27. Does surgery increase the risk of cancer metastasis? The answer will change the way you view medical procedures

Surgery can wake up dormant cancer cells—even if the surgery is unrelated to cancer. In this striking episode, Drs. Dawn Lemanne and Deborah Gordon uncover how surgical trauma and anesthesia suppress immune function for weeks, creating an ideal window for tumor growth. Listen in as they discuss powerful, little-known tools to counteract this: a flu shot given within 24 hours before surgery can preserve immune surveillance; which painkillers to avoid after surgery; and how Cialis may reduce metastatic risk when used preoperatively. Bonus: Learn how heart rate variability reveals immune strength and insulin sensitivity. 

Dawn Lemanne, MD
Oregon Integrative Oncology
Leave no stone unturned.

Deborah Gordon, MD
Northwest Wellness and Memory Center
Building Healthy Brains

Chapters

• 2:05 Does cancer have its origins before birth?
• 4:00 Surgery suppresses the immune system for 4 weeks
• 16:44 Morphine Weakens Cancer-Fighting Cells
• 32:00 Blood Transfusions Increase Cancer Risk
• 49:34 A flu shot given 24 hours before surgery may help prevent cancer spread
• 50:05 Erectile Dysfunction Drugs Can Prevent Cancer Spread
• 52:29 Heart rate variability reflects real-time insulin resistance or sensitivity

Transcript

Dr. Lemanne: 0:00

Cancer cells, if they're dormant and far away from the surgical site, you know, they get this message, wake up everybody and grow. So a flu shot given within 24 hours of surgery helps prevent the natural killer cell impairment that we see otherwise after surgery. Morphine suppresses the activity of natural killer cells. Erectile dysfunction drugs, Cialis. given preoperatively can decrease the risk of metastasis. Heart rate variability is an instantaneous measurement of your insulin resistance. I'm Dr. Dawn Lemanne. I treat cancer patients. I'm Dr. Deborah Gordon.

Dr. Gordon: 1:04

I work with aging patients. We've been in practice a long time. A very long time. We learn so much talking to each other. We do. What if we let people listen in? Hey there. Always great to be with you, Dawn, and with all of you listening, of course. Today, we've got a fascinating episode. And honestly, under-discussed topic. It's about surgery, but not just cancer surgery. Exactly.

Dr. Lemanne: 1:33

I mean, we're going to be talking about any kind of surgery. If you're planning a hip replacement, if you're going to have your gallbladder removed, even cosmetic surgery. It might affect you if you've already had cancer, or if you've had it in the past, or if you've never been diagnosed but something's brewing. that may be dormant and... Maybe you want to keep it that way if that's the case. And I think that's all of us, you know.

Dr. Gordon: 2:26

who are focused on cognitive health, healthy aging. We don't want chronic illness. I hear that surgery can impact long-term brain function, right? Especially in older adults. And not

Dr. Lemanne: 2:41

just older adults. And it can wake up dormant cancer cells that are just quietly lurking. So we're going to pull back the curtain on that today when we talk about surgery. And again, not just cancer surgery. We'll talk about How this works, like inflammation, immune suppression. Do you know that immune suppression lasts for four to eight weeks after surgery? Wow. But there are things we can do. We'll talk about that.

Dr. Gordon: 3:08

Well, that is going to be really helpful. And I know we're going to hear about flu shots. Sometimes they can be given not just for the flu. Beta blockers, perhaps, multi-purposed, not just for blood pressure. And even some more common anti-inflammatory meds during surgery. Is that right? Oh, yeah. We're going to

Dr. Lemanne: 3:28

talk about all of those things. So yeah, I think this is going to be a little bit uncomfortable because surgery is common and sometimes we just have to have surgery. But for people who are thinking about having minor cosmetic surgery, you might want to hear this and weigh the risks and benefits.

Dr. Gordon: 3:53

Okay, well now we've got everybody all warmed up and chomping at the bit. Let's talk about what surgery does to the body and how we can work with it, not just react to it.

Music: 4:04

Music

Dr. Lemanne: 4:07

One of the things that I thought was really fascinating and that I started learning about five or six years ago was that surgery, the trauma of surgery, both the incision and also the things that go along with surgery like hypothermia. You know, the body gets cold just lying in a room temperature room. operating room at 70 degrees or so, sometimes they cool the rooms down a little bit more because the surgeons have to wear a lot of different layers and they get really warm. So sometimes the operating room is rather cold. And if the person under anesthesia isn't kept carefully warmed during the surgery, that is immunosuppressive. So we have the trauma of surgery, meaning the knife cutting into the skin, the underlying layers, the fascia, the muscle, the fat, and then into whatever organ is being operated on. All of those traumatic events lead to a big, big response by the immune system. And you'd think that'd be good, but the immune system isn't necessarily our friend in all ways, especially if it's traumatized. So it can overreact and basically it gives a big grow, grow, grow. We've been wounded. Everybody grow and fill in the wound. And cancer cells, if they're dormant and far away from the surgical site, you know, they get this message. This is a chemical message put out by the immune system that goes through the blood to every part of the body and And so if there's a little nest of micrometastasis, we call it, you can't see it on scans or anything like that, but there's a little tumor, a little micrometastasis. Those cells get that wake up everybody and

Dr. Gordon: 5:49

grow message. Just to get a little technical, but mostly I want to be practical in this discussion. Do we know what those messenger immune markers are like IL-6 or I mean, are there... Are they identified, named?

