Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Clinical Procedures
2.3. Immunometric and Biochemical Assays
2.4. Determination of Serum Levels of Oxysterols
2.5. Statistical Analysis
3. Results
3.1. Study Population
3.2. Analysis of Oxysterols in the Study Population
3.3. Effect of Nutraceutical Treatment on Oxysterols Plasma Levels
4. Discussion
5. Conclusion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Whole Cohort | Placebo Arm | Nutraceutical Combination Arm | Difference between Arms at Baseline (p-Value) | |
---|---|---|---|---|
Sex (M/F) | 16/14 | 8/7 | 8/7 | - |
Age (years) | 57.5 (48, 64) | 48 (41, 58) | 63 (57, 65) | 0.006 |
Weight (kg) | 65 (62, 79) | 65 (63, 80) | 63 (60, 77) | 0.57 |
BMI (kg/m2) | 23.84 (21.3, 27.7) | 23.58 (20.75, 27.94) | 23.9 (22.77, 27.63) | 0.71 |
Abdominal Circumference (cm) | 87.25 (83.5, 94) | 87.5 (82, 94) | 87 (84, 94) | 0.75 |
Waist Circumference (cm) | 94.5 (88, 99) | 95 (87, 101.5) | 94 (90, 99) | 0.91 |
BIA (%) | 30.9 (27.2, 38.5) | 30.6 (25.5, 39.7) | 32.3 (27.3, 38.5) | 0.62 |
VFR (%) | 10.5 (7.5, 11.5) | 9.5 (6, 13.5) | 10.5 (8.5, 11.5) | 0.72 |
SBP (mmHg) | 120 (120, 130) | 125 (110, 130) | 120 (120, 130) | 0.53 |
DBP (mmHg) | 80 (80, 80) | 80 (80, 80) | 80 (80, 80) | 0.97 |
HR (bpm) | 64 (60, 68) | 65 (64, 68) | 64 (60, 68) | 0.28 |
TC (mg/mL) | 270 (246, 288) | 270 (255, 290) | 270 (233, 288) | 0.51 |
LDL-C (mg/mL) | 179 (169, 195) | 187 (172, 195) | 176 (165, 196) | 0.33 |
HDL-C (mg/mL) | 56.5 (43, 77) | 54 (47, 67) | 65 (42, 83) | 0.67 |
non-HDL-C (mg/mL) | 209.5 (192, 230) | 214 (196, 234) | 207 (188, 216) | 0.31 |
TG (mg/mL) | 114.5 (95, 153) | 112 (92, 130) | 127 (95, 159) | 0.57 |
apoAI (mg/dL) | 114.5 (95, 132) | 113 (95, 129) | 125 (91, 141) | 0.39 |
apoB (mg/dL) | 146 (135, 155) | 143 (133, 146) | 155 (142, 158) | 0.03 |
oxLDL (U/L) | 76.6 (70, 85.2) | 71.7 (67.3, 84.6) | 76.8 (74.5, 123.8) | 0.17 |
24-OHC (ng/mL) | 89 (73, 109) | 89 (73, 103) | 90.9 (71.8, 110) | 0.72 |
24-OHC/TC (ng/mg) | 34 (27, 41) | 33 (27, 39) | 35 (26, 43) | 0.71 |
25-OHC (ng/mL) | 84.2 (60.5, 96) | 86 (63, 106) | 81 (57, 96) | 0.55 |
25-OHC/TC (ng/mg) | 29 (25, 38) | 31 (25, 39) | 28 (22, 38) | 0.87 |
27-OHC (ng/mL) | 183.5 (152, 211) | 174 (115, 219) | 190 (166.3, 211) | 0.6 |
27-OHC/TC (ng/mg) | 72 (51, 80) | 72 (47, 74) | 73 (51, 88) | 0.3 |
Lp(a) (mg/dL) | 6 (4, 11) | 4 (2, 9) | 7 (5, 13) | 0.09 |
PCSK9 (ng/dL) | 339.87 (283.17, 403.96) | 340.04 (279.63, 402.52) | 339.7 (283.17, 410.09) | 0.89 |
FPG (mg/dL) | 93.5 (89, 97) | 95 (89, 97) | 92 (89, 103) | 0.98 |
Insulin (mUI/L) | 3.38 (2.42, 5.04) | 3.08 (2.49, 6.2) | 3.38 (2.13, 5.04) | 0.77 |
HOMA-IR | 0.75 (0.56, 1.18) | 0.72 (0.57, 1.44) | 0.77 (0.47, 1.18) | 0.81 |
FGF19 (pg/mL) | 222.87 (173.05, 330.6) | 232.4 (106.58, 333.98) | 215.61 (176.79, 237.12) | 0.94 |
FGF21 (pg/mL) | 174.86 (118.32, 237.14) | 157.08 (71.66, 226.57) | 178.62 (158.16, 364.15) | 0.25 |
Creatinine (mg/dL) | 0.8 (0.7, 0.9) | 0.8 (0.7, 1) | 0.8 (0.7, 0.9) | 0.76 |
24-OHC | 24-OHC/TC | 25-OHC | 25-OHC/TC | 27-OHC | 27-OHC/TC | |
---|---|---|---|---|---|---|
Sex | 0.68 | 0.42 | 0.14 | 0.07 | 0.02 | 0.008 |
Age | −0.269/0.151 | −0.279/0.135 | −0.29/0.121 | −0.285/0.127 | 0.191/0.313 | 0.218/0.248 |
Weight | 0.025/0.895 | 0.158/0.403 | 0.133/0.483 | 0.225/0.232 | 0.236/0.209 | 0.339/0.067 |
BMI | 0.069/0.728 | 0.198/0.313 | 0.124/0.528 | 0.23/0.238 | 0.148/0.453 | 0.265/0.173 |
Abdominal Circumference | −0.034/0.859 | 0.118/0.536 | 0.06/0.754 | 0.159/0.401 | 0.272/0.146 | 0.414/0.023 |
Waist Circumference | 0.037/0.847 | 0.109/0.567 | −0.003/0.988 | 0.04/0.833 | 0.042/0.824 | 0.104/0.586 |
BIA | −0.054/0.776 | 0.06/0.753 | −0.253/0.178 | −0.171/0.367 | 0.026/0.89 | 0.136/0.475 |
VFR | 0.021/0.912 | 0.168/0.376 | 0.138/0.468 | 0.253/0.177 | 0.292/0.118 | 0.42/0.021 |
SBP | −0.051/0.789 | −0.094/0.62 | 0.172/0.365 | 0.182/0.336 | −0.11/0.561 | −0.135/0.477 |
DBP | −0.132/0.485 | −0.194/0.304 | −0.16/0.397 | −0.175/0.354 | −0.126/0.505 | −0.18/0.34 |
HR | 0.095/0.617 | −0.012/0.95 | 0.128/0.499 | 0.073/0.7 | −0.002/0.992 | −0.105/0.569 |
TC | 0.219/0.246 | −0.193/0.307 | 0.23/0.221 | −0.088/0.643 | 0.158/0.405 | −0.295/0.115 |
LDL-C | 0.022/0.909 | −0.314/0.091 | 0.12/0.528 | −0.151/0.426 | 0.23/0.221 | −0.148/0.435 |
HDL-C | 0.066/0.729 | −0.153/0.419 | −0.033/0.864 | −0.188/0.319 | −0.252/0.179 | −0.489/0.006 |
non-HDL-C | 0.215/0.253 | −0.131/0.49 | 0.29/0.12 | 0.013/0.946 | 0.341/0.065 | −0.041/0.828 |
TG | 0.517/0.004 | 0.41/0.024 | 0.481/0.007 | 0.401/0.028 | 0.353/0.056 | 0.253/0.178 |
apoAI | 0.104/0.586 | −0.183/0.333 | 0.04/0.833 | −0.164/0.387 | −0.052/0.783 | −0.361/0.05 |
apoB | 0.455/0.012 | 0.306/0.1 | 0.155/0.415 | 0.025/0.897 | 0.201/0.287 | 0.032/0.866 |
oxLDL | 0.202/0.285 | 0.155/0.414 | −0.094/0.62 | −0.136/0.472 | −0.04/0.835 | −0.045/0.815 |
24-OHC | - | 0.912/<0.0001 | 0.626/0.00021 | 0.552/0.0015 | −0.084/0.655 | −0.177/0.347 |
24-OHC/TC | 0.912/<0.0001 | - | 0.518/0.0033 | 0.580/0.00078 | −0.145/0.443 | −0.049/0.793 |
25-OHC | 0.626/0.00021 | 0.518/0.0033 | - | 0.945/<0.0001 | 0.053/0.779 | −0.060/0.749 |
25-OHC/TC | 0.552/0.0015 | 0.580/0.00078 | 0.945/<0.0001 | - | −0.0001/0.999 | 0.032/0.865 |
27-OHC | −0.084/0.655 | −0.145/0.443 | −0.053/0.779 | −0.0001/0.999 | - | 0.892/<0.0001 |
