Advances in Nutritional Therapy for Attention Deficit Hyperactivity Disorder

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Advances in Nutritional Therapy for Attention Deficit Hyperactivity Disorder

By Laurie Barclay, MD

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Recent advances in understanding the origins of attention deficit

hyperactivity disorder (ADHD) may allow symptoms to be managed with nutritional

therapy

and without the adverse side effects of commonly prescribed stimulant drugs

such as Ritalin®. Essential fatty acids, B vitamins, choline,

phosphatidylserine, amino acids, zinc, and herbal extracts all show promise in

managing

symptoms of ADHD.

Understanding ADHD

In the past, children’s discipline problems, poor grades, and roughhousing

with playmates might be dismissed as “rambunctious behavior.†The growing

trend today, however, is to label increasing numbers of children—and even

adults—

with the psychiatric diagnosis of attention deficit hyperactivity disorder,

or ADHD.

At least 3-10% of children and 1-6% of adults in the US have been diagnosed

with ADHD.1-4 Boys diagnosed with ADHD outnumber girls by a ratio of three to

one. Symptoms of ADHD include an inability to concentrate or complete tasks,

hyperactivity, compulsive or impulsive behavior, temper flares and mood

swings, problems with short-term memory and learning, clumsiness, and distorted

perception of time.3,5

ADHD affects school performance,6 social adjustment, and the likelihood of

cigarette smoking and substance abuse.2 In a follow-up study of 55 young

adults at the age of 22 who were diagnosed with ADHD at the age of seven, 58%

had

poor outcomes, including antisocial personality, alcohol abuse, criminal

record, reading disorders, and low educational level.7 “Childhood ADHD . . .

appears to be a most important predictor of poor psychosocial functioning in

early adulthood,†the investigators concluded. “It would seem appropriate to

screen for such disorders in schools and clinics so that therapies may be

started early.â€7

Although conventional pharmacological treatment of ADHD with stimulant drugs

reduces symptoms of inattentiveness and hyperactivity, the most commonly

prescribed, amphetamine-like drugs such as Ritalin® (methylphenidate) have the

potential for addiction, growth suppression,2 and other serious

complications.8,9

In a study of more than 200,000 preschoolers in three different health care

settings, about 12% were prescribed stimulant drugs, and 90% of these

prescriptions were for Ritalin®. Even more frightening, from 1991 to 1995, the

use

of Ritalin® tripled in 2- through 4-year-olds,10 and by 1997, 2 million US

children were being treated with stimulants.2

Nutrients Show Promise

Fortunately, recent advances in understanding the biochemical and

neurophysiological roots of ADHD may allow these symptoms to be managed with

nutritional therapy, without the adverse side effects of stimulants.

Particularly

promising are essential fatty acids, B vitamins, choline, phosphatidylserine,

amino acids, acetyl-L-carnitine, zinc, and herbal nutrients that improve brain

circulation. Because of the numerous and potentially adverse consequences of

ADHD if left untreated, nutritional supplementation should be started as soon

as possible.

In a recent study, 20 children diagnosed with ADHD were treated with either

Ritalin® or food supplements containing a mix of vitamins, minerals,

phytonutrients, amino acids, essential fatty acids, phospholipids, and

probiotics

targeting biochemical risk factors for ADHD.11 Following treatment, both groups

of children recorded similar and significant improvements on psychological

tests. The results offer support for the effectiveness of food supplements in

improving attention and self-control in children with ADHD, and suggest that

food supplements may be as effective as Ritalin® in treating ADHD.11

“I have worked with ADHD for over 30 years, which has allowed me exposure to

a range of treatments,†study coauthor Richard Judah, PhD, told Life

Extension. “For many years, I was skeptical about nutritional supplementation

as an

effective way of addressing problems of inattention, distractibility, and

motor-impulse control.â€

Dr. Judah, a psychologist at Vermont College in Brattleboro, adds, however, “

I have come to the conclusion that the natural approach can indeed be

effective in reducing the symptoms of ADHD. The biggest challenge in providing

support for good supplementation to alleviate the condition involves

establishing

good research protocols to prove and quantify that it works.â€

Disconnects in the Neural Network

To be able to detect, discriminate, and respond appropriately to the barrage

of sensory information encountered in everyday life, the neural network

underlying attention must be intact and functioning properly. Just as severing

phone lines and computer cables can significantly affect communication

capability, disrupting nerve connections can affect communication in the human

brain.

Sophisticated brain-imaging techniques, such as magnetic resonance imaging

(MRI) and functional imaging, reveal abnormalities in ADHD patients.12 These

abnormalities involve both the gray matter and white matter of the brain.

In the gray matter, tests show that blood flow and energy use are decreased

in much the same areas that show anatomical abnormalities—namely, the

prefrontal cortex and striatum.3,12 Structural deficits of the white matter are

also

apparent and may represent breakdown of the protective myelin coating of

nerve fibers, which could decrease communication speed.12 These studies also

show

impaired regulation of neurotransmitters used by nerve cells to communicate

with each other, including the catecholamine system, which is crucial to

maintaining attention.3

Other studies of children with ADHD support the hypothesis that impaired

catecholamine regulation is involved in the development of ADHD.13 This “

fight-or-flight†system, which also involves the adrenal gland and its

hormones,

allows an individual to respond to stress via activation of the sympathetic

nervous system, and to fight off or retreat from an attacker or other threat.

Impaired catecholamine regulation of brain areas involved in ADHD may reduce

the energy available to brain cells.14

Other research highlights deficiencies in dopamine neurotransmitter systems,

which regulate movement and mood, in patients with ADHD.4,8 The inherited

basis for ADHD may involve a gene coding for the dopamine D4 receptor,15 or a

gene controlling receptors for serotonin, another neurotransmitter.16

Some studies suggest that abnormal genes may interact with environmental

culprits to trigger or aggravate ADHD in susceptible individuals. Among these

potential triggers: food additives; food intolerances; sensitivities to

chemicals, molds, and fungi; heavy metals such as lead; pollutants such as

polychlorinated biphenyls (PCBs); and nutritional deficiencies.1,8

“Nutrient deficiencies are common in ADHD; supplementation with minerals, the

B vitamins (added in singly), omega-3 and omega-6 essential fatty acids,

flavonoids, and the essential phospholipid phosphatidylserine can ameliorate

ADHD symptoms,†notes Parris M. Kidd, PhD, in a recent review of the

scientific

literature on ADHD.8

In correspondence with Life Extension, Dr. Kidd notes, “Many if not all of

the drugs used to treat ADHD have poor benefit-risk profiles. An integrated

approach using diet, nutritional supplements, and detoxification is consistently

effective in benefiting individuals with ADHD. Children are far better

served by using nutrients first and turning to pharmaceuticals only as a last

resort.â€

Limitations of Drug Treatment

Ritalin® and other stimulant drugs that increase dopaminergic activity may

improve ADHD symptoms—particularly inattentiveness, hyperactivity, mood

swings,

and impulsive behavior—in about 60% of patients.2,4 Paradoxically, however,

these drugs are unlikely to improve school performance.6 Combining

psychosocial interventions with medications may improve response to

treatment.3,4,6,17,18

About one third of children with ADHD either do not respond to stimulant

drugs or cannot tolerate their side effects.2,19,20 “Psychiatric medication

has

major risks in children,†cautions Dr. Josep Berdonces of the University of

Barcelona in Spain.9 Science journalist Brian Vastag warns that

“Ritalin® acts much like cocaine.â€21 In individuals who later develop

bipolar disorder, taking stimulant drugs in childhood may cause an earlier

onset of

the disease.22

Other drugs thought to be effective in some ADHD patients include those

affecting the neurotransmitters noradrenaline, dopamine, or acetylcholine;

bupropion; tomoxetine;23 atomoxetine;24 theophylline;20 and gabapentin.25 While

better tolerated than Ritalin®, these drugs may also be limited by side

effects.

Nutritional Therapy for ADHD

Alternative therapies for ADHD include nutritional supplementation, dietary

management, exercise and neurofeedback strategies, laser acupuncture, massage,

and vestibular stimulation.2,26-28 Some scientists have noted that ADHD is

very common among individuals with generalized resistance to thyroid hormone,8

and others have noted that thyroid treatment improves ADHD in individuals

with documented thyroid abnormality.26

A study of 114 parents of children with ADHD showed that more than half had

used complementary and alternative therapies, such as nutritional supplements,

in the past year.29 An Australian study had similar results,30 and a US

study showed that about 20% of parents had given herbal therapies to their

children with ADHD.31

Because 90% of total brain growth occurs in the first three years of life,

nutrients required for its development must be supplied to support optimal

brain health in these early years. However, fewer than 1% of US children and

adolescents receive the US recommended daily allowance (RDA) for the five food

groups (fruits, vegetables, meat, dairy, and grains), and 16% do not consume

the RDA of any of the five food groups, according to a US Department of

Agriculture survey of 3,300 participants.32

In a controlled study of nearly 500 schoolchildren, those who were randomly

assigned to receive daily multi-vitamin/mineral supplements containing 50% of

the RDA for four months had a 47% lower rate of antisocial behavior than did

those who received placebo.33

“A group of children confined in a psychiatric correctional facility all had

clinical signs of poor nutrition that were confirmed with blood analysis,â€

lead author Stephen Schoenthaler, PhD, a professor of criminal justice at

California State University, Stanislaus, told Life Extension. “Correction of

those

deficiencies with better food and daily supplements produced a reduction in

serious violent acts while they were confined, from 137 during the previous

three months to nine while under treatment for the next three months.â€

“What our research has suggested is that poor nutrition negatively affects a

whole host of parameters related to delinquency, including behavior and

academic performance issues, which are definitely linked,†coinvestigator Ian

D.

Bier, ND, PhD, of the Dietary Research Foundation in Durham, NH, told Life

Extension. “As nutritional intake is improved, either through diet or

nutritional supplementation, you start to see a return to sufficient levels of

vitamins

in the blood, and correction of these issues.â€

Another dietary approach to treating ADHD involves avoiding sugar,

sweeteners, and other additives such as dyes and preservatives. While some

studies

suggest that avoiding food dyes and preservatives can improve ADHD

symptoms,9,26,34,35 other studies, particularly those examining the effects of

sugar and

sweeteners, are inconclusive.36,37

“Although the results of several controlled studies are contradictory, there

is no scientific evidence that sugar, artificial food colorings, or

sweeteners are responsible for behavior or learning problems in children,â€

according

to Dr. Enrique Chaves-Carballo of the University of Kansas Medical Center’s

Department of Pediatrics.38

Benefits of Essential Fatty Acids

When considering nutritional supplementation in the management of ADHD,

omega-3 essential fatty acids may be the best place to start, as they play a key

role in the structure and function of membranes enclosing brain cells, as well

as in the transmission of impulses between nerve cells.

Long-chain polyunsaturated fatty acids are more fluid and less rigid in

structure than saturated fatty acids—such as the hydrogenated shortenings

found

in commercial baked goods—and therefore help promote healthy brain cell

function.39,40 The fatty acid composition of membrane phospholipids in brain

cells

reflects their intake from supplements or dietary sources such as cold-water

fatty fish. The ratio of omega-3 to omega-6 polyunsaturated fatty acids

affects transmission in nerve networks controlled by serotonin and

catecholamines.39 When present in excess, omega-6 polyunsaturated fatty acids

may increase

inflammation and neuronal dysfunction, because their breakdown generates

pro-inflammatory prostaglandins. 39 These inflammatory prostaglandins are more

likely to cause inflammation than are the breakdown products of omega-3

polyunsaturated fatty acids. 39

Some features of ADHD may relate to abnormalities of fatty acid metabolism.41

Several studies have identified abnormal membrane fatty acids in individuals

with ADHD.42 Preliminary data suggest that some patients with ADHD have

higher rates of oxidative breakdown of omega-3 polyunsaturated fatty acids.42

This observation provides an additional rationale for supplementation with

omega-3 essential fatty acids in the management of ADHD.42

Compared to children without ADHD symptoms, those with ADHD are more likely

to have low levels of the essential fatty acids arachidonic acid and DHA

(docosahexaenoic acid),43 and children with low omega-3 levels have more temper

tantrums, learning disabilities, and sleep disturbances than those with high

levels.44 Adults with ADHD have similar deficiencies of essential fatty acids

relative to controls, with significantly lower levels of total

polyunsaturated fatty acids, total omega-6 fatty acids, and DHA.45

In a controlled study of 41 children, aged 8-12 years, who had specific

learning difficulties and above-average ADHD ratings, those who were randomly

assigned to receive supplementation with highly unsaturated fatty acids for 12

weeks showed significant improvements in behavior and cognitive problems

characteristic of ADHD compared to those receiving placebo.46

A preliminary study of 50 children showed some improvements in ADHD-like

symptoms (compared to placebo) from four months of treatment with a

polyunsaturated fatty acid supplement providing a daily dose of 480 mg of DHA,

80 mg of

EPA (eicosapentanoic acid), 40 mg of arachidonic acid, 96 mg of GLA

(gamma-linoleic acid), and 24 mg of alpha-tocopherol acetate (vitamin E).47

Areas of

improvement included conduct and behavior reported by parents, poor attention

as

rated by teachers, and rebellious attitudes and acting-out episodes.47

Another four-month study, however, showed no improvement in ADHD symptoms

with DHA supplementation (345 mg daily) compared to placebo,48 and a two-month

study in which 3600 mg of DHA were administered weekly also produced negative

results.49 “Treatment of ADHD with fatty acids deserves further

investigation, but careful attention should be paid as to which fatty acid(s)

is used,â€

concluded Japanese investigators who conducted the latter study.49

A prominent investigator in this field, Dr. Alex Richardson of the University

Lab of Physiology and Mansfield College in Oxford, UK, recently noted that

both omega-3 and omega-6 polyunsaturated fatty acids are crucial to brain

development and function, and that modern diets in developed countries often

lack

sufficient omega-3 polyunsaturated fatty acids.50

“Increasing evidence …indicates that [polyunsaturated fatty acid]

deficiencies or imbalances are associated with childhood developmental and

psychiatric

disorders including ADHD,†he writes. “Preliminary evidence from controlled

trials also suggests that dietary supplementation with [polyunsaturated

fatty acids] might help in the management of these kinds of childhood

behavioral

and learning difficulties.â€50

Phosphatidylserine is a phospholipid nutrient related to fatty acids. Its

structure combines an amino acid component and a fatty acid component. Like

essential fatty acids, phosphatidylserine is vital to normal functioning of

neurotransmitter systems, brain metabolism, connections between brain cells, and

fluidity of the brain cell membrane.51 It may also help lower cortisol levels,

which are increased in conditions of chronic stress.52

ADHD, dyslexia, and certain behavioral disorders in children are referred to

as “phospholipid disorders.â€53 Future research should help clarify

phosphatidylserine’s role in the nutritional treatment of ADHD.

Brain Biochemistry Maps Offer Clues

A new technique related to magnetic resonance imaging (MRI) is proton

magnetic resonance spectroscopy (1H-MRS), which reveals important information

about

chemical compounds in different brain areas.

Recent studies using 1H-MRS suggest that choline, creatine, glutamate, and

other specific compounds may play a role in ADHD. Choline is one of the

building blocks of acetylcholine, an important neurotransmitter involved in

memory.

Glutamate and glutamine are amino acids involved in the production of GABA

(gamma-aminobutyric acid), a neurotransmitter that inhibits certain nerve

impulses and may affect hyperactivity.

In one study, 1H-MRS analysis showed that children with inherited and

structural features linked to poor memory had lower concentrations of

creatine-phosphocreatine and choline-containing compounds, whereas creatine and

N-acetyl

aspartate were associated with good memory, reflecting differences in energy

metabolism in the frontal lobes of the brain.54

Paradoxically, however, a 1H-MRS study of ADHD showed a mild increase in the

ratio of choline to creatine on one side of the striatum, a deep brain region

in which about one quarter of the nerve cells were lost or severely

dysfunctional. The investigators concluded that neurotransmission involving

acetylcholine was mildly hyperactive.55

In another 1H-MRS study, eight children with ADHD but without learning

disabilities had increased glutamate-to-glutamine ratios in both frontal areas,

and increased N-acetyl aspartate and choline in the right frontal area, compared

to eight controls.56

Investigators from Venezuela found diminished blood levels of the amino acids

glutamine and phenylalanine in ADHD patients. They hypothesized that this

imbalance could cause alterations in amino acid metabolism and transport to the

brain, which might alter central nervous system function. Their findings

support the theory that ADHD represents a disorder of the inhibitory

neurotransmission system.57

Choline supplementation is theoretically more beneficial for diminished

memory and learning than for other ADHD symptoms such as hyperactive, impulsive

behavior. Choline has an unpleasant taste, so children may prefer DMAE

(dimethylaminoethanol), a supplement that increases brain levels of choline.58

DMAE

may speed up production of acetylcholine in the brain, and it has been used

in ADHD treatment for reduced attention span, learning and reading problems,

hyperactivity, and poor coordination.59,60

Acetyl-L-Carnitine Boosts Brain Energy

Abnormalities in energy production and fatty acid oxidation may underlie

behavioral and brain changes in ADHD. Acetyl-L-carnitine helps transport fatty

acids into the mitochondria, the energy-producing powerhouses within each cell.

