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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

Clinical Overview

Use

Hawthorn may have a role as adjunctive therapy in mild heart failure and exhibits some advantages over digoxin. 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.

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

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 noted in a systematic review have been as an alternative therapy for angina, hypertension, hyperlipidemia, and arrhythmia.(Rastogi 2016

Heart failure

Animal data

Large-scale clinical trials have been conducted using hawthorn extracts, making animal data largely irrelevant.

Clinical data

Several randomized, double-blind clinical trials have been conducted with objective measurements in cardiac performance in heart failure.Vogel 2005 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

Clinical trials evaluating hawthorn in CHF conducted since the meta-analysis include 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 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

Blood pressure

Animal data

Hawthorn extracts decrease peripheral vascular resistance and hypertension in animal models.WHO 1999

Clinical data

Studies in humans have not established a role for hawthorn in the management of hypertension. Modest reductions in diastolic pressure alone, and in both diastolic and systolic pressure, have been demonstrated.Walker 2002, Walker 2006, Asgary 2004, Schröder 2003 In some studies a short-term increase in diastolic pressure was foundWerner 2009, Schandry 2008 and efficacy in preventing orthostatic hypotension was shown in limited clinical studies.Belz 2002, Kroll 2005 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

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-beingWalker 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 extractsAkila 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

Antihypertensives: Herbs (Hypotensive Properties) may enhance the hypotensive effect of Antihypertensives. Monitor therapy.Richard 2005, Ernst 2003

Digoxin: Hawthorn interacts significantly with digoxin; avoid use in patients with heart failure.Page 2016

Herbs (Hypotensive Properties): May enhance the adverse/toxic effect of other Herbs (Hypotensive Properties). Excessive blood pressure lowering may manifest. Monitor therapy.Richard 2005, Ernst 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 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases was caused by herbals and dietary supplements whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to 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 number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, hawthorn was among the 22% (116) of the 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

