Effects of Ketone Ester on Brain Metabolism and Cognition in Older Adults

Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults >= 55 Years Old. A Double-Blinded Randomized Controlled Clinical Trial.

This study tests if a ketone ester drink can boost brain energy and improve thinking skills in older adults with metabolic syndrome.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT04421014 on ClinicalTrials.gov

What this trial studies

This study investigates the impact of a ketone ester supplement on brain metabolism and cognitive performance in cognitively intact adults aged 55 and older with metabolic syndrome. Participants will be randomly assigned to receive either the ketone ester drink or a placebo for 28 days, with assessments of brain ketone levels and cognitive function conducted throughout the study. The research aims to determine if the supplement can enhance brain energy metabolism and improve cognitive abilities. The study will involve multiple visits for screening, testing, and follow-up evaluations.

Who should consider this trial

Good fit: Ideal candidates are cognitively intact adults aged 55 and older who have metabolic syndrome.

Not a fit: Patients with significant cognitive impairment or those not meeting the criteria for metabolic syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new dietary interventions that enhance cognitive function and brain health in older adults.

How similar studies have performed: While the use of ketone esters in cognitive enhancement is a relatively novel approach, preliminary studies suggest potential benefits, though further research is needed to confirm these findings.

Eligibility criteria

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Ability to provide informed consent and willingness to sign a written informed consent document
2. Male or female, age \>=55 years old
3. Cognitively intact status ascertained during screening (defined as absence of significant memory or cognitive changes in the last 2 years by subjective report, Clinical Dementia Rating (CDR) of 0, and Montreal Cognitive Assessment (MoCA) \>= 26)
4. Ability to take oral medications
5. Willingness to adhere to all study procedures including having MRI/MRS.
6. Presence of Metabolic Syndrome (MetS). Specifically, they should meet three of the five following MetS diagnostic criteria to be eligible:

   * Receive drug treatment for elevated triglycerides (TGs) or have serum TGs \>=150 mg/dL (1.7 mmol/L)
   * Receive drug treatment for low HDL-cholesterol or have serum HDL-cholesterol \<40 mg/dL (1.0 mmol/L) in males; \<50 mg/dL (1.3 mmol/L) in females
   * Receive drug treatment for high Blood Pressure (BP) or have BP \>=130/85 mmHg
   * Receive drug treatment for high blood glucose or have fasting plasma glucose \>=100 mg/dL
   * Central obesity, defined as a waist circumference \>=102 cm (40 in) in men and \>=88 cm (35 in) in women.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Previously diagnosed with a condition causing clinically significant cognitive impairment, such as MCI, AD or other type of dementia (such as vascular dementia, Lewy body dementia and frontotemporal dementia).
2. History of clinically significant brain disorders, such as stroke, multiple sclerosis, Parkinson s disease or other movement disorders, brain tumors, history of meningitis or encephalitis, history of moderate or severe traumatic brain injury (defined as Glasgow Coma Scale of 12 or less), epilepsy. Certain common neurological disorders not considered relevant (e.g. migraine, essential tremor) or incidental neuroimaging findings that are common and of uncertain clinical significance (e.g. mild-moderate microvascular changes on MRI) may be allowed.
3. Chronic and significant psychiatric conditions (e.g. history of bipolar disorder, schizophrenia, PTSD, moderate to severe depression or treatment-resistant depression. Unipolar depression or anxiety disorder may be allowed if mild or if successfully treated with single anti-depressant or anti-anxiety agents.
4. Positive urine drug screen (and no prescription medication accounting for the positive test).
5. Positive HIV, HBV or HCV status during screening.
6. Contraindications for MRI (pregnancy, pacemakers or other implanted devices, ferrous metal implants or shrapnel in or around the head etc.).
7. Anemia (defined as HGB \< 12 for men or \< 11 g/dl for women)
8. Poor venous access.
9. Lactation or Pregnancy (positive urine pregnancy test. Pregnancy tests will not be done on post-menopausal women defined as one of the below criteria:

   1. prior bilateral oophorectomy
   2. Amenorrhea for 12 months or more
10. Known severe allergic reactions to the KE drinks or other ketogenic supplement or stevia products.
11. Following high fat/low carb diet (ketogenic) diet or very low calorie (\<500 calories) diet or taking other ketogenic supplements (such as Medium Chain Triglycerides (MCTs), Ketone Salts) or fasting intermittently and unwilling to stop it while on the KE drink/Placebo.
12. Very high or severe hypertriglyceridemia (\>=886 mg/dL or 10.0 mmol/L)
13. Severe Hypertension (systolic blood pressure \>=180 mmHg and/or diastolic blood pressure \>=120 mmHg)
14. Weight \>= 300 lbs (MRI scanner weight limit)
15. Diabetes Mellitus (type 1 or 2)
16. Taking the drug metformin.
17. Non-English speakers (given staffing constraints for cognitive testing administration and need for decreased variability in testing procedures for a small N study).
18. Participant has any concurrent medical condition, so that participation in the clinical study would not be in her/his best interest, in the PI s judgement.
19. To be eligible to consent for optional thigh MRI: Individuals with joint replacements that may be affected by the defined exercise protocol or which may prevent MRI analysis or any condition, in the opinion of the investigator, that would prevent successful completion of the exercise protocol such as, but not limited to reported osteoarthritis, rheumatoid arthritis and/or fibromyalgia.

Where this trial is running

Baltimore, Maryland

• National Institute of Aging, Clinical Research Unit — Baltimore, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Dimitrios I Kapogiannis, M.D. — National Institute on Aging (NIA)
• Study coordinator: Sarah Park, R.N.

Conditions: Metabolic Syndrome, Normal Cognition, Ketogenic, Brain Metabolism, BETA-HYDROXYBUTYRATE, Dietary Supplement, Alzheimer's Disease