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Iron, Methylation, and Why Your rs7385804 Genotype Matters

Iron is more than a simple mineral. It helps form heme, a key piece of many enzymes, and supports enzymes that connect methylation with antioxidant defense and neurotransmitter metabolism. Iron-dependent enzymes help route homocysteine toward glutathione production in the transsulfuration pathway and help break down neurotransmitters like dopamine, norepinephrine, and serotonin. When iron is low, these enzyme activities can slow. That may shift homocysteine away from antioxidant production, increase oxidative stress, alter neurotransmitter turnover, and raise demand on the methylation cycle.

How to interpret this result

This report explains how your rs7385804 genotype can influence iron uptake and downstream effects on methylation and antioxidant systems. It also gives practical steps to monitor and support healthy iron status. PlexusDx does not provide medical advice. Always discuss genetic results and treatment decisions with your healthcare provider before changing diet, supplements, or medications.

Signs that may suggest lower iron status

  • Unexplained fatigue or low exercise tolerance
  • Difficulty concentrating or brain fog
  • Pale skin or brittle nails
  • Elevated resting heart rate or lightheadedness
  • Laboratory evidence on blood tests such as low ferritin, low hemoglobin, or low transferrin saturation

Recommended blood tests to check iron and related function

  • Serum ferritin to measure iron stores
  • Hemoglobin and hematocrit to screen for anemia
  • Transferrin saturation to assess iron transport
  • Optional: serum iron and total iron binding capacity
  • Consider homocysteine and markers of oxidative stress if advised by your clinician
Two effect alleles (CC) — higher chance of reduced iron uptake

If you have the CC genotype for rs7385804, you carry two copies of the effect allele linked to reduced iron uptake and an increased risk of lower blood iron. This variant affects how the body takes up and regulates iron. Because iron helps form heme and supports enzymes in the transsulfuration pathway and neurotransmitter breakdown, reduced iron uptake can reduce activity of those enzymes. That may shift homocysteine away from glutathione production and slow breakdown of neurotransmitters, increasing strain on methylation and antioxidant systems.

Potential impacts

  • Higher risk of iron deficiency symptoms such as fatigue and low exercise tolerance
  • Weaker antioxidant defenses due to reduced glutathione production
  • Subtle increases in methylation demand or homocysteine if not balanced

Actionable steps

  • Get blood tests: serum ferritin, hemoglobin, and transferrin saturation to confirm iron status
  • Increase heme iron foods: lean red meat, poultry, and fish are the best sources for improving iron status
  • Eat vitamin C rich foods at meals to boost iron absorption, for example citrus, bell peppers, and strawberries
  • If labs show deficiency, consider clinician-guided iron supplementation. Avoid self-prescribing iron
  • Avoid taking iron with calcium, or with tea and coffee, as they reduce absorption
  • Consider monitoring homocysteine if recommended by your clinician
One effect allele (AC) — modestly reduced iron transport

If you have the AC genotype for rs7385804, you carry one copy of the effect allele. This can modestly reduce how efficiently iron is moved and used in the body. Because iron is a key cofactor for transsulfuration enzymes and monoamine oxidases, this genotype may slightly shift the balance between antioxidant production and methylation demand.

Potential impacts

  • Slightly higher risk of lower iron stores and related symptoms like tiredness
  • Possible mild increases in oxidative stress that place more demand on methylation nutrients

Actionable steps

  • Check baseline iron tests such as ferritin and hemoglobin
  • Support iron intake with both heme and nonheme sources: lean red meat, poultry, beans, lentils, and iron-fortified grains
  • Pair plant-based iron sources with vitamin C rich foods to increase absorption
  • Consider iron supplements only if lab tests and a clinician recommend them
  • Balance iron-supportive strategies with attention to nutrients that support methylation such as B12, folate, and B6 when advised
No effect alleles (AA) — expected normal iron transport

If you have the AA genotype for rs7385804, you carry two copies of the non effect allele. Iron transport to tissues is expected to be normal and efficient. Normal iron delivery supports the transsulfuration and neurotransmitter-related enzymes that rely on iron as a cofactor, helping maintain balanced routing of homocysteine toward glutathione and proper neurotransmitter breakdown.

Potential impacts

  • Lower chance that iron-related problems will interfere with methylation and antioxidant defenses
  • Normal risk for iron-related symptoms unless other factors are present

Actionable steps

  • Maintain a balanced diet with iron-rich foods: lean red meat, poultry, fish, beans, lentils, and iron-fortified grains
  • Pair iron-containing meals with vitamin C rich foods to enhance absorption
  • Consider routine blood tests such as ferritin and hemoglobin rather than self-supplementing iron
  • Seek clinician advice before starting any iron supplementation

Diet, supplements, and lifestyle tips to support iron and methylation balance

  • Prioritize heme iron when possible. Heme iron from animal foods is absorbed more efficiently than plant iron.
  • Combine plant-based iron sources with vitamin C. Example meal: lentil soup with a squeeze of lemon and a side salad with bell peppers.
  • Watch inhibitors of iron absorption. Coffee, tea, and high-calcium foods reduce iron absorption when taken with iron-rich meals. Space them away from iron-containing meals.
  • Focus on nutrients that support methylation and antioxidant systems: adequate B12, folate, and B6 for methylation and cysteine precursors to support glutathione when appropriate.
  • Regular, moderate exercise supports healthy iron turnover and cardiovascular fitness, but very intense training can increase iron needs. Monitor if you train heavily.
  • If you notice symptoms of deficiency, get labs before supplementing. Iron excess can be harmful.

When to talk to your healthcare provider

  • If blood tests show low ferritin, low hemoglobin, or low transferrin saturation
  • If you have persistent fatigue, breathlessness, or cognitive changes that impact daily life
  • Before starting iron supplements, particularly if you have a chronic condition, take other medications, or suspect an absorption problem
  • If you are pregnant, breastfeeding, or planning pregnancy, as iron needs change

PlexusDx provides education about genetic predispositions only. This information is not medical advice and is not a substitute for professional medical care. Always consult your healthcare provider to interpret test results and design a plan tailored to your medical history, current medications, and individual needs.