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Hawthorn

Botanical Name: Crataegus laevigata (Poir) DC, Crataegus monogyna Jacq. (Lindm.).
Pharmacopoeial Name: Folium cum Flore Crataegi.
Synonym: Crataegus oxyacantha L. (for C. laevigata). Also as Crategus spp.
Common Names: Hawthorn, English hawthorn, whitethorn, may flower.

Summary Table
Drug/Class Interaction TypeMechanism and SignificanceManagement
Digoxin, digitoxin
Cardiac glycosides
/
Plausible additive inotropic and antiarrhythmic effects. Interaction not established, possibly overstated.
Crataegus may enable lower drug levels, reducing digoxin toxicity.
Coadminister with professional management and monitoring.
Doxorubicin
Anthracycline chemotherapy
/
Theoretical reduction of drug-induced cardiotoxicity.Adopt, and continue Crataegus long-term postchemotherapy.
Hydrochlorothiazide
Thiazide diuretics
/
Additive beneficial effects on heart failure parameters.Adopt.
Coadminister.
herb description

Family

Rosaceae.

Related Species

Crataegus apiifolia Medik. non Michx., Crataegus piperi Britton, Crataegus rivularis Nutt.

In Chinese herbal medicine, Crataegus pinnatifida Bunge.; the fruit has traditionally been used.

Habitat and Cultivation

Thorny shrub or small tree, widespread throughout northern and eastern Europe and northeastern America in temperate zones. Hawthorn species hybridize freely, and in commerce, several related species may be used.

Parts Used

Leaf, flower.

Note: Hawthorn fruits, berries, or haws (Fructus Crataegi) are also traditionally used but lack comprehensive pharmacological and clinical data and are not considered separately here. The fruit is monographed separately in the official European Pharmacopoeia and the unofficial American Herbal Pharmacopoeia 1 and is “unapproved” by the German Commission E. 2

Common Forms

Dried leaf and flower.

  • Tincture:   40% to 60% alcohol

  • Standardized Extracts:   30 mg 5:1 5% oligomeric proanthocyanidins (OPCs) (Crataegutt, W Schwabe Pharmaceuticals); 80 mg 5:1 18.75% OPCs, ethanol extracted (Crategutt forte WS1442, W Schwabe); 300 mg 4:1 to 7:1 standardized to 2.25% flavonoids (Faros LI 132, Lichtwer Pharma AG).

Note: Oligomeric procyanidins, oligomeric proanthocyanidins, procyanidins, procyanidolic oligomers, and pycnogenols are synonymous terms, with the last also being a trademarked brand name for pine bark extract.

herb in clinical practice

Overview

Hawthorn is currently one of the most popular herbal remedies in Europe and is among the top-20 best-selling botanical products in the United States. In the past 20 years, hawthorn has been studied primarily as an adjuvant therapy for early congestive heart failure (New York Heart Association [NYHA] stage I-II), which is currently one of the principal clinical trial–driven indications for the herb. However, because of the broad spectrum of its pharmacology, resulting in part from the characteristic properties of the flavonoid and oligomeric procyanidin constituents, and its negligible toxicity and favorable adverse effect profile, practitioners of botanical medicine have long regarded hawthorn as a pivotal “all-round cardiovascular wellness remedy,” as well as the most significant herb for ischemic heart disease. It has antioxidant, anti-inflammatory, hypocholesterolemic, cardioprotective, angioprotective, hypotensive, antiarrhythmic, and positively inotropic properties, with additional beneficial actions on the digestive system and peripheral circulation, including collagen stabilization.

Hawthorn is suitable for extended duration of consumption, and official sources specify a minimum 4 to 6 weeks of administration to obtain maximum benefits in cardiac insufficiency. The German Commission E, 2 European Scientific Cooperative on Phytotherapy (ESCOP), 3 American Herbal Pharmacopoeia, 4 and World Health Organization (WHO) 5 provide monographs on hawthorn leaf and flower.

