Fear and Loathing in Clinical Nutrition – Part I

A Perspective on Glutamate, Glutamic Acid, Glutamine and Neurotoxicity

“We are turning into a nation of whimpering slaves to Fear…”

From Extreme Behavior in Aspen – February 3, 2003 by Hunter S Thompson, author of books such as Fear and Loathing in Las Vegas and Fear and Loathing on the Campaign Trail, 1972

“So, first of all, let me assert my firm belief that the only thing we have to fear is fear itself-nameless, unreasoning, unjustified terror which paralyzes needed efforts to convert retreat into advance.”

Franklin D. Roosevelt – First inaugural address

If you were expecting to read more on iodine in this issue, you are not alone.  Until recently, I fully expected to continue my exploration on this subject and indeed I will after part II of this series.  However, another issue that, to me, is related in a somewhat unusual way has now risen to such a level of concern for both patients and practitioners that I felt compelled to set iodine aside temporarily.  Hopefully, I will be able to add some clarity and a sense of calm to the misunderstandings and attendant fears that, today, seem to invariably accompany nutritional controversies.  What is this issue?  As you can see from the title, I will be delving into an issue that appears to be literally creating panic for some people, the potential neurotoxicity of glutamate and all of its various related forms including monosodium glutamate (MSG), glutamic acid, and glutamine.

However, before exploring the anecdotal claims and research on one of today’s most attention-grabbing nutritional controversies, I would like to explore another, “big picture” issue that I feel is just as relevant, if not more so, in terms of understanding all the current concern revolving around glutamate/glutamic acid/glutamine and its impact on brain function.  As I have been emphasizing in the iodine series, very often public perceptions of nutrients, based often on advertising and sometimes less than totally objective reports in the mass media, seem to take precedence over biochemical and physiological reality.  Therefore, as I also mentioned before, in the 1990s, there was a perception that nutrients, being natural, could not only do no wrong but had almost supernatural healing properties.  Thus, the perception of nutrients as benign panaceas was born and certainly propagated.  However, as we entered the 21st century, perceptions of nutrients, as that of many other aspects of modern living, made a major shift.  As we are seeing, the 21st century is becoming the century of fear.

Why is this occurring?  Certainly as I sit here in front of my computer shortly after the seventh anniversary of the events of 9/11/01, even casual contemplation of what occurred seven years ago provides part of the answer.   However, as I leave the newspaper articles discussing the anniversary of 9/11 and turn to those discussing the collapse of the financial markets in which so many wealthy and not so wealthy Americans have invested, it can certainly be concluded that the nature of fear in the 21st century is not a simple phenomenon that can be neatly packaged into a sound-byte relating to 9/11.    In fact, as today’s newspaper headlines suggest, the fear that we see today not only has a fairly complex etiology but fairly complex and sometimes illogical manifestations.  How illogical is it?  To answer this question, I would like to go back to my inference about a relationship between iodine and glutamate physiology.  On the one hand, we are now seeing what I hope to prove to be a somewhat irrational fear of an amino acid that is present in varying amounts in virtually every food source, both animal and vegetable: glutamate/glutamic acid.  On the other hand, as I hope I have already proven to you, we are now seeing a somewhat irrational lack of fear of milligram dosing of iodine among many in this country.  Therefore, how can we even begin to understand the complexities and inconsistencies of 21st century fear?  For, as suggested above by President Roosevelt during the height of the Great Depression, fear can evolve into an entity that becomes so much of a part of our daily lives that it begins to take on a life of its own.  Furthermore, as suggested above by Hunter S. Thompson, this is now happening in post-9/11 America.  In turn, as I will point out, when fear becomes an integral part of our lives, we begin to lose the ability to decide what, realistically and logically, we truly need to fear.  This can ultimately lead us to have a level of fear, either too much or too little, that is greatly out of proportion to the level of risk posed by certain entities.  Of course, when our fear no longer corresponds to the level of danger for any given situation, the end result is that we overreact to certain situations, wasting time and effort that could be spent on threats that truly deserve thoughtful and decisive action.  Thus, thoughtful and decisive action with difficult challenges can only come about when we keep fear in proper perspective as we consider what actions we will take when facing the myriad of decisions that need to be made as part of our daily lives.  Are we in the clinical nutrition community in danger of letting fear become an independent, omnipresent entity in our lives such that we lose the ability to correctly decide how much fear any particular entity deserves?  As I suggested above, when I look at the response of many in our community to glutamate versus iodine, I must conclude that the answer may be “Yes.”

