NICEVIVA
DRUG INTERACTION RECORDED 1 Prescription Drug Interaction(s) Reported — Review the pharmacokinetic interaction matrix below before use.
Pharmacokinetic Alert
MONOGRAPH SPEC LATEST 2026

Iron (Ferrous Sulfate)

MINERALS · Evidence Monograph

Iron (Ferrous Sulfate) is an evidence-graded minerals monograph evaluated across 41 peer-reviewed PubMed studies (4 meta-analyses, 2 systematic reviews, and 10 randomized controlled trials, encompassing n = 36,860 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 41 Studies
Meta-Analyses · Reviews 4 Meta · 2 Systematic Reviews
Randomized Trials (RCT) 10 RCTs (2 Double-Blind)
Cumulative Participants n = 36,860
Reported Trial Dosages 500 mg · 1500 mg · 60 mg
Trial Duration Range 7 days · 8 weeks · 20 weeks
Reading Time ~21 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity (supported by 41 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (500 mg · 1500 mg · 60 mg) over a structured 7 days evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Amino-Acid Chelate (Bisglycinate) or Organic Citrate Salt
Avoid low-bioavailability inorganic oxides or carbonates if you have a sensitive stomach; organic chelates minimize GI irritation and transporter competition.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Smooth gastrointestinal tolerance without bloating, cramps, or osmotic loose stools.
Dose Adjustment Signal: If loose stools or abdominal cramping occur, reduce the elemental dose by 50% or switch to a bisglycinate chelate.
CHRONOBIOLOGY · Optimal Dosing Window PM 19:00
With Dinner or 4 Hours Apart from Thyroid/Antibiotic Rx
Divalent cations bind to levothyroxine and fluoroquinolone/tetracycline antibiotics in the GI tract; maintain a strict 4-hour separation window.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary minerals clinical efficacy (41 PubMed studies)
Quantitative biomarker & outcome analysis (18 studies with effect-size/sample data)
Randomized controlled trial verification (10 RCTs · 2 double-blind)
Systematic review & meta-analysis synthesis (4 meta-analyses · 2 reviews)
01

What Is Iron (Ferrous Sulfate) & Why Does Form Matter?

Iron (Ferrous Sulfate) is classified under MINERALS and has been investigated across 41 peer-reviewed PubMed publications for its role in electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (500 mg, 1500 mg, 60 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Iron (Ferrous Sulfate) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (10 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Iron (Ferrous Sulfate) acts on pathways governing electrolyte balance, neuromuscular signaling, and enzymatic cofactor activity. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Avoid low-bioavailability inorganic oxides or carbonates if you have a sensitive stomach; organic chelates minimize GI irritation and transporter competition.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Iron (Ferrous Sulfate) an overall evidence rating of GRADE High (4.0 / 4.0) based on 41 PubMed studies: 4 meta-analyses, 2 systematic reviews, and 10 randomized controlled trials (2 double-blind, n = 36,860 total participants).

Representative peer-reviewed findings include: • PMID:12075109 (2002) — "Mechanisms of 2-butoxyethanol carcinogenicity: studies on Syrian Hamster Embryo (SHE) cell transformation." (Both DNA lesions were decreased by cotreatment of ferrous sulfate with antioxidants.) • PMID:42067065 (2026) — "Effect of calcium supplementation in pregnancy on maternal anemia and iron status: Secondary analyses of two randomized trials in India and Tanzania." (CONCLUSIONS: Low- and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes.) • PMID:42061720 (2026) — "Improved iron status, but not protein source, is related to appetite, satiety, and mood in women of reproductive age with iron deficiency: a randomized controlled trial." (Changes in transferrin saturation (r = 0.4, P < 0.01) and hemoglobin (r = 0.3, P = 0.04) and hematocrit (r = 0.3, P = 0.03) were positively associated with changes in prospective food consumption, and changes in transferrin saturation were negatively associated with satiety (r = )

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)RR Effect Size & 95% CI DistributionEstimate (95% CI)PMID 420670651PMID 418620010.72 (0.58–0.9)PMID 417059960.89 (0.56–2.62)PMID 417017740.7 (0.53–0.91)0.2Null (1)5Metric: RR
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Amino-Acid Chelate (Bisglycinate) or Organic Citrate Salt. Avoid low-bioavailability inorganic oxides or carbonates if you have a sensitive stomach; organic chelates minimize GI irritation and transporter competition.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 500 mg · 1500 mg · 60 mg · 38 g over 7 days · 8 weeks · 20 weeks · 38 weeks. Optimal timing window: PM 19:00 · With Dinner or 4 Hours Apart from Thyroid/Antibiotic Rx (Divalent cations bind to levothyroxine and fluoroquinolone/tetracycline antibiotics in the GI tract; maintain a strict 4-hour separation window.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Smooth gastrointestinal tolerance without bloating, cramps, or osmotic loose stools.

Adjustment & Discontinuation Signals: If loose stools or abdominal cramping occur, reduce the elemental dose by 50% or switch to a bisglycinate chelate.

07

Prescription Drug Interactions & Contraindications

• [MODERATE] Levothyroxine: Pharmacokinetic or pharmacodynamic interaction reported in clinical literature (PMID:11131757). Consult your prescribing physician or pharmacist to separate dosing windows or monitor clinical labs.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 19:00 · With Dinner or 4 Hours Apart from Thyroid/Antibiotic Rx) with a full glass of water.
  • Stay within clinically studied daily dosages (500 mg · 1500 mg · 60 mg) and re-evaluate efficacy after 7 days.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist before use if taking Levothyroxine.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (41 Studies) · 18 Quantitative Analyses

01
CLINICAL STUDY Toxicological sciences (2002) PMID: 12075109 ↗
Mechanisms of 2-butoxyethanol carcinogenicity: studies on Syrian Hamster Embryo (SHE) cell transformation.
Clinical Trial Synthesis 2002 Clinical Study published in Toxicological sciences. Key conclusion: Both DNA lesions were decreased by cotreatment of ferrous sulfate with antioxidants.
View Original PubMed Abstract ↓

Previous studies showed that 2-butoxyethanol increased liver tumors in B6C3F1 mice following chronic exposure. While the mechanism of 2-butoxyethanol-induced liver carcinogenicity has not been defined, 2-butoxyethanol has been shown to induce hemolysis in rodents via 2-butoxyacetic acid, the major metabolite of 2-butoxyethanol. This toxic effect, coupled with the observation that continued treatment with 2-butoxyethanol results in hemosiderin deposition in the liver, has led to our hypothesis that liver carcinogenicity by 2-butoxyethnaol is mediated via oxidative stress (iron catalyzed) and Kupffer cell activation. The present study used Syrian Hamster Embryo (SHE) cell transformation, a surrogate in vitro model for carcinogenesis in vivo, to examine whether 2-butoxyethanol, 2-butoxyacetic acid, or iron (ferrous sulfate) produced cell transformation. SHE cells were treated with either 2-butoxyethanol (0.5-20 mM), 2-butoxyacetic acid (0.5-20 mM), or ferrous sulfate (0.5-75 microg/ml) for 7 days. 2-Butoxyethanol and 2-butoxyacetic acid did not induce cellular transformation. In contrast, treatment with ferrous sulfate (2.5 and 5.0 microg/ml) increased morphological transformation. Cotreatment of ferrous sulfate with the antioxidants alpha-tocopherol (vitamin E) or (-)-epigallocatechin-3-gallate (EGCG) prevented ferrous sulfate-induced transformation, suggesting the involvement of oxidative stress in SHE cell transformation. The level of oxidative DNA damage (OH8dG) increased following ferrous sulfate treatment in SHE cells; additionally, using single cell gel electrophoresis (comet assay), ferrous sulfate treatment produced an increase in DNA damage. Both DNA lesions were decreased by cotreatment of ferrous sulfate with antioxidants. These data support our proposal that iron, produced indirectly through hemolysis, and not 2-butoxyethanol or its metabolite 2-butoxyacetic acid, is responsible for the observed carcinogenicity of 2-butoxyethanol.