Dr. Lemanne: 6:07

Yes, IL-6 is definitely one of them. And I'm not an expert on the names of all of the various pro-inflammatory cytokines, but yes, that's exactly right. So the immune system puts out its own cytokines. using cytokines like IL-6. And IL-6 isn't bad. It's got its task. But one of its tasks is to wake up the growth pathways. So if you're a cancer cell or if you have cancer cells, that may not be the path you want to go. really stimulate for very long.

Dr. Gordon: 6:41

And interestingly, I mean, I threw that out because it is one of the, when I'm doing somebody's genetics and looking to see if they're at greater or lesser risk for cognitive impairment, and we could do a whole talk sometime about the genetics of all that, but one of the co-conspirators with the Alzheimer's gene is IL-6. So if you have the Alzheimer's gene and APOE4, and one other gene, and then you have a variant of the IL-6 gene, you're more prone to have a greater rate of inflammation in your brain, which can contribute to cognitive impairment. So IL-6, that's why it came up for me, was not just evidently a cancer risk, but also a Well,

Dr. Lemanne: 7:32

that's really interesting. I was going to ask you about the cognitive sequelae of surgery. And, you know, I hear that even 36% of young people can have long-term cognitive issues after an operation. And I... I think that there's some evidence that you are going to be more conversant on than I am about the number of surgeries over a lifetime increasing the risk of dementia.

Dr. Gordon: 7:58

Well, actually, I'm not particularly familiar with that. So I will look into it and get it for the show notes. But it's so clearly, you know, I see people before they are going to surgery and get ready as much as they can. And I'm always interested to do a cognitive test on people before they head for surgery. You know, just their normal cognitive staging test. And in fact, I saw a mutual patient of ours yesterday who's a year out from his last cognitive test and about eight to nine months out from his multiple cancers. And I said, he said, why do you want me to take this test? And he said, I said, because we actually... Even going up towards surgery, he had a dip because of the problem that needed the surgery. But I want to see that he's better at this point because I know he was not better for at least three months after the surgery. And I will have to get the specifics about cognitive impairment, but it's very well known that general anesthesia, and you know it was a saying in my surgical rotations in training that if you took somebody in, got them all ready for surgery, gave them anesthesia, cut them open, did nothing, and sewed them up again, they'd have almost as much impairment as if you actually do the surgery itself, which speaks to the comments you made about the temperature in the room and the trauma of even just an incision. So I am wary of it. I watch it happen, and I usually see people with good support saying, recover from it. I hope I'm going to learn from you today some better tools to help people recover from it.

Dr. Lemanne: 9:41

Yes, well, I certainly, you know, want to leave people with some tools. I, you know, and it's, you know, we talked about this trauma of surgery, the hypothermia that can occur in terms of immune suppression, and then the type of anesthesia. matters for the amount and strength of the immune suppression that occurs with surgery. So inhaled anesthetics, gas, seems to be much worse than intravenous anesthesia and things like propofol, very minimal immune suppression with that. So fortunately, there are a lot of procedures that can be done with propofol, and in my opinion, should be when that's possible for this reason. And I think you might have something to say about the type of anesthesia and

Dr. Gordon: 10:37

cognitive injury. Absolutely. There's a very common gene variant, so not only the IL-6 gene, but... When somebody says, do my genes contribute, there's about half a dozen genes that we just have to look at. That many? Yes. I would say, really, to be generous, 20. But half a dozen we have to look at. But one of them is the BCHE gene, which has something to do with cholinesterase. But if they have a variant in the BCHE gene, I tell them, and they're going for surgery, I tell them, If your anesthesiologist looks at all disinterested, don't tell them that you have a genetic variant, but tell them that you've had really slow waking up to inhaled anesthesia before, or that your family member has, because that gene does... put them not at common, but at an increased risk. If they have the APOE4 gene and a variant in the BCHE gene, they really would be better off with a spinal anesthesia or intravenous anesthesia. Absolutely. Okay. Okay.

Dr. Lemanne: 11:52

So you So for two reasons then, you want to ask your anesthesiologist, not your surgeon, but the anesthesiologist. You want to do this well before the day of surgery. Don't be on the gurney being wheeled into the operating room and then ask for this because to– be able to care for you. The anesthesiologist and the surgeon, they prepare ahead of time. They order what they need for this operation. They order the correct drugs and things. They can't do that if you're on your way into the operating room. So you must have an appointment beforehand so that they can I really want to stress that. offered with a little box next to it on the list. You have to... Get that in there well before the

Dr. Gordon: 13:06

surgery. Okay. Well, I'm going to suggest that for your brain, whether you know you have the gene or not, your brain would rather you not have the inhaled anesthesia. It's a little bit of a challenge for everyone, but particularly so if you are at added risk for Alzheimer's disease.

Dr. Lemanne: 13:23

So you know something else that there are a couple other things that I think people aren't aware of, and that's that morphine and related drugs can... you know, really Suppress the immune system after surgery. Morphine? Yeah. Wait. Limiting morphine. The doctor's friend. The patient's friend. Sure, sure. So when possible, you want to use some other types of pain, analgesia, like maybe NSAIDs, if you can. Sometimes morphine and opioids can't be avoided, but you certainly want to limit them.

Dr. Gordon: 14:03

So I think of morphine as a special category of opioids. Are you saying that opioids across the board, from codeine to hydrocodone?

Dr. Lemanne: 14:16

Whether they're artificial or natural, morphine is a wonderful natural medication. But just because something's natural doesn't mean that it's great in all circumstances. So certainly you want to just be mindful of

Dr. Gordon: 14:30

And that what the action of an opioid compared to an NSAID. I know there's sort of a big push to try and use more NSAIDs and avoid opioids for everything, which I thought was just sort of a swing in the absolutely opposite direction. We definitely overdid opioids for a while, thanks to the Purdue pharmacy family. Oh,

Dr. Lemanne: 14:52

I remember the days when the... when the OxyContin reps would aggressively come by the office several times a week and try to talk to us. It's

Dr. Gordon: 15:01

not addictive. Don't worry about it.

Dr. Lemanne: 15:01

Suddenly pain was a vital sign, and you had to address it with, you know, not a bad idea, but it was certainly linked to that particular moment in the history of opioid marketing, let's put it that way.

Dr. Gordon: 15:16

It really is. You know, there's a lot of attention these days– for reasons that I'm not going to name him or them. But, you know, how medicine is practiced is under a lot of scrutiny. And one of the biggest stains on our medical history has to be the Purdue family's influence on OxyContin prescriptions. I think so. I

Dr. Lemanne: 15:42

don't want to blame doctors. I mean, you know, a lot of times drug reps for a lot of doctors... That's where they get their continuing medical education. That's it. And they would bring lunch and give lunch to your whole staff and everybody would be happy. It was usually pizza or sandwiches in a little plastic container. Well,

Dr. Gordon: 16:08

I get

Dr. Lemanne: 16:11

lunch from

Dr. Gordon: 16:14

supplement companies. Which, you know, used to be in practically over-the-counter cough syrup to... morphine, which of course requires a doctor's prescription, what do those do to your immune system? So that's

Dr. Lemanne: 16:44

a really good question. What's the mechanism? So morphine suppresses the activity of natural killer cells. Natural killer cells are... They sound problematic, but they're not, are they? No, they're your friend, and that really is the true medicalese term. I'm not, you know... I'm making a metaphor here. The natural killer cells mediate anti-tumor activity of the immune system. They kind of lead the way, the generals. And also infection, anti-infection, kind of part of what we call the cellular immunity system. And so that suppresses the activity of these natural killer cells, morphine, by 40 to 60 percent. Neutrophil and monocyte. White blood cells. Cancer cells, if they're there sometimes under the direction of the natural killer cells, but they impair their ability to eat their prey, these neutrophils and monocytes. So opioids are bad news in that sense. And morphine is included in this. So that's the innate immunity part of things. And then the adaptive immunity, T cells and B cells, both suppressed by opioids. And this can... It lasts for weeks. It's not a, you know, one and done thing for a couple of days. But morphine and fentanyl are the strongest ones. And oxycodone is a little milder. And tramadol is even less. So there are some options there, you know, if you have to choose. And

Dr. Gordon: 18:40

marching down from oxycodone to hydrocodone to codeine, they're probably all closer together. tramadol seems to be, you know, I think it's divided whether people consider it an opiate. It's a non-opioid pain medicine, but it really deserves the same respect as an opioid, both in its strength and its potential and evidently less so, but can suppress your immune system in that same way. So, you know, what are the kind of things people that, you know, there are doctors telling them, you know, no way you're getting out of this recovery without some opioids. What are the kind of things they can do to, you know, keep their natural killer cells awake and functioning?

Dr. Lemanne: 19:24

Yeah. So some of the things that increase natural killer cell activity are really interesting. So So mushrooms are a good one. Really? Yes, yes. In fact, we talked about this at one point, ergothionine. I'm going off on a tangent, but ergothionine turns out to be a great mitochondrial tonic. So we can talk about that a little bit more in another podcast. But mushrooms, medicinal mushrooms, are particularly helpful in this regard. Okay. Sleep optimization is probably one of the most important things. And the reason is that sleep normalizes metabolism. You cannot have a normal insulin-glucose axis if you don't have deep, good sleep the night before. And so that's another thing that can be done. I

Dr. Gordon: 20:16

mean, while you're anxious and you're thinking about getting to the surgery center early the next morning, you also have to have a good night's sleep. Well, no,

Dr. Lemanne: 20:24

I meant afterwards to recover. Oh, okay. how to recover natural killer cell function. We were talking about how natural killer cell activity can be boosted. I actually test natural killer cell activity. I don't just test the quantification. Most of the tests, when you order natural killer cell and you check it off on the lab test sheet, what they'll give you is how many natural killer cells you have per little tiny unit of blood. I don't really care. I want to know how well... Hang on, Tom, I'm going to get this. I don't know why she's calling. Sorry. Yeah. Hi, Nancy. Hello. Hello, Nancy. Oh, must have been a pocket dial. I'm so sorry, guys. I'm going to turn off my phone. Our cat's sick, so I thought she was going to tell me something about the sick cat. Oh, I love your cat. Yeah, yeah. So, sorry, I turned off my phone ringer anyway.

Dr. Gordon: 21:21

Right, so you were saying

Dr. Lemanne: 21:22

you don't care about how many natural killer cells there are. I don't care about how many natural killer cells you have. I care about how well the ones you have work. So there's only one lab that I know of in the country. There may be others, but this is the only one that I can find right now. It's called Cincinnati Children's Hospital, and they will do a natural killer cell. for me. And it's a fussy test. The patient needs to have the blood drawn and the blood has to be taken to the airport and sent to Cincinnati. The whole process has to take less than 28 hours from when the blood is drawn until they finish their test. And it costs, I think it's $500 and something plus whatever the overnight FedEx shipping is, which is over $100, something like that. So I think it's about $750 to $790 Don't quote me on those prices, but to get the whole thing done, I think that's how much it is. Maybe insurance will pay for it sometimes. I have cancer patients, so they all mostly have cancer-related immunosuppression, which is codable with the ICD-10. But insurance may not pay for it. But that is what I look at to see how well my patient's natural killer cell activity is. And I check it periodically if it's low, and we try to boost it. We don't just say, oh, I heard that mushrooms increase this, so let's just take some mushrooms. We never check. I check and I recheck and we make sure that we're going in the right direction and getting that up to optimal. And that's really gratifying when you see that activity level go from suboptimal and below normal up to high normal, which is where we aim in cancer.

