Omega-3 Omega-3 Supplementation Supplementation

and ADHD: A Reviewand ADHD: A ReviewJennifer M. AkullianJennifer M. Akullian

ADHD: Attention Deficit ADHD: Attention Deficit Hyperactivity DisorderHyperactivity Disorder

Facts about ADHD:Facts about ADHD: One of the most One of the most prevalent prevalent psychiatric psychiatric illnesses of illnesses of childrenchildren

Virtually unheard Virtually unheard of and unnamed only of and unnamed only 50-years ago50-years ago

Among most Among most treatable of treatable of psychiatric psychiatric disordersdisorders

70 percent of those 70 percent of those diagnosed use diagnosed use pharmacology to pharmacology to reduce reduce incapacitating incapacitating

Impact:Impact:

- 32-40% of students with - 32-40% of students with ADHD drop out of schoolADHD drop out of school

- Only 5-10% will complete - Only 5-10% will complete collegecollege

- 50-70% have few or no - 50-70% have few or no friendsfriends

- 70-80% will under-- 70-80% will under-perform at workperform at work

- 40-50% will engage in - 40-50% will engage in antisocial activitiesantisocial activities

- More likely to - More likely to experience teen pregnancy & experience teen pregnancy & sexually transmitted diseasessexually transmitted diseases

- Have more accidents & - Have more accidents & speed excessivelyspeed excessively

- Experience depression & - Experience depression & personality disorders personality disorders 

Prevalence:Prevalence:

3-6 % of school aged children (in some cities reaching 3-6 % of school aged children (in some cities reaching 10-15%)10-15%)

1990: 902,000 US children diagnosed with ADHD1990: 902,000 US children diagnosed with ADHD 1993: > 2 million US children diagnosed with ADHD1993: > 2 million US children diagnosed with ADHD Currently as many as 4 million carry the ADHD diagnoses Currently as many as 4 million carry the ADHD diagnoses (30-50% child mental health service referrals)(30-50% child mental health service referrals)

Diagnosis and Progression Diagnosis and Progression of ADHD:of ADHD:

6 or more 6 or more inattentive inattentive symptomssymptoms

6 of more 6 of more hyperactive/impulhyperactive/impulsive symptomssive symptoms

6 or more of both6 or more of both symptoms persist symptoms persist for 6 months or for 6 months or moremore

DSM-IV Diagnosis of DSM-IV Diagnosis of ADHD:ADHD:

symptoms must appear before the symptoms must appear before the age of 7age of 7

symptoms were present before age 7symptoms were present before age 7 symptoms present in 2 or more symptoms present in 2 or more settingssettings

impairment in social, academic or impairment in social, academic or occupational functioningoccupational functioning

symptoms must not be secondary to symptoms must not be secondary to another disorderanother disorder

Attention Deficit Attention Deficit Hyperactivity Disorder Hyperactivity Disorder

Three essential varieties: Three essential varieties: characterized by inattention, characterized by inattention, another by hyperactivity, another by hyperactivity, and third combines the bothand third combines the both

Inattention:Inattention: Often fails to give a close Often fails to give a close

attention to details or attention to details or makes careless mistakes in makes careless mistakes in schoolwork, work, or other schoolwork, work, or other activities.activities.

Often has difficulty Often has difficulty sustaining attention in sustaining attention in tasks or play activities.tasks or play activities.

Often does not seem to Often does not seem to listen when spoken to listen when spoken to directly.directly.

Often does not follow Often does not follow through on instructions and through on instructions and fails to finish schoolwork, fails to finish schoolwork, chores, or duties in the chores, or duties in the workplace (not due to being workplace (not due to being obstructive or failure to obstructive or failure to understand instructions).understand instructions).

Often has difficulty Often has difficulty organizing tasks and organizing tasks and activities.activities.

Often avoids, dislikes, Often avoids, dislikes, or is reluctant to or is reluctant to engage in tasks that engage in tasks that require sustained require sustained mental effort (such as mental effort (such as schoolwork or schoolwork or homework).homework).

Often loses things Often loses things necessary for tasks or necessary for tasks or activities (e.g., toys, activities (e.g., toys, school assignments, school assignments, pencils, books, or pencils, books, or tools).tools).

Is often easily Is often easily distracted by distracted by extraneous stimuli.extraneous stimuli.

Is often forgetful in Is often forgetful in daily activities.daily activities.

Hyperactivity-Hyperactivity-Impulsitivity:Impulsitivity:

Often fidgets with hands or feet or squirms in seat.Often fidgets with hands or feet or squirms in seat. Often leaves his or her seat in the classroom or in Often leaves his or her seat in the classroom or in

other situations in which remaining seated is expected.other situations in which remaining seated is expected. Often runs about or climbs excessively in situations in Often runs about or climbs excessively in situations in

which it is inappropriate (in adolescents or adults, they which it is inappropriate (in adolescents or adults, they might be limited to subjective feelings of restlessness).might be limited to subjective feelings of restlessness).

Often has difficulty playing or engaging in leisure Often has difficulty playing or engaging in leisure activities quietly.activities quietly.

Is often on the go or often acts as if driven by a motor.Is often on the go or often acts as if driven by a motor. Often talks excessively.Often talks excessively. Often blurts out answers before questions have been Often blurts out answers before questions have been

completed.completed. Often has difficulty awaiting turn.Often has difficulty awaiting turn. Often interrupts or intrudes on others (American Often interrupts or intrudes on others (American

Psychiatric Association 1994).Psychiatric Association 1994).

ADHD Co-morbidity:ADHD Co-morbidity:1.1. Learning DisordersLearning Disorders2.2. Oppositional Defiant DisorderOppositional Defiant Disorder3.3. Other Conduct DisordersOther Conduct Disorders4.4. DepressionDepression

Pharmacological Options:Pharmacological Options:StimulantsStimulants

Ritalin-one dose lasts up to 4 Ritalin-one dose lasts up to 4 hourshours

Metadate – Ritalin – once a Metadate – Ritalin – once a day lasts up to 12 hrsday lasts up to 12 hrs

Focalin – New Ritalin Focalin – New Ritalin derivative lasts up to 4 hoursderivative lasts up to 4 hours

Attenade-Newest Ritalin Attenade-Newest Ritalin derivative-lasts 6 hoursderivative-lasts 6 hours

Concerta- once a day lasts up Concerta- once a day lasts up to 12 hoursto 12 hours

Dexedrine-last 4 hoursDexedrine-last 4 hours Adderall- New Dexedrine - Adderall- New Dexedrine -

once or twice a day (lasts once or twice a day (lasts longer than Ritalin)longer than Ritalin)

Cylert-requires liver function Cylert-requires liver function testing due to history of testing due to history of hepatic failure with children hepatic failure with children who were on itwho were on it

Pharmacological Options:Pharmacological Options: Stimulant and Pharmacological Stimulant and Pharmacological

Alternative Intervention ApproachesAlternative Intervention Approaches Catapres[R]Catapres[R] Tenex[R]Tenex[R] Parent TeamParent Team Home ModificationsHome Modifications Parent-Teacher TeamParent-Teacher Team Consistency of parent-teacher-Consistency of parent-teacher-

doctor team doctor team Food allergies, diet and sleep Food allergies, diet and sleep

regulationregulation AND . . .AND . . .

Pharmacological Options: Pharmacological Options: Stimulant and Pharmacological Stimulant and Pharmacological

Alternative Intervention ApproachesAlternative Intervention Approaches

Essential Fatty Acid Essential Fatty Acid Supplementation Supplementation

Neurobiology of ADHD:Neurobiology of ADHD:

Central pathological deficits of ADHD Central pathological deficits of ADHD are linked to several specific brain regions:are linked to several specific brain regions: frontal corticalfrontal cortical frontal-basal gangliafrontal-basal ganglia

Neurotransmitters:Neurotransmitters: alteration in dopaminergic alteration in dopaminergic and nonadrenergic transmitter functionsand nonadrenergic transmitter functions

Dietary Supplementation Dietary Supplementation and ADHDand ADHD

Multiple vitamin-mineral Multiple vitamin-mineral supplements:supplements:

B Vitamins in CombinationB Vitamins in Combination Vitamin B6Vitamin B6 IronIron ZincZinc

B Vitamins in B Vitamins in CombinationCombination Commonly grouped as the vitamin B Commonly grouped as the vitamin B

complex are the following water-complex are the following water-soluble vitamins:soluble vitamins:

Thiamine (vitamin B 1 or Thiamine (vitamin B 1 or antiberiberi factor) is a antiberiberi factor) is a necessary ingredient for the necessary ingredient for the biosynthesis of the coenzyme biosynthesis of the coenzyme thiamine pyrophosphate; in this thiamine pyrophosphate; in this latter form it plays an important latter form it plays an important role in carbohydrate metabolism. role in carbohydrate metabolism.

Riboflavin (vitamin B 2 or Riboflavin (vitamin B 2 or lactoflavin) is used to synthesize lactoflavin) is used to synthesize two coenzymes that are associated two coenzymes that are associated with several of the respiratory with several of the respiratory enzymes of plants and animals enzymes of plants and animals (including humans) and is (including humans) and is therefore important in biochemical therefore important in biochemical oxidations and reductions. oxidations and reductions.

The B vitamins niacin (nicotinic The B vitamins niacin (nicotinic acid) and niacinamide acid) and niacinamide (nicotinamide) are commonly known (nicotinamide) are commonly known as preventives of pellagra , which as preventives of pellagra , which in 1912 was shown by American in 1912 was shown by American medical researcher Joseph medical researcher Joseph Goldberger to result from a Goldberger to result from a dietary deficiency. dietary deficiency.

The molecular structure of vitamin B The molecular structure of vitamin B 12 (cobalamin), the most complex of 12 (cobalamin), the most complex of all known vitamins Vitamin B 12 and all known vitamins Vitamin B 12 and closely related cobalamins are closely related cobalamins are necessary for folic acid to fulfill necessary for folic acid to fulfill its role; both are involved in the its role; both are involved in the synthesis of proteins. synthesis of proteins.

Pantothenic acid, another B vitamin, Pantothenic acid, another B vitamin, is present in perhaps all animal and is present in perhaps all animal and plant tissues, as well as in many plant tissues, as well as in many microorganisms. Good sources of it microorganisms. Good sources of it include liver, kidney, eggs, and include liver, kidney, eggs, and dairy products. dairy products.

Biotin is a B vitamin that functions Biotin is a B vitamin that functions as a coenzyme in the metabolism of as a coenzyme in the metabolism of carbohydrates, fats, and amino carbohydrates, fats, and amino acids. Although it is vitally acids. Although it is vitally necessary to the body, only necessary to the body, only exceedingly small quantities are exceedingly small quantities are needed, and since biotin is needed, and since biotin is synthesized by intestinal bacteria, synthesized by intestinal bacteria, naturally occurring biotin naturally occurring biotin deficiency disease is virtually deficiency disease is virtually unknown unknown

Folic acid (pteroylglutamic acid, Folic acid (pteroylglutamic acid, folacin, or vitamin B 9 ) occurs folacin, or vitamin B 9 ) occurs abundantly in green leafy abundantly in green leafy vegetables, fruits (e.g., apples and vegetables, fruits (e.g., apples and oranges), dried beans, avocados, oranges), dried beans, avocados, sunflower seeds, and wheat germ. sunflower seeds, and wheat germ.

Vitamin B6 (pyridoxine)Vitamin B6 (pyridoxine)

Pyridoxine, pyridoxal, and pyridoxamine make up the vitamin B 6 Pyridoxine, pyridoxal, and pyridoxamine make up the vitamin B 6 group. They all combine with phosphorus in the body to form the group. They all combine with phosphorus in the body to form the coenzyme pyridoxal phosphate, which is necessary in the coenzyme pyridoxal phosphate, which is necessary in the metabolism of amino acids, glucose, and fatty acids. The best metabolism of amino acids, glucose, and fatty acids. The best sources of B 6 vitamins are liver and other organ meats, corn, sources of B 6 vitamins are liver and other organ meats, corn, whole-grain cereal, and seeds. Deficiency can result in central whole-grain cereal, and seeds. Deficiency can result in central nervous system disturbances. The recommended dietary allowance nervous system disturbances. The recommended dietary allowance for adults is 2.0 to 2.2 mg for men and 2 mg for women. for adults is 2.0 to 2.2 mg for men and 2 mg for women. Additional doses are required in pregnancy and by those taking Additional doses are required in pregnancy and by those taking oral contraceptives or the tuberculosis drug izoniazid. Severe oral contraceptives or the tuberculosis drug izoniazid. Severe nerve damage has been reported from megadoses. nerve damage has been reported from megadoses.

IronIron

metallic chemical element; symbol Fe. Because iron metallic chemical element; symbol Fe. Because iron is a component of hemoglobin, a red oxygen-is a component of hemoglobin, a red oxygen-carrying pigment of the red blood cells of carrying pigment of the red blood cells of vertebrates, iron compounds are important in vertebrates, iron compounds are important in nutrition; one cause of anemia is iron deficiency. nutrition; one cause of anemia is iron deficiency.

ZincZinc

metallic chemical element; symbol Zn. Zinc is metallic chemical element; symbol Zn. Zinc is essential to the growth of many kinds of organisms, essential to the growth of many kinds of organisms, both plant and animal. It is a constituent of both plant and animal. It is a constituent of insulin, which is used in the treatment of diabetes. insulin, which is used in the treatment of diabetes. Chief sources of zinc are the sulfide ore, zinc Chief sources of zinc are the sulfide ore, zinc blende, or sphalerite (called also blende or “black blende, or sphalerite (called also blende or “black Jack” ); zincite, an oxide; calamine, a silicate; and Jack” ); zincite, an oxide; calamine, a silicate; and smithsonite, the zinc carbonate smithsonite, the zinc carbonate

Essential Fatty Acids: Essential Fatty Acids: What are they?What are they?

