Antioxidative Stress, Cold, Influenza, Aging, Inflammation
Conditions
Keywords
Phagocytosis, Immunosenecence, Cytokine, Antioxidant, Metabolome, Microbiome
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTTaxifolin
A naturally occurring polyphenol found in apples, onions and other fruits and bark extracts.
DIETARY_SUPPLEMENTErgothioneine
An amino acid found in mushrooms, oats and some bean varieties.
DIETARY_SUPPLEMENTControl
Microcrystalline cellulose.
Sponsors
Blue California
University of Southampton
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Alphabetically labelled treatments, with de-blinding envelope held by an independent researcher at the University of Southampton.
Intervention model description
A n=90 study (3 treatment arms, each n=30) providing participants with either 250mg/day Taxifolin/DHQ, 80mg/day Ergothioneine, or control.
Eligibility
Sex/Gender
ALL
Age
50 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* age 50-65yr * BMI 18.5-30kg/m2 * Willing to avoid consumption of foods rich in Taxifolin/DHQ and Ergothioneine during the study period * Willing to avoid taking any other food supplements or high doses of vitamins during the study period * Able to provide written informed consent.
Exclusion criteria
* Use of prescription medication which may influence immune function, such as anti-inflammatory or immunosuppressant medication * Diabetes requiring any medication * Liver cirrhosis * A history of drug or alcohol misuse * Asplenia or other acquired or congenital immunodeficiencies * Any autoimmune disease including connective tissue diseases * Malignancy * Laboratory confirmed SARS-CoV-2 infection within last 3 months * self-reported symptoms of acute or recent infection (including use of antibiotics within the last 3 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phagocytosis activity by granulocytes ex vivo | 8 weeks post intervention | Mean fluorescence intensity per cell will be assessed by flow cytometry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phagocytosis activity by monocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Mean fluorescence intensity per cell will be assessed by flow cytometry. |
| Percentage phagocytosis by granulocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Percentage of cells undergoing phagocytosis will be assessed by flow cytometry. |
| Phagocytosis activity by granulocytes ex vivo | 4 weeks, 3 months post intervention | Mean fluorescence intensity per cell will be assessed by flow cytometry. |
| Percentage oxidative burst by monocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Percentage of cells undergoing oxidative burst will be assessed by flow cytometry. |
| Oxidative burst activity by monocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Mean fluorescence intensity per cell will be assessed by flow cytometry. |
| Percentage oxidative burst by granulocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Percentage of cells undergoing oxidative burst will be assessed by flow cytometry. |
| Oxidative burst activity by granulocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Mean fluorescence intensity per cell will be assessed by flow cytometry. |
| Frequencies of naive T cells | 8 weeks | The proportion of naive T cells will be assessed by flow cytometry. |
| Frequencies of memory T cells | 8 weeks | The proportion of memory T cells will be assessed by flow cytometry. |
| CD57 expression upon T cells. | 8 weeks | 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. |
| CD28 expression upon T cells. | 8 weeks | 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. |
| Percentage phagocytosis by monocytes ex vivo | 4 weeks, 8 weeks, 3 months post intervention | Percentage of cells undergoing phagocytosis will be assessed by flow cytometry. |
| Urinary isoprostanes | 4 weeks, 8 weeks, 3 months post intervention | Participant urinary isoprostanes will be measured by commercially available ELISA. |
| Plasma isoprostanes | 4 weeks, 8 weeks, 3 months post intervention | Participant plasma isoprostanes will be measured by commercially available ELISA. |
| Cytokine production by cryopreserved peripheral blood mononuclear cells in response to lipopolyssaccharide | 4 weeks, 8 weeks | A panel of pro- and anti-inflammatory cytokines secreted by immune cells ex vivo will be assessed by Luminex array. |
| Cytokine production by cryopreserved peripheral blood mononuclear cells in response to influenza or coronavirus vaccine products | 4 weeks, 8 weeks | A panel of pro- and anti-inflammatory cytokines secreted by immune cells ex vivo will be assessed by Luminex array. |
| Metabolomic analysis of urine samples | 4 weeks, 8 weeks, 3 months post intervention | Full metabolic profiling of first-morning urine samples will be used to assess changes to metabolic activity of participants and their microbiome. |
| Metabolomic analysis of serum samples | 4 weeks, 8 weeks, 3 months post intervention | Full metabolic profiling of serum samples will be used to assess changes to metabolic activity of participants. |
| Faecal microbiome analysis | 4 weeks, 8 weeks, 3 months post intervention | 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. |
| Incidence of self-reported seasonal cold, coronavirus and influenza-like illness. | 4 weeks, 8 weeks, 3 months post intervention | A daily online form will be completed by participants to log any seasonal cold, coronavirus and influenza-like illness. |
| Duration of self-reported illness. | 4 weeks, 8 weeks, 3 months post intervention | A daily online form will be completed by participants to log any self-reported illness. |
| Severity of self-reported illness. | 4 weeks, 8 weeks, 3 months post intervention | A daily online form will be completed by participants to log any self-reported illness. |
| Self-reported medication use. | 4 weeks, 8 weeks, 3 months post intervention | A daily online form will be completed by participants to log any medication use. |
| Plasma lipid peroxides | 8 weeks | Participant plasma lipid peroxides will be measured by colorimetric analysis. |
Countries
United Kingdom
Outcome results
None listed