RUNNING HEAD: HAWTHORN POTENTIAL ADJUNCT FOR ADHD TREATMENT

Hawthorn

Anti-inflammatory Implications for ADHD Treatment

Kimmer Collison-Ris, MSN, FNP-C, WOCN

9/22/2013

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Abstract

Hawthorn (Crataegus laevigata) is a commonly used herb in the management of

cardiovascular disease due to its anti-inflammatory affects. Attention Deficit Hyperactivity

Disorder (ADHD) is manifested by behavioral and cognitive disruption as well as impulsivity;

believed to be a caused by central nervous system inflammation. Hawthorn’s benefits may

translate as a potentially useful anti-inflammatory in the treatment of ADHD. Its chemical

constituents and its clinical uses as an anti-inflammatory will be delineated. This paper will

discuss Hawthorn’s history and traditional use, herbal constituents, anti-inflammatory properties,

current research, and treatment implications. The question, “is there enough evidence to suggest

that Hawthorn may be a possible anti-inflammatory botanical in reducing symptoms of ADHD

and its various subtypes in adolescents and adults?”

Retrieved from asgap.org.au

Introduction

Hawthorn has been considered a valuable anti-inflammatory often used in treating

cardiovascular conditions. Recent studies demonstrate hawthorn fruit exhibits anti-oxidant, anti-

atherosclerotic, hypolipidemic activities, and anti-inflammatory properties (Li and Wang, 2011).

P. Balch (2002) reports that Ayurvedic medicine and Herbalists have been using Hawthorn for

some time to treat ADHD; however, the literature is sparse confirming this directly. One cause

of ADHD is inflammatory conditions of the brain and central nervous system that results in

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inattention, impulsivity, and hyperactivity (Doney and Thome, 2010). Patients placed on an anti-

inflammatory diet or given anti-inflammatory botanicals or food supplements often exhibit a

reduction in hyperactive behaviors and impulsiveness with increased focus (Burton, 2011).

Hawthorn may be an adjunctive anti-inflammatory in decreasing symptoms of inflammation in

adolescents and adults with ADHD. This paper discusses the properties and affects of Hawthorn

and its potential role in treating ADHD related inflammation; suggesting that Hawthorn may

reduce symptoms of ADHD.

Attention Deficit Hyperactivity Disorder (ADHD)

ADHD is a neurological condition characterized by the inability to concentrate in a sustained

manner, pay attention to tasks, and to control impulsive actions (Sorgi, Hallowell, Hutchins, and

Sears 2007) and hyperkinetic behavior. The exact etiology is unknown but major multifactorial

contributors include adverse food additive responses, chronic inflammation, food intolerances,

exposure to environmental chemicals, molds, and fungi, and exposures to neurodevelopmental

toxins (ie. heavy metals and organohalide pollutants). Adolescents and adults with ADHD

struggle with development in emotional, educational, and social deficits; the consequences of

poor therapy negatively affects their future possibilities; many adolescents and adults fail to

respond to conventional stimulant therapy alone, but nutritional (and botanical) intervention has

complimented conventional therapy; playing a significant role in the etiology of ADHD

syndrome (Starobrat-Hermelin and Kozielec 1997).

Inflammation

Inflammation is a complex biological response to pathogens and damaged cells in the human

body (Li and Wang, 2011). Chronic and uncontrolled inflammation is common in

cardiovascular disease, autoimmune rheumatoid arthritis, systemic lupus erythmatosus, cancer,

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Alzheimer's and Parkinson's diseases (Li and Wang, 2011). Inflammation is designed to be a

short-term, acute response to illness or injury, where the immune system identifies the offending

agent and targets those foreign invaders. Mounting a powerful response, pro-inflammatory

compounds are released to assault and aid in healing. Once the threat is eliminated, the immune

system then activates anti-inflammatory compounds to calm the inflammation, rebalancing the

body. Chronic inflammation results when the immune system is unable to completely shut down

the immune response; leaving potent inflammatory compounds still circulating, further damaging

healthy tissues (http://come2balance.com/uploads/AccessClinInflNutr.pdf)

ADHD and Inflammation

Inflammatory responses in the brain have been long recognized as critical in

neurodegeneration and behavior in many neurological and psychiatric disorders, their role in the

development, treatment and prevention of ADHD has been largely overlooked. Initially, ADHD

symptoms were observed in patients who survived an ONJ infection, ie. inflammation (Donev

and Thome 2010); brain cell inflammation results in increased neurological disorders, including

ADHD. The primary drugs used to treat ADHD are amphetamine derivatives that have the

ability to stimulate dopamine receptors in the brain. It has been found that children with ADHD

have lower levels of long-chain omega-3 fatty acids in the blood compared to control children

(Sears, 2011). New evidence, reveals that ADHD is associated with: oxidative stress; decreased

methylation capacity; limited production of glutathione; mitochondrial dysfunction; intestinal

dysbiosis; increased toxic metal burden; immune dysregulation, characterized by a unique

inflammatory bowel disease and immune activation of neuroglial cells; and ongoing brain

hypoperfusion (Bradstreet, Smith, Baral, and Rossignol, 2010).