How can attitudes about clinical nutrition affect behavior? 

Given that it is possible that some of you may disagree with the provocative and controversial conclusion made above, I feel I need to give a specific example of how fear can play a negative role in clinical nutrition.  As most of us are well aware, methods of motivating patients to ingest healthy food and healthy supplements that are based on biochemistry and physiology seem to be less and less successful.  What is the best evidence of this?  I would guess the best answer would be the various weight loss regimes that, according to most published papers, fail over 90% of the time.  As suggested in the article “Instead of eating to diet, they’re eating to enjoy” by Tara Parker-Hope that appeared in the September 17, 2008 edition of The New York Times, these methods often are based on the biochemistry and physiology of foods we need to fear.  In this fascinating article, Parker-Hope suggests that dieters will be much more successful if they focus less on the biochemistry and physiology of avoidance and much more on healthy foods that can bring joy into their lives:

“After decades of obsessing about fat, calories, and carbs, many dieters have made the unorthodox decision to simply enjoy food again.

That doesn’t mean they’re giving up on health or even weight loss.  Instead, consumers and nutritionists say they are seeing a shift toward ‘positive eating’ – shunning deprivation diets and instead focusing on adding seasonal vegetables, nuts, berries and other healthful foods to their plates.”

Can a diet that focuses on foods that should be added to the diet, as opposed to foods that should be subtracted, create successful weight loss?  Parker-Hope states:

“Last year, the American Journal of Clinical Nutrition reported on a study of 97 obese women, all of whom were avoiding high-fat foods.  Half of the women were instructed to increase their consumption of fruits and vegetables.  By the end of the year, the women who were focused on adding vegetables lost an average of 17 pounds, 20 percent more than the women who were just paying attention to fat consumption.”

At the end of the article, a quote from Marion Nestle, a New York University nutritionist, to me, sums up the wisdom of this approach to food best:

“‘If you are eating something you really like, maybe you won’t feel like you need to eat so much of it…'”

“‘If you want a muffin, then eat a gorgeous muffin with marvelous blueberries that’s moist and crispy on the outside with a little sugar on it. Yum.'”

If, as suggested by Parker-Hope, we can do better with patient motivation if we understand the fears and other emotions relating to food intake, can we also do better with patient motivation in terms of supplements and individual nutrients if we understand the fears and emotions that come into play today when we make recommendations?  I believe the answer is “Yes.”  In turn, I also believe that we need to have a better understanding of the rapidly expanding sense of fear in general that is engulfing so many Americans today.  For, there is no doubt in my mind, as I suggested, that this creeping fear that, almost paradoxically, contains both rational and irrational aspects, is creating both rational and irrational attitudes and actions towards certain constituents in foods and supplements.

Why is there such a disparity between what we fear and actual degree of risk?

Approximately three years ago in the adrenocortical hypofunction series I discussed fear from a neuroendocrine perspective with an examination of the relationship between dopamine and stress physiology.  While I would guess that many of us would agree that the expanding sense of fear we are now witnessing could be explained by the fact we are now seeing more and more dopamine plus other neurotransmitter imbalances, I would now like to approach fear from a more sociological/psychological perspective.  For, while I feel it is important to understand the neuroendocrinology of fear, I also feel that by understanding the whys and wherefores of fear we can better understand why some, on one hand, are now fearing ingestion of even small amounts of one of the world’s most ubiquitous food constituents, glutamic acid/glutamate and then, in a seemingly paradoxical manner, are having virtually no fear of high milligram doses of iodine that are well documented to cause thyroid-related side effects in a small but significant percentage of the population.

Jeffrey Kluger, in the December 4, 2006 issue of Time Magazine explored this dualistic nature of fear in a fascinating article entitled “Why we worry about the things we shouldn’t…and ignore the things we should.”  To begin the article, Kluger describes the nature of the problem:

“We pride ourselves on being the only species that understands the concept of risk, yet we have a confounding habit of worrying about mere possibilities while ignoring probabilities, building barricades against perceived dangers while leaving ourselves exposed to real ones.” 

