Articles

Attention Deficit (Hyperactivity) Disorder (ADD/ADHD)

Introduction

Attention deficit hyperactivity disorder (ADHD) is one of the most frequently diagnosed childhood psychiatric condition. (1) One in every four children with ADHD has a biologic parent with a current or prior diagnosis of ADHD. In addition, children with fetal alcohol syndrome, lead poisoning, meningitis, or genetic resistance to thyroid hormone have a higher incidence of ADHD symptomatology. (2) , (3) Although not a primary cause, a positive association exists between family environment adversity factors (severe marital discord, low social class, large family size, paternal criminality, maternal mental disorder, foster care) and ADHD. (4) , (5)

Prior to 1980, a child presenting with short attention span, impulsivity, and hyperactivity was diagnosed with Minimal Brain Dysfunction. However, this diagnosis was controversial because clinicians could not consistently identify specific neurologic deficiencies. In 1980, the American Psychiatric Association made a decision to de-emphasize neurological dysfunction as a basis for diagnosis, and instead, use behavior. The syndrome was called ADD (Attention Deficit Disorder) with or without Hyperactivity. Hyperactivity has now been defined as an essential component and the name has been changed to ADHD.

Although brain studies show no definitive pathophysiologic markers of ADHD, a dysequilibratory disorder of the frontal-neostriatial dopamine systems with widely varying states of arousal has been proposed. Children with ADHD tend to have phasic outbursts of activity and inactivity, resulting in insufficient alertness during dull and repetitive tasks, and overarousal at other times, resulting in ineffective performance. Stimulant drugs may serve as a homeostat to stabilize arousal and thereby temper the spontaneous fluctuations that are characteristic of ADHD. (6) , (7) The clinical response with stimulants is not paradoxical and is not diagnostic for ADHD, because asymptomatic children also experience increased attention, decreased motor activity, and improvement on learning tasks when given stimulants.

Onset is typically seen by the age of three, and must be seen by the age of seven. However, the disorder may not require professional attention until the child enters school.

Conventional treatment is often pharmaceutical, but evidence is mounting that many ADHD sufferers can achieve dramatic results with dietary, nutritional, and environmental interventions. Particularly among young children, non-pharmaceutical interventions provide a risk free alternative that can be explored as a first line of treatment. Nutritional interventions include supplementation with magnesium, chromium, and other minerals, elimination of food additives and allergens, and the examining the role of dysbiosis.

Mineral status among those with ADHD has been the subject of several published clinical trials. Deficiencies in magnesium, copper, iron, zinc, and calcium have been identified among children diagnosed with ADHD more often than among "healthy" children. Magnesium deficiency is the most common of the mineral deficiencies associated with ADHD

ADHD may be influenced by dysbiosis. The presence of dysbiotic flora is encouraged by the use of antibiotics, which can destroy "friendly" or probiotic flora normally inhabiting the intestinal mucosa. The average child undergoes multiple courses of antibiotic treatment in the first five years of life, typically without replacement of probiotics. The resulting overgrowth of yeast and other pathogenic flora has been linked to alterations of immune function, food sensitivities, and ADHD. A study reported that high levels of antimetabolites, consistent with fungal or Candida related complex, were identified in the urine of children with ADHD. (8) Supplementing with probiotics is an important measure in preventing and treating dysbiosis and its complications. The judicious use of antibiotics is critical to minimizing dysbiosis, as well as preventing the development of further drug resistant bacteria.

A deficiency in essential fatty acids (EFAs) is being singled out by some as a cause of ADHD. EFAs influence ADHD primarily in two ways: they influence gut permeability and are needed for the proper development of brain tissue. Essential fatty acids are the substrates for prostaglandin synthesis. (9)

Statistic

National Attention Deficit Disorder Association, 1999.

    4-6% of the United States population has ADHD. 1/2 - 2/3 of all children with ADHD will continue to have problems with ADHD as adults. 1/3 of people with ADHD do not have the hyperactive or overactive behavior component. There is a 25-35% chance that if one family member has ADHD another member will also, compared to 4-6% of general population.

Centers for Disease Control, 2004.

