The Benefits of Therapeutic Peptides: Exploring Thymosin alpha 1 and Thymosin beta 4

James Odell, OMD, ND, LAc

The Bioregulatory Medicine Institute

Thymosin alpha 1 and Thymosin beta 4 are small peptides naturally produced in the body. They play critical roles in regulating immune function and promoting tissue repair and regeneration. Peptides, particularly thymic peptides like thymosin alpha-1 and thymosin beta-4, have carved out a crucial niche in modern medicine. Their ability to modulate the immune system and enhance recovery from serious illnesses makes them valuable tools in treating a wide range of conditions, from cancer to viral infections. As research continues, the role of peptides in healthcare is likely to expand, offering new therapeutic options for patients worldwide. This article will explain some basics of peptide science relative to the thymus gland, primarily focusing on thymus peptides (thymosin alpha-1 and thymosin beta-4) and their beneficial use as bioregulatory immunological agents.

What Are Peptides?

Peptides are strings of amino acids, which are the "building blocks" of proteins. The fundamental difference between proteins and peptides is that peptides are shorter strings of amino acids than proteins, as most scientists refer to chains with over 100 amino acids as proteins. 

They play crucial roles in various physiological processes within the body, acting as hormones, enzymes, and structural components of cells. Several organs and tissues produce specific types of peptides that perform distinct functions. The pancreas, for instance, produces insulin, a peptide hormone that regulates blood glucose levels, while the pituitary gland synthesizes peptide hormones such as growth hormone and adrenocorticotropic hormone (ACTH). The hypothalamus produces releasing hormones, including thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH). In the digestive system, the stomach and intestines produce peptides like gastrin and cholecystokinin (CCK) to aid in digestion. The liver produces angiotensinogen, a precursor to the peptide hormone angiotensin, which is involved in blood pressure regulation, and adipose tissue produces leptin, a peptide hormone that regulates energy balance and hunger.

Overall, peptides serve various functions depending on their structure and origin, influencing metabolic processes, social bonding, and water balance. They are also utilized in therapeutic settings for their potential benefits in muscle building, anti-aging, and reducing inflammation, highlighting their integral role in maintaining homeostasis and overall health.

Development of Peptide Therapy

The first half of the 20th century witnessed the discovery of several life-saving bioactive peptides, such as insulin and adrenocorticotrophic hormone, which were initially studied and isolated from natural sources. The discovery and development of insulin, a peptide with 51 amino acids, has been considered one of the monumental scientific achievements in drug discovery. Research into therapeutic peptides started with fundamental studies of natural human hormones, including insulin, oxytocin, vasopressin, and gonadotropin-releasing hormone, and their specific physiological activities in the human body. 1

Since the synthesis of the first therapeutic peptide, insulin, in 1921, remarkable achievements have been made resulting in the approval of more than 100 peptide compounds worldwide. Peptide discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts.

In the 1960s research into the isolation and characterization of thymic peptides began. A 1966, paper in the Proceedings of the National Academy of Sciences, U.S., first named these thymic-derived peptides “Thymosins.”2 

Thymus Gland and Thymic Peptides

The thymus gland produces enzymes and hormone-like peptides that play an important role in the development, maturation, differentiation, and activation of T-cell lymphocytes.3

Thymic peptides act as chemical messengers to activate, regulate, and stabilize the immune system. In addition to thymosins, thymus peptides include thymopoietin, thymulin, and other thymic humoral factors, which all have both central and peripheral biological activities. Studies with thymic peptides have shown a variety of beneficial effects on the immune system. 

Over the years there developed two groups of injectable thymus peptide products available for use in treatment: Purified extracts from animal (mostly calf) thymus glands which contain peptides (pTE), and synthetically produced thymus gland peptides (sTP) Both injectable purified thymus extracts (pTE) and synthetic thymic peptides (sTP) have been demonstrated to enhance the immune system of cancer patients to assist in fighting tumor cell growth and resist infections due to immunosuppression induced by the disease and antineoplastic therapy.

Unfortunately, regulatory agencies have removed numerous thymic peptides (most of European origin) from the US market. Two still available and remain on the US market are thymosin alpha 1 (commonly abbreviated Tα1) and thymosin beta 4 (thymosin β4).

