Nutrition and Chemistry

posted:  20 Nov 2011
updated: 15 Sept 2012

How do nutritional needs of the body translate into chemical needs? How does the brain mediate this process by finding ways to satisfy those needs? This seems like a simple process, but any time the brain is involved, complexity is increased. The brain has to determine what nutrients we need using ALL of its resources. Since the brain stores more than just physiological information about the body, like emotional needs, memory of past evens associated with certain foods, it also affects motivation toward what, how, where, when and why we eat.

Much of what I present here has not been discussed in either the professional literature, or the news and represents a viewpoint of how the body works that I am presently developing for a book. This viewpoint is critical for understanding how nutrition works and clearly is not understood by the researchers since it has no effect on what and how nutrition is studied.  Names of many centers in the brain that I use here are not being used by other neuroscientists, nor are most of them even understood as separate centers or have been located by researchers. All of what I say is a guess by me based upon a theoretical map of the brain that I am presently working on. See my blog post “Nutrition Reviews” for closely relevant information to this post.

I also include comments on relevant news reports.


Background

I first got very interested in the chemistry of nutrition as I tried to remove toxins from the body that would not come out on their own.  As I trained my nervous system to do things in the body, like move ions, nutrients in the hypodermal fluids, I had to learn what the nervous system seemed to know about chemistry first. I learned how to do this with Muscle Reflex Testing (MRT, Applied Kinesiology, see also “MRT 1.0: Using MRT“). I learned how both conscious and unconscious processes dictate what we need to eat and what we actually do eat. I have written reviews of news reports on nutrition before (“Nutrition Reviews”).

Nervous System and Chemistry

I learned from MRT that at the brainstem level, the nervous system knows basic physical chemistry like molecular weight and electrical charge and that information is stored in an area of the brain I call the Chemical Analysis Center, positioned near the pons in the anterior medulla. It communicates with what I call the “Chemical Strip” in the pons where all commands are carried out. These areas are responsible for providing information to the Decision-making center in the Prefrontal Cortex, where broad-based commands are formulated and delivered to various centers in the brain, sometimes directly to the Chemical Strip.

The chemistry of the food we eat is first determined at various points at the junction between inside the body and outside the body–the epithelium covering the tongue, mouth, and gut. There are two levels of filtering agents residing there:

  1. taste buds on the tongue
  2. acid receptors in the gut

These filtering agents send information about what is going to be available to our bodies once those chemicals cross the epithelial barrier.  The brain prioritizes the use of different parts of our bodies based upon predictions it makes from the chemical information received by these filtering agents. Most critical to the brain are chemical and physical properties like pH, electrical charge of transport fluids, and potential energy levels, some of which can be applied to the foods, and all of which are critical inside the body.

Taste Buds

Taste buds are the first filtering agents because they categorize the signals they get in each of the “tastes” of the tongue that we know about: salt, sweet, sour, bitter, and umami. We already know from earlier neuroscientific research (see my post “Sweetness Preferences Change at Puberty“), that salt receptors detect the presence of sodium. Sodium is important for regulating the electrical charge of interstitial fluids so that ions can be transported from blood vessels to cells needing them. However, NaCl triggers not only salt receptors, but also acid receptors (sour taste) because of the presence of chlorine. Likewise, other “salts” like magnesium chloride, calcium chloride are detected by sour taste receptors. That is why there is a “snap” to the taste of salts made up of mostly sodium chloride.

Sour taste receptors are needed because acids (and thus, potential changes in electric charge) must be regulated by the body for the activity of enzymes, both at the gut epithelium level, but also in other organs, particularly those carrying endocrine cells where pH determines how much hormone gets produced.

Sweet taste receptors are critical because they tell us how much energy may be carried in our foods in the form of readily useable potential energy, sugar. Since all organic compounds are broken down to basic sugars for conversion into energy eventually, sugar detected at this level only tells us what in our food will give us enough energy for aerobic activities for the next 20-50 minutes (depending upon how much energy our activity consumes), including the act of eating.

