Hawthorne

HAWTHORN (Crataegus oxyacantha)
INTERNATIONAL SCIENTIC AND CLINICAL STUDIES

Highlights of Hawthorn Research

A four year study on the benefits of hawthorn, commissioned by the German Ministry of Health, found that it improves contractions in the veins and heart while dilating the heart. This increases blood flow in the heart as well as flow speed throughout the body for increased circulation to organs and musculature. The researchers concluded that hawthorn is best used for low heart function, congestion, arrhythmia and tightness in the chest and no side effects were noted (Hoffmann 1995) .

In a German clinical trial with 78 patients with class 2 congestive heart failure, hawthorn flower and leaf increased heart working capacity, lowered blood pressure and improved fatigue and endurance while relieving difficult breathing (Schmidt, et. al. 1994) . Comparable results from other clinical trials for class 2 as well as class 3 patients have been reported (Hobbs & Foster 1990).

In a controlled Chinese clinical trial with 46 patients suffering from angina, a Chinese variety of hawthorn decreased the number of angina attacks by 85% compared to 37% on placebo (Weilang, et. al. 1984) . Other clinical trials have found comparable results for varieties of hawthorn (Weiss 1988) (Chang & But 1986) .

A German clinical trial with 18 healthy patients found that hawthorn lowered heart rate and blood pressure during exercise and maintained resting heart rate while elevations were noted in the control group (Hellenbrecht, et. al. 1990) .

Chinese laboratory and clinical trials have reported that hawthorn lowers cholesterol and triglycerides by improving excretion (Chang & But 1986) . Hawthorn is also reported to increase urination (DJumlija 1994) (Hoffmann 1995) , often an important modality in heart condinons.

Laboratory studies suggest that hawthorn’s actions on the heart and circulatory system may be created through effects on the central nervous system (Foldi, et. al. 1959) .  Oxygen levels increase in the heart and provide a better balance of oxygen supply and demand

(Lianda, et. al. l984).

World Health Organisation (WHO)

Drawing from a total of 86 international references the WHO includes among hawthorn’s uses – “supported by clinical data” – “the treatment of chronic congestive heart failure stage !!”, its antihypertensive effects and “the support of cardiac and circulatory functions” (page 71 of the WHO monograph for Folium cum Flore Crataegi).

Under “Inotropic effects” it cites among hawthorn’s many positive effects its ability to “prolong the refractory period in cardiac myocytes” and to increase the contractility of the heart. In one dramatic example it reports that a “standardized extract of leaves and flowers “increased the contractility of myocardial cells by 153%”

Making reference to hawthorn’s effect on coronary blood flow the WHO monograph reports increased myocardial blood flow and cardiac output ranging from 48% to 163%.

Under “Clinical Pharmacology” (page 73) a review of clinical date indicates that hawthorn increases myocardial performance, improves myocardial circulatory perfusion and tolerance in cases of oxygen deficiency. Its anti-arrhythmic effects are specially noted, along with reduced cardiac “afterload”.

Further noted are hawthorn’s positive therapeutic effects in patients with “characteristic symptoms of hypertension, tachycardia and arrhythmia “, while hawthorn’s ability to improve stage II cardiac insufficiency and ventricular ejection fraction – the latter by more than 10% – are noted on page 76.

It is interesting to note that WHO’s Hawthorn monograph shows Contra-indications, Precautions and Adverse reactions as ‘None’. This forms a strong contrast with recent drug recalls by the pharmaceutical industry and the announcement that the fourth greatest cause of deaths in the United States is adverse reactions to pharmaceutical drugs.

Hawthorn – The German Commission E Monographs

In January 1984 all the preparations of Hawthorn berry, leaf, and flower were approved in one monograph on the basis of historical experience, many pharmacological studies, about 20 open clinical studies, and many patient case reports (Schilcher, 1997b).

The originally approved monograph indications were for functional stages I and II of NYHA (New York Heart Association assessment of the four stages of heart disease). This earlier monograph also included sensation of pressure in the chest, cardiac degeneration not yet requiring digitalis ( Altesherz ), and slight forms of bradycardic arrhythmias (Steinhoff, 1997).

The German Commission E monograph notes no contraindications or side effects for the use of hawthorn. However; in combining hawthorn with medications, it is recommended that the consumer consult with their physician or pharmacist.

