Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participants
2.3. Interventions
2.4. Statistical Analyses
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Joseph, P.; Leong, D.; McKee, M.; Anand, S.S.; Schwalm, J.D.; Teo, K.; Mente, A.; Yusuf, S. Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors. Circ. Res. 2017, 121, 677–694. [Google Scholar] [CrossRef] [PubMed]
- Kobiyama, K.; Ley, K. Atherosclerosis. Circ. Res. 2018, 123, 1118–1120. [Google Scholar] [CrossRef] [PubMed]
- Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001, 285, 2486–2497. [Google Scholar] [CrossRef]
- Michos, E.D.; McEvoy, J.W.; Blumenthal, R.S. Lipid Management for the Prevention of Atherosclerotic Cardiovascular Disease. N. Engl. J. Med. 2019, 381, 1557–1567. [Google Scholar] [CrossRef]
- Redberg, R.F.; Katz, M.H. Statins for Primary Prevention: The Debate Is Intense, but the Data Are Weak. JAMA Intern. Med. 2017, 177, 21–23. [Google Scholar] [CrossRef] [PubMed]
- Catapano, A.L.; Graham, I.; De Backer, G.; Wiklund, O.; Chapman, M.J.; Drexel, H.; Hoes, A.W.; Jennings, C.S.; Landmesser, U.; Pedersen, T.R.; et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur. Heart. J. 2016, 37, 2999–3058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Santini, A.; Novellino, E. Nutraceuticals in hypercholesterolaemia: An overview. Br. J. Pharm. 2017, 174, 1450–1463. [Google Scholar] [CrossRef] [Green Version]
- Pirro, M.; Vetrani, C.; Bianchi, C.; Mannarino, M.R.; Bernini, F.; Rivellese, A.A. Joint position statement on “Nutraceuticals for the treatment of hypercholesterolemia” of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA). Nutr. Metab. Cardiovasc. Dis. 2017, 27, 2–17. [Google Scholar] [CrossRef] [Green Version]
- Farkouh, A.; Baumgartel, C. Mini-review: Medication safety of red yeast rice products. Int. J. Gen. Med. 2019, 12, 167–171. [Google Scholar] [CrossRef] [Green Version]
- Younes, M.; Aggett, P.; Aguilar, F.; Crebelli, R.; Dusemund, B.; Filipič, M.; Frutos, M.J.; Galtier, P.; Gott, D.; Gundert-Remy, U.; et al. Scientific opinion on the safety of monacolins in red yeast rice. EFSA J. 2018, 16, e05368. [Google Scholar] [CrossRef] [Green Version]
- Bonfigli, A.R.; Protic, O.; Olivieri, F.; Montesanto, A.; Malatesta, G.; Di Pillo, R.; Antonicelli, R. Effects of a novel nutraceutical combination (BruMeChol) in subjects with mild hypercholesterolemia: Study protocol of a randomized, double-blind, controlled trial. Trials 2020, 21, 616. [Google Scholar] [CrossRef] [PubMed]
