INTRODUCTION

Hawthorn is a large shrub or small tree (15-30 feet on average) in the genus Crataegus, native to temperate North America, Europe, and East Asia.¹ The plants are indeterminately thorny, with variable shape, and have perfect, radially symmetrical, 5-petaled white to pink flowers (red in some cultivars) in corymbs (flat-topped clusters).^2,3 The red fruit are drupes (one-seeded and fleshy) but are commonly called berries in the trade. The genus Crataegus comprises approximately 250-280 species, the most commonly used in Western medicine being C. laevigata (syn. C. oxyacantha) and C. monogyna, both native to Europe; these 2 species are the subject of this article.² The European Pharmacopoeia accepts the interchangeable use of these 2 species or their hybrids, or other European Crataegus species such as C. azarolus, C. nigra, and C. pentagyna.⁴ Crataegus species are highly variable, making species boundaries unclear.² Additionally, hybridization among hawthorn species is very common, suggesting that there are few pure populations.^2,3

Traditionally, preparations of the fruit, such as syrups, were the most commonly used medicinal form, but preparations made from the flowers, leaves, and seeds also have been used in traditional European medicines and phytotherapy.^5-7 Plant material used in commercial products is primarily obtained from wild collection in Albania, Bosnia and Herzegovina, Bulgaria, Romania,⁸ Hungary, Macedonia,⁹ Poland,¹⁰ and the United Kingdom.¹² Some of the commercial supply of C. monogyna is actually wild collected in non-native countries, namely in Chile, where it was introduced and has since escaped from cultivation.

HISTORY AND CULTURAL SIGNIFICANCE

The generic name, Crataegus, comes from the Greek kratos, meaning hard or strong, referring to the plant’s wood.^13,14 The common name refers to the plant’s thorns and fruit, known as haws, and may also refer to its use to form hedges, which were called haws in earlier times.¹³ Other common names for C. laevigata include English hawthorn, white thorn, May tree (referring to when it blooms), and two-style hawthorn; and English hawthorn, one-seed hawthorn, and one-style hawthorn for C. monogyna.^3,12,15,16 General common names for the genus include haw, mayhaw, thornapple (not to be confused with Datura stramonium [Solanaceae], which is also called thornapple).

At least 1 hawthorn species that is not the focus of this article (C. pinnatifida) has been used in Chinese medicine dating back to 659 CE to treat arteriosclerosis, high blood pressure, and heart pain.¹⁷ In current practice, the dried ripe fruit, either “stir-baked” (by placing the dried berries in a pot, stirring constantly over gentle heat until color darkens, removing and cooling) or “charred” (by stir-baking until the berries become burnt-brown externally and yellowish-brown internally), is indicated for treating stagnation of undigested meat with epigastric distension, diarrhea and abdominal pain, amenorrhea due to blood stasis (local stoppage or slowness of the blood flow or general sluggishness of blood circulation), epigastric pain (over the pit of the stomach), or abdominal colic after childbirth, hernial pain, and for hyperlipemia (aka hyperlipidemia; excessive quantity of fat in the blood).¹⁸ Additionally, hawthorn fruit has been used in China for stomach complaints and for its vitamin C content to treat scurvy, as well as to make jam, sweet wine, and candied fruit slices.¹⁷

Infusions and decoctions of the bark, fruit, leaves, root and root bark, sap and sapwood, thorns, twigs, and young shoots of at least 11 species of Crataegus have been used by various North American tribes to treat conditions including back pain, bladder ailments, consumption (pulmonary tuberculosis), diarrhea, mouth sores, and stomach complaints, and also as a mild laxative, to promote appetite, to prevent spasms, to poultice swellings, and to stop menstrual flow.¹⁹ Additional external and internal uses include treating “large stomachs,” “female weakness,” “general debility,” and “to ward off tacklers.” At least 1 tribe, the Cherokee, used an infusion of the bark of 1 species, C. spathulata, to promote circulation. Furthermore, the berries have been used as food, both fresh and dried, and were considered by the Thompson tribe as a good health food for general sickness. The inner bark was chewed as gum, and the thorns were used as fish hooks, awls, pins, and to probe boils and areas of arthritic pain.

