How to Become Smarter (65 page)

(L
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UMMARY
): The precise mechanism of action of artificial dietary ingredients on the central nervous system is not known at present. It would be safe to say that biological systems are complex and minor chemical modifications, such as introduction of a novel chemical into the diet of a species, may have numerous unpredictable effects on the functioning of some organs or systems of organs. The intricately interconnected system of neurons in the brain may be affected by these unusual chemicals, such that the level of “noise” in this system increases, which in turn will contribute to errors.

People who have dealt with cell culture in a laboratory know that mammalian cells are extremely sensitive to the composition of the cell culture medium. Minor changes to the medium, such as adding or removing a single chemical can have profound effects on biological properties of the cells, such as proliferation rate, viability, cell morphology, responsiveness to growth factors, etc. Similarly, the brain cells (neurons) may also be sensitive to the chemical modifications of the diet. It can be theorized that a minor malfunction of interrelated components of a neural network can be translated into a more pronounced disorganization of the whole network. For example, administration of low doses of some pharmacological agents, such as NMDA receptor antagonists, can disrupt organized burst activity of neurons projecting to the frontal cortex and increase disorganized spiking activity of these cells [
605
]. These changes may reduce the signal-to-noise ratio in the neural networks of the brain [
606
]. The resulting problems may manifest themselves as a low processing speed, increased error rate, or reduced mental clarity (the symptom of “brain fog”). Conversely, elimination of all “unusual” chemicals from the diet may increase the signal-to-noise ratio within the neural network and thereby improve cognitive performance.

(L
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UMMARY
): see the
main text
.

The weight of available evidence from animal models of ADHD and from clinical studies suggests that this disorder may be associated with a dysfunction of the dopaminergic system in the striatum and prefrontal cortex [
294
,
296
,
297
].

A dysfunction of the norepinephrine system in the prefrontal cortex may also play a role in the pathophysiology of ADHD because noradrenergic agents such as the reuptake inhibitor atomoxetine and alpha
_2A
-adrenoceptor agonist guanfacine can also be beneficial for ADHD patients (although less effective than stimulants) [
294
,
298
,
607
].

As explained in the main text, ADHD patients exhibit some signs of insufficient protein consumption or impaired protein assimilation. Insufficient consumption/assimilation of protein will reduce the level of dopamine in the striatum and frontal cortex [
329
], which is consistent with hypofunctioning dopaminergic pathways in ADHD, according to the influential Dynamic Developmental Theory of ADHD [
604
]. A diet containing elevated amounts of protein-rich foods should be beneficial for ADHD patients according to the arguments presented in the main text.

In addition to the research we discussed in the main text, there are other studies showing that dietary protein manipulations can affect cerebral dopaminergic pathways [
579
,
608
]. These effects may in part be due to dietary tyrosine and essential amino acids phenylalanine and tryptophan (all present in protein-rich foods) because the first two are metabolic precursors of dopamine [
329
,
609
-
612
], and the latter can increase the level of brain dopamine and norepinephrine via yet unknown mechanisms [
613
] (see also
endnote J
). Limited psychoactive properties of dietary tyrosine are known [
614
,
615
], but dietary supplementation with tyrosine and phenylalanine (separately) results in only a temporary improvement of symptoms in ADHD patients with a return to baseline within 3-12 weeks [
616
,
617
]. On the other hand, dietary protein has different effects on the metabolism and turnover of dopamine and norepinephrine in the brain compared to supplementation with individual amino acids [
608
,
618
]. Therefore, increased consumption of dietary protein should have a more sustained effect on attention function. For example, the effect on striatal and frontal dopamine and on behavior was sustained for at least 36-weeks in an experiment by Farooqui
et al.
[
329
]. In view of the above arguments, high-protein foods that are rich in tyrosine and essential amino acids, such as fish and meat [
120
,
319
], should have a stronger effect on striatal and frontal dopamine compared to other protein-rich foods (such as dairy and some plant products). The total level of catecholamines in the brain is not affected by high-protein diets [
619
].

High-protein diets can cause overactive behavior (not to be confused with impulsivity [
297
]) in healthy laboratory animals [
329
,
333
,
575
], which is also similar to the effects of psychostimulant drugs on healthy subjects (at moderate-to-high doses) [
615
,
620
,
621
]. Overactive behavior can also result temporarily from dietary supplementation with tyrosine in normal mice [
612
]. Paradoxically, stimulants at therapeutic (low) doses tend to
reduce
rather than enhance hyperactivity in ADHD patients and in animal models of ADHD [
298
,
326
]. These opposing effects of stimulants in patients and in normals may be related to dosage of psychostimulants as well as the different state of dopaminergic pathways in normals compared to ADHD patients [
604
]. The related ADHD symptom of impulsiveness (reduced self-control [
622
]) is thought to derive from dysfunction of dopaminergic circuits in the nucleus accumbens (ventral striatum), and drugs that can elevate extracellular accumbal level of dopamine tend to improve impulse control [
296
,
326
,
623
]. It is not clear, however, if the increased extracellular level of dopamine overall inhibits or facilitates dopaminergic transmission [
294
,
331
,
606
,
624
,
625
].

High-fat diets may affect cognitive performance by changing the activity of the cholinergic system in the brain [
626
]. Cholinesterase inhibitors improve cognitive performance in patients with head trauma and neurodegenerative diseases, but not in healthy people [
627
]. The authors of the Swiss study of cognitive effects of a single high-fat meal attribute the beneficial effects of this kind of meals to high stability of the blood glucose level after the high-fat meal, which was not the case with high-protein and high-carbohydrate meals [
117
].

(L
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UMMARY
): Diets containing increased amounts of high-quality protein are likely to improve attention, whereas low-carb diets may or may not have this beneficial effect. Drugs that improve attention in most people and especially people with deficient attention function tend to worsen this mental ability in people with excellent attention function.

Many neural processes underlying attention function take place in the prefrontal cortex (the anterior part of the frontal cortex [
628
]). In particular, stimulation of dopamine D1 receptors, which have a high density in the prefrontal cortex compared to other brain regions, can improve attentional performance in both healthy subjects and patients with ADHD [
294
]. The magnitude and direction of this effect depend on the baseline function of attention and working memory, and there is an inverted U-shaped curve that characterizes the relationship of the dose of dopamine agonists and cognitive performance [
294
]. People with high levels of baseline attentional performance can experience deterioration of the performance after administration of dopamine agonists. People with lower levels of baseline attentional performance can experience improvement at low-to-moderate doses of dopamine agonists. They experience no improvement or deterioration of cognitive performance at high doses of dopamine agonists. In line with these observations, diets that contain excessive amounts of dietary protein may not necessarily improve attentional performance, due to the inverted U-shape of the above relationship. In addition, ketogenic diets, which contain tiny amounts of carbohydrates and large amounts of fat, may worsen some cognitive abilities. This is because the supply of blood glucose, the main energy source of the brain, decreases. Ketone bodies provide the main source of energy for the brain during ketosis, and they may not be the most optimal source. Ketosis typically reduces the activity level of laboratory animals and humans [
629
,
630
]. On the other hand, a balanced high-protein diet, which contains sufficient amounts of dietary carbohydrates and elevated amounts of high-quality protein, may improve attentional performance at least in part due to the effects on the cerebral dopamine system.

The author is a healthy subject who does not satisfy diagnostic criteria for ADHD [
340
]. He received a clean bill of health (both physical and mental) on April 25, 2008, after a comprehensive medical examination by the Military Registration and Enlistment Office of the Sovetskiy District, Kutateladze Street, 16b, Novosibirsk, 630128, Russia. The author underwent psychiatric evaluation, which was a part of the above examination, at the Municipal Healthcare Institution, Consulting-Diagnostic Polyclinic #2 (MUZ KDP #2, Russkaya Street, 37, Novosibirsk, 630058, Russia).

A possible clinical study protocol
(L
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UMMARY
): The proposed clinical trial of high-protein diets in ADHD patients consists of two groups, each serving as a control and an experimental group for approximately one half of the duration of the trial, in a cross-over manner. This section also describes the calculations for the necessary number of patients for the trial. In addition, an experiment is outlined that can test the productivity benefits of high-protein diets for knowledge workers.

In principle, the modified protein supplement or the modified high-protein diet (
Appendix II
and
Chapter Three
) will be safe to test in a clinical trial with ADHD patients for a period of four weeks. The modified high-protein diet must include boiled grains if a person follows this diet longer than a week (otherwise impulsivity may become a problem). The only exclusion criteria will be kidney disease and
constipation
. Test subjects with milk allergy or lactose intolerance can use goat milk, cultured milk or lactose-free milk. The patients who are opposed to consumption of meat can test either the protein supplement consisting of unprocessed unsalted cheese plus ground nuts or the antidepressant diet plus ground nuts (vegetarian high-protein diets). The proposed study design is AB/BA crossover with wait-list controls [
631
,
632
] or, alternatively, with a specially designed control diet that contains a normal amount of protein (0.8 g/kg). The trial can be double-blind if it uses a control diet that is as difficult to comply with as the experimental diet. Researchers can avoid most of the complexities associated with a control diet if they use an
open
trial and compare the experimental diet to a drug known to be more effective than a placebo. Approximately forty ADHD patients can be distributed randomly into two groups: AB and BA. We will discuss the sample size in more detail below. Group AB will use the modified high-protein diet for four weeks followed by two weeks of washout and four weeks of control diet (or no treatment). The protocol uses the reverse order for group BA. The total duration of the trial is ten weeks.