New Study On SLU-PP-332 Just Released
A new study just dropped on SLU-PP-332, or as we call it around here, SLUPE. It's not a full human trial, but they did something pretty interesting. They took muscle samples from women undergoing hip surgery and treated those samples with SLU in a dish. The results give us a real molecular look at what this stuff is doing.
I want to break this one down because it tells us a lot about why SLU works for fat loss, energy, and now potentially muscle preservation in aging.
What They Actually Did
The researchers wanted to evaluate how targeting estrogen-related receptors (ERRs) affects muscle decline tied to aging and inactivity.
They took 20 women undergoing hip surgery for coxarthrosis. They split them into two groups based on self-reported activity, 10 active and 10 inactive. During surgery, they took muscle biopsies from each woman.
Then they took the muscle cells from the inactive group and treated them with SLU-PP-332 in culture. The goal was to see if SLU could push sedentary muscle cells toward looking like trained muscle cells.
The Baseline Differences
Before treatment, the active vs inactive groups looked very different at the molecular level.
The inactive group had 67% higher NOX4, which is a main driver of oxidative stress and a marker of muscle atrophy. They had 42% lower SIRT1, which helps with muscle repair and hypertrophy. PGC-1 alpha was 38% lower. ERR alpha was 42% lower.
Muscle fiber diameter was also dramatically different. Active women had fibers around 49 micrometers. Inactive women were down at about 19 micrometers.
If you needed motivation to lift weights as you age, there it is.
Why ERR Alpha Matters
ERR alpha is the receptor SLU activates. It's required for mitochondrial biogenesis in adult skeletal muscle and during muscle regeneration.
When researchers delete ERR alpha in mouse models, mitochondrial oxidative capacity gets impaired. Muscle cells also struggle to transition from myoblasts into mature muscle fibers. Translation, harder to build and maintain muscle.
So if we can activate ERR alpha with SLU, we should be able to push the system in the opposite direction.
What SLU Did to the Muscle Samples
This is where it gets interesting. After treating the inactive muscle samples with SLU, here's what happened.
LDH activity dropped 16.1%, meaning less cell damage. Reactive oxygen species dropped 37.7%. Intracellular glutathione jumped 117.4%, which is a big jump in antioxidant capacity. Markers of cellular senescence (zombie cells) dropped 26.1%.
On the protein side, NOX4 came down to levels seen in active subjects. SIRT1 went up to active levels. PGC-1 alpha went up to active levels. ERR alpha went up active levels. FNDC5 also climbed.
They also saw increases in AKT and BCL-2, which support cell survival and prevent cell death. And SLU promoted abundant myotube formation, the structures that become muscle fibers.
Basically, they took sedentary muscle and transformed it at the molecular level to look like trained muscle. Without exercise.
Why This Matters
A few things to take away from this.
SLU isn't just a fat loss molecule. It's hitting the same pathways that exercise hits, and those pathways control mitochondrial function, antioxidant capacity, and muscle preservation.
For older folks, sedentary people, or anyone dealing with muscle atrophy, this is a meaningful target. Falls and muscle loss are some of the leading drivers of decline and mortality, especially in women.
It also makes me think about pairing SLU with a GLP-1. One of the biggest issues with GLP-1s is muscle loss. If SLU can activate the same machinery that exercise activates, that combo starts to make a lot of sense.
The Caveats
Small sample size. Self-reported activity. Muscle samples treated in a dish, not oral or injectable administration in living humans. We still need real clinical trials.
But for me, this study is a strong signal that we're aimed at the right target with SLU.
My Take
I've been using SLU long before I ever sold it, and studies like this are why I keep using it. The molecular data lines up with what people are reporting in real life. Better energy, better fat loss, better endurance, and now evidence it could help preserve muscle in people who can't or don't train hard.
Studies don't make or break a compound. Real-world results do. But when the molecular data backs up what you're already feeling, that's a good sign you're on the right path.
SLU stays in my rotation.
Full transcript click any paragraph to jump video
Hey everybody, this is Hunter Williams. I hope you're doing amazing wherever you are in the world today. Doing something a little bit different with this video and I'm actually just gonna be reviewing a study that came out and this study was done on our affectionately known molecule known as SLUPE, otherwise AKA known SLUPP-332, we call it SLOOP for short. But I thought this would be pretty cool. Obviously, if you watch my channel regularly, you probably know about Sloop. You've probably been using Sloup, but I felt this was pretty good because we did get back some data, at least somewhat in human trials.
It wasn't really human trial, meaning that they administered it orally. But they did take muscle sections from humans that were undergoing surgery and evaluated what it was doing to those muscle section. So it's actually pretty cool because we get this cross section of understanding molecularly what Sloop is doing. Now, practically speaking, does any of this matter? Not really, because at the end of the day, if something works, we know it works. We figure out how to use it, works studies are great, but they don't really get us to the end goal, which is to look good, feel good be healthy.
