Effects of simvastatin on carotenoid status in plasma.
OBJECTIVE
Carotenoids are potent antioxidants mainly transported in the low density lipoprotein (LDL) fraction. They may also influence the immune response and inverse associations with inflammatory markers have been reported. We investigated whether simvastatin, by exerting both lipid-lowering and anti-inflammatory effects, altered the carotenoid status in plasma.


RESULTS
A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. Lipids, oxidized LDL (ox-LDL), C-reactive protein (CRP), interleukin (IL)-6, oxygenated carotenoids (lutein, zeaxanthin, β-cryptoxanthin) and hydrocarbon carotenoids (α-carotene, β-carotene, lycopene) were measured in plasma. Simvastatin use was associated with significant reductions in total cholesterol, LDL, ox-LDL and CRP. Simvastatin therapy also resulted in reduced plasma levels of both oxygenated and hydrocarbon carotenoids. However, when adjusted for lipids, all carotenoids except β-cryptoxanthin showed significant increases after simvastatin therapy. Both crude and lipid-adjusted carotenoids were inversely correlated with CRP and IL-6 in plasma but the change in carotenoid status during simvastatin therapy was not specifically related to any changes in inflammatory markers.


CONCLUSIONS
To summarize, the change in carotenoid status during simvastatin therapy was mainly attributed to the lowering of cholesterol and not to the suppression of inflammatory activity. After adjustment for lipids, the levels of lutein, lycopene, α-carotene and β-carotene were significantly increased by simvastatin suggesting an increased ratio of carotenoids per particle.
Rydén
M
M
Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
Leanderson
P
P
Kastbom
K-O
KO
Jonasson
L
L
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001055:Apolipoproteins B / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002338:Carotenoids / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*
D000975:Antioxidants; D001055:Apolipoproteins B; D015415:Biomarkers; D015850:Interleukin-6; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002338:Carotenoids; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin