Trial Outcomes & Findings for Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults 55 Years Old or Older (NCT NCT04421014)
NCT ID: NCT04421014
Last Updated: 2026-04-02
Results Overview
β-hydroxybutyrate (BHB) was quantified in the posteromedial cortex (PMC) using ¹H-MRS (PRESS). Acute and acute-on-chronic responses were defined as the within-visit ratios of \~75 minutes post-drink to pre-drink (post/pre) at Weeks 0 and 4, respectively. The chronic effect was defined as the ratio of pre-drink BHB at Week 4 to pre-drink at Week 0 (Week 4 pre / Week 0 pre). BHB values were derived from spectral fitting with predefined quality-control criteria.
COMPLETED
NA
99 participants
Week 0 and Week 4 (pre-drink and ~75 minutes post-drink)
2026-04-02
Participant Flow
Recruitment took place between September 29, 2020 and August 16, 2023.
99 participants provided informed consent and underwent screening; 41 were ineligible, 4 withdrew prior to randomization, and 54 participants were randomized, 26 to KE and 28 to Placebo.
Participant milestones
| Measure |
Ketone Ester Drink
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
28
|
|
Overall Study
COMPLETED
|
25
|
25
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
Reasons for withdrawal
| Measure |
Ketone Ester Drink
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults 55 Years Old or Older
Baseline characteristics by cohort
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.9 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
65.8 years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
65.9 years
STANDARD_DEVIATION 6.0 • n=10 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
12 Participants
n=5 Participants
|
24 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
13 Participants
n=5 Participants
|
26 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
5 Participants
n=5 Participants
|
12 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=5 Participants
|
20 Participants
n=5 Participants
|
38 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=10 Participants
|
|
Body Mass Index, Continuous
|
33.4 kg/m^2
STANDARD_DEVIATION 4.7 • n=5 Participants
|
31.9 kg/m^2
STANDARD_DEVIATION 3.9 • n=5 Participants
|
32.6 kg/m^2
STANDARD_DEVIATION 4.3 • n=10 Participants
|
|
Waist Circumference, Continuous
|
115.9 cm
STANDARD_DEVIATION 11.1 • n=5 Participants
|
112.3 cm
STANDARD_DEVIATION 8.2 • n=5 Participants
|
114.1 cm
STANDARD_DEVIATION 9.8 • n=10 Participants
|
|
Montreal Cognitive Assessment (MoCA) score, Continuous
|
28.2 units on a scale
STANDARD_DEVIATION 1.4 • n=5 Participants
|
27.6 units on a scale
STANDARD_DEVIATION 1.2 • n=5 Participants
|
27.9 units on a scale
STANDARD_DEVIATION 1.3 • n=10 Participants
|
PRIMARY outcome
Timeframe: Week 0 and Week 4 (pre-drink and ~75 minutes post-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS PRESS assessment. BHB estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 40% were excluded from analysis.
