Table 1.

Ketone studies investigating cardiac outcomes.

Year	Author	Study	Population	No. participants	Formulation	Fasting	Intervention	Total average BHB dose	Insulin used	Findings overview	Concentration BHB	ADR
1993	Vanoverschelde et al. (12)	Cross-over	Healthy	6	Dextro-3-OHB 576 mM.	Fasting	40 μmol/kg/min for 20 min followed by 17 μmol/kg/min		No	Decreased 11C-Palmitate myocardial uptake indicating reduced fatty acid oxidation.	0.06 ± 0.05 to 1.15 ± 0.30 mM	Nil noted
2017	Gormsen et al. (13)	Randomized placebo-controlled single blinded crossover	Healthy	8	Racaemic Na-3-OHB 7.5%	Fasting	0.18 g/kg/h for 6.5 h		Yes - EG	Increased myocardial blood flow in all coronary artery vascular territories (~75%) with an increased HR potentially associated with alkalosis and reduced potassium. Myocardial glucose uptake halved.	<50 microM to 3.78 ± 0.47 mM post-infusion	Nil noted
2019	Nielsen et al. (14)	Randomized placebo-controlled single blinded crossover	HFrEF NYHA Class II-III + Healthy	Study 1: 24/10 HFrEF/controls; Study 2: 8 HFrEF	Racaemic Na-3-OHB 7.5% + KCl 60 mM	Fasting	Study 1: 0.18 g/kg/h for 3h; Study 2: 0.045 g/kg/h for 2 h then separately 0.09 g /kg/h for 2h; Study 3: 0.18 g/kg/h for 3h		Yes - EG	Dose dependent increase in CO in patients with HF, potentially related to decreased SVR.	Study 1: 0.4 ± 0.3 mM baseline to 3.3 ± 0.4 mM after 3 h infusion. Study 2: <0.1 mM to 0.7 ± 0.1 mM following 0.045 g/kg/h; 1.6 ± 0.3 mM following 0.09 g/kg/h. Study 3: 0.4 ± 0.3 mM to 3.4 ± 0.6 mM.	Asymptomatic VT in one patient with a history of VT. Two episodes of nausea (one during placebo, other following infusion of 3-OHB).

ADR, adverse drug reaction; BHB, beta-hydroxybutyrate; CI, continuous infusion; CO, cardiac output; EG, euglycaemic clamp; FFA, free fatty acids; NEFA, non-esterified fatty acids; GFR, glomerular filtration rate; GH, growth hormone; HFrEF, heart failure with reduced ejection fraction; HR, heart rate; NYHA New York Heart Association; SVR, systemic vascular resistance; T1DM, type 1 or insulin-dependent Diabetes mellitus; T2DM, type 2 or non-insulin-dependent Diabetes mellitus; VT, ventricular tachycardia.

Data presented as mean ± standard error.