Applied nutritional investigationYeast-derived β-1,3/1,6 glucan, upper respiratory tract infection and innate immunity in older adults
Introduction
Upper respiratory tract infection (URTI) is the most frequent infectious illness in humans, with an estimated prevalence of two to four episodes per person per year in adults [1]. Although usually self-limiting, URTIs have marked social and economic consequences due to sickness-related absence, need for caregiving, and primary care attendance [2], [3]. Effective antiviral treatment strategies remain elusive and the wide variety of causal pathogens and associated antigenic shift provide significant challenges to the development of vaccines [4]. Within primary care in the United Kingdom, the proportion of antibiotic prescriptions for cough and cold presentations increased from 39 to 51% between 1999 and 2011 [5], despite considerable attention to appropriate prescribing, with respiratory tract infection reported as the leading indication for antibiotic prescription [6]. Novel strategies to prevent URTIs are urgently required to reduce the burden of infection, associated antibiotic use, and the subsequent development of antimicrobial resistance [7].
Innate immune cells, including neutrophils and macrophages, form the front line of host defense to pathogenic viral and bacterial challenges [8]. Modification at the initial, nonspecific, level of innate immunity may confer benefit in the prevention or amelioration of URTI. Wellmune is a β-1,3/1,6 glucan derived from the cell wall of Saccharomyces cerevisiae (“baker's yeast”). Wellmune has European Food Safety Authority approval for use as a novel food ingredient [9] and is available to the general public as a supplement. Wellmune upregulates phagocytosis and chemotaxis of innate immune cells via priming of lectin-sites on complement-receptor 3 and results in enhanced resistance to infection in animal models [10], [11], [12], [13], [14], [15]. A previous trial with 100 healthy young adults (mean age ∼21 y) conducted during the winter months demonstrated reduction in the concentration of the chemokine monocyte chemoattractant protein (MCP)-1 during symptomatic URTI, a reduction in the total number of days with cold and flu symptoms, and a tendency toward reduced symptom severity in those treated with 250 mg/d Wellmune compared with placebo [16]. Furthermore, a significant reduction in reported URTI symptoms was seen postevent in marathon runners taking Wellmune [17] and in individuals with moderate lifestyle stress [18]. To our knowledge, effects in older people have not been investigated. Therefore, this study investigated the effect of daily Wellmune supplementation on URTIs and selected innate immune markers in older community-dwelling individuals.
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Study design, participants, and sample collection
This study was a randomized double-blind, placebo-controlled trial of 250 mg Wellmune (Biothera, Eagan, MN, USA; n = 50) once daily for 90 d versus an identical-in-appearance rice-flour placebo capsule (n = 50). The study was approved by the South Central Hampshire B Research Ethics Committee, received Clinical Trial Authorization from the Medicines and Healthcare Products Regulatory Agency, and is listed on the European Clinical Trials Database.
Recruitment and study commencement were completed
Participant characteristics
Table 1 lists the characteristics of the 100 participants who entered the study. The groups did not differ according to age or age distribution, sex distribution, weight or BMI, cigarette smoking or recent seasonal influenza vaccination. Figure 1 shows the flow of participants through the study.
Forty-nine participants completed the study in each group and supplementation was well tolerated. One participant in the placebo group left the trial due to constipation as a reported side effect within
Discussion
Finding effective prevention and management strategies for URTI remains an area of unmet health care need. Despite the usually self-limiting nature of illness, the high incidence of URTI causes significant health, social, and economic affects, which was estimated by Fredrick et al. to cost the US economy nearly $40 billion per annum due to use of health care resources and lost productivity [2]. Given the scale of the problem, even interventions with a modest ability to reduce URTI incidence,
Conclusion
Daily supplementation with Wellmune is well tolerated in older community-dwelling individuals and may have a role in the prevention and faster resolution of URTI. This effect may be related to differences in innate immune responses in individuals consuming Wellmune. Larger studies seem warranted to explore the role of Wellmune for the prevention and control of common infections.
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This study was funded by a grant to RF and PCC from Biothera (Eagan, MN, USA), the manufacturer of Wellmune; Biothera is now part of Kerry. RF and PCC designed the study. RF recruited the participants, carried out the intervention, and collected saliva and blood samples under the supervision of MVM and GL. RVO, HLF, and PSN conducted the laboratory analysis under the supervision of PCC. RF and BLS conducted the statistical analysis. RF and PCC drafted the manuscript. All authors had input into the manuscript and approved the final version.