You may have heard of Stenabolic on a podcast, or from someone in the gym taking about the latest and greatest performance enhancing products, to help with building more size and strength. Stenabolic, SR9009 is a metabolic modulator, developed by the Scripps Research Institute, with has a unique ability to activate Rev-erbα a member of the nuclear receptors, superfamily which are key regulatory components of the circadian clock. We are going to discuss what Stenabolic is, how Stenabolic works, and the current research.
Commonly mistaken for a selective androgen receptor modulator, (SARM), Stenabolic SR9009, is a metabolic modulator, specifically a circadian nuclear receptor Rev-erB agonist which has a direct effect on the circadian clock and heart ergogenics.
REV-ERB, is the core clock component, and essential for heart function. It was first developed by Thomas Burris of the Scripps Research Institute. The Scripps Research institute is the largest non-profit biomedical research institute in the U.S with over 1,100 patents, and 11 FDA-approved therapeutics.
Stenabolic is very complex compound. Although the exact mechanisms of how Stenabolic effects REV-ERB proteins, is not well understood, it has shown to have cardiac protective function and indirectly affect other proteins, in non-cardiac tissues.
Studies show that Stenabolic ameliorates heart remodeling and pressure overload with transverse aortic constriction. Disruption of circadian rhythm has long been associated with cardiovascular disease.
Further studies have shown that SR9009 and specific synthetic agonists of the nuclear receptors REV-ERB-α and -β (REV-ERBs) have produced benefits on sleep and metabolism [R].
So what does all this mean? To really begin understanding how stenabolic works, you must first understand what nuclear receptors, and how REV-ERB-α and -β (REV-ERBs) works.
Nuclear receptors comprise a class of transcription factors that regulate several metabolic processes, such as reproduction, development, and metabolism. They also regulate skeletal muscle energy and remodeling, or building.
There are two members in the REV-ERB subfamily of nuclear receptors: REV-ERBα and REV-ERBβ. REV-ERBs are active components of the circadian clock. Circadian rhythms are physical, mental, and behavioral changes that follow a 24-hour cycle.
Pre-clinical data shows, that Stenabolic could help repair tissue damage after myocardial infarction (heart attack). Mild or severe tissue damage occurs with restoration of blood flow after a period of ischemia or lack of oxygen, when a heart attack occurs. The inflammation from a heart attack leads to heart failure [R].
Circadian mechanisms are critical regulators of reperfusion injury. SR9009 has demonstrated that short term targeting of the Rev-ERB benefits long-term cardiac repair post-myocardial ischemia reperfusion in mice, promoting efficient repair, and reduced inflammation [R].
Stenabolic is what’s called an exercise mimetic, or as some call it “exercise in a pill”. The unique properties of stenabolic, enhance or even substitute for the beneficial effects of physical exercise, by improving cardiovascular performance, as well as increasing mitochondria production, and energy metabolism. Physical exercise essentially remodels skeletal muscle, and adapts to physical stress, enhancing its ability to burn calories.
Pre-clinical animal studies show that activation of the Rev-erbα by SR9009 increases exercise capacity by increasing mitochondria in skeletal muscle. Rev-erbα is expressed at higher levels in oxidative muscles compared to glycolytic muscles and exercise can further induce its expression [R].
The physiological changes in are thought to be mediated and activated by the AMPK pathway. AMPK is an energy sensor that, when activated in certain tissues, has many beneficial effects on our bodies. It stimulates metabolism, improves insulin sensitivity, decreases inflammation, and improves muscle performance.
There’s a reason, why the World Anti-Doping Agency (WADA) has banned Stenabolic. The properties, show that it’s potential as an ergogenic aid could greatly enhance cardiovascular performance, exercise capacity, and induce fat burning effects, from increase energy metabolism and basal metabolic rate.
Other investigational studies show that SR9009 may have a chemotherapeutic effect on Human Glioblastoma T98G cells. Glioblastoma multiforme is the most aggressive type of brain tumor.
Research suggests that Stenabolic, decreases reactive oxygen species (ROS), also known as oxidative stress, via free radicals, as well as significant reduction in cell viability with consequences on cell cycle progression and tumor cell viability.
The pharmacological modulation of the tumor-intrinsic clock by REV-ERB agonists severely affects cell metabolism and promotes cytotoxic effects on cancer cells [R]
Currently, there are no human clinical trials that have been conducted on SR9009. Thus, other than anecdotal side effects, clinically determined side effects are hard to determine.
Anecdotal reported side effects include but are not limited to
Nausea
Headache
Wakefulness
Trouble Sleeping
Stenabolic is not a hormone modulator, but a metabolic modulator, modulating or inducing metabolic effects. Thus, post cycle therapy is not required with the use of Stenabolic or nuclear receptor agonists. Dosage is also undetermined, to elicit ergogenic benefit.
Pre-clinical data shows that Stenabolic SR9009, has therapeutic potential to help improve endurance capacity, heart ergogenics, and enegy metabolism, through the Rev-ERB pathway and cyclic AMPK. Human safety and efficacy trials to verify correct dosage and pharmacokinetics, are required to determine and validate relative clinical benefit.
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