REV-ERBα/β agonists: how to use anabolic steroids without damaging your body (SR9009, SR9011)

The circadian rhythm doesn't just regulate sleep cycles, it plays a critical role in metabolic regulation and by extension determines ones level of disease & inflammation. In order to maintain homeostasis and promote survival, the circadian clock coordinates and maintains the 24-hour rhythmicity of various physiological processes, the most evident are the sleep/wake and fasting/feeding cycles. Disruption of the clock has been associated with an increased susceptibility and/or development of sleep and metabolic disorders. Proper circadian function occurs in response to synchronous expression of the molecular machinery of the circadian clock, composed of a central pacemaker in the suprachiasmatic nucleus (SCN) residing in the hypothalamus. While the master clock is entrained by light, almost all cells in the body harbor peripheral clocks that are entrained by both signals from the master clock and environmental cues.
​

The REV-ERBα/β complex is one of the key gene suppressors/activators that is responsible for the function of the circadian core clock machinery. Before I explain REV-ERB's function you need to understand how the circadian rhythm functions:​

​

Spoiler: for the nerds

The activation of the genes BMAL1 (brain and muscle arnt-like protein 1) and CLOCK (circadian locomotor output cycles kaput) positively regulate the activation/transcription of Per (period) and Cry (cryptochrome) causing a negative feedback loop that suppresses BMAL1/CLOCK. In doing this the Per/Cry complex is repressing CLOCK from activating Per/Cry in the first place which causes a 24h oscillation in Per/Cry levels. To break down further:

BMAL1 and CLOCK, heterodimerize and drive the expression of Cryptochrome (Cry1, 2) and Period (Per1-3). Once Cryptochrome and Period proteins reach a critical threshold, PER:CRY complexes translocate to the nucleus to repress Bmal1:Clock transactivation.

BMAL1/CLOCK (CLOCK complex) → activation of Per/Cry → suppression of CLOCK → suppression of Per/Cry

Okay, so how does REV-ERBα/β play a role in this cascade?

REV-ERB operates on a different part of the clock machinery. It doesn't directly interact with the CLOCK complex. Instead, REV-ERB represses Bmal1 expression. This means that when REV-ERB is active, less BMAL1 is available, which weakens the ability of CLOCK to drive the expression of Per/Cry. In the daytime, REV-ERB levels are high, so Bmal1 is repressed. In the nighttime, REV-ERB levels fall, allowing Bmal1 expression to rise again, which enables the next cycle of Per and Cry transcription. So to break it down again:

REV-ERBα/β → suppression of BMAL1/CLOCK → weakened expression of Per/Cry → inhibition of the negative feedback loop

When we agonise REV-ERBα/β with a synthetic ligand (SR9009 or SR9011) we are interrupting this process by positively bolstering REV-ERB's ability to suppress the negative feedback loop via it's inhibition of BMAL1/CLOCK expression

​

Okay, so why is any of this important for our heatlh and by extension, our looks?​

Because, REV-ERB and the cascade of gene expression/suppression plays a VITAL role in circadian-contingent regulation of inflammation, lipid synthesis, mitogenesis/mitochondrial function, muscle function, cancer progression, bile synthesis (hepatoprotection) and more. For those of you who are hesistant to use steroids because of their effects on dyslipidemia (hyperlipidemia) and hepatotoxicity, this is everything you need to know about REV-ERB and it's ligands:

SR9009 and SR9011 are potent agonists at REV-ERBα (most activity occurs here) and REV-ERBβ (very potent but less so than at alpha). These drugs are responsible for directing metabolic function in a circadian manner. To make this guide more digestible I'll break down SR9009/11's effects into categories, starting with Lipids:

Mice lacking REV-ERBα show impaired lipid metabolism, leading to elevated levels of triglycerides and free fatty acids in the liver. In contrast, activation of REV-ERBα reduces triglycerides and free fatty acids in mice. This lipid-lowering effect is linked to the transcriptional repression of ApoC-III, which plays a crucial role in triglyceride metabolism by inhibiting the breakdown of triglyceride-rich particles, and Elovl3, which is involved in the elongation of fatty acids to generate very long-chain fatty acids[1] The REV-ERB nuclear receptors have been shown to play a key role in regulating lipid metabolism. It has been demonstrated that pharmacological activation of Rev-erb reduced plasma cholesterol levels in mice, while others found that mice lacking Rev-erb had elevated plasma cholesterol levels. Findings reveal that Rev-erb coordinately regulates most of the genes encoding critical enzymes involved in the cholesterol biosynthesis pathway[2]. It seems to inhibit the rate limiting enzyme in cholesterol synthesis (cyp7a1/cholesterol 7α-hydroxylase)[3]

In the aforementioned study it was found that these mice experienced a reduction of 36% and 41% in total cholesterol and LDL cholesterol upon activation of the Rev-erb. A previous study reported an increase in plasma LDL and cholesterol in REV-ERB knockout mice which further supports the notion that REV-ERB negatively regulate cholesterol levels. This is incredibly important for users of steroids because AAS cause a dose-dependent increase in LDL and a decrease in HDL. In another study, the plasma cholesterol analysis of rats that were fed a high-cholesterol diet showed significant reduction in total cholesterol (36%), LDL-C (41%) and triglycerides (40%) in response to SR9009 treatment. HDL-C levels were not affected by SR9009[4]

Not only does REV-ERB activation significantly reduce total cholesterol levels, it regulates macrophages M1 and M2, the ratio of which plays an important role in the development of atherosclerosis. Dyslipidemia and inflammation is responsible for plaque build up in the arteries and REV-ERB knockout mice are proven to have dysregulated ratios between M1 and M2. M1 is pro-inflammatory and cytotoxic, whereas M2 is anti-inflammatory. REV-ERB deficient mice have higher levels of M1 and in conjunction with hyperlipidemia (high total cholesterol) the development of atherosclerosis is majorly increased. SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to pro-inflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Essentially, the introduction of SR9009 normalized the aberrant levels of M1 and increased the levels of M2.[5]

By extension of REV-ERB's effect on macrophages and lipid synthesis, it is highly cardioprotective. However, the inhibition of cardiac fibrosis plays a much larger role in it's cardioprotection. SR9009 prevents cardiomyocyte hypertrophy, reduces fibrosis, and halts heart failure progression in mice. Additionally, SR9009 improves left ventricular function and increases survival rates following myocardial infarction. It also reduced the expression of cytokines IL-6, MMP9, and limited immune cell infiltration (pro-inflammatory macrophages) in the heart. In mice with pressure-induced cardiac hypertrophy caused by transverse aortic constriction, SR9009 lowered protein kinase B (AKT) expression and reduced cardiac hypertrophy[6]

REV-ERBα plays a key role in glucose homeostasis and the development of diabetes by regulating glucose synthesis and the function of pancreatic α and β cells. Activation of REV-ERBα lowers both cellular and plasma glucose levels. Similarly, mice lacking REV-ERBα exhibit elevated plasma glucose levels.[7] Anecdotally, my hba1c levels haven't breached 5mmol/L since starting SR9009.

REV-ERBα activation by SR9009 inhibits transcription of inflammatory factors IL-1β, IL-6, MMP-9, and Ccl2 in astrocytes. SR9009 significantly attenuates hepatic damage and inflammatory responses, it is effective in suppressing clinical markers of liver damage, circulating lipids, hepatic fibrosis, and markers of inflammation. In addition, pharmacological activation of REV-ERBα by SR9009 alleviated hepatic steatosis, insulin resistance, liver inflammation, and fibrosis in CL diet-induced NASH mice. These effects were accompanied by improved gut barrier function and altered microbial composition and function in NASH mice, and the effect tended to be stronger when SR9009 was injected at ZT0 (night time) Moreover, SR9009 treatment at different time points resulted in a marked difference in the composition of the microbiota, with a stronger effect on the enrichment of beneficial bacteria and the diminishment of harmful bacteria when SR9009 was administrated at night.[8, 9, 10]

SR9009 potently regulates mitogenesis (the formation of new mitochondria) and mitochondrial respiration. In one study dealing with REV-ERBα knockout mice, cellular effects resulted in both impaired mitochondrial biogenesis leading to compromised exercise capacity. On a molecular level, REV-ERBα deficiency resulted in deactivation of the Lkb1-Ampk-Sirt1-Ppargc-1α signaling pathway.[11] Additionally, genes encoding enzymes of fatty acid β-oxidation, like carnitine palmitoyltransferase 1b (Cpt1b), long chain acyl-CoA dehydrogenase (Acadl), short chain acyl-CoA dehydrogenase (Acads), Ucp2, and Ucp3, genes involved in skeletal muscle metabolism, were also upregulated with REV-ERBα overexpression.[12] Researchers have demonstrated that mice lacking REV-ERBα had decreased skeletal muscle metabolic activity and running capacity. Burris’ group showed that activation of REV-ERBα with SR9009 led to increased metabolic activity in skeletal muscle in both culture and in mice. The treated mice had a 50 percent increase in running capacity, measured by both time and distance.[13].

“The animals actually get muscles like an athlete who has been training,” said Burris. “The pattern of gene expression after treatment with SR9009 is that of an oxidative-type muscle— again, just like an athlete.”

