Integrative Treatments for Behavioral Problems in Children

There are many underlying causes of ADHD including genetic, neurological, environmental, and nutritional influences. Nutritional factors are often overlooked, yet imbalances of many minerals are frequently seen in ADHD. Fortunately, replenishing these nutrients has been proven to reverse ADHD symptoms.

It was not until the 1960’s that researchers discovered zinc was an essential trace mineral needed for normal growth and development. Zinc is needed for the activity of 300 enzyme systems and it plays a role in antioxidant defense and immune function. Zinc is a vital component of the central nervous system, maintaining neurotransmitter activity. This mineral enhances GABA, one of our main inhibitory/relaxation neurotransmitters. What’s more, zinc is necessary to produce melatonin which helps regulate dopamine function.

Multiple studies have confirmed that not only are zinc levels lower in children with ADHD, but zinc levels correlate with ADHD symptoms including inattention, hyperactivity, impulsivity, and conduct problems. In one early assessment, almost one-third of 43 ADHD children aged 6-16 were severely deficient in serum zinc while none of the 28 control children had zinc levels that low (Toren et al., 1996). In a study on 48 ADHD children aged 5-10, most children had serum zinc levels in the lowest 30% of the reference range. There was a highly significant inverse correlation between zinc level and parent and teacher ratings of inattention (Arnold et al., 2005). When researchers analyzed the zinc in the hair of 45 children with ADHD aged 5-15 and 44 controls, they found that those with ADHD had a lower hair zinc concentration and there was a relationship between low zinc and worse overall ADHD symptoms (Shin et al., 2014). In a recent study, 70% of the 20 ADHD cases were zinc deficient. Those with lower hair zinc levels had the worst inattention, hyperactivity, and impulsivity (Elbaz et al., 2016). In a larger group of 118 children with ADHD, those with the lowest blood levels of zinc had the most severe conduct problems, anxiety, and hyperactivity as rated by their parents (Oner et al., 2010).

In children with ADHD, plasma zinc levels were shown to directly affect information processing via event related potentials which reflect brain activity. In 28 ADHD children compared to 24 controls, the amplitudes of P3 waves in frontal and parietal brain regions were significantly lower (worse working memory) and the latency of P3 in parietal region was significantly longer (slower information processing). Unsurprisingly, plasma zinc levels were significantly lower in the ADHD children compared to the control children. When a low-zinc ADHD subgroup was compared to a nondeficient ADHD subgroup, the latencies of N2 in frontal and parietal brain regions were significantly shorter (worse information processing and inhibition) (Yorbik et al., 2008).

Zinc supplements both improve symptoms more than placebo and enhance the effectiveness of stimulant medications. When 400 ADHD children aged 6-14 were randomized to zinc sulfate 150 mg/day or placebo for 12 weeks, those taking zinc had significantly reduced symptoms of hyperactivity, impulsivity, and impaired socialization (Bilici et al., 2004). Similarly, when over 200 children were randomized to zinc 15 mg/day or to placebo for 10 weeks, those taking zinc saw significant improvement in attention, hyperactivity, oppositional behavior, and conduct disorder. And these children had normal zinc levels to begin with (Üçkardeş et al., 2009). In a small study of 18 boys with ADHD, higher baseline hair zinc levels predicted better behavioral response to amphetamine (Arnold et al., 1990). In a six-week double blind, placebo controlled trial, researchers assessed the effects of zinc in combination with methylphenidate (Ritalin). 44 children aged 5-11 were randomized to methylphenidate plus zinc sulfate 55 mg/day or methylphenidate plus placebo. At week 6, those taking zinc had significantly better scores on the Parent and Teacher ADHD Rating Scale (Akhondzadeh et al., 2004). Importantly, zinc can reduce the optimal dose of stimulant medications. 52 children aged 6-14 with ADHD were randomized to zinc glycinate 15 mg/day or placebo for 13 weeks. For the first 8 weeks, they only took zinc then for the last 5 weeks they also took d-amphetamine. The optimal absolute mg/day amphetamine dose with zinc was 43% lower than with placebo (Arnold et al., 2011).

Copper is an essential trace mineral that plays an active role in the synthesis of dopamine and norepinephrine. However, too much copper is toxic and can manifest as aggression, hyperactivity, insomnia, and anxiety. Those who consume water with high amounts of copper or those who have a zinc or manganese deficiency will have elevated levels of copper in the body. Elevated copper levels cause low zinc levels and reduce the effectiveness of ADHD medications.

