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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: 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 http://www.terrywahls.com. 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.

Figures

Figure 1

Flowchart of the screening, enrollment, and follow-up of participants in the study. Abbreviations: S, subject; NMES, neuromuscular electrical stimulation; MS, multiple sclerosis.

Figure 2

Subject’s nine-item Fatigue Severity Scale scores during the study. Notes: Red dots represent individual subject scores and dotted lines represent mean scores. P<0.0005, statistical significant change from baseline to 3, 6, 9 and 12 months. Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months.

Figure S1

Subject’s Performance Scales-fatigue scores during the study. Notes: Upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median and + sign represents mean. The whisker error bars represent minimum and maximum values. **** represent median values overlapping with upper quartile values. ------ represent lower quartile values overlapping with minimum values. P= significant difference from baseline. Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months.

Figure 3

SF-36 energy, SF-36 general health and FSS-9 scores during the study, and correlation of mean SF-36 energy and mean SF-36 general health scores with mean FSS-9 scores at different time-points during the study. Notes: Data is shown as mean ± SE. r= Pearson’s correlation coefficient. **P<0.005, *P<0.05 for significant difference from baseline. Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months; SF-36, Short Form-36; FSS-9, nine-item Fatigue Severity Scale; SE, standard error.

Figure S2

Health related quality of life scores: (A) SF-36 physical functioning, (B) role physical, (C) bodily pain and (D) social function scores during the study. Notes: Upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median and + sign represents mean. The whisker error bars represent minimum and maximum values. **** represent median values overlapping with upper quartile values. ------ represent lower quartile values overlapping with minimum values. Abbreviations: B, baseline; 3M, 3 months; 6M, 6 months; 9M, 9 months; 12M, 12 months, SF-36, Short Form-36.

Figure S3

Comparison of baseline characteristics of good- and fair-responders in terms of (A) EDSS scores, (B) PDDS scores, (C) Sf-36 physical functioning scores and (D) mean daily serving of Gl + D + E. Notes: Red dots represent each subject’s score. In figures A–C, upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median. The whisker error bars represent minimum and maximum values. Overlapping values are indicated in the figure. In figure D, values are mean + SD. Abbreviations: EDSS, Expanded Disability Status Scale; Gl + Dr + E, gluten-containing grains + dairy products + eggs; max, maximum; md, median; min, minimum; PDDS, Patient Determined Disease Steps; SD, standard deviation.

Figure 4

Comparison of good- and fair-responders’ dosage of (A) average massage duration, (B) average duration of stretch per muscle, (C) average duration of meditation per day and (D) average exercise-NMES adherence during 12 months. Notes: Upper and lower borders of the boxes represent 25th and 75th percentiles respectively. The line within the boxes represents median and + sign represents mean. The whisker error bars represent minimum and maximum values. Red dots represent each subject’s score. Abbreviation: NMES, neuromuscular electrical stimulation.

Figure 5

Correlations between changes in FSS-9 scores and (A) duration since MS diagnosis, (B) baseline PDDS scale scores, (C) baseline EDSS scores. Notes:r, Pearson’s correlation coefficient; rs, Spearman’s correlation coefficient. After excluding data of two subjects (circled dots in C) with much lower baseline EDSS scores than other subjects, correlation stayed moderately positive (rs=0.482, P=0.022). Abbreviations: EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; PDDS, Patient Determined Disease Steps; FSS-9, nine-item Fatigue Severity Scale.