Supplementation with beta-carotene in vivo and in vitro does not inhibit low density lipoprotein oxidation
Gaziano, J.M.; Hatta, A.; Flynn, M.; Johnson, E.J.; Krinsky, N.I.; Ridker, P.M.; Hennekens, C.H.; Frei, B.
Atherosclerosis 112(2): 187-195
ISSN/ISBN: 0021-9150 PMID: 7772078 Accession: 009491214
The inhibition of low density lipoprotein (LDL) oxidation has been postulated as one mechanism by which antioxidants may prevent the development of atherosclerosis. Available data on the ability of beta-carotene to inhibit LDL oxidation are conflicting. We examined the role of in vivo and in vitro supplementation with beta-carotene on metal ion-dependent (cupric ions, CU-2+) and metal ion-independent (2,2'-azobis(2-amidinopropane)dihydrochloride, AAPH) oxidation of LDL as measured by the formation of conjugated dienes (absorbance at 234 nm). Sixteen subjects were supplemented with 50-100 mg of beta-carotene on alternate days for 3 weeks following a week-long loading dose of 100 mg/day. Plasma beta-carotene levels rose 5.5-fold, while LDL beta-carotene levels rose 8.5-fold. Oxidation of LDL by CU-2+ or AAPH was not significantly delayed after in vivo supplementation with beta-carotene compared with base- line. For AAPH, the lag phase (in minutes) was 75 +- 8 at baseline and 83 +- 14 after supplementation (P = 0.07). For CU-2+, the lag phase was 172 +- 41 at baseline and decreased to 130 +- 24 after supplementation (P lt 0.01). Similarly, no protective effect against Cu-2+-induced oxidation was observed when beta-carotene was added to LDL in vitro. Supplementation of plasma with beta-carotene in vitro prior to LDL isolation also did not enhance LDL's resistance to Cu-2+ or AAPH-induced oxidation, despite a 5-fold increase in LDL beta-carotene levels over vehicle control. These data indicate that supplementation with beta-carotene in vivo or in vitro does not enhance the protection of LDL against metal ion-dependent and -independent oxidation; rather, in vivo beta-carotene supplementation may lead to a shortening of the lag phase of Cu-2+-induced lipid peroxidation in LDL.