Speaking of muscles, glucocorticoids seem to negatively regulate REV-ERB expression, REV-ERBα mRNA levels were shown to be down-regulated by dexamethasone in the liver and in both rat and human primary hepatocyte cultures in one study[14]. In another study, REV-ERBα overexpression partially or totally blunted dexamethasone-mediated induction of the catabolic (Atrogin, Murf1, Foxo1 and Foxo3a) and anti-anabolic (Klf15, Redd1 and Bcat2) genes[15]. This means SR9009 is HIGHLY anticatabolic because cortisol/glucocorticoid agonism is one of the most potent regulators of muscle catabolism. The fact that SR9009 was able to completely abate dexamethasone induced catabolism is astounding, imagine what it's capable of doing in the presence of anabolics.
​

It's exercise in pill form essentialy, and it doesn't cause cancer like Cardarine, quite the contrary actually.​

​

Spoiler: REV-ERB and cancer

​

REV-ERBs are potently anticarcinogenic. It's getting too good to be true.​

In one study, it was found that cancer cell proliferation was reduced with the use of the REV-ERBα agonist SR9011 as well as with an RORα agonist. Regarding gastric cancer, it was determined that REV-ERBα expression was decreased in tissues of patients with gastric cancer, which was correlated with poor differentiation and lymph node metastasis. In addition, decreased REV-ERBα expression was associated with poor prognosis. Another study focusing on glioblastoma investigated the proliferation dependence on clock genes among different cell states of glioblastoma cells, namely, the glioblastoma stem cells, differentiated glioblastoma cells, and non-malignant brain cells. The GSCs only exhibited a strong dependence on clock-related transcription factors. The treatment with the small-molecule agonists of REV-ERBs SR9011 and SR9009 led to a reduction in the GSC proliferation rate.[16]
​

Okay so how do we use SR9009?​

SR9009 has an estimated half life of around 4-6h, that means it's in and out of the body relatively quickly and that's exactly what we want, REV-ERB regulates orexinergic genes (orexin 1/2 are neuropeptides involved in sleep onset and maintenance) if taken during the day (SR9009) orexin is supressed, if you take it too close to bedtime you'll have an underactive orexingergic system, not only this, but SR9009 negatively regulates GABA transmission so wakefullness is definitely a perceptible effect of this drug. It also blocks melatonin receptor. The immediate effect of this drug is intense but non-anxiety inducing alertness. Once this drug is out of the body, however, orexin, melatonin & gaba are sensitized. Sleep onset is rapid and sleep maintenance is perfect. SR9009 will positively regulate your circadian rhythm more than any drug supplement (melatonin).

The issue however, is the fact that SR9009 has next to no oral bioavailability, we are required to either brew SR9009 into an oil based injectable, or we can dissolve SR9009 into DMSO and it apply it transdermally (wrists, scrotum and thin veiny areas have the best absorption rates). SR9009 will hold in DMSO at 30mg/ml[17]​

​

Spoiler: recipe for oil-based injectable

For an injectable solution (30ml) we get around 30mg/ml

900mg/.9g of SR9009 raw powder
20% benzyl benzoate
2% benzyl alcohol
78% MCT oil

Spoiler: recipe for DMSO transdermal solution

For a DMSO based solution we can achieve 30mg/ml

30ml 99% pharmaceutical grade DMSO
900mg/.9g of SR9009 raw powder

Only apply/inject in the morning and never after midday.​

​

Spoiler: sources

10.1016/j.bcp.2017.02.006

Redirecting

10.3390/ijms232112954
10.7150/thno.43834

REV-ERB agonism improves liver pathology in a mouse model of NASH

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to...

doi.org

https://doi.org/10.1080/07420528.2023.2207649

Frontiers | Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway

Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathw...

doi.org

10.1038/nm.3213

Distinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle

The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to be core members of the circadian clock and participate in the regulation of a diverse set of metabolic functions. Due to their overlapping tissue expression patterns and gene expression profiles, REV-ERBβ is thought to be...

doi.org

Circadian and Glucocorticoid Regulation of Rev-erbα Expression in Liver*

Abstract. Rev-erbα [NR1D1], a member of the nuclear receptor superfamily, is an orphan receptor that constitutively represses gene transcription. Rev-erbα

doi.org

Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass - Scientific Reports

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression...

doi.org

The Role of REV-ERB Receptors in Cancer Pathogenesis

REV-ERB receptors are members of the nuclear receptor superfamily of proteins, which act as both intracellular receptors and transcription factors, therefore modulating the expression of target genes. REV-ERBs act as transcription repressors because of their unique structure. Their predominant...

doi.org

 

[incel194012940]

stenabolic is neither a steroid or an anabolic dumbass, all it does is increase your endurance a little bit

 

[TitusA]

The circadian rhythm doesn't just regulate sleep cycles, it plays a critical role in metabolic regulation and by extension determines ones level of disease & inflammation. In order to maintain homeostasis and promote survival, the circadian clock coordinates and maintains the 24-hour rhythmicity of various physiological processes, the most evident are the sleep/wake and fasting/feeding cycles. Disruption of the clock has been associated with an increased susceptibility and/or development of sleep and metabolic disorders. Proper circadian function occurs in response to synchronous expression of the molecular machinery of the circadian clock, composed of a central pacemaker in the suprachiasmatic nucleus (SCN) residing in the hypothalamus. While the master clock is entrained by light, almost all cells in the body harbor peripheral clocks that are entrained by both signals from the master clock and environmental cues.
​

The REV-ERBα/β complex is one of the key gene suppressors/activators that is responsible for the function of the circadian core clock machinery. Before I explain REV-ERB's function you need to understand how the circadian rhythm functions:​

​

Spoiler: for the nerds

The activation of the genes BMAL1 (brain and muscle arnt-like protein 1) and CLOCK (circadian locomotor output cycles kaput) positively regulate the activation/transcription of Per (period) and Cry (cryptochrome) causing a negative feedback loop that suppresses BMAL1/CLOCK. In doing this the Per/Cry complex is repressing CLOCK from activating Per/Cry in the first place which causes a 24h oscillation in Per/Cry levels. To break down further:

BMAL1 and CLOCK, heterodimerize and drive the expression of Cryptochrome (Cry1, 2) and Period (Per1-3). Once Cryptochrome and Period proteins reach a critical threshold, PER:CRY complexes translocate to the nucleus to repress Bmal1:Clock transactivation.

BMAL1/CLOCK (CLOCK complex) → activation of Per/Cry → suppression of CLOCK → suppression of Per/Cry

Okay, so how does REV-ERBα/β play a role in this cascade?

REV-ERB operates on a different part of the clock machinery. It doesn't directly interact with the CLOCK complex. Instead, REV-ERB represses Bmal1 expression. This means that when REV-ERB is active, less BMAL1 is available, which weakens the ability of CLOCK to drive the expression of Per/Cry. In the daytime, REV-ERB levels are high, so Bmal1 is repressed. In the nighttime, REV-ERB levels fall, allowing Bmal1 expression to rise again, which enables the next cycle of Per and Cry transcription. So to break it down again:

REV-ERBα/β → suppression of BMAL1/CLOCK → weakened expression of Per/Cry → inhibition of the negative feedback loop

When we agonise REV-ERBα/β with a synthetic ligand (SR9009 or SR9011) we are interrupting this process by positively bolstering REV-ERB's ability to suppress the negative feedback loop via it's inhibition of BMAL1/CLOCK expression

​

Okay, so why is any of this important for our heatlh and by extension, our looks?​

Because, REV-ERB and the cascade of gene expression/suppression plays a VITAL role in circadian-contingent regulation of inflammation, lipid synthesis, mitogenesis/mitochondrial function, muscle function, cancer progression, bile synthesis (hepatoprotection) and more. For those of you who are hesistant to use steroids because of their effects on dyslipidemia (hyperlipidemia) and hepatotoxicity, this is everything you need to know about REV-ERB and it's ligands:

SR9009 and SR9011 are potent agonists at REV-ERBα (most activity occurs here) and REV-ERBβ (very potent but less so than at alpha). These drugs are responsible for directing metabolic function in a circadian manner. To make this guide more digestible I'll break down SR9009/11's effects into categories, starting with Lipids:

Mice lacking REV-ERBα show impaired lipid metabolism, leading to elevated levels of triglycerides and free fatty acids in the liver. In contrast, activation of REV-ERBα reduces triglycerides and free fatty acids in mice. This lipid-lowering effect is linked to the transcriptional repression of ApoC-III, which plays a crucial role in triglyceride metabolism by inhibiting the breakdown of triglyceride-rich particles, and Elovl3, which is involved in the elongation of fatty acids to generate very long-chain fatty acids[1] The REV-ERB nuclear receptors have been shown to play a key role in regulating lipid metabolism. It has been demonstrated that pharmacological activation of Rev-erb reduced plasma cholesterol levels in mice, while others found that mice lacking Rev-erb had elevated plasma cholesterol levels. Findings reveal that Rev-erb coordinately regulates most of the genes encoding critical enzymes involved in the cholesterol biosynthesis pathway[2]. It seems to inhibit the rate limiting enzyme in cholesterol synthesis (cyp7a1/cholesterol 7α-hydroxylase)[3]

In the aforementioned study it was found that these mice experienced a reduction of 36% and 41% in total cholesterol and LDL cholesterol upon activation of the Rev-erb. A previous study reported an increase in plasma LDL and cholesterol in REV-ERB knockout mice which further supports the notion that REV-ERB negatively regulate cholesterol levels. This is incredibly important for users of steroids because AAS cause a dose-dependent increase in LDL and a decrease in HDL. In another study, the plasma cholesterol analysis of rats that were fed a high-cholesterol diet showed significant reduction in total cholesterol (36%), LDL-C (41%) and triglycerides (40%) in response to SR9009 treatment. HDL-C levels were not affected by SR9009[4]

Not only does REV-ERB activation significantly reduce total cholesterol levels, it regulates macrophages M1 and M2, the ratio of which plays an important role in the development of atherosclerosis. Dyslipidemia and inflammation is responsible for plaque build up in the arteries and REV-ERB knockout mice are proven to have dysregulated ratios between M1 and M2. M1 is pro-inflammatory and cytotoxic, whereas M2 is anti-inflammatory. REV-ERB deficient mice have higher levels of M1 and in conjunction with hyperlipidemia (high total cholesterol) the development of atherosclerosis is majorly increased. SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to pro-inflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Essentially, the introduction of SR9009 normalized the aberrant levels of M1 and increased the levels of M2.[5]

By extension of REV-ERB's effect on macrophages and lipid synthesis, it is highly cardioprotective. However, the inhibition of cardiac fibrosis plays a much larger role in it's cardioprotection. SR9009 prevents cardiomyocyte hypertrophy, reduces fibrosis, and halts heart failure progression in mice. Additionally, SR9009 improves left ventricular function and increases survival rates following myocardial infarction. It also reduced the expression of cytokines IL-6, MMP9, and limited immune cell infiltration (pro-inflammatory macrophages) in the heart. In mice with pressure-induced cardiac hypertrophy caused by transverse aortic constriction, SR9009 lowered protein kinase B (AKT) expression and reduced cardiac hypertrophy[6]

REV-ERBα plays a key role in glucose homeostasis and the development of diabetes by regulating glucose synthesis and the function of pancreatic α and β cells. Activation of REV-ERBα lowers both cellular and plasma glucose levels. Similarly, mice lacking REV-ERBα exhibit elevated plasma glucose levels.[7] Anecdotally, my hba1c levels haven't breached 5mmol/L since starting SR9009.

