Effects of Ketones and Niacin in Heart Failure Patients

Summary

Ketones, 3-hydroxybutyrate (3-OHB), have shown to have beneficial hemodynamics effect in patients with hearth failure with reduced ejection fraction. The mechanisms behind these marked hemodynamic effects are currently unknown, but could involve prostaglandin-release. 3-OHB is the endogenous ligand for the G protein-coupled receptor hydroxy-carboxylic acid 2 (HCA2) receptor. This receptor has proven downstream effects on cAMP and systemic effects via release of prostaglandins. In this present study we will investigate the cardiovascular effects of HCA2-receptor stimulation in heart failure patients.

Timeline

Start

2021-02-15

Primary completion

2021-09-03

Completion

2021-09-03

Outcome

Mixed primary results

paper The primary end point was CO. 3-OHB increased CO (2.3 L/min, P<0.01) PMID 37301762 ↗

paper Niacin increased prostaglandin D2 levels by 330% (P<0.02) and reduced free fatty acids by 75% (P<0.01) but did not affect CO. PMID 37301762 ↗

Publications

• Gopalasingam N, Christensen KH, Berg Hansen K, Nielsen R, Johannsen M, Gormsen LC, Boedtkjer E, Norregaard R, Moller N, Wiggers H. Stimulation of the Hydroxycarboxylic Acid Receptor 2 With the Ketone Body 3-Hydroxybutyrate and Niacin in Patients With Chronic Heart Failure: Hemodynamic and Metabolic Effects. J Am Heart Assoc. 2023 Jun 20;12(12):e029849. doi: 10.1161/JAHA.123.029849. Epub 2023 Jun 10.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Na-3-OHB	Unknown	—	—
Subject	Niacin	Small molecule	—	—

Indications