Dosages of Nutrient Supplements and Potential Long-Term Toxicity in Attention-Deficit/Hyperactivity Disorder Micronutrient Study.

We read with interest the article by Johnstone et al.1 reporting their vitamin-mineral randomized trial that found that children with attention-deficit/hyperactivity disorder (ADHD) showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Because some of the mineral dosing was in potentially toxic ranges, we sought to examine the trial findings. Given that the producing company is promoting their supplement for long-term use,2 the scientific and consumer communities might value some additional information about potential toxicity from long-term dosing.

COVID-19 in Pregnancy: Influence of Body Weight and Nutritional Status on Maternal and Pregnancy Outcomes-A Review of Literature and Meta-Analysis.

In the last two and a half years, COVID-19 has been one of the most challenging public health issues worldwide. Based on the available evidence, pregnant women do not appear to be more susceptible to infection than the general population but having COVID-19 during pregnancy may increase the risk of major complications for both the mother and the fetus. The aim of this study is to identify the correlation between BMI and nutritional status and the likelihood of contracting COVID-19 infection in pregnancy, its severity, and maternal pregnancy outcomes. We carry out a systematic literature search and a meta-analysis using three databases following the guidelines of the Cochrane Collaboration. We include 45 studies about COVID-19-positive pregnant women. Compared with normal-weight pregnant women with COVID-19, obesity is associated with a more severe infection (OR = 2.32 [1.65-3.25]), increased maternal death (OR = 2.84 [2.01-4.02]), and a higher rate of hospital admission (OR = 2.11 [1.37-3.26]). Obesity may be associated with adverse maternal and pregnancy outcomes by increasing symptom severity and, consequently, hospital and Intensive Care Unit (ICU) admission, and, finally, death rates. For micronutrients, the results are less definite, even if there seems to be a lower level of micronutrients, in particular Vitamin D, in COVID-19-positive pregnant women.

Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients.

OBJECTIVE: The occurrence of side effects related to the use of combined oral contraceptives (COCs) - or even the fear of them - often affects patients' compliance and their quality of life. Such adverse effects include both physical and psychological alterations. Therapies based on COCs are related to lower levels of vitamins and minerals, including vitamins B, C and E, zinc, magnesium, and selenium. This review gathers scientific evidence about the effectiveness of the administration of specific micronutrients to address nutritional needs and recover adverse conditions. MATERIALS AND METHODS: We reviewed literature searching through different databases (MEDLINE, Scopus, Google Scholar). We used different keywords, including micronutrients, COCs, side effects, B vitamins, vitamin C, vitamin E, vitamin D, zinc, magnesium, selenium and Centella Asiatica. We narrowed the search down to English literature, including both preclinical and clinical studies. The outcome of database search was to highlight beneficial effects of specific micronutrients on the evaluated side reactions. RESULTS: Based on the collected evidence, dietary supplementations of specific micronutrients, whose depletion occurs during COC treatments, have significant beneficial effects. By acting on different aspects and pathways, such supplementation prevents and counteracts discomforts and side effects related to COC treatments. CONCLUSIONS: Considering the wide use of OCs, taking appropriate dietary supplements could be an effective approach in clinical practice, tailoring therapies and improving both safety and tolerability.

Interventions for the Prevention of Preterm Premature Rupture of Membranes: A Systematic Review and Meta-Analysis.

