Herbal Medicine: Expanded Commission E
Hawthorn flower
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Latin Name: Crataegus monogyna or C. laevigata
Pharmacopeial Name: Crataegi flos
Other Names: whitethorn herb, hawthorn tops, haw, mayhaw
Overview
There are approximately 280 known species of hawthorns in the genus Crataegus. The species referred to in this monograph is a spiny shrub native to the northern wooded temperate zones of Europe, from England to Latvia and from the Pyrenees Mountains (southern France) to northern Italy (Leung and Foster, 1996). It has become naturalized in parts of North America as a garden escape (Budavari, 1996; Leung and Foster, 1996). The material of commerce for the phytomedicine industry is obtained from the United Kingdom and other European countries (BHP, 1996), including Albania, Bulgaria, Romania, the former Yugoslavia, and Poland (Wichtl and Bisset, 1994). Hawthorn has a long history of use, confirmed safety, and clinical evidence to support its cardiovascular benefits, especially cardiotonic activity. There is significant evidence to support its use in clinical cardiology and by the general public. The fruits (berries) of various species, long used in traditional European herbal medicine, are edible (Hedrick, 1972). Hawthorn is one of the oldest known medicinal plants used in European medicine; its cordial actions on the heart were first reported by first century Greek herbalist Dioscorides and later by Swiss physician Paracelsus (1493–1541) (Weihmayr and Ernst, 1996). Other sources state that its clinical use for heart disease and cardiovascular disorders did not begin in Europe until the nineteenth century (Anschutz, 1900; Hobbs and Foster, 1990). In phytomedicine, hawthorn refers to the fruit, leaf, and/or flower of the genus Crataegus (usually C. laevigata, syn. C. oxyacantha) and C. monogyna. Commission E in 1984 published one monograph on hawthorn (often commonly referred to as crataegus, based on the Latin name of the genus) that included all of its aerial parts and was based on historical experience, many pharmacological studies on various preparations on the three different plant parts, about 20 open clinical studies, and many patient case reports (Schilcher, 1997). The original indications were for functional Stages I to II of the New York Heart Association (NYHA) assessment of the four stages of heart disease. Other indications included sensation of pressure in the chest, cardiac degeneration not yet requiring digitalis, and slight forms of bradycardic arrhythmias (Steinhoff, 1997). In 1994, however, the original monograph was replaced by four: an approved monograph for hawthorn leaf with flower and three unapproved monographs for hawthorn fruit (berry), leaf, and flower, respectively. There was good reason for this change. When the first monograph had been produced, none of the scientific data on hawthorn included studies carried out according to good clinical practices (GCP). Both experimental and clinical studies that have been conducted since around 1991 have confirmed activity of hawthorn leaf with flower preparations. A subsequent review of clinical literature revealed the availability of pharmacodynamics (the effects of a substance on the physiological processes) of a 45% ethanol extract, or 70% methanol extract of flowering leaf tops with defined content of flavonoids and proanthocyanidins. The other three hawthorn components were re-evaluated and "the flowers, leaves, and fruits as single compounds received a negative assessment because there no longer seemed to be sufficient scientific evidence to justify their inclusion" (Steinhoff, 1993–1994). This also brought the monographs in line with the tenth edition of the French pharmacopeia, which specifies "dried flowering tops" of C. monogyna. The approval of the one hawthorn preparation based on the extract of leaf with flower is an example of the trend later adopted by the Commission to rely on new scientific data for evaluations and to re-assess and approve specific, well-defined extract preparations that are often proprietary commercial products. A recent monograph on hawthorn berry (fruit) acknowledges the lack of research on the cardioactivity of the berry (Upton et al., 1999a). The literature review also resulted in a more precise indication for the approved monograph: "decreasing cardiac output according to functional Stage II of the NYHA." According to NYHA, Stage II is defined as "Patients with cardiac disease but without resulting limitations of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain" (NYHA, 1994). The use of hawthorn appears to be extremely safe; Commission E noted no contraindications or adverse side effects, nor have more recent reviews (e.g., Upton et al., 1999a, 1999b). Hawthorn has been extensively studied in Germany. A review on hawthorn preparations used in cardiology found that hawthorn can be employed for indications for which digitalis is not yet indicated (Blesken, 1992). In a later review of its therapeutic effectiveness, the authors found that recent research supported its usefulness in congestive heart failure (CHF) (Weihmayr and Ernst, 1996). Rigorous clinical trials showed benefit concerning objective signs and subjective symptoms of Stage II NYHA congestive heart failure. No adverse drug reactions had been reported. The authors concluded that hawthorn is an effective and safe therapeutic alternative for CHF. One placebo-controlled, randomized, double-blind study on 30 patients for eight weeks was performed with hawthorn leaf with flower extract WS 1442 (Crataegutt® forte; W. Schwabe, Germany) at a dose of 160 mg per day (Leuchtgens, 1993). The hawthorn group showed a statistically significant advantage over placebo in all parameters: Alteration in the pressure-x-rate product under standardized stationary bicycle endurance test, a score of subjective improvement of complaints elicited by a questionnaire, exercise tolerance, and changes in heart and arterial blood pressure (systolic and diastolic blood pressure was mildly reduced in both groups). No adverse reactions occurred. Studies with early-stage CHF patients, using daily doses of leaf with flower extract ranging from 160 to 900 mg, showed improved heart function and exercise tolerance, and a lessening in shortness of breath and postexercise fatigue (Reuter, 1994; Zapfe et al., 1993). Schulz and co-authors cite 14 clinical studies published from 1981 to 1994 on the therapeutic efficacy of hawthorn preparations on a total of 808 patients (Schulz et al., 1998). A recent monograph on hawthorn leaf with flower extract cites 10 clinical studies on standardized preparations (3 open studies, 7 controlled) (Upton et al., 1999b). Reuter discussed 15 clinical trials on 872 patients given single preparations of Crataegus extracts (160–900 mg) standardized to 5% oligomeric proanthocyanidins (OPC), 19% OPC, and 2.2% flavonoids. Tolerability was generally very good, with higher dosages resulting in occasional mild side effects. Significant improvements in stress tolerance and anaerobic threshold occurred with daily doses of 300–900 mg over a four-week period, and to a greater extent after eight weeks. Subjective complaints, however, improved with much lower doses of 160–180 mg (Reuter, 1994). An eight-week multicenter, placebo-controlled, double-blind trial using WS 1442 in 136 patients with Stage II NYHA cardiac insufficiency focused on changes in the blood pressure and heart rate output measured at the beginning and end of treatment (Weikl et al., 1996). A clear improvement in the performance of the heart in the treatment group was seen, while the placebo group progressively worsened. The therapeutic difference between the groups was statistically significant. Patient assessment of improvement in the main symptoms (reduced performance, shortness of breath, ankle edema, etc.) confirmed the superiority of hawthorn, with better quality of life and mental well-being reported. Tolerability was very good, with overall results confirming the extract to be an effective and low-risk phytotherapeutic form of treatment for patients with Stage II NYHA cardiac insufficiency. Another study provided evidence that hawthorn extract can improve heart function in patients with chronic heart disease (Schmidt et al., 1994). This eight-week, multicenter, double-blind, placebo-controlled study tested the effects of 600 mg/day of Faros® 300, (LI 132, an extract manufactured by Lichtwer Pharma, Berlin). Seventy-eight patients with Stage II heart disease taking hawthorn had significant gains in their stamina and endurance (as measured by a stationary bicycle), had lower blood pressure and lower heart rates while exercising, and pumped more blood at lower pressure. Also, patients taking hawthorn had fewer overall symptoms, felt less fatigue, and experienced less shortness of breath. Hawthorn extract (LI 132) at a dose of 900 mg daily