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AHuman RCT or meta-analysis

Hawthorn Berry

Crataegus

Hawthorn (Crataegus spp.; "hawthorn berry," though most standardized clinical extracts such as WS 1442 use leaf-with-flower) is a botanical traditionally used as an adjunct in chronic heart failure and marketed as an "organ-support"/cardiac ancillary. Standardized extracts are rich in oligomeric procyanidins and flavonoids and have shown modest improvements in exercise capacity and heart-failure symptoms in some randomized trials and a Cochrane meta-analysis, but the two most rigorous modern trials (HERB-CHF and the large 2-year SPICE mortality trial) found no benefit on functional endpoints or on the primary cardiac event endpoint. This is a cardioactive substance and should never be used as a substitute for guideline-directed heart-failure therapy; self-treating cardiac symptoms with hawthorn instead of seeking medical care is the primary risk. It is generally well tolerated with mild, transient adverse effects (nausea, dizziness, GI upset), and one trial found more (mostly non-cardiac) adverse events on hawthorn. Anyone with heart disease should only use it under a cardiologist's supervision. This is not an anabolic or performance agent and there is no human data supporting use for "organ support" outside heart failure.

Clinical readoutAncillary · organ-support
Hepatic strainLow
CardiovascularModerate
HPTA suppressionNone
Half-life
Not well characte…
Route
Oral
Evidence
A
Active
Clinical dosing is divi…
1·t½2·t½3·t½4·t½5·t½
Illustrative single-compartment washout · each mark = one half-life · t½ ≈ Not well characterized in humans. Individual flavonoid/procyanidin constituents have short plasma half-lives (hours) with low oral bioavailability; no validated single half-life exists for the whole standardized extract.
Pharmacology

Mechanism of action

Standardized Crataegus extracts (e.g., WS 1442, standardized to ~18.75% oligomeric procyanidins) act on the myocardium and vasculature. Preclinical and mechanistic data attribute effects to flavonoids and oligomeric procyanidins producing: cyclic-AMP-independent positive inotropy (proposed via inhibition of Na+/K+-ATPase and prolongation of the refractory period), coronary and peripheral vasodilation with enhanced endothelial nitric oxide synthesis, antioxidant/free-radical scavenging activity, anti-inflammatory effects, and protection against ischemia-reperfusion injury and pressure-overload hypertrophy. These mechanisms are largely derived from in-vitro and animal studies; the extent to which they translate to clinically meaningful effects in humans is uncertain given negative modern trials.
Kinetics

Pharmacokinetics

Half-life

Not well characterized in humans. Individual flavonoid/procyanidin constituents have short plasma half-lives (hours) with low oral bioavailability; no validated single half-life exists for the whole standardized extract.

Active duration

Clinical dosing is divided (typically twice daily), consistent with a short-acting profile; sustained clinical effects in trials required continued daily dosing over weeks to months rather than reflecting a long single-dose duration.

Route

Oral (film-coated tablets, capsules, tinctures, dried extract of leaf-with-flower or berry).

Metabolism & clearance

Polyphenolic constituents undergo extensive gut-microbial and hepatic phase-II metabolism (glucuronidation, sulfation, methylation) with renal and biliary excretion of metabolites. Human PK of the standardized extract is poorly defined; washout data are not well established, so no reliable clearance/washout figure can be stated. Not intended for and not to be used for drug-test evasion.

For monitoring and washout planning, not drug-test evasion.

Reported effects

Physiological & performance effects

  • In a Cochrane meta-analysis of 10 RCTs (855 patients, NYHA I-III), hawthorn extract as an adjunct improved maximal workload, exercise tolerance, the pressure-heart-rate product (an index of myocardial oxygen consumption), and symptoms of shortness of breath and fatigue versus placebo.
  • In the HERB-CHF RCT (120 patients on contemporary heart-failure therapy), hawthorn produced no improvement in 6-minute walk distance, quality of life, peak oxygen consumption, or neurohormones; only a small LVEF difference favored hawthorn.
  • In the large SPICE trial (2681 patients, 24 months), WS 1442 900 mg/day had no significant effect on the primary combined cardiac-event endpoint and no significant effect on cardiac mortality; a post-hoc subgroup with less impaired LVEF (>=25%) suggested reduced sudden cardiac death, a hypothesis-generating finding only.
  • Net picture: possible modest symptomatic/exercise benefit in older/adjunctive trials, not confirmed on rigorous functional or hard clinical endpoints in modern trials.
Safety

Adverse effects by system

Cardiovascular

Generally well tolerated; reported cardiac adverse events in trials were infrequent, and in the SPICE trial adverse events were comparable to placebo. Because hawthorn is cardioactive (proposed inotropic/vasodilatory effects), theoretical risks include hypotension and interaction with the effects of cardiac glycosides; palpitations and dizziness have been reported. The greatest cardiovascular danger is indirect: using hawthorn in place of proven heart-failure therapy.

Hepatic

No signal of hepatotoxicity in the reviewed heart-failure RCTs or the WS 1442 benefit-risk review; no adequate dedicated human hepatic-safety data. No established cases of hawthorn-induced liver injury in the retrieved primary literature.

Endocrine / HPTA

No known effect on the hypothalamic-pituitary-testicular/gonadal axis or other endocrine systems; no human data. Hawthorn is not a hormonal or SERM-type agent.

Reproductive

No adequate human data on fertility, pregnancy, or lactation. Use in pregnancy/breastfeeding is not recommended due to lack of safety data and theoretical uterine/cardiovascular activity.

Neuropsychiatric

No established psychiatric adverse effects; dizziness/lightheadedness reported (likely vasomotor rather than psychiatric). No adequate human data on mood/cognition.

Renal

No known nephrotoxicity; renal function was not adversely affected in the reviewed trials. No adequate dedicated human renal-safety data beyond heart-failure trial populations.

Hematologic

No established hematologic toxicity. Theoretical additive effects with anticoagulant/antiplatelet drugs are proposed based on flavonoid content but are not confirmed by human interaction studies.

Dermatologic

Rare, mild; isolated reports of rash have been described in the broader literature. In the reviewed RCTs skin reactions were not a prominent signal.

Recovery

HPTA suppression & recovery

Suppression: None expected / not applicable

Hawthorn has no known androgenic, estrogenic, or gonadotropic activity and is not a SERM; no HPTA suppression is expected and no post-cycle or single-SERM recovery framing applies. Any endocrine concerns in an individual should be evaluated and managed by an endocrinologist rather than self-managed.

Bloodwork & vitals

Monitoring

Recommended labs & checks
Baseline and periodic assessment of cardiac status by a clinician (blood pressure, heart rate, symptom review)Electrolytes and renal function if used alongside diuretics/ACE inhibitors/heart-failure medicationsDigoxin level if co-administered with digoxin (clinical prudence, despite a negative PK interaction study)LFTs are reasonable if any signs of hepatic dysfunction arise, though no specific hepatic signal is established

Cadence: Under the direction of a treating physician; any cardiac-symptom monitoring should follow the clinician's heart-failure follow-up schedule rather than a fixed self-directed interval.

Warning signs — seek care
  • Worsening shortness of breath, edema, or exercise intolerance (may signal decompensating heart failure requiring urgent medical care, not more supplement)
  • Lightheadedness, fainting, or symptomatic low blood pressure
  • Palpitations or new/irregular heartbeat
  • Chest pain (seek emergency care)
  • Allergic reaction (rash, swelling, difficulty breathing)
Do not use if

Contraindications

  • Should not replace guideline-directed medical therapy for heart failure or any cardiac condition.
  • Known hypersensitivity to Crataegus or Rosaceae-family plants.
  • Use only under cardiologist supervision in anyone with diagnosed heart failure, arrhythmia, coronary disease, or hypotension.
  • Caution/medical oversight with cardiac glycosides (digoxin/digitoxin), antihypertensives, nitrates, and other cardioactive drugs due to potential additive pharmacodynamic effects (even though a formal digoxin PK interaction study was negative).
  • Pregnancy and breastfeeding: avoid due to absence of human safety data.
  • Not for use to enhance athletic performance, body composition, or 'organ optimization'—no evidence supports these uses.
Combinations

Interaction profile

  • ContraindicatedWith DNP: Additive cardiovascular strain

Check a specific combination in the interaction checker.

