Does increased oral iron supplementation decrease iron absorption?

From the Guidelines

Taking more oral iron can actually decrease iron absorption due to the saturation of intestinal iron transport mechanisms and the increase in hepcidin production, which reduces iron absorption. When you take large amounts of iron supplements, your body absorbs a smaller percentage of the total dose. For example, while you might absorb 30-40% of the iron from a small 50-100 mg dose of ferrous sulfate, this can drop to just 10-15% absorption with doses of 200 mg or higher 1. This happens because the intestinal cells have limited capacity to transport iron, and this system becomes saturated at higher doses. Additionally, your body activates protective mechanisms against iron overload, including increasing production of hepcidin, a hormone that reduces iron absorption.

Some key points to consider when taking oral iron supplements include:

• Taking iron once a day at most, as every-other-day iron dosing may be better tolerated for some patients with similar or equal rates of iron absorption as daily dosing 1
• Taking smaller doses (typically 60-100 mg of elemental iron) two or three times daily rather than one large dose
• Taking iron with vitamin C (like orange juice) can enhance absorption, while calcium, dairy products, tea, coffee, and antacids can inhibit it 1
• Spacing doses throughout the day and away from these inhibitors will maximize the total amount of iron your body actually absorbs
• Alternate day dosing leads to a significantly increased fractional iron and total iron absorption in iron-depleted healthy women 1

It's also important to note that certain dietary manipulations may improve iron absorption, such as taking iron with 80 mg ascorbic acid on an empty stomach, which improves iron absorption by forming a chelate with iron that prevents the formation of insoluble iron compounds and by reducing ferric to ferrous iron 1. However, evidence supporting vitamin C administration to improve iron absorption is mixed, and further study is needed to clarify the effectiveness of this practice.

From the Research

Iron Absorption and Oral Iron Supplementation

• The relationship between oral iron dosage and iron absorption is complex, with evidence suggesting that taking more oral iron can actually decrease iron absorption 2, 3.
• Studies have shown that daily dosing and split dosing of oral iron supplements can increase serum hepcidin, a hormone that regulates iron absorption, and decrease iron absorption from subsequent doses 2, 3.
• In contrast, providing iron supplements on alternate days and in single doses may optimize iron absorption and be a preferable dosing regimen 2.

Mechanisms of Iron Absorption

• The hepcidin-ferroportin iron regulatory pathway plays a crucial role in regulating iron absorption, and excessive oral iron doses can lead to increased hepcidin levels, which can limit gastrointestinal iron uptake and efficacy of oral iron 4.
• Unabsorbed iron can also propagate side effects such as dyspepsia and constipation, which can be exacerbated by excessive oral iron doses 4.

Optimal Dosing Strategies

• Research suggests that daily low-dose and every-other-day dosing protocols may be more effective than high-dose regimens in promoting iron absorption and minimizing side effects 2, 3.
• The use of novel iron formulations, such as lipophilic iron donors and nanoparticle-encapsulated iron, may also offer improved efficacy and tolerability compared to traditional oral iron supplements 5.