A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Eligibility Criteria
2.3. The Intervention
2.4. Procedures
2.5. Blinding
2.6. Outcome Measures: Blood Biomarker Assessments
2.7. Outcome Measures: Epigenetics
2.8. Statistical Analysis
3. Results
3.1. Study Cohort
3.2. Outcomes: Blood Biomarker Assessments
3.3. Outcomes: Epigenetics
3.4. Safety and Tolerability
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sites Analysed | Gene |
---|---|
cg10501210 | C1orf132 |
cg24724428 | ELOVL2 |
cg10804656 | Island (intergene) |
cg10604476 | ICAM5 |
cg11705975 | PRLHR |
cg12934382 | GRM2 |
cg07553761 | TRIM59 |
cg16867657 | ELOVL2 |
cg13108341 | DNAH9 |
Active/Placebo | Placebo/Active | Total | |
---|---|---|---|
Sex | |||
Female | 7 (46.7) | 9 (60.0) | 16 (53.3) |
Male | 8 (53.3) | 6 (40.0) | 14 (46.7) |
Age, years | 66.5 (8.2) | 67.5 (6.9) | 67.0 (7.5) |
BMI, kg/m2 | 29.2 (3.4) | 28.2 (2.5) | 28.7 (3.0) |
HbA1c, mmol/mol | 38.4 (3.5) | 41.7 (8.5) | 40.0 (6.6) |
Glucose, mmol/L | 6.4 (1.6) | 6.4 (1.9) | 6.4 (1.7) |
Cholesterol | |||
HDL, mmol/L | 1.3 (0.4) | 1.4 (0.3) | 1.4 (0.4) |
LDL, mmol/L | 3.8 (1.5) | 4.0 (1.2) | 3.9 (1.4) |
Active/Placebo | Placebo/Active | Total | |
---|---|---|---|
NAD+ (µM) | 23.8 (5.2) | 25.5 (4.9) | 24.6 (5.0) |
CD38 (µM) | 128.7 (41.3) | 110.5 (32.4) | 119.6 (37.6) |
TAC (µM) | 181.5 (28.6) | 175.0 (28.0) | 178.3 (28.0) |
IL-6 (pg/mL) | 1.3 (1.0) | 0.8 (0.7) | 1.0 (0.9) |
IL-8 (pg/mL) | 8.5 (2.2) | 7.1 (2.7) | 7.8 (2.5) |
IL-10 (pg/mL) | 6.3 (4.4) | 2.9 (3.7) | 4.6 (4.3) |
TNF-α (pg/mL) | 20.4 (10.3) | 16.8 (7.1) | 18.6 (8.9) |
Protein carbonyl (nmol/mg) | 103.8 (30.5) | 108.6 (32.2) | 106.2 (30.9) |
4-HNE (pg/mL) | 27,367.1 (19,872.1) | 20,620.1 (8292.1) | 23,993.6 (15,349.5) |
Baseline | At One Week | Difference | p-Value | Adj. p-Value | ||
---|---|---|---|---|---|---|
Main outcomes | ||||||
NAD+ | Active | 23.7 (4.4) | 23.3 (3.6) | 0.4 (3.8) | 0.600 | 0.936 |
Placebo | 24.3 (4.1) | 23.7 (3.8) | 0.6 (3.1) | 0.309 | 0.936 | |
CD38 | Active | 123.6 (34.8) | 121.1 (31.9) | 2.6 (27.2) | 0.610 | 0.857 |
Placebo | 116.4 (32.7) | 124.2 (34.7) | −7.8 (20.6) | 0.046 | 0.215 | |
Secondary outcomes | ||||||
TAC | Active | 180.2 (22.0) | 170.7 (25.9) | 9.5 (28.1) | 0.076 | 0.218 |
Placebo | 176.4 (25.4) | 181.5 (50.8) | −5.2 (50.0) | 0.576 | 0.849 | |
IL-6 | Active | 1.1 (1.0) | 1.4 (2.2) | −0.3 (2.1) | 0.368 | 0.611 |
Placebo | 1.1 (0.9) | 1.3 (1.4) | −0.2 (1.6) | 0.479 | 0.611 | |
IL-8 | Active | 7.6 (2.4) | 8.3 (3.3) | −0.6 (3.1) | 0.282 | 0.645 |
Placebo | 7.3 (2.5) | 7.5 (2.4) | −0.1 (2.0) | 0.711 | 0.467 | |
IL-10 | Active | 4.6 (4.4) | 4.3 (4.2) | 0.3 (2.6) | 0.510 | 0.223 |
Placebo | 4 (4.1) | 3.9 (4.5) | 0.1 (1.3) | 0.606 | 0.223 | |
TNF-α | Active | 15.8 (9.3) | 16.5 (9.3) | −0.7 (4.8) | 0.443 | 0.435 |
Placebo | 17.8 (9.3) | 16 (8.6) | 1.8 (5.2) | 0.073 | 0.009 | |
Protein carbonyl | Active | 110.7 (26.8) | 104.5 (23.0) | 6.2 (33.3) | 0.315 | 0.966 |
Placebo | 104.9 (27.5) | 106.3 (26.1) | −1.3 (26.6) | 0.787 | 0.636 | |
4-HNE | Active | 25,593.8 (16,185.3) | 26,231.7 (16,413.5) | −637.9 (7937.9) | 0.663 | 0.074 |
Placebo | 23,210.5 (12,309.6) | 21,791.1 (10,535.9) | 1419.3 (10,453.7) | 0.463 | 0.299 |
NAD+ | CD38 | ||||
---|---|---|---|---|---|
Time | Treatment | Difference | p-Value | Difference | p-Value |
T0 vs. T1 | Active | −0.50 (0.6) | 0.936 | - | - |
T0 vs. T2 | Active | −0.82 (0.6) | 0.936 | - | - |
T0 vs. T24 | Active | −0.32 (0.6) | 0.936 | −8.47 (5.4) | 0.215 |
T0 vs. T1 | Placebo | 0.19 (0.6) | 0.943 | - | - |
T0 vs. T2 | Placebo | 0.16 (0.6) | 0.943 | - | - |
T0 vs. T24 | Placebo | −0.06 (0.6) | 0.963 | −16.88 (5.4) | 0.019 |
Sequence | Side Effects Week 1 | Side Effects Week 2 |
---|---|---|
Active/Placebo | Bloated all week, stomach-ache morning of day 2, itchy skin every day from day 2 (cold with a temperature on days 4 and 5) | Loose stools, diarrhoea |
Placebo/Active | Bloating, heartburn | Bloating, headache, temperature, nausea, diarrhoea |
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Chong, J.R.; de Lucia, C.; Tovar-Rios, D.A.; Castellanos-Perilla, N.; Collins, C.; Kvernberg, S.M.; Ballard, C.; Siow, R.C.; Aarsland, D. A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing. Antioxidants 2024, 13, 995. https://doi.org/10.3390/antiox13080995
Chong JR, de Lucia C, Tovar-Rios DA, Castellanos-Perilla N, Collins C, Kvernberg SM, Ballard C, Siow RC, Aarsland D. A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing. Antioxidants. 2024; 13(8):995. https://doi.org/10.3390/antiox13080995
Chicago/Turabian StyleChong, Joyce Ruifen, Chiara de Lucia, Diego Alejandro Tovar-Rios, Nicolas Castellanos-Perilla, Christopher Collins, Silje Meihack Kvernberg, Clive Ballard, Richard C. Siow, and Dag Aarsland. 2024. "A Randomised, Double-Blind, Placebo-Controlled, Cross-Over Clinical Trial to Evaluate the Biological Effects and Safety of a Polyphenol Supplement on Healthy Ageing" Antioxidants 13, no. 8: 995. https://doi.org/10.3390/antiox13080995