High-Dose Vitamin C in Advanced-Stage Cancer Patients
Abstract
:1. Introduction
2. Over 50 Years of History of the Anti-Cancer Properties of Vitamin C
3. Vitamin C Intravenous Versus Oral Route
4. Biological Properties of Vitamin C
5. Vitamin C Plasma Concentrations in End-Stage Cancer Patients
6. Potential Anticancer Properties of Vitamin C
7. Does High-Dose IVC in Monotherapy Is an Effective Anti-Cancer Agent in Patients with Advanced-Stage Malignancies?
8. Does High-Dose IVC Increase the Effectiveness of Chemotherapy in Patients with Advanced-Stage Cancer?
9. Does High-Dose IVC Reduce the Chemotherapy-Induced Toxicity in Patients with Advanced-Stage Cancer?
10. Does High-Dose IVC Affect the Quality of Life in Advanced-Stage Cancer Patients?
11. Does High-Dose IVC Affect the Cancer-Related Fatigue in Advanced-Stage Cancer Patients?
12. Potential Analgesic Properties of High-Dose Vitamin C in Cancer-Related Pain
13. Safety of High-Dose Vitamin C Treatment in Advanced-Stage Cancer Patients
14. Summary
Author Contributions
Funding
Conflicts of Interest
References
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Type of Study | Patients | Intervention | Outcome | References |
---|---|---|---|---|
Prospective | 39 terminal cancer patients | 10 g IVC twice with a 3-day interval for one week, followed by oral intake of 4 g daily for one week | Improved QoL assessed by the EORTC QLQ-C30 questionnaire:
| Yeom et al. [120] |
Prospective | 24 patients with advanced cancer and hematological malignancy refractory to standard therapy | IVC three times a week at fixed doses 0.4, 0.6, 0.9 and 1.5 g/kg for average 10 weeks | QoL assessed by the FACT-G questionnaire:
| Hoffer et al. [29] |
Prospective | 60 patients with cancer, anti-cancer therapy administered in 34 patients | 4 weeks of IVC therapy, median single dose 50 g (range 25–100 g) | Improved QoL assessed by the EORTC QLQ-C30 questionnaire:
| Takahashi et al. [102] |
Prospective | 17 patients with advanced solid tumors refractory to standard therapy | IVC for 4 consecutive days a week for 4 weeks, starting at 30 g/m2, a dose was increased by 20 g/m2 until a maximum tolerated dose (110 g/m2) | Improved QoL assessed by the EORTC QLQ-C30 questionnaire:
| Stephenson et al. [28] |
Prospective | 23 patients with metastatic castration-resistant prostate cancer | IVC once weekly: 5 g in 1st week, 30 g in 2nd week, 60 g in 3–12 weeks | QoL assessed by the EORTC QLQ-C30 questionnaire:
| Nielsen et al. [27] |
Controlled retrospective | 125 patients with breast cancer on anti-tumor therapy (study group n = 53 ; control group n = 72) | Study group: IVC 7.5 g once a week during adjuvant therapies for a minimum 4 weeks Controls: no IVC during adjuvant therapies | Improved performance status assessed by the Karnofsky index and the ECOG scale during the 6 months of study * and the next 6 months of aftercare * Reduced intensity of complains (study group vs. controls):
| Vollbracht et al. [105] |
Controlled retrospective | 39 patients with bone metastases, radiotherapy-resistant (n = 15 on chemotherapy; n = 15 on IVC therapy; n = 9 controls) | IVC group: 2.5 g IVC during pain | Improved performance status assessed by the ECOG scale in 27% of IVC group and 7% of the chemotherapy group, while worsened in the control group | Günes-Bayir et al. [123] |
Case study | A 45-year old female with recurrent breast cancer | IVC 50 g twice a week for 4 weeks | Improved QoL assessed by the EORTC QLQ-C30 questionnaire:
| Carr et al. [121] |
Case study | A 81-year-old male with recurrent pulmonary angiosarcoma | IVC 30 g daily for 1 week | Improved QoL assessed by the EORTC QLQ-C30 questionnaire:
| Carr et al. [122] |
Study Type | Characteristics of Study Participants | Intervention | Outcome | References |
---|---|---|---|---|
Prospective | 39 terminal cancer patients | 10 g IVC twice with a 3-day interval in the first week, followed by oral intake of 4 g daily for one week | Reduced intensity of pain after IVC treatment | Yeom et al. [120] |
Prospective | 60 patients with newly diagnosed cancer, anti-cancer therapy administered in 34 patients | 4 weeks of IVC therapy, median single dose 50 g (range 25–100 g) | Reduced intensity of pain after IVC treatment | Takahashi et al. [102] |
Prospective | 17 patients with advanced solid tumors refractory to standard therapy | IVC for 4 consecutive days a week for 4 weeks, starting at 30 g/m2, increased until a maximum tolerated dose (110 g/m2) | Reduced intensity of pain during IVC with complete pain relief after 4 weeks of IVC therapy | Stephenson et al. [28] |
Controlled retrospective | 39 patients with bone metastases, radiotherapy-resistant (n = 15 on chemotherapy; n = 15 on IVC therapy; n = 9 controls) | IVC group: 2.5 g IVC during pain | Median 50% reduction in pain intensity in IVC group | Günes-Bayir et al. [123] |
Uncontrolled retrospective | 11 cancer patients with bone metastases, unresponsive to standard cancer treatment | IVC 2.5 g once weekly for 3–10 weeks | Mean 55% reduction in pain intensity | Kiziltan et al. [138] |
Case study | A female aged 53 with breast carcinoma with visceral and skeletal metastases, after mastectomy, radiotherapy, and hormonotherapy, terminal state with severe pain requiring opioids | 5 g IVC for 7 days, followed by 8 g daily for 70 days orally (total 595 g) | Complete relief from bone pain Reduced need for opioids | Cameron and Campbell [7] |
A male aged 44 with poorly differentiated transitional cell cancer of bladder with bone metastases, intense pain inadequately controlled by opioids | 10 g IVC for 10 days, followed by 10 g daily for 24 days orally (total 340 g) | Complete relief from bone pain No further need for opioids | Cameron and Campbell [7] | |
A female 49 with disseminated carcinoma of unknown origin, innumerable osteolytic bone metastases, severe bone pain | 10 g IVC for 7 days, followed by 10 g daily for 27 days orally (total 340 g) | Complete relief from bone pain | Cameron and Campbell [7] | |
A male aged 49 with large malignant tumor of right temporal lobe, unknown histology, intolerable headache | 10 g IVC for 11 days, followed by 10 g daily for 2 days orally (total 360 g) | Significant relief from headache | Cameron and Campbell [7] | |
Case study | A female aged 45 with recurrent breast cancer | 50 g IVC twice a week for 4 weeks | Reduction in pain intensity | Carr et al. [121] |
Case study | A male aged 81 with recurrent pulmonary angiosarcoma | 30 g IVC daily for 1 week | Reduction in pain intensity | Carr et al. [122] |
Patients | Intervention | Adverse Effects | References |
---|---|---|---|
24 terminal cancer patients | 150–710 mg/kg/day IVC for up to 8 weeks | Frequently reported: nausea, edema, dry mouth or skin Grade 3 adverse events: kidney stone (n = 1), hypokalemia (n = 1) | Riordan et al. [58] |
24 patients with advanced metastatic solid tumor or hematological malignancy refractory to standard therapy | IVC 3 times a week at fixed doses 0.4, 0.6, 0.9 and 1.5 g/kg for average 10 weeks | Mild subjective symptoms: nausea (n = 3), diarrhea (n = 2), headache (n = 2), dizziness (n = 2), fatigue (n = 2), facial flushing (n = 2), abdominal cramps (n = 1), vomiting (n = 1), perspiration (n = 1) | Hoffer et al. [29] |
14 patients with metastatic stage IV pancreatic cancer | IVC 50–100 g/d three times a week for 8 weeks along with standard treatment of gemcitabine and erlotinib | Frequently reported: dizziness, nausea Grade 1–2 adverse events: low platelet count (n = 8), low hemoglobin count (n = 1), low neutrophil count (n = 1), hyperglycemia (n = 1), gastrointestinal discomfort (n = 1), conjunctival infection (n = 1), ascites (n = 1) Grade 3–4 adverse events: internal bleeding (n = 1), pulmonary embolism (n = 2), hospitalization due to anemia and UTI (n = 1), ileus (n = 1) Grade 5 adverse events: death from disease progression (n = 1) | Monti et al. [32] |
