Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations

Abstract

Background: Vitamin C (ascorbate) is likely to be essential for skeletal muscle structure and function via its role as an enzyme cofactor for collagen and carnitine biosynthesis. Vitamin C may also protect these metabolically active cells from oxidative stress.

Objective: We investigated the bioavailability of vitamin C to human skeletal muscle in relation to dietary intake and plasma concentrations and compared this relation with ascorbate uptake by leukocytes.

Design: Thirty-six nonsmoking men were randomly assigned to receive 6 wk of 0.5 or 2 kiwifruit/d, an outstanding dietary source of vitamin C. Fasting blood samples were drawn weekly, and 24-h urine and leukocyte samples were collected before intervention, after intervention, and after washout. Needle biopsies of skeletal muscle (vastus lateralis) were carried out before and after intervention.

Results: Baseline vastus lateralis ascorbate concentrations were ~16 nmol/g tissue. After intervention with 0.5 or 2 kiwifruit/d, these concentrations increased ~3.5-fold to 53 and 61 nmol/g, respectively. There was no significant difference between the responses of the 2 groups. Mononuclear cell and neutrophil ascorbate concentrations increased only ~1.5- and ~2-fold, respectively. Muscle ascorbate concentrations were highly correlated (P < 0.001) with dietary intake (R = 0.61) and plasma concentrations (R = 0.75) in the range from 5 to 80 μmol/L.

Conclusions: Human skeletal muscle is highly responsive to vitamin C intake and plasma concentrations and exhibits a greater relative uptake of ascorbate than leukocytes. Thus, muscle appears to comprise a relatively labile pool of ascorbate and is likely to be prone to ascorbate depletion with inadequate dietary intake. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12611000162910.

Figures

FIGURE 1.

Study design. Parallel arms comprised 0.5 or 2 kiwifruit/d for 6 wk.

FIGURE 2.

Mean ± SEM plasma ascorbate concentrations in the 0.5-kiwifruit/d (•; n = 18) and 2-kiwifruit/d (○; n = 17) groups during the lead-in, intervention, and washout phases of the study. Significant differences (P < 0.001) were observed between the 2 interventions from weeks 6 to 11; no differences were observed during the washout phase. *,**For comparison with baseline (week 5; 2-factor ANOVA with Fisher's pairwise multiple-comparison procedure): *P < 0.01, **P < 0.001.

FIGURE 3.

Mean ± SEM relative increases in ascorbate concentrations in peripheral blood mononuclear cells, neutrophils, and skeletal muscle tissue after supplementation with 0.5 kiwifruit/d (n = 18; black bars) or 2 kiwifruit/d (n = 18; gray bars). Baseline values are shown in Table 3. *,**For intervention compared with baseline (paired t test): *P < 0.01, **P < 0.001.

FIGURE 4.

Correlation of muscle tissue ascorbate status with plasma ascorbate concentrations (A) and muscle tissue ascorbate status relative to quintiles of plasma ascorbate concentrations (B). Box plots show medians with 25th and 75th percentiles as boundaries, whiskers are for the 10th and 90th percentiles, and symbols indicate outliers. For trend across quintiles, P < 0.001 (1-factor ANOVA with Fisher's pairwise multiple-comparison procedure) (n = 67).