Applied nutritional investigationInfluence of yeast-derived 1,3/1,6 glucopolysaccharide on circulating cytokines and chemokines with respect to upper respiratory tract infections
Introduction
Upper respiratory tract infection (URTI) is the most frequent infectious disease in humans, with an average of two to four episodes per year in adulthood and 6 to 10 episodes per year in childhood [1], [2]. Often referred to as the “common cold,” there are 100 to 400 viruses that have been implicated in the onset of symptoms such as a runny nose, a sore throat, nasal congestion, fever, and headache [3], [4]. The common cold is usually self-limiting but carries a risk of secondary bacterial infection and morbidity and has an enormous impact on socioeconomic performance [5], [6]. According to data from the USA, there are approximately 500 million non–influenza-related URTI episodes per year, with an estimated annual economic impact of $40 billion [5]. Therefore, strategies to decrease the frequency and severity of URTI symptoms and to decrease physician attendance would have a highly beneficial impact on health and socioeconomic performance. The control of infectious disease often has been targeted by vaccine approaches facilitating an adaptive immune response. Efforts to create a vaccine against the common cold have failed thus far and remain a distant possibility because of the heterogeneity of causal viruses that are also capable of seasonal mutation [3]. Non-prescription medications such as decongestants and cough suppressors may decrease the severity of some cold symptoms but do not decrease the frequency or duration of illness, and some have been associated with undesirable side effects [7], [8], [9]. Various nutritional and herbal supplements such as zinc, vitamin C, and Echinacea have shown promise, yet studies have suggested that no supplement confers a reliable and clinically relevant protection against URTI symptoms [10], [11], [12], [13], [14].
The innate immune system is essential for the initial detection and control of invading viruses and bacteria and for the subsequent activation of adaptive immunity. Rapid and non-specific recognition occurs by pathogen-associated molecular patterns and complement binding [15]. Novel strategies have focused on the biological response modifiers of the innate immune system to support resistance to viral and bacterial infection. This approach is highly appealing because it has the benefit of potentially conferring non-specific protection to a wide variety of pathogens without the need for a diagnosis of the specific causal virus to determine a treatment strategy and may confer an ability to prevent and treat infection. Wellmune WGP contains a highly refined 1,3/1,6 glucopolysaccharide (also referred to as 1,3/1,6 β-glucan) derived from the cell wall of baker’s yeast (Saccharomyces cerevisiae). This glucopolysaccharide has previously demonstrated an ability to increase the antimicrobial response of human innate immune cells in vitro [16], [17], [18], [19] and increase the survival in animals challenged with a variety of pathogens in vivo [20], [21], [22]. A mechanism of action has been defined for 1,3/1,6 glucopolysaccharide to increase the immune response by a priming of complement receptor-3 (also known as CD11b/CD18), which is found on innate immune cells such as neutrophils, macrophages, and natural killer cells. Complement receptor-3 interacts with the complement protein (C3b) that is bound to pathogenic targets and to non-self carbohydrate structures such as 1,3/1,6 glucopolysaccharide, in a process capable of inducing phagocytosis [23], [24]. Therefore, priming innate immune cells with 1,3/1,6 glucopolysaccharide has the potential to improve the antimicrobial activity against opsonized foreign challenges [24].
Previous randomized, double-blinded, placebo-controlled clinical trials of 1/3,1/6 glucopolysaccharide have demonstrated an increased resistance to postoperative infection [25] and a decreased frequency of URTI symptoms in moderately stressed individuals [26] and in physically challenged groups such as marathon runners during the 4-wk period after a race [27]. A significant improvement in psychological mood state has also been noted [26], [27]. However, further studies are required to evaluate the efficacy of 1,3/1,6 glucopolysaccharide on infection. In the present study, we tested the hypothesis that 1,3/1,6 glucopolysaccharide (in the form of Wellmune WGP, a commercially available product with generally recognized as safe recognition [28]) can decrease the frequency, duration, and severity of URTI symptoms over a 90-d period during the winter months. We also monitored plasma cytokine and chemokine profiles.
Section snippets
Study design, subjects and sample collection
The study was a double-blind, randomized placebo-controlled trial of 1/3,1/6 glucopolysaccharide (in the form of Wellmmune WGP, Biothera, Inc., Eagen, Minnesota, USA; 250 mg/d, n = 50 subjects) versus rice flour as a placebo (n = 50 subjects). Previous research in marathon runners did not show a significant difference in outcomes with 250 versus 500 mg/d [27]; therefore, the lower dose was selected for this study. The study was approved by the Berkshire research ethics committee and all
Subject characteristics
One hundred male and female subjects 18 to 65 y old were recruited into the study from the Southampton University Medical School. Ninety-nine participants were 18 to 30 y old and one participant was 50 y old. Table 1 lists the characteristics of subjects in each group at study entry. There were no differences between the two groups in any of these characteristics. Figure 1 shows the flow of subjects through the study. Fifty subjects were randomized to each arm of the study. Three subjects were
Discussion
Viral URTI is a leading cause of lost work and school days, with a considerable impact on health and socioeconomic performance [1], [5], [6]. Despite the common nature of this problem, it remains a medical challenge to decrease the frequency, duration, and severity of episodes [3]. The present study of a healthy student population taking Wellmune 250 mg/d demonstrated a tendency to a decreased number of days with cold or flu symptoms (18% less) compared with placebo (P = 0.06). This finding is
Conclusion
Wellmune WGP was well tolerated and tended to decrease the number of days with reported cold and flu symptoms (P = 0.06) compared with placebo. Further studies are warranted to clarify the potential role of this food supplement to increase the innate immune response and decrease the burden of viral URTI.
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Cited by (0)
This study was funded by a grant from Biothera, Inc., the manufacturer of Wellmune WGP.