Wahls Multimodal Pilot Studies in Progressive Multiple Sclerosis

Table of Contents

1. 1. From One Case to a Pilot Study
2. 2. How the Pilot Study Was Set Up
3. 3. The Five Parts of the Intervention
4. 4. The 2014 Feasibility and Fatigue Report
5. 5. Fatigue and Quality of Life in Twenty Participants
6. 6. Walking and Balance
7. 7. Mood and Thinking
8. 8. Blood Fats and Fatigue
9. 9. Cardiometabolic Markers
10. 10. The Remote Program for Newly Diagnosed People
11. 11. What the Authors Say About Their Own Results
12. Key Research Papers
13. Connections

1. From One Case to a Pilot Study

Wahls was diagnosed with relapsing-remitting multiple sclerosis in 2000 and, by her own account, had moved to the secondary progressive form by 2003. She writes that she used a tilt-recline wheelchair for four years and that in December 2007 she began the program she later named the Wahls Protocol. Within a year, she reports, she was walking through the hospital without a cane and completed an 18-mile bicycle tour.

Two short publications came before the pilot study. The first was a 2009 case report in Cases Journal by a physical therapist, a neurologist, Wahls and two University of Iowa rehabilitation scientists. It describes a 52-year-old woman with secondary progressive multiple sclerosis who had been scooter- and cane-dependent for four years. She asked for and received a trial of neuromuscular electrical stimulation; two months later she added several nutritional changes intended to lower oxidative stress and excitotoxicity. The therapist observed modest gait gains in the first two months and faster gains in strength and endurance after the diet was added, including in muscles that were not being stimulated. After eight months of stimulation (six months of the nutritional changes) she no longer used a scooter or cane and rode her bicycle routinely for 8 miles, including hills. A later paper from Wahls’s group identifies this case as her own.

The second was a 2010 case series that Wahls led in the Journal of Alternative and Complementary Medicine. It reviewed the clinic notes of nine people with progressive multiple sclerosis (seven secondary progressive, two primary progressive) treated in a private physical-therapy practice between June 2007 and June 2009 with neuromuscular electrical stimulation plus a home-exercise program. They had been diagnosed for a mean of 10.4 years and had a mean Expanded Disability Status Scale score of 5.9 at presentation. Over a mean of 140 days of stimulation, the mean disability score improved by 0.78 points. The authors concluded that additional studies were warranted. The stimulation side of the program is covered in more detail on the exercise, electrical stimulation and stress reduction page.

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2. How the Pilot Study Was Set Up

The pilot study was registered on ClinicalTrials.gov as NCT01381354, with Wahls as the responsible investigator; the registry lists a start in October 2010 and the study as completed. The published papers describe it as a single-arm, open-label intervention study in an outpatient setting — one group of participants, all receiving the program, with no comparison group and with participants and staff aware of the treatment. The 2017 gait paper calls it a prospective longitudinal pilot study; the 2017 mood paper calls it a one-arm, open-label feasibility trial.

The study ran for 12 months. Participants kept daily logs of what they did, from which the team calculated adherence to each part of the program. Side effects were tracked with a monthly questionnaire and blood tests. The main assessments were made at the start and at 3, 6, 9 and 12 months; the first report also collected fatigue data at months 1 and 2.

The participants all had progressive forms of the disease. The first report enrolled 13 people with secondary progressive multiple sclerosis into a two-week run-in phase, of whom 10 were eligible to continue. The later papers describe a 12-month group of 20 people with progressive multiple sclerosis whose average Expanded Disability Status Scale score was 6.2 (range 3.5 to 8.0) and whose mean age was 51.7 years. The lipid and cardiometabolic papers analysed the 18 and 19 participants who had the relevant blood samples.

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3. The Five Parts of the Intervention

The 2017 mood paper lists the home-based program in four numbered parts, and the other papers add the supplements as a separate item:

• A modified Paleolithic diet. The 2019 lipid paper describes it as a diet that recommended a high intake of vegetables and fruits, encouraged animal and plant protein, and excluded gluten-containing grains, dairy and eggs. The fuller food rules of the Wahls diets are set out on The Wahls Protocol page.
• Nutritional supplements. The first report notes that supplement intake “varied among and within subjects”.
• An exercise program of stretching and strengthening of the trunk and lower-limb muscles.
• Neuromuscular electrical stimulation of the trunk and lower-limb muscles, applied during the strengthening exercises.
• Stress management through meditation and self-massage.

