Exercise and immunity

Exercise is good for the immune system but what about high volume, high intensity, chronic (long-term) exercise?  For cancer patients, a couple of things may be worth considering, but first a few things about immune cells.  In a general sense, cancer is a failure of the immune system to detect and eliminate defective cells, or maybe more accurately, the ability of cancer cells to evade detection from immune cells.

Two categories of immune cells are: innate immune cells; and, adaptive immune cells.  Natural Killer cells (NK cells) are a part of the innate immune system and they respond quickly to tumor formation and virally infected cells.  T-cells are a part of the adaptive immune system.  T-cells remember previous invaders, and cancer, and respond faster the second time to the same invader.  Moderate intensity exercise and life long aerobic fitness improves aspects of both of these immune cell types.  However, high volume, high intensity, long-term extreme exercise can have negative effects (1,2).

A study (3) followed Ironman competitors training for 6 months prior to the event and for a few weeks afterwards.  The researchers found that by the end of study period the ratio of  some T-cell subtypes changed to a composition that an older person is more likely to have.  Naive T-cells, which are highly responsive mature T-cells, decreased, while terminally differentiated T-cells (senescence) increased.  Terminally differentiated T-cells are not as ‘nimble’ as naive T-cells in responding to invaders, and the ratio between the two can change as one ages – more terminally differentiated T-cells accumulate and less naive T-cells are found.  This change is thought to make the elderly more susceptible to infections.  However, increasing aerobic fitness can lower the proportion of age-related senescent T-cells and increase naive T-cells, regardless of age (4), but maybe only to a point, as elite endurance athletes are known to get more upper respiratory infections and changes in immune cells are thought to play a role in this (5).

streaming blood cells

Another piece in this exercise puzzle is a virus, Cytomegalovirus (CMV).  CMV is a common herpes virus infecting approximately 50% of American adults, and that percentage increases with age.  CMV affects the exercise response of NK cells, increasing their numbers and cytotoxicity (killing ability).  However, that changes at exercise intensities eliciting a blood lactate concentration of 4 millimoles, which is about +15% of the blood lactate threshold (as defined by Weltman, A., 1995).  This is an intensity that many endurance athletes periodically train at in order to improve performance – tempo runs for marathon runners are an example.  After exercise that induces 4 millimoles blood lactate, NK cell numbers and cytotoxicity are decreased, but not in healthy individuals, only in CMV infected individuals, and regardless of sex (6).

So what does this mean for cancer patients wanting to do a triathlon, marathon, or ultra?  Right now there isn’t enough evidence to change the general American College of Sports Medicine (ACSM) guidelines of 150 minutes per week of moderate intensity exercise or 75 minutes per week of vigorous exercise.  Although a recent breast cancer study (7) found that 300 minutes per week of moderate intensity exercise was best for post-menopausal breast cancer patients who were not on hormones.  Surprisingly, another study found that higher levels of cardiorespiratory fitness was associated with higher risk of prostate cancer (8), the CMV status of those subjects was not reported and may not be known.  Outside Magazine recently did an article (9) on the deleterious effects ultra-marathons has had on some participants.  Perhaps CMV status or changes in T-cell proportions may be emerging as important markers to follow.  Exercise can help protect us against infection and fight tumors but that does not also mean greater amounts of exercise is better.  Until more evidence is presented, the ACSM exercise recommendations, as generic as they are, appear to be about right for cancer patients, and maybe particularly for those who are CMV positive.

For more in-depth information about exercise and immunity, a couple of recent articles are worth reading (10,11,12), if you can get full access (12).

  1. Special issue on exercise immunology: Current perspectives on aging, health and extreme performance. Richard J. Simpson, Jos A. Bosch. Brain Behav Immun. 2014 Jul;39:1-7.
  2. Is immunosenescence influenced by our lifetime ‘‘dose’’ of exercise? Jmes E. Turner. Biogerontology (2016) 17:581–602.
  3. The impact of 6-month training preparation for an Ironman triathlon on the proportions of naïve, memory and senescent T cells in resting blood.  Coagrove, C., et al. Eur J Appl Physiol (2012) 112:2989–2998.

  4. Aerobic fitness is associated with lower proportions of senescent blood T-cells in man.  Spielmann, G., et al.  Brain, Behavior, and Immunity 25 (2011) 1521–1529.

  5. Upper respiratory tract infections and exercise.  D.C. Nieman. Thorax. 1995 Dec; 50(12): 1229–1231.
  6. Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Part II: Impact of latent cytomegalovirus infection and catecholamine sensitivity.  Bigley, A.B., et al. (Article in Press) Brain, Behavior, and Immunity xxx (2015) xxx–xxx.

  7. Effects of a High vs Moderate Volume of Aerobic Exercise on Adiposity Outcomes in PostmenopausalWomen. A Randomized Clinical Trial.  Friedenreich C.M., et al.,  JAMA Oncol. doi:10.1001/jamaoncol.2015.2239.

  8. Midlife Cardiorespiratory Fitness, Incident Cancer, and Survival After Cancer in Men. The Cooper Center Longitudinal Study.  Lakoski, S.G., et al.,  JAMA Oncol. 2015;1(2):231-237. doi:10.1001/jamaoncol.2015.0226.

  9.  Running on empty.  Meaghan Brown.  Outside, June 12, 2015.
  10. Human cytomegalovirus infection and the immune response to exercise. Simpson, R.J., et al., Exerc Immunol Rev. 2016;22:8-27.
  11. Does Regular Exercise Counter T Cell Immunosenescence Reducing the Risk of Developing Cancer and Promoting Successful Treatment of Malignancies? James E. Turner and Patricia C. Brum. Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 4234765, 18 pages.
  12. Mobilizing Immune Cells With Exercise for Cancer Immunotherapy. Simpson, R.J., et all., Exerc. Sport Sci. Rev., Vol. 45, No. 3, pp. 163–172, 2017.
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A little exercise for me, a lot for you?

 

bikes,vintage  Cycling on twilight time

I often read stories about cancer patient’s (survivor, warrior, thriver, whatever we want to be called) physical accomplishments before, during, or after treatments – marathons, triathlons, ultras, century rides – all impressive stuff, even outside the realm of cancer.  The accomplishments seem understandable too, since exercise has been found to:

  • Improve survival in breast (1) and colorectal cancers by 50% (2).
    • Brisk walking of 2 1/2 hours per week produced the breast cancer results, but more vigorous exercise of 6 hours per week was needed for colon cancer;
  • Other researchers found moderate intensity physical activity to reduce risk of death from all causes by 60% among breast cancer patients (5);
  • and, cancer specific mortality from brain (4),andhigh grade, advanced, or fatal prostate cancers (3), were also reduced 43% and 70% respectively.
    • running 7.5 to 15.5 miles per week or walking briskly 12 to 23 miles per week for the brain cancer results, and 3 hours per week of vigorous exercise for prostate cancer.

Interestingly, more exercise did not reduce risk any further in the breast (1) or brain cancer studies.  However, for their results, the brain cancer subjects had to exceed the recommended physical activity levels (6) of 150 minutes of moderate intensity exercise per week.  Walking was also as good as running in the brain cancer study, subjects just had to walk farther.

What does this all mean for those of us affected by cancer?  Well, for the cancers mentioned above, if you’re not moving at the levels showing significance, perhaps it is time to get clearance from your physician, and start.  Practically, make exercise or physical activity a part of your weekly schedule.  It is easy to fill up your calendar with other things and people but forget to plan you into your week. Take a good look at your week, find days and times that work best to accomplish what you want, then write you into those time slots, and keep the appointment.  Book others to meet with you if needed, guilt can be the right motivator sometimes.

African American Family Parents and Children Cycling  Walking_2

Hypothetically, what if completing an Ironman Triathlon improved survival by 80%, would cancer patients, the majority of whom are sedentary, start training?  I wouldn’t be surprised if many did, determination can be great when faced with a cancer diagnosis.  However, even if willing to simply change their lifestyle, or intensely train for an Ironman, are we already hindering patients’ ability to do so by not pre-habilitating (8) them for the insult some treatments inflict on the body?  If most cancer patients do not already like to exercise, how are we ever going to convince them to start if we let their physical function decline further prior to or during the treatment process?