REV-ERBα activation by SR9009 inhibits transcription of inflammatory factors IL-1β, IL-6, MMP-9, and Ccl2 in astrocytes. SR9009 significantly attenuates hepatic damage and inflammatory responses, it is effective in suppressing clinical markers of liver damage, circulating lipids, hepatic fibrosis, and markers of inflammation. In addition, pharmacological activation of REV-ERBα by SR9009 alleviated hepatic steatosis, insulin resistance, liver inflammation, and fibrosis in CL diet-induced NASH mice. These effects were accompanied by improved gut barrier function and altered microbial composition and function in NASH mice, and the effect tended to be stronger when SR9009 was injected at ZT0 (night time) Moreover, SR9009 treatment at different time points resulted in a marked difference in the composition of the microbiota, with a stronger effect on the enrichment of beneficial bacteria and the diminishment of harmful bacteria when SR9009 was administrated at night.[8, 9, 10]

SR9009 potently regulates mitogenesis (the formation of new mitochondria) and mitochondrial respiration. In one study dealing with REV-ERBα knockout mice, cellular effects resulted in both impaired mitochondrial biogenesis leading to compromised exercise capacity. On a molecular level, REV-ERBα deficiency resulted in deactivation of the Lkb1-Ampk-Sirt1-Ppargc-1α signaling pathway.[11] Additionally, genes encoding enzymes of fatty acid β-oxidation, like carnitine palmitoyltransferase 1b (Cpt1b), long chain acyl-CoA dehydrogenase (Acadl), short chain acyl-CoA dehydrogenase (Acads), Ucp2, and Ucp3, genes involved in skeletal muscle metabolism, were also upregulated with REV-ERBα overexpression.[12] Researchers have demonstrated that mice lacking REV-ERBα had decreased skeletal muscle metabolic activity and running capacity. Burris’ group showed that activation of REV-ERBα with SR9009 led to increased metabolic activity in skeletal muscle in both culture and in mice. The treated mice had a 50 percent increase in running capacity, measured by both time and distance.[13].

“The animals actually get muscles like an athlete who has been training,” said Burris. “The pattern of gene expression after treatment with SR9009 is that of an oxidative-type muscle— again, just like an athlete.”

Speaking of muscles, glucocorticoids seem to negatively regulate REV-ERB expression, REV-ERBα mRNA levels were shown to be down-regulated by dexamethasone in the liver and in both rat and human primary hepatocyte cultures in one study[14]. In another study, REV-ERBα overexpression partially or totally blunted dexamethasone-mediated induction of the catabolic (Atrogin, Murf1, Foxo1 and Foxo3a) and anti-anabolic (Klf15, Redd1 and Bcat2) genes[15]. This means SR9009 is HIGHLY anticatabolic because cortisol/glucocorticoid agonism is one of the most potent regulators of muscle catabolism. The fact that SR9009 was able to completely abate dexamethasone induced catabolism is astounding, imagine what it's capable of doing in the presence of anabolics.
​

It's exercise in pill form essentialy, and it doesn't cause cancer like Cardarine, quite the contrary actually.​

​

Spoiler: REV-ERB and cancer

View attachment 3208730

​

REV-ERBs are potently anticarcinogenic. It's getting too good to be true.​

In one study, it was found that cancer cell proliferation was reduced with the use of the REV-ERBα agonist SR9011 as well as with an RORα agonist. Regarding gastric cancer, it was determined that REV-ERBα expression was decreased in tissues of patients with gastric cancer, which was correlated with poor differentiation and lymph node metastasis. In addition, decreased REV-ERBα expression was associated with poor prognosis. Another study focusing on glioblastoma investigated the proliferation dependence on clock genes among different cell states of glioblastoma cells, namely, the glioblastoma stem cells, differentiated glioblastoma cells, and non-malignant brain cells. The GSCs only exhibited a strong dependence on clock-related transcription factors. The treatment with the small-molecule agonists of REV-ERBs SR9011 and SR9009 led to a reduction in the GSC proliferation rate.[16]
​

Okay so how do we use SR9009?​

SR9009 has an estimated half life of around 4-6h, that means it's in and out of the body relatively quickly and that's exactly what we want, REV-ERB regulates orexinergic genes (orexin 1/2 are neuropeptides involved in sleep onset and maintenance) if taken during the day (SR9009) orexin is supressed, if you take it too close to bedtime you'll have an underactive orexingergic system, not only this, but SR9009 negatively regulates GABA transmission so wakefullness is definitely a perceptible effect of this drug. It also blocks melatonin receptor. The immediate effect of this drug is intense but non-anxiety inducing alertness. Once this drug is out of the body, however, orexin, melatonin & gaba are sensitized. Sleep onset is rapid and sleep maintenance is perfect. SR9009 will positively regulate your circadian rhythm more than any drug supplement (melatonin).

The issue however, is the fact that SR9009 has next to no oral bioavailability, we are required to either brew SR9009 into an oil based injectable, or we can dissolve SR9009 into DMSO and it apply it transdermally (wrists, scrotum and thin veiny areas have the best absorption rates). SR9009 will hold in DMSO at 30mg/ml[17]​

​

​

Spoiler: recipe for oil-based injectable

For an injectable solution (30ml) we get around 30mg/ml

900mg/.9g of SR9009 raw powder
20% benzyl benzoate
2% benzyl alcohol
78% MCT oil

Spoiler: recipe for DMSO transdermal solution

For a DMSO based solution we can achieve 30mg/ml

30ml 99% pharmaceutical grade DMSO
900mg/.9g of SR9009 raw powder

Only apply/inject in the morning and never after midday.​

​

Spoiler: sources

10.1016/j.bcp.2017.02.006

Redirecting

10.3390/ijms232112954
10.7150/thno.43834

REV-ERB agonism improves liver pathology in a mouse model of NASH

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to...

doi.org

https://doi.org/10.1080/07420528.2023.2207649

Frontiers | Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway

Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathw...

doi.org

10.1038/nm.3213

Distinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle

The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to be core members of the circadian clock and participate in the regulation of a diverse set of metabolic functions. Due to their overlapping tissue expression patterns and gene expression profiles, REV-ERBβ is thought to be...

doi.org

Circadian and Glucocorticoid Regulation of Rev-erbα Expression in Liver*

Abstract. Rev-erbα [NR1D1], a member of the nuclear receptor superfamily, is an orphan receptor that constitutively represses gene transcription. Rev-erbα

doi.org

Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass - Scientific Reports

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression...

doi.org

The Role of REV-ERB Receptors in Cancer Pathogenesis

REV-ERB receptors are members of the nuclear receptor superfamily of proteins, which act as both intracellular receptors and transcription factors, therefore modulating the expression of target genes. REV-ERBs act as transcription repressors because of their unique structure. Their predominant...

doi.org

Does this have some connecton with adrenaline. I found when running anabolics for allong time i end up in endless high adrenaline state. Quick to get mad and worse sleep. When u drop down to legit trt dose u feel way more relaxed. Also ive noticed if im sleeping bad in general tht alone will throw off my cholesterol slightly (not out of range but it makes it worse).

 

[Dyorotic]

stenabolic is neither a steroid or an anabolic dumbass, all it does is increase your endurance a little bit

Get the fuck out of my thread you colossal faggot. WHEN did I say it was a steroid you moron?

 

[Dyorotic]

Does this have some connecton with adrenaline. I found when running anabolics for allong time i end up in endless high adrenaline state. Quick to get mad and worse sleep. When u drop down to legit trt dose u feel way more relaxed. Also ive noticed if im sleeping bad in general tht alone will throw off my cholesterol slightly (not out of range but it makes it worse).

It won't do anything for adrenaline you need propranolol or nebivolol unfortunately

 

[Deleted member 80937]

just be natty bro

 

[Rigged]

Jesus christ reading this was a mess
1. The format sucks
2. As 1st guy said SR9009 and SR9011 have 0 to do with roids as ur trying to imply
3. Even if they did have correlation ur science is shit


My final score (i try to rate with no bias and strictly)

1/10

 

[Dyorotic]

1. The format sucks

the format is absolutely readable, kill yourself

2. As 1st guy said SR9009 and SR9011 have 0 to do with roids as ur trying to imply

you are an astounding fucking moron. The entire purpose of this thread is to employ SR9009 ALONGSIDE steroids to mitigate the negative effects of hormones (dyslipidemia, nephrotoxicity, hepatotoxicity cardiotoxicity).

I NEVER said SR9009 was a hormone, an androgen or an anabolic substance.

Even if they did have correlation ur science is shit

You didn't read a molecule of it you fucking imbecile. The 'science' has nothing to do with steroids because IT quite literally has nothing to do with them, intentionally.