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Research Methods & Analysis

A systematic electronic literature review was conducted using a multiple search strategy from

PubMed, Medline, Cochrane database, E-journals, and ClinicalTrials.gov. Non electronic

published medicinal herb literature and books were also utilized. Keywords and phrases were

used in the research retrieval process; the terms used in the searches included: Hawthorn,

Attention Deficit, Hawthorn and inflammation, ADHD and inflammation, ADHD and alternative

medicine, and Hawthorn benefits, Hawthorn and inflammation, and Hawthorn and anti-

inflammatory to assist in producing this document.

Retrieved from wildplanthealing.com

Latin Name:

Hawthorn [Crataegus monogyna Jacq. and Crataegus oxyacantha L.; sin. Crataegus laevigata

(Poiret) DC., Rosaceae]

Common Names

Crataegus laevigata; Crataegus monogyna; Crataegus oxyacantha; Hedgethorn.

Plant Description

Hawthorn is a common thorny shrub in the rose family that grows up to 5 feet tall on hillsides

and in sunny wooded areas throughout the world. Its flowers bloom in May. They grow in small

white, red, or pink clusters. Small berries, called haws, sprout after the flowers. They are usually

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red when ripe, but they may also be black. Hawthorn leaves are shiny and grow in a variety of

shapes and sizes.

Collection

The flowering tops are harvested in late spring and early summer, the berries in September

and October (http://www.purplesage.org.uk/profiles/hawthorn.htm)

Growth/harvesting/storage

The best locations for the deciduous hawthorn shrub are where they can receive direct

exposure to sunlight throughout the day and grows best when it is irrigated during dry weather

but it tolerates most types of soil and dry growing conditions. It can grow in areas with soils

heavy in clay, loam or sand with an acidic or alkaline pH. The root system of this tree can

tolerate compacted soils that are dry, but it does not do well in low areas with poorly drained soil

and other areas that flood regularly (Thompson, 2013).

Cautions/Precautions

Hawthorn is not recommended for children and is contraindicated during pregnancy and

lactation. Side effects of Hawthorn are rare, but have included headache, nausea, and

palpitations (a feeling of a racing heart). A recent review of 29 clinical studies with more than

5,500 patients found that hawthorn was safe when used in recommended dosages. Doses found

to be safe were from 160 - 1,800 mg daily and from 3 - 24 weeks in length.

Pharmacological Use and History

The medicinal properties of hawthorn (Crataegus spp., a genus comprising approximately 300

species) have been utilized by many cultures for a variety of therapeutic purposes for many

centuries (Tassell MC, Kingston R, Gilroy D, Lehane M, and Furey A, 2010). According to

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European Pharmacopoeia 6.0, hawthorn berries consist of the dried false fruits of these two

species or their mixture (Tadić, Dobrić , Marković , Dordević , Arsić , Menković , Stević, 2008).

Practicing herbalists noted preference for berry over flower, flowers and berries being utilized

more interchangeably, and in some cases blended. Historical texts in Western medicine record

the use of berries, seeds, leaves, and flowers. Leaves, flowers, and berries are used in traditional

medicine in the treatment of chronic heart failure, high blood pressure, arrhythmia, and various

digestive ailments, as well as geriatric and antiarteriosclerosis remedies (Tadić et al 2008).

Constituents

Berries, leaves, and flowers of hawthorn are phytochemically similar in composition,

differing primarily in the ratio of specific flavonoids and procyanidins present. The berries are

rich in hyperoside. The flowers contain significant levels of vitexin-2-rhamnosid, higher levels of

flavonoids, and cardiotonic amines. The leaves had the highest levels of oligomeric procyanidins

(OPCs),high levels of procyanidins, and higher levels of vitexin-2-rhamnoside (Tassell, et al,

2010). The fruit contained saponins, glycosides, flavonoids, cardioactive glycosides, ascorbic

acid, and condensed tannins (Haughton, 2013).

Therapeutic Application

Hawthorn is used to strengthen the cardiovascular system and as an anti-inflammatory. It has

demonstrated cardioprotective effects in controlling high blood pressure and high cholesterol.

Both animal and human studies demonstrate hawthorn increases coronary artery blood flow,

improves circulation, and lowers blood pressure. It has also been used on the skin to treat boils

and skin sores. Ayurvedic medicine recommends hawthorn for heart and circulatory complaints

(Haughton, 2013) and ADHD (Balch, 2002). Its beneficial effects have been attributed to the

presence of Oligomeric proanthocyanidins (Elango and Devaraj, 2010).

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The antioxidant activity of Crataegus preparations contributes significantly to its therapeutic

profile. Gou et al. noted that of 28 fruit pulps tested, the hawthorn pulp (Chinese hawthorn)

produced the highest measure of antioxidant activity. A similarly high antioxidant activity in

Crataegus aronia, a hawthorn indigenous to Israel, Jordan, and the Palestine, has been found.