Music: 23:07

Right.

Dr. Lemanne: 23:07

So yeah, so that's, I hope that answers your question about one of

Dr. Gordon: 23:12

the things. It does. I mean, but I think, you know, for most of us who are not going to probably post-operatively arrange for that tests to be done on our patient's blood when they just had their knee replaced, they can still take into account what you know and what you've learned about increasing the activity of natural killer cells. Absolutely. And

Dr. Lemanne: 23:39

I'll push back a little bit. You know, I I am moving away from just assuming that what works for one person works for another. I'm moving toward actually checking more. It is expensive, though.

Dr. Gordon: 23:54

Right, right. I'm not going to do it on every patient. I mean, I can imagine that someday I'm going to call you and say, okay, now I have a patient where I really want to check. But in general... There's a lot of people who are going to go in for surgery who might want to know, gee, what are the things I could do that are good for me anyway? And we've actually talked about this before because I made a note to myself in my general medical virtual training. Cheat sheet. You know those books we used to carry around when we were in medical school? Yes, the pocket guide to blah, blah. I could find that would boost natural killer cell activity. And I see that mushroom extracts, especially reishi mushrooms. Is that how you pronounce it? That's how I pronounce it. Okay. The other things I have on the list that I'm going to have to add, sleep optimization, because I don't have that on my list, but exercise. That's a good one. Absolutely.

Dr. Lemanne: 25:03

You know, and the things that don't hurt you are, you know, the first stop. And they're not very sexy. Sleep, exercise. But they're our good friends. They are. And that's where, you know, you want to start. Sleep is so important for immune function. I tell patients that, you know, if you're not sleeping and you have cancer, it's kind of, you know, and you do all these other things, you You exercise, you eat the right diet for your cancer and metabolism, and you take all these supplements. It's kind of like you're trying to paint the walls while the… house is burning down. It's just not the right action to take first. Yeah, sleep is important.

Dr. Gordon: 25:47

Sleep is really important. I also have on here, so I just want to, some of the low-hanging fruit that people might be able to do and ask you about, high-dose B12 probiotics.

Dr. Lemanne: 25:58

I think those are good. B12 has a caveat, though, in cancer. So high B12 levels are associated with, in a Danish observational study, are associated with, in patients in people who don't have cancer, they're associated with higher risk rate of cancer diagnosis over the next, I believe the study was over two to five years, something like that. And if you already have a cancer diagnosis, a high B12 level, I mean higher than average or normal, is associated with a greater risk of cancer death. And I'm not sure if that's causal related to the taking of excess B12 or if it has something to do with liver dysfunction because a stressed liver will release B12 in the bloodstream. So it could be something like that. Did not know that. But it's something to just be aware of and that's That's why I really am getting to the point where I'm like, you know, that's great. You heard B12, you know, to my patients, you know, B12 is good. Let's measure yours and see where you're at and kind of go from there.

Dr. Gordon: 27:05

I think I want to put an embroidered, embossed, gold flashing light sign in my office saying, let's measure that. You know, there's so much we do in... medicine that can be measured. And the topic that came up for me with a patient yesterday was Oh, you're going to measure my estrogen level? My gynecologist just gave me a patch to use. Can you measure that? And it's incredible to me all the things we can measure that can help a patient or hurt them if they're not in the area we want them to be. And yes, high dose, I've learned this from you that high dose, high levels of B12 can pose a potential hazard. And I didn't know that liver for a long time. mechanism of doing that. But yeah, we should measure what we can. And I hope insurance companies, Medicare particularly, continue to cover those tests. A

Dr. Lemanne: 28:12

lot of these things have to be done preoperatively. So we talked a little bit about how to increase natural killer cell activity after the activity has been damaged by surgery. And that takes several weeks, four weeks or longer to recover from. But beta blockers, giving that right before surgery and also giving an NSAID, a non-steroidal anti-inflammatory drug, before surgery. This has to be done before surgery. It doesn't work if you give it after surgery. The damage is done. It's like, you know, having the airbag go off five minutes after the accident. Well, it's not going to help. So it has to be given. There was one study, I think, in France by Patrice Forget found that giving an injection of ketorolac 40 minutes Exactly 40 minutes before incision prevented this particular immunosuppression. And these were controlled trials. And compared to not giving it, the risk of metastatic disease blooming and being found about, I think it was 18 months later, was much lower. These were patients with breast cancer. I think the operation was breast reconstruction. And again, it's not the type of operation. It's not because it was breast reconstruction that the operation was carcinogenic. It's because any surgery causes this particular inflammatory response and reduction of immune activity after surgery. So I think it was 18 months later, the group that did have the injection given exactly 40 minutes before incision had much less risk of infection. So this is,

Dr. Gordon: 30:04

is this an over-the-counter anti-inflammatory? pain-relieving injection that is rivaled... It's very effective, right? I mean, it rivals... opioid analgesics. And that's something that, yes, you, okay, now you're going to ask your anesthesiologist to give it to you before surgery. And it's not going to do the same benefit after surgery. But if you're trying to avoid opioids, they might want to keep that vial handy for a... Sure. So it can be