02
RANDOMIZED TRIAL (RCT) The American journal of clinical nutrition (2026) PMID: 42067065 ↗
Effect of calcium supplementation in pregnancy on maternal anemia and iron status: Secondary analyses of two randomized trials in India and Tanzania.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The American journal of clinical nutrition involving n = 11,000 participants (RR 1). Key conclusion: CONCLUSIONS: Low- and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes.
View Original PubMed Abstract ↓

BACKGROUND: Although recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal anemia and iron status remain unclear. OBJECTIVES: This study evaluated the effects of 500 mg daily calcium supplementation as compared to 1500 mg calcium supplementation during pregnancy on maternal anemia and iron indices. METHODS: We conducted two individually randomized, noninferiority trials in India and Tanzania (N = 11,000 each) comparing daily 500 to 1500 mg calcium supplementation during pregnancy. All participants received standard iron and folic acid (IFA) (60 mg iron) and were counseled to take calcium supplements several hours apart from the IFA. All participants had hemoglobin measured at baseline and at 32 wk of gestation, whereas a random subset of participants had ferritin quantified at the same time points. Using an intention-to-treat approach, we assessed effects of 500 mg compared with 1500 mg calcium supplementation on mean hemoglobin and inflammation-adjusted serum ferritin (log-scale) using generalized linear models, and on anemia and iron deficiency anemia using log-binomial models. RESULTS: Third-trimester hemoglobin and serum ferritin were measured in 8953 and 1336 participants in India, respectively. In Tanzania, 8496 participants had hemoglobin, and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester hemoglobin [India: mean difference (MD) 0.01 (95% confidence interval (CI): -0.03, 0.04); Tanzania: MD -0.02 (95% CI: -0.07, 0.03)], anemia [India: relative risk (RR) 1.01 (95% CI: 0.95, 1.07); Tanzania: RR 1.00 (95% CI: 0.96, 1.05)], or iron deficiency anemia [India: RR 1.20 (95% CI: 0.93, 1.57); Tanzania: RR 0.94 (95% CI: 0.77, 1.15)]. CONCLUSIONS: Low- and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of coadministering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. This trial was registered at ClinicalTr

03
RANDOMIZED TRIAL (RCT) The Journal of nutrition (2026) PMID: 42061720 ↗
Improved iron status, but not protein source, is related to appetite, satiety, and mood in women of reproductive age with iron deficiency: a randomized controlled trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The Journal of nutrition; statistical significance reported at p = 0.05. Key conclusion: Changes in transferrin saturation (r = 0.4, P < 0.01) and hemoglobin (r = 0.3, P = 0.04) and hematocrit (r = 0.3, P = 0.03) were positively associated with changes in prospective food consumption, and changes in transferrin saturation were negatively associated with satiety (r =
View Original PubMed Abstract ↓

BACKGROUND: Iron deficiency (ID) is associated with decreased appetite and altered mood, which can contribute to feelings of early satiety and reduced overall well-being. Few studies have examined differences in appetite, satiety, and mood between meals containing animal meat and plant-based meat, or whether improving iron status in those with ID improves these outcomes. OBJECTIVES: The objective of this study was to determine appetite, satiety, and mood after consumption of a meal containing animal meat or plant-based meat at baseline and after consuming the meal with an iron supplement once a day for 8 weeks in women of reproductive age (WRA) with ID. METHODS: In this randomized, double-blind, parallel-arm study, 52 nonpregnant WRA (24 ± 7 y; BMI: 22.9 ± 3.0 kg/m2) with ID (serum ferritin: 13.7 ± 6.0 μg/L) consumed an iron supplement with a lunch meal containing either 4 oz. of beef (Animal) or Beyond Meat (Plant) once a day for 8 weeks. Meals were calorically matched but differed in macro- and micronutrient composition due to the inherent differences between protein sources. For this secondary analysis, at baseline and endpoint, fasted participants consumed a standardized lunch meal containing beef or plant-based meat and rated appetite (fullness, hunger, desire to eat, and prospective consumption) using 100 mm visual analog scales. A composite satiety score was calculated. The Profile of Mood States questionnaire was assessed at baseline and endpoint. RESULTS: Indicators of iron status and anemia improved after 8 weeks (P < 0.05 for all) but did not differ between Animal and Plant. Hunger and desire to eat decreased, and fullness and composite satiety score increased after the meal (P-time < 0.0001 for all). Measures of appetite, satiety, and mood did not differ between Plant and Animal at baseline or endpoint. Changes in transferrin saturation (r = 0.4, P < 0.01) and hemoglobin (r = 0.3, P = 0.04) and hematocrit (r = 0.3, P = 0.03) were positively associated with changes in prospective food consumption, and changes in transferrin saturation were negatively associated with satiety (r = -0.3, P = 0.02). Changes in transferrin saturation (r = 0.3, P = 0.03) an