Copper may affect ADHD through its role in antioxidant status. Copper/Zinc superoxide dismutase (SOD-1) is a key enzyme in our antioxidant defense system. Both copper and zinc participate in SOD enzymatic activities that protect against free radicals. In a study on 22 ADHD children and 20 controls, serum Copper/Zinc SOD levels of ADHD children were significantly lower than all controls. Serum Copper/Zinc SOD was significantly lower in individuals with high serum copper. It is possible that too much copper damages dopamine brain cells by destroying antioxidant defenses, such as lowering Copper/Zinc SOD levels (Russo, 2010).

In a randomized controlled trial on 80 adults with ADHD, lower baseline copper levels were associated with better response to treatment with a vitamin-mineral supplement (Rucklidge et al., 2014). Unfortunately, even copper levels that are considered normal can negatively affect cognition. In a group of 600 adolescents with normal copper levels, blood copper was associated with decreased sustained attention and short-term memory (Kicinski et al., 2015).

Magnesium is part of 300 enzymes that utilize ATP (cellular energy) and is important for nerve transmission. It plays a role in the function of the serotonin, noradrenaline, and dopamine receptors. Magnesium has been progressively declining in our food supply due to food processing and soil depletion. Medications, stress, soft drinks, and caffeine also deplete magnesium. It is not surprising then that 50% of Americans of all ages have inadequate intakes of magnesium (Mosfegh et al., 2009). Symptoms of magnesium deficiency include irritability, difficulty with concentration, insomnia, depression, and anxiety. A prospective population-based cohort of over 600 adolescents at the 14- and 17-year follow-ups found that higher dietary intake of magnesium was significantly associated with reduced externalizing behaviors (attention problems, aggressiveness, delinquency) (Black et al., 2015). Because up to 95% of those with ADHD are deficient in magnesium, almost all ADHD children can benefit from magnesium supplementation (Kozielec & Starobrat-Hermelin, 1997).

In a recent study on 25 patients with ADHD aged 6-16, 72% of children were deficient in magnesium and there was a significant correlation between hair magnesium, total IQ, and hyperactivity. The magnesium deficient children were randomized to magnesium supplementation 200 mg/day plus standard medical treatment or to standard medical therapy alone for 8 weeks. Those taking magnesium saw a significant improvement in hyperactivity, impulsivity, inattention, opposition, and conceptual level while those taking medication alone did not see these improvements (El Baza et al., 2015).

Supplements of magnesium plus vitamin B₆, which increases magnesium absorption, have shown promise for reducing ADHD symptoms. One study on 52 children with ADHD found that 58% had low red blood cell magnesium levels. All the children were given preparations of magnesium plus vitamin B₆ 100 mg/day for a period of 1 to 6 months. In all patients, physical aggression, instability, attention at school, muscle rigidity, spasms, and twitching were improved. One of the treated children was six-year-old J.  Initially he suffered from aggressiveness, anxiety, inattention, and lack of self-control. After taking magnesium supplements, he had better sleep and concentration and no methylphenidate was needed (Mousain-Bosc et al., 2004).  A later study by the same researchers also found that 40 children with ADHD had significantly lower red blood cell magnesium values than control children. Likewise, a magnesium-vitamin B₆ regimen for at least 2 months significantly improved hyperactivity, aggressiveness, and school attention. The researchers concluded, “As chronic magnesium deficiency was shown to be associated to hyperactivity, irritability, sleep disturbances, and poor attention at school, magnesium supplementation as well as other traditional therapeutic treatments, could be required in children with ADHD” (Mousain-Bosc et al., 2006). In a larger study of 122 children with ADHD aged 6-11, 30 days of magnesium-vitamin B₆ supplementation led to improved anxiety, attention, and hyperactivity. On a battery of tests, magnesium treatment increased attention, work productivity, task performance, and decreased the proportion of errors. The EEG of treated children showed positive changes as well, with brain waves significantly normalizing (Nogovitsina & Levitina, 2007).

Lithium is a mineral we must consume from our food supply. As a mineral, it is distributed throughout the world in soil and water, but the distribution varies considerably leaving many falling short of the estimated required dose of 1 milligram per day (Schrauzer, 2002). High-dose pharmaceutical lithium is currently the most widely used medication for the treatment of bipolar disorder. However, low-dose nutritional lithium can be used among nondrug treatments for mood and behavioral disorders. Lithium studies have shown improvement in irritability, anger, and aggression in children with ADHD.