Composition of Berry

Hawthorn berry consists of the dried fruit of Crataegus monogyna Jaquin emend. Lindman or C. laevigata (Poiret) de Candolle or others in a valid pharmacopeia citing Crataegus [Fam. Rosaceae], as well as preparations thereof.
Pharmacological Properties, Pharmacokinetics, Toxicology

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 preparations from the fruit and preparations combining leaf and flower. One may assume pharmacodynamics similar to those shown for the preparation containing both leaf and flower.

Clinical Data
1. Claimed Areas of Application

Preparations of hawthorn berry may be applied to the treatment of coronary circulation, coronary complications and weak heart, heart and circulatory disturbances, hypotension, and arteriosclerosis.
2. Risks

None known.
Evaluation

Since the effectiveness of hawthorn berry 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 utilized traditionally to strengthen and invigorate heart and circulatory function.

These statements are based exclusively on historical record and long experience.

NOTE: A preparation from Hawthorn leaf with flower is listed in the Approved Herbs section. (See Introduction).

Composition of Flower

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], as well as preparations thereof.
Pharmacological Properties, Pharmacokinetics, Toxicology

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 leaf.

Clinical Data
1. Claimed Areas of Application

Preparations of hawthorn flowers may be 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.
2. Risks

None known.
Evaluation

The herb as a water extract, water-alcohol extract, wine infusion and fresh juice has been utilized traditionally to strengthen and invigorate heart and circulatory function.

These statements are based exclusively on historical record and experience. (See abstracts that follow for clinical studies completed in the US , the UK , Switzerland and Germany)

CAM Hawthorn Study – U.S.A.

The herb hawthorn, with active constituents that include flavonoid pigments and procyanidin pigments in its flowers, berries and leaves, is said to lower blood pressure and cholesterol. The CAM hawthorn study, the “most scientific” of three carried out, according to Bolling, examines a dietary supplement extracted from the flowers and leaves of the hawthorn tree as a treatment for congestive heart failure. Headed by Dr. Keith Aaronson , assistant professor of internal medicine , and Suzanne Zick, a research investigator in the Department of Family Medicine, the project involves researchers ranging from world-renowned scholars to undergraduates from the U-M Health System, the College of Pharmacy , and LS&A (Biology).

Biology Professor Emeritus Peter Kaufmann explains that the hawthorn project is a double-blind, randomized, controlled trial of patients with congestive heart failure. (In a blind study, patients don’t know whether they are taking the test drug or a placebo. In a double-blind study, the researchers don’t know either.) “We’ve got 72 patients now and hope to get 120,” Kaufmann says. Patients who are taking digoxin (a standard commercial preparation) are excluded. Patients are interviewed to obtain their medical histories and given several tests-a six-minute walk test, blood tests, an electrocardiogram and an exercise test.

In another phase of the study Kaufmann and his team, which includes a number of undergraduates, are analyzing hawthorn caplets from a company in Germany , where the drug is taken much more than in the United States . Their aim is to establish a consistent standard and also to compare the German product to hawthorn preparations available here. In addition they are testing to identify which, if any, of the 150 active ingredients in hawthorn may be effective in lowering blood pressure and cholesterol, and using chromatography to measure varying amounts of those constituents in the plant’s flowers, leaves and fruits.

According to Warber, the researchers will complete data collection in 2002 and analyze their data the following year. Publication of the results is expected in 2004

CLINICAL ABSTRACT – U.S.A – Cardiovascular disease.

Gavagan T.

Department of Family and Community Medicine, Baylor College of Medicine, 5510 Greenbriar, Houston, TX 77005, USA. tgavagan@bcm.tmc.edu

The primary care physician is in a position to advise patients on the efficacy of alternative and complementary therapies as they relate to cardiovascular diseases. Anti-oxidant vitamin supplementation has not been shown to be efficacious in decreasing cardiovascular events. N-3 fatty acids appear to be beneficial in secondary prevention of cardiovascular events but their use in primary prevention is not clear. Adoption of vegetable-based diets, including whole grains, can be recommended to decrease cardiovascular events, lower cholesterol and help lower blood pressure. For patients with hypercholesterolemia, cholestin, a red-yeast rice supplement, has been shown to be effective. Herbal therapies with hawthorn and ubiquinone (Q10) are of possible benefit in congestive heart failure . An integrated program of rigorous diet, exercise and stress reduction in motivated patients with cardiovascular disease may have value as an alternative to cardiovascular medications and surgical interventions

PMID: 12391714 [PubMed - indexed for MEDLINE]

CLINICAL ABSTRACT – Switzerland

A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II.

Degenring FH, Suter A, Weber M, Saller R.

Bioforce AG, Roggwil , Switzerland .

A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator.

In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.

CLINICAL ABSTRACT – United Kingdom

Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials.

Pittler MH, Schmidt K, Ernst E .

Complementary Medicine, Peninsula Medical School , Universities of Exeter and Plymouth , 25 Victoria Park Road , Exeter EX2 4NT , United Kingdom . M.H.Pittler@exeter.ac.uk

The aim of this meta-analysis was to assess the evidence from rigorous clinical trials of the use of hawthorn extract to treat patients with chronic heart failure . We searched the literature using MEDLINE, EMBASE, the Cochrane Library, CINAHL, CISCOM, and AMED. Experts on and manufacturers of commercial preparations containing hawthorn extract were asked to contribute published and unpublished studies. There were no restrictions about the language of publication. Two reviewers independently performed the screening of studies, selection, validation, data extraction, and the assessment of methodological quality. To be included, studies were required to state that they were randomized, double-blind, and placebo controlled, and used hawthorn extract monopreparations . Thirteen trials met all inclusion criteria. In most of the studies, hawthorn was used as an adjunct to conventional treatment. Eight trials including 632 patients with chronic heart failure (New York Heart Association classes I to III) provided data that were suitable for meta-analysis. For the physiologic outcome of maximal workload, treatment with hawthorn extract was more beneficial than placebo (weighted mean difference, 7 Watt; 95% confidence interval [CI]: 3 to 11 Watt; P < 0.01; n = 310 patients). The pressure-heart rate product also showed a beneficial decrease (weighted mean difference, -20; 95% CI: -32 to -8 ; n = 264 patients) with hawthorn treatment. Symptoms such as dyspnea and fatigue improved significantly with hawthorn treatment as compared with placebo. Reported adverse events were infrequent, mild, and transient; they included nausea, dizziness, and cardiac and gastrointestinal complaints . In conclusion, these results suggest that there is a significant benefit from hawthorn extract as an adjunctive treatment for chronic heart failure.

PMID: 12798455 [PubMed - indexed for MEDLINE]

CLINICAL ABSTRACT – Denmark

High-dose Crataegus extract WS 1442 in the treatment of NYHA

stage II heart failure] [Article in German]

Tauchert M, Gildor A, Lipinski J.

Klinikum Leverkusen. tauchert@klinikumvlev.de

The efficacy and tolerance of the standardized hawthorn (crataegus) extract WS 1442 were tested in a multicenter utilization observational study. We monitored 1,011 patients with cardiac insufficiency stage NYHA II, treated with this extract (Crataegutt novo 450, 1 tablet b.i.d.) over a period of 24 weeks.

During and at the end of the observation period a significant improvement in clinical symptoms (reduced performance in the exercise tolerance test, fatigue, palpitation and exercise dyspnea) was observed . Ankle edema and nocturia disappeared by 83%, and by half of the patients respectively manifesting these symptoms before treatment.

The improvement and economization of cardiac performance were additionally shown by a reduction in blood pressure, an increased maximal exercise tolerance and a reduction in the difference in the pressure/heart rate product (PHRP). The positive effects of WS 1442 were further demonstrated by an improved ejection fraction and an increased percentile shortening fraction measured using M-mode echocardiography.

The stabilizing effect of the hawthorn extract on the heart rate was shown by a slower rest pulse, as well as by an increase in the number of day and night normorhythmic patients, as documented by long-term ECG.

The reduction in the number of patients showing ST depressions, arrhythmias and ventricular extrasystoles at the maximum exercise level is regarded as an indication for an improved myocardial perfusion . Fourteen side effects were noted. In two cases (abdominal discomfort and facial pains accompanied by tachycardia) a possible relationship with the hawthorn therapy, was postulated which however was considered unlikely by the treating physicians. Almost 2/3 of the patients felt better or much better following the 24 weeks of treatment.

More than 3/4 of the participating physicians noted a good or a very good efficacy, and 98.7% noted a good or a very good tolerance. High-dose hawthorn therapy is an efficient, well-tolerated and easily regulated therapeutic alternative for patients suffering from cardiac insufficiency stage NYHA II. ( PMID: 10546150 PubMed)