The histaminergic system is phylogenetically one of the oldest parts of the nervous system but it is a relatively recent discovery. It is involved with several vegetative functions like sleep, attention and learning, feeding and satiety, working memory, cognition, depression, and most of all arousal and energy

1. Establish in an open label clinical trial the tolerability and safety of various doses of l-histidine and lodosyn that may increase levels of l-histidine and histamine in the serum and cerebrospinal fluid (CSF).
2. Perform pharmacokinetic studies in serum and CSF of study subjects the levels of l-histidine and histamine after treatment with various combination of l-histidine and lodosyn.
3. Preliminary information will also be collected on the effects of this intervention on alleviation of fatigue.

The findings from this study go beyond the effects of histamine on fatigue. If central histamine can be increased by the strategy outlined above, a number of other vegetative hypothalamic functions intricately associated with fatigue including sleep, cognition and satiety need to be examined in MS patients in future studies.

Inclusion Criteria for Healthy Volunteers:

1. Male or female subjects between the ages of 18 and 60 will be eligible.
2. Subjects should be in good physical health without history of chronic illness and should be generally considered healthy.
3. Spouses or caregivers of patients with MS would be encouraged to participate.

Inclusion Criteria for Patients with Multiple Sclerosis (MS):

1. Patients with MS regardless of the disease type, who experience severe fatigue will be eligible to participate.
2. Fatigue Severity Score of >/= 4.0 will qualify as long as all other inclusion / exclusion criteria are met.
3. Established MS by McDonald Criteria - 2010 Revision (24). Relapse Remitting (RR) and progressive forms of MS are eligible
4. Severe fatigue that has lasted greater than 6 months
5. Clinically stable on a current therapy with any Disease Modifying Therapy (DMT)

Exclusion Criteria for Healthy Volunteers:

1. Adults unable to give informed consent due to cognitive impairment or mental disorders.
2. Children below the age of consent
3. Pregnant women
4. Prisoners
5. History of chronic disorders like hypertension, diabetes, hyperlipidemia, depression, hypothyroidism etc. that require chronic treatment
6. Known chronic fatigue syndrome
7. Blood disorders or coagulopathy
8. Chronic allergies or history of asthma.
9. Using antihistamines, bronchodilators or H2 blockers for hyperacidity
10. Using medications for sleep, or known sleep disorders
11. Any medication or condition deemed unsuitable by the PI

Exclusion Criteria for Patients with Multiple Sclerosis (MS):

1. Adults unable to give informed consent due to cognitive impairment or mental disorders.
2. Children below the age of consent
3. Pregnant women
4. Prisoners
5. Systemic disorders known to cause fatigue such as severe anemia, infections, chronic systemic infectious or inflammatory disorders, including known autoimmune disorders.
6. Chronic fatigue syndrome
7. Hypothyroidism
8. Systemic malignancy
9. Undergoing chemotherapy
10. Depression
11. Sleep disorders including narcolepsy, excessive day-time sleep.
12. History of substance abuse
13. Excessive consumption of coffee or over-the-counter stimulants
14. Concomitant medications of amantadine, methylphenidate, amphetamines, pemoline, barbiturates, tizanidine, Monoamine oxidase inhibitor (MAO) inhibitors, benzodiazepines, barbiturates, tricyclic antidepressants, antihistamines, H2 blockers for gastro-esophageal reflux disease (GERD), selective serotonin reuptake inhibitors (SSRIs) and any other medication that in the opinion of the PI should be excluded.
15. Patients who were using modafinil for treatment of fatigues prior to the study may participate but will be required to undergo a washout of 2 weeks prior to entry into the trial.