Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial

Abstract

Background: As the worldwide dietary pattern becomes more westernized, the metabolic syndrome is reaching epidemic proportions. Lifestyle modifications including diet and exercise are recommended as first-line intervention for treating metabolic syndrome. Previously, we reported that a modified Mediterranean-style, low glycemic load diet with soy protein and phytosterols had a more favorable impact than the American Heart Association Step 1 diet on cardiovascular disease (CVD) risk factors. Subsequently, we screened for phytochemicals with a history of safe use that were capable of increasing insulin sensitivity through modulation of protein kinases, and identified hops rho iso-alpha acid and acacia proanthocyanidins. The objective of this study was to investigate whether enhancement of a modified Mediterranean-style, low glycemic load diet (MED) with specific phytochemicals (soy protein, phytosterols, rho iso-alpha acids and proanthocyanidins; PED) could improve cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia.

Methods: Forty-nine subjects with metabolic syndrome and hypercholesterolemia, aged 25-80, entered a randomized, 2-arm, 12-week intervention trial; 23 randomized to the MED arm; 26 to the PED arm. Forty-four subjects completed at least 8 weeks [MED (n = 19); PED (n = 25)]. All subjects were instructed to follow the same aerobic exercise program. Three-day diet diaries and 7-day exercise diaries were assessed at each visit. Fasting blood samples were collected at baseline, 8 and 12 weeks for analysis.

Results: Both arms experienced equal weight loss (MED: -5.7 kg; PED: -5.9 kg). However, at 12 weeks, the PED arm experienced greater reductions (P < 0.05) in cholesterol, non-HDL cholesterol, triglycerides (TG), cholesterol/HDL and TG/HDL compared with the MED arm. Only the PED arm experienced increased HDL (P < 0.05) and decreased TG/HDL (P < 0.01), and continued reduction in apo B/apo A-I from 8 to 12 weeks. Furthermore, 43% of PED subjects vs. only 22% of MED subjects had net resolution of metabolic syndrome. The Framingham 10-year CVD risk score decreased by 5.6% in the PED arm (P < 0.01) and 2.9% in the MED arm (P < 0.05).

Conclusion: These results demonstrate that specific phytochemical supplementation increased the effectiveness of the modified Mediterranean-style low glycemic load dietary program on variables associated with metabolic syndrome and CVD.

Figure 1

Flow chart of participant enrollment and study design.

Figure 2

Structural formula of (A) rho iso-alpha acids from Humulus lupulus L. and (B) proanthocyanidins from Acacia nilotica bark extract (N = 4–10 for oligomeric, and > 10 for polymeric fractions). rho iso-alpha acids formulation contains approximately 25% inorganic salts, eg., Mg⁺², K⁺, and SO₄^-2, 5% low-molecular resin and 68% total rho iso-alpha acids, as a mixture of related analogs and diastereomers with a ratio of cis to trans of 3:1 and a ratio of co- to n- of 1:2.2. The aqueous/methanol acacia extract consists of approximately 16% small molecule catechins and gallates, 28% oligomeric proanthocyanidins with a degree of polymerization of 4–8 and 56% polymeric proanthocyanidins with a degree of polymerization of 58.

Figure 3

Individual responses in serum lipid parameters (A, total cholesterol; B, LDL; C, HDL; D, non-HDL cholesterol; E, TG; F, TG/HDL; G, LDL particle number; H, apo B/apo A-I) in the intervention (PED) and control (MED) arms at baseline and 12 weeks. Shaded bars indicate mean responses.