In case you aren’t a part of my email list or my private Fully Optimized Health group, I AM working on what I believe will be my best, my 3rd, and most definitive fat loss book ever created.
30 Days 2 Shredz is expected to launch by no later than the end of June and I can’t wait to share what the Golden Age has unearthed in the past 4 years.
You wouldn’t think weight loss can get much faster or more effective than Guaranteed Shredded, but the world is not the same place it was pre-pandemic.
Especially when it comes to the discovery of novel fat-burning agents.
That’s why I want to dedicate this article to GW0742, one of the compounds to be featured in 30 Dayz 2 Shredz.
Despite its highly experimental nature and relative newness in the fitness world, I’ve had the chance to try it for myself and was blown away by my increased capacity to train at balls-to-the-wall intensity not to mention the dramatic fat burning and glycogen repartitioning I experienced from its effects.
So let’s take a look at GW0742 and see how this multi-use endurance enhancer managed to get on my radar.
What Is GW0742?
GW0742 (also known as “Lipoline” in underground bodybuilding circles) is a peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) agonist that is manufactured by pharmaceutical company GlaxoSmithKline (GSK).
It’s important that I start with this sentence because many people on the Internet see this compound sold by vendors selling selective androgen receptor modulators (SARMs) and then assume GW0742 is a SARM as well.
The first instance I could find of this compound being mentioned in the medical literature was in 2003, when GSK was attempting to figure out the distinct function of each PPAR subtype:
“The Peroxisome Proliferator-Activated Receptors (PPARs) comprise a family of ligand-activated transcription factors belonging to the nuclear receptor gene superfamily…
Each subtype contains a signature DNA binding domain (DBD) anda ligand-binding domain (LBD), both of which are necessary for ligand-activated gene transcription.
The role of PPARα in the regulation of hepatic lipid metabolism was uncovered when it was shown to be the target receptor for the fibrate class of antihyperlipidemic drug molecules.
Likewise, the role of PPARγ in the regulation of insulin sensitivity was discovered when it was shown to function as the cellular receptor of the glitazone class of antidiabetic drugs.
In contrast, PPARδ does not appear to be a receptor for any known classes of drugs… part of the challenge in determining the function of PPARδ has been the identification of potent and selective ligands for use as chemical tools“
(We now know full and well what functions PPARδ serves in the human body, and I’ll talk about this in the next section)
After doing some thorough structural analysis and running some binding assays against human PPARδ receptors, two compounds were the most selective agonists by 1,000-fold:
(Source; A = GW0472, B = GW501516 (Cardarine)
For those of you deeply entrenched in the world of SARMs, you’ll recognize Compound B in the picture above as Cardarine (GW501516):
“Cardarine works by increasing muscle cell metabolism and decreasing fat deposits by stimulating lipolysis or fat breakdown.
Its active ingredient can significantly increase muscle growth and endurance.
Cardarine also helps regulate cholesterol levels and maintain liver health.
All of these beneficial effects can be attributed to cardarine’s ability to activate the peroxisome proliferator-activated receptor-delta (PPAR-delta) pathway.”
And if you look closely at the two structures, they are virtually identical with the exception of the additional fluorine atom added to the benzyl ring on the right side of the molecule (A).
So really, what’s the point of GW0742 when a compound like GW501516 exists?
There are several speculations, some of which include:
- GW501516 is no longer being pursued as a pharmaceutical drug by GSK due to a higher-than-acceptable incidence of cancer in animal studies (more on that in the Side Effects section)
- The addition of a fluorine atom to form GW0742 allows GSK to extend their likely-expired patent on GW501516 (since its discovery was in the early 1990s)
- Creating a more powerful version of GW501516 with respect to cardiovascular endurance and fat loss, but hopefully with a lower degree of toxicity
Even though both GW0742 and GW501516 are identical in their affinity for the PPARδ receptor, I couldn’t find anything about either compound’s affinity for the PPARβ receptor.
So perhaps there’s something much more unique about GW0742 that GSK isn’t revealing to the public?
Hard to say.
But this brief history lesson takes us to why there is so much growing interest among the underground bodybuilding community for the compound.
