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Understanding Iron, HFE, and What Your Genetic Result Means

Iron is an essential mineral required to form hemoglobin, the protein in red blood cells that carries oxygen. It also supports energy production, immune function, and DNA synthesis. The HFE gene helps regulate iron absorption by influencing hepcidin, the hormone that controls how much iron your intestines absorb and how much is released from storage. Variations in HFE can change hepcidin signaling and increase the risk of iron accumulation in organs such as the liver, heart, and pancreas.

How HFE Variants Influence Health

When HFE function is altered, the body may absorb more iron than it needs. Chronically elevated iron can lead to tissue damage from oxidative stress and increase the risk of conditions such as liver disease, diabetes, joint pain, and heart disease. Effects are generally dose dependent. People with two effect alleles are at highest risk, those with one allele have intermediate risk, and those without effect alleles tend to regulate iron normally.

Two effect alleles (GG for rs1799945)

If your genotype is GG, you carry two copies of the effect allele. This is associated with impaired HFE function and a higher risk of iron overload. Your intestines may absorb more iron from food than your body needs, even if stores are already adequate. Over time excess iron can build up in liver, heart, pancreas, and other tissues, increasing risk for organ damage and metabolic complications.

Key actions to consider

  • Schedule baseline blood tests: serum ferritin, transferrin saturation, and liver function tests. Repeat testing at intervals recommended by your healthcare provider.
  • Avoid iron supplements and iron-fortified foods unless clinically indicated by a provider.
  • Limit high heme iron foods such as red and processed meats. Emphasize nonheme iron sources from plants, which are absorbed less efficiently.
  • Avoid alcohol or keep intake very low to reduce liver stress and risk of iron-related liver injury.
  • Do not eat raw shellfish due to increased infection risk in the context of iron overload.
  • If iron overload is confirmed, treatment options include therapeutic phlebotomy or other interventions under medical supervision.
One effect allele (CG for rs1799945)

If your genotype is CG, you carry one copy of the effect allele. This is associated with moderately reduced HFE function and an intermediate risk of elevated iron levels. Your body may absorb slightly more iron than someone without the variant, which can lead to gradual accumulation over time in some people.

Key actions to consider

  • Check iron status with periodic blood tests: serum ferritin and transferrin saturation are useful screening measures.
  • Prefer a balanced diet rich in fruits, vegetables, legumes, and whole grains. These foods support overall health and often contain compounds that reduce iron absorption.
  • Limit frequent consumption of red and processed meats. If you eat these, pair them with foods that inhibit iron absorption such as dairy or tea.
  • Avoid routine iron supplementation unless tests show deficiency and your provider prescribes it.
  • Minimize alcohol intake and avoid raw shellfish as a precaution.
Zero effect alleles (CC for rs1799945)

If your genotype is CC, you carry two copies of the non-effect allele. This indicates typical HFE function and normal regulation of iron absorption in most circumstances. Your hepcidin signaling should help balance iron uptake and release, which lowers the likelihood of iron overload for most people.

Key actions to consider

  • Follow routine health screening and discuss iron testing with your healthcare provider if you have symptoms of iron imbalance.
  • Maintain a balanced diet with a variety of iron sources. If you are at risk of iron deficiency due to menstruation, pregnancy, or dietary restriction, speak with your provider about testing and supplementation.
  • Limit excessive alcohol and avoid raw shellfish to protect liver health and reduce infection risk.

Diet Recommendations

  • Emphasize fruits, vegetables, whole grains, legumes, nuts, and seeds. Plant based meals are generally lower in bioavailable iron than red meat centered meals.
  • Limit red and processed meats. Replace with poultry, fish, tofu, beans, and lentils.
  • When reducing iron absorption is desirable, consume calcium rich foods, dairy, or a cup of tea with meals. These lower the absorption of nonheme and heme iron.
  • Be mindful of iron fortified cereals and breads if you are at risk for iron overload.
  • For people at risk of iron deficiency, pair plant iron sources with vitamin C containing foods to boost absorption, but only under medical guidance if you also carry HFE risk variants.

Supplement Recommendations

  • Avoid over the counter iron supplements unless prescribed after blood testing confirms deficiency.
  • If iron deficiency is confirmed by your provider, follow the dosing and monitoring plan they recommend and recheck iron panels during therapy.
  • Discuss multivitamins with your provider. Some contain iron. Choose formulations without iron if you are avoiding extra iron.
  • Supplements such as vitamin C or probiotics are not replacements for medical management of iron overload. Use only after discussing with your healthcare provider.

Lifestyle Recommendations

  • Limit alcohol intake. Alcohol increases liver vulnerability and can exacerbate iron related liver damage.
  • Avoid raw or undercooked shellfish. People with iron overload are at higher risk for certain bacterial infections from shellfish.
  • Maintain a healthy weight and regular physical activity to support metabolic and cardiovascular health.
  • Inform healthcare providers and dentists that you carry HFE variants so they consider iron status when evaluating symptoms.

Testing and Monitoring

Recommended blood tests to monitor iron status include serum ferritin, transferrin saturation, serum iron, and total iron binding capacity. If blood tests suggest iron overload, liver function tests and evaluation by a specialist may be appropriate. Frequency of testing depends on your genotype, baseline iron markers, symptoms, and clinical judgment by your healthcare provider.

When to Talk to Your Healthcare Provider

  • If screening tests show high ferritin or transferrin saturation.
  • If you have symptoms such as unexplained fatigue, joint pain, abdominal pain, darkening of the skin, or signs of liver disease.
  • Before starting or stopping iron supplements or making major dietary changes tied to iron.
  • To create a monitoring plan tailored to your genetic result and overall health.

Limitations and Important Disclaimer

PlexusDx provides educational information about genetic predispositions only. This report does not provide medical advice, diagnosis, or treatment. Genetic results are one piece of your health picture and should be interpreted with your medical history, symptoms, and clinical lab tests. Always consult with your healthcare provider or a qualified medical professional before making decisions about testing, supplements, medications, or treatment plans.