The author then presents some interesting examples of this phenomenon:

“Shoppers still look askance at a bag of spinach for fear of E. coli bacteria while filling their carts with fat-sodden French fries and salt-crusted nachos.  We put filters on faucets, install air ionizers in our homes and lather ourselves with antibacterial soap.  ‘We used to measure contaminants down to the parts per million,’ says Dan McGinn, a former Capitol Hill staff member and now a private risk consultant, ‘Now it’s parts per billion.’

At the same time, 20% of all adults still smoke, nearly 20% of drivers and more than 30% of backseat passengers don’t use seat belts; two-thirds of us are overweight or obese.  We dash across the street against the light and build our homes in hurricane prone areas-and when they’re demolished by a storm, we rebuild in the same spot.”

Kluger then goes on to describe the two areas of the brain involved in the adaptation to fearful circumstances based on the work by Joseph LeDoux as described in his book, The Emotional Brain.  The amygdala initially orchestrates the intuitive reaction to stress that is mediated by the stress hormones about which we are all well aware.  Very shortly thereafter, the higher regions of the brain come into play to determine if the perceived danger is for real.

Then, the author discusses the two classic possible reactions to fearful situations, fight and flight.  Both have advantages and disadvantages from a survival standpoint:

“If we’re mindful of real dangers and flee when they arise, we’re more likely to live long enough to pass on our genes.  But evolutionary rewards also come to those who stand and fight, those willing to take risks-and even suffer injury-in pursuit of prey or a mate.”

Next, Kluger presents a working model of how these different aspects of fear, intuitive versus intellectual responses and fight versus flight, come together in relationship to how we, so often, incorrectly determine risk:

“These two impulses-to engage danger or run from it-are constantly at war and have left us with a well-tuned ability to evaluate the costs and payoffs of short-term risk…That, however, is not the kind we tend to face in contemporary society, where threats don’t necessarily spring from behind a bush.  They’re much more likely to come to us in the form of rumors or news broadcasts or an escalation of the federal terrorism-threat level from orange to red.  It’s when the risk and the consequences of our response unfold more slowly, experts say, that our analytic system kicks in.  This gives us plenty of opportunity to overthink-or underthink-the problem, and this is where we start to bollix things up.”

How do all these different aspects of fear perception play out in today’s real-world circumstances?  Kluger addresses this question with the following:

“Which risks get excessive attention and which get overlooked depends on a hierarchy of factors.  Perhaps the most important is dread.  For most creatures, all death is created pretty much equal.  Whether you’re eaten by a lion or drowned in a river, your time on the savanna is over.  That’s not the way humans see things.  The more pain and suffering something causes, the more we tend to fear it; the cleaner or at least quicker the death, the less it troubles us. 

Kluger continues:

“…the more we dread, the more anxious we get, and the more anxious we get, the less precisely we calculate the odds of the thing actually happening. ‘It’s called probability neglect,’ says Cass Sunstein, a University of Chicago professor of law specializing in risk regulation.”

Therefore, a sense of dread does more to determine how we react to a risky situation than the odds that the situation will actually have negative consequences.  To what do we tend to dread and, as a consequence, overreact?  Kluger gives examples:

“We…dread catastrophic risks, those that cause the deaths of a lot of people in a single stroke, as opposed to those that kill in a chronic, distributed way.  ‘Terrorism lends itself to excessive reactions because it’s vivid and there’s an available incident,’ says Sunstein.  ‘Compare that to climate change, which is gradual and abstract.”

What else causes dread?

“Unfamiliar threats are similarly scarier than familiar ones.  The next E. coli outbreak is unlikely to shake you up as much as the previous one, and any that follow will trouble you even less.”

A sense of dread is also determined by how much we perceive that we have control over a situation.  Therefore, if we perceive we have control over a situation, we will tend to underestimate the risk.  Kluger elaborates:

We similarly misjudge risk if we feel we have some control over it, even if it’s an illusionary sense.  The decision to drive instead of fly is the most commonly cited example, probably because it’s such a good one.  Behind the wheel, we’re in charge; in the passenger seat of a crowded airline, we might as well be cargo.  So white-knuckle flyers routinely choose the car, heedless of the fact that at most a few hundred people die in U.S. commercial airline crashes in a year, compared with 44,000 killed in motor-vehicle wrecks.” 

