Episode 17: Cancer Prevention and Management: A Conversation with Dr. Lise Alschuler

Dr. Lise Alschuler, ND, FABNO practices naturopathic oncology out of Naturopathic Specialists, LLC. She is the co-author of Definitive Guide to Cancer and Definitive Guide to Thriving After Cancer. Dr. Alschuler is the Executive Director of TAP Integrative, a nonprofit educational resource for integrative practitioners.  She co-hosts a radio show, Five To Thrive Live!and is co-founder of the iTHRIVE Plan, a mobile web application that creates customized wellness plans for cancer survivors. Dr. Alschuler works as an independent consultant in the area of practitioner and consumer health education.

Contact

• www.drlise.net(consumers)
• www.ithriveplan.com(consumers)
• www.listenandcare.com (clinical practice)
• www.tapintegrative.org (professional resource)

Research Papers referenced on podcast:

• a. Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States
• b. Combined effect of CYP1B1, COMT, GSTP1, and MnSOD genotypes and risk of postmenopausal breast cancer

Podcast sponsored by Designs For Health, Dr H Rejoint & Genova Diagnostics

Designs for Health is a professional brand, offered exclusively to health care professionals and their patients through referral. By providing comprehensive support through our extensive line of nutritional products, our research and education division, and our practice development services, we are able to maximize the potential for successful clinical health outcomes.

Kara Fitzgerald:
Hi, everybody. Welcome to New Frontiers in Functional Medicine. I’m Dr. Kara Fitzgerald. Today I’m delighted to have with me Dr. Lise Alschuler. Dr. Alschuler is a naturopathic physician. She’s also a fellow of the American Board of Naturopathic Oncology. Again, we’re going to be focusing on cancer, and Dr. Alschuler has a lot to offer us in this arena. You are probably actually already familiar with her work. She practices naturopathic oncology. She maintains a practice called Naturopathic Specialists LLC, and you can access information on that with this podcast. She’s the co-author of Definitive Guide to Cancer, and Definitive Guide to Thriving After Cancer. Definitive Guide to Cancer, if you don’t have it, has been a great resource for me in my practice, and also it’s a really nice reference for patients.

Dr. Alschuler is the Executive Director of TAP Integrative, a non-profit educational resource for integrative practitioner. She co-hosts a radio show, Five to Thrive Live, and is co-founder of the iTHRIVE Plan, a mobile web application that creates customized wellness plans for cancer survivors. Dr. Alschuler works as an independent consultant in the area of practitioner and consumer health education. I just want to say that Dr. Alschuler has been a mentor to many of us over the years, myself included. I’ve learned much from her teaching and I’ve also had the privilege to receive some assistance on patient cases. Again I’m just really delighted to have you here Lise, welcome to New Frontiers.

Lise Alschuler:
Well thank you, that was a very generous introduction and I’m really happy to be with you and all of your practitioners and patient listeners today.

Kara Fitzgerald:
Great. Let’s just jump right in and talk about the huge, huge topic of cancer prevention. I know there is amazing research coming down the pike around this, what are your thoughts on cancer as a preventable illness and just some of the research out there?

Lise Alschuler:
Yeah it’s interesting because the question about is cancer preventable is still very much alive in the scientific literature and a topic of debate among researchers and oncologists. I think it’s actually a legitimate debate honestly. I would articulate that yes absolutely, we can reduce our risk of cancer, so in that sense cancer is preventable. I think that we can confidently say that a third of all cancers and in some cases depending on the cancer, half of all cancers and maybe even more in the case of colon cancer maybe 75% of colon cancers are preventable through lifestyle changes. That being said I think for an individual when you’re contemplating this question it really becomes, how much can I lower my risk through how I live my life?

I think most people can’t get their risk down to zero but they can significantly reduce their risk. I think it’s really a matter of risk reduction because there are still the spontaneous mutations that happen that can arise regardless of what somebody does, what somebody eats, et cetera. There are environmental factors that are hard to control and there are genetic SNPs that increase susceptibility, so certain elements that are not changeable.

Kara Fitzgerald:
Right. Okay. I know we’re going to jump into some of the things that you recommend for prevention but I just want to throw out there that I’ll be pinging you on the idea of periodic fasting and just a ketogenic diet as a periodic tool to aid in prevention. Then actually how you use that therapeutically, but we’ll jump into that in a second. You have a personal connection to cancer, you want to talk about that and maybe …

Lise Alschuler:
I do.

Kara Fitzgerald:
Maybe how that’s informed your work?

Lise Alschuler:
I think it’s important because it’s not just a abstract concept for me, it’s very much relevant to me as a person. I lost my father to pancreatic cancer and he was just an amazing testament to the power of integrated therapies. He was diagnosed with advanced pancreatic cancer as many people are, he was given about a three month’s prognosis which was true given what I saw on his scans. He ended up living for 17 months and what was most remarkable was that the majority of that time really up to the last couple of months of his life was really high quality life. He felt very well, and to me that gave me a huge motivation to make sure that every single person diagnosed with cancer has the ability to use integrated therapies.

