NOT FOR HUMAN CONSUMPTION

RAD-140 (testolone) is an oral, non-steroidal selective androgen receptor modulator (SARM) engineered to deliver anabolic effects in muscle and bone with comparatively less stimulation of prostate/skin than testosterone. It binds the androgen receptor (AR), recruits muscle/bone-biased co-activators, and, unlike testosterone, does not aromatize to estradiol or undergo 5-α reduction. RAD-140 is not FDA/EMA-approved and is prohibited by WADA as an anabolic agent.

Additional Benefits of RAD-140 Now Under Investigation

Benefit	Key take-aways
1 Potent lean-mass accrual (preclinical → early translational)	In castrate/ovariectomy and diet-induced models, RAD-140 increases fat-free mass and myofiber CSA with limited prostate stimulation, per-mg potency among the higher in the SARM class. <br/><em>Journal of Pharmacology & Experimental Therapeutics; FASEB Journal</em>
2 Strength & function	Improves specific force, grip strength, and stair/peak torque surrogates in animal/bench models; human functional datasets remain limited. <br/><em>Medicine & Science in Sports & Exercise; AJP–Endocrinology</em>
3 Bone-anabolic effects	Raises BMD, enhances trabecular architecture, and improves biomechanical strength with modest prostate changes. <br/><em>Journal of Bone and Mineral Research; Bone</em>
4 Anti-catabolic under stress	Down-shifts atrogenes (MAFbx/MuRF1) and preserves CSA during glucocorticoids, disuse, or illness in preclinical studies. <br/><em>Endocrine Reviews; Molecular Metabolism</em>
5 Body-composition “repartitioning”	In obese models, reduces fat mass while preserving or increasing lean tissue, largely via AR-mTOR activation and improved oxidative programs. <br/><em>Obesity; Metabolism</em>
6 Neuroprotection signals	AR agonism with RAD-class ligands protects hippocampal neurons, enhances synaptic markers, and improves memory tasks in injury/aging models (translational relevance pending). <br/><em>Neurobiology of Aging; Brain Research</em>
7 AR-positive breast cancer (preclinical)	In ER⁺/AR⁺ models, selective AR agonism inhibits proliferation and shows additivity with CDK4/6 inhibitors, clinical validation needed. <br/><em>Cancer Research; Annals of Oncology</em>
8 Rehab synergy	Pairing with progressive resistance training yields additive hypertrophy/function vs either alone in translational paradigms. <br/><em>Sports Medicine; Journal of Physiology</em>
9 Oral convenience	Once-daily oral administration with long detection metabolites supports adherence in trials, also increases anti-doping scrutiny. <br/><em>Clinical Pharmacology & Therapeutics; Drug Testing & Analysis</em>

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

RAD-140 binds AR → nuclear translocation → ARE-driven transcription. In muscle it up-regulates mTOR/S6K/4E-BP1 and local IGF-1, while suppressing FoxO-atrogenes; in bone, AR signaling promotes osteoblastogenesis (Wnt/β-catenin/Osterix) and may indirectly restrain resorption. Lack of aromatization/5-α reduction contributes to tissue selectivity vs testosterone.

2.2 Down-stream Biology

Pathway	Functional outcome	Context
AR → mTOR/S6K/4E-BP1	↑ protein synthesis, myofiber hypertrophy	Skeletal muscle
AR ↔ Wnt/β-catenin/Osterix	↑ osteoblast activity, ↑ BMD	Bone
FoxO → MAFbx/MuRF1↓	↓ proteolysis (anti-catabolic)	Catabolic stress
Myostatin/activin crosstalk	Net anabolic bias	Muscle
Neurotrophic signaling (AR-dependent)	Synaptic support, neuroprotection (preclinical)	CNS

3. Pharmacokinetics

Route: Oral.
Exposure/half-life: Human PK has not been formally published; industry/forensic reports suggest a long terminal half-life compatible with once-daily dosing and multi-week metabolite detection in urine.
Metabolism: Hepatic oxidative/conjugative clearance; no aromatase/5-α pathways.
Protein binding: High (class feature).
Food effect: Not well characterized publicly.

4. Pre-clinical and Translational Evidence

4.1 Muscle & Function

Robust lean-mass and force improvements in rodent models, with lower prostate stimulation than testosterone for comparable anabolic effects.

4.2 Bone

In ovariectomized models, spine/femur BMD and three-point-bend strength improve, supporting exploration as an osteopenia adjunct (preclinical).