How GW0742 Works
Since GW0742 is a PPARβ/δ agonist, the easiest way to understand its mechanism of action is to understand the biological roles of both the beta and delta receptors.
As it turns out, when these receptors are inactivated, less expressed and/or lacking in number, what you end up with is “impaired wound healing, an increase in adipose mass, and disturbed inflammatory reactions in skin” (Source).
Let’s dive into these outcomes in greater detail…
“PPARβ/δ has been directly linked to the development of obesity. Indeed, several groups have reported a decrease in adiposity after PPARβ/δ activation. By stimulating fatty acid oxidation, PPARβ/δ activation leads to loss of adipose mass in different mouse models of obesity.
Similar effects on fatty acid oxidation have been observed in heart, resulting in improved muscle contraction. In addition to increasing fatty acid oxidation, activation of PPARβ/δ in muscle also increases the number of type I muscle fibers, which leads to enhanced endurance performance.”
if I’m a betting man, I would expect to see overweight and obese people with lowered PPARβ/δ expression in their fat tissue.
“The number of studies that have addressed the role of PPARβ/δ during inflammation is limited. So far, an anti-inflammatory effect has been observed in macrophages suggesting a possible role for PPARβ/δ in the process of atherogenic inflammation.
It appears that PPARβ/δ acts as an inflammatory switch in which inactivated PPARβ/δ is proinflammatory and activated PPARβ/δ promotes an anti-inflammatory gene expression profile.”
“Atherogenic dyslipidaemia, often observed in patients with obesity, insulin resistance, metabolic syndrome and type 2 diabetes mellitus, is a significant risk factor for cardiovascular disease. This dyslipidaemia is characterized by the presence of low high-density lipoprotein (HDL) cholesterol levels, elevated triglyceride (TG)-rich very low-density lipoprotein (VLDL) amounts and an increased proportion of small and dense low-density lipoprotein (LDL) particles.”
“…The assessment of PPARβ/δ agonists in several small-scale clinical trials mainly for the treatment of atherogenic dyslipidaemia has confirmed that these drugs reduce plasma TG levels, increase the amounts of HDL-cholesterol and decrease the levels of small dense LDL particles in humans, indicating that treatment with these drugs initiates a transition towards a less atherogenic lipoprotein profile”
“PPARβ/δ agonists improve glucose tolerance and insulin sensitivity in animal models. The antidiabetic effects of these drugs are exerted in different tissues. For instance, macrophage infiltration into adipose tissue and polarization towards the pro-inflammatory M1 phenotype promotes inflammation and correlates with the degree of insulin resistance. As mentioned above, PPARβ/δ activates polarization towards the anti-inflammatory M2 phenotype in macrophages”
“PPARβ/δ activation in the small intestine potentiates the production of glucagon-like peptide (GLP)-1, which preserves β cell morphology and function, thereby increasing systemic insulin sensitivity. This is consistent with a recent study reporting that intestinal PPARβ/δ protects against diet-induced obesity and insulin resistance”
“PPARβ/δ agonists also increase mitochondrial oxidation in β cells, enhance glucose-stimulated insulin secretion (GSIS) from pancreatic islets and protect GSIS from the adverse effects of prolonged FA exposure. In fact, PPARβ/δ is critical for the expression of the genes involved in mitochondrial function and consequently ATP production, in β cells, which is required for GSIS”
Last but certainly not least, we also have the increase of glucose uptake into skeletal muscle tissue through the activation of AMP-activated protein kinases (AMPK) by GW0742, which is done primarily through PPARβ.
All of this sets us up for exploring GW0742 as a possible tool to help us get more reps in the gym while improving our blood work at the same time.
Benefits of GW0742
I should warn you that the GW0742 benefits listed in this article are (a) largely borrowed from what we know about how GW501516 (Cardarine) works in the body, and (b) taken from preclinical studies since it hasn’t reached human testing just yet.
Even though this compound has been in the medical literature for 20 years, it hasn’t graduated much beyond rat studies and speculations about its safety.
So with that out of the way, let’s see what GW0742 can do for aspiring biohackers…
Improves Cardiovascular Endurance
This right here is why I wanted to write an article on GW0742 in the first place:
When Maxime Jean-Noel of Cuerpoymente first introduced this compound to me, I was blown away at how much it boosted my total workout capacity.