What other factors can cause us to incorrectly estimate risk?  One is optimism bias.  What is optimism bias?  Basically, it is the belief that a risky behavior is less dangerous when I do it versus when someone else does it.  The example Kluger gives is the risk of talking on a cell phone while driving:

“We tell ourselves we’re different, because our call was shorter or our business was urgent or we were able to pay attention to the road even as we talked.  What optimism bias comes down to, however, is the convenient belief that risks that apply to other people don’t apply to us.”

The last factor the author discusses that makes us incorrectly evaluate risk is the degree of potential benefit risky behaviors may confer:

“Finally, and for many of us irresistibly, there’s the irrational way we react to risky behavior that also confers some benefit.  It would be a lot easier to acknowledge the perils of smoking cigarettes or eating too much ice cream if they weren’t such pleasures.”

The biochemical realities of glutamate/glutamic acid

Is fear of glutamate/glutamic acid based on reality or misinterpretation related to the factors mentioned above?  Given that we have so little fear of high doses of iodine, is fear of glutamate/glutamic acid completely inconsistent and illogical?  Or visa versa?  While exploration of these questions is important, I feel they can be most completely evaluated only with a good understanding of the realities of glutamate/glutamic acid biochemistry and physiology.

Glutamate/Glutamic acid – Basic biochemistry and physiology

Lipton and Rosenberg, in their review of the literature entitled “Excitatory amino acids as a final common pathway for neurologic disorders” (1), provide an excellent basic description of the function of glutamate from a neurologic standpoint:

“Glutamate is the principal excitatory neurotransmitter in the brain, and its interactions with specific membrane receptors are responsible for many neurologic functions, including cognition, memory, movement, and sensation.  In addition, excitatory neurotransmitters are important in influencing the developmental plasticity of synaptic connections in the nervous system.”

What happens when glutamate receptors are over stimulated?  The authors continue:

“…in a variety of pathologic conditions, including stroke and various neurodegenerative disorders, excessive activation of glutamate receptors may mediate neuronal injury or death.  Olney coined the term ‘excitotoxicity’ for this condition, which may constitute a final common pathway for neuronal injury due to diseases with diverse pathophysiologic processes.”

Russell Blaylock, from whom most of us first learned about this issue, relies heavily on the work of Olney to form the basis for his statements and conclusions.  I will be exploring both the writings of Blaylock and Olney in part II.

What exactly happens when glutamate receptors experience excessive activation?  According to Lipton and Rosenberg (1):

“This form of injury appears to be predominantly mediated by excessive influx of calcium into neurons through ionic channels, triggered by activation of glutamate receptors.”

The authors then go into more detail concerning the role of calcium influx in neuronal injury and death:

“Intracellular calcium is important for a number of physiologic processes, but excessive amounts may contribute to the overstimulation of normal processes, thus damaging neurons.”

What happens next is somewhat complicated but, as you will see, it involves phenomena about which most of us are aware, including arachidonic acid-mediated inflammation and formation of free radicals:

“NMDA-receptor activation, neuronal increases in calcium, or both can activate a series of enzymes, including protein kinase C, phospholipases, proteases, protein phosphates, and nitric oxide synthase.  After phospholipase A2 is activated, arachidonic acid, its metabolites and platelet-activating factor are generated.  Platelet-activating factor increases neuronal calcium levels, apparently by stimulating the release of glutamate.  Arachidonic acid potentiates NMDA-evoked currents and inhibits reuptake of glutamate into astrocytes and neurons, further exacerbating the situation; oxygen free radicals can be formed during arachidonic acid metabolism, leading to further phospholipase A2 activation, which represents positive feedback.”

What is the net result?”

“These processes can cause the neuron to digest itself by protein breakdown, free-radical activation, and lipid peroxidation.”

Given that neurons are so extraordinarily sensitive to excessive amounts of glutamate, maintaining proper amounts of glutamate in the brain is extremely important to neuronal health.  In particular, as noted by Lipton and Rosenberg (1), the balance between extracellular and intracellular glutamate is extremely important:

“The intracellular glutamate concentration in brain tissue is approximately 10 mmol per liter.  Because of the activity of glutamate transporters, most of the glutamate is intracellular.  The extracellular glutamate concentration in brain tissue has been estimated to be approximately 0.6 µmol per liter.  Substantial excitotoxic damage to cortical neurons or hippocampal neurons in intact tissue is expected to occur when the glutamate concentration reaches 2 to 5 µmol per liter.  Therefore, the ambient concentrations of glutamate are close to those that can destroy neurons, and it is important that the extracellular glutamate concentration and compartmentalization be exquisitely controlled to prevent excitotoxicity.  On the other hand, since each cell contains 10 mmol of glutamate per liter, the potential for disaster is obviously great.”

As I hope you can see, due to the extreme potential for causing great tissue damage extracellularly, glutamate is very effectively sequestered inside brain cells.  However, circumstances exist that greatly increase the chances of extracellular accumulation of glutamate.  Two of these are, according to the authors, defects in glutamate transport and abnormal release from storage sites in neuronal vesicles.  However, one very basic cause is cellular injury:

“The simplest cause of excess extracellular glutamate is injury to cells.  If each cell contains 10 mmol of glutamate per liter, then the death of even one cell puts all its neighbors at risk, reduced only by their ability to remove the glutamate released on their doorstep.  One cause of injury is excitotoxicity itself, and this might be a sufficient explanation for the self-propagating property of excitotoxicity-that is, injured neurons release large quantities of glutamate that in turn injures more neurons.  In addition, traumatic injury to neurons may be followed by excitotoxic injury to neighboring neurons…”

Knowing the above, it should no longer be surprising that we can sometimes encounter clinical situations where even seemingly minor head trauma can have an impact on neurologic function that seems out of proportion to the nature of the initial trauma.

Of course, as we all know, there is another very common cause of brain injury that is not caused by physical trauma.  What is this cause?  Stroke, which injures by depriving neurons of oxygen and glucose.  Lipton and Rosenberg (1) elaborate:

“Deprivation of oxygen and glucose-for example, during ischemia-decreases the production of high-energy phosphate compounds and causes energy failure.  However, energy failure itself is not particularly toxic to neurons.  What makes it neurotoxic is the activation of glutamate-receptor-dependent mechanisms.”

Thus, contrary to the belief of many, the damage done to the brain by strokes is not a simple matter of neuronal death due to lack of oxygen and nutrients.  Rather, it is resultant disturbance in glutamate metabolism leading to excitotoxicity that causes the massive brain cell death often seen with stroke patients.

Finally, according to Lipton and Rosenberg (1), chemical toxicity can adversely affect glutamate metabolism in the brain:

“Toxins that inhibit electron transport in mitochondria are another possible cause of energy failure leading to increased vulnerability to glutamate.  Cyanide inhibits complex IV of the electron-transport chain (cytochrome oxidase), and it causes energy failure and increased susceptibility to excitotoxicity in cultures of hippocampal and cortical cells in vitro.  Interestingly, the neurotoxin 1-methyl-4-phenylpyridium, which can induce parkinsonism, is a complex I inhibitor.”

Interestingly, Lipton and Rosenberg (1) did not mention one of the most controversial sources of excessive glutamate in CNS extracellular spaces, the diet.  Given that this aspect of glutamate metabolism is the one that has provided the impetus for this monograph, I would now like to feature a paper that examines glutamate and its role as a dietary constituent in creating neurologic damage.  In “Understanding safety of glutamate in food and brain,” Mallick (2) provides both an excellent description of the role of glutamate in the brain and glutamate as a dietary constituent.  First, consider what Mallick (2) has to say about glutamate in the brain.  As you will see, it is not only the principal neuroexcitatory neurotransmitter in the brain, it is also the most abundant amino acid in the brain:

“Glutamate is the most abundant amino acid in the brain.  It is synthesized at rates in proportion to the metabolic demand.  Plasma glutamate concentrations may fluctuate during the day due to dietary intake, metabolism and protein turnover.  The assumptions are that if these changes are transferred directly to the brain interstitial space, there can be a disrupting effect on the brain level.  Interestingly, brain levels are much higher than plasma levels.  The presence of the blood brain barrier (BBB) prevents exogenous glutamate from entering the brain to a large extent.”

The author continues:

“The brain in general is a net exporter of glutamate and the presence of the blood brain barrier prevents exogenous glutamate from acting on the brain.”

However, the BBB does not function perfectly in its ability to prevent excessive uptake of glutamate into the brain:

“The fact that glutamate at high doses does not induce parallel changes in the brain level does not necessarily convey that discrete areas of the brain are impermeable to circulating glutamate.  There are some areas of the brain that do not have a good blood brain barrier and do allow rapid l-glutamate uptake from the circulation.”

What is the impact of this highly effective but less than perfect barrier?  I will be exploring this question in much more detail in the next issue.

Now, consider Mallik’s (2) description of the physiology and biochemistry of glutamate outside the brain:

“Glutamate is a component of organs and tissues as a building block of protein.  A 60 kg adult body contains 1.4 kg of glutamate on average.  It has a key role in the metabolism of major nutrients and is important for the reconstruction of body protein and the metabolism of energy.  The dietary glutamate is absorbed from the intestinal tract, and more than half of it is utilized as a major energy source for the intestines, and other are converted to different amino acids such as alanine, proline, and arginine in the intestinal wall.  These amino acids are delivered first to the liver to maintain amino acid balance in the blood and then to the various organs and tissues of the body where it serves in the reconstruction of body protein and energy.  Dietary glutamate is also a specific precursor for the biosynthesis of glutathione.  In the case of protein bound glutamate, it is degraded in the gastrointestinal tract into small peptides or free glutamate, and they are absorbed from the intestinal tract in a similar way to free glutamate.”

Before continuing, I would like to emphasize two key points from the above quote.  First, glutamate is a key amino acid, both qualitatively and quantitatively, for many aspects of human health, not just the brain.  Therefore, fear of glutamate can be compared very closely to fear of water.  While fear of excess or improper use is certainly justified, any suggestions of total avoidance are completely without merit.  Second, even though free and protein bound glutamate are absorbed in a similar manner, well over half of what is absorbed will not be delivered to the CNS, instead being used either as an energy source for the intestines or as a precursor for the formation of other amino acids or glutathione.  Thus, fears that dietary glutamate will have a major impact on neurologic function, which are also justified to a certain extent, tend to be greatly exaggerated based on the realities of how much dietary glutamate actually enters the CNS.  I will explore the issue of glutamate absorption in much more detail in part II.

Now, with this understanding that glutamate plays an integral role in human physiology both inside and outside the brain, I would like to explore in more detail the presence of glutamate in the human food supply.  Mallick (2) states:

“Glutamate is one of the most abundant amino acids in nature.  Since glutamate is a building block of protein and free glutamate exists in organs and tissues, it is found naturally in virtually all foods such as milk, vegetables, seafood, poultry, meats, traditional seasonings like fish sauce and soy sauce and many other foods.” 

Knowing that glutamate in the form of monosodium glutamate (MSG) is added to foods to improve taste, what impact does protein-bound glutamate found naturally in foods have on taste?  The author comments:

“…protein bound glutamate does not have any taste…”

However, as suggested above:

“…free glutamate plays an important role in food as a tastant.”

What is the history of the use of glutamate as a taste enhancer?  It begins with the discovery that seaweed can enhance the taste of foods.  Mallick (2) elaborates:

“The history of glutamate in food is older than the history of the science of nutrition.  The practice of adding large seaweed (Laminaria japonica) to soup stocks has been in use in Japan for the last 12 centuries.  This seaweed markedly increases the taste of the soup.  But what was unknown was that it contained high amounts of glutamate.  It was not until 1908 that the link between the seaweed and glutamate was discovered.  The brown crystals left behind after evaporation of a large amount of kombu broth, was scientifically identified as glutamate by Prof Ikeda of Tokyo University.  He termed this unique flavour as ‘unami.'”

The author continues:

“Subsequently in 1909, monosodium glutamate (MSG), the sodium salt of glutamate, was first marketed in Japan as a seasoning agent.  In fact, glutamate has long been used around the world to enhance the palatability of foods before the discovery of its taste.  Foods rich in free glutamate, such as tomatoes, cheese and mushrooms have been used in cooking for their flavour favoring qualities.”

What other foods generally considered to be healthy, natural source foods contain high amounts of free glutamate?  Mallick (2) states:

“…cauliflower…gourd, most of the Indian breads (Nan, chapatti, and parantha) and basmati rice contained relatively high amounts of glutamate.  These glutamate levels are comparable or higher than that of published data.  Interestingly, glutamate content of basmati rice was found far higher than that of ordinary rice, which suggests correlation between glutamate content and its deliciousness.”

Interestingly, there is another food that is an extremely important part of the human food supply that is high in free glutamate.  Mallick (2) points out:

“It was reported that glutamate is the most abundant amino acid in mother’s milk in all the species analyzed.  The total glutamate content (free and protein bound) in human milk is 161.5 mg/dl to 230.0 mg/dl.  However, human breast milk contains rather high amounts of free glutamate; ten times as high as cow’s milk.  Interestingly, this high level of free glutamate is found only in the milk of humans and higher primates such as chimpanzees, and the milk of other species has much lower free glutamate levels.  The reason for this difference in unclear, but the amount of glutamate is enough to give a taste, so that human infants may experience ‘unami’ as one of the first tastes after birth.”

With this information in mind, what is the typical intake of glutamate for breast-fed infants?  The author notes:

“The daily intake of free glutamate in a breast fed infant is about 36.0 mg/kg body weight while the daily intake of protein bound glutamate is approximately 357.0 mg/kg body weight.  Human infants ingest more glutamate than human adults on a body weight basis and they have the clear ability to metabolize large amounts of glutamate.”

With all the information above in mind, you might conclude that Mallick (2) is of the opinion that any fears concerning the role of dietary glutamate as an excitotoxin are overstated.  However, this is not entirely true.  In fact, the author hypothesizes that adverse sequelae occur as the result of excessive glutamate and one other factor, impaired transport function.  On one hand, the author notes:

“The key event that triggers the entire excitotoxic cascade is the excessive accumulation of glutamate in the synaptic space.”

On the other hand:

“The linkage between impaired transporter function and excitotoxic concentration of glutamate suggests that transporter malfunction is a plausible mechanism of neurodegenerative diseases.  The inadequate clearance of the excitatory amino acid glutamate may contribute to the neurodegeneration seen in a variety of conditions.”

As you recall from my description of the Lipton and Rosenberg (1) paper, these authors felt, like Mallick (2), that defects in glutamate metabolism were just as important as the amount of glutamate in creating neurodegeneration.  Therefore, with this dualistic model of neurodegeneration in mind, Malllick (2) concludes:

“There is no doubt today that glutamate is the principal excitatory neurotransmitter in the CNS.  Its role as a signaling molecule in non-neuronal tissues is fast emerging.  It is unfortunate that we term it as an endogenous toxin, killer transmitter or a taste to kill.  Available knowledge presented in this review does not support glutamate as the sole culprit in the process of neurotoxicity and neurodegeneration.  Glutamate is important and indispensable for the functioning of the CNS and important in food.  The physiological control mechanisms of our body keep a check on its excitotoxic properties.”

Thus, I hope you can see that, while it is probably true that dietary glutamate presents a potential threat to optimal brain health, any suggestions of eliminating glutamate from the food supply are not only impractical if not impossible, but overly simplistic in terms of totally preventing glutamate mediated neurological damage.  For, as we found with so many other health controversies over the years ranging from infections to heavy metal toxins, the ultimate impact of any agent that disrupts optimal function often depends as much or more on the health of the host and host resistance than on the harmful potential of the offending agent.  As I hope I have demonstrated in part I and will continue to demonstrate in part II, this is certainly true for glutamate/glutamic acid/glutamine.

In the next issue I will explore glutamate physiology in more detail, focusing on the interesting relationship between glutamate and the gut.  In addition, I will explore in detail the science behind all the accusations that dietary glutamate in general and MSG in particular represents a major threat to optimal brain function.  As you will see, not unlike many controversies I have explored over the years, the truth lies not with the extremists who claim that dietary glutamate, especially in the form of MSG, is either totally benign or a modern day plague.  Rather, the truth lies somewhere in between.  However, will dissemination of truth eliminate fear and loathing ?  In my opinion, not necessarily.  For, as we have seen all too often in our society, elimination of fear and loathing, as suggested by Hunter S. Thompson, is not as simple as exposing and publicizing truth.  Therefore, I will also go back to my exploration of fear, demonstrating, based on the principles outlined by Kluger, why fear and loathing of glutamate and total lack of fear of iodine that goes way beyond healthy respect of anything ingested in excess will probably continue for many in our society no matter what I ultimately state concerning truth and reality.

Moss Nutrition Report #223 – 10/01/2008

REFERENCES

  1. Lipton SA & Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. Engl J Med. 1994;330(19):613-622.
  2. Mallick HN. Understanding safety of glutamate in food and brain. Indian J Physiol Pharmacol. 2007;51(3):216-234.