Follistatin 344 increased muscle mass and strength in every species in which it was tested: in mice, in monkeys and in people with muscle diseases. Mice carrying an extra follistatin gene had muscles several times larger than ordinary animals. In patients with Becker muscular dystrophy who received the follistatin 344 gene into the thigh muscles, the 6-minute walk distance improved in four of six people, by as much as 125 metres. Below we go through these studies one by one, from the laboratory to the first patients.
What is follistatin 344?
Follistatin is a protein the body makes on its own. It binds myostatin, the signal that holds back muscle growth. Once follistatin captures myostatin, the muscle no longer receives the "enough" message and can keep growing.
The number 344 marks one of the forms of follistatin made from the same gene. Researchers in Ohio chose it on purpose, because it circulates in the blood and attaches only weakly to other cells. It therefore acts mainly on skeletal muscle. We wrote more about myostatin and its blockers in the guide on what follistatin 344 and ACE-031 are.
What did the first studies in mice show?
The first evidence came from the team of Se-Jin Lee at Johns Hopkins University. In 2001 the researchers bred mice whose muscles produced a lot of follistatin. The animals had clearly larger muscle mass, comparable to mice without the myostatin gene.
In 2007 the same researcher combined both approaches. Mice without myostatin that also produced extra follistatin had about four times more muscle than ordinary mice. The result showed that follistatin binds more than myostatin alone and also acts on other brakes on muscle growth.
| Study | Model | Result |
|---|---|---|
| Lee and McPherron, 2001 | mice with high follistatin in muscle | muscle mass like mice without myostatin |
| Lee, 2007 | mice without myostatin with extra follistatin | about 4 times more muscle than ordinary mice |
| Haidet et al., 2008 | single gene dose, healthy and dystrophic mice | greater muscle mass and strength for over 2 years |
| Rose et al., 2009 | ready-made follistatin protein, mice with muscle wasting | greater mass of several muscle groups, life 30 percent longer |
Does follistatin also work in older animals?
Yes, and for a long time. In a 2008 study the Ohio team gave mice the follistatin gene only once. Muscle mass and strength kept rising for more than two years, practically for the rest of the animals' lives. The effect appeared in both healthy mice and mice with muscular dystrophy.
The researchers stressed that it also worked in animals that received the gene at an older age. This matters, because other ways of blocking myostatin worked differently depending on the age at which treatment began. The muscles of older animals still responded to follistatin with growth.
Does the follistatin protein alone, without the gene, also build muscle?
Researchers at the University of Missouri tested exactly this in 2009. Mice with spinal muscular atrophy received ready-made follistatin protein rather than the gene. This is the form found in a vial of freeze-dried powder: the finished molecule.
In the treated mice the mass of several muscle groups increased and movement improved. There were also more of the nerve cells in the spinal cord that control the muscles. Average lifespan rose by 30 percent compared with untreated animals. The study showed that the protein given from outside is enough to produce the effect.
How did follistatin 344 work in monkeys?
Monkeys are physiologically much closer to humans than mice, which is why this study was a breakthrough. In 2009 the Ohio team delivered the follistatin 344 gene into the quadriceps of macaques. The muscles grew clearly and lastingly, and their strength increased.
The researchers also examined the animals' organs after a long period. They found no abnormal changes in the structure or function of the main organs. In a review from the same year the team noted that the 344 form did not change the animals' fertility. It was this result that opened the way to studies in humans.
What did the studies in humans show?
In humans follistatin 344 was tested in two studies at Nationwide Children's Hospital in Columbus. In both, patients received the follistatin 344 gene by injection into the muscles of both thighs. The main measure was the distance covered in a 6-minute walk test.
The 2015 study included six patients with Becker muscular dystrophy, a disease in which the muscles gradually weaken. Four of them improved their walk result:
- lower dose: by 58 metres and by 125 metres, the third patient unchanged,
- higher dose: by 108 metres and by 29 metres, the third patient without improvement.
