The complexities of the immune system make measuring the impact of dietary interventions upon its function challenging. The immune system is highly responsive to environmental influences, including the diet. An individual's diet provides the energy required to mount a strong and protective immune response, the building blocks required for synthesis of immune mediators such as antibodies and cytokines, and can also indirectly affect immune function via changes in the gut microbiome. Immune function varies across the lifecourse, with a well understood decline in immune function with age, resulting in impaired vaccination responses and an increased risk of infections and of severe complications and mortality arising from common communicable diseases such as influenza. This impaired immunity with ageing is known as immunosenescence and this affects both innate and acquired arms of the immune system.
Expert guidance is available to inform the design of human nutrition trials to ensure they include the most relevant immunological outcomes (Albers, 2013). In this study, ex vivo phagocytosis and oxidative burst of immune cells will be the primary outcome, supported by other ex vivo immune measures of high clinical relevance including functional assessment of cytokine production and expression of activation markers. Human nutritional trials frequently omit to monitor the degree of immunosenescence in participants, even amongst studies conducted amongst older adults. For example, a recent review of pre- and probiotic trials which assessed immune responses in older adults identified that only two of thirty-six studies assessed any marker of immunosenescence (Childs \& Calder, 2017). Taxifolin/DHQ is a naturally occurring polyphenol found in apples, onions and other fruits and bark extracts. Ergothioneine is an amino acid found in mushrooms, oats and some bean varieties. We hypothesise that Taxifolin/DHQ and/or Ergothioneine will alter immune function via their established antioxidant effects, and that the effects observed will vary between older adults relative to their degree of immunosenescence. Though current dietary guidelines advise consumption of 5 portions of fruits and vegetables per day, recent surveys reveal that fewer than 30% of adults achieve this. Antioxidants found within fruits and vegetables are understood to be one of the important aspects by which our diet can influence health. It is important to investigate the effects of such antioxidants through well designed and conducted human trials.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
90
A naturally occurring polyphenol found in apples, onions and other fruits and bark extracts.
An amino acid found in mushrooms, oats and some bean varieties.
Microcrystalline cellulose.
NIHR Southampton Biomedical Research Centre
Southampton, Hampshire, United Kingdom
Phagocytosis activity by granulocytes ex vivo
Mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 8 weeks post intervention
Percentage phagocytosis by monocytes ex vivo
Percentage of cells undergoing phagocytosis will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Phagocytosis activity by monocytes ex vivo
Mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Percentage phagocytosis by granulocytes ex vivo
Percentage of cells undergoing phagocytosis will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Phagocytosis activity by granulocytes ex vivo
Mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 4 weeks, 3 months post intervention
Percentage oxidative burst by monocytes ex vivo
Percentage of cells undergoing oxidative burst will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Oxidative burst activity by monocytes ex vivo
Mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Percentage oxidative burst by granulocytes ex vivo
Percentage of cells undergoing oxidative burst will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Oxidative burst activity by granulocytes ex vivo
Mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Frequencies of naive T cells
The proportion of naive T cells will be assessed by flow cytometry.
Time frame: 8 weeks
Frequencies of memory T cells
The proportion of memory T cells will be assessed by flow cytometry.
Time frame: 8 weeks
CD57 expression upon T cells.
The proportion of T cells expressing CD57 (a marker associated with chronic immune activation) and the mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 8 weeks
CD28 expression upon T cells.
The proportion of T cells expressing CD28 (a cell surface marker required for T cell activation and survival) and the mean fluorescence intensity per cell will be assessed by flow cytometry.
Time frame: 8 weeks
Plasma lipid peroxides
Participant plasma lipid peroxides will be measured by colorimetric analysis.
Time frame: 8 weeks
Urinary isoprostanes
Participant urinary isoprostanes will be measured by commercially available ELISA.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Plasma isoprostanes
Participant plasma isoprostanes will be measured by commercially available ELISA.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Cytokine production by cryopreserved peripheral blood mononuclear cells in response to lipopolyssaccharide
A panel of pro- and anti-inflammatory cytokines secreted by immune cells ex vivo will be assessed by Luminex array.
Time frame: 4 weeks, 8 weeks
Cytokine production by cryopreserved peripheral blood mononuclear cells in response to influenza or coronavirus vaccine products
A panel of pro- and anti-inflammatory cytokines secreted by immune cells ex vivo will be assessed by Luminex array.
Time frame: 4 weeks, 8 weeks
Metabolomic analysis of urine samples
Full metabolic profiling of first-morning urine samples will be used to assess changes to metabolic activity of participants and their microbiome.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Metabolomic analysis of serum samples
Full metabolic profiling of serum samples will be used to assess changes to metabolic activity of participants.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Faecal microbiome analysis
Sequences of ribosomal RNA (rRNA) in participant faecal samples will be measured to assess changes in the numbers or proportions of bacterial genera and species/strains.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Incidence of self-reported seasonal cold, coronavirus and influenza-like illness.
A daily online form will be completed by participants to log any seasonal cold, coronavirus and influenza-like illness.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Duration of self-reported illness.
A daily online form will be completed by participants to log any self-reported illness.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Severity of self-reported illness.
A daily online form will be completed by participants to log any self-reported illness.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
Self-reported medication use.
A daily online form will be completed by participants to log any medication use.
Time frame: 4 weeks, 8 weeks, 3 months post intervention
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