Andarine (S-4): the selective SARM for cutting and strength

May 17

Information Note: This article is for research and educational purposes only. Andarine (S-4) is not approved as a drug by the EMA or FDA and must not be used by humans outside of controlled clinical trials. The content does not constitute medical advice and does not encourage the use of the substance.

Andarine S-4 belongs to the group of selective androgen receptor modulators, more commonly known as SARMs. The substance was originally synthesized by the Japanese pharmaceutical company Kaken Pharmaceuticals and then further evaluated by GTx Inc. as a potential drug against muscle atrophy, osteoporosis and benign prostatic hyperplasia. Phase I and II studies published on PubMed showed promising results for skeletal muscle preservation, but the program was never discontinued and reached clinical approval phase. Even so, S-4 circulates widely in discussions of arm cutting and physical performance — which warrants a careful review of what the research actually says.

—

How does andarine S-4 work at the molecular level?

Brief: S-4 selectively binds to androgen receptors in muscle and bone with high affinity, but acts as a partial agonist in prostate tissue — theoretically reducing androgenic side effects compared to anabolic steroids.

The androgen receptor is a ligand-dependent transcription factor protein that is activated by testosterone and dihydrotestosterone (DHT). Classic anabolic steroids bind to the receptor with full agonist activity in all tissues, which produces muscle building but also side effects such as prostate hypertrophy, hair loss and suppression of endogenous testosterone. The S-4 is designed to separate these effects.

In preclinical studies in rats (Kearbey et al., 2007, Endocrinology), S-4 maintained muscle mass and bone mineral density in castration-induced atrophy, while prostate weight increased by only 15–20% compared to 100% with testosterone supplementation. The mechanism is based on S-4 recruiting a different set of coreceptor proteins than DHT, which results in tissue-specific gene transcription.

The binding affinity for the androgen receptor is measured as Ki value. For S-4, Ki of approximately 4 nM was reported in muscle cells, to compare with testosterone’s Ki of approximately 1 nM. Lower affinity is compensated by the substance’s resistance to aromatization — S-4 is not converted to estrogen, which keeps water retention low during a cutting protocol.

—

What dosages and protocols are discussed in the research for S-4 as a SARM?

Brief: Preclinical data and informal human reports hover around 25–75 mg per day, divided into 1–2 doses, with cycle lengths of 6–8 weeks.

No approved human dosing protocol exists. The animal studies used effective doses of 0.1–3 mg/kg body weight, which roughly provides a benchmark for what is discussed within the scientific community. The table below summarizes the dose levels found in the literature and in official testosterone deprivation models.

Dose range (mg/day)	Tissue effect (animal data)	Observed risk

| 12,5–25 |Minimal anabolic response, bone protection|Low visual impact|

| 25–50 |Muscle mass preservation, fat reduction|Moderate visual impairment at >4 yrs|

| 50–75 |Pronounced muscle anabolism|Clear vision impact, stronger suppression|

| >75 |Not studied clinically|Unknown risk level|

Regarding s4 sarm dosing, it should be noted that the half-life in animal studies was estimated to be 4–6 hours, which speaks for a divided daily dose. GTx protocols in phase II trials used intermittent dosing schedules (5 days on, 2 days off) in an attempt to reduce vision-related side effects — with mixed results.

The combination protocol with Cardarine (GW-501516) appears in bodybuilding literature as a pair for sarm cutting, but there is a lack of human data proving the benefit and safety of such stacks.

—

What are the side effects of andarine, and why are visual disturbances a particular problem?

Brief: Andarine side effects include visual disturbances (yellowish syntony, night blindness), testosterone suppression, and liver effects — the visual effects are unique to S-4 among SARMs.

The mechanism behind S-4’s visual effects

S-4’s most talked about side effect is the visual one. It is explained by the fact that the retina and conjunctiva of the eye contain androgen receptors. S4 vision occurs when S-4 binds to these receptors and disrupts photoreceptor function, primarily rods and cones in the periphery. Clinical reports and animal studies describe:

• Yellowish syntone (everything looks yellowish in daylight)

• Impaired night vision and adaptability

• Peripheral loss that reduces the field of vision

The effect is dose-dependent and in most reported cases reversible upon discontinuation, but the recovery time varies from days to several weeks. The intermittent dose schedule (5/2) that GTx tested was precisely aimed at allowing the receptors in the retina to recover during the rest days, but the reduction in s4 vision was not consistent in all cases.

