The cognitive abilities of older persons vary dramatically. There are tell tale signs in the brain that doctors use to make a definitive diagnosis of Alzheimer Disease (AD). These are referred to as "plaques" and "tangles." When they achieve a threshold degree and distribution, the neuropathologist doing the examination establishes that the brain findings are consistent with the diagnosis of AD. Interestingly, it has been established in many studies that approximately 40% of the subjects whose brains house this degree of pathology on post mortem exam have no evidence of mental impairment. This suggests that some brains are able to tolerate these potentially devastating findings much better than others. The "Million Dollar Question" is why. At present, the neurobiologic basis for this robust observation is not well understood.

The concept of "compensation" is commonly applied to many organ systems throughout the body and is an important determinant of health outcomes. When a relative donates a kidney, for example, the donor experiences no loss of renal function because of the large amount of reserve function in the remaining kidney. Hence, it easily compensated for the loss of its neighbor. The only change observed is that it may enlarge slightly over ensuing months due to enhanced physiologic demands. Is it possible that similar changes can occur in the brain.

Brain transplants have not been performed, at least yet. However, interesting findings noted on functional brain scans such as PET (Positron Emission Tomography) scans and fMRI (functional Magnetic Resonance Imaging) scans suggest there is an innate ability of one part of the brain to compensate for diminished function elsewhere. Thus, the brain, de facto, has a component of brain reserve. This is consistent with the notion that the functional organization of the brain is felt to be redundant. In addition, it has been postulated that there are differences between brains in their efficiency and ability to respond to certain environmental challenges.

Neuroimaging data of the type just mentioned support this view. When performing a cognitive task, aging is associated with lower activation of brain regions used by young subjects while performing the same task, and increased activation in other regions. This phenomenon has been interpreted as demonstrating compensation by alternate networks. Surprisingly, a similar pattern of brain activation has been observed in both young patients with mild AD and older subjects without AD. The implication is that the process of compensation (manifested by the engagement of additional brain resources) is a normal process during aging and in pathologic states such as AD (and presumable stroke, head injury and other disease states).

The concept of brain reserve was first referenced in a study of individuals with high levels of AD pathology post mortem who remained nondemented in life and had almost twice the number of neurons throughout their cerebral cortex in comparison to those who developed mental symptoms. It was felt that "those people might have started with a larger brain and more neurons and thus might be said to have a greater reserve."This neurocentric version of reserve relies on a genetically endowed advantage based on increased neuronal numbers.

Another perspective regarding brain reserve involves the concept of "neurocomputational flexibility" wherein certain individuals who have developed a range of cognitive strategies for solving complex problems are more likely to remain normal cognitively for longer despite progression of underlying disease. They may also have a greater number of potential neural pathways for execution of these cognitive processes, thus permitting maintenance of function despite neurological insult. In essence, this suggests that an individual who utilizes a specific brain network more efficiently, or is able to bring alternative brain networks on-line in response to increased demand may thus have greater brain reserve. Such a construct links brain reserve with performance of complex mental activities, increased neural and synaptic (a synapse is the point where one nerve cell contacts another) numbers and consequently enhanced brain function.

Numerous population-based cohort studies have examined the link between complex mental activity and risk of developing dementia. When analyzed together, they revealed an overall risk reduction of 46%. The separate effects of education, occupational complexity and cognitive lifestyle activities were similar in magnitude. The issue is whether such mental activity-related dementia risk remains modifiable in late life. Interestingly, participation in cognitive and social lifestyle activities in later life (independent of either education or occupational experiences) showed significant (50-66%) protection against risk of dementia.

What are the possible mechanisms behind this robust effect? Mental stimulation is a strong stimulator for the generation of a neurochemical called BDNF (Brain-Derived Neurotrophic Factor) and Nerve Growth Factor (NGF). They play critical roles in nerve cell survival, neuronal connectivity, resistance to disease and learning and memory. An enriched mental environment increases generation of new synapses by 150-200%. This effect is especially important for dementing illnesses because of the dramatic loss of synapses in these disorders. Even more intriguing is the suggestion that mental activity may diminish the production of AD neuropathology. These insights are potent incentives to engage in a mentally active lifestyle to ensure a vibrant future life.

During the billions of years of human (and pre-human) evolution, time has been divided into daily, seasonally, and yearly repeating cycles. Based on these imposed cycles, biological processes have developed that have enabled organisms to exploit temporal niches in their environment and to coordinate physiological responses to optimize metabolic efficiency and survival.

In humans, because of evolutionary pressures, these rhythms have become entrained within our nervous systems. They are generated by the approximately 20,000 neurons located in the master clock in the suprachiasmatic nucleus (SCN) of the brain. It’s proximity to the optic nerves (the nerves connecting the eyes to the brain) is not surprising given the role the day-night (light-dark) cycle plays in this physiology. Its nexus with a part of the brain called the hypothalamus, the region that monitors and controls the body's internal milieu (fluid and electrolyte balance, temperature regulation, and hormonal status, etc.) has important implications as well.

The pacemakers for these rigidly regulated functional ebbs and flows are generated endogenously within the network of SCN nerve cells. More interestingly, each cell in this grouping has intrinsic clock-like abilities incorporated within its genetic makeup. Specific genes (referred to as clock genes) generate the rhythm. This is done using a biological trick called a negative feed back loop. It works as follows. The gene turns on and does what genes do. That is, it creates a protein that is released within the cell. Among other duties, this protein then interacts with the gene that created it and in so doing, turns it off. This process is repeated over and over again. The time it takes for one complete cycle is 24 hours. This nifty process constitutes the molecular basis for the biological clock that forms the basis for the circadian (within a day) cycles that coordinate many bodily processes. Circadian rhythmicity is abolished by damage to the SCN.

These clock genes, and their associated daily cycles, are genetically conserved over numerous species. They play vital roles in many biological phenomena including metabolism, hormonal regulation, fertility/reproduction, thermoregulation, bone formation, fat accumulation and sleep-wake cycles. As such, alterations in circadian periodicity might affect these processes. Mood disorders are even associated with rhythm disruption and clock gene variations. Under conditions of constant light or constant darkness, the synchronicity of the SCN neurons is lost. “Jet lag” seems to be a likely consequence of this environmentally induced perturbation. The advent of the “24 hour society” likely has had adverse impacts on the SCN and probably contributes to the prevalence of sleep disorders estimated to affect 20% of Americans.

In the regulation of hormonal function, timing is everything. This depends intimately on the internal clock mechanism that orchestrates the synthesis, secretion and control of hormones. It is well-known that differing exposure to light modulates hormonal regulation and melatonin levels. Other environmental stimuli such as social signals, poor nutrition, physical activity levels, sleep habits and stress produce effects that are integrated in to the functioning of this intricately balanced system. Common examples of adverse effects are altered menses, infertility, mood swings and difficulty concentrating and learning. Cortisol, the “stress” hormone can single-handedly reset the circadian clock.

It should be obvious that changes in many of the factors discussed above can induce functional alterations in our biological clock mechanism producing adverse health changes in many bodily systems.

There is increasing evidence for the presence of vitamin D, its receptor (VDR), and enzymes that activate vitamin D (change its chemical structure so it becomes biologically active in cells) in brain cells (neurons), brain supporting cells (glial cells, which outnumber neurons 10:1), spinal neurons and peripheral nerves in the arms and legs. These findings support roles for vitamin D in nervous system development and function. Such observations initiated a significant paradigm shift from vitamin D as the hormone that increased the absorption of calcium from the intestines to a hormone with systemic (throughout the entire body) actions.

On the microscopic scale, vitamin D is able to modulate and change the structure of neurons, their release and uptake of a diverse array of neurotransmitters (chemicals that enable neurons to communicate with each other), and how they carry out many daily functions. VDRs have been identified in the cerebral cortex, the cerebellum (balance center), and most interestingly of all, the limbic system (center of emotional processing). It has been recognized for many years that vitamin D deficiency is accompanied by irritability, anxiety and depression. Because it plays a central role in the regulation of seasonal rhythms, vitamin D deficiency has been linked to the incidence of SAD (Seasonal Affective Disorder). This is in keeping with its well known mood-elevating effects.

Mounting clinical evidence reveals a potentially important role for vitamin D in the aging brain.  As we age, dietary consumption of vitamin D and sun exposure are restricted and may lead to profound insufficiencies in serum vitamin D levels in the elderly. These have been associated with well-documented behavioral and cognitive declines. In line with such observations are animal data that reveal serotonin-elevating effects of a vitamin D rich diet. Serotonin is the feel good chemical that the group of anti-depressants including Zoloft, Prozac and Paxil elevate.

The region of the brain called the hippocampus is the center of memory function. As it ages, so do our memories. Recent reports support the role for vitamin D as a potent anti-inflammatory agent in rat hippocampi. Another study demonstrated that vitamin D supplementation in animals slowed the development of biomarkers of aging in the hippocampus. Given the important role of the hippocampus in cognitive information processing, it is not surprising that vitamin D status influences the development of age-related mental functioning.

Global vitamin D deficiency is on the rise, not only in the elderly, but in the young and middle-aged as well. Experts in vitamin D metabolism and preventative medicine have published studies demonstrating the safety of daily amounts of vitamin D in the 4000 to 5000 IU range. The current recommended daily amount is in the 400 IU range. It is clear that this level is woefully inadequate. Because vitamin D is inexpensive and easily produced, there is no reason to permit such deficiencies, and their associated diseases, to exist!

Multiple Sclerosis (MS) is a slowly progressive, often disabling disease of the nervous system. It consists of regions of nerve injury characterized by demyelination or loss of the protective fatty coating of the nerves. When this fatty myelin coating is damaged, it is akin to removal of the plastic coating of the wires in your home. If the wire connecting a light to a wall outlet loses its insulation, the light will go out because the electricity stops being conducted. When nerves lose their myelin, or insulation, the same thing happens. Conduction from one nerve to the next is interrupted. If this develops in a group of nerves responsible for sensation on the hand, for example, numbness will be the result. The disease produces multiple and varied neurological symptoms. There are activations and remissions during the course of the disorder. The exact cause of MS is unknown. Inheriting genetic risk factors for MS is not sufficient to cause this disease. Exposure to environmental risk factors is also required. MS may thus be preventable if these unidentified factors can be avoided.

An interesting observation regarding the incidence of MS is that it increases with decreasing exposure to solar radiation. Incidence of MS is lowest in the tropics.This suggests that sunlight may be protective for MS. Since the vitamin D system is exquisitely responsive to sunlight and MS is highest where environmental supplies of vitamin D are lowest, it has been suggested that vitamin D may protect genetically susceptible individuals. Studies on MS and vitamin D have found that periods of low vitamin D precede the occurrence of high MS activity, while periods of high vitamin D precede low MS activity.

To study the relationship between vitamin D and the risk of developing MS, Dr. Walter Willett and his associates at Harvard and the University of California at Irvine used data from two large prospective human cohorts to determine whether or not vitamin D intake is associated with risk for developing MS.

Over 180,000 women were followed for 10 years. Diet and total vitamin D intake (including that from vitamin supplements) were assessed at baseline and every 4 years thereafter. During the follow up period, 173 cases of MS were confirmed. The study results identified a 40% reduction in the risk of developing MS in those subjects who used daily supplemental vitamin D in amounts greater than or equal to 400 IU, versus those who took no supplemental vitamin D. The authors interpreted the results as supporting a protective effect of vitamin D intake on the risk of developing MS.

In the 1950s, it was noted that the average annual sunshine exposure and the winter daily solar radiation at a person's birthplace correlated strongly and inversely with the life time incidence of MS. This was subsequently confirmed in other studies. It was later observed that the season of birth in those who later developed MS differed significantly from the general population. The consensus of these studies appears to suggest a higher risk if the first or second trimester of pregnancy were during the fall or winter, the seasons of low or absent synthesis of vitamin D by the skin in mothers living at moderate to high latitudes.

There are numerous examples where simple dietary supplementation has been quite effective in preventing specific diseases. This is best exemplified by the connection between folate supplementation during pregnancy and prevention of neural tube defects (spina bifida and anencephaly). It seems this preventive effect works not by correcting a simple, nutritional deficiency, but by influencing specific pathways in early brain development. A related influence may be true for vitamin D due to its beneficial impact on oligodendrocytes (the cells responsible for making the fatty coating of nerves (myelin)). For this reason, if these arguments have validity, the potential health and economic benefits of vitamin D supplementation in areas of high MS prevalence are large. Routine vitamin D provision in pregnancy and childhood is a simple and cost-effective strategy to try and reduce the burden of a potentially devastating disease that destroys many lives.

We last spoke about the daily intake of vitamin D being suboptimal for most persons. Production of vitamin D by the skin is rapid and prolific. When light-skinned individuals sunbathe in the summer for about 20 minutes they are able to generate at least 10,000 IUs of vitamin D within 24 hours. A pregnant mother would have to drink 100 glasses of milk or consume 50 prenatal vitamins to equal this amount of vitamin D. Because of medical advice over the past 20 years to limit sun exposure and use sun-blocking agents, along with recommendations of the American Medical Association's Council on Scientific Affairs to "keep infants out of the sun as much as possible," generation of vitamin D by the skin has fallen dramatically. The consumption of vitamin D in food and supplemental form has not offset this deficit. This dramatically limits the exposure of the brain to optimal vitamin D during pregnancy and thereafter. Such limited exposure of the brain to vitamin D during key developmental stages is novel in the history of mankind and is chronologically associated with rising rates of autism.

Animal data from studies in vitamin D deficient maternal rats have documented abnormal nerve cell growth and proliferation. Reduced expression of a number of genes involved in determination of neuronal structure were observed as were alterations in memory and learning. Another group showed that vitamin D deficiency disrupts 36 proteins involved in mammalian brain development. This is consistent with anatomical studies in rats that revealed increased brain size and enlarged ventricles (the fluid spaces in the brain) similar to children with autism.

A human clinical study in 20 autistic children found that even low daily doses (150 IU) of vitamin D improved sleep and gastrointestinal problems. In other human studies investigating childhood cognition in 'normal' kids, improvements from 1% to 6% have been documented. In one fifth of the children, improvements of about 15% were detected. This may have been the most vitamin D deficient cohort. Recently, low maternal seafood consumption (a rich source of vitamin D) was linked to infants with low verbal IQs and poor outcomes in fine motor skills, communication, and social development. These are all seen to some degree in the autistic spectrum. Consistent with this observation is the association of increased fish intake during pregnancy with improved infant cognition.

When formula fed babies (formula contains significant amounts of vitamin D) are weaned to various juices, such as apple and grape juice, one might expect to see more cases of autism develop. A prospective study of 87 infants, some at high risk for development of autism, and others not, found no difference in cognition at age 6 months (prior to weaning to juice type diets). However, around the age of weaning initial signs developed in those who developed autism with rapid progression between 1 and 2 years of age. This timeline correlates with the age many children with autism deteriorate.

If vitamin D is somehow linked with autism, the prevalence should be lower in sunny climates or near the equator. Recent CDC (Center for Disease Control) data from 14 states showed the state with the highest prevalence was New Jersey (the second most northern state); Alabama, with the lowest prevalence, was the most southern state.

If there is an association between vitamin D deficiency and autism, drugs which lower vitamin D should be more likely to be related to the development of autism. There is little known about drugs that interfere with vitamin D metabolism, but sodium valproate is in this category. It is one of the few gestational drugs that are linked with autism.

Melanin is the skin pigment that makes skin dark and is also an efficient sunscreen. If this is the case, children born to dark skinned mothers might be expected to have more neurodevelopmental disorders. Four recent US studies found a higher incidence of autism in black children. Similar findings exist for dark-skinned immigrants in Europe. Low vitamin D levels are 150% more likely in pregnant black females than in white females. Furthermore, 45% of pregnant black females are severely deficient compared to only 2% of pregnant white women. The most startling observation is that prenatal vitamins containing 400 IUs of vitamin D offered little protection for mother or infant in either population.

The hormones estrogen and testosterone have dramatically different effects on vitamin D levels. Estrogen seems to be associated with higher vitamin D while testosterone is not. If estrogen increases neuronal vitamin D during pregnancy, while testosterone does not, this suggests male brains may not be as protected from vitamin D deficiencies.

These observations are consistent with the genetic basis of autism, the male and dark-skinned predominance, the timeline for development, and the timing of recommendations for sun avoidance.

If vitamin D deficiency contributes to the cause of autism, it has medical, social, and financial consequences. Simple preventative measures are at hand that are both widely available and inexpensive.

This blog entry will be the first in a several part series on the brain and vitamin D. Vitamin D has come to be known as the sunshine vitamin because it is almost exclusively synthesized in the skin upon sun exposure, or exposure to a limited band of UV light. Unlike most other vitamins and minerals, vitamin D is not found in many foods. Based on current estimates, prior to the migration of earlier bands of pre-humans away from the equator to higher latitudes, levels of vitamin D in their bloodstream are estimated to be about 50 ng/ml. This was largely due to prolonged sun exposure. That was the norm for our ancestors who lived near the equator and were not in the habit of covering their skin with clothing. In cities like NY or Boston, because of the tangential nature of the sun during Winter months, negligible vitamin D can be generated. For this reason and others such as dark skin color and religious beliefs requiring almost total skin coverage, more than half of all Americans are vitamin D deficient. This is the case even with the current meager basal standards. There are many published reports suggesting that the present daily recommendations for 400 - 600 International Units (IU) are woefully inadequate. Experts in the field are recommending daily amounts of 1,000 IU, 2,000 IU, or more. Under these proposed guidelines, the percentage of Vitamin D deficiency would likely be in the 75% range or higher. This observation is clearly contributing to the epidemic of osteoporosis. But there may be other implications as well.

To manifest its effect, vitamin D acts by binding to a 'receptor' that is a protein triggering molecule. When this receptor comes in contact with vitamin D, it is 'turned on' and activates certain signaling pathways responsible for carrying out the intracellular biological functions of vitamin D. The receptors for vitamin D are aptly called vitamin D receptors (VDR). Without them, vitamin D would float around in the body without being recognized. Hence, when VDRs are detected in an organ such as the intestines or bone, vitamin D clearly has a place to 'dock' and subsequently manifest its action in that tissue. Because of its major impact on calcium metabolism (by increasing the absorption of calcium from the intestinal tract, for example) it is not surprising that there are VDRs in bone and gut. What is more interesting is the identification of VDRs in the brain, an organ not generally believed to play much of a role in bone health. This finding has spurred much research investigating the possible role of Vitamin D in the brain. It has also generated many hypotheses regarding a possible role for vitamin D as being a 'neuoprotectant' nutrient.

I would like to present a discussion based upon an article by a psychiatrist, Dr. John Cannell. It is about the potential role that vitamin D, and vitamin D deficiency, may play in the etiology, or causation, of what has become a very common neurodevelopmental disorder. The prevalence of autism has increased dramatically in the past twenty years suggesting an environmental contribution. It also has a well-documented genetic basis. There is a male preponderance (4/1, M/F) and it tends to occur more frequently in African Americans. These unique observations suggest an environmental modulator of an underlying genetic contribution.

VDRs are identified throughout the brain very early in the developmental process. They have potent regulatory effects on factors responsible for formation and connectivity of nerve cells, or neurons. In 2006, it was suggested they played key roles in many other brain processes including inflammation, neurotransmission, seizure generation, and behavioral regulation.

In addition to being a hormone, vitamin D is a steroid hormone. As such it has the ability to modulate the activity of many genes. 200 human genes are currently believed to be primary targets of vitamin D. Until recent times, vitamin D was the only neurosteroid hormone generated almost exclusively in the skin. Now large numbers of pregnant women are ingesting small amounts of vitamin D orally, instead of producing large amounts in their skin. This dramatic change is novel to the human race in general, and human brain development in particular. Until modern times, especially during the past twenty years when sun-avoidance campaigns were instituted, this variance in human vitamin D physiology was unheard of.

The next article in the series will discuss the potential impact of this profound alteration.

The brain is essentially a post-mitotic organ. That is science-speak that can be loosely translated to mean each nerve cell (also called a neuron) is as old as the owner of the brain. Many of the other organs of the body produce individual cells on a continuous basis. For example, the lining cells of the intestinal tract are recycled about every 3 to 5 days. Because of this, 'aging' has a very different meaning to a cell that lives for a week than it does for cells that must survive for 80 or 90 years. Neurons live a long time and are exposed to numerous dents and dings every day. They must also contend with insults that don't individually affect cell function in any meaningful fashion, but when such 'sub-threshold' changes accumulate over time, they collectively conspire to produce alterations that very dramatically impair neuronal characteristics. One example of this type of insult is called oxidation. That is what happens when a nail rusts. The same process can affect living cells and tissues by chemically altering vital structural attributes subsequently producing detrimental functional implications. When nerve cell membranes are oxidized, they become stiffer. There are proteins imbedded within the membranes that act as 'receptors' for molecules that enable nerve cells to communicate. These molecules are called neurotransmitters and go by the familiar names serotonin (important in mood disorders), dopamine (the 'feel-good' transmitter), and norepinephrine (for focus and attention). There are many others, more than 50 all together, that serve a variety of uses. For them to do their job, they must attach to a receptor molecule that lives in the membrane. When this pair (neurotransmitter-receptor) is formed, it changes shape. A mental picture of this process might be a key in a lock. After being inserted, the key is turned which opens the lock. Some locks can become 'sticky' or even 'frozen.' When this occurs, the key may be inserted without unlocking the lock. A similar process can develop in neuronal membranes. When they are oxidized, they get stiff and receptors respond less actively when bound to a neurotransmitter. Since this process is the basis for nerve cell communication, when it is impaired brain function is compromised. This is one mechanism that is associated with aging and contributes to memory alterations, for example. Short-lived cells are not around long enough for the buildup of multiple oxidative changes to occur, which takes longer than the 5 days these cells live. 

Neurons must also contend with more catastrophic insults such as strokes, traumatic events, and hemorrhages. These tend to produce damage in a local, isolated region of the brain. They tend to kill cells at the center, leave cells at a distance alone, and produce an intermediate zone of cells that are alive but not functioning optimally.

If part of another organ, such as the liver, is lost, the remaining cells take over and cover for their lost compatriots because each cell in these organs does essentially the same thing. The brain is quite different in this regard. No two neurons are identical and different regions of the brain are wired differently and provide different functions. Given these constraints, how is it possible to 'recover' lost function, and how does the brain cope with chronic disease such as that which accumulates as we age? In other words, what is the brain's backup plan?  

Generally speaking, there are several processes involved. The sick nerve cells can be made healthier. Other functioning nerve cells can learn to compensate for their neighbors who have died, and new nerve cells can be formed. To understand how the brain addresses such problems, it is helpful to consider a simpler example. For this I will use a severed nerve in the hand whose job it is to provide sensation to a specific area of skin. When such a peripheral nerve is cut, several things happen. You lose sensation to a portion of the skin. The body detects this and initiates a response. New nerve cells start to grow out from the spinal cord and the surrounding nerves in the hand start to respond. The nerves supplying touch sensation to contiguous areas of skin realize the presence of the damaged nerve nearby and start to grow and expand into the 'denervated' numb spot. Various nerve growth factors and other chemicals and electrical signals orchestrate this complex process.

The brain reacts in a similar fashion. Neighboring neurons sense the nearby injury and send out branches that integrate into the network of nerves that were injured. Because of the high degree of connectivity between one brain cell and thousands of others, many widely separated regions of the brain are put on notice. They start to reconfigure, or rewire, their connections in ways designed to return functions that were lost or decreased. This process can be visualized on special brain scans called fMRI scans (for functional Magnetic Resonance Imaging). When we perform certain tasks, whether it is moving a finger or adding 3+5, it requires brain activity in specific regions of the brain. This activity is identified by the fMRI scan and is identified as an area of the brain that 'lights up.' Certain tasks cause a portion of the left frontal lobe to light up. When this portion of the brain gets sick or is injured, it lights up less vigorously. However, in time, when the same task is undertaken, something interesting is seen on the fMRI scan. Nearby areas 'turn on' as do brain regions at a distance from the damaged area. Sometimes they show up as mirror image regions on the other side of the brain, in this case the right frontal lobe. Other times they show up as bright spots on the same side of the brain but in the left parietal or left occipital lobe region. These represent signs that the brain is compensating for the loss of function at another area. Again, a host of growth factors, proteins and electrical signals coordinate the process.

What is important to know is that we have a degree of control over what is happening. By training our brains we can facilitate this entire process. In part, this helps explain why different types of therapy work to help stroke patients. Physical activity of various sorts, unrelated to the area involved, acts to enhance the recovery response. You would think the mechanism would be merely augmented blood flow to the brain, yet there are many other pathways that are switched on in the brain by physical exercise of all sorts. They make nerve cells more resistant to future insults, speed up nerve communication, and increase nerve to nerve contact points. Proper sleep is restorative to healthy brains and has additional benefits for sick brains. Stress causes neurons to shrivel up; something that is counterproductive to a healing brain. Stress reduction facilitates brain health and healing. Dietary approaches that lower insulin levels and are anti-inflammatory reinforce each of the above mechanisms and healing pathways. So, the brain can do a lot to heal itself, but the power to turbocharge the response is in your hands!  

During recent human evolutionary history (about 1.5 million years ago), the human brain increased in size by 33% in less than a million years.  For this extraordinary expansion to occur required exceptionally favorable circumstances.  By any measure, the modern human brain is large.  Brains generally increase in size as body size increases.  However, the human brain is about 3.5 times larger than that of chimpanzees which, as adults, have a lean body weight not very different from ours. 

This massive expansion is even more remarkable when the nutritional demands it places on the body are considered.  In adult humans the brain weighs 1400 grams, or approximately 2.3% of the body weight.  However, it consumes almost one quarter of the body's daily energy requirement.  In infants this disparity is even greater.  At birth, the brain weighs 400 grams and constitutes 11% of the body weight yet consumes almost three quarters of the energy intake!  Thus, any theory of human brain evolution must account for the environmental circumstances that would allow our ancestors to commit a large, disproportionate and continuous nutrient supply to the brain, especially early in life.

Most theories are plagued by the 'chicken or the egg' dilemma.  This refers to the fact that hunting, tool use and other more cerebral pursuits have been considered as being forces that drove this rapid brain expansion.  However, for these to exist in the first place, a large brain would have been a prerequisite.  So how did improvements in brain anatomy and wiring develop before a larger brain existed that would have facilitated the formulation of higher brain functions?  And how could this have happened over such a brief period of evolutionary time?  Moreover, the main period of brain expansion was during late fetal and early post-natal development.  At this stage a bigger brain would not have conferred any survival value.

Recent clues have suggested the role of a nutrient dense diet. This meant a diet higher in meat and fat with a lower plant content.  As a possible means of procuring such a diet, hunting would have exceeded the mental capacity at this stage of development and brain size.  A likely solution for attaining a high quality diet without the necessity for a sophisticated procurement system appears to be a shore-based diet.  This meant exploiting the abundant, sustained, and easily accessible food supply at the waters edge.  It probably involved harvesting bird eggs, mollusks, and crustaceans which were nutrient and energy rich.  This diet could have been easily harvested by humans of all ages, both genders and required no special skills or bodily strength.  

Because of the incessant demands for a nutrient and calorie dense diet, especially during the most rapid period of brain growth perinatally, during a time of absolute dependency, it was vital to prevent periods of nutrient deprivation.  This is of interest in light of the fact that although the brains of newborn humans and chimps are similar in size, human infants have about one pound of body fat.  Body fat is almost nonexistent in chimp newborns.  This fat store provided calories that could last for three weeks and thus constituted a formidable buffer against environmental variability.  Fat deposition in the human fetus accounts for 90% of the weight gain leading up to delivery.  This represents an exceptional metabolic commitment and suggests that it somehow  facilitates the survival of the infant.

From a caloric perspective, the brain is able to utilize glucose but can't tap into fat or protein sources to any degree.  It does posses the metabolic machinery to generate energy from ketone bodies, which are compounds that occur due to partial fat combustion.  These are efficiently burned in the brain and can provide 30% of its caloric demands during the newborn period.  Ketones are also a source of carbon for the synthesis of brain lipids and cholesterol that comprise a large fraction of neuronal cell membranes.  Neurons work by being active electrically.  Most cells manifesting high electrical activity (such as neurons, photoreceptor cells and cardiac cells) have a high concentration of DHA (docosahexanoic acid-a long chain omega 3 fatty acid that provides membrane flexibility and function).  The DHA concentration in the fat stores at birth is higher than it is at any other time.  A shore-based diet provides a continuous supply of this vital nutrient for the synthesis and recycling of neuronal membranes and synaptic connections.

These dietary demands are vital at birth, but are no less important for the aging brain.  High energy requirements and the demand for a nutrient dense diet with abundant long-chain omega 3 fatty acids are critical for optimal brain function and act to slow brain aging.  The efficiency with which the brain metabolizes glucose declines as we age.  If energetic demands are to be successfully met as we age, ketone bodies are an ideal fuel source because they generate energy with lower oxygen use and are delivered to the brain via a different transporter than glucose uses.  For these reasons current dietary choices should more closely mirror the shore-based diet responsible for the rapid evolution of the flexible thinking machine we call our brain.