Meroë Morse, M.D. Hi, I'm Dr. Meroë Morse, an assistant professor of Integrative Medicine at MD Anderson Cancer Center. And today I'm joined with Dr. Santhosshi Narayanan, associate professor of Integrative Medicine here at MD Anderson Cancer Center. And this is the Cancerwise Podcast. Welcome, Santhosshi. Thanks for being here. Today, we're here to talk about what cancer patients need to know about vitamins and supplements.  

Santhosshi Narayanan, M.D. Thank you for having me, Dr. Morse. I look forward for our conversation. I think it's a very important topic. Patients are very vulnerable when they're going through cancer journey, and they have a lot of questions about what they can do for their health. 

Meroë Morse, M.D. Wonderful. I think this is a really important topic as well. One study showed that about 70% of patients who are receiving treatment for cancer are taking some form of supplement or vitamin, and this is really important for their primary physicians to know. And it's wonderful to be able to speak with them and give them advice on moving forward with the safest, most effective approach. So, I look forward to chatting with you about this. I think cancer patients are uniquely vulnerable to misinformation and wanting to do everything possible to help treat their cancer, and this vulnerability drives a real desire to get information, but also make decisions and implement practices that aren't always the safest for them.  

Santhosshi Narayanan, M.D. I agree, it's a very tough spot for patients to be when they're dealing with a cancer, and to be in the cancer journey, and being lost with all the misinformation, and glad we are talking about it today.  

Meroë Morse, M.D. Absolutely. Another point is, I think a lot of clinicians want to be able to have this conversation openly and transparently with their patients. They don't want their patients to be withholding information out of fear that they're going to be judged, or that that something negative will happen. And yet, this is not really something that we were taught in our training. It's becoming more and more common to give clinicians a framework of how to discuss that. But you and I wrote a paper about this very topic. Could you give us a rehash of that paper and how we have recommended to approach this? 

Santhosshi Narayanan, M.D. Yeah, absolutely. So, open communication, where we create a space for the patients to discuss about supplements is very important. So, in our paper we thought about how to create this framework. Like, what are all the things that we need to consider when we are talking about supplements? We first obtain the list of supplements that patient wants to use. And then we go over the risks and benefits. What are the risks of combining the supplement with their chemotherapy or with radiation? What are the adverse effects of such supplements? What organ toxicity that these supplements can cause? So, these are all the factors that we consider in our consultation with our patients. And in the paper that we wrote together, I think we put that together in the form of a flowchart where we classify the supplements based on the risk and benefit. So, if the, if a supplement has a high risk and low benefit, then there is no point in using it. Whereas if a supplement has medium risk and medium benefit, then we have that conversation with the patient and understand what is the patient's goals. What are they looking for? Is that to decrease the side effects? Can we do something else like acupuncture, for example, to help with the joint pain which is caused by letrozole or other aromatase inhibitors. So, things like that which can be managed, symptoms which can be managed by other measures, which does not involve the use of supplements, which can actually interact with a potential chemotherapy. I think that kind of framework that we put together in that paper helps decision making by clinicians, by oncology providers at MD Anderson, and also outside to come up with a plan on what they can do to help their patients safely handle their supplements. 

Meroë Morse, M.D. And I think the framework is valuable. But also, we need to consider the personalized approach. Every patient has a different cancer type. They're at a different stage of their cancer treatment. A lot of them are using newer agents. And and each of these immunotherapies and chemotherapies have different interactions. So, it's not a one-size-fits-all approach. We can't just hand them a paper saying take these supplements or don't take these supplements. It really requires that nuanced conversation and certainly establishing this clinician-patient relationship. To continue the conversation is the most important part that they are trusting of us, and that we have their best interest in mind. It's very interesting to me to meet each patient where they are and speak with them, and have an educational conversation about moving forward with the best case approach. Can you share with me some of the more common herbs and supplements that you've been seeing in your clinic these days? I think there's often a pattern. So, what are you finding patients are taking or asking about these days? 

