The Science of Exercise for Cancer | Kerry Courneya, PhD

low muscle mass is really the critical thing driving risk of recurrence and death from cancer and there's some really interesting research suggesting that if you exercise while the tumors are shedding these um circulating tumor cells those uh circulating tumor cells are less likely to survive because of the increased sheer stress so when blood's flowing through uh uh the vascul it's under a certain amount of pressure but of course that's dramatically increased when you exercise and these circulating tumor cells are far more likely to die and not survive that Journey if you're exercising so I think

of it kind of as stirring the biological soup and the more intense the exercise more more these biological changes get stirred up and what we found is the patients who exercise well getting this chemor radiation therapy were more likely to have a complete response meaning the tumors were completely gone prior to having the surgery exercise is no longer at The Fringe of oncology emerging evidence has revealed that exercise really has become one of the pillars of Cancer Care whether we're talking about prevention or treatment and at the Forefront of This research is Dr Carrie Kier

who has done a remarkable remarkable amount of research looking at how exercise affects cancer outcomes and much much more he's a professor and a chair at the University University of Alberta in Canada I'm very very excited to have this conversation with you Carrie um I've been a big fan of your research read many of your studies over the years and um have been looking forward to this conversation with you today thank you for having me Ronda it's a pleasure to be here well I was thinking maybe we could kind of start at the top and

just talk a little bit about why effortful exercise is not only beneficial for cancer but also for health in general yeah as as you know from previous podcast exercise has a lot of benefits for the cardiovascular system the muscular system the immune system uh and many other organs benefit from exercise so it's really one of those behaviors that has positive health benefits throughout the body and the improvements um in those uh Health parameters throughout the body really reduce the risk of various chronic diseases and help you manage those chronic diseases if you are diagnosed with

them so um maybe we can talk a little bit about cancer prevention you often hear about how cancer prevention occurs you know decades before you get a diagnosis from your research what is the single best lifestyle shift that someone can do right now to positively you know affect their lifetime cancer risk so every year in the us about 2 million Americans are diagnosed with cancer and the American Cancer Society estimates that about 40% of those cancers could be prevented if everybody followed sort of the optimal lifestyle uh um uh suggestions that they make so we

could reduce those 2 million diagnoses every year to about 1.2 million so they're not all preventable but we could certainly prevent a bunch of them so number one on the list I'm sure everyone will know is smoking that's the big risk factor for cancer and it's the one that many of the public health people have focused on for many years reducing cancer rates making great gains in cancer uh reductions in cancer rates because of reductions in smoking uh assuming you're not smoking which is 80 to 85% of the American population obesity is actually the second

on the list of risk factors for developing cancer unfortunately obesity is going in the other direction as smoking rates go down obesity rates are going up so we're starting to see more obesity related cancers assuming you're not smoking and you're not obese next on the list is actually alcohol consumption you might have heard of the surgeon general's warning recently about the link between alcohol and cancer that many people are not aware of so there's a lot of alcohol rated cancers as well after those sort of big three lifestyle changes yes exercise and diet are important

and exercise has has been shown to reduce the risk of you know maybe 8 to 10 of those cancers there's over a 100 different types of cancer so it's a it's a very complicated disease all different cancer types but we now have evidence suggesting that exercise will lower the risk of getting some of those cancers particularly colon cancer breast cancer endometrial cancer and several other cancers as well such as stomach cancer esophageal cancer and a few others so yes some evidence that these lifestyle chances really can reduce your risk of getting cancer if if someone

had limited time and resources in the sort of 802 cents so if you were going to put in 20% of your effort to kind of get 80% of the reward do you think that you know what are some of the prevention strategies that would give you the biggest bank for your bug like cancer screenings exercise things like that so for sure if you're a smoker that's absolutely the best thing you can do is quit smoking and you can really substantially reduce your risk by quitting smoking and and it has um fairly quick benefits in terms

of lowering uh cancer rates if you're obese then yes going on a weight loss program and reducing obesity would be the biggest thing if you're a heavy drinker then that's going to be a key thing assuming you're none of the above you're not particularly overweight or smoking or uh drinking heavily then I think exercise really is next on the list um and you know the general recommendation is the public health guidelines of about 150 minutes per week of moderate to vigorous intensity aerobic exercise some evidences suggested muscular strength training can lower the risk of some

of these cancers as well but most of the recommendations are really around sort of um moderate to vigorous intensity physical activity do you find that these um these recommendations are so like if you're going going to do aerobic exercise versus like the resistance training or high-intensity interval training do you do you think there's any differences between them or is it really just kind of do something I don't think there's large differences in terms of the length so you know ultimately exercise is energy expenditure so you're causing the system to engage in energy expenditure and that

has a whole sort of cascade of biological effects that occur they're a little bit different if it's strength training we know there's going to be particular adaptations or if it's aerobic exercise there's going to be other adaptations but in terms of some of these biological changes like the anti-inflammatory effects the stimulation of the immune system and stuff doesn't seem to matter which type of exercise certainly some support from more the moderate intensity exercise is having more of a stimulation effect on on the biological system so you want little a little bit of a stronger stress

to cause that immune immune adaptation for example or the metabolic adaptations yeah exactly so all these recommend recommendations will generally be at the level of at least moderate intensity there's definitely been some research on the light intensity physical activity just getting up and moving around and what are some of the benefits and and uh uh outcomes related to that type of exercise but more compelling evidence once you get into the moderate intensity exercise uh Zone and certainly even more benefits with the the vigorous intensity or the higher intensity exercise I know I know um the

major area of focus of your research is looking at how exercise affects cancer treatment but I I there are some interesting questions I have with prevention as well you're mentioning obesity being a big risk factor for for a variety of different obesity related cancers and perhaps there's people that have genetic predispositions um maybe they have you know some of these bricka one bricka 2 um single nucleotide polymorphisms that may increase the risk of breast cancer for example um is there any evidence or do you have any opinions on whether someone that may have those risk

factors if they're if they incorporate you know exercise into their their personal hygiene is that um something that can help negate some of that cancer risk even if they still have the genetic predisposition or even are obese for example yeah there is good evidence on that so one of the mechanisms how how exercise might lower the risk is through managing obesity but what we also see is exercise lowers the risk of cancer regardless of your obesity status so we can do the subgroup analysis of those who are BMI above 30 overweight caly healthy weight all

of them show a reduction so obesity is not the only mechanism by which exercise um is lowering the risk so even if you're obese and you don't lose weight exercise can help you lower the risk of developing cancer we even see this with smokers so we can break them into sort of the smokers and the non-smokers with lung C cancer risk and even those who are smoking exercise will help them lower the risk of course that's small compared to the impact of not smoking but it shows that Exercise Works Within These groups to lower the

risk whatever is kind of driving your risk whether it's obesity whether it's smoking you can benefit from it the the genetic um stuff we haven't seen quite as much evidence yet um you know the the bracka jees you talked about there is like an 80% chance of getting breast cancer and very high with ovarian and some of these other ones so you're almost on a kind of genetic trajectory that would be very hard to stop you know with a lifestyle change so I haven't seen as much evidence there suggesting that it can be beneficial for

those patients there's other options for those patients and trying to reduce their risk yeah that was probably the most extreme genetic uh predisposition case I mean there's other other um genetic predispositions as well or maybe a family history if someone's like a family history and we've seen some of the studies look at that trying to look at kind of and just do it as you say by family history a very simple way of looking at it and we do find that exercise lowers the risk of developing some of these cancers even in those who have

a family history there's um it seems like it's really just a Panacea I mean in some regards obviously you know if you're a smoker you don't want the take-home message to be I'm going to exercise but still smoke right like know like you should you should quit smoking right that's like the number one thing but but the fact of the matter is and we I'd love to get into to some of these mechanisms in a minute about how exercise is you know how it's playing a role in cancer prevention and you know affecting tumor biology

through metabolic signals I mean glucose regulation being a big one right I mean even if if you're someone that who who is obese and you're exercising and you're increasing glucose uptake into your muscle I mean that's that's very beneficial to not have it then available for a lot of cancer cells you know which you primarily do use glucose for for fuel um so what about someone who is let's say not obese they're healthy maybe they're in their 40s and they're someone that's more like a weekend warrior maybe I don't even know if that would be

the term maybe there's someone that just goes for a jog on the weekends only would there would there be a case to make for those people to maybe push a little bit higher intensity than just going for your your jog on the weekends in terms of like making um an impact on their cancer prevention yeah so what we see in the cancer prevention literature is there is a dose response Association as we say so that means the more exercise you do the greater the risk reduction so even though we can kind of look at different

cut points and say Here's kind of uh amount of exercise that will give you a benefit we know that more is better and there's various ways of getting that more one of it as you've pointed out is increasing the intensity but also increasing the frequency or increasing the duration and what you see with the exercise guidelines nowadays if they've almost backed off any um recommendations in terms of the frequency duration component doesn't really matter how you slice and dice that exercise so this guideline of 150 minutes per week we used to say 5 days per

week for 30 minutes and then we used to say okay well spread it out over at least 3 days and in minimum durations of 10 minutes and now they're not even saying to spread it out over multiple days and they're not even saying it needs to be a minimum of 10 minutes at once so the whole weekend warrior thing Pro well you can probably go on a Saturday and Sunday and do 50 minutes you know if you're out doing a a hiking or or some other activity and that might be just as beneficial as spreading

