Table 4.

Randomized clinical studies in cancer patients treated with ASC.

Study	Type of Cancer	Administration	Outcomes
Padayatty, S. [110]	Advanced cancers	Intravenous administration	Increased survival
Hoffer, L et al. [119]	Advanced cancer or hematologic malignancy	Intravenous administration	Adverse events and toxicity were minimal
Vollbracht, C. et al. [120]	125 breast cancer patients	Intravenous administration	Significant reduction incomplaints induced by the disease and chemo-/radiotherapy, in particular, nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and hemorrhagic diathesis.
Takahashi, H. et al. [121]	Advanced cancer patients	High-dose intravenous administration	Improved Quality of Life (QoL) in cancer patients
Stephenson, C. et al. [122]	Advanced cancer patients	High-dose intravenous administration	Ascorbic acid administered i.v. at 1 g/min for 4 consecutive days/week for 4 weeks produced up to 49 mM ascorbic acid in patient’s blood and was well tolerated. The recommended dose for future studies is 70–80 g/m2
Monti, D. et al. [123]	Metastatic pancreatic cancer	Intravenous administration	The initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients.
Welsh, J. et al. [124]	Metastatic and node-positive pancreatic cancer	Intravenous administration	Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well-tolerated. Initial data from this small sampling suggest some efficacy.
Hoffer, L. et al. [125]	Advanced cancer patients	High-dose intravenous administration	ASC was safe and generally well tolerated. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of ASC increases after chemotherapy, with no increase in urinary oxalic acid excretion.
Nielsen, T. et al. [126]	Castration-resistant prostate cancer patients	Intravenous administration	Treatment with ASC did not result in disease remission.
Polireddy, K. et al. [128]	Pancreatic cancer patients	High-dose intravenous administration	Treatment with ASC was safe in patients and showed the possibility to prolong patient survival. There was no interference with gemcitabine pharmacokinetics by ASC administration.
Zhao, H. et al. [129]	Patients with acute myeloid leukemia	Intravenous administration	Patients who received ASC + DCAG (decitabine with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor) regimen had a higher complete remission (CR) rate than those who received the DCAG regimen (79.92% vs. 44.11%; p = 0.004) after one cycle of chemotherapy. The median overall survival (OS) was better in the ASC-DCAG group compared with the DCAG group (15.3 months vs. 9.3 months, p = 0.039).
Lv, H. et al. [130]	Hepatocellular carcinoma	Intravenous administration	Administration of ASC improved disease-free survival (DFS) in hepatocellular carcinoma patients (adjusted HR = 0.622, 95% CI = 0.487 to 0.795, p < 0.001)
Wang, F. et al. [131]	Metastatic colorectal cancer or gastric cancer	Intravenous administration	The favorable safety profile and preliminary efficacy of ASC plus mFOLFOX6/FOLFIRI support further evaluation of this combination in patients with metastatic colorectal cancer or gastric cancer
Fritz, H. et al. [132]	Cancer patients	Intravenous administration	Good safety profile and potentially important antitumor activity. ASC administration may improve the quality of life and symptom severity of patients with cancer, and several cases of cancer remission have been reported.
Jacobs, C. et al. [133]	Cancer patients	Intravenous administration	No high-quality evidence to suggest that ASC supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity.
Nauman, G. et al. [135]	Cancer patients	Intravenous administration	An 8.75 month increase in progression-free survival (PFS) and an improved trend in overall survival (OS) in the ASC-treated arm were seen