Hawthorn
Scientific Name(s): Crataegus monogyna Jacquin., Crataegus oxyacantha L., Crataegus pinnatifida (in China)
Common Name(s): Cardiplant, Crataegisan, Crataegutt, English hawthorn, Faros, Haw, Hawthorn, Korodin, LI 132, Maybush, Whitethorn, WS 1442
Medically reviewed by Drugs.com. Last updated on Jan 10, 2023.
Clinical Overview
Use
Hawthorn may have a role as adjunctive therapy in mild heart failure with some advantages over digoxin described. In more severe cases of congestive heart failure (CHF), its place in therapy is less clear. Studies in animals suggest that hawthorn extracts exert effects on the CNS, including anxiolytic and analgesic action; however, clinical studies are limited. Although limited clinical studies have shown improvement in hyperlipidemia with hawthorn extracts, specific, well-designed trials are needed before hawthorn extracts can be recommended.
Dosing
Trials have evaluated dosages ranging from 160 to 1,800 mg/day standardized extracts (mostly WS 1442) in divided doses over 3 to 24 weeks. A minimum effective dose for adjunctive therapy in mild CHF is suggested to be standardized extract 300 mg daily, with maximum benefit after 6 to 8 weeks of therapy. Clinical trials conducted in patients with class II and III CHF found hawthorn extract 900 mg daily to be safe, but not superior to placebo.
Contraindications
Known allergy to members of the rose family.
Pregnancy/Lactation
In the absence of clear data, hawthorn extracts should be avoided in pregnancy and during lactation. Animal studies, however, have not shown any adverse effect on embryonic development.
Interactions
None well documented.
Adverse Reactions
Serious adverse reactions are rarely reported. Mild to moderate dizziness, headache, rash, palpitations, and nausea and other GI symptoms have been reported.
Toxicology
Hawthorn is reportedly toxic in high doses; low doses of hawthorn usually lack adverse effects. No increase in the frequency of fetal malformations or teratogenicity has been found in animal studies.
Scientific Family
- Rosaceae (rose)
Botany
Some 280 species of hawthorn exist, with C. oxycantha (synonym Crataegus laevigata [Poir]) and C. monogyna commonly used in commercial preparations. Hawthorn is a spiny bush or small tree that grows up to 7.5 m in height. Its deciduous leaves are divided into 3 to 5 lobes. The white, strong-smelling flowers grow in large bunches and bloom from April to June. The spherical bright red fruit contains 1 nut (C. monogyna) or 2 to 3 nuts (C. oxyacantha). The flowers, leaves, and fruits are all used for therapeutic preparations.PLANTS 2000, WHO 1999, Daniele 2006
History
The use of hawthorn dates back to the Greek physician Dioscorides (40 to 90 AD). Hawthorn has been traditionally used as a diuretic for kidney and bladder disorders, to treat stomach ache, stimulate appetite, and improve circulation. Other traditional uses for hawthorn include treatment of stress, nervousness, and sleep disorders.
Preparations containing hawthorn remain popular in Europe for the treatment of high or low blood pressure, tachycardia, or arrhythmias, with the revised Complete German Commission E Monographs approving the use of leaves and flowers for the treatment of long-term heart failure classes I and II (New York Heart Association [NYHA] classification). Some acceptance has also been gained in the United States, with clinical trials being conducted in cardiac failure.WHO 1999, Daniele 2006, Blumenthal 2000
Chemistry
The leaves, flowers, bark, and fruits primarily contain flavonoids, oligomeric proanthocyanidins, tyramine, and tannins. The flavonoids and proanthocyanidins are considered to be the most pharmacologically active compounds and preparations are standardized for these constituents. Most trials have used extracts standardized to 2.2% flavonoids or 18.75% oligomeric proanthocyanidins.(WHO 1999, Daniele 2006)
Hawthorn berries are rich in the triterpene carboxylic acid crataegus acid considered responsible for coronary vasodilating effects noted. Further observed cardiovascular effects (positive inotropic activity, activity on blood vessel walls, improved coronary blood flow and oxygen utilization) are attributed to the flavonoid content.(Rigelsky 2002)
A complete characterization of the chemical constituents of all plant parts has been conducted.(Barros 2011)
Uses and Pharmacology
Pharmacodynamic properties of hawthorn have been elucidated, and relevant cardiovascular actions include positive inotropic effects, peripheral vasodilation, increased myocardial perfusion, as well as stroke volume and decreased afterload. Hawthorn also increases the refractory period, an action thought to be one reason for observed antiarrhythmic activity.(Vogel 2005, Pittler 2008)
Cardiovascular disease
Trials have demonstrated efficacy of hawthorn in the prevention and treatment of cardiovascular diseases with the strongest evidence of benefit shown as an adjunct to standard therapy for chronic CHF. Other claims include as an alternative therapy for angina, orthostatic hypotension, hyperlipidemia, and arrhythmia.(Rastogi 2016)
Animal data
Observed cardiovascular effects include positive inotropic activity, activity on blood vessel walls, improved coronary blood flow and oxygen utilization.(Rigelsky 2002)
Large-scale clinical trials have been conducted using hawthorn extracts, making animal data largely irrelevant.
