Supplements · Diets
exogenous ketones improves cardiac output
In plain terms: Can drinking ketones help the heart pump better?
Leans support Supplements 💰 Industry COI noted🔬 Includes disconfirming
Part of: 🧪 exogenous ketones
RefutedContestedStrong support
consensus score 0.38
Yes in heart-failure patients, but trials are short, from one group, and measure performance not survival.
📅 Last reviewed: 2026-07-15 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: All trials, pooled (Meta-analysis)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
8 support 3 contradict 2 tested null 2 mixed · 15 sources, 11 independent groups · 1 superseded — pooled inside a review, counted once
What the evidence shows
Exogenous ketones acutely raise cardiac output and myocardial efficiency in heart failure (HCA2-mediated) - the best clinical ketone signal. But short-term, surrogate endpoints (not mortality), and essentially one research group (Aarhus).
The evidence (22)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Chevli PA, Mirzai S, Kazibwe R, Kingsley J, Wood AC, Yeboah J, Slipczuk L, Mehta A, Bhatia HS, Pandey A, Shapiro MD 2026 · J Am Heart Assoc | observational | tested-null | low | UK Biobank: higher circulating ketone bodies associated with incident CV outcomes/mortality - endogenous KB are a stress marker, not a benefit signal |
| Hørsdal OK, Larsen AM, Wethelund KL, Dalsgaard FF, Seefeldt JM, Helgestad OKL, Moeslund N, Møller JE, Ravn HB, Nielsen RR, Wiggers H, Berg-Hansen K, Gopalasingam N 2025 · Basic Res Cardiol | animal | supports | high | Blinded crossover in porcine cardiogenic shock: 3-OHB increased cardiac output and contractility |
| Selvaraj S, Karaj A, Chirinos JA, Denney N, Grosso G, Fernando M, Chambers K, Demastus C, Reddy R, Langham M, Kumar D, Maynard H, Pourmussa B, Prenner SB, Cohen JB, Ischiropoulos H, Rickels MR, Poole DC, Church DD, Wolfe RR, Kelly DP, Putt M, Margulies KB, Zamani P 2025 · JACC Heart Fail | RCT | supports | moderate | KETO-HFpEF 2025 crossover n=20 resting CO +0.6 L/min though peak VO2 null; independent group |
| Solis-Herrera C, Qin Y, Honka H, Cersosimo E, Triplitt C, Neppala S, Rajan J, Acosta FM, Moody AJ, Iozzo P, Fox P, Clarke G, DeFronzo RA 2025 · Diabetes | RCT | supports | high | Independent group: graded beta-OHB infusion dose-dependently raised cardiac output, LVEF and stroke volume in T2DM+HF; NaHCO3 control negative |
| Berg-Hansen K, Gopalasingam N, Christensen KH, Ladefoged B, Andersen MJ, Poulsen SH, Borlaug BA, Nielsen R, Møller N, Wiggers H 2024 · (RCT) | RCT | supports | moderate | 14-day oral ketone-ester n=24 HFrEF resting CO 5.2 vs 5.0 L/min lower wedge pressure |
| Tominec D, Stalmans M, Narang BJ, Millet GP, Poffé C, Debevec T 2025 · Medicine and science in sports and exercise | RCT | contradicts | high | RCT, n=33 healthy adults (IEK n=16 vs placebo n=17), ketone monoester ingestion during high-altitude acclimatization; altitude increased cardiac output similarly in both groups (P=0.529-0.828) — no ketone effect on cardiac output. |
