High Dietary Iron in Patients With Elevated Transferrin Saturation May Increase Cancer Risk

Laurie Barclay, MD

March 29, 2005

March 29, 2005 — High intake of dietary iron in patients with elevated transferrin saturation increases the risk of cancer, according to the results of a cohort study published in the March/April issue of the Annals of Family Medicine.

"Transferrin saturation of more than 60% has been identified as a cancer risk factor," write Arch G. Mainous III, PhD, from the Medical University of South Carolina in Charleston, and colleagues. "It is unclear whether dietary iron intake increases the risk of cancer among individuals with transferrin saturation of less than 60%."

Using data from the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study, the investigators followed 6,309 U.S. adults, aged 25 to 74 years at baseline, from 1971-1974 to 1992.

Serum transferrin saturation was more than 45% at baseline in 7.3% of the population. Intake of dietary iron was not correlated with transferrin saturation (r = .04). Compared with individuals who had normal serum transferrin saturation and low dietary iron intake, individuals who had serum transferrin saturation greater than 45% and high dietary iron intake had an increased adjusted relative risk of cancer (2.24; 95% confidence interval [CI], 1.02 - 4.89).

Individuals with a transferrin saturation of more than 45% but a normal dietary iron intake were not at increased risk (hazard ratio [HR], 1.02; 95% CI, 0.69 - 1.49). Even if transferrin saturation levels were set as low as 41%, the individuals with high transferrin saturation and high dietary iron intake would still have an increased adjusted relative risk of cancer (HR, 2.00; 95% CI, 1.04 - 3.82).

"Among persons with increased transferrin saturation, a daily intake of dietary iron more than 18 mg is associated with an increased risk of cancer," the authors write. "Future research might focus on the benefits of dietary changes in those individuals with increased serum transferrin saturation."

Study limitations include the use of a 24-hour dietary history to assess iron intake; assessment of exposure for total dietary iron made only once and by recall rather than objective measurement; lack of data on dietary patterns after baseline; ascertainment of cancer based on death certificates in some patients and on family or self-report in others; inability to assess causality; and relatively small number of individuals with high transferrin saturation and high dietary iron who developed cancer.

"The current evidence suggests that if a large proportion of the adult US population ingests high levels of dietary iron, then they have a significantly increased risk for deleterious consequences," the authors write. "Although severe iron deficiency causes serious adverse health effects, these data call into question the strategy of the addition of iron to food by manufacturers."

The Health Resources and Services Administration and the Delaware Division of Public Health helped support this study.

The authors report no conflicts of interest.

Ann Fam Med. 2005;3:131-137

Reviewed by Gary D. Vogin, MD

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