Of course I got to learn that lesson really well myself when I was diagnosed with breast cancer and again through my own experience through conventional treatments, a lot of them. At the same time obviously used naturopathic and lifestyle based therapies and really felt like a healthy person going through breast cancer with a healthy person getting chemo, a healthy person getting radiation, et cetera. Which is a big deal in oncology treatment so having now been through cancer of course I have heightened concern about cancer re-appearing in my life and take all this pretty seriously from a personal perspective. Yeah it’s imbued for me all of this with a lot of acute relevance.

Kara Fitzgerald:
Yeah. Indeed. Anything that you learned in the process, any pearls from your own experience or the process of working with your dad? Or do you want to share with me when I get into some of the specifics around your book?

Lise Alschuler:
There are so many pearls, really this is something that I can do deep guide on a regular basis, I guess what comes to mind right off the bat, there is something very clarifying about a diagnosis of cancer because it typically happens to people when they’re generally feeling well in other respects. All of a sudden they’re sort of blasted with this, “You could die sort of diagnosis,” and “In order to move you out of that threatening place we’re going to offer you some really toxic treatments.” It’s very disruptive but with that disruption comes the ability to reaffirm what’s important in life and decisions that are made, are made with a lot of attention to the why. I think that there’s a clarity and a sense of congruence which comes from a diagnosis.

When you’re working with people, who are going through or have gone through this experience, the, pardon my language, the BS meter for people who have been through this diagnosis is pretty acute. I think as a practitioner it’s really important to be very honest with yourself, to be very present with people because they’ll pick up on that very quickly. The more present, the more sensitive you are to just being very true to the moment with your patient, the more healing potentially you’re going to reap through that relationship. That’s just the first thing that comes to mind.

Kara Fitzgerald:
All right, actually that’s such an important pearl, just being really authentic, truthful.

Lise Alschuler:
Yeah.

Kara Fitzgerald:
Okay. You focus a lot on prevention and in the Definitive Guide to Cancer and then the Definitive Guide to Thriving After Cancer. You talk about five key bodily pathways that are really linked, can you just articulate what your thinking is on these pathways? What they are and some thinking around them?

Lise Alschuler:
Sure. I think for all of us involved especially in integrated health where we’re just inundated with the millions and millions of data bits out there, it’s helpful to create categories to house the information that we’re trying to assimilate. For me as I’m looking through the literature linking various therapies and understandings with cancer prevention and cancer treatment, it became very clear that there were essentially five buckets. These areas had the most influence on somebody’s potential to develop cancer or to develop its recurrence. That’s been a helpful way for me to think about all my therapies, so for example when people come in to see me for initial primary prevention of reoccurrence; I go through this checklist of these five areas in my head.

Make sure that I have therapies that are addressing all these areas. The areas are inflammation and by that of course I mean chronic inflammation typically. Although there is some interesting data that suggests that perhaps acute inflammatory events might also create opportunity for signals to develop that could create cancer development. Let’s just leave it at chronic inflammation for now. Second area is immunity and we know that people who develop cancer tend to have a depressed, toxic immunity. The imbalance is one that really calls us to stimulate both cytotoxic T-cell activity as well as innate immunity in primarily natural killer cell activity.

Third area is what I call hormonal balance which by itself doesn’t really mean much but specifically with regards to cancer what I’m really thinking of is balancing the stress response system, the role of stress in a hyperactivated or up regulated, hypothalamic pituitary and adrenal access is quite significant. So we really want to make sure we address that, and then included of course for people who are at risk for or who are have had a history of estrogen or other hormonal dependent cancers, we need to pay attention to those hormones as well.

Kara Fitzgerald:
Right.

Lise Alschuler:
The fourth area would be insulin resistance, and this is kind of a big umbrella for me now which is about insulin resistance which is really emerged as a primary driver for cancer because insulin is such a strong mitogen. But having said that, there’s also within this umbrella now this idea of just being inundated with calories, being over fed and the implications of that, as well as this composition of our macronutrients . Then the final category would be detoxification, this is really where I look at not only what people are bringing into the system that they have to detoxify but trying to tie in the environmental component of their life. If I have in my approach something that addresses people’s health in all those areas, then I can be pretty confident that I have a fairly comprehensive approach to that individual.

Kara Fitzgerald:
Wow. That’s great. That’s really useful breakdown of the areas that we need to be thinking about, thank you so much. I appreciate it. In thinking about preventative strategies you’re looking at five areas here as well, specifically spirit, movement, diet, dietary supplements and rejuvenation. Talk about how you look at these in guiding patients with regard to prevention.