Lithium treatment has been shown to be as effective as Ritalin in young adults with ADHD. In a randomized, double-blind, crossover trial, 32 adults (average age 25) with ADHD were treated with Ritalin up to 40 mg/day or lithium up to 1,200 mg/day. The participants took the first medication for 8 weeks, then did not take any medication for 2 weeks (to allow the first medication to leave to body), then took the second mediation for another 8 weeks. Lithium and Ritalin were equally effective in improving many symptoms: hyperactivity, impulsivity, learning problems, irritability, aggressive outbursts, antisocial behavior, anxiety, and depression (Dorrego et al., 2002).

Lithium was also shown to be as effective as the antipsychotic haloperidol for decreasing behavioral symptoms. One study was conducted on 61 treatment-resistant, hospitalized children aged 5-12 with conduct disorder. Conduct disorder occurs in up to 45% of children and adolescents with ADHD. The children were randomized to haloperidol, lithium carbonate, or placebo for 4 weeks. Haloperidol and lithium both significantly reduced hyperactivity, hostility, and aggression compared to baseline and compared to placebo. Although both medications equally reduced symptoms, haloperidol interfered with daily functioning more than lithium. “The [blinded] staff agreed that lithium carbonate reduced explosiveness, and because of this, other positive changes took place, whereas haloperidol made the child only more manageable” (Campbell et al., 1984).

In 2014 Dr. Deepmala discussed a compelling case study in the Journal of Child and Adolescent Psychopharmacology. H. was a six-year-old girl diagnosed with ADHD, disruptive behavior disorder, anxiety, and mood disorder. She was treated with antipsychotics, mood stabilizers, antidepressants, and stimulants but her condition did not improve. After exhausting many different medication regimens, H.’s parents agreed to begin lithium carbonate. “With the addition of lithium, H.’s symptoms improved remarkably. Her inattention, hyperactivity, and restlessness attenuated, and irritability reduced by 60-70%. Sleep initiation improved. Improvement in her academic performance was noted, as concentration improved and hyperactivity decreased. Mood regulation was significantly improved as well” (Deepmala & Coffey, 2014).

Lithium works by balancing neurotransmitters; it increases the action of monoamine oxidase, an enzyme that regulates neurotransmitters. Lithium decreases the neurotransmitter glutamate which can damage brain cells if levels become too high. Lithium may also work as a central nervous system depressant to calm hyperactivity, reduce aggression, and improve sleep in ADHD patients. More research is needed to determine if lithium can address the underlying structural and functional abnormalities common in ADHD as well.

HPHPA is an organic acid produced in the gut by the bacterium Clostridium. Elevated urinary levels are commonly seen in ADHD children, especially those with poor response to stimulants. HPHPA inhibits the conversion of dopamine to norepinephrine. This causes increased dopamine and decreased attention and focus. Amphetamines further increase dopamine and exacerbate symptom of irritability and aggression. HPHPA must be cleared before medications will be helpful. Probiotics or antibiotics can be used to lower HPHPA.

Intestinal overgrowth of Candida yeast is seen in some children with ADHD, mostly in those with a high-sugar diet that feed Candida or in those who have received many rounds of antibiotics for recurrent ear infections. In fact, one study found that children with the greatest history of ear infections (and presumably the greatest frequency of antibiotic use) had the greatest chance of later hyperactivity (Hagerman & Falkenstein, 1987). Antibiotics wipe out good bacteria, giving Candida the opportunity to multiply. Toxins produced by Candida can enter the bloodstream and then the brain where they can cause changes leading to hyperactivity and poor attention span. Yeast can be detected with an organic acids test or with a stool sample. Candida can be treated with probiotics, antifungal foods (e.g. garlic, oregano, ginger), and a lower sugar diet.