11 patients with advanced pancreatic cancer | IVC 15–125 g/d twice a week for 8 weeks along with standard treatment (gemcitabine) | Frequently reported grade 1–2 adverse events: nausea (n = 6), diarrhea (n = 4), dry mouth (n = 4) Grade 3–4 adverse effects: elevated plasma GGT (n = 2), hypokalemia (n = 1), leukopenia (n = 1), lymphopenia (n = 1), neutropenia (n = 2), thrombocytopenia (n = 1) | Welsh et al. [30] |
17 patients with advanced solid tumors refractory to standard therapy | IVC for 4 consecutive days a week for 4 weeks, starting at 30 g/m2, doses increased by 20 g/m2 until a maximum tolerated dose (110 g/m2) | Grade 1–2 adverse events: HT (n = 4), hypernatremia (n = 2), hypoalbuminemia (n = 1), hypokalemia (n = 1), hyperglycemia (n = 1), hypercalcemia (n = 1), increased creatinine (n = 1), elevated plasma LDH (n = 1), proteinuria (n = 1), bacteremia (n = 1), granular casts (n = 1), lower back pain (n = 1), tumor fever (n = 1), pedal edema (n = 1), headache (n = 1), peripheral neuropathy (n = 1) Grade 3–4 adverse events: hypokalemia (n = 2), hypernatremia (n = 2), anemia (n = 2), headache (n = 1) | Stephenson et al. [28] |
14 patients with advanced cancer | IVC 1.5 g/kg body weight 2 or 3 times a week in combination with chemotherapy | Frequently reported mild adverse events: thirst, increased urinary flow Others: nausea and occasional vomiting (n = 1), thirst and unpleasant sensation in the upper abdomen (n = 1), chills, thirst, headache, leg edema (n = 1) | Hoffer et al. [26] |
23 patients with metastatic castration-resistant prostate cancer | IVC once weekly: 5 g in 1st week, 30 g in 2nd week, 60 g in 3–12 weeks | Grade 1–2 adverse events: anemia (n = 7), HT (n = 5), UTI (n = 4), elevation of plasma aminotransferase (n = 3), ↓GFR (n = 3), flu-like symptoms (n = 3), limb pain (n = 3), musculoskeletal lesion (n = 2), shortness of breath (n = 2), pneumonia (n = 1), diarrhea (n = 1), dry eyes (n = 1), osteoporotic fracture (n = 1), pre-syncope (n = 1), leukemia (n = 1), AF (n = 1), elevated plasma bilirubin (n = 1), hydronephrosis (n = 1), hypercalcemia (n = 1), hyponatremia (n = 1) Grade 3–4 adverse event: pulmonary embolism (n = 1), pneumonia (n = 1) | Nielsen et al. [27] |
Myths | Facts |
---|---|
High-dose IVC is a potent anticancer treatment because of its proven effectiveness in preclinical in vitro and animal studies | No consistent evidence for anti-cancer efficacy of high dose IVC therapy in patients with advanced-stage cancer in terms of objective tumor-related response or improved survival outcomes. |
High-dose IVC treatment enhances effectiveness of conventional anticancer therapy | No reliable evidence for increased effectiveness of combined IVC/conventional therapy compared to standard chemotherapy. |
High-dose IVC treatment reduces chemotherapy-induced toxicity | No reliable evidence for decreased chemotherapy-induced toxicity after combined IVC/conventional therapy compared to standard chemotherapy. |
High-dose IVC reduces fatigue in cancer patients | Positive effect of high-dose IVC on cancer-related fatigue comprises various factors and it can be more expressed in patients with basically better performance status and in those with chemotherapy-related fatigue. |
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Zasowska-Nowak, A.; Nowak, P.J.; Ciałkowska-Rysz, A. High-Dose Vitamin C in Advanced-Stage Cancer Patients. Nutrients 2021, 13, 735. https://doi.org/10.3390/nu13030735
Zasowska-Nowak A, Nowak PJ, Ciałkowska-Rysz A. High-Dose Vitamin C in Advanced-Stage Cancer Patients. Nutrients. 2021; 13(3):735. https://doi.org/10.3390/nu13030735
Chicago/Turabian StyleZasowska-Nowak, Anna, Piotr Jan Nowak, and Aleksandra Ciałkowska-Rysz. 2021. "High-Dose Vitamin C in Advanced-Stage Cancer Patients" Nutrients 13, no. 3: 735. https://doi.org/10.3390/nu13030735