CoQ10Phytosomes Improve Cellular Ubiquinone Uptake in Skeletal Muscle Cells: An Ex Vivo Study Using CoQ10-Enriched Low-Density Lipoproteins Obtained in a Randomized Crossover Study

Abstract

Coenzyme Q₁₀ (CoQ₁₀) bioavailability in vivo is limited due to its lipophilic nature. Moreover, a large body of evidence in the literature shows that muscle CoQ₁₀ uptake is limited. In order to address cell specific differences in CoQ uptake, we compared cellular CoQ₁₀ content in cultured human dermal fibroblasts and murine skeletal muscle cells that were incubated with lipoproteins from healthy volunteers and enriched with different formulations of CoQ₁₀ following oral supplementation. Using a crossover design, eight volunteers were randomized to supplement 100 mg/daily CoQ₁₀ for two weeks, delivered both in phytosome form (UBQ) as a lecithin formulation and in CoQ₁₀ crystalline form. After supplementation, plasma was collected for CoQ₁₀ determination. In the same samples, low density lipoproteins (LDL) were extracted and normalized for CoQ₁₀ content, and 0.5 µg/mL in the medium were incubated with the two cell lines for 24 h. The results show that while both formulations were substantially equivalent in terms of plasma bioavailability in vivo, UBQ-enriched lipoproteins showed a higher bioavailability compared with crystalline CoQ₁₀-enriched ones both in human dermal fibroblasts (+103%) and in murine skeletal myoblasts (+48%). Our data suggest that phytosome carriers might provide a specific advantage in delivering CoQ₁₀ to skin and muscle tissues.

Keywords: CoQ bioavailability; CoQ10 plasma; CoQ10phytosome; dermal fibroblasts; skeletal muscle.

Figure 1

CONSORT flowchart. A total number of 8 patients were enrolled. Volunteers were randomized in 2 groups (CoQ₁₀, crystallized CoQ₁₀ and UBQ, Ubiqsome) according to a crossover design. For for LDL extraction plasma was subsequently pooled into 2 groups, each one containing plasma from 4 patients.

Figure 2

Layout of the study design. A and A’: pre-supplementation; B and B’: post-supplementation; C and C’: pre-supplementation after wash-out; D and D’: post-supplementation post wash-out. After collecting the blood samples, a total of 32 plasma samples were obtained and divided into 16 plasma samples (pre- and post-supplementation) each for crystalline CoQ₁₀ (CoQ) and Ubiqsome (UBQ). From these plasma samples, 4 pools of enriched LDLs were extracted and divided into 2 each for CoQ and UBQ.

Figure 3

Plasma CoQ₁₀ levels. (A) CoQ₁₀ normalized to cholesterol (CHOL) levels (B) and percent of oxidized CoQ₁₀ (C) in human healthy volunteers supplemented for 2 weeks with UBQ and crystalline CoQ₁₀ (CoQ) at the same dose (i.e., 100 mg/day of CoQ₁₀). Data are expressed as boxes and bar plots (mean value) (n = 8). Statistical significance was calculated using unpaired t-tests with Welch’s correction compared with pre-supplementation (PRE) (* p < 0.05, ** p < 0.01, *** p < 0.001).

Figure 4

Cellular CoQ₁₀ (A) and total CoQ levels (B) in human dermal fibroblasts (white clear box plots) and murine skeletal myoblasts (small dot box plots) treated with p medium (controls, Ctrl), enriched LDL derived from the plasma of volunteers supplemented with Ubiqsome (UBQ) or crystalline CoQ₁₀ (CoQ) at the same concentration of CoQ₁₀ 0.5 µg/mL for 24 h. Data are expressed as boxes and bar plots (mean value) (n = 3). Statistical significance was calculated using two-way Anova with Tukey’s multiple comparisons tests compared with the control cells (Ctrl) (*** p < 0.001, **** p < 0.0001) or crystalline CoQ₁₀ (CoQ) (## p < 0.01, #### p < 0.0001).

Figure 5

Cellular CoQ₁₀ oxidized levels in human dermal fibroblasts (white clear box plots) and mouse skeletal myoblasts (small dot box plots) treated with medium (controls, Ctrl), enriched LDL derived from the plasma of subjects supplemented with Ubiqsome (UBQ) or crystalline CoQ₁₀ (CoQ) at the same concentration of CoQ₁₀ 0.5 µg/mL for 24 h. Data are expressed as boxes and bar plots (median value) (n = 3). Statistical significance was calculated using two-way Anova with Tukey’s multiple comparisons tests compared with the control cells (Ctrl) (** p < 0.01, **** p < 0.0001) or crystalline CoQ₁₀ (CoQ) (# p <0.05).