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.

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.

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

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