Hawthorn berry is proposed as a possible anti-inflammatory treatment in the management of Attention Deficit Hyperactivity Disorder (ADHD). This is not to be undertaken without supervision and management by a qualified licensed medical provider educated in CAM modalities. This novel paper implicates inflammation as one of the key causes of ADHD/ADD and suggests the use of a carefully prescribed and monitored supplement of Hawthorn might be beneficial in managing this condition.

1. 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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ResearchMethods & 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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