Xanthophylls, phytosterols and pre-β1-HDL are differentially affected by fenofibrate and niacin HDL-raising in a cross-over study.
Fenofibrate and extended-release (ER) niacin similarly raise high-density lipoprotein cholesterol (HDL-C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre-β1-HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER-niacin (0.5 g/day for 3 week, then 1 g/day) in a cross-over study. Both treatments increased HDL-C (16 %) and apolipoprotein (apo) A-I (7 %) but only fenofibrate increased apoA-II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low-density lipoprotein cholesterol and positively correlated with end of treatment apoA-II. ApoA-II in isolated HDL in vitro bound more lutein than apoA-I. Xanthophylls were increased by ER-niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre-β1-HDL was significantly decreased by fenofibrate (-19 %, p < 0.0001), with little change (3.4 %) for ER-niacin. Although fenofibrate and ER-niacin similarly increased plasma HDL-C and apoA-I, effects on plasma xanthophylls, phytosterols and pre-β1-HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA-II in xanthophyll metabolism.
Pharma Research and Early Development, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd, Metabolic DBA, Bldg. 70/411 Grenzacherstrasse 124, 4070, Basel, Switzerland, eric_j.niesor@roche.com.
Eric J
EJ
Niesor
Kekulawalage
K
Gauthamadasa
R A Gangani D
RA
Silva
Gabriela
G
Suchankova
David
D
Kallend
Helena
H
Gylling
Bela
B
Asztalos
Elisabetta
E
Damonte
Simona
S
Rossomanno
Markus
M
Abt
W Sean
WS
Davidson
Renee
R
Benghozi
D016633:Apolipoprotein A-II / Q000097:blood; D018592:Cross-Over Studies; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D014975:Lutein / Q000097:blood; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D010840:Phytosterols / Q000097:blood*; D024341:Xanthophylls / Q000097:blood*; D065146:Zeaxanthins
D016633:Apolipoprotein A-II; D053442:High-Density Lipoproteins, Pre-beta; D000960:Hypolipidemic Agents; D010840:Phytosterols; D024341:Xanthophylls; D065146:Zeaxanthins; D009525:Niacin; D011345:Fenofibrate; D014975:Lutein