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8 support 3 contradict 2 tested null 2 mixed · 15 sources, 11 independent groups · 1 superseded — pooled inside a review, counted once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 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 |
| Horsdal 2025 · Basic Res Cardiol | animal | supports | high | Blinded crossover in porcine cardiogenic shock: 3-OHB increased cardiac output and contractility |
| Selvaraj 2025 · JACC Heart Fail | RCT | supports | moderate | [FT-verified] KETO-HFpEF 2025 crossover n=20 resting CO +0.6 L/min though peak VO2 null; independent group |
| Solis-Herrera 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 et al] # corrected 2026-08-17 from PubMed; was [(HFrEF 14-day) 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 et al 2025 · study_type: RCT | 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 | [FT-verified] Double-blind randomized crossover, n=19 healthy young adults (MSNA subset n=14), NCT04881526: KME 0.4 g/kg vs isocaloric placebo left CARDIAC OUTPUT unchanged - 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 BP waveform, not directly measured). Resting HR, BP, MAP, brachial blood flow, total vascular conductance and MSNA also null (all interactions p>0.23), as were responses to handgrip and mental stress. Caveats: peak capillary beta-HB only ~1.5 mM with no participant above 3 mmol/L, vs the 3-4 mM at which effects are reported; study powered for HR/MSNA not CO, and the authors state it may have been underpowered. |
| Lyhne 2025 · Intensive Care Med Exp | animal | tested-null | moderate | 3-OHB increased cardiac output and reduced pulmonary vascular resistance in porcine pulmonary embolism |
| Crabtree CD et al 2025 · study_type: RCT | 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 et al 2026 · World J Crit Care Med | meta-analysis | supports | low | [FT-verified, PMC13248031] 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 et al 2025 · study_type: observational | 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 et al 2025 · study_type: observational | 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 2024 · Sci Rep | animal | mixed | moderate | 3-OHB raised cardiac output via stroke volume but caused inotropy-resistant vasoplegia in transplant |
| Sun Q et al 2025 · study_type: animal | 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 et al 2025 · study_type: observational | 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 et al 2026 · study_type: observational | 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 et al. 2025 · Nutrients | RCT | supports | moderate | [FT-verified, PMC12525594] 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 et al 2025 · study_type: observational | 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, et al. 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 2025 · Circ Res | animal | mixed | moderate | Independent group: enhancing cardiac ketone-body oxidation improved exercise performance/cardiac function in mice |
| Bech 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 |
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