04
SYSTEMATIC REVIEW JMIR mHealth and uHealth (2026) PMID: 41955565 ↗
Effectiveness of mHealth-Based Nutritional Interventions on Iron Status of Pregnant Women: Systematic Review of Randomized Controlled Trials.
Clinical Trial Synthesis 2026 Systematic Review published in JMIR mHealth and uHealth; statistical significance reported at p = 0.33. Key conclusion: Approximately 82% (9/11) of the included studies reported a positive effect (P values ranging from <.001 to .047) of the intervention on Hb level, whereas 2 studies reported no statistically significant ass
View Original PubMed Abstract ↓

BACKGROUND: Anemia is a global health concern. It is disproportionately prevalent among pregnant women in low-resource regions, where iron deficiency is the leading cause. Given the multifactorial nature of anemia, a range of nutritional interventions is recommended. However, effective implementation is often hindered by limited health care access, poor adherence to supplementation, and gaps in nutrition knowledge and counseling. To address these challenges and optimize hemoglobin (Hb) levels among pregnant women, mobile health (mHealth)-based nutritional interventions offer a promising alternative. OBJECTIVE: The aim of the study is to review available evidence on the effectiveness of mHealth-based nutritional interventions on iron status (Hb and/or serum ferritin concentration) among pregnant women. METHODS: Searches were conducted in Embase, CINAHL, Cochrane Library, PubMed, Web of Science, and Scopus, and supplemented by snowballing to identify additional relevant studies from citation lists. The key search strings comprised 4 concepts: "mobile health," "nutritional intervention," "Hb, anemia or iron deficiency anemia," and "pregnant women." Predefined inclusion and exclusion criteria were applied during screening. The methodological quality of included studies was assessed using the Risk of Bias 2 tool. The primary end point was the change in mean Hb concentration or serum ferritin level. Effect sizes (ESs) were calculated as standardized mean differences, including Cohen d and Hedges g. RESULTS: Of the 14,284 studies identified, only 11 randomized controlled trials were included. These studies used various modes of delivery, including mobile phone calls (n=1), SMS text messaging (n=3), and mobile apps (n=4), with some using more than 2 modes (n=3). The effect of mHealth-based nutritional interventions on iron status varied significantly. In total, 4 studies demonstrated a large ES (>0.8), with 3 relying on WhatsApp Messenger as an mHealth delivery mode. Approximately 82% (9/11) of the included studies reported a positive effect (P values ranging from <.001 to .047) of the intervention on Hb level, whereas 2 studies reported no statistically significant ass

05
SYSTEMATIC REVIEW BMJ global health (2026) PMID: 41927311 ↗
The effects of antenatal interventions on gestational weight gain in low and middle-income countries: a systematic review.
Clinical Trial Synthesis 2026 Systematic Review published in BMJ global health. Key conclusion: CONCLUSIONS: Well-structured antenatal interventions, initiated before 20 weeks of gestation and continuing beyond this period, tailored to loca
View Original PubMed Abstract ↓

BACKGROUND: Gestational weight gain (GWG) during pregnancy is a critical factor that affects maternal and child health outcomes. The considerable burden of inadequate GWG and the rising tide of excessive GWG are overlooked challenges in low and middle-income countries (LMICs). METHODS: This systematic review assessed the impact of antenatal interventions on GWG in LMICs. Randomised controlled trials (RCTs) on antenatal interventions on GWG in LMICs were included. These interventions included educational, behavioural, nutritional supplementation and pharmacological therapies. A systematic literature search was conducted using PubMed, Embase, Web of Science, CINAHL and the Cochrane Library from the start of each database through September 2025. RESULTS: Out of the 33 642 unique articles identified, 70 articles were included in our systematic review, with 59 individual RCTs and 11 cluster RCTs. Nutritional interventions (31 studies) included food and micronutrient supplementations. Micronutrient supplementation such as multiple micronutrient supplementations was found to reduce the risk of severely inadequate or inadequate GWG among pregnant women compared to iron only or iron and folic acid supplementation (Grading of Recommendations Assessment, Development and Evaluation [GRADE]: moderate certainty). Food supplementation showed mixed results, although most trials demonstrated higher mean GWG among undernourished pregnant women and a greater likelihood of achieving Institute of Medicine-recommended ranges (GRADE: moderate certainty). Behavioural (counselling/education) interventions (20 studies) were associated with significant reductions in excessive GWG among pregnant women with overweight or obesity and improved adequacy of GWG (GRADE: moderate certainty). Physical activity (seven studies) was found to reduce the risk of excessive GWG (GRADE: moderate certainty). Combined dietary and physical activity interventions (six studies) were found to reduce the risk of excessive GWG among pregnant women (GRADE: low certainty). CONCLUSIONS: Well-structured antenatal interventions, initiated before 20 weeks of gestation and continuing beyond this period, tailored to loca