Santhosshi Narayanan, M.D. So, recently I see that a lot of patients are using artificial intelligence to create a supplement list. That is one trend that I've been seeing in my clinic. People usually need a read about it and they create their own list. So, some of the supplements that I see that other patients use are mushroom supplements. People like to use some mushroom teas, then they use mushroom capsules. Then a lot of people use vitamins and other herbs. Some people use astralagus, which is an antioxidant. Some people use ashwagandha, which comes from traditional Ayurvedic medicine. People use turmeric capsules. People use green tea capsules. So, people use a lot of things. And the other pattern I see is that sometimes it's very unclear if it is specific to their cancer. For example, turmeric is a blood thinner. So, one patient may not experience an adverse effect from turmeric, but another patient with a brain tumor with a potential bleeding, they may bleed more into the tumor and may not realize it. It might happen because of turmeric. And there is also some hepatotoxicity reported. So if a patient already has elevated liver enzymes, then there may be a risk. And similar situation happens with green tea extract, as you know. We both know that green tea has EGCG, which is highly potent. At the same time, when people use green tea as pills instead of drinking as tea, there is a risk of liver toxicity. So, balancing this and helping patients to make an informed decision about their care and making an informed decision about the supplement to use, I think is important in our practice. So on a similar note, I was thinking, I'll ask you what you are seeing in your clinic? 

Meroë Morse, M.D. I do see a lot of turmeric use and green tea extract use. And you completed a certificate in Ayurvedic medicine on top of your integrative training. And I remember you and I did a talk last year regarding herbs and supplements, and we showed the research on the uptick of hepatotoxicity in the, in the setting of tumeric. And what I found to be so interesting is the, in the supplement world, which is not a regulated world, and I think it's important for our patients to know that, that although it's a $5 billion a year industry, it is not regulated by a body like the FDA. And so, the quality of supplements is variable. There can be adulterants the content and the potency is really difficult to maintain. When we saw the addition of piperine, the black pepper component, into tumeric supplements, we saw the rates of hepatotoxicity double in the liver tox case series. And I think that speaks to the potency of of tumeric and black pepper in that combination and how plants are very powerful. But it also speaks to the the vulnerability of the consumers and how they may not have realized that this new this new formulation had increased toxicity. Most patients aren't monitoring their labs when they're taking these supplements. They don't think they need to because it's a na- it's a natural product, quote unquote. So, I do see a lot of tumeric and green tea extract in, in my clinic. Because we work very closely with our patients with breast cancer who have a lot of side effects related to the treatments, I do see some patients taking formulations that are intended to help with hot flashes, some of those vasomotor symptoms. And my concern whenever I hear about this and look deeper into it, is that these herbs have estrogenic potential. So, they have the potential to, to stimulate estrogen release or, or stimulate the estrogen receptors in the body and, and certainly in hormone positive breast cancer, that's something we're trying to avoid. So, while we don't want them to be having these negative side effects related to the endocrine therapy, we also don't want them to be doing something potential, potentially harmful. This is where I, I love to be able to explore the benefits of non-pharmacological approaches to, to side effects like our acupuncture treatments and our massage therapists, so really leading them towards safer, non-pharmacological alternatives. I do see a lot of vitamin use in, in the clinic, and so I would love to talk on a few of the more popular vitamins that I come across. And I'd love to have you chime in. Vitamin D, we know from the VITAL study, is a very important vitamin for immune health, certainly for bone health. And the VITAL study found that patients with cancer who had vitamin D levels replete to a normal level tended to have better outcomes in their, in their cancer journey. And so, that is really important information. It's an intervenable test that we can, can make moves on. I will say, though, that a lot of patients tend to overdo it when they are taking vitamin D. The thought that, well, if a little bit is good, then maybe more is better. And that's not entirely true. So, I have unfortunately been seeing an uptick of hypervitaminosis D levels above 100 and the side effects that come with it. So, this is something where we want to be very cautious and measure, make sure they're being dosed properly. So, vitamin D is important, but in moderation. The other vitamin group is B vitamins. I wonder if you see that a lot in your clinic. 

Santhosshi Narayanan, M.D. I do, actually, very often. So, I see hypervitaminosis D, and, as you mentioned, it is good to check the level and then dose it appropriately because we know that in patients with bone metastases, there is a risk of hypercalcemia which will have other adverse effects, and it may harm the patient. So, it's always good to check and also B. So, we know that in studies excess B6 has been shown to be toxic, especially neurotoxicity. And sometimes patients take B6 and B12 to help the neuropathic symptoms, which happens with chemo. And it is thought that that is going to help the neuropathy. But actually it may harm because excess of B6 can cause neurotoxicity. So, I suggest usually to, for patients to check the levels and then take it, or we would check it in our clinic and then dose it appropriately so that we protect the our patients from toxicity. And in terms of other vitamins I see similar pattern like you.  

Meroë Morse, M.D. Yeah, the B vitamin is very interesting. And I always have patients read labels. So, so that's one other kind of safety aspect. If they have the, the vitamin bottles or the supplements available to them, I ask them to bring it to the visit and we review what the amounts are on the back. And most of the the B complexes that I see have levels upwards of 1,000% daily value. One brand has 44,000% daily value of B12. So, while we want to be repleting low vitamins, we also don't want to be overdoing it. There's mounting evidence to show that excess B12 might have an association with colorectal cancer. We saw that in the B-PROOF study. It was a secondary analysis. I think testing is paramount. We want to make sure we are neither too high or too low, but kind of Goldilocks-style, just right. The other vitamin that patients often will chat with me about or inquire about is vitamin C, particularly high dose vitamin C delivered through intravenous therapy. Do you see that in your clinic?  

Santhosshi Narayanan, M.D. Yeah, I do see that too. I get a lot of questions about IV vitamin C and also oral vitamin C. I see that a lot of patients are on oral vitamin C, and I always worry about the antioxidant effect of oral vitamin C. And when it comes to IV vitamin C, we know that a systematic review showed mixed results. So, the the evidence is not in favor of using IV vitamin C in cancer. There is also a risk of financial toxicity for our patients because it is very expensive. I'm sure more studies will give us more answers on what is the right approach on, on these areas of some IV infusions, IV vitamin infusions. But I would like to reiterate a couple of points that you mentioned for our patients. So, one is "all natural" does not mean "all safe." So, supplements are "all natural," but it doesn't automatically mean that it is going to be safe. So, natural compounds, natural supplements also have side effects. And the second is appropriate dosing. That is another point I would like to reiterate because something which is safe, something which is shown for cancer prevention, cancer control, important in cancer does not mean more is good. Appropriate levels are always beneficial. So, testing is better than just blindly taking it.  

Meroë Morse, M.D. Like pharmacotherapy, like prescribed medication doses, dosages make a huge difference. So, you know, melatonin is a good example. At a very low dose, we know that that is more of a sleep aid supplement. Melatonin is a natural hormone that our brain makes that helps us to get to sleep. And we do a lot of things in our daily lives to suppress melatonin production, like reading screens, being, being in an artificial light. And so, a lot of patients will take melatonin to help with sleep. The higher doses of melatonin, ten milligrams or up, paradoxically cause wakefulness. So, this is another example where too much of a good thing can actually be working against you. And patients don't realize that. So, really, the details are very important here.  

Santhosshi Narayanan, M.D. Dr. Morse, I heard that you have an interesting research article that you're writing on gut microbiome. So, could you please tell us a little bit about probiotics and what you found in your research, and how we should educate our patients on the use of probiotics?  

Meroë Morse, M.D. Yeah, absolutely. And thank you. I am very close to publishing an article on the microbiome gut-brain axis and how our gut microbiome impacts our nervous system. So, look out for that. We at MD Anderson have a wonderful team of physician researchers who explore the microbiome, so I won't go into too much detail about the, the clinical research behind that. Just to say that there's a lot of ongoing interest in how the gut microbiome changes through food and how that impacts outcomes in, in cancer treatment. Particularly, the melanoma team has been very forward thinking in this realm. I always, I always talk to patients about the power of their their gut microbiome and how their food choices can really impact the way their body has inflammation, the way their immune system can respond to the treatments they're receiving, and generally how food can be medicine in this way. So, a lot of patients will either be already taking probiotics or ask me what the best probiotic to take is. And I try to, as always, understand a little bit about why they're taking a probiotic if they are. Some patients do take probiotics chronically for very specific medical conditions, and that's important for me to know because I wouldn't want to disrupt this balance of flora. But most patients will just be taking it because they've heard that it's good for their gut health. And in those situations, I like to explain that having a diverse microbiome is really the healthiest thing they can do, and they can't always get that from a single probiotic pill. The probiotic pills often will have 1 to 10 different strains in there, and that is not going to allow for the diversity of the microbiome that we're really looking for. When we analyzed the stool samples of people who are on probiotics, we see, actually, in most cases, a very limited diversity compared to people who are eating prebiotic and probiotic-rich foods. So, this is where I really try to educate patients on the power of fiber, prebiotic-rich foods like your cruciferous vegetables, probiotic foods. So, fermented food sources like yogurt, kefir, kimchi, sauerkraut and figure out ways that they can incorporate that into their eating patterns. Do you have recommendations for patients from the Ayurvedic perspective on fermented foods and probiotics?  

Santhosshi Narayanan, M.D. Yeah. So, there is some recommendations which are which comes from an Ayurvedic perspective, not specifically on the pre- and probiotics, but Ayurvedic diet recommendations would naturally improve the microbiome. As you mentioned, the gut microbial diversity is connected to immune system. A shoutout to our melanoma team for helping us understand that in greater depth. And I look forward to reading your paper and learn more. But I think the nature of the microbial diversity is such that naturally, if patients can develop it and help it grow further with fiber, that is always beneficial. And when it connects to Ayurveda as, I just graduated from master's in Ayurveda, so there was quite a lot of learning to do, and I'm still continuing to learn Ayurveda. So, Ayurvedic diet is very personalized. So, we recommend AICR, the American Institute of Cancer Research-based diet in our clinic and our practice. And it is, it's along the lines of those. But it adds in an additional layer of personalization for each individual. So, in Ayurveda, people are classified based on their body constitution. And we just submitted a book chapter for Society of Integrative Oncology, where we expand on this for people to learn about how we classify. So, that's a very detailed process. And once you are able to understand the body constitution, we can make adjustment in their diet based on their body constitution. So, that will help personalize the diet. But gut microbiome when a person eat healthy diet rich in fibers, vegetables as you said, cruciferous vegetables, other vegetables, plant-based proteins, beans, lentils, Ayurvedic diet is heavy in lentils and beans, it helps the gut microbial diversity.  

Meroë Morse, M.D. I would love to hear a separate podcast on Ayurvedic practice. I think right now we're at a point where a lot of patients are seeing us during their cancer treatments, and so they may be off of their supplements at the recommendation of their oncologist or their surgical team or their radiation oncology team. But we also see patients in survivorship mode who are finished with their treatments and they're being monitored. And they, a lot of them are enticed to restart some of the supplements that they had been on or that that they had withheld during their treatment. Can you speak a little bit about survivorship stage of cancer, and whether the same rules apply, or if a different perspective is used for supplements in survivorship?  

Santhosshi Narayanan, M.D. Thank you Meroë. That's a very important question because often I see patients in my clinic who would come to me because they have completed their cancer treatment, and now they want to restart their supplements, and they want to know if it's okay to restart the supplement. And first of all, I would like to thank them for making that appointment and not taking it on their own, because it is very important that they discuss it with us. And sometimes in the setting of survivorship, as you know, the interaction part is not worrisome. So, we don't have the interaction with chemotherapy and radiation to worry about. But we still have other concerns. The other concerns being are these supplements indirectly helping the tumor growth? So, in earlier part of our conversation you were talking about the estrogenic effects of some supplements. So, I worry about that, too. So, in my patient with a hormone positive breast cancer or other hormone-dependent cancer who have completed their treatment, is this supplement going to help fuel the cancer cell growth, which otherwise may not happen? So, that is my worry. So, I often talk to patients about it and and tell them that the supplement that they are taking may have estrogenic effects or estrogenic potential, or other hormone-stimulating potential. So, that is something to watch out for in survivorship setting. And the other concerns that I will discuss openly with my patients is the side effects, because the side effect still remains the same. We discussed about the green tea and on the hepatotoxicity and cases of hepatotoxicity from turmeric reported in Europe. So, these are some of the concerns which are still there. And now that they're in survivorship, they probably are also getting less monitoring. So, the adverse effects may not even be known or it may not be caught early. So, I think one needs to be cautious in this setting, too. And again, as all of our approach is about open communication, I think that having that conversation, open communication and following up with patients at even during survivorship and having that conversation on integrative approach to survivorship, which includes discussion on herbs and supplements, and using non-pharmacological approaches. We both know that ASCO-SIO, American Society of Clinical Oncology and Society of Integrative Oncology, combine guidelines are very supportive of use of non-pharmacological approaches. And these guidelines are put together by many experts with a very detailed review. So, we know that based on evidence, there are so many non-pharmacological approaches that we can do. And if patients want to, want to take supplements, a proper guidance and helping them understand what is what and what side effects are happening, and directing them to food sources can be helpful so that their supplement list can be smaller. For example, often people ask me about medicinal mushroom supplement and we published a systematic review. I reviewed almost 2,300 papers in the last ten years to see what was the effect of mushroom supplements on people with cancer. What does the study show? What we found is that mushroom supplements had a mineralogical potential. They do have very low side effects. They do improve quality of life. But there is also one study which showed that the immune effect, the positive stimulation and the inhibition may happen with the same mushroom supplement in the same population. So, we need to clarify what happens in terms of immunological effects. And there is a risk of liver toxicity also. So, that is another thing to think about. And people are also taking other drugs even though it's not cancer drugs. And for example, reishi mushroom interacts with cytochrome P450, which is a common metabolizing enzyme for many of the other drugs. So, other drug interaction risk is always there. So, I think survivorship is an important area and careful discussion and guiding the patient patients appropriately and full disclosure by patients of what they're taking to Integrative Medicine team is very helpful in making sure that people are safe and they're able to make informed decisions.  

Meroë Morse, M.D. Absolutely. And I think that systematic review on the mushrooms is such a helpful piece of literature for integrative oncologists out there who are looking for more guidance. So, kudos to you for, for digesting that information. And I hope that there is additional research. The strength of the evidence base is growing. And for now, I think the the evidence in lifestyle, in the role of nutrition and all of the various types of nutrition and diets that are out there, is really growing. The role of exercise and physical activity is very strong. So, this is where I lean into in my clinical practice and, and try to reduce pill burden for patients and really empower them to make these changes. So, I'm glad to see that we have similar clinical experiences and an application to our integrative training.  

Santhosshi Narayanan, M.D. Yeah. Yeah. Dr. Morse, can you tell us a little more about what we want our patients to know in terms of our practice like diet, exercise, mind-body stress reduction, social, spiritual aspects? Can you expand a little bit more for our patients?  

Meroë Morse, M.D. Well, of course. We want to see patients wherever they are in their treatment journey. And and the virtual door's always open to discuss everything from a lifestyle perspective to a psychosocial spiritual perspective. When the body is supported both mentally and physically, it has the potential for great healing. And that's what we do in our Integrative Medicine Center. We we really try to optimize patient-centered approach and apply these lifestyle interventions and spiritual interventions, if that's what is important to them, to a personalized toolkit, I like to say. So, I think there are always areas where we can improve upon in nutrition and exercise, making sure that they're prioritizing sleep and not relying on pharmacotherapy, and then making sure that they're embracing their community, whatever that looks like to them. All of these have been shown in the research to work synergistically to really optimize health and optimize the body's healing potential. So, every patient is different. We, we approach it in a very personalized way. But essentially, getting to these basics is as what I think our consults are about and why patients appreciate meeting with us and feeling reassured with what they're already doing, or having this new knowledge to to move forward and make a difference instead of sitting around worrying about what what will happen with their their cancer. So, I think an integrative approach is very empowering for patients.  

Santhosshi Narayanan, M.D. Yeah, I agree that is wonderful. And I'm so fortunate to be able to work with our team, yourself. I learn a lot by talking in a formal setting and informal setting, as we always do, and we have a team of our nutritionists that we we learn from, learn from each other, psychologists and physical therapists and mind body specialists, yoga therapists, music therapists and acupuncturists and massage therapists. And it's a blessing to be able to have that team at MD Anderson so we can offer a real, whole person approach to our patients. And I think that helps the patients and patients appreciate it, and we are able to address them as a whole person. And I think it is very important when people are dealing with a very distressful situation in life, such as their cancer journey. So, I feel fortunate to be able to have the team of people that we work with and offer our services to our patients.  

Meroë Morse, M.D. Absolutely. We work with some expert healers in our clinic. Santhosshi, thank you so much for joining me today. This was wonderful to talk about herbs and supplements with you. I thoroughly enjoyed our conversation.  

Santhosshi Narayanan, M.D. Thanks for having me today, Meroë. It was wonderful conversation and look forward to speaking more with you.  

Meroë Morse, M.D. And thank you for tuning in today. If you enjoyed this episode, be sure to follow or subscribe on Apple Podcasts, Spotify, YouTube, or wherever you get your podcasts. And don't forget to comment or review. For more information or to request an appointment at MD Anderson, call 1-877-632-6789 or visit MDAnderson.org. Thanks for listening to the Cancerwise Podcast from MD Anderson Cancer Center.