References

Akila M, Devaraj H. Synergistic effect of tincture of Crataegus and Mangifera indica L. extract on hyperlipidemic and antioxidant status in atherogenic rats. Vascul Pharmacol. 2008;49(4-6):173-177.18755296
Ammon HP, Handel M. Crataegus, toxicology and pharmacology, Part I: Toxicity [in German]. Planta Med. 1981;43(2):105-120.
Asgary S, Naderi GH, Sadeghi M, Kelishadi R, Amiri M. Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study. Drugs Exp Clin Res. 2004;30(5-6):221-225.15700749
Asher GN, Viera AJ, Weaver MA, Dominik R, Caughey M, Hinderliter AL. Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial. BMC Complement Altern Med. 2012;12:26.3350435
Barros L, Carvalho AM, Ferreira IC. Comparing the composition and bioactivity of Crataegus Monogyna flowers and fruits used in folk medicine. Phytochem Anal. 2011;22(2):181–188.
Belz GG, Butzer R, Gaus W, Loew D. Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension. Phytomedicine. 2002;9(7):581-588.12487321
Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000.
Can OD, Ozkay UD, Oztürk N, Oztürk Y. Effects of hawthorn seed and pulp extracts on the central nervous system. Pharm Biol. 2010;48(8):924-931.20673180
Chen JD, Wu YZ, Tao ZL, Chen ZM, Liu XP. Hawthorn (shan zha) drink and its lowering effect on blood lipid levels in humans and rats. World Rev Nutr Diet. 1995;77:147-154.7732698
Crataegus monogyna Jacq. USDA, NRCS. 2010. The PLANTS Database (http://plants.usda.gov, August 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
Daniele C, Mazzanti G, Pittler MH, Ernst E. Adverse-event profile of Crataegus spp.: a systematic review. Drug Saf. 2006;29(6):523-535.16752934
Elango C, Jayachandaran KS, Niranjali Devaraj S. Hawthorn extract reduces infarct volume and improves neurological score by reducing oxidative stress in rat brain following middle cerebral artery occlusion. Int J Dev Neurosci. 2009;27(8):799-803.19712738
Ernst E. Cardiovascular adverse effects of herbal medicines: a systematic review of the recent literature. Can J Cardiol. 2003;19(7):818-27.12813616
Furey A, Tassell M. Towards a systematic scientific approach in the assessment of efficacy of an herbal preparation: Hawthorn (Crataegus spp.). Eur J Heart Fail. 2008;10(12):1153-1157.18996738
Fürst R, Zirrgiebel U, Totzke F, Zahler S, Vollmar AM, Koch E. The Crataegus extract WS 1442 inhibits balloon catheter-induced intimal hyperplasia in the rat carotid artery by directly influencing PDGFR-beta. Atherosclerosis. 2010;211(2):409-417.20435310
Hanus M, Lafon J, Mathieu M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin. 2004;20(1):63-71.14741074
Hawthorn. In: WHO Monographs on Selected Medicinal Plants. Vol 1. Geneva, Switzerland: World Health Organization; 1999.
Holubarsch CJ, Colucci WS, Meinertz T, Gaus W, Tendera M. Survival and prognosis: investigation of Crataegus extract WS 1442 in congestive heart failure (SPICE)--rationale, study design and study protocol. Eur J Heart Fail. 2000;2(4):431-437.11113721
Holubarsch CJ, Colucci WS, Meinertz T, Gaus W, Tendera M; Survival and prognosis: investigation of Crataegus extract WS 1442 in CHF (SPICE) trial study group. The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial. Eur J Heart Fail. 2008;10(12):1255-1263.19019730
Horoz M, Gok E, Genctoy G, et al. Crataegus orientalis associated multiorgan hypersensitivity reaction and acute renal failure. Intern Med. 2008;47(23):2039-2042.19043257
Hosseinimehr SJ, Mahmoudzadeh A, Azadbakht M, Akhlaghpoor S. Radioprotective effects of Hawthorn against genotoxicity induced by gamma irradiation in human blood lymphocytes. Radiat Environ Biophys. 2009;48(1):95-98.18769933
Hwang HS, Bleske BE, Ghannam MM, et al. Effects of hawthorn on cardiac remodeling and left ventricular dysfunction after 1 month of pressure overload-induced cardiac hypertrophy in rats. Cardiovasc Drugs Ther. 2008;22(1):19-28.18210194
Kroll M, Ring C, Gaus W, Hempel B. A randomized trial of Korodin Herz-Kreislauf-Tropfen as add-on treatment in older patients with orthostatic hypotension. Phytomedicine. 2005;12(6-7):395-402.16008114
Lin Y, Vermeer MA, A Trautwein E. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters. Evid Based Complement Alternat Med. 2009 Feb 19. [Epub ahead of print]
Luo Y, Chen G, Li B, et al Dietary intervention with AHP, a functional formula diet, improves both serum and hepatic lipids profile in dyslipidemia mice. J Food Sci. 2009;74(6):H189-H195.19723204
Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399-1408.25043597
Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016;134(6):e32-69.27400984
Pittler MH, Guo R, Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane Database Syst Rev. 2008;1:CD005312.18254076
Quettier-Deleu C, Voiselle G, Fruchart JC, et al. Hawthorn extracts inhibit LDL oxidation. Pharmazie. 2003;58(8):577-581.12967038
Rastogi S, Pandey MM, Rawat AK. Traditional herbs: a remedy for cardiovascular disorders. Phytomedicine. 2016;23(11):1082-1089.26656228
Richard CL, Jurgens TM. Effects of natural health products on blood pressure. Ann Pharmacother. 2005;39(4):712-20.15741425
Rigelsky JM, Sweet BV. Hawthorn: pharmacology and therapeutic uses. Am J Health Syst Pharm. 2002;59(5):417-422.11887407
Schandry R, Duschek S. The effect of Camphor-Crataegus berry extract combination on blood pressure and mental functions in chronic hypotension—A randomized placebo controlled double blind design. Phytomedicine. 2008;15(11):914–922.18929475
Schröder D, Weiser M, Klein P. Efficacy of a homeopathic Crataegus preparation compared with usual therapy for mild (NYHA II) cardiac insufficiency: results of an observational cohort study. Eur J Heart Fail. 2003;5(3):319-326.12798830
Swaminathan JK, Khan M, Mohan IK, et al. Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury. Phytomedicine. 2010;17(10):744-752.20171068
Tadić VM, Dobrić S, Marković GM, et al. Anti-inflammatory, gastroprotective, free-radical-scavenging, and antimicrobial activities of hawthorn berries ethanol extract. J Agric Food Chem. 2008;56(17):7700-7709.18698794
Vogel JH, Bolling SF, Costello RB, et al. Integrating complementary medicine into cardiovascular medicine. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Writing Committee to Develop an Expert Consensus Document on Complementary and Integrative Medicine). J Am Coll Cardiol. 2005;46(1):184-221.15992662
Walker AF, Marakis G, Morris AP, Robinson PA. Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension. Phytother Res. 2002;16(1):48-54.11807965
Walker AF, Marakis G, Simpson E, et al. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial. Br J Gen Pract. 2006;56(527):437-443.16762125
Werner NS, Duschek S, Schandry R. D-camphor-crataegus berry extract combination increases blood pressure and cognitive functioning in the elderly—a randomized, placebo controlled double blind study. Phytomedicine. 2009;16(12):1077-1082.19560327
Xu H, Xu HE, Ryan D. A study of the comparative effects of hawthorn fruit compound and simvastatin on lowering blood lipid levels. Am J Chin Med. 2009;37(5):903-908.19885950
Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of hawthorn. J Ethnopharmacol. 2008;118(1):127-132.18485639
Ye XL, Huang WW, Chen Z, et al. Synergetic effect and structure-activity relationship of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors from Crataegus pinnatifida Bge. J Agric Food Chem. 2010;58(5):3132-3138.20131788
Zick SM, Gillespie B, Aaronson KD. The effect of Crataegus oxycantha Special Extract WS 1442 on clinical progression in patients with mild to moderate symptoms of heart failure. Eur J Heart Fail. 2008;10(6):587-593.18490196
Zick SM, Vautaw BM, Gillespie B, Aaronson KD. Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) trial. Eur J Heart Fail. 2009;11(10):990-999.19789403

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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