About 15% of US adults are vitamin C deficient (plasma vitamin C < 11 μmol/L) [1]. Twenty-five years ago, this percentage was much lower, 3–5% of US adults [2]. Concomitant with this recent rise in the prevalence of vitamin C deficiency, America experienced a major epidemic of overweight and obesity [3]. Indeed, survey data suggest an inverse relationship between vitamin C status and body weight [4, 5] and waist measurements [6]. The underlying systemic oxidative stress associated with obesity has been proposed to explain the inverse relation between adiposity and plasma vitamin C concentrations [6]. Since vitamin C is an essential cofactor for the biosynthesis of carnitine, a molecule required for the oxidation of fatty acids [7, 8], a reduction in the ability to oxidize fat may contribute to the relationship between vitamin C status and adiposity. To examine this possibility, we conducted a preliminary trial to evaluate the impact of vitamin C nutriture on fat oxidation during submaximal exercise in a small sample of young adults.

Seventy-eight sedentary, non-smoking men and women, aged 18–38 y, from a campus population were screened for plasma vitamin C status. Nearly 40% of the sample had marginal vitamin C status (n = 30; plasma vitamin C concentration <34 μmol/L), and 15 of these individuals (mean age, 21.1 ± 0.8 y) agreed to participate in exercise testing. An additional 7 of the screened individuals with adequate vitamin C status (plasma vitamin C concentration ≥ 34 μmol/L) were included as the vitamin C adequate (control) group. All participants provided informed consent, and the study was conducted in accordance with the guidelines of the University Institutional Review Board.

Participants were free of medical conditions contraindicated for exercise testing as set by guidelines of the American College of Sports Medicine. Participants did not regularly use nutritional supplements and were unaware of their vitamin C status or the intent of the study. Maximal oxygen consumption (VO₂ max) using a graded walking protocol was determined. Within 7–10 days of VO₂ max testing, participants returned to the laboratory for a submaximal, 60-minute treadmill walk at 50% of their VO₂ max. Participants were instructed to fast for 4–6 h prior to the exercise test and to remain sedentary for the previous 24 h period. Urine samples were collected pre- and post-exercise to assess urea nitrogen. During the exercise test, oxygen consumption and respiratory exchange ratio (RER) were measured from three minute gas samples collected at 10 minute intervals corresponding to minutes 7–10, 17–20, 27–30, etc. Substrate utilization was then calculated using the non-protein respiratory quotient derived from the urinary nitrogen and metabolic (VO₂ and VCO₂) measures. The data reported represent averaged values from samples collected at steady state toward the end of exercise (i.e., 37, 47, and 57 minutes). Immediately after testing, participants completed the POMS questionnaire (Profile of Moods States; EdiTS/Educational and Industrial Testing Service, San Diego, CA).

Data from the descriptive study showed that RER during submaximal exercise was significantly higher for individuals with marginal vitamin C status as compared to the vitamin C adequate controls (p = 0.034; Table 1). Furthermore, fat oxidation during exercise was reduced 25% for the marginal versus adequate vitamin C groups (p = 0.045). Plasma free carnitine was significantly lower in the controls as compared to the subjects with marginal vitamin C status (Table 1). (Although carnitine concentrations in muscle are directly related to vitamin C status, plasma carnitine concentrations appear to be inversely related to vitamin C status [11].) Fat oxidation during the walking test was inversely correlated to fatigue as scored by the POMS questionnaire (r = -0.611, p = 0.009) and to plasma carnitine (r = -0.489, p = 0.034). Plasma vitamin C was inversely related to plasma carnitine (r = -0.794, p = 0.000), but the correlation between plasma vitamin C and fat oxidation or RER did not achieve significance (r = 0.309 and r = -0.329 respectively).

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 [16].

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 [20]. 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 [20]. 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 [17]. 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 [28], altered norepinephrine responses in vivo may have impacted fat oxidation in this trial [see [29]].

These preliminary results show that low vitamin C status may reduce fat oxidation during submaximal exercise and that reduced fat oxidation during exercise was related to fatigue. It is possible that increased fatigue and less reliance on fat as a fuel during activity may influence eventual weight gain. Thus, in addition to emphasizing calorie control and physical activity, attention to specific diet components such as vitamin C may be necessary for effective weight management.