This process boosts energy production when the fatty acids are burned, or

oxidized, as cellular fuel.61

In a rat model of ADHD, treatment with acetyl-L-carnitine reduced impulsive

behavior and increased levels of the neurotransmitter noradrenaline in the

medial frontal cortex.62 “[Acetyl-L-carnitine], a drug devoid of

psychostimulant

properties, may have some beneficial effects in the treatment of ADHD

children,†according to Italian investigators.

In a randomized, controlled study, 13 of 24 boys treated with carnitine

improved significantly (by 20-65%) in behavior at home and school.63

“Treatment

with carnitine significantly decreased the attention problems and aggressive

behavior in boys with ADHD,†reported researchers in the Netherlands.

Effects of Vitamins and Minerals

Vitamins and minerals may be helpful in some ADHD patients because they act

as cofactors that facilitate the actions of enzymes involved in energy

metabolism and neurotransmitter synthesis.9,64 B vitamins are needed to burn

carbohydrates as fuel and support neurotransmitter synthesis and

nerve-insulating

myelin.65 Vitamin B6 supplementation may help boost low levels of serotonin in

hyperactive children.66

Zinc is an important cofactor for the production of neurotransmitters and the

metabolism of dopamine and fatty acids. Alterations in these biochemicals

may play a role in the pathophysiology of ADHD.64 Zinc deficiency in children

with ADHD is associated with decreased blood levels of fatty acids.67 The

relationship between zinc and fatty acids was demonstrated in a study showing

that evening primrose oil, a supplement rich in GLA, improved school behavior

in

children with ADHD but only in those who were deficient in zinc.64

In a well-controlled, randomized study of 400 children with ADHD, zinc

sulfate was statistically superior to placebo in reducing symptoms of

hyperactive

or impulsive behavior and impaired socialization. Patients most likely to

benefit from zinc were older and more overweight, and had low levels of zinc

and

fatty acids.68

Children with ADHD treated with Ritalin® for six weeks had better behavioral

ratings by teachers and parents when they also received zinc sulfate (55

mg/day) compared to children who received Ritalin® and a placebo.69

Magnesium levels in blood plasma and red cells may be low in patients with

ADHD. Supplementation with magnesium, alone or in combination with vitamin B6,

may reduce hyperactivity.70,71

In a recent study, iron deficiency, which causes abnormalities in dopamine

neurotransmission, was present in 84% of 53 children with ADHD.72 Because

measures of iron deficiency were correlated with more severe ADHD symptoms,

French

researchers concluded, “low iron stores contribute to ADHD and . . . ADHD

children may benefit from iron supplementation.â€

Herbs May Improve Brain Circulation

In those with ADHD, blood flow and energy metabolism are decreased in

specific brain regions, notably the prefrontal cortex and striatum.3 While

Ritalin®

increases blood flow in these areas,73 certain herbs may achieve this benefit

without dangerous side effects. These include ginseng, ginkgo biloba,

ginger, and other “hemorheological†agents used in traditional Chinese

medicine to

dilate blood vessels and reduce blood viscosity.26,74

In a preliminary study, 36 children with ADHD were treated for four weeks

with American ginseng (200 mg/day) and ginkgo biloba (50 mg/day). Between one

third and three quarters of the children experienced reduced anxiety, shyness,

social problems, hyperactivity, and/or impulsiveness.75

A few case studies suggest that some ADHD patients may benefit from

pycnogenol, an extract of French maritime pine bark that is a potent

antioxidant and

supports blood vessel dilation.76 Sedating herbs such as passionflower,

valerian, or lemon balm may help control symptoms of hyperactivity in children

with ADHD.9

Combination Therapy May Hold the Key

Exciting advances in understanding the origins and mechanisms of ADHD

suggest multiple strategies for treatment with nutritional supplements. ADHD is

characterized by disrupted communication networks in the brain and local

abnormalities in neurotransmitter systems, blood flow, and energy metabolism.

Moreover, ADHD is aggravated by deficiencies of vitamins, minerals, and

essential

fatty acids.

Time and future research will tell which nutrients—and in which combinations

and dosages—are best suited to treating ADHD symptoms. At present, omega-3

fatty acids, acetyl-L-carnitine, choline, B vitamins, zinc, magnesium, and

herbal therapies that improve blood flow appear especially promising.

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