ADHD, Food Additives, and Histamine

I'll get back to the wild world of Alzheimer's research in a day or two.  My September issue of the Green Journal arrived via USPS this afternoon, and of course this paper caught my eye:

"The Role of Histamine Degradation Gene Polymorphisms in Moderating the Effects of Food Additives on Children's ADHD Symptoms."

A colleague rolled her eyes at me when I squeaked while reading the title.  But do you know how many diet-related articles are published in my specialty journal (the oldest specialty journal in publication, by the way) every year?  Maybe one or two.  And I've laid out the groundwork for evaluating this study.  If you didn't read them the first time around, maybe take a moment now to go back to the archives to look at Hyperactivity and Diet and A Closer Look at Tartrazine.   The recap is that some food additives have been shown to worsen the symptoms in ADHD (or hyperactivity) in some children, but other children seem to be impervious.

ADHD in children is diagnosed when kids have symptoms of inattention, impulsivity, and hyperactivity, to the point where severe problems interfere with daily functioning.  The disorder is highly inherited, and a few genes have been found in some families that seem to explain the symptoms - the dopamine transporter genes and dopamine receptor genes, among others.  Issues with these genes make sense for the symptoms you would see in ADHD - dopamine is the neurotransmitter, in our frontal lobes, especially, that is responsible for helping us pay attention and keeping us from saying things we shouldn't.  If our dopamine system doesn't work efficiently, then you could see how someone could have ADHD.

But what in the world does this have to do with food dyes?  Azo food dyes like yellow number five are known to cause allergic reactions in susceptible people, typically hives.  That means artificial food colorings may result in the release of histamine, a chemical we let loose during an allergic reaction.  The theory the researchers are working with here is that exposure to food dyes may cause some kids to release histamine, maybe not to a degree to where there is a full-on allergic reaction and hives, but where it could possibly affect behavior or impulsivity.  Since the H3 receptor is prevalent in the human brain, histamine could certainly have a behavioral effect.

Researchers took the same kids who were involved in the Southampton study and checked the their genes for dopamine transporter, dopamine receptor, COMT, and ADRA2A genetic polymorphisms.  All these genes have been associated with select groups of families with ADHD.  In addition, the researchers tested for differences in the histamine N-methyltransferase (HNMT) genes to check out the histamine hypothesis.  An efficiently functioning HNMT system means you clear histamine from the body in a timely manner.  If your gene codes for a protein that is less efficient, you might be more vulnerable to allergy and other histamine-mediated problems.  These kids were a random community sample and didn't necessarily have ADHD, and had gone through a double-blind crossover placebo controlled trial of two mixes of food dyes and preservatives and a control.  The kids' behavior overall worsened significantly in the eyes of the parents and independent observers during the weeks they drank the additive-laden juice compared to the additive-free control juice.  But, once again, individual reactions to the hyper juice were highly variable.  Individual reactions were checked against the individual genotype to see if any connections could be made.

Of the 297 kids, about half were three years old, and the other half were eight and nine.  Among the three year-olds, certain histamine and dopamine gene polymorphisms were associated with higher baseline hyperactivity - prior to drinking any hyper juice.  That is to be expected if the genetic theory is sound.  Among the 8/9 year-olds, there wasn't a connection found.

But what about when we added the additives?  Overall, the three year-olds had significant reactions to the hyper juice (more Mix A than Mix B) if they lacked certain alleles of the histamine N-methyltransferase (HNMT) gene.  There seemed to be no differences in the reactions depending on the dopamine or other checked genotypes.   In the 8/9 year-olds, the results were quite similar.  Not too much difference when dopamine may be off, but a significant difference depending on the HNMT gene allele. 

The study was relatively short term, and obviously should be replicated before we jump up and down too much.  But genetic differences in our histamine systems may explain why some kids react very badly to azo food dyes, and others don't seem to bat an eye.   And this would mean that ADHD, in some people, is very likely a food allergy.  Those kids might also be vulnerable to environmental allergies that affect the histamine system.  There is also some evidence that methylphenidate (ritalin) and atomoxetine (strattera), medications used for ADHD, work not only via dopamine but also via histamine interactions.

The editorial in the same issue says it all:  "The links are clear, and the paper is a watershed, although still falling far short of definitive proof.  As with every breakthrough, more questions emerge than are answered...[the Southampton study didn't separate preservatives from additives which is an issue, as removing preservatives has economic and food safety issues] but there is no cost to health or safety in giving up artificial food colors.  It certainly appears that over and above this set of studies, the cumulative evidence is sufficient for society to demand adherence to the precautionary principle and to... restrict the use of artificial dyes, at least in foods that target children."

From the conservative American Journal of Psychiatry, that is a clarion call.  Amen.