INTRODUCTION: Preterm prelabour rupture of membranes (PPRoM) is a significant cause of maternal and perinatal morbidity and mortality. The aim of this project was to identify interventions that reduce the prevalence of PPRoM. METHODS: Search strategy included a systematic literature search of MEDLINE, EMBASE, PubMed, and Cochrane Library. The selection criteria included randomized control studies that compared a therapy to standard care (no therapy or placebo) in pregnancy and included PPRoM as an outcome. Risk of bias was assessed according to the Cochrane risk-of-bias tool for randomized trials. Odds ratios with 95% confidence intervals were calculated using random-effects models. Quality of evidence was assessed using the GRADE methodology. RESULTS: Twenty-nine studies examining 10 interventions met the inclusion criteria. Therapies included docosahexaenoic acid (DHA), aspirin, rofecoxib, vitamin C alone and with vitamin E, folic acid (alone, with iron, with iron and zinc, within a multiple micronutrient supplement), zinc, calcium, copper, and treatment of bacterial vaginosis. There was no significant difference in the prevalence of PPRoM in the treatment groups compared to placebo, except for rofecoxib which showed an increased risk of PPRoM (RR 2.46, 95% CI 1.28-4.73; p = 0.007, 1 trial, 98 women; very low quality of evidence) and a multiple micronutrient supplement which showed a reduction in PPRoM (RR 0.40, 95% CI 0.19-0.84; p = 0.01, 1 trial, 1,671 women; very low quality of evidence). CONCLUSIONS: No interventions have been convincingly shown to reduce the prevalence of PPRoM. Given this is a common problem leading to significant morbidity and mortality, further research is required.

Zinc homeostasis in immunity and its association with preterm births.

Preterm birth is among the most common adverse pregnancy outcomes and is the leading cause of neonatal mortality and morbidity. While trace elements are essential for humans, their specific roles in the prenatal period remain unexplored. Zinc, a ubiquitous element, plays a pivotal role in protein synthesis, cell division, nucleic acid metabolism, apoptosis, ageing, reproduction, immunological and antioxidant defence mechanism. Although zinc quantities are very small in body tissue, it is involved in every conceivable biochemical pathway, which is critical for the performance of various functions necessary to sustain life. Owing to the multifactorial role of zinc, it is not possible to attribute a certain zinc-dependent mechanism in preterm births. Although the effect of zinc deficiency on immunity, its impact on maternal function and health as well as its role in the developing foetus is well documented, much less attention has been given to the understanding of micronutrient zinc homeostasis in immunity and its association with preterm births. Despite extensive research, the pathway by which zinc regulates pregnancy outcomes as well as the function of immune cells in controlling the delivery status (term/preterm) is still obscure. The present review aims to focus on the understanding of relationship of micronutrient zinc homeostasis in immunity and its association with preterm births.

Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.

OBJECTIVE: To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD: A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS: Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred. CONCLUSION: Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level. CLINICAL TRIAL REGISTRATION INFORMATION: Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.

Micronutrients in Adverse Pregnancy Outcomes.

About 10 to 20% of reported pregnancies have complications like spontaneous abortion (SA), preeclampsia (PE), preterm birth (PTB), and fetal growth restriction (FGR); 60% are attributed to maternal nutritional alterations. Multiple micronutrients (MMN) are supplemented in the antenatal period, but no proper validation/guidelines are available regarding dosing/time, the need for initiation, and the duration of supplementation. Studies have reported adverse pregnancy complications related to the overuse/unwanted use of multiple micronutrient supplementations during pregnancy. Identifying the exact population requiring supplementation is necessary to prevent its abuse. This article attempts to review the impacts of micronutrient deficiency/supplementation in cases of SA, FGR, and gestational diabetes mellitus (GDM), preterm delivery and PE. The study used a literature search using PubMed, Google Scholar, Mendeley, and Scopus Databases using search words pregnancy, spontaneous abortion, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), preterm delivery, preeclampsia (PE) or "adverse pregnancy" associated with minerals, micronutrients, or supplementation. The review also considered in-house literature databases, a single-window search at Kasturba Medical College (KMC) Health sciences library, MAHE (Manipal Academy of Higher Education). The figures included in the study were created by Biorender.com. Micronutrients play multiple roles during pregnancy and fetoplacental growth stimulating growth hormone secretion, Lysyl oxidase (LOX), involved in the crosslinking between collagen and elastin in the amniotic membrane, downregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, Il-10, IL-12, tumor necrosis factor (TNF)-alpha and several chemokines involved in hypertension, immune-inflammatory pathways, attenuate insulin resistance, structural development of neurons and glia. Over-supplementation has led to complications such as spontaneous abortion and gestational diabetes mellitus. Since there is a lack of standardization concerning micronutrient supplementation during pregnancy, there is a need for systematic study related to the role of micronutrients during each trimester of pregnancy to optimize its supplementation and to prevent hazards associated with its abuse.

Associations between Maternal Iron Supplementation in Pregnancy and Changes in Offspring Size at Birth Reflect Those of Multiple Micronutrient Supplementation.

It was previously observed that in a population of a high-income country, dietary multiple micronutrient supplementation in pregnancy was associated with an increased risk of gestational diabetes (GDM) and increased offspring size at birth. In this follow-up study, we investigated whether similar changes are observed with dietary iron supplementation. For this we used the prospective Cambridge Baby Growth Study with records of maternal GDM status, nutrient supplementation, and extensive offspring birth size measurements. Maternal iron supplementation in pregnancy was associated with GDM development (risk ratio 1.67 (1.01-2.77), p = 0.048, n = 677) as well as offspring size and adiposity (n = 844-868) at birth in terms of weight (ß' = 0.078 (0.024-0.133); p = 0.005), head circumference (ß' = 0.060 (0.012-0.107); p = 0.02), body mass index (ß' = 0.067 (0.014-0.119); p = 0.01), and various skinfold thicknesses (ß' = 0.067-0.094; p = 0.03-0.003). In a subset of participants for whom GDM statuses were available, all these associations were attenuated by adjusting for GDM. Iron supplementation also attenuated the associations between multiple micronutrient supplementation and these same measures. These results suggest that iron supplementation may mediate the effects associated with multiple micronutrient supplementation in pregnancy in a high-income country, possibly through the increased risk of developing GDM.

Effect of Fortification with Multiple Micronutrient Powder on the Prevention and Treatment of Iron Deficiency and Anaemia in Brazilian Children: A Randomized Clinical Trial.

Fortification with multiple micronutrient powder has been proposed as a public health intervention able to reduce micronutrient deficiencies in children. Our objective was to compare the effectiveness of fortification with multiple micronutrient powder with drug supplementation in the prevention and treatment of iron deficiency and anaemia. This was a cluster trial with anemic and non-anaemic children between six and 42 months old, in randomization data. Non anaemic children received fortification with multiple micronutrient powder or standard drug supplementation of ferrous sulfate associated with folic acid in a prevention dose. Anaemic children who were randomized to receive multiple micronutrient powder also received the recommended iron complementation for anaemia treatment. A total of 162 children were evaluated. The prevalence of anaemia decreased from 13.58 to 1.85%. Iron deficiency decreased from 21.74% to 7.89% (by serum ferritin) and iron deficiency decreased from 66.81 to 38.27% (by soluble transferrin receptor). No difference was identified between interventions for hemoglobin (p = 0.142), serum ferritin (p = 0.288), and soluble transferrin receptor (p = 0.156). Fortification with multiple micronutrient powder was effective in preventing iron deficiency and anaemia in children aged six to 48 months. In anaemic children; it was necessary to supplement the dose of multiple micronutrient powder with ferrous sulfate.

Dietary nutrients and their control of the redox bioenergetic networks as therapeutics in redox dysfunctions sustained pathologies.

Electrons exchange amongst the chemical species in an organism is a pivotal concomitant activity carried out by individual cells for basic cellular processes and continuously contribute towards the maintenance of bioenergetic networks plus physiological attributes like cell growth, phenotypic differences and nutritional adaptations. Humans exchange matter and energy via complex connections of metabolic pathways (redox reactions) amongst cells being a thermodynamically open system. Usually, these reactions are the real lifeline and driving forces of health and disease in the living entity. Many shreds of evidence support the secondary role of reactive species in the cellular process of control apoptosis and proliferation. Disrupted redox mechanisms are seen in malaises, like degenerative and metabolic disorders, cancerous cells. This review targets the importance of redox reactions in the body's normal functioning and the effects of its alterations in cells to obtain a better understanding. Understanding the redox dynamics in a pathological state can provide an opportunity for cure or diagnosis at the earlier stage and serve as an essential biomarker to predict in advance to give personalized therapy. Understanding redox metabolism can also highlight the use of naturally available antioxidant in the form of diet.

Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.

A Pilot Randomized Treatment-Controlled Trial Comparing Vitamin B6 with Broad-Spectrum Micronutrients for Premenstrual Syndrome.

Objective: Premenstrual syndrome (PMS) affects 20%-30% of women but current medical treatments are limited in their efficacy. The objective of this study was to compare efficacy of a broad-spectrum micronutrient formula (consisting mainly of minerals and vitamins) to a single vitamin (B6) for treatment of PMS, for which B6 has already been shown to be efficacious. Methods: This double-blind, randomized, treatment-controlled trial allocated 78 (72 completed) regularly menstruating women with PMS to consume micronutrients or vitamin B6 (80 mg/day) daily following a two-cycle baseline period, for three menstrual cycles. The primary outcome measure, Daily Record of Severity of Problems (DRSP), established PMS as well as tracked change in five PMS symptoms: psychological, somatic, total symptoms, impact ratings, and worst day ratings. Results: Linear-mixed model analyses indicated both treatments produced comparable reduction in PMS symptoms with medium effect sizes (ES) across all PMS variables as measured by the DRSP (micronutrient ES = 0.50-0.56; B6 ES = 0.43-0.56), with 72% of the micronutrient and 60% of the vitamin B6 group identified as in full remission in PMS symptoms after three cycles. The micronutrient-treated participants showed greater improvement than the B6 group (between group d = 0.51, p < 0.05) in health-related quality of life. For those women (n = 28) who met criteria for premenstrual dysphoric disorder (PMDD), the DRSP ES were larger for those who had been in the micronutrient condition (ES = 1.28-1.67) as compared with those on B6 (ES = 0.50-0.75), although the group differences were not statistically reliable. There were no group differences in side effects, nor any serious adverse effects reported. Conclusions: Both treatments provided similar benefit for reducing PMS symptoms, with greater effect of micronutrients on quality of life as well as potential clinical benefit of micronutrients for PMDD. This study provides further efficacy data on B6 and also identifies the nutritionally broader spectrum intervention as possibly having specific advantages for those whose symptoms are more severe. As this is the first study to investigate these treatments for PMDD, systematic replication is required.

Impact of multi-micronutrient supplementation on lipidemia of children and adolescents.

BACKGROUND: Micronutrient supplementation has been extensively explored as a strategy to improve health and reduce risk of chronic diseases. Fat-soluble vitamins like A and E with their antioxidant properties and mechanistic interactions with lipoproteins, have potentially a key impact on lipid metabolism and lipidemia. OBJECTIVE: The impact of micronutrients on lipid metabolism requires further investigation including characterization of plasma lipidome following supplementation and any cause-effect on circulating lipids. DESIGN: In this study, we elucidate the effect and associations of a multi-micronutrient intervention in Brazilian children and teens with lipoprotein alterations and lipid metabolism. RESULTS: Our analysis suggests a combination of short and long-term impact of supplementation on lipid metabolism, potentially mediated primarily by α-tocopherol (vitamin E) and retinol (vitamin A). Among the lipid classes, levels of phospholipids, lysophospholipids, and cholesterol esters were impacted the most along with differential incorporation of stearic, palmitic, oleic and arachidonic acids. Integrated analysis with proteomic data suggested potential links to supplementation-mediated alterations in protein levels of phospholipases and pyruvate dehydrogenase kinase 1 (PDK1). CONCLUSIONS: Associations between the observed differences in lipidemia, total triglyceride, and VLDL-cholesterol levels suggest that micronutrients may play a role in reducing these risk factors for cardiovascular disease in children. This would require further investigation.

Diabetes, Diabetic Complications, and Phosphate Toxicity: A Scoping Review.

This article presents a scoping review and synthesis of research findings investigating the toxic cellular accumulation of dysregulated inorganic phosphate-phosphate toxicity-as a pathophysiological determinant of diabetes and diabetic complications. Phosphorus, an essential micronutrient, is closely linked to the cellular metabolism of glucose for energy production, and serum inorganic phosphate is often transported into cells along with glucose during insulin therapy. Mitochondrial dysfunction and apoptosis, endoplasmic reticulum stress, neuronal degeneration, and pancreatic cancer are associated with dysregulated levels of phosphate in diabetes. Ectopic calcification involving deposition of calcium-phosphate crystals is prevalent throughout diabetic complications, including vascular calcification, nephropathy, retinopathy, and bone disorders. A low-glycemic, low-phosphate dietary intervention is proposed for further investigations in the treatment and prevention of diabetes and related diabetic pathologies.

The ABCs of Nutrient Deficiencies and Toxicities.

Vitamins and minerals are part of a well-balanced diet. They are essential for normal growth and development, which is especially crucial for the pediatric population. Vitamins are divided based on their solubility into fat-soluble vitamins, which include vitamins A, D, E, and K and water-soluble vitamins, which include the B vitamins and vitamin C. Minerals include calcium, magnesium, and phosphorus. Trace minerals are micronutrients and include copper, zinc, selenium, chromium and manganese. The pediatrician is often the first health care provider to interface with patients, allowing them to pick up on nutritional derangements. This article reviews the basic sources, absorption, metabolism as well as the signs and symptoms that arise in deficient and toxic states of fat-soluble vitamins, water-soluble vitamins, minerals, and trace elements. [Pediatr Ann. 2019;48(11):e434-e440.].

Geographic Atrophy and micronutritional supplements: A complex relationship.

In 2019, the Age-Related Eye Disease Study (AREDS) remains the basis for micronutritional supplement guidelines aiming to slow the progression of Age-Related Macular Degeneration (AMD) and reduce the risk of neovascularization. However, for Geographic Atrophy (GA) patients specifically, there seem to be more arguments for prescribing micronutritional supplements for the prevention of neovascular complications than to slow the progression of the atrophy. The AREDS report 8 showed a significant decrease in AMD progression over a five-year follow-up associated with a formulation containing antioxidants and zinc. It is noteworthy that the protective effect that was demonstrated was mainly related to the risk of a neovascularization and that the AREDS did not really demonstrate a protective effect that would slow the progression of GA. The 2013 AREDS II results have led to a change in the AREDS formulation. Nevertheless, the replacement of beta-carotene by lutein and zeaxanthine and the addition of Omega-3 did not add any further evidence for a protective effect on GA. Furthermore, the AREDS study used color photographs rather than fundus autofluorescence or OCT to assess the presence or the evolution of patches of atrophy. Over the last 10 years, it has been shown that OCT is far more accurate than color photographs to measure the size of the atrophic areas and to evaluate the extent of alterations in the chorioretinal layers. While lack of evidence of a protective effect of the AREDS formulation for GA is not a proof of the absence of effect, many publications seem to have taken the results of the AREDS in such a global way that the lack of evidence concerning GA seems to have been ignored. Micronutrition supplements are well prescribed for AMD patients, and the key factor for adherence is explanation to the patient. So far, it appears worth explaining to GA patients that prescription of the AREDS formulation is mainly aimed at reducing the risk of neovascularization.