Immune Mechanism of Thymosin alpha 1 and Thymosin beta 4

Thymosin alpha 1(Tα1) and thymosin beta 4 (thymosin β4) are two hormone peptides secreted from the thymus and each has vastly different chemical compositions and immunological actions. These peptides are separated from thymosin fraction 5 and can potentially change various immune functions in mammals. 

Thymosin beta 4

Thymosin Beta-4 is a small, endogenous peptide that is originally isolated from the Thymus gland and comprises 43 amino acids. It belongs to the ‘Thymosin’ family of lymphocyte growth factors initially extracted from calf thymuses, with Thymosin Beta-4 being the most abundant of Beta-Thymosins. This peptide is mainly found in the thymus gland but is also present in the spleen and peritoneal macrophages.4

Thymosin beta 4, has a strong response to virally infected cells. It is currently being tested as a possible therapy against influenza, HIV, and acquired immune deficiency syndrome.5, 6, 7, 8

Tα1 is clinically relevant in various types of cancer, specifically hepatocellular carcinoma, lung cancer, and melanomas. Tα1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Tα1 has been used to support immunity in over 3,000 patients in over 70 clinical studies. Tα1 has a wide range of biological activities that range from anti-tumor to immune-modulating properties. In clinical trials, Tα1 strengthens the effects of immunomodulators in immunodeficiency, autoimmune diseases, and neoplastic malignancies. 

The immune response of Tα1 is partly due to its action in elevating the activity of T cell maturation into CD4+/CD8+ T cells. It works to directly activate natural killer cells as well as CD8+ T cells through which it kills virally infected cells. Thymosin alpha 1 reduces IL-1β and tumor necrosis factor-α, which in turn leads to a decreased inflammatory response and is quite beneficial in conditions such as chronic hepatitis and acute pancreatitis.

Tα1 was first discovered in 1972 and was isolated from tissue of the thymus gland and is a potent immune function modulator. Tα1, initially selected for its activity in restoring immune function to thymectomized mice, was the first peptide to be isolated from thymic tissue.9, 10, 11 

Cancer

Many cancers are associated with significant deficiencies in cellular immunity. In addition, conventional cancer treatments (i.e., surgery, radiotherapy, and chemotherapy) usually depress cellular immunity. In animal studies Tα1 has exhibited the ability to restrain tumor growth, hence its use in the treatment of various cancers.12, 13, 14 

Tα1 has been shown to restore immunity, increase resistance to progressive tumor growth, and reverse or ameliorate the immunosuppressive effects of chemotherapy or radiotherapy. It has anti-proliferative properties which have been exhibited in lung and liver tumor metastases. According to studies conducted by Moody et al. the anti-tumor activity of thymosin alpha 1 worked best with small tumor size.15 Ta1 treatment also leads to an increase in intracellular glutathione (GSH), important for antiviral effects, and directly inhibits the in vitro growth of certain cancer cells.16, 17, 18, 19, 20

Infections

Tα1 has been utilized in treating immunocompromised states and malignancies and as a means of curbing morbidity and mortality in sepsis and numerous infections.21 Studies have postulated that Tα1 could help improve the outcome in severely ill coronavirus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how Tα1 could prevent the excessive activation of T cells. 

Tα1 supplementation showed improvement and restoration of T cell counts in COVID-19 patients with severe lymphocytopenia and, in the end, thymosin alpha 1 supplementation reduced mortality in patients severely ill with COVID-19.22 

Within the context of COVID-19 infection, it has been shown to reduce mortality in those with severe disease and aid in restoring some immune function through increasing thymic activity. Due to its known immunological properties, many physicians use tα1 to mitigate immune dysfunction relative to the COVID-19 inoculation. 

Safety of Thymosin alpha 1

Tα1 is well-tolerated and considered generally safe when used as recommended by a physician familiar with thymic peptides. Most studies observed only local irritation at the injection site. The absence of adverse side effects with Tα1 is in sharp contrast to other major immune response modulators such as IFN and IL-2, which can lead to flu-like symptoms including malaise, fever, headache, chills, and pulmonary edema (especially with IL-2). 

Safety of Thymosin beta 4

Thymosin beta-4 is also well tolerated and considered safe when used as recommended by a physician familiar with thymic peptides. However, thymosin beta 4 is considered a performance-enhancing substance and is banned in sports by the World Anti-Doping Agency due to its effect of aiding soft tissue recovery and enabling higher training loads.23 

Dosage

Individual dosage requirements vary based on clinical presentation. They are commonly prescribed by a primary care physician familiar with peptide therapy. Tα1 is usually administered twice a week via a subcutaneous route. The standard single dosage ranges from 1 to 1.5mg every three days. Treatment courses usually range from 2 weeks for viral infection and 3 months or longer for HIV, cancer, Hepatitis B, C, or complicated immune suppression from COVID-19 inoculation.24, 25, 26

Thymosin beta 4 is usually dosed at 300 mcg and upward via a subcutaneous route, depending upon the clinical presentation. It is used less for immune enhancement and more for tissue repair. It is not recommended to use concurrently for more than 3 months, and it is best to cycle if needed long-term (3 months on, 6 weeks off, or 6 weeks on 6 weeks off) Individual dosage requirements vary based on clinical presentation.27

Availability

Both Thymosin alpha 1 and Thymosin beta 4 are commercially available and are administered in injection form. Ta1 is sold in over 30 countries worldwide under the names Thymosin alpha 1, Thymalfasin, Zadaxin®. 28

Peptide Science (https://www.peptidesciences.com/) sells Thymosin alpha-1 in 3 and 10 mg vials. According to their Website: This PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. All product information available on this website is for educational purposes only. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals. This product is not a drug, food, or cosmetic and may not be misbranded, misused or mislabeled as a drug, food or cosmetic.

Biotech Peptides (https://biotechpeptides.com/) sells Ta1 in 5 and 10 mg vials and Thymosin beta 4.

Oral Forms

Efforts are also underway to improve the oral availability of peptide therapeutics by increasing drug stability in the GI tract and formulating peptides with permeability enhancers such as enzymes.29 

Currently, several companies manufacture oral thymus peptides: 

Ecological Formulas markets “LTP” Lyphoactivated Thymic Peptides dietary that is derived from organically raised lamb. It features lyphoactivated thymic peptides blended with papain for enhanced absorption.

Standard Process markets “Thymus PMG” that contains nucleotides and peptides from bovine thymus.

Biotics Research markets Cytozyme-Thy which contains thymus peptides from neonatal bovine thymus. 

Conclusions

From humble beginnings as substances isolated from livestock glands, peptides have established a unique therapeutic niche and will continue to be an important element in the pharmaceutical landscape. Peptide development has entered a new era with advances in structural biology, recombinant biologics, and new synthetic and analytic technologies. We now see an increase in dozens of peptides used as regenerative and bioregulatory therapy for tissues and organs of the body. Meanwhile, the technologies used for protein purification and synthesis, structure elucidation, and sequencing made substantial progress, thus accelerating the development of peptide drugs, leading to dozens being approved worldwide. 

Immune senescence or immune suppression occurs during aging and is a hallmark of infectious disease and cancer. It is related to a gradual decline in thymus function and thymic hormone production. Thus, the lack of thymic peptides may contribute to the decline in immune function, particularly the T cell component. Unfortunately, thousands if not millions of individuals have undergone the experimental mRNA Covid-19 inoculations and have developed immune deficiency syndrome and or turbo cancer.  

Thymosin alpha 1 induces IL-2 and B cell growth factor production, differentiation of immature cord blood lymphocytes, raises efficiency of macrophage antigen presentation, and the modulation and partial normalization of function and number of T-lymphocytes. The effects of immune stimulation occur in both the myeloid and plasmacytoid dendritic cells with the production of cytokines. Tα1 is used to treat immune-sensitive diseases, including acute and chronic viral, bacterial, and fungal infections, and multiple types of cancers. Tα1 can decrease toxicity from chemotherapy and radiotherapy and significantly improve the quality of life in cancer patients. Patients receiving Tα1 report few serious drug-related toxicities during treatment, even in combination with other agents, making Tα1 particularly effective in immune-depressed patients from all causes.

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