Heart failure
Clinical data
Several randomized, double-blind clinical trials have been conducted with objective measurements in cardiac performance in heart failure(Vogel 2005); however, the efficacy of hawthorn extract in the treatment of heart failure is uncertain because randomized trials have yielded mixed results.
A meta-analysis of trials found that hawthorn, as adjunctive therapy, is superior to placebo in the treatment of long-term heart failure I and II (NYHA classification), as measured by exercise tolerance tests. Symptomatic measurements (shortness of breath, fatigue) also improved with hawthorn over placebo. In the trials included in the meta-analysis, most patients were also treated concomitantly with diuretics, angiotensin-converting enzyme inhibitors, or calcium antagonists.(Pittler 2008)
Two clinical trials evaluating hawthorn in CHF not included in the meta-analysis found no benefit from hawthorn extract. These trials were the Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB-CHF) and Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in Congestive Heart Failure (SPICE) trials.(Holubarsch 2000, Holubarsch 2008, Zick 2008, Zick 2009) Both trials evaluated the extract WS 1442 (Crataegutt forte) 900 mg/day versus placebo over a period of 6 and 24 months, respectively, in patients with CHF class II or III (NYHA). In the HERB-CHF trial, no difference was found for the primary end point of a 6-minute walk distance or for quality of life and functional capacity measures for hawthorn over placebo.(Zick 2008, Zick 2009) In the SPICE trial, no difference was found for hawthorn in the primary measures of time to first cardiac event and no difference in trend for cardiac mortality reduction.(Holubarsch 2008) In a subgroup analysis, patients with a left ventricular ejection fraction of at least 25% experienced a reduction in sudden cardiac death with hawthorn.(Holubarsch 2008, Furey 2008)
A study conducted in healthy adults (N=20) reported no effect on electrocardiographic parameters for a single dose of oral hawthorn.(Trexler 2018)
Clinical efficacy, therefore, remains unclear in CHF.(Furey 2008) Adverse events in these clinical trials were similar to those of placebo, suggesting certain advantages for hawthorn over digoxin, including a wider therapeutic range, a lower risk in cases of toxicity, is safer in renal impairment, and can safely be used with diuretics.(Vogel 2005)
Orthostatic hypotension
Clinical data
Studies of the effect of hawthorn on blood pressure in humans report equivocal findings.
