A manufactured copy of the main thyroid hormone, taken once daily. Where the gland has genuinely failed, benefit is clear: hormone levels normalize, deficiency symptoms lift, cholesterol falls. Where the gland is only mildly underperforming, trials past the mid-sixties find no gain, while too much brings irregular heart rhythm, faster bone loss, and fracture. (Full Review)

Protocol

Standard full-replacement dose

~1.6 µg/kg daily

Lean or ideal body weight, once daily, for established overt hypothyroidism in an adult under 65 without cardiac disease. A 70 kg adult lands near 100–112 µg.

Conservative initiation dose

12.5–25 µg daily

Used over 65, in known coronary disease, and in mild deficiency generally; increased by 12.5–25 µg every 6–8 weeks. Mild deficiency typically requires only 25–75 µg.

Best time of day

Fasting, morning

At least 30–60 minutes before food or coffee. Bedtime dosing, at least 3 hours after the last meal, is a validated alternative; what matters more is that it stays constant.

Time to effect

Energy and cognition

3–6 months

In overt deficiency. Subjective change lags the objective markers considerably.

Cholesterol

6–12 weeks

Objective markers move first; the pituitary signal falls within 4–6 weeks and blood levels reach steady state after about 6 weeks.

Skin, hair, body composition

6–12 months

In mild deficiency, no subjective change by 6 months at a properly titrated dose means further increases are unlikely to help.

Benefits

High: Correction of overt hypothyroidism; lipid improvement in overt hypothyroidism; prevention of progression to severe deficiency

Medium: Cardiovascular event reduction in younger adults; modest lipid and blood pressure improvement in mild deficiency; improvement in cardiac structure and arterial wall thickness; reduction of pregnancy loss and preterm birth in mild deficiency and thyroid autoimmunity

Low: Symptom, fatigue, and quality-of-life improvement in mild deficiency; cognitive function; reduction of liver fat in metabolic fatty liver disease

Speculative: Preservation of muscle mass and physical performance; slowing of autoimmune thyroid destruction

Contraindications

Untreated adrenal insufficiency (absolute)

Untreated thyrotoxicosis of any cause (absolute)

Use for weight loss or obesity with normal thyroid function (absolute)

Acute myocardial infarction within 90 days, or unstable angina (avoid or defer)

Established atrial fibrillation, or osteoporosis with a T-score below −2.5 (extreme caution)

Adults over 80 with TSH below 10 mIU/L (extreme caution)

Hypertrophic cardiomyopathy, severe uncontrolled hypertension (caution)

Key Interactions

Absorption-blocking minerals and binders (calcium, iron, magnesium, aluminium antacids, sucralfate, bile acid sequestrants, phosphate binders, orlistat)

Acid-suppressing medication (proton pump inhibitors, H2 blockers)

Enzyme-inducing anticonvulsants and antibiotics (rifampin, phenytoin, carbamazepine, phenobarbital)

Estrogens and androgens (oral estrogen, raloxifene, tamoxifen, testosterone, danazol, high-dose glucocorticoids)

Warfarin

Cardiac and metabolic drugs (digoxin, insulin and oral glucose-lowering drugs, amiodarone, tyrosine kinase inhibitors)

Sympathomimetics (pseudoephedrine, amphetamine salts, methylphenidate, high-dose caffeine, ketamine)

Supplement interactions (calcium, iron, magnesium, zinc, chromium picolinate, coffee, soy, fibre, walnuts, high-dose iodine and kelp, biotin above 5 mg, cannabidiol, alpha-lipoic acid, resveratrol)

Supplements with additive thyroid-hormone effects (desiccated thyroid extract, liothyronine, "thyroid support" and glandular products, guggul, tyrosine)

Other intervention interactions (sustained calorie restriction, prolonged fasting, prolonged ketogenic dieting, heavy endurance training)

Risk & Side Effects

High: Iatrogenic thyrotoxicosis from over-replacement; atrial fibrillation; accelerated bone loss and fracture

Medium: Cardiovascular disease and excess mortality with suppressed signal; adrenergic symptoms; precipitation of adrenal crisis in undiagnosed adrenal insufficiency; angina and myocardial ischemia in coronary disease

Low: Transient hair loss; excipient hypersensitivity and formulation intolerance; dementia risk

Speculative: Erasure of a longevity-associated thyroid phenotype; long-term neoplastic risk from sustained hormone exposure

Monitoring

Marker	Target	Why
TSH	1.0–2.5 mIU/L under 65; 3.0–5.0 over 70	Primary dosing target and the single best over-replacement marker
Free T4	1.0–1.5 ng/dL	Confirms adequate replacement and detects excess even when TSH looks acceptable
Free T3	3.0–4.0 pg/mL	Measures the active hormone actually available to tissues, which T4 alone does not report
Reverse T3	Below 20 ng/dL; free T3 to reverse T3 ratio above 0.20	Detects diversion of T4 into the inactive form rather than the active one
TPO antibodies	Undetectable or below 9 IU/mL	Establishes whether the underlying cause is autoimmune, which determines whether a withdrawal trial is reasonable
LDL cholesterol	Below 100 mg/dL, or below 70 with cardiovascular risk	Tracks the reversible lipid elevation caused by deficiency and confirms adequate replacement
Ferritin	70–150 ng/mL	Low iron stores blunt hormone conversion and independently cause the fatigue and hair loss attributed to the thyroid
25-hydroxyvitamin D	40–60 ng/mL	Deficiency is common in autoimmune thyroid disease and independently worsens fatigue and bone loss
Sex hormone-binding globulin	Mid-range for sex and age	A tissue-level readout of thyroid hormone action in the liver, independent of the pituitary
Resting heart rate	55–70 bpm, stable against the individual's own baseline	The earliest and cheapest daily signal of over-replacement
Bone density T-score	Above −1.0	Detects the accelerated bone loss that is the principal long-term cost of over-replacement

Cadence: 6–8 weeks after starting and 6–8 weeks after every dose, brand, formulation, or interacting-drug change, then every 6 months during the first year, then every 12 months once stable. Bone density every 2 years while on therapy; an electrocardiogram annually after age 65 or whenever the pituitary signal falls below the reference range.

Qualitative Assessment

Energy stability through the day
Cognitive clarity and word retrieval
Cold tolerance and extremity temperature
Sleep quality and ease of falling asleep
Palpitations, tremor, and inner restlessness
Bowel regularity
Skin dryness, hair texture, and nail strength
Exercise recovery and perceived effort at a fixed workload

Levothyroxine for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment