Supplement Spotlight: Hawthorn

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    Supplement Spotlight: Hawthorn


    Supplement Spotlight: Hawthorn
    - Article originally appeared online December 2, 2006
    Dana Houser, MD, MHSA, CISSN

    Author’s Note: The author has made every effort to ensure the accuracy and completeness of the information presented in this article. In fact, I am willing to suggest this to be the most complete piece offered on this supplement to date. However, the author, nor Anablolic Minds can or should be held responsible for the continued currency of the information, any inadvertent errors or omissions, or the application of this information. Therefore, all of the aforementioned parties shall have NO liability to any person or entity with regard to claims, loss, or damage caused or alleged to be caused, directly or indirectly, by the use of information contained herein.

    The inclusion of any product in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grant of authority to exercise any right or privilege protected by such patent or trademark. All such rights or trademarks are vested in the patent or trademark owner, and no other person may exercise the same without expressed permission, authority, or license secured from such patent or trademark owner.

    The inclusion of a brand name does NOT mean the author nor any of the aforementioned parties has any particular knowledge that the brand listed has properties different from other brands of the same product, nor should its inclusion be interpreted as an endorsement by the author or said parties. Similarly, the fact that a particular brand does not indicate the product has been judged to be in any way unsatisfactory or unacceptable. Further, no official support or endorsement of this article by any federal or state agency or pharmaceutical company is intended or inferred.

    You will read herein about signs, symptoms, and a classification system as applied by the New York Heart Association (NYHA) in regards to congestive heart failure (CHF). This is NOT to replace the diagnostic and treatment modality supplied by an examining physician, but potentially encourages accurate discussion of complimentary and alternative medicine (CAM) treatment strategies as an adjunct to potential care received.


    Introduction

    The hawthorn tree has a storied past that includes significant acknowledgement in Christian tradition. The name Crataegus (genus of
    Hawthorn species – see later) is said to be a Greek derivation from the word for “strong” or “always having been there.” It is suggested that the crown of thorns placed on the head of Christ was of its origin. In fact, a grove of hawthorn trees still stands outside of Jerusalem on the Mount of Olives.

    Medicinal use of Hawthorn can be traced back to the 1st Century AD. Dioscorides, Pliny, and Galen all referred to hawthorn in their writings but gave little explanation of its use. The use of its leaves and flowers in particular, as a remedy for heart disorders dates back to the nineteenth century. Quercetanus, physician of Henry IV of France, used syrup made from hawthorn fruit to treat heart ailments.
    Many species of hawthorn are distributed throughout the moderate zones of the Northern Hemisphere. The fruit, leaves, and flowers of hawthorn species have been used medicinally for centuries and were in use by North American Indians before the ar***** of Europeans to treat sleep and digestive disorders, as well as a diuretic for kidney and bladder disorders (later this effect would likely contribute to both its blood pressure lowering properties as well as the heart tonic effect described well before). Hawthorrn has a long history of use in traditional Chinese medicine.

    Recently, it has gained acclaim as a potential adjunct in the battle against hypertension (high blood pressure). It contains rutin, magnesium, chromium, catechin, and several other phytochemicals, all of which work to combat high blood pressure.

    By Any Other Name

    It is all too often that I hear complaints that these scientific names continue to crop up and I agree, but Hawthorn is rather basic. It tends to go by one of its 3 predominate genus and/or species names. You may see Hawthorn referenced in supplements by any of the following:
    - Crataegus monogyna
    - Crataegus laevigata
    - Crataegus oxyacantha
    - Crataegus oxyacanthoides
    Please note that the last two on this list of four reference the same species. How these names come about sometime is very funny, these just stem from standard botanical classification schemes as discussed below.

    Family, Genus & Species

    Although Crataegus oxycantha and Crataegus monogyna, species of European shrubs, are generally named as the source of hawthorn extracts, Petrides (1086) points out that the number of hawthorn species native to North America have been variously estimated from 100 to 1000 with considerable hybridization, making identification difficult. It is likely that all species of these shrubs and low trees possess similar chemical constituents. Chang and colleagues (2002) name 6 species of Hawthorn used medicinally around the world. Hawthorn are members of the Rosaceae family.



    Plant Part Used

    Hawthorn is a European shrub with thorny branches. Much of its action on the cardiovascular system is attributed to its flavanoid concentration. Its flowers & leaves

    Active Constituents

    The best cited active constituents are the
    - Flavanoids (1.8%)
    Hyperoside (0.28%)
    Rutin (0.17%)
    - Oligomeric Procyanidins (2-3%)
    The procyanidins and flavanoids in hawthorn are thought to determine its therapeutic actions. As seen below, these substances are projected to be responsible for vasodilatory effects thought to be responsible for the efficacious benefit seen in cardiac insufficient states (i.e. – CHF, HYHA class I-II).
    Other cited active constituents include:
    - Catechins
    - Triterpenoids
    - Aromatic Carboxylic Acids
    - Cardioactive Amines
    - Amino & Purine Derivatives
    - Others
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    Mechanism of Action

    Cardiotonic effect
    cAMP-independent Positive inotropic / Negative chronotropic, dromotropic effects

    Phosphodiesterase Inhibition
    Increased coronary blood flow / Increased cardiac output / Reduced O2 consumption

    Blockade of Angiotensin Converting Enzyme (ACE)
    Vasodilatory (peripheral and coronary) effect


    Potassium Channel Activation

    Inhibition of Thromboxane Synthesis

    Antilipidemic Effect
    Positive suggested effect on total cholesterol, triglycerides, LDL, VLDL lipid fractions as well as upregulation of LDL receptors in the liver.

    Antiarrythmic Effect
    Usually protects against ischemia-induced ventricular arrhythmias

    Hypotensive Effect*
    suspect through multiple pathways, rationale for Peri-cycle/PCT use potential.

    Antioxidative Action

    Antiinflammatory Effects

    Pharmacokinetics
    Procyanidins have been found unmetabolized in renal and intestinal elimination pathways (for other similar cpds), suggesting limited metabolic degradation. The procyanidins of hawthorn are reported to have a higher degree of polymerization, yet a lower concentration of flavanoids and procyanidins...this area is still being considered though. Stay tuned...

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    USES

    Typical Therapeutic Uses

    Approved Uses: Commission E approves hawthorn leaf and flowers in the treatment of heart failure (NYHA, Stage II). This herb is as well studied as any for cardiovascular disease and is commonly used in combination with cardiac glycosides (i.e. – digoxin) to potentiate their effects and thereby lessen the dose of cardiac glycoside drugs. Clinical trials support its use for mild to moderate congestive heart failure. It has been the subject of a number of major long-term multi-center clinical trials on the survival and prognosis of congestive heart failure as well.

    Unproven Uses: More research is needed to determine hawthorn’s value in treating hypertension, atherosclerosis, hyperlipidemia, asthma, arrthythmia in the elderly, and orthostatic hypertension. Due to its high flavanoid content, it may be used to decrease capillary fragility, lessen inflammation, and prevent collagen destruction of joints. This herb has been used as a coffee substitute and to flavor cigarettes.

    Literature Review – 15 studies to date:

    (1) Congestive Heart Failure (CHF):

    - 11 randomized clinical trials to date showing statistically significant results, most recently 1 in 2003
    - 1 systematic review
    - 1 meta-analysis (2003)
    - 1 equivlence trial
    - 1 non-randomized, cohort, non-inferiority study (2003)

    (2) Coronary Artery Disease:
    - 1 randomized clinical trial to date showing statistically significant results, unfortunately most recent

    (3) Functional Cardiovascular Disorders
    - 2 randomized clinical trials to date showing statistically significant results, most recently 1 in 2000; 1 of the trials hawthorn was in combo with camphor, 1 of the trials hawthorn was in combo with garlic (so, somewhat hard to draw true conclusions)

    Post-Cycle Therapy (PCT)
    There has been a recent resurgence of Hawthorn use amongst the bodybuilding community – namely with the advent of more highly animated adjunct schedules for PCT regimes. I have explored this agent and its potential use in light of its potential to lower blood pressure and lipid (cholesterol) values as discussed in this article and PCT: A Clinician’s View article series.

    A few things worth noting here is that there are NO clinical trials or the like to support the use of such agents with concurrent administration of PH/PS/AAS and any resultant blood pressure and/or hyperlipidemic effects. However, with the current plethora of quoted anti-estrogenic agents and aromatase-inhibiting agents being marketed, yet not even 1/1000th of the same amount of money being driven toward health benefits of supplements regarded generally safe, with relatively few, if any noted side effects that are substantiated (see toxicology section of this very article) – the employment of such an agent as a “safety-net” may be in better taste than the purported UN-tested agents described above.

    Well dinoiii, with all this talk of treatment for congestive heart failure and seemingly lack of support to surround the theory of lowering blood pressure, why would you suggest employment of this agent as an adjunct for PCT? Great question!

    Rationale 1.
    In a study conducted by Schmidt of Cologne, Germany on 40 patients (avg. age 60 years old) with high blood pressure and “stable coronary insufficiency” who took hawthorn dosed at 200mg, three times per day, for eight weeks – saw statistically significant drops in blood pressure spanning that time frame. Before taking the hawthorn, they tired easily and had diminished physical ability, but after eight weeks on hawthorn, these symptoms occurred 42% fewer times. Maybe that’s not all too exciting, however, blood pressure dropped an from an average of 171/115 --> 164/110 and the patient’s ability to tolerate the heart stress of physical work increased.
    Rationale 2. In a related study by German physicians (again, Eastern bloc trumps the West!) Bodigheimer and Chase studied 36 patients (average age of 61) who had angina, a history of heart attacks and arrhythmia, and who were 20% overweight, taking 300mg daily of hawthorn extract for 28 days. Cardiovascular health improved and significant blood pressure declinations (average 10 points systolic, 5 points diastolic) were seen after about a two week treatment span.

    This being said, due to the indication of some of the antihypertensive effects to take a few weeks to kick in and adequate dosing may entail addition of such an agent two to three weeks prior to cycle. There is good clinical suggestion that starting it at a point when blood pressure is already above baseline may be unwarranted.

    Typical Forms & Dosage

    - Suggested Daily Dose: 3.5-19.8mg flavanoids, calculated as hyperoside (DAB 10), or 160-900mg extract (3:1 - 7:1 with ethanol 45% v/v or methanol 70% v/v), corresponding to 30-168.7mg oligomeric procyanidins, calculated as epicatechol. Hawthorn leaf/flower can be used for unlimited time periods.
    - How this translates if not concentrated (See short topic series IV for more on concentration): 0.75mg – 6 grams per day of dried flower, leaf, or by infusion; 3 – 6 mL per day of a 1:2 liquid extract of hawthorn leaf or equivalent in tablet/capsule form; 3.5 – 17.5 mL per day of a 1:5 tincture of hawthorn leaf.
    - Doses for leaf and flower extracts tested in clinical trials ranged from 160-1800mg/day, while the berry extracts were tested from 300-1000mg three times per day.
    - Products containing standardized extract WS 1442: (18.75% OPCs): statistically significant trials have used doses of 60mg three times per day or 80mg twice daily. The U.S. brand HeartCare (Nature's Way) is standardized in this fahsion.

    - Products containing standardized extract LI 132: (2.2% flavanoids): statistically significant trials have used doses of 100mg three time daily, 200mg twice daily, and up to 300mg three times per day.
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    Toxicology

    Contraindications
    It is generally considered safe; however relative contraindications exist with cases of hypersensitivity or a history of an allergic reaction to crataegus or any of its components. An absolute contraindication has been suggested in children under the age of 12.

    Side Effects

    (1) Rats
    Studies involving excessive dosing of hawthorn flower extract (600mg/kg/day; undefined strength; 4.4% flavanoids) over 30 days showed UNREMARKABLE adverse events.

    (2) Humans
    The acute oral toxicity in undefined animals of hawthorn was 6 g/kg. No target-organ toxicity was defined at 100 times the human dose (2.7 mg/kg) of concentrated hawthorn extract. Standard mutagenic and clastogenic tests were also negative.
    Hawthorn was well tolerated in studies lasting up to 16 weeks. Some side effects, while rare, may have been related to hawthorn extracts cited in the literature are:
    - mild rash
    - headache
    - sweating
    - dizziness
    - sleepiness
    - agitation
    - gastrointestinal complaints

    Drug Interactions
    Drug interaction profiles are not well studied; therefore most drug interactions are theoretical based on the pharmacologic properties. Most hawthorn products do warn against the concurrent use with the pharmaceutical agent digoxin due to the perceived potentiation of digoxin’s effects. This interaction was later refuted in only one study cited in the literature to date showing no significant alteration of digoxin’s pharmacokinetic parameters. However, the two treatments should NOT be employed at the same time unless perhaps monitored closely by a physician.

    While digoxin is the only cited interaction that tends to be challenged in the literature, recall that there are also vasodilatory properties that are seen with Hawthorn secondary to the mechanisms suggested earlier in this article. That being said, it has been suggested to also find potential efficacy in the treatment of angina, hypertension, and atherosclerosis. Accordingly, someone taking concurrent agents with vasodilatory properties (arginine-based dietary supplements, anti-hypertensive agents, or anti-anginal agents – for example, beta-blockers) should also be closely monitored if employing the use of both because the potential to see a synergistic effect is there.

    Additonal Notes
    Hawthorn may increase the sedative effects of central nervous system depressants such as alcohol, barbiturates, and psychotropics; avoid concurrent use – especially while driving or operating heavy machinery. Hawthorn tea may decrease the absorption of iron salts; separate by at least 2 hours. There is also some anecdotal evidence to suggest that supplemental potassium may be otherwise best avoided while using this supplement.

