Benefits
Exercise tolerance and heart-related symptom scores
In a pooled analysis of 10 placebo-controlled trials (855 people with chronic heart failure, mostly also on standard medicines), leaf and flower extract raised maximal workload by about 5 watts and eased shortness of breath and fatigue. One 209-person trial saw a larger workload gain at 1,800 than at 900 mg/day. A later 6-month, 120-person trial found no gain in walking distance or quality of life.
Cardiac event rates over two years alongside standard medicines
In a 2-year trial of 2,681 adults with heart failure and reduced pumping function, 900 mg/day of WS 1442 did not lengthen time to a first cardiac event (27.9% vs 28.9% had one), and the lower cardiac death rate was not statistically significant. A later analysis of a 6-month trial found overall worsening was similar, but early worsening was more common with the extract.
Diastolic blood pressure alongside prescribed medicines
In a 16-week trial in 79 adults with type 2 diabetes, most already on blood pressure drugs, 1,200 mg/day lowered diastolic pressure from 85.6 to 83.0 mmHg, while it rose from 84.5 to 85.0 mmHg on placebo; systolic pressure did not differ. Pooling 6 small placebo-controlled trials (428 people) gave systolic pressure about 6.7 mmHg lower, with no significant diastolic difference.
Mechanism of action
Stronger heart muscle contraction in lab tissue
In strips of failing human heart muscle removed at transplant, WS 1442 raised the force of contraction to about 130% of baseline in the lab. Lab studies suggest it partly blocks the sodium potassium pump and phosphodiesterase, raising calcium in heart cells; one study found no effect on adenylate cyclase. These are test-tube findings, not effects shown with capsules.
Blood vessel relaxation through nitric oxide in isolated vessels
In artery rings from bypass patients, the extract relaxed the vessel, but not when nitric oxide production was blocked or the vessel lining was removed, and it released nitric oxide from human coronary artery cells. In people, however, 1,000 to 2,500 mg/day for 3.5 days did not change flow-mediated dilation, a nitric oxide dependent test of vessel function.
Heart protection in rat models
In rats given leaf and flower extract by mouth for 7 days before a blocked coronary artery, 100 mg/kg/day cut ventricular fibrillation (67% to 27%) and death (47% to 9%) and shrank the damaged area. In rats with long-term pressure overload, the extract did not lower deaths. These animal results have not been shown in people.
Clinical trials
Cochrane systematic review of double-blind, randomized, placebo-controlled trials of hawthorn leaf and flower extract taken by mouth; 14 trials met inclusion criteria and 10 provided data for pooling. (Pittler et al. 2008, Cochrane Database Syst Rev)
855 patients with chronic heart failure (NYHA classes I to III) in the pooled trials; in most studies hawthorn was added to conventional treatment.
Maximal workload rose by 5.35 watts more than placebo (95% CI 0.71 to 10.00, 380 patients); exercise tolerance and the pressure-heart rate product also improved, and shortness of breath and fatigue scores fell. Cardiac events were not reported except deaths in one trial (3 on hawthorn, 1 on placebo). Reported side effects were infrequent, mild and transient.
Randomized, double-blind, placebo-controlled multicenter trial of WS 1442 900 mg/day or placebo for 24 months; primary endpoint was time to first cardiac event. (Holubarsch et al. 2008, Eur J Heart Fail)
2,681 adults with NYHA class II or III heart failure and left ventricular ejection fraction of 35% or less (1,338 extract, 1,343 placebo).
The primary endpoint did not differ: average time to first cardiac event was 620 vs 606 days, with event rates of 27.9% vs 28.9% (HR 0.95, p=0.476). The trend toward fewer cardiac deaths was not statistically significant (HR 0.89, p=0.269). In a subgroup with ejection fraction of 25% or more, sudden cardiac death was lower (HR 0.59, p=0.025), a secondary finding. Adverse events were comparable in both groups.
Randomized, double-blind, placebo-controlled NIH-supported trial (NCT00343902) of hawthorn 450 mg twice daily (WS 1442) added to conventional medical therapy; primary outcome was change in 6-minute walk distance. (Zick et al. 2009, Eur J Heart Fail)
120 ambulatory adults with NYHA class II or III chronic heart failure.
Change in 6-minute walk distance did not differ from placebo (p=0.61), nor did quality of life, functional capacity, neurohormones or blood markers. Ejection fraction differed slightly in favor of hawthorn (p=0.04). More adverse events were reported on hawthorn (p=0.02), most not heart-related. A later retrospective analysis of this trial found heart failure progression in 46.6% vs 43.3% overall (p=0.86) but a higher early risk with the extract.
Randomized, placebo-controlled multicenter trial of WS 1442 1,800 mg/day, 900 mg/day or placebo for 16 weeks, added to existing diuretic treatment. (Tauchert 2002, Am Heart J)
209 patients with chronic stable NYHA class III heart failure.
At 1,800 mg/day, maximal tolerated workload on a bicycle rose significantly more than with placebo or with 900 mg/day. Patient-rated heart failure symptoms fell more than with placebo at both doses. Adverse events, particularly dizziness and vertigo, were least frequent in the 1,800 mg group. The abstract does not give effect sizes.
Randomized, placebo-controlled trial in general practices in Reading, UK, of Crataegus laevigata extract 1,200 mg/day or placebo for 16 weeks. (Walker et al. 2006, Br J Gen Pract)
79 adults with type 2 diabetes (39 hawthorn, 40 placebo); 71% took blood pressure drugs, and participants took an average of 4.4 diabetes or blood pressure drugs.
Diastolic pressure fell from 85.6 to 83.0 mmHg with hawthorn and went from 84.5 to 85.0 mmHg with placebo, a significant group difference (p=0.035). Systolic pressure did not differ between groups (falls of 3.6 vs 0.8 mmHg, p=0.329). No herb and drug interaction was found.
Randomized, double-blind, placebo-controlled pilot with four arms: magnesium 600 mg, hawthorn extract 500 mg, both, or placebo daily for 10 weeks. (Walker et al. 2002, Phytother Res)
36 adults with mild essential hypertension completed; 19 were assigned hawthorn, alone or with magnesium.
Blood pressure fell in all groups, including placebo, and the main analysis found no difference between treatments. A factorial contrast showed a trend toward lower resting diastolic pressure at week 10 in the hawthorn groups that did not reach significance (p=0.081).
Randomized four-period crossover of placebo and 1,000, 1,500 and 2,500 mg/day of extract standardized to 50 mg OPC per 250 mg, taken in two daily doses for 3.5 days with 4-day washouts; extract and placebo capsules were donated by Gaia, Inc. (Asher et al. 2012, BMC Complement Altern Med)
21 adults with prehypertension or mild hypertension completed the study.
No dose-response effect was found on brachial artery flow-mediated dilation (the main outcome), artery diameter or blood pressure. The authors concluded that any blood pressure effect of hawthorn is likely not driven by nitric oxide.