Vitamin C has traditionally been considered a fundamental component of human health, mainly associated with immune support and the prevention of common illnesses. In the context of cancer, its role was often seen as secondary, without a clear relevance in treatment. However, in recent years, this perception has begun to change. Today, we understand that vitamin C not only supports general physiological functions, but can also influence important processes related to how tumors develop and behave.

In a study conducted by researchers from Shandong University, the role of vitamin C in cancer was explored across multiple levels, including resistant tumor cell populations, the surrounding microenvironment, and the immune system . What makes this approach particularly interesting is that it does not focus on a single mechanism, but rather on how multiple processes are interconnected. This helps frame cancer not just as uncontrolled cell growth, but as a complex system where structural, metabolic, and immune factors all play a role.

From a biological perspective, vitamin C functions as an electron donor. In simpler terms, this means it participates in many cellular reactions that help maintain normal function. Among these are processes such as the production and stabilization of collagen, as well as the regulation of proteins involved in how tumors adapt to their environment, including factors like HIF-1. This highlights that vitamin C does not only act on tumor cells directly, but also on the environment in which they exist .

One of the most relevant aspects is its effect on cancer stem cells (CSCs), a subpopulation within tumors known for their ability to resist treatment and drive recurrence. These cells are particularly important because they can regenerate the tumor even after therapy. In this context, vitamin C behaves in a dose-dependent manner. At higher concentrations, it can induce a type of stress within the cell, known as oxidative stress, which ultimately damages cellular components and compromises cell survival . This is especially relevant because cancer cells, due to their altered metabolism, are often more vulnerable to this kind of stress.

Beyond this direct effect, vitamin C also plays a role in epigenetic regulation, meaning it can influence how genes are turned on or off without changing the DNA sequence itself. Acting as a cofactor for enzymes involved in DNA demethylation, it can help reactivate genes associated with tumor suppression and cellular differentiation. In simple terms, this suggests that vitamin C may not only affect whether cancer cells survive, but also how aggressive or controlled their behavior becomes .

The tumor environment is equally important, particularly the extracellular matrix (ECM), a structural network that surrounds and supports cells. Although often overlooked, this matrix plays a key role in tumor progression. Vitamin C contributes to the production and stabilization of collagen, one of its main components, helping maintain a more organized structure . When this structure remains intact, it can act as a barrier to tumor invasion; when it breaks down, cancer cells can more easily spread to other tissues.

Another critical factor is tumor hypoxia, a condition where oxygen levels are low. In this environment, cancer cells activate adaptive mechanisms, largely driven by genes such as HIF-1, that allow them to survive, grow, and become more aggressive. Vitamin C can interfere with this process by promoting the degradation of HIF-1, limiting the tumor’s ability to adapt to these conditions .

Figure 1. Vitamin C exerts multi-level effects within the tumor microenvironment, influencing oxidative balance, gene regulation, tissue structure, and immune response, contributing to altered tumor behavior.

When it comes to the immune system, the picture is more nuanced. Traditionally, in the medical field, vitamin C has not been considered to have a significant clinical impact on the immune response against cancer. While it is essential for general immune function, it has not been widely viewed as a key therapeutic tool in oncology. However, more recent findings suggest that vitamin C may support the activity of immune cells such as T lymphocytes and natural killer cells, and may even enhance responses to immunotherapies targeting pathways like PD-1 and PD-L1. Still, this area remains under active investigation.

An important point to consider is concentration. Many of the effects described are only observed at high levels of vitamin C, which cannot be achieved through normal dietary intake. For this reason, research has focused on high-dose administration, often delivered intravenously to reach pharmacological concentrations.

Building on this, an even more precise approach emerges: intratumoral administration. Delivering vitamin C directly into the tumor could allow these higher concentrations to act locally within the tumor microenvironment. This may enhance its effects on cancer cells, increase oxidative stress (ROS) in a targeted way, support collagen production and stabilization within the extracellular matrix (ECM), modulate hypoxia-related pathways such as HIF-1, and potentially stimulate a more localized immune response. In this context, vitamin C is no longer seen simply as a systemic supplement, but as a molecule that could be strategically applied at the tumor site to maximize its biological impact.

In this sense, rather than acting as a standalone solution, vitamin C appears to gain relevance when integrated into more precise and targeted therapeutic strategies. Understanding not only its mechanisms, but also how and where it is delivered, may be key to unlocking its full potential in cancer treatment.

Main reference:

Fu, J., Wu, Z., Liu, J., & Wu, T. (2020). Vitamin C: A stem cell promoter in cancer metastasis and immunotherapy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 131, 110588. https://doi.org/10.1016/j.biopha.2020.110588 

Other references:

Drouin, G., Godin, J. R., & Pagé, B. (2011). The genetics of vitamin C loss in vertebrates. Current genomics, 12(5), 371–378. https://doi.org/10.2174/138920211796429736 

Deutsch J. C. (2000). Dehydroascorbic acid. Journal of chromatography. A, 881(1-2), 299–307. https://doi.org/10.1016/s0021-9673(00)00166-7 

Linster, C. L., & Van Schaftingen, E. (2007). Vitamin C. Biosynthesis, recycling and degradation in mammals. The FEBS journal, 274(1), 1–22. https://doi.org/10.1111/j.1742-4658.2006.05607.x