Written by: Dr. Adam McLeod, ND, BSc (Hons)
The word “chemotherapy” often strikes fear into patients because they immediately focus on the long list of side effects that can accompany the drug. When patients hear “immunotherapy” they are left with the impression that this is entirely different than chemotherapy and that they should not expect the same side effects as chemotherapy. Although the mechanism of immunotherapy is different than chemotherapy, it is still associated with a number of common serious side effects. As a result, the natural therapies used with immunotherapy are very different than those used with chemotherapy.
The mechanism of action of chemotherapy is through the drugs cytotoxic effect. Although this is an over simplification, chemotherapy is a toxin that damages rapidly dividing cells more than healthy cells which divide much slower. Immunotherapy works to improve the effectiveness of the immune system and to understand why this can cause serious side effects we need to look at the mechanism of immunotherapy in the context of cancer.
When your immune cells interact with a cancer cell there are a number of pathways which must be activated in order for the immune system to become activated and attack the cancer cell. There are several checkpoints in the immune system which prevent the immune system from attacking friendly cells. It is critical that these check points work so that your healthy cells will not become targets of your activated immune system. Cancer cells take advantage of these checkpoints to prevent your immune system from recognizing them as abnormal. This allows them to grow unnoticed by your immune system. Immunotherapy disables one or more of these checkpoints to increase the likelihood of the immune system becoming activated in the presence of the cancer cell. As a consequence the immune system can engage these cells and destroy them. The obvious problem with this approach is that we are essentially turning off the safety checks for the immune system which increases the risk of developing a number of serious health concerns including autoimmune diseases.
There are wide ranging patient responses to these immunotherapies and it is not well understood why some people have incredible lasting responses while others have no response and develop serious side effects. A key difference with immunotherapy versus chemotherapy is that it takes time to assess whether the patient is indeed responding to the drug. With chemotherapy you tend to see rather rapid reductions in tumour mass when the correct drug is used. After initiating immunotherapy, it can sometimes take months to know if the tumours are actually responding to the drug. This lag time must be considered when deciding on a future treatment plan after failing chemotherapy.
There are several naturopathic therapies which can help to support cancer patients through immunotherapy. It is critical that you have professional guidance when developing a treatment plan in the complicated clinical context of cancer. Just because something is natural does not mean that it is safe. It is necessary to have a qualified Naturopathic physician develop a safe and effective treatment plan.
Avoid Natural Immune Stimulants
The biggest mistake that patients tend to make is that they assume the more the immune system is stimulated the better. This is simply not true when it comes to immunotherapy. The immune system is already being significantly activated and we want to avoid additional immune stimulation. Remember, the safety checkpoints of the immune system have been removed so stimulating the immune system may activate the immune system against your own healthy cells. The potential benefit of a stronger immune system is out weighed by the risk additional side effects in the context of immunotherapy.
There is no direct scientific evidence showing that additional immune stimulation is dangerous, but there is none to show it is safe. Immunotherapy is a relatively new therapy so the interactions with natural immune stimulants have not been well studied. Until there is research to conclusively support that it is safe, I would advise patients avoid these immune stimulants. There some medical oncologist who use mistletoe therapy with immunotherapy in Germany and they have reported a good synergy between the two. I have had several patients in my practice use mistletoe therapy with immune therapies based on the advice of another doctor. In these handful of cases they continued to have good responses to the immunotherapy without any negative side effects. The bottom line is that we need more research to determine that this combination is safe and until that research is completed, based on the mechanism of action I would advise patients to avoid natural immune stimulation with immunotherapy.
The most common side effects from immunotherapy are often related to the gastrointestinal tract. In one clinical trial a significant number of patients who were given a combination of Opdivo and Ipilimumab developed gastrointestinal side effects. Out of 313 patients, 52 developed diarrhea, 40 developed nausea and 28 experienced vomiting1. Several patients also developed stomatitis or intestinal perforation. Many of these patients were unable to continue with the therapy due to these side effects. You do not have to be a physician to recognize that these are significant numbers and that supporting gastrointestinal health is necessary.
The good news is that there are many natural therapies which are effective at supporting the gastrointestinal tract. In this article I will only discuss a few of many therapies which may be helpful in this unique clinical context. L-Glutamine is a great place to start and in my practice I regularly recommend this to patients undergoing immunotherapy. L-Glutamine increases intestinal villous height, stimulates gut mucosal cellular proliferation, and maintains mucosal integrity2. It also prevents intestinal hyperpermeability and bacterial translocation, which may be involved in sepsis and the development of multiple organ failure5. This is an example of a supplement where dose matters, so you must have a qualified health professional develop a gastrointestinal support plan for you.
Probiotics can also be helpful at supporting gastrointestinal health but once again, dose matters and the strain used makes a big difference. The decision about dosing and strains used depends on a number of factors and it takes clinical experience to use probiotics properly. On several occasions I have heard from patients that they were told to avoid probiotics as it could cause a infection while on the immunotherapy. This is complete nonsense and it is not based on scientific data. In fact, virtually all of the research indicates that probiotics decrease risk of infection4. Extensive safety testing has shown no pathogenic potential in humans or animals3. If you have concerns about the safety of probiotics, think about this, is the food that you eat sterile? Is there anything that you eat which is not completely covered in bacteria? Of course there is bacteria on everything that you eat! This is unavoidable and this is normal, our bodies are designed to consume bacteria on a constant basis. When you have a probiotic the bacteria are not leaking into your blood stream, they are staying in your digestive tract. There are very few circumstances where probiotics must be avoided and immunotherapy is not one of them. By taking probiotics you are supporting your digestive tract health which has potential to reduce some of the most common immunotherapy side effects.
The most effective plan is a collaborative integrative plan that is developed based on the best available scientific evidence. Integrating naturopathic medicine with conventional medicine should be every patients first resort, not their last. If you are about to start immunotherapy or if you are on immunotherapy then contact a Naturopathic physician who can develop a safe and effective plan to support your gastrointestinal health. Do not wait until side effects develop before deciding to seek help, it is critical that you be proactive and develop a plan right from day one.
Dr. Adam McLeod is a Naturopathic Doctor (ND), BSc. (Hon) Molecular biology, Motivational Speaker and International Best Selling Author. He currently practices at his clinic in Vancouver, British Columbia where he focuses on integrative oncology. https://www.yaletownnaturopathic.com
1) Scott, Lesley J. “Nivolumab: a review in advanced melanoma.” Drugs 75.12 (2015): 1413-1424.
2) Miller, Alan L. “Therapeutic considerations of L-glutamine: a review of the literature.” Alternative medicine review: a journal of clinical therapeutic 4.4 (1999): 239-248.
3) Gorbach, Sherwood L. “Probiotics and gastrointestinal health.” The American journal of gastroenterology 95.1 (2000): S2-S4.
4) Gill, Harsharnjit S. “Probiotics to enhance anti-infective defences in the gastrointestinal tract.” Best Practice & Research Clinical Gastroenterology 17.5 (2003): 755-773.
5) De-Souza, Daurea A., and Lewis J. Greene. “Intestinal permeability and systemic infections in critically ill patients: effect of glutamine.” Critical care medicine 33.5 (2005): 1125-1135.