9-cis beta-carotene-rich powder of the alga Dunaliella bardawil increases plasma HDL-cholesterol in fibrate-treated patients

Shaish, A.; Harari, A.; Hananshvili, L.; Cohen, H.; Bitzur, R.; Luvish, T.; Ulman, E.; Golan, M.; Ben-Amotz, A.; Gavish, D.; Rotstein, Z.; Harats, D.

Atherosclerosis 189(1): 215-221


ISSN/ISBN: 0021-9150
PMID: 16413556
DOI: 10.1016/j.atherosclerosis.2005.12.004
Accession: 011673948

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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 (PPAR alpha). Upon ligand binding, PPAR alpha 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 P-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 P-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 P-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 P-carotene-rich Dunaliella powder amplifies the effect of the drug on HDL-cholesterol levels. (c) 2005 Elsevier Ireland Ltd. All rights reserved.