Lise Alschuler:
It’s one thing to say we have these five sort of physiological areas that we need to address, the ones I just went through, inflammation, immunity influence, et cetera. Then the next question okay that’s all fine but how then do I address those areas? This is another layer to this matrix that I build in my head and that the five ways in which I try to address each of areas is those ways we just mentioned. Just to take those one at a time, I’ll start with spirit because spirit is something that is I think perhaps underutilized in integrated practice. It’s such an important part of healing, if the spirit is not religious per se it’s really a values based life.

For us as practitioners it’s, do we talk to our patients about what it is that gets them excited about being alive in this world? Do they have love in their life? Do they feel that they’re a part of community? How does that heal them, how does that show up for them? Those are the kind of questions that we need to help them ask themselves and then be in a position to support them in optimizing.or me spirit is where we ask ultimately the questions of the sake of what. The sake of what I’m I spending all this effort changing my diet, for the sake of what I’m I taking these supplements everyday? When we get to that core level, that’s what people’s motivation is, that’s what their wellness truly arises from. A really important part.

Kara Fitzgerald:
Okay. When you talk about how, you’ve just mentioned how the BS meter is just very heightened and sensitive with patients in active cancer and they need to be real in spirit, and these kinds of conversations are really a natural outcropping of that. Yet you’re talking about this in prevention, like bringing these important conversations from the center, I mean not just in our patients but obviously in ourselves. Walking the talk so it’s just a great point on both ends, bringing spirit into life.

Lise Alschuler:
Yeah. Can you still hear me okay because you are breaking up a little bit so I’m not sure you can hear me well?

Kara Fitzgerald:
Yup I can hear you fine.

Lise Alschuler:
Okay. Perfect. Yeah so it’s so important for all the reasons you just said exquisitely important for people diagnosed with cancer. That’s one strategy as I call it, another is to always talk to my patients about movement or exercise and it really has two aspects to it. Of all the strategies available to us people who regularly exercise across the board will reduce the risk of most major cancers by about 50%. That’s more than any dietary strategy, that’s more than anything else that so far we have been able to measure. It’s a pretty important strategy to talk to people about, exercise. We know more too about the fact that not only is that 30 minute of moderate brisk walking five days a week the baseline, but we now know that more is better.

Getting more vigorous exercise adds prevention benefits, exercising longer adds more prevention benefits. Then the second part to movement which is equally as important actually is not being sedentary. I told the story before about four years ago or so, I mean three years ago, I was doing a lot of reading on [sedentary-ism00:16:30], it’s called the new smoking when talking about cancer risk and I exercise every day and I was, “Oh my gosh, I exercise everyday but I’m sedentary because I would be in front of my computer all day long. Sometimes for hours on end and it was a really good awareness for me that it’s easy to be sedentary in our modern world.

Making sure people get up every 90 minutes, do their two minutes of activity is so important and actually can also reduce cancer risk and risk of cancer occurrence quite significantly. Movement is really important to talk to people about.

Kara Fitzgerald:
That’s great that the research is moving beyond the 30 minute vigorous walk five days a week and intensity is recognized as beneficial. Obviously this would be within the patient’s tolerance level or the individual’s tolerance level. Pushing beyond certainly wouldn’t be useful until the body is ready for it. Just thinking about you know when I was in school I rode my bike everywhere, I didn’t own a car and I was active just all the time. I’d have to ride to clinic and then ride to class and I’m a desk jockey now and it really is a struggle to get my movement. I’m trying to hold myself accountable with one of those wearable fitbits , just little things to remind me and I’ve just gotten this funky chair that rolls around a little bit.

It’s been really challenging for me but I’m doing it.

Lise Alschuler:
For practitioners this is a really big issue, because think about it, we sit and listen to patients most of the day, then we sit and do our charting, and then we’re tired. When we come home we sit and eat dinner and maybe we sit and watch TV, I mean we can be very sedentary as practitioners. It’s a really important thing for us to be aware from a selfreflection stand point and then as we -develop strategies that help us, we can impart those to our patients as well. I want to go back to your comment about tolerance, the way that I describe this to patients is that I want patients to always be at the edge of their fitness and Susie’s edge is doing to be different than Mark’s edge, is going to be different than my edge.

That they are always kind of at that place where they’re not totally comfortable with activity and it’s always causing them to push just a little bit. For people who tend to over push, generally I havecome up with things to really help people self-regulate. I tell them that if they go out and do a walk for 30 minutes, that it should take them no more than half of that time period that they’ve exercised to recover their pre-energy exercise level. So they walk for 30 minutes, they should come back and if they’re tired they should be back to feeling good within 15 minutes. If it takes them longer than that, they’ve overdone it. It seems to help people self moderate their level as they’re especially getting out of recovery.

Kara Fitzgerald:
There is just so much cool research around exercise, just the hormesis ideas around it, obviously we’re increasing oxidative stress because we’re turning on mitochondria and energy production. Then we sweep right in with the various tools to clean it up, we’re up regulating detoxification and glutathione and superoxide dismutase and all of that so it’s quite remarkable.

