When is the best time to take iron supplements? Does vitamin C improve absorption, and is it really necessary to avoid having it with breakfast? Conclusive answers have finally been offered to all these questions in the wake of a new study.

The findings suggest that ‘less is more’, with the optimal regimen being lower doses less frequently to avoid binding and removal of iron in the intestine by hepcidin – as well as the GI intolerance.

In an attempt to separate fact from fiction on the topic, researchers recruited 34 iron-deficient women, who were each given a dose of 100mg of ferrous fumarate in six different conditions.

These were either: (1) 80mg of ascorbic acid, (2) 500mg of ascorbic acid, (3) coffee, (4) breakfast (semi-brown bread and yogurt) with coffee and orange juice (containing 90mg of ascorbic acid), and finally, (5) water in the afternoon.

There was also a control condition of taking iron alone with water in the morning, making 204 doses in total.

Using erythrocyte incorporation of multiple isotopic labels, fractional iron absorption (FIA) was calculated after each dose, with the researchers finding dramatic differences depending on both time of day and what the iron was taken with.

Interestingly, FIA increased by 30% with the low dose of ascorbic acid, when compared with control. But it did not increase further when the vitamin C dose was raised to 500mg, the researchers reported in American Journal of Hematology (link here).

On the other hand, taking coffee with the iron supplement resulted in a greater than 50% reduction in absorption. And FIA was still negatively impacted when coffee was consumed with a breakfast (including orange juice with 90mg of ascorbic acid), falling 66%, they said.

Finally, doses taken in the afternoons had poorer absorption versus those in the mornings, likely related to regular diurnal increases in hepcidin levels.

In an accompanying editorial (link here), haematologists Dr Jacquelyn Powers of Baylor College of Medicine and Dr Michael Auerbach of Georgetown University said the data provided some much-needed solid evidence on the topic.

“These data, directly applicable to real-world clinical practice, support the conclusion that to maximise efficacy, iron supplements should be consumed in the morning, away from meals or coffee, but with an ascorbic acid rich food or beverage (i.e., glass of orange juice),” they wrote.

“By doing so, compared with other methods of ingestion of 100mg of oral iron, a fourfold increase in iron absorption occurs, providing approximately 20 more mg of absorbed iron per dose. In practical terms, this new work informs practitioners how best to advise their parents requiring iron therapy.”

The other frequent question addressed by the research was whether iron could be taken with food to reduce its gastrointestinal side effects. Perhaps unfortunately, the study found conclusively that taking it with meals may lessen these effects, but also substantially reduced efficacy – resulting in the need for a longer treatment course in the long run, they said.

“Giving lower or less frequent doses of iron, but with ascorbic acid alone, is likely the best way to move forward to allow for the optimal therapeutic response and shortest treatment duration overall,” Dr Powers and Dr Auerbach added.