This study aims to determine whether a keto-like supplement relative to placebo results in functional brain changes during fMRI tasks evaluating positive and negative valence in individuals with moderate to severe depression. In this double-blind randomized placebo-controlled trial, 75 individuals with a Patient Health Questionnaire (PHQ-9) scale score ≥ 10 (MDD) will be enrolled to participate in an 8-week treatment study to obtain 60 completers. Participants will be randomized with a 1-1 ratio to receive the keto-like supplement (n= 30 completers) or placebo (n=30 completers) taken orally three times per day for 8 weeks. Participants will undergo a 10.5-hour screening/baseline evaluation visit split over 2 days at week 0 including questionnaires, neuroimaging before and after supplement or placebo administration and blood draws, office visits at week 2 (1.5 hours), week 4 (3 hours), week 6 (0.5 hours), week 8 (6 hours), a follow-up visit at week 10 (1.5 hours) and two phone calls between visits (weeks 1 and 3) during which a brief clinical assessment will be obtained (10 minutes each). The total time involved in the study is approximately 23.5 hours.

Inclusion Criteria:

• Meets the Diagnostic and statistical manual - 5 (DSM-5) diagnostic criteria for MDD without psychotic features (past or present), as confirmed by the M.I.N.I v7.0
• PHQ-9 score of ≥10
• C-Reactive Protein (CRP) value > 1
• Age 18-65
• Consent ability and written consent
• Body Mass Index (BMI) between 19 and 38 kg/m2
• Medically stable based on clinical laboratory tests, medical history and vital signs
• No intention to become pregnant during the study
• A woman of childbearing potential must have a negative serum pregnancy test at screening
• Consent that possible random finding is reported (e.g. brain abnormality during imaging)

Exclusion Criteria:

• Has a current or recent history of clinically significant suicidality
• Has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 12 months before screening
• Has positive test result(s) for alcohol or drugs of abuse (including methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine and ecstasy)
• Has a current diagnosis of a psychotic disorder (e.g. schizophrenia, bipolar disorder), an eating disorder (e.g. anorexia, bulimia), or learning disability or a personality disorder that is considered by the investigator to interfere with the ability of the subject to adhere to the protocol (e.g. narcissistic personality, borderline personality disorder)
• Change in medication dose and/or frequency within the last 6 weeks. Participants must be on stable medications for 6 weeks prior to enrollment.
• Plans to change medication dose/frequency during the course of the study. Must plan to remain on stable dose for the duration of the study, unless otherwise indicated by their provider during the course of the study.
• Plans to take vitamins and/or mineral supplements during the study. Must refrain for the duration of the study
• Unable to complete MRI scans
• Is a woman who is pregnant or breast feeding
• Plans to conceive a child while enrolled in this study or within 3 months after the last dose of the keto-like supplement
• Has received an investigational drug/vaccines, used an invasive investigational medical device within 60 days before the planned first dose of the keto-like supplement or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in any drug or non-drug interventional study.
• Has had major surgery, (i.e. requiring general anesthesia) within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time they are expected to participate in the study.
• Intake of Omega 3 fatty acids (DHA, EPA, fish oil supplements)
• Significant cognitive impairment, clinically relevant or progressive disease (e.g., liver, kidney, cardiovascular system, respiratory tract, vascular system, brain, metabolism, thyroid) that could affect the course of the study
• Known metabolic disorders (e.g., fatty acid oxidation disorders, ketolysis/ketogenesis or glucogenesis disorder, hyperinsulinism (e.g., pancreatic neuroendocrine tumor), pyruvate carboxylase deficiency, Type 1 and Type 2 diabetes
• Allergy to Stevia sweetener, malic acid or orange flavoring
• Concern for inability to maintain adherence to the keto-like supplement administration protocol
• Currently practicing a ketogenic or paleo diet or planning to do so during the study period.
• Change in body weight of more than 5 kg within one month before the start of the intervention
• Medical, psychiatric or other conditions that restrict the patient's following abilities: to interpret the study information, to give informed consent, to adhere to the rules of the protocol, or to complete the study
• Contraindications to MRI examinations [persons with metallic implants (e.g., intracranial metal clips) and carriers of electronic devices (e.g., pacemaker) or persons with claustrophobia]