Holy shit .org is a complete joke

 

[TitusA]

It won't do anything for adrenaline you need propranolol or nebivolol unfortunately

I have propanolol but it blunts my mood and only lasts a couple hours unfortunately.

 

[Dyorotic]

I have propanolol but it blunts my mood and only lasts a couple hours unfortunately.

The half life is ideal. You don't want to have adrenergic signalling low when you're lifting or doing anything tangentially related to working out

 

[Dyorotic]

reading this

You didn't read it. JFL

 

[TitusA]

The half life is ideal. You don't want to have adrenergic signalling low when you're lifting or doing anything tangentially related to working out

Yeah i used to take it post workout when running tren (since bp stays high after workout and steroids put it up). Nowadays i just take it if my around a girl tht gets me mad since i do trt only for the most part.

 

[Rigged]

the format is absolutely readable, kill yourself

you are an astounding fucking moron. The entire purpose of this thread is to employ SR9009 ALONGSIDE steroids to mitigate the negative effects of hormones (dyslipidemia, nephrotoxicity, hepatotoxicity cardiotoxicity).

I NEVER said SR9009 was a hormone, an androgen or an anabolic substance.

You didn't read a molecule of it you fucking imbecile. The 'science' has nothing to do with steroids because IT quite literally has nothing to do with them, intentionally.

Holy shit .org is a complete joke

Jesus i wasnt gonna reply cause i dont usually bother but u call “.org” a joke when u clearly have no knowledge on the subject ur talking about

Ur description of Per/Cry feedback loop is shit, it looks like u just learned about this an hour ago u completely ignored how recruitment of BMAL1/CLOCK complex to E-boxes on circadian gene promoters is fully based on chromatin accessibility managed by histone modifications and nucleosome remodeling which anyone with basic knowledge would know that they modulate the expression of circadian genes, and should be automatically mentioned when referencing them

Even worse you didn’t say anything about PTMs role, one of the most important things to understand and explain when presenting to people, for the stability and nuclear translocation of PER:CRY complexes. Kinases like CK16/3 for example change phosphorylation dependent degradation of PER proteins, which in turn affevts the periodicity of the circadian rhythm ignoring this makes ur point on this irrelavent and makes u look like a retard

Again keeping it at a first grade ur understanding the function of REV-ERBa/B, ignores its MORE IMPORTANT affect in metabolic regulation anyone who read on this for an hour would know it unites circadian rhythms with energy homeostasis which would impact lipid metabolism and glucose control and how REV-ERBa/B interacts with metabolic regulators like PGC-1a and SIRT1 links circadian control to metabolic health, again you dont bring this up and fully ignore this

Even tho this part isnt as relevant if you wanted to make this post you couldve talked more about ligand receptor dynamics when you were talking about “pharmacological modulation of REV-ERB using synthetic agonists like SR9009 or SR9011” could also talked more about ligand induced conformational changes in “REV-ERB stabilizing repressive functions”

 

[Rigged]

Jesus i wasnt gonna reply cause i dont usually bother but u call “.org” a joke when u clearly have no knowledge on the subject ur talking about

Ur description of Per/Cry feedback loop is shit, it looks like u just learned about this an hour ago u completely ignored how recruitment of BMAL1/CLOCK complex to E-boxes on circadian gene promoters is fully based on chromatin accessibility managed by histone modifications and nucleosome remodeling which anyone with basic knowledge would know that they modulate the expression of circadian genes, and should be automatically mentioned when referencing them

Even worse you didn’t say anything about PTMs role, one of the most important things to understand and explain when presenting to people, for the stability and nuclear translocation of PER:CRY complexes. Kinases like CK16/3 for example change phosphorylation dependent degradation of PER proteins, which in turn affevts the periodicity of the circadian rhythm ignoring this makes ur point on this irrelavent and makes u look like a retard

Again keeping it at a first grade ur understanding the function of REV-ERBa/B, ignores its MORE IMPORTANT affect in metabolic regulation anyone who read on this for an hour would know it unites circadian rhythms with energy homeostasis which would impact lipid metabolism and glucose control and how REV-ERBa/B interacts with metabolic regulators like PGC-1a and SIRT1 links circadian control to metabolic health, again you dont bring this up and fully ignore this

Even tho this part isnt as relevant if you wanted to make this post you couldve talked more about ligand receptor dynamics when you were talking about “pharmacological modulation of REV-ERB using synthetic agonists like SR9009 or SR9011” could also talked more about ligand induced conformational changes in “REV-ERB stabilizing repressive functions”

Cant have ur shit reply ruin my rep @matka @wastedspermcel

 

[Deleted member 80937]

Cant have ur shit reply ruin my rep @matka @wastedspermcel

dw i got you

 

[Rigged]

the format is absolutely readable, kill yourself

you are an astounding fucking moron. The entire purpose of this thread is to employ SR9009 ALONGSIDE steroids to mitigate the negative effects of hormones (dyslipidemia, nephrotoxicity, hepatotoxicity cardiotoxicity).

I NEVER said SR9009 was a hormone, an androgen or an anabolic substance.

You didn't read a molecule of it you fucking imbecile. The 'science' has nothing to do with steroids because IT quite literally has nothing to do with them, intentionally.

Holy shit .org is a complete joke

To add ur post is the equivelant of saying

“Testsosterone will give big muscle”

Edit: i know ur not trying to say its an anabolic the other guys reply confused me into thinking thats what u said (b4 i read it) doesnt change the fact that this post is shit

 

[Dyorotic]

Even worse you didn’t say anything about PTMs role, one of the most important things to understand and explain when presenting to people, for the stability and nuclear translocation of PER:CRY complexes. Kinases like CK16/3 for example change phosphorylation dependent degradation of PER proteins, which in turn affevts the periodicity of the circadian rhythm ignoring this makes ur point on this irrelavent and makes u look like a retard

Why on earth would I over complicate something that is already relatively complicated? I explained very simply how the CLOCK complex interacts with Per/Cry and how REV-ERB fits in the scheme of things. It's an incredible oversimplification but it isn't wrong.

Even tho this part isnt as relevant if you wanted to make this post you couldve talked more about ligand receptor dynamics when you were talking about “pharmacological modulation of REV-ERB using synthetic agonists like SR9009 or SR9011

What would the purpose of this be? This isn't relevant whatsoever. The only thing relevant in this thread is the data regarding lipids, glucose, cancer and mitogenesis. Talking about "ligand dynamics" would be completely moot and overly verbose.

To add ur post is the equivelant of saying

“Testsosterone will give big muscle”

You're so unbelievably disingenuous it's unreal

I cited multiple studies that indicate SR9009 is highly beneficial for lipid & glucose control as well as endurance/stamina/energy expenditure. The cancer part is all backed by evidence too.

On what planet is this the equivalent to saying testosterone builds big muscles? Most people don't know how SR9009 works, or they utilize it orally and discover it's doing nothing and then discard it.

WHY would ANYONE need to know about muh phosphorylation dependent degradation [...]. I know you love sniffing your own farts and getting high to the smell of them.

doesnt change the fact that this post is shit

The post isn't shit just because I didn't include a bunch of overly verbose garbage that NO one will read. The CLOCK/per/cry part is oversimplified and I SPOILER'd it because no one wants to read something like that anyway.

but u call “.org” a joke

Yes .org is a joke. People like you, pompous faggots who are somehow denoted as the arbiters of information derail threads and farm reps. You're a subhuman dog as well, aren't you like 5'6?

 

[Rigged]

Why on earth would I over complicate something that is already relatively complicated? I explained very simply how the CLOCK complex interacts with Per/Cry and how REV-ERB fits in the scheme of things. It's an incredible oversimplification but it isn't wrong.

Its not simplifying its ignoring?, me saying “injecting tren will make u stronger” isnt wronger either but it would be a shit post

What would the purpose of this be? This isn't relevant whatsoever. The only thing relevant in this thread is the data regarding lipids, glucose, cancer and mitogenesis. Talking about "ligand dynamics" would be completely moot and overly verbose.

I said its uneccessary just wouldve been nice + it would explain how REV-ERB agonists like SR9009 and SR9011 actually work at a molecular level

You're so unbelievably disingenuous it's unreal

I cited multiple studies that indicate SR9009 is highly beneficial for lipid & glucose control as well as endurance/stamina/energy expenditure. The cancer part is all backed by evidence too.

Im not denying it working, im saying ur post on it is trash

On what planet is this the equivalent to saying testosterone builds big muscles? Most people don't know how SR9009 works, or they utilize it orally and discover it's doing nothing and then discard it.

Its a metaphor bud

WHY would ANYONE need to know about muh phosphorylation dependent degradation [...]. I know you love sniffing your own farts and getting high to the smell of them.

Because its relevant to the post? U sound like a nerd who cant admit hes wrong lmao ur replies for all my points were “muh why would i put more effort into this post to make it higher quality and more accurate”

The post isn't shit just because I didn't include a bunch of overly verbose garbage that NO one will read. The CLOCK/per/cry part is oversimplified and I SPOILER'd it because no one wants to read something like that anyway.

Again as a metaphor thats like me saying “inject testosterone for muscles” and then ignoring ancillaries because its garbage people wont read?

Yes .org is a joke. People like you, pompous faggots who are somehow denoted as the arbiters of information derail threads and farm reps. You're a subhuman dog as well, aren't you like 5'6?

My looks height doesnt make me wrong, wise fold tho going for me instead of my points what a great arguement this was , u got mad and started cussing me out thats embarrasing lock in gng

 

[Dyorotic]

Its not simplifying its ignoring?, me saying “injecting tren will make u stronger” isnt wronger either but it would be a shit post

No, it's a simplification. REV-ERB suppresses CLOCK/BMAL1 and CLOCK drives the expression of Per/Cry which suppresses the CLOCK complex, oscillating every 24h. Nothing was ignored, just because I didn't explain the minute intricacies doesn't mean it's wrong.

