Douglas Lobay, BSc, ND
Rose was a bubbly, single, and slim 90-year-old concert pianist who still worked as a music teacher in part because of the current economic pressures. She came to our office one day complaining about fatigue, shortness of breath and slightly swollen ankles. Physical examination revealed normal blood pressure and high normal heart rate. Laboratory examination revealed good kidney function and normal electrolytes, normal iron, B12 and thyroid function. BNP (brain natriuretic peptide) was elevated indicating a moderate degree of congestive heart failure. A handheld office electrocardiogram appeared to be unrevealing and normal. She did not want to go to her allopathic doctor for further diagnostic workup, including a recommended chest x-ray and cardiac ultrasound, as she liked and trusted us. A low-dose loop diuretic was prescribed every other day as we felt this would work better than herbal diuretics. We also prescribed coenzyme Q10 and hawthorn. My question: Is hawthorn a clinically useful cardiovascular tonic or another herb that disappoints?
Hawthorn (Crataegus laevigata, monogyna, and oxyacantha), a member of the Rose family, is a shrub or tree that grows up to a height of 6 metres and is native to Europe, East Asia, and eastern North America. Hawthorn has white flowers that bloom in spring, bright red fruit containing one to three nuts, and long slender thorns along its stem. Hawthorn has been the focus of May time rituals in England, and the fruit has been used in Europe to make jam and wine. Hawthorn has been historically used to treat heart disorders, anemia, dyspepsia, respiratory ailments, and as a diuretic and astringent in menstrual complaints.1
The chemical composition of Crataegus species includes aromatic carboxylic acids like caffeic and chlorogenic acids, pentacyclic terpenes like oleanolic and ursolic acids, flavonoids, saponins, amines, amino acids and trace amounts of several vitamins and minerals. At least 30 different flavonoids have been isolated from Crataegus. Allied flavonoid derivatives include flavones, flavonols, flavonoids, catechins, proanthocyandins and oligomeric procyandins. They all share a common two phenolic ring backbone linked together to a third phenolic ring. The leaves, fruit, flowers and bark are all particularly high in flavonoid content. Flavonoids are responsible for imparting the color of the fruits of this plant. The flavonoid content of Hawthorn varies from 0.05 to 5.0% dry weight of the plant. Five active flavonoid compounds, including vitexin-4-O-glucoside, vitexin-2-O-rhamnoside, vitexin, rutin and hyperoside, have been identified as flavonoid markers. Hawthorn also contains tannins, which are responsible for the astringent effects of this plant.2,3
The ability of Crataegus to dilate coronary arteries and increase coronary blood flow has been widely demonstrated in both animal and human subjects. Crataegus consistently increases the heart muscle contractile force as measured by amplitude of heart muscle contractility and increase in blood volume pumped.Crataegus has demonstrated to decrease heart arrhythmias in aconite-induced heart rhythm disorders. Variable, insignificant effects on heart rate have been observed. Crataegus has been shown to increase blood flow to skeletal muscle while at the same time decreasing blood flow to the digestive tract, kidneys, and the skin. Crataegus has also demonstrated to decrease blood pressure while certain flavonoids in Crataegus have been shown to increase blood pressure.4
Hawthorn extract LI 132, a standardized 2.2% flavonoid content from leaves and flowers, was used to evaluate its effect on rat cardiac myocytes. The extract showed a moderate positive inotropic effect on heart muscle with a modest increase in mechanical and ionic turnover. Furthermore, a prolonged heart muscle refractory period was also observed, which indicated its potential as an anti-arrhythmic agent.5
Hawthorn flavonoids have demonstrated an inhibitory effect of the enzyme PDE or phosphodiesterase on rat heart muscle, which results in concomitant increase in cyclic AMP. This results in an increase in intra-cellular calcium and smooth muscle relaxation and vasodilation with increased calcium a positive inotropic effect on heart muscle is observed.6
Crataegus has cardioactive properties similar to digoxin. Hawthorn may interfere with serum digoxin measurement using immunoassays. Both hawthorn extracts increased intracellular calcium levels, but the lack of additive response with digoxin suggests both may bind to the same site of Na/K adenosine triphosphatase.A randomized, crossover trial with 8 healthy volunteers was performed evaluating digoxin alone for 10 days and digoxin with Crataegus special extract WS 1442. Pharmacokinetic studies were performed for 72 hours. There were no statistically significant differences in any measured pharmacokinetic parameters.7,8
