Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Recruitment and Randomization of the Study Population
2.3. Intervention
2.4. Clinical Tests and Questionnaires
2.5. Analytical Procedures, Outcomes and Statistical Methods
2.5.1. Blood Tests
2.5.2. SOD Determination
2.5.3. Glutathione Assay
2.5.4. Catalase Activity Assay
2.5.5. Isoprostanes
2.5.6. Insulin and Glucose
2.5.7. Handling of Semen Samples
2.5.8. Compliance
2.5.9. Primary and Secondary Outcomes
2.5.10. Statistical Analyses
Crossover Analyses
Subgroup Analyses
Test for Carry Over-Effect
3. Results
3.1. Participant Characteristics
3.2. Markers of Cytoprotection
3.2.1. Glutathione
3.2.2. Isoprostanes
3.3. Sperm Quality
3.3.1. Sperm DNA Fragmentation
3.3.2. Percentage of Motile Sperm (PM)
3.4. Serum Lipids
3.4.1. Total Cholesterol
3.4.2. LDL-Cholesterol
3.4.3. HDL-Cholesterol and Triglycerides (TG)
3.5. Side Effects
4. Discussion
4.1. Effects of Aronia on Cytoprotective Targets
4.2. Glutathione
4.3. DNA Fragmentation and Percentage of Motile Sperm
4.4. Significant Cytoprotective Effects of Aronia among Coffee Drinkers
4.5. Effects of Aronia on Blood Lipid Levels
4.6. Side Effects
4.7. Strengths
4.8. Limitations
5. Conclusions
6. Registration
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BMI | Body mass index |
CAT | Catalase |
CMS | Concentration of motile sperm |
CPMS | Concentration of progressive motile sperm |
CRP | C-reactive protein |
CVD | Cardiovascular disease |
DFI | DNA Fragmentation Index |
GLU | Glutathione |
HbA1c | Hemoglobin A1c |
HDL-C | High-density lipoprotein cholesterol |
Hs CRP | High-sensitivity C-reactive protein |
LDL-C | Low-density lipoprotein cholesterol |
OS | Oxidative stress |
PM | Percentage of motile sperm |
RCT | Randomized controlled trial |
ROS | Reactive oxidative species |
SOD | Superoxide dismutase |
TC | Total cholesterol |
TG | Triglycerides |
TMSC | Total Motile Sperm Count |
TPMSC | Total Progressive Motile Sperm Count |
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Group A (n = 54) | Group B (n = 55) | p Value [95% CI] | |
---|---|---|---|
Age (years) | 47.7 ± 9.7 | 51.9 ± 9.3 | 0.03 [−7.9; −0.4] |
BMI (kg/m2) | 27.2 ± 3.2 | 27.3 ± 3.5 | 0.87 [−1.4; 1.2] |
Smoking, n (%) | 3 (6.1) | 5 (9.3) | |
Baseline total cholesterol (mM) | 5.5 ± 0.8 | 5.6 ± 0.9 | 0.73 [−0.4; 0.3] |
Baseline blood pressure (systolic) (mmHg) | 133.4 ± 14.4 | 131.9 ± 15.4 | 0.59 [−4.1; 7.2] |
Baseline blood pressure (diastolic) (mmHg) | 87.0 ± 10.8 | 85.3 ± 11.0 | 0.41 [−2.4; 5.9] |
Fasting blood glucose (mM) | 5.8 ± 0.4 | 6.0 ± 1.2 | 0.32 [−0.5; 0.2] |
Hs CRP (mg/L) | 2.3 ± 2.3 | 2.3 ± 3.0 | 1.00 [−1.0; 1.0] |
Glutathione (nM) | 56.8 ± 69.9 | 64.5 ± 83.4 | 0.60 [−36.9; 21.5] |
DFI (%) | 19.6 ± 14.0 | 19.7 ± 12.2 | 0.98 [−6.3; 6.1] |
TPMSC (mio.) | 108.9 ± 106.3 | 85.5 ± 87.7 | 0.31 [−22.4; 69.2] |
Analysis of All Participants Incl. Subgroups | Glutathione (mM) | DNA Fragmentation (%) | Motile Sperm (%) (PM) | ||||
---|---|---|---|---|---|---|---|
Treatment Order | Aronia Then Placebo | Placebo Then Aronia | Aronia Then Placebo | Placebo Then Aronia | Aronia Then Placebo | Placebo Then Aronia | |
N | 51 | 42 | 33 | 27 | 33 | 29 | |
Treatment effect [CI] | +19.8 [−7.6;47.1] | −1.2 (−3.3;0.8) | +2.7 | ||||
Crossover analysis 1 | 0.15 | 0.230 | 0.067 | ||||