Harm reduction

Reducing harm & when to stop

  • Do not use hawthorn as a substitute for prescribed heart-failure or cardiac medication; it is at best an adjunct and modern rigorous trials did not confirm benefit.
  • If you have any cardiac diagnosis, use it only with your cardiologist's knowledge and supervision.
  • Stop and seek prompt medical care for worsening breathlessness, swelling, fainting, chest pain, palpitations, or signs of an allergic reaction.
  • Tell every prescriber and pharmacist you are taking it, especially if you use digoxin, blood-pressure medications, nitrates, or anticoagulants.
  • Avoid in pregnancy and breastfeeding due to lack of human safety data.
  • Do not use it to try to 'optimize' organ function or performance—there is no evidence for such uses and self-medicating cardiac symptoms delays real care.
  • Prefer standardized products and disclose use during any bloodwork or clinical monitoring your physician orders.
Evidence

Citations (6)

Every clinical claim above is tied to a primary source. Overall evidence grade A graded to the best available evidence for its core claims.

  1. 01

    A Cochrane meta-analysis of 10 RCTs (855 patients, NYHA I-III) found hawthorn extract improved maximal workload, exercise tolerance, pressure-heart-rate product, and symptoms vs placebo, with infrequent, mild, transient adverse events (nausea, dizziness, cardiac/GI complaints) and no adequate mortality/morbidity data.

    Meta-analysisDOI 10.1002/14651858.CD005312.pub2

  2. 02

    In the SPICE trial (2681 patients, NYHA II-III, LVEF<=35%, 24 months), WS 1442 900 mg/day had no significant effect on the primary combined cardiac-event endpoint or cardiac mortality; adverse events were comparable to placebo; a post-hoc LVEF>=25% subgroup suggested reduced sudden cardiac death.

    RCTDOI 10.1016/j.ejheart.2008.10.004

  3. 03

    In the HERB-CHF RCT (120 patients on standard therapy), hawthorn 450 mg twice daily produced no improvement in 6-minute walk distance, quality of life, functional capacity, neurohormones, oxidative stress, or inflammation; a small LVEF difference favored hawthorn; significantly more (mostly non-cardiac) adverse events occurred in the hawthorn group.

    RCTDOI 10.1093/eurjhf/hfp116

  4. 04

    WS 1442 is a standardized leaf-with-flower dry extract (17.3-20.1% oligomeric procyanidins); nonclinical studies show positive inotropic, antiarrhythmic, endothelial-NO-enhancing, antioxidant and ischemia-protective properties; clinical trials and post-marketing surveillance show a favorable safety profile with no observed drug interactions and no specific known adverse reactions.

    ReviewDOI 10.1007/s40256-017-0249-9

  5. 05

    Proposed pharmacological mechanisms of standardized Crataegus extract include cAMP-independent positive inotropy, peripheral/coronary vasodilation, protection against ischemia-induced ventricular arrhythmias, antioxidative and anti-inflammatory effects (SPICE rationale/design).

    ReviewDOI 10.1016/s1388-9842(00)00109-4

  6. 06

    A randomized crossover study in 8 healthy volunteers found WS 1442 hawthorn 450 mg twice daily for 21 days did not significantly alter any digoxin pharmacokinetic parameter, suggesting the two may be coadministered without a PK interaction at the doses studied.

    RCTPMID 12817526

Last reviewed 2026-07-06 · Verified against PubMed · Educational, not medical advice