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Attention Deficit/Hyperactivity Disorder (ADHD)

Integrative Interventions

Fatty Acids

An analysis of several published studies of “non-pharmacological” (ie, dietary and psychological) interventions for ADHD found that supplementation with free fatty acids and exclusion of artificial food coloring from the diet had statistically significant effects on reducing ADHD symptoms (Sonuga-Barke 2013). Considering that dopamine-producing nerve endings contain up to 80% omega-3 fatty acids (Rucklidge 2009), these molecules appear to have a role in the central nervous system and its functions.

Children with ADHD may have lower levels of omega-3 fatty acids in their blood (Colter 2008). While the typical Western diet often contains excessive levels of certain omega-6 fatty acids, it is lacking in omega-3 fats, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Patterson 2012; Carlson 2013). In children, the severity of ADHD symptoms are linked to lower levels of omega-3 and higher levels of omega-6 fatty acids. Hyperactivity and inattention in general are also linked to omega-3 deficiency, thus indicating that this may be a risk factor for ADHD (Arnold 2013). A UK-based study on 493 school children aged 7-9 years found that omega-3 fatty acid insufficiency was very common and associated with ADHD-related symptoms such as oppositional behavior and emotional instability (Montgomery 2013). Research from another group found that low blood levels of omega-3 fatty acids correlated with callous-unemotional behavior, antisocial traits, and impaired emotional processing (Gow, Sumich 2013; Gow, Vallee-Tourangeau 2013).

Swedish scientists studied the effects of combined omega-3 (558 mg EPA, 174 mg DHA daily) and the beneficial omega-6 fatty acid gamma linolenic acid (GLA) (60 mg daily) supplementation in 75 children and adolescents with ADHD over a 6-month period. They found that after 6 months, nearly half of subjects responded to omega-3/6 treatment with a reduction in ADHD symptoms (Johnson 2009). In a subsequent analysis of these study data, the same researchers found that subjects with at least a 25% reduction in symptoms exhibited a significantly greater decrease in the ratio of omega-6’s to omega-3’s in their blood at 3 and 6 months (Johnson 2012).

A comprehensive review conducted by researchers at Yale University examined evidence from 10 trials involving 699 children with ADHD. It was found that supplementation with omega-3 fatty acids modestly improved ADHD symptoms among study participants. In their concluding remarks, the researchers noted “…it may be reasonable to use omega-3 fatty supplementation to augment traditional pharmacologic interventions…” (Bloch 2011).

Blood fatty acid levels can be measured with blood tests, and people taking fatty acid supplements can have repeat blood tests to measure their effect.

Phosphatidylserine

Phosphatidylserine (PS) is a major component of cell membranes and is considered one of the most important brain nutrients. PS has a variety of functions within the brain including supporting cell membrane fluidity and beneficially influencing neurotransmitter systems (eg, acetylcholine, dopamine, serotonin). Several clinical trials have examined the role of PS on improving ADHD symptoms (Hirayama 2013).

In a 2013 randomized controlled trial, 36 children diagnosed with ADHD were given either 200 mg per day of PS or placebo for 2 months. PS supplementation resulted in significant improvement in ADHD symptoms including inattention, impulsivity, and short-term memory. No adverse effects were reported and the supplement was well tolerated (Hirayama 2013).

Another randomized controlled trial of 15 weeks duration studied the effects of PS combined with omega-3 fatty acids. In this study, 200 ADHD children were given either 300 mg of PS plus 120 mg EPA and DHA or placebo. The treatment resulted in significant improvement in ADHD symptoms. A subgroup analysis revealed this treatment may be especially effective in ADHD children with more pronounced hyperactive and impulsive behavior (Manor 2012).

Acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a natural derivative of L-carnitine. It serves a key role in the metabolism of fatty acids and cellular energy production (Torrioli 2008). Evidence from both animal and human studies suggests it may help alleviate ADHD symptoms. In an animal model of ADHD, long-term administration of ALC to rats consistently decreased impulsivity. This study also found that impulsive animals had altered levels of certain neurotransmitter metabolites, and ALC helped improve this imbalance (Adriani 2004). In a placebo-controlled trial on 112 subjects, ALC was found to improve symptoms in children with the inattentive ADHD subtype (Arnold 2007). In a separate randomized, double-blind trial, ALC was found to have a beneficial effect on hyperactivity and social behavior in 51 subjects with ADHD (Torrioli 2008).

Vitamins and Minerals

Vitamin B6 and magnesium. Vitamin B6 (pyridoxine) is involved in the production of serotonin, and B6 supplementation increases serotonin levels and may improve hyperactivity in ADHD (Pellow 2011). In a nutritional survey comparing 100 people with ADHD to 150 healthy individuals, vitamin B6 intake levels were significantly lower in those with ADHD (Dura Trave 2013). An 8-week study on 40 children with ADHD found that supplementation with magnesium and vitamin B6 led to improvements in hyperactivity and school attention. Interestingly, when the treatment regimen was discontinued, the children’s symptoms reappeared in a few weeks (Mousain-Bosc 2006). A similar regimen of vitamin B6 and magnesium therapy improved hyperexcitability symptoms in a previous study by the same researchers. In this study, the magnesium-B6 combination was given to 52 hyperexcitable children for 6 months, and symptoms such as physical aggressiveness and attention in school improved in all subjects during treatment (Mousain-Bosc 2004).

Studies have shown that magnesium deficiency is common among individuals with ADHD (Ghanizadeh 2013; Kozielec 1997). In a placebo-controlled trial, 200 mg magnesium per day for six months showed a significant decrease of hyperactivity in 7-12 year old children with ADHD (Starobrat-Hermelin 1997).

Zinc and iron. Zinc and iron are both involved in dopamine production, so deficiencies in these minerals could have effects on dopamine neurotransmission in ADHD (Patrick 2007). Children with ADHD treated with Ritalin® for six weeks received better behavioral ratings from teachers and parents when they also took zinc sulfate (55 mg/day) compared to children who received Ritalin® and a placebo (Akhondzadeh 2004).

Iron deficiency is present in a significant percentage of children with ADHD, and the severity of the iron deficiency is related to the severity of symptoms (Konofal 2004). Children who have ADHD in conjunction with sleep disorders such as restless leg syndrome have also been observed to have low iron levels (Cortese, Angriman 2012). A randomized, placebo-controlled study in 23 subjects aged 5–8 years showed that 80 mg iron daily for twelve weeks resulted in a significant decrease in symptoms (Konofal 2008). Another trial with fourteen subjects (7–11 years old) showed that 5mg/kg iron per day for 30 days significantly reduced parent ratings of ADHD symptoms (Sever 1997).  Higher doses of iron (such as those used in these trials) should only be used under medical supervision for iron deficiency.

Plant-Based Interventions

Ginkgo biloba and ginseng. Among plant-based supplements tested for ADHD, a combination of ginseng extract and Ginkgo biloba improved a range of symptoms from social problems to impulsivity (Lyon 2001). Ginkgo alone was shown to be effective in another trial. In this study, ginkgo (80-120 mg daily in 25 children with ADHD for 6 weeks) produced a significant improvement in subjective teacher and parent ratings; however, it did not outperform methylphenidate (20-30 mg daily under the same parameters) (Salehi 2010). In another trial, eighteen children (6–14 years old) received a 1000 mg dose of Korean red ginseng twice daily. At the end of the eight-week trial, a significant reduction in attentional symptoms and level of anxiety was observed (Lee 2011).

Pycnogenol. Pycnogenol is an extract from the French maritime pine, Pinus pinaster. It is often used in ADHD for its antioxidant and vasodilatory properties (ie, it may increase cerebral blood flow, a measure of brain activity, to affected regions). A double-blind, randomized trial on 61 children receiving 1 mg/kg Pycnogenol or placebo per day for 4 weeks showed a significant decrease in hyperactivity, improvement in attention, and increase in visual and motor coordination in the Pycnogenol group (Trebaticka 2006). Another double-blind, randomized, placebo-controlled trial showed that Pycnogenol decreased hyperactivity and oxidative stress in children with ADHD (Dvorakova 2007).

Study: Multinutrient Formula as Effective as Methylphenidate for ADHD Management

The multifactorial origins of ADHD suggest that an intervention targeting multiple specific underlying contributing factors might be beneficial. To test this hypothesis, researchers at McLean hospital in Massachusetts divided 20 children with ADHD into 2 groups. One group of 10 children received 5–15 mg of Ritalin® 2-3 times daily and the other received a comprehensive multi-nutrient formula designed to target several factors that possibly play a role in ADHD development (Harding 2003).

The multi-nutrient formula used in this study included gastrointestinal support (eg, lactobacillus acidophilus and bifidus), amino acids (eg, tyrosine, histidine, glutamine, glycine, methionine and cysteine), essential fatty acids and phospholipids (eg, EPA, DHA, and phosphatidylcholine), and vitamins and minerals.

A standardized assessment of visual and auditory attention was administered to the children at the beginning of the study to quantify their ADHD symptoms. Then, the children took either Ritalin® or the multi-nutrient formula for 4 weeks. At the end of the 4-week period, the researcher administered the same ADHD symptom assessment again.

Impressively, ADHD symptoms among children who took the multi-nutrient formula improved just as much as among those who received Ritalin®. Upon concluding their study, the researchers noted “Improvements … were … found to be significant and essentially identical in both groups…