Iron Therapy Boosts Hemoglobin Levels in Deficient Patients with Obesity

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Obesity status notably impacted iron metabolism, leading to higher hemoglobin (Hb), soluble transferrin receptor (sTfR), and hepcidin levels, compared with healthy-weight individuals in the findings of a recent analysis.¹

Based on a large population-based representative data set in Spain, a team of investigators measured differences in iron status biomarkers between non-anemic men and women aged 16 to 92 years, revealing marked differences in iron metabolism and a predominance of mixed iron deficiency (ID) across both sexes.

“These findings contribute to a better understanding of iron metabolism in obesity and underscore the importance of tailored interventions to correctly address iron deficiency in this population,” wrote the investigative team, led by Laura Tarancon-Diez, Gregorio Marañón Institute of Health Research.

Both obesity and ID impact millions worldwide, with ID a known comorbidity of weight disorders, although the mechanisms have not been fully discovered.¹ Literature has suggested the exacerbated secretion of adipokines and proinflammatory cytokines in obesity, including IL-6, generates hepcidin production, the primary regulator of iron metabolism.

Although the correlation is likely in children and adolescents, few data have explored the connection in adults, with reviews and meta-analyses limited by the lack of studies and the presence of significant heterogeneity.³ Notably, limitations also include the lack of standardization in the diagnosis of ID, as well as the use of alternative iron-related biomarkers.

For the current analysis, Tarancon-Diez and colleagues sought to determine how obesity-associated inflammation affects iron metabolism in pre-obese (body mass index [BMI] 25.0–29.9 kg/m2) and obese individuals (BMI, >30 kg/m2) and the effect of intravenous (IV) iron supplementation on absolute ID (ferritin levels, <50 ng/mL) in this population.¹

The team measured iron-related, hematological, inflammatory biomarkers, and erythropoietin (EPO) levels based on BMI among 721 non-anemic participants who fulfilled inclusion criteria (67% women; median age, 48 years). A subgroup of participants (n = 11) with absolute ID was measured for the same biomarkers after the conclusion of IV iron therapy.

Upon analysis, Tarancon-Diez and colleagues found elevated levels of ferritin, Hb, sTfR, and hepatic in pre-obese and obese cohorts, compared with a healthy weight group. Approximately 55%, 39%, and 30% of healthy weight, pre-obese, and obese patients had ferritin levels <50 ng/mL, respectively.

Sex-based differences were additionally reported, with marked differences based on sex, including elevated levels of ferritin, Hb, and hepcidin, and low levels of anisocutosis, for men, compared with women. However, no sex-based differences were observed for sTfR levels.

Further analysis, using a multivariate-adjusted logistic regression model, revealed BMI (P <.001), Hb (P = .016), hepcidin (P = .008), ansiocytosis index (P = .002), sideremia (P = .043), and transferrin (P <.001) levels remained significantly associated with high sTfR levels.

To determine the potential impact of BMI on erythropoiesis, EPO was measured in 76 participants. Those with obesity experienced elevated levels of EPO, compared with the healthy weight group, although it did not reach statistical significance. In a multivariate logistic regression model adjusted by sex, age, BMI, C-reactive protein (CRP), Hb, and hepcidin, only BMI (P = .048) and Hb (P = .004) remained independently linked to EPO levels.

Across all screened participants, 110 patients with absolute ID received complete treatment with IV iron infusion. After the receipt of IV iron therapy, obese participants experienced significant improvements in iron-related parameters and Hb levels, according to Tarancon-Diez and colleagues.

“We demonstrated marked differences in iron metabolism between obese women and men, with a predominance of mixed ID (absolute coupled with functional ID) in both sexes,” they wrote. “We showed that obese patients undergoing IV iron therapy restored their iron metabolism, with a notable increase in Hb levels compared to healthy weight participants."

References

1. _{Tarancon-Diez L, Iriarte-Gahete M, Sanchez-Mingo P, et al. Impact of obesity on iron metabolism and the effect of intravenous iron supplementation in obese patients with absolute iron deficiency. Sci Rep. 2025;15(1):1343. Published 2025 Jan 8. doi:10.1038/s41598-024-84498-7}
2. _{Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287(2):153-170. doi:10.1111/joim.13004}
3. _{Cheng HL, Bryant C, Cook R, O'Connor H, Rooney K, Steinbeck K. The relationship between obesity and hypoferraemia in adults: a systematic review. Obes Rev. 2012;13(2):150-161. doi:10.1111/j.1467-789X.2011.00938.x}