it out over different days now that's on the prevention side of things things get trickier I think on on treatment side of things where maybe maybe more frequent bouts are important because you're looking at the acute effects of excise accumulating acute effects but in terms of the general prevention strategy the the more you do the better and it doesn't really matter how you slice it up over the course of a week as long as you get to that 150 minutes is there a limit on that so we're saying 150 minutes of moderate intensity exercise you

know depending on where you what Journal you read for the definition of moderate intensity exercise you'll find it's you know your your heart your heart rate Max is going to like what 70% 75% heart rate Max um so I mean you're you're getting some sweat on your brow there if you were to do let's say 300 minutes a week you were to double that of moderate intensity or you were going to also increase the intensity right so you're doing more vigorous types of exercise you're going above that 70 75% you're going to 80% start rate

would you continue to see decreases in cancer risk in that I mean is there is there a limit like does it yeah it's a good it's a good question so the general recommendation is actually 150 to 300 minutes so you know 150 we kind of VI as the minimum to getting these benefits and then those benefits will continue to crew up to about 300 minutes and then the curves kind of plateau after that you know you can certainly do more than that but in terms of bang for your buck and really getting the benefit is

getting up to that 150 minutes and then further increases uh as you get to 300 minutes but it does kind of plateau after that okay so really it's better to be on the higher end of the recommendations whether that's you know the moderate intensity exercise 300 minutes a week or vigorous intensity the higher end being what 150 minutes that's right okay yeah so it is viewed more is the minimum of achieving that and all these guidelines note that further benefits can be gained by doing more so we set that guideline around 150 and additionally getting

up to 300 can be more and generally the guidelin is just sort of double weight vigorous minute so when we say it can be 150 minutes of moderate or 75 minutes of vigor she kind of get double credit for the vigorous intensity exercise or any combination of the two it doesn't have to be all moderate or all vigorous you can mix it up as well but that's roughly uh um the extra benefit of the vigorous is this kind of double weighting that you're probably getting about twice the benefit as you might get with moderate intensity

exercise it seems as though people that let's say do have a family history of cancer would really benefit from knowing this information as well as their Physicians that they you know speak with because you would imagine someone with a family history would want to hit the top end of that you know recommendation right and so and not the the minimum so you often only hear the minimum when hearing recommendations which I don't I don't think I think that's kind of you know a problem to be honest I think we should be talking about more of

the upper end especially if you're getting a dose response and people really do want to get and maximize their their benefits that they're going to get from exercise um for someone who is exercising and has been and say they still come down with cancer is there any preemptive benefits they get so in other words like does the fact that they've been let's you know say exercising for decades before cancer diagnosis does that seem to change the trajectory of their their outcome at all like do they have a benefit yeah it's a great question and so

there is some studies that link both pre-diagnosis exercise and post- diagnosis exercise to better cancer outcomes and some of those studies show that yes even the amount of exercise you were doing before diagnosis might improve your outcomes after diagnosis independent of what you do after diagnosis some of it is that the exercise might alter the cancer itself so even if it doesn't prevent the cancer it might be a less aggressive cancer or genetically different type of cancer or it might be more of an early stage cancer so some of it's related um to changing the

cancer itself but even if exercise doesn't prevent the cancer it may delay the cancer so someone who gets diagnosed at age 70 might say oh I exercise all my life and I still got cancer but they might have been diagnosed at 65 without the exercise so sometimes it's just delaying um the cancer and then I think the the pre-diagnosis exercise helps you get fit and ready for cancer treatments and so you can think of exercise kind of this whole pre-diagnosis time as the entire prehabilitation part it's preparing you for getting diagnosed with these chronic diseases

because once you get diagnosed with a chronic disease sometimes the treatments happen fairly quickly and that window of getting fit and ready for chronic disease and its treatments might be short so the other way to look at this sort of prevention lifestyle one is really prehabilitation for the eventuality um most Americans will be diagnosed with a chronic disease at some point in their life and many of them will be diagnosed with multiple chronic diseases it's the rare person that's going to make it the age 90 with no chronic disease so you are kind of preparing

uh for those chronic diseases and getting yourself into the best shape and the best fitness for then having deal with that chronic disease so yeah lots of benefits I think the exercising throughout your lifetime even if it doesn't ultimately you know prevent you from getting a particular disease what kind of exercise prepares people the most for a cancer treatment that they're going to undergo I mean we're you strength training resistance training is obviously you do get your heart rate up um it's it's not the same as aerobic exercise or vigorous intensity high-intensity exercise but you're

you're you're building muscle mass you're building muscle strength very very important for aging where does the aerobic versus like resistance training come into play in terms of preparing someone for a cancer diagnosis so most of the research we have has been on the aerobic side of things so somebody gets diagnosed with cancer they do oftentimes go onto these treatments fairly quickly so it can be a short window in terms of getting ready um but prehabilitation is this very important concept step that you can prepare for these treatments and potentially reduce your complications reduce your length

of Hospital stay improve your quality of life and your recovery afterwards most of the studies have looked at fairly simple aerobic programs walking programs and often times they're combined with nutrition psychological counseling stress reduction uh in the general literature um these programs have been shown to be effective for patients going on to surgery onto a major surgery and show that they have fewer complications from the surgery shorter Hospital stay in the cancer area we haven't demonstrated quite as strong a benefits we can show that if you get some exercise before surgery that you are a

fitter prior to surgery and that you end up being fitter and and able to function better physically after surgery but not really the reductions in say length of Hospital stay or the complication rate which is some of the key outcomes that we're seeing in other um surgical Endeavors got it yeah I I I would imagine also um if there would be some evidence looking at resistance training added on to that it it would be beneficial because you know post surgery in particular you're you're less mobile after right and and you know so you end up

losing muscle mass and it's really hard to gain that muscle M Mass back after after at least when you're older um after an event like that yeah the muscle mass in cancer is critical cancer can become a wasting disease this phenomenon called CIA where You' get muscle wasting especially once you get Advanced or metastatic cancer but now there's a lot of research showing that low muscle mass is really the critical thing driving risk of recurrence and death from cancer so these patients who have low muscle mass or lose muscle mass when they're going through these

difficult treatments tend to have the worst outcomes so it's prompted a lot of research now into the resistance training angle versus the aerobic exercise angle wow does resistance training counter cancer caia I know that's a little bit of a different mechanism is that an inflammatory driven mechanism that's breaking down muscle yeah I don't think they know all the mechanisms right now of why that's going on but they've attempted to address it mostly with nutritional interventions and supplement uh types of interventions but not had great success there is some research looking at um exercise and strength

training seems to have modest benefits um but I think ideally we'd want to intervene earlier and prevent patients getting from that cic state because then things you know progress very rapidly once you get into that cexi and it's very hard to reverse it at that stage but if we can prevent it up front and delay it I think that would be a really important benefit yeah that's a really good point I mean and on the prevention stage it would be you have to be incorporating regular resistance training strength training into your your your workout routine

because you want to have you want to basically build up that muscle Reserve that you have more to pull from if a terrible thing like a cancer diagnosis occurs and cancer caia I don't know exactly what drives it all but if it you know kicks in at least you have more muscle to start with right like that would be and there is and of course that feeds into the whole obesity Paradox right which is obesity is a risk factor for getting a chronic disease but it actually helps you live longer after a chronic disease so

we've seen that in a few of the studies say with lung cancer that once you're diagnosed with lung cancer patients who are actually larger more obese have a little bit longer survival and I think it gets into this idea of the reserves that you've built up and sort of this rapid decline that's going to occur I think um the Obesity angle may be important but it's probably even more important with the muscle mass right the larger amount of muscle mass is going to help you live longer you know as cancer sort of takes this toll

over the course of um months or years do people with obesity also have more muscle mass are they just eating more calories including from protein which is a signal for muscle protein synthesis yeah and the research shows there's no necessary link between that there is this phenomenon we call sarcopenic obesity so yeah there's High rates of obes but those people have fairly low lean body mass as well so there's different kind of phenotypes if you will of the Obesity and you're right the real issue we want to look at in obesity is how much muscle

mass versus how much fat mass and look at kind of that fat to lean ratio and that's really the more important factor some people who have very high weight might have a lot of muscle mass and be in very good shape others might have a balanced muscle mass and then others might have very small muscle mass despite these high levels of obesity you know the other thing I wonder Carrie is often times you'll you'll see in some of the scientific literature obesity defined as a BMI of X Fillin the blank right and if they're measuring

BMI you know some people that are lifting weights that are very muscular have a high BMI and if you were just to look at BMI only and not like hip to waist ratio and other factors um you might actually Mis categorize someone as obese and so I wonder it'd be interesting to see if there's anyone that's looked at this obesity Paradox and whether or not like that's contributing to confounding that that data yeah and that's definitely one of the explanations for the Obesity Paradox and that is it's not a it's not a good quality measure

of body composition so in our research and other research we'll either look at dexas scans that allow you to look at fat mass and lean mass but what they've done in the cancer field is all these uh patients are getting scans to track the tumors and these scans will go through the skeletal muscle uh in different places and they're able to get really good quality measures of how much skeletal muscle mass you have and they' they're the ones who have pointed out that's really what's driving these um survival rates is this low muscle mass um

which also drives low physical functioning and poor quality of life as well so I think you know in in the cancer field um muscle mass and strength training are turning out to be critically important yeah that's really not something that at least you know in the past decade or so or more was really talked about at least within the context of why it's important to be fit um with a cancer diagnosis right usually you think about aerobic exercise and the stress of aerobic exercise and of course there's all these mechanisms that occur but um it

is really interesting to think about how important having that muscle Reserve is if you are going to get diagnosed because I mean it really does affect you know it it's almost it affects the trajectory of almost any kind of illness not just cancer I mean a respiratory illness a surgery anything that's going to have you immobilized for a period of time because you're you're recovering or um you know anything like that so um I know for myself I've really gone on this personal Journey I've always been really into endurance training I've loved being you know

outside and running that's been something I love to do for many decades but um in the last year I've taken strength training resistance training really serious and you know I I'm doing I'm doing a I went from doing like 30 minutes a week to like 2 and a half hours a week of resistance training so I've really gone up on and and we're talking you know compound lifts and things that are that are working multiple muscle groups at once and joints and affecting strength as well as you know bone density and and everything like that

okay so I want to get into exercise treatment in a minute cuz I know that's really um where the bulk of your research is but a couple more questions before we get there on the prevention side so I've I've talked to some people and I've heard them say things like oh I do a lot of house chores I walk around I'm on my feet at work therefore I'm getting enough exercise and I don't really need to make structured exercise a part of my my my my physical fitness routine um what would you say to that

in terms of affecting cancer risk well the the recommendations for the 150 moderate in in uh intensity exercise minutes per week is above and beyond sort of what we call background activity just sort of what you might do over the course of the day so getting up and moving around uh is important but it's not a replacement for a structured exercise program the way I think of it is I view those types of things where you're getting up standing around you know parking at the far end of the parking lot and and walking in or

getting off the bus stop uh a stop early to get a little bit of walking in I view those kind of as activity supplements uh to be added to a good quality exercise program and just the same way when you talk about nutrition you know you don't live on nutritional supplements right you want a good quality healthy diet and then you might take uh nutritional supplement depending on um health issues so at the core of exercise is a good quality structured exercise program combining aerobic and strength exercise then on top of that yes getting up

and moving around not sitting for extended periods of time and building activity into your day I think are also important so you're heading on my next question which is these the concept of exercise snacks because there's there's some studies that I've read where sedentary time so the time that you're sitting at your desk or sitting down at work accumulates and that sedentary time is an independent risk factor for cancers which kind of raises the question of whether or not if you do these sort of structured exercise snacks where you you you know every hour so

you get up and you do a minute of high knees or you do some you know burpees or jumping jacks or whatever your favorite exercise snack is to kind of get the blood flow and and break up that sedentary time is that is that uh something that would be beneficial there's a little bit of research supporting it it's not as strong as the moderate to vigorous intensity exercise so if I had to rank them you know that would certainly be above the sedentary um Behavior part of the challenge in those studies it's very very much

harder to measure um you know all these little things that people do over the course of the day where they're a little bit better at recalling vigorous intensity and moderate intensity exercise but nevertheless um those movements are going to be beneficial because we know they are going to expend energy so it's going to be similar um to these other exercise benefits and as I mentioned you know we're no longer recommending this at least 10minute duration as the minimum of a of a exercise break so if it's moderate intensity and you're able to accumulate it in

a few minutes here in a few minutes there there could be beneficial uh effects of that type of exercise I think there's some evidence showing that as well at least with the um the vpa studies the vigorous intermittent lifestyle activity where people are accumulating these short bursts of a couple of minutes throughout the day all the way I think they accumulate up to between 6 and 9 Minutes of that you know those short bursts of intense actually exercise more intense yeah yeah no it's very interesting research and there of course they're using the objective accelerometer

so they're not relying on the person's recall and they get a better indication of that but yeah if you're engaged in this type of vigorous intensity exercise even if it's only for a minute here couple minutes there depending on how much you accumulate during the day there's going to be beneficial effects to that so you mentioned um supplements people take supplements sort of as insurance and it's funny cuz I've I've even used that term before like I take a multivitamin you know there's a lot of Trace Elements and Minerals in there that I may or

may not get from my diet but it's kind of like an insurance that I'm at least going to get some of these you know minerals and and elements um that I may not be meeting the the recommended um intake for and I I think of exercise almost as like the best long-term insurance for reducing my cancer risk would you agree with that in terms of yeah in the absence of smoking and obesity yeah exercise is really uh important for lowering the risk of cancer yeah okay so let's shift gears and talk about the role of

exercise in cancer treatment maybe um maybe we could start just a little bit with explaining this sort of cancer treatment landscape like when someone's newly diagnosed with cancer like what kind of treatments are they potentially looking at for these different types of cancers so there's been a lot of exciting progress in cancer treatment over the last couple of decades you know the main stage of cancer treatment in the past were surgery very important radiation therapy chemotherapy and hormone therapies and now over the last couple decades uh there's been a lot of research on so-called targeted

therapies and immunotherapies and these have really changed how these patients are treated what it does mean though is many of these patients are in for extensive treatments uh I think cancer patients are probably the most heavily treated chronic disease group that we have so uh patients get what we call multimodal treatment so it's rare that you would only get one of those treatments and some of these patients get surgery followed by radiation therapy followed by chemotherapy and then they may get immunotherapy there's over 100 different types of chemotherapy drugs with all different side effects there's

dozens and dozens of immunotherapies that are now approved so patients get treated with all these combinations and sequencies of these treatments so it's not a quick and dirty sort of disease where you're in the door you're treated you're out these treatments go on for many months and in some cases many years so patients kind of face this treatment Gauntlet and it can take a physical toll and a mental toll on these patients over an extended period of time and when you get into advanced cancer which you might have for many many years we have what

we call First Line treatments second line treatments and some of these cancers we have sixth and seventh line treatments so you're looking down knowing that ahead of you you've got all these different treatment options that may be available they help with the cancer but they do have a lot of side effects and and um and so it can be a real challenge you know to go through these Cancer Treatments how does that complicate you know the role of exercise in in cancer treatment yeah so we have to think about exercise as a cancer treatment so

that means we have to think about combining exercise with other treatments and sequencing exercise you know is exercise more beneficial before this treatment during this treatment after this treatment and What treatments What treatments does exercise add benefit to and What treatments does exercise not add benefit to or What treatments might it interfere with so this sort of old straightforward question does exercise help with cancer you know sort of was in the days of independent of any other treatments now that all these other treatments are being given to these patients we have to think uh about

exercise in a little more sophisticated way about when and how we combine exercise with these other treat that patients are receiving I've heard you say don't take cancer lying down how do you how does a patient who is newly diagnosed with cancer who is scared um confused how do they transform that fear into motivation to exercise you know how do they transform their fatigue into that motivation to to to move and and exercise yeah so a cancer diagnosis is a very difficult time these patients can be overwhelmed and very stressed to find out you have

cancer and then they're learning what type of cancer what stage of cancer they have what's the grade of cancer and then the oncologist is talking about all these treatments we're going to give you six months of chemo and then we're going to put you on hormone therapy so it's a very overwhelming and difficult time and so we have to look at you know what's the opportune time to present exercise to these patients and help them intervene but I think many patients tell us that cancer makes everything feel abnormal they lose control it's just the cancer

has taken over and many of them feel that exercise helps them maintain control helps them feel normal so once they kind of settle in the initial shock and realize they have cancer and they're in for these series of treatments many of them start looking for what can I do to help myself yes I've got to show up and get all these treatments but what can I I do to potentially benefit myself and when they start looking into the literature exercise is one of these things that they're quickly seeing is potentially very beneficial for them not

just for the disease itself but yeah many of these sort of side effects symptoms quality of life issues that they're going to face the declines in physical health and mental health um and I think once they start seeing these cancer specific benefits right cancer patients aren't motivated to increase their V2 Max or their muscular strength they want to know what's going to help me get through these treatments what's going to help me benefit from these treatments what's going to help me manage the side effects and once they start seeing the research there that exercise is

not just this General health behavior for cancer patients but it's actually going to help them manage their cancer that can be very motivating for them so what are some of these you know effects that exercise can help improve whether we're talking about chemo tolerance side effects effect you know improved survival what what are what are some of the effects that exercise helps with yeah so one of the big ones is managing some of these side effects of the treatments you mentioned fatigue which is one one of the most important ones many cancer patients experience fatigue

from these treatments as well as symptoms and in the past oncologists used to recommend take it easy rest this is the best way to get through these treatments and so some of the early studies started showing the patients that rested during chemotherapy actually reported more fatigue than the patients who exercise and this is very counterintuitive for patients and it's counterintuitive for doctors you know when you're tired and not feeling well rest seems like the best medicine but it's not the best medicine and we've demonstrated that consistently in the exercise oncology field that uh patients who

exercise going through these treatments have lower fatigue so that's a huge Factor the other benefits um have been that have been shown definitively are improvements in Sleep Quality so you can imagine the stress and the anxiety of going through these treatments not knowing whether the treatments are working whether or not you're going to have recurrence very difficult um with sleep and exi has been shown to benefit Sleep Quality reduce some of the anxiety associated with cancer depression levels and some of these other um side effects as well pereral neuropathy there's been some studies showing some

potential benefits so that's one of the key benefits is managing the side effects you mentioned treatment tolerance which is your ability to complete these treatments very very important every cancer patient learns very quickly that I need to get all of these drugs that I'm supposed to get and I need to get them on time if the oncologist has to reduce the dose of those drugs or delay them that increases the chances of recurrence in other words it reduces the chances of being cured so the last thing oncologists want to do is sort of reduce these

drugs or delay them but if the side effects are so bad they have to do that some of these patients the side effects are so bad they can't complete these treatments so early on when we were looking at exercise the concern was that we might interfere with patients ability to complete these treatments that we're going to make it harder you know we're piling on this exercise on top of all these side effects where they're sick and nauseous and diarrhea and vomiting and and so on and so some of these Studies have actually shown that it's

