RESTORE ME -- RCT of Oxaloacetate on Improving Fatigue in ME/CFS

Inclusion Criteria: * Patients who meet all of the following criteria are eligible to participate in the study: * Provision of signed and dated informed consent form * Ability to read, understand or speak English * Diagnosed with ME/CFS and meet the IOM Diagnostic Criteria for ME/CFS (2015) * Relatively stable state of illness for the past 3 months that is characterized by \>2 and \<6 hours of daily upright activity * Male or female, between the ages of 18 and 65 years old * No evidence of active infection with SARS-CoV-2 documented by a negative test at Visit 1 * Agree to refrain from taking medications that would affect assessment of the effectiveness of study dietary supplement for the duration of the study * Females of childbearing potential should be on adequate contraception such as oral, implantable, injectable or transdermal hormonal contraceptives (should have been used for a minimum of one full cycle prior to administration of study drug), intrauterine devices (IUD), vasectomized partner, double barrier method (male or female condom, sponge, diaphragm or vaginal ring with simultaneous use of spermicidal jelly or cream) * Each patient of child-bearing potential must have a negative urine pregnancy test at Visit 1. The urine test at Visit 1 must both be confirmed negative prior to randomization. Women of child-bearing potential will have a urine pregnancy test at each visit (2-4) and it must be negative to continue. Women who are confirmed to be of non-childbearing potential do not require pregnancy testing. To be considered of non-child-bearing potential, the patient must be: post-menopausal (defined as no menses for at least one year); or surgically sterile (s/p hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to randomization); or at least 3 months s/p a non-surgical permanent sterilization procedure * History of fatigue and post-exertional malaise (PEM) * Stated willingness to comply with all study procedures and remain available for the study duration * Have mobile (smart) phone and access to the internet * Willingness to wear a device on their ankle Exclusion Criteria: * A patient who meets any of the following criteria will be excluded from participation in this study: * A positive rapid COVID-19 antigen test at Visit 1 * Alternate medical or psychiatric illness that could explain the ME/CFS symptoms * Severe ME/CFS with less than 2 hours of upright activity a day * Active or uncontrolled co-morbidities which in the opinion of the PI may interfere with the ability of the patient to participate in the study. Co-morbidities may include acute infection, Crohn's disease, diabetes mellitus (Type 1 or Type 2, evidenced by a history of HbA1c \> 7 at any time), Guillain-Barre syndrome, lupus, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, or other such diseases that may be exclusionary. Particularly conditions or medications that cause immunodeficiency or immunosuppression will be excluded. Examples of such conditions can be found in the tables "Causes of Secondary Immunodeficiency" and "Some Drugs that Cause Immunosuppression" in the "Merck Manual" * Body Mass Index \> 35 * Participating in another clinical treatment trial, or symptoms improving as a result of treatment intervention in the past 3 months * Current treatment with stimulants including methylphenidate, amphetamine-dextroamphetamine, lisdexamfetamine, modafinil, armodafinil * Pregnancy, or while breast feeding. Women should not be enrolled within 6 months of giving birth and within 3 months of cessation of breast feeding. * History of: * Major depression with psychotic or melancholic features before the diagnosis of ME/CFS, or active depression (major depression with psychotic or melancholic features) as determined by self-report * Untreated endocrine diagnoses including hypothyroidism (Hashimoto's, etc.), Grave's disease, adrenal insufficiency, hypogonadism (testosterone deficiency), diabetes mellitus or insipidus * Significant head injury in the last 3 years, concussion with loss of consciousness, brain surgery, an automobile accident with head/neck injury, and/or other traumatic brain injury * A supra-ventricular tachycardia or ventricular tachycardia, e.g., atrial fibrillation or flutter, paroxysmal atrial fibrillation, junctional tachycardia, ventricular tachycardia * Symptomatic hypotension defined as rested sitting systolic BP \< 100 mmHg or rested sitting diastolic BP \< 60 mmHg * Substance abuse in the past 12 months as determined by self-report • Improvement in overall ME/CFS symptoms as a result of any treatment intervention in the past 3 months