CYP7A1, NPC1L1, ABCB1, and CD36 Polymorphisms Are Associated with Increased Serum Coenzyme Q10 after Long-Term Supplementation in Women

Abstract

Coenzyme Q₁₀ (CoQ₁₀), an essential component for energy production that exhibits antioxidant activity, is considered a health-supporting and antiaging supplement. However, intervention-controlled studies have provided variable results on CoQ₁₀ supplementation benefits, which may be attributed to individual CoQ₁₀ bioavailability differences. This study aimed to investigate the relationship between genetic polymorphisms and CoQ₁₀ serum levels after long-term supplementation. CoQ₁₀ levels at baseline and after one year of supplementation (150 mg) were determined, and eight single nucleotide polymorphisms (SNPs) in cholesterol metabolism and CoQ₁₀ absorption, efflux, and cellular uptake related genes were assessed. Rs2032582 (ABCB1) and rs1761667 (CD36) were significantly associated with a higher increase in CoQ₁₀ levels in women. In addition, in women, rs3808607 (CYP7A1) and rs2072183 (NPC1L1) were significantly associated with a higher increase in CoQ₁₀ per total cholesterol levels. Subgroup analyses showed that these four SNPs were useful for classifying high- or low-responder to CoQ₁₀ bioavailability after long-term supplementation among women, but not in men. On the other hand, in men, no SNP was found to be significantly associated with increased serum CoQ₁₀. These results collectively provide novel evidence on the relationship between genetics and CoQ₁₀ bioavailability after long-term supplementation, which may help understand and assess CoQ₁₀ supplementation effects, at least in women.

Keywords: bioavailability; cholesterol; coenzyme Q10; single nucleotide polymorphisms.

Figure 1

Flow chart describing the study design.

Figure 2

Serum ΔCoQ₁₀ and Δ[CoQ₁₀/TC] levels after 1 year of supplementation. Beeswarm box-plots of ΔCoQ₁₀ and Δ[CoQ₁₀/TC] for (a) men and (b) women. The bottom of the box is the 25th percentile, the line that intersects the box is the median, the multiplication sign within the box is the mean, and the top of the box is the 75th percentile. Whiskers above and below the box represent the 10th and 90th percentiles, and the points above and below the whiskers indicate the outliers. Differences between the two groups were analyzed using Welch’s t-tests (p < 0.05). ΔCoQ₁₀, increased serum coenzyme Q₁₀; Δ[CoQ₁₀/TC], cholesterol-adjusted increased serum CoQ₁₀.

Figure 3

Genotypic frequency of the SNPs identified as correlated with the high-responders/low-responder (HR/LR) classification. The frequency of the genotypes of ABCB1 rs2032582 and CD36 rs1761667 associated with the ΔCoQ₁₀, and CYP7A1 rs3808607 and NPC1L1 rs2072183 with the Δ[CoQ₁₀/TC] in women were shown. ΔCoQ₁₀, increased serum coenzyme Q₁₀; Δ[CoQ₁₀/TC], cholesterol-adjusted increased serum CoQ₁₀; HR, high-responder; LR, low-responder.

Figure 4

Box plots showing the serum CoQ₁₀ levels at baseline and after 1 year of supplementation, ΔCoQ₁₀, and Δ[CoQ₁₀/TC] in women. The bottom of the box is the 25th percentile, the line that intersects the box is the median, the multiplication sign within the box is the mean, and the top of the box is the 75th percentile. Whiskers above and below the box represent the 10th and 90th percentiles, and the points above and below the whiskers indicate the outliers. Differences between the two groups were analyzed using Welch’s t-tests (p < 0.05). ΔCoQ₁₀, serum coenzyme Q₁₀; Δ[CoQ₁₀/TC], cholesterol-adjusted serum CoQ₁₀.