How to Inhibit Myostatin for Muscle Growth and Longer Life

Myostatin is a hormone that regulates muscle growth negatively, so that higher myostatin means less muscle. Weightlifting decreases the level of myostatin, which is to be expected, since weightlifting promotes muscle growth.

The level of myostatin rises with age, and this is thought to be one of the mechanisms that causes the loss of muscle as people get older, a well-documented phenomenon in which both men and women lose muscle beginning in their fourth decade (after age 30). The average person loses a full 50% of his muscle mass by age 80, a condition known as sarcopenia.

Deletion of a myostatin gene in mice so that they are heterozygous for it (+/-) results in increased lifespan. Centenarians were found to have an increased rate of myostatin gene variant, such that someone who possesses this variant has about a 3.5 times higher likelihood of reaching the age of 100 than someone without it.(1)

Longtime readers may recognize a paradox here, namely that growth and longevity are inversely related. The bigger and faster that an organism grows, the faster it ages and the shorter the lifespan, in general.

But myostatin appears to both increase growth — muscle growth — and longevity.

How to inhibit myostatin

There are several ways to inhibit myostatin to promote muscle growth. Please keep in mind that this is important not just for those of us who want to boost the results of weight lifting. It’s very important for older people, who lose muscle and become frail and become dependent on assistance to perform tasks of everyday life, and who in a worst-case scenario end up in a nursing home for that reason.

Testosterone

The male hormone testosterone decreases with age, and also is decreasing over time. Check out the chart below, which shows three different cohorts of men, by age. Testosterone is declining, rapidly. This trend spells disaster for older men in terms of their ability to retain muscle and have normal life activities. In younger men, this may explain some of the epidemic of obesity, man boobs, and generally effeminate demeanor.

testosterone secular decline

In old mice, testosterone treatment abolished muscle loss, besides suppressing oxidative stress. It does this through multiple muscle pathways, one of which is the inhibition of myostatin.(2)

We already know that testosterone treatment of men greatly increases muscle mass. Now we have a better idea why.

If you need more muscle, have symptoms of low energy and/or libido, or depression, get your T level checked. To raise testosterone, you can consider, in order of ease

  1. Changing your diet to eliminate sugar and most refined carbohydrates, and increase fat content
  2. Lifting weights, if you don’t do so already
  3. An aromatase inhibitor, like DIM or berberine
  4. Testosterone replacement therapy

Epicatechin

Epicatechin is a polyphenol found in green tea and chocolate. Giving it to old mice decreases myostatin by 18% and increases follistatin, a myostatin inhibitor, by 56%. In humans, epicatechin increased grip strength by 7% in only 7 days, and the follistatin/myostatin ratio increased 49%.(3)

The human dose used was 50 mg/d, in two divided doses.

You can get large doses of epicatechin in chocolate and tea (4), which varies quite a bit depending on quality and quantity. Dark chocolate and cocoa powder appear to have the most. If you drank several cups of cocoa and tea daily,  you could get quite a bit of epicatechin. (Note: “cocoa” means made yourself with real, 100% cocoa powder, not that processed, sugared so-called hot chocolate that comes in a little envelope.)

Leucine and creatine

Leucine, one of the branched-chain amino acids, as well as creatine, decrease expression of myostatin-related genes.(5)

Creatine can be supplemented at 5 grams a day. Leucine can be supplemented at 2 to 3 grams up to 3 times a day.

Follistatin

Follistatin is the hormone that is an antagonist of myostatin, and it may be of use in the treatment of muscle atrophy.(6)

In humans, the use of follistatin, isolated from egg yolks, increased muscle mass in recreational bodybuilders. With 10 grams a day and after 12 weeks of resistance training, they gained 1.7 kg (3.75 lbs) of lean mass, while the placebo group had no significant gains.(7)

The follistatin product used in this study was Myo-X, and it’s available at Amazon, and presumably elsewhere. It reduces myostatin by an average 46% in 12 to 18 hours, after which myostatin increases, necessitating daily dosing.

Synergy

You could of course combine all of these methods of decreasing myostatin; whether they might be synergistic isn’t known.