    4.5 million children 3-17 years of age (7.4%) had ADHD. Between the ages of 3-17 years, boys were more than twice as likely as girls to have ADHD (10.2% and 4.5%).

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

There are three essential features of ADHD: the first involves a developmentally inappropriate inattention that manifests as failing to finish tasks, not seeming to listen, becoming easily distracted, having difficulty concentrating on school work or sticking to play activities. The second is impulsivity, and often manifests as acting before thinking, shifting excessively from one activity to another, needing much supervision, frequently calling out in class, and difficulty awaiting a turn in games or group activities. The third feature is hyperactivity, which generally involves excessive running about or climbing, difficulty sitting or staying seated, and excessive movement during sleep. (10)

Children with ADHD have difficulty maintaining a consistent direction, seemingly distracted by stimuli that, for most children, are easily organized and filtered. Tasks that require concentration are nearly impossible and cause frustration, resulting in irritability, agitation, and often recklessness. Intelligence among ADHD children is typically normal. ADHD is more prevalent among boys than girls. (11)

Developmentally inappropriate inattention
  • Failing to finish tasks
  • Not seeming to listen
  • Becoming easily distracted
  • Having difficulty concentrating on school work or sticking to play activities
Impulsivity
  • Acting before thinking
  • Shifting excessively from one activity to another
  • Needing much supervision
  • Frequently calling out in class
  • Difficulty waiting a turn in games or group activities
Hyperactivity
  • Excessive running about or climbing
  • Difficulty sitting or staying seated
  • Excessive movement during sleep

Treatment Options

Conventional

The primary factor in the decision to initiate drug treatment is the severity of symptoms, with drug treatment being reserved for those with moderate to severe symptom intensity. The use of methylphenidate, the most commonly prescribed drug for the management of ADHD, has increased 700 percent in the past five years. (12) The use of psychotropic drugs in children should be approached very differently from the way they are used for psychiatric disorders in adults. The child, family, and caregivers need to be familiar with the risks and benefits of drug therapy and alternate non-drug therapies.

Stimulants (methylphenidate, dextroamphetamine, and pemoline) are the most effective drug treatment options. Dosing should be titrated for maximum efficacy and minimum side effects. Disorders comorbid with ADHD will impact drug selection. For example, a child with ADHD plus a depressive or anxiety disorder may require an antidepressant as first line therapy.

Nutritional Supplementation


Omega-3, Omega-6

It has been suggested that a lack of essential fatty acids is a possible cause of hyperactivity in children. It is more likely the result of varying biochemical influences. These children have a deficiency of essential fatty acids (EFA's) either because they cannot metabolize linoleic acid normally, cannot absorb EFA's effectively from the gut, or because their EFA requirements are higher than normal.

Evidence supporting that fatty acids are deficient includes:

    Most of the food constituents, which cause trouble in these children are weak inhibitors of the conversion of EFA's to prostaglandins (PG's). Boys are much more commonly affected than girls, and males are known to have much higher requirements for EFA's than females. A high proportion of these children have abnormal thirst, and thirst is one of the signs of EFA deficiency. Many hyperactive children have eczema, allergies, and asthma, which some reports suggest can be alleviated by EFA's. Many hyperactive children are deficient in zinc, which is required for the conversion of EFA's to PG's. Some of these children are badly affected by wheat and milk, which are known to give rise to exorphins in the gut, which can block conversion of EFA's to PGE1. (13) Children with ADD/ADHD may have yeast metabolites in their urine signaling dysbiosis, subsequent alterations in absorption of nutrients, and a rich antibiotic use history.

Study reported that children with hyperactivity have significantly lower levels of docosahexaenoic acid (DHA), dihomogammalinolenic acid (DGLA), and arachidonic acid (AA) compared to normal controls. (14) , (15)

Some of the physical symptoms reported in ADHD are similar to symptoms observed in essential fatty acid (EFA) deficiency in animals and humans. Researchers report that a subgroup of patients expressing many symptoms similar to those seen in EFA deficiency had lower plasma levels of docosahexaenoic acid and arachidonic acid compared to those with fewer symptoms. Children with low levels of total omega-3 fatty acids exhibited significantly more behavioral problems, temper tantrums, and learning, health, and sleep problems than did those with high proportions of omega-3 fatty acids. (16)


Magnesium

Magnesium is one of the most commonly deficient nutrients in children with attention deficit and hyperactivity disorders. In one study, investigations evaluated 116 children (94 boys and 20 girls), aged 9-12 years, with recognized ADHD. Magnesium levels were determined in blood serum, red blood cells, and in hair with the aid of atomic absorption spectroscopy. Magnesium deficiency was found in 95 percent of those examined, most frequently in hair (77.6 percent), in red blood cells (58.6 percent), and in blood serum (33.6 percent) of children with ADHD. (17)

Another study evaluated 50 hyperactive children, aged 7-12 years, who fulfilled DSM IV criteria for ADHD syndrome, with recognized deficiency of magnesium in the blood (blood serum and red blood cells). In this six-month trial, one group of children took 200mg/day of magnesium while the control group consisted of 25 children with ADHD and magnesium deficiency, who were treated in a standard way, without magnesium preparations. Magnesium supplementation resulted in a significant decrease of hyperactivity compared to their clinical state before supplementation and compared to the control group, which had not been treated with magnesium. (18) Deficiency symptoms include anxiousness, nervousness, restless limbs, and muscle aches. The chief sources of magnesium in the diet are fruits and vegetables.


N-Acetyl Cysteine (NAC)

N-acetyl cysteine is a sulfur-containing amino acid that is an effective agent for chelation and removal of heavy metal toxins from the body. (19) , (20) Studies reveal that exposure to toxic metals such as mercury (21) and lead (22) result in declines in attention and memory, as well as many other negative effects. If patients with ADD/ADHD are found to have elevated levels of toxic metals, N-acetyl cysteine is an effective agent to utilize in a detoxification program.


Bifidobacteria, Lactobacillus acidophilus

Studies report an association between recurrent otitis media infections in infancy and the subsequent development of hyperactivity in a high percentage of these children. (23) The authors of the following study report a positive correlation between an increasing number of otitis media infections in early childhood and the presence and severity of hyperactive behavior. Ninety-four percent of children medicated for hyperactivity had three or more otitis infections, and 69 percent had greater than 10 infections. In comparison, 50 percent of non-hyperactive school-failure patients had three or more infections, and 20 percent had greater than 10 infections. Twenty-two of 28 children (79 percent) known to have more than 10 infections experienced recurrent otitis before one year of age. (24)

The frequent use of antibiotics can result in dysbiosis, a disturbed balance between beneficial and pathologic bacteria in the gastrointestinal tract, leading to a wide variety of health problems. The intestinal tract in a healthy person is predominantly populated with beneficial bacteria. Antibiotics can destroy a large percentage of the beneficial bacteria. If probiotics are not taken following a course of antibiotics, pathological bacteria that are normally present in only small concentrations can compete equally with the few remaining friendly bacteria. If substantial amounts of pathological bacteria proliferate, it is quite possible the toxins excreted from their metabolism can enter the systemic circulation, causing hyperactivity, blood sugar anomalies, malabsorption of nutrients as well as other conditions. Since studies have documented the fact that many children with hyperactivity have had inner ear infections with multiple courses of antibiotics, there is a high probability that most of these children have a disturbed intestinal microflora. Steps can be taken to recolonize the intestinal tract. After cleaning out the GI tract, probiotics should be administered twice daily with meals for a minimum of two to six months in order to recolonize the GI tract with beneficial bacteria.

Herbal Supplementation


Olive Leaf

Olive trees, widely cultivated throughout Mediterranean countries as a source of olives and olive oil, have been traditionally used not only in foods but in health conditions including malaria, infections, cardiovascular diseases and general well-being. (25) The natural antioxidants including oleuropein from the olive tree may play a role in prevention of cardiovascular diseases through a decreased formation of atherosclerotic plaques by inhibiting LDL oxidation. (26)

Olive leaf extract has been reported to be an effective antimicrobial agent against a wide variety of pathogens, including Salmonella typhi, Vibrio parahaemolyticus, and Staphylococcus aureus (including penicillin-resistant strains); Klebsiella pneumonia and Escherichia coli, causal agents of intestinal or respiratory tract infections. (27) The component usually associated with olive leaf’s antimicrobial properties is oleuropein. (28) , (29) Oleuropein has also been reported to directly stimulate macrophage activation in laboratory studies. (30)

Olive leaf extract has antiviral activity, reportedly caused by the constituent calcium elenolate, a derivative of elenolic acid. (31) , (32) Recent laboratory studies in laboratory animals reported hypoglycemic and hypolipidemic activity. (33) , (34) The active constituent was reported to be oleuropein, with a proposed mechanism of action being the potentiation of glucose-induced insulin release, and an increase in peripheral blood glucose uptake.