    Known Herbal Interactions
    Hawthorn increases the action of Adonis vernalis (Adonis), Convalaria majalis (Lily of the Valley), and Scillae bulbus (Squill) when taken concurrently.
    ------------------------------------------------------------------------------------------------------------
    * FEMALE-SPECIFIC CONCERNS *

    Pregnancy Category: B1 (what’s this mean? No increase in frequency of malformation or other harmful effects on the fetus from limited use in women. No evidence of increased fetal damage in animal studies).

    Lactation Category: C (what’s this mean? Compatible with breastfeeding)
    ------------------------------------------------------------------------------------------------------------

    Dinoiii’s Safety Grade Report
    Reviewing all of the toxicology data above, this product gets an overall safety score of

    (1) Healthy Populace:
    A+ (when used as cardioprotective preventative medicine strategy)

    (2) PCT adjunct:
    A (as monotherapeutic agent against high Blood Pressure);
    B+ (when used concurrently with arginine-based (NO) compounds or alternative blood pressure treatment modality [please see PCT: ACV series of articles for complete listing of dietary supplement agents that possess anti-hypertensive properties]
    (3) Individual Undergoing Concurrent Treatment for Cardiovascular Comorbidity:
    A (when used under the supervision of a physician managing comorbidity)
    C+ (when used as self-applied treatment modality)
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    Regulatory Status


    ------------------------------------------------------------------------------------------------------------

    Congestive Heart Failure
    Congestive heart failure is more a clinical syndrome versus a particular disease state in isolation resulting from the heart’s inability to meet the body’s circulatory demands under normal physiological conditions.

    The NYHA has classified CHF based on its symptomatic production as described in the table below:


    ------------------------------------------------------------------------------------------------------------

    Conclusion
    Clinical studies demonstrating the efficacy of hawthorn leaf/flower in NYHA class I-II heart failure are available, however, likely most significant for class II. The potential downside of trials using hawthorn for the treatment of CHF, NYHA Class II were that were not all well controlled. Nonetheless, it is the strongest correlative efficacy data to date despite some positive support shown in relation to hypertension, angina, minor arrythmias, as well as dyslipidemias.

    This agent’s recent employment in the very illustrious PCT regimes remains untested in the placebo-controlled setting; however, current suggestion would imply its use better estimated to begin PRIOR to beginning a PH/PS/AAS cycle.
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    References

    Ammon HP, Handel M. Crataegus, toxicology and pharmacology. Part II: Pharmacodynamics (author’s translation). Planta Med. 1981; 43 (3): 209-239.

    Bahorun T, Gressier B, Trotin F, et al. Oxygen species scavenging activity of phenolic activities, fresh plant organs and pharmaceutical preparations. Arzneim Forsch 1996; 46: 1086-1089.

    Bahorun T, Trotin F, Pommery J, Vasseur J, Pinkas M. Antioxidant activities of Crataegus monogyna extracts. Planta Med. 1994; 60 (4): 323-328.

    British Herbal Medicine Association’s Scientific Committee: British Herbal pharmacopoeia, Bournemouth, 1983; BHMA, 74-75; 198.

    Chang Q, Zuo Z, Harrison F, Chow MS. Hawthorn. J Clin Pharmacol. 2002; 42: 605.

    Degenering FH, Suter A, Weber M, et al. A randomized double blind placebo controlled clinical trial of a standardized extract of fresh Crataegus berries (Crataegisan ®) in the treatment of patients with congestive heart failure NYHA II. Phytomedicine. 2003; 10:363-369.

    Fong HHS, Bauman JL. Hawthorn. J Cardiovasc Nurs. 2002; 16(4):1-8.

    Holubarsch CJ, Colucci WS, Meinertz T, et al. Survival and prognosis: investigation of crataegus extract WS 1442 in congestive heart failure (SPICE): rationale, study design, and study protocol. Eur J Heart Fail. 2000; 2: 431-437.

    Houser, D. PCT: A Clinician’s View – Part II, Post Cycle Supplements: In Theory. Available at ..................... 2005.

    Houser, D. PCT: A Clinician’s View – Part III, Post Cycle Supplements: In Practice. Available at ..................... 2005.

    Houser, D. PCT: A Clinician’s View – Part III and 1/2, Special Edition: On Site in St Louis. Available at ..................... 2006.

    Leuchtgens H. Crataegus Species Extract WS 1442 in NYHA II heart failure. A placebo-controlled randomized double-blind study. Fortschr Med. 1993; 111 (20-21): 352-354.

    Mashour NH, Lin GI, Frishman WH. Herbal medicine for the treatment of cardiovascular medicine. Arch Intern Med. 1998; 158: 2225.

    Miller LG. Herbal medicinals: Selected clinical considerations focusing on known or potential herb-drug interactions. Arch Intern Med. 1998; 158: 2200.

    Monographs: DAB 1998; ESCOP; Commission E

    Morelli V, Zoorob RJ. Alternative therapies: Part II. Congestive heart failure and hypercholesterolemia. Am Fam Physician. 2000; 62: 1325.

    Perkov E, et al. Inhibitory effect of some flavanoids and flavanoid mixtures on cyclic AMP phosphodiesterase activity of rat heart. Planta Med. 1981; 43:183-186.

    Petrides GA. Trees and Shrubs: Roger Tory Peterson Field Guides. Norwalk, Conn: Easton Press; 1986: 197.

    Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure:meta-analysis of randomized trials. Am J Med. 2003; 114: 665-674.

    Popping S, Rose H, Ionescu I, Fischer Y, Kammermeier H. Effect of a hawthorn extract on contraction and energy turnover of isolated rat cardiomyocytes. Arzneimittelforschung. 1995; 45 (11): 1157-1161.

    Rigelsky JM, Sweet BV. Hawthorn: pharmacology and therapeutic uses. Am J Health Syst Pharm. 2002; 59: 417.

    Scmidt U, et al. Effects of herbal crataegus-camphor combination on the symptoms of cardiovascular diseases. Arzneimittelforschung. 2000; 50 (7): 613-619.

    Scmidt U, et al. Efficacy of the hawthorn (Crataegus) preparation LI 132 in 78 patients with chronic congestive heart failure defined as NYHA functional class II. Phytomedicine. 1994; I: 17-24.

    Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. New York, NY: Springer-Verlag; 1998.

    Schussler M, Holzl J, Fricke U. Myocardial effects of flavonoids from from Crataegus species. Arzneimittelforschung. 1995; 45 (8): 842-845.

    Schussler M, Holzl J, Rump AF, Fricke U. Functional and antiischaemic effects of Monoacetylvitexinrhamnoside in different in vitro models. Gen Pharmacol. 1995; 26 (7): 1565-1570.

    Shanthi S, Parasakythy K, Deepalakshmi PD, Devaraj SN. Hypolipidemic activity of tincture of Crataegus in rats. Indian J Biochem Biophys. 1994; 31 (2): 143-146.

    Schlegelmilch R, Heywood R. J Am. Coll Toxicol. 1994; 13:103-111.

    Tankanow R, Tamer HR, Streetman DS, et al. Interaction study between digoxin and a preparation of hawthorn (Crataegus oxycantha). J Clin Pharmacol. 2003; 43: 637-642.

    Tauchert M. Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Am Heart J. 2002; 143: 910-915.

    Uchida S, et al. The effect of condensed tannins on angiotensin converting enzyme. Jpn J Pharmacol. 1987; 43: 242-245.

    Weikl A, Assmus KD, Neukum-Schmidt A, Schmitz J, Zapfe G, Noh HS, et al. Crataegus Special Extract WS 1442. Assessment of objective effectiveness in patients with heart failure (NYHA II). Fortschr Med. 1996; 114 (24): 291-296.

    Yao M, Brown- Woodman PDC, Ritchie H. Teratology. 2001; 64: 320-325
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    That's an exhaustive list of hawthorn! But good read, I'll have to read more later when I have more time after class. Thanks for taking the time to put this together. What do you think about its efficacy for heart health in combination with ubiquinol? If I remember right, I read that they are synergistic together.
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    Quote Originally Posted by kingjameskjf View Post
    That's an exhaustive list of hawthorn! But good read, I'll have to read more later when I have more time after class. Thanks for taking the time to put this together. What do you think about its efficacy for heart health in combination with ubiquinol? If I remember right, I read that they are synergistic together.
    It actually shares some of the benefits of CoQ10 (ubiquinone or ubiquinol) in that it can increase heart muscle function by relaxes blood vessels and improves central blood flow to the heart.

    These are both supplements that I do not see unfavorable data on personally, but if anyone has anything to add - by all means...


    D_
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    Quote Originally Posted by dinoiii View Post
    It actually shares some of the benefits of CoQ10 (ubiquinone or ubiquinol) in that it can increase heart muscle function by relaxes blood vessels and improves central blood flow to the heart.

    These are both supplements that I do not see unfavorable data on personally, but if anyone has anything to add - by all means...


    D_

    Thanks for the quick reply. Sounds like both together will not only be cardio-protective but also reduce HBP.
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