**1. Introduction**

In contrast to most mammals, humans cannot synthesis vitamin C (ascorbate) due to mutation of the terminal biosynthetic enzyme [1]. Thus, the micronutrient must be obtained from dietary sources in order to prevent hypovitaminosis C and the potentially fatal deficiency disease scurvy [1]. Vitamin C was first isolated from fruit and vegetables and the adrenal glands of animals in the early 1930s and was chemically synthesized in 1933 [2]. Although synthetic and food-derived vitamin C is chemically identical, fruit and vegetables contain numerous nutrients and phytochemicals, e.g., flavonoids, which may affect the bioavailability of food-derived vitamin C. Flavonoids can act as antioxidants via direct scavenging of free radicals [3] and/or chelation of redox-active metal ions [4,5]. Thus, it has been proposed that food-derived flavonoids may "spare" vitamin C and thus increase its bioavailability.

Due to the low bioavailability of flavonoids [6] and tight sequestration of metal ions *in vivo* [7], this vitamin C "sparing" mechanism may be expected to occur primarily in the intestinal lumen. Vitamin C is actively transported through the intestinal epithelium via the sodium-dependent vitamin C transporter 1 (SVCT1) [8]. This transporter is also responsible for renal reabsorption of vitamin C, which helps to maintain whole body homeostasis [9]. SVCT1 has a higher capacity, but lower affinity, for vitamin C than the SCVT2 isoform, which is found in most other metabolically active cells and tissues [9].

Although food matrix interactions can influence the bioavailability of some nutrients, such as carotenoids [10], the bioavailability of vitamin C does not appear to be influenced by the food matrix. Kamp *et al.* [11] found no difference in vitamin C bioavailability from a micronutrient supplement administered in the absence or presence of a corn-based porridge. Mangels *et al*. [12] also found no difference between vitamin C bioavailability from oranges compared with orange juice, and although there was a difference in bioavailability between raw and cooked broccoli, this was likely due to differences in mechanical homogenization (chewing), a similar effect to that observed for carotenoid absorption from raw *versus* cooked carrots.

Vitamin C bioavailability can be determined using either steady-state or pharmacokinetic study designs. The former monitors ascorbate levels in blood, cells, tissues and/or urine following a number of weeks of supplementation, while the latter monitors transient changes in plasma levels and/or urinary excretion over the hours following ingestion of the test substance. We have carried out a steady state bioavailability study comparing synthetic with kiwifruit-derived vitamin C in healthy non-smoking males supplemented with a vitamin C tablet or the equivalent dose of vitamin C from gold kiwifruit [13]. No differences in steady state bioavailability were observed in plasma, urine, semen, leukocytes, or muscle tissue following six weeks of supplementation, despite significant differences being observed in our earlier animal model study [14].

Transient differences between synthetic vitamin C and that from different fruit juices have been observed using pharmacokinetic models [15–18]. Therefore, the aim of the current study was to compare the relative bioavailability of synthetic *versus* kiwifruit-derived vitamin C using a randomised cross-over pharmacokinetic study design to determine whether there are any transient differences between the two interventions. Uptake of vitamin C exhibits sigmoidal steady state kinetics between doses of 30–400 mg/day, with plasma uptake decreasing at doses of >200 mg/day and urinary excretion increasing at doses ≥100 mg/day [19]. Therefore, we chose a dose of 200 mg vitamin C and the comparable dose derived from gold kiwifruit (*Actinidia chinensis* var. *Sungold*). Our study participants were young non-smoking men with "healthy" (*i.e.*, >50 μmol/L) baseline levels of plasma vitamin C.