the patients who exercise during chemotherapy that end up completing more of their chemotherapy they have fewer reductions in the chemotherapeutic drugs and fewer delays and that portends a better outcome a higher chance at cure and a lower risk of recurrence so that's been a huge uh finding that's very motivating for patients and then ultimately this link to survival you know does it reduce the risk of recurrence does it improve survival we have a growing amount of research preclinical studies in the animal models look at exercise and tumor growth and spread but also these epidemiological studies

showing that cancer patients who report more exercise seem to have a lower risk of recurrence of the disease and a lower risk of dying from uh the cancer many years down the road so yeah lots of benefits across the board uh in terms of quality of life benefits and also uh disease and survival benefits so when when it comes to the the exercise type um do you think that more intense exercise is more beneficial with respect to cancer treatment and some of some of the at least mechanisms that may be occurring to have these beneficial

outcomes so some of it's been showing that the the higher intensity exercise is better a lot of these Studies have done high-intensity interval training but it very much depends on the patient ability and how they're responding to treatments some patients will get a very first chemotherapy infusion and they are completely wiped out they got nausea and vomiting they have diarrhea they have sickness and it's very difficult so we have to individualize the exercise for them other patients don't even know they're on chemotherapy they continue working and continue going through it and they're able to do

a much more demanding exercise program uh but the weight training has also been shown to be very important I mentioned that Improvement in chemotherapy completion in one of the studies that we did it was actually the weight training group that completed more of their chemotherapy compared to the aerobic exercise group or the usual Care Group and so this weight training group was able to put on uh over a kilogram of lean muscle while they were on chemotherapy and this might help with the metabolism of these chemotherapy drugs so higher intensity exercise seems to be good

weight training seems to be very good during these treatments what kind of what kind of Protocols are we talking about with respect to the weight training protocol the aerobic exercise training protocol that um some of the the patients in your trials have been on most of the protocols we've tested are three days per week of weight training maybe eight exercises covering all the major muscle groups Moder intensity so 8 to 12 repetitions before failure so I would consider kind of a standard fullbody type of weight training program many of the other trials have done two

days per week so lots of good evidence suggesting that even two days of uh a week of weight training can be very beneficial for these outcomes have you ever combined the aerobic exercise with we weight training and see if there's like a like Synergy or additive effect yes we did one trial we call the care trial which stands for Combined aerobic and resistance exercise in breast cancer patients and we did find some additional benefits we did a high dose of aerobic exercise we did a moderate dose of aerobic exercise and then we did a combined

aerobic and resistance exercise and of course additional benefits in things like muscular strength uh improvements in lean body mass but even in some of the symptom side effects small additional benefits of combining the two but the best evidence definitely is exercise compared to nothing at all that's that really drives the benefits and once you start manipulating the exercise prescription we can see some additional benefits um for patients who are able and willing to do more exercise or uh able and willing to do a combined exercise program when you say high aerobic exercise versus moderate is

this guidelines like per week or what what was the kind of protocol yeah so it was 75 minutes of vigorous in the in the sort of moderate group and then 150 minutes per week of vigorous in the high aerobic so it was more kind of the minimum guideline versus the the optimal guideline for aerobic exercise what so I want to talk a little bit about some of the the mechanisms for improved survival for um reduced cancer recurrence I mean you mentioned one which was continuing the the treatment right so obviously that's one important um but

perhaps some other ones that may also affect cancer metastasis right like that would also affect survival and perhaps recurrence later down the line as well what do you find can we talk a little bit a bit about some of these mechanisms like immune related metabolic related I've heard you talk about increased blood flow as well and maybe what's most compelling if there's any that's most compelling so if we talk about influencing the primary tumor uh and we've seen this in preclinical models but also in the human studies sometimes when we've got an existing primary tumor

uh the first treatment is not to surgically remove it the first treatment is to treat it with chemotherapy or radiation therapy and try and Shrink or eliminate the tumor that way and so what they've shown in some of these preclinical models is with if you're giving these uh uh mice um a particular chemotherapy drug and exercise versus neither versus both um exercise combined with chemotherapy is more effective than exercise alone or chemotherapy alone and what they've shown in these studies is um that these primary tumors have a very poor vasculature it's poor quality blood vessels

they're leaky uh and they're chaotic in there but all these tumors in order to grow they need to draw blood vessels they only grow to a very small size and unless they get blood vessels within them they can't grow any larger so they all start developing these blood vessels what they were able to show uh in these uh exercise studies that excise improves the quality of these blood vessels and the density of these blood vessels and while you're improving the quality of these blood vessels what that improved was chemotherapy delivery to the tumor so it

improved the delivery of the drugs to the tumor what it also does is imp improve profusion to the tumor and these um tumors become better oxygenated that's critical because radiation therapy is effective with well oxygenated tumors if they are hypoxic tumors they're not radiosensitive so now we start thinking if you're exercising while getting radiation therapy or well- getting chemotherapy we might improve delivery of the drugs to the tumor and improvements uh and making them more radio sensitive and we've seen this in actual human studies so in actual studies with patients we did a study in

rectal cancer patients and the treatment for them is a combination of chemor radiation therapy prior to having the tumor surgically removed 12 weeks later so they want to shrink and try and eliminate that tumor and what we found is the patients who exercise well getting this chemoradiation therapy were more likely to have a complete response meaning the tumors were completely gone prior to having the surgery um so this is a very uh profound and important benefit of exercise potentially in these patients who are getting treated with what we call Neo adant therapy this kind of

chemo and radiation therapy prior to surgery so that's one very important mechanism and perhaps the most compelling um once the tumor is surgically removed you're no longer concerned about the primary tumor you're concerned that a small number of cancer cells have been Shed from the primary tumor and might spread throughout the body so these cells have to go on an arduous Journey Through the uh um vasculature so they can spread through the lymph system but also through blood vessels and there's some really interesting research suggesting that if you exercise while the tumors are shedding these

um circulating tumor cells those uh circulating tumor cells are less likely to survive because of the increased sheer stress so when blood's flowing through uh uh the vascul it's under a certain amount of pressure but of course that's dramatic increased when you exercise and these circulating tumor cells are far more likely to die and not survive that Journey if you're exercising so this is another really interesting mechanisms for how exercise might be able to uh prevent the spread of a primary tumor and once those um cells are circulating or they've kind of disseminated elsewhere in

the body this is where some of these other mechanisms can be important um the metabolic uh uh effects of exercise such as reducing insulin and igf these are all things that help cancer cells grow and divide more rapidly the anti-inflammatory effects of exercise can be very important and probably one of the key ones is immune system tracking down and killing these cancer cells right this is why we have the whole new treatment now immunotherapy we've realized how important it is to call on the immune system to be able to track down and kill these cancer

cells so exercise in some ways was the original IM immunotherapy you know this was stimulating the immune system uh and improving natural killer cell cytotoxicity the number of natural killer cells the number of t- cells and B cells that were all doing immunos surveillance of these cancer cells so lots of good biological mechanisms for how exercise might improve these cancer outcomes that was phenomenal um thank you for that explanation a couple of follow-up questions so one well what you're just talking about you know the the immune surve surveillance and I'm wondering so I I've read

some studies about exercise and these are normal healthy people and I you know for a long time it was thought like oh if you're if you're sick if you have a respiratory illness uh you should you should not not exercise um because some studies that were done found that exercise acutely lowered the number of circulating te- cells in in the bloodstream the vascular system but then subsequent studies were done and found that actually those circulating tea cells were going somewhere they were actually going to the lungs so they were immobilizing going to the lungs to

help fight off you know pathogens right the respiratory the causing the respiratory illness does exercise affect the immune cells like the cytotoxic tea lympocytes or the natural killer tea cells um immobilization to go to the side of the tumor as well as you know surveiling in the vascular system so that's been demonstrated in those preclinical Mouse models so they've shown that the mice that exercise will have higher numbers of te- cells uh um natural killer cells within the tumor itself so that improved blood flow allows everything to get into the tumor uh in order to

be able to kill it so yeah the improved uh immunity it will push all the immune cells out into the system to potentially track down some of these circulating or disseminating tumor cells but it also increases amuno delivery to the actual primary tumor as well now uh exercise to your uh Point can be immunosuppressive as well right we know these very high levels of exercise the kind of triathletes and the marathon runners right it can cause immunosuppression and this was one of the reasons some oncologists early on were concerned about exercise right these patients can

become immunosuppressive from the chemotherapy treatments and other treatments so they were a bit concerned with the very high-intensity exercise in these uh patients but most of what we're studying and looking at is more the moderate intensity or or the higher intensity exercise but for reasonable amounts of exercise not sort of these marathon runners or these triathletes where you might overwhelm the patient and most people aren't out there running marathons so it seems kind of silly to be so concerned about immunos supression when a very small percentage of people are overtraining in that in that regard

right yeah we don't have a public health concern about too many people exercising too much it does there is such a thing as exercise addiction and overdoing it and overtraining so on but that is a very small slice of the population um my second question is you were talking about the shearing forces of you know increasing blood flow and that can kill these circulating tumor cells there's a variety of ways you can increase blood flow through various forms of exercise so for example aerobic exercise it's on a Continuum right the higher the intensity you go

the stronger the sort of push blood flow you know cleaning out the system resistance training so so lifting lifting weights can also cause blood blood pressure changes and changes in blood flow um do you do you think both of those types of exercise could affect that that pathway or is it mostly the more higher intensity sort of aerobic exercise yeah based on the mechanism then anything that increases that blood flow should work so some of the research that's been done done has been more of a preclinical invitro model so there's researchers who developed these plastic

