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4 Benefits of Follistatin + Side Effects

Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Matt Carland, PhD (Neuroscience) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Reviewed by Matt Carland, PhD (Neuroscience) | Last updated:

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Bodybuilder

Follistatin is involved in muscle growth, inflammation, and fertility. While it has gained attention in bodybuilding circles, the benefits of follistatin on muscle growth may not be all they’re cracked up to be. Read on to learn more about follistatin and how you can boost its levels with foods and supplements.

What Is Follistatin?

Follistatin is a compound made of protein and sugar molecules – a glycoprotein.

As shown by studies in rats and mice, follistatin is primarily produced in the liver, although it can also be found in almost all body tissues [1, 2].

Follistatin increases in muscle tissue in response to muscle damage and plays a role in promoting cell growth throughout the body [3].

However, there are many different forms of follistatin, which play different roles in different parts of the body:

  • Follistatin 344 (FS-344): The most basic form of follistatin. It is primarily used in gene therapy, where the gene that helps create more follistatin is injected into the body using specially-designed viruses. Different parts of the body can then convert this “general” form of follistatin into more specific types in order to target different parts of the body [4, 5, 2, 6, 7].
  • Follistatin 315: The main form of follistatin found in the bloodstream. It primarily targets muscle tissue, which suggests it may be the best form of follistatin to supplement with [3, 7, 4].
  • Follistatin 288: A type of follistatin involved primarily in reproductive health. It also plays a role in tumor and cancer cell development [5, 4].
  • Follistatin 300: Another type of follistatin, involved in re-shaping nerve connections and in cardiac inflammation [8].

Follistatin Mechanisms

Follistatin blocks the action of many different proteins and hormones such as:

  • Activins, which are involved in apoptosis, metabolism, endocrine homeostasis, bone growth, fibrosis inflammation, neurogenesis, tubulogenesis of endothelial cells, and cancer development [9, 4].
  • Myostatin, which inhibits muscle growth [10].
  • GDF-11, a growth factor involved in bone development [11].
  • Follicle-stimulating hormone (FSH), involved in the development of eggs and sperm (gametes) [12].

Most of the follistatin’s effects on cancer and in reproductive health stem from its interactions with activins [4].

In contrast, follistatin’s effects on muscle growth are related to interactions with myostatin [13].

Health Benefits of Follistatin

Insufficient Evidence for:

1) Muscle Growth

Follistatin has gained attention in the bodybuilding community due to claims that it can significantly boost muscle mass, although there are relatively few scientific studies that directly back this up in healthy human subjects.

A study found that supplementation with egg yolk-derived follistatin (MYO-X) led to increased muscle mass in 37 college males when taken at 10 to 30 grams per day together with resistance training for 8 weeks [14].

One way that follistatin may accelerate muscle growth is by inhibiting myostatin, a protein that limits muscle development [15, 16, 17].

For example, a monkey study found that increasing the production of follistatin led to a corresponding decrease in myostatin activity and a significant increase in muscle growth [18].

In mice, follistatin stimulated the development of muscle cells, leading to enhanced muscle growth and repair [6, 10].

However, follistatin increased muscle growth even in mice that were genetically modified to lack myostatin, showing that follistatin affects muscle growth in other ways that are not directly related to myostatin [16, 19].

Although this is the most common use of follistatin, the evidence to support it is insufficient. More clinical trials on larger populations are needed to confirm these preliminary findings.

2) Preventing Muscle Loss

In a study of 6 male patients with Becker muscular dystrophy (a muscular disorder that specifically affects the legs and pelvis), follistatin injections increased muscle strength, leading to improvements in the patients’ symptoms without any adverse side effects [5].

Boosting follistatin levels has also been tested as a treatment for sarcopenia, an age-related muscle-wasting disease. In old mice, daily injections of epicatechin (a natural compound that increases follistatin levels) led to increased overall muscle strength. The same treatment in 6 human subjects increased their hand grip strength after seven days [20].

Follistatin also increased life expectancy in mice with spinal muscular atrophy, a genetic disease that involves muscle wasting. This suggests that follistatin could be used as a therapy technique due to its positive effects on muscle maintenance and growth [21].

Taken together, the evidence is insufficient to claim that follistatin helps prevent muscle loss until further clinical research is conducted.

3) Baldness

A small trial on 26 men with male-pattern baldness found that a single injection of follistatin with other growth factors increased the number of hairs on the head as well as their thickness (follicle density and hair shaft thickness). These beneficial effects lasted for up to a year with only a single treatment without needing repeated administrations [22].

A single clinical trial, despite its promising results, cannot be considered sufficient evidence that follistatin helps with male-pattern baldness. Larger, more robust clinical trials are needed.

