To say that obesity is caused by merely eating too many calories is like saying that the only cause of the American Revolution was the Boston Tea Party

–Adele Davis

Articles in this Series:
Part 1 – Magnesium and the Mind/Body Connection in Disease
Part 2 – Magnesium – Nature's Calcium Blocker
Part 3 – The Calcium–To–Magnesium Ratio
Part 4 – Glutamate in Mood Disorders
Part 5 – Addiction
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity

he brain chemistry which governs our appetite for energy–rich foods is rightly designed to be incredibly powerful.  Our craving for food, the biological drive necessary to obtain it, and the reward experienced when food is ingested, all serve as automatic processes ultimately ensuring the survival of our species.  In many respects, however, it’s this same brain chemistry which is hijacked by non–nutritive substances like drugs and alcohol in the process of addiction.  Knowing this, it’s not surprising to find that both food and traditionally–addictive substances can have similar effects upon brain chemistry.  In recent years, for example, brain–imaging technology has repeatedly shown that certain foods can stimulate the reward centers of the brain in a manner akin to highly addictive drugs like cocaine and heroin.  This research has sparked intense debate within the scientific, medical, legal, and political communities as to whether certain foods can rightly be called addictive.

Lawmakers and public health organizations have begun to clamor for stricter regulations upon sellers of “junk foods,” and various “sin taxes” have been proposed to serve as disincentives for junk food consumption similar to the taxes and regulations which have largely helped to curtail cigarette smoking in recent decades.

But many, including substance abuse specialists, have rightly pointed out that brain imaging studies are poor predictors of actual behavior; and as such, are insufficient to provide evidence of true addiction. Similar surges of pleasure–chemicals in the brain, for example, are well–documented to occur in response, not only to addictive drugs or sugary, fatty meals; but also to many pleasurable experiences such as listening to music, exercise, or human touch.

But critics of the idea that food can be addictive often fail to recognize one important point.  Regardless of whether the underlying biology is sufficient to prove addiction, many overweight and obese individuals could already be characterized as suffering from addiction clinically, as evidenced by the following universal symptoms of addiction:

• Persistent desire or repeated unsuccessful attempts to quit (or, in this case, to lose weight)

• Important social, occupational, or recreational activities given up or reduced

• Continued use despite knowledge of adverse consequences

Whether sellers of junk foods should be increasingly regulated, or whether they should be held legally (and financially) accountable for the effects of their wares are questions better left in the political and legal realm.  As is so often the case with billions of dollars at stake, governmental, legal, and commercial interests only serve to obfuscate the scientific literature needed to derive meaningful solutions.

In other words, the true solution to our current obesity epidemic won’t be achieved through government regulation, taxation, or litigation.  An unbiased look at the scientific literature, on the other hand, gives us many reasons to think that a solution can be achieved through rectifying our uniquely nutrient–depleted diets and food supply.   

Micronutrient Deficiency Epidemic in Modern Diets

The biological response to the taste of various foods is an evolutionary strategy designed to offer automatic feedback on the suitability of food for consumption. The sweet and pleasing taste of sugar, for example is likely to have served as an automatic signal to our distant ancestors that a sugar–containing food (such as fruit) would serve as a rich source of quick energy. The pleasing taste of salt is likely to be a clue as to the biological importance of minerals such as sodium, while conversely, the aversion to bitter substances likely allowed our ancestors to avoid substances which were potentially toxic.

In recent years, through brain imaging and extensive studies of taste receptors, scientists have essentially confirmed what any reasonable layperson would assume – i.e., that the most addictive components of food are usually those which make food pleasurable to consume. In examining the literature, several nutritional suspects (usually acting in combination with one another) emerge as uniquely prone to trigger addiction biology. These include:

• Glucose / Sugar and Carbohydrates

• Salt (Sodium Chloride)

• Fat

• Glutamate

It’s likely that biological cravings for these food components allowed our distant ancestors to automatically ingest a reasonably balanced array of many supporting vitamins and minerals. An affinity for the sweet taste of fruit, for example would certainly have ensured the intake of easily absorbable calories in the form of sugars, but would have also supplied important micronutrients such as vitamin C, carotenes, B–complex vitamins, and potassium.

But, in our uniquely–modern food supply, while there’s sure to be no shortage of the above–mentioned addictive substances (all of which are added to foods in artificially–high amounts), many of the nutrients needed for the proper metabolism of these substances are often woefully lacking. These missing nutrients are often the exact ones needed to curb addiction biology.

So, rather than making our diets unnecessarily restrictive (by cutting calories, or by drastically reducing our intake of fat, sodium, or sugar), it seems more likely that simply supplying our bodies with nutrient–rich traditional foods and certain nutritional supplements will go a long way towards rectifying the intense cravings, addiction biology, and overall metabolic disruption fostered by modern foods.

There are sure to be many nutrients lacking from our modern diet, but it’s interesting to note that the epidemic deficiency of a single nutrient, magnesium, may be a common thread uniting all aspects of food addiction and its negative consequences for overall health. Magnesium deficiency has been shown to make all of the potentially–addictive components of food: sugars, sodium, fat, and glutamate, significantly more toxic. Magnesium deficiency has been implicated in the metabolic syndrome and all of its related pathologies, including: obesity, diabetes, heart disease, elevated blood lipids, and the presence of chronic systemic inflammation. As we’ve seen in previous articles in this series, magnesium deficiency also creates the perfect biological environment for the development of intense cravings and the perpetuation of addiction biology.

Diets Don’t Work

Part of the reason why addiction is so often difficult to define, quantify, or diagnose is because of the wide variation in people’s ability to consciously override their brain’s signals – or more colloquially, the wide variation in people’s ability to exercise their willpower.

Each individual, of course, has a widely different threshold where willpower yields the reigns of behavior to the biology of addiction.  In some instances, for example, full–blown alcoholics may be able to quit alcohol consumption “cold turkey” without the help of medication or organized counseling.  It’s certain that their brain chemistry would still be characteristic of addiction, but, for whatever reason, these people may be able to exert will over their disorder even in the presence of intense cravings driven by powerful chemical signals. Such cases, however, are generally the exception and not the rule. Appeals for the addict to exert greater willpower are usually of little to no help in combating addiction. Along these lines, in the realm of weight loss, we find that approaches which rely almost exclusively upon willpower and personal responsibility are nearly complete failures as well.

By some estimates, the weight loss and diet industry in the United States generates nearly 60 billion dollars annually – providing evidence that Americans are, very much, trying to lose weight. While a significant portion of this total revenue may include money spent on “diet foods” and “snake oil–like” nutritional supplements which offer little chance of proving effective, a larger portion includes money spent on weight–loss centers and physician–assisted weight loss programs which offer seemingly reasonable guidance as to the importance of portion control, food selection, and calorie counting.

But overwhelming evidence in the scientific literature shows the long–term futility of even these rational sorts of weight–loss diets. As evidence, even though recent changes in Medicare policy allow for funding of obesity treatments with proven efficacy, extensive reviews of the research have shown that, over the long–term, calorie–restricted diets are not effective obesity treatments.  More often than not, in fact, those engaging in calorie–restricted diets seem to ultimately gain back more weight than they lose:      

Study Link – Medicare's search for effective obesity treatments: diets are not the answer.

Quote from the above study:

It appears that dieters who manage to sustain a weight loss are the rare exception, rather than the rule. Dieters who gain back more weight than they lost may very well be the norm, rather than an unlucky minority. If Medicare is to fund an obesity treatment, it must lead to sustained improvements in weight and health for the majority of individuals. It seems clear to us that dieting does not.

Noting that calorie–restricted diets are characterized by intense cravings and significant relapse, researchers have begun to investigate the many biological parallels between obesity and drug addiction:

Study Link – How can drug addiction help us understand obesity?

Study Link – Neural mechanisms underlying obesity and drug addiction.

Study Link – Compulsive overeating as an addiction disorder. A review of theory and evidence.

Study Link – Factors common to successful therapy for the obese patient

Quote from the above study:

There may be a need to conceptualize obesity as a food dependency disorder not amenable to self–control strategies.

Glutamate, NMDA, and Obesity

In the previous edition of the Integrated Supplements Newsletter we examined the role of the amino acid and neurotransmitter, glutamate in addiction. We saw how excessive glutamate signaling in certain areas of the brain may be involved in reinforcing the pleasurable reward associated with addictive substances. We also saw that substances which block glutamate signaling at the NMDA receptor have shown promise in treating addiction:

Study Link – In search of a new pharmacological treatment for drug and alcohol addiction: N–methyl–d–aspartate (NMDA) antagonists.

Quote from the above study:

It is hypothesized that NMDA receptors mediate the common adaptive processes that are involved the development, maintenance, and expression of drug and alcohol addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists offers a novel treatment approach.

Similarly, drugs which block glutamate signaling have also proven effective in combating binge–eating disorders – perhaps the clearest example of addition–like behavior as relates to food:

Study Link – A new anti–obesity drug treatment: First clinical evidence that, antagonising glutamate–gated Ca2+ ion channels with memantine normalises binge–eating disorders.

Quote from the above study:

Memantine treatment markedly decreased appetite within few hours and complete suppressed the binge–eating disorder within 24 h. Body weight decreased markedly within a few days. The findings strongly support the hypothesis that elevated levels of nutritional [glutamate] play an important role in the pathomechanism of human obesity.

The researchers who conducted the above study have advanced the hypothesis that increasing amounts of glutamate in the industrialized food supply may be a major contributing factor in the modern obesity epidemic:

Study Link – Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite.

We’ve also seen in previous articles in this series, that magnesium is the primary nutritional element needed to counter excessive glutamate signaling. As magnesium is among the nutrients most conspicuously absent from our modern food supply, it’s likely that the effects of dietary glutamate will be amplified in direct proportion to the degree of magnesium deficiency.

Glutamate, MSG, Appetite, and Obesity

In recent years, scientist’s understanding of taste buds has evolved beyond the traditionally–known tastes of bitter, sweet, sour, and salty. A unique taste known as umami, from the Japanese meaning “good taste,” is now known to contribute the savory, brothy, or meaty flavor of many foods. Perception of the umami flavor on the tongue is known to be triggered by glutamate, and evolutionarily, the pleasing taste of glutamate may be a biological trigger leading us to consume the protein–rich foods necessary for tissue growth and repair.

In traditionally–prepared foods like slow–cooked meats and soup stocks, some glutamate can be liberated from intact protein structures, and this effect is likely to be responsible for the uniquely satisfying savory experience of such foods. In modern times, however, where traditional time–intensive means of cooking and food preparation aren’t compatible with the maximal profit sought by the food industry, glutamate is often added to commercial food to improve the food’s flavor and palatability.

The most recognizable source of glutamate in processed food is monosodium glutamate (MSG), but because MSG has such a negative connotation with consumers, in the ingredient lists of processed foods (if glutamate is listed at all) we often find glutamate called by more “label–friendly” terms such as hydrolyzed protein or yeast extract.

Glutamate and/or MSG is commonly used as an ingredient in soups and soup mixes, flavored snack chips, condiments, salad dressings, and sauces. But even many supposedly healthy fast–food items such as sandwich meats and processed chicken breasts are notorious sources of added glutamate.

As we’ve seen previously, glutamate is both a component of food and a remarkably important signaling molecule in the human nervous system. Though the party line of food producers and most scientists is that MSG is a safe food additive, for decades, MSG has been suspected of causing various neurological and mood–related symptoms in susceptible individuals.

But, when it comes to the obesity–inducing effects of MSG, it’s not the acute safety of MSG which is in question. Even if MSG doesn’t cause any observable physical pathologies or mental symptoms when consumed (though much research shows that it may in susceptible populations), it may still play an important role in the modern obesity epidemic.

At first glance, much of the research pertaining to MSG and obesity seems conflicting. In some relatively short–term animal studies, MSG appears to have either no effect (and in a few studies, a beneficial effect) on caloric consumption or weight gain. Many animal and human studies, on the other hand, show that MSG does lead to increases in caloric consumption and weight gain. For example, the following study demonstrated that appetite for subsequent feedings developed more rapidly after consuming soup containing MSG:

Study Link – Umami and appetite: Effects of monosodium glutamate on hunger and food intake in human subjects.

Quote from the above study:

…the most important finding concerning MSG showed that motivation to eat recovered more rapidly following a lunchtime meal in which MSG–supplemented soup was served as the first course (compared both with the effect of unsupplemented soup and no preload).

And, in what is likely to be a particularly important study as it relates to real–world patterns of MSG usage in humans, researchers examining MSG consumption among rural villagers in China found that the rate of obesity in MSG users was significantly higher than that of non–users. In this study, a direct correlation was found between the amount of MSG used and the degree of obesity:

Study Link – Association of Monosodium Glutamate Intake With Overweight in Chinese Adults: The INTERMAP Study.

Quote from the above study:

With adjustment for potential confounders including physical activity and total energy intake, MSG intake was positively related to BMI. Prevalence of overweight was significantly higher in MSG users than nonusers.

The association between MSG and obesity in this study, surprisingly, persisted even when adjusted for calories, meaning that MSG use didn’t simply cause people to eat more food or calories. These findings hint at major metabolic disruption being caused by MSG, or, in other words, a given amount of calories may be more “fattening” when excess glutamate is present in the diet.

Glutamate in Traditional Diets

One of the objections often raised whenever MSG is proposed as a unique contributor to the modern obesity epidemic is that glutamate is a natural component of traditional foods consumed in cultures known for their particularly low incidence of obesity. The discovery and production of isolated MSG, for example, was made possible in Asia by the analysis of seaweed broths which had been consumed for centuries without the apparent neurological or weight–related harm often attributed to MSG. Other common foods such as tomatoes, cheese, and slow–cooked meats are sure to contain significant levels of free glutamate as well.

But while it is true that the avoidance of free glutamate in food is nearly impossible, there are several factors to consider when assessing the true role of dietary glutamate in modern obesity and neurological disorders. First off, traditional dietary sources of glutamate were sure to also contain many of the very nutrients which are needed to prevent excessive glutamate signaling. Edible seaweeds, for example contain glutamate, but also contain a relative balance of other amino acids, calcium and magnesium (in a physiologically–sound ratio), and various polysaccharides and fibers with the unique ability to slow down digestion, and therefore, regulate appetite.

Some evidence, for example, shows that the increase in food intake, and the negative metabolic effects caused by MSG can be prevented when dietary fiber is added to the food supply of rats:

Study Link – Monosodium glutamate in standard and high–fiber diets: metabolic syndrome and oxidative stress in rats.

Quote from the above study:

The fiber–enriched diet prevented changes in glucose, insulin, leptin, and triacylglycerol levels that were seen in the MSG group.

And not only may naturally–occurring glutamate be generally safer than its isolated counterpart, it’s also important to realize that the current consumption of MSG per capita far exceeds any exposure to glutamate previously encountered at any other time in human history.

In 1969, the global population was an estimated 3.6 billion people. By 2001, the global population had increased by 70% to approximately 6.1 billion people. Worldwide production of MSG in 1969 has been estimated to have been 200,000 tons. But, by 2001 (a time interval in which the obesity rate had been increasing at its most precipitous pace), the worldwide production of MSG was estimated at 800,000 tons – a 400% increase. So, clearly, the rate of increase in the consumption of MSG has far exceeded the rate of increase in population growth. This in no way proves that MSG causes obesity, but it does provide clear evidence that the effects of MSG in the modern diet are likely to be far different and far more pronounced than glutamate in traditional diets as the overall quantity has increased, and the presence of protective nutritional components like magnesium has simultaneously decreased.

Critics of the idea that MSG plays a role in obesity also point out that serum and brain levels of glutamate don’t always rise when MSG is consumed – which is why the well–known practice of inducing obesity in laboratory animals by injecting MSG may not be directly applicable to human oral intake. Animal studies have shown, however, that high oral doses of glutamate are capable of exerting toxicity to the very areas of the brain involved in both addiction and the regulation of appetite (this effect occurs especially in young animals, or in the offspring of pregnant animals given MSG):

Study Link – Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite.

Quote from the above study:

We demonstrated that MSG maintains its toxicity even when administered orally.

Study Link – Effect of monosodium glutamate given orally on appetite control (a new theory for the obesity epidemic).

Quote from the above study:

A nearly total destruction of the arcuate nucleus can be observed with the parenteral administration of MSG but also with the highest oral dose.

Study Link – Brain damage in infant mice following oral intake of glutamate, aspartate or cysteine.

Quote from the above study:

We describe here experiments which demonstrate hypothalamic damage in infant mice following relatively low oral doses of glutamate…

In humans, it’s unclear if oral glutamate can directly damage brain structures, but studies have shown that oral intake of glutamate (and similar excitatory food additives) may, at the very least, be associated with neurological symptoms and mood disorders in susceptible populations:

Study Link – Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins.

Given the fact that MSG is able to exert such neuroendocrine effects, it may be reasonable to suspect that overweight and obese individuals may constitute yet another population of people with a unique sensitivity to glutamate.

Glutamate in the Gastrointestinal Tract

Many researchers, however, fail to recognize that dietary glutamate can affect brain chemistry even without entering the brain (or general circulation) directly. Receptors for glutamate exist throughout the gastrointestinal tract – not only on the tongue, but in the stomach, and in the intestines. Activation of these receptors by dietary glutamate is able to activate the vagus nerve which transmits chemical signals to the brain and throughout the body. Glutamate signaling via the GI tract has been shown to activate many areas of the brain directly involved in appetite, energy homeostasis, emotion, learning and addiction:

Study Link – Brain Activation by Umami Substances via Gustatory and Visceral Signaling Pathways, and Physiological Significance.

Quote from the above study:

Notably, the medial preoptic area (mPOA), dorsomedial nucleus of the hypothalamus (DMH), and habenular nucleus (Hb) are activated by MSG alone. On the other hand, the nucleus accumbens (NAC) is activated by glucose alone. The amygdala is activated by both glucose and MSG. Other areas such as the insular cortex (ICx), anterior cingulated cortex (ACC), caudate–putamen (CPu), hippocampus (HIP), and LHA are activated by glucose, MSG, and NaCl. These results suggest that GLU may have some essential role on the thermoregulation, energy homeostasis, and emotional behavior.

Study Link – Brain Functional Changes in Rats Administered with Monosodium L–Glutamate in the Stomach.

Quote from the above study:

Recent studies have demonstrated the existence of receptors for l–glutamate (GLU) and their transduction molecules in the gut mucosa as well as in the oral cavity. Among 20 amino acids, gastric vagal afferent fibers respond only to intragastric administration of GLU. Functional magnetic resonance imaging revealed activation of several forebrain regions in response to intragastric infusion of taste solutions (d–glucose [sweet], monosodium l–glutamate [MSG; umami], and NaCl [salty] at 60 mM) in rats. Glucose activated the nucleus accumbens. MSG activated the medial preoptic area, dorsomedial nucleus of the hypothalamus, and habenular nucleus. Both glucose and MSG activated the amygdala.

From studies such as these, we can see that glutamate acts, at the very least, as a stimulant upon structures of the brain involved in memory, emotion, learning and addiction. Some evidence suggests that glutamate may even play a role in triggering the brain to reduce appetite, but like other stimulants, it may be that chronic ingestion of glutamate alters the brain in such a way as to induce tolerance to its stimulatory effects.

For example, addictive substances are universally associated with dopamine release. With repeated stimulation, the dopamine signaling system becomes less sensitive and increasing amounts of a substance are needed to trigger the dopamine–driven reward system. In drug abuse, for example, it’s well known that there occurs decreased sensitivity of the dopamine system in the brain:

Study Link – Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans.

Quote from the above study:

In vivo findings additionally suggest that not only D2 receptor binding but also the extent of dopamine release is lower in individuals with a history of drug abuse.

And, like drug abusers, obese individuals have been shown to exhibit similar malfunction in the dopamine–reward system:

Study Link – Brain dopamine and obesity.

Quote from the above study:

The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI [body–mass index]. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits.

Human research has even shown that the addiction to drugs and the addiction to food may simply be different manifestations of the same biological pathology. In individuals with bipolar disorder (a psychological condition characterized by a particularly high rate of addiction), overweight/obesity was found to be inversely related with substance abuse disorders (which means that the two different “addictions” rarely coexisted with one another). The researchers who conducted the study below proposed that drug addiction and obesity don’t generally coexist in patients with bipolar disorder because each engages the same brain reward system:

Study Link – Substance use disorders and overweight/obesity in bipolar I disorder: preliminary evidence for competing addictions.

Quote from the above study:

An inverse relationship between the presence of comorbid overweight/obesity and substance use disorders was observed in bipolar I disorder. These results suggest that comorbid addictive disorders (i.e., substance use and compulsive overeating) may compete for the same brain reward systems.

Magnesium in Obesity

There is strong evidence linking low magnesium levels with all known symptoms of the metabolic syndrome (e.g., high blood sugar, high blood pressure, elevated blood lipids, and obesity):

Study Link – Low serum magnesium levels and metabolic syndrome.

Quote from the above study:

This study reveals a strong relationship between decreased serum magnesium and [metabolic syndrome].

For this reason alone, magnesium represents a remarkably important nutrient for combating the effects of overweight and obesity. But, as we now know, magnesium is also likely to be of additional benefit in curbing the excessive glutamate signaling and addiction biology which may be commonly found in overweight individuals.

We saw in the previous Integrated Supplements Newsletter that magnesium can reduce dependence on addictive drugs like morphine and nicotine, but because the concept of food addiction is a recent development in the scientific literature, magnesium’s role in curbing the addictive nature of food has yet to be studied directly. From the existing evidence, however, it seems logical that replacing nutrients such as magnesium, which play a fundamental role in addiction biology, and which are conspicuously absent from our modern food supply, would be a good first step in combating food cravings and the related problems of obesity.

The case for magnesium’s uniquely important role in countering food addiction doesn’t just involve the mineral’s ability to counter an excess of dietary glutamate. Other components of food which have been implicated as having addictive potential (i.e., sugar, salt, and fat) may also exert uniquely harmful effects in the absence of magnesium. Like glutamate, each of these food components is added to our nutrient–depleted food supply in artificially–high amounts, and it may be that the harmful effects of these substances could be eliminated by an increased intake of magnesium and related nutrients needed for their proper metabolism. Such strategies will be the focus of the next Integrated Supplements Newsletter.

Articles in this Series:
Part 1 – Magnesium and the Mind/Body Connection in Disease
Part 2 – Magnesium – Nature's Calcium Blocker
Part 3 – The Calcium–To–Magnesium Ratio
Part 4 – Glutamate in Mood Disorders
Part 5 – Addiction
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity

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