Harding KL, Judah RD, Gant C.
Harvard Medical School Fellow,
internship in child/adolescent psychology,
post-doctoral program, neuropsychology
Twenty children with attention deficit/hyperactivity disorder (AD/HD) were treated with either Ritalin (10 children) or dietary supplements (10 children), and outcomes were compared using the Intermediate Visual and Auditory/Continuous Performance Test (IVA/CPT) and the WINKS two-way analysis of variance with repeated measures and with Tukey multiple comparisons. Subjects in both groups showed significant gains (p less than 0.01) on the IVA/CPT’s Full Scale Response Control Quotient and Full Scale Attention Control Quotient (p less than 0.001). Improvements in the four sub-quotients of the IVA/CPT were also found to be significant and essentially identical in both groups: Auditory Response Control Quotient (p less than 0.001), Visual Response Control Quotient (p less than 0.05), Auditory Attention Quotient (p less than 0.001), and Visual Attention Quotient (p less than 0.001). Numerous studies suggest that biochemical heterogeneous etiologies for AD/HD cluster around at least eight risk factors: food and additive allergies, heavy metal toxicity and other environmental toxins, low-protein/high-carbohydrate diets, mineral imbalances, essential fatty acid and phospholipid deficiencies, amino acid deficiencies, thyroid disorders, and B-vitamin deficiencies. The dietary supplements used were a mix of vitamins, minerals, phytonutrients, amino acids, essential fatty acids, phospholipids, and probiotics that attempted to address the AD/HD biochemical risk factors. These findings support the effectiveness of food supplement treatment in improving attention and self-control in children with AD/HD and suggest food supplement treatment of AD/HD may be of equal efficacy to Ritalin treatment.
From the Full-Text Article:
Attention deficit/hyperactivity disorder (AD/HD) is classified by the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) as a mental disorder primarily characterized by a “persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development.” The DSM IV explicitly defines the meaning of the term “disorder.” 
“In DSM-IV, each of the mental disorders is conceptualized as a clinically significant behavioral or psychological syndrome or pattern that occurs in an individual and that is associated with present distress (e.g., a painful symptom) or disability (i.e., impairment in one or more important areas of functioning)…. Whatever its original cause, it must currently be considered a manifestation of a behavioral, psychological, or biological dysfunction in the individual…. In DSM-IV, there is no assumption that each category of mental disorder is a completely discrete entity with absolute boundaries dividing it from other mental disorders or from no mental disorder. There is also no assumption that all individuals described as having the same mental disorder are alike in all important ways. The clinician using the DSM-IV should therefore consider that… individuals sharing a diagnosis are likely to be heterogeneous even in regard to the defining features of the diagnosis and that boundary cases will be difficult to diagnose in any but a probabilistic fashion.”
Although individuals diagnosed with AD/HD share a similar range of outward behavioral symptoms, the underlying causalities are “likely to be heterogeneous,”  a term defined as “of unlike natures, composed of unlike substances” and “consisting of dissimilar or diverse ingredients or constituents.”  Such heterogeneity could be within biological, psychological, and/or social levels of organization (The Biopsychosocial Model)  or could vary widely within each level of organization for each individual with AD/HD. At least at the biological level of the biopsychosocial model, an extensive literature review by Kidd strongly supports a heterogeneous molecular etiology for AD/HD, with each individual likely to have a unique array of abnormalities expressed symptomatically as AD/HD. 
There is a complex body of information suggesting multiple, heterogeneous, biochemical etiologies for AD/HD. For purposes of discussion and clinical utility, the information can be assembled into eight general etiological categories:
(1) food and additive allergies; [6-25]
(2) heavy metal toxicity and other environmental toxins; [26-36]
(3) low-protein, high-carbohydrate diets;37-39
(4) mineral imbalances; [40-52]
(5) essential fatty acid (EFA) and phospholipid deficiencies; [53-57]
(6) amino acid deficiencies; [58-63]
(7) thyroid disorders; [64-67] and
(8) B-vitamin and phytonutrient deficiencies. [68-74]
Each of the publications noted above examines only the relationship of AD/HD to a single or a few risk factors. Furthermore, within each etiological category, the studies primarily examine only the relationship of AD/HD to a single or a few variables within each category. Exemplary variables included, but were not limited to, various food and additive allergies, two toxic metals (aluminum and lead), several B-vitamin (B1, B3, and B6) deficiencies, several amino acid (tryptophan, tyrosine, and D- and L-phenylalanine) deficiencies, thyroid abnormalities, a high-carbohydrate and low-protein diet, endogenous protein and carbohydrate metabolic abnormalities, EFA deficiencies of the omega-3 series, and abnormalities in several essential minerals (iron, selenium, zinc, copper, phosphorus, calcium, and magnesium).
The neurobiological etiology of AD/HD has been postulated to be associated with deficiencies in catecholamines, such as norepinephrine and dopamine,  with little discussion concerning the physiological origins of the multifaceted mechanisms required to generate such neurotransmitters. Likewise, the therapeutic effect of Ritalin® is thought to be linked to its effects on norepinephrine and dopamine.  In contrast to this view of neurotransmitters as isolated variables that exist independent of the whole organism, this study protocol attempted to restore and regulate neurotransmitters in test subjects by supplementing the diet with amino acid precursors (e.g., tyrosine) likely to be deficient in the subject as determined by symptoms. For instance, since tyrosine is the precursor for dopamine and norepinephrine, and deficiencies in these excitatory neurotransmitters are likely to be a factor in inattentiveness, subjects who displayed predominantly inattentive symptoms (as opposed to hyperactivity) were provided with extra tyrosine as part of their supplement regimen. In addition, vitamin and mineral co-factors for neurotransmitter formation were supplemented. Other etiological factors were addressed by nutrients as indicated.
This study compared outcomes of two distinct paradigms of AD/HD treatment – the pharmaceutical (Ritalin) and the nutraceutical (dietary supplements). Ritalin’s therapeutic effect has been hypothesized to result from presynaptic dopamine transporter inhibition, thus increasing the availability of the neurotransmitter dopamine,  especially in the frontal lobes of the cerebral cortex.  Dietary supplements used in this study also potentially increase catecholamine (dopamine, norepinephrine, and epinephrine) synthesis by precursor loading (tyrosine is the precursor to dopamine and norepinephrine ) and delivering B-vitamin (vitamins B3, B6, and folic acid) and mineral (iron and copper) cofactors. Vitamin C is also a cofactor for the synthesis of the neurotransmitter norepinephrine, imbalances of which are also linked to AD/HD,  and may be beneficial in reducing toxicity of some heavy metals, such as lead. Phospholipids and essential fatty acids are necessary for cell membrane repair, especially in the developing central nervous system, and may improve synaptic physiology and neurotransmitter efficiency.  These essential lipids have also been utilized for gut enterocyte repair, which, along with reinnoculation of friendly flora and the administration of probiotics, could mitigate food allergy. Formal allergy testing, desensitization procedures, or rotation/elimination of potentially allergenic foods were not done in this study.
Reviews of the physiological and anatomical brain abnormalities in AD/HD suggest AD/HD arises idiopathically or that such brain abnormalities are caused by a genetic predisposition.  If such anatomical and physiological abnormalities were to arise spontaneously in genetically susceptible individuals, without known biochemical cause(s), it would follow that optimal treatment of AD/HD should be palliative, symptom management with medications. The 70 studies that support the eight risk factor categories as well as the positive outcomes in this study suggest AD/HD does not arise spontaneously, but in fact is caused by a combination of factors. This evidence suggests the physiological and anatomical brain abnormalities in AD/HD are not pre-programmed and inevitable, but are instead an expression of genetic vulnerabilities to the noted risk factors. Certain individuals may have genetically-imposed, heightened requirements for certain nutrients. If such individuals are not provided with optimum targeted nutrition, they may be significantly more vulnerable to the physiological and anatomical brain abnormalities associated with AD/HD symptoms.
Regardless of the various biological, psychological, or psychosocial factors that are ultimately found to cause AD/HD, this study found that synergistic combinations of dietary supplements directed at the more probable underlying etiologies of AD/HD, as determined by previous studies, [6-74] were equivalent to Ritalin treatment as measured by improvements of attention and self-control using IVA/CPT testing. The means for both treatment groups demonstrating the greatest subject impairment were found in the Full Scale Attention Control Quotient and the Visual Attention Quotient. This is consistent with the validity study for the IVA/CPT, where “comparisons of pre- and post-IVA/CPT scores can reliably be interpreted to reflect possible medication, treatment, or environmental effects.” 
These findings support the effectiveness of a combined vitamin, mineral, amino acid, probiotic, essential fatty acid, and phospholipid treatment in improving attention and self-control in children with AD/HD. This combined nutritional approach more or less addressed eight likely risk factors. Further studies that target nutritional treatments to the unique, a priori, laboratory-determined risk factors of each test subject would go far beyond such vague empiricism and potentially achieve even better outcomes, based on treatment of the unique biochemical heterogeneity of each individual test subject.