Hormonal suppression and liver values

In addition to vision, suppression of endogenous LH and FSH is reported at doses above 25 mg/day, which means that the natural testosterone surge is dampened. The degree of suppression appears to be lower than with classic steroids but significant enough to justify follow-up with a hormone panel. Animal studies also show transaminase elevations at higher doses, suggesting hepatotoxic potential — a finding seen in several SARMs with incompletely investigated metabolite profiles.

—

How does S-4 compare to other SARMs for cutting and strength?

Brief: Compared to Ostarine and LGD-4033, S-4 offers stronger anabolism when cutting but with a specific visual side effect that the others lack.

The correct comparison context requires that one distinguish between the targets for which the substances were evaluated. Ostarine (MK-2866) is the most clinically studied SARM and reached Phase II for muscle atrophy and breast cancer. LGD-4033 was tested in a randomized placebo-controlled phase I study published in 2013 in the Journals of Gerontology and showed pure muscle mass gain without significant impact on PSA or liver values ​​at low doses.

• S-4 vs Ostarine: S-4 exhibits higher androgen receptor affinity and, according to animal data, provides stronger muscle mass preservation, but the synarty distinguishes S-4 negatively.

• S-4 vs LGD-4033: LGD-4033 is more anabolic per mg and has a better human database, but lacks S-4’s direct effect on BMD in comparable models.

• S-4 vs RAD-140: RAD-140 shows higher selectivity (anabolic/androgen ratio of >90:1 in animal data), no reported visual effects, but lacks published human clinical data.

• S-4 vs GW-501516 (Cardarine): Cardarine is technically not a SARM but a PPARδ agonist and the comparison is categorically incorrect, but the combination is discussed for endurance and fat mobilization.

None of these substances are approved for human use. Sarm cutting as a concept lives in a gray zone where preclinical results are extrapolated directly to human use without intermediate safety data.

—

Frequently asked questions about andarine S-4

Is andarine legal to buy in Sweden?

S-4 is classified as a health hazard according to the Swedish Act on Prohibition of Certain Health Hazards (SFS 1999:42). Possession, transfer and acquisition for the purpose of using the substance can be punishable. The rules for research and licensed laboratory use differ from consumer use — always consult a lawyer or authority before any handling.

How long does it take before andarine side effects on vision occur?

Visual disturbances are reported in animal studies and informal case reports usually after 2–4 weeks of continuous use at doses above 25 mg/day. Onset is dose-dependent — lower doses produce later and milder effects. Reversibility after discontinuation takes 1–4 weeks in most cases, but occasional reports describe longer recovery times.

Does S-4 affect natural testosterone production?

Yes. Although suppression is lower than with anabolic steroids, animal studies and informal blood test series show that LH and FSH decrease at doses above 25 mg/day. The endogenous testosterone surge normally resumes after the end of the cycle, but the time span varies between individuals and has not been systematically studied in human trials.

Why was the clinical development of S-4 suspended?

GTx focused resources on Ostarine and Enobosarm, which showed better pharmacological profile in human data. S-4’s visual side effect was a complicating factor in the risk assessment for a drug approval, especially for populations with pre-existing vision impairment or eye disease. No official statement on definitive closure has been published.

Can S-4 be detected in doping tests?

WADA listed SARMs on the Prohibited List in 2008 (Category S1 Anabolic Agents). Modern urinalysis with LC-MS/MS methodology can detect S-4 and its metabolites. The detection window is estimated to be 10–28 days depending on dose and metabolism, but exact cutoff values ​​vary between laboratories and sampling protocols.

What does current research say about the future of SARMs as drugs?

Research is ongoing, but no SARM has yet received marketing authorization (2024). Enobosarm (Ostarine) was rejected by the FDA for cancer-related muscle wasting in 2013 but was further evaluated for breast cancer. The scientific community sees SARMs as a promising substance class for sarcopenia and osteoporosis, but clinical documentation for safety and efficacy in long-term use is still lacking.

—

All content in this article is based on published preclinical and clinical literature and is produced for educational purposes. It does not constitute medical advice. Always consult a doctor or pharmacologist before handling pharmacologically active substances.

.entry-content