CAN A VITAMIN FOUND IN ORANGES HELP CANCER PATIENTS: THE ROLE OF HIGH-DOSE INTRAVENOUS VITAMIN C IN CANCER MANAGEMENT

Oranges are everyone’s favorite fruit, and their taste and benefits are unmatchable. Available in winter, oranges are especially rich in Vitamin C. It is also called by the names ascorbate or ascorbic acid. This vitamin dissolves in water and plays an essential part in various physiological mechanisms in the human body (1). The discovery of Vitamin C and its isolation is a big advancement to enhance human nutrition because the human body cannot synthesize Vitamin C itself. Therefore, it is necessary to supplement vitamin C from outside of the body (2).

WHAT DOES VITAMIN C DO IN THE BODY?

Vitamin C helps with the healing of wounds as it is required for the synthesis of collagen in the body. Collagen is a vital part of the connective tissues (2,3). Besides, this vitamin also takes part in the formation of neurotransmitters and L-carnitine inside the body. Vitamin C’s necessary action in humans is its antioxidant activity (4). It also helps regenerate other antioxidants in the human body, such as alpha-tocopherol, called vitamin E (5). In addition, protein metabolism in the body also takes help from vitamin C (2,3).

Furthermore, the immune function also benefits from vitamin C besides its antioxidant and biosynthetic functions (5). Vitamin C also enhances the non-heme iron absorption in the body (6). Iron in this form usually exists in food derived from plants. The miracles of vitamin C do not stop here. Research is being executed to observe whether vitamin C’s damage-limiting impact by its antioxidant activity against free radicals can aid in delaying or averting the progress of cardiovascular diseases or diseases caused by oxidative stress, especially “cancer”.

HOW DOES THE USE OF VITAMIN C FOR CANCER TREATMENT START?

The notion that vitamin C can help with cancer treatment was first postulated in the 1970s by physician Ewan Cameron and chemist Linus Pauling. They proposed that the survival of cancer patients at a terminal stage can increase by a high vitamin C dose (7–9). During the same period, Pauling and Cameron also piloted the first-ever recorded research in which cancer patients were treated with vitamin C. The research outcome demonstrated when 10 grams of vitamin C was administered to one hundred terminally sick patients with cancer, and the results were excellent compared to one thousand patients with cancer who were given only the conventional treatment (7). 

The research also observed that 10% of the patients with cancer who were treated with vitamin C along with the conventional treatment lived. In contrast, those patients with cancers who did not receive vitamin C with the conventional treatment did not go on to survive (7). The investigations carried out as follow-ups also supported the data of the research. Murata and Morishige performed research on Japanese patients who were suffering from uterine malignancies. The research demonstrated that cancer patients who were administered five to thirty grams of vitamin C daily survived for six times longer than cancer patients who were only administered four grams daily. Also, a comparison between cancer patients taking vitamin C supplements and those not taking vitamin C showed that the survival rate increased by 15% in those patients taking vitamin C supplements (10).

WHAT DOES THE NEW RESEARCH SAY ABOUT VITAMIN C USE IN THE CANCER MANAGEMENT?

The new research also supports the notion presented by Pauling and Cameron that a diminished risk of stomach, oral cavity, pancreas, oesophagus, rectum, cervix, and breast cancers (11,12) and also the cancers that do not have any hormonal origin are associated with high-dose intake of vitamin C (13,14). Besides, food also plays a significant role as an amenable factor when it comes to the risk of cancer. Quite a lot of study committees and panels working independently have concluded that the risk of various kinds of cancer development lowers with a high intake of vegetables and fruits (15,16). Notably, it was observed that the fatality rate is inversely linked with the intake of vitamin C (17). Moreover, some studies observed the beneficial results of intravenous vitamin C injections in the treatment therapy applied for advanced malignancies (18,19).

HOW DOES VITAMIN C HELP IN THE CANCER MANAGEMENT?

There are quite a few mechanisms that are thought to support Vitamin C and its role in the avoidance and management of cancer. It includes Vitamin C’s action to increase the immune system’s activity, encouraging the synthesis of collagen, inhibiting specific reactions catalyzed by enzymes, preventing metastasis, and inhibiting viruses that can cause tumors. In addition, cancer patients usually have a lack of vitamin C, which is corrected by vitamin C intake during the cancer treatment. Vitamin C also helps in the early healing of wounds following surgery in cancer patients, it improves the sensitivity of chemotherapy while decreasing the toxicity and also neutralizes certain substances that can cause cancer (19).

Numerous current experimental research has observed that when high vitamin C doses are used against tumor cells, their growth faces arrest (20,21). Some current studies also reported that tumor development, metastasis, and cytokine production associated with inflammation were also inhibited by the administration of vitamin C, tumor inclusion, and enhancement in the performance of chemotherapy (22,23). Some studies also stated that the levels of vitamin C increase over seventy-fold with intravenous injections in comparison to oral intake, and there is an inverse relationship between the extra vitamin C amount and the effectiveness of the therapy (17,24). Because of this, studies are being carried out to find the ideal administration method, treatment duration, and dosage.

ROS AND THE HIGH-DOSE VITAMIN C TREATMENT 

Reactive oxygen species or ROS is highly dependent on the therapeutic impact of high vitamin C doses. ROS is a group of extremely reactive chemical species that are developed in the body when electrons discharge from the electron transport chain (coenzyme Q; ETC) of mitochondria, the powerhouse of a human cell, and these electrons react with molecular oxygen which is enzymatically converted into superoxide and after oxidation and reduction reaction produces hydrogen peroxide. The partial reduction of hydrogen peroxide forms hydroxyl radicals, hydroxide ions, and water (25,26). Together, the hydroxyl radical and superoxide are known as ROS free radicals (26). Moreover, several external factors are also responsible for the formation of ROS in the body, such as radiation, heavy metals, drugs, cigarette smoke, and xenosensors (27–31).

In normal physiology of the human body, several metabolic pathways take benefits from ROS, and that is why these are being continuously made and eliminated according to the need. In addition, body cells have their own scavenging machinery that controls levels of ROS under normal circumstances (32). However, increased ROS levels under oxidative stress can cause impairment of protein, lipids, and DNA, ultimately resulting in cancer formation (33). Still, at the molecular level, ROS plays an essential role in eradicating cancers. Due to this, studies have been carried out to establish strategies to enhance or decrease ROS levels. For example, those tumors that have higher levels of ROS are dependent highly on the anti-oxidative stress defence mechanism (34,35). 

Also, those drugs that enhance the ROS levels can help to elevate the concentration of ROS intracellularly directly by producing massive amounts of ROS and leading to the death of cancer-cells (34,35). Nevertheless, when there is less oxidative stress, the response of normal cells is positive against high levels of ROS (35). Consequently, if ROS levels are increased in all cells, it can help in the selective obliteration of cancer cells. This is the most commonly discussed strategy concerning high vitamin C dose therapies.

WHAT IS THE MECHANISM OF ACTION OF VITAMIN C IN ANTI-CANCER TREATMENT? 

It should be taken into consideration that because of the faulty mitochondria and increased reliance on metabolism, the cancer cells have high sensitivity against oxidative stress in comparison to normal cells (36). Tumor growth may take help from oxidative stress via ROS, by increasing the growth of cells and enhancing the genetic imbalance. Nonetheless, cancer cells may get destroyed by excess ROS and to counter this effect, several mechanisms are used by cancer cells to inhibit the negative influence of ROS (37,38). 

Vitamin C has the properties to perform antioxidant and pro-oxidant activities at different concentrations, and it has demonstrated pro-cancer activities at high concentrations. When vitamin C is administered in higher concentrations, it increases ATP production by enhancing the electron flux in the mitochondria (this is the opposite of what happen when ROS are formed). This probably occurs due to vitamin C’s pro-oxidant action (39). A 0.3 to 20 millimolar vitamin C concertation is enough to form hydrogen peroxide and other radicals inside the cancer cells resulting in their death (40).

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