Muscle samples showed less fibrous tissue, and the muscle fibres were larger, especially after the higher dose. The researchers recorded no side effects.
The 2017 study treated six people with inclusion body myositis, a disease that usually affects people over 50. Treated patients improved their walk distance by 56 metres a year on average. Eight matched untreated people lost 25.8 metres on average over the same time. Four treated patients improved by 58 to 153 metres.
How do the human studies differ from the product in a vial?
In the human studies a gene was given that itself produced follistatin 344 in the muscle over a long time. A vial holds the finished protein, which works for as long as it circulates in the body. In mice the finished protein also increased muscle mass, as the 2009 study showed.
No study has yet been published in which healthy people received finished follistatin 344 protein by injection. The results in patients therefore show the direction in which this molecule acts, not the effect of a particular dosing schedule. Follistatin 344 is not an approved medicine.
Where to buy follistatin 344 and how much does it cost?
The shop has three variants of follistatin 344, all in stock:
| Product | Amount | Price | Price per milligram |
|---|---|---|---|
| Follistatin 344 Nouveaux Ltd. | 2 mg | 70 EUR | 35 EUR |
| Follistatin 344 Genheal | 1 mg | 45 EUR | 45 EUR |
| Follistatin 344 Bio-Peptide | 1 mg | 45 EUR | 45 EUR |
The lowest price per milligram is the 2 mg vial from Nouveaux Ltd. All variants are gathered on the follistatin 344 page. How follistatin compares with other muscle peptides is covered in the guide on what studies showed about peptides in bodybuilding. The products in the shop are material for laboratory research, not a medicine.
Frequently asked questions
Does follistatin 344 increase muscle mass?
Yes, in studies in mice and macaques follistatin 344 clearly increased muscle mass and strength. In mice the effect of a single gene dose lasted more than two years.
Are there studies of follistatin 344 in humans?
Yes, two gene therapy studies from 2015 and 2017 in patients with Becker muscular dystrophy and inclusion body myositis. Most treated patients walked further in the 6-minute walk test.
How much did the walk result improve in patients?
In the 2015 study four of six patients improved their distance by 29 to 125 metres. In the 2017 study treated patients gained 56 metres a year on average, while untreated ones lost 25.8 metres.
Does the finished follistatin protein work like the gene?
In mice the finished follistatin protein also increased muscle mass and extended life by 30 percent. No studies of the finished protein in humans have been published yet.
How much does follistatin 344 cost in the shop?
The 2 mg Nouveaux Ltd. vial costs 70 EUR, and the 1 mg Genheal and Bio-Peptide vials cost 45 EUR each. All are in stock.
Sources
- Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proceedings of the National Academy of Sciences, 2001, 98(16): 9306-9311. https://doi.org/10.1073/pnas.151270098
- Lee SJ. Quadrupling muscle mass in mice by targeting TGF-beta signaling pathways. PLoS One, 2007, 2(8): e789. https://doi.org/10.1371/journal.pone.0000789
- Haidet AM, Rizo L, Handy C 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, 2008, 105(11): 4318-4322. https://doi.org/10.1073/pnas.0709144105
- Rose FF Jr, Mattis VB, Rindt H, Lorson CL. Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy. Human Molecular Genetics, 2009, 18(6): 997-1005. https://doi.org/10.1093/hmg/ddn426
- Kota J, Handy CR, Haidet AM et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Science Translational Medicine, 2009, 1(6): 6ra15. https://doi.org/10.1126/scitranslmed.3000112
- Rodino-Klapac LR, Haidet AM, Kota J et al. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle and Nerve, 2009, 39(3): 283-296. https://doi.org/10.1002/mus.21244
- Mendell JR, Sahenk Z, Malik V et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Molecular Therapy, 2015, 23(1): 192-201. https://doi.org/10.1038/mt.2014.200
- Mendell JR, Sahenk Z, Al-Zaidy S et al. Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Molecular Therapy, 2017, 25(4): 870-879. https://doi.org/10.1016/j.ymthe.2017.02.015