T4 (Levothyroxine, Synthroid, Levoxyl) is the primary thyroid hormone produced by the thyroid gland. It serves as the "storage" or "prohormone" form of thyroid hormone, which is converted to the active form T3 (triiodothyronine) by deiodinase enzymes in peripheral tissues (liver, kidneys, brain, muscle). T4 accounts for approximately 80% of thyroid hormone output, while T3 accounts for approximately 20%. In the performance context, T4 is used as a milder alternative to T3 for metabolic enhancement and fat loss, as the body controls the conversion rate, providing a more gradual and physiological effect. It is also the standard treatment for hypothyroidism.
Notes
Levothyroxine is one of the most prescribed medications in the world. It is FDA-approved and considered extremely safe at replacement doses. Supraphysiological use for fat loss carries the same risks as any thyroid excess state but is generally well-tolerated in healthy individuals for limited durations.
T4 itself has minimal direct activity at thyroid receptors. Its primary role is as a prohormone that is converted to T3 by type 1 and type 2 deiodinase enzymes in peripheral tissues. The body tightly regulates this conversion based on metabolic needs, providing a natural "buffering" effect that prevents the rapid fluctuations seen with exogenous T3. Once converted to T3, the mechanism of action is identical: nuclear receptor binding, gene transcription modulation, increased metabolic rate, thermogenesis, and energy expenditure. The body can also convert T4 to reverse T3 (rT3), an inactive metabolite, as a protective mechanism against excessive thyroid hormone activity.
T4 is approximately 40-80% absorbed orally, highly dependent on stomach pH and concurrent food/medication intake. Fasting absorption is at the higher end. Peak plasma levels occur at 2-4 hours. The very long half-life of 6-7 days means steady state is not reached until approximately 4-6 weeks of consistent dosing. T4 is highly protein-bound (>99%) to thyroxine-binding globulin (TBG), transthyretin, and albumin. Only the free fraction (approximately 0.03%) is biologically active. Metabolism is through deiodination (to T3 or rT3), conjugation, and decarboxylation.
Typical Dose
Replacement dose (hypothyroidism): 1.6-1.8 mcg/kg/day (typically 75-200 mcg/day). Performance/fat loss: 100-200 mcg/day (above replacement to mildly elevate metabolic rate). Most users in the performance context use 150-200 mcg/day. T4 is much less potent mcg-for-mcg than T3, so higher doses are needed for metabolic effects.
Frequency
Once daily, in the morning on an empty stomach. The long half-life provides very stable blood levels with once-daily dosing.
Administration
Oral tablets, taken on an empty stomach (30-60 minutes before food) for optimal absorption. Absorption is significantly reduced by food, calcium, iron, and certain medications.
Half-Life
6-7 days
Contraindications
No traditional PCT required. Thyroid function recovers naturally after discontinuation. Due to the long half-life, the effective taper is built-in. TSH may take 4-8 weeks to fully normalize after stopping supraphysiological T4 doses. Check thyroid labs 6-8 weeks post-cycle.