Ketone Ester Supplementation and Nocturnal Blood Pressure

Cardiovascular Diseases Clinical Trial

Official title:

The Effects of Ketone Ester Supplementation on Nocturnal Blood Pressure in Middle-Aged and Older Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05888506
• Other study ID #: H23223
• Status: Completed
• Phase: N/A
• Start date: August 1, 2023
• Est. completion date: October 3, 2023

Study information

• Verified date: October 2023
• Source: Georgia Southern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cardiovascular disease (CVD) is the number one cause of death globally and high blood pressure (i.e., hypertension) is the leading modifiable risk factor for CVD and all-cause mortality. Advancing age is the primary risk factor for hypertension and CVD. Moreover, compared to younger adults, older adults exhibit reduced nocturnal dipping of blood pressure resulting in elevated nighttime blood pressure values, which are a better predictor of cardiovascular outcomes than daytime blood pressure. Intriguingly, recently published rodent data suggests that ketone supplementation protects against hypertension, blood vessel dysfunction, and kidney injury. Whether ketone supplementation provides vascular health benefits in humans remains to be determined. Therefore, the investigations seek to conduct an acute ketone supplementation study to determine whether ketone supplementation may restore a more healthy nighttime blood pressure phenotype in middle-aged and older adults. The investigations will also determine whether ketone supplementation influences nocturnal heart rate variability, a non-invasive of autonomic function that may be influenced by ketone supplementation in a manner that influences blood pressure.

Description:

Cardiovascular disease (CVD) is the leading cause of death globally, killing one American approximately every 40 seconds. Among known risk factors, hypertension, or high blood pressure (BP), is the most important risk factor for the development of CVD. While sleeping, a healthy adult will experience a blood pressure dip of about 10% compared to resting values while awake. However, advancing age is associated with reduced blood pressure dipping, which is linked with an increased risk for CVD. Moreover, attenuated blood pressure dipping results in elevated nighttime blood pressure, which is in general a better predictor of cardiovascular outcomes than daytime blood pressure.

The autonomic nervous system plays a key role in blood pressure regulation and autonomic dysregulation is implicated in the pathophysiology of hypertension. Advancing age is associated with structural and function changes in the autonomic nervous system, which likely contribute, at least in part, to the marked elevation in the prevalence of hypertension and CVD that is observed in older adults. Heart rate variability (HRV) is an inexpensive and accessible index of autonomic function that is shown to decline rapidly form the second to fifth decades of life. Thus, strategies to improve nocturnal HRV may help to restore a more healthy nighttime blood pressure phenotype. However, this remains to be proven. Moreover, the link between aging, nocturnal HRV, and nighttime blood pressure is unclear.

Hypertension costs the United States between $131 and $198 billion dollars each year. Therefore, there exists a critical need to find ways to mitigate these negative health effects and costs to both the American public, and populations across the globe. Interestingly, there is a small but emerging body of evidence suggesting that ketone bodies may positively impact endothelial function and vascular health. In rodents, ketone supplementation prevents high-salt induced increase in blood pressure, blood vessel dysfunction, and kidney injury. However, there is a lack of data regarding whether ketone supplementation may provide similar cardiovascular health benefits in humans. Thus, in this first-of-kind placebo-controlled, randomized crossover design acute ketone supplementation study the investigations will evaluate the hypothesis that acute ketone supplementation will improve nocturnal blood pressure and HRV in middle-aged and older adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 3, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Greater than or equal to 50 years of age

• Body mass index (BMI) below 40 kg/m^2

• No alterations to use of prescription medication within the past 6 months

Exclusion Criteria:

• Alterations to use of prescription medication within the past 6 months

• Allergy to any of the ingredients in the ketone beverage

• Communication barriers

Related Conditions & MeSH terms

• Aging
• Cardiovascular Diseases
• Cardiovascular Diseases in Old Age
• Sleep

Intervention

Dietary Supplement:
• Ketone Ester
Participants will consume the ketone ester beverage produced by KetoneAid prior to bedtime. Participants will consume 60 mL (30 grams ketones) of the ketone beverage.
• Placebo
Participants will consume the placebo supplement prior to bedtime. The placebo supplement will be a ketone ester-free, taste and viscosity-matched, beverage produced by KetoneAid.

Locations

Country	Name	City	State
United States	Biodynamics and Human Performance Center	Savannah	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Georgia Southern University	Auburn University

Country where clinical trial is conducted

United States, 

References & Publications (3)

Chakraborty S, Galla S, Cheng X, Yeo JY, Mell B, Singh V, Yeoh B, Saha P, Mathew AV, Vijay-Kumar M, Joe B. Salt-Responsive Metabolite, beta-Hydroxybutyrate, Attenuates Hypertension. Cell Rep. 2018 Oct 16;25(3):677-689.e4. doi: 10.1016/j.celrep.2018.09.058. — View Citation

Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008 Jan;51(1):55-61. doi: 10.1161/HYPERTENSIONAHA.107.100727. Epub 2007 Nov 26. — View Citation

Valensi P. Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications. Cardiovasc Diabetol. 2021 Aug 19;20(1):170. doi: 10.1186/s12933-021-01356-w. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nocturnal blood pressure dipping	The investigations will use ambulatory blood pressure monitoring to characterize night-to-day blood pressure ratio	Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary	Nighttime blood pressure	The investigations will use ambulatory blood pressure monitoring to characterize nighttime blood pressure (mmHg)	Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary	Nighttime heart rate variability	The investigators will use a single-lead electrocardiograph to characterize nocturnal heart rate variability (ms)	Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary	Objective sleep duration	Actigraph accelerometers will be used to quantify sleep duration	Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary	Objective sleep efficiency	Actigraph accelerometers will be used to quantify % of time in bed actually spent sleeping to calculate sleep efficiency	Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary	Subjective sleep quality	A single-item visual analogue sleep scale will be used to quantify subjective sleep quality (i.e., 0 to 100, with a higher score indicating better sleep)	Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary	Subjective sleep quality	The investigators will use the Pittsburgh Sleep Quality Index (PSQI) to assess perceived sleep quality reflective of the one month period leading into the study. PSQI scores range from 0-21, with a higher score indicting worse sleep.	Pre-intervention
Secondary	Pulse wave analysis	The investigators will use the SphygmoCor XCEL system to assess pulse wave analysis (PWA) The sampling site is the brachial artery (upper alarm instrumented with a cuff for oscillometric sphygmomanometer).	Pre-intervention
Secondary	Pulse wave velocity	The investigators will use the SphygmoCor XCEL system to assess pulse wave velocity (PWV). A high-fidelity strain-gauge transducer is used to obtain the pressure waveform at the carotid pulse. Distances from the carotid artery sampling site to the femoral artery (upper leg instrumented with a thigh cuff for oscillometric sphygmomanometry), and from the carotid artery to the suprasternal notch will be recorded. PWV will be expressed as m/s.	Pre-intervention