This is an open-label, phase II study that may provide evidence that taking S-adenosylmethionine (SAMe) supplementation prevents oxaliplatin, a type of chemotherapy drug, associated liver toxicity in patients with resectable colorectal liver metastases. Resectable means that it is able to removed with surgery. Patients will take two SAMe tablets in the morning and one tablet in the evening for 3-6 months (about 6-8 cycles of chemotherapy) in addition to oxaliplatin based chemotherapy followed by surgical removal of the colorectal liver metastases.

Inclusion Criteria:

• Stage IV patients with resectable liver predominant metastatic colorectal cancer (new diagnosis or recurrent) referred to Cedars Sinai Medical Center for oxaliplatin based systemic therapy.

• Age ≥ 18 years.

• Patients who are planning to undergo liver resection following oxaliplatin based chemotherapy treatment.

• ECOG Performance Status 0-2 or Karnofsky Performance Status (KPS) ≥ 60%.

• Demonstrate adequate organ and marrow function (within 28 days of study treatment initiation)

• Female subjects of childbearing potential should have a negative urine or serum pregnancy within 14 days prior to receiving the first dose of study medication for eligibility verification purposes. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• Female subjects of childbearing potential should be willing to use adequate methods of birth control (hormonal or barrier method of birth control) or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.

• Male subjects should agree to use an adequate method of contraception starting with the first dose of therapy through 120 days after the last dose of therapy.

• Subjects taking vitamin E ≥800 IU/day must be on a stable dose defined as:

  1. No changes in prescribed dose within 180 days of the screening visit and
  2. No new vitamin E-containing medications within 180 days of the screening visit or
  3. Discontinuation of vitamin E ≥800 IU/day for at least 180 days prior to the screening visit.

• Subjects taking anti-diabetic medications must be on a stable dose for at least 90 days prior to the date of the screening visit.

• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

Exclusion Criteria:

• Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• No other anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) or investigational agent may be used from 28 days prior to registration and until the end-of-study visit.
• Has previously received chemotherapy for metastatic disease (neoadjuvant or adjuvant therapy is allowed as long as treatment was completed ≥6 months prior to recurrence).
• Has pre-existing grade ≥ 3 neuropathy precluding use of oxaliplatin.
• Has known additional malignancy that is progressing or requires active treatment.
• Has a known hypersensitivity to any of the study supplement/drugs (SAMe, oxaliplatin, flourouacil, folinic acid and capecitabine).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has any gastrointestinal disorder (e.g., bowel obstruction) or neurologic condition (e.g., oropharyngeal dysphagia) that may result in impairment of oral intake, inability to swallow the oral supplement, and/or impairment of absorption of study drug in the opinion of the treating investigator.
• Has previous clinical diagnosis of cirrhosis, has had known history of Hep A/B/C or nonalcoholic fatty liver disease (NAFLD), liver transplantation, or any other cause for decompensated liver disease.
• Known human immunodeficiency virus (HIV) infection.
• Any of the following within 6 months prior to the screening visit: unstable cardiovascular disease, myocardial infarction, coronary artery bypass surgery, coronary angioplasty, transient ischemic attack, or cerebrovascular accident.
• Any other condition that, in the investigator's opinion, would impede competence or compliance or delay completion of the study.
• History of Parkinson's disease or bipolar disorder.

Patients taking the following prohibited medications:

• Olanzapine

• MAO inhibiters, including:

  • Isocarboxazid
  • Linezolid
  • Methylene blue injection
  • Phenelzine
  • Rasagiline
  • Selegiline
  • Tranylcypromine
  • Any other MAO inhibitors The above prohibited medications cannot be taken -14 days prior to Day 0 and during study treatment.. Patients currently on or plan to be prescribed anti-psychotic medications not listed above may be excluded at the discretion of the Investigator. - Active infection as evidenced by positive urine culture, blood culture, or pneumonia.