I said its uneccessary just wouldve been nice + it would explain how REV-ERB agonists like SR9009 and SR9011 actually work at a molecular level

Right, but this thread isn't about sniffing our own farts and including unnecessary verbiage about SR9009. All I wanted to do was present a potential tool to mitigate side effects from steroids. I laid down the facts as they pertain to lipids, glucose, hepatoprotection etc.

As far as I can tell SR9009 is a fantastic tool. Statins cause muscle weakness and wasting, ezetimibe is weak and cardarine causes cancer. SR9009 cuts lipids in half and doesn't seem to have any negative side effects.

Im not denying it working, im saying ur post on it is trash

Trash to who? The people who are barely knowledgeable on this stuff don't need to understand the nuances of REV-ERB, CLOCK, Per/Cry and everything that sequence of genes entails.

Its a metaphor bud

You're astoundingly retarded it's almost comical. Yes, it's a metaphor, and my point is that it's a horrible metaphor which isn't at all analogous to what my post entails.

Why does testosterone build muscle? [...] would be the equivalent. You're an idiot.

Because its relevant to the post?

Dude even explaining how CLOCK works is irrelevant to the crux of the post. SR9009, regardless of whether you understand how BMAL/CLOCK works, will reduce the enzymes responsible for lipid synthesis, it'll increase endurance and mitogenesis [...] blah blah blah

“muh why would i put more effort into this post to make it higher quality and more accurate”

It's already high quality. I've written about everything relevant to SR9009, backed by multiple papers.

This post was targeted at people who desire to be healthier whilst taking drugs that cause hyperlipidemia (steroids).

Again as a metaphor thats like me saying “inject testosterone for muscles” and then ignoring ancillaries because its garbage people wont read?

That's not at all what you said. You're moving the goalposts massively with this.

Writing in depth about Per/Cry IS not the equivalent to mentioning ancillaries when using testosterone. These are not the same things and if you can't see that you're fucking imbecilic.

If you're suggesting that the post lacks depth then sure, I didn't write an essay on circadian gene expression.

My looks height doesnt make me wrong

No but I can write you off as a subhuman so It makes me feel a lot better!

u got mad

I was never mad. You came in here, left a big stinky shit, proceeded to sniff your own farts whilst misconstruing the purpose and title of the post.

This thread isn't supposed to be an encyclopedia about the circadian rhythm. It's a looksmaxxing site and this information is relevant to those who want to LOOKSMAX in a healthy manner.

 

[Rigged]

No, it's a simplification. REV-ERB suppresses CLOCK/BMAL1 and CLOCK drives the expression of Per/Cry which suppresses the CLOCK complex, oscillating every 24h. Nothing was ignored, just because I didn't explain the minute intricacies doesn't mean it's wrong.

Its not simplistic its overly simplistic, chromatin accessibility and pos translational modifications should be talked about for people to undertstand the circadian clock and how REV-ERB modulation works

Right, but this thread isn't about sniffing our own farts and including unnecessary verbiage about SR9009. All I wanted to do was present a potential tool to mitigate side effects from steroids. I laid down the facts as they pertain to lipids, glucose, hepatoprotection etc.

Ur point of trying to say u just tried to keep it simple and tell people about this guide and remove the stuff people wouldnt read goes null when you can rewrite your guide in 30 words and it would be the exact same stuff without what people wouldnt read

As far as I can tell SR9009 is a fantastic tool. Statins cause muscle weakness and wasting, ezetimibe is weak and cardarine causes cancer. SR9009 cuts lipids in half and doesn't seem to have any negative side effects.

not gonna argue about the other drugs right now but the efficacy and safety profile should be discussed in context

Trash to who? The people who are barely knowledgeable on this stuff don't need to understand the nuances of REV-ERB, CLOCK, Per/Cry and everything that sequence of genes entails.

The people who are barely knowledgable on this wont understand 99% of this guide, if u wanted to make it simplified for those who werent knowledgeable this couldve been written in 30-60 words

You're astoundingly retarded it's almost comical. Yes, it's a metaphor, and my point is that it's a horrible metaphor which isn't at all analogous to what my post entails.

Yes it does, the mataphor is talking about over simplification i dont get how its hard to see

Why does testosterone build muscle? [...] would be the equivalent. You're an idiot.

Again over simplification not a metaphor relating to exactly what u said

Dude even explaining how CLOCK works is irrelevant to the crux of the post. SR9009, regardless of whether you understand how BMAL/CLOCK works, will reduce the enzymes responsible for lipid synthesis, it'll increase endurance and mitogenesis [...] blah blah blah

The main point is more important but ignoring other mechanisms will just leave people without a full understanding of how it works, u couldve left a short mention of these mechanisms and it wouldve made ur post more credible for users who wouldve actually read this, when u make a guide like this the only people who will be reading are people who already know everything about this like me and people who already know 90% and wanna learn the rest

U think the kids who came here actually read anything? No because if u dont understand atleast 80% then reading this post is pointless

It's already high quality. I've written about everything relevant to SR9009, backed by multiple papers.

It being backed by multiple papers doesnt mean u wrote everything relevant, i already explained how u didnt and ur replies were the equivalent of saying “people wont read it anyways” acting like anyone will read it wether u add it or not, again as i said before ur target audiance for this post is people who know 90% of this already and want to learn the rest, when u miss things it makes ur post less valuable since the people who know 90% will read this and realize u only talked about 70% of ur post

This post was targeted at people who desire to be healthier whilst taking drugs that cause hyperlipidemia (steroids).

great couldve made it in 30 words simplfied and 100x more ppl would know what ur saying and be willing to try it

That's not at all what you said. You're moving the goalposts massively with this.

I literally repeated my past metaphor tf did i move

Writing in depth about Per/Cry IS not the equivalent to mentioning ancillaries when using testosterone. These are not the same things and if you can't see that you're fucking imbecilic.

Again the metaphor is about oversimplifcation and not directly refering to the science, i feel like anyone with a brain would realise this

If you're suggesting that the post lacks depth then sure, I didn't write an essay on circadian gene expression.

Yes thats what im suggesting

No but I can write you off as a subhuman so It makes me feel a lot better!

Im 5’7, but im htn, and ill get to lite at peak, also i have ideal male physique

I was never mad. You came in here, left a big stinky shit, proceeded to sniff your own farts whilst misconstruing the purpose and title of the post.

Sure bud thats an ad hominem

This thread isn't supposed to be an encyclopedia about the circadian rhythm. It's a looksmaxxing site and this information is relevant to those who want to LOOKSMAX in a healthy manner.

This info is relevant to people who know about this, if u wanted it to be relevant to people who looksmax u wouldve made a guide on how to use it and wrote it in 60 words

 

[Dyorotic]

Ur point of trying to say u just tried to keep it simple and tell people about this guide and remove the stuff people wouldnt read goes null when you can rewrite your guide in 30 words and it would be the exact same stuff without what people wouldnt read

The exclusion of unnecessary information that goes beyond the core mechanism behind SR9009 is not the same as "ignoring" or "oversimplifying". It's explained incredibly simply and you're being pedantic for criticizing it.

but the efficacy and safety profile should be discussed in context

SR9009 is safe according to my understanding. Stuff like Cardarine is not safe and my risk tolerance drops drastically at anything carcinogenic. I wouldn't post about something If I knew it was potentially dangerous.

The people who are barely knowledgable on this wont understand 99% of this guide, if u wanted to make it simplified for those who werent knowledgeable this couldve been written in 30-60 words

Right so because I didn't explain the entire sequence of gene expression/suppression/activation of REV-ERB and everything that entails, I shouldn't have bothered writing anything at all? What kind of fucking deranged and nonsensical logic is that?

I wrote it as simply as I could because the barrier of entry for understanding this stuff is higher than the usual biochemistry talked about on here. Everyone knows what an androgen receptor is, no one knows what CLOCK/BMAL1 are/is.

You're acting as though me writing everything you mentioned makes it any easier for people to understand/engage with.

The main point is more important but ignoring other mechanisms will just leave people without a full understanding of how it works

No it won't. If someone genuinely gives a fuck about this type of stuff they'll look into it further. I'm hoping no one reads a looksmax thread and then takes everything at face value. If someone cares about the MOA of SR9009 they'll research beyond this thread.

I'm demonstrating a potential tool to mitigate the sides of steroids, that's it. Everything I wrote and backed up with citations pertains to it's usage and immediate perceptible (blood test to confirm) effects in the body.

i already explained how u didnt and ur replies were the equivalent of saying “people wont read it anyways”

Strawman. I'm not saying people won't read, I'm saying that those who will won't simply read what I've written and take it at face value, they'll most likely research the circadian rhythm, which goes way beyond the CLOCK complex. I wrote what I thought was necessary, anything more obscures the point of the post (mitigating AAS sides and why SR9009 is a perfect candidate)

when u miss things it makes ur post less valuable since the people who know 90% will read this and realize u only talked about 70% of ur post

You are probably the only person on this site that even knows what SR9009 does in full detail, stop acting like there are other people on this site who care/know anything about what we're discussing.

great couldve made it in 30 words simplfied and 100x more ppl would know what ur saying and be willing to try it

Why is that necessary? You can read everything highlighted if you don't want to read the rest. Everything highlighted pertains to SR9009's effect in the body.

Again the metaphor is about oversimplifcation and not directly refering to the science, i feel like anyone with a brain would realise this

You're a dumbass and you made a horrible metaphor that isn't at all analogous to what I wrote. Everything that pertains to SR9009 (valuable information regarding it's actual EFFECTS on lipid synthesis, mitogenesis [...] etc, is included. It's not SIMPLE just because I didn't recite the entire circadian gene complex. How the FUCK is that relevant to the fact that it might help someone with hyperlipidemia?