4) Role in Reproductive Health

A number of findings indicate that follistatin seems to have some role in reproductive health, although its precise role is not yet entirely clear [23, 24].

In men, seminal fluid is rich in follistatin, although the levels of follistatin don’t seem to be directly related to sperm count [25, 26].

For women, follistatin promotes folliculogenesis, the process that prepares eggs to be released from the ovaries during ovulation [27, 24].

Follistatin levels are reduced during menopause but can be elevated using hormone replacement therapy [28].

A study of 7 women found that increased follistatin levels during the third trimester of pregnancy were associated with healthy labor and child delivery [29].

Follistatin also inhibits the activity of activins, which play a role in many aspects of reproductive health.

For example, activins are involved in the development of reproductive organs (testes and ovaries), and problems in normal activin function are related to tumors in those organs [30].

An increase in activin levels in women is correlated with reproductive aging [30].

Abnormalities in follistatin and activin activity have also been linked to polycystic ovary syndrome and problems during pregnancy [30].

Further clinical research is required to clearly establish the role of follistatin in reproductive health and determine if it can be therapeutically used for reproductive issues.

Animal and Cell Research (Lack of Evidence):

Scientists are also investigating the potential effects of follistatin on other health conditions. Because the research is still at the animal and cell stage, there is no evidence that follistatin will have the same effects in humans.

Preventing Fat Gain

Boosting follistatin levels in mice led to reduced fat gain and also decreased the size of the fat-storing cells (adipocytes) [31].

A series of related mice studies suggest that these effects may also be due to follistatin’s ability to inhibit myostatin [32, 19, 33].

By reducing myostatin levels, follistatin may have the potential to fight obesity as well as prevent diabetes as seen in mice studies [31, 32].

Arthritis

Follistatin significantly reduced joint inflammation and cartilage degeneration in mice with arthritis. This suggests that follistatin has potential as an anti-inflammatory drug for treating arthritis, but clinical research is needed [34].

Cancer Development.

Preliminary research suggests that follistatin may play a role in either inhibiting or promoting cancer growth, depending on the type of cancer. Because most of this research is still at the animal and cell stage, there is no evidence that follistatin will have the same effects in humans. Do not under any circumstances attempt to replace conventional cancer therapies with follistatin.

So far, follistatin has been found to play a beneficial role in many different types of cancer, including:

  • breast cancer
  • lung cancer (non-small cell lung cancer)
  • liver cancer
  • ovarian cancer

However, follistatin may play a negative role in other types of cancers, such as:

  • esophagus cancer
  • stomach cancer
  • skin cancer (melanoma, basal cell carcinoma)
  • prostate cancer

Follistatin’s Beneficial Effects on Cancer

A study analyzing tissue samples of human breast cancer patients found higher follistatin levels in those of survivors. This suggests that follistatin may play a protective role in this type of cancer [35].

In several cell studies, follistatin was found to reduce the survival rate of breast cancer cells, while also preventing the spread of cancerous cells in the body (metastasis) [35, 36].

In a study of mice with breast cancer, follistatin had no impact on tumor growth but did prevent the cancer cells from spreading to the rest of the body [37].

Cell studies of non-small cell lung cancer and ovarian cancer showed that follistatin and follistatin-like proteins prevented the growth and spread of cancer cells [38, 39, 40].

In living mice with lung and ovarian cancers, follistatin reduced tumor growth and prevented cancer cells from spreading, which allowed the mice to survive longer [41, 42].

In liver cancer, follistatin increased the growth and recovery of the liver after tumor-removing surgery in rats [43, 44].

However, it has also been found that liver tumors in rats and mice tend to have increased follistatin levels, making follistatin’s role in liver cancer a bit unclear [45].

Follistatin’s Negative Effects on Cancer

On the other hand, follistatin may play a distinctly negative role in some other types of cancer.

For example, cell studies of esophagus, skin, and prostate cancer found that follistatin acts as a growth factor for these types of cancer cells. This means that follistatin actually helps these cancers spread, and may even reduce the effectiveness of chemotherapy [46, 47, 48, 49].

In mice with stomach cancer, follistatin levels were found to be elevated in tumor cells, suggesting that follistatin play have a role in their development [50].

Follistatin may also stimulate the development of prostate cancer. For example, rapamycin, a compound that decreases follistatin levels, inhibits the growth of prostate cancer cells [51].

Other cell studies have found that foods containing soy isoflavones may inhibit the growth of prostate cancer cells by deactivating the genes responsible for creating follistatin. Foods rich in soy isoflavones, such as soy milk and miso, are particularly common in Asian diets, and their ability to lower follistatin levels may be one explanation for why prostate cancer is less common in Asian populations [52].