Kava

Kava has been used for centuries by South Pacific natives. In European phytomedicine, kava has long been used as a safe, effective treatment for mild anxiety states, nervous tension, muscular tension, and mild insomnia. (35) , (36) Studies have reported that kava preparations compare favorably to benzodiazepines in controlling symptoms of anxiety and minor depression, while increasing vigilance, sociability, memory, and reaction time. (37) , (38) Reports are conflicting as to whether kava’s anti-anxiety actions are GABA mediated. (39) , (40) Kavalactones appear to act on the limbic system, in particular the amygdala complex, the primitive part of the brain that is the center of the emotional being and basic survival functions. (41) It is thought that kava may promote relaxation, sleep, and rest by altering the way in which the limbic system modulates emotional processes. Tolerance does not seem to develop with kava use. (42) , (43)


Evening Primrose

Evening primrose oil (EPO) is rich in gamma-linolenic acid, which is an omega-6 fatty acid. (44) , (45) Omega-6 fatty acids reportedly reduce the arachidonic acid cascade and decrease inflammation through inhibiting the formation of inflammatory mediators in this process. Supplementation with essential fatty acids such as EPO has been reported to prevent zinc deficiency, thereby potentially improving immunity. (46) Fatty acids are an important part of normal homeostasis. The human body can produce all but two fatty acids: omega-3 and omega-6 fatty acids. Both must be obtained through the diet or with the use of supplements. Obtaining a balance of these two fatty acids is essential. Essential fatty acids are needed for building cell membranes and are precursors for production of hormones and prostaglandins. Modern diets tend to be lacking in quality sources of fatty acids.


Grapefruit Seed

Grapefruit seed extract has been reported to be a broad spectrum antimicrobial both in vitro and in vivo. Studies indicate that the antimicrobial activity of grapefruit seed extract exists in the cytoplasmic membrane of the invading bacteria, where the uptake of amino acids is prevented. There is disorganization of the cytoplasmic membrane and leakage of low molecular weight cellular contents, ultimately resulting in inhibition of cellular respiration and death. (47)

Grapefruit seed extract also inhibits the growth of H. pylori and C. jejuni, both causative agents in gastrointestinal ulcers. (48) By inhibiting causative agents of bowel dysbiosis (the imbalance of normal bacterial flora in the GIT) including Candida sp. in vivo, grapefruit seed extract is a useful agent in maintaining bowel integrity. (49) In this human study, an improvement in constipation, flatulence, abdominal distress, and night rest were noticed after four weeks of therapy. Many clinicians are now recognizing the importance of maintaining homeostasis of the microflora in health and disease. (50)


Bacopa

Bacopa or water hyssop, is a plant used since approximately the sixth century A.D. in the traditional Ayurvedic Medical System of India as an extract with cognition-enhancing benefits. Termed "Brahmi" in the Hindu language Sanskrit, bacopa is the foremost tonic for the nervous system in Ayurvedic medicine. It has been traditionally used for epilepsy, mental illness, and to improve memory and mental capacities. (51) The saponin compounds (bacosides) are attributed with the capability to enhance nerve impulse transmission and thereby strengthen memory and general cognition. Bacopa was reported to increase learning ability in laboratory animals. (52) Clinically, bacopa has been reported to be a useful agent for improving intellectual behavior in children. In adults, bacopa has been reported to be effective in reducing anxiety levels, thereby allowing improved brain functioning in terms of memory enhancement and elevated mental performance. (53)

Bacopa is also reported beneficial in children. Bacopa is still given in India to school age children for improving intellectual behavior. A single-blind trial in India was conducted to study the effects of bacopa on children (ages 6-8) and learning behavior. (54) Maze learning improved, as did immediate memory and perception and the reaction/performance times. Based on these findings, bacopa may be a potential agent in ADHD therapy.

