Wahls Diet Randomized Trials in Multiple Sclerosis

Dr. Terry Wahls is an American internal-medicine physician and clinical professor of medicine at the University of Iowa Carver College of Medicine who has secondary progressive multiple sclerosis (MS) and built the Wahls Protocol, a nutrient-dense, modified Paleolithic diet that she credits with her own return to walking and cycling. After a first set of single-arm pilot studies that combined the diet with exercise, electrical muscle stimulation, meditation and massage, her research group at the University of Iowa turned to randomized trials that test the diet on its own.

This page walks through those randomized trials in the order they were published: the 2017 pilot of a modified Paleolithic diet against usual eating, the three-arm pilot that added a ketogenic diet, the larger WAVES trial that compared the Wahls Elimination diet with the low-saturated-fat Swank diet, the follow-up papers drawn from WAVES, a pooled analysis of the two pilots, a randomized trial of a web-based wellness course, and the EDQ-MS trial that is now under way. Each result is given as the paper’s own abstract states it. The last section describes, neutrally, what later systematic reviews of diet trials in multiple sclerosis have reported. For the trials that bundled diet with other parts of the program, see Wahls Multimodal Pilot Studies in Progressive Multiple Sclerosis.

Table of Contents

  1. Why Fatigue Became the Trial Target
  2. The 2017 Pilot: Modified Paleolithic Diet Against Usual Diet
  3. Paleolithic, Ketogenic and Usual Diet: The Three-Arm Pilot
  4. How the WAVES Trial Was Designed
  5. WAVES Results: Fatigue and Quality of Life
  6. WAVES Follow-Up Papers: Mood, Metabolism, Function and Nutrients
  7. The Pooled Analysis of the Two Pilot Trials
  8. A Randomized Trial of a Web-Based Wellness Course
  9. EDQ-MS: The Trial Now Under Way
  10. What Later Reviews of Diet Trials Found
  11. Key Research Papers
  12. Connections

1. Why Fatigue Became the Trial Target

Fatigue is the outcome that runs through almost every one of these trials. In the published protocol for the WAVES trial, Wahls and her co-authors write that fatigue is one of the most disabling symptoms of multiple sclerosis, that it contributes to a loss of quality of life, and that the treatments available at the time had had limited success in relieving it.

The protocol explains how the group arrived at a diet-only design. Clinically significant reductions in fatigue had been reported in their earlier multimodal pilot study, which combined a Paleolithic diet with stress reduction, exercise and electrical muscle stimulation. Because that pilot changed several things at once, it could not show how much of the effect came from food. The randomized trials on this page were built to isolate the diet: they compare one eating pattern with another, or with a person’s usual diet, and measure fatigue as the main outcome, alongside quality of life, mood, thinking and physical function.

Wahls had described the earlier pilot in a 2016 University of Iowa news release that announced the WAVES trial: “In three months the fatigue was gone,” she said of what participants had reported (University of Iowa Carver College of Medicine, 2016).

Most of these trials measure fatigue with two questionnaires that people fill out themselves: the Fatigue Severity Scale and the Modified Fatigue Impact Scale. Quality of life is measured with the Multiple Sclerosis Quality of Life-54 questionnaire, which gives separate physical and mental scores. A lower fatigue score and a higher quality-of-life score are better.

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2. The 2017 Pilot: Modified Paleolithic Diet Against Usual Diet

The first randomized trial of the diet was published in 2017 by Amanda Irish, Wahls and colleagues in the University of Iowa’s Department of Health and Human Physiology. Earlier work had tested the Paleolithic diet in people with progressive multiple sclerosis, but always together with other treatments such as exercise. This pilot set out to test a modified Paleolithic dietary intervention on its own in people with relapsing-remitting multiple sclerosis, the form of the disease marked by attacks followed by partial or full recovery.

Design and participants

Thirty-four people were randomly assigned either to keep their usual diet (the control group) or to follow the modified Paleolithic diet. Nine people (one man) completed the control arm and eight people (one man) completed the diet arm, so the analysis covered 17 people.

What the abstract reports

The authors conclude that a Paleolithic diet “may be useful in the treatment and management of MS”, by reducing perceived fatigue, raising mental and physical quality of life and improving hand and leg function, and that the rise in vitamin K might reduce inflammation. The small number of completers — 17 of 34 — is part of the record of this pilot.

