Pomegranate Extract and Inflammageing

Study Overview
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Brief Summary
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The growing ageing population has resulted in an increase in the prevalence of frailty, cognitive disorders and cardiovascular diseases, representing a major cause of disability in older adults. Inflammation has been suggested as a pivotal factor leading to these disorders and is exacerbated by obesity. Polyphenols are antioxidants and anti-inflammatory agents that have been previously linked to a decrease in inflammation and cardiometabolic risk factors and an improvement in physical and cognitive function, yet research remain limited and inconclusive. This study aims to assess the effect of daily pomegranate extract supplementation on inflammatory response, cognitive and physical function and cardiometabolic risk factors in older adults. Seventy-one normal weight and overweight participants (60-70 years) will be assigned to consume either pomegranate extract capsules or placebo capsules for 12 weeks. Anthropometric measures (weight, height, waist circumference and hip circumference), body composition, blood pressure and a fasted venous blood sample will be collected during each visit at baseline, week 6 & week 12. Participants will also undergo computerised cognitive tests and physical function tests. Inflammatory markers, telomerase activity, serum glucose and lipid levels will be analysed. Diet diaries will be collected 3 times (at baseline, week 6 & week 12) during the intervention. This study will help elucidate the effects of pomegranate supplementation and inform future longitudinal trials looking at the combination of antioxidants and other lifestyle factors (such as physical activity) on the promotion of well-being and healthy ageing.

Detailed Description
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After signing an informed consent, participants will be asked to attend the Physiology Lab at Manchester Metropolitan University at baseline, week 6 and week 12. Anthropometric measures (weight, height, waist circumference and hip circumference) will be collected during each visit, and body composition will be measured using air displacement plethysmography (BOD POD®). Blood pressure will be measured 3 times after a 10-minute rest based on the World Health Organisation (WHO) protocol and a fasted venous blood sample (20 ml) will be collected. Participants will then undergo physical assessment tests (to assess isokinetic knee extension, isokinetic knee flexion, standing balance, gait speed, and chair sit to stand) and computerised cognitive tests (to assess executive function, memory, vigilance and attention). Participants will also answer a general demographic and lifestyle questionnaire during the first visit. To control for changes in the diet, they will be asked to fill a paper-based 3-day food diary 3 times (at baseline, week 6 & week 12) during the intervention. Food diaries will be analysed using Nutritics (v.4) dietary analysis software.

Official Title
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Effects of Pomegranate Extract on Inflammatory Markers, Physical and Cognitive Function and Cardiometabolic Risk Factors in Older Adults: A Randomized Parallel Trial

Conditions
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Aging

Intervention / Treatment
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* Dietary Supplement: Pomegranate extract
* Dietary Supplement: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60-70 years; Normal weight (BMI 18.5-24.9 Kg/m2) and overweight (BMI 25- 29.9 Kg/m2); All genders; No diagnosed metabolic diseases. Exclusion Criteria: Participants who have been on a weight loss regimen over the past 2 months, those with diagnosed chronic disease (diabetes, cardiovascular disease (CVD), renal disease etc…) or taking any medications that could modulate inflammation (statins etc..).

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two-arm double blind parallel trial where participants will be randomly assigned to receive either placebo capsules (control) or pomegranate extract capsules (500mg) for 12 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>Capsules with no pomegranate extract One capsule to be administered once a day for 12 weeks. | Dietary Supplement: Control<br>* One capsule of containing no pomegranate extract will be taken daily at any time of the day for a period of 12 weeks.<br>|
| Experimental: Intervention<br>Capsules with 500 mg of pomegranate extract One capsule to be administered once a day for 12 weeks. | Dietary Supplement: Pomegranate extract<br>* One capsule of pomegranate extract (500 mg) will be taken daily at any time of the day for a period of 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin-6 (IL-6) levels | Changes in IL-6 levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRP (C-reactive protein) levels | Changes in CRP levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Interleukin 1 (IL-1) levels | Changes in IL-1 levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Interleukin 2 (IL-2) levels | Changes in IL-2 levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Insulin growth factor-1 (IGF-1) levels | Changes in IGF-1 levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Tumour necrosis factor (TNF-α) levels | Changes in TNF-α levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Plasminogen Activator Inhibitor-1 (PAI-1) levels | Changes in PAI-1 levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Telomerase activity | Changes in telomerase activity will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Corsi block-tapping test | Changes in working memory will be assessed using Corsi block-tapping computerised cognitive test. | Baseline, week 6 & week 12 | 
| Rey Verbal Learning test | Changes in working memory will be assessed using Rey Verbal Learning computerised cognitive test. | Baseline, week 6 & week 12 | 
| Tower of Hanoi test | Changes in executive function will be assessed using Tower of Hanoi computerised cognitive test. | Baseline, week 6 & week 12 | 
| Wisconsin test | Changes in executive function will be assessed using Wisconsin computerised cognitive test. | Baseline, week 6 & week 12 | 
| Stroop test | Changes in executive function will be assessed using Stroop computerised cognitive test. | Baseline, week 6 & week 12 | 
| Digits span test | Changes in working memory will be assessed using Digits span computerised cognitive test. | Baseline, week 6 & week 12 | 
| Hand grip strength | Changes in muscle strength will be assessed using hand grip strength physical test. | Baseline, week 6 & week 12 | 
| isokinetic knee extension | Changes in muscle strength will be assessed using isokinetic knee extension physical test. | Baseline, week 6 & week 12 | 
| Isokinetic knee flexion | Changes in muscle strength will be assessed using isokinetic knee flexion physical test. | Baseline, week 6 & week 12 | 
| Standing balance | Changes in muscle function will be assessed using standing balance physical test. | Baseline, week 6 & week 12 | 
| Gait speed | Changes in muscle function will be assessed using gait speed physical test. | Baseline, week 6 & week 12 | 
| Chair sit to stand | Changes in muscle function will be assessed using chair sit to stand physical test. | Baseline, week 6 & week 12 | 
| Fasting serum glucose levels | Changes in glucose levels will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Fasting lipid levels | Changes in lipid levels (TC, HDL, LDL & TG) will be measured in a fasted blood sample using a commercially available assay kit. | Baseline, week 6 & week 12 | 
| Blood pressure | Changes in blood pressure will be Blood pressure will be measured 3 times after a 10-minute rest based on the WHO protocol. | Baseline, week 6 & week 12 |