tubes uh rubber kind of tubes and they can spin blood through these tubes faster or slower and then they can put these circulating tumor cells in these this sort of microfluidic system that they've developed and they can spin them around faster and slower and they show that the faster you spin these around consistent with what might happen during exercise the more of these cells that die so they've not looked at what's causing that increase um in blood uh uh hemodynamic sheer stress so yeah in theory both strength training and aerobic exercise should be able to

do it the one study that's been done in humans showing that exercise uh improves or reduces circulating tumor cells was an aerobic exercise program but in theory both should work and if you do reduce the number of circulating tumor cells in your vascular system is that associated with is there data showing that um is associated with lower you know cancer recurrence lower cancer mortality for example that's right so the way that cancer spread is the these um it has to shed cells from the primary tumor and they have to circulate throughout the um blood vessels

and they have to get somewhere else and so if you're preventing that or reducing that you should be able to reduce um the number of metastases that's absolutely critical because that's what ultimately kills cancer patients right so breast cancer prostate cancer you think of these cancers um the breast is not a vital organ women can live without a breast so how do you die from breast cancer prostate cancer men can live without a prostate how do you die from prostate cancer it's because these tumors shed these cells and they disseminate throughout the system and then

they arrive at places like the brain the lungs the liver and the but and they set up uh what we call sort of colony tumors there and they begin to grow and invade those organs and that's how you ultimately die from breast cancer if it's localized you're not going to die from breast cancer and so preventing that spread is really the critical aspect and so reducing the number of circulating tumor cells is critical how long does cancer metastasis take and I does that vary by a tumor type so if someone's diagnosed with or let's say

someone has stage one don't they don't even know they have say what stage one breast cancer prostate cancer color rectal cancer what's what's the timeline typically like to get to the next stages yeah and it it varies dramatically by the types of cancer for sure so sometimes we see very small tumors might shed cancer cells so even though we find what we think is a small tumor it may have already shed these cancer cells and theyve may have already spread sometimes the tumor can be fairly large and not have disseminated any tumor cells yet yet

and the the the real challenge there is these these tumors can disseminate these um tumor cells and metastasis may not happen right away sometimes they sit dormant for years so this is where someone with breast cancer may go in we've got a primary tumor there we cut it out we don't know if any um cells have disseminated but 5 years later 8 years later 10 years later we detect a brain metastas or there a lung metastasis so these cells can sit dormant for an extent ended period of time before they sort of start to regrow

and so um metastasis can be a very very long process or it can be a fairly short process other cancers these cells spread quickly and they grow quite rapidly at these other um metastatic sites is there any type of tracking that can be done for tracking these types of I mean is it can you get a blood test and measure circulating tumor cells is that something that that that a test is sensitive enough to do so that's the new area of hot research so in the past we could essentially only detect these cancers based on

Imaging so these metastases would have to grow to a certain size like 1 millimeter 2 millimeters before they would show up on these scans so small numbers of cancer cells we couldn't detect and so you're waiting many many years you know doing a follow-up scan five years later and all of a sudden you see a spot on the lungs or a spot on the liver and say okay that could be cancer so um this whole idea of can we find them earlier through um blood tests what they're calling liquid biopsies and this is an area

of a lot of research now where they're trying to develop these blood tests to detect small numbers of circulating tumor cells or small numbers of circulating tumor DNA because these cancer cells will grow divide undergo cell death as well and they'll shed some elements um into the system um but this is very experimental it's not being used in clinical practice right now but there's a ton of research um on these blood tests and liquid biopsy so that would revolutionize Cancer Care if we can actually go in at the time you know do a surgery remove

the tumor and then test a few weeks later to say are there any elements of circulating tumor cells still around giving us an indication okay well maybe we need further treatments with chemotherapy or immunotherapy so it would revolutionize the field but it's not in clinical practice yet well there are consumer available tests like Grail that are available these liquid biopsy tests that are done um do you think what are your thoughts on on like someone that's healthy without like a family history or perhaps with a family history of cancer doing a liquid biopsy like the

Grail test versus maybe like your the situation that you're saying which maybe may be a little more applicable where someone has had a cancer diagnosis has successfully qu quote unquote successfully under gone treatment in that the primary tumor seems to have gone away um by all means and they go and do a Grail test and perhaps maybe find something or don't find something or maybe monitor maybe someone does it yearly annually you know I don't know what what are your thoughts on on those those test it's probably too early for the science so you're talking

about using it on sort of the prevention side of thing or the early detection side of things as opposed to the um the treatment recurrence side of things just reading a study today in colon cancer ' got a blood test now out for colon cancer they're comparing it to colonoscopy because that's the gold standard way we detect and it is fairly effective it was like 80% sensitivity and 90% specificity but they still were not recommending that for the general population but I think it's coming down the pipeline I mean if it is available privately and

you want to uh get that test done you know you want to check with your doctor in terms of how to interpret it and and make sure you're looking at things properly um but I think that technology is coming down the road and it may not be too many more years when the average person is getting a Blood Plus on on the early detection side of things um on the on the cancer recurrence side of it let's say someone wants to pay out of pocket and they're going to go do I say Grail because that's

like the biggest probably um most uh studied one that's out there for consumers um and let's say they find oh I have a positive test I've got you know some some tumor cell DNA that was detected and it's the same kind of cancer that I was previously diagnosed with what would be the next steps with for someone do they go to the oncologist and then somehow verify I mean is there any way to verify if that's you know if the if the test you know is accurate or so on the post diagnosis the recurrent side

of things it is being used in clinical practice to some extent so their oncologists may already be recommending that so I would check with your oncologist to see if that is something that's recommended the whole Advantage the idea of this is um we have to be careful that we're not overt treating cancer and of course we're not undertreating cancer so right now we overtreat a lot of patients because we're not sure if they have any uh remaining disease but we just want to be sure and so they get all these treatments that they ultimately didn't

end up needing so one of the advantages of this testing uh on the post- treatment side of things is if there is no evidence of any circulating tumor cell circulating tumor DNA we can potentially deescalate the treatments and say you don't need any further treatments right now for the patient that test is positive we probably do want additional treatments if there's evidence that there still small number of cancer cells around so usually we'll recommend additional chemotherapy or immunotherapy depending on what the doctors find so yeah check with your oncologist um if that's already built into

the clinical care or whether that's something that would be recommended well back to this exercise as insurance and the fact that you know aerobic exercise in particular anything that's really increasing blood flow does seem to really have an effect on these circulating you know tumor cells then it would seem silly for someone who is has been diagnosed has been treated for cancer to not be just moving like their life dependent on it right exercising as much as possible because it seems like that would be your best bet for uh reducing the cancer metastasis and and

ensuring that these circulating tumor cells do not go and take Camp into another organ yeah yeah so again we have a lot of research suggesting that it's still experimental but I still think it is one of the few things that patients can do themselves right everything else is done to them done for them in terms of the chemotherapy the surgery and so on so patients are looking for what sorts of things can I do myself and exercise probably has the strong evidence of additional P potential benefit Beyond sort of their current treatments um so yeah

and I think in some of these cancers we are going to be able to show that there's AB absolutely benefits to improved outcomes for these patients are there so you've done a lot of research on a variety of different types of cancer in conjunction with exercise and and you know standard care treatment prostate breast coloral um on and on so have you noticed that their different types of exercise affect these different types of cancers differently in terms of combined treatment yeah there are some differences among the cancers so even though we use the term cancer

like it's a singular disease you know it's a collection over of over a 100 different diseases and all the mutations that drive these cancers can be different so um not everything is going to be uh sensitive or receptive to an exercise intervention but we see this with all treatments right some some cancers are chemosensitive some are chemoresistant some are radio sensitive some are radioresistant we've even seen in immunotherapy that we make incredible gains with certain types of cancers uh but in other cancers immunotherapy doesn't seem to be effective at all so we need to think

this way about exercise you know exercise is not going to be a Magic Bullet for all these cancers so it seems to help with certain cancers more so than others and you know when you think on the prevention side of things their strongest Association seems to be with colon cancer so those cells might be particularly sensitive breast cancer has a strong Association where some other cancers we don't see much of an association like rectal cancer prostate cancer and stuff as well so the the different types of cancer we might find cancers that are exercise resistant

and Cancers that are exercise sensitive depending on the types of mutations that are driving those cancers but in addition to the types of cancers affecting um you know the type and and benefits of exercise it's also really the treatments What treatments the patients on might determine what type of exercise is best what amount of exercise is best and to give you one example um we've really found a really good fit between weight training and a treatment for prostate cancer called Androgen deprivation therapy so men get diagnosed with prostate cancer one of the main treatments is

to eliminate their testosterone because testosterone fuels the growth of pro at cancer so they given these drugs which take them down to castrate levels of testosterone that's fantastic for the prostate cancer but is not very good for the man in terms of health strength U muscle weakness and these types of things so these guys who are on these Androgen deprivation therapies we've done multiple studies with weight training and that seems to be a really effective intervention for these guys to regain their strength regain their muscle and improvements in things like fatigue and energy so again

depending on the types of treatment certain certain types and amounts of exercise may be more beneficial I wonder if um it's interesting because compound lifts and lifting heavy is probably one of the strongest lifestyle factors that can increase testosterone actually I'm wondering if it's it's having more of a local effect on muscle and not you know going to the prostate versus you know I guess I guess other other things that would increase testosterone yeah yeah so that was one of the concerns of the clinicians when we first approached them about the patients oh maybe exercise

