Exercise as it relates to Disease/High Intensity Interval Exercise and Colon Cancer

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The following is a critque of the journal article "acute high intensity interval exercise reduces colon cancer cell growth[1]" written by James L. Devin, Michelle M. Hill, Marina Mourtzakis, Joe Quadrilatero, David G. Jenkins and Tina L. Skinner.

What is the background to this reasearch?[edit]

Exercise is known to have significant preventative effect on the prevelance of cancer. [2] [3] [4] Excercise also has a profound effect on decreasing mortality rates in colorectal cancer survivors. [5] A suggested mechanism for these benefits of exercise has to do with the release of anti-inflamatory chemicals, called cytokines, after exercise. [6] This study aimed to observe the immediate and long term effects of these cytokines on colorectal cancer cell growth after high intensisty interval exercise. High intensity exercise was chosen due to it causing a larger release of these cytokines than moderate intensity exercise. [7]

Where is the research from?[edit]

This study comes from the University of Queensland in Brisbane, Australia. It was funded by the Univerity of Queensland's HABS/MABS Collaboration Seeding Grant, as well as their Graduate School International Travel Award. Additional funding for this project came from the Sports Medicine and Research Foundation. The research was published in The Journal of Physiology, a long running, reputable journal. Due to the majority of the funding coming from the University of Queensland, and not a major company, it is assumed that no agenda was being pushed by the funding bodies.

What kind of research was this?[edit]

2 Components:

It is important to note that "in vitro" studies are not always reflective of all the physiological mechanisms occuring at the cellular level due to the separation of the cells from the whole organism and therefore all the other reactions going on that may also affect these cells.

What did the research involve?[edit]

Human Clinical Trial[edit]

A group (20 people) of male, colorectal cancer survivors, at least one month into remission, were split into 2 groups of 10. The participants were all older than 40 years of age however the average age was 66. It is known that as aging occurs, the levels of inflammatory cytokines are decreased as well as there is a decreased anti-inflammatory cytokine response post exercise [8] [9] Due to this impaired cytokine response to exercise, the effects on cancer cells may be different when exercising younger patients. One group (Acute) completed a single exercise session of 4 sets of 4 minute work intervals at 85-95% of their maximum heart rate. 3 minutes of active recovery was given between sets and a 10 minute warm up was completed prior to the first work interval commencing. The exercise was completed on an exercise bike. Cytokine response to exercise is typically lower in cycling when compared to running,[10] however, cycling is likely to be more appropriate for this population due to the age of the participants and the higher impact nature of running. The other group (Short Term) completed the same exercise session 3 times a week for 4 weeks. In the acute treatment group, venous blood was sampled prior to exercise (fasted), immediately after exercise and 120 minutes post exercise. The short term treatment group had venous blood samples taken 3-7 days proir to beginning the intervention and following the intervention. Serum samples in this group were taken at the same time of day, this is an important control measure as cytokine sercretion from muscles, when not prompted by exercise, follow a ciradian rhythm.[11] Blood samples were ananlysed for both groups to determine levels of the cytokines: interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF-a).

In Vitro Study[edit]

Two genetically different colorectal cancer cell lines were obtainined. The genetic difference in cells was purposefully chosen due to different critical genes produce different types of mutation in colorectal cancer cells.[12] By doing this, the research from this leg of the study may have broader implications on differing mutations of colorectal cancer. Cells were then incubated in serum from pre exercise, imediately after or 120 minutes post. Serum was obtained from the blood samples from the acute treatment group. Incubation lasted for 72 hours with measures of cell number and cell death collected at 24, 48 and 72 hours.

What were the basic results?[edit]

  • All cytokines were significantly elevated from rest levels immediately after exercise but returned to resting levels 120 minutes after exercise.
  • No change of in resting levels of the cytokines measured was observed after a 4 week high intensity interval exercise training intervention.
  • Both genetic strains of colorectal cancer cells had a significantly decreased cell count at 24, 48 and 72 hours when incubated in serum from immediately after exercise when compared to serum collected at rest.
  • When incubated in serum from 120 minutes post exercise, neither genetic cancer cell variation decreased in cell count over 72 hours when compared to resting serum incubation.

What conclusions can we take from this research?[edit]

High intensity interval exercise causes elevations in cytokines which return to resting levels after 120 minutes. No long term changes in the resting levels of these cytokines are caused by this style of exercise. Due to the isloated nature of the in vitro study it cannot be said that these elevations of cytokines in the body would have the same effect or magnitude of effect on colorectal cancer cells as seen in the in vitro arm of the study. However, when exposed to serum with elevated levels of these cytokines, colorectal cancers experience decreases in cell count over 72 hours. It is of important note that the cell count decrease was seen when exposed to a consistent level of these cytokines for at least 24 hours, whereas in the body the cytokine levels were only seen to remain elevated for less than 2 hours. This significantly decreases the window of time the cytokines have to induce cell death and highlights the need for research into the in body effect high intensity interval exercise has on colorectal cancer cells. Further research could also be conducted into the changes in the cytokine response to exercise over a period of high intensity interval exercise training intervention.

Practical advice[edit]

While the body is a complex integrated system and colorectal cancer is a multifactorial disease, exercise is known to decrease mortality in survivors of the disease[5]. The cytokine effect on cell decreases in colorectal cancer could be one of many mechanisms causing this outcome and may even have implications for prevention of the disease as well. For this reason engaging in an exercise program involving high intensity interval training for colorectal cancer survivors and the general population may be of great benefit. It is critical not to forget all the other health benefits of exercise not focussed on by this study. Always consult a doctor before commencing an exercise program, especially if you wish to engage in high intensity exercise.

Further information/resources[edit]

The following websites provide information on the signs, symptoms, diagnosis and treatment for colorectal cancer.

References[edit]

  1. Devin, J. L., Hill, M. M., Mourtzakis, M., Quadrilatero, J., Jenkins, D. G., & Skinner, T. L. (2019). Acute high intensity interval exercise reduces colon cancer cell growth. The Journal of Physiology, 597(8), 2177-2184.
  2. Radak, Z., Tolvaj, D., Ogonovszky, H., Toldy, A., & Taylor, A. W. (2005). Exercise and cancer. Exercise and Diseases, 168-190.
  3. Kruk, J., & Aboul-Enein, H. Y. (2006) Physical activity in the prevention of cancer. Asian Pacific Journal of Cancer Prevention, 7:11-21.
  4. Rogers, C., Colbert, L. H., Greiner, J. W., Perkins, S. N., & Hursting, S. D. (2008) Physical activity and cancer prevention: pathways and targets for intervention. Sports Medicine, 38(4), 271-296.
  5. a b Meyerhardt, J.A., Giovannucci, E. L., Holmes, M. D., Chan, A. T., Chan, J. A., Colditz, G. A., & Fuchs, C. S. (2006) Physical activity and survival after colorectal cancer diagnosis. Journal of Clincal Oncology 24, 3527–3534.
  6. Dethlefsen, C., Pedersen, K. S., & Hojman, P. (2017). Every exercise bout matters: linking systemic exercise responses to breast cancer control. Breast Cancer Research and Treatment, 162, 399–408.
  7. Cullen, T., Thomas, A. W., Webb, R., & Hughes, M. G. (2016). Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume. Applied Physiology Nutrition and Metabolism 41, 803–808.
  8. Jozsi, A. C., Dupont-Versteegden, E. E., Taylor-Jones, J. M., Evans, W. J., Trappe, T. A., Campbell, W. W., & Peterson, C. A. (2000). Aged human muscle demonstrates an altered gene expression profile consistent with an impaired response to exercise. Mechanisms of ageing and development, 120(1-3), 45-56.
  9. Toft, A. D., Jensen, L. B., Bruunsgaard, H., Ibfelt, T., Halkjær-Kristensen, J., Febbraio, M., & Pedersen, B. K. (2002). Cytokine response to eccentric exercise in young and elderly humans. American Journal of Physiology-Cell Physiology, 283(1), C289-C295.
  10. Nieman, D. C., Nehlsen-Cannarella, S. L., Fagoaga, O. R., Henson, D. A., Utter, A., Davis, J. M., ... & Butterworth, D. E. (1998). Influence of mode and carbohydrate on the cytokine response to heavy exertion. Medicine and Science in Sports and Exercise, 30(5), 671-678.
  11. Perrin, L., Loizides-Mangold, U., Skarupelova, S., Pulimeno, P., Chanon, S., Robert, M., ... & Lefai, E. (2015). Human skeletal myotubes display a cell-autonomous circadian clock implicated in basal myokine secretion. Molecular metabolism, 4(11), 834-845.
  12. Ahmed, D., Eide, P. W., Eilertsen, I. A., Danielsen, S. A., Eknaes, M., Hektoen, M., ... & Lothe, R. A. (2013). Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis, 2(9), e71.