- Lee, P.H.; Macfarlane, D.J.; Lam, T.H.; Stewart, S.M. Validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF): A systematic review. Int. J. Behav. Nutr. Phys. Act. 2011, 8, 115. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Tuomilehto, J.; Jousilahti, P.; Wang, Y.; Antikainen, R.; Hu, G. Total and high-density lipoprotein cholesterol and stroke risk. Stroke 2012, 43, 1768–1774. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Protic, O.; Bonfigli, A.R.; Antonicelli, R. Nutraceutical Combinations in Hypercholesterolemia: Evidence from Randomized, Placebo-Controlled Clinical Trials. Nutrients 2021, 13, 3128. [Google Scholar] [CrossRef]
- Alonso, R.; Cuevas, A.; Cafferata, A. Diagnosis and Management of Statin Intolerance. J. Atheroscler. Thromb. 2019, 26, 207–215. [Google Scholar] [CrossRef] [Green Version]
- De Smet, E.; Mensink, R.P.; Plat, J. Effects of plant sterols and stanols on intestinal cholesterol metabolism: Suggested mechanisms from past to present. Mol. Nutr. Food Res. 2012, 56, 1058–1072. [Google Scholar] [CrossRef]
- Othman, R.A.; Moghadasian, M.H. Beyond cholesterol-lowering effects of plant sterols: Clinical and experimental evidence of anti-inflammatory properties. Nutr. Rev. 2011, 69, 371–382. [Google Scholar] [CrossRef]
- Lamiquiz-Moneo, I.; Giné-González, J.; Alisente, S.; Bea, A.M.; Pérez-Calahorra, S.; Marco-Benedí, V.; Baila-Rueda, L.; Jarauta, E.; Cenarro, A.; Civeira, F.; et al. Effect of bergamot on lipid profile in humans: A systematic review. Crit. Rev. Food Sci. Nutr. 2020, 60, 3133–3143. [Google Scholar] [CrossRef] [Green Version]
- Nauman, M.C.; Johnson, J.J. Clinical application of bergamot (Citrus bergamia) for reducing high cholesterol and cardiovascular disease markers Integr. Food Nutr. Metab. 2019, 6, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Ferlazzo, N.; Visalli, G.; Smeriglio, A.; Cirmi, S.; Lombardo, G.E.; Campiglia, P.; Di Pietro, A.; Navarra, M. Flavonoid Fraction of Orange and Bergamot Juices Protect Human Lung Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Stress. Evid. Based Complement Altern. Med. 2015, 2015, 957031. [Google Scholar] [CrossRef]
- Impellizzeri, D.; Bruschetta, G.; Di Paola, R.; Ahmad, A.; Campolo, M.; Cuzzocrea, S.; Esposito, E.; Navarra, M. The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease. Clin. Nutr. 2015, 34, 1146–1154. [Google Scholar] [CrossRef] [PubMed]
- Karković Marković, A.; Torić, J.; Barbarić, M.; Jakobušić Brala, C. Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health. Molecules 2019, 24, 2001. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rietjens, S.J.; Bast, A.; Haenen, G.R. New insights into controversies on the antioxidant potential of the olive oil antioxidant hydroxytyrosol. J. Agric. Food Chem. 2007, 55, 7609–7614. [Google Scholar] [CrossRef]
- Harshman, S.G.; Shea, M.K. The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis. Curr. Nutr. Rep. 2016, 5, 90–98. [Google Scholar] [CrossRef] [Green Version]