Lise Alschuler:
I could talk about exercise all day long if you have to cut me off but I actually really love that you brought up hormesis because the research shows that when you do an intense bout of exercise your oxidative stress is super high …

Kara Fitzgerald:
Picks up.

Lise Alschuler:
Even right afterwards but then people who regularly exercise overall have a much better redox potential on a cellular level so there’s just something that happens with that even day in day out kind of thing. Then there is the myokines which are excreted by exercising muscles, those were just discovered several years ago so we didn’t know about those 10 years ago but those directly counter the effects of insulin. That’s one of the reasons why it’s so important to exercise when you have insulin resistance.

Kara Fitzgerald:
Yes. Thank you for that, I’ll have to look into myokines it’s really interesting. Then I’ll hush on this just because it is such an interesting area. Research coming out that taking, actually it’s not even that new, that taking antioxidants right after exercise and quenching that oxidative process and the hormetic response is a bad idea. Just thinking about timing with regard to when we take our supplements and I know we’re going into talking about that in a minute but I think quenching that action, that post exercise metabolic clean up isn’t a good idea. There is an appropriate time to take them. I don’t know if the research is out on that, if it’s actually defined when the optimal time is to take our supplements and our various antioxidants.

I always advise not after exercise maybe in the morning or at night after your events but have you seen anything on that as far as timing goes for supplementation?

Lise Alschuler:
Yeah the only data I’ve seen is probably the data you’re referring to which is pretty old by now actually in Vitamin E and timing that, and I think it seems like just taking it either before or away from exercise. Just at least avoid that immediate quenching effect of those oxidants.

Kara Fitzgerald:
Yes and just allows the body to do it. Okay. Massive topic that you and I have talked about over the years, diet. Now I would say two things, we’re talking about prevention and also I’d love to hear your comments in as a part of therapy for cancer patients.

Lise Alschuler:
Well, I’ll make a couple of general comments and then I think you can ask me specific questions because this is such a broad topic. I’ll just say generally speaking that from a prevention standpoint, I think hands down the basis for diet should be a Mediterranean style of eating, that’s the best researched, evidence-based diet plan for prevention of cancer. It’s essentially translated to a plant-based diet so it’s also very easily adapted by most people. It’s a great place to start and then on top of that there’s a whole bunch of nuances from a prevention standpoint. The other generalization I’ll make is that it is absolutely with diet inappropriate to automatically assume that what is useful from a dietary perspective in active disease is also useful from a prevention standpoint or vice versa.

In many cases it’s the exact opposite. That what you saw from a prevention standpoint is actually potentially harmful from a treatment standpoint, case in point, anti-oxidants. This is a little bit diet and dietary supplements but high doses of anti-oxidants or strongly glutathione rich diet, wonderful from a prevention standpoint for lots of reasons, but it actually can be harmful to somebody who has active cancer. It helps cancer cells gain resistance to cytotoxic therapies and facilitates various mechanisms that allow them to become more invasive. That’s just one example but there are many like that so we have to be very careful when we’re talking about diet and applying what we’ve learned to make sure that we are applying it in the right context.

Kara Fitzgerald:
Okay. Thank you for that. You and I were just chatting about methylation so I want to ask you about that in a sec with your thoughts on how you might approach that with prevention and active disease. Mediterranean has a major preventative tool and then in active treatment, you do prescribe the calorie restrictive ketogenic diet I believe but any comments on diets you’re using on active treatment?

Lise Alschuler:
It depends, the ketogenic diet can be useful for certain patients, it’s a hard diet to follow for people who are in active disease because cancer is a very catabolic process so it’s hard for people to energy restrict. The ketogenic diet that can be helpful that anti-proliferating diet is not just eating most of your calories from fat but it’s significantly calorically restrictive as well. I would say for a fairly small size of the pie in terms of your patient population. Having said that, there are certain cancer types where I immediately think of it, the most obvious one would be brain cancer, gliomas,in particular because the database is fairly good. It’s not great, there’s not a lot of results on this in general but there are some good case studies that have been published and it seems that the metabolism of cancer in the brain is quite different.

There’s more reliance on ketones in the brain for healthy cells but malignant cells in the brain are not able to take up those ketones so it creates a bigger differential in the brain. I think there’s potential for this diet. Have I seen it cure cancer? I have not. Have I seen it slow cancers down? I believe I have seen that in my practice. Have I had a patient that’s been able to sustain this for years and years and years? Not yet, my longest patient was able to hang in there for about a year and then she said, “I’m done with this diet, I can’t do it anymore,” she’s not on it anymore. There’s so there’s some adherence issues too.

Kara Fitzgerald:
I was actually talking to Tom Seyfried who really put it on the map with his research advice and he is looking at it as being a tool similar to chemotherapy and that we really need to talk about pulsing it when we apply it for duration and that’s big stuff. I have patients, I have people coming to my practice often having already initiated it themselves, and you’re right it’s extremely difficult to follow and it’s difficult to achieve the therapeutic levels of ketone production and corresponding drop in glucose. It’s hard and fatigue is often a really big fall out . There’s much to be learned here, I agree with you I think it can be a helpful tool and I also have seen what appears to be success in a handful of patients.

