Thymosin beta-4 (TB-4)

Thymosin beta-4 is a small, naturally occurring protein of 43 amino acids. It is present in essentially all cells and body fluids [1]. After an injury it is released by platelets, macrophages and many other cells, and it has been studied for healing skin, eye, heart and brain tissue [2]. It is also the parent of TB-500, a veterinary product built on a synthetic fragment of it and promoted for healing [8].

Eye. As 0.1% eye drops (RGN-259), it was tested in two small phase 2 trials in dry eye. In 9 patients with severe dry eye, it reduced discomfort by 35% and corneal staining by 59% compared with vehicle [3]. In a 72-person trial it missed both primary endpoints, discomfort and inferior corneal staining. Some secondary measures improved, and no adverse events were reported [4].

Intravenous safety. Synthetic Tβ4 was given to 40 healthy volunteers in single doses of 42–1,260 mg, then daily for 14 days. Side effects were infrequent and mild to moderate, with no dose-limiting toxicity [5]. A recombinant version was well tolerated in 84 healthy Chinese volunteers, and both studies were aimed at future use in heart attacks [5][6].

There are no controlled human trials of injected Tβ4 for tendon, muscle or joint injuries. The only related report is a retrospective phone survey in which 4 people received it with BPC-157 in the knee [9].

Tβ4 binds single actin molecules (G-actin) and stops them joining into filaments. In resting human neutrophils it is present at about 149 µM and holds most of the unpolymerised actin. It releases actin quickly when the cells are stimulated to move [10].

Different parts of the molecule seem to do different things. The N-terminal four amino acids (Ac-SDKP) mainly block inflammation and fibrosis. The central actin-binding stretch LKKTETQ (amino acids 17–23) promotes angiogenesis, wound healing and cell migration [1]. In the heart, Tβ4 formed a complex with PINCH and integrin-linked kinase and activated the survival kinase Akt. After coronary artery ligation in mice, treatment improved early heart-muscle survival and heart function [11]. Reviews also describe fewer myofibroblasts in wounds, which means less scarring [2].

In the intravenous studies, adverse events were infrequent and mild to moderate, with no dose-limiting toxicity or serious adverse events [5][6]. Anti-drug antibodies were rare with the recombinant version [6]. The dry-eye trials reported the drops as safe and well tolerated [3][4].

Because Tβ4 promotes cell migration and blood-vessel growth, its link with cancer is worth knowing. It is expressed in most colorectal cancers, most strongly at the invasive front [12]. Pancreatic cancer cells make more of it than normal cells, and added Tβ4 raised their inflammatory cytokine output [13]. These are associations and lab findings, not evidence that taking Tβ4 causes cancer.

It is prohibited by the World Anti-Doping Agency, and products claiming to contain Tβ4 or a fragment of it are sold online [7].