The first mention of hawthorn’s cordial actions on the heart may have been made by the Swiss physician Paracelsus (1493-1541).¹² The English physician Nicholas Culpeper (1616-1654) wrote that dried, powdered hawthorn berries added to wine would help with “stones” and dropsy (edema of lower extremities caused by congestive heart failure); an infusion of the flower would stop diarrhea or flux; and that the seed, bruised and boiled in wine, was “good for inward tormenting pains.”²⁰ In her 1931 classic, A Modern Herbal, Maud Grieve attributes cardiac, diuretic, astringent, and tonic actions to C. oxyacantha.¹³ While the plant mainly was used as a cardiac tonic, the flowers and berries also were used, due to their astringency, to treat sore throats.

The use of hawthorn for heart conditions had entered European clinical practice by the 17^th century and became popular in the late 19^th through early 20^th centuries.³ In North America, hawthorn was used for cardiac medicine by 1896. Today, hawthorn preparations are one of the best-selling botanical medicines in Germany.¹⁶ Tea made from the leaf and flower are available loose and in teabags; dry and fluid extracts, tinctures, soft extracts, and injectable forms are also available. In France, hawthorn is used for anxiety and insomnia.²¹ It also is utilized as a mild sedative, often in combination with lavender (Lavandula spp., Lamiaceae) or lemon balm (Melissa officinalis, Lamiaceae) in cases where mild heart disease is accompanied by nervousness.¹⁴

Hydroalcoholic extract of hawthorn leaf with flower (flowering twig tips of C. monogyna, C. laevigata, or other species of the genus   cited in a valid pharmacopeia and effective dosage preparations made from them) was approved by the German Commission E for decreasing cardiac output as described in functional Stage II (slight limitation of physical activity; comfortable at rest) of the New York Heart Association’s 1994 Revisions to Classification of Functional Capacity and Objective Assessment of Patients with Diseases of the Heart (NYHA).²² Hawthorn berry, flower, and leaf as single components received negative evaluations from the German Commission E in 1994 due to insufficient scientific evidence at that time supporting their use, although combined leaf with flower extracts were approved that year.¹² Other sources recommend it for Stage I of NYHA as well as cardiac degeneration that does not yet require digitalis, bradycardic arrhythmias, and a sensation of pressure in the chest. The European Scientific Cooperative on Phytotherapy (ESCOP) also recommended herbal tea and preparations other than a hydroalcoholic extract for support of cardiac and circulatory function in nervous heart complaints.²³

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES

In 2011, the European Medicines Agency (EMA) called for scientific data to be used by its Committee on Herbal Medicinal Products (HMPC) for assessment work toward the establishment of Community herbal monographs and/or Community list entries for both hawthorn and hawthorn leaf and flower preparations.^24,25 Once these monographs are established, they will have relevance for the registration of traditional herbal medicinal products and/or well-established use herbal medicinal products in the European Community. A prerequisite of product registration is that quality complies with the corresponding quality standards monographs of the European Pharmacopoeia, in which there are presently 4 hawthorn monographs (i.e., Hawthorn Berries PhEur, Hawthorn Leaf and Flower PhEur, Hawthorn Leaf and Flower Dry Extract PhEur, and Quantified Hawthorn Leaf and Flower Liquid Extract PhEur).²⁶ Concerning use in cosmetic products, the European Commission Health and Consumers Directorate lists several hawthorn ingredients for skin-conditioning function, including Crataegus Monogyna Flower Extract, Crataegus Monogyna Flower Water (aqueous solution of the steam distillate), Crataegus Monogyna Fruit Extract, Crataegus Monogyna Leaf Extract, Crataegus Oxyacantha Extract (extract of the whole plant), Crataegus Oxyacantha Flower Extract, and Crataegus Oxyacantha Fruit Extract. However, Crataegus Oxyacantha Flower Water is listed for masking function while Crataegus Oxyacantha Stem Extract is listed for antimicrobial function.²⁷