But I do appreciate studies because they kind of give us this insight into things that we're using, like sloop and explain like what's actually going on. And for me, at least this helps give me an indication of like long-term, okay, is this something that I really know is worth having, or is it just kind like a short term thing? And I think for, me what this indicates to me is that sloop not only is a good for fat loss, it's a Good for energy, So I'm going to talk about that and what that means, and we're going get into that. So, I thought this was pretty cool. I know it's a little bit different than what I normally do, but I want to break this down, put some slides together on the study,
explain what went down and explain why that would matter for you. Before I do that, check out the Peptide Cheat Sheet. The link is down in the description of every video. And as always, Check out Fully Optimized Health, which is the private group. If you're in that group, you are ahead of the curve when it comes to this stuff, because we were talking about this way before we talked about it publicly, so you kind of find out. about stuff like that before it goes mainstream. So without further ado, I'm going to share my screen and today we're going micrograms, 250 micro grams and 500 micro gram versions.
But we're going to be looking at it as this study exploring how estrogen related receptors can be targeted to combat muscle decline associated with aging and physical inactivity, which is something that we all I think can get on board and agree is probably worth pursuing. So. Let's look at the study and before I forget the studied link will be in the description so you can click on it and go read it for yourself. What I did in this slide deck presentation is just try to condense it out into something that's understandable for you guys because a lot of these things can be pretty complex. the TLDR will be just take SLU at the end of the day.
But basically what they set out to do was evaluate the targeting of these estrogen-related receptors in myoblasts isolated from the skeletal muscle of inactive women by assessing the metabolic and expression changes associated with its activation. So basically we're taking muscle fibers from some of these women that are undergoing a hip arthroplasty for coxarthorosis. Sorry, that's a weird word. And they divided these 20 women into active and inactive groups based on self-reported physical activity.
So they basically had 10 women who said they weren't active, and then 10 that said that they were active. They're going to compare what's going on with their. Basically, they took muscle biopsies during the surgery from the, and they looked at that with a histological and Western body analysis and the primary cultures of myoblast from inactive women were treated with ERR agonist SLUPP332. So of those 10 women that said they were in active that were having the surgery, they took biopsies of their muscle and then they treated those biopsy. They didn't administer it to them, but they're seeing how the sloop interacts with the cultures or the bioptics from these women.
That are very sedentary. They didn't say that ages, but they're obviously elderly and they are undergoing hip surgery. So it looks at how targeting the ERRs, which is what SLU does, could present a promising therapeutic strategy to counteract muscle atrophy in elderly, and sedentary people. Let's look at the challenge with age-related muscle atrophy. And this is kind of what I talked about, but I think this relevant, especially for my audience, depending on your age. So aging obviously involves dramatic structural and metabolic changes in the musculoskeletal system.
This leads to muscle Atrophy, which is basically just the wasting of our muscle. When we don't use it, we lose it. That's regardless of whatever age you are, as we age, it tends to happen more. And this obviously compromises muscle strength and function. So muscle cells play an important role in muscle decline during aging as their content has been suggested to be a strong predictor of muscle fiber size in elderly people. Obviously, elderly have reduced physical activity levels and they are at a significant risk for disability during ageing linked to increased risk of falls
and mortality. If you look at Women, one of the, I don't know where it ranks. I've probably read it somewhere before, but actually falling for women is one the leading causes of death because what it does, they fall, break a bone and then they're sedentary and that just leads into this cascade of age-related decline. So muscle decline is often associated with musculoskeletal pain which promotes a sedentary lifestyle which even further exacerbates muscle tissue depletion. Basically as someone ages they get in pain, they don't exercise, and then this creates this vicious loop to where they start to age really fast.
If you've ever had a grandparent or parent that's been through this, maybe you're going through it yourself, you kind of know what I'm talking about. You can kind like see it happen before your eyes. Let's look at just exercise in general. So exercise promotes numerous physiological adaptations and muscle tissue that collectively preserve its structure and function. Again, if we don't use it, we lose it. Exercise has also been identified as the best strategy to prevent frailty, improve sarcopenic status and physical function in elderly people. Also in regular people too.
I say regular like they're different. They're just a different age than us. We're all people, but muscle regeneration. So resistance exercise has been proposed as a countermeasure to increase the number of satellite cells and reverse muscle atrophy during aging. What's really cool is if you look at studies on resistance training, lifting weights in general, regardless of the age, even regardless the hormone status, to which I would say you should always be using testosterone if you're in your seventies and eighties, if your man or woman, but you can still build muscle at those ages when they take people that are not trained individuals and they train them.