Homeopathic

Agaricus muscarius

Typical Dosage: 6X or 6C, 30X or 30CDifficulty in learning; Nervous children; Aversion to mental tasks

Baryta carbonica

Typical Dosage: 6X or 6C, 30X or 30CPhysically and intellectually backward children, anxiousness; Aversion to play; Poor memory; Inattention to studies

Hyoscyamus niger

Typical Dosage: 6X or 6C, 30X or 30CInsomnia and nightmares; Fearful; Very talkative

Stramonium

Typical Dosage: 6X or 6C, 30X or 30CVery restless; Impulsive; Talkative; Sometimes hysterical; Obstinate; Uncontrolled fury

Tarentula hispana

Typical Dosage: 12CIrritable and moody; Constantly moving; Headaches; Indifference; Anger; Poor memory

Aromatherapy

Aromatherapy for ADD/ADHD

Aromatherapy may prove useful in ADD/ADHD by promoting relaxation to an individual who is over-stimulated and may also assist in promoting concentration.

Relaxation
To promote relaxation, the following oils may be mixed together and then added to a bath:

  • Basil (Osimum basilicum) 3 to 5 drops
  • Bergamot (Citrus bergamia) 3 to 5 drops
  • Chamomile (Matricaria chamomilla) 2 to 4 drops
  • Lavender (Lavendula augustifolia) 2 to 3 drops

Concentration
To promote concentration, Basil oil (Osimum basilicum) has been used in either a room diffuser or by simply inhaling the oil directly periodically through out the day. Caution should be exercised when working directly with concentrated oils as burns may occur.

Caution: Essential Oil therapies should not be used during pregnancy or lactation and should always be used under the direction of an experienced aromatherapist.

Diet & Lifestyle

The effect of diet on children with hyperactivity disorder has been the subject of debate for over 30 years. During the 1960's, Dr. Benjamin Feingold, a California pediatrician, studied the effects of a low salicylate diet in the treatment of ADHD after observing an exacerbation of symptoms among hyperactive children when they ate salicylate-containing foods. Feingold’s observations led to a controlled clinical trial, which demonstrated that in addition to artificial colors and preservatives (which contain high amounts of salicylates), 90 percent of the ADHD children in the study had additional food intolerances. (55) The most common allergenic foods among children have been identified as cow’s milk, corn, wheat, soy, peanuts, and eggs. Additional "problem foods" have been identified. An experimental diet among preschool boys with sleep problems and hyperactive behavior demonstrated that after removal of artificial flavors and colors, dairy products, caffeine, MSG, and chocolate, over 50 percent of the children improved. (56) One study compared the treatment success of dietary restriction with methylphenidate and found that while 44 percent responded to the drug treatment, 24 percent had equal success with dietary modifications alone. (57)

The Lancet published a study in 1985, which reported that 79 percent of hyperactive children improved when suspect foods were eliminated from their diets, only to become worse again when the foods were reintroduced. Artificial colorings and flavorings were the most serious culprits; sugar was also found to have a noticeable effect. The New York public school system initiated an experimental design in which sugar, food additives, and preservatives were gradually eliminated from the school cafeterias. During the four-year period of dietary modifications, the mean academic performance percentile rating increased from 39.2 percent to 54.9 percent. (58) Additives include artificial flavors and colors, preservatives including BHA and BHT, and sugars that can be identified in the forms of sucrose, fructose, corn syrup, mannitol, sorbitol, and other sweeteners.

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for the diagnosis and treatment of ADD/ADHD. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Amino Acids

Deficiencies or imbalances in amino acids can indicate fundamental reasons for hyperactivity, fatigue, pain, insomnia, depression, poor digestion, and other symptoms. For example, tryptophan levels can have direct implications in ADD/ADHD, since tryptophan is a precursor for serotonin production, and serotonin levels are often implicated in the sleep pattern disturbances common in ADD/ADHD.

Mineral Analysis

The evaluation of essential and/or toxic elements can be of use in the evaluation of ADD/ADHD. Toxic elements, especially lead, mercury, and cadmium, have been implicated in syndromes with fatigue as a primary symptom. Zinc is necessary in fatty acid synthesis, and zinc deficiency is common in ADD/ADHD. (59) Magnesium and chromium status have been implicated as well.

Allergy and Food Sensitivity Response Assessment

Allergies may have a significant correlation with ADD/ADHD. (60)

Dysbiosis Metabolic Markers

Several studies report the presence of yeast metabolites in the urine of children with ADD/ADHD. This would be of special interest for individuals with a strong history of antibiotic use (ear infections, sore throats).

Fatty Acids

Individuals with ADHD commonly demonstrate disordered fatty acid metabolism, (61) with some characteristic low values in those essential fatty acids critical to neurotransmitter function. (62)

Clinical Notes

Salicylates: Dr. Benjamin Finegold is a California pediatrician who popularized the Finegold diet, which attempted to eliminate coloring agents, flavoring agents, preservatives, and many other artificial agents from the diet. Although somewhat controversial, many children reportedly improved. Dr. Finegold also found that some hyperactive children had a biochemical hypersensitivity to salicylates, which are aspirin-like substances that are found in many foods, food dyes, and medicines.

Full Spectrum Light: Dr. John Ott reported doing time lapse photography of a hyperactive child in a Sarasota, Florida elementary school. Over the weekend, the standard cool white fluorescent lights in this classroom were changed from their original tubes to full spectrum fluorescent lights. Within a week after the new full spectrum lights had been installed, the films revealed a reduction in the amount of hyperactive behavior with the new full spectrum lighting. (63)

Biofeedback: Numerous trials support the use of biofeedback as a retraining tool for brain patterning. Look to the diet that is high in refined sugar, a history of antibiotic use, and the potential for heavy metal toxicity as keys to case development. Nutrient repletion will many times provide immediate improvement, but it is still necessary to move up the causal chain.

References

  1. View Abstract: McGough JJ, McCracken JT. Assessment of attention deficit hyperactivity disorder: a review of recent literature. Curr Opin Pediatr. Aug2000;12(4):319-24.
  2. View Abstract: Cantwell CB. Attention Deficit Disorder: A review of the last 10 years. J Am Acad Child Adolesc Psychiatry. 1996;35:978-987.
  3. Zametkin AJ. Attention Deficit Disorder: Born to be hyperactive? Grand rounds at the Clinical Center of the National Institutes of Health. JAMA. 1995;16:174-184.
  4. View Abstract: Cantwell CB. Attention Deficit Disorder: A review of the last 10 years. J Am Acad Child Adolesc Psychiatry. 1996;35:978-987.
  5. View Abstract: Biederman J. Family-environmental risk factors for attention deficit hyperactivity disorder. Arch Gen Psychiatry. 1995;52:464-470.
  6. View Abstract: Cantwell CB. Attention Deficit Disorder: A review of the last 10 years. J Am Acad Child Adolesc Psychiatry. 1996;35:978-987.
  7. View Abstract: Pliszka SR, McCracken JT, Maas JW. Catecholamines in Attention Deficit Hyperactivity Disorder: Current Perspectives. J Am Acad Child Adolesc Psychiatry. 1996;35:264-272.
  8. View Abstract: Hanna GL, Ornitz EM, Hariharan M. Urinary catecholamine excretion and behavioral differences in ADHD and normal boys. J Child Adolesc Psychopharmacol. 1996;6(1):63-73.
  9. View Abstract: Burgess JR, Stevens L, Zhang W, Peck L. Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr. Jan2000;71(1 Suppl):327S-30S.
  10. DiPiro JT, et al. Pharmacotherapy, A Pathophysiologic Approach, 4th edition. Stamford, Conn: Appleton & Lange; 1999:1046-1049.
  11. National Institutes of Health, National Institute of Mental Health ADHD brochure. NIH Publications #96-3572, reprinted 1996.
  12. Attention Deficit Disorder. The Harvard Mental Health Letter (I,II). Apr1995:1-8.
  13. View Abstract: Colquhoun I, Bunday S. A lack of essential fatty acids as a possible cause of hyperactivity in children. Med Hypotheses. May1981;7(5):673-9.
  14. View Abstract: Mitchell EA, et al. Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr (Phila). Aug1987;26(8):406-11.
  15. View Abstract: Stevens L, Zentall SS, Deck JL. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr. 1995;62:761-768.
  16. View Abstract: Burgess JR, et al. Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr. Jan2000;71(1 Suppl):327S-30S.
  17. View Abstract: Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnes Res. Jun1997;10(2):143-8.
  18. View Abstract: Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res. Jun1997;10(2):149-56.
  19. View Abstract: Ottenwalder H, Simon P. Differential effect of N-acetylcysteine on excretion of the metals Hg, Cd, Pb and Au. Arch Toxicol. Jul1987;60(5):401-2.
  20. Ballatori N, et al. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect. May1998;106(5):267-71.
  21. View Abstract: Grandjean P, et al. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol. Nov1997;19(6):417-28.
  22. View Abstract: Tuthill RW. Hair lead levels related to children's classroom attention-deficit behavior. Arch Environ Health. May1996;51(3):214-20.
  23. View Abstract: Adesman AR, et al. Otitis media in children with learning disabilities and in children with attention deficit disorder with hyperactivity. Pediatrics. Mar1990;85(3 Pt 2):442-6.
  24. View Abstract: Hagermann RJ, Falkenstein AR. An association between recurrent otitis media in infancy and later hyperactivity. Clin Pediatr (Phila). May1987;26(5):253-7.
  25. View Abstract: Ferro-Luzzi A, et al. Changing the Mediterranean diet: effects on blood lipids. Am J Clin Nutr. Nov1984;40(5):1027-37.
  26. View Abstract: Visoli F, et al. Oleuropein protects low density lipoprotein from oxidation. Life Sciences. 1994;55:1965-71.
  27. View Abstract: Bisignano G, et al. On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. J Pharm Pharmacol. Aug1999;51(8):971-4.
  28. Petkov V, Manolov P. Pharmacological analysis of the iridoid oleuropein. Drug Res. 1972;22(9):1476-86.
  29. Juven B, et al. Studies on the mechanism of the antimicrobial action of oleuropein. J Appl Bact. 1972;35:559.
  30. View Abstract: Visioli F, et al. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci. 1998;62(6):541-6.
  31. Renis HE. In vitro antiviral activity of calcium elenolate. Antimicrob. Agents Chemother. 1970;167-72.
  32. Heinze JE, et al. Specificity of the antiviral agent calcium elenolate. Antimicrob Agents Chemother. Oct1975;8(4):421-5.
  33. View Abstract: Bennani-Kabchi N, et al. Effects of Olea europea var. oleaster leaves in hypercholesterolemic insulin-resistant sand rats. Therapie. Nov1999;54(6):717-23.