In the United States, hawthorn is regulated as a dietary supplement component requiring manufacturer notification to the US Food and Drug Administration within 30 days of marketing a product (if a “structure-function” claim is made), while in Canada hawthorn is regulated as an active ingredient of licensed natural health products (NHPs) requiring pre-marketing authorization from the Natural Health Products Directorate (NHPD). The authorized use for labeling of hawthorn berry NHPs (decoction or infusion, dried hydroalcoholic extract, fluidextract, or tincture) is “(Traditionally) used in Herbal Medicine to help maintain and/or support cardiovascular health in adults.”²⁸ For labeling of hawthorn leaf and flower NHPs (infusion or decoction, or standardized hydroalcoholic extract), the authorized statement is the same as for the berries, except the qualifier “Traditionally” is removed because the claim statement in this case is based on clinical data rather than on traditional use evidence. The finished hawthorn NHP must comply with the minimum specifications outlined in the current NHPD Compendium of Monographs and the medicinal ingredient may comply with the specifications outlined in the aforementioned European pharmacopeial monographs or with those of the United States Pharmacopeia (USP).²⁸ For quality specifications of hawthorn dietary supplement components in the US and/or hawthorn NHP active ingredients in Canada, the USP has 2 monographs available, Hawthorn Leaf with Flower and Powdered Hawthorn Leaf with Flower.²⁹

MODERN RESEARCH

Pharmacological studies suggest that the primary active components of hawthorn leaf and flower are the flavonoids and oligomeric procyanidins, specifically those with a lower degree of polymerization.¹ Hawthorn fruit consists mainly of oligomeric and polymeric procyanidins and relatively low levels of flavonoids.

In the 1990s, 13 clinical studies with 6,815 participants showed positive effects on cardiac insufficiency.¹ Most of these studies were conducted using a dry extract of hawthorn leaf and flower standardized to a dose of 9 mg or more per day of oligomeric proanthocyanidins (OPCs). Since the turn of this century, more than a dozen clinical trials have been conducted assessing the safety of hawthorn (occasionally in combination with other botanical components) and its cardiovascular benefits, especially cardiotonic activity.

Hawthorn’s ability to lower blood pressure (BP) has been linked to nitric-oxide (NO)-mediated vasodilation, and brachial artery flow-mediated dilation (FMD) is an indirect measure of NO release. A 2012 randomized, placebo-controlled, double-blind, 4-period crossover study investigated the relationship between various dosages of hawthorn extract and FMD to determine a guide for dosing to help lower BP.³⁰ Randomly sequenced doses of hawthorn extract (1,000 mg, 1,500 mg, and 2,500 mg of Hawthorn Supreme Liquid Phyto-Caps [250 mg dried extract hawthorn leaf and flower standardized to 50 mg oligomeric procyanidins]; Gaia Herbs, Inc., Brevard, NC) were given to 21 prehypertensive or mildly hypertensive adults twice daily for 3.5 days followed by FMD measurement. There was no evidence of dose-response effect and the authors concluded that any BP-lowering effect hawthorn might have could be due to mechanisms other than NO. They noted that the subjects of the study may have had a more limited ability to produce NO as their average age was 51 and NO production declines after age 40. Additionally, the authors suggested that the preparation used in their study might not be representative of all hawthorn products.

A 2010 double-blind, placebo-controlled pilot study investigated the beneficial effects of C. laevigata on coronary heart disease (CHD) biomarkers.³¹ For 6 months, 49 diabetics with CHD took a micronized leaf and flower preparation (400 mg standardized to 5% procyanidins and 2% flavonoids; Crataesor, Soria Natural SL, Spain) or placebo 3 times per day in addition to their existing conventional treatment. Participants in the hawthorn group showed decreased neutrophile elastase (NE) and a trend toward lowered low-density lipoprotein cholesterol compared to placebo. Since NE is elevated in patients with CHD and is correlated with the complexity and severity of blocked arteries (coronary stenosis), the inhibition of NE could provide a viable therapeutic option.

