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

The following is a critque of the journal article "acute high intensity interval exercise reduces colon cancer cell growth" 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 research?

According to the World Cancer Research Fund, colorectal cancer is the third most common form of cancer in men and second most common in women. Exercise is known to have significant preventative effect on the prevalance of cancer. Exercise also decreases mortality rates in colorectal cancer survivors. A suggested mechanism for these benefits of exercise has to do with the release of anti-inflammatory chemicals, called cytokines, after exercise. The study by Devin et al. aims to observe the immediate and long term effects of these cytokines on colorectal cancer cell growth after high intensity interval exercise (HIIE). HIIE was chosen because it causes a larger release of these cytokines than moderate intensity exercise. The results of this study will help health professionals to better understand one of the possible mechanisms behind the benefits of exercise as it relates to colorectal cancer and inform a more accurate prescription of exercise to colorectal cancer survivors. This research also fills a gap in current knowledge in regards to the acute and chronic impact exercise has on colorectal cancer growth.

### Where is the research from?

This study comes from The University of Queensland in Brisbane, Australia. It was funded by The University 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, there is reason to assume that no bias is being caused by the financial bodies behind the study.

### What kind of research was this?

This study consisted of 2 kinds of research:
* Human Clinical Trial
* In Vitro
It is important to note that "in vitro" studies are not always reflective of all the physiological mechanisms occurring at the cellular level due to the separation of the cells from the whole organism. Since the cells are looked at in isolation, other reactions or processes that may affect the cells within the body cannot be observed.

### What did the research involve?
#### Human Clinical Trial

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, there is a decreased cytokine response to exercise. Due to this impaired cytokine response to exercise, the effects on cancer cells may be different when exercising younger patients. Group 1 (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, 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. Group 2 (short term) completed the same exercise session 3 times a week for 4 weeks. In the acute treatment group, blood was sampled prior to exercise (fasted), immediately after exercise and 120 minutes post exercise. The short term treatment group had blood samples taken 3-7 days prior to beginning the intervention and following the intervention. Blood samples in this group were taken at the same time of day, this is an important control measure as cytokine secretion from muscles, when not prompted by exercise, follow a circadian rhythm. Blood samples were centrifuged to create serum and were analysed 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

Two genetically different colorectal cancer cell lines were obtained. The genetic differences in cells were chosen as different genes produce different types of mutation in colorectal cancer cells. 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, immediately after, or 120 minutes post exercise. Serum used was obtained from the blood samples of 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?

* All cytokines were significantly elevated from rest levels immediately after exercise but returned to resting levels 120 minutes after exercise.
* No change in resting levels of the cytokines measured was observed after a 4 week HIIE 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?

HIIE 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 isolated nature of the in vitro study, which the author acknowledges, 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 important to note that the cell count decrease was seen when cancer cells were 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. The author also brings to light other limitations to the study such as the lack of a non-exercising control and the small sample size used. The author appropriately suggests that further research could also be conducted into the changes in the cytokine response to exercise over a multiple week period of HIIE training.

### Practical advice

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. 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.
* Reduced Risk: Research suggests that regular physical activity, including HIIE, is associated with a decreased risk of colon cancer. A meta-analysis published in the British Journal of Cancer in 2016 found that higher levels of physical activity were associated with a 24% lower risk of colon cancer compared to individuals with low levels of physical activity.
* Mechanisms: HIIE and other forms of exercise may influence multiple biological mechanisms that could reduce the risk of colon cancer. These mechanisms include decreased inflammation, improved insulin sensitivity, regulation of hormone levels (such as insulin and insulin-like growth factor-1), and enhanced immune function. These effects may collectively contribute to a lower risk of developing colon cancer.
* Body Weight and Fat Reduction: HIIE can be particularly effective in reducing body weight and fat mass. Obesity and excess body fat are established risk factors for colon cancer. By helping individuals achieve and maintain a healthy weight, HIIE may indirectly lower the risk of colon cancer.
* Improved Gut Health: Exercise, including HIIE, may positively influence gut health by promoting a diverse and healthy gut microbiota composition. A balanced gut microbiota has been linked to a reduced risk of various diseases, including colon cancer.
* Enhanced Detoxification: Regular exercise, including HIIE, can enhance detoxification processes within the body, potentially reducing the accumulation of harmful substances in the colon that could contribute to carcinogenesis.
* Adherence to Guidelines: Current guidelines for cancer prevention typically recommend regular physical activity as part of a healthy lifestyle. HIIE can offer a time-efficient way to meet these guidelines, as it involves short bursts of intense exercise interspersed with brief periods of rest.
* HIIE can be particularly effective in reducing body weight andfat mass

### Further information/resources

The following websites provide information on the signs, symptoms, diagnosis and treatment for colorectal cancer.
* Cancer Council Australia - Bowel/Colorectal Cancer
* American Cancer Society - What is Colorectal Cancer?

### References

* ↑ 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.
* ↑ World Cancer Research Fund. (2018). Colorectal Cancer Statistics. Retrieved from World Cancer Research Fund: https://www.wcrf.org/dietandcancer/cancer-trends/colorectal-cancer-statistics
* ↑ Radak, Z., Tolvaj, D., Ogonovszky, H., Toldy, A., & Taylor, A. W. (2005). Exercise and cancer. Exercise and Diseases, 168-190.
* ↑ Kruk, J., & Aboul-Enein, H. Y. (2006) Physical activity in the prevention of cancer. Asian Pacific Journal of Cancer Prevention, 7:11-21.
* ↑ 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.
* 1 2 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.
* ↑ 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.
* ↑ 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.
* ↑ 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.
* ↑ 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.
* ↑ 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.
* ↑ 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.
* ↑ 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.
* ↑ Malik, Nishant. "Birthday wishes quotes".
* ↑ Nishant, malik (2024-07-08). "Insta Bio | Facebook Bio | WhatsApp Bio -". Retrieved 2024-07-09. {{cite web}}: Check |archive-url= value (help)
* ↑ Malik, Nishant (22-02-24). "Happy Birthday Wishes – Happy Birthday Wishes-". Birthday wishes Quotes. Retrieved 2024-02-22. {{cite web}}: Check date values in: |date= (help)CS1 maint: url-status (link)