Dylan S Mackay1, Sarah K Gebauer1, Peter K Eck1, David J Baer1, Peter J H Jones1. 1. From the Richardson Centre for Functional Foods and Nutraceuticals (DSM, PKE, and PJHJ) and the Departments of Food Science (PJHJ) and Human Nutritional Sciences (DSM, PKE, and PJHJ), University of Manitoba, Winnipeg, Manitoba, Canada, and the USDA, Agricultural Research Service, Beltsville Human Nutrition Research Center, Beltsville, MD (SKG and DJB).
Abstract
BACKGROUND: Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with nonresponse to PS consumption; however, prospective studies that show this association have yet to be conducted. OBJECTIVE: The goal was to test whether the lathosterol-to-cholesterol ratio (L:C ratio), a surrogate marker of endogenous cholesterol synthesis, serves as an a priori predictor of cholesterol lowering in response to PS consumption. DESIGN:Sixty-three mildly hypercholesterolemic adults who were preselected as possessing either high endogenous cholesterol synthesis [HS; n = 24; L:C = 2.03 ± 0.39 μmol/mmol (mean ± SD)] or low endogenous cholesterol synthesis (LS; n = 39; L:C = 0.99 ± 0.28 μmol/mmol) on the basis of baseline L:C consumed 2 g PS/d or a placebo for 28 d with the use of a dual-center, single-blind, randomized crossover design. Plasma lipid and noncholesterol sterol concentrations were measured at the end of each phase. RESULTS:PS consumption lowered total cholesterol (TC; -0.25 ± 0.05 mmol/L; P < 0.0001) and LDL cholesterol (-0.17 ± 0.04 mmol/L; P < 0.0001) overall. Specifically, LS individuals responded to PS treatment with a reduction in TC (-0.40 ± 0.07 mmol/L; P < 0.0001) and LDL cholesterol (-0.29 ± 0.05 mmol/L; P = 0.0002), whereas HS individuals failed to show cholesterol lowering (TC: -0.09 ± 0.09 mmol/L; P = 0.2843; LDL cholesterol: -0.05 ± 0.07 mmol/L; P = 0.4917). The odds of LS participants responding to PS consumption with cholesterol lowering better than the mean cholesterol lowering in all participants were 4.25 (95% CI: 1.242, 14.556; P = 0.0211) for TC and 3.36 (95% CI: 1.112, 10.161; P = 0.0317) for LDL cholesterol, which was higher than for HS participants. CONCLUSIONS: The L:C ratio predicts the extent of reduction in circulating TC and LDL cholesterol in response to PS consumption. Cholesterol synthesis assessment may thus have a use in identifying responders and nonresponders to PS therapy.
RCT Entities:
BACKGROUND: Benefits of plant sterols (PS) for cholesterol lowering are compromised by large variability in efficacy across individuals. High fractional cholesterol synthesis measured by deuterium incorporation has been associated with nonresponse to PS consumption; however, prospective studies that show this association have yet to be conducted. OBJECTIVE: The goal was to test whether the lathosterol-to-cholesterol ratio (L:C ratio), a surrogate marker of endogenous cholesterol synthesis, serves as an a priori predictor of cholesterol lowering in response to PS consumption. DESIGN: Sixty-three mildly hypercholesterolemic adults who were preselected as possessing either high endogenous cholesterol synthesis [HS; n = 24; L:C = 2.03 ± 0.39 μmol/mmol (mean ± SD)] or low endogenous cholesterol synthesis (LS; n = 39; L:C = 0.99 ± 0.28 μmol/mmol) on the basis of baseline L:C consumed 2 g PS/d or a placebo for 28 d with the use of a dual-center, single-blind, randomized crossover design. Plasma lipid and noncholesterol sterol concentrations were measured at the end of each phase. RESULTS:PS consumption lowered total cholesterol (TC; -0.25 ± 0.05 mmol/L; P < 0.0001) and LDL cholesterol (-0.17 ± 0.04 mmol/L; P < 0.0001) overall. Specifically, LS individuals responded to PS treatment with a reduction in TC (-0.40 ± 0.07 mmol/L; P < 0.0001) and LDL cholesterol (-0.29 ± 0.05 mmol/L; P = 0.0002), whereas HS individuals failed to show cholesterol lowering (TC: -0.09 ± 0.09 mmol/L; P = 0.2843; LDL cholesterol: -0.05 ± 0.07 mmol/L; P = 0.4917). The odds of LS participants responding to PS consumption with cholesterol lowering better than the mean cholesterol lowering in all participants were 4.25 (95% CI: 1.242, 14.556; P = 0.0211) for TC and 3.36 (95% CI: 1.112, 10.161; P = 0.0317) for LDL cholesterol, which was higher than for HSparticipants. CONCLUSIONS: The L:C ratio predicts the extent of reduction in circulating TC and LDL cholesterol in response to PS consumption. Cholesterol synthesis assessment may thus have a use in identifying responders and nonresponders to PS therapy.
Authors: Peter J H Jones; Maryam Shamloo; Dylan S MacKay; Todd C Rideout; Semone B Myrie; Jogchum Plat; Jean-Baptiste Roullet; David J Baer; Kara L Calkins; Harry R Davis; P Barton Duell; Henry Ginsberg; Helena Gylling; David Jenkins; Dieter Lütjohann; Mohammad Moghadasian; Robert A Moreau; David Mymin; Richard E Ostlund; Rouyanne T Ras; Javier Ochoa Reparaz; Elke A Trautwein; Stephen Turley; Tim Vanmierlo; Oliver Weingärtner Journal: Nutr Rev Date: 2018-10-01 Impact factor: 7.110
Authors: Dragan Milenkovic; Christine Morand; Aedin Cassidy; Aleksandra Konic-Ristic; Francisco Tomás-Barberán; José M Ordovas; Paul Kroon; Raffaele De Caterina; Ana Rodriguez-Mateos Journal: Adv Nutr Date: 2017-07-14 Impact factor: 8.701
Authors: Bianca Scolaro; Marina S Nogueira; Aline Paiva; Adriana Bertolami; Lucia P Barroso; Tomas Vaisar; Sean P Heffron; Edward A Fisher; Inar A Castro Journal: Mol Metab Date: 2018-02-20 Impact factor: 7.422
Authors: Valéria Sutti Nunes; Angela de Oliveira Godoy Ilha; Guilherme da Silva Ferreira; Renata de Paula Assis Bombo; Milessa Silva Afonso; Maria Silvia Ferrari Lavrador; Roberta Marcondes Machado; Edna Regina Nakandakare; Eder Carlos Rocha Quintão; Ana Maria Lottenberg Journal: Clinics (Sao Paulo) Date: 2022-04-06 Impact factor: 2.365