Sponsored Linksby Dave Mihalovic
High-dose vitamin C has been studied as a treatment for patients with cancer since the 1970s. It can completely shut down specific types of tumors. According to a new study from Weill Cornell Medicine investigators, scientists could one day harness vitamin C to develop targeted treatments.
Vitamin C has a broad spectrum antioxidant function with the ability to protect cell structures and DNA from free radical damage. It is remarkably safe even in enormously high doses. Compared to commonly used prescription drugs, side effects are virtually nonexistent. No matter how high the concentration, vitamin C does not harm healthy cells. Yet, through an array of enzymatic and metabolic reactions, vitamin C has an impressive ability to protect and treat and wide range of diseases, including cancer.
Colorectal cancer is the third most-common cancer diagnosed in the United States, with about 93,090 new cases each year. Around half of those cases harbor mutations in specific KRAS and BRAF genes; these forms of the disease are more aggressive and don’t respond well to current therapies or chemotherapy.
In a recent study published in Science, a team of researchers from Weill Cornell Medicine, Cold Spring Harbor Laboratory, Tufts Medical Center, Harvard Medical School and The Johns Hopkins Kimmel Cancer Center found that high doses of vitamin C -- roughly equivalent to the levels found in 300 oranges -- impaired the growth of mutant colorectal tumors in cultured cells and mice. The findings could lead to the development of new natural treatments and provide critical insights into who would most benefit from them.
The benefits of long-term vitamin C consumption in excess of the U.S. government recommended daily allowance (RDA) are widely acknowledged and include reduced risks of cancer, cardiovascular disease and cataracts. Higher-than-RDA vitamin C intakes have been associated with increases in good HDL cholesterol, decreases in LDL cholesterol oxidation, decreased blood pressure and decreased cardiovascular mortality.
The first physician to aggressively use vitamin C to treat disease was Frederick R. Klenner, M.D., beginning in the early 1940s. Dr. Klenner successfully treated chicken pox, measles, mumps, tetanus and polio with huge doses of vitamin C. He used massive doses of vitamin C for more than 40 years of family practice. Many practioners who practice with IV vitamin C consider the treatment more effective than any vaccine ever invented.
"Our findings provide a mechanistic rationale for exploring the therapeutic use of vitamin C to treat colorectal cancers that carry KRAS or BRAF mutations," said senior author Dr. Lewis Cantley, the Meyer Director of the Sandra and Edward Meyer Cancer Center and the Margaret and Herman Sokol Professor in Oncology Research at Weill Cornell Medicine.
Laboratory studies have shown that high doses of vitamin C may slow the growth and spread of prostate, pancreatic, liver, colon, and other types of cancer cells
The second mechanism of action is actually a pro-oxidant effect. Doses above 15 grams are proven to have a “pro-oxidant” effect by generating hydrogen peroxide, which in turn selectively destroys cancer cells. High doses of vitamin C are preferentially delivered to the areas surrounding the tumour because the vitamin molecule looks similar to a sugar molecule and cancer cells have an increased demand for sugar to fuel their unregulated growth. When in the area surrounding the cells, the vitamin C molecule reacts with a metal ion such as iron or copper and forms a hydrogen peroxide molecule that damages the cancer cell.
The conventional wisdom is that vitamin C improves health in part because it can act as an antioxidant, preventing or delaying some types of cell damage. However, Dr. Cantley and his colleagues discovered that the opposite was true in regards to high-dose vitamin C’s therapeutic effects for the KRAS and BRAF forms of colorectal cancer -- they occur as a result of inducing oxidation in these cancer cells.
In an oxygen-rich environment such as human arteries, a fraction of vitamin C, also called ascorbic acid, becomes oxidized and is transformed into a new compound called dehydroascorbic acid (DHA). Scientists have known for some time that a specific membrane protein, known as glucose transporter GLUT1, enables both glucose and DHA to enter cells -- an activity not afforded to ascorbic acid. But it was less clear what DHA does once inside the cells.
In the study, investigators show that DHA acts like a Trojan horse. Once inside, natural antioxidants inside the cancer cell attempt to convert the DHA back to ascorbic acid; in the process, these antioxidants are depleted and the cell dies from oxidative stress.
"While many normal cells also express GLUT1, KRAS-mutant and BRAF-mutant cancer cells typically have much higher levels since they require a high rate of glucose uptake in order to survive and grow," Dr. Cantley said. "Also, KRAS and BRAF mutant cells produce more reactive oxygen species than normal cells and therefore need more antioxidants in order to survive. This combination of characteristics makes these cancer cells far more vulnerable to DHA than normal cells or other types of cancer cells."
Although Dr. Cantley cautioned that these results need to be evaluated in the setting of a human clinical trial, the pre-clinical findings may offer a promising new treatment strategy for the KRAS or BRAF forms of the disease, perhaps as part of a combination therapy. The investigators say their study could lead to the development of new biomarkers that could help physicians determine who would most benefit from treatment. These insights may also have implications for other hard-to-treat cancers that express high levels of GLUT1 transporter, such as renal cell carcinoma, bladder cancer and pancreatic cancer.
Vitamin C has multiple effects on cellular functions in addition to its anti- or pro-oxidant functions, so it will be important to study the effects of high-dose vitamin C on normal and immune cells, said lead author Dr. Jihye Yun, a postdoctoral fellow in Dr. Cantley’s lab.
Some human studies of high-dose IV vitamin C in patients with cancer have shown improved quality of life, as well as improvements in physical, mental, and emotional functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss (see
"Further study is definitely needed to expand our understanding of these processes. But now that we know the mechanisms, we can utilize the knowledge wisely to get the desired effects," she said.
"This is not a therapy that you would want to wander into blindly without knowledge of what is going on in your tumor," Dr. Cantley added.
Dosing recommendations also need to be determined. Therapeutic benefit would likely require intravenous injections, as oral doses are not absorbed efficiently in the intestine to achieve the high serum concentration of vitamin C needed to cause toxicity to these cancer cells. Recent phase I clinical trials conducted on humans to test toxicity have shown that intravenous infusion of vitamin C at doses that converted to similar levels of serum as the Cantley mice trials had good safety profiles.
The dosage and route of administration of vitamin C is essential to determine if it has a direct anti-tumour action or a supportive, antioxidant function. The levels needed to achieve direct tumorcidal effects are at least 200-1000 micromol/L. To achieve these higher anti-cancer levels, IV doses of 25-50 grams are required. 50 grams of IV vitamin C can achieve a plasma level of over 14,000 micromol/L. Oral supplementation is insufficient due to very limited absorption in the digestive tract. Plasma vitamin C levels peak after 200 mg of oral supplementation, and maximal oral dosing before loose stools occur is around 4 grams. Oral absorption can be increased if doses are split up during the day, taken with a meal, or in a sustained released formula. Even when using the same 10 gram dose, intravenous administration achieved a 50-150 fold greater plasma vitamin C level compared to oral supplementation.
Vitamin C (and in turn hydrogen peroxide) levels peak within 30 minutes after IV administration and then return to normal within 24 hours. This makes the direct anti-cancer treatment effective for only a short period time and therefore frequent treatments are needed. The benefit of this is that other therapies can be used in short succession after vitamin C without fear of interactions. Most integrative oncologists recommend IV treatments once or twice a week, with oral supplementation on all the other days, for at least 12 months, with regular lab testing to assess tumour markers and progression.
"Our hope is that our study will inspire the scientific community to take a fresh look at this safe and inexpensive natural molecule and stimulate both basic and clinical research regarding vitamin C as a cancer therapy," Dr. Yun said.