Non-pharmacological and Lifestyle Approaches to Attention-Deficit/Hyperactivity Disorder: 2. Nutritional Supplements

It sometimes surprises people to learn that the FDA does not currently regulate the production of supplements and herbal products. Therefore their purity and contents may vary considerably. Though most of them are fine, there have been endless examples of supplements that contained no active ingredients or were adulterated with heavy metals or prescription medicines.

Amino Acid Supplementation
The idea of using amino acid supplementation is based on reports of low levels of amino acids in ADHD, including the particular amino acids – tyrosine, phenylalanine and tryptophan – that are the building blocks of catecholamines and serotonin.

Several open and controlled studies in both adults and children have reported a short-term benefit from tryptophan (precursor of serotonin), tyrosine (precursor of catecholamines), or phenylalanine (precursor of catecholamines) and S-adenosyl-methionine supplementation.

However, no lasting benefit beyond 2–3 months has been demonstrated: both children and adults develop tolerance. Even short term, there is a lot of dispute about whether these supplements work at all.

Vitamins
Three strategies for vitamin supplementation are:

1. Recommended Daily Allowance (RDA) multivitamin preparations
2. Megavitamin multiple combinations
3. Megadoses of specific vitamins

The first is not controversial, although there is always a discussion about whether the RDA’s is correct. There has not been any credible research on the effects of his kind of supplementation in diagnosed ADHD even though some reports suggest mild deficiencies in diet and blood levels. There is some evidence that micro-nutrient supplementation will help the intelligence and ability to concentrate in children without ADHD, but whether the same holds in ADHD, we simply do not know.

The second strategy, megavitamin multiple combinations, has not been found effective in double-blind placebo-controlled short (2 weeks) and longer (up to 6 months) trials in ADHD and the related comorbidity of learning disorder, although it is always possible that the researchers did not use the correct mixture of vitamins and minerals.

As things stand megavitamin combinations do not seem worth pursuing for children or adults, and some may be risky.

The third strategy, the use of single vitamins in huge doses to alter neural metabolism has not been explored despite some encouraging early reports.

Minerals
Deficiencies of iron, zinc, and magnesium have been noted more commonly among children with ADHD than among normal children.

Iron
Iron is a coenzyme involved in the synthesis of catecholamines, so there has been a lot of interest in iron deficiency as a possible cause of a number of neurocognitive problems. Iron deficiency may be due to poor diet, celiac disease, excessive milk ingestion, infection, gastrointestinal losses or lead. And of course in adults, many women are chronically iron deficient. Children with ADHD may have lower iron stores and in a study of nearly 100 children, there was a significant inverse correlation between ferritin levels and scores on a standard ADHD rating scale.

Zinc
Zinc is a co-factor for 100 enzymes, many involved in neural metabolism. It is also necessary for fatty acid absorption and for the production of melatonin, the light–related hormone that helps regulate dopamine function. Zinc is so important for the normal functioning of the brain that it is plausible that deficiency would adversely affect behavior and that restoring optimal levels may provide some benefit.

Zinc has been found to be lower in some children with ADHD. In a study of 44 children with diagnosed ADHD, zinc had a significant inverse correlation with attention, even controlling for gender, age, income, and diagnostic subtype. In large randomized, controlled trial, children given zinc sulfate (150 mg/day) or placebo, the zinc-takers had significantly more improvement for impulsive behavior and socialization; the best response was observed in those children who had low zinc levels to begin with. We do not know if using mega-doses of zinc will confer any benefit.

Magnesium
Magnesium deficiency can cause a wide spectrum of neurological and psychiatric disturbances and can result from a many factors including increased requirement during childhood.

In one study, 30 out of 52 children with ADHD had low levels of magnesium in their red blood cells. An open-label study supplementing them with 100 mg daily of magnesium and viamin B6 for 3-24 weeks led to reduced symptoms of hyper-excitability (physical aggression, instability, attention to school work, muscle tension and spasms) after 1 to 6 months of treatment.

Conclusions
It is usually just enough to ensure that children with ADHD have a decent diet. But in some it may be necessary to take supplements to ensure that they are getting an adequate dietary intake of iron, zinc, and magnesium.

Other Supplements

Essential Fatty Acid Supplementation
The membranes of nerve cells are composed of phospholipids containing large amounts of polyunsaturated fatty acids, especially the n-3 and n-6 (or omega-3 and omega-6) acids. What these terms mean is simply that the first unsaturated bond is 3 or 6 carbons, respectively, from the noncarboxyl “tail” of the molecule). Humans cannot manufacture these fatty acids and hence are “essential” and needed in the diet. Essential fatty acids (EFAs) are also metabolized to prostaglandins and other eicosanoids, which modify many metabolic processes, activate eicosanoid receptors, and interact with pro-inflammatory cytokines.

Rats that have low levels of omega-3 fatty acids in their brains, tend to be hyperkinetic.

Fish oil/omega-3 fatty acids
Children with lower levels of omega-3 fatty acids seem to have significantly more behavioral problems, temper tantrums, and learning, health, and sleep problems than did those with high proportions of omega-3 fatty acids.

In a 4-month trial of 63 children with ADHD, DHA (one of the essential fatty acids found in fish oil) supplements alone had no significant impact on behavior. In a randomized, controlled trial of fatty acids supplementation for 117 children with developmental coordination disorder, there were significant improvements for children on active treatment in reading, spelling, and behavior over 3 months of treatment. But when the tratments were crossed over, similar changes were seen in the placebo group. We definitely need more research on fish oils. Most experts think that children need around 1000mg/day and adults up to 3000mg/day.

There may be a downside: large doses of fish oil may inhibit platelet aggregation and increase the risk of bleeding; its use should be discontinued 48 hours before having surgery. Many people do not like the taste of fish oil, though in capsules that is not normally a problem.

Gamma-Linolenic Acid
Evening primrose oil contains gamma linoleic acid. Two small randomized, controlled trials conducted in the 1980s showed only marginal benefits of evening primrose oil for children with ADHD.

L-Carnitine
The mixed results with essential fatty acids might have something to do with the transport and metabolism of the fatty acids. One essential component of these metabolic pathways is L-carnitine, so it too has been tried in ADHD, but so far there are no good trials to help us.

Glyconutritional Supplements
Glyconutritional supplement contains basic saccharides necessary for cell communication and the formation of glycoproteins and glycolipids.

In an open trial of glyconutritional and phytonutritional (flash freeze-dried fruits and vegetables) supplementation with 17 ADHD children, researchers found significant reductions in parent ratings of inattention, hyperactivity, impulsivity, and oppositional symptoms, with similar trends on teacher ratings. In a second open trial of the same supplements in 18 children, researchers found reductions in parent inattention ratings from 2.47 to 2.05 and hyperactivity-impulsivity ratings from 2.23 to 1.54. There was an impressive statistical value for this trial and the results were sustained for 6 weeks. However, a third open trial reportedly failed to duplicate such results. There have not been any reported trials of glyconutritional supplements in adults.

Dimethylaminoethanol
Dimethylaminoethanol (DMAE) has several accepted names, including deanol and dimethylethanolamine. It is the immediate precursor of choline (trimethylaminoethanol) and is claimed to increase production of acetylcholine. There have been several studies claiming a small effect on vigilance, alertness and mood, but there are questions about its safety.

Melatonin
Melatonin helps regulate dopamine function in the brain, so it has been a natural candidate for the treatment of ADHD. A randomized, controlled trial 25 children with ADHD and chronic insomnia were either given melatonin (5 mg) or placebo daily at 6pm; the melatonin significantly improved sleep onset, decreased sleep latency, and increased total sleep time. Although there was no significant change in ADHD behavior over the 4-week study, all the parents in the trial felt the improvements in sleep were enough to justify continuing to give it for 1 year after the study. These results have been replicated in another study: melatonin helps with sleep problems in chdlren wth ADHD, but had no efect on problem behavior, cognitive performance or quaity of life. Melatonin may be helpful for children with ADHD who have trouble with sleep.

As you can see there are a great many options, but despite all those articles in magazines and online that promise the earth, the evidence for most of the approaches is thin.

At the moment the best option that may help seems to be fish oils. Choosing the best supplement is not easy, but the one for which there is most evidence, and which seems to be the most pure and mercury-free is OmegaBrite.