"Integrative Treatments for Behavioral Problems in Children" by Dr. Greenblatt from Mosaic Diagnostics on Vimeo.

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Integrative Treatments for Behavioral Problems in Children

Overview

Attention deficit/hyperactivity disorder (ADHD) is a multifactorial condition that is influenced by genetic, biological, environmental, and nutritional factors. While there are numerous integrative therapies available including vitamins, minerals, herbs, neurofeedback, exercise, and meditation, individuals are unique and thus require personalized treatments based on their own biological needs identified through laboratory testing. In this article, we will discuss commonly overlooked mineral deficiencies and imbalances in the gastrointestinal flora that can exacerbate behavioral symptoms and impede the therapeutic effect of pharmacological treatment.

Attention deficit/hyperactivity disorder (ADHD) is a multifactorial condition that is influenced by genetic, biological, environmental, and nutritional factors. While there are numerous integrative therapies available including vitamins, minerals, herbs, neurofeedback, exercise, and meditation, individuals are unique and thus require personalized treatments based on their own biological needs identified through laboratory testing. In this article, we will discuss commonly overlooked mineral deficiencies and imbalances in the gastrointestinal flora that can exacerbate behavioral symptoms and impede the therapeutic effect of pharmacological treatment.In the early 1960s, researchers discovered that zinc was an essential trace mineral necessary for normal growth and development. Zinc is also critical for immune function, and the activity of over 300 enzymes is dependent on zinc bioavailability. Zinc is a vital component of the central nervous system, maintaining neurotransmitter activity. This mineral enhances GABA, one of our main inhibitory/relaxation neurotransmitters. Moreover, zinc is needed as a co-factor to produce melatonin which helps regulate dopamine function.

Multiple studies have confirmed that not only are zinc levels lower in children with ADHD, but the extent of the deficiency is proportionately correlated with the severity of ADHD symptoms including inattention, hyperactivity, impulsivity, and conduct problems:

  • Toren et al. (1996) found that almost one-third of 43 ADHD children aged 6-16 were severely deficient in serum zinc.
  • Another study involving 48 ADHD children aged 5-10 demonstrated that most of the participants had serum zinc levels in the lowest 30% of the reference range.
  • There is a highly significant inverse correlation between zinc level and parent and teacher ratings of inattention among children with ADHD (Arnold et al., 2005). A more recent study echoed the same findings, when researchers analyzed the zinc in the hair of 45 children with ADHD against 44 controls. They found that there was a relationship between hair zinc levels and worse overall ADHD symptoms (Shin et al., 2014).
  • In a recent study, 70% of the 20 ADHD cases examined were zinc deficient. Those with lower hair zinc levels reported significantly increased symptoms of 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 ADHD children compared to controls, the amplitudes of P3 waves in frontal and parietal brain regions were significantly lower (worse working memory) and the latency of P3 in the 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).

Supplementation with zinc is more effective at improving ADHD symptoms when compared to placebo, and can also be an effective adjuvant therapy to enhance the therapeutic effect of stimulant medication without increasing the dosage. 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., 200452 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, excess copper can manifest as displays of aggression, hyperactivity, insomnia, and anxiety. Elevated copper levels can also cause low zinc levels and reduce the efficacy of medications commonly used to treat ADHD.

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 radical damage. In a study on 22 ADHD children and 20 controls, serum Copper/Zinc SOD levels of ADHD children were significantly lower in individuals with high serum copper when compared to controls. It is also hypothesized that excess copper can damage 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 is involved in the function of the serotonin, noradrenaline, and dopamine receptors. Magnesium has been progressively declining in our food supply due to increased consumption of processed foods. The use of medications, presence of stress, and caffeine and soft drink consumption also deplete magnesium, and it is estimated that 50% of Americans are deficient in 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 a six-year old identified as “J”. Initially, J suffered from aggressiveness, anxiety, inattention, and lack of self-control. After taking magnesium supplements, he reported 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).

There has also been a considerable amount of research illustrating the symbiotic, bidirectional relationship between the brain and the gut, and animal studies have demonstrated how certain strains of bacteria, or lack thereof, can alter cognitive and emotional processes. In the presence of dysbiosis, where “bad” bacteria outnumber the “good,” harmful strains of bacteria can proliferate and cause behavioral disturbances.

HPHPA is a harmful byproduct of some strains of the bacterium Clostridium that can disrupt the normal gut environment. 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 dopamine to accumulate, resulting in decreased attention and focus. A patient should especially be tested for HPHPA if he or she experiences stimulant side effects such as irritability, agitation, or anxiety. ADHD medications work by increasing dopamine. But high HPHPA levels prevent the breakdown of dopamine, exacerbating symptoms. HPHPA must be cleared before medications will be helpful. Probiotics, good bacteria found in fermented food such as yogurt, 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 diet high in sugar that feed Candida, or in those who have received many rounds of antibiotics for recurrent ear infections. Antibiotics are effective at resolving infections by eradicating all bacteria, including the good bacteria. An early study found that children with the greatest history of ear infections (and presumably the greatest frequency of antibiotic use) had an increased chance for developing hyperactivity later (Hagerman & Falkenstein, 1987). Toxins produced by Candida can enter the bloodstream and then enter the brain where they can cause changes leading to hyperactivity and poor attention span. Fortunately, the presence of HPHPA and other yeast overgrowth can be easily 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. In some cases, a regimen of antibiotics and probiotics can be useful in reestablishing a healthy gut flora.

Nutritional augmentation strategies are frequently used as part of the integrative clinician’s toolbox to treat behavioral disorders in children. It is important for healthcare providers to collaborate and communicate with caregivers of children with behavioral disorders to discern whether other complementary therapies could be incorporated into treatment. By carefully assessing a patient’s whole health history and conducting appropriate laboratory testing, providers can make informed treatment recommendations that is tailored specifically for the individual.

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. 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.
  8. El Baza et al. (2016). Magnesium supplementation in children with attention deficit hyperactivity disorder. Egyptian Journal of Medical Human Genetics, 17(1), 63-70.
  9. Hagerman & Falkenstein. (1987). An Association Between Recurrent Otitis Media in Infancy and Later Hyperactivity. Clinical Pediatrics, 26(5), 253.
  10. Kicinski et al. (2015). Neurobehavioral function and low-level metal exposure in adolescents. International Journal of Hygiene and Environmental Health, 218(1), 139-146.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Toren et al. (1996). Zinc deficiency in attention-deficit hyperactivity disorder. Biological Psychiatry, 40(12), 1308-1310.
  21. 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.
  22. 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.
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About the Author

James Greenblatt, MD

James M. Greenblatt, MD, dually board-certified psychiatrist, has treated patients since 1988 and is a pioneer of integrative medicine. He serves as the Chief Medical Officer at Walden Behavioral Care. He is the author of seven books, including Answers to Anorexia, Finally Focused, and upcoming book Functional & Integrative Medicine for Antidepressant Withdrawal. Dr. Greenblatt was inducted into the Orthomolecular Hall of Fame in 2017. He is also the founder of Psychiatry Redefined, an educational platform dedicated to the transformation of psychiatry, and Medical Director of TZ Health, a national virtual consultation clinic dedicated to the personalized, integrative treatment of mental illness.