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Evidence has shown unambiguously that, in certain contexts, vitamin C is effective against the common cold. However, in mainstream medicine, the views on vitamin C and infections have been determined by eminence-based medicine rather than evidence-based medicine. The rejection of the demonstrated benefits of vitamin C is largely explained by three papers published in 1975—two published in JAMA and one in the American Journal of Medicine—all of which have been standard citations in textbooks of medicine and nutrition and in nutritional recommendations. Two of the papers were authored by Thomas Chalmers, an influential expert in clinical trials, and the third was authored by Paul Meier, a famous medical statistician. In this paper, we summarize several flaws in the three papers. In addition, we describe problems with two recent randomized trial reports published in JAMA which were presented in a way that misled readers. We also discuss shortcomings in three recent JAMA editorials on vitamin C. While most of our examples are from JAMA, it is not the only journal with apparent bias against vitamin C, but it illustrates the general views in mainstream medicine. We also consider potential explanations for the widespread bias against vitamin C.

Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.

Many cancer patients on intensive chemotherapy lack vitamin C. Vitamin C stimulates the production and activation of immune cells, so perhaps supplementation could be used to improve the immunity in those patients. This review assesses the effectiveness and safety of vitamin C administration in cancer. The PubMed and EMBASE databases were searched and all study designs except for phase I studies, and case reports were included in this review. A total of 19 trials were included. In only 4 trials randomization was used to determine if patients received vitamin C or a placebo. The result of this review does not prove that there is a clinically relevant positive effect of vitamin C supplementation in cancer patients in general on the overall survival, clinical status, quality of life (QOL) and performance status (PS), since the quality of the studies published is low. Interventions and patient groups are very diverse, hence an effect in some patient groups is possible. There seems to be a better effect with intravenous than oral administration. Nevertheless, treatment with vitamin C is safe with minimal side effects. Thereby, we think it is safe to examine the effects of vitamin C on specific groups of patients in a randomized controlled setting.

While surgery is the definitive treatment for early-stage melanoma, the current therapies against advanced melanoma do not yet provide an effective, long-lasting control of the lesions and a satisfactory impact on patient survival. Thus, research is also focused on novel treatments that could potentiate the current therapies. In the present study, we evaluated the effect of potassium ascorbate with ribose (PAR) treatment on the human melanoma cell line, A375, in 2D and 3D models. In the 2D model, in line with the current literature, the pharmacological treatment with PAR decreased cell proliferation and viability. In addition, an increase in Connexin 43 mRNA and protein was observed. This novel finding was confirmed in PAR-treated melanoma cells cultured in 3D, where an increase in functional gap junctions and a higher spheroid compactness were observed. Moreover, in the 3D model, a remarkable decrease in the size and volume of spheroids was observed, further supporting the treatment efficacy observed in the 2D model. In conclusion, our results suggest that PAR could be used as a safe adjuvant approach in support to conventional therapies for the treatment of melanoma.

Activation of the transcription factor hypoxia-inducible factor (HIF)-1 allows solid tumors to thrive under conditions of metabolic stress. Because HIF-1 is switched off by hydroxylation reactions that require ascorbate, inadequate intracellular ascorbate levels could contribute to HIF-1 overactivation. In this study, we investigated whether the ascorbate content of human endometrial tumors [known to be driven by HIF-1 and vascular endothelial growth factor (VEGF)] influenced HIF-1 activity and tumor pathology. We measured protein levels of HIF-1α and three downstream gene products [glucose transporter 1 (GLUT-1), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), and VEGF], as well as the ascorbate content of tumor and patient-matched normal endometrial tissue samples. HIF-1α and its downstream gene products were upregulated in tumor tissue, with the highest levels being present in high-grade tumors. High-grade tumors also had reduced capacity to accumulate ascorbate compared with normal tissue; however, all grades contained tumors with low ascorbate content. Tumors with the highest HIF-1α protein content were ascorbate deficient. Low ascorbate levels were also associated with elevated VEGF, GLUT-1, and BNIP3 protein levels and with increased tumor size, and there was a significant association between low tissue ascorbate levels and increased activation of the HIF-1 pathway (P = 0.007). In contrast, tumors with high ascorbate levels had lesser levels of HIF-1 activation. This study shows for the first time a likely in vivo relationship between ascorbate and HIF-1, with low tumor tissue ascorbate levels being associated with high HIF-1 activation and tumor growth. Cancer Res; 70(14); 5749–58. ©2010 AACR.