ADAPT: Efficacy of a Dietary Supplement to Increase Resilience and Inhibit the Oxidative Stress Response During and After Exercise
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Aberdeen
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Markers of Oxidative Stress
Study Overview
Brief Summary
Since 1948, health has been defined as "a state of complete physical, mental and social well-being, and not merely the absence of disease and infirmity" . However, a growing school of thought suggests that health represents an ability to be adaptable and flexible in response to daily stressors. It has been proposed that instead, the view of health should be "towards the ability to adapt and self-manage in the face of social, physical and emotional challenges", which has been termed "resilience".
The theory of "resilience" relates health to the body's capacity to manage daily stressors (such as physical activity or oxidative fluctuations) that challenge homeostasis, with the return to homeostasis resulting from several physiological stress responses. Although this is an all-encompassing model, and the effects of pathogens and other stress factors are also relevant, this study will centre on the physiological aspects on this theory, focussing on the disruption through exercise.
Detailed Description
The Nrf-2 pathway is the major cellular defence against oxidative and electrophilic stresses. Briefly, following dissociation from Keap1 (a scaffolding protein which binds Nrf2 and Cul3 ubiquitin ligase for proteasome degradation), Nrf-2 accumulates in the nucleus where it activates the antioxidant response element (ARE) in the promoter region of many antioxidant genes, including catalase, glutathione peroxidases (GPX), and superoxide dismutase (SOD). As such, it is an attractive target for both dietary and pharmacological interventions aiming to increase resilience to oxidative stress. Most diet-derived bioactive Nrf-2 inducers contain Michael acceptor groups (an α, β-unsaturated carbonyl moiety). Curcumin, for example, contains two Michael acceptor groups and is a known activator of Nrf-2. An additional bioactive with a Michael accepter group is trans-cinnamaldehyde (CA) (a component found in the stem bark of Cinnamomum cassia), which, like curcumin, is an Nrf-2 activator in a dose-dependent manner.
Therefore, the purpose of this study will be to assess the effect of bioactive Nrf-2 inducers, based on the presence of an α, β-unsaturated carbonyl moiety, on resilience markers such as antioxidant enzyme activities and markers of oxidative stress, such as TBARS, to an exercise challenge. The hypothesis is that specific plant bioactive increase the production of antioxidant enzyme activities at baseline, and thereby decrease levels of TBARS upon an exercise challenge. Ultimately, the use of novel resilience markers and signatures could significantly improve the ability to prove the efficacy by which pro-oxidant dietary bioactive improve lifelong health, as well as targeting those with lowest resilience as a way to make best use of limited healthcare resources.
The intervention supplement will consist of a mix of dietary bioactive with an α, β-unsaturated carbonyl moiety (provided in individual capsules), of which the efficacy to beneficially affect platelet activity, with and without a H2O2 (Hydrogen Peroxide) challenge, was recently established: sulforaphane (SUL), green tea extract (epigallocatechin gallate) (EGCG) and cinnamaldehyde (Cin).
It is intended to use a mix of dietary bioactive for the proposed human intervention study, as different compounds could affect multiple pathways and therefore, have a broader efficacy. In addition, bioavailability of compounds may be influenced by presence of other compounds, as has been suggested in the literature (effect of piperine on EGCG bioavailability).
Bioavailability data for each of these compounds were extracted from the literature and these have been used, alongside practical considerations, to decide on the dosing strategy. The desired composition of the supplement mix has been set as follows:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy, recreationally active men and women aged 18-25 BMI 18.5-30
- •Healthy, recreationally active men and women aged 50-75 BMI 18.5-30
Exclusion Criteria
- •Physician diagnosed diabetes or chronic disease including asthma
- •Pregnancy
- •Uncontrolled Hypertension
- •Musculo-skeletal problems
- •Use of some dietary supplements (e.g. antioxidants, fish oils, vitamins_
- •Taking of prescription medicines
- •In the 18-25 group, Physical Activity levels below moderate (Moderate = greater than 2.5 and less than 5.0 hrs /week including 0.5-1.5 hr/week moderate to intense exercise)
- •In the 50-75 group, activity levels below the minimal recommendations for daily physical activity (less than 30 min/day, 5 days/week)
- •Participation in another research study
- •Not being able to speak or understand English
Arms & Interventions
Intervention
For presentation to volunteers, the daily capsules will be divided into two servings, one serving to be taken in the morning with breakfast, and one serving to be taken in the evening with dinner. Each serving containing 5 capsules, as follows:
- EnduraCell broccoli sprout powder: 3 capsules
- Bulk Powders Green tea extract: 1 capsule
- Bulk Powders Cinnamon Bark Extract: 1 capsule to be taken for two days prior to the study supervised exercise period and then one dose taken on the morning of the exercise test with the first meal
Intervention: Intervention (Dietary Supplement)
Placebo
5 capsules of placebo (microcrystalline cellulose) taken once in the morning with breakfast and once in the evening with dinner for two days prior to the study supervised exercise period and then one dose taken on the morning of the exercise test with the first meal
Intervention: Placebo (Dietary Supplement)
Outcomes
Primary Outcomes
Markers of Oxidative Stress
Time Frame: 18months
Plasma TBARS:Plasma TBARS will be measured by HPLC (High Performance Liquid Chromatography).
Secondary Outcomes
- Plasma Tumour-Necrosis Factor - alpha (TNF-α)(18months)
- Antioxidant enzyme activity(18months)
- Marker of Oxidative Stress(18months)
- Markers of Inflammation(18months)
- Plasma Interleukin-6 (IL-6)(18months)
- Plasma non-esterified fatty acids (NEFA)(18months)
- Counter Movement Jump(18months)
- Metabolic risk markers(18months)
- Plasma glucose(18months)
- Markers of platelet function(18 months)
- Markers of muscle damage(18 months)
- Subjective Ratings(18months)
- Wellness Questionnaire(18months)
- Perceived Soreness of quadriceps(18months)
- Perceived Exhaustion(18months)