**4. Discussion**

Our pharmacokinetic study has shown comparable plasma uptake of synthetic and kiwifruit-derived vitamin C in subjects with "healthy" (*i.e.*, >50 μmol/L) baseline ascorbate status. Several other pharmacokinetic studies have shown comparable plasma uptake of vitamin C supplied in synthetic form *versus* that in fruit juices [15,23,25]. Nelson *et al.* [26] used an intestinal triple lumen tube perfusion model to investigate the absorption of synthetic vitamin C and that from an orange juice solution. This method allowed direct measurement of intraluminal events and showed no difference in the absorption of vitamin C from the two test solutions. Some pharmacokinetic studies have shown small or transient decreases in plasma ascorbate levels in the presence of fruit juices [16,18]. The physiological relevance of these small or transient differences is, however, likely minimal.

Vinson and Bose are the only investigators to have shown increased uptake of vitamin C, in the presence of citrus fruit extract, using a pharmacokinetic study design [27,28]. Their initial study, carried out in guinea pigs, indicated that vitamin C provided in a citrus fruit medium took longer to reach peak plasma concentrations compared with a synthetic vitamin C solution and also provided a larger area under the plasma ascorbate concentration-time curve [27]. These investigators also observed a comparable trend in human subjects supplemented with 500 mg vitamin C in the presence or absence of a citrus fruit extract [28]. The citrus extract delayed maximal plasma levels by one hour and provided a 35% increase in vitamin C levels.

The different outcomes observed in the pharmacokinetic studies discussed above could be explained by differences in study design and subjects. For example, the doses of vitamin C used varied by more than 10-fold, from 30 mg to 500 mg. Vitamin C bioavailability is non-linear [29] and although ~100% bioavailability is observed at a vitamin C dose of 200 mg, doses exceeding this exhibit decreased intestinal uptake [19]. Doses of 500 mg vitamin C are also significantly higher than would be obtained through a normal daily diet. Furthermore, the participants in these pharmacokinetic studies exhibited varying baseline plasma ascorbate levels, from 35 μmol/L to 75 μmol/L, the former being non-saturating and the latter being saturating levels of ascorbate [21]. These different baseline levels may affect vitamin C uptake and clearance kinetics as it is likely that there will be preferential uptake into cells and tissues in individuals with suboptimal vitamin C status [21,30]. Thus, it is possible that kiwifruit-derived vitamin C may exhibit different uptake kinetics in individuals with sub-optimal ascorbate status at baseline.

We observed a transient increase in urinary excretion when ascorbate was supplied as kiwifruit compared with tablets. Vinson and Bose [28] observed increased excretion of ascorbate when given in the presence of citrus fruit extract, but only in individuals who had been saturated with vitamin C prior to beginning the study. Similarly, others have shown small or transient increases in ascorbate excretion in the presence of fruit juice in pre-saturated subjects [17,18]. In contrast, Uchida *et al*. [15] recently reported decreased ascorbate excretion when given in the presence of acerola juice. Decreased excretion of fruit-derived vitamin C was observed in subjects with low baseline ascorbate status [15,28], supporting the premise that baseline ascorbate status may affect comparative vitamin C bioavailability.

The mechanism whereby kiwifruit enhances urinary excretion of ascorbate without affecting plasma levels is unkown. Certain dietary fibres, such as hemicellulose, which is present in kiwifruit [31], have been shown to increase the excretion of ascorbate [32]. The flavonoid quercetin, found in kiwifruit [33], is a reversible, non-competitive inhibitor of ascorbate transport by SVCT1 [34]. Due to the low intestinal bioavailabiltiy of flavonoids [6], this mechanism would be expected to occur primarily in the intestinal lumen. Although we did not observe an effect of kiwifruit on plasma uptake of ascorbate, alternative mechanisms for intestinal uptake have been implicated using SVCT1 knockout mice [35]. An alternative, hypothetical mechanism may involve a kiwifruit-derived metabolite, which is excreted into urine and thus selectively inhibits ascorbate reabsorption via SVCT1 in the kidney tubules. Urinary excretion of ascorbate may be advantageous with respect to diseases or infections of the urinary tract [36,37].