27-OHC/TC | −0.117/0.347 | −0.049/0.793 | −0.06/0.749 | 0.032/0.865 | 0.892/<0.0001 | - |
Lp(a) | 0.324/0.081 | 0.419/0.021 | 0.369/0.045 | 0.448/0.013 | 0.084/0.658 | 0.168/0.374 |
PCSK9 | 0.035/0.852 | −0.188/0.321 | 0.067/0.724 | −0.107/0.574 | −0.223/0.236 | −0.45/0.013 |
FPG | 0.1/0.598 | 0.097/0.609 | −0.015/0.938 | −0.023/0.905 | 0.227/0.228 | 0.247/0.189 |
Insulin | 0.019/0.92 | 0.92/0.419 | 0.073/0.7 | 0.176/0.352 | 0.14/0.46 | 0.272/0.146 |
HOMA-IR | 0.029/0.879 | 0.153/0.42 | 0.085/0.654 | 0.181/0.339 | 0.166/0.38 | 0.292/0.117 |
FGF19 | −0.099/0.637 | −0.003/0.987 | 0.133/0.528 | 0.231/0.267 | −0.225/0.279 | −0.118/0.573 |
FGF21 | −0.178/0.454 | −0.208/0.379 | 0.218/0.357 | 0.197/0.405 | 0.013/0.956 | 0.043/0.857 |
Creatinine | −0.064/0.738 | 0.069/0.716 | 0.101/0.597 | 0.218/0.247 | 0.433/0.017 | 0.567/0.001 |
Placebo | Nutraceutical | Difference of Changes between Arms | |||
---|---|---|---|---|---|
Baseline | 12 Weeks | Baseline | 12 Weeks | p-Value | |
24-OHC (ng/mL) | 89 (73, 103) | 97 (87, 118) | 91 (72, 110) | 94 (75, 139) | 0.2 |
25-OHC (ng/mL) | 86 (63, 106) | 79 (52, 96) | 81 (57, 96) | 81 (62, 91) | 0.91 |
27-OHC (ng/mL) | 174 (115, 219) | 179 (111, 232) | 190 (166, 211) | 170 (133, 187) | 0.03 |
24-OHC/TC (ng/mg) | 33 (27, 39) | 34 (30, 41) | 35 (26, 43) | 40 (35, 51) | 0.57 |
25-OHC/TC (ng/mg) | 31 (25, 39) | 25 (20, 34) | 28 (22, 38) | 35 (27, 41) | 0.36 |
27-OHC/TC (ng/mg) | 72 (47, 74) | 67 (43, 82) | 73 (51, 88) | 74 (54, 94) | 0.09 |
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Cicolari, S.; Pavanello, C.; Olmastroni, E.; Puppo, M.D.; Bertolotti, M.; Mombelli, G.; Catapano, A.L.; Calabresi, L.; Magni, P. Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study). Nutrients 2021, 13, 427. https://doi.org/10.3390/nu13020427
Cicolari S, Pavanello C, Olmastroni E, Puppo MD, Bertolotti M, Mombelli G, Catapano AL, Calabresi L, Magni P. Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study). Nutrients. 2021; 13(2):427. https://doi.org/10.3390/nu13020427
Chicago/Turabian StyleCicolari, Stefania, Chiara Pavanello, Elena Olmastroni, Marina Del Puppo, Marco Bertolotti, Giuliana Mombelli, Alberico L. Catapano, Laura Calabresi, and Paolo Magni. 2021. "Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study)" Nutrients 13, no. 2: 427. https://doi.org/10.3390/nu13020427
APA StyleCicolari, S., Pavanello, C., Olmastroni, E., Puppo, M. D., Bertolotti, M., Mombelli, G., Catapano, A. L., Calabresi, L., & Magni, P. (2021). Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study). Nutrients, 13(2), 427. https://doi.org/10.3390/nu13020427