As cancer progresses, tumors need access to nutrients from the bloodstream in order to continue growing. The growth of new blood vessels is called angiogenesis, and follistatin can sometimes promote tumor growth by inducing angiogenesis as shown in cell-based and mice studies [53, 54, 55].

Limitations and Caveats

The most widely-known usage of follistatin is for bodybuilding purposes. However, the effectiveness of follistatin in healthy human users has yet to be fully backed up by scientific research.

Although there are multiple scientific studies indicating that follistatin can increase muscle growth, the majority of data on muscle growth in humans comes from clinical patients suffering from muscle-wasting diseases.

Meanwhile, data on muscle growth in non-clinical populations comes from animal studies.

Only one study (on healthy college males) found that follistatin was able to increase muscle growth. Therefore it remains an open question whether follistatin will reliably boost muscle growth in healthy humans.

There is also a considerable number of users that have reported no beneficial effects on muscle gains, which is another cause for skepticism.

However, while many users report no muscle changes after using follistatin, this could be due to the different forms of follistatin available. Because the most common form of follistatin found in the bloodstream is follistatin 315, this form would probably be the best type of follistatin to supplement with if you’re looking to benefit from increased muscle growth or any of follistatin’s other health benefits.

Boosting Follistatin

The following strategies are aimed at naturally boosting your follistatin levels. Work with your doctor to determine if you could obtain any health benefits from them. Never implement these strategies in place of what your doctor recommends or prescribes.

Foods with Follistatin

Soy isoflavones and epicatechin are two components found in several common foods that can help naturally boost follistatin levels in the body [52, 20].

Foods that are rich in soy isoflavones include:

  • Soy milk
  • Miso
  • Soybeans (edamame)

Foods that are rich in epicatechins include [56]:

Another food that can increase follistatin in the body is Ecklonia cava, a type of brown algae [57].

Some foods also directly contain follistatin, such as egg yolks (especially from fertilized eggs). Follistatin from egg yolks can also be found in some supplements that increase muscle mass (when used with training), like MYO-X [14].

So far, most scientific studies that have found benefits from follistatin have directly injected follistatin into the body or used genetic modifications in animals to boost the genes that help create follistatin. So, it is possible that follistatin’s beneficial effects might be weaker if it is ingested.

Exercise and Follistatin

Another natural way to boost follistatin in the body is through exercise.

In a study of 14 post-menopausal women, eccentric exercise (exercise that focuses specifically on muscle strengthening, commonly used in rehabilitation for sports injuries) increased body levels of follistatin, though this effect lasted less than 24 hours. However, there was a greater increase in follistatin levels when the treatment was used with hormone replacement therapy [28].

A separate study in healthy human males found that several types of exercise increased follistatin during a fasting period [1].

Follistatin Interactions

Rapamycin is a drug commonly used to prevent organ transplant rejection and to generally suppress the immune system. In cell studies, treatment with rapamycin reduced follistatin levels, particularly working with prostate cancer cells. If you are taking rapamycin for any conditions, consult your doctor about its potential interactions with follistatin supplements [51].

Follistatin Side Effects

Keep in mind that the safety profile of follistatin is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is, therefore, not a definite one. You should consult your doctor about other potential side effects based on your health condition and possible drug or supplement interactions.

Some side effects commonly reported by the bodybuilding community include muscle soreness or swelling after working out, as well as temporarily weakened ligaments and tendons. However, these effects may just be a result of muscle strain, rather than follistatin itself [58].

According to long-term studies of patients receiving bone marrow and blood stem cell transplants, people with higher levels of follistatin may have a higher risk of organ rejection (graft versus host disease). While the reasons for this are not clear, this may have something to do with follistatin’s role in inflammation and tissue repair [59].

User Experiences

The opinions expressed in this section are solely those of follistatin users who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.

Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare providers because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.

Though there are relatively few clinical studies on the use of follistatin for muscle growth, many users have shared their experiences with follistatin supplementation on bodybuilding forums.

The typical daily dosage among these users is 100 to 300 micrograms, injected directly into the specific muscles the user would like to boost.

Many commenters on bodybuilding forums have claimed not to have found any significant effects on muscle growth after injecting follistatin. Meanwhile, although some users claimed significant mass gain, this was usually associated with a notable increase in appetite and caloric intake, which could partially explain the gain in muscle mass these users observed.

There are mixed reviews regarding the effectiveness of supplements in boosting follistatin levels. The supplements that get more positive reviews usually do not directly contain follistatin, but instead, increase follistatin levels indirectly through natural compounds such as epicatechin or Ecklonia cava.

Want Better Results from Your Training?

If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this fitness DNA wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.

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About the Author

Carlos Tello

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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