Crataegus spp. supports the cardiovascular system
Brenna Hendrick
American College of Healthcare Sciences RES 502
Dr. Lupin Demuth
Abstract
Hawthorn, Crataegus spp., has been used for centuries. The effectiveness of this herbal remedy as an alternative to conventional medicine, or in conjunction with conventional medicine for cardiovascular support, is approved by the European Union; however, clinical evaluations both support and deny hawthorn's therapeutic actions on the cardiovascular system. The purpose of this study was to assess whether the medicinal plant hawthorn, Crataegus spp., provides cardiovascular support by means of improved exercise tolerance. Cratageous spp. has been used by indigenous nations throughout the Americas. There is a plethora of primary evidence that both supports and denies the plant having statistically significant therapeutic properties for cardiovascular support. The main therapeutic property evaluated in this study is exercise tolerance. The potential use of the herbal remedy Cratageous spp. to improve exercise tolerance for heart failure patients was evaluated by reading and assessing primary and secondary peer-reviewed scholarly journals. The clinical studies evaluated used walking or bicycle tests to measure exercise tolerance. Peer-reviewed journal articles were primarily accessed through PubMed and American College of Health Care Sciences University's library databases. The clinical studies reviewed were assessed in detail and looked at pre-treatment and post-treatment exercise tolerance before and after administering Cratageous spp. amongst patients with type II and type III New York Heart Association (NYHA) heart failure. The clinical evaluations varied in dosage and duration of time. The results show that Cratageous spp. ability to support the cardiovascular system is dependent on the dosage of the herb administered.
Keywords: Hawthorn, Crataegus, Cardiovascular, Heart Failure, New York Heart Association, Clinical, Herbal Remedy, Phytotherapy, Herbal Pharmaceutical.
Introduction
The purpose of this study is to assess if Hawthorn, Crataegus spp., supports the cardiovascular system. Hawthorn has historical relevance to cardiovascular support worldwide. The plant has documented usage since the late 1800s for Westerners (Edwards et al., 2012). The European Union and China recognize this plant as an approved herbal pharmaceutical for its cardiovascular supporting properties (Edwards et al., 2012). The clinical results substantiating hawthorn's supportive cardiovascular properties have inconsistent data demonstrating a statistical significance.
There is debate among how many Crataegus species exisit. A journal article in the American family physician notes that up to 300 Crataegus spp. exist (Dahmer & Scott, 2010). Another journal article by Edwards et al. (2012) notes that Crataegus may have been overclassified, and that 150-200 is probably a more accurate representation of species size (Edwards et al., 2012). The quantity of species can impact variation in constituents, and variation in the active constituents of the species can impact medical efficacy. For hawthorn, the flavonoid content needs to be at least 7% to claim therapeutic benefits in China and at least 1.5% in the European Union (Edwards et al., 2012). 1.5% is also the dosage recommended by the American Herbal Pharmacopoeia (Edwards et al., 2012). In addition to variation in flavonoid level, most countries agree that the constituent oligomeric procyanidin needs to be above 1% to provide therapeutic actions (Edwards et al., 2012). This type of standardization is essential as it helps ensure the medicinal constituents of the herb are equal amongst different approved phytotherapy pharmaceuticals. Crataegus spp. as a phytotherpahy with no known contraindictions (Mills & Bones, 2005). It is recommended that Crataegus spp. be taken under supervision of a qualified proffesional if taking with heart and bloode pressure medication (Mills & Bones, 2005). The clinical studies evaluated in this research paper will look at dosage and length of time Crataegus spp. was administered to determine if Crataegus spp. is beneficial for patients experiencing heart failure. The focus will be on exercise tolerance as a sedentary lifestyle is the greatest threat for heart failure (Pinckard et al., 2019). This paper aims to determine the clinical outcomes of Crataegus spp. amongst patients with heart failure.
Results
Degenring et al. (2003) conducted a clinical trial on New York Heart Association (NYHA) type II cardiac failure patients (Degenring et al., 2003). The study included 143 patients, 71 female and 72 male, with an average age of 64 (the age range was 44-79) (Degenring et al., 2003). Patients with a history of malignant tumors, renal insufficiency, obstructive diseases of the respiratory tract, anemia, and thyroid disease were exempt from the study (Degenring et al., 2003). The study administered an extract of hawthorn berries, Crataegus oxyacantha, and Crataegus monogyna, or a placebo for 8 weeks at a dosage of 30 drops 3 times per day (Degenring et al., 2003). The medicine administered was trademarked Crataegisan® (Degenring et al., 2003). This dosage equaled a daily dose of 6.4 mg oligomeric procyanidins (Degenring et al., 2003). A change in exercise tolerance was evaluated by bicycle exercise testing. An initial measurement was taken at time 0, starting with an initial bike load of 25 watts, which increased by 25 watts every 2 minutes until subjective or objective discontinuation (Degenring et al., 2003). At the end of each watt setting, an electrocardiogram (ECG), blood pressure, and pulse measurement were taken. Changes in the S.T. segment were noted, and any symptoms experienced were recorded. The bicycle test was repeated at the 2, and 3-month visits for both the placebo and the group administered Crataegisan®. Statistical software was used to analyze the results (Degenring et al., 2003). The results showed a significant improvement in the exercise tolerance for people taking Crataegisan® (Degenring et al., 2003). In addition, adverse reactions were rare, and 98.6% of participants did not experience negative results associated with Crataegisan® (Degenring et al., 2003). There were no conflicts of interest presented in this study.