was shown to compare favorably with the cardiac drug Captopril (37.5 mg daily) in the treatment of 132 Stage II cardiac insufficiency patients (Tauchert et al., 1994). Captopril is used to reduce resistance to blood flow in peripheral arteries. Hawthorn performed equally well, with the added benefit of working on the heart. Exercise tolerance significantly increased in both test groups, and the incidence and severity of symptoms decreased by 50%. There was no placebo control. Another report evaluated the efficacy of high doses of hawthorn leaf with flower extract (900 mg daily of Faros® 300) in 1,476 patients with Stage I and Stage II cardiac insufficiency, with therapy lasting four and eight weeks (Loew et al., 1996). Treatment-related changes were evaluated for the typical symptoms of heart failure. The symptom score decreased by a mean of 66% at the conclusion of therapy, with the Stage I NYHA patients largely symptom-free. A subgroup of patients with symptoms including borderline hypertension showed decreases in systolic and diastolic pressure. This group also showed a drop in heart rate from 89 to 79 beats per minute, and arrhythmias were significantly reduced independently of heart failure. Although the Commission E no longer recognizes this use, hawthorn berry preparations have been shown to combat angina, a condition resulting from insufficient blood flow to the heart muscle. In one study demonstrating the usefulness of a combined extract of hawthorn berry, leaf, and flower in the treatment of patients with stable angina pectoris (Hanack and Br ckel, 1983), 60 angina patients were given either 180 mg of hawthorn berry-leaf-flower extract (Crataegutt® novo, W. Schwabe, Germany) or placebo for three weeks. The ECG measures improved in the hawthorn patients, and blood flow and oxygen delivery to the heart muscle rose. Hawthorn patients also exercised for longer periods of time without an angina attack. A double-blind crossover study tested the effects of Crataegutt® novo hawthorn berry-leaf-flower extract in 36 patients, averaging 74 years in age, with Stage I or Stage II cardiac insufficiency (O'Connolly et al., 1986; O'Connolly et al., 1987). The study found that patients treated with this preparation had a decreased heart rate and improved cardiac output under resting and exercise conditions, which was not evidenced in the control group. Treated patients also had significant improvement in psychological assessment ratings and sleep behavior. In Germany, hawthorn leaf with flower is official in the German Pharmacopeia (DAB, 1997), approved in the Commission E monographs, and the tea infusion dosage form is official in the German Standard License monographs (Braun et al., 1997). The alcoholic fluidextract dosage form is official in the German Pharmacopeia, tenth edition, third supplement (DAB 10, 1993). Hawthorn is used as a component in over 100 drug preparations, especially cardiotonics, coronary remedies, and antihypertensives, in various dosage forms, including the hydro-alcoholic native dry extract in drages (coated tablets), fluidextract (drops) (Wichtl and Bisset, 1994), and aqueous infusion (Braun et al., 1997; Meyer-Buchtela, 1999). German pharmacopeial grade hawthorn leaf with flower consists of the whole or cut, dried flower-bearing tips, up to about 7 cm long, of C. monogyna Jaquin emend. Lindman or C. laevigata (Poiret) de Candolle (syn: C. oxyacantha L.p.p. et auct.), and rarely some other European species such as C. pentagyna Waldstein et Kitaibel ex Willdenow, C. nigra Waldstein et Kitaibel, and/or C. azarolus L. It must contain not less than 0.7% flavonoids calculated as hyperoside. Botanical identity must be confirmed by a thin-layer chromatography (TLC) test, macroscopic and microscopic examinations, and organoleptic evaluations (DAB, 1997). Under proper storage conditions, the raw material shelf life is three years (Braun et al., 1997). It is interesting to note that the only form of hawthorn that is official in the 1998 European Pharmacopoeia is the dried false-fruit, which is an unapproved herb in the Commission E monographs. It must contain not less than 1.0% procyanidins, calculated as cyanidin chloride, based on the dried material (Ph.Eur.3, 1998).
Description
Hawthorn flower consists of the dried flower of Crataegus monogyna Jaquin emend. Lindman or C. laevigata (Poiret) de Candolle or others in a valid pharmacopeia citing Cratageus [Fam. Rosaceae] and preparations thereof.