Decreasing myostatin looks like a much healthier way of growing muscle than using drugs for that purpose. Since myostatin increases in aging, decreasing it may mean reversing aging. In fact, myostatin is homologous with the hormone GDF11, the increase of which may promote aging.(8)

For lots more on the relation between muscle and health, check out my book, Muscle Up.

PS: Check out my Supplements Buying Guide for Men.

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Leave a Comment:

31 comments
Simon says June 26, 2016

You know what, I’m sure you could make a killing selling anti-ageing supplements that rolled all these things into a single, daily dose.

I imagine there are nightmarish hoops to jump through however for such things.

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Kindke says June 26, 2016

Does the MYO-X really work, alot of reviews on amazon saying it did nothing

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Antonio says June 26, 2016

And maybe sulforaphane (with myrosinase)
https://goo.gl/rcEkdf

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charles grashow says June 26, 2016

Here’s a study that used Ensure!!

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3947792/
Acute effects of an oral supplement of (−)-epicatechin on postprandial fat and carbohydrate metabolism in normal and overweight subjects

Results show that EPI increased postprandial lipid catabolism, as evidenced by a significant decrease in the respiratory quotient, which implies an increase in fat oxidation. The effect was associated with significantly lower postprandial plasma glucose and triglycerides concentrations. The effects were more prominent in overweight subjects.

In conclusion, EPI modulates postprandial metabolism by enhancing lipid oxidation accompanied by reductions in glycemia and triglyceridemia.

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    P. D. Mangan says June 26, 2016

    Ensure, my favorite! Wait, there’s epicatechin in Ensure?

    Reply
Benjamin Blehm says June 26, 2016

I work at a company that develops diagnostics and it turns out, many major chemical companies sell products that are not what they claim…I find that extremely worrisome, and wondered if you had specific recommendations/knowledge of a company that verifies claims of the components in a supplement. I would be more than willing to pay a bit extra to know I was getting was I was paying for. Great article though.

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    P. D. Mangan says June 27, 2016

    Benjamin – in my experience, some companies do have 3rd party certification, others don’t.

    Reply
    Brett says September 10, 2016

    ConsumerLab.com

    Reply
Joseph Moroco says June 28, 2016

We have chickens and a lot of eggs. On recommendation of PHD, I eat three yolks for choline most days. I would guess, however, that would not give one sufficient follistatin?

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    P. D. Mangan says June 28, 2016

    My guess is that’s correct. Follistatin comes from fertile eggs.

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Joshua says June 30, 2016

The mention of berberine as an aromatase inhibitor is interesting. Berberine definitely seems like it has potential to be a health-giving supplement, but I’m not sure it’s compatible with the goal of inhibiting myostatin to ramp up hypertrophy. It seems that it’s actually quite similar to metformin. I did a bit of research and found that Examine.com says that berberine will increase AMPK. From there, it says, “The increase in AMPK will inherently suppress muscle hypertrophy in muscle cells.” Assuming that the science here is correct, it seems that berberine might run counter — at least on some pathways — to the goal of maintaining/increasing muscle mass.

I’m unsure about the follistatin as well. Myostatin inhibitors seem to be in their infancy, at least on a commercial scale. I guess for now I’ll just stick to creatine, protein, dark chocolate (esp. since it’s delicious!), and of course, good old fashioned liftin’ weights. I’m glad you addressed this topic….I’m keen to learn more about myostatin inhibition.

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bigmyc says July 5, 2016

The possible problem with cocoa powder (cacao powder) is the incidence of mycotoxin in the powders or really, any chocolate. Now, hopefully, the impact of such inherent poison is minimal or even, negligible but it is something to be mindful of since I would imagine the effects would manifest themselves on a spectrum for different people like say, gluten intolerance…I also would hope that the positive impact of the polyphenols like ECGC, beneficial fats and the like might overcome or at least, mitigate any deleterious results of the mycotoxin.

Any opinions on the impact and implications of mold by-products in such a beneficial food item?

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    P. D. Mangan says July 5, 2016

    I think, as you say, that any impact would be negligible. However, mycotoxins are active at very low doses – that being said, I don’t know what the mycotoxin content of cocoa is. BTW, Dave Asprey of Bulletproof Coffee fame makes a lot of claims about mycotoxins and how they fog your brain, and I categorically don’t believe that.

