on July 04, 2026
Vitamins are essential nutrients for metabolic processes, determining the development and functionality of the entire organism. In addition to their basic nutritional properties, scientific research documents their decisive role in the prevention and treatment of cancer. In particular, numerous epidemiological, in vitro, and in vivo studies confirm the antineoplastic properties of vitamin D and vitamin C, highlighting significant clinical findings, especially when these substances are combined with standard cancer therapies.
Vitamin C (ascorbic acid) is a water-soluble micronutrient that must be regularly consumed through the diet, as the body is unable to store it. The debate over optimal therapeutic dosages for the treatment of neoplastic diseases is long-standing and was initiated by Nobel Prize winner Linus Pauling, who advocated the effectiveness of doses exceeding 1 gram per day. Although such claims have long been controversial in mainstream medicine, clinical studies and case reports on the effectiveness of high-dose ascorbate have increased significantly over the past decade. About 60 years ago, Dr. McCormick highlighted that cancer patients had extremely low blood levels of vitamin C, associated with symptoms similar to scurvy. Later, surgeon Cameron hypothesized that ascorbate could suppress tumor progression by inhibiting hyaluronidase, the enzyme responsible for breaking down hyaluronic acid and the subsequent breakdown of the extracellular matrix that allows metastasis. The extensive trials conducted by Cameron and Pauling, based on prolonged oral and intravenous administrations, demonstrated a fourfold increase in survival and a marked improvement in the quality of life of terminal patients, data that were also confirmed by subsequent Japanese clinical studies. In contrast, studies conducted by Moertel found no positive effect; however, the methodological discrepancy is evident: in Moertel's protocols, ascorbate was administered exclusively orally (which limits plasma bioavailability) and abruptly discontinued after only 2.5 months, unlike the long-term monitoring (up to 12 years) of the Cameron-Pauling model.
From a biological mechanism standpoint, the effectiveness of high-dose vitamin C focuses on altering the glycolysis of neoplastic cells. In line with Warburg's observations, cancer cells consume large quantities of glucose and produce lactate even in the presence of oxygen. In colorectal cancers (CRC) featuring activating mutations in the K-RAS or B-RAF genes, a pronounced upregulation of the GLUT1 transporter occurs. This channel transports both glucose and dehydroascorbic acid (DHA), the oxidized form of vitamin C. The massive absorption of DHA into mutated cells generates severe oxidative stress due to the increase in reactive oxygen species (ROS). To reduce DHA to vitamin C, the neoplastic cell consumes glutathione, exhausting its own antioxidant defenses. Consequently, the DNA repair enzyme PARP (activated by ROS) consumes large amounts of NAD+. The depletion of NAD+ selectively inhibits the glycolytic enzyme GAPDH, causing a fatal energy block and the selective death of mutant cancer cells.
Vitamin D is a fat-soluble compound accumulated in the liver and released in small doses. Low serum levels of this vitamin are associated with an increased risk of developing breast, colon, prostate, and blood cell cancers. Its most active form is vitamin D3 (1,25-dihydroxycholecalciferol or calcitriol), which acts entirely as a hormone. The main endogenous source is cutaneous synthesis mediated by UVB rays from 7-dehydrocholesterol, while dietary intake is limited. Plant-based vitamin D2 is rapidly eliminated by the body, while D3 requires dual hydroxylation to be activated: the first in the liver (at position 25) and the second in the kidney or at the epithelial and immune level (at position 1), by enzymes of the cytochrome family (CYP2R1, CYP27A1, CYP27B1). Once activated, vitamin D3 binds to the nuclear receptor VDR, determining the formation of heterodimers with the RXR receptor. This complex binds to DNA, promoting epigenetic modifications that regulate the transcription of genes responsible for cell proliferation, differentiation, and survival.
The mechanisms of action of vitamin D against carcinogenesis involve immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial responses. On the immune level, vitamin D suppresses the activation of Th1 lymphocytes, reducing the production of pro-inflammatory cytokines (IFN-$\gamma$, IL-6, IL-2, and TNF-$\alpha$), blocks Th17 cells (involved in autoimmune pathogenesis), and simultaneously stimulates both Treg cells and Th2 lymphocytes, increasing the synthesis of anti-inflammatory interleukins such as IL-10 and IL-4. Antioxidant activity is exerted through the induction of key enzymes in ROS detoxification, such as superoxide dismutase and thioredoxin reductase. Furthermore, vitamin D strengthens the epithelial barrier, improves phagocytosis, and counters intestinal dysbiosis caused by its own deficiency. At the cellular level, it promotes the repair of DNA damage, halts the hyperproliferative cell cycle, induces autophagy, and promotes apoptosis by blocking anti-apoptotic proteins (bcl-2, bcl-xl) and activating caspases. Large-scale clinical evidence, such as the VITAL randomized controlled trial involving 25,871 subjects given a daily supplement of 2000 IU of vitamin D3, has confirmed the preventive benefits of this molecule, while extensive meta-analyses associate proper D3 supplementation with a significant reduction in overall mortality.
Bibliographic References and Clinical Sources
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