Dr. Lemanne: 30:59

used after surgery for pain suppression. It decreases inflammation caused by the coccyx pathway. And that particular pathway, prostaglandins, which is what's made by that pathway, is pro-carcinogenic. I mean, it drives the growth of cancer. So you definitely want to... Oh,

Dr. Gordon: 31:20

you want your immune system to work on the left foot, but not the right foot, or you know, you've got to

Dr. Lemanne: 31:25

tailor its response. There's some caveats there. So Toradol and other NSAIDs, they can increase the risk of bleeding. So if you're having open heart surgery or a big colon resection or something like that, maybe you don't want to use that because of that risk of bleeding. And then if you have bleeding, blood transfusions given after surgery also increase the risk of metastasis. What? Yeah, you don't want to have a blood transfusion. So you've got to weigh these things. So

Dr. Gordon: 31:55

I have– I know that– Because it's a blood product, there can be side effects from it. But does anybody getting a blood transfusion at any point have an increased risk of cancer?

Dr. Lemanne: 32:06

You know, that's a really good question. And the answer is probably yes. So here's what we know. Cancer patients who get blood transfusions during their surgery actually tend to do worse afterward. Now, you might think, well... Maybe that's just because patients with worse tumors need transfusions in the first place. But that's not it. The stats, the statistics, especially for colorectal and lung cancer, clearly show that getting a transfusion during that surgical period really does link to higher chances of the cancer spreading and, unfortunately, death from cancer. I'm not saying everyone who gets a transfusion during cancer treatment will die from cancer. Not at all. but your risk definitely goes up. And there's even a study showing slightly higher risks of liver cancer and non-Hodgkin's lymphoma in people without cancer who got blood transfusions for completely different reasons. The risk isn't huge, but it's there. So bottom line, you really, really don't want to get a blood transfusion unless you absolutely need one to save your life. I

Dr. Gordon: 33:21

have a friend who she bled for some reason that then was eventually controlled, but her blood count was very, very low. And they stopped transfusing her at a level that still left her incredibly fatigued, having difficulty carrying out your thou shalt exercise well part of her protocol protocol. But they were probably– they were stopping it, not just because the blood bank was running out of blood, but because there's some risks besides blood quality and getting a blood transfusion. Yeah,

Dr. Lemanne: 33:59

yeah. You know, it's considered a modifiable risk in cancer care, meaning we can– We don't want to increase it. There are drugs like erythropoietin, which seem to increase cancer growth rate, even though they also increase the hemoglobin level and can help treat anemia. That's another consideration. So, yeah, these are not simple questions, and these treatments are not completely benign.

Music: 34:34

Right.

Dr. Lemanne: 34:34

There's a lot of heavy, heavy trade-offs.

Dr. Gordon: 34:37

Right. So one of the ones that we glossed right over then was the use of beta blockers. Because I think of beta blockers, even though they're highly used drugs for treating hypertension. they can have some terrible side effects for people in diminishing their exercise tolerance and their exercise ability.

Dr. Lemanne: 35:03

Well, this is just a one-time dose before surgery, so we're not talking about continuing it. Uh-huh. Yeah, yeah.

Dr. Gordon: 35:10

But also, to be clear, it's not an over-the-counter drug. So again, this is something people would have to have the cooperation of their surgeon, physician to have the... ketorolac, retoradol, and the propranolol before surgery.

Dr. Lemanne: 35:27

Yes, exactly. It's given just before surgery. You know, tumors really love epinephrine. It's actually one of the main reasons exercise is so important and helps reduce the risk of cancer coming back. When you don't exercise and your body produces epinephrine, also known as adrenaline, any cancer cells hanging around will grab that epinephrine and use it to grow. They use it to develop blood vessels that bring them oxygen and nutrients and carry away waste. And that's definitely not what we want for our cancer cells. That is why people under a lot of stress and who are producing a lot of epinephrine or adrenaline might face higher cancer risks, especially if they're not offsetting that stress with exercise. We all have stress, but we need to deal with it. in a constructive way. And think about it this way. Your body produces all of this adrenaline so you can run away from the proverbial tiger, right? That's what the whole epinephrine or adrenaline response is for. But if you don't actually run, cancer cells basically say, oh, great. They're not using all this wonderful growth-promoting stuff, the muscles, the heart. We'll take it. And cancerous tumors actually hoard epinephrine or adrenaline, they sequester it. They keep it for themselves. They take it out of the bloodstream and hold on to it. And you can find 70 times more epinephrine or adrenaline around cancer tumors in the peritumoral matrix, we call it, more than you find in the blood. So 70 times more adrenaline around cancer cells than in and about normal cells and in the blood.