You're unbelievably pedantic.

Im 5’7, but im htn, and ill get to lite at peak, also i have ideal male physique

Not going to respond to this because I don't like lowblowing people for things they can't change, but I did chuckle IRL.

if u wanted it to be relevant to people who looksmax u wouldve made a guide on how to use it and wrote it in 60 words

IT IS relevant to those who want to looksmax you fucking bafoon. I wrote about it's anticatabolism, it's effects on mitogenesis, it's effects on lipids (can't have sex if you're dead) etc etc. Just because I didn't consider the fact that some nerd like you would come in and derail for absolutely no reason other than pure pedanticism doesn't mean the thread is bad.

 

[lestoa]

mirin

übermensch or death

never thought that you are going to make a guide again
will read now
will start my cycle december when my cut is finished

 

[lestoa]

@Clavicular

Yall rather pin skincare guides instead of high IQ threads like this

pin this asap

 

[Clavicular]

Jesus miring dude, gonna read this whole shit.

ADHDcels wont reap the benefits of this thread, high entry barrier to roiding safely

 

[Clavicular]

It also blocks melatonin receptor.

I didnt even know this shit this is golden now i can spam melatonin megadose and reap all the benefits without feeling shit

SR9009 is gods gift to roiders

 

[Clavicular]

Jesus christ reading this was a mess
1. The format sucks
2. As 1st guy said SR9009 and SR9011 have 0 to do with roids as ur trying to imply
3. Even if they did have correlation ur science is shit


My final score (i try to rate with no bias and strictly)

1/10

God you are such a retard its unbelievable, quote within the thread or anywhere he said SR9009 is a steroid FFS. This thread is about prevention of roid induced side effects (fixing lipids). You have to be baiting because theres just no way someone this retarded had the balls to put “top 5 highest iq” in their status a few weeks ago. What an utter disgrace you are to this forum.

And jfl at “your science” as if this is some lame theory, he has a source in EVERY line of the thread.

You really got him with the format! Sorry your 82 iq brain cant process a thread without bright colors and pictures scattered everywhere. Im really not suprised in the slightest considering every thread you have ever made is chat gpt ramblings (also dogshit). The fact that you beg for the contributor badge while being a complete pseudo intellectual retard should be ban worthy, cheers.

 

[Dyorotic]

will start my cycle december when my cut is finished

Mogger, get some SR9009 and you'll be good to go honestly

I'll take bloods in a month and post results here. I'm hoping to see my LDL eviscerated

 

[cyprian_tomaszewski]

The circadian rhythm doesn't just regulate sleep cycles, it plays a critical role in metabolic regulation and by extension determines ones level of disease & inflammation. In order to maintain homeostasis and promote survival, the circadian clock coordinates and maintains the 24-hour rhythmicity of various physiological processes, the most evident are the sleep/wake and fasting/feeding cycles. Disruption of the clock has been associated with an increased susceptibility and/or development of sleep and metabolic disorders. Proper circadian function occurs in response to synchronous expression of the molecular machinery of the circadian clock, composed of a central pacemaker in the suprachiasmatic nucleus (SCN) residing in the hypothalamus. While the master clock is entrained by light, almost all cells in the body harbor peripheral clocks that are entrained by both signals from the master clock and environmental cues.
​

The REV-ERBα/β complex is one of the key gene suppressors/activators that is responsible for the function of the circadian core clock machinery. Before I explain REV-ERB's function you need to understand how the circadian rhythm functions:​

​

Spoiler: for the nerds

The activation of the genes BMAL1 (brain and muscle arnt-like protein 1) and CLOCK (circadian locomotor output cycles kaput) positively regulate the activation/transcription of Per (period) and Cry (cryptochrome) causing a negative feedback loop that suppresses BMAL1/CLOCK. In doing this the Per/Cry complex is repressing CLOCK from activating Per/Cry in the first place which causes a 24h oscillation in Per/Cry levels. To break down further:

BMAL1 and CLOCK, heterodimerize and drive the expression of Cryptochrome (Cry1, 2) and Period (Per1-3). Once Cryptochrome and Period proteins reach a critical threshold, PER:CRY complexes translocate to the nucleus to repress Bmal1:Clock transactivation.

BMAL1/CLOCK (CLOCK complex) → activation of Per/Cry → suppression of CLOCK → suppression of Per/Cry

Okay, so how does REV-ERBα/β play a role in this cascade?

REV-ERB operates on a different part of the clock machinery. It doesn't directly interact with the CLOCK complex. Instead, REV-ERB represses Bmal1 expression. This means that when REV-ERB is active, less BMAL1 is available, which weakens the ability of CLOCK to drive the expression of Per/Cry. In the daytime, REV-ERB levels are high, so Bmal1 is repressed. In the nighttime, REV-ERB levels fall, allowing Bmal1 expression to rise again, which enables the next cycle of Per and Cry transcription. So to break it down again:

REV-ERBα/β → suppression of BMAL1/CLOCK → weakened expression of Per/Cry → inhibition of the negative feedback loop

When we agonise REV-ERBα/β with a synthetic ligand (SR9009 or SR9011) we are interrupting this process by positively bolstering REV-ERB's ability to suppress the negative feedback loop via it's inhibition of BMAL1/CLOCK expression

​

Okay, so why is any of this important for our heatlh and by extension, our looks?​

Because, REV-ERB and the cascade of gene expression/suppression plays a VITAL role in circadian-contingent regulation of inflammation, lipid synthesis, mitogenesis/mitochondrial function, muscle function, cancer progression, bile synthesis (hepatoprotection) and more. For those of you who are hesistant to use steroids because of their effects on dyslipidemia (hyperlipidemia) and hepatotoxicity, this is everything you need to know about REV-ERB and it's ligands:

SR9009 and SR9011 are potent agonists at REV-ERBα (most activity occurs here) and REV-ERBβ (very potent but less so than at alpha). These drugs are responsible for directing metabolic function in a circadian manner. To make this guide more digestible I'll break down SR9009/11's effects into categories, starting with Lipids:

Mice lacking REV-ERBα show impaired lipid metabolism, leading to elevated levels of triglycerides and free fatty acids in the liver. In contrast, activation of REV-ERBα reduces triglycerides and free fatty acids in mice. This lipid-lowering effect is linked to the transcriptional repression of ApoC-III, which plays a crucial role in triglyceride metabolism by inhibiting the breakdown of triglyceride-rich particles, and Elovl3, which is involved in the elongation of fatty acids to generate very long-chain fatty acids[1] The REV-ERB nuclear receptors have been shown to play a key role in regulating lipid metabolism. It has been demonstrated that pharmacological activation of Rev-erb reduced plasma cholesterol levels in mice, while others found that mice lacking Rev-erb had elevated plasma cholesterol levels. Findings reveal that Rev-erb coordinately regulates most of the genes encoding critical enzymes involved in the cholesterol biosynthesis pathway[2]. It seems to inhibit the rate limiting enzyme in cholesterol synthesis (cyp7a1/cholesterol 7α-hydroxylase)[3]

In the aforementioned study it was found that these mice experienced a reduction of 36% and 41% in total cholesterol and LDL cholesterol upon activation of the Rev-erb. A previous study reported an increase in plasma LDL and cholesterol in REV-ERB knockout mice which further supports the notion that REV-ERB negatively regulate cholesterol levels. This is incredibly important for users of steroids because AAS cause a dose-dependent increase in LDL and a decrease in HDL. In another study, the plasma cholesterol analysis of rats that were fed a high-cholesterol diet showed significant reduction in total cholesterol (36%), LDL-C (41%) and triglycerides (40%) in response to SR9009 treatment. HDL-C levels were not affected by SR9009[4]

Not only does REV-ERB activation significantly reduce total cholesterol levels, it regulates macrophages M1 and M2, the ratio of which plays an important role in the development of atherosclerosis. Dyslipidemia and inflammation is responsible for plaque build up in the arteries and REV-ERB knockout mice are proven to have dysregulated ratios between M1 and M2. M1 is pro-inflammatory and cytotoxic, whereas M2 is anti-inflammatory. REV-ERB deficient mice have higher levels of M1 and in conjunction with hyperlipidemia (high total cholesterol) the development of atherosclerosis is majorly increased. SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to pro-inflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Essentially, the introduction of SR9009 normalized the aberrant levels of M1 and increased the levels of M2.[5]

By extension of REV-ERB's effect on macrophages and lipid synthesis, it is highly cardioprotective. However, the inhibition of cardiac fibrosis plays a much larger role in it's cardioprotection. SR9009 prevents cardiomyocyte hypertrophy, reduces fibrosis, and halts heart failure progression in mice. Additionally, SR9009 improves left ventricular function and increases survival rates following myocardial infarction. It also reduced the expression of cytokines IL-6, MMP9, and limited immune cell infiltration (pro-inflammatory macrophages) in the heart. In mice with pressure-induced cardiac hypertrophy caused by transverse aortic constriction, SR9009 lowered protein kinase B (AKT) expression and reduced cardiac hypertrophy[6]

REV-ERBα plays a key role in glucose homeostasis and the development of diabetes by regulating glucose synthesis and the function of pancreatic α and β cells. Activation of REV-ERBα lowers both cellular and plasma glucose levels. Similarly, mice lacking REV-ERBα exhibit elevated plasma glucose levels.[7] Anecdotally, my hba1c levels haven't breached 5mmol/L since starting SR9009.

