complementary and alternative medical therapies for...

Review Article

Complementary and Alternative MedicalTherapies for Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

Janice Pellow, M.Tech (Horn); Elizabeth M. Solomon, HD, ND, DO, BA;Candice N. Barnard, M.Tech (Hom), B.Phys.Ed

Janice Pellow, M.Tech(Hom) (TWR)-RegisteredHoniioeopath, Faculty ofHealth Sciences, University ofJohannesburg, Department ofHomeopathy, Johannesburg,South AfricaE-mail: [email protected]

Elizabeth M. Solomon, HD,ND, DO, BA-RegisteredHomoeopath, Senior Lecturerat University of Johannesburg,Department of Homeopathy,Johannesburg, South Africa

Candice N. Barnard, M.Tech(Hom),B.Phys.Ed-Registered Homoeopath

AbstractAttention-deficit/hyperactivity disorder (ADHD) is a commonlydiagnosed childhood disorder characterized by impulsivity,inattention, and hyperactivity. ADHD affects up to 1 in 20children in the United States. The underlying etiologies ofADHD may be heterogeneous and diverse, and many possiblerisk factors in the development of ADHD have been identified.Conventional treatment usually consists of behavioralaccommodations and medication, with stimulant medicationmost commonly being prescribed. Parents concerned aboutthe side effects and long-term use of conventional medica-tions are increasingly seeking alternatives to pharmacologietreatment. Complementary and alternative medicine (CAM)offers parents various treatment options for this condition,including dietary modifications, nutritional supplementation,herbal medicine, and homeopathy. CAM appears to be mosteffective when prescribed holistically and according to eachindividual's characteristic symptoms. Possible etiologies andrisk factors for the condition also need to be considered whendeveloping a treatment plan. This article serves to highlightthe latest research regarding the most commonly used CAMfor children with ADHD.(kitem Med Rev 2011;16(4):323-337)

IntroductionAttention-deficit/hyperactivity disorder (ADHD)

is a common childhood behavioral conditioncharacterized hy persistent symptoms of inatten-tion, hyperactivity, and impulsivity.^ ADHD isdiagnosed according to the Diagnostic andStatistical Manual of Mental Disorders - FourthEdition (DSM-IV), which defines three types ofADHD: Predominantly Inattentive, PredominantlyHyperactive-Impulsive, and Combined.' The

symptoms of ADHD afïect cognitive, behavioral,emotional, and social functioning."* Its incidence isthought to range conservatively from 3-7 percent,with its diagnosis made 3-9 times more often inboys. ' ADHD is a heterogeneous disorder thatoften continues from childhood and adolescenceinto adulthood and often carries a high risk ofco-morbidity with learning disabilities and conductdisorder.^ Around 25 percent of ADHD childrenalso suffer from anxiety, and 15-75 percent have aco-morbid mood disorder.^ Concerns about sideeffects and questions regarding the long-termsafety of pharmacological treatment, as well aspersonal preference to avoid stimulant medication,has led many parents to seek complementary andalternative medical therapies.^

PathogenesisThe underlying etiologies for ADHD are diverse.^

Neurological and biochemical anomalies, as well asgenetic influences, are discussed below.

Neurological Anomalies in ADHDADHD has been associated with conditions that

cause neurological impairment, such as leadpoisoning, chromosomal abnormalities, neu-rotransmitter deficits, oxygen deprivation at birth,smoking during pregnancy, and fetal alcoholsyndrome.''^^ A further non-genetic factor thoughtto contribute to ADHD is oxidative stress, whichcauses damage to DNA." Most ADHD children,however, have no gross structural damage to thecentral nervous system (CNS). While certainneuro-imaging studies have shown anatomical

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Table 1. Risk Factors for ADHD

differences of certain areas of the brain in patientswith ADHD, findings have been inconsistent, and itis now hypothesized that the brain in ADHD isaltered in a more widespread manner. ' ^

Biochemical Anomalies in ADHDThe biochemical etiology of ADHD has been

postulated to be related to low levels of catechol-amines (namely epinephrine, norepinephrine, anddopamine) and serotonin in certain areas of thebrain. These neurotransmitters are responsible foractivating the areas of the brain needed for focusand concentration. -"^^ Somerecent studies have also shownevidence for abnormalities ofglutamate/glutamine andcreatine in the brain.-' ' ^ Adisturbance in the interactionbetween the glutamatergic anddopaminergic systems has beenproposed as a key pathogeneticfactor in ADHD;-" ^ however, moreresearch is needed in this area.While conventional ADHDmedications attempt to restoreneurotransmitter balance in thebrain, there has been'littlediscussion concerning thepossible physiological causes ofsuch low levels of neurotrans-mitters, e.g., dysfunction in themanufacture of these com-pounds, poor uptake into thebrain, or increased transport outof the brain to the presynapticterminal of the neuron. ' *

Genetic EffectsNumerous studies have shown

evidence supporting geneticcauses and associations withADHD, with a five- to six-foldincrease in occurrence amongrelatives of ADHD patients beingnoted. -' ''' ^ Several genes areexpected to be involved; however,ultimately the search is not for aspecific ADHD gene but ratherfor genes that regulate braingrowth and receptordevelopment.^^

Risk FactorsNumerous risk factors for ADHD have been

proposed. The following potential etiologicaldomains all appear to exacerbate existing ADHDsymptoms and have a plausible neural mechanismof action,^^ as outlined in Table 1.

Dietary Influence and Nutritional DeficienciesPoor diet and resultant deficiencies of various

nutrients can contribute to oxidative stress andaltered neuronal plasticity, both of which have animpact on children with ADHD. Deficiencies of zinc.

Key words: ADHD, attention-deficit hyperactivitydisorder, ADD, inattention,hyperactivity, impulsivity,behavioral problems, anxiety,homeopathy

Risk Factor

Dietary Factors and Nutrient Deficiencies

Hypersensitivity to foods and/or additives

Phospholipid deficiencies

Omega-3 fatty acid deficiency

Amino acid deficiencies

Refined carbohydrates

Mineral deficiencies

Antioxidant deficiencies

Mechanism

Increase in inflammatory mediators andneuropeptides in the blood

Possible impairments in neuronal structure andfunction, especially during early developmen't

Impaired neurotransmitter reception in brairaltered neuronal plasticity

Decreased production of amino acid-basedneurotransmitters

Abnormal glucose metabolism, causing disrup-tions in hormone and neurotransmitter regulation

Impaired dopaminergic transmission

Oxidative damage to DNA

Exposure to Environmental Toxins

Heavy metals, solvents, pesticides,neurotoxins

Disrupted neurotransmitter and neuromodulatorfunction 1

Exposure to Electronic Media

Television

Cell phones

Over-stimulation, sensory addiction, increasedstimulus-seeking behavior I

Pre-and post-natal exposure linked to increase inADHD symptoms. Exact mechanism unknown!

Abnormal Lighting

Natural light deficiency / Exposure tofluorescent lighting

Hyperactive behavior and decreased learningability

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magnesium, glutathione, and/or omega-3 fattyacids, for instance, have been linked to concentra-tion, memory, and learning problems in childrenwith ADHD."

Hypersensitivity to Foods and/or AdditivesA high proportion of children with ADHD tend

to exhibit atopic symptoms, leading to a recenthypothesis by Pelsser et al that ADHD may complywith the criteria for hypersensitivity.^" Exposure tosensitizing foods appears to increase inflammatorymediators and neuropeptides in the blood,* andhypersensitive children are likely to exhibit atopy,irritability, sleep disturbances and prominenthyperactive-impulsive symptoms.^* Future researchregarding a genetic atopic link is needed. Probiotictherapy has been shown to be beneficial in childrenwith atopic conditions such as eczema, " thus maybe useful for immune-mediated h3rpersensitivityreactions in ADHD.2°

A potential link between ADHD and foodadditives (preservatives, artificial flavorings andcolorings) has been debated for decades.' '•^^ Astudy published in Lancet in 2007 put forward thefindings that sodium benzoate and commonly usedfood colorings may exacerbate hyperactive behav-ior in 3-year- and 8/9-year-old children.^^Dissimilarities in the behavioral responses of thesechildren when consuming additives suggested agenetic influence.^^ Indeed, this was confirmed in a2010 follow-up study of the same children, whichshowed adverse effects of food additives on ADHDsymptoms to be moderated by polymorphisms inthe genes controlling histamine degradation.^* Arelationship between food additives and behavioris concluded to be clinically relevant for individualchildren, particularly those with a tendency towardhyperactivity.^^

Essential Fatty Acid and Piiosphoiipid DeficienciesEssential fatty acids (EFAs) and phospholipids

are both essential for normal neuronal structureand function and must be supplied through thediet.*' ' ^ The myelin sheath, which insulates everyneuron in the brain, is made up of roughly 75-per-cent phospholipids, with each molecule having anattached saturated and unsaturated fatty acid, thelatter being either an omega-3 or an omega-6 fattyacid.^' The brain and nervous system dependheavily on these essential nutrients, especiallyduring critical periods of development such aschildhood, and dietary deficiency during theseperiods may increase the risk of developingADHD-type symptoms.*

Omega-3 fatty acids, specifically docosahexae-noic acid (DHA) and eicosapentaenoic acid (EPA),appear to improve neurotransmitter reception inthe brain. DHA, in particular, protects neurons andglia from death by maintaining brain-derivedneurotrophic factor (BDNF), a protein formedwithin the brain that aids in maintaining neuronalplasticity. ' ^ The ratio between omega-3 andomega-6 fatty acids is especially important, andour modern Western diet has produced an imbal-ance in this ratio, with more foods rich in omega-6(e.g., canola oil, sunflower oil) being consumed.This imbalance is considered to be a risk factor forADHD.2823 ADHD children may also have aninability to metabolize EFAs correctly.^^ Childrenwith ADHD frequently manifest EFA deficiencysymptoms, which may include dry hair and skin,eczema, recurrent infections, increased thirst andbehavioral problems.^" Correcting underlying EFAdeficiencies may improve ADHD symptoms inmany individuals.

Low-Protein, High-Carbohydrate DietsAmino acids are the building blocks of proteins,

as well as precursors for most of the neurotrans-mitters in the brain (Figure 1). Certain amino acidsare considered essential, as they need to be takenin through the diet; as a result, low protein dietsmay foster amino acid deficiency symptoms.^ Manyof the amino acids needed by the body to manufac-ture neurotransmitters, such as phenylalanine,tyrosine, and tryptophan, are found to be low inthe blood of adults and children with ADHD. - i sDeficiencies of these neurotransmitter precursors,together with their vitamin and mineral cofactors,may result in ADHD-type symptoms.' Correctingunderlying metabolic imbalances through aminoacid supplementation may be an importanttreatment strategy in individual cases where adeficiency exists.

Excessive consumption of refined carbohydratesand sugar can negatively affect learning ability andincrease aggressive and restless behavior in allchildren, although evidence for a direct link toADHD is lacking. In one study, comparing 17ADHD children with nine age-matched normalchildren, assessing the effects of sugar ingestion onbehavior, the children with ADHD displayed moreinattention.^^ It has been suggested that theseresults could be due to a relative glucose intoler-ance occurring in ADHD sufferers; however,evidence for this is contradictory. One studyconducted by Langseth and Dowd on 261 hyperac-tive children found that after five-hour oral glucose


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tolerance tests, 74 percent displayed abnormalglucose tolerance.^^ Other studies have failed tofind differences in overall glucose metabolismbetween normal children and children with ADHD.35,36 However, these studies did find significantdifferences in glucose metabolism within specificregions of the brain, such as the frontal lobe, wherereduced metabolism was inversely correlated withsymptom severity.^' Reactive hypoglycemia aftersugar ingestion typically causes a rise in plasmaepinephrine and norepinephrine; however, the risein ADHD children is nearly 50-percent lower thanin normal children.^'' The data suggest that ADHDchildren have diffictilty regulating hormones andneurotransmitters, which may be further aggra-vated by refined sugar consumption.

Mineral DeficienciesNumerous studies have shown evidence of

mineral deficiencies in children with ADHD,namely, zinc, iron, calcium, magnesium, andselenium. ' " ^ As zinc and iron are associated withdopamine metabolism, a deficiency of either of

these minerals might be associated with significantimpairment in dopaminergic transmission.''^Consumption of certain artificial food additives canlead to various nutrient deficiencies in someindividuals, in particular zinc deficiency, which canexacerbate anxiety and conduct disorder prob-lems.-" ^ A disturbance in the zincxopper ratio is alsoevident, with high levels of copper being found inmany ADHD children.38

Environmental Toxins and ContaminantsExposure to metals (lead, cadmium, mercury,

aluminum), solvents, pesticides, polychlorinatedbiphenyls, or other environmental toxins has beenlinked to ADHD. ' ' Minerals such as zinc areneeded to help metabolize and eliminate heavymetals; thus, a deficiency of such nutrients canexacerbate the problem.^^ The vast majority oftoxicants released into the environment and theireffects on a child's developing nervous system have,however, not been adequately researched. It hasbeen proposed that prenatal and perinatal insultsto the developing brain, including environmental

Figure 1. Key Neurotransmitters in ADHD and their Amino Acid Precursors

Serotonin /Melatonin

' Tryptophan

I5-Hydroxytrptophan

| (B6 )

Serotonin

; Y (SAMe)li Melatonin

IrÍ

Catecholamines

Phenylalanine

'(Fe)

r

Tyrosine

iDopa

| ( B 6 )

Dopamine

>(Vitamin C, Cu)

r

Norepinephrine

(SAMe)

Epinephrine

GABA

Glutamine

1Glutamate

| ( B 6 )

GABA

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toxins, can disturb the timetable of expression ofneurotransmitters and their receptors.^^ If so, thismight have the effect of producing permanentchanges in the brain that predispose to ADHDduring childhood or adolescence. Although exactmechanisms were not clear, a literature reviewrevealed a more than two-fold increased risk ofADHD among children whose mothers smokedduring pregnancy.'*' Other studies suggest thatthese contaminants may disrupt two key sets ofpsychological mechanisms that are also disruptedin ADHD: higher-order executive functions andreinforcement responses.^^ Chelation therapy forbinding heavy metals in the body may provebeneficial in cases of ADHD associated with toxicoverload. In one small study conducted on childrenwith both autism and ADHD, using chelationtherapy in combination with other nutritional,behavioral, and educational approaches, all 10children showed a significant improvement insocial interaction, cognitive function, and behavior,as well as a significant reduction in urinary leadburden."«