For those of us already in the exercise choir, and for cancer types other than those listed above, how much exercise is enough, and what may warrant caution (9) or be too much?  Unfortunately, most fitness stories remain just that, stories, unless we happen to be in a study, because, until physical activity is routinely recorded in oncology we will never know to what extent many physical accomplishments affect cancer survivorship (the ‘survivorship beginning at diagnosis’ definition).  Most of us in the cancer exercise choir, myself included, are just figuring it out as we go along, sometimes overdoing it (7), or maybe we’re not doing enough, and we share what we’ve learned with others.  Ironically, in spite of all the data we generate when training with our consumer fitness tools, there still isn’t the right statistical data to guide many of us.

senior man exercising in wellness club

Missing data …

A physical activity profile (using a short, scientifically validated, questionnaire) is not routinely recorded when extracting biopsy tissue from patients.  Is there evidence in tissue samples that could correlate physical activity to cancer treatment response rates and survival?  How are tissue samples different, if at all, between those who exercise versus those who don’t?  If different, can the differences be exploited to improve cancer treatment outcomes or to develop new drugs?  Exercise and physical activity are positively affecting survival for those cancers listed above, but how is this happening?  What are the physiological mechanisms, and are we overlooking routine biopsies as sources of evidence?  Exercise physiologists sometimes pay study volunteers and take muscle biopsy samples to find out what exercise did.  In oncology, other than pathology, how much thought is given to our biopsy samples, which patients pay for, and exorbitantly too?

I wouldn’t limit recording patients’ physical activity to biopsies only, we should be updating fitness profiles at diagnosis, first treatment, scans, and subsequent healthcare visits too.  The studies mentioned above were observational ones done over a number of years, some only assessing physical activity every two years (1,3), which doesn’t allow for teasing out information in the weeks specifically surrounding a cancer diagnosis or treatment.  Some physical activity questionnaires have gone electronic, but collecting data using paper forms, interviews, and calls to subjects is still done.  In today’s electronic world this sounds archaic, but this is how the best observational evidence has been obtained so far.Exercising on gym bikes.

Or … data to nowhere

With all the new consumer fitness products available we are still unable to get much of the data they generate into our electronic health records (EHRs).  My Garmin data, Moves data, and the information I type into my training and treatment log, all just sit there in electronic form somewhere in cyberspace.  My information cannot be pooled with the fitness data from others to search for statistical significance.  You can be sure the consumer fitness developers know a lot of things about me, but the products they have developed are generating data that goes nowhere – lots of data rather than ‘Big Data’ – my cancer and fitness story has no statistical power even though plenty of Information Technology (IT) is attached to it.

Recent announcements regarding consumer fitness and IT may change this and move us closer to continuously updated physical activity profiles by using data automatically uploaded through privacy ensured patient portals (EPIC’s ‘MyChart’ would be a good example).  Physical activity information could then be accessible when needed by clinicians from EHRs, and more importantly, tied to pathology, treatment, and other information within EHRs.  Apple’s collaboration with The Mayo Clinic, Nike, and the prominent EHR system, EPIC, appears to be headed in this direction.  However, without the broad use of internationally standardized exercise and physical activity codes for the common measures most exercise stakeholders are recording – steps, calories, heart rate, etc. – integrating the fitness data into EHRs will remain problematic.  Medicine wants valid standardized data and evidence before they will change clinical practice.  Our fitness stories, with isolated data on only one person, will not change clinical practice.

There is interest among cancer patients in allowing their data to be shared for research purposes, 87% reporting a willingness to do so (10) as long as privacy was adequately addressed.  How many of them have stories on the extreme ends of the physical activity spectrum and how is cancer survivorship going for them out there?  Fitness stories may motivate or guide others, but we also need statistical significance in order to impact clinical practice.

Swimming competition  Young Couple Jogging in Park

 

References:

1.  Holmes MD, et al., Physical activity and survival after breast cancer diagnosis. JAMA. 2005;393:2479-86.

2.  Meyerhardt JA, et al., Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803.  J. Clin Oncol. 2006: 24:3535-41.

3.  Giovannucci EL, et al., A prospective study of physical activity and incident and fatal prostate cancer.  Arch. Intern. Med.  2005:165:1005-10.