REV-ERBα activation by SR9009 inhibits transcription of inflammatory factors IL-1β, IL-6, MMP-9, and Ccl2 in astrocytes. SR9009 significantly attenuates hepatic damage and inflammatory responses, it is effective in suppressing clinical markers of liver damage, circulating lipids, hepatic fibrosis, and markers of inflammation. In addition, pharmacological activation of REV-ERBα by SR9009 alleviated hepatic steatosis, insulin resistance, liver inflammation, and fibrosis in CL diet-induced NASH mice. These effects were accompanied by improved gut barrier function and altered microbial composition and function in NASH mice, and the effect tended to be stronger when SR9009 was injected at ZT0 (night time) Moreover, SR9009 treatment at different time points resulted in a marked difference in the composition of the microbiota, with a stronger effect on the enrichment of beneficial bacteria and the diminishment of harmful bacteria when SR9009 was administrated at night.[8, 9, 10]

SR9009 potently regulates mitogenesis (the formation of new mitochondria) and mitochondrial respiration. In one study dealing with REV-ERBα knockout mice, cellular effects resulted in both impaired mitochondrial biogenesis leading to compromised exercise capacity. On a molecular level, REV-ERBα deficiency resulted in deactivation of the Lkb1-Ampk-Sirt1-Ppargc-1α signaling pathway.[11] Additionally, genes encoding enzymes of fatty acid β-oxidation, like carnitine palmitoyltransferase 1b (Cpt1b), long chain acyl-CoA dehydrogenase (Acadl), short chain acyl-CoA dehydrogenase (Acads), Ucp2, and Ucp3, genes involved in skeletal muscle metabolism, were also upregulated with REV-ERBα overexpression.[12] Researchers have demonstrated that mice lacking REV-ERBα had decreased skeletal muscle metabolic activity and running capacity. Burris’ group showed that activation of REV-ERBα with SR9009 led to increased metabolic activity in skeletal muscle in both culture and in mice. The treated mice had a 50 percent increase in running capacity, measured by both time and distance.[13].

“The animals actually get muscles like an athlete who has been training,” said Burris. “The pattern of gene expression after treatment with SR9009 is that of an oxidative-type muscle— again, just like an athlete.”

Speaking of muscles, glucocorticoids seem to negatively regulate REV-ERB expression, REV-ERBα mRNA levels were shown to be down-regulated by dexamethasone in the liver and in both rat and human primary hepatocyte cultures in one study[14]. In another study, REV-ERBα overexpression partially or totally blunted dexamethasone-mediated induction of the catabolic (Atrogin, Murf1, Foxo1 and Foxo3a) and anti-anabolic (Klf15, Redd1 and Bcat2) genes[15]. This means SR9009 is HIGHLY anticatabolic because cortisol/glucocorticoid agonism is one of the most potent regulators of muscle catabolism. The fact that SR9009 was able to completely abate dexamethasone induced catabolism is astounding, imagine what it's capable of doing in the presence of anabolics.
​

It's exercise in pill form essentialy, and it doesn't cause cancer like Cardarine, quite the contrary actually.​

​

Spoiler: REV-ERB and cancer

View attachment 3208730

​

REV-ERBs are potently anticarcinogenic. It's getting too good to be true.​

In one study, it was found that cancer cell proliferation was reduced with the use of the REV-ERBα agonist SR9011 as well as with an RORα agonist. Regarding gastric cancer, it was determined that REV-ERBα expression was decreased in tissues of patients with gastric cancer, which was correlated with poor differentiation and lymph node metastasis. In addition, decreased REV-ERBα expression was associated with poor prognosis. Another study focusing on glioblastoma investigated the proliferation dependence on clock genes among different cell states of glioblastoma cells, namely, the glioblastoma stem cells, differentiated glioblastoma cells, and non-malignant brain cells. The GSCs only exhibited a strong dependence on clock-related transcription factors. The treatment with the small-molecule agonists of REV-ERBs SR9011 and SR9009 led to a reduction in the GSC proliferation rate.[16]
​

Okay so how do we use SR9009?​

SR9009 has an estimated half life of around 4-6h, that means it's in and out of the body relatively quickly and that's exactly what we want, REV-ERB regulates orexinergic genes (orexin 1/2 are neuropeptides involved in sleep onset and maintenance) if taken during the day (SR9009) orexin is supressed, if you take it too close to bedtime you'll have an underactive orexingergic system, not only this, but SR9009 negatively regulates GABA transmission so wakefullness is definitely a perceptible effect of this drug. It also blocks melatonin receptor. The immediate effect of this drug is intense but non-anxiety inducing alertness. Once this drug is out of the body, however, orexin, melatonin & gaba are sensitized. Sleep onset is rapid and sleep maintenance is perfect. SR9009 will positively regulate your circadian rhythm more than any drug supplement (melatonin).

The issue however, is the fact that SR9009 has next to no oral bioavailability, we are required to either brew SR9009 into an oil based injectable, or we can dissolve SR9009 into DMSO and it apply it transdermally (wrists, scrotum and thin veiny areas have the best absorption rates). SR9009 will hold in DMSO at 30mg/ml[17]​

​

​

Spoiler: recipe for oil-based injectable

For an injectable solution (30ml) we get around 30mg/ml

900mg/.9g of SR9009 raw powder
20% benzyl benzoate
2% benzyl alcohol
78% MCT oil

Spoiler: recipe for DMSO transdermal solution

For a DMSO based solution we can achieve 30mg/ml

30ml 99% pharmaceutical grade DMSO
900mg/.9g of SR9009 raw powder

Only apply/inject in the morning and never after midday.​

​

Spoiler: sources

10.1016/j.bcp.2017.02.006

Redirecting

10.3390/ijms232112954
10.7150/thno.43834

REV-ERB agonism improves liver pathology in a mouse model of NASH

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to...

doi.org

https://doi.org/10.1080/07420528.2023.2207649

Frontiers | Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway

Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathw...

doi.org

10.1038/nm.3213

Distinct roles for REV-ERBα and REV-ERBβ in oxidative capacity and mitochondrial biogenesis in skeletal muscle

The nuclear receptors REV-ERBα and REV-ERBβ have been demonstrated to be core members of the circadian clock and participate in the regulation of a diverse set of metabolic functions. Due to their overlapping tissue expression patterns and gene expression profiles, REV-ERBβ is thought to be...

doi.org

Circadian and Glucocorticoid Regulation of Rev-erbα Expression in Liver*

Abstract. Rev-erbα [NR1D1], a member of the nuclear receptor superfamily, is an orphan receptor that constitutively represses gene transcription. Rev-erbα

doi.org

Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass - Scientific Reports

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression...

doi.org

The Role of REV-ERB Receptors in Cancer Pathogenesis

REV-ERB receptors are members of the nuclear receptor superfamily of proteins, which act as both intracellular receptors and transcription factors, therefore modulating the expression of target genes. REV-ERBs act as transcription repressors because of their unique structure. Their predominant...

doi.org

mogger thread

Not only does it not increase anxiety while increasing alertness like you mentioned but it's actually anxiolytic.

https://www.nature.com/articles/ncomms6759 Mice spent almost 7x more time with novel objects, are lower inhib when taking part in mazes (this is a legit measure), they spend more time in the centre an open field assay (if they sit in the corners they are abused dogs)

Also, what are your thoughts on SR10067? It's presumably even stronger but it's not studied very much

​

 

[Dyorotic]

mogger thread

Not only does it not increase anxiety while increasing alertness like you mentioned but it's actually anxiolytic.

https://www.nature.com/articles/ncomms6759 Mice spent almost 7x more time with novel objects, are lower inhib when taking part in mazes (this is a legit measure), they spend more time in the centre an open field assay (if they sit in the corners they are abused dogs)

Also, what are your thoughts on SR10067? It's presumably even stronger but it's not studied very much

​

Apparently there are strongest agonists (like the one you mentioned) but they aren't commercially available. SR9009 is already really potent, and the dosage can be pushed really high.

I did 50mg in the morning the other day and my workout felt like nothing, literally could have gone on for hours. That isn't even the good part tbh, its the lipid reducing effect. 50% slashed is utterly absurd.

And yeah good point about the anxiety. I should have mentioned, fuck.

 

[Fartmaxxing]

Holy fuck steroids keeping getting better and better

 

[Fartmaxxing]

Imma give my friends who roid SR9009

 

[NZb6Air]

mogger thread

Not only does it not increase anxiety while increasing alertness like you mentioned but it's actually anxiolytic.

https://www.nature.com/articles/ncomms6759 Mice spent almost 7x more time with novel objects, are lower inhib when taking part in mazes (this is a legit measure), they spend more time in the centre an open field assay (if they sit in the corners they are abused dogs)

Also, what are your thoughts on SR10067? It's presumably even stronger but it's not studied very much

​

So basically the actual low inhib stack is sr9009 + nicotine + NPS when it comes out
https://sci-hub.se/10.1016/j.neuron.2004.08.005 https://sci-hub.se/10.1016/0306-4603(84)90012-1

and the psycho stack is SR9011 + cocaine

rest is cope or low reward

 

[cyprian_tomaszewski]

So basically the actual low inhib stack is sr9009 + nicotine + NPS when it comes out
https://sci-hub.se/10.1016/j.neuron.2004.08.005 https://sci-hub.se/10.1016/0306-4603(84)90012-1

and the psycho stack is SR9011 + cocaine

rest is cope or low reward

I'm not sure about the nicotine, in your study they gave people who smoked 20 ciggaretes per day one to smoke and that showed lower anxiety after. It could just be that they are addicted and they are fullfilling their cravings caused by addiction and that causes them stress relief. Here's a newer one:

Increasing neurogenesis while doing whatever you want to do without fear should work too (for fear extinction in the future)

 

[halloweed]

Imma give my friends who roid SR9009

Where did you get it from bro ?

 

[MA_ascender]

Bump

 

[MA_ascender]

Great thread I love you bhai

 

[halloweed]

its the lipid reducing effect. 50% slashed is utterly absurd.