06
RANDOMIZED TRIAL (RCT) The Lancet. Global health (2026) PMID: 41871585 ↗
Effect on birthweight of an antenatal multiple micronutrient supplementation programme compared with iron-folic acid supplementation: a cluster-randomised, controlled trial in 85 698 Ethiopian women.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The Lancet. Global health. Key conclusion: INTERPRETATION: The findings of this trial are consistent with those from efficacy trials in other settings, indicating that the transition from IFA to MMS as part of routine antenatal care in Ethiopia could lead to a small but clear improvement in birthweig
View Original PubMed Abstract ↓

BACKGROUND: Prenatal multiple micronutrient supplementation (MMS) including iron, folic acid, and other essential micronutrients, has shown potential to improve birth outcomes in controlled studies. We did an effectiveness study in Ethiopia to determine the effect on mean birthweight of MMS provided as part of routine antenatal care, relative to iron-folic acid supplementation (IFA). METHODS: A pragmatic, two-arm, facility-based, cluster-randomised controlled trial was conducted across 42 districts in five regions of Ethiopia to determine the effect on birthweight of MMS relative to IFA. Districts were randomly assigned to either retain IFA as part of routine antenatal care or switch to MMS. Randomisation was stratified by region and done using a random number generator within statistical software. All live singleton births at participating health facilities were eligible for inclusion and birthweights were recorded. Additionally, data were collected on maternal receipt and utilisation of MMS or IFA. The primary outcome was birthweight, analysed in the intention-to-treat population. This completed trial is registered at ClinicalTrials.gov, NCT05708183. FINDINGS: Between Jan 1, 2023, and Dec 31, 2024, birthweights were recorded for 47 325 babies in the 21 IFA districts and 36 473 babies in the 21 MMS districts. Mean age of mothers was 26·2 years (SD 5·3) and median gestational age of babies at birth was 38 weeks (IQR 38-39). The effect of MMS on birthweight was a mean increase of 38 g (95% CI 20-55) in the MMS arm relative to the IFA arm after adjustment for time, geographical region stratification factor, gestational age, sex of baby, and parity. Among women who reported taking at least 90 tablets of their assigned supplement, the increase in mean birthweight in the MMS arm relative to the IFA arm was 58 g (38-79). Stillbirth risk was 7·5 per 1000 births in the IFA arm and 6·9 per 1000 births in the MMS arm. INTERPRETATION: The findings of this trial are consistent with those from efficacy trials in other settings, indicating that the transition from IFA to MMS as part of routine antenatal care in Ethiopia could lead to a small but clear improvement in birthweig

07
RANDOMIZED TRIAL (RCT) The American journal of clinical nutrition (2026) PMID: 41862001 ↗
Comparative efficacy of biweekly preventive supplementation, with multiple micronutrients and iron folic acid or iron folic acid alone, on hemoglobin concentrations and anemia prevalence in children aged 6-59 months: a randomized controlled trial in rural India.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The American journal of clinical nutrition involving n = 1,300 participants (RR 0.72). Key conclusion: Lack of improvement in biochemical markers and a small rise in hemoglobin concentrations suggest that a reduction in the prevalence of anemia may be driven by shifts near diagnostic thresholds, rather than meaningful physiological benefits.
View Original PubMed Abstract ↓

BACKGROUND: Anemia affects more than two-thirds of children aged <5 y in India, despite biweekly iron folic acid (IFA) supplementation under the Anemia Mukt Bharat national program. Multiple micronutrient (MMN) deficiencies may also contribute to the presence of anemia, but the incremental benefit of MMN supplementation in addition to IFA remains unclear. OBJECTIVES: We aimed to compare the efficacy of biweekly preventive supplementation with MMNs plus IFA compared with IFA alone on hemoglobin concentrations and prevalence of anemia in children aged 6-59 mo. METHODS: In this individually randomized, open-label trial, eligible children received biweekly supplementation with either MMN plus IFA (intervention) or IFA alone (control) for 100 doses over 50 wk. Primary outcomes were mean hemoglobin concentration and anemia prevalence. Secondary outcomes included serum ferritin, soluble transferrin receptor, vitamin B12, folate, and zinc. RESULTS: Among 1300 children enrolled (648 intervention and 652 control), supplementation compliance exceeded 75%. At the endline, the mean hemoglobin was slightly higher in the intervention group [adjusted mean difference, 0.12 g/dL; 95% confidence interval (CI): 0.00, 0.25]. The prevalence of anemia was 17.6% in the intervention group and 24.0% in the control group (adjusted relative risk, 0.72; 95% CI: 0.58, 0.90). No significant differences were observed in serum biomarkers of iron status or other micronutrients. CONCLUSIONS: Biweekly supplementation with MMN plus IFA resulted in a modest increase in hemoglobin concentrations and a relative reduction in anemia prevalence compared with IFA alone, particularly in older children. Lack of improvement in biochemical markers and a small rise in hemoglobin concentrations suggest that a reduction in the prevalence of anemia may be driven by shifts near diagnostic thresholds, rather than meaningful physiological benefits. MMN adds minimal value where IFA adherence is already high. The study was registered at Clinical Trial Registry of India as #CTRI/2020/10/028299 (https://ctri.nic.in/Clinicaltrials/login.php).

08
META-ANALYSIS Reviews on recent clinical trials (2026) PMID: 41832627 ↗
Comparative Effectiveness of Pharmacological and Non-pharmacological Therapies for ADHD: A Systematic Review and Meta-analysis of Randomized Controlled Trials (2008-2023).
Clinical Trial Synthesis 2026 Meta-Analysis published in Reviews on recent clinical trials. Key conclusion: Non-stimulants, such as viloxazine and guanfacine, showed significant improvements on ADHD-RS scores, but these improvements were only clinically modest.
View Original PubMed Abstract ↓

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition that affects attention, impulse control, and the ability to remain still. These challenges can make it harder for individuals with ADHD to succeed at school, work, and in social situations. Stimulant medications, such as methylphenidate and amphetamines, are commonly used as first-line treatments and are effective at reducing symptoms. However, their use can be limited by side effects, such as insomnia, appetite loss, cardiovascular risks, potential for misuse, and variability in individual response. Since current treatments have drawbacks, many people are exploring nonstimulant options, such as behavioral therapy, dietary changes, and neurofeedback. These approaches may be safer and easier to maintain, but research on their effectiveness remains uncertain. This systematic review and meta-analysis aim to compare the effectiveness of pharmacological and nonpharmacological therapies for ADHD. METHOD: We systematically searched PubMed, PsycINFO, Cochrane Library, ClinicalTrials.gov, and IEEE Xplore for randomized controlled trials (2008-2023) evaluating pharmacological (e.g., stimulant medications), non-pharmacological (e.g., behavioral therapy, cognitive training), or combined interventions in children and adolescents with ADHD. The search yielded 318 records. After screening titles and abstracts, 249 were excluded. Sixty-nine full-text articles were assessed, and 18 RCTs met the inclusion criteria for analysis. Primary outcomes were reductions in ADHD symptoms measured by standardized rating scales; secondary outcomes included academic performance, social functioning, and clinical global impression. RESULTS: Eighteen RCTs were pooled. ADHD symptoms were consistently reduced with stimulant medications (methylphenidate and amphetamines), although effects on academic performance were modest. Non-stimulants, such as viloxazine and guanfacine, showed significant improvements on ADHD-RS scores, but these improvements were only clinically modest. In contrast, some nutritional supplements, particularly iron and omega-3 fatty acids, showed more pronounced benefits in sympt

09
RANDOMIZED TRIAL (RCT) The American journal of clinical nutrition (2026) PMID: 41831611 ↗
Preconception micronutrient supplementation positively affects offspring perceptual reasoning at 10-11 years of age: follow-up of a randomized controlled trial in Vietnam.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The American journal of clinical nutrition involving n = 1,599 participants. Key conclusion: CONCLUSIONS: Preconception MM and IFA supplementation improved certain a
View Original PubMed Abstract ↓

