Selenium (Selenomethionine) vs Thyroid (Levothyroxine / Liothyronine T3/T4)

Mechanism

Selenium is incorporated as selenocysteine (the 21st amino acid) into 25 selenoproteins. Key enzymes: glutathione peroxidases (GPx1-4, reduce hydrogen peroxide and lipid hydroperoxides), thioredoxin reductases (TrxR1-3, maintain cellular redox balance), iodothyronine deiodinases (DIO1-3, convert T4 to T3 and regulate thyroid hormone metabolism), selenoprotein P (selenium transport and brain antioxidant), and selenoprotein W (muscle antioxidant). Selenium is essential for thyroid function, immune defense, reproductive health, and cancer chemoprevention.

Standard Dosing

200 mcg selenomethionine daily

Timing

With meals. Can be taken any time of day.

Cycle Duration

ongoing

Side Effects

• Garlic breath/body odor (selenosis)
• GI upset
• Hair loss and nail brittleness (toxicity)
• Fatigue
• Peripheral neuropathy (chronic excess)
• Potential type 2 diabetes risk at high doses (SELECT trial observation)

Contraindications

• Selenium excess (>400 mcg/day — narrow therapeutic window)
• Non-melanoma skin cancer history (SELECT trial concern)

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Mechanism

Levothyroxine (T4) is a prohormone converted to the active triiodothyronine (T3) by type 1 and type 2 deiodinase enzymes (DIO1/DIO2) in peripheral tissues. T3 binds nuclear thyroid hormone receptors (TRa and TRb), forming heterodimers with retinoid X receptors (RXR) that bind thyroid response elements (TREs) in DNA, directly modulating transcription of genes controlling basal metabolic rate, thermogenesis, mitochondrial biogenesis (via PGC-1a), cardiac output, and neuronal development. T3 also exerts rapid non-genomic effects on mitochondrial respiration, ion channels, and cell membrane transport.

Standard Dosing

Research indicates Levothyroxine (T4): 25-200 mcg daily based on TSH and free T4 levels. Liothyronine (T3): 5-25 mcg daily, often split into 2-3 doses. Combination T4/T3 ratio typically 4:1 to 3:1 when using both.

Timing

Levothyroxine: Take on empty stomach, 30-60 minutes before breakfast or at bedtime (3+ hours after last meal). Separate from calcium, iron, and antacids by 4 hours. Liothyronine: Split into 2-3 daily doses due to short half-life (2.5 hours for T3 vs. 6-7 days for T4).

Cycle Duration

Ongoing for diagnosed hypothyroidism. Optimization protocols may be shorter-term (3-6 months) with reassessment.

Side Effects

• Tachycardia and palpitations (overdose or too-rapid titration)
• Anxiety and insomnia (particularly with T3)
• Tremor
• Weight loss (excessive dosing)
• Hair loss (temporary during initiation or dose changes)
• Heat intolerance and sweating
• Bone density loss at suppressive doses (TSH <0.1)

Contraindications

• Untreated adrenal insufficiency (correct cortisol before thyroid replacement)
• Acute myocardial infarction
• Thyrotoxicosis
• Known hypersensitivity to levothyroxine or liothyronine

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