9-cis beta-carotene-rich powder of the alga Dunaliella bardawil increases plasma HDL-cholesterol in fibrate-treated patients.
The effect of fibrates on high density lipoprotein (HDL)-cholesterol levels is suggested to be mediated by its binding to peroxisome proliferator-activated receptor-alpha (PPARalpha). Upon ligand binding, PPARalpha heterodimerizes with the 9-cis retinoic acid receptor (RXR) and it is this heterodimer which regulates gene expression. We assessed the hypothesis that a combined treatment with fibrate plus 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil, as a source of 9-cis retinoic acid, would improve the drug's effect on HDL-cholesterol levels. In an open-labeled first trial, 20 fibrate-treated men with plasma HDL-cholesterol levels below 40 mg/dl were given Dunaliella capsules, providing 60 mg beta-carotene/day, containing all-trans and 9-cis beta-carotene (1:1 ratio, w/w). Twenty-two fibrate-treated patients participated in a double-blind placebo-controlled second trial. Eleven patients were treated with Dunaliella capsules, and 11 patients were treated with beta-carotene-deficient Dunaliella capsules. Following 6 weeks of the dual treatment plasma HDL-cholesterol increased by 24.5 and 12.7% in the first and second trials, respectively (P=0.002 and 0.012). The dual treatment also increased HDL-cholesterol levels in human apolipoprotein A-I transgenic mice by 87.5% (P=0.021). The results show that a combination treatment of fibrate plus 9-cis beta-carotene-rich Dunaliella powder amplifies the effect of the drug on HDL-cholesterol levels.
Shaish
Aviv
A
The Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel-Hashomer 52621, Israel.
Harari
Ayelet
A
Hananshvili
Lea
L
Cohen
Hofit
H
Bitzur
Rafael
R
Luvish
Tamar
T
Ulman
Esfir
E
Golan
Moria
M
Ben-Amotz
Ami
A
Gavish
Dov
D
Rotstein
Zeev
Z
Harats
Dror
D
D000328:Adult; D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D000460:Chlorophyta; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D002995:Clofibric Acid / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011208:Powders; D016896:Treatment Outcome; D014815:Vitamins / Q000627:therapeutic use*; D019207:beta Carotene / Q000627:therapeutic use*
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D018680:Cholinergic Antagonists; D011208:Powders; D014815:Vitamins; D019207:beta Carotene; D002995:Clofibric Acid