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.

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 2 site study visits (month 0 and 24). 24-hour dietary recalls will be collected by a study registered dietitian (RD) (who did not provide training on the respective participants assigned study diet) on three non-consecutive days at baseline, and one per month, at months 10-12, and 22-24. Participants will be given a 3-month window to complete dietary recalls in the event of scheduling conflicts. Participants will be instructed to record key study diet components each day using a study specific questionnaire in the study related (MyCap) application on their smart device. The online questionnaires sent to participants every 2 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.

Arms

Interventions