Increased oxidative stress and coenzyme Q10 deficiency in juvenile fibromyalgia: amelioration of hypercholesterolemia and fatigue by ubiquinol-10 supplementation

Abstract

Fibromyalgia (FM) is characterized by generalized pain and chronic fatigue of unknown etiology. To evaluate the role of oxidative stress in this disorder, we measured plasma levels of ubiquinone-10, ubiquinol-10, free cholesterol (FC), cholesterol esters (CE), and free fatty acids (FFA) in patients with juvenile FM (n=10) and in healthy control subjects (n=67). Levels of FC and CE were significantly increased in juvenile FM as compared with controls, suggesting the presence of hypercholesterolemia in this disease. However, plasma level of ubiquinol-10 was significantly decreased and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) was significantly increased in juvenile FM relative to healthy controls, suggesting that FM is associated with coenzyme Q10 deficiency and increased oxidative stress. Moreover, plasma level of FFA was significantly higher and the content of polyunsaturated fatty acids (PUFA) in total FFA was significantly lower in FM than in controls, suggesting increased tissue oxidative damage in juvenile FM. Interestingly, the content of monoenoic acids, such as oleic and palmitoleic acids, was significantly increased in FM relative to controls, probably to compensate for the loss of PUFA. Next, we examined the effect of ubiquinol-10 supplementation (100 mg/day for 12 weeks) in FM patients. This resulted in an increase in coenzyme Q10 levels and a decrease in %CoQ10. No changes were observed in FFA levels or their composition. However, plasma levels of FC and CE significantly decreased and the ratio of FC to CE also significantly decreased, suggesting that ubiquinol-10 supplementation improved cholesterol metabolism. Ubiquinol-10 supplementation also improved chronic fatigue scores as measured by the Chalder Fatigue Scale.

Figure 1.

Plasma levels of free cholesterol (FC) and cholesterol esters (CE), and the ratio of FC to CE in patients with juvenile fibromyalgia (JFM, n = 10) and in healthy control (HC, n = 67) subjects. Data are means ± SD, *P < 0.05, ***P < 0.001 vs. HC.

Figure 2.

Plasma levels of total cholesterol (TC) and vitamin E (VE), and the ratio of VE to TC in patients with juvenile fibromyalgia (JFM, n = 10) and healthy control (HC, n = 67) subjects. Data are means ± SD, *P < 0.05, ***P < 0.001 vs. HC.

Figure 3.

Plasma levels of ubiquinol-10 and ubiquinone-10, and the ratio of total coenzyme Q10 (TQ10) to total cholesterol (TC) and ubiquinone-10 to TQ10 (%CoQ10) in patients with juvenile fibromyalgia (JFM, n = 10) and healthy control (HC, n = 67) subjects. Data are means ± SD, ***P < 0.001 vs. HC.

Figure 4.

Plasma level of total free fatty acids (FFA), the ratios of polyunsaturated fatty acids (PUFA) to total FFA (%PUFA), oleic acid to total FFA ratio (%18:1), and palmitoleic acid to total FFA ratio (%16:1) in patients with juvenile fibromyalgia (JFM, n = 10) and healthy control (HC, n = 67) subjects. Data are means ± SD, *P < 0.05, ***P < 0.001 vs. HC.

Figure 5.

Plasma level of vitamin E (VE), total coenzyme Q10 (ubiquinol-10 + ubiquinone-10), and the ratio of ubiquinone-10 to total coenzyme Q10 (%CoQ10) in patients with juvenile FM (n = 10) during supplementation with reduced coenzyme Q10 (100 mg/day for 12 weeks, 0 mg/day for 8 weeks, and 100 mg/day for 8 weeks). Data are means ± SD, **P < 0.01, ***P < 0.001 vs. baseline value at week 0. Mesh shows the means ± SD values in healthy control (n = 67) subjects.

Figure 6.

Plasma levels of total free fatty acids (FFA), and the ratios of palmitoleic acid and oleic acid to total FFA (%16:1 and %18:1, respectively) in patients with juvenile FM (n = 10) during supplementation with reduced coenzyme Q10 (100 mg/day for 12 weeks, 0 mg/day for 8 weeks, and 100 mg/day for 8 weeks). Data are means ± SD. Mesh shows the mean ± SD values in healthy control (n = 67) subjects.

Figure 7.

Plasma levels of free cholesterol (FC) and cholesterol esters (CE), and the ratio of FC to CE in patients with juvenile FM (n = 10) during supplementation with reduced coenzyme Q10 (100 mg/day for 12 weeks, 0 mg/day for 8 weeks, and 100 mg/day for 8 weeks). Data are means ± SD, *P < 0.05, **P < 0.01, ***P < 0.001 vs. baseline value at week 0. Mesh shows the mean ± SD values in healthy control (n = 67) subjects.

Figure 8.

Chalder Fatigue Scale in patients with juvenile FM (n = 10) during supplementation with reduced coenzyme Q10 (100 mg/day for 12 weeks, 0 mg/day for 8 weeks, and 100 mg/day for 8 weeks). Data are means ± SD, *P < 0.05, **P < 0.01 vs. baseline value at week 0. Repeated-measure ANOVA indicates a significant time course effect of 12 weeks supplementation of reduced coenzyme Q10 (P = 0.041).