April 20 2020
A recent study from Italy, in mice, for the first time is showing the potential of high doses of vitamin C stimulate the immune system to enhance the effectiveness of popular immune therapy cancer drugs known as checkpoint inhibitors (i.e. Yervoy, Optivo, Keytruda, etc.). Vitamin C was studied looking at the adaptive part of the immune system that involves a part of the white blood cells known as lymphocytes or T cells. The experiments suggest that vitamin C could be critical in priming the immune system as well as during lymphocyte-linked cancer killing. In part, the vitamin C increased the number of tumor-infiltrating lymphocytes (T cells) and enhanced activation of CD4 and CD8 T cells that are important signs in immune cancer killing. This may help to explain why, on its own, vitamin C could slow the growth of tumors in those having an intact immune system. High dose vitamin C enhanced the effectiveness of combined checkpoint inhibitors (i.e. anti–CTLA-4 and anti–PD-1 blockade) in breast, pancreatic, and colorectal MMR-proficient mice models (i.e. a triplet therapy). Not only did this combination delay tumor growth in most cases, but also in a few mice, complete regressions were observed. Furthermore, in colorectal cancers where checkpoint inhibitors appear to have greater immune system roles (i.e. MMR-deficient), the combination with vitamin C opened the doorway of response producing significant and lasting tumor shrinkage. These same cancers were also more anti-cancer sensitive to vitamin C when used on its own as well. No signs of immune-related adverse events or other toxicities were seen in animals treated with vitamin C and check point inhibitors, suggesting that combination approaches may be tolerated by people with cancer. The doses used of vitamin C would only be possible by using intravenous doses in humans.
Anecdotally, experimentally, we have been incorporating the use of vitamin C along with checkpoint inhibitors for several years now. For example, when the use of Yervoy (Ipilimumab) was first used in clinical trials for advanced melanoma and before it became an indication for this cancer (i.e. forever changing the landscape for this disease and others), some of our patients also used intravenous vitamin C along side. Later combination approaches such as Optivo (Nivolumab) began to follow showing enhanced outcomes and, once again, high doses of vitamin C were also experimentally utilized by some of our patients along side. Such checkpoint inhibitors and a growing list of others (i.e. Keytruda, etc.) have now become common place in oncology used and approved for a wide variety of cancers. We have applied vitamin C to many of these checkpoint inhibitors. I feel privileged to have been in practice for 20 years and to see the gradual growth and acceptance of immune treatment now common in oncology. There was much skepticism and criticism about this area that perhaps younger oncologists may not be aware of who now walk onto a much smoother and laid out path in an oncology world more open to this area. While yet to be published, we have noticed similar trends to this Italian animal study that a positive relationship appears to exist between vitamin C and checkpoint inhibitors and without any obvious added immune system toxicities. Vitamin C appears to support the immune system plus other parts of the body as well. After all it is an essential nutrient that the body does not make and needs to use to survive. Mice can make vitamin C while humans do not. We suspect, the value of vitamin C becomes even more important when a person has a poor performance status or simply when a person is becoming and looking more tired as the disease progresses and begins to take a toll on the body. We know, especially in advanced cancers, that vitamin C levels are lower than the general population and may even be deficient. Is the immune system response weaker in such cases as a result? We suspect if you are tired so can your immune system in its ability to respond.
This study deserves attention as the Italian researchers have performed a very good and detailed first step in this area of vitamin C immuno-oncology. I am certain we will be seeing more of this kind research and eventually applied to humans as time moves forward. We also suspect this will be an area where vitamin C used in high doses, by intravenous, will shine when combined with such immune checkpoint inhibitors.