| Seto, Nardone, Thiessen, Teixeira, Bommarito, Pocchi, McCarthy, Millar 2025 · Physiol Rep | RCT | contradicts | moderate | Double-blind randomized crossover, n=19 healthy young adults (MSNA subset n=14), NCT04881526: KME 0.4 g/kg vs isocaloric placebo (MCT oil + bitters). Primary comparison (time x condition interaction) null for resting cardiac output - 5.2+/-1.4 to 5.8+/-1.0 L/min placebo vs 5.3+/-1.3 to 6.1+/-1.8 L/min KME, interaction p=0.63; CO Windkessel-estimated from the BP waveform. No interaction for CO responses to mental stress or handgrip, but in the mental-stress block the authors report main effects of condition with 'HR, cardiac output, total vascular conductance, and MSNA were higher in KME' (CO 6.4 vs 5.8 L/min at pre-stressor baseline, condition p=0.04; handgrip block condition p=0.70). Peak capillary beta-HB ~1.5 mM, no participant >3 mmol/L, below the 3-4 mM of studies reporting CV effects; authors state time effects and placebo instability 'may have led our study to be underpowered to detect differences between conditions over time'. |
| Lyhne MD, Gopalasingam N, Berg-Hansen K, Dragsbaek SJ, Homilius C, Seefeldt J, Hansen JV, Kramer AD, Christensen LJ, Ellegaard MS, Hørsdal OK, Overgaard A, Larsen AM, Boedtkjer E, Andersen A, Nielsen R 2025 · Intensive Care Med Exp | animal | tested-null | moderate | Randomised, assessor-blinded porcine study of acute pulmonary embolism (16 pigs, 8 per arm): 3-hour 3-OHB infusion vs saline. Primary outcome cardiac output: an underpowered trend toward the claim that 'did not statistically increase' (+0.7 L/min, 95% CI -0.2 to 1.6, p = 0.131); heart rate rose 18 bpm (8 to 28), stroke volume stayed stable, and the PVR/SVR ratio fell more than control (p = 0.046). Animal PE model, not heart failure; the authors note control animals appeared more severely affected by the embolism. |
| Crabtree CD, Pan Y, Chandrasekaran P, Wang Y, Scandling D, Bedell T, Stoner J, Decker D, Kackley M, Robinson B, Buga A, Han Y, Volek J, Simonetti OP 2025 · Physiological reports | observational | supports | moderate | Placebo-controlled acute cardiac MRI study, n=21 healthy adults (BH-BD n=11 vs placebo n=10); BH-BD raised R-BHB to 2.1mM, CO increased +31% (p<0.001) via +SV and +HR, myocardial blood flow +29%; placebo showed no change. |
| Siddiqi AK, Javaid SS, Kumar A, Kumar N, Ahmad M, Akhtar S, Raja AR, Ladhani D, Kumari N, Kumar S 2026 · World J Crit Care Med | meta-analysis | supports | low | Systematic review + random-effects meta-analysis of FOUR randomized crossover trials, 94 patients (85% men) with heart failure - the pooled denominator for cardiac output. Ketone supplementation raised CO vs placebo: MD = 1.11 L/min, 95%CI 0.13-2.09, P = 0.03 (CI lower bound 0.13, i.e. barely clear of null). SUBGROUP DENOMINATORS, each its own: HFrEF MD = 1.49 (95%CI 0.22-2.76, P = 0.02) from THREE trials with I2 = 88%, becoming MD = 2.04 (1.51-2.57) with heterogeneity 0% only after leave-one-out removal of Berg-Hansen 2024; HFpEF MD = 0.20 (95%CI 0.09-0.31) is a SINGLE trial, Gopalasingam 2024, n = 24, and the authors state subgroup analyses 'particularly HFpEF - were based on one study and should therefore be regarded as hypothesis-generating only'. LVEF also rose (MD = 3.31, 95%CI 0.39-6.22, P = 0.03). THE AUTHORS' CONDITIONS ARE PART OF THE FINDING: 'All included studies were randomized crossover trials conducted in Denmark'; exposures ran from acute 3-OHB infusion to a 14-day oral ester, so this is short-term haemodynamics on surrogate endpoints; two of four trials were at moderate risk of bias (RoB 2); 'Due to the limited number of included studies, formal meta-regression and funnel plot-based publication bias assessment were not feasible', with the authors themselves 'raising concern for potential small-study effects'; and the conclusion is that 'these results should be viewed as hypothesis-generating rather than definitive'. Structural endpoints did NOT move - GLS (MD = 0.45, 95%CI -0.61 to 1.50), LVEDV and TAPSE were all null - which is recorded here as context, not as a vote