Immune-modulatory effects of dietary Yeast Beta-glucan

Abstract

Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect.

Introduction

A well-functioning immune system is crucial for staying healthy. Therefore, the potential of natural substances to strengthen the immune system has long been the subject of investigation. There are many synthetic and natural preparations claiming to be immunomodulators. Probably the best known herbal preparations that exhibit effects on the immune system are preparations made from Echinacea, Viscum (mistletoe), and Pelargonium. There is, however, another very interesting and, by now, properly investigated class of immunomodulators - the β-glucans.

Long before the substance class of β-glucans themselves were identified as immunomodulators, the beneficial effects of β-glucan-containing mushrooms such as Shiitake (Lentinus edodes) in Japan or Lingzhi (Ganoderma lucidum) in China were utilized in the traditional Oriental medicine for the strengthening of the body’s immune system.

Characteristics of the proprietary yeast β-glucan preparation 

Yeast beta glucan is an insoluble β-glucan made from Spent Brewers’ Yeast (Saccharomyces cerevisiae). The brewers’ yeast used in Yeast beta glucan is grown exclusively on malt and clean spring water with no other nutrients added. It is a natural by-product of the fermentation process used for beer production. Following gentle autolysis with the yeast’s own enzymes, high-performance centrifuges are used to separate the yeast autolysate into the soluble yeast extract and the insoluble yeast cell wall. Yeast cell walls contain typically about 30% of β-glucans of dry weight. During several separation processes, the β-glucans are further purified without the use of strong alkaline in the hydrolysis process, and soluble compounds are removed. Furthermore, the process does not involve an acidic hydrolysis, leaving the acid-sensitive β-1,6-glucan side chains mainly intact. This results in an average of 22% relative linkage percentage from β-1,6 glucan (H-NMR analysis according to FCC VII, 3rd suppl.; reference-glucan at 14%), with a minimum of purity of 85% (dry mass).

 

Mode of action/structure function relationship

As humans cannot metabolize the β-glycosidic bonds from β-glucans, it has long been suspected that the bacterial fermentation process taking place within the intestinal system is involved in the health promoting effect of β-glucans.

Meanwhile, different possible mechanisms have been identified on how oral β-glucans modulate the immune system .

In general, humans cannot synthesize β-glucans. Therefore, the immune system recognizes these compounds as foreign. The innate immune system responds to invading pathogens through pattern recognition receptors (PRR), which are typically expressed by immune cells but also by other cells. PRRs recognize conserved microbial structures, the so-called microbe-associated molecular patterns (MAMPs) , formally called PAMPs . β-glucans are considered as one of the major MAMPs for the PRR-mediated sensing of fungal infection. So far, the most important PRRs for β-glucans are the dectin-1 receptor, the complement receptor 3 (CR3) and toll-like-receptors (TLR), which are found on various immune cells such as monocytes, macrophages, dendritic cells, neutrophils, eosinophils, and natural killer cells, but also on intestinal epithelial cells . Binding of β-glucans to dectin-1 induced a cascade of innate and adaptive immune response such as phagocytosis, oxidative burst, and the production of cytokines and chemokines in dendritic cells and macrophages . Kankkunen et al. showed that particulate yeast β-glucan triggered interleukin-1β (IL-1β) mediated cellular response in human primary macrophages via dectin-1 signaling . Earlier in vitro studies showed that yeast β-glucan is a strong stimulant of macrophages  and induced mitogenic activity in rat thymocytes, indicating immunostimulatory effects .

Clinical trials with other dietary yeast β-glucans

A search for other placebo-controlled human trials performed with β-glucans derived from yeast (Saccharomyces) in the field of respiratory tract infection or common cold was performed in PubMed database. The main search terms were “controlled clinical trial” AND, “common cold OR respiratory tract infection” in combination with “β-glucan AND yeast”. Apart from the clinical trials performed with Yestimun®, we found nine other studies that fit our search criteria . The publications by Babineau et al. and Dellinger et al.  will not be discussed further, since the β-glucans were applied intravenously and not orally, to a group of high-risk surgical patients.

Conclusion

Many investigations on the immunomodulatory effects of β-glucans were performed using parenteral applications. In the meantime, those effects have also been shown for orally applied β-glucans. Therefore immune stimulating effects may be achieved by dietary intake of yeast β-glucans. Despite those positive effects the European Food Safety Authority did not accept health claim applications of β-glucans in the area immune system. Based on several weaknesses regarding study design and statistical evaluations the panel concluded that a cause and effect relationship has not been established.

All the performed human clinical trials demonstrated that intake of β-glucans isolated from brewers’ yeast is very well tolerated. Based on the clinical trials presented in this review, an increased intake of dietary β-glucans might help to improve immune functions.