The program follows the reasoning Wahls set out from her own case: that nutrition aimed at the nervous system and the cells’ energy supply, combined with stimulation and gradual exercise of weakened muscles, might help function in progressive disease. Her team’s later review describes the Wahls diet as designed “to reduce oxidative stress and excitotoxicity, nourish the mitochondria, prevent nutrient deficiencies, minimize food allergies and reduce toxic load, feed the microbiome, activate anti-inflammatory genes and increase nerve growth factors.” Her argument about nutrients and mitochondria is described on the Minding My Mitochondria page.

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4. The 2014 Feasibility and Fatigue Report

The first paper, by Bisht and colleagues with Wahls as senior author, appeared in the Journal of Alternative and Complementary Medicine in 2014. Its two questions were whether people with secondary progressive multiple sclerosis could carry out such a demanding program at home, and whether their fatigue changed. Fatigue was measured with the Fatigue Severity Scale, a questionnaire on which higher scores mean more fatigue.

The abstract reports:

• Of 13 people who entered the two-week run-in, 10 were eligible to continue to the 12-month main study; 8 of those 10 completed it, and 6 fully adhered to the program for the full 12 months.
• Over the year, average adherence to the diet exceeded 90% of days, and adherence to exercise and muscle stimulation exceeded 75% of days.
• The group’s daily averages were 13.3 minutes of meditation and 7.2 minutes of massage.
• No adverse side effects were reported.
• The group’s average Fatigue Severity Scale score fell from 5.7 at the start to 3.32 at 12 months (p=0.0008).

The authors described the work as a “small, uncontrolled pilot study” in which there was a significant improvement in fatigue among those who completed it, and wrote that, given the small sample and the completion rate, further evaluation of the multimodal therapy was warranted.

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5. Fatigue and Quality of Life in Twenty Participants

The full 12-month group of 20 people with progressive multiple sclerosis was reported in 2015 in Degenerative Neurological and Neuromuscular Disease. Besides the Fatigue Severity Scale, the team used the fatigue subscale of the Performance Scales and the RAND 36-item Health Survey (Short Form-36), a general quality-of-life questionnaire.

According to the abstract, participants showed good adherence, based on their daily logs, and reported no serious side effects. Fatigue Severity Scale and Performance Scales fatigue scores fell over the 12 months (P<0.0005), and the energy and general-health scores of the Short Form-36 rose (P<0.05).

The team then split the group by how much each person’s fatigue changed:

• Eleven participants had a reduction in average fatigue score of more than two points by 3 months — called a high response — and that improvement was sustained to 12 months.
• The other nine (low responders) showed either inconsistent changes or a decrease of less than one point.
• Larger falls in fatigue were associated with shorter disease duration and with lower disability scores at the start.
• Compared with low responders, high responders had less physical disability and a lower intake of gluten, dairy products and eggs at the start (P=0.036), and they spent longer on massage and on stretches per muscle over the year.

The authors concluded that a multimodal intervention “may reduce fatigue and improve quality of life” in progressive multiple sclerosis, and that “Larger randomized controlled trials with blinded raters are needed to prove efficacy of this intervention on MS-related fatigue.”

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6. Walking and Balance

A 2017 paper in the same journal looked at walking performance and balance in the same 20 participants (mean age 51.7 years, Expanded Disability Status Scale score 6.2). The tests included the timed up-and-go test (standing up from a chair, walking a short distance, turning and sitting down again), the timed 25-foot walk and the Berg Balance Scale.

For the whole group, the abstract reports no significant changes in any assessment over 12 months, apart from a faster walking speed toward the 10-foot mark of the timed up-and-go test at 6 months compared with the start (a mean change of 7.9 cm per second, p=0.041).

The team then divided the group in half according to how their timed up-and-go time changed:

• Ten responders — people whose time fell from the start at three or more of the four follow-up visits. Over 12 months their mean timed up-and-go time fell by 31%, their median Berg Balance Scale score rose from 42 to 47, and their mean timed 25-foot walk speed rose by 30% (the paper notes that more than 20% is considered clinically significant), with longer steps and shorter step duration.
• Ten non-responders, whose walking ability deteriorated over the 12 months.

The two subgroups did not differ significantly in how closely they followed the program, but the responders had better stride duration and longer step length at the start. The authors wrote that the intervention may improve walking and balance in people with progressive multiple sclerosis who have mild-to-moderate gait impairment, “whereas subjects with severe gait impairments may not respond to this intervention”, and that future trials could test it in earlier stages of the disease.

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7. Mood and Thinking

Also in 2017, Lee and colleagues reported mood and cognitive results from the program in the Journal of the American College of Nutrition. Mood was measured with the Beck Anxiety Inventory and Beck Depression Inventory; thinking was measured with the Cognitive Stability Index, a cognitive screening test, the Delis-Kaplan Executive Function System and the Wechsler Adult Intelligence Scale. The team also measured the “dosage” of the program each person actually carried out at 3, 6, 9 and 12 months.

The abstract reports that the more participants took part in the program’s activities, the greater their improvements from the start to 12 months in self-reported anxiety, depression, cognitive function and executive function. Further findings:

• Mood and cognitive improvements were more closely related to a higher intake of the modified Paleolithic diet than to the amount of exercise and stress management.
• Changes in anxiety and depression appeared after a few months, while changes in cognitive function were generally not seen until later in the year.
• Changes in mood and thinking were significantly associated with improvements in fatigue.

The authors concluded that an intervention like this one “has the potential to improve the mood and cognitive symptoms” that cause considerable suffering in people with multiple sclerosis.

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8. Blood Fats and Fatigue

In 2019 a team from the State University of New York at Buffalo, working with Wahls and her Iowa colleagues, published an analysis in PLoS One of blood fats in 18 participants who had fasting blood samples at the start and at 12 months. They measured high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol and triglycerides, as well as body mass index.

The abstract reports, for this subgroup:

• The average Fatigue Severity Scale score fell from 5.51 at the start to 3.03 at 12 months (p<0.001).
• High-density lipoprotein (HDL) cholesterol rose by a mean of 6.0 mg/dl (p=0.049).
• Low-density lipoprotein (LDL) cholesterol fell by a mean of 10.4 mg/dl (p=0.029), triglycerides by 29.2 mg/dl (p=0.001) and body mass index by 2.6 kg/m² (p<0.001); the triglyceride-to-HDL and total-cholesterol-to-HDL ratios each fell by 0.6.
• Improvements in fatigue were associated with increases in high-density lipoprotein cholesterol and with changes in total cholesterol.

The authors concluded that lipid profile variables “are associated with improvements in fatigue” in people with progressive multiple sclerosis on a diet-based multimodal intervention.

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9. Cardiometabolic Markers

A secondary analysis of the same pilot, published in Nutrients in 2025, looked at further heart-and-metabolism markers in 19 participants: apolipoproteins A1, B and E (the protein carriers of blood fats), creatine kinase (a muscle enzyme), fasting glucose and insulin, and two measures calculated from glucose and insulin — insulin resistance (the Homeostasis Model Assessment of Insulin Resistance) and insulin-producing cell function.

The abstract reports that at 12 months:

• Apolipoprotein B showed a marginally significant decrease (mean change −7.17 mg/dL, p=0.06).
• There were no significant changes in apolipoprotein A1, apolipoprotein E, creatine kinase, insulin resistance or insulin-producing cell function.
• An increase in insulin resistance was linked with an increase in fatigue (p=0.02), but this association was no longer significant after outliers were excluded.

The authors concluded that the program “did not negatively impact glycemic and lipid profiles”, that the improvements seen in blood markers were not statistically significant, and that larger, controlled studies would be needed to confirm any cardiometabolic benefit in people with progressive multiple sclerosis.

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10. The Remote Program for Newly Diagnosed People

Following the gait paper’s suggestion to test the approach earlier in the disease, Wahls’s team ran a second multimodal study (ClinicalTrials.gov NCT04009005) in people newly diagnosed with clinically isolated syndrome (a first episode of symptoms typical of multiple sclerosis) or relapsing-remitting multiple sclerosis. Its main results appeared in 2024 in Degenerative Neurological and Neuromuscular Disease.

The design was a 12-month prospective quasi-experimental non-inferiority pilot: participants were not randomized but chose their group. Twenty-nine people who had voluntarily declined disease-modifying therapies formed the health-behavior group and were coached remotely on the study diet, moderate-intensity walking and breathing exercises; 15 people who followed the standard of care formed the comparison group. A non-inferiority design asks whether one approach gives results that are not worse than another, rather than whether it is better.

The abstract reports:

• Over 12 months, the health-behavior group improved in mental quality of life, fatigue (on the Modified Fatigue Impact Scale) and perceived cognitive function.
• A difference between the two groups was seen only for one planning subscale of the cognitive questionnaire (p=0.048).
• The 12-month changes in the health-behavior group were not worse than those in the standard-of-care group for fatigue, anxiety, depression, physical quality of life and cognitive difficulties.

The authors concluded that, for newly diagnosed people who voluntarily decline disease-modifying therapies, the program “did not yield patient-reported outcomes worse than those observed in the SOC group” (the standard-of-care group) for mental quality of life, mood, fatigue and cognitive function. The outcomes were questionnaires completed by the participants; the abstract does not report relapse rates or brain scans.

A companion 2024 paper in Frontiers in Nutrition examined three-day self-reported dietary recalls from the same two groups. More than 80% of both groups completed them at 12 months. From the start to 12 months the health-behavior group ate fewer total grains and added sugars and more cured meats, while the standard-of-care group ate less beef, veal, pork, lamb and game meat. At 12 months, more than 20% of the health-behavior group had inadequate intake of vitamin D (43.5%), vitamin E (29.1%), calcium (69.9%) and copper (27.8%). The standard-of-care group, on its own diet, had inadequate intakes of the same nutrients except copper, and also of vitamin A, thiamin, riboflavin, folate, vitamin B12 and zinc, each above 20%. The authors wrote that, compared with the usual diet, the modified Paleolithic elimination diet within the program may lead to reduced intake of some food groups such as added sugars and a lower risk of severe inadequacy for certain nutrients.

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11. What the Authors Say About Their Own Results

The pilot papers state their own design limits plainly. The 2014 report calls itself a “small, uncontrolled pilot study” and points to the small sample and completion rate. The 2015 paper writes that larger randomized controlled trials with blinded raters are needed to prove the effect on fatigue. The 2017 gait paper reports that half of the group improved and half declined, and that people with severe gait impairment may not respond. The 2025 cardiometabolic paper calls for larger, controlled studies.

Three features of the design are stated in the papers themselves: all participants in the progressive-disease pilot received the whole program, so the separate effect of the diet, the supplements, the exercise, the stimulation and the stress management cannot be told apart; there was no untreated comparison group; and several outcomes, including fatigue, mood and quality of life, were measured with questionnaires completed by participants who knew they were in the program. The 2017 mood paper is the one analysis that compared the parts with one another, and it found the diet more closely linked to the improvements than the exercise or stress-management dose.

Wahls’s group went on to test the diet itself in randomized trials: a 2017 randomized pilot of a modified Paleolithic diet in relapsing-remitting multiple sclerosis, a three-arm comparison with a ketogenic diet, and the larger WAVES trial comparing the Wahls Elimination and low-saturated-fat Swank diets. Those studies, and the later systematic reviews of diet in multiple sclerosis, are described on the randomized diet trials page. In a 2022 review Wahls herself wrote that no dietary pattern has yet been proven effective for reducing relapses or enhancing lesions, while several pilot studies show reduced multiple sclerosis-related symptoms.

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Key Research Papers

1. Bisht B, Darling WG, Grossmann RE, Shivapour ET, Lutgendorf SK, Snetselaar LG, Hall MJ, Zimmerman MB, Wahls TL. A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med. 2014;20(5):347-55. — PubMed PMID: 24476345
2. Bisht B, Darling WG, Shivapour ET, Lutgendorf SK, Snetselaar LG, Chenard CA, Wahls TL. Multimodal intervention improves fatigue and quality of life in subjects with progressive multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2015;5:19-35. — PubMed PMID: 30728736
3. Bisht B, Darling WG, White EC, White KA, Shivapour ET, Zimmerman MB, Wahls TL. Effects of a multimodal intervention on gait and balance of subjects with progressive multiple sclerosis: a prospective longitudinal pilot study. Degener Neurol Neuromuscul Dis. 2017;7:79-93. — PubMed PMID: 30050380
4. Lee JE, Bisht B, Hall MJ, Rubenstein LM, Louison R, Klein DT, Wahls TL. A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis. J Am Coll Nutr. 2017;36(3):150-168. — PubMed PMID: 28394724
5. Fellows Maxwell K, Wahls T, Browne RW, Rubenstein L, Bisht B, Chenard CA, et al. Lipid profile is associated with decreased fatigue in individuals with progressive multiple sclerosis following a diet-based intervention: Results from a pilot study. PLoS One. 2019;14(6):e0218075. — PubMed PMID: 31211794
6. Martinez AS, Bastian AJ, Shemirani F, Titcomb TJ, Bisht B, Darling WG, et al. Effects of a Multimodal Lifestyle Intervention on Cardiometabolic Markers in People with Progressive Multiple Sclerosis: A Secondary Analysis of a Pilot Study. Nutrients. 2025;17(7):1163. — PubMed PMID: 40218921
7. Saxby SM, Shemirani F, Crippes LJ, Ehlinger MA, Brooks L, Bisht B, et al. Effects of a Remote Multimodal Intervention Involving Diet, Walking Program, and Breathing Exercise on Quality of Life Among Newly Diagnosed People with Multiple Sclerosis: A Quasi-Experimental Non-Inferiority Pilot Study. Degener Neurol Neuromuscul Dis. 2024;14:1-14. — PubMed PMID: 38222092
8. Saxby SM, Ehlinger MA, Brooks L, Titcomb TJ, Ten Eyck P, Rubenstein LM, et al. Feasibility and assessment of self-reported dietary recalls among newly diagnosed multiple sclerosis: a quasi-experimental pilot study. Front Nutr. 2024;11:1369700. — PubMed PMID: 39464680
9. Reese D, Shivapour ET, Wahls TL, Dudley-Javoroski SD, Shields R. Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report. Cases J. 2009;2:7601. — PubMed PMID: 19918474
10. Wahls TL, Reese D, Kaplan D, Darling WG. Rehabilitation with neuromuscular electrical stimulation leads to functional gains in ambulation in patients with secondary progressive and primary progressive multiple sclerosis: a case series report. J Altern Complement Med. 2010;16(12):1343-9. — PubMed PMID: 21138391
11. Chenard CA, Rubenstein LM, Snetselaar LG, Wahls TL. Nutrient Composition Comparison between a Modified Paleolithic Diet for Multiple Sclerosis and the Recommended Healthy U.S.-Style Eating Pattern. Nutrients. 2019;11(3):537. — PubMed PMID: 30832289
12. Wahls TL. Dietary Approaches to Treating Multiple Sclerosis-Related Symptoms. Phys Med Rehabil Clin N Am. 2022;33(3):605-620. — PubMed PMID: 35989054

PubMed Topic Searches

1. Multimodal intervention in progressive multiple sclerosis (Wahls)
2. Modified Paleolithic diet and fatigue in multiple sclerosis
3. Neuromuscular electrical stimulation and gait in multiple sclerosis
4. Lifestyle interventions in newly diagnosed multiple sclerosis

Further Reading

• ClinicalTrials.gov NCT01381354 — nutrition, neuromuscular electrical stimulation and secondary progressive multiple sclerosis
• ClinicalTrials.gov NCT04009005 — the newly diagnosed multimodal study
• University of Iowa Wahls Lab — Terry Wahls, MD, MBA

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Connections

• Dr. Terry Wahls and the Wahls Protocol
• Terry Wahls: Life and Career
• The Wahls Protocol Diet Levels and Food Rules
• Minding My Mitochondria: Nutrients for the Brain
• Wahls Diet Randomized Trials in Multiple Sclerosis
• Exercise, Electrical Stimulation and Stress Reduction in the Wahls Protocol
• Terry Wahls: Books and Legacy
• Contemporary Practitioners
• Multiple Sclerosis
• Meditation
• Mitochondria
• Elimination Diet

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