What is Follistatin 344 and Does it Build Muscle?

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Follistatin is fascinating protein that can increase muscle mass beyond natural potential by suppressing myostatin. Scientists first identified follistatin while examining porcine (re: pig) follicular fluid in the ovaries. [1]

Follistatin is naturally found in the skeletal muscle of almost all mammals with advanced or developed characteristics, such as humans, rodents, and cows. Follistatin is high in the non-essential amino acid cystine but unlike most proteins discussed in the fitness world, follistatin has carbohydrates attached to it. [2]

Follistatin, specifically Follistatin 344 (FS344), quickly gained popularity in the bodybuilding community as a potential supplement to rapidly increase lean tissue mass. Another protein, follistatin-related gene (FLRG) acts on similar pathways as FS344 regarding its muscle building properties. Increased lean tissue mass could give a bodybuilder an advantage in a competitive setting and be the differentiating factor between first and second place.

Follistatin and Muscle Growth

Follistatin VialFollistatin works by binding to and inhibiting transforming growth factor-β (TGF-β) peptides such as myostatin which is responsible for regulating and limiting muscle growth. [3] It’s also worth pointing out that myostatin may have a regulatory role in skeletal muscle fibrosis; too much myostatin can impair tissue function and cause chronic disease in vital organs, tissues, and bone marrow. [4] [5]

In additional to suppressing the degenerative properties of myostatin, follistatin also suppresses the pituitary gland synthesis and secretion of follicle-stimulating hormone (FSH). [1] High FSH levels in men may indicate that testicles are not functioning correctly; this condition limits muscle growth, recovery, and normal hormonal function. [6] However, FSH levels that are too low can also negatively impact health and reproductive capabilities.

Whereas some myostatin inhibitors like Trichostatin A (TSA) require daily administration, increased levels of FS344 were observed up to 15 months after initial injection. [7][3] The lack of need for daily administration makes follistatin an attractive alternative for suppressing myostatin.

The recent increase in attention in the science community on follistatin and other myostatin inhibitors is primarily due to the desire to find an alternative means to treat muscle disorders; the most popular current option is androgen steroids which pose a number of side-effects and long-term health risks. At this point you might be wondering why follistatin use isn’t more widespread in bodybuilders and other athletes. In the next section we will examine the current research on follistatin and whether it builds muscle mass.

Does Follistatin Build Muscle?

In short, follistatin does build muscle but not necessarily in humans. A number of studies support the muscle-building and anti-degenerative effects follistatin in rodents. Unfortunately there is no formal research examining follistatin usage in human subjects but a quick Google search will yield countless amateur follistatin logs on bodybuilding and fitness forums.

When scientists bred a mouse producing no myostatin and extra follistatin it had 117% larger muscle fibers and 73% more total muscle fibers compared to the mice in the control group. [8] This study demonstrates that follistatin positively impacts muscle growth in ways beyond simply suppressing myostatin. Mice with suppressed myostatin had twice the muscle mass but mice with the follistatin transgene and suppressed myostatin had four times as much muscle mass compared to the control group. [7]

Administering FS344 via a small virus (re: adeno-associated virus/AAV) can increase muscle size and strength in animal species ranging from mice to monkeys with no significant adverse effects on organs, reproductive capabilities, serum estradiol (re: primary female sex hormone), luteinizing hormone (LH), and FSH levels.[1] [3] When scientists administered follistatin in mice with spinal muscular atrophy, the mice experienced increased muscle mass, improved motor function, and a 30% longer lifespan compared to mice in the control group. [2]

Not only do increased follistatin levels correlate to increased muscle mass, but a lack of the follistatin protein at birth directly correlates to less muscle mass. [7] Less muscle mass at birth can negatively impact bone, organ, and tissue development as well as normal hormonal function.

Bodybuilder Using Follistatin

Human-grade follistatin is extremely expensive; costing more than $4,500 for just 1 milligram.

Human Grade Follistatin – the Bad News

Human-grade follistatin is extremely expensive; costing more than $4,500 for just 1 milligram. [9] Even the websites selling bulk follistatin insist it only be used for research and not used in humans. However, this doesn’t stop bodybuilders from experimenting with this product; amateur logs online typically dose FS344 at one injection of 100 micrograms (mcg) per day for anywhere from 10 to 30 days.

Some users even experimented with 200+ mcg but the effects didn’t become more pronounced. In fact, most users found the product did nothing at all. A handful of users claimed injections of FS344 to have miraculous effects on mass gain but if you examine their logs, FS344 appears to increase their appetite; some users increasing their caloric intake from 4000 to more than 6000 calories.

Any time you dramatically increase your caloric intake above your daily caloric requirement, you’re going to gain weight. The users logging FS344 while undergoing a fat loss phase found that it didn’t help to maximize fat loss or preserve muscle mass any more effectively than without using FS344. It’s also worth noting that all of these FS344 logs were on pro-anabolic-androgenic steroids (AAS) with nearly every user running FS344 alongside numerous other pro-hormones and AAS’s.

In conclusion, follistatin is a protein that can play a powerful role in reversing muscle loss and building new muscle mass, but given the cost and lack of research in human subjects, it’s not recommended for the average or even the advanced athlete.

References

1) Rodino-Klapac, Louise R. et al. “Inhibition of Myostatin with emphasis on Follistatin as a Therapy for Muscle Disease.” Muscle & nerve 39.3 (2009): 283–296. PMC.
2) Rose, Ferrill F. et al. “Delivery of Recombinant Follistatin Lessens Disease Severity in a Mouse Model of Spinal Muscular Atrophy.” Human Molecular Genetics 18.6 (2009): 997–1005. PMC.
3) Kota, Janaiah et al. “Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates.” Science translational medicine 1.6 (2009): 6ra15. PMC.
4) Li, Zhao Bo, Helen D. Kollias, and Kathryn R. Wagner. “Myostatin Directly Regulates Skeletal Muscle Fibrosis.” The Journal of Biological Chemistry 283.28 (2008): 19371–19378. PMC.
5) Mann, Christopher J., et al. “Aberrant Repair and Fibrosis Development in Skeletal Muscle.” Skeletal Muscle Journal. N.p., 4 May 2011.
6) Storck, Susan. “Follicle-stimulating Hormone (FSH) Blood Test.” MedlinePlus Medical Encyclopedia. National Library of Medicine – National Institutes of Health, 30 Sept. 2013.
7) Haidet, Amanda M., et al. “Long-term Enhancement of Skeletal Muscle Mass and Strength by Single Gene Administration of Myostatin Inhibitors.” Proceedings of the National Academy of Sciences. N.p., 5 Feb. 2008.
8) Zagorski, Nick. “‘Mighty Mice’ Made Mightier.” EurekAlert!. Johns Hopkins Medicine, 28 Aug. 2007. Web. <http://www.eurekalert.org/pub_releases/2007-08/jhmi-mm082407.php>.
9) “Follistatin, Human Recombinant.” BioVision Inc. N.p., 2015.

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Name: Nick Ludlow

Bio: When it comes to fitness I enjoy reading about historic weight lifters, non-conventional weightlifting approaches, nutritional protocols, and the science behind supplements.