β-hydroxybutyrate (BHB) was quantified in the posteromedial cortex (PMC) using ¹H-MRS (PRESS). Acute and acute-on-chronic responses were defined as the within-visit ratios of \~75 minutes post-drink to pre-drink (post/pre) at Weeks 0 and 4, respectively. The chronic effect was defined as the ratio of pre-drink BHB at Week 4 to pre-drink at Week 0 (Week 4 pre / Week 0 pre). BHB values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=24 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=22 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in β-hydroxybutyrate in the Posteromedial Cortex Measured by ¹H-MRS (PRESS)
Acute ratio (Week 0 Post/Pre)
|
1.847 Ratio
Standard Error 0.130
|
0.922 Ratio
Standard Error 0.076
|
|
Change in β-hydroxybutyrate in the Posteromedial Cortex Measured by ¹H-MRS (PRESS)
Acute-on-chronic ratio (Week 4 Post/Pre)
|
1.265 Ratio
Standard Error 0.081
|
1.172 Ratio
Standard Error 0.095
|
|
Change in β-hydroxybutyrate in the Posteromedial Cortex Measured by ¹H-MRS (PRESS)
Chronic ratio (Week 4 Pre/Week 0 Pre)
|
1.064 Ratio
Standard Error 0.089
|
0.900 Ratio
Standard Error 0.072
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink and ~60 minutes post-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Serum β-hydroxybutyrate
Acute ratio (Week 0 Post/Pre)
|
6.136 Ratio
Standard Error 0.540
|
0.970 Ratio
Standard Error 0.085
|
|
Change in Serum β-hydroxybutyrate
Acute-on-chronic ratio (Week 4 Post/Pre)
|
5.737 Ratio
Standard Error 0.500
|
0.174 Ratio
Standard Error 0.015
|
|
Change in Serum β-hydroxybutyrate
Chronic ratio (Week 4 Pre/Week 0 Pre)
|
1.072 Ratio
Standard Error 0.092
|
1.015 Ratio
Standard Error 0.087
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink and ~60 minutes post-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Serum Acetoacetate
Chronic ratio (Week 4 Pre/Week 0 Pre)
|
1.180 Ratio
Standard Error 0.110
|
1.095 Ratio
Standard Error 0.102
|
|
Change in Serum Acetoacetate
Acute ratio (Week 0 Post/Pre)
|
9.862 Ratio
Standard Error 1.090
|
1.655 Ratio
Standard Error 0.183
|
|
Change in Serum Acetoacetate
Acute-on-chronic ratio (Week 4 Post/Pre)
|
8.217 Ratio
Standard Error 0.862
|
1.453 Ratio
Standard Error 0.152
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink and ~60 minutes post-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Serum Non-Esterified Fatty Acids
Acute-on-chronic ratio (Week 4 Post/Pre)
|
0.611 Ratio
Standard Error 0.059
|
0.720 Ratio
Standard Error 0.070
|
|
Change in Serum Non-Esterified Fatty Acids
Chronic ratio (Week 4 Pre/Week 0 Pre)
|
1.030 Ratio
Standard Error 0.105
|
1.051 Ratio
Standard Error 0.108
|
|
Change in Serum Non-Esterified Fatty Acids
Acute ratio (Week 0 Post/Pre)
|
0.785 Ratio
Standard Error 0.084
|
0.884 Ratio
Standard Error 0.094
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Body Mass Index
|
0.447 kg/m²
Standard Error 0.264
|
0.386 kg/m²
Standard Error 0.264
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Waist Circumference
|
0.368 cm
Standard Error 0.863
|
-1.745 cm
Standard Error 0.908
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Fasting Glucose
|
2.68 mg/dL
Standard Error 1.77
|
1.28 mg/dL
Standard Error 1.77
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Fasting Insulin
|
1.436 μIU/mL
Standard Error 1.63
|
-0.676 μIU/mL
Standard Error 1.63
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Total Cholesterol
|
0.28 mg/dL
Standard Error 2.94
|
4.88 mg/dL
Standard Error 2.94
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Glucose/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Glucose was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a glucose-to-creatine (Glucose/Cr) ratio. The chronic response was defined as the ratio of pre-drink Glucose/Cr at Week 4 to pre-drink Glucose/Cr at Week 0 (Week 4 pre / Week 0 pre). Glucose/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=24 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Glucose in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.10 Ratio
Standard Error 0.052
|
1.06 Ratio
Standard Error 0.051
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. N-acetyl-aspartate/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
N-acetyl-aspartate was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a N-acetyl-aspartate-to-creatine (N-acetyl-aspartate/Cr) ratio. The chronic response was defined as the ratio of pre-drink N-acetyl-aspartate/Cr at Week 4 to pre-drink N-acetyl-aspartate/Cr at Week 0 (Week 4 pre / Week 0 pre). N-acetyl-aspartate/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in N-acetyl-aspartate in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.978 Ratio
Standard Error 0.023
|
0.965 Ratio
Standard Error 0.023
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Lactate/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Lactate was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Lactate-to-creatine (Lactate/Cr) ratio. The chronic response was defined as the ratio of pre-drink Lactate/Cr at Week 4 to pre-drink Lactate/Cr at Week 0 (Week 4 pre / Week 0 pre). Lactate/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Lactate in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.07 Ratio