is going to increase the testosterone and help um this prostate cancer grow so couple things one um these drugs are so powerful they take testosterone down to castrate levels the small impact of exercise the doctors are not word that it's going to override that um but also those um effects you're talking about tend to be just acute effects The Chronic effect can be a little bit of a reduction in testosterone but it is is one of the explanations for why exercise might increase a prostate cancer risk some of the studies are mixed on that well

if it's driving testosterone levels but in the context of cancer treatment it would be very very small compared to what these powerful drugs do well I'd love to kind of on the flip side of that talk about uh exercise as a monotherapy so there's been some pretty recent large scale trials that you're involved in aace um the prevent trial that are potentially going to be looking at exercise you know exercise as a monotherapy in you know lowgrade early stage cancer um this is an area that really excites me so I'd love to hear a little

bit more about that so as I mentioned you know most Cancers get treated with a combination of treatments that we give in different combinations in different sequences so these patients are very heavily treated when we think about exercise as a monotherapy we think about exercise by itself what's the effects of exercise by itself on cancer so we've done the preclinical studies in mice um we can take uh uh these mice we can inject small number of cancer cells or implant small uh cancer tumors and we can randomly assign them to exercise versus no exercise just

like the drug uh uh researchers would do drug versus not and we can show in those studies that exercise by itself independent of any other treatments tends to slow the growth and spread of these cancers uh most of the studies are showing that not all but most the studies so then you think of clinical scenarios well if all these patients are getting treated what's the relevance of that clinical scenario but there's a new clinical scenario in cancer and as I mentioned before there's concern that some of these small low-grade cancers maybe were overtreating them maybe

we're jumping in and treating these patients causing all sorts of side effects not to mention the medical costs and and so on maybe they don't need to be treated and this whole approach to managing cancer is now called active surveillance so these cancers are so small and so lowgrade slow growing that we're not going to jump in and treat these cancers with anything it's being used mostly right now in prostate cancer that's where they've pioneered this active surveillance but it's starting to get attention even in other cancers about maybe maybe some of these cancers we

don't need to jump in and treat right away so now you've got these guys diagnosed with prostate cancer and they're not giving any treatments whatsoever so this is allowed lifestyle researchers to kind of jump in and say what's the role of Lifestyle here can we help these guys out at all so we've done a recent study looking at high-intensity interval training um in these men with prostate cancer who are on active surveillance no other treatments and addition to improvements in Fitness and function and the types of things you might expect we also showed that this

high-intensity exercise lowered prostate specific antigen levels PSA levels so this is how men are sometimes screed for prostate cancer looking at PSA levels can be an indication of how much cancer there is in in the prostate so we showed that this high-intensity exercise lowered PSA levels and then we also looked at these prostate cancer cells in a Petri dish just a invitro model where we exposed those prostate cancer cells to the serum of The Men Who exercised or the serum of the men who didn't exercise and we showed that exposing them to the serum in

The Men Who exercise reduce the growth of those prostate cancer cells suggesting that there's something that exercise is doing and we think it's the anti-inflammatory the insulin igf immune system effects that are slowing the growth of these prostate cancer cells so this is a very exciting area because many of these guys who are on active surveillance ultimately will require treatments so if you can delay the need for treatments or prevent treatments you can substantially improve their quality of life so very promising exercise in uh uh intervention in that clinical setting why did you choose high-intensity

interval training as your exercise intervention type versus something perhaps uh more moderate intensity like jogging is there something about hit and vigorous exercise that you felt uh was maybe more beneficial for for for the for the prostate cancer or is it just easier to adopt that type of routine for people I think it's the evidence suggesting that high-intensity activate activates more of these biological changes so I think of it kind of as stirring the biological soup right the body's got all these biological processes and the more intense the exercise more more these biological changes get

stirred up so you're going to send more immune cells into the peripheral blood more of the uh changes in insulin and igf more of the anti-inflammatory markers so there seems to be a a dose intensity effect on some of these biological changes and because we're targeting biological changes as opposed to functional changes we want to go with what we think is the optimal exercise prescription for re really driving biological changes that might be relevant for cancer growth so how how does um how do you guys and maybe in this trial or in generally speaking you

know take someone who's under active surveillance maybe they they have been sedentary they're not someone that's really done structured exercise you you know as a routine and help transform Their Fear because I'm sure it's scary to be diagnosed with prostate cancer as early or as you know um I would say you know lowgrade as it is it's still probably a very scary fearful process uh are there any sorts of programs structured programs that can help like having a coach or group classes things like that that what what would help for someone in that situation what

did you guys use in the study yeah so many of these guys are quite motivated to do something for themselves so that's one of the big motivating factors right waiting around just for treatments or just getting the surveillance which is you know regular PSA screenings and and biopsies and those types of things so many of these patients um uh cancer diagnosis can be a bit of a a wakeup call it can be a bit of a teachable moment in the sense that oh you know I am not a mortal maybe I do need to take

care of my health so oftentimes it prompts patients to say what can I be doing to try to improve my health so some of it is just the experience of a chronic disease can be very scary and thinking about taking your health more seriously than you might have done you when you're focused on the prevention side of things so we um motivate those guys by talking about the cancer specific benefits as I say if it's just improvements in Fitness just improvements in strength yeah these are the standard benefits that everybody gets but what about me

right and cancer patients are very concerned about their cancer once you're diagnosed with breast cancer or liver cancer or brain cancer you become focused on what what kind of diet should I eat for someone with brain cancer what kind of exercise should I do with brain you're not interested in general health benefits so they want to know about these cancer specific benefits and so we'll usually talk about those types of benefits to try and motivate them say hey this might actually help with your cancer it might help with your treatments getting through the treatments recovering

from treatments and of course we all work with them where they're at and we tell them you know we'll never ask you to do more exercise than you can do we'll progress you slowly we'll build you up to the prescription one of the other key things for cancer patients is uh the opinion of the oncologist the oncologist is absolutely crucial you know if they if the oncologist says that that patient should be exercising or think about exercising they take that very seriously so we've been able to get the oncologists on board or the urologist and

say hey your urologist thinks you know with your prostate cancer that you should be exercising as well so it's really building that team of support uh and motivating patients with the benefits that are going to be specific to them and their unique situation with with the oncologists and getting them on board um is that something you know you often do still hear again even oncologists will say to take it easy to rest especially if they're going to undergo you know they're not in active surveillance but perhaps they're going to undergo a treatment like a chemotherapy

treatment or radiation and so how do you sort of change the you know the Paradigm here and help perhaps a patient give the right information to their oncologists like giving them studies or what what what can help sort of change the oncologist from a you should rest and take it easy or just a light walk around the neighborhood to okay we should do some high intensity interval training classes to help with treatment so the short simple answer is evidence so oncologists will recommend for patients things that are evidencebased and one of I think the real

strength of the exercise oncology field is we've subjective exercise to the same rigorous research that they would subject their drugs to so we do randomized controlled trials which are sort of the gold standard research methodology with large sample sizes showing these benefits for their patients and then we publish them in the top cancer journals that the oncologists read so that's what they're looking for is evidence not that anecdotal stories about hey my uncle Fred did this and his cancer went away they want to see these uh high quality research studies and so that's been building

over the last couple of decades slowly at first but now um much more quickly where the evidence is getting out there and most oncologists are now aware of it in fact um two years ago so only in 2022 two years ago the American Society of clinical oncology put out its first exercise guidelines so this is cancer doctors so it's one thing for exercise Specialists to say hey cancer patients should exercise but now we have the cancer doctors themselves their Professional Organization ASCO the American Society of clinical oncology says all cancer patients who are being treated

with Curative intent should be recommended aerobic and resistance exercise while they go through treatments and those guidelines are adhered to very closely by oncologists so they almost all of them now will be aware of these new ASCO guidelines saying you need to be recommending and referring your patients to a good quality exercise program to help them get through treatments um well that's really good news to hear uh I want to kind of circle back to something you mentioned earlier with respect to the benefits of exercise along with treatment in cancer patients on psychological health and

maybe you can talk a little bit about how important these benefits are compared to maybe some of the anti-cancer benefits or perhaps even you know you have um one of the big takeaways from the erase trial was that exercise seemed to reduce the fear of progression and you know along with fear and that the stress you get stress hormones and stress hormones really can help fuel tumor growth as well so maybe you can sort of talk about the psychological benefits and sort of are they uncoupled from the anti-cancer benefits yeah so in one in one

way it's one of the surprising I think findings in this lure when we talk to some of our patients they will tell us that the psychological benefits are more important to them than even what it's doing to the cancer or the some of these other outcomes because it can be very difficult to cope with cancer psychologically as I mentioned cancer patients will say everything about cancer is not normal and when they exercise they start to feel like they have some control over the cancer and that their normal life I'm out playing tennis or I'm out

golfing I feel like I'm normal again so these psychological benefits can be things like improve self-confidence improve self-esteem certainly managing the anxiety associated with cancer and you mentioned the the finding related to fear of cancer progression or fear of cancer recurrence this is a huge issue in cancer patients you can imagine being diagnosed with cancer you go through the different treatments at the end of the treatments we tell the patient there's no evidence of disease we've done the scans we've done the various other tests we think it's gone how will we know it's gone U

well we're going to follow up every six months and we're going to do these tests and then we're going to tell you whether the cancers come back so we can't tell you definitively at the end of treatment that your Cancer's gone go back to your normal life we know these recurrences happen and now you can imagine every 6 months the anxiety and stress of going in and getting these Imaging tests and blood tests and then meeting with your oncologist who's going to say the cancer's back or it's not and patients will tell you that finding

