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From the Townsend Letter Archives
August/September 1999

Exercise Therapeutics Update & Commentary:
Exercise and Autoimmune Diseases
by Anna MacIntosh, PhD, ND
Dean of Research, National College of Naturopathic Medicine

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Effects of aerobic conditioning in lupus fatigue: A pilot study. Brit J Rheumatol. 1989; 28:500.
Summary: Even in a patient whose lupus is considered inactive, fatigue can still be debilitating. Treatment options to deal with this problem of fatigue are extremely limited. These authors wanted to investigate determinants of fatigue and test whether a mild aerobic exercise-training program would favorable impact fatigue in a group of patients with lupus.

Each of the 25 patients recruited for the study was given a variety of questionnaires to complete. These included a depression scale, a Profile of Mood States (this has a subscale for fatigue), and a specific scale to evaluate fatigue. Standard lab tests were done (i.e., complete blood counts and ESR – an indication of active inflammation). All patients underwent a bicycle ergometer test to assess Vo2max (a physiological indicator of aerobic fitness). The patients were divided into a treatment and control group. The treatment group was asked to walk, bicycle, or jog at least three times per week, at 60-80% of their maximum heart rate, for 30 minutes at a time. The control group was given stretching exercises to be performed at the same duration and frequency as the aerobic exercises for the treatment group.

At baseline, 39% of the patients met the criteria for depression (more than a normal population). According to the Profile of Mood States, these patients were no more fatigued than the average person. However, fatigue scores from this questionnaire were inversely correlated to duration of the baseline exercise test. The aerobic capacity of these patients at baseline was severely limited (45% of normal). After eight weeks of training, patients in the treatment group exhibited a 19% increase in Vo2max and a 12% increase in endurance on the post-training exercise test. In the control group, endurance times fell by four percent after eight weeks of flexibility exercises. Also, according to the fatigue scale, there was a significant decrease in fatigue ratings for the treatment compared to the control group.

Commentary: In conventional medicine, fatigue is often ignored or treated with anti-depressant medications. This may be especially true for patients with lupus who are not exhibiting any symptoms of an active disease state. Although these patients have a higher than usual chance of being depressed – and the Merck Manual suggests that in 80% of the patients who present with fatigue, the cause is depression – it is still worth determining (by using a questionnaire or clinical judgment) if the patient with lupus is truly depressed before prescribing anti-depressant medications. It is also noteworthy that this author thoroughly disagrees with the Merck Manual's description of the etiology of fatigue typically being depression. There are many "subclinical" organ dysfunctions that could account for fatigue, even with patients who have lupus. These include hypofunction of adrenals and/or thyroid and those organs important in helping to control blood sugar (i.e., pancreas, liver, adrenals).

It is also important to consider that significant detraining in patients with lupus may be an important etiological factor in their fatigue. The patients in this study had less than half the aerobic capacity that sex- and age-matched normal individuals would be expected to have. Since oxygen is an absolutely essential nutrient in order to "burn" fuels to provide energy to the whole body, it is not surprising that an individual’s ability to consume and utilize adequate amounts of oxygen could have a major impact on one's energy level. It appears that a moderate aerobic exercise program (done at home) is able to significantly lessen the fatigue in individuals with lupus. Perhaps a more moderate intensity exercise program would achieve the same effects if done for more than eight weeks. In fact, for individuals who are very fatigued, it makes good clinical sense to prescribe a progressive aerobic exercise program that can be readily accomplished on a daily basis and even during periods of mild disease activity.

Effectiveness of minimally supervised home aerobic training in patients with systemic rheumatic disease. Brit J Rheumatol. 1995;34:1064.
Summary: In this study as in the previous study, the investigators are interested in the impact of aerobic exercise training and the symptom of fatigue. Seventy-one individuals who had either rheumatoid arthritis (RA) or lupus agreed to participate in this exercise study. These investigators wanted to determine if aerobic exercise prescribed as a home-exercise program would lead to the same decline in indices of fatigue as exercise-training patients have done in a supervised environment.

The study was conducted in two phases. The first phase lasted three months, and the patients were split into control and exercise groups. Treatment group patients were given a stationary bicycle to take home, a specific exercise prescription (standard of three days per week, 30 min sessions, at 60-70% maximum heart rate), and were contacted by phone on a regular basis. The second phase of the study gave a similar exercise prescription, however, no phone contact was made, and the stationary bicycle was taken away. Before each phase, baseline measurements of endurance time, fatigue, depression, and helplessness were taken. These same measures were repeated at the end of each phase.

Although all measures in the exercising group compared to control group demonstrated greater improvement, none were significantly different. In general, patients with RA had greater improvements in all scores compared to patients with lupus. For the second phase of the study, the results were similar to the first phase, however, the differences between treatment and control groups were even smaller.

Commentary: These authors designed a good study to test the efficacy of an at-home exercise program on fatigue and depression indices in patients with systemic autoimmune diseases. Their results were somewhat disappointing when contrasted to other studies where the patients exercised under supervision. This suggests that compliance to the exercise program is a significant factor or that there is a selection bias in the study population. This means that only those patients motivated enough to engage in exercise training at home were already more active (i.e., aerobically trained). Whenever you start with a relatively trained group, the differences after a specific exercise program are going to be less significant. However, the low levels of endurance of all patients at the beginning of this study were similar to patient populations in supervised exercise studies.

Study subjects did report exercising 2.2 days per week; the authors did not report exercise compliance regarding duration of exercise sessions. This information does not rule out the confounding factor of compliance in explaining the results from this study. Perhaps the next step in utilizing exercise as a means of reducing fatigue and depression in patients with systemic autoimmune diseases would be to test an exercise program that is less intense, but of greater frequency (i.e., five to seven days per week rather than three days per week). Compliance may be improved if mild exercise becomes a daily habit of enjoyment rather than a periodic undertaking.

Exercise in ankylosing spondylitis: How much is optimum? J Rheumatol. 1998;25:2156.
Summary: Ankylosing spondylitis (AS) is essentially rheumatoid arthritis but affects the spinal joints rather than peripheral joints. Conventional treatment includes both non-steroidal anti-inflammatory drugs (NSAIDS) and therapeutic exercises to maintain normal posture and activity. Although the effectiveness of supervised, short-term exercise prescriptions have been demonstrated in a number of studies, it is not clear how well patients adhere to exercise programs on a long-term, at-home basis. If patients are continuing their exercise at home, the long-term effects of this exercise on disease activity and function are unknown.

Four thousand patients with AS were studied in a retrospective fashion. These patients were sent questionnaires asking about amounts and types of exercises they engage in and to rate how effective they thought exercise was to their improved functional capacity. Standardized AS symptom questionnaires were also filled out. Patient groups were established based on the number of hours per week that they exercised. Correlations were then sought between different patient groups, symptom scores, and functional capacity scores.

Those individuals who exercised two to four hours a week had higher functional capacity scores and lower disease activity scores compared to patients with AS who reported no exercise. When comparing these same parameters in individuals who exercised ten hours or more a week with those who did not exercise at all, the only difference was in functional capacity. Adherence to a regular exercise program was associated with number of visits to a rheumatologist, beliefs in the benefits of exercise, and a higher education level.

Commentary: It does appear that moderate, consistent activity levels can have long-term beneficial effects on both functional capacity and disease activity in patients with AS. Interestingly, there was not a dose-response benefit to amount of exercise and disease activity. In fact, at ten or more hours a week of exercise, there was no better control of disease symptomology than those individuals who did no exercise. This suggests that there might be an upper limit to the amount of exercise that is beneficial to patients with AS.

Again, the issue of patient compliance or adherence is crucial in determining success of an exercise program. Perhaps a practitioner could consider ways to alter patients' beliefs about the benefits of an exercise program. Education is one approach, but a specific written exercise prescription may lend credibility to the exercise program as a therapeutic modality and possibly influence beliefs of the patient regarding exercise as a medication.

Reduced muscle uptake of oxygen during exercise in patients with systemic lupus erythematosus. J Rheumatol. 1995;22:1483.
Summary: These authors wanted to investigate whether a limited oxygen supply to the exercising muscles may contribute to the limited aerobic capacity in patients with lupus. As a matter of comparison, three groups of patients underwent exercise testing to measure oxygen consumption as related to submaximal workloads. Group 1 patients consisted of women with a variety of diseases (none autoimmune), group 2 patients were women with chronic anemia, and group 3 patients were those with diagnosed lupus.

Aerobic exercise capacity was significantly lower in group 3 patients compared to the other two patient groups. Oxygen consumption indices were also significantly lower in the lupus patients compared to both other patient groups. A correlation was found between degree of disease activity and aerobic capacity, i.e., the higher the disease-activity index, the lower the aerobic capacity of the patient.

Commentary: The results of this study suggest that patients with lupus have an impairment in either oxygen diffusion into working skeletal muscles or are unable to adequately utilize the oxygen when delivered. Both factors may be important in explaining the limited aerobic capacity measured in patients with lupus. In particular, these authors speculate that chronic muscle inflammation may account for impairment of oxygen diffusion into skeletal muscles of patients with lupus. They go on to suggest that this may then account for the fatigue that is so prevalent in patients with lupus. It would be interesting to test whether altering an exercise prescription for the purpose of "hyperoxygenation" would be beneficial to patients with lupus. Alternatively, there are a number of oxygen solution products now available, and these may be beneficial for patients with lupus and they may enhance their aerobic capacity.

Many authors have suggested that deconditioning is the cause of the fatigue in patients with autoimmune diseases. Perhaps with aerobic exercise conditioning, there is an improvement in not only cardiovascular fitness, but also an improvement of oxygen uptake by the working skeletal muscles.

Sex as a determining factor in the effect of exercise on in vivo autoimmune response adjuvant arthritis. J Appl Physio. 1994;76(3): 1172.
Summary: A number of previous studies have investigated the immune-modulating effects of an exercise bout. However, no study has analyzed the effect of daily endurance exercise on the incidence and severity of an animal model autoimmune disease. Male and female rats were exercised daily for ten days before the onset of autoimmune disease symptoms. This autoimmune disease in rats is induced by the injection of a highly antigenic mixture in a certain strain of rats and is used as a model to study human rheumatoid arthritis. The rats were divided into four groups: male and female control groups and male and female exercise groups. Severity of arthritis was scored in each rat every two days. The incidence, maximum severity of the disease, and the day of disease onset was recorded for each of the four groups.

The incidence of disease was greater in the female compared to male rats and higher in female trained compared to female control, but lower in male trained compared to male controls. Disease severity was slightly better in the trained female compared to control female rats, while just the opposite was true in the male rats. These differences were not statistically significant.

Commentary: There were two surprising results from this study: 1) the clear difference in incidence of autoimmune disease in females compared to male rats; and 2) that the incidence of this autoimmune disease was greater in female, exercised animals compared to untrained controls. Perhaps the explanation for the different impact of the stress of daily exercise on males vs. females is based on sex steroid hormone differences. Testosterone tends to exacerbate autoimmune disease incidence in animals, whereas estrogens tend to lessen autoimmune disease incidence. Daily exercise would tend to decrease estrogens and allow testosterone effects to go unopposed, while in male rats, daily exercise would tend to suppress testosterone release.

It is important to understand that in this study the animals were not exercised over a sufficient period of time to become trained. It may be that the daily exercise imposed on the rats was of such intensity as to be too much of a stressor for the female rats. In general, with mild to moderate aerobic exercise training, exercise itself becomes less of a stressor. Perhaps the results would have been significantly different if the animals were exercised at a more moderate intensity for a sufficient amount of time (before inducing the disease) to allow for training adaptations to occur.

Column Summary
The results of a number of studies strongly suggest that a moderate aerobic exercise program can be beneficial to enhancing aerobic capacity and lessening fatigue in patients with systemic autoimmune diseases. Attention needs to be given by practitioners to discussing how to improve long-term adherence to an exercise program that is prescribed on an outpatient basis. Consider what is best for that patient, i.e., referral to supervised exercise program or ideas they can use to enhance at-home exercising (e.g., record keeping). Remember that the severely limited aerobic capacity often measured in patients with lupus may be a pathological impairment of oxygen delivery rather than "couch potato syndrome." Consider other ways to improve oxygenation in these patients.

Finally, consider that an aerobic exercise prescription which is more frequent, lower intensity (i.e., 40-50% of maximum vs. 70-80% of maximum) may be a more prudent exercise prescription for patients with autoimmune diseases. This may be especially important for female patients who have previously been very sedentary.


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