Effect of Micronutrient Powder (MNP) with a Low-Dose of Iron on Hemoglobin and Iron Biomarkers, and Its Effect on Morbidities in Rural Bangladeshi Children Drinking Groundwater with a High-Level of Iron: A Randomized Controlled Trial.

Micronutrient Powder (MNP) is beneficial to control anemia, but some iron-related side-effects are common. A high level of iron in the groundwater used for drinking may exacerbate the side-effects among MNP users. We conducted a randomized controlled trial examining the effect of a low-dose iron MNP compared with the standard MNP in children aged 2-5 years residing in a high-groundwater-iron area in rural Bangladesh. We randomized 327 children, who were drinking from the "high-iron" wells (≥2 mg/L), to receive either standard (12.5 mg iron) or low-dose iron (5.0 mg iron) MNP, one sachet per day for two months. Iron parameters were measured both at baseline and end-point. The children were monitored weekly for morbidities. A generalized linear model was used to determine the treatment effect of the low-dose iron MNP. Poisson regressions were used to determine the incidence rate ratios of the morbidities. The trial was registered at ISRCTN60058115. Changes in the prevalence of anemia (defined as a hemoglobin level < 11.0 g/dL) were 5.4% (baseline) to 1.0% (end-point) in the standard MNP; and 5.8% (baseline) to 2.5% (end-point) in the low-dose iron MNP groups. The low-dose iron MNP was non-inferior to the standard MNP on hemoglobin outcome (ß = -0.14, 95% CI: -0.30, 0.013; p = 0.07). It resulted in a lower incidence of diarrhea (IRR = 0.29, p = 0.01, 95% CI: 0.11-0.77), nausea (IRR = 0.24, p = 0.002, 95% CI: 0.09-0.59) and fever (IRR = 0.26, p < 0.001, 95% CI: 0.15-0.43) compared to the standard MNP. Low-dose iron MNP was non-inferior to the standard MNP in preventing anemia yet demonstrated an added advantage of lowering the key side-effects.

Associations between dietary micronutrient intake and molecular-Bacterial Vaginosis.

OBJECTIVES: Bacterial vaginosis (BV), a clinical condition characterized by decreased vaginal Lactobacillus spp., is difficult to treat. We examined associations between micronutrient intake and a low-Lactobacillus vaginal microbiota as assessed by molecular methods (termed "molecular-BV"). METHODS: This cross-sectional analysis utilized data collected at the baseline visit of the Hormonal Contraception Longitudinal Study, a cohort of reproductive-aged women followed over 2 years while initiating or ceasing hormonal contraception (HC). The Block Brief 2000 Food Frequency Questionnaire was administered and micronutrient intakes were ranked. Vaginal microbiota composition was assessed using 16S rRNA gene amplicon sequencing and clustered into community state types (CSTs) based on the types and relative abundance of bacteria detected. Associations between the lowest estimated quartile intake of nutrients and having a low-Lactobacillus CST (molecular-BV) were evaluated by logistic regression. Separate models were built for each nutrient controlling for age, body mass index, behavioral factors, HC use and total energy intake. We also conducted a literature review of existing data on associations between micronutrient intakes and BV. RESULTS: Samples from 104 women were included in this analysis. Their mean age was 25.8 years (SD 4.3), 29.8% were African American, 48.1% were using HC, and 25% had molecular-BV. In adjusted multivariable analyses, the lowest quartile of betaine intake was associated with an increased odds of molecular-BV (aOR 9.2, p value < 0.01, [CI 2.4-35.0]). CONCLUSIONS: This is the first study to assess the association between estimated micronutrient intake and molecular-BV. Lower energy-adjusted intake of betaine was associated with an increased risk of molecular-BV. Betaine might have direct effects on the vaginal microenvironment or may be mediated through the gut microbiota. Additional research is needed to determine reproducibility of this finding and whether improved intake of select micronutrients such as betaine decreases the risk of BV and its sequelae.