So the molecular mechanisms underlying these adaptations are extremely complex and still partially unexplored, which highlights the need for substantial research to identify potential therapeutic agents. And that's what me and you and all of this in this community are doing for. What they kind of looked at was these key molecular players and muscle metabolism. So we're going to use these as more or less like our KPIs, key performance indicators of what SLU is doing. Let's just look at them first. We have FNDC5.
This is a precursor of the hormone irisin. which releases significant increases in response to exercise influencing the metabolism of several organs and systems. We also have ERR alpha, so this forms a transcriptional complex with PGC1 alpha which promotes the activation of exercise-responsive genes and regulating mitochondrial function. We have CERT1, and this is an NAD plus dependent deacetylase that promotes the increase in myonuclei and muscle fibers, which stimulates muscle repair
processes and induces muscle hypertrophy. So you would probably want more of that, right? Then we have PGC-1 alpha, which is a transcriptional co-activator that plays a central role in regulating cellular energy metabolism by stimulating mitochondrial biogenesis. So we probably want more of that, right? Because we're going to have healthier mitochondria, thus more energy in doing so. Let's look at this ERR alpha because this is really where Shloop comes into play. I promise we'll get to what it's doing in a second, but I want to frame this. ERR alpha appears to be required for mitochondrial biogenesis in adult skeletal muscle and during muscle regeneration, suggesting its role to the regulation
of muscle adaptations in response to physiological and pathological stimuli. So the deletion of the ERr alpha in mouse models significantly impairs mitochondria oxidative capacity, confirming its central role in the regulations of cellular energy metabolism. So if you didn't understand what Sloop did before, hopefully that makes more sense because we need this in order to help improve our mitochondria and help the oxidative capacity of mitochondrias is basically just how well they burn for fuel.
ERR alpha also participates in myoblast differentiation and myotube formation. So in primary myocytes isolated from ERRR alpha-deleted mice, the early transition from proliferating myo blast to fused multi-nucleated myiotubes was inhibited. What does that mean? It becomes harder to have muscle and put on muscle on the frame. So the PGC-1 alpha and ERR alpha transcription axis plays a crucial role in regulating mitochondrial function and significantly contributes to the exercise
capacity of skeletal muscle. What we were basically saying is that these two things are crucial for mitochondria function, and muscle, on our body. Now, this is where SLUPE comes in. So SLUUPE is a pan agonist of ERRs and has recently been synthesized and appears to replicate the muscle responses induced by exercise. What does it do? It promotes mitochondrial biogenesis and function in muscle cells. It also enhances cellular respiration, so it improves cellular restoration in the urine C2C12 muscle cell line.
It also increases oxidative muscle fibers. So administration to mice promoted an increase in oxidatives type 2A skeletal muscle fiber and improves exercise capacity. And this is probably where you will see the biggest bang for your buck, at least from a field standpoint, it enhances endurance and exercise, capacity in animal models. So the activation of ERRs could modulate the expression of key molecules involved in muscle responses to exercise, such as NOx4, FMDC5, CERT1, and PGC1α, which are known to be downregulated during aging.
So remember what we just talked about. Remember these molecules that we were talking about in the body that play a very crucial role in muscles and metabolism. and they down regulate as we age. So if we tap into ERR alpha, can it increase some of these things to help us burn fat, build muscle and live longer? Let's find out. So let's look at this just first from the clinical evaluation. So when they measured them first, they were looking like, okay, active versus inactive, what is the difference between these people so we can actually
see that they're like okay this person's active and this persons active. inactive. So active subjects are less functional limitation than active, active subject. Makes sense. If you report that you exercise, it's probably what you're going to say. They had higher hand grip strength values in the active group. they had significantly reduced pain in that active. Group. That had better hip function in active groups, even though they're still getting hip surgery, they also had a negative correlation between pain and muscle strength. And they have a positive correlation. Muscle strength and hip functions. We know before they are starting, there is a difference in these people.
The reason we want to look at this is because we are going to see what the SLU is doing to the muscle samples from these people to say, OK, the inactive people obviously have very deficient of these molecules in their muscles. So the histological and morphometric analysis showed impaired muscle quality in the active subjects characterized by small fiber diameter compared with the muscles of active subject. You can see there that there was obviously a big difference in active group versus the inactive group they had 49.3 i think that's micrometers and then 19.8
micromeeters in terms of how how small the the fiber diameter of their muscle was excuse me i was lost my place on the screen but so let's look at this so when we look The inactive group had a 67% higher increase in NOx4, which is the main inducer of oxidative stress and a marker of muscle atrophy in sedentary subjects compared to active subjects. So for people that didn't exercise, this NOX4 was 67 percent higher.
CERT1 was 42 percent lower. If the people didn' exercise going into the surgery, CERT1 is 42% lower than in the active people. Hopefully, this is motivation for you to exercise. PGC1 alpha, there was 38% less in the inactive subjects than in active subjects. And then ERR alpha had 42%... The inactives subjects have 42 percent less ERRR alpha in in-active subject compared to active subject. So, they confirmed these results. Obviously, we are dealing with two different sets of muscle type individuals.
What they do, they take a muscle sample out of the surgery from these women and then they treat it in a Petri dish with SLU. So let's see what happened. When they did so, 16.1% reduction in LDH activity, which is a marker of cell damage and treated myoblasts compared to untreated cells. There was a 37.7 reduction and intracellular reactive oxygen species levels in treated Myoblast compared two untreat themselves. There was a 117.4% increase in intracellular glutathione levels treated in treated myoblasts indicating substantial enhancement of cellular antioxidant capacity.
That's pretty cool. And they also had a 26.1% reduction in SA beta-galactivity, which is basically just a marker of cell aging or senescence, a zombie cell, and treated Myoblast compared to untreated cells. So what this means ultimately is that the SLU treatment significantly influenced cellular metabolism by reducing cytotoxicity and cellular senescence associated with aging while enhancing antioxidant capacity within the body. So what happened to the proteins that they treated with SLU?
So they had a decrease in NOx4 which reached levels similar to those in active subjects. phrase what that means. They took people that are inactive, treated a piece of their muscle that they removed during surgery with SLU, and the NOx4 reached levels similar to those of active subjects. Let's look at Cert 1. There was a significant increase in Cert I expression in treated myoblasts reaching levels comparable to that of those in active subject. Again, so these are people who are non-trained, they're sedentary, and they are transforming their muscle with SLU to reach the levels of people that are training.
PGC-1-alpha, significant increase in PG-C1 alpha expression, reaching levels compared to those in active subjects. ERR- alpha, a significant in ERRR-Alpha expression in treated myoblasts, which also reached the same levels as active subject. And there was also a signficant increase FNDC5, reach levels comparable to inactive subjects, so what does this mean? SLUPE treatment promoted upregulation of AKT and BCL-2 and myoblasts from inactive subjects reaching levels comparable to those in active subjects.
So AK-T is a key regulator of cell proliferation and survival. And BC-L2 is an anti-apoptotic protein that prevents cell death. This indicates the inhibition of apoptic pathways in response to ERR activation potentially contributes to muscle preservation. SLUE treatment, promoted abundant myotube formation an expression in cells from inactive subjects comparable to that observed in cell from active subjects. So this suggests ERRs play a crucial role in muscle differentiation and countering atrophy.
We took these inactiv people and treated them with SLU and their muscle fibers reached to the levels of similar elderly women who are active, which was pretty cool. I think if you look at it considering they didn't do anything or at least the muscle wasn't being trained. So obviously this is a small sample size we can't say you know sleep is the greatest thing ever although it's one of the great things ever. This is obviously based on self-reported activity we also need genetic studies and then this needs to be looked at clinically from a human use standpoint.
Just to walk away The ERR activation modulates muscle responses to aging and inactivity. An SLU treatment reduced oxidative stress and cytotoxicity in myoblast. The treatment promoted expressions of key factors that we talked about involved in muscle function and mitochondrial biogenesis. And targeting ERR receptors could represent a promising approach to preserve muscle function in the elderly and individuals with pathological conditions
characterized by muscle atrophy. And this could potentially complement exercise interventions, especially for those unable to exercise due to physical limitations. or medical conditions, or it just enhances the exercise that you're doing, that much better, helps with muscle growth, muscle preservation, so I don't know, does SLU go really well with a GLP-1 because it helps preserve muscle? food for thought. So anyway, that is it for the slides. And that, is a review of the new study on SLU. Obviously I think there's going to be more stuff like this to come, assuming that people want to invest money in studying SL U.
But for me, when I look at those things and knowing what I know about the human body, to me this is the signal that we are on the right path with SLUs. Again, studies by no means, they're not the end all be all, but they can give us a good indicator of where we're going. Looking at things like these are pretty cool. So I know it's a little bit more technical. I Know this is a bit outside the wheelhouse that I do, but I'd love to hear your feedback on this. It's pretty cool. And for me, like I said again as a reminder, is that Sloop is right over the target. So, I love hearing your feed back on that one.
If you have experience with Sloope using it, drop that in the comments. Its really cool for other people to see other talk about it. Not so much myself because I can talk anything and people are like, oh yeah, you just sell SOU or whatever. But I used SLU long before I ever sold it, so it is a really good product. I love it. We'll continue to use it and we will likely see, again, assuming people invest money into it more and more data come out about the benefits of it so thank you guys so much from the bottom of my heart.
or you get on the email list and buy the products, I can't express how much gratitude I have for you because it is abundant and far reaching to infinity. So thank you guys so much and I will talk to you in the next one. Peace.