Standard Error 0.061
|
1.01 Ratio
Standard Error 0.058
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Glycine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Glycine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Glycine-to-creatine (Glycine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Glycine/Cr at Week 4 to pre-drink Glycine/Cr at Week 0 (Week 4 pre / Week 0 pre). Glycine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=24 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=23 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Glycine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.957 Ratio
Standard Error 0.056
|
1.047 Ratio
Standard Error 0.064
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Glutamate/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Glutamate was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Glutamate-to-creatine (Glutamate/Cr) ratio. The chronic response was defined as the ratio of pre-drink Glutamate/Cr at Week 4 to pre-drink Glutamate/Cr at Week 0 (Week 4 pre / Week 0 pre). Glutamate/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Glutamate in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.955 Ratio
Standard Error 0.019
|
0.992 Ratio
Standard Error 0.020
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Gamma-aminobutyric acid/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Gamma-aminobutyric acid was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Gamma-aminobutyric acid-to-creatine (Gamma-aminobutyric acid/Cr) ratio. The chronic response was defined as the ratio of pre-drink Gamma-aminobutyric acid/Cr at Week 4 to pre-drink Gamma-aminobutyric acid/Cr at Week 0 (Week 4 pre / Week 0 pre). Gamma-aminobutyric acid/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Gamma-aminobutyric Acid in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.025 Ratio
Standard Error 0.056
|
0.957 Ratio
Standard Error 0.056
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Glutamine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Glutamine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Glutamine-to-creatine (Glutamine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Glutamine/Cr at Week 4 to pre-drink Glutamine/Cr at Week 0 (Week 4 pre / Week 0 pre). Glutamine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Glutamine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.926 Ratio
Standard Error 0.062
|
0.942 Ratio
Standard Error 0.060
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Glutathione/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Glutathione was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Glutathione-to-creatine (Glutathione/Cr) ratio. The chronic response was defined as the ratio of pre-drink Glutathione/Cr at Week 4 to pre-drink Glutathione/Cr at Week 0 (Week 4 pre / Week 0 pre). Glutathione/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Glutathione in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.969 Ratio
Standard Error 0.035
|
0.980 Ratio
Standard Error 0.036
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Myo-inositol/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Myo-inositol was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Myo-inositol-to-creatine (Myo-inositol/Cr) ratio. The chronic response was defined as the ratio of pre-drink Myo-inositol/Cr at Week 4 to pre-drink Myo-inositol/Cr at Week 0 (Week 4 pre / Week 0 pre). Myo-inositol/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Myo-inositol in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.994 Ratio
Standard Error 0.020
|
0.951 Ratio
Standard Error 0.019
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. N-acetyl-aspartyl-glutamate/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
N-acetyl-aspartyl-glutamate was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a N-acetyl-aspartyl-glutamate-to-creatine (N-acetyl-aspartyl-glutamate/Cr) ratio. The chronic response was defined as the ratio of pre-drink N-acetyl-aspartyl-glutamate/Cr at Week 4 to pre-drink N-acetyl-aspartyl-glutamate/Cr at Week 0 (Week 4 pre / Week 0 pre). N-acetyl-aspartyl-glutamate/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=22 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=24 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in N-acetyl-aspartyl-glutamate in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.20 Ratio
Standard Error 0.148
|
1.28 Ratio
Standard Error 0.165
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Aspartate/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Aspartate was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as an Aspartate-to-creatine (Aspartate/Cr) ratio. The chronic response was defined as the ratio of pre-drink Aspartate/Cr at Week 4 to pre-drink Aspartate/Cr at Week 0 (Week 4 pre / Week 0 pre). Aspartate/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=24 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Aspartate in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.910 Ratio
Standard Error 0.041
|
0.914 Ratio
Standard Error 0.041
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Ascorbate/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Ascorbate was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as an Ascorbate-to-creatine (Ascorbate/Cr) ratio. The chronic response was defined as the ratio of pre-drink Ascorbate/Cr at Week 4 to pre-drink Ascorbate/Cr at Week 0 (Week 4 pre / Week 0 pre). Ascorbate/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Ascorbate in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.974 Ratio
Standard Error 0.045
|
1.015 Ratio
Standard Error 0.046
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Alanine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Alanine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as an Alanine-to-creatine (Alanine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Alanine/Cr at Week 4 to pre-drink Alanine/Cr at Week 0 (Week 4 pre / Week 0 pre). Alanine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=21 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=23 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Alanine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.939 Ratio
Standard Error 0.044
|
1.023 Ratio
Standard Error 0.047
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Scyllo-inositol/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Scyllo-inositol was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Scyllo-inositol-to-creatine (Scyllo-inositol/Cr) ratio. The chronic response was defined as the ratio of pre-drink Scyllo-inositol/Cr at Week 4 to pre-drink Scyllo-inositol/Cr at Week 0 (Week 4 pre / Week 0 pre). Scyllo-inositol/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=24 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=20 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Scyllo-inositol in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.06 Ratio
Standard Error 0.055
|
1.02 Ratio
Standard Error 0.061
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Phosphocholine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Phosphocholine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Phosphocholine-to-creatine (Phosphocholine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Phosphocholine/Cr at Week 4 to pre-drink Phosphocholine/Cr at Week 0 (Week 4 pre / Week 0 pre). Phosphocholine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=23 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=23 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Phosphocholine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.041 Ratio
Standard Error 0.068
|
0.852 Ratio
Standard Error 0.056
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Glycerophosphocholine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Glycerophosphocholine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Glycerophosphocholine-to-creatine (Glycerophosphocholine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Glycerophosphocholine/Cr at Week 4 to pre-drink Glycerophosphocholine/Cr at Week 0 (Week 4 pre / Week 0 pre). Glycerophosphocholine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=14 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=13 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Glycerophosphocholine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.999 Ratio
Standard Error 0.921
|
5.464 Ratio
Standard Error 5.340
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Phosphoethanolamine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Phosphoethanolamine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Phosphoethanolamine-to-creatine (Phosphoethanolamine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Phosphoethanolamine/Cr at Week 4 to pre-drink Phosphoethanolamine/Cr at Week 0 (Week 4 pre / Week 0 pre). Phosphoethanolamine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Phosphoethanolamine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
0.971 Ratio
Standard Error 0.049
|
1.007 Ratio
Standard Error 0.051
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline ¹H-MRS J-PRESS assessment. Taurine/Cr estimates with Cramér-Rao lower bounds (CRLB, %SD) ≥ 20% were excluded from analysis.
Taurine was quantified in the posteromedial cortex (PMC) using ¹H-MRS (J-PRESS) at pre-drink assessments and expressed as a Taurine-to-creatine (Taurine/Cr) ratio. The chronic response was defined as the ratio of pre-drink Taurine/Cr at Week 4 to pre-drink Taurine/Cr at Week 0 (Week 4 pre / Week 0 pre). Taurine/Cr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=10 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=13 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Taurine in the Posteromedial Cortex Measured by ¹H-MRS (J-PRESS)
|
1.057 Ratio
Standard Error 0.188
|
0.785 Ratio
Standard Error 0.156
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline thigh ³¹P-MRS assessment. Assessments were excluded from analysis if the τPCr relative fit error (SD/estimate) ≥ 0.20, if PCr drop area \< 30%, or if intramuscular minimum pH \< 6.8.
