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. 

No, this is not a blog entry about sinusitis, rhinitis or epistaxis (how doctors refer to a bloody nose). It involves an evolutionary discussion of nasal function, anatomy, and connections with prevalent modern day health problems.

In human physiology, the chemical senses (smell and taste) play minor roles compared to vision, hearing and touch.  However, it is well-known that a number of odors can involuntarily elicit access to memories, thought to be forgotten.  Likewise, intense memories can sometimes produce specific olfactory (smell related) experiences.  Olfaction also has a significant impact on human social behavior and mood.

The olfactory system provides for the detection of volatile chemical substances. The receptor cells are located in the mucosal surface of the nose.  They reside high in the nasal cavity where it comes into intimate contact with the base of the brain cavity (located behind the bridge of the nose). This is where receptor neurons (called bipolar olfactory receptor neurons) reside.  They are able to detect the roughly 5,000 odors humans are able to differentiate.  Once stimulated, these neurons transmit an impulse to a relay station (the olfactory bulb) located within the brain cavity. From here the impulse is transmitted directly to the cerebral cortex - that thin layer of nerves that comprises the gray matter overlying the brain.  It forms a series of hills and valleys and is what you first observe when you look at the surface of the brain. The primary destinations of the nerve cells that originate in the olfactory bulb are the entorhinal cortex and the amygdala. The entorhinal cortex is where much of the processing occurs that creates mental awareness of a specific odor.  The amygdala is part of the limbic system, an ancient anatomic region that contributes to memory function and visceral responses including fear, anxiety and stress. It is no accident these are described as being visceral, because, as you can see from their anatomic connection with the nose (a key participant in detecting and processing the aroma of freshly cooked food) they are linked with the digestive tract.  The intimate relationship of the 'nose brain' with memory, learning, and emotional traits is also intriguing.

Specific odorants (volatile chemicals that contact the olfactory receptor neurons which generate an electrical signal that is transmitted to the brain) are stimuli our nose detects and our brain uses to create a mental image it associates with that chemical. This mental picture the brain creates is what is referred to as an odor.  Think of a bottle of chemicals used to clean paint brushes.  That is the odorant.  When we smell it, the mental image of 'turpentine' is generated.  This is the odor, or smell we perceive.  Using a visual analogy, the wooden platform with four legs used for writing is perceived as a desk. Since odors are mental constructs, they may be subject to additional mental processing and may even be perceived differently dependent on subsequent personal experiences.

Chemical senses, including smell, play an important role in the animal kingdom.  They have been used as a method of communication with other members of the species, for detection of food, for identification of potential environmental dangers such as larger animals on the prowl or rancid potentially toxic food, and for reception of biological signals pertinent to mating and reproductive processes.  Olfactory signals differ from typical visual or auditory stimuli in that they are frequently transient, but are often extraordinarily complex.  For example, the aroma of coffee is made up of more than 800 volatile components.  It is also difficult to 'label' smells and as a result they are often described by the situation in which they are encountered such as "this smells like Christmas."

Olfactory signals also provide discriminatory functions in social interactions by allowing for the identification of individuals.  For example, mothers are able to identify their newborn babies by odor after only a brief exposure (less than an hour).

These examples serve to underscore the intimate connectivity between odors, nasal function, and the brain.  The anatomical infrastructure is primitive and the link to survival benefits for the organism suggests a long-standing important nexus between the olfactory system and and vital aspects of human physiology. 

If we fast forward to modern times, the current epidemics we are confronted with include obesity (and the closely associated disorders diabetes and cardiovascular disease) and various states of mental decline including Alzheimer's disease (AD).  These conditions don't exist in isolation.  Obesity increases the risk of developing AD two or three-fold.  There have also been links established between impaired olfactory function and AD.  This is not surprising given the close proximity, intimate connectively, and anatomic overlap between the nose brain and the vital memory center called the hippocampus.  In fact, the earliest neuropathological findings identified in the brains of patients with AD occur in the nose brain (entorhinal cortex).  From here, they spread throughout the brain. Convergent data reveal that AD patients show impaired olfactory performance, specifically in tasks of odor identification.  Recently, an association was found between decreased olfaction and diminished left hippocampal volume in persons with probable AD.  Loss of the sense of smell (not related to sinus and other local diseases) has been identified as a predictor for later cognitive decline in non-demented elderly retirees.  There are starting to be early hints that obesity might also be associated with altered olfactory function.  A study documented modified olfaction in obese children aged 10 to 16 years.  Clearly, more studies are required to investigate this correlation.  Hence, there are links between impairments of olfactory function and both AD and the obese state.

Thus it appears there is a link between obesity, AD and the nose brain.  The question might be asked, what is its substrate.  Clues to this exist.  Numerous investigators have identified decreased insulin signaling in the brains of patients with AD.  This has been documented in animal models of AD.  In addition, when insulin levels in the brain are evaluated, they are lower in AD than in age equivalent normals.  AD patients are frequently found to be insulin resistant.  This means their bodies don't react normally to the hormonal effects of insulin.  Insulin is the hormone that regulates and controls blood sugar levels.  With a diminished response to insulin, blood sugar levels rise and higher insulin levels are needed to bring them back to normal.  As insulin levels rise in the bloodstream, they fall in the brain.  One reason for this is that insulin in the blood can't be as effectively transported to the brain because of modifications in the blood-brain-barrier (BBB).  Animals with lowered brain insulin develop mental decline and memory loss.  In short, they become demented.

The same findings exist in obese, non demented persons.  That is, they have lower brain insulin levels.  One effect of brain insulin is that it decreases appetite.  This makes the connection seem potentially causal.  It would be interesting to find out whether deviations in olfaction constitute a common feature of states of insulin deficiency in the brain associated with obesity and AD.  This is not far fetched because there are high levels of insulin receptors in the nose brain.

Whether this is true, or not, the nose-brain connection may provide a therapeutic route for treatment.  Over the years spontaneous passage from the nose to the brain has been documented for viruses, heavy metals and bioactive peptides such as CCK (cholecystokinin).  More recently, investigators have documented the passage of nasally applied insulin (the same hormone used to regulate blood sugar) across the nasal mucosa into the brain.  In addition, they have shown enhanced focus, memory, and performance of daily activities in patients with early AD who had been studied after intra-nasal application of insulin. 

These astounding observations should serve as an incentive to pursue additional research in the nose-brain connection including its potential as a therapeutic conduit for some of the common health concerns afflicting many persons today.

We have all heard about the 'Fight or Flight' response in the Neanderthal context.  This basically refers to the hormonal changes  triggered when a caveman met a wild beast.  It was designed to preserve the species.  He, or she, was suddenly forced to fight the beast or leg it out and out-run or out-climb the more powerful animal.  The response being referred to involves the activation of a set of neuro-endocrine pathways designed to enhance performance in what was usually a short term yet very intense struggle.

Another, possibly more precise way of describing these neuro-endocrine responses is to characterize them as sympatho-adrenal.  'Sympatho' refers to activation of the sympathetic nervous system.  Activation of the sympathetic nervous system (SNS) causes the release of epinephrine (adrenalin) and norepinephrine into the bloodstream.  These have a panoply of metabolic actions including the elevation of blood pressure and blood glucose.  Increased propensity of the blood to coagulate is another indirect effect which would act to stem bleeding from an artery that might be injured.  Activation of the SNS also produces a rise in serum triglyceride levels.  Triglyceride-rich particles facilitate the neutralization of multiple hostile invaders such as bacteria, viruses and protozoans.  As is apparent, these responses are designed to maximize outcomes in the field of battle. 

The 'adrenal' part of the sympatho-adrenal response refers to release of the stress hormone cortisol into the bloodstream from the adrenal gland.  Because of this, serum cortisol levels rise.  Cortisol is in the category of 'glucocorticoid' hormones.  'Gluco' refers to the link with sugar and  the subsequent elevation of blood sugar levels caused by cortisol.  The benefit of enhanced blood glucose availability is that the muscles (those organs necessary for transporting you away from an angry tiger) will then have an uninterrupted supply of the fuel source they rely on.

In the past, most serious threats were usually resolved one way or another relatively rapidly.  However, in modern times the typical triggers of this primordial hormonal response are chronic in nature and thus produce a prolonged activation of the hormonal responses just described. They were never designed for chronic use.  Modern day stressors are the primary triggers of the fight or flight hormonal response.  In most circumstances stress develops not from crossing paths with a wild animal, but from the unremitting demands at home or at work, financial pressures, lack of sleep and trying to cram too much into too little time.  The hormonal responses are then activated in a continuous fashion.  The persistence of these hormonal responses is at the root of many modern day illnesses including high blood pressure, weight gain, weak bones and heart disease.  This observation is especially germane for the brain.  When exposed to persistently elevated cortisol levels, neurons suffer.  They lose contacts with their neighbors, shrink, and are less resistant to the daily insults all cells are continuously exposed to.  In rodent studies, when infused for just three weeks with the rat equivalent of cortisol, brains wither and memory suffers.  This is in only three weeks!  Imagine how many of us are exposed to chronic stress lasting for months or years.  In the animal studies, the amazing observation is that if the stress hormone infusion is stopped, the brain atrophy reverses!  If this didn't happen, there would be little more to discuss.  However, because it does reverse the question remains, "What can be done about modern brains exposed to chronic stress?"

This is where complete understanding of the flight or fight response is important.  As it evolved over millions of years, it consisted of two related phases. The first phase involves the stress response and subsequent hormonal activation.  It is followed almost immediately by the second phase, the flight response-the most likely reaction to the (generally) physical stressor.  The flight response involves running, jumping, climbing or other similar strenuous activities.  These are identical to what we refer to today as exercise!  When we exercise we trigger the same physiological responses.  They tend to counteract the effects of the stress inducer.  That is the beauty of the combination of stress and vigorous physical activity.  As a result, blood pressure falls, glucose levels fall and triglycerides fall after exercise.  Exercise even reverses the hormonal changes.  It appears to provide the best and most natural antidote for stress.  When the two phases of the fight or flight response are dissociated, or uncoupled, and one is engaged without the other (the situation occurring in most of us today) we experience only the bad effects and it takes its toll on our health. Hence, the optimal way to reverse the ill effects of our stressful lives and the associated adverse impact on our health is to exercise vigorously on a daily basis.  By understanding our ingrained physiology (the fight or flight response) and what goes awry when it is only partially turned on (especially in a continuous fashion), it is clear what the best approach is to address the problem.  Daily exercise is Mother Nature's solution to one aspect of our modern day lifestyles.        

Sounds pretty healthy at first blush, doesn't it?  How could anything having to do with fruit be anything but healthy?  After all, it is recommended that we consume five to eight servings of fruits and vegetables each day.  They contain many healthy nutrients such as antioxidants-the compounds that counteract the harmful effects of 'free radicals', those damaging compounds that age cells, injure the genetic material they depend on, and cause clumping of our functional proteins and lipids- those fatty compounds that enhance function in each cell in the body.  For example, grapes contain resveratrol, a unique ingredient that has been purported to lengthen the life span of various organisms.  I believe there are many healthy nutrients in fruits and veggies.  However, try to imagine in your mind's eye how these foodstuffs might have appeared in the distant past.  For example, take an apple.  It would clearly not have been the large, succulent type of fruit that appears on today's grocery shelves.  It would have been small, tough, and shriveled.  Nothing resembling what is eaten today.  The major difference is that the current varietals are aptly described as tasting sweet, for good reasons.  They are large and starchy; full of sugar. The typical apple contains approximately 1.5 grams of glucose, 6 grams of fructose (fruit sugar), and 3 grams of sucrose (read table sugar).  

 As our gene pool evolved over the past several million years, one of the major influences shaping genetic alterations is the diet.  Of note is the observation that, aside from the past 10,000-20,000 years, we have been exposed to food that included essentially no rapidly absorbed carbohydrates (other than for seasonal honey-like substances).  The rapid absorption of the glucose in starchy foods such as potatoes and bread has been studied along with the related rapid rise in blood insulin levels (associated with the Glycemic Index concept).  Books have been written discussing the Glycemic Index and what it implies.  However, in my opinion, equal emphasis has not been given to the impact that fruit sugar, or fructose, as it is otherwise called, has upon our health.  As an example, the GI (Glycemic Index) of white bread is 100.  That represents the exaggerated rate of rise in blood glucose, and with it the tightly correlated rise in blood insulin levels.  If you consume the same number of carbohydrates in the form of table sugar (or sucrose, which consists of a molecule of glucose and fructose linked together), the GI is only about 60, roughly two-thirds as high as the white bread.  This makes it seem like eating sugar is healthy because its GI is much lower than that of bread.  This couldn't be further from the truth.... for reasons other than those reflected by their glycemic index.