Not surprising when you learn people use GW501516 (Cardarine) for the same reason:
“The claims that it is like having a 3rd lung our true IMO.
Taking it for cardio/endurance makes a very noticeable difference. You will smash PBs using it. No side effects to report.” (Source)
“Using cardarine is hard to explain but you have this HIDDEN energy that just mentally tells you “I could easily be here for the next 3 hours” but you don’t necessarily have the adrenaline rush or tingles that pre-workout gives you that makes you physically feel like you can stay 3 hours but the energy is most certainly there. it gets confirmed by the fact that you’ll go from exercise to exercise and wonder why you’re still not tired yet.
Which is when I usually think: damn I could be here for another two hours.” (Source)
“Goddamnit, first dose and after doing a death set at 80% 1rm i felt like sprinting back to my car.
I even had the energy to sprint back from the parking lot to point out to a fellow gym member that he had left his car open and lights on.
Then took off and ran at a solid 70% speed back to my car.
Jesus it takes all the bad out of exercise and leaves you with just the high.
10/10 will hop on it again after these 8 weeks are over (in due course)” (Source).
And there are plenty of studies to back up Cardarine’s effectiveness for hard exercise, such as this one done in mice:
“…small molecule ligands that specifically activate PPARδ, including GW501516 (GW), have revealed multiple beneficial metabolic effects, including (1) increased energy expenditure, (2) elevated [fatty acid] oxidation, (3) reduced obesity and insulin resistance, (4) exercise-induced muscle remodeling, and, collectively, (5) enhanced running endurance by 80% or more.”
“Here we show that activation of muscle PPARδ not only increases fat oxidation, but also coordinately decreases glucose catabolism to forestall hypoglycemia and facilitate progressively longer running time.
Unexpectedly, this substrate prioritization does not depend on either oxidative fiber-type transformation or mitochondrial biogenesis”
But what about GW0742?
One study in mice found that GW0742 was able to shorten the early phases of skeletal muscle regeneration by targeting PPARβ, which was done by increasing the degree of their body’s immune response and increasing the anti-inflammatory response of muscle injury.
Another study in mice took things further and decided to see what would happen if you combined GW0742 with AICAR:
“Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPAR δ agonist GW0742 for 4 weeks. AICAR treatment potentiated endurance, but the combination of AICAR and GW0742 further potentiated endurance and increased all running parameters significantly relative to exercised and nonexercised groups (138–179% and 355% increase in running time, respectively).”
“Our data show that combined pharmacological activation of AMPK and PPAR δ potentiates endurance in trained mice by transcriptional changes in muscle and liver, increased available energy substrates, delayed hypoglycemia through glycogen sparing accompanied by increased NEFA availability, and improved substrate shift from carbohydrate to fat.”
Fortunately, the science does back up the experiences of myself and a few brave souls who jumped in with both feet and used GW0742 on themselves:
“I’m currently have been bulking for the last 6 weeks, yes bulking with GW0742, training at home and for the first time in my life I’m getting crazy quad veins popping.
Every day I’m discovering new and more veins in my legs and arms whilst I’m meant to be getting “fatter” (bulking) .
So in terms of fat loss I would say it’s pretty freaky.
I’m running it at 10mg daily. 5mg am 5mg pre bed” (Source)
“I only use Cardarine (gw501516) on training days,
I feel it subtly improves my ability to work out Tried one dose of GW0742….my god the difference at least for the first dose anyway was day and night in comparison with normal cardarine.
Let me elaborate i took it when I trained and at no other time, I was doing press-ups and squats, really noticed it on the press-ups, lactic acid didn’t seem to kick in and felt I could do an extra 10 reps over normal cardarine.
Also felt like I was slightly more stimulated, not over the top but just able to tap into my energy. And definitely felt that I was able to breath deeper and get more oxygen into my body.” (Source)
“I’ve ran 3 cycles of 0742, and honestly it feels insane, i could lift 2-3 more reps per exercise, and in terms of cardio, it was as if I’d been training for a race, it’s effects are fast and progressively get better towards the mid-latter end of the cycle, however the heart stuff is 100% true, once I finished the 4 separate cycles my heart was basically pounding out of my chest for 3 weeks and I could hear and feel it, but after 3 weeks going into the 4-5 week mark, the effects completely wore off, gonna go into my next cycle soon” (Source)
“…you should notice that cardio gets significantly easier right away. Especially at 20Mgs.