Post-exercise phosphocreatine (PCr) recovery time constant (τPCr) was measured by thigh ³¹P-MRS at pre-drink assessments. The chronic response was defined as the ratio of pre-drink τPCr at Week 4 to pre-drink τPCr at Week 0 (Week 4 pre / Week 0 pre). τPCr values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=17 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=13 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Post-exercise Phosphocreatine (PCr) Recovery Time Constant (τPCr) Measured by Thigh ³¹P-MRS
|
1.06 Ratio
Standard Error 0.072
|
1.17 Ratio
Standard Error 0.090
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline thigh ³¹P-MRS assessment. Assessments were excluded from analysis if the τPCr relative fit error (SD/estimate) ≥ 0.20, if PCr drop area \< 30%, or if intramuscular minimum pH \< 6.8.
Phosphocreatine (PCr) depletion area during exercise (PCr drop area) was measured by thigh ³¹P-MRS at pre-drink assessments. The chronic response was defined as the ratio of pre-drink PCr drop area at Week 4 to pre-drink PCr drop area at Week 0 (Week 4 pre / Week 0 pre). PCr drop area values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=17 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=13 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Phosphocreatine (PCr) Depletion Area During Exercise (PCr Drop Area) Measured by Thigh ³¹P-MRS
|
1.178 Ratio
Standard Error 0.057
|
0.993 Ratio
Standard Error 0.055
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline thigh ³¹P-MRS assessment. Assessments were excluded from analysis if the τPCr relative fit error (SD/estimate) ≥ 0.20, if PCr drop area \< 30%, or if intramuscular minimum pH \< 6.8.
Intramuscular minimum pH during exercise was measured by thigh ³¹P-MRS at pre-drink assessments. The chronic response was defined as the difference between pre-drink PCr drop area at Week 4 and pre-drink PCr drop area at Week 0 (Week 4 pre - Week 0 pre). Intramuscular minimum pH values were derived from spectral fitting with predefined quality-control criteria.
Outcome measures
| Measure |
Ketone Ester Drink
n=17 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=13 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Intramuscular Minimum pH During Exercise Measured by Thigh ³¹P-MRS
|
-0.042 pH units
Standard Error 0.014
|
0.037 pH units
Standard Error 0.017
|
SECONDARY outcome
Timeframe: Week 0 and Week 4 (pre-drink)Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline brain MRI (T1-weighted MP-RAGE) assessment.
G-BrainAGE was derived from pre-drink 3D T1-weighted MP-RAGE brain MRI using FreeSurfer (longitudinal pipeline) features processed through the CentileBrain platform with sex-specific pretrained models. G-BrainAGE represents the difference between the model-predicted brain age and chronological age (predicted age - chronological age), with higher values indicating an "older-appearing" brain relative to age and lower values indicating a "younger-appearing" brain. The chronic effect was assessed as the change in G-BrainAGE from Week 0 to Week 4.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Global Brain-age Gap (G-BrainAGE) Measured by Brain MRI (T1-weighted MP-RAGE)
|
0.713 years
Standard Error 0.402
|
0.311 years
Standard Error 0.391
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
The Logical Memory test assesses verbal episodic memory for short stories. Participants recall two stories immediately and after a 20-30 minute delay. Outcomes include immediate and delayed recall subscores, each ranging from 0 to 50 (25 units/story × 2 stories), with higher scores indicating better performance. Verbatim subscores reflect exact recall; gist subscores reflect recall of essential elements.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Logical Memory Test
Immediate Verbatim Recall
|
3.72 points
Standard Error 0.866
|
2.00 points
Standard Error 0.866
|
|
Change in Logical Memory Test
Immediate Gist Recall
|
3.84 points
Standard Error 0.904
|
2.24 points
Standard Error 0.904
|
|
Change in Logical Memory Test
Delayed Verbatim Recall
|
2.84 points
Standard Error 1.05
|
1.88 points
Standard Error 1.05
|
|
Change in Logical Memory Test
Delayed Gist Recall
|
4.68 points
Standard Error 1.17
|
3.44 points
Standard Error 1.17
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