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3. Paleolithic, Ketogenic and Usual Diet: The Three-Arm Pilot

The second randomized pilot (ClinicalTrials.gov NCT01915433, registered as “Wahls Paleo Diet and Progressive Multiple Sclerosis”) compared two versions of her approach against usual eating. It was published in 2021 by Jennifer Lee, Tyler Titcomb, Babita Bisht, Linda Rubenstein, Rebecca Louison and Wahls. The ketogenic arm reflects the strictest level of her book series, Wahls Paleo Plus, which is a high-fat ketogenic approach.

Design and participants

Fifteen people with multiple sclerosis were randomized to three groups:

  1. a modified Paleolithic diet (6 people);
  2. a ketogenic diet based on medium-chain triglycerides that included coconut as a fat source (5 people);
  3. their usual diet, as a waitlist control (4 people).

Blood was drawn every 4 weeks to check for nutritional ketosis, the state in which the body burns fat for fuel and produces ketones such as β-hydroxybutyrate. Participants kept 4-day weighed food records and were tested for disability, fatigue, quality of life, thinking and physical function at the start and at 12 weeks.

What the abstract reports

The authors write that the ketogenic diet produced ketosis but was not associated with significant clinical improvement in this study, while the modified Paleolithic diet was associated with significant clinical improvements. They add that larger randomized controlled trials are needed to determine the safety and efficacy of both diets in multiple sclerosis. With four to six people per arm, this was the smallest of the randomized studies on this page.

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4. How the WAVES Trial Was Designed

WAVES — registered as the “Dietary Approaches to Treat Multiple Sclerosis-Related Fatigue Study” (ClinicalTrials.gov NCT02914964, registered 24 August 2016) — is the largest completed randomized trial of the Wahls diet. Its protocol was published in the journal Trials in 2018, with Wahls as first author and Linda Snetselaar of the University of Iowa College of Public Health as senior author.

The two diets compared

WAVES did not compare the Wahls diet with a usual diet. It compared two diets that are widely followed by people with multiple sclerosis:

Timeline

The protocol describes a 36-week study in three 12-week periods:

  1. Observation (run-in). Participants keep eating their usual diet while baseline fatigue, quality of life, motor and cognitive function, physical activity, sleep, diet quality and social support for eating are measured.
  2. Intervention. Participants are randomized to one of the two diets and are supported by a registered dietitian through in-person coaching, telephone calls and emails.
  3. Follow-up. Participants continue the study diet for another 12 weeks with minimal dietitian support, to see whether they can sustain it on their own.

The primary outcome was perceived fatigue. Ethical approval came from the University of Iowa Institutional Review Board.

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5. WAVES Results: Fatigue and Quality of Life

The main WAVES results were published in 2021 in Multiple Sclerosis Journal – Experimental, Translational and Clinical, with Wahls as first author.

Participants

Eighty-seven people with relapsing-remitting multiple sclerosis were randomized to the Swank or Wahls diet. Of these, 77 completed 12 weeks and 72 completed 24 weeks. A later WAVES paper gives the group sizes at randomization as 44 Swank and 43 Wahls.

Changes at 12 weeks, from the abstract

All outcomes were maintained or further improved at 24 weeks. The authors’ conclusion reads: “Both diets were associated with clinically meaningful within-group reductions in fatigue and improvements in [quality of life].”

Reading the result

The abstract reports changes within each group from its own starting point. It does not report a head-to-head difference between the two diets as the main finding, and there was no usual-diet arm in the randomized phase; the run-in period, when everyone ate as usual, served as each person’s reference. On the Modified Fatigue Impact Scale and on both quality-of-life scores, the numbers moved further in the Wahls group; on the Fatigue Severity Scale, they moved further in the Swank group.

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6. WAVES Follow-Up Papers: Mood, Metabolism, Function and Nutrients

The Iowa group has used the WAVES data for a series of secondary analyses, each asking a narrower question. All of them compare the same two diets in the same people with relapsing-remitting multiple sclerosis.

Micronutrient intake (2021)

Because both diets restrict certain foods, the team checked whether participants were getting enough vitamins and minerals, using three-day weighed food records. At 12 weeks, the Swank group had fewer people with inadequate intake from food of vitamins C, D and E; the Wahls group had fewer with inadequate intake of magnesium and vitamins A, C, D and E. The share with inadequate intake from food rose for calcium, thiamin and vitamin B12 in the Wahls group and for vitamin A in the Swank group. Counting supplements reduced inadequate intake for every nutrient except calcium in the Wahls group, but raised the share with excessive intake of vitamin D and niacin in both groups and of magnesium in the Swank group.

Metabolic markers and fatigue (2023)

Both groups had significant reductions in weight, body mass index, total cholesterol and low-density lipoprotein (LDL) cholesterol at 12 and 24 weeks. The Swank group also had a significant fall in high-density lipoprotein (HDL) cholesterol; the Wahls group had a significant fall in diastolic blood pressure. Both groups reported less motor and cognitive fatigue. The authors found that the improvements in fatigue were independent of the changes in these metabolic markers.

Homocysteine, folate, vitamin B12 and mood (2023)

In 77 participants, both groups showed significant improvement in depression and anxiety scores on the Hospital Anxiety and Depression Scale and on the Mental Health Inventory at 12 and 24 weeks. Serum homocysteine fell and serum vitamin B12 rose in both groups, and every participant exceeded the laboratory’s upper measuring limit for folate. These blood changes were not associated with, and did not explain, the improvements in mood. The authors note that both diet arms included folate and vitamin B12 supplements.

Functional disability (2023)

Using a composite of the nine-hole peg test, the timed 25-foot walk and an oral symbol-digit thinking test, the Swank group’s scores rose significantly at 12 and 24 weeks. The Wahls group showed no change at 12 weeks but a significant rise at 24 weeks. Both groups improved on the peg test and the thinking test at 24 weeks, and the analysis found that the changes in function were mediated by the reduction in fatigue. The authors conclude that both diets reduced functional disability as mediated by fatigue.

Fatty acids and thinking (2024)

Both groups had significant improvements in serum fatty acids, including the omega-3 fats eicosapentaenoic acid and docosahexaenoic acid (but not arachidonic acid), and in measures of cognitive function. The 12-week change in the omega-3 index was associated with the change on the symbol-digit test, but the fatty-acid changes did not mediate the diets’ effect on thinking scores.

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7. The Pooled Analysis of the Two Pilot Trials

In 2024 the group combined the data from the two 12-week randomized pilots described in sections 2 and 3 — the 2017 Paleolithic-versus-usual-diet trial and the three-arm trial — to look at functional disability, which neither small pilot could test well on its own.

Disability was scored with the Multiple Sclerosis Functional Composite, built from the nine-hole peg test, the timed 25-foot walk and the Paced Auditory Serial Addition Test, a test of attention and mental speed. The abstract reports:

The authors describe these as preliminary observations on the efficacy of a modified Paleolithic diet for reducing or maintaining functional disability.

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8. A Randomized Trial of a Web-Based Wellness Course

A 2023 trial (ClinicalTrials.gov NCT05057676), with Titcomb as first author and Wahls among the co-authors, asked whether the program’s lifestyle elements could help people when delivered as a self-paced online course with no one-to-one coaching. The 7-week course covered diet, stress-reduction techniques, sleep habits and exercise.

Design and participants

One hundred people with a self-reported physician’s diagnosis of relapsing-remitting multiple sclerosis or clinically isolated syndrome (a first episode of symptoms that can precede multiple sclerosis) were randomized either to start the course at once (51 people) or to a waitlist that started it after 12 weeks (49 people). Both groups were followed for 24 weeks; 95 completed the 12-week primary endpoint.

What the abstract reports

The authors conclude that the web-based wellness program, without tailored support, resulted in significant improvements in fatigue compared with control.

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9. EDQ-MS: The Trial Now Under Way

The newest trial in the program is EDQ-MS, short for Efficacy of Diet on Quality of life in Multiple Sclerosis (ClinicalTrials.gov NCT05007483, registered 16 August 2021). Its protocol was published in Trials in 2025, with Titcomb, Snetselaar and Wahls as joint senior authors. No results have been published yet.

The planned design

The protocol states that there is an unmet need for rigorous randomized controlled trials of diet in multiple sclerosis. EDQ-MS is longer than any of the earlier trials and is the first in the program to include imaging and disease-activity measures, the outcomes that earlier pilots did not test.

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10. What Later Reviews of Diet Trials Found

Several systematic reviews have pooled randomized diet trials in multiple sclerosis, including the Iowa trials above. Their findings are reported here as the papers state them.

Cochrane review, 2020

A Cochrane review by Natalie Parks and colleagues, an update of a review first published in 2003, examined 30 trials of dietary interventions in multiple sclerosis — mostly supplements of polyunsaturated fats, antioxidants and other nutrients, with three trials of dietary programmes. Every trial had at least one methodological issue leading to unknown or high risk of bias. The authors concluded that, at present, there is insufficient evidence to determine whether supplementation with antioxidants or other dietary interventions have any impact on outcomes related to multiple sclerosis. The review’s search ran to May 2019, before the WAVES results were published.

Rapid review and meta-analysis, 2022

A Spanish group pooled eight randomized trials (515 patients) through December 2021. Dietary intervention was associated with a trend toward lower fatigue and higher quality of life, no significant effect on the Expanded Disability Status Scale, and no severe adverse events. The authors call for large prospective clinical trials.

Network meta-analysis, 2023

A network meta-analysis in Neurology by Snetselaar, Titcomb and other University of Iowa researchers (Wahls was not an author) compared 8 dietary approaches across 12 trials with 608 participants. The Paleolithic, low-fat and Mediterranean diets showed greater reductions in fatigue than control; the Paleolithic and Mediterranean diets also showed greater improvements in physical and mental quality of life. The authors rated the credibility of the evidence for all direct comparisons as very low, because most included trials had high or moderate risk of bias and small samples, and wrote that the findings must be confirmed in high-quality randomized controlled trials.

Inflammation markers, 2026

A meta-analysis from her group of 13 randomized trials (891 participants) found that several dietary interventions may reduce markers of systemic inflammation such as C-reactive protein, with larger effects in trials of six months or longer; calorie restriction did not change the hormones leptin or adiponectin. The evidence was rated low, and the authors call for larger and longer trials.

Wahls’s own summary

In a 2022 review of dietary approaches to multiple sclerosis symptoms, Wahls writes that no dietary pattern has yet been proven effective for reducing relapses or enhancing lesions on scans, while several pilot studies — of the Swank, McDougall, Wahls, gluten-free, Mediterranean and fasting approaches — report reduced symptoms. That framing matches the trials on this page: they measured how people feel and function, not relapse rates or imaging, which EDQ-MS is now designed to measure.

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Key Research Papers

  1. Irish AK, Erickson CM, Wahls TL, Snetselaar LG, Darling WG. Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2017;7:1-18. — PubMed PMID: 30050374
  2. Lee JE, Titcomb TJ, Bisht B, Rubenstein LM, Louison R, Wahls TL. A Modified MCT-Based Ketogenic Diet Increases Plasma β-Hydroxybutyrate but Has Less Effect on Fatigue and Quality of Life in People with Multiple Sclerosis Compared to a Modified Paleolithic Diet: A Waitlist-Controlled, Randomized Pilot Study. J Am Coll Nutr. 2021;40(1):13-25. — PubMed PMID: 32213121
  3. Wahls T, Scott MO, Alshare Z, Rubenstein L, Darling W, Carr L, et al. Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial. Trials. 2018;19(1):309. — PubMed PMID: 29866196
  4. Wahls TL, Chenard CA, Snetselaar LG. Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic. Nutrients. 2019;11(2):352. — PubMed PMID: 30736445
  5. Chenard CA, Rubenstein LM, Snetselaar LG, Wahls TL. Nutrient Composition Comparison between the Low Saturated Fat Swank Diet for Multiple Sclerosis and Healthy U.S.-Style Eating Pattern. Nutrients. 2019;11(3):616. — PubMed PMID: 30871265
  6. Swank RL, Bourdillon RB. Multiple sclerosis: assessment of treatment with a modified low-fat diet. J Nerv Ment Dis. 1960;131:468-88. — PubMed PMID: 13774215
  7. Wahls TL, Titcomb TJ, Bisht B, Eyck PT, Rubenstein LM, Carr LJ, et al. Impact of the Swank and Wahls elimination dietary interventions on fatigue and quality of life in relapsing-remitting multiple sclerosis: The WAVES randomized parallel-arm clinical trial. Mult Scler J Exp Transl Clin. 2021;7(3):20552173211035399. — PubMed PMID: 34377527
  8. Titcomb TJ, Brooks L, Smith KL, Ten Eyck P, Rubenstein LM, Wahls TL, et al. Change in Micronutrient Intake among People with Relapsing-Remitting Multiple Sclerosis Adapting the Swank and Wahls Diets: An Analysis of Weighed Food Records. Nutrients. 2021;13(10):3507. — PubMed PMID: 34684508
  9. Villa AT, Tu BH, Titcomb TJ, Saxby SM, Shemirani F, Ten Eyck P, et al. Association between improved metabolic risk factors and perceived fatigue during dietary intervention trial in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES trial. Front Neurol. 2022;13:1022728. — PubMed PMID: 36742040
  10. Shemirani F, Titcomb TJ, Saxby SM, Eyck PT, Rubenstein LM, Hoth KF, et al. Association of serum homocysteine, folate, and vitamin B12 and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial. Mult Scler Relat Disord. 2023;75:104743. — PubMed PMID: 37148578
  11. Crippes LJ, Saxby SM, Shemirani F, Bisht B, Gill C, Rubenstein LM, et al. Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial. Mult Scler J Exp Transl Clin. 2023;9(4):20552173231209147. — PubMed PMID: 37916030
  12. Saxby SM, Haas C, Shemirani F, Titcomb TJ, Eyck PT, Rubenstein LM, et al. Association Between Improved Serum Fatty Acid Profiles and Cognitive Function During a Dietary Intervention Trial in Relapsing-Remitting Multiple Sclerosis. Int J MS Care. 2024;26(2):61-68. — PubMed PMID: 38482513
  13. Groux AR, Walker ES, Shemirani F, Lee JE, Irish AK, Rubenstein LM, et al. Diet-Induced Changes in Functional Disability among People with Multiple Sclerosis: A Secondary Pooled Analysis of Two Randomized Controlled Pilot Trials. Sclerosis. 2024;2(3):156-165. — PubMed PMID: 39296470
  14. Titcomb TJ, Sherwood M, Ehlinger M, Saxby SM, Shemirani F, Eyck PT, et al. Evaluation of a web-based program for the adoption of wellness behaviors to self-manage fatigue and improve quality of life among people with multiple sclerosis: A randomized waitlist-control trial. Mult Scler Relat Disord. 2023;77:104858. — PubMed PMID: 37399671
  15. Shemirani F, Klein AM, Groux AR, Kilpatrick R, Brooks L, Ehlinger MA, et al. Efficacy of Diet on Quality of life in Multiple Sclerosis (EDQ-MS): a study protocol for a randomized controlled clinical trial. Trials. 2025;26(1):437. — PubMed PMID: 41146285
  16. Parks NE, Jackson-Tarlton CS, Vacchi L, Merdad R, Johnston BC. Dietary interventions for multiple sclerosis-related outcomes. Cochrane Database Syst Rev. 2020;5(5):CD004192. — PubMed PMID: 32428983
  17. Guerrero Aznar MD, Villanueva Guerrero MD, Cordero Ramos J, Eichau Madueño S, Morales Bravo M, López Ruiz R, et al. Efficacy of diet on fatigue, quality of life and disability status in multiple sclerosis patients: rapid review and meta-analysis of randomized controlled trials. BMC Neurol. 2022;22(1):388. — PubMed PMID: 36266639
  18. Snetselaar LG, Cheek JJ, Fox SS, Healy HS, Schweizer ML, Bao W, et al. Efficacy of Diet on Fatigue and Quality of Life in Multiple Sclerosis: A Systematic Review and Network Meta-analysis of Randomized Trials. Neurology. 2023;100(4):e357-e366. — PubMed PMID: 36257717
  19. Pingel WR, Titcomb TJ, Saxby SM, Arsalandeh F, Salari-Moghaddam A, Mangalam A, et al. The effect of dietary interventions on peripheral markers of inflammation among people with multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials. Mult Scler Relat Disord. 2026;106:106913. — PubMed PMID: 41422672
  20. 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. Wahls TL — randomized trials in multiple sclerosis
  2. WAVES trial — Swank and Wahls diets
  3. Paleolithic diet and multiple sclerosis
  4. Diet and fatigue in multiple sclerosis — randomized controlled trials

Further Reading

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Connections