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, called a glycoprotein.
Follistatin increases in muscle tissue in response to muscle damage and plays a role in promoting cell growth throughout the body .
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 and is probably 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 .
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 .
- GDF-11, a growth factor involved in bone development .
- Follicle-stimulating hormone (FSH), involved in the development of eggs and sperm (gametes) .
Most of the follistatin’s effects on cancer and in reproductive health stem from its interactions with activins .
Follistatin Affects Cancer Development. Follistatin can play a role in either inhibiting or promoting cancer growth, depending on the type of cancer.
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
Human breast cancer patients with higher follistatin levels are significantly more likely to survive. This suggests that follistatin plays a protective role in this type of cancer .
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 .
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 .
Follistatin’s Negative Effects on Cancer
On the other hand, follistatin can 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 [25, 26, 26, 27, 28].
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 .
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 .
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 .
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 [32, 33, 34].
Health Benefits of Follistatin
1) May Enhance 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 .
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 .
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 [37, 40].
2) May Prevent Fat Gain
In addition to boosting muscle growth, follistatin may also prevent the accumulation of fat in the body.
For example, boosting follistatin levels in mice led to reduced fat gain and also decreased the size of the fat-storing cells (adipocytes) .
3) Prevents 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 .
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 .
Follistatin also increased life expectancy in mice with spinal muscular atrophy, a genetic disease that involves muscle wasting. Follistatin could be used as a therapy technique due to its positive effects on muscle maintenance and growth .
4) May Fight Arthritis
Follistatin significantly reduced joint inflammation and cartilage degeneration in mice with arthritis. This indicates that follistatin can potentially be used as an anti-inflammatory drug for treating arthritis .
5) May Treat Baldness
A study (DB-RCT) of 26 patients 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 .
6) Reproductive Health
Follistatin levels are reduced during menopause but can be elevated using hormone replacement therapy .
A study of 7 women found that increased follistatin levels during the third trimester of pregnancy were associated with healthy labor and child delivery .
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 .
An increase in activin levels in women is correlated with reproductive aging .
Abnormalities in follistatin and activin activity have also been linked to polycystic ovary syndrome and problems during pregnancy .
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.
Foods with Follistatin
Foods that are rich in soy isoflavones include:
- Soy milk
- Soybeans (edamame)
Foods that are rich in epicatechins include :
Another food that can increase follistatin in the body is Ecklonia cava, a type of brown algae .
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 .
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 .
A separate study in healthy human males found that several types of exercise increased follistatin during a fasting period .
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 .
Follistatin Side Effects
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 .
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 .
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.
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