MoCA is a brief assessment of global cognitive function across multiple domains (e.g., attention, executive function, memory, language, visuospatial abilities, and orientation). Total scores range from 0 to 30, with higher scores indicating better cognitive performance.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Montreal Cognitive Assessment (MoCA)
|
0.007 points
Standard Error 0.393
|
0.040 points
Standard Error 0.386
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
The Eriksen flanker task assesses selective attention and inhibitory control by requiring responses to a target stimulus while ignoring distracting flankers. The outcome is a composite score integrating response accuracy and response time into a single performance metric. Composite scores range from 0 to 10, with higher scores indicating better performance.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Eriksen Flanker
|
0.052 scores on a scale
Standard Error 0.082
|
0.010 scores on a scale
Standard Error 0.087
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
The Dimensional Set Shifting task assesses cognitive flexibility (ability to shift between rules or stimulus dimensions). The outcome is a task-derived composite performance score; scores range from 0 to 10, with higher scores indicating better performance.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Dimensional Set Shifting
|
0.156 scores on a scale
Standard Error 0.196
|
0.170 scores on a scale
Standard Error 0.202
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
The Digit Symbol Substitution Test (DSST) assesses processing speed, attention, and visuomotor coordination by requiring participants to match symbols to digits using a provided key within a fixed time. The outcome is the total number of correct symbol-digit matches. Total scores range from 0 to 93, with higher scores indicating better performance.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Digit Symbol Substitution Test (DSST)
|
2.64 correct responses
Standard Error 1.27
|
1.92 correct responses
Standard Error 1.27
|
SECONDARY outcome
Timeframe: Week 0, Week 4Population: Analysis was performed in a modified intention-to-treat population, which included all randomized participants who received ≥ 1 dose of the intervention and had ≥ 1 post-baseline efficacy assessment.
The Free and Cued Selective Reminding Test (FCSRT) assesses verbal episodic memory using controlled learning and recall of a 16-word list with semantic cues. Total Free Recall (TFR) is the sum of freely recalled words across three learning trials (range 0 to 48). Total Delayed Free Recall (TDFR) is the number of freely recalled words after a delay (range 0 to 16). Higher scores indicate better memory performance.
Outcome measures
| Measure |
Ketone Ester Drink
n=25 Participants
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=25 Participants
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Change in Free and Cued Selective Reminding Test (FCSRT)
Total Free Recall
|
4.12 words recalled
Standard Error 0.843
|
3.84 words recalled
Standard Error 0.843
|
|
Change in Free and Cued Selective Reminding Test (FCSRT)
Total Delayed Free Recall
|
0.92 words recalled
Standard Error 0.348
|
0.92 words recalled
Standard Error 0.348
|
Adverse Events
Ketone Ester Drink
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ketone Ester Drink
n=25 participants at risk
The KE group received 25 g of the Veech ketone monoester ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate) three times daily in a water-based drink.
|
Placebo
n=26 participants at risk
The Placebo group received a dextrose drink containing \~35 g dextrose three times daily and providing the same calories as the KE drink (140 calories per dose). The drink also contained fruit flavor and stevia, plus denatonium benzoate (Bitrex) to approximate KE bitterness.
|
|---|---|---|
|
Investigations
ALT and AST elevation (~3× ULN)
|
4.0%
1/25 • 4 weeks
|
0.00%
0/26 • 4 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/25 • 4 weeks
|
3.8%
1/26 • 4 weeks
|
|
Gastrointestinal disorders
Abdominal bloating
|
0.00%
0/25 • 4 weeks
|
3.8%
1/26 • 4 weeks
|
|
General disorders
Dizziness postural
|
0.00%
0/25 • 4 weeks
|
3.8%
1/26 • 4 weeks
|
Additional Information
Dimitrios Kapogiannis
National Institute on Aging, NIH
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place