If you’re looking into Myostatin inhibitors then I’m guessing you already know a little bit about Myostatin and what it does in your body and to your muscles.
In case you don’t know and you bounced onto this page, and want to know more, I’ll give you a brief primer on it before getting into the meat of the subject.
What is Myostatin?
Myostatin is a natural protein active in multiple species of animal, including us humans. It’s a negative regulator of muscle growth and can regulate the number and size of muscle fibers.
It does this to keep muscle growth in check. Most bio-chemical processes in the body have countering processes which form cycles to ensure there are no runaway reactions.
In myostatin’s case, it prevents runaway anabolic muscle hypertrophy.
Obviously, anyone looking to build muscle would be interested in a safe way to inhibit the myostatin protein, even just a little, to allow for greater muscle growth gains.
Even more advantageous to some people are the potential medical applications for treating (some) muscle-wasting diseases or conditions where retaining muscle mass is problematic.
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What is Myostatin Inhibition?
Myostatin obviously has a necessary function with respect to muscle growth and regulation thereof.
What’s particularly interesting is a core finding from scientific studies involving “knock-out mice”, where laboratory mice essentially have their myostatin encoding gene switched off at the embryonic stage, and studies involving myostatin-inhibited adult mice.
Myostatin inhibition in the case of the adult mice involves injection of natural or synthetic myostatin inhibitors such as Follistatin.
The different methods show there are two specific periods of muscle growth development that myostatin regulates heavily.
- Muscle Fiber Number during development in the womb (embryogenesis)
- Muscle Fiber Size during adult muscle growth
Muscle Fiber Number has long been known to be set at the early stages of pre and post-natal development. In a very real sense, you are born with a large factor of your muscular potential already dialled in.
The contractile force generation of those fibers on the other hand is open for improvement. In other words, it’s what you do with it that counts.
Muscle Fiber Size, however, is extremely variable and gains in muscle hypertrophy relative to your “starting” muscle mass are again a product of variables you can control – such as resistance training, diet, rest – and some variables that you can’t control, i.e. your genetics.
So, scientists have known how to inhibit myostatin in animal studies for a long time now and they’ve experimented with different ways of doing it, and at different stages in the life-cycle.
But before you run off and find some Follistatin – or other Myostatin inhibitor – to inject yourself with, there are some things you should know.
What Are the Effects of Myostatin Inhibition on Muscle Size?
Glad you asked, because that’s one of the problems with oversimplifying this issue. Knocking out the myostatin gene at birth or inhibiting the protein it encodes later in life appears to positively affect muscle growth, in mice at least.
There has also been cases of human children who have been born with abnormally low myostatin activity that have highly developed muscle tissue. Basically, as toddlers, they look like miniature bodybuilders.
That’s because myostatin inhibits muscle protein synthesis. Muscle protein synthesis is the process of building proteins which will ultimately make up the protein content of muscle fibers.
In fact, some research implies that myostatin actively triggers muscle atrophy (muscle wasting) when growth triggers are abnormally reduced such as during periods of extended inactivity like hospital bed rest, and chronic muscle disuse atrophy.
Age-related muscle loss, aka Sarcopenia, might also be attributed to myostatin activity.
The full cycle has been shown in studies by injecting mice with myostatin, seeing them enter advanced muscle wastage, and then reversing it by administering one of the myostatin inhibitors (e.g. follistatin or myostatin-propeptide).
However, yet more research indicates that myostatin might simply be an anti-hypertrophy agent rather than the main muscle atrophy trigger. The difference is discrete but likely important.
Needless to say, we are still quiet a way from understanding the intricacies of myostatin’s effects on muscle hypertrophy.
What About Muscle Strength and Function?
Studies investigating the effects of myostatin inhibition have shown that there is most likely a resultant increase in muscle mass, and probably through multiple biological pathways.
The hypertrophic pathway triggered by resistance training is one of them, and a very important one when deciding whether or not to try taking a commercial or lab grade myostatin inhibitor (keep reading and I’ll get to that part soon).
Other hypertrophic pathways include creatine, leucine and HMB signalling (which I’ll also get to later, so stay on track).
However, muscular development is not solely defined by size, but also strength and function. Some research highlights this in the context of myostatin by showing that knockout mice have significantly increased muscle mass but no strength increase compared to wild mice.
Not only were they no stronger than their wild, less massive counterparts, but when specific force was measured (i.e. strength as a function of muscle size) they were weaker.
More recent research investigating myostatin inhibition following a stroke (in mice) contradicts the above knockout study and shows an increase in muscle mass and strength.
However, recovery from the side effects of a stroke (cerebral ischemia) can’t be compared with the study with wild mice and knockout mice, and neither can there be any solid conclusions drawn.
Perhaps a more enlightening piece of scientific literature is found in the Gerontology mini-review of Myostatin and Sarcopenia (age-related muscle wastage).
By pooling studies on the subject, that report (which is also fairly recent, from 2014) tells us that more studies have found myostatin inhibition to help with muscle function/strength improvements in addition to the increases in mass.
It appears to me that if the muscle weakness is a function of muscle mass wastage then there is a correlation between myostatin inhibition and improvements in muscle strength, largely because of the rehabilitation of muscle tissue.
In contrast, it appears as though naturally healthy muscle mass growth maybe increased via myostatin inhibition, but its strength potential might not.
You Mentioned Resistance Training and Myostatin Inhibition?
Resistance training triggers muscle hypertrophy, that much is obvious, but it does so via a few bio-chemical pathways.
These findings make me think myostatin expression hasn’t necessarily evolved to be a negative growth factor to all types of muscle hypertrophy pathways. If it had, then it would make no sense that resistance training inhibits myostatin.
What seems logical to me is that myostatin functions as a limiter to natural, hormone triggered muscle growth, particularly at the two stages in life when we develop our muscle fiber number (as embryos) and when we grow our base adult muscle mass, often referred to as “filling out” as teenagers.
Of course, it’s possible, even probable, that myostatin steps in again if we reach a certain muscle mass potential though bodybuilding and resistance training.
Male and female bodybuilders can get huge, but the elite professionals of the heaviest weight class generally stay within a few pounds of one another at their peak.
You Also Talked about Supplements and Myostatin Inhibition…
Yes I did. Technically there’s four supplements I’ll talk about here, and although there will undoubtedly be more to come in the future, these are of particular relevance to this discussion.
MYO-X from MHP (Maximum Human Performance)
You can’t talk about myostatin inhibitors and not mention MYO-X. This was a product branded by MHP, the New Jersey based sports and bodybuilding ergogenic supplement company.
It’s been discontinued now, but MYO-X is probably the bodybuilding world’s most well known patented myostatin inhibitor.
Scientific studies on the stuff knocked out some pretty decent figures too. The follistatin-rich egg yolk extract called MYO-T12 that the product contained demonstrated somewhere around 50% reduction in myostatin levels.
That follistatin extract was from fertilized eggs. Quite a number of years ago now, guys looking to get jacked used to eat raw fertilized eggs to get a dose of follistatin. MHP just made the process less disgusting.
The issue with MYO-X was that it just didn’t seem to translate to more muscle in real-world observational studies.
Why is that?
Well, that’s best answered by talking about the other three supplements, I mentioned earlier in this article.
Creatine, Leucine and HMB
Decades of supplement research hasn’t produced anything much more impressive for muscle growth than creatine – an organic nitrogenous acid that we produce in our bodies; and leucine, the chief branched chain amino acid (BCAA) that a huge portion of our muscle mass is literally built from, and that we consume in our diets daily.
Together, they trigger much of the anabolic processes that lead to muscle hypertrophy. One of the pathways is, you’ve guessed it, myostatin inhibition.
In one study, all 3 of these supplements featured. Leucine and beta-hydroxymethylbutyrate (HMB) essentially reversed the 30% muscle fiber wastage that myostatin-treated myotubes exhibited.
Creatine compensated for the myostatin induced muscle fiber loss and even boosted the growth of the control fibers which hadn’t even been touched.
This nice little study actually highlights the already well documented body of evidence that’s led many scientists and experts to believe creatine is anabolic while Leucine and HMB are anti-catabolic.
The study concludes that further tests are needed to see whether creatine, leucine and HMB are synergistic with respect to myostatin inhibition (and other growth pathways) or not.
Back to MYO-X…these fairly common supplements: creatine, leucine and HMB are a large part of the reason Myo-X never really worked out.
Most people who take resistance training seriously probably already take 2 if not all 3 of those supplements. Myo-X’s follistatin probably can’t have an additive effect because they are already reducing the body’s myostatin levels.
Coupled with the myostatin inhibition that resistance training itself elicits, there may be no room for another inhibitor to work.
It’s not well elucidated in the research I’ve found but there is likely a feedback loop that prevents too much myostatin inhibition to occur, whether its through receptor saturation or some rate-limiting step in the reaction chain that we are not fully aware of yet.
Whatever the reason, one thing is clear: there are enough natural and common ways to inhibit myostatin without the need to buy expensive supplements that won’t really work anyway.
Philosophy and The Future of Myostatin Inhibitors
We probably haven’t seen the last of the dedicated, patented, even synthetic inhibitor products.
Physical enhancement is big business and people are always looking for shortcuts.
While the research into various drugs has its advantages for people suffering from health conditions in which myostatin over-expression is a problem, it might prove to be fruitless for bodybuilders and athletes.
An interesting finding in some of the research is that certain myostatin inhibitors might help with muscle growth, but strength and performance are possibly weakened, relative to size.
The other thing is that we don’t really need to take more substances. We appear to have all we need in the form of creatine, leucine, HMB in addition to resistance training itself. That said, we also can’t rule out the possibility that some new scientific research somewhere will lead to better/different technology.
Training with heavy weight likely provides a feedback stimulus that inhibits myostatin, partially to allow for functional muscle growth processes to kick in. If this didn’t happen, we might go back to the gym time and again with minimal gains to show for it.
I’ll leave you with my final thoughts on the matter.
If you’re training then your body is making all kinds of metabolic and neurological adaptations after each workout, in order to prepare you for the next. It makes perfect sense that this type of adaptive process can inhibit a portion of the negative growth factors in your body.
With that in mind, it makes perfect sense that myostatin expression is increased at certain times to prevent unnecessary/non-functional muscle mass growth, for without it being “used” it would merely burden the untrained cardio-vascular system.
The more I research and learn about the human body (there is, it seems, too much information for one lifetime), the more I see it all come down to balance.
For every anabolic reaction, there is a catabolic counterpart. You can tip the scales in your favour by eating well, training efficiently and sleeping a lot. You can even do it – at least in the short term – by tricking your body with steroids and performance enhancers.
In the case of myostatin inhibition, we appear able to get levels down to about half that of a sedentary person by lifting weights and taking creatine and leucine. Beyond that, it appears difficult to force more change.
That’s probably a good thing. When your body tells you something, you should definitely listen. In this case, it’s saying “don’t try and fully suppress myostatin expression, because it can’t be done anyway.”
Besides, if it could be done, I’m not sure you’d like the results. We’re going for aesthetic physique here, not ooh look at that freak.