- Simes, D.C.; Viegas, C.S.B.; Araújo, N.; Marreiros, C. Vitamin K as a Powerful Micronutrient in Aging and Age-Related Diseases: Pros and Cons from Clinical Studies. Int. J. Mol. Sci. 2019, 20, 4150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Koosha, P.; Roohafza, H.; Sarrafzadegan, N.; Vakhshoori, M.; Talaei, M.; Sheikhbahaei, E.; Sadeghi, M. High Sensitivity C-Reactive Protein Predictive Value for Cardiovascular Disease: A Nested Case Control from Isfahan Cohort Study (ICS). Glob. Heart 2020, 15, 3. [Google Scholar] [CrossRef] [Green Version]
- Damen, M.S.M.A.; Popa, C.D.; Netea, M.G.; Dinarello, C.A.; Joosten, L.A.B. Interleukin-32 in chronic inflammatory conditions is associated with a higher risk of cardiovascular diseases. Atherosclerosis 2017, 264, 83–91. [Google Scholar] [CrossRef] [Green Version]
- Yang, Z.; Shi, L.; Xue, Y.; Zeng, T.; Shi, Y.; Lin, Y.; Liu, L. Interleukin-32 increases in coronary arteries and plasma from patients with coronary artery disease. Clin. Chim. Acta 2019, 497, 104–109. [Google Scholar] [CrossRef]
- Xu, Z.; Dong, A.; Feng, Z.; Li, J. Interleukin-32 promotes lipid accumulation through inhibition of cholesterol efflux. Exp. Med. 2017, 14, 947–952. [Google Scholar] [CrossRef] [Green Version]
- Xu, W.D.; Huang, A.F. Role of Interleukin-38 in Chronic Inflammatory Diseases: A Comprehensive Review. Front. Immunol. 2018, 9, 1462. [Google Scholar] [CrossRef]
- Lai, M.; Peng, H.; Wu, X.; Chen, X.; Wang, B.; Su, X. IL-38 in modulating hyperlipidemia and its related cardiovascular diseases. Int. Immunopharmacol. 2022, 108, 108876. [Google Scholar] [CrossRef] [PubMed]
- Olivieri, F.; Rippo, M.R.; Procopio, A.D.; Fazioli, F. Circulating inflamma-miRs in aging and age-related diseases. Front. Genet. 2013, 4, 121. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Elisa, T.; Miriana, S.; Davide, P.; Michele, T.; Ersilia, L.; Lara, T.; Angelo, B. Efficacy of Plant Sterol-Enriched Food for Primary Prevention and Treatment of Hypercholesterolemia: A Systematic Literature Review. Foods 2022, 11, 839. [Google Scholar] [CrossRef]
- Piepoli, M.F.; Hoes, A.W.; Agewall, S.; Albus, C.; Brotons, C.; Catapano, A.L.; Cooney, M.T.; Corrà, U.; Cosyns, B.; Deaton, C.; et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur. Heart J. 2016, 37, 2315–2381. [Google Scholar] [CrossRef]
- Jellinger, P.S.; Handelsman, Y.; Rosenblit, P.D.; Bloomgarden, Z.T.; Fonseca, V.A.; Garber, A.J.; Grunberger, G.; Guerin, C.K.; Bell, D.S.H.; Mechanick, J.I.; et al. American association of clinical endocrinologists and american college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr. Pract. 2017, 23, 1–87. [Google Scholar] [CrossRef] [Green Version]
- Cabral, C.E.; Klein, M.R.S.T. Phytosterols in the Treatment of Hypercholesterolemia and Prevention of Cardiovascular Diseases. Arq. Bras. Cardiol. 2017, 109, 475–482. [Google Scholar] [CrossRef]
