The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial.
OBJECTIVE
Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism.


METHODS
In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers.


RESULTS
The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), P<0.0001) and 79% higher fecal cholesterol excretion (1322±112 (1083.2, 1483.3) vs 739±97 mg/day (530.1, 930.2), P<0.0001) relative to the phytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), P<0.0001). LDL-cholesterol was similar between diets.


CONCLUSIONS
Intrinsic phytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.
Lin
X
X
Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
Racette
S B
SB
Lefevre
M
M
Spearie
C A
CA
Most
M
M
Ma
L
L
Ostlund
R E
RE
D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D004032:Diet; D005260:Female; D005502:Food; D006801:Humans; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000378:metabolism / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D010840:Phytosterols; C001521:lathosterol; D002784:Cholesterol
J Lipid Res. 2009 Sep;50(9):1927-35
19436064
Proc Soc Exp Biol Med. 1951 Oct;78(1):143-7
14891948
Circulation. 1953 May;7(5):702-6
13042924
Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G931-5
19246636
Am J Clin Nutr. 1999 Nov;70(5):826-31
10539742
FEBS Lett. 2003 Feb 11;536(1-3):6-11
12586329
Circulation. 2006 Jul 4;114(1):82-96
16785338
Circulation. 2006 Jun 20;113(24):2826-34
16769916
Br J Nutr. 2001 Feb;85(2):137-9
11242480
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7604-9
12032330
Annu Rev Nutr. 2002;22:533-49
12055357
J Lipid Res. 1993 Jun;34(6):1039-46
8354951
J Nutr. 2009 Feb;139(2):271-84
19091798
Am J Clin Nutr. 1984 Oct;40(4 Suppl):927-30
6486101
Clin Chem. 1972 Jun;18(6):499-502
4337382
Am J Clin Nutr. 2010 Jan;91(1):32-8
19889819
Am J Clin Nutr. 2003 Jun;77(6):1385-9
12791614
Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):841-9
17218600
J Am Diet Assoc. 2009 Dec;109(12):2043-51
19942022
J Lipid Res. 1998 Apr;39(4):892-900
9555952
Clin Chem. 1982 Jun;28(6):1379-88
7074948
Metabolism. 1989 Feb;38(2):136-40
2913464
Prev Cardiol. 2003 Winter;6(1):29-33, 64
12624559
JAMA. 2001 May 16;285(19):2486-97
11368702
Am J Clin Nutr. 1995 Feb;61(2):392-6
7840080
Am J Clin Nutr. 2000 Apr;71(4):908-13
10731496
Am J Clin Nutr. 2006 Oct;84(4):756-61
17023701
Am J Clin Nutr. 2002 Jun;75(6):1000-4
12036805
Eur J Clin Nutr. 2001 Dec;55(12):1084-90
11781675