Iron supplements may cause side effects for EPP patients

Side effects include photosensitivity, liver damage: Study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Oral iron supplements may help people with erythropoietic protoporphyria (EPP) build back their iron reserves and increase the levels of hemoglobin — the iron-containing protein that carries oxygen in red blood cells — a small study in Denmark suggests.

However, even when taken at small doses over a short period of time, iron supplements may also increase the levels of protoporphyrin IX (PPIX), a compound that builds up in people with EPP, causing oversensitivity to sunlight and liver damage.

Researchers noted that if iron supplements are needed, patients should be monitored for photosensitivity and levels of liver enzymes to manage any possible side effects.

The study, “Effects of iron supplements in individuals with erythropoietic protoporphyria,” was published in the journal Photodiagnosis and Photodynamic Therapy.

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EPP caused by mutations in FECH gene

EPP is caused by mutations in the FECH gene, which provides instructions for making an enzyme that mediates the chemical reaction whereby iron is added to PPIX to produce heme, a component of hemoglobin and other iron-containing proteins.

Mutations impair the activity of the enzyme and limit the amount of heme that can be produced. As a result, PPIX builds up to toxic levels in red blood cells, leaks into the bloodstream, and spreads to the skin and other tissues in the body, causing sunlight hypersensitivity and liver damage.

People with EPP may also develop hypochromic microcytic anemia, which occurs when red blood cells are smaller and paler than normal, likely due to iron deficiency. Iron supplements may help restore the body’s iron reserves, but most data come from case reports.

In one pilot study involving 13 people with EPP, side effects of iron supplementation with 650 mg ferrous sulfate included gastrointestinal discomfort. Most patients saw their levels of PPIX increase, and two had more photosensitivity. Patients who completed one year of treatment had higher levels of iron and hemoglobin.

In the new study, researchers evaluated changes in the levels of PPIX in 10 people with EPP, who were a mean age of 45, and who took 330 mg of ferrous fumarate daily for two months. Other measures included side effects and changes in the levels of iron and hemoglobin.

“Given case reports of increased photosensitivity during iron treatment, we initiated treatment during the winter season when daylight is at its minimum,” the researchers wrote, adding that none of the patients developed skin problems.

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After 2 months, median levels of PPIX had increased by 30%

All patients had low levels of iron, and five also had anemia. After two months, the median levels of PPIX had increased by about 30%. Seven patients had higher levels than when they started iron supplementation, two had lower levels, and in one, they remained unchanged.

Median blood levels of ferritin, a measure of the body’s iron reserves, nearly doubled over the two months of treatment. Of the five patients with anemia, four saw their levels of hemoglobin increase. Two remained anemic after two months of iron supplementation.

Side effects included mild gastrointestinal discomfort in three patients. There was a small, transient elevation in the levels of alanine transaminase, a liver enzyme, from a median of 24 to 34 units per liter, in patients with or without anemia. However, they returned to normal within two months.

“The elevation was less than double, resolved within two months after treatment, and had no clinical significance,” the researchers wrote. “It is, however, worth noting that the patients only received a small iron dose over a short period.”

While iron supplements may help restore the levels of iron, they may also increase those of PPIX. Based on these findings, the researchers “recommended monitoring key health markers in EPP patients receiving iron supplements.”