Holubarch et al. (2008) conducted a clinical study on the efficacy and safety of Crataegus spp. extracts for patients with NYHA type II and III heart failure (Holubarch et al., 2008). This study included 2,681 patients with congestive heart failure (Holubarch et al., 2008). A total of 1,338 patients above the age of 18 took the registered trademark extract of Crataegus spp.,Crataegus WS® 1442, and 1,343 patients were administered a placebo (Holubarch et al., 2008). Crataegus WS® 1442 is a dry extract of the leaf and flower that uses 45% ethanol as the solvent (Holubarch et al., 2008). The species within Crataegus WS® 1442 were not listed. However, research shows Crataegus WS® 1442 is standardized to have 18.75% oligomeric procyanidins (Dahmer & Scott, 2010). Crataegus WS® 1442 is a registered European phytotherapy medication for NYHA type II heart failure (Holubarch et al., 2008). The study was single-blind, and patients were administered 450 mg/day for 24 months. There was no significant difference in exercise tolerance (measured by the bicycle method) or the reduction of cardiac mortality between the groups. For the group taking Crataegus WS® 1442 extract, a 39.7% reduction in sudden cardiac death was observed. The results from this clinical evaluation show that the administration of Crataegus WS® 1442 extract has no significant impact on the outcome (Holubarch et al., 2008). This study did not indicate any conflict of interest; however it was sponsored. The authors did not share who the sponsor was, which could be a conflict of interest if the sponsor is a competing trademarked supplier of a Crataegus spp. medicine.
Hawthorn, Crataegus spp., was clinically evaluated in a double-blind multicentric study as a therapy for patients with chronic congestive heart failure (Schmidt et al., 1994). The study included 78 males and 78 females aged between 45 to 73 (Schmidt et al., 1994). All participants were diagnosed with NYHA type II heart failure (Schmidt et al., 1994). Excluded from the study were individuals with NYHA type III and IV heart failure or overweight or had obstructive respiratory tract disease (Schmidt et al., 1994). Other medications, excluding diuretics, were not taken during the study (Schmidt et al., 1994). The study took place over 8 weeks with a placebo group and a group that took an extract of hawthorn called LI 132 (Schmidt et al., 1994). LI 132 is a 200 mg extract of hawthorn that was taken 3 times a day (Schmidt et al., 1994). LI 132 is trademarked as Faros 300® and is standardized to have 2.2% flavonoids (Dahmer & Scott, 2010). The species or part of the plant used within Faros 300® were not listed in the study.
Exercise ability was evaluated using the bicycle method (Schmidt et al., 1994). Before the study began, it was determined that an improvement of over 12.5 watts could be considered clinically relevant (Schmidt et al., 1994). On day 0, median values were obtained for both groups (Schmidt et al., 1994). At the end of the study, it was found that patients taking the placebo saw around a 5-watt improvement, while patients taking LI 132 displayed an improvement of 28 watts (Schmidt et al., 1994). These results demonstrated a significant improvement while taking hawthorn in exercise tolerance (Schmidt et al., 1994). In addition, a significant decrease in systolic blood pressure and heart rate was observed in the patients taking Hawthorn (Schmidt et al., 1994). There we no adverse events reported in this clinical trial (Schmidt et al., 1994). Conflict of interest is unknown as the sponsor was not listed.
Thauchert's (2002) clinical evaluation of Hawthorn, Crataegus spp. was on NYHA type III heart failure patients over 16 weeks (Thauchert, 2002). The study was a randomized, double-blind, multicentric trial including a placebo. A total of 209 patients were spread through 18 centers in Germany (Thauchert, 2002). All patients were greater than or equal to 40 years old and both genders were included (Thauchert, 2002). The patients evaluated were simultaneously taking diuretics (Thauchert, 2002). A placebo and Crataegus extract W.S. 1442® were administered at 450 mg and 900 mg twice daily (Thauchert, 2002). The specific Crataegus spp. within Crataegus extract W.S. 1442® were not listed in the study. Patients taking the placebo, 900 mg, and 1,800 mg extract quantities were evaluated for exercise tolerance through the bicycle method (Thauchert, 2002). The results showed that the 1,800 mg quantity resulted in a statistical improvement in exercise tolerance compared to the placebo; the 900 mg did not demonstrate a statistically relevant improvement (Thauchert, 2002). In addition, in both groups taking the extract, symptoms of congestive heart failure decreased (Thauchert, 2002). The most adverse events noted were in the placebo group, with dizziness being the most commonly reported (Thauchert, 2002). Dizziness was the most common reported of other clinical evaluations in literature reviews as well (Daniele et al., 2006). There were 36 adverse events in the placebo group compared to 20 in the 900 mg group and 18 in the 1,800 mg group (Thauchert, 2002). A grant by the manufacturer of Crataegus extract W.S. 1442® supported this study. This grant money could be considered a conflict of interest as the financial contributions came from a source that wants to show the medicine is efficacious to the cardiovascular system.
Zick et al. (2009) conducted a clinical trial to see if adding Crategous spp. to conventional therapies would increase exercise capacity for patients experiencing heart failure (Zick et al., 2009). This double-blind study looked at 120 ambulatory patients at or above 18 years of age with class II-III chronic heart failure (Zick et al., 2009). The patients took either Crataegus spp. extract (Crataegus extract W.S. 1442®) or a placebo at a dosage of 450 mg twice daily for 6 months (Zick et al., 2009). The specific Crataegus spp. within Crataegus extract W.S. 1442® were not listed in the study. All patients were simultaneously taking conventional medicine (Zick et al., 2009). The results did not demonstrate a significant improvement in a 6-minute walk, and the quality of life was not improved either (Zick et al., 2009). There was a slight improvement in the left ventricular ejection fraction for the patients taking the extract, and there were more adverse events reported in the group taking Hawthorn (Zick et al., 2009). There were no conflicts of interest declared. The University of Michigan Complementary and Alternative Medicine Research Center funded this research.
Discussion
Evidence suggests Crataegus spp. can improve cardiovascular health; however, not all clinical evidence supports this thesis. A sum of 5 clinical studies were evaluated, and 3 out of the 5 clinical evaluations observed demonstrated significant improvement in exercise tolerance when taking an extract of hawthorn. Degenring et al. (2003), Schmidt et al. (1994), and Trauchert (2002) all showed a statistically significant result. Degenring et al. (2003) used hawthorn berry at a dosage equivalent to 6.4 mg oligomeric procyanidins (Degenring et al., 2003). Schmidt et al. (1994) used LI 132, a leaf and flower extract standardized to 2.2% flavonoids. Trauchert (2002) used Crataegus extract WS 1442, a leaf and flower extract standardized to 18.75% oligomeric procyanidins. All 3 of these studies that demonstrated significant improvements compared to the placebo were at least 8 weeks in duration. Degenring et al. (2003) was dosed as 2.25 ml/day while Schmidt et al., (1994) was 600 mg/day and Trauchert (2002) was 1,800 mg/day. The hawthorn used in clinical studies for cardiovascular support is inconsistently standardized; for example, LI 132 standardizes flavonoid content, and WS 1442 standardizes oligomeric procyanidins. The 2 studies that did not demonstrate a significant improvement in exercise tolerance were Zick et al. (2009) and Holubarch et al. (2008). These studies both used Crataegus extract WS 1442 at a lower dosage than the 3 studies that demonstrated statistical improvement. Trauchert (2002) also used WS 1442, but at a greater dosage than Holubarch et al. (2008) and Zick et al. (2009). Holubarch et al. (2008) patients were administered 450 mg/day for 24 months, and Zick et al. (2009) was at 450 mg/day for 6 months. Holubarch et al. (2008) was the longest study evaluated and did not demonstrate significant improvement. Zick et al. (2009) had the same mg/day dosage and also did not demonstrate significant improvement. More data needs to be collected to determine if dosage impacts the results or if conventional medicine potentially interferes with results and or adverse events.
The data suggest that WS 1442, a standardized leaf and flower extract, decreases myocardial oxygen usage and improves oxygen uptake (Thauchert, 2002). It also shows that improved exercise function is seen in class III NYHA heart failure patients and that efficacy is dose-dependent (Thauchert, 2002). Hawthorn benefits the myocardial system and the vascular muscles by reducing peripheral vascular resistance (Schmidt et al., 1994). Reduced resistance improves cardiac capabilities resulting in strengthened cardiac muscle (Schmidt et al., 1994). Other research has shown exercise improves oxygen uptake when performed regularly and can help reduce the risk of a cardiac event (Morris & Froelicher, 1993). Morris & Froelicher (1993) also noted that there is a 50% less chance of a cardiac event for people who perform exercise at least 2 days a week (Morris & Froelicher, 1993).
The results from the studies demonstrate that Crataegus spp. can improve cardiovascular health through improved exercise tolerance if the dose is substantial. More data needs to be collected on the minimum acceptable dose, length of time, and active constituent content to truly understand hawthorn's benefits to patients experiencing heart failure (Lalukota et al., 2004). Crataegus spp. could also be studied more to prevent sudden cardiac death (Holubarch et al., 2008)
Conclusions
Evidence suggests Crataegus spp. can improve cardiovascular health by increasing exercise tolerance; however, the plant fails to produce statistically significant results without the correct dosage. The purpose of this study is to assess whether Crataegus spp. improves cardiovascular health. The primary sources show that Crataegus spp. can be therapeutic for people with type II and type III heart failure with the proper dosage. More research is needed to standardize oligomeric procyanidins and flavonoids content to produce consistent therapeutic actions.
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