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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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.
• Препарат 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.

Первичные конечные точки

• Change from Baseline in Patient-Reported Iron Deficiency Symptom Scores After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy [Срок оценки: Baseline, Week 8 (post-nutritional intervention), Week 12 (post-oral iron therapy)]

Вторичные конечные точки (5)

• Change from Baseline in Hemoglobin and Red Blood Cell Indices After 2-Month Nutritional Intervention and 1-Month Oral Iron Therapy [Срок оценки: 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 [Срок оценки: Baseline, Week 8, Week 12]
• Incidence of Progression to Anemia After 2-Month Nutritional Intervention [Срок оценки: Baseline to Week 8]
• Proportion of Participants Demonstrating Hematologic Response to 1-Month Oral Iron Therapy (Hb increase ≥1.0 g/dL) [Срок оценки: 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) [Срок оценки: Week 8 to Week 12]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Turkey (Türkiye) · 1 центр

• Kagıthane No. 5 Family Health Center — Kâğıthane

Публикации

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• Stefan MW, Gundermann DM, Sharp MH, Jennings BA, Gheith RH, Lowery RP, LowDog T, Ghatak SB, Barbosa J, Wilson JM. Assessment of the Efficacy of a Low-Dose Iron Supplement in Restoring Iron Levels to Normal Range among Healthy Premenopausal Women with Iron Deficiency without Anemia. Nutrients. 2023 Jun 3;15(11):2620. doi: 10.3390/nu15112620. PMID 37299583
• Nemeth E, Ganz T. Hepcidin and Iron in Health and Disease. Annu Rev Med. 2023 Jan 27;74:261-277. doi: 10.1146/annurev-med-043021-032816. Epub 2022 Jul 29. PMID 35905974
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Идентификаторы

NCT: NCT07263529 · 2024-KAEK-22 · E-14028348-302.14.02-985103 · E-15916306-604.01-281470566

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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