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      bigmyc says July 5, 2016

      I think that I have come across some of Asprey’s opinions on that as well. He seems to take a very serious stance regarding this. I also remember that it slightly “scared me,” as well. Now, using his logic, I can see how mold toxin could and does present a problem with cocoa but I wonder to what extent, essentially. Also, how is it that you use the word, “categorically” in refute of his claims of brain fog? I would hope to agree with you for obvious reasons but in the spirit of scientific reasoning, what cause do you have for eschewing his claims?

      Reply
        P. D. Mangan says July 5, 2016

        That’s a good question. probably because he doesn’t present any evidence that mycotoxins affect brain function or cognition, at least any evidence that I’ve seen. Maybe “categorically” is too strong a word and if he presented evidence I’d be open to the possibility. There must be trace mycotoxins in all kinds of plant foods, not just coffee or cocoa, including grains and anything made with them – stuff that people ingest in huge quantities daily. If mycotoxins had such a large impact on cognition, I’m thinking we would know more about it beyond Asprey’s assertion. He makes money from it – “Upgraded Coffee”.

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          bigmyc says July 5, 2016

          Not all endeavors, as you are aware, need be diminished simply because there is a business model behind it. Mark Sisson’s empire comes to mind but I am always aware of that angle. What I feel is the most compelling logic that you mentioned is about the ubiquity of other foods being prone to mycotoxin such as peanuts or grains. Both are foods that are consumed in quantity. You would think that there would be more to know about mold and fungus by products in our foods by now because of these items alone.

          What keys me into this subject is that I have been struggling with a candida overgrowth and before I recognized it, I would be forced to slug through lazy, murky days of cloudy thinking, among other detriments. Now that I’m attacking the stuff en mass, I don’t experience much of that on a weekly basis but at times, the herxheimer reactions (die off of the fungus) is so pronounced, I will experience immediate symptoms including, but not limited to, patchy itching, blurred vision, headache and yes, brain fog.

          So, I can tell you first hand that brain fog is indeed a reality for mycotoxin sufferers. I also have noticed mild bouts of that same phenomenon when I’ve ingested chocolate though I haven’t singled out other foods that I had eaten previously such as turmeric, garlic, oregano, etc, which can be powerful anti-fungals.

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          P. D. Mangan says July 5, 2016

          Well, you’re right about the money angle, but it does make one suspicious. As for brain fog and Candida, I would guess that you’re getting much larger amounts in your system, not to mention that you’re not getting just mycotoxins, but the remnants of the whole organism. Similar to lipopolysaccharides from gut bacteria.

          Reply
Robert says January 26, 2017

Very nice article ! Thanks !

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JT Smith says February 3, 2017

So at this point, we know what causes muscular aging.

Brain aging can be inhibited by l-theanine.

What other systems do we need to fix? Bones? Someone should make a detailed chart of system that age in the body and what anti-aging methods we have for those systems.

If you blame evolution for these things, it seems like each system in the body has independently developed its own aging mechanism. Taking a look at each system individually may be the secret to real longevity.

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David Kelderman says March 27, 2017

Ir you take myo-x and miss a day say after 18 hrs dies myostatin fo back to u ta normal or soes it increase beyond the amount you ioriginally had
Dows it also affect igh-1

