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The Use of Convallaria and Crataegus in the Treatment of Cardiac Dysfunction

Abstract

Herbal medicines have been effectively used for the treatment of cardiovascular diseases for many years. Herbs such as Convallaria (Lily of the Valley) root and Crataegus (Hawthorne) have shown significant benefits as adjunctive or stand alone therapies for the treatment of cardiac disorders such as arrhythmia, mitral valve prolapse and shortness of breath. Convallaria has been used for the treatment of congestive heart failure and cardiomyopathy, whereas Crataegus contains flavonoids with anti-inflammatory, anti-oxidant and protective cardiac effects. Crataegus functions as a natural angiotensin converting enzyme inhibitor, and it is therefore beneficial for the treatment of hypertension. Convallaria and Crataegus have been used in combination with other herbal remedies such as Selenocereus (Night Blooming Cereus), Leonorus (Motherwort), Melissa (Lemon Balm),Lepidium (Maca), and Ginkgo (Ginkgo). Convallaria may interact with digoxin and should not be used during pregnancy, whereas Crataegus is a safe herb when used as indicated. Although accidental poisoning resulting from the ingestion of Convallaria has been reported, toxicity from this medicinal herb is rare because of its poor absorption and short half life. Studies have shown that at the appropriate doses, Convallaria and Crataegus are safe and effective alternative treatments for the management of cardiac dysfunction.

AARM REFERENCE REVIEWS:

These are AARM reference reviews in which clinicians can obtain a quick overview of understanding with respect to how herbs, nutrients, and hormones can be used effectively in clinical practice. The dosages recommended are based on therapeutic results. Side effects that have not been seen in clinical experience or found in clinical studies but only been theorized have been identified and depicted as Unsubstantiated Theoretical Concerns.

Since many nutrients and herbs on the market have not gone through double-blind studies but have been used extensively in clinical settings for hundreds, and for some thousands of years, these reference reviews have attempted to give a unified opinion on how to use these herbs effectively. The opinions expressed are from different professors and experts in the field of nutritional and botanical medicine. Some information is based on personal opinions and can not be quantified as fact. However, if clinicians only restricted themselves to what is fully proven by double-blind studies, the art of healing and restoring health with nutrients and herbs would be lost.

CLINICAL IMPLICATIONS

There are effective herbal remedies to treat cardiac dysfunctions (e.g., arrythmias) that may complement or replace standard pharmaceutical options. In the 20th century, researchers have demonstrated that some herbal remedies not only improve cardiac health, but may even decrease the symptoms of cardiac dysfunction such that medications may be unnecessary (or the dosages reduced). Herbs used by Complementary Alternative Medicine (CAM) practitioners (such as Convallaria and Crataegus) are generally considered safe supplements. Modern clinical research suggests a significant benefit in symptom control and physiologic outcomes when Crataegus is used as an adjunctive treatment in patients with chronic heart failure.

KEY HERBS DISCUSSED:

Convallaria (Lily of the Valley) root; Crataegus (Hawthorne) leaf, flower, and berry

PRIMARY INDICATION:

Stachycardia, mitral valve prolapse, shortness of breath, arryhthmia

ADJUNCTIVE OR STAND-ALONE TREATMENT:

Both

DOSE OF BIOACTIVE CONSTITUENTS:

Hawthorne (Crataegus) (whole plant extracts) 80-900 mg per day; containing 1.5 mg Vitexin (Crataegus flavanoid) bid

Lily of the Valley Root (Convallaria) 100-400 mg per day, containing Convallatoxin (Convallaria alkaloid) 0.4 mg bid

SYNERGISTIC HERBAL FORMULA:

Lily of the Valley (Convallaria), Hawthorne (Crataegus) Night Blooming Cereus (Selenocereus), Motherwort (Leonorus), Lemon Balm (Melissa), Maca (Lepidium), Ginkgo (Ginkgo) and bioflavinoids are among the herbal agents that may be complementary.

SIDE EFFECTS (AND CAUTIONS):

Hawthorne (Crataegus) can be safely consumed when used appropriately.

Lily of the Valley (Convallaria) should not be taken during pregnancy.

Convallaria may interact with digoxin. Cardiac patients being treated with herbal remedies specifically for Convallaria along with cardiac medications such as Digoxin should be evaluated for interactions to ensure pharmaceutical dosages are still appropriate. Other than the medical setting in which the drug Digoxin is administered, acute intoxications from cardiac glycosides is rare. There has been a few cases of reported accidental deaths from eating digitails (the plant which Digoxin is made from). However reported adverse reactions reported from Convallaria is very rare with no reported deaths. The most common cause of adverse reaction is acute accidental poisoning of eating Convallaria. Symptoms of mild to moderate intoxication of cardiac glycoside poisoning based on the drug Digoxin is fatigue, ventricular ectopic beats, bradycardia, and ventricular tachycardia. Toxicity from Convallaria as a medicinal herb is very rare partly due to its poor absorption and fast half life.

DISCUSSION

Convallaria and Crataegus have been used for centuries by herbalists in the treatment of certain cardiac dysfunctions. Convallaria has been used for congestive heart failure and cardiomyopathy, while Crataegus has been used as an all-purpose cardiac and vascular tonic.

Positive ionotropic effects may also be accomplished with Crataegus and some other herbs. In these plants, the primary mechanism involves cyclic AMP (adenosine monophosphate). When stimulated, receptors on the outsides of muscle cell membrane enable the synthesis of adenylyl cyclase, the enzyme that catalyzes the production of intracellular cAMP. The presence of cAMP activates the calcium channels in the muscle cell membranes. In heart muscle cells, calcium influx promotes increased heart contractility. When epinephrine and norepinephrine bind to membrane receptors, a chain reaction is initiated; the increased calcium level results in increased ionotropic capacity.

CRATAEGUS AS A TREATMENT FOR CARDIAC DYSFUNCTION

Crataegus (Hawthorne Tree) species are actually several varieties of the Hawthorne tree, and it was used in early European medicine for a wide variety of cardiac and vascular conditions. As this tree (in the rose family) flowers in Europe in May, it became commonly known as the “Mayflower”.

Crataegus does not contain cardiac glycosides, but rather a group of flavonoids. These flavonoids have anti-inflammatory, anti-oxidant, and protective cardiac effects. The berries and other constituents present in the buds of the flowers have particularly positive effects. Crataegus contains large amounts of flavonoid anthocyanidins and proanthocyanidins, as well as condensed polyphenolic tannins known as procyanidolic oligomers (PCOs). The flavonoids have a stabilizing effect on capillaries, and serve to reduce vascular permeability and fragility. Crataegus extracts (and particularly their flavonoids) may support cardiac mitochondrial respiration.

Crataegus flower buds contain quercitin, other anti-inflammatory flavonoids, and volatile amines. Hawthorne berries also contain sugar, pectin, Vitamin C, and glycosides. The leaves contain catechins and traces of sterols. Chemically, these procyanidins (such as 1-epicatechol) are small dimers of epicatechin (a tannin derivative). Other flavonoids found in Crataegus include vitexin-4-rhamnoside, rutin, and quercitin. Other constituents include ursolic, oleanic, and cinnamic organic acids, along with sterols, purines, triterpenes, and cardiotonic amines including trimethylamine, isobutylamine, and tyramine. Currently, many Crataegus supplements are standardized to 10-28% PCO content.

The procyanidins found in Crataegus also inhibit phosphodiasterase, the enzyme that degrades cAMP into inactive AMP. Since the breakdown of cAMP is prevented by Crataegus, calcium levels remain high; this leads to sustained myocardial contractility. While elevations in cAMP and intracellular calcium promote contractions of coronary muscle, the same conditions promote relaxation of blood vessel smooth muscle. Thus, blood flow through the heart is not impaired due to vasoconstriction. Crataegus enhances myocardial contractility, yet coronary arteries are dilated rather than contracted.

jrm-2012-2012012_fig1

Convallaria majallis of the Liliacea family

© Steven Foster Group, Inc.

Extracts of Crataegus leaf, flower, and berry have been shown to promote calcium influx via effects on sodium and potassium ATPase mechanisms,and to promote calcium concentrations affecting myocontractility.

CRATAEGUS AS AN ACE INHIBITOR

Crataegus constituents act as natural angiotensin converting enzyme (ACE) inhibitors. ACE is an important enzyme involved with blood pressure regulation and also sodium and electrolyte balance in tissues. Inhibiting ACE also serves to lower blood pressure and strengthen heart muscle function. Crataegus inhibits ACE, presumably due to its procyanidin oligomers. When this enzyme is inhibited, angiotensin I is not converted to angiotensin II. As a result, the production of aldosterone is reduced. Since aldosterone promotes water and sodium retention, sodium and water (in the absence of aldosterone) are more easily excreted. Additionally, angiotensin II promotes vasconstriction and inactivates bradykinin—a polypeptide with vasodilating action. When ACE is inhibited, bradykinin promotes the release of other vasodilatory prostaglandins which, in turn, improve blood flow and oxygen delivery to the heart muscle. (Fig 1)

jrm-2012-2012012_fig2

BIOLOGICAL EFFECTS OF CRATAEGUS AND ACE INHIBITORS

© AARM.

CRATAEGUS FOR BLOOD PRESSURE CONTROL

Crataegus has long been used as a heart tonic for both hyper- and hypotension. Researchers have demonstrated that Crataegus may also be helpful in treating elevated cholesterol levels, high blood pressure, angina pectoris, and atherosclerosis.Crataegus may also regulate heart rhythm in patients with heart failure. There have been clinical trials using Crataegus extracts in patients with Congestive Heart Failure (CHF) showing significant improvements in symptoms. In animal models, studies have shown Crataegus to improve aortic contractility in heart failure.

Studies on the use of Crataegus along with standard pharmaceutical treatments for heart failure have not revealed any negative drug-herb interactions, and have suggested that Crataegus may slow the progression of heart failure. One study reported that the addition of Crataegus to the overall protocol for heart failure patients reduced the incidence of sudden cardiac death.

CONVALLARIA (LILY OF THE VALLEY)

In cardiomyopathy, the heart muscle progressively weakens and becomes increasingly ineffective at pumping blood. Typical chronical management is with chemical pharmaceuticals, and the only definitive cure is by heart transplant. Many medications used to treat cardiomyopathy have stemmed fromDigitalis and its cardiac glycosides (e.g., digoxin and digitalin).

Cardiac glycosides (steroid-like molecules that act on cardiac smooth muscle) are sometimes termed “positive ionotropic agents” because they positively affect the flow of ions across cardiac muscle cell membranes. Muscle cells (including cardiac muscle cells) need to be able to contract and expand—and it is the flow of charged calcium, potassium and other ions across the cell membrane that serves to establish electrical currents, enabling depolarization and repolarization.

Convallaria majallus (Lily of the Valley) contains cardiac glycosides. For centuries, many herbalists and medical practitioners considered Convallaria majallus to be safer than Digitalis. For centuries, herbalists have considered the roots of the Convallaria plant to be a treatment for a weak heart, shortness of breath tachycardia and arrythmia. Convallaria majalis contains at least around 40 cardiac glycosides (including convallarin, convallotoxin, convalloside, convallasaponin, cholestane glycoside, strophanthidin, cannogenol, sarmentogenin, dipindogenin and hydroxysarmentogenin).

The Convallaria plant transforms convalloside (the basic metabolic glycoside) into convallatoxin and other cardiac glycosides. Convallatoxin affects vasoconstriction and vasodilation, and cardiac stroke volume, pulse pressure and cAMP activity are all enhanced by Convallaria.Convallamaroside may reduce angiogenesis and have anti-tumor effects.Convallaria has also been shown to be a lipoxygenase inhibitor.

HERBAL MEDICINE TO MAINTAIN HEART HEALTH

These herbs described hererin may be used alone or in combination to support heart function. A 2008 meta-analysis on a Crataegus clinical trial reported no adverse advents, and the only significant side effects to be mild and transient. Studies have shown Crataegus to be safe when used in tandem with conventional pharmaceutical therapies in the management of congestive heart failure and other cardiac maladies. The use of Convallaria and Crataegus are both medicinal herbs that in appropriate doses can be used safely and effectively to manage basic cardiac dyfunction.

DISCLOSURE OF INTERESTS

Dr. Saunders reports personal fees related to employment or seeing patients from CCNM, the Dundas Naturopathic Centre, and from Beaumont Health Systems, Troy Hospital, MI, outside the submitted work. Dr. Winston reports personal fees from Herbalist & Alchemist, Inc, outside the submitted work. Dr. Stansbury and Dr. Zampieron have nothing to disclose.

REFERENCES

  1. Murray, M. Nutritional Influences on Illness. Third Line Press: Tarzana, CA; 1994, p. 279.
  2. Bernatoniene J, Trumbeckaite S, Majiene D, Baniene R, Baliutyte G, Savickas A, Toleikis A. The effect of crataegus fruit extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart. Phytother Res 2009; 23:1701–7.
  3. Uchida S, Ikari N, Ohtaa H, et al. Inhibitory effects of condensed tannins on angiotensin converting enyme. Jap J Pharmacol 1987, 43:242–5.
  4. Rewerski VW, et al. Some pharmacologic properties of oligomeric procyanidin isolated from hawthorne (Crategus oxyacantha). Arzneim Forsch1967, 17:490–1.
  5. Petkov, V. Antiatheromatous and coronary dilating action. A J Chinese Med 1979, 7:197–236.
  6. Bernatoniene J, Trumbeckaite S, Majiene D, Baniene R, Baliutyte G, Savickas A, Toleikis A. The effect of crataegus fruit extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart. Phytother Res 2009, (12):1701–7.
  7. Rodriguez ME, Poindexter BJ, Bick RJ, Dasgupta A. A comparison of the effects of commercially available hawthorn preparations on calcium transients of isolated cardiomyocytes. J Med Food 2008, 11:680–6.
  8. Uchida S, Ikari N, Ohta H, et al. Inhibitory effects of condensed tannins on angiotensin converting enzyme. J Pharmacol 1987, 43:242–5.
  9. Petkov V. Plants with hypotensive, antiatheromatous and coronary dilating action. A J Chinese Med 1979, 7:197–236.
  10. Ammon H, and Handel M. Crataegus, toxicology and pharmacology. Planta Medica 1981, 43:318–22.
  11. Baklykova OB, Sizova Z, Shikh EV. Possible use of standardized Crataegus sanguinea extract in correction of cardiac rhythm impairment in patients with chronic heart failure. Antibiot Khimioter 2009, 54:47–52.
  12. Leuchtgens H. Crataegus special extract WS 1442 in NYHA II heart failure: A placebo controlled randomized double-blind study. Fortschr Med1993, 352–4.
  13. Hwang HS, Boluyt MO, Converso K, Russell MW, Bleske BE. Effects of hawthorn on the progression of heart failure in a rat model of aortic constriction.
  14. Pittler MH, Guo R, Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane Database Syst Rev 2008, 23(1).
  15. Dimov N, et al. The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: the SPICE trial. Eur J Heart Fail 2008, 10:1255–63.
  16. Kopp B, and Kubelka W. New Cardenolides from Convallaria majalis. Planta Med 1982, 45:195–202.
  17. Higano T, Kuroda M, Sakagami H, Mimaki Y. Convallasaponin A, a new 5beta-spirostanol triglycoside from the rhizomes of Convallaria majalis.Chem Pharm Bull 2007, 55:337–9.
  18. Tittel G, Habermeier H, Wagner H. Qualitative and Quantitative HPLC-Analysis of Cardiac Glycosides. Planta Med 1982, 45:207–15.
  19. Schrutka-Rechtenstamm R, Kopp B, Löffelhardt W. Studies on the Turnover of Cardenolides in Convallaria majalis. Planta Med 1985, 51:387–90.
  20. Lehmann HD. Effect of plant glycosides on resistance and capacitance vessels. Arzneimittelforschung 1984, 34:423–9.
  21. Choi DH, Kang DG, Cui X, Cho KW, Sohn EJ, Kim JS, Lee HS. The positive inotropic effect of the aqueous extract of Convallaria keiskei in beating rabbit atria. Life Sci 2006, 79:1178–85.
  22. Nartowska J, Sommer E, Pastewka K, Sommer S, Skopińska-Rózewska E. Anti-angiogenic activity of convallamaroside, the steroidal saponin isolated from the rhizomes and roots of Convallaria majalis. Acta Pol Pharm 2004, 61:279–82.
  23. Ogorodnikova AV, Latypova LR, Mukhitova FK, Mukhtarova LS, Grechkin AN. Detection of divinyl ether synthase in Lily-of-the-Valley (Convallaria majalis) roots. Phytochemistry 2008, 69:2793–8.
  24. Pittler MH, Guo R, Ernst E. Hawthorn extract for treating chronic heart failure. Cochrane Database Syst Rev 2008, 23(1):CD005312.

DOI: http://dx.doi.org/10.14200/jrm.2012.1.1012

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