Environment, Electronic Media, and CultureIt is a well-established theory that electronic

media can influence children's development.'Research has shown that early television watching(ages 1-3) is associated with the development ofattention problems in children by age seven."'Another study showed that children who watch twoor more hours of television per day had increasedattention problems in adolescence, suggesting thatthe adverse effects of television may be cumula-tive.^" One possible explanation for these findingsis that television watching replaces other activitiesthat encourage concentration and attention, suchas reading. Also, children's television programs mayoverstimulate the developing brain of a young child,leading to sensory addiction.^" One result ofsensory addiction is difficulty coping with slowness.In children, this can manifest as an inability toregulate their own behavior, motivating the needfor more stimulus-seeking behavior. Restlessness,anxiety, and impulsivity may result from a per-ceived lack of stimulation.'-' Further studies areneeded in this field for a fuller evaluation of theassociation between television and ADHD. «

According to a study published in the journal.Epidemiology, children exposed to mobile phonesprenatally and, to a lesser extent, postnatally, were80-percent more likely to exhibit ADHD-typesymptoms, such as hyperactivity and behavioral

problems, at school-going age.'^ Although thisassociation has yet to be substantially proven, itdoes raise cause for concern due to the widespreaduse of this technology.

Natural light deficiency has been suggested as arisk factor for ADHD.' Exposure to cool-whitefluorescent lights appears to affect learning abilityin children, and research suggests that it may alsobe linked with the incidence of attention-deficitdisorder and hyperactivity. One study showed thatthere was a 32-percent reduction in hyperactivebehavior in children when fluorescent lighting wasremoved from their classrooms.^'' As a result, it hasbeen suggested that radio-frequency (RF)-shieldedfull-spectrum lighting and/or natural unfiltereddaylight preferably be used. ^ Spending timeoutdoors in "green" natural settings appears toimprove ADHD symptoms.'^ Moreover, the greenerand more natural the environment compared toindoor or relatively built up outdoor settings (e.g.,parking lots, downtown areas), the less severe theADHD symptoms.

Conventional TreatmentConventional treatment for ADHD usually

consists of medication, behavioral interventions,and educational accommodations to enhancelearning.'^ The three major classes of drugs usedinclude stimulant medications, non-stimulants,and antidepressant medications.^* Stimulant drugs,such as methylphenidate (e.g., Ritalin® andConcerta®), are structurally similar to and mimicthe action of norepinephrine and dopamine.^'Stimulants improve ADHD symptoms in mostchildren;^" however, as many as 20-30 percent ofchildren either do not respond to this class of drugor are unable to tolerate them due to the widerange of adverse effects they may produce.''''^Short-term side effects may include loss of appetite,insomnia, anxiety, mood swings, increased bloodpressure and heart rate, tics, and "behavioralrebound." Higher doses may result in paranoidpsychoses. ' ^ Long-term side effects may includesuppression of growth and cardiovascular effects.^'Stimulant drugs also may promote physical and/orpsychological dependence.^^

Atomoxetine (Strattera®), a non-stimulant drugthat acts as a norepinephrine reuptake inhibitor,has been shown to improve ADHD symptoms. •®''However, side effects are possible, includingcardiovascular symptoms, psychotic symptoms, orincreased suicidal tendencies.^'


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Antidepressants are believed to increase sero-tonin and/or dopamine and norepinephrine in thebrain by blocking their reabsorption in the brain,and are often beneficial in those individuals with aco-morbid mood disorder. There are numerouspotential side effects associated with these drugsas well, such as dry mouth, fatigue, insomnia,decreased appetite, headaches, and nausea.^^

Complementary and AlternativeMedicine

Complementary and alternative medicine (CAM)is increasingly being used for children with ADHD.CAM therapies focus on treating the patientholistically and individually, and aim to treatunderlying etiologies.^^ Various commonly usedCAM modalities will be discussed in the followingsection.

DietParents who are troubled with medicating their

children are often more comfortable with theinitiative of dietary interventions.^* Propernutrition is essential for growing children, andchildren who eat a diet high in "junk food" in earlychildhood are more likely to exhibit hyperactivityby age seven; this may reflect a long-term nutri-tional imbalance.*^ Regular meals and snacks areadvised, consisting of low-glycemic index carbohy-drates, proteins, and essential fatty acids. Refinedcarbohydrates, sugars, and processed foodscontaining additives should be completely elimi-nated from the diet. When possible, organic fruitsand vegetables and free-range meats should beconsumed. Vegetable proteins, such as soy, quinoa,and beans are beneficial, in terms of blood sugarcontrol and avoidance of chemical and hormonaladditives in meat products. Foods rich in EFAs,especially omega-3 fats, include cold-water fish(e.g., salmon and sardines), walnuts, almonds,pumpkin seeds, and flax seeds.''^•"

Evidence has shown the effectiveness of arestricted elimination diet (i.e., the "few foods"approach) in children with ADHD. According toparent ratings on both the Conners- and ADHDRating Scales in one study, 62 percent of ADHDchildren showed at least 50-percent improvementin behavior.^' The children who followed thedietary intervention no longer met the DSM-IVcriteria for ADHD. This research further highlightsthat hypersensitivity to foods and additives mayexacerbate ADHD symptoms.