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Phil says April 4, 2017

I’ve been using Myo-X for around 2 years now so I feel like I have pretty significant experience with it. A little background on me; for nearly a decade I’ve experimented and researched literally hundreds of fitness methods for gaining explosive lean muscle mass and growth. Methods ranging from types of workouts, to when to workout, to workout duration, rest vs. work, concentric vs. eccentric, high rep vs. low rep, time under tension vs. explosive power, low intensity steady state cardio vs. H.I.T, fasting vs. 5-6 small meals per day to the chemical methods including everything from various forms of Creatine, to HMB, to BetaTOR, to dozens of various OTC Test Boosters, to “bug juice”, and multitudes of protein variants to even less than legal drugs such as steroids and HGH…the list goes on and on. But, if I could tell you the top 3 things that stood out to me in that long list of methods, outside of training and dedication, that would be easy. #1 would definitely be a cocktail of steroids and HGH, bar none. But, we all know the health problems and issues associated with that mix, so I won’t go there or recommend it. You’ll look and feel like an absolute power house, true, bit you might be playing a dangerous game with your life and longevity. I experimented with it, but no thanks. #2 however, would honestly be Myo-X. Shocked? Me too, because when I first started taking it O thought “no way” but after nearly 2 years, I’m a believer. When I first started using it and training, within 2-3 months I had steroid using friends asking me if I was back on the juice, and that’s when I truly felt like this product was doing something. One nice thing about it, I feel as though it lowered my myostatin overall and in general, even when I was off of it for 2-3 months I was able to more easily maintain my lean hard muscle mass and physique, something that I couldn’t even do on the juice. Honestly, it’s amazing. And its not just Myo-X, that’s just the only real concentrated product available right now, it’s about lowering myostatin in general. Daily I consume 3 fertile eggs and about 4 blocks of Lindt’s 90% Dark Chocolate on top of my Myo-X, just to help stack the effect. If there were any other true myostatin blocking supplement, I’d advocate for that too, but right now the only decent one I’ve found is Myo-X, so it’s my current go-to. But honestly, I hope there’s more research into this supplement, because there’s definitely something there and out of everything I’ve researched and tried, its the only supplement that I had very noticeable results with. And, my #3 supplement would be any form of Creatine, just choose what feels best for you (as in your stomach and bloating) and use about 5-10 grams per day after your 20 gram loading phase. Then, just eat right with high protein’s and good fat’s in the mix and you WILL see results. Oh, and avoid alcohol during any cut, especially beer. Hope this helps.

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    Keaton says May 22, 2017

    You had no issues after cutting Myo-X for those 2-3 months!

    Reply
Keaton burcheri says May 22, 2017

I have heard of cases in which it can be harmful or resulting in “man boobs” when the body’s testosterone levels are continually high for long periods of time then followed by very low levels.
Can there be any affect on the body when myostatin levels are low due to supplementation followed by high levels of myostatin after supplements are extinguished?

I’m 20 years old and wanna gain more muscle mass provided I can avoid issues.
any issues noted pertaining to a post supplemental period?

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    P. D. Mangan says May 23, 2017

    Hi Keaton – I doubt it. Man boobs are caused by estrogens, not testosterone or myostatin. Testosterone itself, whether high or low has no effect, although fluctutations in T are usually accompanied by changes in estrogens (estradiol and estrone). Myostatin is another hormone altogether and has no effect on man boobs one way or another.

    Reply
      Keaton says June 1, 2017

      Thank you

      Reply
Graham says July 4, 2017

Inhibiting Myostatin looks like a really interesting way to promote muscle growth. I’m sure that ideally, most of us would like to put on significant amounts of muscle, but don’t want to take on the health risks that come with the use of anabolic steroids.

Is there any reason why you didn’t include something like Myo-X in your recommended supplements book PD? I haven’t tried it because it seems quite expensive ($40 for a 30 day supply on Amazon). But I probably will at some point.

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    P. D. Mangan says July 4, 2017

    Hi Graham – I probably should have put Myo-X in my book, but I haven’t used it myself. I’d like to see more research on it, such as whether it extends rodent lifespan or the extent to which it can increase muscle growth in humans.

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Duane says September 27, 2017

Always had a small waist until I started taking 20 grams a day of creatine….Within a month of starting that crap my pants size went from 34 to 38….The worst part of it was it took a while for me to correlate it to the creatine…..The belly mostly disappeared with stopping creatine….

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Jose Pando says October 22, 2017

Iam trying to locate some were to purchase Myo x but cannot locate a distributor would appreciate your attention

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Jonathan says November 1, 2017

Interesting research. If myostatin is bad for muscle growth AND bad for longevity, I wonder why we evolved to have it?

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    P. D. Mangan says November 1, 2017

    That’s a good question. However, it’s evolutionarily conserved, i.e. other species, at least mammals, also have it, so for the answer we’d need to look at biology as a whole, not merely the human race.

    Reply
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