@sb23

 

[halloweed]

@Fartmaxxing said he got it for 30$

 

[sb23]

@sb23

Truly a god send. I heard about these a while ago but didn't look into them because apparently they were really expensive (I guess not according to some). They are really blowing on this forum atm. Good to see people being more longevity oriented.

 

[MA_ascender]

Truly a god send. I heard about these a while ago but didn't look into them because apparently they were really expensive (I guess not according to some). They are really blowing on this forum atm. Good to see people being more longevity oriented.

Ong bro roids just keep getting better and better I can't wait till we make some money for a good cycle

 

[everyone]

red but im retarded

 

[devonhendryx999]

inb4 botb

 

[Blonde]

is SR9009 better than SR9011?

 

[Rigged]

God you are such a retard its unbelievable, quote within the thread or anywhere he said SR9009 is a steroid FFS. This thread is about prevention of roid induced side effects (fixing lipids). You have to be baiting because theres just no way someone this retarded had the balls to put “top 5 highest iq” in their status a few weeks ago. What an utter disgrace you are to this forum.

Keep reeding dumbass after i replied i stated i got confused based on what the 1st user said before i read it then corrected myself, the thread is shit and i already replied multiple times in the replies

And jfl at “your science” as if this is some lame theory, he has a source in EVERY line of the thread.

R u retarded im stating his science is incomplete

You really got him with the format! Sorry your 82 iq brain cant process a thread without bright colors and pictures scattered everywhere. Im really not suprised in the slightest

No the format sucks formatting is important i read it fine tho

considering every thread you have ever made is chat gpt ramblings (also dogshit).

I dont use gpt, ive directly talked with people about this stuff, and gpt cant do this level of knowledge especially by the fact its updated only to 2023

The fact that you beg for the contributor badge while being a complete pseudo intellectual retard should be ban worthy, cheers.

I didnt beg tf, i applied once and never cared again, ur guides are ass and ur only relevant for posting your face


If u read my replies to this thread ive already explained how its wrong, ur just dickriding for no reason


Gonna @ the niggas who repped u, cuz ur reply had no substance and was directing it at me when u clearly only read my first reply to this post
@MA_ascender @NZb6Air @halloweed

 

[halloweed]

Keep reeding dumbass after i replied i stated i got confused based on what the 1st user said before i read it then corrected myself, the thread is shit and i already replied multiple times in the replies

R u retarded im stating his science is incomplete

No the format sucks formatting is important i read it fine tho

I dont use gpt, ive directly talked with people about this stuff, and gpt cant do this level of knowledge especially by the fact its updated only to 2023

I didnt beg tf, i applied once and never cared again, ur guides are ass and ur only relevant for posting your face


If u read my replies to this thread ive already explained how its wrong, ur just dickriding for no reason


Gonna @ the niggas who repped u, cuz ur reply had no substance and was directing it at me when u clearly only read my first reply to this post
@MA_ascender @NZb6Air @halloweed

SR9009 afaik has great benefits I’m not as smart as @9898 but I’ve researched about it and it’s great for preventing hepatoxicity, cardiovascular risks and imbalanced cholesterol. What are you even arguing about anyways?

 

[Rigged]

The exclusion of unnecessary information that goes beyond the core mechanism behind SR9009 is not the same as "ignoring" or "oversimplifying". It's explained incredibly simply and you're being pedantic for criticizing it.

removing info to make it simple is differant than leaving out important mechanisms which lowers ur post’s value its not about being pedantic, understanding the mechanisms fully would help educated people (the only ones who should take this) make better choices , its not about simplifcation it’s about completeness

SR9009 is safe according to my understanding. Stuff like Cardarine is not safe and my risk tolerance drops drastically at anything carcinogenic. I wouldn't post about something If I knew it was potentially dangerous.

Even tho SR9009 seems safer than Cardarine “safe according to my understanding” doesnt remove the need for a convo on its safety profile 100% of compounds have risks and talking about those here would give other people more knowledge about this

Right so because I didn't explain the entire sequence of gene expression/suppression/activation of REV-ERB and everything that entails, I shouldn't have bothered writing anything at all? What kind of fucking deranged and nonsensical logic is that?

No one said that u should write nothing at all, but omitting key biological pathways lowers the depth of your guide having those details in this post even discussed a little, would give the post more value without making it “overly complex”

I wrote it as simply as I could because the barrier of entry for understanding this stuff is higher than the usual biochemistry talked about on here. Everyone knows what an androgen receptor is, no one knows what CLOCK/BMAL1 are/is.

You're acting as though me writing everything you mentioned makes it any easier for people to understand/engage with.

its not even about overwhelming people with every detail it’s only about having a balance simplification is perfectly fine, but ur original post isnt simplified and when key mechanisms are left out in a complex post (yours) it makes the info incomplete, ofcourse for those who would need a better understanding of its function instead of learning it just for the first time

No it won't. If someone genuinely gives a fuck about this type of stuff they'll look into it further. I'm hoping no one reads a looksmax thread and then takes everything at face value. If someone cares about the MOA of SR9009 they'll research beyond this thread.

Sadly this is the part where ur wrong for a fact, people take things at face value at here, they see smart words and think “has to be right” ive written theory threads that were purely theory and users were telling me they were gonna try them, and thats for theory, imagine one where its a non theory, way more users would try it and have, ofcourse i make sure to include everything possible, but its sad when users dont try looking for even a little bit and its 99% of the time

I'm demonstrating a potential tool to mitigate the sides of steroids, that's it. Everything I wrote and backed up with citations pertains to it's usage and immediate perceptible (blood test to confirm) effects in the body.

Blood tests are only the top layer they cant capture the complicated and long term gene expression changes caused by circadian regulation that affect metabolic homeostasis and mitochondrial function

Strawman. I'm not saying people won't read, I'm saying that those who will won't simply read what I've written and take it at face value, they'll most likely research the circadian rhythm, which goes way beyond the CLOCK complex. I wrote what I thought was necessary, anything more obscures the point of the post (mitigating AAS sides and why SR9009 is a perfect candidate)

It’s not a strawman if the post omits important info that could prevent issues u assuming people will research more doesnt change the fact that ur responsible to give correct and complete info in the post itself

You are probably the only person on this site that even knows what SR9009 does in full detail, stop acting like there are other people on this site who care/know anything about what we're discussing.

Yes thats the point your getting it great!, either make the post full complex with everything in it so the people who know 80% can learn the rest, or make it hyper simplistic with steps so that every user on this forum can understand

Why is that necessary? You can read everything highlighted if you don't want to read the rest. Everything highlighted pertains to SR9009's effect in the body.

highlights help but condensing the important points and having critical mechanisms would make the post easier to understand and use while still providing the important info it originally was, simplification doesnt have to mean dumbing down

You're a dumbass and you made a horrible metaphor that isn't at all analogous to what I wrote. Everything that pertains to SR9009 (valuable information regarding it's actual EFFECTS on lipid synthesis, mitogenesis [...] etc, is included. It's not SIMPLE just because I didn't recite the entire circadian gene complex. How the FUCK is that relevant to the fact that it might help someone with hyperlipidemia?

holy shit AGAIN the metaphor was about oversimplification not a direct analogy to science, ovesimplifying does make the post less complete and even tho you added some effects ignoring the mechanisms that cause those effects leaves issues in peoples understanding of how this would work

You're unbelievably pedantic.

Not going to respond to this because I don't like lowblowing people for things they can't change, but I did chuckle IRL.

I have ways to change my height that im trying to keep to myself, just gotta get enough money for everything first

IT IS relevant to those who want to looksmax you fucking bafoon. I wrote about it's anticatabolism, it's effects on mitogenesis, it's effects on lipids (can't have sex if you're dead) etc etc. Just because I didn't consider the fact that some nerd like you would come in and derail for absolutely no reason other than pure pedanticism doesn't mean the thread is bad.

ur post is relevant in its intent but relevance without depth threatens its use, u do talk about the things u mentioned but failing to talk about the molecular mechanisms creates a huge gap in understanding how it interacts with cellular and metabolic pathways, this is not pedantic, scientific rigor requires a throrough explanation of how REV-ERB agonists affect circadian gene expression and in turn impact metabolism, lipid synthesis, and endurance

Mitigating steroid sides without talking about biochemical complexity causes an incomplete post andfor anyone who is serious about “looksmaxing” through biohacking they NEED a full understanding of what these compounds do to the body at a molecular level and by u ignoring circadian regulation pathways, u risk oversimplifying the mechanisms that make it effective which reduces the posts value for anyone who has knowledge on this

 

[Rigged]

SR9009 afaik has great benefits I’m not as smart as @9898 but I’ve researched about it and it’s great for preventing hepatoxicity, cardiovascular risks and imbalanced cholesterol. What are you even arguing about anyways?

i replied to him just now

But to answer were arguing on the fact that he tried to “oversimply” it by removing info while the whole guide is complex, u either target the audiance with no knowledge and simplify it to and extreme so they can understand, or the people who have knowledge and would want to learn everything else which this post fails providing since it removed important info

 

[halloweed]

i replied to him just now

But to answer were arguing on the fact that he tried to “oversimply” it by removing info while the whole guide is complex, u either target the audiance with no knowledge and simplify it to and extreme so they can understand, or the people who have knowledge and would want to learn everything else which this post fails providing since it removed important info

He’s outputting all the knowledge he knows about the compound. He hasn’t done anything bad tbh, just bringing info to the light.

 

[Rigged]

He’s outputting all the knowledge he knows about the compound. He hasn’t done anything bad tbh, just bringing info to the light.

I get that im not saying he did anything bad im saying the post isnt good, bringing something into light is different when u try to teach people about it, which brings me to my original point, the one u just replied to

 

[halloweed]

I get that im not saying he did anything bad im saying the post isnt good, bringing something into light is different when u try to teach people about it, which brings me to my original point, the one u just replied to

What should he have done differently?