I’ve also seen a lot of people not be able to follow it and side effects such as probably fatigue. Dr. Eugene Fine, are you familiar? He published a small pilot study where he did look at cancers as outside of brain tumors with some success. There’s folks who were able to get to the highest level of ketone production appear to have some reduction. Very small pilot study, breast cancer I believe, lung cancer and a handful of others. It’s super small so you can’t extrapolate too much from that but I agree with you I think there is a place for it and there’s much to be learned. We’re probably over using it, certainly patients appear to be, individuals just jumping on it aggressively and with some fall out.

Lise Alschuler:
Right. Then that study by Fine it was very small like at 10, 10 patients and only five had stable disease or partial remission so we’re not talking about cures. Really 50% had some relative response to that treatment, I think from a clinical translation perspective that means that you’re going to theoretically have to get 10 patients on this to have five who have some disease stabilization. Another pilot study that was published by Schmidt, he actually had very limited success because he had such a high dropout rate, so from a clinical perspective to get those five you’re actually probably going to have to start with a lot more patients because you’re going to have to count for all the drop offs.

You’re going to get due to the challenges with adherence.

Kara Fitzgerald:
Right. That’s right. I think those five that were successful, did get into the most aggressive ketosis and he didn’t calorie restrict in his either, interestingly. I’m with you, there’s much to be learnt and just jumping into it without some attention is I think potentially damaging. Okay. Let’s talk about supplements, another huge area with tons of mixed I think data and also just mixed internet lore around what to do. What are you thinking about …

Lise Alschuler:
Yeah obviously it’s a huge topic but I prescribe dietary supplements to all of my patients so right there tells you that I believe that they have a role to play. I think the way I describe it to my patients is that diet and exercise are broad sweeping tools and with dietary supplements I’m attempting to apply a more finer tool. I’m actually trying to manipulate pathways in the body. I think that’s in fact what I believe supplements are doing in reality I think that they’re even kind of broad tools. That what we’re actually manipulating are very precise and very dynamic pathways that are up and down regulated by a variety of things that we’re not even thinking about nowadays. Even getting out there and thinking about light wavelengths and the implication on that.

All these kinds of things, so that being said, I do think that dietary supplements are a way to offer some degree of precision to our therapies. I think that what we can see with these supplements is that from a prevention standpoint we can effect those five pathways really effectively. We know that there are supplements that can help reduce insulin resistance, so we would first assess to see if somebody has insulin resistance, we check the fasting glucose and insulin and throw those values into a HOMA-IR calculator to determine if they are insulin resistant. If they are or they’re pre-diabetic or diabetic, then we want to make sure we’re addressing insulin resistance and supplements really help with that.

We know that there are supplements that are really good at reducing chronic inflammation and again there’s biomarkers of inflammation in the body that we can assess for and watch those to make sure that those go down. Even if they’re not elevated and people seem inflamed, they have issues which are suggestive of chronic inflammation then I’m going to assume that that’s happening on a tissue level and apply flavonoids like curcumin and things like that to reduce inflammation. I think that supplements are really important and there are good studies now for several of these supplements that really do show benefit in terms of both prevention. Then of course if somebody has cancer helps to modify that outcome as well.

Kara Fitzgerald:
Well give me a couple of ideas, I would be remiss if I didn’t try to nail you down on some supplements that you’re using routinely. Insulin resistance, what are the couple of things that you’re going to offer and these are in cancer patients so we’re not talking about prevention now we’re talking about your cancer patients.

Lise Alschuler:
Okay. With insulin resistance, one of the first things that comes to mind is berberine andberberine restores insulin sensitivity, it activates AMPK, reduces hepatic gluconeogenesis, inhibits fatty acid synthesis particularly in the liver. It really has very clear mechanisms by which it reduces insulin resistance. We’ve seen it on a dose milligram per milligram basis to be comparable with Metformin in a couple of clinical studies. I think that that’s one of the first things that I look at. Berberine per se doesn’t have necessarily good evidence as an anti-cancer therapy but because of what’s it’s doing to insulin resistance and the insulin resistance to insulin receptor pathway, I’ve inferred some things in terms of having some anti-neoplastic effects.

That would be one my first go-tos. Another one that I would mention and I don’t know how many people are aware of tocotrienols but these Vitamin E isomers different than tocopherols very small flexible molecules, so they have very different molecular effects. They also have been shown to improve glucose balance and improve insulin sensitivity, they reduce inflammatory markers in a variety of different cellular and animal studies primarily. They have pretty good effects in terms of improving insulin sensitivity, so from a prevention standpoint in particular I think tocotrienals have a really important role to play. I guess that would be my second go to, if somebody is in active disease I still think about tocotrienals because they do actually induce apoptosis they do have an anti-neoplastic effect.

I probably would say I think about them more often in a preventive standpoint.

Kara Fitzgerald:
Okay. Let’s see what else did I want to ask you here, anything jumps to mind in terms of supplementation for hormone balancing? I guess specifically I’m just thinking about estrogen mediated cancers, what you might go to there?

Lise Alschuler:
Yeah. This is complicated. Let’s say we’re talking about somebody who’s been diagnosed obviously already, so they’ve had some diagnosis with an estrogen receptor positive cancer. Most typically those individuals are going to be on an anti-estrogen type of therapy whether it’s a therm or a [C 00:36:55] they’re either blocking estrogen production or they’re blocking estrogen receptors. In that context let’s take those two separately. We could first say they’re on an estrogen blocking medication like Tamoxifen, I don’t really care what their estradiol level is because that drug provides such redundant and ubiquitous estrogen blockade that it really doesn’t matter to me what their estrogen level is.

I don’t even care what kind of estrogen they’re producing. Once they’re off that therapy then it matters a little bit more however, I don’t actually ever measure estrogen metabolites, the data on using estrogen metabolites in somebody who’s already been diagnosed with cancer and been treated, the correlation between the testing results and actually the estrogenic effect is very poor. There’s actually been a couple of studies on that and theories that there’s been too much impact by both the disease and the treatment, to make the metabolites a reliable measure. I don’t really use metabolites but what I do do is that I will often test for SNPs in estrogen metabolism, because what I’m more concerned about is if this person is somebody who is going to be hydroxylating their estrogen down before hydroxylation pathways.

Which is the most carcinogenic metabolites, and if they’re pushing the full hydroxylation pathway, are they then able to methylate those metabolites so that they don’t form the [klinones 00:38:34] which bind to the DNA and damage DNA. I want to know about methylation, I want to know about COMT] and those become very important in some of the glutathione transfers enzymes. I look at SNPs because that tells me if somebody has a lot of SNPs which is quite common in people with an estrogen receptor positive cancer then I know that I really need to pay attention to estrogen metabolism at that level. I’m looking now at prescribing something like [dianomethylene 00:39:06] or [dian 00:39:08] as people refer to it. I’m looking at sulfuracinine, I’m looking at methylation support to really help modify how estrogen is metabolised.

To me that’s more important than looking at the ratios that are in the body.

Kara Fitzgerald:
Thank you. Really nicely stated, very clear. Now when I’m looking at the literature on COMT which is the enzyme catechol-o-methyltransferase for converting the hydroxylated estrogen metabolites to their methoxy counterparts. When I’m looking at the literature I’ll see the mutation commonly in my patients in practice, it’s a pretty ubiquitous finding. I haven’t seen a ton of data on it being associated with increased risk for estrogen sensitive cancers but have you? I mean where is the literature with regard to it?

Lise Alschuler:
Yeah. There’s one study which I don’t know if I can pull it fast enough to talk about at this second in detail, but there was a study where they looked at combination of SNPs and it was kind of a landmark study actually … Okay I got it. This is the study looking at the combined effect of SNPs in [Cip1 B1 00:40:29], COMT, GSTPI or glutathione sulfur transferase, and then manganese SOD. They found that the risk of breast cancer, or they use breast cancer cases and translate that into a risk and that the risk of having those SNPs was additive. For example, if somebody had a SNP in CYP1B1 which means they’re going to produce more (four?) hydroxylated estrogen and the COMT SNP than they have 100% percent increased risk.

If they have a COMT SNP and an SOD risk they have 100% increase risk. If they have CYP1B1, COMT and glutathione S-transferase, they have 170% increase risk. If they have CYP1B1 , COMT, glutathione, GSTP1 plus manganese SOD, 1,100% increase risk.

Kara Fitzgerald:
Geez. There you go.

Lise Alschuler:
To me this study is really important, it was published in the Journal of Gynecological Oncology, in 2011, [inaudible, 41:41] colleagues and I think that that’s the best data point that we have. There are some other data points and studies on COMT specifically and especially polymorphisms of COMT increase and the risk of breast cancer. I think on the order of about 30% increase risk.

Kara Fitzgerald:
Okay. Thanks so much for that citation and folks I’ll get the reference and put it on the transcripts page so look for it. Shit’s just really huge. It’ll be interesting to see because we can manipulate naturally, we can impact how functionality of those enzymes just really support them in certain ways. It will be nice to actually have our own data pool to add to the conversation.

Lise Alschuler:
Yeah. Absolutely. Just to really make an important footnote on this, this is another good example of where we want to support methylation for this when I was thinking about prevention but in some of these active disease, a whole category of new therapies in oncology care are de-methylating agents. That there’s some thought that if you support methylation actually in active tumors you add more chromosomal stability within malignant cells and you actually support tumorigenesis. Questionable about whether we want to really give too much methylation support during active disease, that needs to be taken up on an individual basis. I would just put a footnote of caution on that.

Kara Fitzgerald:
Awesome. That brings us back, I wanted to talk to you about methylation, my own approach to it has evolved considerably and I’m working upstream with diet and lifestyle interventions which I think the data are suggesting they can profoundly impact healthy methylation DNA. We’re talking about the epigenome folks, cool research on exercise and supporting global balanced methylation. Actually there are some pretty neat research out there on flavonoids actually having the ability to inhibit DNA methylation, and almost like an adaptogenic thing we’ve been calling it. I think there’s a good reason to be cautious with this high dose methyl donor intervention because the epi genome is in our research there’s a bit of the Wild West but hyper methylation as you pointed out is a big player in oncogenesis.

Lise Alschuler:
Yeah. It’s interesting because still though from a preventive standpoint I would err on the side of giving people methylation support only because the first epigenetic event in carcinogenesis global hypomethylation. Then what happens after that is you get these hyper methylated EPG islands that are sitting right in front of tumor repressor and tumor repair genes so you want to direct the traffic and I think that’s where these flavonoids are so fascinating. You’re right that EGCG they sort of pull those methyl groups off of those hyper methylated areas, it’s like they know exactly where methyls are supposed to be sitting.

Kara Fitzgerald:
Right. It’s just extremely interesting and cool. You’re right this hypo methylation it’s almost like the folate story, which is of course key in healthy methylation. Methylation has a U curve as much any of these other things that we’re talking about so insufficient folate of course can allow for the development of cancer whereas excess folate clearly and probably through imbalance methylation can promote. Thank you. I’d love to pick your brain on this more because you’ve been thinking about it a lot and it’s been an interest of ours over here. Just finalizing the supplements, I mean we don’t have endless amount of time here but, any key supplements that come to mind just for prevention, I know we were talking about antioxidants before and how you put the brakes on them during active therapy.

Just prevention coupled with supplements you might you use that you wouldn’t use in active treatment.

Lise Alschuler:
Yeah. My top list of supplements to consider for prevention maybe talk about categories but these aren’t necessarily precluded during active disease, Vitamin D of course is first on my list, there’s clear evidence now that Vitamin D insufficiency is associated with increased risk of developing cancer, increased risk of progressing with cancer if already diagnosed, very important. Test and treat according to people’s values. I think another really important area of supplementation with regards to prevention are flavonoids in general, I rely on them a lot actually. Flavonoids have such, we just talked about directing traffic in terms of the methylation but flavonoids also influence a lot of intra cellular redox pathways and translate oxidative insults on the cell membranes sub-membranes.

They help to maintain or to protect the cell from sustaining a lot of mutational damage that being shorthand to the complex back chemistry but having said that some of the heavy hitters are curcumin for sure, EGCG from green tea, resveratrol, quercetin, these would be some of the top ones that I would think about. Then stepping back a little bit more, I think about just nutritional repletion with things that lower inflammatory potential like essential fatty acids both EPA and DHA and again there’s good data on the reduction of inflammation for oxidation which can be carcinogenic. That would be another consideration from a prevention standpoint. The area of the microbiome and its relationship to carcinogenesis is just being explored, there is definitely a relationship there and there’s a lot of translation that happens through the immune system.

It’s clear that we have to pay attention to the microbiome so I think particularly somebody has digestive issues then it’s really important to get those corrected and then to make sure people have as best as we can tell, a good microbiome. Probiotics therefore might play a role and I guess in my sixth area I would say I tend to look at anti-oxidative support, I like tocotrienols a lot because it seems that they do have that apoptotic potential. I’m recently becoming quite enamored of lipoic acid and there’s just some really interesting effect of lipoic acid from a prevention standpoint. I’ll mention one just because it’s interesting stuff. There’s a series of cancer occurrence which has to do with stem cells that are very immune unfortunately to chemotherapy and sometimes radiation.

They feed tumors and then they can stay dormant and even float around as the what we call mesenchymal stem cells in the blood. They’re apparently very un-differentiated and they can be dormant for a long time and they can also be retriggered to invade back into tissue and re-start a tumor. Let’s pay attention to these circulating tumor cells especially these ENT transition cell. Back to lipoic acid, it turns out that alpha lipoic acid helps to prevent this mesenchymal transition, so it’s a really nice way to help to mitigate some of the danger if you will of these circulating cancer stem cells. Plus, it just has a really nice potential within the cells to prevent some of the mutational damage that can exist there, it helps regulate and improve mitochondrial function. I’m quite enamored of lipoic acid lately.

Kara Fitzgerald:
Yeah it’s understood. I used to call it, when I was at the lab and we were researching for the laboratory vowels book, it was the anti-oxidant’s anti-oxidant, and its capacity to … anti-oxidants because it can regenerate so many of these players like Vitamin C and so forth.

Lise Alschuler:
Yeah. Right.

Kara Fitzgerald:
Okay. What else do we want to talk about here, I mean obviously having a background in laboratory science I find a lot of utility in some of the like doing stool analysis and some of the broader investigations, specialty testing, what are you using in practice? What are some of the go-to tests you might use in prevention and maybe even when you’re treating cancer patients, anything?

Lise Alschuler:
Yeah. I do like to get some laboratory evaluation when possible so at a basic level I like to look for certain biomarkers of inflammation and insulin resistance, I talked about fasting glucose and insulin, hemoglobin A1C. Some information, some of the things that we look at are at a basic level I definitely want to see what high sensitivity CRP is, look at fibrinogen, sometimes we may do some cytokine analysis depending on the history. Like if somebody’s had pretty aggressive cancer in the past we might look at IL-6 and IL-8 . From a hormonal level I tend like I said to look more at SNPs in some of those methylation and detoxification enzymes . A morning cortisol though or even better a four- point cortisol test can be quite helpful.

I don’t do a lot of digestive analysis unless people have digestive issues and then I really want to make sure that you get your digestive tract online for lots and lots of reasons. In that case I think it can be quite helpful if I am worried about inflammatory bowel disease or IBS Calprotectin or some of these other just good comprehensive digestive stool analysis. Then the only other test that I do run sometimes is an organic acid test, I think that can really help me get a view into metabolism, and methylation, just touch points in a lot of different areas.

Kara Fitzgerald:
Thanks. This is …

Kara Fitzgerald:
Thanks. This has been a real tour de force, Lise. I just really … This has been very valuable. I think a lot of people really enjoyed this as well. I just learned a lot. People wanting to pursue additional training, so clinicians looking to do some of the drill down and explore some of these areas you’ve talked about, what are some resources folks can turn to?

Lise Alschuler:
Kara, that’s a great question, and the answer’s going to be just completely unsatisfying, I think. First of all the Oncology Association of Naturopathic Physicians, OncANP is a great resource for naturopathic doctors and allied professionals as well can join as allied members.

Kara Fitzgerald:
Oh good.

Lise Alschuler:
We have a great conference every year. There’s a really active forum so there’s a good data exchange there. There’s not really a text per se that I would direct clinicians to, to kind of dive deep into these areas. The way I and most of my colleagues try to keep ourselves up to date is just to be really avid. We have a voracious appetite for pub med and we’re on list serves, and we’re just looking at articles of interest and combing through them on a regular basis to try to pick up these tidbits and sort of piece the tidbits together into our own understanding.

I can’t really offer more than that. I think that finding clinicians that you trust and that are open to having a mentor relationship with is another great opportunity to learn. There are good conferences, I think, available now in addition to the OncANP which has a nice training of oncology in there, too. Just going to conventional oncology conferences is a great way to pick up knowledge. You don’t get the natural side of things, but you can get a really deep dive into the molecular biology and just understanding the disease process.

Kara Fitzgerald:
You are … You’ll consult with clinicians. Are you doing that, consulting, doing case consultations still? Are you offering that service?

Lise Alschuler:
I will. In my practice what I tend to do is if a clinician has a patient that they want some help on, I can set up a professional consult with the clinician and we’ll get some information about the patient ahead of time, and then kind of guide the clinician with what I would think would be important considerations. Yeah, I do offer those, and some of my colleagues offer that as well. Yeah, that would be another resource.

Kara Fitzgerald:
What about TAP Integrative? That’s a good …

Lise Alschuler:
Yeah, what about TAP?

Kara Fitzgerald:
Are you guys going to –

Lise Alschuler:
That is awesome.

Kara Fitzgerald:
Are you jumping into this topic at TAP? Would this be another resource?

Lise Alschuler:
We do have some. We actually have … We have a great TAP feature on colon cancer prevention and an upcoming one on prostate cancer. I have to just thank you for being a TAP expert on autoimmune disease. That in fact is our current expose, our free entrée into TAP. People can check it out by looking at TAP Integrative sneak peek. One other thing I should say about tapintegrative.org is that for practitioners who really want to just kind of get clinically relevant information, there’s great resources on there. We have a member benefit which is that you can request full text articles from pub med of your choosing, whenever you’d like.

Kara Fitzgerald:
Wow.

Lise Alschuler:
Super easy to do, and it’s free. You pay your membership after 3 articles typically. People who are like yeah I love pub med, but I can’t get the full text, this is a great way to get that.

Kara Fitzgerald:
Well, you need to be blasting that out. That’s huge.

Lise Alschuler:
I know, right. That is huge.

Kara Fitzgerald:
You really need to blast that. Folks, the link to TAP will be on the page for this webinar, so you guys can head over there and check it out. It is a really wonderful resource. All right, Dr. Alschuler, it was wonderful to touch base with you, and thank you so much for sharing your brain with us today. I really appreciate it.

Lise Alschuler:
Absolutely, my pleasure. Thank you.