4.1. What is a glucan and what determines its immune stimulating

All macro-molecules containing glucose as the only building block are called glucans (macro-molecules containing sugars other than glucose are called glycans). Starch and cellulose are well-known examples of glucans, where the glucose molecules are linked together in so-called alpha- and beta-1,4- linkages, respectively. Such glucans have no effect on the immune system.

The common feature of glucans which have the ability to activate the immune system is a chain of glucose molecules linked together in so-called beta-1,3-linkages. However, to be active there must also be “branches” of glucose molecules attached (by beta-1,6-linkage) to this beta-1,3-glucan chain. For example, the sea-weed beta-1,3-glucan laminarin, which is almost deplete of such branches, is not active as an immune stimulant. On the other hand, branched beta-glucans (called beta-1,3/1,6-glucans according to chemical nomenclature rules) are very potent, non-toxic immune-stimulants.

The beta-1,3/1,6-glucans scleroglucan, lentinan and schizophyllan which are extracted from medicinal mushrooms are active immune-stimulants. Their efficacy is lower, however, than that of a fully branched beta-1,3/1,6-glucan extracted from baker’s yeast because the side branches of the mushroom products consist of only one glucose whereas the side branches of the beta-1,3/1,6-glucan from yeast consists of chains of glucose molecules (Engstad and Robertsen, 1993; 1994 and 1995; Bohn and BeMiller 1995; Suzuki et al.1998). To match perfectly into the receptor on the white blood cells, the length of the branches should be at least 2 glucose molecules (Engstad and Robertsen 1995).

The beta-1,3/1,6-glucan present as a structural component inside the cell walls of baker’s yeast has a molecular structure that fits with the glucan receptor on the white blood cells. Baker’s yeast is therefore a suitable raw material for extraction of a beta- 1,3/1,6-glucan with high biological efficacy. However, it is difficult to release this beta-1,3/1,6-glucan molecule from the cell wall structure. The challenge has been to remove those molecules (e.g. manno-proteins) which, in the intact cell wall, are attached to the end-points of the side-branches without causing de-branching of the beta-1,3-glucan chain and, as a consequence, loss of efficacy.

The high efficacy of yeast beta-1,3/1,6-glucan compared to glucans and glycans from other sources as an immune stimulant was shown by Seljelid et al. in 1981.

4.2. Brewer’s yeast

Brewer’s yeast is not a suitable source of bio-active beta-glucan for two reasons. First, the total content of beta-1,3-glucan is very low compared to baker’s yeast and second, the beta-1,3-glucan present has a low number of side-branches.

4.3. Oat and barley glucans

The beta-glucans present in oat and barley have a different composition than those present in yeast and mushrooms. In the beta-glucans of oat and barley, the glucose molecules are joined partly by beta-1,3- and partly by beta-1,4- linkages. These are soluble polymers which lower serum cholesterol and glucose levels when used in the human diet at high inclusion levels (15 grams per day) (Davidson et al. 1991). However, these effects are thought to be due to a “fiber process” whereby cholesterol and bile salts are eliminated from the ileum along with the glucan fiber. The effect is probably not mediated via the immune system.

4.4. Micro-particulate beta-1,3/1,6-glucan from baker’s yeast

The conventional procedure for extraction and purificaton of the beta-1,3/1,6-glucan from baker’s yeast consists of removal of cytoplasmic proteins by alkali treatment followed by treatment in acid to remove the minerals, lipids and mannoseproteins. The mannose-proteins cover the surface of the intact yeast cell and they are covalently bound to the beta-1,3/1,6-glucan which constitutes a net-like structure in the inner part of the cell wall. The mannose-proteins have to be removed for two reasons-first, to expose the beta-1,3/1,6-glucan structure (the active principle), and second because the mannose-proteins are a potential allergenic constituent of yeast. Removal of mannose-proteins is a critical step in the extraction process during manufacture of bioactive beta-1,3/1,6-glucan. It is quite probable that one may easily end up with a beta-1,3-glucan where the side branches have been stripped off and the immune stimulating activity is gone.

The result of the extraction of a beta-1,3/1,6-glucan with high biological activity (US Patent No. 5,401,707, EP No. 0466037) is small “bags” with a size in the range 1 to 3 microns. These micro-particles expose a great number of free glucose ends that can bind to receptors on white blood cells.

The high bioactivity of yeast beta-1,3/1,6-glucan compared to other beta-1,3/1,6-glucans (from mushroom) is one of the reasons why yeast beta-1,3/1,6-glucan attracts more and more attention as a pharmaceutical product candidate and as health supplement. Another reason is that the product comes from a so-called GRAS-organism (Generally Regarded As Safe): food grade baker’s yeast produced under the regulations of good manufacturing practice.

4.5. Soluble beta-1,3/1,6-glucans from baker’s yeast

To make a bioactive soluble beta-1,3/1,6-glucan, one has to start with a pure and bioactive micro-particulate product. There are several ways to do this. The most straight forward is to react the beta-1,3/1,6-glucan micro-particles with Cl-acetic acid, a process called carboxy-methylation, which introduces negatively charged acetate groups at random in the beta-1,3/1,6-glucan molecule. The product, CM-glucan, has been used in cosmetic products. But the disadvantage is that the beta-1,3/1,6-glucan looses much (sometimes all) of its bioactivity when end-positioned glucose molecules (which bind to glucan receptors) are carboxy-methylated. Another solubilization procedure consists of reacting the micro-particulate beta-1,3/1,6-glucan with phosphoric or sulphuric acid to produce phosporylated or sulphated beta-1,3/1,6-glucans that become water soluble as a result of introduction of negatively charged groups on the molecule. But these soluble products also have the disadvantage of lost bioactivity due to altered structure of the end-positioned glucose molecules.

Much work has been invested to find ways to solubilize the yeast beta-1,3/1,6-glucan in native form, without chemical modifications as described above. One procedure is described in Norwegian patent (300.692) and EPO-patent (EPO759089) where the resulting product is a 100 % pure native yeast beta-1,3/1,6-glucan with very high biological activity and excellent safety profile (see 6.4).


Abstract 1. A functional description of immunity 2. Activation of innate immunity by microbial products 3. The history of beta-1,3/1,6-glucans 4. Chemistry, properties and manufacture of glucans and beta-1,3/1,6-glucans 5. Mode of action and biological effects 6. Safety 7. Selected pre-clinical "proof-of-concept" studies 8. Description of selected clinical trials 9. Skepticism to beta-1,3/1,6-glucan 10. Conclusion References