**5. Clinical Studies**

Cases of apparent responses of malignancies to intravenous vitamin C therapy have been reported, although they were reported without sufficient detail [15,41–46]. A recent study showed that oral administration of the maximum tolerated dose of vitamin C (18 g/day) produced peak plasma concentrations of only 0.22 mM, whereas intravenous administration of the same dose produced plasma concentrations approximately 25-fold higher. Larger doses (50–100 g) given intravenously resulted in plasma concentrations of approximately 14 mM [41].

Some case reports stated that high dose i.v. vitamin C has been used by Complementary and Alternate Medicine (CAM) practitioners [47]. Phase I evaluation of intravenous vitamin C in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer data did not reveal increased toxicity with the addition of ascorbic acid [48]. No side effects were reported for most patients, while 59 were reported to have lethargy or fatigue out of 11,233 patients that received intravenous vitamin C in 2006 and 8876 in 2008 [47]. Overall, it was reported that high dose intravenous vitamin C did not appear to cause serious side effects in patients.

Another clinical study reported the depletion of L-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes [49]. During the supplementation phase, patients received daily i.v. administration of vitamin C. A pre-therapy *in vitro* assay was performed for vitamin C sensitivity of leukemic cells from individual patients. Of the nine patients with the *in vitro* assay indicating their leukemic cells were sensitive to vitamin C, seven exhibited a clinical response, compared with none of the six patients who were insensitive to vitamin C.
