Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Subjects
2.3. Study Variables
2.4. Randomization
2.5. Pharmacological Intervention
2.6. Blinding
2.7. Procedures
2.7.1. Clinical Determinations
2.7.2. Laboratory Determinations
2.7.3. Calculations
2.8. Follow-Up for Treatment Adherence
2.9. Ethical Considerations
2.10. Statistical Analysis
3. Results
3.1. Study Population
3.2. Clinical Results
3.2.1. Primary Outcomes
3.2.2. Secondary Outcomes
3.3. Laboratory Results
3.3.1. Primary Outcomes
3.3.2. Secondary Outcomes
3.4. Adverse Events
4. Discussion
4.1. Abdominal Obesity
4.2. Arterial Hypertension
4.3. Plasma Glucose
4.4. Insulin Sensitivity and Secretion
4.5. Triglicerides
4.6. HDL-c
4.7. Uric Acid
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Selection Criteria |
---|
Inclusion criteria Male and female 30 to 59 years old Diagnosis of MetS according to the International Diabetes Federation criteria [22] Signed informed consent |
Exclusion criteria Prior diagnosis of liver, kidney, pancreas, heart, or thyroid disease T2DM or arterial hypertension History of alcoholism, drug abuse or tobacco use SBP ≥1 40 mmHg and/or DBP ≥90 mmHg Body mass index ≥35.0 kg/m2 Triglycerides ≥ 5.7 mmol/L FPG ≥ 7.0 mmol/L LDL-c > 4.9 mmol/L Body weight variability ≥ 5% throughout the prior last three months Suspected or confirmed pregnancy Lactation Known allergy to any of the interventions Impossibility to swallow capsules Hormonal contraceptive or replacement therapy Physical activity < 3 or >5 metabolic equivalents Pharmacological, dietary, or herbal therapy in the last three months before the trial. |
Elimination criteria Withdrawal of informed consent Intolerance to EA or placebo Loss of follow-up Adherence to treatment < 80% |
Placebo | Ellagic Acid | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | n = 16 | Week 12 | n = 15 | Baseline, | n = 16 | Week 12 | n = 15 | p *** | |
Mean | (SD) | Mean | (SD) | Mean | (SD) | Mean | (SD) | ||
MetS diagnosis criteria | |||||||||
WC, cm | ♂101.4 | (1.1) | ♂ 101.8 | (1.2) | ♂102.2 | (4.2) | ♂99.5 | (3.2) * | 0.010 |
♀ 95.5 | (10.1) | ♀ 96.70 | (10.7) | ♀ 99.8 | (6.7) | ♀ 96.0 | (4.7) ** | 0.011 | |
SBP, mmHg | 112.0 | (10.0) | 112.5 | (6.8) | 118.1 | (10.5) | 113.7 | (7.8) ** | 0.011 |
DBP, mmHg | 74.0 | (5.6) | 74.3 | (5.5) | 77.8 | (7.8) | 75.2 | (5.8) ** | 0.013 |
FPG, mmol/L | 6.2 | (0.6) | 6.4 | (0.6) | 6.5 | (0.5) | 5.7 | (0.6) ** | 0.001 |
TG, mmol/L | 2.7 | (0.8) | 3.1 | (1.1) * | 2.8 | (1.1) | 2.1 | (0.7) ** | 0.001 |
HDL-c, mmol/L | ♂ 0.7 | (0.1) | ♂ 0.7 | (0.1) | ♂ 0.7 | (0.2) | ♂ 0.8 | (0.2) * | 0.019 |
♀ 0.8 | (0.2) | ♀ 0.8 | (0.2) | ♀ 0.8 | (0.2) | ♀ 0.9 | (0.2) | 0.175 | |
Insulin sensitivity | |||||||||
Matsuda index | 1.8 | (0.4) | 1.6 | (0.5) | 1.7 | (0.8) | 3.1 | (1.7) ** | 0.001 |
Insulin secretion | |||||||||