In some studies a short-term increase in diastolic pressure was found(Werner 2009, Schandry 2008) and efficacy in preventing orthostatic hypotension was shown in limited clinical studies.(Belz 2002, Kroll 2005) Modest reductions in diastolic pressure alone, and in both diastolic and systolic pressure, have been demonstrated.(Walker 2002, Walker 2006, Asgary 2004, Schröder 2003) One small, placebo-controlled study in patients with prehypertension or mild hypertension found no significant difference between hawthorn extract and placebo for measures of brachial artery diameter or blood pressure following 3 1/2-day courses of treatment.(Asher 2012) A meta-analysis of studies using a combined Crataegus and camphor preparation reports increased systolic and diastolic blood pressure based on 4 clinical studies (N=221) and low quality evidence.(Csupor 2019)
Central nervous system
Animal data
Studies in animals suggest hawthorn extracts exert CNS effects, including anxiolytic and analgesic actions.(Can 2010, Tadić 2008) Antagonism of naltrexone has also been reported.(Can 2010) Reduced oxidative stress in induced ischemia/reperfusion cerebral injury in rats has been demonstrated.(Elango 2009)
Clinical data
Limited clinical studies have been conducted. One trial found no effect on anxiety, mood, or sense of well-being(Walker 2006) while other studies have evaluated hawthorn in combination with other agents. Conclusions cannot be drawn.(Werner 2009, Hanus 2004)
Hyperlipidemia
Animal data
Animal studies have demonstrated lipid-lowering effects with hawthorn extracts(Akila 2008, Luo 2009, Xu 2009, Ye 2010, Lin 2009) and inhibition of low-density lipoprotein (LDL) oxidation in laboratory models.(Quettier-Deleu 2003)
Clinical data
In limited studies in patients with hyperlipidemia, beneficial effects of hawthorn extract included reductions in total cholesterol, LDL cholesterol, and the total cholesterol:high-density lipoprotein cholesterol ratio.(Rigelsky 2002, Chen 1995) Specific, well-designed trials are required before recommendations for hawthorn extracts in hyperlipidemia can be made.
Other uses
Animal studies suggest a role for hawthorn in preventing angioplasty-related restenosis and reperfusion injury, possibly facilitated by preventing oxidative stress.(Fürst 2010, Swaminathan 2010) Other antioxidant activities have been explored in animal models.(Tadić 2010, Akila 2008) Hawthorn extracts exert protective effects against irradiation in animal models and in vitro with human cells.(Hosseinimehr 2009)
Dosing
Trials have evaluated dosages ranging from 160 to 2,500 mg/day standardized extracts (mostly WS 1442) in divided doses, over 3 to 24 weeks.Daniele 2006, Hanus 2004, Asher 2012
CHF
A minimum effective dose is suggested to be standardized extract 300 mg daily, and maximum benefit appears after 6 to 8 weeks of therapy.Vogel 2005 Clinical trials conducted in patients with class II and III CHF found hawthorn extract 900 mg daily to be safe, but not superior to placebo.Holubarsch 2008, Zick 2009
Pregnancy / Lactation
In the absence of clear data, clinical texts suggest that hawthorn extracts should be avoided in pregnancy and during lactation.Daniele 2006, Tadić 2008 Animal studies, however, have not shown any adverse effect on embryonic development.WHO 1999, Yao 2008 An older study suggests hawthorn extract to be contraindicated.Ammon 1981
Interactions
Digoxin: Hawthorn may increase the serum concentration of digoxin. No action needed.(Dasgupta 2010, Page 2016, Palmer 2019, Tankanow 2003)
Adverse Reactions
Except for known allergy to members of the Rosaceae family, there are no known contraindications to hawthorn.Daniele 2006
A review of clinical trial data found only rare serious adverse reactions that included palpitations, chest pain, GI hemorrhage, and migraine.Daniele 2006 Most adverse reactions reported are mild to moderate and include moderate dizziness, nausea, GI symptoms, rash, and headache. Hawthorn extracts are considered to be relatively safe.Daniele 2006, Tadić 2008
A case report exists of a multisystem hypersensitivity reaction with acute renal failure to consumption of the fruit and tea of the related species Crataegus orientalis.Horoz 2008
In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, hawthorn has been recognized as a product with antiplatelet activity which may increase bleeding risk when used with anticoagulants. The guidance noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].Page 2016
Data collected between 2004 and 2013 from 8 US centers in the Drug-induced Liver Injury Network revealed that 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (709) of cases were related to prescription medications. Of the 130 cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanics/Latinos compared with non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the proportion of severe liver injury cases was significantly higher for supplements than for conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, 175 had identifiable ingredients, of which hawthorn was among the 32 (18%) single-ingredient products.Navarro 2014
Toxicology
No increase in the frequency of fetal malformations or teratogenicity has been found in animal studies.WHO 1999, Daniele 2006, Yao 2008
Index Terms
- Crataegus laevigata (Poir)
References
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