Lactate infusion and oral lactate improve heart function in chronic heart failure trial

Lactate, long dismissed as a harmful waste product of anaerobic metabolism, has delivered a striking result in a small randomized trial of patients with chronic heart failure. In a double-blind crossover study, intravenous sodium lactate raised cardiac output by 1.5 liters per minute compared with placebo, while an oral formulation increased it by 0.4 liters per minute, according to findings published in Critical Care. The trial enrolled 12 patients with heart failure with reduced ejection fraction, a condition in which the heart muscle pumps too weakly to meet the body’s demands.

The study, registered at ClinicalTrials.gov as NCT06121323, was designed to answer a question that has puzzled researchers as views of lactate have shifted. Elevated blood lactate concentrations are associated with adverse outcomes in acute heart failure and critical illness, and clinicians routinely track lactate as a warning sign. Yet emerging evidence identifies lactate as an important metabolic substrate and signaling molecule, and the acute hemodynamic effects of lactate in patients with chronic heart failure had remained unknown until now.

Each participant completed two study days. On one day, researchers infused sodium lactate intravenously and compared it with an isovolumic saline placebo. On a separate day, patients took oral sodium lactate alongside an isocaloric placebo. Hemodynamics were assessed hourly using pulmonary artery catheterization and echocardiography, allowing the team to measure pressures and flows inside the heart and lungs directly rather than relying on peripheral estimates.

The interventions did what they were meant to do chemically. Intravenous lactate increased blood lactate concentrations by 2.3 millimoles per liter compared with placebo, and oral lactate raised them by 0.9 millimoles per liter, both differences statistically significant at P less than 0.001. Those elevations translated into measurable cardiac changes. Intravenous lactate increased cardiac output by 1.5 liters per minute, while the oral route produced a 0.4 liter per minute increase, significant at P equal to 0.01.

Stroke volume and heart rate both rose during intravenous administration, each with P values below 0.001, indicating that the extra output came from stronger pumping and faster beating together. During oral administration, heart rate increased with P less than 0.001. Systemic vascular resistance, a measure of the load the heart pumps against, fell during intravenous lactate infusion with P less than 0.001. Meanwhile, pulmonary capillary wedge pressure and central venous pressure, both markers of cardiac filling pressures, decreased during oral administration, with P values of 0.02 and 0.004 respectively.

Echocardiographic measures added further detail. The left ventricular outflow tract velocity-time integral, an ultrasound index of blood ejected through the aortic valve with each beat, increased during both routes of administration. Global longitudinal strain, a sensitive measure of the coordinated contraction of the heart muscle, improved following intravenous lactate. Indices of diastolic function, which describe how well the heart relaxes and fills between beats, also improved during lactate administration by both routes.

The authors concluded that in patients with chronic heart failure, lactate administration improved systolic and diastolic function and reduced afterload and cardiac filling pressures.

The results carry important caveats. The trial involved only 12 patients, and the crossover design, while efficient, means each participant served as their own control on separate study days. The hemodynamic assessments captured acute effects over single days of exposure, so the durability of these benefits, their effect on symptoms, exercise capacity or long-term outcomes, and the safety of repeated dosing remain open questions. The study was published as an early version, subject to further edits before the final Version of Record.

Subject of Research: Acute hemodynamic effects of intravenous and oral lactate in chronic heart failure

Article Title: Lactate improves hemodynamics in chronic heart failure: a randomized crossover study

Article References: Jespersen, N. A., Berg-Hansen, K., Tougaard, R. S., Gopalasingam, N., Nielsen, B. R., Møller, N., & Wiggers, H. (2026). Lactate improves hemodynamics in chronic heart failure: a randomized crossover study. Critical Care. https://doi.org/10.1186/s13054-026-06433-8

Image Credits: AI Generated

DOI: 10.1186/s13054-026-06433-8

Keywords: lactate, chronic heart failure, cardiac output, randomized crossover trial, hemodynamics, echocardiography, sodium lactate, reduced ejection fraction, diastolic function, afterload, improves, chronic