These preliminary data indicate that vitamin C status impacts fat oxidation. Free-living individuals with marginal vitamin C status oxidized 25% less fat per kg body weight during a 60-minute treadmill walk as compared to individuals with adequate vitamin C status. Moreover, fat oxidation during exercise was enhanced in these individuals by normalizing plasma vitamin C concentrations. Vitamin C is a cofactor for two enzymes required for the biosynthesis of carnitine, ε-N-trimethyl-L-lysine hydroxylase and γ-butyrobetaine hydroxylase [12–15]. Since the oxidation of fatty acids in skeletal muscle is dependent on carnitine [7, 8], this is a possible mechanism by which vitamin C affects fat oxidation. We also observed a reduction in protein oxidation in the vitamin C repleted subjects which is consistent with the protein-sparing effect of supplemental carnitine .
Numerous trials have demonstrated that tissue carnitine levels are directly related to vitamin C nutriture [11, 17, 18], and that plasma vitamin C and carnitine concentrations are inversely related [11, 19]. However, to our knowledge, only one other study has examined the relationship between vitamin C, carnitine metabolism, and fat oxidation . In cultured hepatocytes, Ha et al. demonstrated that ascorbic acid directly stimulated carnitine synthesis and the β-oxidation of fatty acids, and reduced triglyceride accumulation . This observation that vitamin C reduces fat deposition may explain the reported inverse relationship between adiposity and vitamin C status [4–6]. Interestingly, in patients with an inborn error of carnitine metabolism, carnitine deficiency is associated with lipid accumulation in tissues [21–23]. In fact, activation of the carnitine system has been cited as a possible treatment for obesity [24–26].
Carnitine deficiency is also associated with fatigue and exercise intolerance [21–23], and Hughes et al postulated several decades ago that the lassitude and tiredness of scurvy may be attributed to carnitine deficiency . Our data indicated that reduced fat oxidation during exercise was related to fatigue. It is tempting to speculate that the reduced fat oxidation associated with vitamin C depletion may result in weight gain by two mechanisms: indirectly by fatigability and exercise intolerance and directly by lipid accumulation. Since 15% of Americans are reportedly vitamin C deficient, and one-third of Americans have below adequate vitamin C status [1, 27], these issues deserve further investigation.
Our study had several limitations. The sample sizes were small, 22 for the descriptive study and eight for the intervention trial, which limits the generalizability of results. Furthermore, muscle carnitine, the most sensitive marker of tissue carnitine status, was not assessed in this trial. Also, since vitamin C is a required cofactor for dopamine beta-hydroxylase , altered norepinephrine responses in vivo may have impacted fat oxidation in this trial [see ].