Historical/Ethnomedicine Precedent

Historically, hawthorn fruits were used for hundreds of years before the incorporation of the leaf and flower into medicinal usage. The modern use of hawthorn as a cardiac remedy began with the later Eclectics. Both Ellingwood 6 and Felter 7 experimented in the early 1900s with hawthorn fruit, flowers, and bark for functional heart conditions, along with their primary repertoire of cardiac glycoside–containing plants and their favored heart cardiac remedy Selenicereus grandiflorus . By the mid-twentieth century, a clinical understanding had developed of the differential indications of various cardiac glycoside–containing plants for congestive heart failure (CHF). German phytotherapist Rudolf Weiss's 1960 review of the cardiac glycoside herbs, including Digitalis, Strophanthus, Convallaria, Urginea, and Adonis, remains a classic bridging text to the present. For Weiss, as with the Eclectics, hawthorn was a mild remedy essentially indicated for functional heart problems, especially the “senile heart,” with the glycoside-containing plants reserved for treatment of organic heart disease. 8

As purified pharmaceutical digitaloids replaced the routine use of crude herbal drug cardiac glycoside–containing botanicals in heart failure, the German phytopharmaceutical manufacturers repositioned Crataegus as a CHF “adjunctive” remedy; backed by a shift in research emphasis based on Schwabe's proprietary (Crataegutt and WS 1442) hawthorn preparations for CHF. In this context, the contemporary emphasis on hawthorn as a CHF treatment is a rather recent and restrictive view of hawthorn, dominated by phytopharmaceutical industry priorities rather than the inherent properties of the remedy.

Known or Potential Therapeutic Uses

Cardiotonic and cardiopreventive for the “senile heart,” i.e., mild symptoms, including early angina, nervous heart complaints, myocardial weakness after serious illness, circulatory support, arteriosclerosis, hypertension, low heart rate variability, and peripheral arterial disorders.

Early CHF corresponding to NYHA stages I-II, possibly III.

Feelings of congestion and oppression in the precordium; protection against drug-induced cardiotoxicity.

Key Constituents

Flavonoids, glycosides (e.g., vitexin, vitexin-2-rhamnoside, rutin, quercitin), and related anthocyanidins (cyanidin and others) and oligomeric proanthocyanidins (catechin and epi-catechin derivatives).

Triterpenes (crataegolic acid and others), phenylpropanoids, several amino acids, and various monoamines.

Therapeutic Dosing Range

  • Dried Leaf and Flower:   Up to 1.5 g, three to four times daily, by infusion.

  • Tincture:   3 to 7 mL 1:2 daily.

  • Standardized Extract:   600 to 900 mg daily.

interactions review

Strategic Considerations

Pharmacopoeial sources, including the 1994 German Commission E monograph, deny any interactions between hawthorn and prescription pharmaceuticals. 2 However, the secondary literature persistently suggests that hawthorn may potentiate digoxin and other cardiac glycoside–containing herbs 4,9(see later discussion).

Cumulative cardiac drug polypharmacy is a familiar clinical presentation, especially among elder patients, often combined with one or more psychiatric drugs, such as anxiolytics and sedatives. Such patients constitute a “red flag” population for potential interactions of all permutations (i.e., drug-drug, herb-drug, drug-nutrient). It is relevant to consider the possible benefits of hawthorn in such populations. Is hawthorn beneficial and safe in the cardiac polypharmacy environment?

The indirect evidence, especially from clinical trial data, is reassuring. Pittler et al. 10 conducted a meta-analysis of clinical trials of hawthorn extract for treatment of chronic heart failure. Eight of 13 of the qualifying studies specifically allowed concomitant medications for CHF, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers, in their inclusion criteria. The remaining trials did not specify concomitant medications in their eligibility criteria. The majority of studies were therefore actually “interaction” trials between hawthorn and various cardiac medications in a substantial cohort of NYHA stage I-III CHF patients. The meta-analysis concluded there was a better-than-placebo effect on the surrogate endpoints (maximum workload, pressure–heart rate product, left ventricular ejection fraction) for the reviewed studies. Quality of life was tested by subjective questionnaire in only one of the smaller trials (30 patients) and was significantly improved in the verum over the placebo group. 11

Overall, adverse events were zero in five trials and minimal in the others. Vertigo and dizziness was the most common adverse event, followed by gastrointestinal symptoms. Only two patients (632 total) reported electrocardiologically related symptoms (i.e., palpitations and tachycardia). The implication is that hawthorn is beneficial in the cardiac polypharmacy patient. This is confirmed by the methodological approach of an international multicenter trial examining actual mortality outcomes in NYHA stage II-III CHF patients ( n = 2300). The study is investigating Crataegus WS1442 extract versus placebo and various conventional therapies, with cardiac glycosides, beta blockers, diuretics, and ACE inhibitors accepted in the inclusion criteria. 12

The conclusions from concurrent drug-herb trial data are that addition of hawthorn extracts may be beneficial and may interact positively or at worst may be neutral with a range of cardiac medications in CHF without adverse effects. As Zick et al. 13 indicated in a survey, however, patients in these trials may also be consuming unrelated dietary supplements, some of which may interact with their medications.