against the CO object. QUALITY moderate -> low on those author-stated limits, not on size (size is already in the grade). INDEPENDENCE, flagged not fixed: all four pooled trials are the Danish/Aarhus lineage, two of them (Nielsen 2019, Berg-Hansen 2024) are vault primaries correctly named in but sibling meta-analysis d10-64898 (Gupta 2026) supersedes the same two and pools the same literature at weight 8 - the claim's high-tier weight is several passes over one small Danish evidence base. Venue World J Crit Care Med (Baishideng); authors declare no conflicts of interest; funding not stated. |
| Kodur N, Nguyen C, Tang WHW 2025 · Journal of cardiac failure | observational | supports | low | State-of-the-art narrative review: multiple small short-term clinical trials show exogenous ketone supplementation may improve myocardial function across HF manifestations, though long-term data lacking. |
| Aromiwura AA, Gouwens KR, Nguyen DC, Sztukowska M, Didelot L, Kalra DK 2025 · International journal of molecular sciences | observational | supports | low | Narrative (non-systematic) review of myocardial perfusion regulation; concludes ketone bodies improve myocardial blood flow/ejection fraction in healthy subjects and beneficially affect cardiac output and filling pressures in decompensated |
| Seefeldt JM, Libai Y, Berg K, Jespersen NR, Lassen TR, Dalsgaard FF, Ryhammer P, Pedersen M, Ilkjaer LB, Hu MA, Erasmus ME, Nielsen RR, Bøtker HE, Caspi O, Eiskjær H, Moeslund N 2024 · Sci Rep | animal | mixed | moderate | 3-OHB raised cardiac output via stroke volume but caused inotropy-resistant vasoplegia in transplant |
| Sun Q, Wagg CS, Wong N, Wei K, Ketema EB, Zhang L, Fang L, Seubert JM, Lopaschuk GD 2025 · ESC heart failure | animal | contradicts | moderate | Mouse HFpEF model; 6-week ketone ester (1,3-butanediol) or empagliflozin supplementation restored myocardial ketone oxidation rates but was NOT associated with improvement in cardiac function. |
| Challa AA, Hill BG, Nystoriak MA, Gouwens KR, Kalra DK 2025 · JACC. Basic to translational science | observational | supports | moderate | Narrative review of ketone bodies' vascular effects; cites small clinical studies showing exogenous ketone administration to HF patients reduces systemic vascular resistance and improves myocardial function, plus increased coronary blood fl |
| Shrestha S, Harrison I, Dosunmu A, Song P 2026 · Cells | observational | supports | moderate | Narrative review of ketone biology in cardiovascular health/disease; discusses ketones' effects on cardiac metabolic/structural remodeling and signaling (beta-hydroxybutyrylation), citing preclinical and early clinical benefit in HF. |
| Mohib O, Bomans S, Jimenez Garcia B, Leemans L, Ligneel C, De Waele E, Beckwée D, Janssens P 2025 · Nutrients | RCT | supports | moderate | Systematic review, narrative synthesis only - 'a quantitative synthesis was not feasible' - so it stays zero-weight (evidence_role: review, already correct; unchanged at reread 2026-08-25). THE CARDIAC-OUTPUT FINDING IS A 5-OF-51 SUBSET, and each study carries its own denominator, none of which the previous extract named: chronic HFrEF - Monzo 2021, UNCONTROLLED open-label, 17 participants (11 HFrEF + 6 non-HFrEF), ketone ester 25 g, BHB rose 12.9-fold with the concentration not reported; and Nielsen 2019, four IV ketone-salt sub-studies of n = 16 / 8 / 10 / 10. Chronic HFpEF - Gopalasingam 2024, crossover double-blind RCT, n = 28 at randomization, ester 25 g four times daily for 2 weeks, BHB ~1 mmol/L. Cardiogenic shock - Berg-Hansen 2023, crossover double-blind RCT, n = 13, single 500 mg/kg dose over 3 h, BHB 2.9 +/- 0.5 mmol/L. Pulmonary hypertension - Nielsen 2023, crossover double-blind RCT, n = 20, IV Na-BHB 0.18 g/kg/h for 2 h, BHB 3.4 mmol/L. All five reported an acute CO rise: 'Overall, cardiovascular studies consistently demonstrated improvements in hemodynamic parameters and myocardial energetics, though evidence remains limited to short-term interventions in small samples.' THE AUTHORS' CONDITIONS ARE PART OF THE FINDING: the HFpEF result came with 'potential carry-over effects could not be excluded'; CO was measured by thermodilution and the 'Investigator who performed CO assessment by thermodilution (for Study 1 and 2) was not blinded to the randomization'; and the review concludes 'However, the current body of evidence is insufficient to establish clear clinical efficacy', with benefit 'mostly limited to surrogate endpoints'. INDEPENDENCE, flagged not fixed: four of the five are the Danish/Aarhus ketone-heart-failure lineage and at least two already vote on this claim as primaries under group_id ketone-hf-aarhus - the double count that the review role exists to prevent. GRADE FLAGGED, not edited: this row reads RCT while the paper is a narrative SR and all five sibling review-role rows on this claim read observational; grade is not a settable field and the row is zero-weight either way. Funding: FWO G075423N / WFWG; no declared COI. |
| Crabtree CD, Buga A, Han Y, Simonetti OP, Volek JS 2025 · Current atherosclerosis reports | observational | supports | low | Narrative review: nutritional ketosis acutely elevates cardiac output and myocardial perfusion in healthy and CVD subjects in a dose-dependent manner; effect durable up to 14 days; no long-term studies performed. |
| Gupta A et al 2026 · medRxiv | meta-analysis | supports | high | Systematic review + random-effects meta-analysis of 8 RCTs (oral ketones/infusions vs placebo) in HF/cardiometabolic-risk adults. Exogenous ketones increased CO (MD +1.11 L/min, 95%CI 0.55-1.67), LVEF, and SV, decreased PCWP. |
| Nielsen R, Møller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frøkiær J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Bøtker HE, Wiggers H 2019 · Circulation | RCT | supports | moderate | Landmark crossover n=16 HFrEF 3-OHB raised CO +2.0 L/min P<.001 via SV+HR; LVEF +8% acute ↩ SUPERSEDED — pooled in the review above, counted once |
| Gouwens KR, Pena Calderin E, Okhiria J, Nguyen DC, Schulman-Geltzer EB, Martinez-Ondaro Y, De Silva M, Collins HE, Nong Y, Sears SM, Nystoriak MA, Hill BG 2025 · Circ Res | animal | mixed | moderate | Independent group: enhancing cardiac ketone-body oxidation improved exercise performance/cardiac function in mice |
| Bech SK, Hansen ESS, Nielsen BR, Wiggers H, Bengtsen MB, Laustsen C, Miller JJ 2025 · Sci Rep | animal | supports | moderate | Hyperpolarized-MRS pig study: beta-3-OHB infusion increased cardiac output (1.9 to 3.8 L/min) and heart rate |
Disagree, or know a study we missed?
We grade by evidence, not opinions. The way to weigh in is to point us to a study we haven't cited (check the evidence table above first), or to flag a problem with one we have. Every submission is reviewed; if it holds up, the grade updates and shows in Science Changes Its Mind.
Opens a short form. You'll sign in with Google so submissions are tied to a real account — we don't display your identity, and we only accept a link we can verify (PubMed, DOI, ClinicalTrials.gov).
Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.