SeriousTiming Sensitive
Calcium supplements significantly reduce levothyroxine absorption by 20-25% through chelation in the gastrointestinal tract. This can lead to subtherapeutic thyroid hormone levels, worsening hypothyroid symptoms, and the need for dose adjustments. The interaction is well-documented in multiple controlled studies.
Recommendation: Separate levothyroxine and calcium by at least 4 hours. Take levothyroxine on an empty stomach in the morning, and calcium later in the day. Have TSH monitored when starting or stopping calcium supplements.
SeriousTiming Sensitive
Iron supplements form an insoluble complex with levothyroxine in the GI tract, reducing thyroid hormone absorption by up to 75% in some studies. This is one of the most clinically significant absorption interactions with levothyroxine and frequently leads to treatment failure if timing is not managed.
Recommendation: Separate levothyroxine and iron supplements by at least 4 hours. Take levothyroxine first thing in the morning on an empty stomach, and iron later in the day. Monitor TSH levels when starting or changing iron supplementation.
ModerateTiming Sensitive
Magnesium supplements, particularly magnesium oxide and magnesium hydroxide (antacid forms), can reduce levothyroxine absorption by forming chelate complexes or by raising gastric pH. The magnitude of the interaction is less than calcium or iron but still clinically relevant.
Recommendation: Separate levothyroxine and magnesium supplements by at least 4 hours. Take levothyroxine in the morning on an empty stomach, and magnesium later in the day or at bedtime.
ModerateTiming Sensitive
Zinc supplements may reduce levothyroxine absorption through chelation in the gastrointestinal tract. While the evidence is less robust than for calcium or iron, divalent cations like zinc are known to interact with thyroid hormones and the interaction is clinically plausible.
Recommendation: Separate levothyroxine and zinc supplements by at least 4 hours as a precaution. Take levothyroxine first thing in the morning on an empty stomach.
ModerateTiming Sensitive
Fiber supplements, particularly psyllium, can bind levothyroxine in the gastrointestinal tract and reduce its absorption. Studies have shown that concurrent fiber intake can decrease levothyroxine bioavailability, potentially leading to subtherapeutic thyroid hormone levels.
Recommendation: Separate levothyroxine and fiber supplements by at least 4 hours. Take levothyroxine in the morning on an empty stomach, and fiber supplements with later meals or at bedtime.
InfoTiming Sensitive
CoQ10 may have a minor effect on levothyroxine absorption if taken concurrently. While the interaction is not well-studied, the general recommendation for levothyroxine is to avoid taking it with any supplement to maximize absorption.
Recommendation: As a general precaution, separate levothyroxine and CoQ10 by at least 2-4 hours. This is a conservative recommendation given levothyroxine's well-known sensitivity to co-administered substances.
ModerateTiming Sensitive
Soy Isoflavones
Soy isoflavones (genistein and daidzein) can reduce levothyroxine absorption by binding to the medication in the gastrointestinal tract, forming complexes that are poorly absorbed. Studies show soy can reduce peak T4 levels by approximately 22% and total absorption by nearly 19%. The effect is most clinically significant in infants with congenital hypothyroidism on soy formula and in adults consuming large amounts of soy products near their levothyroxine dose.
Recommendation: Separate levothyroxine from soy products and soy isoflavone supplements by at least 4 hours. Take levothyroxine on an empty stomach with water in the morning, and consume soy products later in the day. If TSH levels rise after increasing soy intake, a dose adjustment may be needed. Inform your prescriber about regular soy consumption.
SeriousCaution
Biotin
Biotin (vitamin B7) does not pharmacologically interact with levothyroxine, but it causes clinically dangerous interference with thyroid laboratory tests used to monitor levothyroxine dosing. Most thyroid immunoassays use biotin-streptavidin technology. Excess biotin produces falsely low TSH and falsely high T3/T4 results in standard assays, which can mimic hyperthyroidism or suggest levothyroxine overdosing, leading to inappropriate dose reductions.
Recommendation: Stop biotin supplementation at least 2-3 days (ideally 5 days for high-dose biotin >5 mg/day) before thyroid function testing. Inform your lab and prescriber about biotin supplement use. Hair/skin/nail supplements commonly contain biotin at 2.5-10 mg, well above the level that causes assay interference. This is a lab interference issue, not a true drug interaction.
ModerateTiming Sensitive
Coffee
Coffee significantly reduces levothyroxine absorption when consumed within 60 minutes of taking the medication. Chlorogenic acids and tannins in coffee bind directly to levothyroxine molecules, forming poorly absorbed complexes. Studies show coffee can reduce T4 absorption by 29-36% in different populations, potentially leading to subtherapeutic thyroid hormone levels and worsening hypothyroid symptoms. Liquid levothyroxine formulations may be less affected.
Recommendation: Take levothyroxine with water only and wait at least 60 minutes before drinking coffee. This timing separation is sufficient to prevent the interaction. If unable to wait 60 minutes, discuss liquid levothyroxine formulations with your prescriber, as these may be less affected by coffee. Decaffeinated coffee has the same effect as it is the non-caffeine compounds that bind levothyroxine.
ModerateCaution
DIM (diindolylmethane) may affect thyroid hormone metabolism by inducing phase II conjugation enzymes. It can alter the estrogen-thyroid axis interaction and may increase levothyroxine clearance in some individuals.
Recommendation: Monitor TSH levels when starting DIM supplementation on levothyroxine. Dose adjustment may be needed. Take DIM at least 4 hours after levothyroxine.
SeriousCaution
High-dose biotin (>5mg/day) interferes with streptavidin-biotin immunoassays used to measure TSH and free T4. This creates FALSELY NORMAL OR ABNORMAL thyroid tests, not a true drug interaction, but can lead to dangerous mismanagement of levothyroxine dosing.
Recommendation: Stop biotin supplementation at least 48-72 hours before thyroid function tests. Inform your lab and doctor about biotin use. This is an assay interference issue, not a pharmacological interaction.
SeriousTiming Sensitive
Iron bisglycinate contains elemental iron and should be handled like other oral iron supplements around levothyroxine. Iron can bind thyroid hormone in the gut and lower absorption, which may raise TSH and bring back hypothyroid symptoms. The strongest human data are with ferrous sulfate, but the same timing precaution is appropriate for bisglycinate because the interacting component is iron.
Recommendation: Take levothyroxine on an empty stomach with water, and take iron bisglycinate at least 4 hours later. Recheck thyroid labs after starting, stopping, or substantially changing iron supplementation.
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