MK-677 (Ibutamoren) vs RAD-140 (Testolone)

Mechanism

MK-677 (ibutamoren) is an orally active, non-peptide growth hormone secretagogue that mimics ghrelin by binding the ghrelin receptor (GHSR1a) in the hypothalamus and pituitary. This triggers pulsatile growth hormone release via the same physiological mechanism as endogenous ghrelin, preserving the natural episodic GH secretion pattern. MK-677 increases GH, IGF-1, and IGFBP-3 levels to those observed in young adults without affecting cortisol levels. It also stimulates appetite through ghrelin receptor activation in the hypothalamus. Unlike exogenous GH injection, MK-677 maintains the pulsatile GH pattern and stimulates all five GH isoforms.

Standard Dosing

Research indicates 10-25 mg daily orally. Clinical trials used 25 mg/day. 10-15 mg may provide GH elevation with fewer side effects.

Timing

Take 30-60 minutes before bedtime. This timing leverages the natural nocturnal GH pulse, maximizes sleep quality benefits, and minimizes daytime appetite increase. Half-life ~24 hours ensures once-daily dosing is sufficient.

Cycle Duration

Can be used continuously for months to years — no cycling required as it works through physiological GH release mechanisms. Clinical trials ran for up to 2 years. Reassess IGF-1 and metabolic markers every 3-6 months.

Side Effects

• Increased appetite (ghrelin mimetic — significant and persistent)
• Water retention and bloating (GH-mediated)
• Numbness and tingling (carpal tunnel-like symptoms)
• Elevated fasting blood glucose and insulin resistance
• Lethargy and increased sleep depth
• Vivid dreams
• Joint pain (less common than exogenous GH)

Contraindications

• Active malignancy (GH/IGF-1 promotes cell proliferation)
• Diabetes mellitus (impairs glucose tolerance — use with extreme caution)
• Active diabetic retinopathy
• History of pituitary tumors
• Congestive heart failure (fluid retention)

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Mechanism

RAD-140 is a potent nonsteroidal SARM with high oral bioavailability and selectivity for muscle and bone AR over prostate. It acts as a full agonist at the AR in muscle tissue, promoting nitrogen retention and protein synthesis via mTOR/p70S6K pathway activation. RAD-140 also demonstrates neuroprotective properties, acting against beta-amyloid-induced neurotoxicity through AR-mediated MAPK/ERK signaling. Preclinical data show greater anabolic potency than testosterone propionate at equivalent doses with significantly reduced prostate stimulation.

Standard Dosing

Research indicates 10-20 mg daily orally for 8-12 weeks. Phase 1 clinical trial (oncology) identified 100 mg as the maximum tolerated dose.

Timing

Once daily, consistent timing. Very long half-life (~60 hours) means stable plasma levels even with once-daily dosing. Morning preferred.

Cycle Duration

8-12 week cycles. PCT mandatory due to significant HPG axis suppression.

Side Effects

• Significant testosterone suppression
• Hepatotoxicity (multiple published case reports of drug-induced liver injury)
• HDL suppression and LDL elevation
• Aggression and mood changes
• Hair shedding (androgenic effect despite 'selective' designation)
• Insomnia
• Headache

Contraindications

• Pre-existing liver disease
• Androgen-sensitive cancers
• Cardiovascular disease (LDL elevation concern)
• Pregnancy and breastfeeding
• Individuals under 21
• Athletes subject to anti-doping testing

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