  34. View Abstract: Gonzalez M, et al. Hypoglycemic activity of olive leaf. Planta Medica. 1992;58:513-515.
  35. View Abstract: Volz HP, et al. Kava-kava Extract WS 1490 Versus Placebo in Anxiety Disorders - A Randomized Placebo-controlled 25-week Outpatient Trial. Pharmacopsychiatry. Jan1997;30(1):1-5.
  36. View Abstract: Singh YN. Kava: An Overview. J Ethnopharmacol. Aug1992;37(1):13-45.
  37. View Abstract: Munte TF, et al. Effects of Oxazepam and an Extract of Kava Roots (Piper methysticum) on Event-related Potentials in a Word Recognition Task. Neuropsychobiology. 1993;27(1):46-53.
  38. Drug Therapy of Panic Disorders. Kava-specific Extract WS 1490 Compared to Benzodiazepines. Nervenarzt. Jan1994;65(1Supp):1-4.
  39. View Abstract: Jussofie A, et al. Kavapyrone Enriched Extract from Piper methysticum as Modulator of the GABA Binding Site in Different Regions of Rat Brain. Psychopharmacology (Berl). Dec1994;116(4):469-74.
  40. View Abstract: Davies LP, et al. Kava Pyrones and Resin: Studies on GABAA, GABAB and Benzodiazepine Binding Sites in Rodent Brain. Pharmacol Toxicol. Aug1992;71(2):120-26.
  41. View Abstract: Holm E, et al. The Action Profile of D,L-kavain. Cerebral Cites and Sleep-wakefulness-Rhythm in Animals. Arzneimittelforschung. Jul1991;41(7):673-83.
  42. View Abstract: Duffield PH, et al. Development of Tolerance to Kava in Mice. Clinical and Experimental Pharmacology and Physiology. 1991;18(8):571-78.
  43. View Abstract: Singh YN. Kava: An Overview. J Ethnopharmacol. 1992;37(1):13-45.
  44. View Abstract: Chapkin RS, et al. Dietary Influences of Evening Primrose and Fish Oil on the Skin of Essential Fatty Acid-deficient Guinea Pigs. J Nutr. 1987;117(8):1360-70.
  45. View Abstract: Dutta-Roy AK, et al. Effects of Linoleic and Gamma-linolenic Acids (Efamol Evening Primrose Oil) on Fatty Acid-binding Proteins of Rat Liver. Mol Cell Biochem. 1990;98(1-2):177-82.
  46. View Abstract: Dib A, et al. Effects of Gamma-linolenic Acid Supplementation on Pregnant Rats Fed a Zinc-deficient Diet. Ann Nutr Meta. 1987;31(5):312-19.
  47. Ionescu G, et al. Oral Citrus seed extract. J Orthomolecula Med. 1990;5(3):72-74.
  48. View Abstract: Arimi SM. Campylobacter infection in humans.East Afr Med J. Dec1989;66(12):851-5.
  49. Ionescu G, et al. Oral Citrus seed extract. J Orthomolecula Med. 1990;5(3):72-74.
  50. View Abstract: Fitzgerald JF. Colonization of the gastrointestinal tract. Mead Johnson Symp Perinat Dev Med. 1977;(11):35-8.
  51. View Abstract: Jain SK. Ethnobotany and Research on Medicinal Plants in India. Ciba Found Symp. 1994;185:153-64.
  52. View Abstract: Singh HK, et al. Effect of Bacopa monniera Linn. (Brahmi) Extract on Avoidance Responses in Rat. J Ethnopharmacol. Mar1982;5(2):205-14.
  53. View Abstract: Kidd PM. A Review of Nutrients and Botanicals in the Integrative Management of Cognitive Dysfunction. Altern Med Rev. Jun1999;4(3):144-61.
  54. Sharma R, et al. Efficacy of Bacopa monniera in Revitalizing Intellectual Functions in Children. J Res Edu Ind Med. 1987;1:1-12.
  55. View Abstract: Egger J, et al. Controlled trial of oligoantigenic treatment in the hyperkinetic syndrome. Lancet. 1985;1:540-545.
  56. View Abstract: Kaplan BJ, et al. Dietary replacement in preschool-aged hyperactive boys. Pediatrics. 1989;83:7-17.
  57. View Abstract: Schmidt MH, et al. Does oligoantigenic diet influence hyperactive/conduct-disordered children: a controlled trial. Eur Child Adolesc Psychiatry. 1997;6:88-95.
  58. Schoenthaler, et al. The impact of a low food additive and sucrose diet on academic performance in 803 New York City public schools. International Journal of Biosocial Research. 1986;8:185-196.
  59. View Abstract: Bekarolu M, et al. Relationships between serum free fatty acids and zinc, and attention deficit hyperactivity disorder: a research note. J Child Psychol Psychiatry. Feb1996;37(2):225-7.
  60. View Abstract: Boris M, Mandel FS. Foods and additives are common causes of the attention deficit hyperactive disorder in children. Ann Allergy. May1994;72(5):462-8.
  61. View Abstract: Burgess JR, Stevens L, Zhang W, Peck L. Long-chain polyunsaturated fatty acids in children with attention- deficit hyperactivity disorder. Am J Clin Nutr. Jan2000;71(1Suppl):327S-30S ISSN: 0002-9165.
  62. View Abstract: Stevens LJ, Zentall SS, et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr. Oct1995;62(4):761-8.
  63. Ott J. Health and Light. New York: Simon & Schuster, Pocket Books; 1973:192-194.