Lathosterol-to-cholesterol ratio in serum predicts cholesterol-lowering response to plant sterol consumption in a dual-center, randomized, single-blind placebo-controlled trial.
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.


METHODS
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.
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).
Dylan S
DS
Mackay
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).
Sarah K
SK
Gebauer
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).
Peter K
PK
Eck
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).
David J
DJ
Baer
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).
Peter J H
PJ
Jones
D000328:Adult; D000368:Aged; D000465:Algorithms; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism; D008297:Male; D008350:Manitoba; D008383:Margarine; D008396:Maryland; D008875:Middle Aged; D010840:Phytosterols / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D010840:Phytosterols; C001521:lathosterol; D008383:Margarine; D002784:Cholesterol
cholesterol lowering; interindividual variability; noncholesterol sterols; plant sterols; randomized controlled trial