References

1. Akhondzadeh, et al (2004). Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial ISRCTN64132371. BMC Psychiatry, 4, 9.
2. Arnold et al. (1990). Does hair zinc predict amphetamine improvement of ADD/hyperactivity? The International Journal of Neuroscience, 50(1-2), 103-7.
3. Arnold et al. (2005). Serum zinc correlates with parent- and teacher- rated inattention in children with attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 15(4), 628-36.
4. Arnold et al. (2011). Zinc for attention-deficit/hyperactivity disorder: Placebo-controlled double-blind pilot trial alone and combined with amphetamine. Journal of Child and Adolescent Psychopharmacology, 21(1), 1-19.
5. Bilici et al. (2004). Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Progress in Neuropsychopharmacology & Biological Psychiatry, 28(1), 181-190.
6. Black et al. (2015). Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents. Public Health Nutrition, 18(10), 1824-30.
7. Campbell et al. (1984). Behavioral Efficacy of Haloperidol and Lithium Carbonate: A Comparison in Hospitalized Aggressive Children With Conduct Disorder. Archives Of General Psychiatry, 41(7), 650-656.
8. Deepmala & Coffey. (2014). Challenges in psychopharmacological management of a young child with multiple comorbid disorders, history of trauma, and early-onset mood disorder: The role of lithium. Journal Of Child And Adolescent Psychopharmacology, 24(9), 519-524.
9. Dorrego et al. (2002). A randomized, double-blind, crossover study of methylphenidate and lithium in adults with attention-deficit/hyperactivity disorder: Preliminary findings. The Journal of Neuropsychiatry and Clinical Neurosciences, 14(3), 289-95.
10. Elbaz et al. (2016). Magnesium, zinc and copper estimation in children with attention deficit hyperactivity disorder (ADHD). Egyptian Journal of Medical Human Genetics, Egyptian Journal of Medical Human Genetics, in press.
11. El Baza et al. (2016). Magnesium supplementation in children with attention deficit hyperactivity disorder. Egyptian Journal of Medical Human Genetics, 17(1), 63-70.
12. Hagerman & Falkenstein. (1987). An Association Between Recurrent Otitis Media in Infancy and Later Hyperactivity. Clinical Pediatrics, 26(5), 253.
13. Kicinski et al. (2015). Neurobehavioral function and low-level metal exposure in adolescents. International Journal of Hygiene and Environmental Health, 218(1), 139-146.
14. Kozielec & Starobrat-Hermelin. (1997). Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD). Magnesium Research: Official Organ Of The International Society For The Development Of Research On Magnesium, 10(2), 143-148.
15. Moshfegh et al. (2009). What We Eat in America, NHANES 2005–2006: Usual Nutrient Intakes from Food and Water Compared to 1997 Dietary Reference Intakes for Vitamin D, Calcium, Phosphorus, and Magnesium. U.S. Department of Agriculture, Agricultural Research Service: Washington, DC, USA.
16. Mousain-Bosc et al. (2004). Magnesium VitB6 intake reduces central nervous system hyperexcitability in children. Journal Of The American College Of Nutrition, 23(5), 545S-548S.
17. Mousain-Bosc et al. (2006). Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders. Magnesium Research: Official Organ Of The International Society For The Development Of Research On Magnesium, 19(1), 46-52.
18. Nogovitsina & Levitina. (2007). Neurological aspects of the clinical features, pathophysiology, and corrections of impairments in attention deficit hyperactivity disorder. Neuroscience and Behavioral Physiology, 37(3), 199-202.
19. Oner et al. (2010). Effects of Zinc and Ferritin Levels on Parent and Teacher Reported Symptom Scores in Attention Deficit Hyperactivity Disorder. Child Psychiatry and Human Development, 41(4), 441-447.
20. Rucklidge et al. (2014). Moderators of treatment response in adults with ADHD treated with a vitamin–mineral supplement. Progress in Neuropsychopharmacology & Biological Psychiatry, 50, 163-171.
21. Russo, A. (2010). Decreased Serum Cu/Zn SOD Associated with High Copper in Children with Attention Deficit Hyperactivity Disorder (ADHD). Journal of Central Nervous System Disease, 2, 9-14.
22. Schrauzer, G. (2002). Lithium: Occurrence, Dietary Intakes, Nutritional Essentiality. Journal of the American College of Nutrition, 21(1), 14-21.
23. Shin et al. (2014). The Relationship between Hair Zinc and Lead Levels and Clinical Features of Attention-Deficit Hyperactivity Disorder. Journal of the Korean Academy of Child and Adolescent Psychiatry, 25(1), 28-36.
24. Toren et al. (1996). Zinc deficiency in attention-deficit hyperactivity disorder. Biological Psychiatry, 40(12), 1308-1310.
25. Üçkardeş et al. (2009). Effects of zinc supplementation on parent and teacher behaviour rating scores in low socioeconomic level Turkish primary school children. Acta Paediatrica, 98(4), 731-736.
26. Yorbik et al. (2008). Potential effects of zinc on information processing in boys with attention deficit hyperactivity disorder. Progress in Neuropsychopharmacology & Biological Psychiatry, 32(3), 662-667.