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Selective, Multi‐Target Protein Kinase Inhibitors, Rho iso‐alpha acids (RIAA) and Proanthocyanidins, Combined with Cholesterol Lowering Foods, Reduced Cardiovascular Risk Factors in Humans with Metabolic Syndrome
Author(s) -
Tripp Matthew,
Lerman Robert,
Lamb Joseph,
Minich Deanna,
Darland Gary,
Konda Veera,
Emma Dennis,
Carroll Brian,
Babish John,
Pacioretty Linda,
Bland Jeffrey
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1112.2
Subject(s) - insulin resistance , metabolic syndrome , proanthocyanidin , phytochemical , medicine , insulin , endocrinology , metformin , biology , pharmacology , biochemistry , diabetes mellitus , antioxidant , polyphenol
Background: Metabolic Syndrome (MetS), insulin resistance and hypercholesterolemia are major cardiovascular disease (CVD) risk factors. Epidemiological studies suggest that a phytochemically poor diet may be implicated, however, the effect of specific dietary phytochemicals on MetS remains largely unexplored. Objective: To identify phytochemicals which improve insulin sensitivity using in vitro models, and investigate their effects in animal models of insulin resistance, and on CVD risk factors in humans with MetS. Results: RIAA and proanthocyanidins improved insulin signaling in an in vitro 3T3L1 adipocyte screen. In cell free assays they were found to be selective, multi‐target protein kinase inhibitors (e.g., GSK3α and β; PKCβ2; IKKβ), possibly explaining their mode of action. In combination they reduced insulin and glucose to a similar degree as metformin in obese db/db mice. Thus, a human clinical study was conducted. In this 2‐arm, open‐label, 12 wk study, volunteers with MetS and hypercholesterolemia were randomized to either a phytochemical rich Mediterranean‐style, low glycemic load diet, MED (n=19) or MED plus tailored phytochemicals (PED) (n=25) including soy protein, plant sterols, RIAA, and proanthocyanidins. Phytochemical supplementation (PED) led to a greater decrease in CVD risk compared with diet alone (P<0.001), a result independent of weight loss or caloric restriction.