Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA

Abstract

It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ10), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ10 decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ10H2, and CoQ10, without affecting the CoQ10H2/CoQ10 ratio. The other lipophilic antioxidants (d-RRR-alpha-tocopherol-vit E-, gamma-tocopherol, vit A, lycopene, and beta-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ10H2, CoQ10, and vit E; other parameters were not investigated. The observed decline of the levels of CoQ10H2 and CoQ10 in plasma and of CoQ10H2, CoQ10 and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the basis of human and animal studies.

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“…Treatment with coenzyme Q10 reverses statin-induced fatigue and neurocognitive symptoms (Langsjoen et al 2005;Passi et al 2003). Curcumin and analogues inhibit ROS-induced lipid peroxidation and protein damage in mitochondria (Wei et al 2006).…”

Reduction of Serum Ubiquinol-10 and Ubiquinone-10 Levels by Atorvastatin in Hypercholesterolemic Patients

“…The widely prescribed statins block the endogenous biosynthesis both of cholesterol and of CoQ10, and the decrease in both substances is related to the does as well as the potency of these drugs (16,20). Ten mg/day of atorvastatin decreased the ubiquinol levels by 31% in plasma and by 35.2% in lymphocytes (21), and 80 mg/ day of atorvastatin decreased those in plasma by 52% (22). In the present study, the percent decrease of ubiquinol-10 level was 43.2%, and the percent decrease of total and LDL-cholesterol levels produced a proportional decrease of ubiquinol-10 and ubiquinone-10 levels.…”

Coenzyme Q10 and Statin Myalgia: What is the Evidence?

“…Littarru and Langsjoen [29] showed that simvastatin, atorvastatin, and pravastatin produced a dose-dependent plasma depletion of cholesterol and CoQ. This reduction in CoQ has also been observed in lymphocytes [30]. Mabuchi et al [28] conducted a randomized, double-blind, placebo-controlled study that examined the effects of CoQ (100 mg/d) and placebo in 49 hypercholesterolemic patients treated with 10 mg/d of atorvastatin for 16 weeks.…”