What are the health consequences of high iron saturation?

Health Consequences of High Iron Saturation

High iron saturation significantly increases risk of cardiovascular morbidity and mortality, infections, and organ damage affecting the liver, heart, pancreas, and brain. 1

Cardiovascular Complications

High iron saturation leads to several cardiovascular consequences:

• Increased risk of cardiovascular events and mortality, particularly sudden death 1
• Impaired endothelial function similar to that seen in hereditary hemochromatosis 1
• Direct promotion of atherosclerosis 1
• Myocardial iron deposits contributing to heart failure 1
• Elevated hepcidin and FGF23 levels that exert cardiac toxicity 1

Increased Infection Risk

Iron overload significantly compromises immune function through multiple mechanisms:

• Impaired function of multiple immune cell lineages including:

  • CD4+ T-cell depletion with shortened cell lifespan
  • CD8+ CD28- T-lymphocyte expansion
  • Reduced phagocytic activity of polymorphonuclear leukocytes and monocytes 1

• Increased susceptibility to specific pathogens:

  • Higher risk of severe Vibrio vulnificus infections with mortality rates >50% 1
  • Increased risk of sepsis (HR: 1.69) in individuals with hemochromatosis genotypes 2
  • Higher death rates from infectious diseases (HR: 2.34) 2

Liver Damage

Excess iron in the liver can cause:

• Progressive fibrosis and cirrhosis 3
• Increased risk of hepatocellular carcinoma 3
• Amplification of liver damage from other causes (alcohol, viral hepatitis) 1

Endocrine and Metabolic Effects

Iron overload affects glucose metabolism and endocrine function:

• Pancreatic damage through apoptosis of insulin-secreting beta cells 1
• Increased risk of diabetes, particularly in patients with pre-existing conditions 1
• Multiple endocrine disorders in severe cases 1

Cancer Risk

High iron saturation is associated with increased cancer risk:

• Higher transferrin saturation linked to increased nonskin cancer risk in women (HR: 1.68) 4
• Greater risk of breast cancer in women with elevated serum iron (HR: 2.45) 4
• Increased cancer mortality associated with high transferrin saturation (HR: 2.48) 4

Neurological Impact

Iron accumulation in the brain is linked to:

• Neurodegenerative diseases including Alzheimer's and Parkinson's disease 5
• Brain iron deposition detectable by MRI T2* imaging 5

Monitoring and Assessment

For patients with suspected iron overload:

• Serum ferritin and transferrin saturation are initial screening tests, but have limitations 1
• MRI is the preferred non-invasive method for quantifying tissue iron in the liver, heart, pancreas, and brain 1
• R2* MRI sequences are best validated for iron quantification 1
• Liver biopsy may be necessary when liver disease is suspected as a cause of iron overload 6

Special Considerations

Alcohol Consumption

• Alcohol downregulates hepcidin transcription in the liver via oxidative stress 1
• This abrogates the protective effect of hepcidin against iron accumulation 1
• Patients with iron overload should avoid or significantly limit alcohol consumption 1

Dialysis Patients

Dialysis patients are at particularly high risk from iron overload:

• Increased mortality with IV iron doses >300 mg/month 1
• Higher risk of hospitalization (HR: 1.12) with monthly iron doses ≥300 mg 1
• Increased cardiovascular events with higher cumulative iron doses 1

Oxidative Stress

• Iron catalyzes free radical reactions (Fenton reaction) 5
• Contributes to tissue damage in multiple organs 5
• May trigger ferroptosis, a cell death program based on iron-dependent lipid oxidation 5

In conclusion, high iron saturation has wide-ranging negative health consequences affecting multiple organ systems, with cardiovascular disease, infections, and organ damage being the most significant concerns for morbidity and mortality.