out they've had a recurrence of the cancer is even more devastating than the initial diagnosis of the cancer so this fear of cancer recurrence can paralyze these patients as they continue ually go through this surveillance and at no point can we ever tell them that the cancer is definitively gone in some cancers there's recurrences 10 15 20 years later so this is very stressful so the impact we showed in this study of exercise helping them manage that fear of cancer progression or fear of cancer recurrence really important helping them get on with their daily lives

to say I have to live my life with cancer in the background even though um you know I have this Psych olical stress so yeah those psychological benefits I think are really important for these patients in addition to some of the functional benefits and the disease related benefits and and controlling the side effects there's been some pretty large randomized control trials over the years and even meta analyses of these randomized control trials comparing exercise whether it is aerobic a lot of times running or cycling um even resistance training has been thrown into the mix uh

comparing them to standard of care treatments for major depressive disorder like ssris right and exercise as a treatment it it seems to work just as good if not better than a lot of these SSRI drugs are working for for the treatment of depression which is amazing because then you're going to get all the cardiovascular benefits the muscular benefits metabolic benefits right like the endless benefits of exercise in addition to the mood benefits right so it it's not that surprising to me that exercise would have a very positive effect on you know on mental health of

of cancer patients on reducing anxiety and fear because it it's been shown in you know outside of the cancer context and other sorts of disease that are affecting the brain and mental health as well um and also it's you mentioned something interesting you said that excise seems to help cancer cancer patients feel like they have control of their lives right because I could imagine a cancer diagnosed does feel like you lose complete control of your life I mean it's like it's very scary and so I wonder also just if there's a almost a placebo effect

a placebo effect is a real biological phenomenon as you know I mean changes an immune system dopamine a lot of things are happening when you have a positive outlook when you feel like you have control of something and so you almost wonder if that spills over to the some of the psychological effects helping the anti-cancer effects as well like there's probably some crossover there yeah I think that's definitely part of the explanation is some of these um um benefits but as you know there's good biological effects as well on depression on neurotransmitters these types of

things so there's a biological basis uh for some of these improvements in things like anxiety and depression but some of these other um uh improvements things like self-esteem is just patients feeling better about themselves because they're doing something that they believe is helping themselves so these are all important psychological changes and the big difference you know we look at all those literatures outside of cancer related to depression and cognitive function and anxiety and so on but in patients you know you're dealing with depression based on a cancer diagnosis and depression based on treatments and stuff

so what we've been able to show is exercise helps with the anxiety the depression and the stress associated with a cancer diagnosis and treatments and side effects um that we weren't sure they were going to help with so it really helps manage some of that psychological stress caused by the cancer and its treatments well it sounds to me like the bottom line is I mean at every stage exercise is something that people need to absolutely focus on for cancer prevention for cancer treatment and and continuing treatment so you know it not only is helping you

get through the treatment perhaps you know even having beneficial outcomes you know with reducing mortality risk reducing cancer recurrence but that psychological let's say you okay you get through the treatment you got rid of the cancer okay it's gone and some people might think okay end end there I'm done but re the reality is then you do have to keep going back for these screenings you do have to worry about a few of those tumor cells that escaped and maybe you know are going to continue growing at the tumor site or somewhere else and so

having exercise as a part of your daily routine is going to make everything easier uh and it's going to improve the the chances that you are not going to have cancer recurrence so there's every reason to exercise and every um you know there's every reason to be motivated to exercise yeah we think about it exercise having benefits across the Continuum of Cancer Care so from the time of diagnosis and for the balance of life so at the initial diagnosis helping you prepare for treatments once you start treatment help you get through those treatments and and

uh and complete those treatments afterwards we're looking at recovery from those treatments and then after treatments when you're in what we call the survivorship phase reducing the risk of recurrence but also reducing the risk for other chronic diseases so unfortunately many of the treatments that cancer patients get increase the risk for cardiovascular disease some of these drugs are cardiotoxic increase the risk of osteoporosis uh they increase the risk of diabetes so now you've kind of survived your cancer but now you're trying to prevent some of these secondary diseases that might occur so there's lots of

good reasons to exercise right across the cancer trajectory before um before we wanted just a couple of Rapid Fire questions is there anything that we didn't cover perhaps that might be important to to discuss I mean the other way I think about exercise in terms of its importance when you look at what's currently being done for cancer patients because a lot is being done so they're offered a lot of complimentary therapies art therapy music therapy acupuncture massage therapy psychological counseling Stress Management and these are all having benefits on symptoms side effects quality of life just

like exercise but none of those other interventions have shown any benefits for survival any benefits for the disease itself or risk of recurrence and then you look at the treatments we give for cancer like chemotherapy radiation therapy all those interventions benefit at the survival side of things but they often times undermine quality of life they make symptoms and side effects worse exercise is one of these few interventions potentially for patients that can help both with quality of life side effect symptoms and also improve disease free survival so it's a real win-win compared to many of

these other uh interventions that we offer cancer patients do you have any idea what percentage of people that are diagnosed with cancer actually do use exercise in conjunction with their with their treatment yeah we've done a lot of those surveys uh and what we show is just to give you the the the pattern of it we asked the many of these long-term survivors what they were doing before diagnosis what they were doing during treatment and what they were doing after treatment and what all this research shows is that um a cancer diagnosis and treatment has

a very negative impact on exercise levels all of these patients report doing dramatically less exercise during treat than they were doing before diagnosis after treatments in survivorship exercise will tend to increase back but not back to pre-diagnosis levels so it's like the diagnosis and treatment of cancers kind of having a permanent negative impact on exercise levels so what this tells me is that if we don't intervene we're not helping patients exercise if oncologists and Cancer Centers aren't working with patients the natural response of anyone diagnosed with cancer is to sort of give up exercise get

through these treatments and try and recover afterwards um so this is why interventions and support uh in Cancer Centers from the American Cancer Society are all very important and when we ask uh during treatments in some of our studies no more than 5 to 10% of patients were meeting the exercise guidelines during treatments bumps up to 30 to 40% after treatments so again there's some sort of recovery afterwards there but there's still lower levels when we compare cancer survivors with the general population it's not much of a difference overall in terms of the physical activity

levels they're similar between the general population and cancer survivors but it varies as you can imagine by cancer type cancer stage so some cancers like breast and prostate and colon the exercise levels are reasonable but some of the more difficult cancers like brain cancer liver cancer pancreatic cancer the exercise levels are much lower and of course for the stage four metastatic disease again we see that having a very negative impact on exercise levels so there's lots of variation um but cancer in general and treatments in general will tend to have a negative impact on patients

exercise levels and they need that support to be able to exercise uh right after diagnosis well how do they get that support and also what about people that are sedentary before diagnosis who aren't even used to working out or exercising and then now they're facing a cancer diagnosis and they should be exercising like H H how do we get that those numbers up great question and you're right so the um patients that we work through exercise before diagnosis they believe in the benefits of exercise they're aware of the benefits of exercise it's not hard to

convince them to try and exercise during treatment once you explain it to them for patients who have never exercised you know walking in as they're about to start chemotherapy and talk about exercise doesn't seem like a good time to start exercise when you've not been exercising all your life so again this is where the support of the oncologist the oncology nurses and the whole Cancer Care team are really important to say exercise isn't an add-on you know it's a critical part of your Cancer Care it's really going to help you with these treatments so some

of it's just the education and the awareness of the of the role of exercise in these newly diagnosed patients and also letting them know we can start with something that's realistic and feasible for them I mean some of them are scared because they think exercise is lifting heavy weights and high-intensity exercise and they're about to start chemo and letting them know that starting even with walking program can be very beneficial uh and then we're seeing a big growth in community- based exercise programs for cancer survivors we have Liv strong at the YMCA which is a

program being rolled out across the US where um you can go and work for with a an exercise specialist specifically working with cancer survivors and many of these um Cancer Centers have fantastic exercise programs MD Anderson Cancer Center in Houston Memorial Sloan ketering in New York Dana Farber in Boston a lot of the top Cancer Treatment Centers now have exercise Specialists working right at the Cancer Treatment Center offering these programs to patients who are newly diagnosed so there's a bunch of things that are going on to try and and help patients um you know they

big concern in the US is the coverage you know these be paid for by the health insurance companies and many of these major cancer centers across the US you see a lot of support from philanthropic dollars so donors who believe in the importance of exercise Say Hey I want to fund an exercise program program because I see this as being really important for these patients so we have to think how about how we can fund it how we can deliver it and make sure that all newly diagnosed cancer patients have access to these exercise programs

