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Understanding Iron and How TFR2 Variants Influence Your Levels

Iron is an essential mineral used to make hemoglobin, the protein that carries oxygen in red blood cells. It also supports immune function, DNA synthesis, and muscle performance. Your body regulates iron carefully to avoid deficiency or overload. One gene involved in that regulation is TFR2, which makes transferrin receptor 2, a protein that helps liver cells sense and control iron uptake and that influences hepcidin, the hormone that determines how much iron is absorbed from food and released from storage.

Why TFR2 Matters

Variants in the TFR2 gene can change how efficiently your cells take up iron and how your body sets hepcidin levels. These changes can increase the chance of low serum iron or, less commonly, affect iron balance in other ways. The single nucleotide polymorphism rs7385804 in TFR2 is one variant that affects iron transport. Below is practical guidance on diet, supplements, lifestyle, and monitoring based on your genotype.

Genetic Interpretation

2 effect alleles — CC (increased risk of iron deficiency)

If you have the CC genotype for rs7385804, you carry two copies of the effect allele. This genotype is associated with reduced iron uptake, increased risk of iron deficiency, and lower serum iron levels. Your TFR2 variant may make it harder for your body to absorb iron from food and to maintain iron balance, potentially leading to lower iron in the bloodstream.

Practical steps

  • Prioritize heme iron sources: lean red meat, poultry, and fish are absorbed most efficiently.
  • For plant-based sources, include beans, lentils, tofu, and dark leafy greens, and always pair them with vitamin C-rich foods like citrus, strawberries, kiwifruit, bell peppers, or tomatoes to boost absorption.
  • Avoid drinking tea or coffee with iron-rich meals and take calcium supplements or high-calcium foods at other times of day because they can reduce iron uptake.
  • Consider routine monitoring: ask your healthcare provider about checking serum ferritin, hemoglobin, transferrin saturation, and serum iron if you have symptoms such as fatigue, pale skin, shortness of breath, or cognitive changes.
  • Discuss supplementation: if dietary measures are insufficient or levels are low, your provider may recommend an iron supplement. Follow their dosing and monitoring plan because excess iron can be harmful.
  • Supportive lifestyle: maintain regular exercise, good sleep, hydration, and stress management to support overall energy and recovery.
1 effect allele — CA (moderately reduced iron transport)

If you have the CA genotype for rs7385804, you carry one copy of the effect allele. This is associated with moderately reduced iron transport and a partial risk of lower iron levels. Your TFR2 variant may mean your body absorbs iron somewhat less efficiently than people without the effect allele.

Practical steps

  • Include both heme and non-heme iron sources regularly: lean meats, poultry, fish, beans, lentils, and dark leafy greens.
  • Improve absorption of plant iron by pairing with vitamin C-rich foods at meals.
  • Limit inhibitors at mealtimes: avoid tea, coffee, and high-calcium foods or supplements close to iron-containing meals.
  • Consider periodic testing: discuss ferritin and hemoglobin checks with your healthcare provider if you have symptoms or if you fall into higher risk groups (pregnancy, heavy menstrual bleeding, endurance athletes, vegetarian or vegan diets).
  • Supplements may be considered if levels are trending low, but only under provider guidance to ensure correct dosing and to avoid side effects.
  • Maintain healthy habits: balanced sleep, stress reduction, and regular physical activity support iron use and overall wellbeing.
0 effect alleles — AA (normal iron transport)

If you have the AA genotype for rs7385804, you carry two copies of the non-effect allele. This genotype is associated with normal iron transport and generally effective iron delivery to cells. With this genotype, your body is expected to handle iron balance efficiently.

Practical steps

  • Eat a varied diet with both heme (lean meats, poultry, fish) and non-heme iron (beans, lentils, leafy greens).
  • Maximize plant iron absorption by pairing with vitamin C-rich foods and consuming inhibitors such as tea, coffee, and calcium separately from iron-rich meals.
  • Routine monitoring is not usually necessary unless you develop symptoms or have life stages or conditions that increase risk (for example, pregnancy or heavy menstrual bleeding).
  • If you follow a vegetarian or vegan diet, pay attention to iron sources and consider periodic ferritin checks to confirm adequate stores.
  • Continue healthy lifestyle habits to support iron use and general health.

Diet and Food Strategies to Support Healthy Iron Levels

  • Heme iron sources (best absorbed): lean beef, lamb, pork, poultry, liver, shellfish, and fish.
  • Non-heme iron sources: beans, lentils, chickpeas, tofu, tempeh, quinoa, fortified cereals, nuts, seeds, and dark leafy greens.
  • Enhancers: vitamin C-rich foods (citrus, berries, peppers, broccoli, tomatoes) taken with iron-containing meals can significantly boost absorption.
  • Inhibitors: polyphenols in tea and coffee, calcium in dairy or supplements, and some whole grains can reduce iron absorption when consumed at the same time as iron-rich meals.
  • Meal timing tip: have tea and coffee between meals rather than with iron-containing foods; take calcium supplements at a different time of day if you are trying to increase iron uptake.

Supplements, Testing, and When to Talk to Your Provider

If testing shows low ferritin, low hemoglobin, or low transferrin saturation, your healthcare provider may recommend an iron supplement and a monitoring schedule. Iron supplements come in different forms and doses and can cause gastrointestinal side effects for some people. Your provider can suggest the right formulation and duration and check iron indices periodically to confirm improvement and to avoid iron excess.

Consider testing if you have symptoms of iron deficiency such as fatigue, unusual tiredness during normal activities, pale skin, brittle nails, hair thinning, shortness of breath, or cognitive difficulties. Also consider testing if you are pregnant, breastfeeding, have heavy menstrual bleeding, follow a restricted diet, or are an endurance athlete.

Lifestyle Tips to Support Iron Balance

  • Regular physical activity supports healthy blood and muscle function but be mindful that high-volume endurance training can increase iron needs.
  • Prioritize sleep and stress reduction; chronic stress and poor sleep can affect appetite and nutrient absorption.
  • Stay hydrated and maintain a balanced diet to support nutrient transport and overall health.
  • If you are pregnant or planning pregnancy, discuss iron needs and testing with your healthcare provider early.

Important Disclaimer

PlexusDx provides educational information about genetic predispositions only. This content is not medical advice. Always consult your healthcare provider before starting or changing supplements, making major diet changes, or if you are concerned about your iron status or overall health. Your provider can interpret genetic results alongside clinical labs, symptoms, medical history, and medications to create a plan tailored to you.