The IC50 values of specific active constituents have been established in relation to the

antioxidant capacity, with values of epicatechin and hyperoside being significantly lower (more

effective) than those of established antioxidant drugs (i.e., glutathione and N-acetylcysteine).

Oligomeric proanthocyanidins appear to possess a higher antioxidant activity used in isolation

than polymeric proanthocyanidins (PPCs) used in isolation. However, the removal of PPCs from

a mixture may result in a less actively protective medicine, possibly partially due to their high

concentration influencing outcome (Tassell et al, 2010).

Mechanism of Action

Hawthorn extract helped alleviate pro-inflammatory immune responses associated with I/R-

induced injury, boosted IL-10 levels, and increased Foxp3-positive Tregs in the brain, which may

have aided in suppression of activated inflammatory cells. Such treatment also minimizes

apoptotic cell death by influencing STAT-3 phosphorylation and Bcl-xL expression in the brain.

Taken together, the immunomodulatory effect of Hawthorn extract may play a critical role in the

neuroprotection observed in this MCAO-induced stroke model. The immunomodulatory role of

Hawthorn extract (OPC rich) has not been explored (Elango and Devaraj, 2010).

Toxicology & Side Effects

Hawthorn fruit, used in traditional medicine, is considered to be safe in existing

pharmacological and toxicological studies (Li and Wang, 2011). Side effects may include

dizziness, vertigo, headaches, migraines, and palpitations. Crataegus preparations have been

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consistently proven to be well tolerated by patients with low/negligible levels of side effects.

Daniele et al. looked at data from 24 clinical trials and a total of 5577 patients. They concluded

that hawthorn preparations are generally well tolerated and noted that adverse effects were

significantly lower in treatment groups using WS1442. There appears to be no substantial body

of evidence to suggest that Crataegus causes anything other than infrequent, mild adverse

effects. There are also no known contraindications to its use during pregnancy, although expert

advice should be sought in this circumstance. Crataegus demonstrates low toxicity, with an

LD50 of 25 mg/kg and a high therapeutic index. The clinical trial conducted by Tauchert et al.

utilized a high dose of WS1442 (1800 mg) with no reported side effects. Animal studies on

Crataegus toxicity, using doses of WS1442 up to 100 times normal dose, showed no evidence of

toxicity. Studies on human models of this nature have not been undertaken. The potential risk

appears to be low in Crataegus treatments due to its wide therapeutic index, coupled with the

minimal incidence of serious side effects (Tassell et al, 2010). Combined with Ginkgo, Crataegus

can enhance poor memory by improving the cerebral circulation and thereby increasing the

amount of oxygen to the brain (Haughton, 2013).

Drug/herb interactions

Hawthorn may enhance the effects of Cardiac medications like medications used to dilate

blood vessels, lower blood pressure, treat angina and erectile dysfunction . One study found a

nasal decongestant that constricts blood vessels, Phenylephrine, when combined with alcoholic

hawthorn fruit extract exhibited reduced effects. The daily dose and duration of treatment with

Hawthorn monopreparations ranged from 160 to 1,800 mg and from 3 to 24 weeks, respectively.

The extracts most used in the clinical trials were WS 1,442 (extract of hawthorn standardised to

18.75% oligomeric procyanidins) and LI 132 (extract of hawthorn standardised to 2.25%

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flavonoids). Overall, 166 adverse events were reported and most were, mild to moderate; eight

severe adverse events were reported with the LI 132 extract. The most frequent adverse events

included dizziness/vertigo, gastrointestinal complaints, headache, migraine, and palpitation; drug

interactions were not reported. The data indicated Hawthorn was well tolerated, but due to

reported severe adverse events; further studies are needed to determine the safety of hawthorn-

containing preparations as unsupervised use can be associated with problems in concomitant

medications (Daniele, Mazzanti, Pittler, and Ernst, 2006)

Available Forms

Hawthorn is available in nonstandardized and standardized capsules and liquid extracts, along

with tinctures and solid extracts. A bitter tasting tea can also be made from dried hawthorn

leaves, flowers, and berries (University of Maryland Medical Center, 2011).

Conclusions & Recommendations

Hawthorn fruit species is a good source of natural antioxidants and consumption of hawthorn

fruit or its products may decrease ADHD symptoms related to inflammation (Çalişkan, Gündüz,

Serçe, Toplu, Kamiloğlu, Şengül, and Ercişli, 2012) to the ADHD diet. Hawthorn, is regarded as

a valuable anti-inflammatory in the treatment of cardiac and vascular conditions; demonstrating a

reduction in inflammation; suggesting that other inflammatory conditions (like ADHD related to

inflammation) could be alleviated with its use. Future clinical trials utilizing Hawthorn extract

on older adolescents and adults with ADHD may reveal its usefulness. Further research could be

expanded to a larger cross-over trial to determine if results could be replicated on larger

populations. In addition, cross over research trials could be conducted on Hawthorn and

compared to anti-inflammatory diets in the management and treatment of ADHD.

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Retrieved from www.agriculturesource.com

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