Early Beta-Glucan Research

Mushroom extracts have had a recognized position in Oriental medicine for centuries, the most well-known are extracts of the Shitake mushroom (Lentinus edodes) in Japan and the “Ling-zhi” mushroom (Ganoderma lucidum) in China. Today we know that the healing effect of these traditional mushroom extracts can be attributed to the content of polysaccharides, in particular β-1,3-glucans.

Also, it has long been known that disrupted cells from Baker’s yeast may have a certain healing effect. More than 50 years ago it was discovered that disrupted and enzyme digested Baker’s yeast contained something that interacted with serum components involved in the destruction of infectious microorganisms and that a crude cell-wall preparation called zymosan activated macrophages in test tube experiments. In the 1960s DiLuzio and his co-workers in New Orleans showed that the active component in zymosan is a polysaccharide containing glucose linked by beta-1,3 and beta-1,6 chemical bonds.

From then on several research groups, mainly in USA, Japan and in Norway have actively persued the goal of producing pure polysaccharides of the β-1,3 type – suitable for experimental and clinical use. Biotec Pharmacon has for more than 20 years performed basic research on the extraction and mode of action of yeast beta-1,3/1,6-glucan. The specific yeast beta-glucan produced by the company interacts directly with cells of the innate immune system, especially the macrophages and orchestrates a number of immune reactions. The product therefore has many potential applications in human medicine, in particular in conditions related to inadequate immune reactions.

Experimental studies. The first experimental study directly related to significant human disease was Chihara’s report from 1967 that a beta-1,3-glucan preparation extracted from the Lentinus edodes mushroom could inhibit the growth of fibrosarcoma in mice (G. Chihara et al. Nature 222:687, 1967). Later, results from de Luzio’s group demonstrasted that soluble as well as particulate yeast polysaccharide – mainly of the beta-1,3-glucan configuration – displayed tumor – inhibitory as well as anti-infectious effects in mice (N.R. de Luzio et al. Int J Cancer 24:773 1979). The results from tumor experiments described above, were difficult to interpret and to reproduce until Seljelid and co-workers demonstrated that a significant regression of experimental tumors in mice treated with beta-1,3-glucan could only be achieved when a strong concomitant adaptive reaction (in itself ineffective) had been established – and before tumor induced immune suppression had set in (R. Seljelid. Bioscience Reports 6:845, 1986). Experiments indicated that the glucan triggered a destructive acute inflammation at the tumor site targeted by the adaptive immune respons (R. Seljelid et al. Scand J Immunol 30:687, 1989). Hong et al later demonstrated the essential involvement of granulocytes – an essential component of an acute inflammatory reaction (Hong F. Cancer Res 63:9023, 2003). It thus appears that the glucan treatment – through its effect on innate immune mechanisms – delivers the effector mechanism necessary for a successful antitumor effect. These early results have later been confirmed by Cheung and co-workers, using proprietary SBG (soluble beta glucan) produced by Biotec Pharmacon. Recently it has also been established that Biotec Pharmacon’s soluble beta-1,3-glucan also can act as a conventional adjuvant to booster humoral and cellular immune responses following vaccination (Ragupathi et al Vaccine 26:4863, 2008).

It has long been known that β-1,3-glucan can protect against otherwise lethal infections in mice (N.R. de Luzio and D.L. Williams. Infect Immun 20:804, 1978; G. Chihara et al. Int. J. Tiss Reac 4:207, 1982). Rasmussen and co-workers studied the mechanisms and found that β-1,3-glucan had no direct effect on the infectious agent, but strongly boostered cellular innate immunity’s bactericidal capacity, as well as inhibited the lethal cytokine storm triggered by microbial products. Rasmussen L-T et al. Scand J Immunol 32:333, 1990).

In 2000 Zykova and co-workers demonstrated that macrophages from diabetic individuals both in mice (S.N. Zykova et al. Diabetes 49:1451, 2000) and humans (S.N. Zykova et al. Scand J Immunol 60:535, 2004) – were dysfunctional, but could be stimulated by immunomodulators. Since macrophages are central actors in wound and ulcer healing, it was pertinent to study – and demonstrate that β-1,3-glucan when topically applied, lead to increased healing of wounds in diabetic mice (Berdal M et al. Wound Rep Reg 15:825, 2007). This obviously motivated our clinical studies of diabetic ulcers.