maturation of BMDCs was induced by lipopolysaccharide (50 ng/mL) stimulation. Treatment with 1,25(OH)2D3 inhibited the expression of phenotypes related to DC function (MHC class Ⅱ, CD86, CD80) and production of IL-12p70 by BMDCs from control and obese mice, regardless of dietary vitamin D supplementation. LC3Ⅱ/Ⅰ and VPS34 protein levels increased, and p62 expression decreased, after 1,25(OH)2D3 treatment of the BMDCs in CON-vDC only. Vdr mRNA levels decreased following 1,25(OH)2D3 treatment of BMDCs in the HFD-vDC. In conclusion, autophagy flux was increased by 1,25(OH)2D3 treatment of the BMDCs in CON-vDC but not in the HFD-vDC group. This suggests that the decreased expression of Vdr following 1,25(OH)2D3 treatment might have affected autophagy flux in BMDCs from obese mice.