Chemistry and Pharmacology
There are no scientific data on which to base the pharmacology and toxicology of the herb. Spectrographic analysis of the chemical constituents of the herb distinguishes only quantitative differences between leaf and flower preparations. One may assume pharmacodynamics similar to those shown for preparations from the leaf.
Uses
It has been claimed that preparations of hawthorn flowers have been applied to the treatment of coronary circulation, support of the heart muscle and attendant improvement in provision for the coronary artery, autonomic heart trouble, autonomic circulatory disturbances, geriatric heart disease, enhancing activity of myocardium, preventing stress-related heart disease, cardiac boost for the elderly, strengthening the heart and circulatory system, strengthening nerves, for coronary insufficiency, angina pectoris, cardiac neurasthenia, cardiac asthma, and arrhythmia. Note: This monograph was published as a negative/unapproved monograph. According to Commission E, since the effectiveness of hawthorn flower (by itself) for its claimed applications has not been documented, therapeutic use cannot be recommended.
The herb as a water extract, water-alcohol extract, wine infusion, and fresh juice has been used traditionally to strengthen and invigorate heart and circulatory function. These statements are based exclusively on historical record and experience.
Contraindications
No risks or contraindications are known.
Side Effects
None known.
Use During Pregnancy and Lactation
No restrictions known.
Interactions with Other Drugs
Hawthorn preparations may potentiate the actions of digitalis though this effect has not been confirmed.
Dosage and Administration
See the approved monograph on hawthorn leaf with flower.
References
Anschutz, E.P. 1900. New, Old and Forgotten Remedies. Philadelphia, PA: Boericke and Tafel. Blesken, R. 1992. [Crataegus in cardiology] [In German]. Fortschr Med 110(15):290292. Braun, R. et al. 1997. Standardzulassungen f r FertigarzneimittelText and Kommentar. Stuttgart: Deutscher Apotheker Verlag. British Herbal Pharmacopoeia (BHP). 1996. Exeter, U.K.: British Herbal Medicine Association. 98101. Budavari, S. (ed.). 1996. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 12th ed. Whitehouse Station, N.J.: Merck & Co, Inc. 435. Deutsches Arzneibuch, 10th ed., 3rd suppl. (DAB 10). 1993. Stuttgart: Deutscher Apotheker Verlag. Deutsches Arzneibuch (DAB 1997). 1997. Stuttgart: Deutscher Apotheker Verlag. Europäisches Arzneibuch, 3rd ed., 1st suppl. (Ph.Eur.3). 1998. Stuttgart: Deutscher Apotheker Verlag. 667668. Hanack, T. and M.H. Br ckel. 1983. The treatment of mild stable forms of angina pectoris using Crategutt novo. Therapiewoche 33:43314333. Hedrick, U.P. (ed.). 1972. Sturtevant's Edible Plants of the World. New York: Dover Publications [reprint of 1919 original]. Hobbs, C. and S. Foster. 1990. Hawthorna literature review. HerbalGram 22:1933. Leuchtgens, H. 1993. [Crataegus special extract WS 1442 in NYHA II heart failure. A placebo controlled randomized double-blind study] [In German]. Fortschr Med 111(2021):352354. Leung, A.Y. and S. Foster. 1996. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, 2nd ed. New York: John Wiley & Sons, Inc. 295297. Loew, D., M. Albrecht, H. Podzuweit. 1996. Efficacy and tolerability of a Hawthorn preparation in patients with heart failure Stage I and II according to NYHAa surveillance study. Munich: 2nd International Congress on Phytomedicine. Meyer-Buchtela, E. 1999. Tee-RezepturenEin Handbuch f r Apotheker und rzte. Stuttgart: Deutscher Apotheker Verlag. New York Heart Association (NYHA). 