Exercise TherapyThere is much evidence to show that physical

exercise enhances brain activity and modulatesneurotransmitter systems, thereby improvingmemory, concentration, learning, and mood.Regular exercise that is cognitively, socially, andaerobicaUy challenging offers the most benefit,facilitating healthy cognitive development andalleviating the symptoms of ADHD.™

Supplementary InterventionsEssential Fatty Acids

Various studies have reported the benefits ofEFA supplementation in varying dosages, ' ^ forreducing anxiety, attention difficulties, andbehavioral piroblems in children. '' ' ^ In oneclinical trial, high daily doses of fish oil (8-16 g),administered to ADHD children, produced asignificant improvement in behavior and attention,as well as reduced hyperactivity and defiance.^^Daily EFA supplementation or eating foods that arerich in EFAs is recommended."*

Vitamin B6 and MagnesiumVitamin B6 facilitates the production of sero-

tonin, and supplementation with vitamin B6 hasbeen shown to increase serotonin levels and reducehyperactivity in ADHD.'"* In one study, 40 childrenwith ADHD were given magnesium (6 mg/kg/d)and vitamin B6 (0.6 mg/kg/d) for eight weeks.Almost all ADHD children showed an improvementin clinical symptoms, namely hyperactivity,hyperemotivity/aggressiveness, and inattention.Clinical symptoms returned a few weeks aftertreatment was stopped.'^

Iron and ZincIn a 12-week, double-blind study, children

supplemented with 150 mg of zinc sulfate showedreductions in hyperactivity, impulsivity, andimpaired socialization.'^ Supplementation withiron and zinc is only recommended in children whoare deficient, and should preferably be in chelatedform (i.e., complexed with picolinic acid, aminoacids, or organic acids) for improved absorption.

Calcium/MagnesiumCalcium and magnesium work synergistically to

relax the nervous system; deficiency symptomsinclude irritability, restlessness, fidgeting, musclecramps, and twitches. Magnesium supplementa-tion has been shown to reduce excitability andimprove concentration in children with lowserum- and RBC magnesium levels.'' • ^


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Acetyl-L-Carnitine (ALC)ALC is the acetyl ester of the amino acid,

L-carnitine, and is responsible for transportingfatty acids into the mitochondria. While researchhas shown L-carnitine supplementation to behelpful in treating ADHD symptoms, particularlyattention problems and aggression, ALC actssimilarly and is more easily absorbed and utilizedby the cells."''^ In an animal model of ADHD, ALCwas shown to consistently reduce the impulsivityindex; thus, it may be a viable treatment option forADHD."

Gamma-AminobutyricAcid (GABA)GABA is a neurotransmitter that has an inhibi-

tory effect on the nervous system; its ability toreduce excitability of neurons accounts for itstranquilizing effects. GABA may be most useful tothose children experiencing predominantlyhyperactivity symptoms, as it calms the body andappears to be beneficial for anxiety and stress.'«

GlycineGlycine is another inhibitory neurotransmitter

that produces post-synaptic inhibition andappears to calmaggression and anxietyin both children andadults.'«

L-TyrosineL-tyrosine, an essential precursor for dopamine

and norepinephrine, has been shown to be benefi-cial for attention in adults with ADHD.« Around5-10 percent of ADHD cases respond to L-tyrosinesupplementation and are most likely those indi-viduals who have impairments in neurotransmittermetabolism.*^ In one case study evaluating theeffect of tyrosine supplements on a patient withADHD and co-morbid phenylketonuria, tyrosinewas found to reduce ADHD symptoms, possiblythrough the action of augmenting dopaminergicactivity.«^

TaurineTaurine is considered essential for infants and

children. The amino acid acts similarly to GABAand glycine as an inhibitory neurotransmitter withanti-anxiety properties.'* While research has beenconducted on its role in thé management of seizuredisorders, very little evidence exists regarding itsuse in children with ADHD.*"

L-TheanineL-theanine is an

amino acid constituentof green tea thatsignificantly increasesthe activity of alphawaves in the brain.Alpha waves play acritical role in attention.Thus, L-theanine canrelax the mind withoutinducing drowsiness."Further research isneeded to investigatean association betweenL-theanine andattention.«" A study onthe effects ofL-theanine on sleepquality in boys withADHD is published inthis journal.

Table 2. Amino Acids and their Mechanisms of Action in ADHD

Amino acid

Acetyl-L-Carnitine (ALC)

Gamma-Aminobutyric Acid (GABA)

Glycine

L-Theanine

L-Tyrosine

Taurine

5-Hydroxytryptophan (5-HTP)

S-Adenosyl-L-Methionine (SAMe)

Proposed Mechanism of Action

Reduces attention problems, impulsivity andaggression

Tranquilizing effect; reduces hyperaaivity andanxiety

Tranquilizing effect; reduces anxiety andaggression

Aids attention by increasing alpha waves in thebrain; calms the mind

Precursor for dopamine and norepinephrine

Tranquilizing effect; reduces anxiety

Anti-depressant effert; increases serotoninsynthesis

Essential for neurotransmitter synthesis; hasanti-depressant activity


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5-Hydroxytryptophan (5-HTP)5-HTP, manufactured in the body from the

amino acid L-tryptophan, readily crosses theblood-brain barrier and increases synthesis ofserotonin. Supplemental 5-HTP is derived from theseeds of Griffonia simplicifolia and may offer analternative to conventional antidepressants forADHD children with co-morbid mood disorders.Use of 5-HTP in combination with serotonin-enhancing drugs should be under medicalsupervision.^^

S-Adenosyl-L-Methionine (SAMe)SAMe, the active form of methionine, has

beta-adrenergic and dopamine receptor agonistactivity.*^ SAMe is a major methyl donor in thebrain and is required for the synthesis of~norepi-nephrine, dopamine, and serotonin. SAMe appearsto be a safe and effective treatment for depression*^and shows promise in the treatment of ADHD. In anine-week, double-blind, placebo-controlled,crossover trial, 75 percent of adult ADHD patientsusing SAMe showed improvement, with minimaland transient side effects.*^ SAMe does not appearto have toxic effects at the recommended dosages;however, it may increase anxiety and mania inpatients with bipolar disorder.*^

Table 2 summarizes the amino acids and theirmechanisms of action in relation to ADHD.

Dimethylaminoethanol (DMAE)DMAE is an acetylcholine precursor that is

converted to choline inside the brain.Supplementation with DMAE is purported toincrease acetylcholine in the brain, thus aiding withmemory, learning, and improved mood. A double-blind study conducted in 1975 involving 74children found that a daily dose of 500 mg ofDMAE for three months was as effective asRitalin.^' DMAE itself is synthesized from phos-phatidylethanolamine and phosphatidylserine,reactions that require other nutrients such asSAMe and magnesium in sufficient supply.'* Sideeffects are rare but can include headaches, insom-nia, and anxiety.**

Phosphatidylserine and PhosphatidykhoiinePhospholipids are essential components of all

cell membranes and the functional ingredients oflecithin. Phosphatidykhoiine supplementation hasbeen found to support healthy brain function dueto the essential nutrient, choline.*' Phosphatidyl-serine (PS) is most concentrated in the brain,where it comprises 15 percent of the phospholipid

pool.*' PS appears to increase the output ofacetylcholine, as well as dopamine. Several studieshave been conducted showing its efficacy inimproving cognitive functioning, mood, andmemory.'°"'^ In a 30-week, exploratory studyevaluating the effect of PS combined with omega-3fatty acids (PS-Omega-3) on 200 children withADHD, an initial 15-week, double-blind, placebo-controlled trial was conducted, followed by a15-week, open-label extension period. ADHDsymptoms were assessed using both home andschool rating scales, and a quality-of-life assess-ment was conducted. Significant reductions inADHD symptoms were noted, particularly withregards to restless/impulsive behavior, and datasuggested an improvement in emotional quality oflife. PS-Omega 3 was well tolerated, with no majoradverse events noted.''

MeiatoninChronic sleep-onset insomnia (SOI) is common

in children with ADHD and impacts academicperformance and social well-being. SOI is acommon side effect of stimulant medication.Meiatonin, a hormone produced in the pineal glandthat helps regulate sleep patterns, has been shownto be a well-tolerated and effective option forADHD patients with SOI,'^ and may even improveinsomnia in children using stimulantmedications.'^

PycnogenoiPycnogenol (Pyc), extracted from grape seeds or

pine bark, consists of bioflavonoids, catechins,procyanidins, and phenolic acids. It has powerfulantioxidant, chelating properties, and enzymestimulating properties. It has been proposed thatone of the risk factors for ADHD may be oxidativestress; studies have shown significantly increasedoxidative damage to DNA in ADHD children whencompared to controls.'^'^ In one study, Pyc wasshown to significantly reduce hyperactivity, andimprove attention, concentration, and visual-motoric coordination in children with ADHD over afour-week period.'* Further studies showed Pyc tonormalize urinary catecholamine concentrations,-' ^plasma copper levels,'* and total antioxidant statusin ADHD children.'^ It also increased levels of theantioxidant, glutathione (GSH) and reduced levelsof oxidized glutathione (GSSG).' Pyc supplementa-tion has been shown to reduce oxidative damage toDNA, leading to less hyperactivity and improvedattention in ADHD children."


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ProbioticsProbiotics are beneficial microorganisms

normally found in the digestive tract. The mostcommon organisms found in probiotics are variousstrains of Lactobacillus and Bifidobacteria.^Overgrowth of pathogenic organisms (bacteria,fungi) in the bowel can trigger the release ofneurotoxic endotoxins. Some of these compoundshave been identified in the urine of children withADHD. ^ As a result, probiotics may be useful inADHD children with atopic symptoms, parasites,and/or intestinal dysbiosis."'^"

Herbal TreatmentCertain herbal medicines, as shown in Table 3,

show promise in the treatment of ADHD; however,very little research exists regarding their specificuse for this condition in children. Those herbs thatmay be potentially beneficial for ADHD arediscussed below.

Rhodiola (Rhodiola rosea)Various studies have revealed that Rhodiola

exhibits an adaptogenic effect, is neuroprotective,and has CNS-stimulating activity.' °" Rhodiola hasbeen shown in rats to enhance the transport ofserotonin precursors (tryptophan and 5-HTP) intothe brain, thereby increasing serotonin levels. °^

Table 3. Botanical Agents and their Mechanisms of Action in ADHD

Proposed Mechanism of Action

Anxiolytic and mildly sedative

Inhibits reuptake of serotonin, norepinephrineand dopamine; has anti-depressant activity;reduces anxiety, restlessness and irritability

Improves cognitive function: memory,learning, concentration; also has anxiolyticeffects

Rhodiola also appears to inhibit acetylcholineesterase, the enzyme that degrades acetylcholine.^"^A number of clinical trials have demonstrated thatRhodiola extract has anti-fatigue and anti-anxietyeffects that serve to increase mental performanceand cognition (particularly the ability to concen-trate) in adult subjects.•'" • " Rhodiola also appearsto be useful for generalized anxiety disorder, aswell as mild-to-moderate depression. " ' "^ However,the use of Rhodiola in combination with conven-tional antidepressants should be medically super-vised, as concurrent use may increase the risk ofadverse effects.^"' General lack of side effects in thecourse of clinical trials makes it potentiallyattractive for use as a safe medication; however, notrials have been conducted on children withADHD.i"" .

Chamomile (Matricaria chamomilla)This plant, belonging to the Compositae family,

has known carminative and mild sedative proper-ties and has traditionally been prescribed forrestlessness and nervous irritability in children.While generally considered safe, allergies to plantsof the Compositae family may predispose to atopicreactions and anaphylaxis. This is, however,extremely rare, and this risk is diminished if usingan ethanolic tincture, as the alcohol in the extract

denatures the proteins responsible for allergic

Neuroprotective; anti-fatigue and anxiolytic;increases serotonin levels; has anti-depressanteffects; CNS-stimulating; increases cognitivefunction

Calmative and antispasmodic; reduces anxiety,restlessness and insomnia

St. John's Wort (Hypericum perforatum)Experimental studies suggest that St.

John's wort is capable of inhibiting thereuptake of serotonin, norepinephrine, anddopamine; many of its compounds appear tocontribute to its antidepressant activity. As aresult, St. John's wort offers an alternativeoption to conventional SSRI antidepressantsfor treating mild-to-moderate depression,even in children under the age of 12, andwith few side effects."""^ The EuropeanScientific Cooperative on Phytotherapy(ESCOP) recommends this herb for thetreatment of restlessness, anxiety, andirritability.^°"'^°' In one small open trial, St.John's wort improved ADHD symptoms,according to the Conners Rating Scale. •"' Theuse of St. John's wort in combination withcertain conventional medications is contrain-dicated and should therefore be used undermedical supervision.^


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Valerian {Valeriana officinalis)Valerian acts primarily on the nervous system,

with calmative and antispasmodic properties."^ Ithas been used for the treatment of anxiety andinsomnia,"^ and more recently for ADHD."3"*Valerenic acid, one of its key compounds, inhibitsthe breakdown of GAB A in the CNS, making it analternative option for disorders characterized byrestlessness."^•' ' ^ Although valerian is generallyconsidered safe, ^^ there are no studies specificallyevaluating its safety in children, and, to date, nocontrolled trials evaluating its use in treatingADHD. ESCOP approves of the use of valerian forchildren ages 3-12 years, assuming medicalsupervision.^^'

Bacopa (Bacopa monniera)Bacopa, an Ayurvedic herb, has been used for

centuries as a brain tonic to promote highercognitive functioning, with more recent researchrevealing its nootropic action (positive effects onmemory, learning, and concentration).^^" In onestudy involving healthy subjects, the Bacopa (300mg) group showed a significant improvement inspeed of visual processing, learning rate, andmemory consolidation, as well as reduced anxiety,when compared to the placebo group. Bacopa wasmost effective after a 12-week period of supple-mentation.•' ' Another study conducted on childrenwith ADHD revealed that Bacopa-treated patients(50 mg twice daily) showed significant improve-ments in memory and learning tasks over a12-week period.^^" Bacopa appears to be welltolerated, with few adverse effects. ^^

Homeopathic TreatmentHomeopathy is increasingly becoming a sought-

after treatment option for ADHD. ^ Homeopathyis a system of medicine which considers that eachindividuid will both present and experience theirillness characteristically and that there will be aspecific medicine best suited to each individual.- ^^This specific remedy is known as the similimum.Because not all children diagnosed with ADHDmanifest symptoms of the condition in an identicalmanner,'^* the task of the homeopathic practitio-ner, in treating with the homeopathic similimum,is to find this remedy based on the individual andcharacteristic symptoms of the patient withADHD. = The homeopath has to know all thepatient's symptoms - mental, emotional, general,or local. All corresponding sensations, concomi-tants, alternating symptoms, as well as rare orpeculiar characteristic manifestations of the

patient and a personal medical history, are neededfor the homeopathic prescription of the similimumremedy.' ^^ Mental and emotional symptoms aregiven priority in understanding the disease processof the sick, as well as symptoms that characterizethe uniqueness of individual symptoms. Thephilosophy of homeopathy thus implies treatingthe patient, not the disease.^^'

Apart from the similimum remedy, manyhomeopaths make use of combination remedies,which are a complex of multiple, individualremedies that clinically relate to a particularcondition. These combination remedies aresometimes used as a substitute for similimum, or

"constitutional," prescribing. Various researchstudies on both similimum and combinationhomeopathic treatment of children with ADHDhave been conducted, many of which have shownsuccess in their treatment regimens.

Strauss, in a study to determine the efficacy ofSelenium Homaccord®, a homeopathic complex, inthe management of ADHD, observed overallimprovement in children's symptoms.^^" A studyconducted by Smith et al found that the homeo-pathic complexes. Cerebro® and Nerva 2®, reducedthe symptoms of inattention and improved thescoring of the Conner's Abbreviated Teacher RatingScale in children with ADHD, ages 7-12 years."'White et al studied the effects of Valeriana officina-lis in mother tincture (MT) and 3X potency andobserved a significant improvement in ADHDchildren's behavior while on the treatment, with nosignificant difference found between the MT and3X potency.^^° Homeopathic complexes mayprovide symptomatic relief without any adverseeffects; however, more research is required to verifythese results.

Several studies have been conducted on simili-mum treatment. In 1997, Lamont conducted adouble-blind, partial crossover study of 43 childrenwith ADHD. Children were treated initially witheither placebo or a similimum homeopathicremedy; after 10 days, the groups were switched.According to behavior rating scores by parents orcaretakers, homeopathic treatment was foundsuperior to placebo for reducing symptoms ofhyperactivity.^ ' A similimum research study byBarnard et al showed that 85 percent of theparticipants in the study group improved insymptoms of ADHD on their homeopathic simili-mum remedy over the 12-week treatment period.-' ^Frei and Thurneysen carried out a study comparingsimilimum homeopathic treatment (using LMpotencies, meaning a 1/50,000 dilution ratio) and


Review Article

Ritalin treatment. Of the 115 participants, 75percent responded sufficiently well to homeopathictreatment, 22 percent did not and needed Ritalin,and three children did not respond to eithertreatment."^ A Swiss randomized, double-blind,placebo-controlled, crossover trial by Frei et al setout to obtain scientific evidence of the effective-ness of homeopathy in ADHD treatment. Each ofthe 83 children diagnosed with ADHD was indi-vidually prescribed homeopathic medication in LMpotency. Sixty-two participants who respondedwell to the treatment were considered eligible forthe study; these children were divided into twogroups and received either their similimum remedyfor six weeks, followed by placebo for six weeks, orvice versa. The results showed that the overallintensity of ADHD symptoms appeared lowerduring treatment compared to placebo and resultedin an improvement in the children's social, emo-tional, and scholastic behavior.'^^

Similimum therapy appears to offer benefits toADHD sufferers. Efficacy of the treatment, however,depends on the accuracy of the prescription.Further research on the homeopathic treatment ofADHD is required in order to establish its efficacyand to develop future treatment protocols.

ConclusionADHD is a complex, chronic, and heterogeneous

condition that affects up to 1 in 20 children in theUnited States. ADHD appears to have multiplepossible etiologies and risk factors associated withits development, requiring long-term case manage-ment using various treatment modalities. CAMoffers many alternatives to conventional medica-tions. Treatment should be tailored to eachindividual. Dietary corrections, exercise therapy,and nutritional supplements all offer potentialbenefits to the ADHD child. Herbal remedies thatare indicated for restlessness, anxiety, and depres-sion may offer viable alternatives to pharmaco-therapy, although further research related tochildren with ADHD is required. Homeopathy mayprovide a safe and gentle approach through bothsimilimum and mixed homeopathic remedytreatment, with various research studies purport-ing its efficacy.

AcknowledgementsThis work was supported by the University of

Johannesburg. The contents of this work are solelythe responsibility of the authors and do notrepresent the official views of UJ.

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