Crossover analysis 2, including baseline data | 0.0095 ** | ||||||
Analysis of subgroups | |||||||
Age > 40 | Effect | −2.4 | +5.4 | ||||
p-value | 0.032 * | 0.004 ** | |||||
n | 41 | 43 | |||||
BMI > 25 | Effect | −2.0 | +3.6 | ||||
p-value | 0.037 * | 0.052 | |||||
n | 42 | 43 | |||||
Glutathione < 42 mM at baseline 1 | Effect | +41.3 | |||||
p-value | 0.038 * | ||||||
n | 54 | ||||||
No D vitamin supplementation | Effect | 0.043 * | |||||
p-value | −1.8 | ||||||
n | 51 | ||||||
No fish oil supplementation | Effect | −2.1 | |||||
p-value | 0.031 * | ||||||
n | 49 | ||||||
High fruit and veggie intake | Effect | −5.6 | |||||
p-value | 0.031 | ||||||
n | 13 | ||||||
Low daily sugar intake | Effect | −2.7 | |||||
p-value | 0.032 * | ||||||
n | 37 | ||||||
Sitting down less than 6 h/day | Effect | −2.3 | |||||
p-value | 0.046 * | ||||||
n | 40 | ||||||
Low alcohol intake | Effect | −1.2 | +4.6 | ||||
p-value | 0.037 * | 0.01 * | |||||
n | 48 | 50 | |||||
No smoking | Effect | −1.9 | +3.4 | ||||
p-value | 0.051 | 0.036 * | |||||
n | 53 | 54 | |||||
High coffee intake | Effect | +32.6 | −3.2 | +5.7 | |||
p-value | 0.045 * | 0.01 * | 0.006 ** | ||||
n | 60 | 37 | 39 | ||||
No magnesium supplementation | Effect | +3.6 | |||||
p-value | 0.024 * | ||||||
n | 50 | ||||||
No calcium supplementation | Effect | +3.6 | |||||
p-value | 0.024 * | ||||||
n | 50 |
Analysis of All Participants Incl. Subgroups | Total Cholesterol (mM) | LDL-Cholesterol (mM) | HDL-Cholesterol (mM) | Triglyceride (mM) | |||||
---|---|---|---|---|---|---|---|---|---|
Treatment order | Aronia then Placebo | Placebo then Aronia | Aronia then Placebo | Placebo then Aronia | Aronia then Placebo | Placebo then Aronia | Aronia then Placebo | Placebo then Aronia | |
n | 51 | 43 | 51 | 43 | 51 | 43 | 51 | 43 | |
Treatment effect (CI) | −0.1 (−0.2; 0.1) | −0.1 (−0.2; 0.1) | −0.0 (−0.1; 0.0) | −0.0 (−0.1; 0.1) | |||||
Cross over analysis p-value | 0.16 | 0.43 | 0.12 | 0.78 | |||||
Analysis of subgroups | |||||||||
Age < 40 years | p-value | 0.046 * | |||||||
Effect (CI) | −0.4 (−0.9; 0.0) | ||||||||
n | 15 | ||||||||
Low daily coffee intake | p-value | 0.052 | 0.033 * | ||||||
Effect (CI) | −0.2 (−0.5; −0.0) | −0.3 (−0.6; 0.0) | |||||||
n | 28 | 28 |
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Sangild, J.; Faldborg, A.; Schousboe, C.; Fedder, M.D.K.; Christensen, L.P.; Lausdahl, A.K.; Arnspang, E.C.; Gregersen, S.; Jakobsen, H.B.; Knudsen, U.B.; et al. Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial. J. Clin. Med. 2023, 12, 373. https://doi.org/10.3390/jcm12010373
Sangild J, Faldborg A, Schousboe C, Fedder MDK, Christensen LP, Lausdahl AK, Arnspang EC, Gregersen S, Jakobsen HB, Knudsen UB, et al. Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial. Journal of Clinical Medicine. 2023; 12(1):373. https://doi.org/10.3390/jcm12010373
Chicago/Turabian StyleSangild, Julie, Anne Faldborg, Cecilie Schousboe, Maja Døvling Kaspersen Fedder, Lars Porskjær Christensen, Astrid Komal Lausdahl, Eva Christensen Arnspang, Søren Gregersen, Henrik Byrial Jakobsen, Ulla Breth Knudsen, and et al. 2023. "Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial" Journal of Clinical Medicine 12, no. 1: 373. https://doi.org/10.3390/jcm12010373