Some specific proanthocyanidins appear to demonstrate mild angiotensin converting enzyme activity similar the prescription ACE inhibitor Captopril, which is responsible for decreasing sodium retention and decreasing hypertension. Another study compared the effectiveness of hawthorn extract compared to the ACE inhibitor Captopril in 132 Stage 2 NYHA or New York Heart Association heart failure patients and found the two treatment medication were about equally effective.9,10
Even though there have been inconsistencies in terms of Hawthorn preparations, dosage, sample size, results have been largely consistent and positive. Vascular vasodilation via endothelial dependent nitrous oxide induction mechanism has been attributed to oligomeric procyanidins. Hawthorn has an excellent safety profile with mild adverse side effects, including dizziness, nausea, upset stomach.11
A review postulated that the four main mechanisms of cardiovascular protection from Hawthorn extract included serum lipid lowering, antioxidant, anti-inflammatory and vascular endothelial protective properties. Hawthorn extract taken for 6 months lowered lipid levels and promoted stabile plaque. Hawthorn decreased lipid absorption from the digestive system and decreased liver production of cholesterol. Hawthorn decreased endothelial inflammation by increased endogenous nitric oxide and prevented oxidative damage to the delicate inner lining. Hawthorn also decreased inflammatory cytokines like interleukin and decreased endothelial macrophage activation.12
Based on the current research the pharmacologic effects of Crataegus can be summarized as follows. It increases coronary blood flow. It increases peripheral blood flow, including to skeletal muscle. It increases the contractile force of heart muscle contraction. It decreases heart muscle oxygen use. It causes variable, minor changes in heart rate depending on heart condition. It mildly decreases blood pressure.
The New York Heart Association stages of loss of cardiac output include 4 stages: Stage 1 – slight loss of capacity, means the patient is symptom free when at rest. Stage 2 – loss of capacity with medium effort and more. Stage 3 – loss of capacity with minor effort that results in obvious labored or difficult breathing. Stage 4 – patient experiences symptoms when at rest. Crataegus is indicated in Stage 2 and 3 of the NYHA scale of loss of cardiac output. A study of 120 patients, designed to test the efficacy of an alcoholic extract of fruits and leaves of Crataegus monogyna and Crataegus oxyacantha was conducted. The results indicated that general condition and heart output were significantly improved, especially in regard to the associated symptoms of shortness of breath and heart palpitations.13,14
In clinical trials, hawthorn extract has shown promising results in treating NYHA class 2 congestive heart failure. The mechanism of action is believed to be threefold involving a positive inotropic effect, increasing the force and strength of muscle contraction, on heart muscle, improved endothelial blood vessel functioning, which increase coronary blood blow flow and positive effects of oxygen utilization. The recommended daily dose of hawthorn extract was equivalent to 30 to 169 milligrams of epicatechin, or 3.5 to 19.8 milligrams of flavonoids of the leaves or flowers administered two to three times per day. Side effects included mild rash, headache, sweating, dizziness, palpitations, sleepiness, agitation, and upset stomach.15
A randomized, double-blind, placebo-controlled trial in 120 ambulatory patients with NYHA class II-III chronic heart failure was conducted. All patients received conventional medical therapy and were randomized to either hawthorn twice daily or placebo for 6 months. The primary outcome was change in 6 min walk distance at 6 months. Secondary outcomes included QOL or quality of life measures, peak oxygen consumption, and anaerobic threshold during maximal treadmill exercise testing, NYHA classification, LVEF (left ventricular ejection fraction), neurohormones, and measures of oxidative stress and inflammation. There were no significant differences between groups in the change in 6 min walk distance, or on measures of QOL, functional capacity, neurohormones, oxidative stress, or inflammation. A modest difference in LVEF favoured hawthorn.16
SPICE was the first, international, randomized, placebo-controlled, double-blind study to investigate the influence of the herbal drug Crataegus Special Extract WS 1442 hawthorn leaves with flowers on mortality of patients suffering from congestive heart failure. In this randomised, double-blind, placebo-controlled multicenter study, adults with NYHA class II or III CHF and reduced left ventricular ejection fraction (LVEF) less than 35% were included and received WS 1442 or placebo for 24 months. Primary endpoint was time until first cardiac event. 2681 patients were randomized with 1338 receiving WS 1442 and 1343 receiving placebo. Average time to first cardiac event was 620 days for WS 1442 and 606 days for placebo. The trend for cardiac mortality reduction with WS 1442 was not statistically significant. In the subgroup with LVEF less than 25% WS 1442 reduced sudden cardiac death by 39.7% at month 24. Also, the LVEF improved by 3 or 4% points in those patients with LVEF between 25% and 35%. Adverse events were comparable in both groups. In this study, WS 1442 had no significant effect on the primary endpoint. WS 1442 was safe to use in patients receiving optimal medication for heart failure. In addition, the data may indicate that WS 1442 can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.17
A Cochrane review of hawthorn extract in the treatment of heart failure was undertaken. A search of several medical databases, including Medline, revealed fourteen studies that met inclusion criteria for analysis. Ten studies from this group involving 855 patients with New York Heart Association stage 1 to stage 3 were suitable for meta-analysis. Maximal workload treatment improved on average 5.3% with hawthorn extract. Exercise tolerance significantly improved by an average of 22% with hawthorn extract. The pressure-heart rate product, an index of cardiac muscle oxygen consumption, decreased significantly, 19% on average compared to placebo. Symptoms such as shortness of breath and fatigue decreased significantly with hawthorn extract. Reported adverse side effects were infrequent and mild including nausea, dizziness, cardiac and gastro-intestinal effects. The author’s concluded that results of this analysis showed that there is significant benefit in symptom control and physiologic outcomes from hawthorn extract as an adjunctive treatment for chronic heart failure.18
Several small Chinese studies of hawthorn have shown that the incidence of angina decreased significantly with Crataegus supplementation for 1 to 2 months duration. Overall, patients felt better, could exercise and walk further, and felt decreased qualitative anginal symptoms.Eighty stable angina pectoris patients between the ages of 45 to 65 years were studied for the effect of hawthorn extract with aerobic exercise on vascular adhesion molecules ICAM or intracellular adhesion molecule and Selectin in this placebo-controlled trial. After 12 weeks of exercise and consumption of Crataegus extract showed a significant decrease in the circulating levels of these adhesion molecules.19,20
Hawthorn extract has been postulated to promote nitrous oxide mediated vasodilation thereby blood vessel relaxation and lowering blood pressure. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation, which is an indirect measure of nitric oxide release. Twenty-two participants participated in the crossover trial and consumed hawthorn extract for four days, then had a washout period and crossover to the placebo group. The researchers found no significant decrease in brachial arterial blood pressure after consumption of Hawthorn extract for the duration of this study.21
Low-dose hawthorn extract lowered diastolic blood pressure significantly more than placebo or magnesium. Patients also notice a subjective reduction in anxiety levels.22
Seventy-nine type 2 diabetic patients were randomized to take hawthorn extract or placebo for 16 weeks. There was no significant change in systolic blood pressure between the two groups, but diastolic blood pressure significantly decreased, albeit a small decrease, in those who consumed the hawthorn extract.23
Crataegus and its extracts are non-toxic and completely safe for long term use. Few adverse side effects have been reported in over a hundred years of clinical use. Toxicity to the fetus is of little concern, since Crataegus is usually indicated for elderly patients with cardiovascular problems.24
A systematic review of the adverse event profile of hawthorn extract was undertaken. Twenty-four studies involving the data of 5,577 patients was available for analysis. The daily dose of different hawthorn extracts was between 160 to 1800 milligrams per day for 3 to 24 weeks. The two most popular extracts used were WS 1442 and LI 132. WS 1442, more commonly known as Craetagutt from Shwabe in Germany, was standardized to contain 18.75% oligomeric procyanidins. LI 132, more commonly known as Faros, was a standardized extract of 2.25% flavonoids. One hundred and sixty-six adverse events were reported. Fifteen people reported dizziness or vertigo, 24 reported nausea and stomach upset, and 11 people reported heart palpitations. No drug interactions were reported.25
Like most herbal medicines from different sources and multiple forms, the degree of active ingredients varies. Dosing is also variable. In most studies the amount of Hawthorn varied from a low of 100 milligrams per day to as high as 1800 milligrams or more. Hawthorn was available in different forms, including raw leaf, flower and fruit, powder, tincture, fluid extract, solid extract and standardized extract. The exact dosing would depend on the form of herb and is typically given one to three times per day. For instance, a standardized extract containing 1.8% of the flavonoid vitexin-4-rhamnside would be administered at 100 to 250 milligrams from one to three times per day.
