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Degener Neurol Neuromuscul Dis. 2015;5:19-35. doi: 10.2147/DNND.S76523. Epub 2015 Feb 27.

Multimodal intervention improves fatigue and quality of life in subjects with progressive multiple sclerosis: a pilot study.

Author information

Department of Internal Medicine, Carver College of Medicine, University of Iowa.
Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa.
Department of Neurology, Carver College of Medicine, University of Iowa.
Department of Psychology, College of Liberal Arts and Sciences, University of Iowa.
Department of Urology, Carver College of Medicine, University of Iowa.
Department of Epidemiology, College of Public Health, University of Iowa.
Department of Internal Medicine, VA Medical Center, Iowa City, IA, USA.



Fatigue is a disabling symptom of multiple sclerosis (MS) and reduces quality of life. The aim of this study was to investigate the effects of a multimodal intervention, including a modified Paleolithic diet, nutritional supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, and stress management on perceived fatigue and quality of life of persons with progressive MS.


Twenty subjects with progressive MS and average Expanded Disability Status Scale (EDSS) score of 6.2 (range: 3.5-8.0) participated in the 12-month phase of the study. Assessments were completed at baseline and at 3 months, 6 months, 9 months, and 12 months. Safety analyses were based on monthly side effects questionnaires and blood analyses at 1 month, 3 months, 6 months, 9 months, and 12 months.


Subjects showed good adherence (assessed from subjects' daily logs) with this intervention and did not report any serious side effects. Fatigue Severity Scale (FSS) and Performance Scales-fatigue subscale scores decreased in 12 months (P<0.0005). Average FSS scores of eleven subjects showed clinically significant reduction (more than two points, high response) at 3 months, and this improvement was sustained until 12 months. Remaining subjects (n=9, low responders) either showed inconsistent or less than one point decrease in average FSS scores in the 12 months. Energy and general health scores of RAND 36-item Health Survey (Short Form-36) increased during the study (P<0.05). Decrease in FSS scores during the 12 months was associated with shorter disease duration (r=0.511, P=0.011), and lower baseline Patient Determined Disease Steps score (r s=0.563, P=0.005) and EDSS scores (r s=0.501, P=0.012). Compared to low responders, high responders had lower level of physical disability (P< 0.05) and lower intake of gluten, dairy products, and eggs (P=0.036) at baseline. High responders undertook longer duration of massage and stretches per muscle (P<0.05) in 12 months.


A multimodal intervention may reduce fatigue and improve quality of life of subjects with progressive MS. Larger randomized controlled trials with blinded raters are needed to prove efficacy of this intervention on MS-related fatigue.


exercise; lifestyle changes; modified Paleolithic diet; neuromuscular electrical stimulation; stress management; supplements; vitamins

Conflict of interest statement

Disclosure Dr Terry Wahls has equity interest in the following companies: Dr Terry Wahls LLC; TZ Press LLC; Xcellerator LLC; RDT LLC; and the website She also owns the copyright to the books Minding My Mitochondria (2nd Edition) and The Wahls Protocol, and the trademarks The Wahls Protocol and Wahls Diet. She receives royalty payments from Penguin Random House. Dr Wahls has conflict of interest management plans in place with both the University of Iowa and the Veterans Affairs Iowa City Healthcare System. All the other authors report no conflicts of interest in this work.

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