1994. Revisions to Classification of Functional Capacity and Objective Assessment of Patients with Diseases of the Heart. O'Connolly, M., G. Bernhft, G. Bartsch. 1987. [Treatment of stenocardia (Angina pectoris) pain in advanced age patients with multi-morbidity] [In German]. Therapiewoche 37:35873600. O'Connolly, M., W. Jansen, G. Bernhft, G. Bartsch. 1986. Behandlung der nachlassenden Herzleistung. [Treatment of decreasing cardiac performance. Therapy using standardized crataegus extract in advanced age] Fortschr Med 104(42):805808. Ph.Eur.3. See Europäisches Arzneibuch. Reuter, H. 1994. Crataegus (Hawthorn): A Botanical Cardiac Agent. Z Phytother 15:7381. Schilcher, H. 1997. Personal communication to M. Blumenthal. Dec. 30. Schmidt, U., U. Kuhn, M. Ploch, W.D. Hubner. 1994. Efficacy of the hawthorn (crataegus) preparation LI 132 in 78 patients with chronic congestive heart failure defined as NYHA functional class II. Phytomedicine 1:1724. Schulz, V., R. Hnsel, V.E. Tyler. 1998. Rational Phytotherapy: A Physicians' Guide to Herbal Medicine. New York: Springer. Steinhoff, B. 19931994. New developments regarding phytomedicines in Germany. Brit J Phytother 3(4):190193. . 1997. Herbal medicines increasingly preferred. Pharmazeutische Zeitung 142(49):44124417. Tauchert, M., M. Ploch, W.D. Hubner. 1994. Effectiveness of hawthorn extract LI 132 compared with the ACE inhibitor Captopril: Multicenter double-blind study with 132 NYHA Stage II. Muench Med Wochenschr 136 suppl:S27S33. Upton, R. (ed.) et al. 1999a. Hawthorn Berry. Santa Cruz, CA: American Herbal Pharmacopoeia. Upton, R. (ed.) et al. 1999b. Hawthorn Leaf with Flower. Santa Cruz, CA: American Herbal Pharmacopoeia. Weihmayr, T. and E. Ernst. 1996. [Therapeutic effectiveness of Crataegus] [In German]. Fortschr Med 114(12):2729. Weikl, A. et al. 1996. Crataegus special extract WS 1442. Assessment of objective effectiveness in patients with heart failure. Fortschr Med 114(24)291296. Wichtl, M. and N.G. Bisset (eds.). 1994. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Medpharm Scientific Publishers. 161166. Zapfe, G., K.D. Assmus, H.S. Noh. 1993. Placebo-controlled multicenter study with Crataegus special extract WS 1442: Clinical results in the treatment of NYHA II cardiac insufficiency. Presented at the 5th Congress on Phytotherapy: Bonn, Germany; June 11.
Additional Resources
Ammon, H.P. and M. Handel. 1981. [Crataegus, toxicology and pharmacology, Part I: Toxicity] [In German]. Planta Med 43(2):105120. . 1981. [Crataegus, toxicology and pharmacology, Part II: Pharmacodynamics] [In German]. Planta Med 43(3):209239. . 1981. [Crataegus, toxicology and pharmacology, Part III: Pharmacodynamics and pharmacokinetics] [In German]. Planta Med 43(4):313322. Ammon, H.P.T. and R. Kaul. 1994. [Crataegus: Activity on heart and circulation of Crataegus extracts, flavonoids and procyanidins. Part 1: History and hormones] [In German]. Dtsch Apoth Zeitg 134(26):24332436. . 1994. [Crataegus: Activity on heart and circulation of Crataegus extracts, flavonoids and procyanidins. Part 2: Actions on the heart] [In German]. Dtsch Apoth Zeitg 134(27):25212527. . 1994. [Crataegus: Activity on heart and circulation of Crataegus extracts, flavonoids and procyanidins. Part 3: Actions on circulation] [In German]. Dtsch Apoth Zeitg 134(28):26312636. Beretz, A., M. Haag-Berrurier, R. Anton. 1978. Choice of pharmacological methods for the study of hawthorn activities. Plantes Med Phytothr 12(4):305314. Brown, D., S. Austin, R. Reichert. 1997. Early-stage congestive heart failure. Seattle: Natural Products Research Consultants. Gabhard, B. et al. (eds.). 1983. Wandlungen in der Therapie der Herzinsuffizienz. Wiesbaden: Friedr. Vieweg & Soyn. Guendjev, Z. 1977. Experimental myocardial infarction of the rat and stimulation of the revascularization by the flavonoid drug crataemon. Arnzeimforsch 27(8):15761579. McGuffin, M., C. Hobbs, R. Upton, A. Goldberg. 1997. American Herbal Product Association's Botanical Safety Handbook. Boca Raton: CRC Press. Newall, C.A., L.A. Anderson, J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press. Occhiuto, F., C. Circosta, R. Costa, F. Briguglio, A. Tommasini. 1986. Study comparing the cardiovascular activity of young shoots, leaves and flowers of C. laevigata L. II: Effects of extracts and pure isolated active principles on the isolated rabbit heart. Plantes Med Phytothr 20:5263. Rakotoarison, D.A. et al. 1997. Antioxidant activities of polyphenolic extracts from flowers, in vitro callus and cell suspension cultures of Crataegus monogyna. Pharmazie 52(1):6064. Roddewig, C. and H. Hensel. 1977. [Reaction of local myocardial blood flow in non-anesthetized dogs and anesthetized cats to the oral and parenteral administration of a Crateagus fraction] [In German]. Arnzeimforsch 27(7):14071410. Stepka, W. and A.D. Winters. 1973. A survey of the genus Crataegus for hypotensive activity [symposium paper]. Proceedings American Society of Pharmacognosy: Jekyll Island, Georgia; Jul 1520. Lloydia 36(4):430443. Sticher, O. and B. Meier. Hawthorn (Crataegus): Biological Activity and New Strategies for Quality Control. In: Lawson, L.D. and R. Bauer (eds.) 1998. Phytomedicines of Europe: Chemistry and Biological Activity. Washington, DC: American Chemical Society. Tyler, V.E. 1994. Herbs of Choice: The Therapeutic Use of Phytomedicinals. New York: Haworth Press. Weng, W.L. et al. 1984. Therapeutic effect of Crataegus pinnatifida on 46 cases of angina pectorisa double blind study. J Trad Chin Med 4(4):293294. This material was adapted from The Complete German Commission E MonographsTherapeutic Guide to Herbal Medicines. M. Blumenthal, W.R. Busse, A. Goldberg, J. Gruenwald, T. Hall, C.W. Riggins, R.S. Rister (eds.) S. Klein and R.S. Rister (trans.). 1998. Austin: American Botanical Council; Boston: Integrative Medicine Communications.
1) The Overview section is new information. 2) Description, Chemistry and Pharmacology, Uses, Contraindications, Side Effects, Interactions with Other Drugs, and Dosage sections have been drawn from the original work. Additional information has been added in some or all of these sections, as noted with references. 3) The dosage for equivalent preparations (tea infusion, fluidextract, and tincture) have been provided based on the following example: - Unless otherwise prescribed: 2 g per day of [powdered, crushed, cut or whole] [plant part]
- Infusion: 2 g in 150 ml of water
- Fluidextract 1:1 (g/ml): 2 ml
- Tincture 1:5 (g/ml): 10 ml
4) The References and Additional Resources sections are new sections. Additional Resources are not cited in the monograph but are included for research purposes. This monograph, published by the Commission E in 1994, was modified based on new scientific research. It contains more extensive pharmacological and therapeutic information taken directly from the Commission E.
Excerpt from Herbal Medicine: Expanded Commission E Monographs
Copyright 2000 American Botanical Council
Published by Integrative Medicine Communications
Available from the American Botanical Council.
This monograph, published by the Commission E in 1994, was modified based on new scientific research. It contains more extensive pharmacological and therapeutic information taken directly from the Commission E.
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