A Peer-Reviewed Journal on Nutraceuticals and Nutrition Editor-in-Chief Pilot Study: Orally-Administered Yeast β β1,3-glucan Prophylactically Protects Against Anthrax Infection and Cancer in Mice Yeast β β1,3-glucan and Its Use Against Anthrax Infection a

In this edition of JANA, the paper by Vetvicka et al. makes an important contribution to our scientific understanding of the nutraceutical stimulation of the immune system in the treatment of both infectious disease and cancer. While abundant evidence demonstrates the ability of β1,3-glucans to activate macrophages and neutrophils when given intravenously or intraperitoneally, there has been little information concerning its efficiency when given orally. In their study, Vetvicka et al. used oral β1,3-glucan (Imucell TM WGP Beta Glucan) from a yeast source in mice infected with Bacillus anthracis. With the high incidence of complications associated with anthrax vaccines, an alternative approach is badly needed in this era of bioterrorism threat. Dr. Ken Alibek, a top-ranking scientist at the Russian bioweapons labs, stated that because of the number of possible bioweapon agents available, something other than mass inoculations would be needed. He suggested non-specific immune stimulation. The most effective form of nonspecific immune stimulation is macrophage activation. The anthrax bacillus secretes two toxins, edema toxin and lethal toxin. Edema toxin stimulates an outpouring of fluid, especially into the lungs. Lethal toxin, inhibits neutrophil phagocytosis and triggers destructive intracellular reactions that destroy macrophage cells. Of primary interest is the fact that anthrax lethal toxin inhibits the macrophages from releasing their immune messengers, primarily IL-1, IL-2, IFN-gamma, and TNF-alpha. Of particular importance in combating infection release from the macrophage, apparently overcoming inhibition by anthrax lethal toxin. This would account for the high survival figures in the β1,3-glucan-treated animals. Some previous studies found no increase in TNF-alpha but a significant increase in IL-1β. 1 Other researchers have demonstrated increased TNF-alpha in response to ß-glucan stimulation. 2 My own review of the literature confirms their statement that the most effective source of β1,3-glucan is from Saccharomyces cerevisiae, the one chosen by most researchers. Purity of the product is vital, since protein contaminants, as seen in the earlier-used source Zymosan, can cause untoward immune reactions. β1,3-glucan also stimulates phagocytosis of neutrophils. In one study, the killing efficiency of neutrophils was increased 20-to 50-fold. 3 This is important since the capsular antigen poly-D-glutamic acid from the anthrax organism inhibits neutrophil phagocytosis. It is the two lethal toxins and the capsular antigen that makes the anthrax organism especially deadly. In addition, β1,3-glucan has been shown to increase clearance of bacteria by the reticuloendothelial system. Thus far, no other solutions have solved this problem. As for β1,3-glucan's effects on tumor growth, several studies have shown a significant effect on tumor growth in animal models. 4,5 Early studies using immune stimulation found occasional tumor growth enhancement. This was later found to be secondary to stimulation of blocking antibody production. A safer and more effective method of immune stimulation is directed at cellular immunity, in particular the stimulation of T-helper cells and NK cells. β1,3-glucan has been shown to increase lymphocyte production, NK cell activation, and activation of macrophages. Several studies have also demonstrated the role played by cytokines in inhibiting tumor growth; again, particular interest is in TNF-alpha release. 6 Of interest also is the role played by IL-1β, which is increased by β1,3-glucan as well. Interleukin 1β has been shown to enhance mobilization of PMLs in the bone marrow and enhance their chemotactic ability. In addition, IL-1β increases the lymphocyte count and increases their activity. 7 The use of β1,3-glucan is of special interest in the cancer patient undergoing chemotherapy and/or radiation treatment, since β-glucans have shown a remarkable ability to accelerate hematopoetic recovery in both sublethally and lethally irradiated mice, even when given after the radiation dose. It can also stimulate recovery of the bone marrow following chemotherapy, something vital to restricting tumor growth and preventing infectious complications during treatment. While data provided in the research by Vetvicka and co-workers is preliminary and needs to be confirmed by a larger controlled trial, this is an important pilot study, in that it demonstrates the effectiveness of oral β1,3-glucan in treating both infectious agents and tumors. ABSTRACT β1,3-glucans from various bacterial, mushroom, yeast, and cereal sources have been established as immunomodulators. In the present paper we demonstrate that orallyadministered yeast β1,3-glucan (WGP Beta Glucan) had significant effects as a prophylactic treatment to reduce the mortality of anthrax infection in mice. In addition, the same type of treatment also inhibited the growth of cancer cells in vivo. The mechanism of action involves the stimulation of three important cytokines: IL-2, IFN-γ, and TNF-α. These results provide preclinical evidence for the beneficial effects of orally-administered yeast β1,3-glucan