The use of complementary and alternative medicine (CAM) such as nutritional supplements is common in children with ADHD, regardless of whether such treatments are evidence-based. While nutritional supplements might not be ready for prime time from the evidence point of view, many consumers use them nonetheless, often without telling their physician. Asking about the use of nutritional supplements allows for a discussion of the risks and benefits of these treatments.
Nutritional supplements include macronutrients such as proteins, fats and carbohydrates, as well as micronutrient products such as vitamins and minerals. Among randomized controlled trials (RCTs) evaluating nutritional supplements for ADHD treatment, few are of high quality, and study results are frequently inconsistent.
Macronutrients
Essential Fatty Acids
The essential fatty acids (EFAs) include the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the omega-6 fatty acids arachidonic acid (AA) and gamma linolenic acid (GLA). Children with ADHD may have low levels of EFAs, especially DHA and AA. There is limited evidence that fatty acids improve core symptoms in children with ADHD. There are 16 published placebo-controlled RCTs of EFAs in children with ADHD, one meta-analysis, and one Cochrane review.
A 2011 meta-analysis of ten RCTs (699 participants) comparing omega-3 fatty acid supplementation with placebo found omega-3 to be modestly effective (0.31 effect size) on inattentive and hyperactivity ADHD symptoms, especially with a higher EPA dose (Bloch MH, Qawasmi A. 2011. Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. Oct; 50(10):991-1000).
The 2012 Cochrane review, which included 13 of the 16 RCTs (7 overlapping with the meta-analysis) did not find benefit of supplementation, but did find that a pooled analysis of two trials (97 participants) found evidence of improvement with a combination of omega-3 and omega-6 fatty acids (Gillies et al. 2012 Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHA) in children and adolescents. Cohrane Database Syst Rev, 2012 Jul 11:7). The differences in results are likely related to the variability of EFA supplements used, and to methodological differences.
Overall, a growing body of evidence supports the use of an EFA supplement for children who have ADHD. In general clinical practice it is reasonable to embark on a trial of EFAs–especially when parents are ambivalent about medications, or medications are not effective or poorly tolerated–as there are a number positive studies and the risks are low. It is best to use combination EFAs, such as fish oil. Phosphatidyl serine might also be a good source, but has limited data at this time. Fish oil is a more efficient source of EFAs than flaxseed oil. Fish oil is inexpensive and comes in a variety of flavors and chewables for children. The label should specify that the product is mercury free.
Acceptable dose is 1000 mg to 2000 mg (with at least 500 mg of EPA) per day from preschool age and up. At least three months should be allowed to see results, and results may be optimal at 6 months. The most common side effects of fish oil include abdominal pain, belching, and a fishy aftertaste.
L-Carnitine and Acetyl L-Carnitine (ALC)
L-carnitine is synthesized from lysine and methionine amino acids. It is a semi-essential nutrient involved in transporting fatty acids into mitochondria. While two foreign RCTs showed benefit, two American RCTs failed to show benefit on intent-to-treat analyses, with those with inattentive subtype responding better. While the evidence to support use of L-Carnitine is weak at this time, L-Carnitine might be beneficial for children with the inattentive subtype of ADHD. Doses used in research study were 500 mg to 1500 mg BID, depending on weight, and no safety concerns or side effects were reported. (Amato, A., Arnold E, Bozzolo H, et al. (2007) Acetyl-l-carnitine in attention-deficit/hyperactivity disorder: a multi-site, placebo-controlled pilot trial. Journal of Child and Adolescent Psychopharmacology. Dec 17.6, p791)
Micronutrients
Zinc
Zinc is an essential mineral and is a cofactor for many enzymes. In the brain zinc inhibits dopamine uptake when it binds to the dopamine transporter. Zinc deficiency symptoms include concentration impairment and jitters. Several studies suggest that zinc levels might be low in children with ADHD, and that optimal stimulant response might depend on adequate baseline zinc levels. Zinc increases the affinity of methylphenidate for the dopamine transporter.
Two Turkish RCTs found benefit from zinc monotherapy in ADHD. A large RCT found that zinc supplements reduced hyperactive, impulsive and impaired socialization symptoms, but did not improve symptoms of inattention. This study used a high dosage of zinc for a period of 12 weeks and more than 50% of placebo and zinc groups dropped out of the study. Another study found that zinc 15 mg improved attention deficit, hyperactivity and oppositional behavior only in the subgroup withmothers with low-level education.
An Iranian RCT found benefit from adjunctive use of zinc with methylphenidate, with a greater improvement in parent and teacher ratings of ADHD symptoms in those on zinc and methylphenidate than those on methylphenidate alone. In an American DBRCT, 52 children ages 6-14 with ADHD (inattentive or combined type) took zinc glycinate (15mg every morning or BID) for 8 weeks as monotherapy and then for 5 weeks with d-amphetamine. While zinc monotherapy or in combination with d-amphetamine was no more effective than placebo, the optimized dose of d-amphetamine was 37% lower with zinc 30mg/day than with placebo. The differences in results between the Middle Eastern and American studies might be due to geographic differences in prevalence of zinc deficiency, as well as differences in study design (Gnizadeh A, Berk, M. (2012). Zinc for treating of children and adolescents with attention-deficit hyperactivity disorder: a systematic review of randomized controlled clinical trials. Eur J Clin Nutr. 2013 Jan;67(1):122-4).
There is no evidence backing zinc monotherapy for treatment of ADHD in US children, unless there is a documented or suspected zinc deficiency. There is weak evidence for zinc as an adjuvant to stimulant treatment. Zinc might be more effective for older children with a higher body mass index, and higher doses such as zinc glycinate 15mg BID might be more effective. In addition, copper should be supplemented in long-term zinc treatment to prevent copper deficiency.
Iron
Iron is an essential trace metal, which plays a role in dopamine function. Iron deficiency is common in the general population. Research studies show mixed results: some studies find that children with ADHD have lower serum ferritin levels and that severity of symptoms correlates with low ferritin levels; others find no association. A single RCT assessing the effects of oral iron supplementation (ferrous sulfate 80mg/day) on ADHD symptoms in children with low serum ferritin levels (<30 ng/ml) was positive on ADHD Rating Scales and Clinical Global Impression Severity, but not on Conner’s parent or teacher ratings. In a 30-day open label trial of iron supplementation (Ferrocal 5mg/kg/day), while clinical symptoms improved, teacher ratings did not show improvement. In addition, two studies suggest that iron deficiency might decrease the effectiveness of psychostimulant treatment. (Cortese S, Angriman M, Lecendreux M, Knofal E. 2012. Iron and attention deficit/hyperactivity disorder: what is the empirical evidence so far? A systematic review of the literature. Expert Review of Neurotherapeutic. Oct 2012, Vol. 12, No. 10, P 1227-1240).
Based on preliminary data, taking iron orally might improve symptoms of attention deficit-hyperactivity disorder in children with iron deficiency. The adverse effects of iron supplementation include abdominal pain, constipation, and vomiting.
Megavitamin vs. multivitamin
Megavitamin doses are several orders of magnitude greater than the Recommended Daily Allowance (RDA). Three placebo-controlled multimegavitamin treatment studies found no benefit for ADHD symptoms. One study found increased disruptive behavior and elevated serum transaminase levels in those taking megavitamins (Haslam R.H., Dalby J.T., Rademaker A.W.,et al: Effects of megavitamin therapy on children with attention deficit disorders. Pediatrics 1984; 74: 103-111). Multivitamin supplements at regular RDA doses have not been examined for the treatment of ADHD. Two placebo-controlled studies of multivitamins for general population schoolchildren found significant improvement on measures of IQ, attention/concentration, fidgeting and reaction time in intent to treat analysis, but only in lower SES subgroups. A third study found no significant effect on reasoning skills.
Megavitamin treatments are not recommended due to potential risks and no demonstrated benefits. If patients are using doses of vitamins or minerals higher than the recommended daily allowance, it is important to monitor serum or cell membrane levels of these nutrients and liver enzymes to avoid toxicity. Since many children with ADHD do not eat a balanced diet, are picky eaters, or have appetite suppression from psychostimulant medications, the use of a multivitamin supplement at regular RDA doses can be recommended for those at risk for nutritional deficiencies (Arnold E, Hurt, E, Lofthouse N. (2013). Attention-Deficit/Hyperactivity Disorder: Dietary and Nutritional Treatments. Child Adolesc Psychiatric Clin N Am 22 (2013) 381–402).
Originally published in The Carlat Child Psychiatry Report