Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial

Daniel M Riche, Krista D Riche, Chad T Blackshear, Corey L McEwen, Justin J Sherman, Marion R Wofford, Michael E Griswold, Daniel M Riche, Krista D Riche, Chad T Blackshear, Corey L McEwen, Justin J Sherman, Marion R Wofford, Michael E Griswold

Abstract

Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL ≥ 100 mg/dL. Subjects were divided into four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6-8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001) which was not seen with GE combination (P = 0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (-7.8 mmHg; P < 0.01) and diastolic blood pressure (-7.3 mmHg; P < 0.001) were reduced with high dose pterostilbene. Patients not on cholesterol medication (n = 51) exhibited minor weight loss with pterostilbene (-0.62 kg/m(2); P = 0.012). Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227.

Figures

Figure 1
Figure 1
Enrollment strategy.
Figure 2
Figure 2
Efficacy analysis: lipids and blood pressure. Interpretation. Expected changes in an outcome (vertical axis) for any given level of baseline value (horizontal axis) across all four treatment groups. Adjusted for age, gender, and race. SBP: systolic blood pressure; DBP: diastolic blood pressure; LD: low dose; LD + Grape: low dose + grape combination; HD: high dose. Units: mg/dL or mmHg.
Figure 3
Figure 3
Lipid treatment effects by baseline cholesterol medication. Interpretation. Bold lines indicate significance. Significant measures to the right of 0 indicate an increased effect with the reported group versus placebo. Significant measures to the left of 0 indicate a decreased effect with the reported group versus placebo. Adjusted for age, gender, and race. TRT: treatment; CI: confidence interval; LD: low dose; LD + G: low dose + grape combination; HD: high dose. Units: mg/dL.
Figure 4
Figure 4
BMI treatment effects by baseline cholesterol medication. Interpretation. Bold lines indicate significance. Significant measures to the right of 0 indicate an increased BMI with the reported group versus placebo. Significant measures to the left of 0 indicate a decreased BMI with the reported group versus placebo. Adjusted for age, gender, and race. TRT: treatment; CI: confidence interval; LD: low dose; LD + G: low dose + grape combination; HD: high dose. Units: kg/m2.

References

    1. Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. National Health Statistics Reports. 2009;(13):1–7.
    1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1) e6:p. e245.
    1. Centers for Disease Control and Prevention. Compressed Mortality File 1999–2009. CDC WONDER Online Database, compiled for Compressed Mortality File 1999–2009 Series 20, No. 20, 2012. Underlying cause-of-death 1999–2009, 2013, .
    1. Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation. 2013;127(2):188–196.
    1. Rimando AM, Nagmani R, Feller DR, Yokoyama W. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor α-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. Journal of Agricultural and Food Chemistry. 2005;53(9):3403–3407.
    1. Park ES, Lim Y, Hong JT, et al. Pterostilbene, a natural dimethylated analog of resveratrol, inhibits rat aortic vascular smooth muscle cell proliferation by blocking Akt-dependent pathway. Vascular Pharmacology. 2010;53(1-2):61–67.
    1. Das DK, Sato M, Ray PS, Maulik G, Engelman RM, Bertelli AAE. Cardioprotection of red wine: role of polyphenolic antioxidants. Drugs under Experimental and Clinical Research. 1999;25(2-3):115–120.
    1. Tugwood JD, Aldridge TC, Lambe KG, Macdonald N, Woodyatt NJ. Peroxisome proliferator-activated receptors: stuctures and function. Annals of the New York Academy of Sciences. 1996;804:252–265.
    1. McCormack D, McFadden D. A review of pterostilbene antioxidant activity and disease modification. Oxidative Medicine and Cellular Longevity. 2013;2013:15 pages.575482
    1. Shaul PW. Regulation of endothelial nitric oxide synthase: Location, location, location. Annual Review of Physiology. 2002;64:749–774.
    1. Lin HS, Yue BD, Ho PC. Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study. Biomedical Chromatography. 2009;23(12):1308–1315.
    1. Kapetanovic IM, Muzzio M, Huang Z, Thompson TN, McCormick DL. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemotherapy and Pharmacology. 2011;68(3):593–601.
    1. Belcaro G, Ledda A, Hu S, Cesarone MR, Feragalli B, Dugall M. Grape seed procyanidins in pre- and mild hypertension: a registry study. Evidence-Based Complementary and Alternative Medicine. 2013;2013:5 pages.313142
    1. Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. Journal of the American Dietetic Association. 2011;111(8):1173–1181.
    1. Riche DM, McEwen CL, Riche KD, et al. Analysis of safety from a human clinical trial with pterostilbene. Journal of Toxicology. 2013;2013:5 pages.463595
    1. Gottumukkala VS, Masna M, Hindupur RM, Thatipally S. Inventors, aptuit laurus private limited, assignee. X. World patent WO, 2010/0101578 A2, July 2009.
    1. Jones DW, Appel LJ, Sheps SG, Roccella EJ, Lenfant C. Measuring blood pressure accurately: new and persistent challenges. The Journal of the American Medical Association. 2003;289(8):1027–1030.
    1. Rasmussen CB, Glisson JK, Minor DS. Dietary supplements and hypertension: potential benefits and precautions. The Journal of Clinical Hypertension. 2012;14:467–471.
    1. Nahas R. Complementary and alternative medicine approaches to blood pressure reduction: an evidence-based review. Canadian Family Physician. 2008;54(11):1529–1533.
    1. Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005;28(7):1547–1554.
    1. Farnier M. Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms of action and rational prescribing. Diabetes Research and Clinical Practice. 2005;70:20–25.
    1. Negro R, Mangieri T, Dazzi D, Pezzarossa A, Hassan H. Rosiglitazone effects on blood pressure and metabolic parameters in nondipper diabetic patients. Vascular Health and Risk Management. 2008;4:991–1000.
    1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013
    1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults report from the panel members appointed to the eighth Joint National Committee (JNC 8) The Journal of the American Medical Association. 2014;311(5):507–520.
    1. Vollmer WM, Appel LJ, Svetkey LP, et al. Comparing office-based and ambulatory blood pressure monitoring in clinical trials. Journal of Human Hypertension. 2005;19(1):77–82.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