Cardiac conduction disturbances are a similar critical area of potential drug interaction. Electrophysiologically, hawthorn corresponds most closely to the Vaughan-Williams class III drugs such as amiodarone (i.e., increase of action potential duration, usually by K+channel block). 14-16Hawthorn extracts have positive inotropic effects, decrease atrioventricular (A-V) conduction time, increase coronary blood flow, and decrease myocardial energy utilization. 17-19However, intracellular recordings of rodent myocytes demonstrate that the effective refractory period (ERP) is prolonged by hawthorn extracts, not shortened as in class III agents. 20 Confirmation of increased ERP has been shown in the ex vivo Langendorff model (perfused guinea pig heart) by Joseph et al. 15

Conventional treatment of arrhythmias with pharmacotherapeutic antiarrhythmic agents remains largely empirical and is confounded by several problems, including the proarrhythmic properties of many of the drugs; also, left untreated, arrhythmias may resolve over time. 14 The post–Cardiac Arrhythmia Suppression Trial (CAST) era has seen a reevaluation of the advisability of treating nonlethal disturbances in cardiac rhythm versus preventing lethal ventricular tachycardia or ventricular fibrillation and sudden cardiac death. 21,22The antiarrhythmic properties of hawthorn make it a suitable agent for mild arrhythmias before empirical treatment with pharmaceutical antiarrhythmic agents. 23 This is further supported by hawthorn's positive effects on coronary flow and reduction of ischemic reperfusion injury, because transient ischemic events often trigger rhythm disturbances. 24,25The high morbidity associated with arrhythmias and CHF make hawthorn an outstanding remedy for this patient group.

Further indirect evidence for the pluripotent cardiovascular effects of hawthorn comes from the pharmacology of isolated constituents, particularly the oligomeric cyanidins and flavonoids. In vitro work has demonstrated nitric oxide (NO)–mediated endothelial relaxation by vitexin-rhamnoside. Phosphodiesterase-inhibiting activity, thromboxane A2(TXA2) inhibition of adenosine 5′-diphosphate–induced platelet aggregation, ACE inhibition, and phospholipase A2inhibition, as well as antioxidant, hypolipidemic, and antiatherosclerotic properties, have all been shown by in vitro studies. 25-33

Weiss's summary remains a succinct statement of the strategic framework for hawthorn administration. He contrasts it to digitalis, noting that “the two drugs are at opposite poles of heart therapy; hawthorn's gentle and long lasting action, lacking risks and unpleasant side effects, [means] that patients can on the whole be left to use it without constant supervision.” It is “particularly suitable for long-term prophylactic use in middle aged patients, … and in follow up therapy for myocardial infarction.” 8

herb-drug interactions
Digoxin, Digitoxin and Related Cardiac Glycosides
Doxorubicin and Related Anthracycline Chemotherapy
Hydrochlorothiazide and Related Thiazide Diuretics, Combined with Triamterene
Citations
  • 1.Upton R. Hawthorn berry. American Herbal Pharmacopoeia. Santa Cruz, Calif; 1999.
  • 2.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998:685.
  • 3.ESCOP. Crataegi Folium cum Flore. ESCOP Monographs: the Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003.
  • 4.Upton R. Hawthorn leaf with flower. American Herbal Pharmacopoeia. Santa Cruz, Calif; 1999.
  • 5.WHO. Folium cum Flore Crataegi. WHO Monographs on Selected Medicinal Plants. 2 vol. Geneva: World Health Organization; 2002:66-82.
  • 6.Ellingwood F, Lloyd J. Crataegus oxyacantha. The American Materia Medica: Therapeutics and Pharmacognosy. Eclectic Medical Publications, Portland, Ore; 1983 ed. Cincinnati; 1919:217-220.
  • 7.Felter H. Crataegus. The Eclectic Materia Medica: Pharmacology and Therapeutics. Eclectic Medical Publications, Portland, Ore; 1985 ed. Cincinnati; 1922:325-326.
  • 8.Weiss R. Organic heart disease, heart failure. Herbal Medicine. Meuss A, Translator. 6th ed. Beaconsfield, UK: Beaconsfield Publishers Ltd; 1988:126-149.
  • 9.Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy, Ore: Eclectic Medical Publications; 2001.
  • 10.Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med 2003;114:665-674.View Abstract
  • 11.Leuchtgens H. [Crataegus special extract WS 1442 in NYHA II heart failure: a placebo-controlled randomized double-blind study]. Fortschr Med 1993;111:352-354.View Abstract
  • 12.Holubarsch CJ, Colucci WS, Meinertz T et al. Survival and Prognosis Investigation of Crataegus Extract WS 1442 in Congestive Heart Failure (SPICE): rationale, study design and study protocol. Eur J Heart Fail 2000;2:431-437.View Abstract
  • 13.Zick SM, Blume A, Aaronson KD. The prevalence and pattern of complementary and alternative supplement use in individuals with chronic heart failure. J Card Fail 2005;11:586-589.View Abstract
  • 14.Beaufils P, Leenhardt A, Denjoy I, Slama R. Antiarrhythmic drugs in the adult population. In: Rosen M, Janse M, Wit A, eds. Cardiac Electrophysiology. Mount Kisco, NY: Futura Publishing Company Inc; 1990:1175-1192.
  • 15.Joseph G, Zhao Y, Klaus W. [Pharmacologic action profile of Crataegus extract in comparison to epinephrine, amirinone, milrinone and digoxin in the isolated perfused guinea pig heart]. Arzneimittelforschung 1995;45:1261-1265.View Abstract
  • 16.Iwamoto M, Sato T, Ishizaki T. [The clinical effect of Crataegutt in heart disease of ischemic or hypertensive origin: a multicenter double-blind study]. Planta Med 1981;42:1-16.View Abstract
  • 17.Muller A, Linke W, Klaus W. Crataegus extract blocks potassium currents in guinea pig ventricular cardiac myocytes. Planta Med 1999;65:335-339.View Abstract
  • 18.Loew D. [Phytogenic drugs in heart diseases exemplified by Crataegus]. Wien Med Wochenschr 1999;149:226-228.View Abstract
  • 19.Loew D. Phytotherapy in heart failure. Phytomedicine 1997;4:267-271.
  • 20.Popping S, Rose H, Ionescu I et al. Effect of a hawthorn extract on contraction and energy turnover of isolated rat cardiomyocytes. Arzneimittelforschung 1995;45:1157-1161.View Abstract
  • 21.Meinertz T, Zehender M, Hohnloser SH. [Clinical evaluation of new anti-arrhythmia drugs after the CAST (Cardiac Arrhythmia Suppression Trial) study]. Z Kardiol 1992;81 Suppl 4:145-149.View Abstract
  • 22.Lucchesi BR, Chi L, Friedrichs GS et al. Antiarrhythmic versus antifibrillatory actions: inference from experimental studies. Am J Cardiol 1993;72:25F-44F.View Abstract
  • 23.Blesken R. [Crataegus in cardiology]. Fortschr Med 1992;110:290-292.View Abstract
  • 24.Schussler M, Holzl J, Rump AF, Fricke U. Functional and antiischaemic effects of monoacetyl-vitexinrhamnoside in different in vitro models. Gen Pharmacol 1995;26:1565-1570.View Abstract
  • 25.Nasa Y, Hashizume H, Hoque AN, Abiko Y. Protective effect of Crataegus extract on the cardiac mechanical dysfunction in isolated perfused working rat heart. Arzneimittelforschung 1993;43:945-949.View Abstract
  • 26.Rajendran S, Deepalakshmi PD, Parasakthy K et al. Effect of tincture of Crataegus on the LDL-receptor activity of hepatic plasma membrane of rats fed an atherogenic diet. Atherosclerosis 1996;123:235-241.View Abstract
  • 27.Rogers KL, Grice ID, Griffiths LR. Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments. Eur J Pharm Sci 2000;9:355-363.View Abstract