- Toth, P.P.; Patti, A.M.; Nikolic, D.; Giglio, R.V.; Castellino, G.; Biancucci, T.; Geraci, F.; David, S.; Montalto, G.; Rizvi, A.; et al. Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study. Front. Pharm. 2015, 6, 299. [Google Scholar] [CrossRef] [Green Version]
- Matacchione, G.; Gurău, F.; Baldoni, S.; Prattichizzo, F.; Silvestrini, A.; Giuliani, A.; Pugnaloni, A.; Espinosa, E.; Amenta, F.; Bonafè, M.; et al. Pleiotropic effects of polyphenols on glucose and lipid metabolism: Focus on clinical trials. Ageing Res. Rev. 2020, 61, 101074. [Google Scholar] [CrossRef]
- Lockyer, S.; Rowland, I.; Spencer, J.P.E.; Yaqoob, P.; Stonehouse, W. Impact of phenolic-rich olive leaf extract on blood pressure, plasma lipids and inflammatory markers: A randomised controlled trial. Eur. J. Nutr. 2017, 56, 1421–1432. [Google Scholar] [CrossRef] [Green Version]
- Beulens, J.W.; Booth, S.L.; van den Heuvel, E.G.; Stoecklin, E.; Baka, A.; Vermeer, C. The role of menaquinones (vitamin K₂) in human health. Br. J. Nutr. 2013, 110, 1357–1368. [Google Scholar] [CrossRef] [Green Version]
- Caesar, L.K.; Cech, N.B. Synergy and antagonism in natural product extracts: When 1 + 1 does not equal 2. Nat. Prod. Rep. 2019, 36, 869–888. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, X.; Xin, Y.; Mo, Y.; Marozik, P.; He, T.; Guo, H. The Bioavailability and Biological Activities of Phytosterols as Modulators of Cholesterol Metabolism. Molecules 2022, 27, 523. [Google Scholar] [CrossRef]
- Di Lorenzo, C.; Colombo, F.; Biella, S.; Stockley, C.; Restani, P. Polyphenols and Human Health: The Role of Bioavailability. Nutrients 2021, 13, 273. [Google Scholar] [CrossRef] [PubMed]
- Olivieri, F.; Prattichizzo, F.; Giuliani, A.; Matacchione, G.; Rippo, M.R.; Sabbatinelli, J.; Bonafè, M. miR-21 and miR-146a: The microRNAs of inflammaging and age-related diseases. Ageing Res. Rev. 2021, 70, 101374. [Google Scholar] [CrossRef] [PubMed]
- Gurău, F.; Silvestrini, A.; Matacchione, G.; Fazioli, F.; Bonfigli, A.R.; Olivieri, F.; Sabbatinelli, J. Plasma levels of interleukin-38 in healthy aging and in type 2 diabetes. Diabetes Res. Clin. Pract. 2021, 171, 108585. [Google Scholar] [CrossRef] [PubMed]
NC n = 59 | Placebo n = 59 | p | |
---|---|---|---|
Age (years) | 56.59 (9.55) | 59.27 (7.91) | 0.100 |
Gender (men) | 24 (40.7) | 25 (42.4) | 0.852 |
Weight (kg) | 73.11 (15.37) | 70.99 (13.39) | 0.426 |
Height (cm) | 168 (160–175) | 166 (160–173) | 0.599 * |
Waist circumference (cm) | 92.65 (10.66) | 91.90 (10.65) | 0.704 |
Hip circumference (cm) | 103.23 (8.68) | 103.09 (8.64) | 0.932 |
Body Mass Index (kg/m2) | 25.4 (23.0–29.7) | 24.5 (22.2–28.6) | 0.236 * |
Systolic Blood Pressure (mm/Hg) | 130 (115–140) | 130 (120–149) | 0.220 * |
Diastolic Blood Pressure (mm/Hg) | 80 (72–85) | 80 (70–85) | 0.605 * |
Heart rate (bpm) * | 66 (60–70) | 67 (61–72) | 0.287 * |
Fasting Glucose (mg/dL) | 95.08 (8.62) | 96.17 (10.66) | 0.544 |
Total Cholesterol (mg/dL) | 225.69 (19.55) | 229.02 (22.04) | 0.388 |
Cholesterol HDL (mg/dL) | 62.03 (16.86) | 68.20 (15.98) | 0.044 |
Cholesterol LDL (mg/dL) | 156.29 (21.61) | 156.53 (19.53) | 0.950 |
Total / HDL Cholesterol (mg/dL) | 3.74 (3.06–4.57) | 3.40 (3.01–3.96) | 0.079 * |
Triglycerides (mg/dL) | 105 (73–148) | 95 (70–143) | 0.557 * |
AST (U/L) | 19 (16–21) | 18 (16–22) | 0.627 * |
ALT (U/L) | 15 (13–23) | 16 (13–24) | 0.760 * |
Creatinine (mg/dL) | 0.8 (0.7–1.0) | 0.9 (0.8–1.0) | 0.779 * |
CKD-EPI eGFR (mL/min/1.73 mq) | 86 (80–90) | 84 (74–90) | 0.167 * |
hs-C-reactive protein (mg/dL) | 0.09 (0.05–0.20) | 0.12 (0.06–0.27) | 0.387 * |
Lipoprotein (a) (mg/dL) | 104 (48–299) | 200 (49–509) | 0.228 * |
Creatine kinase (U/L) | 98 (70–134) | 102 (78–134) | 0.794 * |
Leukocytes (×103/L) | 5.89 (5.01–6.75) | 5.87 (5.06–6.56) | 0.655 * |
Baseline | 6th Week | 12th Week | p Group | p Time | p Interaction | |
---|---|---|---|---|---|---|
AST (U/L) | ||||||
NC | 19.5 (4.7) | 20.2 (5.8) | 20.2 (6.1) | 0.986 | 0.112 | 0.906 |
Placebo | 19.5 (5.5) | 20.0 (5.5) | 20.3 (6.4) | |||
ALT (U/L) | ||||||
NC | 18.4 (8.6) | 21.0 (13.2) | 19.5 (10.2) | 0.975 | 0.218 | 0.207 |
Placebo | 19.5 (10.8) | 19.5 (11.2) | 19.7 (10.9) | |||
Creatinine (mg/dL) | ||||||
NC | 0.87 (0.15) | 0.87 (0.16) | 0.86 (0.14) | 0.240 | 0.200 | 0.581 |
Placebo | 0.90 (0.22) | 0.92 (0.20) | 0.90 (0.21) | |||
CDK-EPI eGFR (ml/min/1,73 mq) | ||||||
NC | 82.6 (9.75) | 81.2 (12.4) | 83.3 (7.7) | 0.057 | 0.094 | 0.784 |
Placebo | 79.7 (12.7) | 77.7 (12.1) | 79.1 (12.5) | |||
Creatine kinase (U/L) | ||||||
NC | 120.1 (95.6) | 122.8 (113.3) | 125.9 (138.0) | 0.798 | 0.079 | 0.376 |
Placebo | 111.3 (47.8) | 114.4 (50.2) | 130.6 (86.1) | |||
Myoglobin (ng/mL) | ||||||
NC | 35.2 (25.6) | 35.0 (32.3) | 33.9 (25.1) | 0.998 | 0.412 | 0.164 |
Placebo | 35.5 (17.9) | 33.0 (16.4) | 35.6 (19.0) |
Baseline | 6th Week | 12th Week | p Group | p Time | p Interaction | |
---|---|---|---|---|---|---|
Total cholesterol (mg/dL) | ||||||
NC | 225.9 (19.7) | 224.9 (21.6) | 229.9 (25.5) | 0.855 | 0.476 | 0.083 |
Placebo | 228.6 (22.0) | 225.6 (24.9) | 224.5 (24.7) | |||
Cholesterol LDL (mg/dL) | ||||||
NC | 156.9 (21.3) | 155.8 (22.6) | 158.8 (25.4) | 0.384 | 0.410 | 0.150 |
Placebo | 156.4 (19.7) | 153.2 (22.7) | 152.1 (23.1) | |||
Cholesterol HDL (mg/dL) | ||||||
NC | 61.7 (16.8) | 62.2 (16.4) | 62.7 (17.6) | 0.078 | 0.880 | 0.158 |
Placebo | 68.1 (16.1) | 67.6 (14.8) | 66.8 (14.4) | |||
Total/HDL Cholesterol (mg/dL) | ||||||
NC | 3.9 (1.1) | 3.8 (1.0) | 3.9 (1.2) | 0.024 | 0.144 | 0.379 |
Placebo | 3.5 (0.8) | 3.5 (0.8) | 3.5 (0.8) | |||
Triglycerides (mg/dL) | ||||||
NC | 115.6 (57.5) | 120.1 (68.2) | 132.1 (81.8) | 0.364 | 0.032 | 0.822 |
Placebo | 107.8 (49.2) | 110.6 (77.3) | 118.0 (78.8) | |||
IPAQ | ||||||
NC | 1384.1 (1911.4) | - | 1306.4 (1683.9) | 0.379 | 0.425 | 0.841 |
Placebo | 1127.1 (1242.8) | - | 1080.6 (1154.9) |
Baseline | 6th Week | 12th Week | p Group | p Time | p Interaction | |
---|---|---|---|---|---|---|
Leukocytes (×103/µL) | ||||||
NC | 6.1 (1.8) | 6.4 (1.4) | 6.1 (1.5) | 0.289 | 0.215 | 0.207 |
Placebo | 5.8 (1.2) | 5.9 (1.3) | 6.1 (1.6) | |||
Neutrophils (×103/µL) | ||||||
NC | 3.3 (1.3) | 3.4 (1.0) | 3.3 (1.1) | 0.764 | 0.243 | 0.105 |
Placebo | 3.2 (1.0) | 3.2 (1.0) | 3.5 (1.3) | |||
C-reactive protein (mg/dL) * | ||||||
NC | −0.98 (0.45) | −0.93 (0.52) | −0.96 (0.43) | 0.694 | 0.488 | 0.179 |
Placebo | −0.92 (0.50) | −0.98 (0.44) | −0.88 (0.48) | |||
Interleukin-32 (pg/mL) | ||||||
NC | 39.97 (56.60) | - | 44.26 (57.23) | 0.408 | 0.452 | 0.587 |
Placebo | 58.61 (82.28) | - | 59.31 (96.92) | |||
Interleukin-38 (pg/mL) | ||||||
NC | 186.98 (124.11) | - | 183.38 (122.10) | 0.095 | 0.667 | 0.930 |
Placebo | 249.08 (147.76) | - | 246.70 (134.76) | |||
miR-21 | ||||||
NC | 4.53 × 10−7 (2.44 × 10−7) | - | 4.47 × 10−7 (3.31 × 10−7) | 0.923 | 0.427 | 0.275 |
Placebo | 4.34 × 10−7 (2.39 × 10−7) | - | 4.77 × 10−7 (3.01 × 10−7) | |||
miR-126 | ||||||
NC | 1.82 × 10−7 (1.51 × 10−7) | - | 1.76 × 10−7 (1.60 × 10−7) | 0.578 | 0.280 | 0.718 |
Placebo | 1.68 × 10−7 (1.55 × 10−7) | - | 1.55 × 10−7 (1.07 × 10−7) | |||
miR-146a | ||||||
NC | 2.23 × 10−8 (9.02 × 10−9) | - | 2.11 × 10−8 (1.04 × 10−8) | 0.821 | 0.611 | 0.206 |
Placebo | 2.37 × 10−8 (1.51 × 10−8) | - | 2.19 × 10−8 (1.05 × 10−8) |
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Protic, O.; Di Pillo, R.; Montesanto, A.; Galeazzi, R.; Matacchione, G.; Giuliani, A.; Sabbatinelli, J.; Gurău, F.; Silvestrini, A.; Olivieri, F.; et al. Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia. Nutrients 2022, 14, 2812. https://doi.org/10.3390/nu14142812
Protic O, Di Pillo R, Montesanto A, Galeazzi R, Matacchione G, Giuliani A, Sabbatinelli J, Gurău F, Silvestrini A, Olivieri F, et al. Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia. Nutrients. 2022; 14(14):2812. https://doi.org/10.3390/nu14142812
Chicago/Turabian StyleProtic, Olga, Raffaele Di Pillo, Alberto Montesanto, Roberta Galeazzi, Giulia Matacchione, Angelica Giuliani, Jacopo Sabbatinelli, Felicia Gurău, Andrea Silvestrini, Fabiola Olivieri, and et al. 2022. "Randomized, Double-Blind, Placebo-Controlled Trial to Test the Effects of a Nutraceutical Combination Monacolin K-Free on the Lipid and Inflammatory Profile of Subjects with Hypercholesterolemia" Nutrients 14, no. 14: 2812. https://doi.org/10.3390/nu14142812