The use of complementary and alternative medicine (CAM), such as nutritional supplements, is common in children with ADHD, despite limited evidence for its effectiveness. Many consumers use these treatments, often without telling their physicians. Asking patients about them allows for a discussion of the risks and benefits.
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 for ADHD
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. While there have been a number of well-designed studies of EFAs in children with ADHD, there is limited evidence that fatty acids improve core symptoms in such children.
A 2011 meta-analysis of 10 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, J Am Acad Child Adolesc Psychiatry 2011;50(10):991–1000).
A 2012 Cochrane review, which included 13 RCTs (seven overlapping with the 2011 meta-analysis) did find that there was evidence of improvement in a pooled analysis of two trials (with a total of 97 participants) of combination omega-3 and omega-6 fatty acids.
None of the other RCTs in the review showed benefit to supplementation (Gillies et al, Cochrane 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 of 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. An acceptable dose is 1,000 mg to 2,000 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 six 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; however, those with inattentive subtype responded better than others.
So, 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 et al, J Child Adolesc Psychopharmacology 2007;6:791).
Micronutrients for ADHD
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 RCTs conducted in Turkey 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 with mothers with low-level education.
An RCT conducted in Iran 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 double blind RCT, 52 children ages six to 14 with ADHD (inattentive or combined type) took zinc glycinate (15 mg every morning or BID) for eight weeks as monotherapy and then for five 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 30 mg/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. Eur J Clin Nutr 2013;67(1):122–124).
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 adjunct to stimulant treatment. Zinc might be more effective for older children with a higher body mass index, and higher doses such as zinc glycinate 15 mg 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 that 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 80 mg/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 by some, but not all measures, teacher ratings did not show improvement.
In addition, two studies suggest that iron deficiency might decrease the effectiveness of psychostimulant treatment (Cortese S et al, Expert Rev Neurotherapeutic 2012;12(10):1227–1240).
Based on preliminary data, taking iron orally might improve symptoms of ADHD in children with iron deficiency. The adverse effects of iron supplementation include abdominal pain, constipation, and vomiting.
Megavitamin vs. Multivitamin
Three placebo-controlled multi-megavitamin treatment studies found no benefit for ADHD symptoms. Megavitamin doses are several orders of magnitude greater than the recommended daily allowance (RDA). One study found increased disruptive behavior and elevated serum transaminase levels in those taking megavitamins (Haslam RH et al, 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 socioeconomic status subgroups. A third study found no significant effect on reasoning skills.
Megavitamin treatments are not recommended due to potential risks and lack of 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 et al, Child Adolesc Psychiatric Clin N Am 2013;22(2013):381–402).
CCPR’s Verdict: At this time the evidence for use of nutritional supplements for the treatment of ADHD is limited. Treatments with best evidence include omega-3 and omega-6 fatty acid combinations, zinc as an adjunct to stimulant treatment, iron for children with iron deficiency, and multivitamins for children at risk for nutritional deficiencies. It is important to have an open-minded attitude that invites discussion with parents of their use of CAM treatments.