LALA Linoleic Acid :Linoleic Acid : This EFA is called This EFA is called Linoleic Acid (LA) and is poly-Linoleic Acid (LA) and is poly-unsaturated. You will see that LA is an unsaturated. You will see that LA is an 18 carbon chain fatty acid with two 18 carbon chain fatty acid with two double bonds in the middle and is missing double bonds in the middle and is missing four hydrogen atoms, all on one side.four hydrogen atoms, all on one side.

ALAALA Alpha Linolenic Acid: Alpha Linolenic Acid: is also polyunstaturated is also polyunstaturated with an 18 carbon fatty acid with three double with an 18 carbon fatty acid with three double bonds at the 3, 6, and 9 carbon positions. bonds at the 3, 6, and 9 carbon positions.  LNA is missing 6 hydrogen atoms, again all  LNA is missing 6 hydrogen atoms, again all from one side. Because of the first double from one side. Because of the first double bond occurring at the 3rd carbon atombond occurring at the 3rd carbon atom

Essential Fatty Acid Essential Fatty Acid Metabolism:Metabolism:

Colquhoun I, Bunday S. A lack of essential Colquhoun I, Bunday S. A lack of essential fatty acids as a possible cause of fatty acids as a possible cause of

hyperactivity in children. Med Hypotheses hyperactivity in children. Med Hypotheses 1981;7:673-679.1981;7:673-679.

Mitchell EA, Aman MG, Turbott SH, et al. Mitchell EA, Aman MG, Turbott SH, et al. Clinical characteristics and serum essential Clinical characteristics and serum essential fatty acid levels in hyperactive children. fatty acid levels in hyperactive children.

Clin Pediatr 1987;26:406-411.Clin Pediatr 1987;26:406-411.

Stevens LJ, Zentall SS, Deck JL, et al. Stevens LJ, Zentall SS, Deck JL, et al. Essential fatty acid metabolism in boys with Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am attention-deficit hyperactivity disorder. Am

J Clin Nutr 1995;62:761-768.J Clin Nutr 1995;62:761-768.

Aman MG, Mitchell EA, Turbot SH. The effects Aman MG, Mitchell EA, Turbot SH. The effects of essential fatty acid supplementation by of essential fatty acid supplementation by Efamol in hyperactive children. J Abnorm Efamol in hyperactive children. J Abnorm

Child Psycho 1987;15:75-90.Child Psycho 1987;15:75-90.

Arnold LE, Kleycamp D, Votolato NA, et al. Arnold LE, Kleycamp D, Votolato NA, et al. Gamma-linolenic acid for attention deficit Gamma-linolenic acid for attention deficit hyperactivity disorder: Placebo-controlled hyperactivity disorder: Placebo-controlled comparison to D-amphetamine. Biol Psychiatry comparison to D-amphetamine. Biol Psychiatry

1989;25:222-228.1989;25:222-228.

Role of Nutrient Role of Nutrient Deficiency in ADHD Deficiency in ADHD

A synapse: Omega 3s may make it A synapse: Omega 3s may make it easiereasier

for signals to cross the gap between for signals to cross the gap between brain cells.brain cells.

Management Options:Management Options:

Psychostimulant Psychostimulant PharmaceuticalsPharmaceuticals

Environmental/Environmental/Social Interaction Social Interaction ChangesChanges

Nutrient and Nutrient and Essential Fatty Essential Fatty Acid Acid SupplementationSupplementation

ADHD in the Future:ADHD in the Future: Common finding in all research = MORE RESEARCH Common finding in all research = MORE RESEARCH NEEDED!!!!NEEDED!!!!

Reasons for the lower proportions of LC-PUFA’s Reasons for the lower proportions of LC-PUFA’s in hyperactive children is not clear.in hyperactive children is not clear.

Specific proteins and genes involved have been Specific proteins and genes involved have been relatively ill-defined.relatively ill-defined.

Controversy still surrounds both the Controversy still surrounds both the identification and management of these identification and management of these conditionsconditions

ADHD etiology is recognized as being complex ADHD etiology is recognized as being complex and multifactor; however, little progress has and multifactor; however, little progress has yet been made in elucidating predisposing yet been made in elucidating predisposing factors at the biological level.factors at the biological level.

Current studies in line with original proposal Current studies in line with original proposal that ADHD involves difficulty in the synthesis that ADHD involves difficulty in the synthesis of HUFA of HUFA

Omega-3 supplementation has shown promising Omega-3 supplementation has shown promising effects in recent studies.effects in recent studies.

Questions: Questions: