Effect of Pterostilbene on Cholesterol, Blood Pressure and Oxidative Stress

• Blood Pressure [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  Change in baseline systolic blood pressure and/or diastolic blood pressure
• Subjective Adverse Effects [ Time Frame: Baseline and 6-8 weeks ] [ Designated as safety issue: Yes ]
  Number of participants with adverse effects as a measure of safety

• Blood Pressure [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  Change in baseline systolic blood pressure and/or diastolic blood pressure
• Oxidative Stress Markers [ Time Frame: 6-8 weeks ] [ Designated as safety issue: No ]
  Change in baseline urine markers of stress (iPF2-Alpha-III/creat; iPF2-Alpha-VI/creat; 2,3 Dinor iPF2 Alpha III/creat)
• Number of Participants With Adverse Effects as a Measure of Safety and Tolerability. [ Time Frame: 6-8 weeks ] [ Designated as safety issue: Yes ]
  Subjective adverse effects, as well as changes in electrolytes, kidney function, or liver function

Pterostilbene is one of several stilbenes found in certain berries, particularly blueberries, that have demonstrated pre-clinical benefit to cholesterol, blood pressure, and oxidative stress. The purpose of this study is to evaluate whether pterostilbene will help control cholesterol and blood pressure, as well as improve markers for oxidative stress in patients with dyslipidemia meeting inclusion criteria. The investigators also want to look at the safety of pterostilbene in these patients.

Subjects will be divided into one of four groups: (1) pterostilbene 50 mg twice daily; (2) pterostilbene 125 mg twice daily; (3) pterostilbene 50 mg/grape extract 100 mg twice daily; (4) matching placebo twice daily taken either one hour before or two hours after a meal. Blood and urine will be collected at enrollment and final study visits. If the patient's low density lipoprotein-C (LDL-C) or total cholesterol (TC) is not within the inclusion criteria based on enrollment blood drawn, the patient will not be allowed to initiate study medication. All study visits will consist of brief clinical examination (including vital signs), subjective adverse event reporting, and fasting donated blood and urine for clinical laboratory tests. Pill counts will be done to assess compliance.

• Hyperlipidemia
• Blood Pressure
• Oxidative Stress

• Drug: Pterostilbene 50 mg twice daily
  Pterostilbene 50 mg twice by mouth daily for 6 to 8 weeks
  Other Name: pTeroPure
• Drug: Placebo
  Matching placebo by mouth twice daily for 6 to 8 weeks
• Drug: Grape Extract
  Grape extract 100 mg twice daily for 6-8 weeks
  Other Name: ShanStar Concord Grape
• Drug: Pterostilbene 125 mg twice daily
  Pterostilbene 125 mg twice daily for 6-8 weeks
  Other Name: pTeropure

• Active Comparator: High Dose
  Pterostilbene 125 mg twice daily
  Intervention: Drug: Pterostilbene 125 mg twice daily
• Active Comparator: Low Dose
  Pterostilbene 50 mg twice daily
  Intervention: Drug: Pterostilbene 50 mg twice daily
• Active Comparator: Low Dose Combination
  Pterostilbene 50 mg/Grape Extract 100 mg twice daily
  Interventions:

  • Drug: Pterostilbene 50 mg twice daily
  • Drug: Grape Extract
• Placebo Comparator: Placebo
  Matching placebo twice daily
  Intervention: Drug: Placebo

• Paul S, Rimando AM, Lee HJ, Ji Y, Reddy BS, Suh N. Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells. Cancer Prev Res (Phila). 2009 Jul;2(7):650-7. Epub 2009 Jun 23.
• Rimando AM, Kalt W, Magee JB, Dewey J, Ballington JR. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem. 2004 Jul 28;52(15):4713-9.
• Rimando AM, Nagmani R, Feller DR, Yokoyama W. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem. 2005 May 4;53(9):3403-7.
• Amarnath Satheesh M, Pari L. The antioxidant role of pterostilbene in streptozotocin-nicotinamide-induced type 2 diabetes mellitus in Wistar rats. J Pharm Pharmacol. 2006 Nov;58(11):1483-90.
• Satheesh AM, Pari L. Effect of pterostilbene on lipids and lipid profiles in streptozotocin-nicotinamide induced type 2 diabetes mellitus. Journal of Applied Biomedine 6(1):31-37, 2008.

Inclusion Criteria:

• Patients ≥18 years of age with a previous TC ≥200 mg/dL and/or a LDL ≥100 mg/dL on either no therapy or stable therapy
• Any concomitant cholesterol medication (not listed in the exclusion criteria) must be at a stable dose for at least 2 months prior to baseline laboratory

Exclusion Criteria:

• Patients with significant hepatic, renal or gastrointestinal tract disease
• Receiving thiazolidinediones or fibric acid derivatives
• Current overt cardiovascular disease
• Women of reproductive potential not receiving birth control
• Pregnant/nursing women