Hawthorn

Overview

Hawthorn is an English shrub that has a long history of medicinal use in herbal medicine, including cardiovascular disorders, digestive complaints, dyspnea and kidney stones. Hawthorn is a popular phytomedicine in Europe for use in cardiovascular disorders today. Hawthorn has the ability to increase the integrity of the blood vessel walls, improving coronary blood flow, improve oxygen utilization, and to possess positive inotropic activity. The cardiovascular effects of hawthorn are thought to be the result of these activities and primarily due to the flavonoid group of compounds present in hawthorn. Clinical trials conducted on congestive heart failure (functional class II) patients have shown good results, including positive implications on the changing of blood lipids (Rigelsky and Sweet, 2002).

Comments

In Europe hawthorn is a widely used phytotherapy used alone and in combination with digitalis for congestive heart failure. As clinical evidence continues to mount in the favor of the use of hawthorn as a cardioprotectant, its popularity in the United States is also increasing.

Scientific Support

Blood Pressure Reduction

Hawthorn extract was tested singly and in combination with magnesium supplements and compared to placebo for its ability to lower blood pressure. Thirty-six mildly hypertensive people were involved in the study and randomly assigned to undergo a 10-week supplementation regimen of either: a) 600 mg of Magnesium, b) 500 mg of hawthorn extract, c) the combination of the two (a and b), or d) placebo. A decline in the systolic and diastolic blood pressure was found in all treatment groups, with no difference found between the groups. Factorial contrast analysis in ANOVA found a reduction in resting diastolic blood pressure at the end of treatment in 19 of the subjects given hawthorn extract, along with a trend in the reduction of anxiety in this group. The authors noted the low dose of hawthorn extract used in the study and thought the results prompted further study for hawthorn (Walker et al., 2002).

Cardiovascular Disease

Pittler et al (2003) conducted a meta-analysis on the studies with hawthorn used to treat chronic heart failure. A variety of database searches were performed and experts commercial manufacturers in the field were asked to contribute published and unpublished studies. Inclusion criteria of randomized, double-blind, placebo controlled studies with hawthorn used alone in therapy resulted in 13 trials. Eight of these trials that involved 632 patients met the meta-analysis criteria. Improvement of outcome measures of workload and pressure-heart rate were found in the hawthorn groups. Symptoms that showed improvement from hawthorn treatment included dyspnea and fatigue. Infrequent, mild and transient side effects of nausea, dizziness, and cardiac and gastrointestinal complaints were found. The authors concluded that hawthorn extract proved to be a beneficial adjuvunct therapy for NYHA class II cardiac disease.

Hawthorn extract (standardized extract of the fresh berries of C. oxyacantha and C. monogyna) was tested in a placebo controlled, randomized, parallel multicenter clinical study in patients with NYHA class II cardiac failure. The 143 participants were given either hawthorn extract (30 drops three times daily) or placebo for 8 weeks. Primary outcome measurements were the changes in exercise tolerance (bicycle exercise tolerance testing), and secondarily, blood presure-heart rate product (BHP). In the hawthorn treatment group there was a significant improvement found, with dyspnoea and fatigue not occuring until a significanly higher wattage of bicycle output had been reached. The authors concluded that NYHA II patients undergoing long term hawthorn therapy could expect improvement in their condition (Degenring et al., 2003).

Hawthorn extract (Rob 10) was tested on exercise tolerance and quality of life in 88 patients in a placebo-controlled, randomized, double-blind clinical study. Patients were given 25 drops, three times daily of the hawthorn extract or placebo for three months. Treatment with hawthorn resulted in a significant increase in exercise time, and beneficially impacted the quality of life assessment, the assessments of dyspnea. The authors concluded that hawthorn extract was able to be used safely and efficaciously in NYHA type II congestive heart failure patients (Rietbrock et al., 2001).

Hawthorn extract (WS 1442-standardized to 18.72% oligomeric procyanidines) was tested in 40 NYHA class II pateints in a randomized, placebo-controlled, double-blind clinical study. Patients were treated with either hawthorn extract (1 capsule three times daily) or placebo for 12 weeks. The primary outcome in this study was the effect on exercise tolerance, and as a secondary outcome the blood pressure-heart rate product was calculated. The treatment group produced a borderline significant improvement in exercise tolerance, and a significant improvement in the blood pressure-heart rate product. Administration of hawthorn extract was found to be safe and well tolerated, and effective for NYHA class II heart failure (Zapfe jun, 2001).

A standardized hawthorn extract (WS 1442) was tested in a multicenter utilization observational study. Hawthorn (Crataegutt novo 450, 1 tablet b.i.d) was administered to 1,011 patients with NYHA type II cardiac insufficiency over 24 weeks. Hawthorn extract administration resulted in a significnat improvement in the clinical symptoms of NYHA II, including reduced exercise tolerance, fatigue, palpitation and exercise dyspnea. Additionally, ankle edema and nocturia was reduced by 83% in half of the patients with these symptoms before treatment. Exercise tolerance was found to be increased overall, as well as a reduction in blood pressure, blood pressure-heart rate product (BHP), a stabilization in the heart rate, improvement in measures of myocardial perfusion, and the overall assessments of improvement by the patient and the physician were found from hawthorn treatment. The authors concluded hawthorn extract to be an efficient, well-tolerated and easily regulated therapeutic alternative for NYHA II patients (Tauchert et al., 1999).

Leuchtgens (1993) studied hawthorn extract (WS 1442) in NYHA II cardiac insufficiency patients in a placebo-controlled, randomized, double-blind study. Hawthorn was administered (1 capsule two times daily) for 8 weeks or placebo, and the blood pressure-heart rate product (BHP) and a subjective assessment of improvement were used as primary outcomes, and exercise tolerance, change in heart rate, and arterial blood pressure were used as secondary outcomes. Hawthorn treatment produced a statistically significant improvement in the measures of BHP, subjective assessments of improvement, and also in the heart rates. Both groups produced a mild reduction in systolic and diastolic blood pressure and no adverse reactions were observed.

Safety / Dosage

Generally, the recommended dosage level for hawthorn is 160-900 mg of a water-ethanol extract (equivalent to 30-169 mg epicatechin or 3.5-19.8 mg flavonoids) 2-3 times daily (Rigelsky and Sweet, 2002).

Side effects of hawthorn are usually mild and transitory, but may include a mild rash, headache, sweating, dissiness, palpitations, sleepiness, agitation and gastrointestinal upset. Drug interactions may occur with other vasodilators, it is thought to potentially potentiate or interact with other drugs used for heart failure, hypertension, angina and arrhythmias (Rigelsky and Sweet, 2002). A recent randomized crossover clinical study was conducted in order to determine the potential interaction with drugs that are P-sglycoprotein substrates, such as digoxin. The authors concluded that in the dosages studied (450 mg two times daily of Hawthorn leaves and flowers extract, and 0.25 mg digoxin), the two medications could be coadministered safely (Tankanow et al., 2003).

References

1.Degenring FH, Suter A, Weber M, Saller R. A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine. 2003;10(5):363-9.

2.Leuchtgens H. [Crataegus Special Extract WS 1442 in NYHA II heart failure. A placebo controlled randomized double-blind study] Fortschr Med. 1993 Jul 20;111(20-21):352-4.

3.Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med. 2003 Jun 1;114(8):665-74.

4.Rigelsky JM, Sweet BV. Hawthorn: pharmacology and therapeutic uses.

5.Am J Health Syst Pharm. 2002 Mar 1;59(5):417-22.

6.Rietbrock N, Hamel M, Hempel B, Mitrovic V, Schmidt T, Wolf GK. [Actions of standardized extracts of Crataegus berries on exercise tolerance and quality of life in patients with congestive heart failure] Arzneimittelforschung. 2001 Oct;51(10):793-8.

7.Tankanow R, Tamer HR, Streetman DS, Smith SG, Welton JL, Annesley T, Aaronson KD, Bleske BE. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). J Clin Pharmacol. 2003 Jun;43(6):637-42.

