Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women.

Systematic review and meta-analysis of 25 studies including 10,996 adolescent and adult menstruating women who were not pregnant or lactating. Studies were conducted across diverse global settings, mostly in low- and middle-income countries, and evaluated intermittent oral iron regimens versus no supplementation/placebo or daily iron supplementation.

Intermittent oral iron supplementation, given one to three times per week on non-consecutive days, was compared with no supplementation/placebo or with daily iron supplementation. Across included trials, weekly elemental iron doses were generally 60 to 120 mg, usually as ferrous sulphate tablets or caplets; some regimens also included folic acid or other micronutrients.

Intermittent iron supplementation reduced anaemia and improved iron status versus no supplementation or placebo, and it was probably as effective as daily supplementation for preventing or controlling anaemia. Compared with no supplementation/placebo, intermittent iron reduced anaemia (RR 0.65, 95% CI 0.49 to 0.87; 3135 participants, 11 studies), increased haemoglobin (MD 5.19 g/L, 95% CI 3.07 to 7.32; 2886 participants, 15 studies), and increased ferritin (MD 7.46 µg/L, 95% CI 5.02 to 9.90; 1067 participants, 7 studies). Compared with daily supplementation, anaemia (RR 1.09, 95% CI 0.93 to 1.29; 1749 participants, 8 studies) and haemoglobin (MD 0.43 g/L, 95% CI -1.44 to 2.31; 2127 participants, 10 studies) were similar, while any adverse side effects were fewer with intermittent regimens (RR 0.41, 95% CI 0.21 to 0.82; 1166 participants, 6 studies).

The evidence base was heterogeneous, with substantial variation in dose, formulation, frequency, and co-administered nutrients. Many outcomes had high statistical heterogeneity, several were based on few studies or single trials, and overall certainty ranged from very low to moderate, limiting confidence in effects on morbidity, malaria, adherence, and other longer-term outcomes.