Iron levels hint at resistance to harmful effects of smoking

Researchers from Japan say that serum iron levels could be a biomarker that indicates which smokers are resistant to the effects of cigarette smoke on lung function.

The team studied a group of elderly (≥70 years), male smokers who, despite having smoked for over 30 years, had normal spirometry results (forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC] ≥0.7, FEV1% predicted ≥80).

Compared with 57 male smokers with impaired lung function, these 60 “smoke-resistant” men had significantly higher mean serum iron levels, at a mean of 121.6 µg/dL versus 107.8 µg/dL, as well as a higher body mass index, at 23.5 kg/m² versus 22.3 kg/m².

Using annual health check data, the team found that men over the age of 40 years with a serum iron level below the lower limit of normal (54 µg/dL) had significantly reduced FEV1/FVC compared with men with normal iron levels, at 74.7% versus 77.1%.

Regression analysis showed that, after adjusting for age, Brinkman index, and homocysteine, uric acid, and hemoglobin levels, serum iron levels were predictive for FVC, FEV1, and FEV1/FVC in male smokers. FEV1/FVC also significantly correlated with serum iron levels in nonsmokers.

And follow-up at 3 to 5 years after the initial visit indicated that for each standard deviation increase in serum iron levels at baseline, there was a 46% reduction in the odds for FEV1 decline over time.

“Serum iron levels may be a simple biomarker indicating resistance to the lung toxicity of cigarette smoke,” the authors, led by Yoko Shibata (Yamagata University), write in PLoS One.

“The mechanism underlying the relationship between serum iron levels and pulmonary function remains to be determined, and the question still remains whether the elevation of serum iron has a protective effect in the lung.”

Yamagata and colleagues note that as their findings remained significant after adjusting for hemoglobin levels, the apparent protective effect of iron is not related to increased carbon monoxide tolerance. Instead, they suggest it may be due to individual differences in the ability to resist oxidative stress through antioxidants such as heme oxygenase-1, which is associated with high serum iron levels; however, they were not able to test this in their study.

They conclude: “Future studies investigating the longitudinal effects of iron supplementation or iron chelation on the decline in pulmonary function in cigarette smokers may help increase our understanding of this phenomenon.”

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