Daily Single-Dose Iron Supplementation May Work Best for Women with Anemia

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Daily single-dose iron supplementation was more effective and better tolerated than alternate-day or twice-daily regimens for treating iron-deficiency anemia in premenopausal women. Alternate-day dosing resulted in less improvement in hemoglobin and ferritin levels compared with daily regimens, and twice-daily treatment demonstrated the highest rates of gastrointestinal side effects.

Iron-deficiency anemia — defined as hemoglobin levels below 11.5 grams per deciliter and ferritin levels below 15 micrograms per liter — currently affects approximately one out of three women of reproductive age and is usually treated with ferrous sulfate. Unfortunately, high doses of iron supplementation have been shown to irritate the gastrointestinal system, possibly due to unabsorbed iron.

“Oral iron replacement therapy is a simple and effective approach for treating iron deficiency, except in cases of nonadherence, intolerance, unresponsiveness, or severe anemia,” wrote a team of investigators from Istanbul Medeniyet University, Turkey. “However, the optimal dosage and frequency of ideal treatment remain subjects of ongoing research.”

To compare the side effects and efficacy of three common oral treatment regimens among premenopausal women with iron-deficiency anemia, investigators performed a single-center observational study of patients beginning iron supplementation with an oral ferrous glycine sulfate (100 milligrams elemental iron).

Eligible participants were aged between 18 and 50 years and initiated therapy at a tertiary care hospital between April and July 2023. Patients were randomly assigned to receive alternate-day dosing, a daily single dose or a daily dose twice a day.

Levels of hemoglobin, transferrin saturation and ferritin were collected prior to initiation and after one month of treatment, with the goal of comparing laboratory changes from baseline and post-treatment both within and between the cohorts. Investigators also sought to compare the frequency of gastrointestinal side effects.

In total, 121 women participated in the study, with a mean age of 41.2 years, a mean ferritin level of 7 ± 3.2 nanograms per milliliter at diagnosis, and a mean hemoglobin level of 10.4 ± 1.1 grams per deciliter.

Post-therapy, levels of hemoglobin, transferrin saturation and ferritin significantly increased across treatment arms (11.9 ± 0.9 grams per deciliter, 0.463 ± 1.48, and 22.2 ± 10 nanograms per milliliter, respectively).

However, gastrointestinal side effects were more common among patients in the twice-daily cohort (66.1%) than in the alternate-day and daily single-dose groups (16.7% and 23.4%, respectively). Additionally, throughout the study period, 4.8% of patients in the alternate-day group, 12.8% in the daily single-dose group, and 32.2% of patients in the twice-daily group discontinued treatment due to gastrointestinal side effects and were excluded from the ultimate analysis.

“This raises the question of whether even lower doses, which were not included in our study, should be considered for treating iron deficiency,” the team wrote.

Further, increases in hemoglobin and ferritin levels were significantly lower in the alternate-day cohort than in the other two treatment regimens. Transferrin saturation was highest in the daily single-dose group.

Investigators noted that while the strength of the study lies in the comparison of the three most commonly used regimens prescribed in clinical practice, there were differences in transferrin saturation levels across treatment arms due to the lack of a prospective study design. Additionally, the relatively short 1-month follow-up period may have also limited the findings, as oral iron supplementations are usually recommended for longer periods of time.

“Considering that iron-deficiency anemia treatment typically requires several months, further studies are needed to evaluate the effectiveness of lower doses and longer treatment intervals in long-term trials,” investigators concluded.