It should be noticeable at 10mgs and the risk-reward benefit is not worth going higher than 10mgs in my opinion.
Real stuff does the job at 10 mgs” (Source)
In effect, you’ll find it a lot easier to lift weights in higher rep ranges when you’re training with a system such as my Positive Muscular Failure program.
And when you’re pedaling hard on a bike for your cardio, you can push yourself far harder and for far longer without building up fatigue.
GW0742 is a great agent when you need faster recovery while in a caloric deficit.
Helps With Fat Loss
I will be discussing this feature much more thoroughly in 30 Days 2 Shredz, as GW0742 can be a profound lipolysis accelerator if used correctly.
But to explain exactly how GW0742 contributes to losing fat tissue and not dragging hard-earned lean muscle along with it, we need to look at how Cardarine works:
- Increases the catabolism of skeletal muscle fatty acids
- Upregulates expression of the genes needed to oxidate fatty acids through the direct activation of PPARδ within adipose tissue
- Helps decrease the amount of body fat gained if you are eating at maintenance, but it WILL NOT over-ride a caloric surplus
- Improves biomarkers and your overall lipid profile (lowered LDL, higher HDL, lowered triglycerides, better insulin sensitivity
But given the improvement in your ability to be active, as we saw with GW0742, the entire point of using Cardarine is to lower your body fat even further by taking full advantage of the newfound energy you now have.
One interesting study involving 24 female diet-induced obese mice had them spend 8 weeks on a training program, GW0742 treatment alone, or a combination or both:
“24 [diet-induced obese female] mice were assigned to groups according to an 8-week exercise training program and/or an 8-week treatment with 3 mg/kg/day of GW0742, a PPARβ/δ agonist.
Our results show metabolic changes of peripheral lymphoid tissues with PPARβ/δ agonist (increase in fatty acid oxidation gene expression) or exercise (increase in AMPK activity) and a potentiating effect of the combination of both on the percentage of anti-inflammatory Foxp3+ T cells.
Those effects are associated with a decreased visceral adipose tissue mass and skeletal muscle inflammation (TNF-α, Il-6, Il-1β mRNA level), an increase in skeletal muscle oxidative capacities (citrate synthase activity, endurance capacity), and insulin sensitivity.”
Both exercise and GW0742 were able to independently increase fatty oxidation through their own pathways, yet the study rightly says that GW0742 is not an exercise mimetic meant to replace hard work.
However, a separate study done in obese male mice shows that it may be possible to eat at caloric maintenance and still lose body fat:
In the graph above, there are only four groups to worry about:
The mice who were fed a control diet without GW0742 (C), the mice who were fed a control diet with GW0742 given after 10 weeks (C-β), the mice who were fed a high-fat diet without GW0742 (HF), and the mice who were fed a high-fat diet with GW0742 given after 10 weeks (HF-β).
Regardless of the diet, GW0742 led to significant weight loss and was responsible for 62% of the variance seen in the final results.
Not bad at all!
The Best GW0742 Dosage For Exercising Longer & Harder
The best GW0742 dose for improving your gym performance all-around will significantly differ depending on the individual.
If you ask Maxime from Cuerpoymente, he’ll tell you to use 10 mg a day taken orally, 30 minutes before you start exercising.
Yet if you ask for the dosages that best served other people, you’ll get a variety of answers:
- 15mg taken 2-3 times a day, 4-5 hours between each dose
- 20mg taken daily for 4 weeks straight before cycling off
- 20mg every day in 8-10 week cycles, cycling off for at least half of your “on” cycle
- 10mg every day for 4 weeks straight
- 4mg on Mondays and Thursdays, going up 1mg at a time every week until you hit the sweet spot (don’t exceed 10mg)
That’s really all the information I have for now.
But if you’ve been following me for a while you know what I’m going to say:
Start low, go up slowly, see what works best for you.
I haven’t been using GW0742 long enough to say what would be the most optimal dosing cycle.
Side Effects of GW0742
GW0742 side effects are rarely reported because… well, barely anybody even knows about the drug and even fewer people have used it in any capacity.
Without a product monograph to refer to, here are some of the things I’ve heard people say when they started using GW0742:
- No benefits were experienced, nausea and headaches were worse compared to Cardarine
- Weird feeling in left ear, as if there was the sound of water and the person had been swimming
But there are two side effects I want to talk about, ones that may alter your decision to use GW0742 or not
This is the one I was most concerned about until Maxime of Cuerpoymente showed me more of the literature and my worries were addressed.
Whenever people make this claim, they point to this study that observed the increase of heart size in mice who were given either GW0742 or GW501516 was due to cardiomyocyte enlargement.
What gets left out are these two details:
“No signs of pathological cardiac hypertrophy (i.e. apoptosis, fibrosis, or deteriorated cardiac function) could be detected.”
“However, the reversibility of cardiac growth and vascularization 4 weeks after the end of GW0742 treatment points to a potential pharmacological use.”
And even if the heart is enlarged, it is only good or bad within a certain context:
Higher Risk of Cancer
This side effect comes up because it was the reason why GW501516 (Cardarine) was discontinued as a pharmaceutical drug:
“By 2007, GW501516 had completed two phase II clinical studies and other studies relating to obesity, diabetes, dyslipidemia and cardiovascular disease, but GSK abandoned further development of the drug in 2007 for reasons which were not disclosed at the time.
It later emerged that the drug was discontinued because animal testing showed that the drug caused cancer to develop rapidly in several organs, at dosages of 3 mg/kg/day in both mice and rats”
Logically, if that’s what happened to GW501516, why would the same thing NOT happen with GW0742? Is this perhaps the reason why we’ve never seen so much of an attempt to take GW0742 to Phase 1 trials in humans?
The only people who can know this answer 100% is GlaxoSmithKline themselves, who has all of the toxicity data on GW0742 and the power to decide whether to share it publicly or not.
We can never really know for sure because if you look at the totality of all the studies examining PPARβ/δ agonists, they all say contradictory things.
This is best exemplified by one paper that attempts to explain why people are seeing completely different results:
“The contradictory findings could be due to differences in the model system (cancer cell line versus in vivo), differences in cell culture conditions (with and without serum) or differences in ligands.
The present study examined the effect of two different PPARb/d ligands (GW0742 and GW501516) in human cancer cell lines (HT29, HCT116, LS–174T, HepG2 and HuH7) cultured in the presence or absence of serum and compared in vitro analysis with in vivo analysis.
Neither PPARb/d ligand increased cell growth or phosphorylation of Akt and no increase in the expression of VEGF or COX2 were detected in any cancer cell line in the presence or absence of serum.
Similarly, liver, colon and colon polyps from mice administered these PPARb/d ligands in vivo did not exhibit changes in these markers.”
Long story short, nobody has any true way to know whether GW0742 and other compounds in its class really do cause cancer or not.
But I can’t imagine cycling on and off with a responsible dosage would increase one’s risk.
Where To Buy GW0742
If you want to know how to buy GW0742 online, I have two pieces of bad news for you.
The first bad news is that my ONLY recommended source is Cuerpoymente, who only ships within Mexico and does not process international orders.
(Yes, I know the true supplier is shown in the picture and recently resurrected from the dead, but I do not know them well enough to give an endorsement)
The second bad news is that both GW0742 and GW501516 are banned by WADA under category “4.4. Hormone and metabolic modulators”.
So if you’re a competitive athlete, sorry to say this compound is NOT for you!
Conclusion: GW0742 Makes Hard Work Easier For Everyone
GW0742 shows a lot of promise as a serious exercise-enhancing, fat-burning tool for people who are stuck in the middle of a difficult program focused on intense weightlifting and extended periods of fasting.
There’s no need to make the easy things hard when the hard things will provide you with more than enough difficulty.
And that’s what I like about GW0742… it makes the easier things even easier, and the hard things a lot more manageable.
If you have the means and the bravery to experiment with this compound, go ahead and do so.
I would love to hear what people in my circle would have to say about whether GW0742 is worth keeping in one’s fat loss toolbox.
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