# Exercise as it relates to Disease/The effect of resistance training on multiple sclerosis

This is a critique of a research article on the effects of resistance exercise on Multiple Sclerosis patients (2016)

## What is the background to this research?

Multiple Sclerosis (MS) is a chronic disease that is characterised by lymphocytes crossing the blood-brain barrier of the brain and damaging the axons and myelin sheaths of the Central Nervous System. This damage can cause many problems in MS patients, such as a variety of physical and cognitive disabilities, and issues in inflammatory cytokine processes. This study examines how certain inflammatory cytokines respond to resistance exercise.

## Where is the research from?

This study was conducted in Denmark, using participants from the Aarhus University Hospital and an MS Clinic in South Jutland. The target population was 18-60-year-old patients that have been diagnosed with relapsing-remitting Multiple Sclerosis, classified by two criteria. This range targets the majority of the MS patient population, particularly those who typically want to start participating in exercise regimes. Patients with comorbidities such as cardiovascular diabetes and pregnancy were excluded from the study. Thus, the study can be generalised to those MS patients who have no other variables, however, the findings are not necessarily applicable to the rest of the population affected by MS. The authors of this study have also conducted a number of other studies on the effects of exercise on Multiple Sclerosis, which can be found in the related readings sections. There was no potential for conflict of interest in the findings due to the researchers coming from different departments between the two clinics used in the target group.

## What kind of research was this?

The research that was conducted was a randomized control trial, investigating the effects of single-bout resistance exercise on acute cytokine response, and long-term progressive-resistance training on the chronic cytokine response. Measurements were taken both before and after the training intervention. In experiments that have no control groups, results are similar for both the PCT group and single-bout resistance group in this study.

## What did the research involve?

This study split the 35 participants into two groups; the training group (n= 18), and the control group (n= 17). The control group continued to live their normal lifestyle over the course of the experiment, while the training group conducted a 24-week Progressive Resistance Training (PRT) program.
Both groups had their condition assessed according to the EDDS, and had a functional capacity and muscle strength test conducted prior to and after the invention. The following protocols were also conducted over the course of the intervention:

### Single-bout resistance program

At the commencement of the study, a single-bout resistance program was performed by the training group. This program was 4 sets of 10 of the following exercises conducted at 10RM:
* Horizontal leg press
* Unilateral hip flexion
* Leg extension
* Prone hamstring curl
There was a 2-minute space between each set, and the program lasted approximately 30 minutes. While the training group exercised, the control group rested for 30 minutes.
After the resistance program, a series of blood sampling tests were conducted on both groups at the 0, 15, 45, 75, 120-minute intervals. The blood tests were used to monitor the response of the following pro- and anti-inflammatory cytokines:
| Pro-inflammatory | Anti=inflammatory |
| Interleukin-1 beta (IL-1β) | Interleukin-4 (IL-4) |
| Interleukin-2 | Interleukin-10 (IL-10) |
| Tumour Necrosis Factor alpha (TNF-α) | |
| Interneferon gamma (IFN-γ) | |
This process was repeated 24 weeks later, at the end of the PRT program.

### Progressive Resistance Training (PRT) program

This program was conducted twice a week for 24 weeks under supervision. It consisted of the lower body exercises from the single-bout session, as well as cable pull downs and cable tricep extensions. The sessions progressed from 10 reps at 15RM to 6 reps at 6RM by the end of the study, and the number of sets progressed from 3-5. Due to the increased load, rest between sets increased to 2-3 minutes.
This very detailed methodology is a very good approach to determine the effectiveness of this training program. There are multiple avenues of showing improvement in the body, and those ways are also physically tested, rather than being relied upon by self-report. It is also a good approach to supervise the training sessions, negating the bias again from the self-report.

### Critique

Although this research does limit a large amount of bias that is present in studies similar to this by having a larger number of experimenters, the inclusion of a control group is a good way of proving whether or not the exercise did have an effect on the specific cytokines studied. However, during the initial blood test, only the training group conducted exercise prior to the blood test. Although both groups were tested at a resting state, to make the results more reliable, having the initial and final blood tests conducted with exercise in both groups may show a better correlation between the effects of exercise on the cytokines. Another limitation of the study is that the participants had no other co-morbidities with their multiple sclerosis. This vastly limits the generalisation of the data. It is also from a select group from 2 hospitals in Denmark, potentially further limiting this generalisation. Also, depending on the number of people taking the blood samples, there may be some inconsistencies in that data.

## What were the basic results?

There were 3 important results that were measured both prior to and after the intervention:

### Resting cytokine levels

There was no observable interaction between time and group in any of the cytokines. However, the study highlighted that the IL-23 cytokine had a significant group effect, with higher levels in the control group than in the training group. When INF-β medication was implemented, there were still no interactions present.

### Single-bout resistance exercise cytokine levels

Like the resting levels, there was no interaction between group and time observed. The IL-17F cytokine however demonstrated a time effect. It was not specified which group this was for by the author, but the data indicates it was the training group by a significant margin.

### Repeated single-bout resistance exercise cytokine levels

In this test, there was no interaction between test number and time for any of the cytokines assessed. IL-17F showed a significant effect of test number, which indicated a higher cytokine fold as a response to the exercise before the intervention. The two other cytokines that indicated higher concentrations before the PRT program were IL-4 and IFN-γ.

## What conclusions can we take from this research?

This study showed that the effects of resistance exercise significantly improved the training group subjects’ functional capacity and muscular strength. However, there is insufficient evidence to determine the effects of exercise on the anti- and pro- inflammatory cytokines. However, IL-17F was brought up frequently in the results, however the cause is unclear, so requires further testing. IL-4, IL-10, IFN-%gamma; have also been shown to have lowered concentrations after training, with TNF-α showing insignificant reductions, and IL-2 and IL-1%beta; not changing at all. In other research, it was found that muscle strength had enhanced by 10% in all subjects and some even improved their aerobic capacity.

## Practical advice

This study has shown that on a grand scale there are health benefits to doing resistance training for people with MS, provided there are no co-morbidities associated with the MS. On a biological level, there is greater functional capacity, which helps employability of these patients, and the strength gains allow them to eventually develop the strength further. However, as mentioned in this critique, it is not generalisable to the whole MS population, so it is essential to consult a General Practitioner before attempting such a program.

## Further information/resources
### Readings

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?
Can aerobic exercise alleviate flu-like symptoms following interferon beta-1a injections in patients with multiple sclerosis?
Can we trust self-reported walking distance when determining EDSS scores in patients with multiple sclerosis?
Aerobic capacity is not associated with most cognitive domains in patients with Multiple Sclerosis – A cross-sectional investigation.
Is there an overlooked “window of opportunity” in MS exercise therapy? Perspectives for early MS rehabilitation.

## References

* ↑ Kjølhede T., Dalgas U., Gade B., Bjerre M., Stenager E., Petersen T., Vissing K. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis. Scand J Med Sci Sports 2016: 26: 824-834.
* ↑ Compston A., Coles A. Multiple sclerosis. Lancet 2008: 372(9648): 1502-1517.
* ↑ Barkhof F., Calabresi PA., Miller DH., Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009: 5(5): 256-266.
* ↑ Ozenci V., Kouwenhoven M., Huang YM., Xiao B., Kivisäkk P., Fredrikson S., Link H. Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment. Scand J Immunol. 1999: 49(5) 544-561.
* ↑ McDonald WI., Compston A., Edan G., Goodkin D., Hartung HP., Lublin FD., McFarland HF., Part DW., Polman CH., Reingold SC., Sandberg-Wolheim M., Sibley W., Thompson A., van den Noort S., Weinshenker BY., Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001: 50(1): 121-127.
* 1 2 Kurtzke JF. Rating neurologic impairment in multiple-sclerosis - an Expanded Disability Status Scale (EDSS). Neurology. 1983: 33(11): 1444-1452.
* 1 2 White LJ., Castellano V., Mc Coy SC. Cytokine responses to resistance training in people with multiple sclerosis. J Sports Sci. 2006: 24(8): 911-914.
* ↑ Sugama K., Suzuki K., Yoshitani K., Shiraishi K., Kometani T. IL-17, neutrophil activation and muscle damage following endurance exercise. Exerc Immunol Rev. 2012: 18: 116-127.
* ↑ Isner-Horobeti M.E., Zaencker P., Lonsdorfer E., Vautravers P., Favret F., De Sèze J. Effect of aerobic and resistance exercise training in multiple sclerosis patients. Annals of Physical and Rehabilitation Medicine. 2014: 57(1): e306.