Efficacy of Diet on Quality of Life in Multiple Sclerosis (EDQ)

The overarching goal of this project is to critically evaluate the efficacy of incorporating dietary guidance within multiple sclerosis (MS) care for improving long-term quality of life (QoL) compared to usual care. The primary objective of this study is to evaluate the effect of two dietary interventions (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination) on MS QoL compared to usual care control (Dietary Guidelines for America), and the secondary objectives and the long-term effects on, motor function, low-contrast vision sensitivity, fatigue, mood, and disease activity assessed by brain imaging.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Dietary supplement: BodyBio Balance Oil; Dietary supplement: Kirunal Fish Oil; Dietary supplement: BodyBio PC; Behavioral: Modified Paleolithic Elimination diet; Behavioral: Time Restricted Olive Oil Based (TROO) Ketogenic Diet; Behavioral: Usual diet with Dietary Guidelines for Americans Diet information

Detailed Description

In the United States, MS affects nearly 1 million people with a 2.8:1 female to male ratio and the highest incidence rates among whites and African Americans. The economic cost of managing MS is substantial. In the U.S., the total medical costs for patients with MS increased from $116 million in 2002 to $198 million in 2013. MS is a chronic, neuroinflammatory, and neurodegenerative disease-causing symptoms of pain, fatigue, and changes in vision, cognition, and movement that greatly reduce quality of life (QoL) and the ability to maintain employment.

The overarching goal of this project is to critically evaluate the efficacy of incorporating dietary guidance within multiple sclerosis (MS) care for improving long-term quality of life (QoL) compared to usual care. The primary objective of this study is to evaluate the effect of two dietary interventions (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination) on MS QoL compared to usual care control (Dietary Guidelines for America), and the secondary objectives and the long-term effects on, motor function, low-contrast vision sensitivity, fatigue, mood, and disease activity assessed by brain imaging.

The proposed study will consist of study participants attending 3 in-person site visits, months 0, 3, and 24, and online surveys every 3 months (months 0-24).

This study will use a randomized single-blind controlled design to test the short-term (6 months) and long-term (an additional 18 months) impact of the intervention diets on symptoms of MS including QoL and related outcomes stated above. We will use a fourteen-day run-in period to identify participants who are most likely to be successful in completing study procedures; this process has been effective in our previous studies. Participants who successfully complete all baseline self-reported outcomes and follow all study procedures during the seven-day run-in period will be scheduled for an on-site baseline visit for randomization to one of three diets (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination and Dietary Guidelines for America).

On-site study visits will include blood draws, motor, cognitive, vision function assessments, and MRI. Motor assessments will include a 6-minute walk test, 25-foot walk test, 9-hole pegboard to test hand function, symbol digit exercise to test thinking functions, and critical flicker fusion test, ocular coherence tomography and low contrast vision sensitivity to test vision. The study participant will be escorted to the MRI unit to complete a non-contrast MRI of the brain. At the baseline visit, participants will be randomized. Participants assigned to the intervention diets will be given intervention specific educational materials including shopping lists, example menus and recipes, and the study supplements. Study participants randomized to the dietary guidelines for Americans diet will receive emails and/or text messages (approximately 3-6 weeks) to receive resources with websites for the Dietary Guidelines of America, and recent multiple sclerosis-related research that does not involve diet.

Study team will provide fish oil, essential fatty acids, and phosphatidylcholine to the two intervention groups only. The participant will be scheduled for a Zoom video conference meeting with the assigned registered dietitian to review the assigned study diet.

In addition, subjects will collect saliva specimens for microbiome analysis at each of the 3 site study visits (months 0, 3 and 24).

Dietary History Questionnaire III will be completed at months 0, 3, 12 and 24 and will be used to assess adherence to the assigned dietary pattern.

The online questionnaires sent to participants every 3 months will also be used to track supplement intake, medication use, and details about health & life events, MS symptoms, fatigue, quality of life, doctor's appointment, and side effects they may be experiencing.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52246
      • Univeristy of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Eligibility for the run-in phase of the study:

Participants will be eligible to enroll in the fourteen-day run-in phase of the study if they meet the following inclusion and exclusion criteria:

INCLUSION CRITERIA:

• A definitive diagnosis of RRMS based on the 2017 revised McDonald Criteria.
• The ability to prepare, or availability of someone to prepare, home-cooked meals.
• Must own a computer, smartphone, or tablet device that has internet access to complete online surveys and capable of running study related applications.
• Must be willing to follow study procedures outlined and explained to them.
• Be between the ages of 18 to 70 at the time of consent.
• Must be able to walk 25 feet without support.
• Willingness to be randomized and follow any of the study diets.
• Must consent to sharing the clinical notes from their primary care and neurology providers during the study period.

EXCLUSION CRITERIA:

• Moderate or severe mental impairment.
• Use of insulin, Coumadin, weight loss medications such as orlistat that causes fat malabsorption.
• Worsening of symptoms resulting in the initiation or change of treatment including steroids (solumedrol, prednisone, etc.) or disease-modifying medications in 4 weeks prior to consent.
• Treatment for cancer by radiation or chemotherapy in 12 months prior to consent, other than skin cancer.
• Diagnosis of clinically significant heart disease, liver disease, kidney disease, or history of oxalate kidney stones.
• Diagnosis of type II diabetes that does not have approval from treating physicians to adopt any of the 3 study diets.
• Clinical diagnosis of moderate to severe psychiatric disease that makes study adherence more difficult (e.g., schizophrenia, bi-polar disease, severe depression and/or anxiety).
• An active eating disorder such as anorexia, bulimia, binge eating, or orthorexia.
• Measurement of BMI <20.
• Confirmation of pregnancy or planning to become pregnant in the next 2 years.
• History of diagnosed fat intolerance/malabsorption such as cholecystectomy or uncontrolled exocrine pancreatic insufficiency.
• Participation in another research study investigating MS treatments, diet, or exercise.
• Presence of a contraindication to completing a brain MRI or having claustrophobia which interferes with completion of MRI studies without the use of sedation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (Modified paleolithic elimination diet).; Modified paleolithic elimination diet.	Dietary supplement: BodyBio Balance Oil; nutraceutical supplement; Other Names: 1400 mg linoleic acid/350 mg linolenic acid; Dietary supplement: Kirunal Fish Oil; nutraceutical supplement; Other Names: 315 mg eicosapentanoic acid/ 105 mg docosahexaenoic acid; Dietary supplement: BodyBio PC; nutraceutical supplement; Other Names: 1300 mg phosphatidylcholine; Behavioral: Modified Paleolithic Elimination diet; Complete elimination of all gluten-, dairy-, and egg-containing foods.; Increase fruit and vegetable intake to 6-9 servings/day comprising of 2-3 servings each of the following categories: intensely colored, sulfur-rich, and leafy greens.; Consume 6-12 ounces/day protein including organ meats and fatty fish.; Consume fermented foods daily.; Consume daily servings of algae, seaweed, and nutritional yeast.
Experimental: Group 2 (TROO); Time Restricted Olive Oil Based (TROO) Ketogenic Diet	Dietary supplement: BodyBio Balance Oil; nutraceutical supplement; Other Names: 1400 mg linoleic acid/350 mg linolenic acid; Dietary supplement: Kirunal Fish Oil; nutraceutical supplement; Other Names: 315 mg eicosapentanoic acid/ 105 mg docosahexaenoic acid; Dietary supplement: BodyBio PC; nutraceutical supplement; Other Names: 1300 mg phosphatidylcholine; Behavioral: Time Restricted Olive Oil Based (TROO) Ketogenic Diet; Restriction of dietary carbohydrates to < 50 grams/day.; Use olive oil (cold-pressed extra virgin preferred) to increase fat intake to >160 grams/day.; Consume <100 grams/day protein.; Limit dairy to 2 servings/day of whole fat options (completely exclude reduced fat dairy).; Consume at least 3 servings/day non-starchy vegetables.
Active Comparator: Group 3 Control; Usual diet with Dietary Guidelines for Americans Diet information	Behavioral: Usual diet with Dietary Guidelines for Americans Diet information; Limit sodium to < 2,300 mg/day.; Limit added sugar and saturated fat intake to <10% of kcal/day, respectively.; Consume 5 servings of fruits and vegetables per day.; Consume 6-9 ounce equivalents/day of grains, making at least half whole grain options.; Consume 3 servings of reduced fat dairy per day.; Consume 6 ounces/day protein foods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)	Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better.	baseline to 3 Months
Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)	Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better.	baseline to 6 Months
Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)	Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better.	baseline to 12 Months
Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)	Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better.	baseline to 18 Months
Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)	Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better.	baseline to 24 Months
Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)	Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better.	baseline to 3 Months
Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)	Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better.	baseline to 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)	Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better.	baseline to 12 Months
Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)	Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better.	baseline to 18 Months
Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)	Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better.	baseline to 24 Months
Modified Fatigue Impact Scale (MFIS)	Change in MFIS survey questions, scores range from 0-84, lower score is better.	baseline to 3 months
Modified Fatigue Impact Scale (MFIS)	Change in MFIS survey questions, scores range from 0-84, lower score is better.	baseline to 6 months
Modified Fatigue Impact Scale (MFIS)	Change in MFIS survey questions, scores range from 0-84, lower score is better.	baseline to 12 months
Modified Fatigue Impact Scale (MFIS)	Change in MFIS survey questions, scores range from 0-84, lower score is better.	baseline to 18 months
Modified Fatigue Impact Scale (MFIS)	Change in MFIS survey questions, scores range from 0-84, lower score is better.	baseline to 24 months
Hospital Anxiety Depression Scale (HADS)	Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence	baseline to 3 months
Hospital Anxiety Depression Scale (HADS)	Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence	baseline to 6 months
Hospital Anxiety Depression Scale (HADS)	Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence	baseline to 12 months
Hospital Anxiety Depression Scale (HADS)	Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence	baseline to 18 months
Hospital Anxiety Depression Scale (HADS)	Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence	baseline to 24 months
Fatigue Severity Scale score (FSS)	Change in FSS survey question mean scores, scores range from 1-7, lower is better.	Baseline to 3 months
Fatigue Severity Scale score (FSS)	Change in FSS survey question mean scores, scores range from 1-7, lower is better.	Baseline to 6 months
Fatigue Severity Scale score (FSS)	Change in FSS survey question mean scores, scores range from 1-7, lower is better.	Baseline to 12 months
Fatigue Severity Scale score (FSS)	Change in FSS survey question mean scores, scores range from 1-7, lower is better.	Baseline to 18 months
Fatigue Severity Scale score (FSS)	Change in FSS survey question mean scores, scores range from 1-7, lower is better.	Baseline to 24 months
Brain volume as measured by non contrast magnetic resonance imaging (MRI)	Change in MRI grey matter brain volume, more is better	baseline to 24 months
Brain lesions as measured by non contrast magnetic resonance imaging (MRI)	Change in inflammatory lesions numbers as measured by non contrast brain MRI, fewer is better	baseline to 24 months
Timed 25 foot walk test	seconds required to walk 25 feet, lower is better	baseline to 3 months
Timed 25 foot walk test	seconds required to walk 25 feet, lower is better	baseline to 24 months
9 Hole peg board test	seconds require to move 9 pegs to various locations on a peg board, fewer seconds is better	baseline to 3 months
9 Hole peg board test	seconds require to move 9 pegs to various locations on a peg board, fewer seconds is better	baseline to 24 months
Low contrast visual acuity	A measure of best corrected vision, measure is log minimal angle of resolution at 2.5% contrast. Lower number is better.	baseline to 3 months
Low contrast visual acuity	A measure of best corrected vision, measure is log minimal angle of resolution at 2.5% contrast. Lower number is better.	baseline to 24 months
Ocular Coherence tomography	Measure of optic nerve and retina depths using infrared light technology	baseline
Neurofilament light chain	blood biomarker of neuroaxonal (brain) damage	baseline to 3 months
Neurofilament light chain	blood biomarker of neuroaxonal (brain) damage	baseline to 24 months
Dietary History Questionnaire IIi	Change in dietary intake measured by survey questions	baseline to 12 months
Dietary History Questionnaire IIi	Change in dietary intake measured by survey questions	baseline to 3 months
Critical flicker fusion	change in The herz at which a flickering light is seen as non-flickering as measured by herz	baseline to 3 months
Critical flicker fusion	change in The herz at which a flickering light is seen as non-flickering as measured by herz	baseline to 24 months
Ocular Coherence tomography	change in the Measure of optic nerve and retina depths using infrared light technology	baseline to 3 months
Ocular Coherence tomography	change in the Measure of optic nerve and retina depths using infrared light technology	baseline to 24 months

Collaborators and Investigators

• Sponsor: Terry L. Wahls
• Investigators: Principal Investigator: Terry L Wahls, MD, University of Iowa

Publications and helpful links

General Publications

• 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 Feb 7;11(2):352. doi: 10.3390/nu11020352.
• Wahls T, Scott MO, Alshare Z, Rubenstein L, Darling W, Carr L, Smith K, Chenard CA, LaRocca N, Snetselaar L. 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 Jun 4;19(1):309. doi: 10.1186/s13063-018-2680-x.
• 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 Mar 1;11(3):537. doi: 10.3390/nu11030537.
• Titcomb TJ, Bisht B, Moore DD 3rd, Chhonker YS, Murry DJ, Snetselaar LG, Wahls TL. Eating Pattern and Nutritional Risks among People with Multiple Sclerosis Following a Modified Paleolithic Diet. Nutrients. 2020 Jun 20;12(6):1844. doi: 10.3390/nu12061844.
• 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 Mar-Apr;36(3):150-168. doi: 10.1080/07315724.2016.1255160. Epub 2017 Apr 10.
• Lee JE, Titcomb TJ, Bisht B, Rubenstein LM, Louison R, Wahls TL. A Modified MCT-Based Ketogenic Diet Increases Plasma beta-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 Jan;40(1):13-25. doi: 10.1080/07315724.2020.1734988. Epub 2020 Mar 26.
• 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 Mar 13;11(3):616. doi: 10.3390/nu11030616.
• 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 Jan 4;7:1-18. doi: 10.2147/DNND.S116949. eCollection 2017.
• 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 May;20(5):347-55. doi: 10.1089/acm.2013.0188. Epub 2014 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 13, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: September 6, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: fatigue; quality of life; nutrition; dietary
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Multiple Sclerosis; Fatigue; Multiple Sclerosis, Relapsing-Remitting; Therapeutics; Fatty Acids; Lipids; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Health Care Economics and Organizations; Diet Therapy; Nutrition Therapy; Diet; Eicosanoids; Fatty Acids, Unsaturated; Diet, Carbohydrate-Restricted; Oils; Dietary Fats; Fats; Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Fish Oils; Membrane Lipids; Glycerophospholipids; Phosphatidic Acids; Glycerophosphates; Phospholipids; Health Policy; Public Policy; Social Control Policies; Policy; Diet, Ketogenic; Eicosapentaenoic Acid; Docosahexaenoic Acids; Phosphatidylcholines; Nutrition Policy
• Other Study ID Numbers: 202104639

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No