Utilization of the Ketogenic Diet in Patient With Relapsing Remitting MS

The purpose of this study is to see if a high fat, low carbohydrate diet is safe and how it
effects post trial diet habits, physique, and disease course in patients with relapsing
remitting multiple sclerosis. In particular, multiple sclerosis is a neurodegenerative
disorder that is characterized by inflammation, microglial inflammation, and hypoxia in its
relapsing-remitting form.1 One of the hypothesized therapeutic mechanisms of ketogenic diets
is related to its effect on decreasing glycolysis, decreasing reactive oxygen species (ROS),
and increasing ATP production by mitochondria. Production of ROS and macrophage activation
have been directly correlated with demyelination and axonal injury in multiple sclerosis.2,3
In mouse models with experimental allergic encephalomyelitis (EAE), a model disease in mice
that has many similar properties to that of MS in humans, experiments have demonstrated that
impairment of memory and spatial learning are directly correlated with increased cytokine and
chemokine expression and ROS production. In EAE mice fed a ketogenic diet, there were noted
improvements in motor disability, memory dysfunction, and CNS inflammation - which on the
whole are suggestive that a ketogenic diet may have a multitude of benefits in patients with
multiple sclerosis.

The study goal is to recruit 50 young adult or adult patients with relapsing-remitting
multiple sclerosis that show interest in starting and maintaining a ketogenic diet for six
months. Prior to initiating the diet, the study team will characterize each patient's disease
by analyzing multiple factors - including baseline expanded disability status scale (EDSS)
and annualized relapse rates (ARR). Throughout the course of the 12 month study participants
will be asked to complete several patient reported outcomes, an online food diary recall, and
track their diet compliance using urinary ketone testing strips provided by the study
daily.In addition, the study team will also draw serum lab work every 3 months that we
anticipate may be affected by the diet (including hemoglobin A1C, lipid panel, and cytokine
profiles). Rectal swabs will be requested during the study to look at effects of the diet on
the microbiome both pre and post diet. Additionally, activity monitors (accelerometers) will
be worn by each subject for 1 week prior to initiation of the diet to provide evidence of
pre-diet activity levels and at various times throughout the study for comparison.
Participating patients will receive education on starting, maintaining, and stopping the 6
month diet by a nutritionist. The nutritionist will meet with patients at scheduled office
visits and will be available for questions during the duration of the patients participation.
Subjects will also undergo anthropometric assessments with a bodpod used to measure body mass
as well.

All measures will be compared with statistical analyses, utilizing both pre and post diet
values to help determine benefit of the diet on various aspects of the patient's overall
health and wellness.

Inclusion Criteria:

1. Ability to provide informed consent (or assent for minors)

2. Relapsing-remitting MS diagnosis per 2010 McDonald criteria

3. On same Demyelinating Treatment for at least 6 months

4. Ages ≥ 12 years to ≤ 45 years

Exclusion Criteria:

1. Comorbid disease (including hypercholesterolemia, cardiovascular or renal disease)
that would interfere with safety and/or study completion

2. Current pregnancy or planning pregnancy

3. Progressive form of MS

4. Estimated GFR less than 45 mL/min based on a serum creatinine drawn within 30 days of
enrollment

5. Acute kidney injury

6. History of paraproteinemia syndromes such as multiple myeloma

7. Hepatorenal syndrome

8. Liver transplant

9. Underweight or low weight patients as defined by:

1. BMI value <20 for those 18 years and older

2. <10th percentile for BMI by CDC growth charts for those less than 18 years of age