4.3 Neuro/CNS

Androgen-axis agonism with RAD-class ligands shows neuronal survival and synaptic plasticity benefits in injury/aging models; human translation is untested.

4.4 Oncology (AR⁺/ER⁺ breast)

Selective AR activation via non-steroidal ligands can inhibit ER-driven proliferation in preclinical systems; RAD-140 is part of this research space.

Evidence quality note: For RAD-140 specifically, human efficacy/safety data are sparse. Most signals derive from animal/in-vitro work and anti-doping forensics rather than registrational trials.

5. Emerging Clinical Interests

Field	Rationale	Current status
Sarcopenia/frailty	Oral anabolic with prostate-sparing intent	Preclinical/early translational
Rehabilitation/immobilization	Preserve/restore FFM & function	Concept pilots
Osteopenia/osteoporosis (adjunct)	Bone-anabolic + anti-resorptive balance	Preclinical
Cachexia	Appetite-neutral anabolism vs ghrelin mimetics	Preclinical
AR⁺/ER⁺ breast cancer	Selective AR agonism as antitumor strategy	Preclinical/early clinical exploration

6. Safety and Tolerability

Endocrine: Dose-dependent HPG-axis suppression (↓ LH/FSH/testosterone) expected; recovery often weeks–months after cessation.
Lipids: HDL-C reduction (± ↑ LDL/TG) common across SARMs, monitor CV risk.
Hepatic: Short controlled datasets are limited; case reports of cholestatic/drug-induced liver injury exist with unregulated RAD-140–containing products (purity/co-ingestants confound).
CV: No outcome data; lipid shifts and possible BP effects warrant caution.
Dermatologic/androgenic: Acne/oily skin, hair shedding in predisposed individuals.
Neuropsych: Insomnia, irritability, anxiety occasionally described in uncontrolled settings.
Hematologic: Mild ↑ hematocrit possible, monitor in at-risk populations.
Drug interactions: Potential with drugs affecting hepatic enzymes/lipids; avoid hepatotoxins and use in pregnancy.

Comparative safety matrix

Concern	RAD-140	LGD-4033	Enobosarm (MK-2866)
Human evidence	Very limited	Small RCT (21 d)	Multiple Phase 2
HPG suppression	Moderate–strong	Moderate	Moderate
HDL impact	↓ Common	↓ Common	↓ Common
Prostate stimulation	Low (preclinical)	Low	Low
Hepatotoxicity signal	Case reports (unregulated)	Case reports	Case reports (rarer)
Route / t½	Oral; long (inferred)	Oral; 24–36 h	Oral; ~24 h

7. Regulatory Landscape

Approvals: None for any medical indication.
Sport: WADA-prohibited (S1, Other Anabolic Agents) at all times; detection of long-term metabolites enables weeks-long windows.
Market quality: Grey-market products frequently show adulteration/mislabeling; medical use outside trials is unsafe.

8. Future Directions

First-in-human PK/PD with GMP material to define half-life, metabolites, exposure–response.
Head-to-head vs other SARMs for anabolic:androgenic ratio, lipid neutrality, and HPG suppression.
Long-term safety: lipids/CV outcomes, hepatic profile, endocrine recovery, mood/CNS effects.
Oncology programs in AR⁺/ER⁺ breast cancer, rational combos (CDK4/6 inhibitors, endocrine therapy).
Rehab/sarcopenia RCTs paired with progressive resistance training and protein targets; standardized functional endpoints (SPPB, stair-climb power, 6MWT).
Doping science: Comprehensive metabolite ID, hair/urine detection windows, and contamination risk mapping.

Selected References

Journal of Pharmacology & Experimental Therapeutics; FASEB Journal, Anabolic and anti-catabolic signaling of RAD-class SARMs in muscle.
Journal of Bone and Mineral Research; Bone, SARM effects on BMD and biomechanical strength in osteopenic models.
Neurobiology of Aging; Brain Research, AR-mediated neuroprotection and synaptic support (preclinical).
Cancer Research; Annals of Oncology, Selective AR agonism in ER⁺/AR⁺ breast cancer models.
Medicine & Science in Sports & Exercise; AJP–Endocrinology, Strength/function correlates under AR activation.
Drug Testing & Analysis, Identification of RAD-140 long-term metabolites and detection windows.
Hepatology Communications; J Clin Transl Hepatol, Case reports of liver injury associated with unregulated SARM products (class context).
Clinical Pharmacology & Therapeutics, Oral PK/PD considerations for non-steroidal SARMs.

Injectable RAD140 500mg vial

Complete the setup