4.  Williams PT, Reduced risk of brain cancer mortality from walking and running. Med. Sci. Sports Exerc. 2014 May;46(5):927-32.

5.  Irwin ML, et al., Influence of pre and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study.  J. Clin. Oncol. 2008:26:3958-64.

6.  Schmitz K.H, et al., American College of Sports Medicine Roundtable on Exercise Guidelines for Cancer Survivors. Med Sci Sports Exerc. 2010 Jul;42(7):1409-26.

7.  Kano S, et al., [A case with myositis as a manifestation of chronic graft-vs-host-disease (GVHD) with severe muscle swelling developed after aggressive muscular exercise.] Rinsho Shinkeigaku. 2003 Mar;43(3):93-7.

8.  Julie K. Silver, MD and Jennifer Baima, M.D.  Cancer Prehabilitation: An opportunity to Decrease Treatment-Related Morbidity, Increase Cancer Treatment Options, and Improve Physical and Psychological Health Outcomes. Am J Phys Med Rehabil. 2013 Aug;92(8):715-27.

9.  Stan, D, et al., Pilates for Breast Cancer Survivors: Impact of Physical Parameters and Quality of Life After Mastectomy. Clinical Journal of Oncology Nursing. Volume 16, Number 2; pp:131-141.

10. Rechis, R, et al., The Promise of Electronic Health Information Exchange: A LIVESTONG Report.

 

Update:

The Future of Medicine Is in your Smartphone.  Eric J. Topol, MD.  The Wall Street Journal, 1/9/2015.

http://www.wsj.com/articles/the-future-of-medicine-is-in-your-smartphone-1420828632

What is exercise for cancer patients? It’s all relative.

Image

In the US most adults do not get the recommended 150 minutes of moderate intensity or 90 minutes of vigorous intensity physical activity per week.  Nothing new about this, however, maybe it doesn’t accurately describe what is physical activity for cancer patients, particularly those in the midst of treatment.  I argue that many cancer patients may be meeting the recommended guidelines but they just don’t know it.

There is a measure in exercise physiology called maximum aerobic capacity, which is recorded as maximum oxygen uptake, or VO2max for short (maximum volume of oxygen).  Elite endurance athletes have values above 80 (it’s recorded as millilitres of oxygen per kilogram of body weight per minute: [ml/kg/min]).  However, in many of the exercise and cancer studies I read, I often see average maximum oxygen uptake for cancer patients below 20.  What does this mean and how does it relate to cancer patients meeting the physical activity guidelines?

Bear with me as I first translate VO2max into something easier to understand.  I noticed one study where the cancer subjects had an average VO2max of 17.5 ml of oxygen/kg/min, this is a convenient number that converts into something we can relate to.  An intermediate conversion is needed to something called a *MET, 1 ‘standard MET’ equals 3.5 ml of oxygen/kg/min, so a 17.5 VO2max = 5 METS.  A 5 MET activity is walking at 4mph, one mile in 15 minutes (4 laps around a high school track).

So there we have it, our cancer subjects have a maximum aerobic capacity to walk 4mph.  However, this doesn’t mean that they can actually walk the entire mile in 15 minutes, none the less, they should not feel inferior about it because an elite endurance athlete can’t go 15 minutes at their maximum aerobic capacity either.  What?  You see, maximum oxygen capacity can only be maintained for about 3-5 minutes regardless of who you are – cancer patient or elite endurance athlete.

For our cancer subjects, just one of those laps around that high school track at a speed of 4mph will take 3 minutes and 45 seconds.  It is an interesting comparison then that the track & field world record for one mile is 3 minutes and 43 seconds (all four laps around that high school track).  However, I guarantee you that the guy who set that world record could not have done another lap at his record pace – he was at his maximal oxygen capacity (actually a little above it as he sprinted the last part of the race, but he didn’t use any more oxygen to do that extra effort).  So it would be no surprise if our cancer subjects also became exhausted after 3:45 of walking only one lap at their maximal oxygen capacity.  This is just like the world record holder who is exhausted after running for 3:43 at his maximum oxygen capacity.  What then can cancer patients do to get 150 or 90 minutes of exercise in a week?  They can slow down.