Dr. Gordon: 37:19

And what action does adrenaline play in a cancer cell? It

Dr. Lemanne: 37:23

promotes growth. It

Dr. Gordon: 37:24

promotes growth,

Dr. Lemanne: 37:26

especially through angiogenesis, the formation of new blood vessels. And here's how it works. When you go for a jog or a fast run, your heart and muscles work harder and essentially signal, we need more blood and oxygen. And the epinephrine then creates the conditions for your body to grow. More blood vessels grow. into your heart and skeletal muscles so they can handle more work next time. And that's the mechanism at play. If you go for a run and you have some excess epinephrine circulating because of that run, it gets used for this healthy purpose. But if you have excess epinephrine around because you're chronically stressed, you're not sleeping well, you're constantly angry about something, and you're generally not taking care of yourself, and on top of that, you never exercise, any cancer cells in your body will basically say, perfect, we can use all this epinephrine. And they'll hijack that epinephrine to create their own blood vessels and help their tumors grow very efficiently. So

Dr. Gordon: 38:32

we could probably talk about angiogenesis till the cows come home, but it's a very mixed bag, which I learned from you. Like if I were in, I'm looking at my patient's cardiology, and I say, oh, yes, you're... Thank you so much. a different kind of breast imaging technique than a mammogram. It detects warmth or increased blood flow in an area that if it wasn't there before, you know, what does something in your breast need extra blood flow for? It's not because it's an exercising muscle. The worry is that it might be a cancer growing. So it's a good thing in your... Where your heart or a muscle needs it and it's a bad thing if it's feeding something else. Exactly. And the way to

Dr. Lemanne: 39:51

get it to not feed the cancer is to have your muscles ask for all that epinephrine.

Dr. Gordon: 39:55

So thinking about exercise, those people who say, oh, I take, you know, I walk for a couple miles every day, that's probably not doing it unless they are, you know, walking on a really busy street with a lot of traffic or something. I don't know.

Dr. Lemanne: 40:10

So yeah, that's a really good point. The type of exercise matters. So walking two miles a day, that's not nothing. And I'm glad. And I tell patients who are doing that, Once a week, they bump it up, and they do a high-intensity workout once a week for older people. If they're young, if they're under 40, they can do it twice a week. But after that, between 40 and 60, maybe one and a half times a week, and after 60, once a week is

Dr. Gordon: 40:37

plenty. You're too soft on people. Well, you need that time to recover. You do need time to recover. But so what I get very specific about high intensity intervals. Well, let's hear what you tell your patients. And I have so many things to think about this. So if somebody is out of shape, I'll say, you know, while you're walking, I want you to get nice and warmed up. And then I want you to exert yourself as hard and fast as you can. And I'd rather it be five seconds as hard and fast as you can. over 30 seconds because somebody told you to do it for 30 seconds. If you really are exhausted after five seconds, so be it, you stop. You recover completely before you do your next interval that day. And my daughter taught me when she was a personal trainer for a while, some of these routines where you're on for 20, off for 20 seconds, back and forth, they don't work And that's where I would say that people over 50 or 60, you need to give yourself the time to recover so your next five seconds all out is as good as the first one. And that's why I like machines like the rowing machine and probably treadmills or bicycles do that too. I know I was pulling on that erg and I got it to a 157 for 10 seconds. I want to get it to 157 for each of my intervals today, even if they only last 10 seconds and even if there's a two-minute recovery period between each one. And then I tell people that they shouldn't do more than they are comfortable with in that day. They can work their way up to more. And I tell them I really do expect them to do it twice a week and no more than that because of recovery and They can't be two adjacent days. They have to be several days in between. And I think of this, and now I'm going to have to think about the cancer prevention part of it, but I think of high-intensity intervals as the most effective part of your exercise regimen for reversing insulin resistance, developing metabolic flexibility, and weight loss. I think you're absolutely

Dr. Lemanne: 42:51

right. And I really like your, I think it's called sprint interval training when you're doing 10 seconds or less rather than high intensity intervals, which tend to be 30 to 60 seconds at a time.

Dr. Gordon: 43:03

Well, I want to make it clear to them that they are doing it as hard as they can, that it is for them a high intensity and not just because they're kind of going a little bit faster, but some benefit in going all out. And you're absolutely right. If I tell some 65-year-old person or, God forbid, even somebody in their 70s to do it. And they said I felt terrible doing it. I didn't recover for four days. I'll say, okay, well, let's back it off a little bit. You know, it can be flexible, but I like to think that, you know, when people get past a certain age, people, you're coming to the Y, are you here for water aerobics? Water aerobics are great. And they're particularly great for people recovering from joint injury. But in general, that's a pretty low exertion form of exercise.

Dr. Lemanne: 43:59

You know, I'll tell you a secret. I went to water aerobics at the Y and fantastic coaches. And I got nothing out of it. I left halfway through because it was so, you know, was not good. And I think that, you know, for people who need to be there, that's where they should be. But it's kind of a form of physical therapy. It's not really for... For people who have most of their faculties and physical faculties at the moment, it should be thought of as a kind of rehab.

Dr. Gordon: 44:56

And you start where you are. And the trick about exercise, whether it's exertional like intervals or weightlifting like bicep curls, you start where you're comfortable. And one way or another, you figure out a way to continually make it a little harder steadily as you're going along. That's where the real benefit from exercise is, is working a little harder this week than you did last week. Absolutely. I completely agree.

Dr. Lemanne: 45:27

You certainly don't want to discourage someone who's starting with three pound weights, but they should be under no illusion that that is the kind of training we're talking about here. Using lightweight, three pounds, is not resistance training. It's physical therapy, rehabilitation. It's for people who have real issues and problems, abnormal movement abilities, and who need that kind of physical therapy and rehabilitation. It's just not intense enough. I mean, it's not going to produce the physiologic results we're going for here, which is to make it hard for cancer cells to thrive. So yes, But I do want to discourage people who start with three-pound weights who should be starting with 25-pound weights. Yeah, exactly. Who think that they're getting somewhere.

Dr. Gordon: 46:19

Yeah, or they get to five pounds and they stop there, you know. And that's one of the good things about programs like the exercise adaptions like the TRX, which I like because it's all body weight and you can position your body weight to do your pull-ups either crosswise moving a lot of your body weight or having you stand practically vertical and have not much body weight that you're moving. Because obviously, if you're going to buy your own weights, it's expensive to go from 3 to 5 to 8 to 10 to 12 to 15 to 20. That's a lot of weights that you're going to keep moving through.

Dr. Lemanne: 46:56

Well, you've seen my house. I have these weights all over the living room. My spouse complains sometimes, and rightly so, I think. Right

Dr. Gordon: 47:03

next to the piano and the violin stand, yes.

Dr. Lemanne: 47:06

And yeah, that can be problematic. I just say, well, it's cheaper than a nursing home, but that's a little snarky and I usually have to apologize

Dr. Gordon: 47:19

afterwards. And that's what's great. So many of the Medicare plans now include a gym membership. And the great thing about the gym is they buy all the weights for you. There's hopefully some people you'll enjoy hanging out with there. And if the trainers are synced to be a little more pushy with older people than they might have once originally thought to be, you should be able to get some good encouragement and tips, too. So a gym's great. And stay safe. And stay safe, yeah.

Dr. Lemanne: 47:51

I think those are great. I like the TRX system because you can get into a lot of different positions than you can with just free weights or barbells and things like that or machines. So the TRX allows a lot of unusual movements movements that are really important, like rotations and things like that.

Dr. Gordon: 48:09

And you can pack it in a corner of your suitcase if you're going away for a week. Yeah. And throw it over a door jam. There you go. Yeah. Love that. Love that. Well, what else do we want to say about surgery? Well, let's see here. Like, we clearly can't, I, you know, when you first raised this talk when we were talking about healthspan and lifespan, I thought, oh good, I touched a bullet, I didn't have that surgery when they wanted to replace my knee. And but some, you know, there's going to come a time, there's a time in everybody's life where some surgery is I needed that cesarean section I had when I was in labor. There's surgeries you absolutely need.

Dr. Lemanne: 48:55

So I have a handout that I give to patients that they can give to their surgeon and anesthesiologist and To my surprise, most surgeons and anesthesiologists consider this and do it. I have the references and everything. And it has the studies about giving the Ketorolac 40 minutes before incision. It talks about– giving a flu shot. We promised to talk about that. So a flu shot given within 24 hours of surgery helps prevent the natural killer cell impairment that we see otherwise after surgery.

Dr. Gordon: 49:34

That is so interesting because, of course, you know, I'm going to divert to my... Let's talk about me for a second. But getting the flu shot correlates very well with the reduced risk of getting Alzheimer's.

Dr. Lemanne: 49:47

That's really interesting.

Dr. Gordon: 49:48

Okay. It is, but not in the 40 minutes before you're going to get Alzheimer's. So this is 24 hours before.

Dr. Lemanne: 49:55

24 hours before surgery. If it's given before or after surgery, before 24 hours or after surgery, either way, it doesn't really have the maximal

Dr. Gordon: 50:05

effect. But it wakes up a specific part of your immune system that is going to be diminished permanently. By the process of surgery. Yes.

Dr. Lemanne: 50:16

And also erectile dysfunction drugs, Cialis. Oh. Given preoperatively can improve... decrease the risk of metastasis. These are some interesting things. Of course, we talked about beta blockers. I think that things people can do would be certain types of self-hypnosis and heart rate variability modulation. I think that's really important, but that has to be I mean, if you tell somebody just go meditate before surgery, I don't think that does anything for most people. I don't think their meditations are necessarily affecting the part of the autonomic nervous system that we want to interact with for this particular situation. So I, again, am asking people to actually measure their heart rate variability with little finger tip heart rate measurements. monitors and apps and things like that that you can get on your iPhone and other smartphones.

Dr. Gordon: 51:21

Do you have a practice that you particularly are fond of recommending to people to increase their heart rate variability? So I like the Whoop Band, which

Dr. Lemanne: 51:32

gives a summary of your overnight heart rate variability each morning. It also tells me whether a patient's truly getting into their high-intensity interval training max heart rate zone and or whether they just think they are. And it gives steps, daily steps. But yes, the heart rate variability measurement from WhoopBand is very, very helpful. And also there's a real-time one called HeartMath.

Dr. Gordon: 51:59

Yes, I like

Dr. Lemanne: 52:00

that.

Dr. Gordon: 52:00

And HeartMath has a, it includes a practice that you do. Yeah, so if somebody doesn't do, is there anything you in general tell people, like we both just gave little high intensity interval or sprint training protocols that we use. Do you have a heart rate variability? Those are the two I like to use, WHOOP and HeartMath. But WHOOP doesn't give you tips about increasing your heart rate variability. It just measures it. It

Dr. Lemanne: 52:29

just measures it and you can see how you're doing. So heart rate variability is an instantaneous measurement of your insulin resistance. What? Yep. So inflammation... Vagal tone and heart rate variability are the same thing looked at from different directions. And they move in sync.

Dr. Gordon: 52:52

Just in case people don't know, heart rate variability is the completely, infinitely variable space between the beats of your heart. Not if your pulse is beating at 60 or 90 or 120, but what's the space between those beats. And it should be varying constantly because you have a speed them up and a slow them down part of your nervous system, and they should both be fully functioning, not just the slow it down part. It's how we measure fetal viability during labor, and now we've expanded it so that you and I and anybody with a good wearable can measure their heart rate variability. But I think it's a... And it's a little bit of a wolf chasing a rabbit kind of pursuit, and it's not always clear what to do about it. You wake up in the morning and all this week your heart rate variability has either been through the roof, that's one kind of worry, or not so good for this week. What does somebody do... who doesn't have heart math for their heart rate variability?

Dr. Lemanne: 54:06

Well, the first thing you do is make sure your sleep is ideal. Number one, without a good night's sleep. you will not have a good heart rate variability that next morning. And we could talk for another six hours about how to have a good night's sleep. And the second thing I change with my patients is the time that they eat. We usually move supper early, and that will usually improve the heart rate variability the next morning.

Dr. Gordon: 54:29

And how much before bed do you like to PCP? Everybody's

Dr. Lemanne: 54:33

different, but it's, you know, the scripture says, I'm being facetious, but the scripture says at least three hours. I like five or six hours. Oh. And I will often see a big improvement in heart rate variability. I certainly see it in myself. If I finish supper by 3 p.m., my heart rate variability is at its maximum the next day.

Dr. Gordon: 54:52

I think I just heard a lot of jaws drop when they heard that you finished dinner by 3 p.m. That's

Dr. Lemanne: 54:58

me. So it may not be the case for someone else, but they have to measure. So that's why I don't– I'm moving away from these prescriptions of it has to be three hours before– it's like some people do well with three hours. Some of us need a lot more. Brian Johnson who's this anti-aging health bro who I think has some interesting ideas, I think he finishes his days eating at 11.30 AM. Wow. Wow. He says it because that maximizes his heart rate variability and his– You know, lowers his heart rate by the time he goes to bed at night. So I don't think everybody needs to be that extreme, but maybe he does. And so there he knows what he needs to do. So, yeah, it's a measurement thing. I don't think it's just a hear about it and, you know, give it a go. I probably sound a little annoying, don't I, about this measurement

Dr. Gordon: 55:56

stuff. No, because you're speaking to the choir because I am just flummoxed by– people getting a prescription for hormones and never being tested for what their levels are. Tell me about that. You mean nobody's tested anything? No, they say there's a good study that they used this kind of patch. They used an estradiol 0.1 milligram patch. And don't get me started that those generic patches three years ago worked great. They don't work this year anymore, the generic ones. They give the dose that was used in the research trial, and they don't measure a woman's estradiol level after putting them on the patch. Oh, my goodness. Okay. Which seems kind of crazy. Because we've learned this year that the generics, I think it's a burgeoning market that women have awakened to the reality that hormones are generally good for aging women, estradiol. And so a lot more people are... I guess, contributing to the flood of generics. And you have to be careful what kind of brand you order and where you can even get it from anymore. And you have to check because some people do fine with generics, but you don't know unless you measure it. You don't know when you have to stop eating dinner three o'clock. Oh my goodness. What do you do on work days?

Dr. Lemanne: 57:20

I'm fine. I take a big lunch. I eat it. You'll see me now that I'm in the same office as you. Just leave me with my desk full of food instead of papers.

Dr. Gordon: 57:29

A big lunch. And then you're done. I'm done. Yeah. Yeah, we have a little, you know, tiff back and forth in the house because so my... parameters around finishing eating before bedtime have to do with a particular cognitive benefit, which is your brain housecleaning. The glymphatic system doesn't work well to clean out the debris from the day, and we all have debris from the day in our brains, it doesn't work if it's still taking incoming information in the form of the food that you most recently ate. And that is a fairly standard recommendation that has to be at least three hours. But from what you're saying, I'm going to experiment with people who have... And we use the Oura Ring more because people tend to have that more. Oh, that's a wonderful device. Yes, for that. And we have some at the office that we loan out so we can see it. Oh, that's a good idea. And tell them they have to stop. So in my household... Right. told me to eat a half a cheese sandwich before I go to bed. And, you know, that has been like Dr. Mercola, that was one of the things that he recommended a long time ago. And I still see doctors recommend, oh, you wake up in the middle of the night, just eat a little cheese sandwich or something before you go to bed and you probably won't wake up in the middle of the night.

Dr. Lemanne: 59:27

Oh, nighttime eating. Yeah, that's pretty carcinogenic,

Dr. Gordon: 59:31

actually. Is it? Yes, it is. Okay, you know what? This is one of those times where somebody has to do it. Somebody has to take the initiative and I'll say, this has been incredible. I've learned so much about how we can prepare ourselves in ourselves and with our doctors ahead of time around surgery and recover more wisely. Is there anything else you want to add to help wrap up today? I think

Dr. Lemanne: 1:00:01

just treat surgery as a major neuroimmune event, okay? It's not a... something that happens to some one particular body part. It happens to your whole body. Your body has a huge response to it. Your immune system is temporarily dinged, damaged by this and has to recover. And the recovery takes weeks.

Dr. Gordon: 1:00:27

Because it's highly distracted. I mean, there's no way around it. Your immune system has to help out, diverts everything and looks at the surgery.

Dr. Lemanne: 1:00:37

Yes, but we can mitigate it. Yes. So there are drugs that can be given before surgery. And again, they have to be given before surgery. Flu vaccine, 24 hours before. NSAID injection, 40 minutes before. Beta blockers in the preoperative situation. And yeah, so those are some things that can be.

Dr. Gordon: 1:00:58

What a brilliant intervention to take care of something our body's doing with all good intentions, but we can reduce the implications of it, the negative implications. Well, it's wonderful to talk to you. Until next time. Until next time. Thanks for all this insight today. I've got a lot of things to look up now when I go home. Bye. Bye.

Music: 1:01:22

Bye.

Dr. Gordon: 1:01:24

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Dr. Lemanne: 1:01:30

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Dr. Gordon: 1:02:58

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