Risk of Anemia and Effects of Oral Iron Therapy in Non-Anemic Iron-Deficient Women (18-55 Years) (NAID-F)

November 23, 2025 updated by: Osman Demir, MD, Istanbul University - Cerrahpasa

Risk of Anemia Development and Clinical Effects of Oral Iron Therapy in Women (18-55 Years) With Non-Anemic Iron Deficiency

This study investigates the risk of anemia development in women aged 18-55 years with non-anemic iron deficiency and evaluates the clinical effects of oral iron therapy. The study consists of a two-month nutritional intervention phase followed by a one-month oral iron treatment phase. Participants first receive dietary counseling aimed at increasing iron intake and absorption. After two months, changes in hematologic parameters and symptoms are evaluated. Women with persistent iron deficiency then receive daily oral ferrous sulfate (80 mg elemental iron) for one month. The study aims to identify early predictors of anemia progression and to assess the impact of dietary modification and oral iron therapy on symptoms and laboratory findings.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study examines the risk of anemia development in women aged 18-55 years with non-anemic iron deficiency (NAID) and evaluates the clinical effects of oral iron therapy in those with persistent deficiency. The objective is to characterize individual and clinical factors associated with progression toward anemia and to assess the impact of nutritional modification and subsequent iron supplementation on hematologic and symptom-based outcomes.

Iron deficiency is one of the most common nutritional deficiencies globally. NAID often remains unrecognized despite its potential to cause fatigue, decreased physical performance, and progression to anemia if untreated. Iron plays a key role in oxygen transport, DNA synthesis, and muscle metabolism. Dietary intake includes both heme (animal-derived) and non-heme (plant-derived) forms with differing bioavailability. Ferritin is the primary biomarker used to diagnose iron deficiency, though inflammatory conditions may influence its accuracy. A careful differential evaluation is important to distinguish NAID from other causes of anemia such as chronic disease, B12 or folate deficiency, thalassemia syndromes, thyroid disorders, or gastrointestinal blood loss.

The study uses a two-phase, single-center prospective design at Kağıthane 5 No'lu Family Health Center (ASM), Istanbul, Turkey, conducted under ethics committee approval and institutional permission. In the initial two-month observational phase, participants receive standardized dietary counseling aimed at increasing iron intake and improving absorption. Health status and adherence are monitored biweekly. After this period, participants are categorized into four groups according to hematologic changes: isolated iron deficiency; microcytosis/hypochromia with minimal hemoglobin decline (<1 g/dL) ; greater hemoglobin decline without meeting anemia thresholds; or overt iron deficiency anemia.

In the subsequent one-month experimental phase, participants with persistent deficiency receive oral ferrous sulfate providing 80 mg elemental iron daily. Clinical and laboratory evaluations are performed at designated time points to assess changes in complete blood count parameters, ferritin, serum iron indices, inflammatory markers, and patient-reported symptoms.

Primary outcomes include changes in symptom scores, while secondary outcomes evaluate hematologic and biochemical responses. Planned analyses explore associations between baseline characteristics, dietary habits, and anemia progression. Power analysis using repeated measures ANOVA indicated a required sample size of 60 participants.

This research highlights the importance of individualized management strategies for iron deficiency, aiming to support appropriate use of supplementation while reducing unnecessary treatment and potential adverse effects. Enhancing dietary iron intake may help prevent anemia progression, promote patient safety, and improve resource utilization in primary care settings.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Turkey (Türkiye)
    • Istanbul
      • Kâğıthane, Istanbul, Turkey (Türkiye), 34413
        • Recruiting
        • Kagıthane No. 5 Family Health Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Osman Demir, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female participants aged 18-55 years (including premenopausal and menopausal women).
  • Normal hemoglobin level (≥ 12 g/dL).
  • Serum ferritin < 15 μg/L (WHO criteria for iron deficiency).
  • Mentzer index > 13.
  • Normal levels of vitamin B12, folic acid, thyroid hormones (TSH and sT4), and C-reactive protein (CRP < 5 mg/L).
  • Non-anemic iron deficiency confirmed by laboratory results.
  • Good general health and cognitive capacity to provide informed consent.
  • Willingness to participate, comply with study procedures, and provide written informed consent.

Exclusion Criteria:

  • Pregnancy or postpartum period.
  • Acute or chronic infections.
  • History or suspicion of malignancy.
  • Chronic inflammatory or autoimmune diseases.
  • Chronic fatigue syndrome or depressive disorders.
  • Chronic kidney disease or renal failure (acute or chronic).
  • Congestive heart failure, ischemic heart disease, or cerebrovascular disease.
  • Coagulopathy or clinically significant bleeding tendency.
  • Hematological disorders (e.g., thalassemia, hemoglobinopathies).
  • Postoperative patients, transplant recipients, or dialysis patients.
  • Currently using any form of iron supplementation or treatment.
  • Any condition that, in the investigator's opinion, may interfere with the participant's safety or the interpretation of study results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ARM 1 - Nutritional Intervention with Post-Intervention Subgrouping

All participants (N=60) begin with isolated non-anemic iron deficiency and receive a 2-month standardized nutritional intervention to improve iron intake and absorption. Afterward, participants are stratified into five subgroups (ARM1-0 to ARM1-4) based on hematologic response. Subgroups ARM1-1 to ARM1-4 represent persistent deficiency (ferritin <15 µg/L with normal CRP) and will receive oral elemental iron.

  • ARM1-0: Normalized or maintained iron status (no deficiency) - no iron therapy administered.
  • ARM1-1: Persistent isolated iron deficiency - receives oral elemental iron.
  • ARM1-2: Minimal hemoglobin decline (<1 g/dL) with microcytosis/hypochromia - receives oral elemental iron.
  • ARM1-3: Hemoglobin decline >1 g/dL but above anemia threshold, with microcytosis/hypochromia - receives oral elemental iron.
  • ARM1-4: Overt iron deficiency anemia - receives oral elemental iron.
Other: Dietary Intervention (2 months)
A two-month nutritional counseling program for all participants (N = 60) with isolated non-anemic iron deficiency. The program emphasized the inclusion of iron-rich foods (both heme and non-heme sources), the use of enhancers of iron absorption (such as vitamin C), and practical strategies to reduce absorption inhibitors (e.g., limiting tea and coffee consumption around meals, reviewing antacid use). Participants received biweekly phone follow-ups to monitor adherence and assess symptoms.
Other Names:
  • Nutritional Intervention (2 months)
Drug: Oral Elemental Iron (Ferrous Sulfate) 80 mg/day
One-month oral therapy with 80 mg elemental iron (ferrous sulfate) daily for participants with persistent iron deficiency after the nutritional phase (ferritin < 15 µg/L). Biweekly phone follow-up for adherence and symptom checks. Adherence and side effects monitored at clinic visit or by phone.
Other Names:
  • Oral Iron Intervention (1 month)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Patient-Reported Iron Deficiency Symptom Scores After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy
Time Frame: Baseline, Week 8 (post-nutritional intervention), Week 12 (post-oral iron therapy)
Change in patient-reported symptoms including fatigue, weakness, dizziness, and cognitive function etc. measured at baseline, after 2-month nutritional intervention, and after 1-month oral iron therapy.
Baseline, Week 8 (post-nutritional intervention), Week 12 (post-oral iron therapy)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in Hemoglobin and Red Blood Cell Indices After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy
Time Frame: Baseline, Week 8, Week 12
Hemoglobin, hematocrit, MCV, MCH, MCHC, and ferritin measured at baseline, Week 8, and Week 12.
Baseline, Week 8, Week 12
Change from Baseline in Serum Iron and Total Iron Binding Capacity After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy
Time Frame: Baseline, Week 8, Week 12
Serum iron, TIBC, and ferritin measured at baseline, Week 8, and Week 12.
Baseline, Week 8, Week 12
Incidence of Progression to Anemia After 2-Month Nutritional Intervention
Time Frame: Baseline to Week 8
Number and proportion of participants who progress from non-anemic iron deficiency (baseline Hb ≥12 g/dL) to anemia (Hb <12 g/dL) measured at Week 8 (post-nutritional intervention). This outcome assesses the short-term risk of anemia development despite dietary counseling focused on iron-rich foods and absorption enhancement.
Baseline to Week 8
Proportion of Participants Demonstrating Hematologic Response to 1-Month Oral Iron Therapy (Hb increase ≥1.0 g/dL)
Time Frame: Week 8 to Week 12
Proportion of participants with an increase in hemoglobin ≥1.0 g/dL between Week 8 (pre-treatment) and Week 12 (post-treatment). Hematologic response defined as hemoglobin increase ≥1.0 g/dL after 1-month oral ferrous sulfate (80 mg/day elemental iron) therapy.
Week 8 to Week 12
Proportion of Participants Demonstrating Ferritin Response to 1-Month Oral Iron Therapy (Ferritin increase ≥15 µg/L or ≥30 µg/L absolute)
Time Frame: Week 8 to Week 12
Proportion of participants with ferritin increase ≥15 µg/L from Week 8 to Week 12, or achieving ferritin ≥30 µg/L at Week 12. Biochemical response reflecting iron store replenishment after oral iron therapy, measured by increase in serum ferritin.
Week 8 to Week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adherence to Nutritional Intervention Over 2 Months
Time Frame: Week 0 to Week 8
Participant adherence to dietary counseling measured via food logs and biweekly phone calls.
Week 0 to Week 8
Adherence to Oral Iron Therapy Over 1 Month
Time Frame: Week 8 to Week 12
Compliance with daily oral iron (ferrous sulfate 80 mg/day) assessed by pill count and self-report.
Week 8 to Week 12
Incidence of Treatment-Related Adverse Events During 1-Month Oral Iron Therapy
Time Frame: Week 8 to Week 12
Gastrointestinal or other adverse events reported during oral iron therapy.
Week 8 to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istanbul University - Cerrahpasa

Investigators

  • Principal Investigator: Osman Demir, MD, Kağıthane No.5 Family Health Center, Istanbul, Turkey
  • Study Director: Ayşen Fenercioğlu, Assoc Prof, Istanbul University - Cerrahpasa, Cerrahpasa Faculty of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2025

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

February 28, 2026

Study Registration Dates

First Submitted

November 16, 2025

First Submitted That Met QC Criteria

November 23, 2025

First Posted (Estimated)

December 4, 2025

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

November 23, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-KAEK-22
  • E-14028348-302.14.02-985103 (Other Identifier: Istanbul Univ. Cerrahpasa Fac. of Medicine)
  • E-15916306-604.01-281470566 (Other Identifier: Istanbul Provincial Health Directorate)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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