1p Stumvoll index | 1494 | (679) | 1568 | (831) | 1573 | (714) | 1191 | (614) * | 0.011 |
Ratio AUC | 72 | (31) | 73 | (31) | 69 | (31) | 58 | (32) * | 0.091 |
Placebo | Ellagic Acid | ||||||||
---|---|---|---|---|---|---|---|---|---|
Baseline | n = 16 | 12-w | n = 15 | Baseline | n = 16 | 12-w | n = 15 | ||
Mean | (SD) | Mean | (SD) | Mean | (SD) | Mean | (SD) | p *** | |
Clinical outcomes | |||||||||
BW, kg | 77.6 | (3.4) | 78.5 | (3.8) | 79.9 | (7.1) | 78.6 | (6.6) * | 0.001 |
BMI, kg/m2 | 30.8 | (1.6) | 31.2 | (2.0) | 30.6 | (2.6) | 30.1 | (2.8) * | 0.001 |
Laboratory outcomes | |||||||||
2h-PG, mmol/L | 8.8 | (1.8) | 9.7 | (1.8) | 9.4 | (1.6) | 7.9 | (1.6) ** | 0.001 |
Glucose AUC, mmol/L/min | 1150 | (198) | 1278 | (176) * | 1219 | (195) | 1089 | (159) ** | 0.001 |
FPI, pmol/L | 133.4 | (38.4) | 142.7 | (50.8) | 153.1 | (66.7) | 93.3 | (43.0) ** | 0.001 |
Insulin AUC pmol/L/min | 80593 | (32748) | 83871 | (41430) * | 92678 | (38379) | 63447 | (37072) ** | 0.001 |
TC, mmol/L | 5.0 | (0.9) | 5.1 | (0.9) | 5.1 | (1.0) | 4.7 | (1.0) | 0.073 |
Uric acid, µmol/L | 336.1 | (66.3) | 348.9 | (63.7) | 357.3 | (68.4) | 344.2 | (53.1) * | 0.002 |
Placebo Group | EA Group | Mean Difference | 95% CI | p | ||
---|---|---|---|---|---|---|
Lower | Upper | |||||
MetS diagnosis criteria | ||||||
WC, cm | 0.200 | −2.533 | 2.733 | 1.537 | 3.930 | 0.010 |
SBP, mmHg | −0.067 | −4.933 | 4.867 | 1.256 | 8.478 | 0.011 |
DBP, mmHg | −0.400 | −3.133 | 2.733 | 0.611 | 4.855 | 0.013 |
FPG, mmol/L | 0.212 | −0.792 | 1.004 | 0.615 | 1.393 | 0.001 |
TG, mmol/L | 0.480 | −0.733 | 1.213 | 0.608 | 1.818 | 0.001 |
HDL-c, mmol/L | −0.066 | 0.054 | −0.120 | −0.190 | −0.049 | 0.015 |
Insulin sensitivity | ||||||
Matsuda index | −0.213 | 1.354 | −1.566 | −2.201 | −0.932 | 0.001 |
Insulin secretion | ||||||
1p Stumvoll index | 66.005 | −375.195 | 441.200 | 107.327 | 775.072 | 0.011 |
Ratio AUC | −1.094 | −11.539 | 10.444 | −1.798 | 22.687 | 0.091 |
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Hidalgo-Lozada, G.M.; Villarruel-López, A.; Martínez-Abundis, E.; Vázquez-Paulino, O.; González-Ortiz, M.; Pérez-Rubio, K.G. Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J. Clin. Med. 2022, 11, 5741. https://doi.org/10.3390/jcm11195741
Hidalgo-Lozada GM, Villarruel-López A, Martínez-Abundis E, Vázquez-Paulino O, González-Ortiz M, Pérez-Rubio KG. Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journal of Clinical Medicine. 2022; 11(19):5741. https://doi.org/10.3390/jcm11195741
Chicago/Turabian StyleHidalgo-Lozada, Gladys Maribel, Angélica Villarruel-López, Esperanza Martínez-Abundis, Olga Vázquez-Paulino, Manuel González-Ortiz, and Karina Griselda Pérez-Rubio. 2022. "Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial" Journal of Clinical Medicine 11, no. 19: 5741. https://doi.org/10.3390/jcm11195741