BACKGROUND: Maternal periconceptional nutrition is important for birth outcomes, but few studies examine long-term effects on offspring growth and development. OBJECTIVES: We assessed the impact of weekly preconception multiple micronutrients (MM) or iron and folic acid (IFA) supplements compared to folic acid (FA) alone, on cognitive function and nutritional status at 10-11 y. We also examined associations with early-life biological and socioenvironmental factors. METHODS: We conducted a follow-up study of 1599 children from a preconception randomized trial in Vietnam, in which females received weekly FA, IFA, or MM before conception and daily IFA during pregnancy. We assessed cognitive function, academic achievement, and nutritional status at ages 10-11 y. Early biological factors included maternal nutritional status, birth characteristics, and postnatal linear growth; socioenvironmental variables were maternal schooling, ethnicity, depression, infant feeding, socioeconomic status (SES), and home environment. Analyses used intention-to-treat and per protocol comparisons with inverse-probability-of-censoring weights to account for loss to follow-up. RESULTS: Offspring in the MM and IFA groups had higher perceptual reasoning scores than the FA group {mean difference [95% confidence interval (CI): MM: 1.68 (0.01, 3.35); IFA: 2.04 (0.33, 3.74)]}. The IFA groups also had higher reading scores [0.78 (0.11, 1.44)] and lower anemia prevalence [-4.26 (-7.60, -0.91)]. No differences were observed in full-scale intelligence quotient (FSIQ) or anthropometric measures. Maternal underweight was negatively associated with FSIQ [β (95% CI): -1.62 (-3.06, -0.18)] and reading scores [-0.59 (-1.12, -0.06)] whereas postnatal linear growth was positively associated with FSIQ [1.67 (0.91, 2.43)], mathematics [0.36 (0.12, 0.61)], and reading scores [0.47 (0.21, 0.74)]. Maternal schooling, home environment, SES, were also linked to improved cognitive and academic outcomes [β range: 0.64 (0.01, 1.27) to 8.89 (5.20, 12.58)], and exclusive breastfeeding was linked with higher mathematics scores [0.73 (0.27, 1.19)]. CONCLUSIONS: Preconception MM and IFA supplementation improved certain a

10
RANDOMIZED TRIAL (RCT) The Journal of nutrition (2026) PMID: 41825741 ↗
Effect of 2-Year Caloric Restriction in the Absence of Malnutrition on Indicators of Anemia, Iron Status, and Hepcidin in Healthy Adults: A Randomized Clinical Trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in The Journal of nutrition involving n = 220 participants; statistical significance reported at p = 0.05. Key conclusion: OBJECTIVES: To determine the effects of a 2-y CR intervention on markers of anemia, iron status, and hepcidin in females and males enrolled in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 2 trial.
View Original PubMed Abstract ↓

BACKGROUND: Caloric restriction (CR) is a promising nutritional intervention for improving metabolic and age-related health outcomes, but its long-term effects on hematologic health remain unclear. Clarifying how prolonged CR affects anemia risk and iron status is essential for evaluating its long-term safety and clinical relevance. OBJECTIVES: To determine the effects of a 2-y CR intervention on markers of anemia, iron status, and hepcidin in females and males enrolled in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 2 trial. METHODS: Participants in CALERIE Phase 2 (n = 220) were randomly assigned to 25% CR or ad libitum (AL) control. AL continued their habitual diet, whereas CR received an intensive intervention to promote CR over 2 y. All participants received a multivitamin/mineral supplement containing 18 mg iron. Fasted blood was collected at baseline (BL) and 12 (M12) and 24 (M24) mo and indicators of iron status (ferritin, soluble transferrin receptor, and serum iron), anemia (hemoglobin and hematocrit), and regulators of iron status (hepcidin, C-reactive protein, and IL-6) were measured. Six-day diet diaries were collected twice at BL and once each at M12 and M24. An anemia surveillance protocol monitored hemoglobin, hematocrit, red blood cell (RBC) count, and serum iron throughout the intervention, with medical evaluation and temporary/permanent CR discontinuation as needed. Linear mixed-effects models were used to evaluate the effect of treatment (CR compared with AL), time (BL, M12, and M24), and their interaction (treatment × time). RESULTS: Participants (n = 218) were mostly female (70%) with an mean age (±SD) of 38.1 ± 7.2 y and a mean BMI of 25.2 ± 1.7 kg/m2. At baseline, ferritin (105.5 ± 126.9 μg/L), hepcidin (8.6 ± 5.8 ng/mL), and dietary iron intake (16.1 ± 5.5 mg/d) were similar between groups (P > 0.05). There were no group × time interactions for markers of anemia, indicators of iron status, or hepcidin (P > 0.05). Despite the anemia surveillance protocol, anemia prevalence remained >5% in both groups across all timepoints. Low RBC count was the most common trigger, and participants who tri

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