Preparatory work for the update of the tolerable upper intake levels for iron

To support EFSA in the preparatory work for the assessment of Tolerable Upper Intake Levels (UL) for iron, a tailored ‘high level’ protocol was developed. Six systematic reviews (SR) and eight narrative reviews (NR) were conducted to gather contextual evidence relevant to the interpretation of the main body of evidence (BoE). In the SR on iron intake and s‐ferritin, the evidence appraisal of 35 studies revealed an overall low to moderate RoB. Studies proposed thresholds ranging between 110 and 400 μg/L for serum ferritin (sF) concentrations to indicate iron overload, but the varying results indicate insufficient evidence for causal associations. In the SR on GI side effects, 58 eligible studies revealed inconsistent results for diarrhoea, nausea, vomiting. The occurrence and severity of GI symptoms may depend on factors such as concentration of iron, type of supplement, co‐supplied preparations, and timing. The SR on high iron intake and growth in infants comprised 31 eligible studies. Data from 16 eligible studies revealed that iron supplementation does not affect either longitudinal growth or weight gain. For the SR on high iron intake and pregnancy outcomes, the evidence appraisal included 18 studies. No adverse effects of iron supplementation of the mother on birth weight of the infant was revealed. Two SR were conducted to identify evidence for a dose‐response relationship between high iron intake and risk of type 2 diabetes (T2D) and of gestational diabetes (GDM). A total of 4685 records from primarily observational studies were identified. The RoB of 14 eligible studies related to the T2D risk was low. The available BoE showed no increased risk of T2D with increased intake of dietary or supplementary intake of iron. The available data suggests no increased risk of GDM with high iron intake.