For energy beyond this point, we need fats. Fats are eventually broken down to lipids and sent to storage inside fat cells as lipid droplets. They are only broken down to sugars when called upon to do so at times when we need energy beyond what the simple sugars in our diet have provided. We have no fat receptors in the tongue, so detecting fat needs at this level is not possible.

Bitter taste is critical for detecting poisons since most poisons have at least a slightly bitter taste.  However, bitter flavor also stimulates appetite. The elderly in past generations used to take “the bitters” before a meal, most likely because their own taste buds had accumulated so much damage by toxins in the air that they could not taste most of their foods. This may explain why some people need to add salt or sugar to their foods, as well. We sometimes add slightly bitter-tasting herbs to our foods (capers, tarragon) to counteract the sour taste of vinegar found in some foods (salad dressings, meat sauces). Bitter tastes cause fewer sour taste receptors to fire off. This is probably why lemon rind (bitter) is often added with lemon juice (sour) in a recipe.

Another source of long-term potential energy comes from proteins. The amino acids making up the proteins we eat are used by the body to make other compounds: hormones and enzymes. Because all proteins can be broken down by all body cells to make sugar, they can provide energy after that provided by dietary sugars is used up. Just knowing that proteins need to supply many different needs suggests how high the protein level in our diet must be.

Obviously as our protein needs wax and wane during a lifetime, so must the dietary level of protein change, more so than all other compounds we eat. Since our protein needs can change fairly abruptly over the course of a day, our brain needs to get accurate predictions of what its protein needs are as well as how much protein is available to satisfy those needs. One of the taste receptor types, umami, detects protein level by detecting the presence of a glutamate (glutamic amino acid) which is present in both animals and plants.

Why this particular amino acid and not the 19 others that we need and use regularly? Glutamate is needed to create calcium glutamate for storage in the heart. Since the heart has enormous calcium needs, the brain finds ways to store it there, and not depend upon a good blood flow to carry needed calcium from elsewhere to the heart, when usage skyrockets (e.g., very high activity, or just preceding it, triggered by the sympathetic nervous system during fight or flight).

Most proteins and fats get broken down, fats to lipids and proteins to amino acids, and stored in those forms in muscle, glands and liver. The hepatic amino acids are the ones that get released into the blood vascular system when cells other than muscle or glandular cells need them. Which of these “other cells” need it the most? Usually connective tissue cells like fibroblasts, macrophages, basophils, and antigen-presenting cells use the most amino acids that we store in the liver, especially when repairing damage to connective tissue (muscle, bone, tendon, ligament). Epithelial cells use the next highest level, including epithelium in the skin, lining all tubes, and covering ligaments and tendons.

We tend to think that most damage done to epithelium comes from trauma from outside the body, but as mentioned in various posts on this website, that trauma can come from inside the body, as well, from toxic chemicals that can attack, damage, or kill epithelium in the hypodermis (blood vessels, coverings of tendons, ligaments, forming sweat and sebaceous glands, as well as the skin and its derivatives like nails and hair).

See the section on Proteins in my post “Nutrition Reviews” for more discussion on the interplay between our activity levels and protein needs.

Gut Acid Receptors

Other receptors that inform the nervous system of the chemistry of the food we eat are found lying within the cardia epithelium of stomach, small intestine and large intestine. Only one of the taste receptor functions is reproduced in the gut–that is for acid detection.  Since we produce acids in the stomach to complete the breakdown of proteins into amino acids, we have to be able to detect not only the acid level in the foods we swallowed but also the level in the chyme that will be passed to the duodenum. The receptors that detect the acid level in the food lie in the fundic epithelium of the stomach, and send signals to other cells in the stomach to release less acid if the food we swallowed is very acidic. Meat that has a lot of extra acid in it, e.g., foods covered in barbecue sauce, has already had the benefit of starting breakdown of quaternary protein bonds. It is only when those acid receptors fail that we suffer from producing too much acid in the stomach.

“Taste Receptors” in the Anus?

An important principle to understand is that the nervous system not only sees the gut in its separate parts, but also as a whole, and lines the gut with critical receptors to monitor changes in the chemistry along its path. Therefore, acid receptors should be found in the small intestine, not only in the first part of the duodenum before bile and pancreatic buffering agents are released (where they have been shown to exist), but after the food passes down farther, to monitor the change in acidity so that the nervous system can react if the acidity does not decrease. We know that changes in commands to the gut do occur if food continues to be acidic or is poisoned, long after it has passed from duodenum to jejunum, mainly in the occurrence of muscle spasms (cramps). Logically, there must be some way that the gut determines that the food is too acidic for absorption, or that it just cannot be absorbed for some reason.  Given what we experience in the colon, where the spasms associated with diarrhea are most prominent, especially with a bacterial infection (like Montezuma’s Revenge), the lack of  spasms with too acidic a waste product suggests that there are few or no acid receptors present in the large intestine.

All such feedback and reaction can be governed by the enteric nervous system, a network of nerves that surround the gut from the esophagus to the anus. We know that this system monitors pressure in the gut, so that it can coordinate and instigate peristalsis and other gut movements (segmentation, reverse peristalsis, haustral churning, mass peristalsis). From what we know about the need for coordination between cells secreting acids, buffers, enzymes, mucus, and cells involved in absorption, there is a very high likelihood that the enteric nervous system is also involved with coordination of signals to appropriate sections that enable full digestion and absorption of the foods we eat. We just do not know the level of control since the brain also has a say in these functions, and the enteric nervous system is innervated by each of the spinal segments, which in turn can monitor local chemistry of its gut segment. Because of the need to monitor chemistry along the entire gut length, no doubt we would see, if we looked for them, cells that monitor chemistry along the entire length of the gut, as well as in the anus. These latter cells would monitor the chemistry of the waste we excrete. This information is critical because the nervous system would have its last chance to determine efficiency from these cells. However, I know of no research that has been done to show that these cells exist.

How the Brain Determines What We Eat

Just as the acts of thinking, memory, learning new skills, learning how to control our own bodily functions through mindfulness (see “Mindfulness Techniques”) involve many areas of the brain and seem to reach a final expression from a series of smaller, hierarchical steps, how we decide what, when, where, how and why we eat probably also reflects the many levels of control of nutritional intake that occur in the brain. At the lowest level in the hierarchy would lie the detection of the chemical nature of the food. At the highest level would lie the actual decisions we make about what and how much we eat. This highest level would be greatly influenced (and is recognized by all as the “motivating factor” in eating) by:

  1. “food “cravings”,
  2. a conscious decision to include in a meal at least something that is “nutritious” (as defined by the nutrition “experts” that abound on TV and books),
  3. the desire to “feel full” after a meal
  4. habit
  5. damage to body which prevents cells from acting normally

To understand why we eat the way we do we have to dissect out all the steps in the brain that could lead to our decisions, all the way down to that lowest of levels, the chemistry. We also have to understand internal motivation as separate from external motivation and how it affects our decisions as well. By learning all these steps, we can better understand why it is so difficult to stay on a diet, how making a major change to our lifestyle because someone told us that we had to is nearly impossible for many people, and how the conflicting results from research be misinterpreted by researchers.

The Unconscious Brain

Embryonic Brain, before it folds up into what we recognize today, from Wikimedia

The unconscious brain is represented largely by the brainstem as composed of mesencephalon, medulla (metencephalon and myelencephalon), and the diencephalon (thalamus, hypothalamus including the pituitary, epithalamus including the pineal body/gland), and parts of the telencephalon (basal ganglia, limbic system [is both conscious and unconscious]). We can see how portions of the 5 segments of the brain–see “Segmentation in the Nervous System“) are represented as unconscious in function. Only parts of the telencephalon are considered as functioning in our consciousness.

The brainstem houses many centers that govern unconscious body activities, like sleep, heart rate, blood pressure, respiration, and metabolism. The chemical strip in the pons and its nearby Chemical Analysis center has already been mentioned, but it will figure prominently in helping to regulate breathing, blood pressure and heart rate as well as metabolic level.

We also know from research that the brainstem houses areas in the Reticular Formation responsible for awakening, as well as awareness and focus (although the latter is often not included as part of an awareness function by psychologists). No doubt it also holds critical areas responsible for our nutrition as well.

I also suggest that it holds important gateways to conscious memory and language because one can see functions critical for their operation present in all vertebrates, even those without much cortical development in telencephalon derivatives.  Only mammals have a defined Neocortex, which most psychological research has identified as being responsible for language, speech, memory, learning, awareness, and emotion.  I suggest that these concepts as defined by these researchers as only being conscious (cognitive) are at the end of a large hierarchy of circuits that begin in the unconscious brain represented by the medulla.

From these observations, I conclude that  eating what we eat is actually determined in the long chain of hierarchical circuitry that begins in the unconscious brain, the medulla.  Critical of the so-called strictly “conscious” activities in eating is emotion, along with memory, learning and awareness. We learn what to eat from our mothers (milk provided by her) being the first “learned” experience. Although some would call it instinctual, it is difficult to ethically test for this difference. No doubt that some aspect of milk chemically, as well as all the associations with being fed milk are part of the “learned” experience. We become aware that drinking milk “satisfies” us.

Many researchers assume that satiety comes from a full stomach, but that has yet to be proved. The fact that an animal stops eating when its stomach is full does not constitute proof, although it has been used as a “proof of concept”. Such researchers have never also monitored the chemistry of the animal before and during eating to see if the chemical change in the blood had any effect at all on when the animal stopped eating. Nor have they consciously added bulk to the stomach suddenly during the time the animal ate, or abruptly changed the blood chemistry intravenously during eating, to determine which caused the animal to stop eating.

I have broken up areas in each brain segment as being devoted to certain mandatory functions. There are four functions that can be assigned to centers which I will give the same name to in each segment. These centers are devoted to the following functions:

  • metabolism
  • emotion
  • analysis
  • satiety

Each brain segment has these functions allocated to centers officially called by different anatomical names in each segment. (I will avoid using most of these anatomical names and instead, use their functional names). Each brain segment has other functions that may vary from other segments. For instance, there is a decision-making center in the telencephalon, motivation centers in the diencephalon, pons’ executive center (“executive” meaning as defined in computer programming as “carrying out the commands”, and not as the commander, as psychologists use this term), as well as centers only found in the brainstem

Other functions are found in more than one brain segment:

  • memory
  • concept storage
  • body physiology
  • body universe map

Functions found in each of the brainstem segments are below. Those likely to be involved with regulating eating are in purple, those of most significance for that segment have *’s, although the number of *’s do not reflect their importance in the act of eating, only their importance to that brain segment activity.

I. Myelencephalon (posterior medulla):

  • metabolism**
  • emotion*
  • analysis*
  • satiety*
  • blood pressure, heart rate, respiration**
  • sleep*
  • awakening*
  • awareness*
  • timing*
  • archival memory storage
  • general memory gateway
  • concept storage

II. Metencephalon (anterior medulla, cerebellum & pons):

  • metabolism
  • emotion*
  • analysis**
  • satiety*
  • blood pressure, heart rate, respiration*
  • sleep
  • awakening
  • awareness
  • timing*
  • archival memory storage*
  • general memory gateway*
  • concept storage*
  • external universe (people, places, objects)**
  • self**
  • executive (pons)**: somatic, visceral, chemical areas (both sensory/incoming and motor/outgoing)
  • chemical analysis**
  • external universe (spatial awareness–cerebellum**, which is a derivative of the metencephalon)
  • control of head, hearing, taste via cranial nerves VII-X

III. Mesencephalon (midbrain)

  • metabolism
  • emotion**
  • analysis**
  • satiety**
  • blood pressure, heart rate, respiration
  • sleep
  • awakening**
  • awareness*
  • timing*
  • general memory gateway**
  • concept storage**
  • self-esteem**
  • prediction of physiological and emotional needs based upon past experiences**
  • dreaming
  • gateway between external universe and conscious brain via the cranial nerve nuclei I-VI (control of seeing, hearing, smell, taste)**
  • executive: pons and red nucleus*

IV. Diencephalon (thalamus, pineal body, hypothalamus, pituitary):

  • metabolism**
  • emotion***
  • analysis
  • satiety***
  • blood pressure, heart rate, respiration
  • sleep, awakening, timing** (suprachiasmatic clock)
  • awareness**

V. Telencephalon (neocortex, basal ganglia/nuclei, eyes):

  • metabolism
  • emotion***
  • analysis***
  • satiety**
  • awakening*
  • awareness**
  • seeing, hearing, smelling***
  • sight***
  • language***
  • speech***
  • math***
  • programming***
  • reconciliation between left and right**
  • music***
  • motivation**
  • memory**
  • conceptual development**
  • planning***
  • body universe map*
  • external universe map*
  • decision-making***

Motivation

Female Body Form, Internal vs External, altered from Wikimedia image, Renan Siqueira Azevedo

Motivation is determined by particular centers in the brain devoted to this concept, not by someone else telling us to “eat right, exercise, get enough sleep”, etc. Such motivational attempts by people constitute what I call “external motivation” which must be translated by the nervous system into a series of steps that ultimately trigger off an “internal motivation” center. This internal center gets most of its direct stimulation by other cells in the nutritional hierarchy, not by any cells in the language and speech centers of the conscious brain.  In fact, most of the input is from unconscious centers. Because of this, the nervous system has to translate external motivation into internal motivation by first going through these unconscious centers. I discussion more about “internal” vs “external” motivation in my post “Mindfulness Techniques.”

This is a complicated act, to say the least, simply because emotional triggers affect every step in the hierarchy at every level in the brain. So what our doctors recommend that we do presents a “push-pull” effect on internal motivation, which runs against everything that some centers are telling the emotional centers and eventually the motivational centers. Because the chain of signals in the brain depends upon feedback at every step in the chain, all the way up to the conscious Metabolism Center in the Prefrontal Cortex, the advice of doctors will inevitably be ignored if the body needs something that the original diet and lifestyle supplied for survival, even if it means a “risk” of heart disease and early death, as defined by the researchers.

Fat Cells 400x320

Motivation is also ruled by other events in the brain and the body. If the gut epithelium is damaged by toxins or microbes, then the person will want to eat more, no matter how full the stomach is. If the body’s fat cells can’t metabolize fats because they are damaged, then the brain will tell us to keep eating and pick fatty foods. This problem ricochets because fat gets metabolized after all the sugar gets used up, usually within 20 min of any activity of high demand, e.g. aerobic activity, but pretty much all energy from sugars (carbs) all gone in 1 hour after eating if we are sedentary. If the cells cannot metabolize fat, we feel tired and hungry in an hour. The brain remembers what we ate in the past and recommends what was successful, but also remembers that we could not get enough energy and so recommends eating more fat. If there is less fat in the food, sugar will have to do to replace it, so we want to eat more sugar at the next meal, even if it is not a good idea for most people’s health.

Along with fat goes salt. Salt figures in here because it helps to create an osmotic gradient, causing the cell to lose water to make room for the incoming lipids. This means that when we eat fat we need more salt to help in storing the fat.

The brain doesn’t care about what your doctor tells you if it doesn’t satisfy your needs NOW. So it gets harder to stay on a diet, simply because you need the fat for long-term energy use, no matter if you already have “too much fat”. You need to last longer than 1 hour til the next sugar intake (whether as simple sugars in soda or candy bar or as complex sugars in carbs).

Other micronutrients also drive our food cravings. If that pizza supplied all of these micronutrients, and it was eaten yesterday at the same time (so the brain anticipated similar needs for today), then it will recommend that item, even if it has excess fat and carbs. Gut epithelium can also be damaged to prevent transport of these chemical ions. The less we can get from our diet the more we need to eat to get what we need.

See my blog post “Food Tips for Weight Loss” for more on the role that motivation plays on diet.

Why Some People Cannot Lose Weight

Comment on “Losing Weight: A Battle Against Fat And Biology”, reported on Morning Edition for 31 Oct 2011, where I discuss the hypodermis and problems with the assumption that diet and exercise are the best ways to wa

ge a war against obesity.

Summary

Dr. Donna Ryan of Pennington Biomedical Research Centerin Baton Rouge, La. explains that losing weight is not just a matter ofwill power. She says that biology tries to prevent us from losing those first few pounds. NPR reporter Patti Neighmond tells us about Mary Grant who faced a lifetime of attempts to lose weight, dating back to the time her father would humiliate her in front of the family by weighing her every Saturday and suggest that she try a different diet. However much weight she lost after a diet, even a medically supervised diet, she would gain it back. Ryan explains why. She says that when you start to lose weight,

Leptin Molecule

the fat cells would send a hormone signal (leptin) to the brain. The brain responds to keep the weight by signaling the body to lower the metabolic rate so that less fat is lost, because it perceives that the body is in “starvation” mode. Then another brain signal says that it is “hungry”and then stimulates the appetite. This causes a “double whammy” when a hunger signal is combined with a lowered metabolism, causing the person who has lost weight to not be able to eat as much as a person who has not lost weight. This translates into having a “calorie handicap’. In order to maintain that weight loss, you have to eat 300, or 500, or fewer calories than a person who weighs the same as you but who hasn’t lost weight. Ryan says that you can fool your metabolism by “kicking” it up–one hour of moderate exercise per day allows you to burn up an extra 450 calories per day.

My Comments

Unfortunately, all of this report is based upon a theory that has little to support it. We know that 85-90% of people who go on a diet and exercise will eventually gain back the weight they lost within a year after starting the diet. Some will admit to having lost the “willpower” battle. Most of the evidence for such a theory is based upon observational studies that compared two groups of people, obese and those with low BMI in calorie intake and amount of exercise, and found that the obese group took in more calories and exercised less than the low BMI group. They also found that obese people who ate a medically supervised diet and exercised a prescribed amount each week lost weight.

However, there are very few studies that followed these experimental participants for more than 1 year. I have heard of no study that showed the obese person lost all of the excess weight and was returned to the optimal body weight of a person who had stopped growing. Theoretically, we all should be able to lose whatever weight we gained one day over a period of 1-3 days by returning to normal activities (normal being a moderate amount of exercise each day). Too many of us cannot do this due to lots of sedentary activity both on the job and when not at work.  Conclusion:  the US has a high obesity rate, but we cannot assume that diet and lack of exercise are the sole causes of that high obesity rate.

Missing in this report is the question why? Why would the brain send a signal to lower metabolism after some weight is lost? Wouldn’t it determine the rate of weight loss first and send  such a signal only if the rate of weight loss is too high? That would be a logical event if the purpose for such a mechanism was to prevent the effects of starvation. Many of us never face that possibility today, but those living in poverty do, now measured as between 25-30% of Americans. I say that the mechanism I suggest as more likely to be selected for in our past evolution because the body needs to have body weight and its equilibrium more tightly controlled than the swings suggested by what Dr. Ryan suggests as the “double whammy” problem. I propose that her “double whammy” problem is a sign that something is not working as it should.

Fat Stem Cells (EM), from Wikimedia

Did Mary Grant’s doctors ever test her hypodermal fluids? Fat that we need to lose or gain sits there. If  “calories in” are not = “calories out”, then the “=”  sign must be examined. What NPR reporter Patti Neighmond means by “biology” cannot be reduced to just looking at hormones, e.g. leptin or ghrelin, as most doctors and nutritionists seem to believe. The fat cells may not be working because they are damaged. If they are damaged, then leptin or ghrelin will not be secreted when they should be. If fat cells are damaged, the brain keeps telling the liver to make more fat cells.

The drive to eat the same foods you had eaten before you lost weight (cravings) has a real purpose–you need the nutrition that you are not getting from your  food that you should be. If you need to eat fats, you are not able to get fat from your own fat cells–a clear sign of failure to work. Most doctors don’t even think about if the fat cells are damaged because they cannot imagine how they could be. If bacteria and viruses can get inside the body via the gingiva in the mouth then toxins can do so too. They do not have to enter via the lungs, inside the foods, or cross the thick external epithelium of the skin or the thinner lining of the mouth and nose. Such toxins, once they gain entrance to the connective tissue surrounding the teeth, can move within the connective tissue by simple diffusion, penetrating every tissue along the way. However diffusion is slow, and toxins will pool, causing damage.

Exercise gets toxins moving, preventing that pooling. Most toxins are broken down to chemical elements in the hypodermis and at best only interfere with flow of needed ions, like calcium, phosphate, boron etc. At worst they do damage to blood vessels that would normally supply/drain the tissues (including fat cells). Exercise induces more blood vessel growth. With diet and exercise the weight lost in a toxin-damaged body will be difficult to keep off, since the fat cells are too damaged and the body will push for the creation of more fat cells to “replace” the damaged ones.

Macrophages are enormously sensitive to toxins and can’t clean up the damaged cells, so fat accumulates. However, the person might lose some weight as long as they are dieting and exercising because that person will be eating less, but craving more because they cannot get the nutrition they need from the food they eat (toxins will travel to the gut and damage the epithelium, or just interfere with absorption. Even if calcium is prevented from being absorbed, it might not prevent proteins from being absorbed–thus, the need to keep eating certain foods to get the calcium, even if they are high in any or all of fat, protein, or carbohydrate. See my blog post “On Healthy Ice Cream”  for more discussion about calcium and food preferences with reference to body weight.

 

Weight-Loss Drugs

Comment on “FDA Approves First New Weight-Loss Drug In More Than A Decade” reported on NPR’s Morning Edition 06/28/12, which discusses the approval of the drug Belviq©, in spite of its side effects. The FDA has not approved a

Prescription Drugs, by J. Troha, National Cancer Institute, at Wikimedia

weight-loss drug for 10 years because of all the side effects of each drug. I discuss how most of these drugs are not attacking the causes of obesity mainly because they all target the same area of the brain. These researchers assume two things: the causes of obesity are entirely due to over-eating, and that the fullness of the stomach is the only determining factor regulating how much we eat.

Summary

NPR Reporter Rob Stein interviewed Janet Woodcock (FDA) about the decision to allow the use of the drug Belviq© (lorcaserin) to be used to help patients lose weight. The action of the drug is hypothesized to be on the hypothalamus where it influences levels of serotonin in such a way to make you feel full after eating a meal. Considering that the FDA did not approve the drug when first proposed because of its effects on the heart, the change “of heart” by the FDA now seems to be due to the manufacturer, Arena Pharmaceuticals, addressing those concerns with new data. Patients taking the drug twice a day lost about 5% of their body weight after a year. Stein says that common side effects have included “headache, dizziness, fatigue, nausea, dry mouth, and constipation”.

Sidney M. Wolfe (Public Citizen Health Research Group) protested the decision by writing that “it would be dangerous and unconscionable” to treat large numbers of obese people with this drug, since they already are “at risk for cardiovascular disease”. He felt that it was dangerous because the drug appears to add a risk of damaged heart valves.

However, the FDA granted approval on condition that Arena continue to conduct studies on the safety of the drug, in particular cardiovascular risks.

The report reviewed past drugs that have been pulled from the market for various reasons or which are still available but not that effective. One drug, Qnexa, is awaiting the FDA’s final decision after its manufacturer, Vivus, submitted more data concerning heart problems and birth defects which were linked to its use earlier.

Posted on NPR

Diet drugs don’t tend to work very well (e.g. the person gains all the weight back after going off the drug) because they do not target the real problem. Doctors who actually talk  with their obese patients have learned of the complexity of the issue. Psychotherapists see the emotional connection in their patients. How many patients of medical doctors realize that there are emotional issues related to their weight problems? Has anyone thought about the nutritional reasons for food choices?

Researchers seem to assume that if our choices were only based on nutritional reasons, we all would eat only “healthy” food (as defined by observational studies as low-fat, low salt, moderate protein, and small portion sizes). That assumption has never been tested (as described in my blog post “Nutrition and Chemistry” at https://marthalhyde.wordpress.com/2011/11/20/nutrition-and-chemistry/ for more discussion). Researchers focus on trying to make the person feel full sooner after eating. The brain feels “satisfied” for a number of reasons:

  1. the stomach is full (mentioned previously)
  2. there are enough needed nutrients being absorbed,
  3. habitual portion sizes are eaten,
  4. emotional comfort is supplied.

Each of these reasons figures in determining “motivation”, a feeling supplied by specific centers in the brain and required before you can do anything

Add to this the fact that pesticides have been linked to obesity and their action on fat cells has been documented (Maillet et al 2009, see my blog post “Obesity and Pesticides” for a discussion on this laboratory study.) We have to conclude that toxins add a reason #5 to the list.

My Extended Comments

All of these needs (based upon the four reasons mentioned on my posted comments) are handled by different areas of the brain. I will propose a scenario as follows (as mentioned previously in this article):  Each area of the brain has its own “satiety center” and all feed into the one in the hypothalamus, which in turn sends signals to a cortical satiety center, the septal nucleus. Each satiety center receives signals from other centers in the brain, and all get signals from cells representing emotions.

Each satiety center also sends signals to an analysis center in each area which takes signals from memory cells used for ongoing bodily processes as well as cells dedicated to archival memory (of past physiological and emotional events). Each analysis center permits the sending of a signal of satisfaction with its area’s neurological processes from its satiety center to the hypothalamic satiety center.

Prefrontal Cortex of Brain, from Erik Lundström at Wikimedia

Reasons #1-3 are all handled by the brainstem. #4 is handled by the prefrontal cortex emotion and analysis centers. Most diet drugs are aimed at the hypothalamic activity. From the description of what it does and its side effects, I can guess that Belviq© also targets the hypothalamus. All physiological processes handled by the brainstem are first analyzed there and a final signal of satiety is sent to the hypothalamus.

The complexity of what the hypothalamus does is not well-understood, since it is rarely the primary influence on physiology, except for its regulation of hormones. There is a lot of just inorganic and organic chemistry of the body that is regulated by the brainstem, independently of hormones produced by the hypothalamus. By ignoring the brainstem input on what we eat and why, we narrow possible solutions too much and may end up ignoring the cause of obesity as a result.

Figures

Filiform and fungiform papillae (taste buds) on surface of tongue. From Gray’s Anatomy of the Human Body, 20th Ed, 1918

Diagram of Taste Bud. Tongue Surface epithelium is up, nerve exists to interior of tongue on the bottom. (from NEUROtiker)

Embryonic Brain, before it folds up into what we recognize today, from Wikimedia.

Internal vs External motivation, altered from Wikimedia (Renan Siqueira Azevedo).

Fat Cells (Adam)

Leptin Molecule, from Vossman at Wikimedia.

Fat Stem Cells (EM). The space between the cells is filled with interstitial fluid, which is mostly water, NOT air, (Wikimedia).

Prescription Drugs, by J. Troha, National Cancer Institute, at Wikimedia.

Prefrontal Cortex of Brain, from Erik Lundström at Wikimedia.

Websites Cited/Recommended in this Article

MRT 1.0-a (Applied Kinesiology): How it Works

Applied Kinesiology

MRT 1.0: Using MRT

Mindfulness Techniques

Sweetness Preferences Change at Puberty

Obesity and Pesticides

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