Sugars, such as glucose and fructose, have the uncanny ability to bind to functional proteins, fats and DNA particles.  When this occurs, they dramatically degrade the vital activity of these molecules.  This forms the basis for a commonly requested lab test called HBA1c that measures the average blood sugar level for the past couple of months.  This is a test that represents adequacy of blood sugar regulation over a long period of time and is important in diabetic control.  It reflects the innate ability of these sugars to bind to the hemoglobin protein that is naturally present in the bloodstream.

What is important to note is that the propensity of fructose to bind to these important biological molecules is ten-fold greater than that of glucose even though glucose has a much higher GI.  This is a shortcoming of the GI.  There are many reasons why this distinction is important, but the one I am most concerned about is the relationship between binding of these sugars to delicate proteins in the body and the correlation with brain atrophy.  Brain atrophy may be viewed as brain shrinkage, which is not a good thing to have going on in your brain.  Clinical investigations have documented the close correlation between brain atrophy and level of HbA1c in the blood-a proxy for the degree of binding of these sugars to functional compounds in the body.  One study even found it to be the most significant indicator of brain atrophy. 

The take home message is to avoid foods that contain high amounts of fructose, or fruit sugar.  In this context it is not necessarily the apple I am referring to, but HFCS (high-fructose corn syrup) and table sugar (sucrose).  Numerous foods contain 20 to 40 or more grams of these ingredients.  Be careful to read labels because they even sneak into ketchup and other condiments.   

Athletes who compete at the highest level are able to do so because they train the muscles they depend on to maintain their competitive edge.  For example, basketball players are required to get high off the court to lob a pass or perform a jump shot over the outstretched arms of an opponent.  The extensor muscles in the leg such as the quadriceps and gastronemius/soleus groups are the ones that must perform. The same principle applies for each sport.  To maximize performance, attention must focus on the appropriate muscle groups.  Brain training follows similar rules .... to a degree.

When the brain performs a task, we see no external movement or activity associated with the neurons that were firing during a particular thought process.  To visualize what parts of the brain were activated, scientists use very sophisticated types of brain scanning devices.  The two most popular are PET scanning, for Positron Emission Tomography, and functional MRI scanning, which is a type of magnetic scan.  When a subject is required to perform a mental function such as an arithmetic calculation in one of these machines, specific regions of the brain 'light up.'  This is a reflection of the increased metabolic activity in the requisite areas of the brain necessary for the particular function required.  If the muscles of an athlete were imaged in a scanner while exercising, we would see analogous findings.

The optimal training for an athlete mandates a training regimen designed to work out specific muscle groups under competitive conditions.  The optimal training regimen for the brain is somewhat different.  The cognitive demands of modern day life necessitate a flexible thinking machine, not a robot that performs one thing well time and time again.  This observation mandates quite a different training approach.  What seems to work best is a program that turns on, activates, or lights up, large regions of the cerebral cortex-the surface of the brain which is the part of the brain most densely packed with nerve-to-nerve connections.

Going back to the lab for a moment, when asked to perform a unique task that has not been done before, it is common to see large areas of the brain turned on when visualized via a functional MRI scan.  This is not unexpected.  What is surprising, however, is when that same task is performed a second time or a third time, there is much less response on the scan.  Much smaller areas light up.  An athlete excels by repetitive training and the enhanced ability to maximally fire certain muscles.  The brain seems to 'learn' how to do something in a way that the second time around it functions better and faster with less work.  However, to get to this point it needs to start out performing a unique task.  Hence, it seems like novel situations are what the brain was built to handle and what it should be trained for and with.

What is the take home message from all of this science-speak?  It is that 'the brain loves novelty.'  Translated into modern living circumstances this means if you want to train your brain most effectively you should choose tasks that are out of the ordinary for your daily circumstances.  Simple examples include such basic chores as using the computer mouse with your left hand if you are right-handed, walking on an irregular surface with bare feet, going backwards up the stairs, or in a non-physical example, approaching a common problem in a unique way.  All of these are brain-training exercises.  What is worth noting is that as you activate, or engage, large regions of the brain for one task, these same regions may be required for the performance of other, possibly more complex and unrelated, demands.  Yet, you have trained them and thus enhanced their connectivity with neighboring neurons with these seemingly simple training tools. 

So, each day it would be a good idea to try and activate your brain in new, novel and different ways in challenging circumstances.  It will also be fun and exciting.  Enjoy your new brain workouts!