If our 5 MET capacity cancer subjects slow down to 60% of their maximum, which is considered to be moderate intensity, they will be at 3 METs, and this intensity they will be able to sustain for longer than 5 minutes.  The relative part of all this is that they can achieved 3 METs by walking a dog!  Yep, according to the 2011 Compendium of Physical Activities, if our cancer subjects do this they are doing moderate intensity physical activity.  Below are some other 3 MET activities from the Compendium:

  • walking 2.5mph (a mile in 24 minutes rather than in 15 minutes), if our subjects were to walk 5 laps around that high school track 5 days a week then they would meet the physical activity guidelines.  Or if you are an in-patient, walk the oncology ward halls before breakfast, before lunch, and before dinner – break it up into three 10 minute segments.
  • home activities – implied walking, putting away household items
  • child care, standing (e.g., dressing, bathing, grooming, feeding, etc.)
  • home repair/maintenance
  • some lawn and garden activities
  • some occupations, work tasks, and work walking
  • bowling (an often maligned recreational activity)
  • mini golf, driving range
  • horseshoes
  • shuffleboard
  • Pilates, tai chi, Qi gong
  • How many more activities become moderate intensity if an ‘adjusted’ or ‘measured MET’ is used rather than a ‘standard MET’?

Considering household and caregiving activities, some cancer patients may be getting close to meeting the physical activity guidelines just by maintaining a near normal work schedule or by puttering around their home while recovering between cycles of chemotherapy.  There was a recent study that was critical of counting household activities as physical activity.  This may be true for healthy adults, however, for cancer patients, some adjustments have to be taken into account.

One important consideration is that some chemotherapies can cause anemia.  Other things too can affect our cancer subjects, some of them are mentioned in a previous blog: Mt. Everest and Cancer.  So, during treatment, rather than our subjects having a maximum aerobic capacity of 5 METS, it may be lower than that.  This means that if they want to sustain their physical activity beyond 5 minutes, their normal 60% intensity will now be at a slower pace, and this brings in  even more Compendium activities.  If they don’t slow down, they will find their normal pace is now more fatiguing and that they have to rest a little longer between activities.  Unfortunately, and mistakenly, this causes many cancer patients to think they are too tired to ‘exercise’, so they nap a lot.  Their old 60% pace is now a 70% or 80% intensity (vigorous), which is ok to do but they will need to walk for shorter periods of time and to rest a little longer.

I recently read an online post by a cancer patient who mentioned becoming fatigued from just walking across a room.  I hope we can now understand that this could actually be viewed as part of a ‘workout’.  The key may be for that patient to start treating a walk across the room as exercise and to mentally incorporate it into a modified ‘workout’ routine.  This is not unlike how that world record miler might workout – he may do an effort at a specific intensity, recover, then repeat this pattern a number of times on a training day.  For our subjects, walking across a room, up some stairs, down a hall, getting tired, resting for a bit, and then repeating this pattern, could be considered a type of workout called interval training.  It may not be at the same pace as the world record miler but the relative intensity can be the same, cancer patients and clinicians just might not realize that it is.

Keep moving!

 

*MET    Metabolic equivalent: one size does not fit all. Byrne, N.M., et al. J Appl Physiol 99: 1112–1119, 2005.  Examining Variations of Resting Metabolic Rate of Adults: A Public Health Perspective. McMurray, R.G., et al. Med. Sci. Sports Exerc., Vol. 46, No. 7, pp. 1352–1358, 2014.  The standard oxygen consumption value equivalent to one metabolic equivalent (3.5 ml/min/kg) is not appropriate for elderly people. M. Kwan, J. Woo and T. Kwok. International Journal of Food Sciences and Nutrition, Volume 55, Number 3 (May 2004) 179 /182.  Activity-Related Energy Expenditure in Older Adults:A Call for More Research. Hall, K.S., et al. Med Sci Sports Exerc. 2014 Dec;46(12):2335-40.  Errors in MET Estimates of Physical Activities Using 3.5 ml·kg–1·min–1 as the Baseline Oxygen Consumption. Kozey, S., et al. Journal of Physical Activity and Health, 2010, 7, 508-516.

 

References: