Restricting iron in the diet protects against vaso-occlusion and organ damage in sickle cell disease (SCD), according to a study published in Blood. 

In SCD, erythrocyte sickling predisposes an individual to vaso-occlusive episodes, which eventually lead to organ damage. In addition, repeated blood transfusions can cause iron overload. Some patients with SCD have the opposite problem—iron deficiency—but they are decidedly in the minority (around 9%). 

The authors of the study previously discovered that gut microbiota in SCD mice are implicated in organ damage. Increased gut permeability in SCD mice allows the translocation of microbial compounds, triggering vaso-occlusive episodes. In addition, they discovered that oral iron worsens inflammatory bowel disease and is associated with gut microbiota changes. 

“To elucidate connections between dietary iron, the microbiome, and SCD pathogenesis, we treated SCD mice with an iron-restricted diet,” they wrote. 

Read more about SCD etiology 

The researchers then assessed its impact on vaso-occlusion by imaging inflamed cremasteric venules 2 hours after intrascrotal injection of tumor necrosis factor-alpha. Organ damage was assessed by evaluating serum levels of liver enzymes such as alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin. 

The authors reported that an iron-restricted diet reduces organ/serum iron concentration in SCD mice. They also discovered that an iron-restricted diet reduces mean corpuscular hemoglobin concentration, which suggests reduced hemolysis. An iron-restricted diet prolongs survival after tumor necrosis factor-alpha challenge, demonstrating protection against vaso-occlusive episodes. 

In terms of the impact of an iron-restricted diet on organ damage, the research team reported that it results in significantly less liver necrosis and fibrosis, as well as reduced serum liver enzymes and bilirubin levels. These findings indicate that dietary iron restriction reduces hepatocyte damage and improves liver function. 

“Dietary iron restriction is a viable therapeutic strategy in iron-overloaded SCD patients and has the potential to modify the disease further,” they concluded. 


Li H, Kazmi JS, Lee SK, et al. Dietary iron restriction protects against vaso-occlusion and organ damage in sickle cell diseaseBlood. 2022;blood.2022016218. doi:10.1182/blood.2022016218