A randomized, double-blind, placebo-controlled trial published in 2009 sought to determine the usefulness of hawthorn in treating 120 ambulatory patients with NYHA class II-III chronic heart failure.³² For 6 months, patients received, in addition to their conventional medicine, either 450 mg twice daily Crataegus Special Extract WS^® 1442 (Crataegutt^®, 80 mg hawthorn leaf with flower dry extract 5:1 [w/w], standardized to 18.75% OPCs; Dr. Willmar Schwabe GmbH, Karlsruhe, Germany) or placebo. Subjects took a 6-minute walking test prior to starting the study and at 3 and 6 months. There was no significant difference between the hawthorn and placebo groups in the 6-minute walking test at 6 months, nor in the secondary quality of life scores, heart failure symptom scores, functional capacity, risk or mortality, neurohormone profiles, or markers of inflammation and oxidative stress. As these results were not consistent with previous studies, the authors suggested various reasons why that might be, including the following: sample size, participants with milder NYHA scores, less rigorous tests, and/or wider variation in accepted medical treatments in earlier studies, or overlap of hawthorn mechanism of action with that of drugs being taken by participants in this study.

A 2008 study involving 2,681 participants investigated the efficacy and safety of hawthorn as an add-on treatment for patients with heart failure.³³ Participants in the hawthorn group received 900 mg daily Crataegus Special Extract WS 1442 for 24 months. While cardiac mortality reduction was insignificant, in a subgroup with left ventricular ejection fraction (LVEF), the hawthorn extract reduced sudden cardiac death by 39.7%.

In 2008, a meta-analysis addressed the benefits of hawthorn leaf and flower extract monopreparations as reported in 14 randomized, double-blind, placebo-controlled clinical trials.³⁴ A total of 1,100 participants took either 160-1800 mg/day of Crataegus Special Extract WS 1442 or Faros^® LI 132 (100 mg hawthorn leaf with flower dry native extract 4–7:1 [w/w], standardized to 2.25% flavonoids; Lichtwer Pharma GmbH; Berlin, Germany). In a majority of the studies, hawthorn was used as an adjunct therapy to conventional treatment. Treatment with hawthorn extract increased maximum workload better than placebo; it significantly increased exercise tolerance; pressure-heart rate product (an index of cardiac oxygen consumption) decreased; and significant improvements in shortness of breath and fatigue occurred compared to placebo. The authors concluded that, while based on small numbers of studies and patients, hawthorn flower and leaf extract has significant effects as adjunct therapy for patients with chronic heart failure, but that further investigation was needed that reported clinical as well as physiological outcomes.

A 2006 study investigated the hypotensive effect of hawthorn.³⁵ For 16 weeks, 79 patients with type 2 diabetes were randomized to receive 1,200 mg hawthorn extract daily (Faros LI 132) or placebo. Data were collected at baseline, 8, and 16 weeks. There was no significant difference between groups regarding BP measurements or indices of glycemic control but there was a significant different in diastolic BP in the hawthorn group, indicating that hawthorn does have a hypotensive effect.

FUTURE OUTLOOK

In EU Member States as well as non-EU countries such as Switzerland, hawthorn dry extracts, fluidextracts, teas, and tinctures are labeled and marketed as non-prescription drug products available at pharmacies and drugstores.³⁶ There are about 4,000 native European plants with known pharmacological effects, of which about 500 are authorized for medicinal use. Of these, the top-10 best-selling medicinal plants account for one-third of the entire EU market. In recent years, hawthorn has ranked tenth in European herbal medicinal product sales.³⁶ In the US, hawthorn dietary supplement retail sales were ranked 24th, at $281,834, in the food, drug, and mass market channel in 2011, a slight increase over the previous year.³⁷

Demand for hawthorn ingredients with sustainability certifications (e.g. Organic Wild and FairWild^®) appears to be increasing, as evidenced by the fact that wild collection firms are implementing ecological and social standards for hawthorn harvesting in a number of countries including Albania and Azerbaijan,³⁸ as well as Bosnia and Herzegovina, Poland,³⁹ and even Chile.⁴⁰

—Gayle Engels and Josef Brinckmann

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