5. Fats and the Brain

Children are especially vulnerable to inadequate fat suppply due to their rapidly developing brain. The brain does not consume fat as fuel -- this would be problematic because it would lead to a cannibalistic behavior where the brain would feed off of itself. According to the Franklin Institute, as much as two-thirds of the brain's mass consists of fats. The membranes of neurons consist of a thin double layer of fatty acid molecules. The myelin sheath that encases each fiber in the network of nerve fibers that make up the "white matter" consists of 70% fat and 30% protein. A child's brain is constantly laying down new connections and reshaping old connections to incorporate new experiences and knowledge into long term memory. This processing requires a steady and reliable supply of fats.



Through a technique known as "diffusion tensor imaging" (DTI), scientists have been able to examine the brains of children with and without a diagnosis of ADHD (Brain Differences in ADHD) [5]. They found several differences, most notably, in the volume of white matter connecting together the frontal cortex, basal ganglia, brainstem, and cerebellum. These areas are involved in higher level thought and reasoning, attention, impulsive behaviour, inhibition, and motor activity. Never-medicated ADHD children had noticeably smaller volume of white matter in these areas, compared to normal children or to ADHD children who had been treated with medications such as Ritalin.

White matter consists of a massively interconnected network of nerve fibers, each of which is coated with a fatty myelin sheath that keeps the message insulated (i.e, keeps the signal strong) and greatly increases the transmission speed. In order to focus attention, the brain releases the hormone dopamine from centers in the midbrain, and dopamine receptors transmit signals over long distance pathways to the frontal cortex, the basal ganglia, and the cerebellum, as shown in the figure on the left. Dopamine is a crucial hormone that orchestrates the brain's thought processes involved in maintaining attention to a task and subsequently acquiring new knowledge. Defective dopamine utilization is widely suspected to play a role in ADHD [36]. Poor quality white matter on these long-distance connections, as a consequence of insufficient supply of fat from the blood, would have a huge impact on the ability to pay attention and to learn new facts.

A very exciting research direction that has been undertaken recently addresses the question of the rate of maturation of the brain [31]. 223 children with ADHD were compared with 223 non-ADHD controls. The research utilized magnetic resonance scans to estimate the thickness of the cerebral cortex at more than 40,000 sample points at different positions along the brain surface. Typically, the thickness increases during childhood and then decreases during adolescence. From samples taken over a period of several years, researchers can pinpoint the point in time when the cortex is thickest. The results of the experiments were remarkable: children with ADHD reached peak thickness much later (on average at 10 and a half years old) than children without ADHD (on average at 7 and a half years old). The biggest delay showed up in regions of the prefrontal cortex (shown in the figure on the right) that control attention and motor planning.

Such a delay in maturation would be a good conservation strategy if there is insufficient fat in the diet. By slowing down the growth rate of the cortex, less demand is placed to acquire adequate fat supply, needed to grow additional neurons and myelinated nerve fibers. The body's stunted growth (another characteristic of ADHD children) could even be a side effect of the need to delay the rate of maturation of the brain. Decreasing the concentration of growth hormone would likely affect both the brain and the body, leading to a consistent slowing down of maturation rates across the board.

6. Managing Homeostasis without Dietary Fats

Fats are a much more stable energy source than carbohydrates. Sugars and starches, especially in the form of high glycemic index "empty carbs," are absorbed very quickly into the blood stream, causing a sharp spike in the glucose level. This in turn triggers the pancreas to inject a large amount of insulin into the blood, to promote the uptake of the glucose into the body's cells. Carbohydrates ingested without fats are absorbed much more rapidly than carbohydrates buffered by fat, because fat slows down the digestive process. Fats, being digested much more slowly, will become available as an alternative fuel source just as the carbohydrate supplies are becoming exhausted. But this is true only if sufficient fats are consumed with the meal.

Very little excess glucose can be stored in the body for later use, unless it is first converted to fat. The liver can provide a small buffer of glucose stored in the form of glycogen, amounting to no more than 5% of its total mass. Once that capacity is exceeded, any remaining glucose in the blood must be converted to fat to be stored.

A thin child whose diet consists mainly of empty carbs cycles between feast and famine in terms of glucose supply, but suffers chronically from an inadequate supply of fats. This places a lot of stress on the homeostasis system because of the gross imbalance between glucose and fat in the external fuel supply. A solution to this problem can be achieved by piling fat stores on the body, except that the fat stores themselves introduce additional energy needs and the strategy snowballs into obesity.

For the ADHD person, instead of steadily accumulating fat stores and programming the muscles to preferentially consume fats, I argue that their bodies have adopted a strategy of fat conservation. The muscles are programmed to prefer glucose over fat, and the body size is minimized by reducing fat deposits, slowing down the maturation process, and stunting growth. As a consequence of the body's reduced needs for fats, more fat (but still not enough) is available to the brain to support its need to build myelin sheath for the expanding network of nerve fibers.

7. The Role of Ketone Bodies

I am becoming increasingly convinced that ketone bodies play an important role in ADHD. Ketone bodies are an alternative fuel source for the brain that becomes critically important when glucose levels in the blood are low [12]. As has been said before, the brain is unable to utilize fatty acids as fuel. However, it can utilize ketone bodies, and thus their presence becomes a protective mechanism for the brain when glucose is in short supply.

Ketone bodies are produced by the liver as a by-product of fat metabolism. In the absence of fats in the diet, significantly fewer ketone bodies are produced; i.e., the body derives more ketone bodies from dietary fat than from internally synthesized fats [38]. Furthermore, and most significantly, certain specialized cells in the brain called astrocytes are also able to scavenge free fatty acids from the blood and manufacture ketone bodies from them. It is hypothesized that ketone bodies in the brain can also act as "cellular substrates, thereby preserving neuronal synaptic function and structural stability." ([12], abstract). I suspect that astrocytes may be able to accumulate stores of ketone bodies that can serve both as fuel for the brain in times of glucose deficiency, and to assure that important signals such as dopamine get transmitted across synaptic junctions. But insufficient dietary fats will significantly reduce the availability of this critical nutritional resource.

8. Explaining the Gender Bias in ADHD

It is curious that the incidence of ADHD is much higher in boys than in girls. Some estimates claim that the ratio of boys to girls diagnosed with ADHD is as high as 10:1. In the context of a theory that ADHD is caused by fat insufficiency, what are the factors that might afford protection for girls?

First of all, the ratio of fat to muscle in girls is generally much higher than in boys. For the same body weight and size, a girl will have significantly more subcutaneous fat, as contrasted with a much higher muscle-to-fat ratio for a boy. This implies that the supply of bioavailable fats will be significantly higher for girls than for boys.

Secondly, and most importantly, the female hormone estrogen is a powerful weapon for increasing fat metabolism. Exactly how this is accomplished remains somewhat unclear, but it has been hypothesized that estrogen achieves this effect by stimulating an increase in both growth hormone and adrenaline. Growth hormone has been demonstrated to increase mobilization of fatty acids from fat tissue [30], and it is well known that adrenaline does this too [24]. Growth hormone also inhibits insulin production, and reduced insulin at the outset would greatly improve the odds of getting insulin levels sufficiently suppressed to allow fat mobilization.

Several investigators have studied gender differences in plasma free fatty acids in response to exercise, and have shown that females end up with significantly higher levels of fatty acids in the blood after an equivalent amount of exercise than do their male counterparts [2].

Thus, the extra fat cells, the enhanced mobilization of fat from these fat cells in general, and the enhanced effect of exercise on fat release all likely contribute to the significantly reduced likelihood of a girl succumbing to ADHD than a boy.

9. Dopamine

Dopamine is an incredibly important hormone that is released from the substantia nigra in the midbrain and relayed to other parts of the brain through three principal neural pathways: the nigrostriatal pathway to the cerebellum to control body movement, the mesolimbic tract to the reward center and seat of emotion, and the mesocortical tract to the frontal lobes of the cerebral cortex that control high level planning and reasoning. These pathways are part of the white matter that is shrunken in size in the ADHD child's brain. With poor transmission speeds and an inability to maintain a strong signal, these poorly insulated pathways dissipate the message that the dopamine is trying to send.

A recent study by Dr. Nora Volkow compared the brains of 53 nonmedicated ADHD adults with those of 44 healthy non-ADHD adults over the period from 2001 to 2009, using positron emission tomography (PET) brain imaging [36]. The study focused on dopamine receptors, which propagate the signal to distant parts of the brain, and dopamine transporters, which recycle excess dopamine after the signal is transmitted. The study found that both receptors and transporters were reduced in number in the ADHD brains as compared with the normal controls. The receptor count is likely reduced as a consequence of the slow and inefficient transport across the networks. The transporters are reduced in turn in order to slow down the process that sends the dopamine back into storage. This allows the dopamine to stay in the synapse for a longer period of time. Ritalin achieves a similar effect, and this is believed to be the main reason why it is effective.

Research on rats has shown that dopamine release is severely impaired in the absence of insulin [9]. This may be an intentional design as protection against releasing dopamine when there is insufficient glucose to fuel the resulting brain activities. However,the ADHD child, who has an efficient glucose metabolism, must deplete the excess insulin before fats from fat stores can be released. Meanwhile, the dopamine supply is exhausted while trying to send signals over faulty networks, and the release of fats comes too late to be effective.

The brain needs fats as well as glucose for acquiring new knowledge - to reconfigure and reinforce the neural connections. The ADHD child is trapped in a catch-22, because, in order to get at the fat stores, the insulin levels must be low, but if the insulin levels are low, glucose is also likely low (since the insulin is so efficient) and, as well, the dopamine release will be suppressed. A child who consumes a low-fat diet and has very efficient glucose metabolism will likely never have, simultaneously, sufficient blood levels of dopamine, fats and glucose. As soon as the insulin levels are sufficiently low to allow the fats to be released, the glucose and dopamine are likely already depleted. With little fat in the dietary sources, and with impoverished and insulin-suppressed fat cells, it is difficult to imagine where the fat supply for the brain is going to come from.

10. Stunted Growth and Vitamin D and Calcium Deficiency

In my article on obesity, I argued that calcium deficiency plays an important role because calcium is necessary for the release of insulin from the pancreas and for the uptake of glucose by the muscles. Obesity is strongly associated with both calcium deficiency and insulin resistance, and I argue that the fat cells compensate by inserting themselves into the energy chain. They take upon themselves the task of converting glucose to fat, and they program the muscles to strongly prefer fat over glucose as an energy source. In the process, they hoard calcium and vitamin D, and cause measurable deficiencies in these important nutrients in the blood serum.

It is likely that some ADHD children may suffer from calcium deficiency as well, mainly as a consequence of vitamin D deficiency, a syndrome that is at epidemic proportions in the U.S (Vitamin D Deficiency Epidmemic). Probably the most significant nutritional role of vitamin D is its ability to promote both the absorption of calcium from the gut and the transport of calcium across membranes, a process that is extremely important in many aspects of metabolism and brain function. ADHD children tend to be stunted in growth, and their levels of growth hormone are abnormally low. Extending the length of a bone requires an enormous amount of calcium. Thus, by keeping the bones short, the calcium that would have gone into bone growth can be diverted to assure an adequate supply of insulin and an efficient glucose uptake mechanism in the muscle and fat cells.

It could be that ADHD children also sacrifice calcium levels in the brain in order to assure enough calcium for the efficient metabolism of glucose, which is extremely essential when the body is relying mainly on glucose as an energy source. Evidence that calcium channels in the brain are important for memory comes from the surprising result from a study involving 1,268 people who were being treated for high blood pressure (Calcium Blockers and Memory). The study found that people who take calcium blockers to lower blood pressure score less well on memory tests than people who use other medicines to lower blood pressure. Studies using Magnetic resonance Imaging (MRI) verified brain damage in the white matter of the brains of the people who used calcium blockers.

If ADHD children are deficient in calcium in their brains, they are also likely less able to utilize ketone bodies as an energy source in the brain. This conclusion comes indirectly from studies involving alzheimer's patients. It has been found that alzheimer's patients' brains are deficient in the ability to utilize glucose for fuel, and, as a result, regulatory control mechanisms have led to an increased supply of calcium in the brain, which plays an essential role in the metabolism of ketone bodies [13]. This allows them to efficiently use ketone bodies instead of glucose as a fuel source. The converse of this observation is that reduced calcium in the brain would interfere with ketone body metabolism, leaving the brain even more vulnerable to situations of reduced blood glucose levels.

Vitamin D itself plays an important role in brain function, in addition to its influence on calcium, as implied by the existence of a wide distribution of vitamin D receptors throughout the brain [20] (Vitamin D and the Brain) . Vitamin D also affects proteins in the brain that are directly involved in learning and memory, as well as motor control. It may be that, for some ADHD children, insufficient vitamin D is even the main cause of their symptoms.

11. ADHD and Anorexia

Fat cells are part of the endocrine system, and, as I've discussed before, they have the power to influence the degree to which muscle cells prefer glucose versus fats as an energy source. They exercise this control by releasing two signaling peptides: leptin and adiponectin. Adiponectin promotes glucose consumption by the muscles, and it also acts directly on the fat cells to encourage them to take up glucose and convert it to fat. Leptin, on the other hand, stimulates the muscles to prefer fat consumption over glucose consumption.

Statistically, children with ADHD have an abnormally efficient glucose metabolism rate, i.e., for the same amount of insulin, blood sugar levels drop more quickly after a meal than in other children. This observation suggests that their fat cells have arranged a set point of a high adiponectin to leptin ratio, such that the muscles prefer glucose over fats, and fat cells are predisposed to convert glucose to fat. The glucose levels drop more quickly because the muscles and fat cells are using more of it.

Anorexics, children who intentionally starve themselves, are known to have extremely efficient glucose metabolism (tend towards hypoglycemia) and also to have a high ratio of adiponectin to leptin concentrations [21]. This strategy maximizes availability of fatty acids to the heart and brain. It is curious that anorexia is much more common in girls, and ADHD is much more common in boys.

Researchers at Harvard Medical School suspected that there might be an association between anorexia and ADHD. To test this hypothesis, they compared girls with ADHD against a control group to see whether the ones with ADHD were predisposed towards anorexia (ADHD and Anorexia). The results showed that girls with ADHD were 3.6 times more likely than the control group to develop an eating disorder. I have come to believe that anorexia is a technique to combat ADHD that girls are able to adopt, whereas boys do not have enough fat cells to carry out the task of converting glucose to fat. Ritalin is well known to reduce appetite, and long term use can lead to an anorexia-like condition. It may well work, in part, because it achieves this ultra-thin state, thus conserving fats by minimizing the consumption of fat by cells that can get by on glucose.