I don't know how the the cost of chemotherapy seems like it'd be much more than the cost of an exercise program obviously we're not talking about exercise as a monotherapy for every Cancer type and every diagnosis because some people are Advanced but it it seems like a drop in the pool of when you're comparing it to the cost of a lot of these treatments these chemotherapies can be very expensive these newer imuno therapies can be very expensive and this is where if we can demonstrate exercise as a benefit for any of these cancer outcomes it

would be game-changing I remember a study we did where we showed that breast cancer patients who exercise during chemo had a lower risk of uh recurrence or dying from breast cancer eight years later and I remember talking to the medical oncologist and says if we can demonstrate in a larger study that exercise lowers the risk of recurrence he said that would change the game he says you know what it costs when a breast cancer patient has a recurrence a million dollars so that's the estimate that the Health Care system is going to be in for

when someone has a recurrence of cancer with all the drugs and treatments and all the medical care that they're going to be entitled to receive so you're right you know even if we can pre prevent a small number of recurrences um the the implic the cost effectiveness of exercise is very high very recent study in in breast cancer patient with metastatic cancer wonderful randomized control trial showing many of these benefits we talked about also did the coste effectivess uh analysis and showed this is a very coste effective intervention as well compared as you've pointed out

to many of these other treatments that we're offering patients but so but these these these treat exercise treatments have been shown to lower recurrence is it just not a large enough study or more studies are needed to convince so most of the stuff linking exercise to lower risk of recurrence has been observational studies epidemiological studies so these are always viewed with a a healthy amount of skepticism by oncologists and by health insurance companies and stuff as well well there's an association between exercise and these cancer outcomes and some of the uh randomized control trials that

have been done have been very small studies 50 patients 60 patients so we're in the process of conducting some of these larger randomized control trials that would be equivalent to a drug trial you know if you were testing a new chemotherapy a new immunotherapy sometimes they're randomizing 500 a th000 or more patients so some of those trials are going on right now in the exercise field and those will be viewed as the definitive trials one way or the other showing whether or not exercise can improve these cancer outcomes I'm assuming that using biomarkers like reducing

circulating tumor cells which would ultimately affect cancer recurrence isn't enough to convince this is a big debate in the oncology field let alone the exercise oncology field yeah we call these surrogate end points you know and are these going to be acceptable and there's a big debate whether or not you know drugs should be approved based on some of these inter immediate or surrogate end points so of course as exercise oncology researchers we just follow along what is acceptable uh within the what would it take to get a drug approved would be the similar outcomes

we look at so in some of these ongoing trials we're looking at disease free survival which is a well accepted endpoint uh we're looking at a pathologic complete response to the um uh uh Intervention which is another accepted one whether or not circulating tumor cells circulating tumor DNA might become an accepted endpoint demonstrating a clinical benefit uh we'll see where where that goes well the good news is is that there are many ways to exercise that are free than you can do at home you can do in your neighborhood at a park right so yeah

it is it is nice to have that support of a group class and it's certainly very beneficial to have a coach a class I think but um at the end of the day if you are if you're looking at you know affecting your mortality your recurrence your mental health your all all the things that you discuss then you know someone's going to be motivated to go go out and do it so okay so I have a few rapid fire questions um I would say if you if there were only one sentence you could permanently tattoo

onto every patient's mind about exercise what would it be don't take Ks are lying down that's what we started with that would be the uh the take-home message for patients it's a great one um what what's a myth about exercise or cancer that drives you crazy okay you might not like this myth but the myth is that exercise improves everything exercise makes everything better improves all outcomes we've seen in the exercise oncology field uh we didn't get a chance to discuss it but there's a few preclinical animal Mo models showing that exercise makes some tumors

grow more quickly so it's not this Panacea for every single tumor in general it slows the growth and spread but we've seen a few Publications showing the mightet exercise the tumors grow more quickly we've also seen a few studies including um a couple of my own showing exercise exacerbating symptoms in cancer patients so in in one of our studies in rectal cancer patients it looks like the exercise intervention made skin irritation from radiation worse exercise making skin irritation worse it looks like it made diarrhea worse in in these patients hand foot syndrome which is sort

of a a healing and tenderness in the feet and hands you can imagine walking on a treadmill or lifting weights and in a couple studies it's shown it's made fatigue worse um so there are these you know we have to be very careful about exercise will benefit everything cure everything and and make everything better and I'll end off there is one cancer we talked about prevention that exercise increases the risk of cancer and I suspect you can probably guess it um which one skin cancer oh cuz you're outside not having some so very compelling it's

not exercise that's doing it it's sun exposure correct so that's that's bit misleading so well well it it's it's misleading one sense yeah but patients who regular exercise have higher rates of skin cancer than non-exercisers it's to this exposure so the American Cancer Society is always reminding where the you know the the sunscreen and stuff when you go out and cover up during exercise as well because you are potentially putting yourself at at higher risk of uh skin cancer so we just have to be uh careful about making sure we're giving good evidence on what

the benefits are for patients and understanding some of the harms and we don't necessarily track all the harms of exercise in these studies but we now are doing that what are some of the Adverse Events what are some of the issues that might um be caused by exercise having said that the benefits of exercise far outweigh the harms of exercise but so we don't have to sort of put the hars under the rug you know to make the case for exercise we want to track those we want to make sure they're clear but what we've

demonstrated in cancer is the same thing the benefits of exercise for these patients far outweigh any risks to harms and we do have to be careful about exacerbating symptoms making sure patients are exercising within their own capacity uh the other thing I forgot to mention is the risk with bone metastasis that's a big concern in the exercise field so one of the most popular places for um for cancer to spread is to the Bone and these bones can become a bit more brittle so the risk of fracture in patients with metastatic bone disease and again

we just have to work around that with the exercise prescription but that's a a risk we have to be aware of with the animal the preclinical animal models what types of tumors were exacerbated by exercise it's a great question and um the problem is we haven't sorted that out so there's no sort of pattern yet to be a okay it's exacerbating you know pancreatic cells but not liver cancer cells or that it's the high intensity exercise making things worse or versus low intensity or when we um look at the cancers with this type of mutations

or if we do um forced exercise versus voluntary exercise so people have looked at all that to try and sort out um these studies it's about 10% of the studies so the majority show exercise slows the growth and spread about 10% are showing this um tumors is growing more quickly but there's no pattern to it that we can say ah we think this is what's what's driving it so it's not like they being the the animals are being injected with a certain type of tumor can be Drac to that type of tumor maybe it's the

background of the mice exactly yeah that's right all those factors are kind of being looked at but there's no pattern yet that would suggest it so it's just something to be aware of as we as we do these types of studies okay um next question have you ever encountered a case where effortful training didn't help and what did you learn I think you just answer yeah exactly so that's I think one of the key things is this exacerbation of symptoms we have to work around the side effects and the symptoms that patients are experiencing to

make sure the exercise is safe and tolerable for them so you know if patients are experiencing peripheral neuropathy um some patients experience issues with a taxia balance and stuff as well so you know we're putting patients on treadmills we have to be careful that um they're going to be able to do that type of exercise and then side effects like like I say like diarrhea skin irritation you know we get into cancers like rectal cancer and anal cancer that whole area down there gets radiated they get radiation Burns and movements with clothing and stuff can

can be uh patients can get dry mouth and stuff from from exercise and and it can lead to increases in diarrhea and stuff as well well so we're just working with the patients with other symptoms they're experiencing and making sure that we're not exacerbating those symptoms yeah sweat I mean if you're sweating a lot you can also exacerbate skin problems and I do think at the end of the day like is there a trade-off like is the skin irritation or the little bit of diarrhea um the price you pay for like even more you know

positive benefits and so that's also probably something you consider as well and discuss with the patient where it's like you don't want them to necessarily stop the treat because they have a little skin irritation but you know it's again it's I mean I guess it's my mentality of thinking too I'm very much like I'll handle like some suffering if it's going to have a net positive effect that's right yeah um what's one habit or purchase under $50 that can help patients stay active at home during tough treatment phases I guess probably one of these activity

trackers or fitness trackers might be very helpful and there's a lot of uh research right now trying to develop mob apps for exercise and cancer survivors one of my own PhD students looking at a a mobile app and and seeing whether or not not it might be helpful for breast cancer survivors so we'll see I think some of these technological things that might be available to help uh cancer survivors get regular exercise if someone only has 15 minutes a day what's the single best use of that time to fight cancer if it's exercise then what

type I'd probably go with the strength training and probably go you know with with some of the the heavier lifting strength training the squats and the compound exercise you've talked about you know I think what we're seeing is this idea of lean muscle mass skeletal muscle mass being extremely important for getting through these treatments predicting recurrence predicting survival strong associations with physical functioning and quality of life so I think targeting the muscle mass if you've only got 15 minutes that's probably how it would spend my time nice I do uh CrossFit training and the you

it's an hourong session all du and there's a lot of strength training at the beginning progressively working up you know and heavier weights and different types of compound lifts but typically at the end of the workout it'll be like a 15 or 20 minute workout and it incorporates you know these what you're basically saying you know squats or deadlifts or these types of strength training and resistance training exercises that do increase heart rate that improving muscle mass improving strength improving function but then it incorporates like some rowing or biking along with it so you're getting

like a high-intensity enal training workout that's including resistance training it's very Dynamic and I think it's very time efficient and I think it's wonderful a wonderful type of training plus you can get a a group go to group CrossFit classes and have that like group setting as well we getting that reinforcement from other people when coach is there so um well thank you so much um Carrie for all of the research that you're doing very very important research and um for anyone that's wanting to continue to read some of your Publications they can obviously look

you up on PubMed but also you've got a a faculty page at the University of Alberta Canada people can go to that um faculty page and find your your faculty page there to look up some of your research as well yeah and the American Cancer Society is a great resource as well they've got a lot of information on exercise for patients and survivors well thank you so much for joining me today I really um enjoy this conversation and appreciate everything that you do my pleasure thank you for having me a big thank you to Dr

Carrie Kier first of all for doing this important research and for taking the time to meet me in person to have this discussion to share with the wider public if you're a healthy person looking for a science back way to structure your training we've put together a free guide that distills insights from nearly a 100 conversations I've had with top experts in exercise physiology and Human Performance it covers everything from resistant training for muscle growth to strength training to interval training for v2 Max as well as key factors like protein timing and creatine supplementation all

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