So, is hawthorn a cardiovascular tonic or another failed herb with high expectations? Based on the summary of the available clinical research, Crataegus has clinical utility in treating patients with mild to moderate congestive heart failure, NYHA stage 1 to 3, with modestly reduced LVEF. Its effect on high blood pressure is mild at best but seems to work well in some individuals perhaps in conjunction with other therapies. Its effect on angina is modest and tempered in some patients. Its effect on cardiac arrhythmias is promising but clearly needs more research. Its use in healthy patients to improve heart function and oxygen uptake in athletic endeavors has not been studied. And more importantly, the music teacher Rose had improved. Her energy has increased, her shortness of breath disappeared, and her ankle swelling is significantly better.
References
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3. Nabavi SF et al. Polyphenolic Composition of Crataegus monogyna Jacq.: From Chemistry to Medical Applications. Nutrients. 2015 Sep; 7(9): 7708–7728.
4. Petkov V: Plants with hypotensive, antiatheromatous and coronarodilating action. Am. J. Clin. Med. 1979; 7:197-236.
5. Popping S et al. Effect of a hawthorn extract on contraction and energy turnover of isolated rat cardiomyocytes. Arzneimittelforschung. 1995 Nov; 45(11):1157-61.
6. Petkov E et al. Inhibitory effect of some flavonoids and flavonoid mixtures on cyclic AMP phosphodiesterase activity of rat heart. Planta Med. 1981 Oct; 43(2):183-6.
7. Dasgupta A et al. Interference of hawthorn on serum digoxin measurement by immunoassay and pharmacodynamic interaction with digoxin. Arch Pathol Lab Med. 2010 Aug; 134(8):1188-92.
8. Tankanow R et al. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). J Clin Pharmacol. 2003 Jun; 43(6):637-42.
9. Uchida S et al. Inhibitory effects of condensed tannins on angiotensin converting enzyme. Jap J Pharmacol.1987; 43:242-5.
10. Tauchert M et al. Effectiveness of the hawthorn extract LI 132 compared with the ACE inhibitor captopril: Multicenter double-blind study with 132 NYHA stage II patients. Munch Med1994; 136(suppl 1):S27-33.
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16. Zick SM et al. Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) Trial. Eur J Heart Fail. 2009 Oct; 11(10): 990–999.
17. Holubarsch JF et al. The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial. Eur J Heart Fail. 2008 Dec; 10(12):1255-63.
18. Pittler MH et al. Hawthorn extract for treating chronic heart failure. Cochrane Database Syst Rev. 2008 Jan 23:(1):CD005312.
19. Weng et al. Therapeutic effect of Crataegus pinnatifida on 46 cases of angina pectoris – a double blind study. J Tradit Chin Med. 1984; 4(4):293-294.
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21. Asher GN et 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.
22. Walker AF et al. Promising hypotensive effect of hawthorn extract: a randomized-blind pilot study of mild, essential hypertension. Phytother Res. 2002 Feb; 16(1):48-54.
23. Walker AF et al. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial. Randomized Controlled Trial. Br J Gen Pract. 2006 Jun; 56(527):437-43.
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Published February 24, 2024
About the Author
Douglas G. Lobay is a practicing naturopathic physician in Kelowna, British Columbia. Dr. Lobay graduated with a Bachelor of Science degree from the University of British Columbia in 1987. He then attended Bastyr College of Health Sciences in Seattle, Washington, and graduated with a Doctor of Naturopathic Medicine in 1991. While attending Bastyr College, he began to research the scientific basis of natural medicine. He was surprised to find that many of the current medical journals abounded with scientific information on the use of diet, nutrition, vitamins, and botanical medicines. Besides practicing naturopathic medicine Dr. Lobay enjoys research, writing and teaching others about the virtues of good health and nutrition. He has authored several books, numerous articles, and papers and has taught many courses at seminars and colleges throughout his career. He is married to Natalie and has two daughters, Rachel and Jessica. He also enjoys hiking, hockey, skiing, tennis, travelling and playing his guitar.