8.Tauchert M, Gildor A, Lipinski J. [High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure] Herz. 1999 Oct;24(6):465-74; discussion 475.

9.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 Feb;16(1):48-54.

10.Zapfe jun G. Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA class II. Phytomedicine. 2001 Jul;8(4):262-6.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Perilla Seed Oil

Overview

Perilla, or shiso (also called beefsteak), is a popular vegetable in Asia that looks like a large-leafed basil. It’s seed oil is used in a variety of foods in Asia, as well, and so it has a long track record of safety in humans. In Asia it is also used as a traditional treatment for lung health and coughs, cold and flu. Perilla seed oil is high in omega-3 fatty acids, especially alpha-linolenic acid, and these have been well tested as anti-inflammatory compounds that are useful for a variety of inflammatory conditions. The omega-3 fatty acids are known to reduce a the production of many allergic mediators when supplemented to the diet. In addition to the essential fatty acids in Perilla, there are also several pharmacologically active phenolic compounds, such as rosmarinic acid, apigenin, luteolin, chrysoleriol, quercetin, and catechin (Ueda et al., 2002; Takeda et al., 2002; Nakazawa et al., 2003; Makino et al., 2003).

Comments

Few human studies yet exist on the therapeutic value of Perilla seed oil, but there are many on some of its chemical constituents, such as the omega-3 fatty acids, and rosmarinic acid. Due to its long use in foods, its interesting mixture of phenolic compounds, promising animal studies, and low cost, it may be an excellent alternative to fish oil supplementation.

Scientific Support

Asthma and Allergies

Perilla seed oil, as a source of alpha-linolenic acid, was tested in asthma patients for the clinical features that accompanied leukotriene inhibition, including its effect on ventilatory parameters and lipid metabolism. The participants were divided into two groups. Group A were those who showed significantly suppressed leucocyte generation of leukotriene C4 (LTC4) by 4 weeks of Perilla seed supplementation. Group B were those who did not show leukotriene inhibition, but rather a significant increase in production after the same treatment. Analysis of the ventilatory clinical features and lipid metabolism between the groups prior to supplementation showed significant differences between groups, and these groups responded differently to Perilla seed oil supplementation. It was concluded that supplementation of Perilla seed oil is able to suppress generation of LTC4 in certain asthma patients, and that its ability to do so is related to clinical features such as respiratory function and lipid metabolism (Okamoto et al., 2000b).

Okamoto et al. (2000a) studied the effects of Perilla seed oil on bronchial asthma compared to the effects of corn oil on pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. Perilla seed oil is rich in the omega-3 fatty acids, whereas corn oil is rich in omega-6 fatty acids. The groups were divided into 7 subjects each, and supplementation of the respective oil proceeded for 4 weeks. Significant differences in pulmonary function and leukotriene production were found between groups, and it was concluded that Perilla seed oil is beneficial for the treatment of asthma due to the suppression of LTB4 and LTC4 generation by leucocytes, and improvement in pulmonary function.

In a small study involving 5 asthma patients, supplementation with Perilla seed oil was reported to be helpful for asthma. After two weeks of supplementation, asthma symptoms, and morning and evening mean and peak flow rates (PFR) were improved significantly. Additionally, the generation of leukotrienes B-4 and C-4 by leukocytes were significantly reduced with supplementation (Kozo et al., 1997).

Cardiovascular Health

The effect of the long-term intake of an omega-3 fatty acid source, Perilla oil (PO), was compared to that of an omega-6 source, soybean oil (SO), on the risk factors of coronary heart disease and serum levels of fatty acids. Twenty elderly Japanese subjects were given SO for at least 6 months as a baseline period, then put on a PO diet for 10 months as the intervention period, and later returned to the SO diet as the washout period. The change in omega-6 to omega 3 ratio between the treatments, was 4:1 for the SO and 1:1 for the PO. At 3 months into the treatment period with PO, the alpha-linolenic acid in the serum increased from 0.8 to 1.6%, and the EPA and DHA increased from 2.5 to 3.6% and 5.3 to 6.4% respectively after 10 months of treatment, and returned to baseline in the washout period. The concentration of the oxidized LDL did not change significantly. It was concluded that in elderly subjects the levels of ALA, EPA and DHA could be increased significantly through dietary change without any adverse effects (Esaki et al., 1999).

Bioavailability

In a study on the bioavailability of enteric-coated (Entrox) perilla seed oil, 12 healthy volunteers were given (enteric) coated or non-coated capsules containing 6 g of a Perilla seed formulation. The Perilla seed formulation was alpha-linolenic acid (ALA)-rich and was given in a single dose followed by a 3 week washout period. There were no difference in the pharmacokinetics of the two formulations, however, the levels of plasma ALA measured within 24 hours were significantly higher for the enteric-coated treatment group (Kurowska et al., 2003).

Safety / Dosage

Although Perilla has few clinical studies in humans, and most of the feeding studies have been done in animals, there has been a long track record of use in humans as a food in Asia, and this has never been associated with safety problems. About 6 grams daily of Perilla seed oil would contribute about 3 grams of alpha-linolenic acid to the diet.

Contact dermatitis develops in about 20-50% of the long-term workers with Perilla culture, and this is thought to be due to the 1-perillaldehyde and perillalcohol content of the shiso oil (Okazaki et al., 1981).

References

1.Ezaki O, Takahashi M, Shigematsu T, Shimamura K, Kimura J, Ezaki H, Gotoh T. Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects. J Nutr Sci Vitaminol (Tokyo). 1999 Dec;45(6):759-72.

2.Kozo A., Fumihiro M, Takashi M, Yasuhiro H, Satoshi Y, Hirofumi T, Yoshiro T, Takao T. A pilot study: Effects of dietary supplementation with alpha-linolenic acid-enriched perilla seed oil on bronchial asthma. Allergology International. 1997 46(3):181-185.

3.Kurowska EM, Dresser GK, Deutsch L, Vachon D, Khalil W. Bioavailability of omega-3 essential fatty acids from Perilla seed oil. Prostaglandins Leukotrienes & Essential Fatty Acids. 2003 March;68(3):207-212.

4.Makino T, Furuta Y, Wakushima H, Fujii H, Saito K, Kano Y.Anti-allergic effect of Perilla frutescens and its active constituents.Phytother Res. 2003 Mar;17(3):240-3.

5.Nakazawa T, Yasuda T, Ueda J, Ohsawa K. Antidepressant-Like Effects of Apigenin and 2,4,5-Trimethoxycinnamic Acid from Perilla frutescens in the Forced Swimming Test. Biol Pharm Bull. 2003 Apr;26(4):474-80.

6.Okamoto M, Mitsunobu F, Ashida K, Mifune T, Hosaki Y, Tsugeno H, Harada S, Tanizaki Y, Kataoka M, Niiya K, Harada M. Effects of perilla seed oil supplementation on leukotriene generation by leucocytes in patients with asthma associated with lipometabolism. Int Arch Allergy Immunol. 2000a Jun;122(2):137-42.

7.Okamoto M, Mitsunobu F, Ashida K, Mifune T, Hosaki Y, Tsugeno H, Harada S, Tanizaki Y.Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma. Intern Med. 2000b Feb;39(2):107-11.

8.Okazaki N, Matunaka M, Kondo M, Okamoto K. Contact Dermatitis Due to Beefsteak Plant Perilla-frutescens-var-acuta. Hifu. 1982 24(2):250-256.

9.Takeda H, Tsuji M, Miyamoto J, Matsumiya T. Rosmarinic acid and caffeic acid reduce the defensive freezing behavior of mice exposed to conditioned fear stress. Psychopharmacology (Berl). 2002 Nov;164(2):233-5.

10.Ueda H, Yamazaki C, Yamazaki M.Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biol Pharm Bull. 2002 Sep;25(9):1197-202.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.