  • 28.Lacaille D, Franck U, Wagner H. Search for potential angiotensin-converting enzyme (ACE) inhibitors from plants. Phytomedicine 2001;8:47-52.
  • 29.Ahumada C, Saenz T, Garcia D et al. The effects of a triterpene fraction isolated from Crataegus monogyna Jacq. on different acute inflammation models in rats and mice: leucocyte migration and phospholipase A2 inhibition. J Pharm Pharmacol 1997;49:329-331.View Abstract
  • 30.Vibes J, Lasserre B, Gleye J, Declume C. Inhibition of thromboxane A2 biosynthesis in vitro by the main components of Crataegus oxyacantha (hawthorn) flower heads. Prostaglandins Leukot Essent Fatty Acids 1994;50:173-175.View Abstract
  • 31.Chen ZY, Zhang ZS, Kwan KY et al. Endothelium-dependent relaxation induced by hawthorn extract in rat mesenteric artery. Life Sci 1998;63:1983-1991.View Abstract
  • 32.Andriantsitohaina R. Regulation of vascular tone by plant polyphenols: role of nitric oxide. Gen Physiol Biophys 1999;18 Suppl 1:3-5.View Abstract
  • 33.Fan C, Yan J, Qian Y et al. Regulation of lipoprotein lipase expression by effect of hawthorn flavonoids on peroxisome proliferator response element pathway. J Pharmacol Sci 2006;100:51-58.View Abstract
  • 34.Koch E. Hawthorn interaction potential [letter]. Herbalgram 2003;59:70-71.
  • 35.Trunzler G, Schuler E. [Comparative studies on the effect of a Crataegus extract, of digitoxin, digoxin and g-strophanthin on the isolated mammalian heart]. Arzneimittelforschung 1962;12:198-202.
  • 36.Schwinger RH, Pietsch M, Frank K, Brixius K. Crataegus special extract WS 1442 increases force of contraction in human myocardium cAMP-independently. J Cardiovasc Pharmacol 2000;35:700-707.View Abstract
  • 37.Long SR, Carey RA, Crofoot KM et al. Effect of hawthorn (Crataegus oxycantha) crude extract and chromatographic fractions on multiple activities in a cultured cardiomyocyte assay. Phytomedicine 2006.View Abstract
  • 38.Tankanow R, Tamer HR, Streetman DS et al. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). J Clin Pharmacol 2003;43:637-642.
  • 39.Conseil G, Baubichon-Cortay H, Dayan G et al. Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci USA 1998;95:9831-9836.View Abstract
  • 40.Johne A, Brockmoller J, Bauer S et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-345.
  • 41.Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). Circulation 1995;92:2764-2784.
  • 42.Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997;336:525-533.
  • 43.Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the Advisory Council to improve outcomes nationwide in heart failure. Am J Cardiol 1999;83:1A-38A.
  • 44.Arnsdorf MF, Wasserstrom JA. A matrical approach to the basic and clinical pharmacology of antiarrhythmic drugs. Rev Clin Basic Pharm 1987;6:131-188.View Abstract
  • 45.Arnsdorf MF. Cardiac excitability and antiarrhythmic drugs: a different perspective. J Clin Pharmacol 1989;29:395-404.View Abstract
  • 46.Arnsdorf MF. Cardiac excitability, the electrophysiologic matrix and electrically induced ventricular arrhythmias: order and reproducibility in seeming electrophysiologic chaos. J Am Coll Cardiol 1991;17:139-142.View Abstract
  • 47.Goldberger AL. Fractal mechanisms in the electrophysiology of the heart. IEEE Eng Med Biol Mag 1992;11:47-52.View Abstract
  • 48.Poon CS, Merrill CK. Decrease of cardiac chaos in congestive heart failure. Nature 1997;389:492-495.View Abstract
  • 49.Glass L. Chaos and heart rate variability. J Cardiovasc Electrophysiol 1999;10:1358-1360.View Abstract
  • 50.Pikkujamsa SM, Makikallio TH, Sourander LB et al. Cardiac interbeat interval dynamics from childhood to senescence: comparison of conventional and new measures based on fractals and chaos theory. Circulation 1999;100:393-399.View Abstract
  • 51.Brouwer CA, Gietema JA, van den Berg MP et al. Long-term cardiac follow-up in survivors of a malignant bone tumour. Ann Oncol 2006.View Abstract
  • 52.Swain SM, Whaley FS, Gerber MC et al. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 1997;15:1318-1332.View Abstract
  • 53.Tauchert M. Efficacy and safety of Crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J 2002;143:910-915.View Abstract
  • 54.Lalukota K, Cleland JG, Ingle L et al. Clinical trials update from the Heart Failure Society of America: EMOTE, HERB-CHF, BEST genetic sub-study and RHYTHM-ICD. Eur J Heart Fail 2004;6:953-955.View Abstract
  • 55.Harkness R, Bratman S. Mosby’s Handbook of Drug-Herb and Drug-Supplement Interactions. St Louis: Mosby; 2003.