After acquiring the book almost a year ago, I (again) started reading Gary Taubes’ book entitled Good Calories, Bad Calories. Based on what I’ve read so far, and knowing Gary Taubes’ background, I believe it’s a very scholarly work, and very thoroughly researched. From the title, it’s obvious that this book considers the scientific evidence for specific types of diets and how they affect body weight regulation.

In the first part of the book, in order to draw parallels with current scientific evidence for the “epidemics of obesity and diabetes,” Taubes puts forth a detailed historical analysis of the decades-long debate on whether dietary fat intake was the definitive cause of, rather than merely correlated with, the rapid rise in the incidence of cardiovascular disease in the developed world that started in the 1920s (when consumption of red meat increased considerably). The upshot of this work is to point out what happens when a researcher, who becomes prominent for various reasons, influences health care policy even when his/her scientific data are far from conclusive. In this particular case, Taubes discusses the work of the prominent physiologist Ancel Keys, who was convinced based on his research that the observed rise in incidence of heart disease was due to increased blood cholesterol levels, which was in turn due to increased total dietary fat intake. Keys was apparently a formidable character who felt very strongly that his data conclusively proved this hypothesis, and was very quick to strongly criticize those who opposed his theories. Throughout this time period, and even into the 1960s, there were many prominent researchers who had serious reservations about Keys’ theories, based on scientific analysis of his data as well as their own. Nevertheless, because Keys was so forceful, Taubes brings various elements to show that the media picked up Keys’ theories, and physicians who were faced with an alarming medical mystery began to recommend low fat diets to their patients, despite serious controversy over Keys’ data.

In such a scenario, the question becomes one of correlation versus causation, i.e., depending on how solid the scientific evidence is for any given observed public health phenomenon, one might be able to say there is a CORRELATION of an observed public health trend with disease, rather than being able to state, through a solid base of scientific evidence, that the observed trend CAUSES the disease. There is considerable scientific evidence demonstrating that the physical attribute of fatness does not conclusively indicate bad health, and that many  “obese” individuals are metabolically healthy.

One reason for this phenomenon of correlation overpowering the media is that it provides a solid message to address what appears to be an alarming trend. Often, people don’t have the patience to wait for conclusive scientific evidence to be produced when faced with a potentially scary scenario. When scientific evidence that contradicts the popular theory is published, it tends to be ignored, because it contradicts what has become DOGMA. This is what has happened with “obesity” research. Taubes skillfully points out that when scientifically observed correlations are not thoroughly researched scientifically, and they become socially accepted as dogma,  real scientific progress breaks down.

It has taken me several weeks to post this reply, which Dr. Christakis sent almost immediately after I sent him my email (see previous entry entitled “An Email to Dr. Nicholas Christakis”). During this time I’ve had the opportunity to learn and think more about Dr. Christakis’ work, and was not shocked to discover that my knee jerk response to his NEJM article on the spread of obesity through social networks was premature. However, I was far from alone in this reaction.

He asked that I post his response verbatim:

Dear Ms. Gordon:

What I learned from my correspondence with Dr. Christakis and a review of some of his vast trove of publications was that what had originally motivated him to study how feelings/perceptions spread through social networks was his work with terminally ill patients, which served as his initiation into clinical medicine. Through his interactions with these patients and their families, he understandably became concerned with the feelings of the family members and how it affected them and their social networks in turn.

I was surprised that as a Sociologist, Dr. Christakis would have been taken aback at the overwhelming attention received by his obesity study. Surely he must have been aware of the hair trigger emotions surrounding obesity in our society. It then occurred to me that perhaps, due to his initiation by fire into what must be one of the most difficult fields a physician can choose (end-of-life care), his attempt to approach the spreading of emotions through social networks through mathematics and statistics took him a step back from what must have been a very potent emotional experience. I felt that there was a certain detachment in the quantitative work involved in these analyses.
When I posited this to him, he explained:

Dr. Christakis is not primarily studying the “obesity epidemic” but rather how social networks work.

A “SNP” is a single nucleotide polymorphism. Within a genetically distinct population, i.e. people of a certain ethnicity, religion, or geographic region, there are several versions of the DNA sequence of any given gene that is almost identical, with the exception of one sequence unit at a specific site. This single nucleotide variation occurs in the population at observable frequencies. The Human Genome Project, a multinational collaboration to sequence the entire human genome (the DNA sequence in all 23 human chromosomes), opened the door to the discovery of many of these SNPs, which were present in genes thought to be very important in disease risk. The differences created by a SNP in a gene could give rise to a protein that could either increase or decrease the risk of getting a disease. Establishing the correlation of the frequency of occurrence of a SNP with the risk of getting a specific disease could lead to improvements in the health of an individual at risk, either by recommending specific therapies or changes in lifestyle or diet.

In a ground-breaking study entitled “Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colon Cancer Risk” (JAMA. 2008 Oct 1;300(13):1523-31), Virginia G. Kaklamani et al found a statistically significant correlation of a SNP in the ADIPOQ gene with incidence of colon cancer in a large cohort of subjects with Ashkenazi Jewish ancestry. This work is ground-breaking because it is the first published study to establish a real statistical correlation of a SNP based variant of the adiponectin gene with the incidence of colon cancer, after many circumstantial, indirect observations. Ironically, the SNP in the ADIPOQ gene was negatively correlated with colon cancer risk. In other words, individuals with the SNP containing GG or GC (found in 48% of all study participants) at the variant site were 27% less likely to develop colon cancer than those with the more common CC genotype. It is very important to remember, however, that as the authors caution, these results must be confirmed with further studies.

Adiponectin is an adipokine, or a hormone secreted by adipose tissue, that facilitates insulin sensitivity. Paradoxically, as adipose tissue mass increases, adiponectin levels decrease, and this is correlated with insulin resistance. Insulin resistance is correlated with elevated levels of other proteins, such as C-peptide and insulin-like growth factor binding protein-1 (IGFBP1) that is linked to increased risk of colon cancer. The results of this study suggest that there may be some identifiable genetic and biochemical connections between obesity, diabetes, and colon cancer.

Metformin, otherwise known as glucophage, is a medication that works to lower elevated blood sugar and help the body process the excess sugar more efficiently. However, if you have the unmitigated gall to eat sweets while taking this medication, you will be punished by having copious diarrhea. I found this out first hand. I guess this is the price I pay for feeding my addiction.

We all know that in this life, there is a price to pay for everything. Supposedly, the metformin I’m taking is helping to lower my blood sugar. So either I get diabetes or I get diarrhea, or I attempt to deprive myself to the point where I am physiologically compelled to binge. This “most appropriate” punishment for those who “dare” to be obese applies also to those taking Xenical, or it’s over the counter version, Alli. If you eat food with excessive fat content while taking these drugs, you will either be sitting on the toilet all day or forced to wear a diaper. So either deprive yourself of the food your brain is screaming at you for, or suffer those consequences. Either way, we are punished for doing what feels natural for us.

Another version of punishment reserved for the fatties amongst us, compliments of the medical establishment, is weight loss surgery. Having your stomach stapled or a lap band put around your stomach internally to restrict the amount of food you can ingest is tantamount to punishing yourself for eating too much. Do you know how violently ill you become if you try to eat more than a few spoonfuls of food after you’ve had this surgery? Bad, bad fattie!! You deserve to be punished for your gluttony and sloth!

The same woman who prescribed the metformin for me gave me a scientific paper to read, by a prominent childhood obesity expert, who questions whether the obesity “epidemic” is based on gluttony and sloth! His take is that children are not at all in control of their nutritional environment, so they are innocent of these cardinal sins. However, what is he saying about the adults? I wonder if the woman who prescribed the metformin for me and gave me this article to read is attempting on a subconscious level to tell me that I am gluttonous and slothful.

If one searches PubMed for articles with the word “obesity” in the title and “gluttony” in the Title or Abstract, 12 papers come up! This proves that there is as much anti-obesity bias amongst the most prominent academic obesity researchers as there is in the general public. Most of these articles attempt to convey that the popular view of fat people as gluttonous and slothful is wrong, and that scientific progress is providing more and more evidence to combat this hideous notion. However, I believe they need to use these words because they are trying very hard to convince themselves of this. After all, from the moment they were born, they were immersed in the same western culture which has held absolute contempt for fat individuals, and it is therefore an intractable part of their consciousness.

There is no need to include incite-ful (no pun intended) words, such as gluttony and sloth, in any publication written to present scientific data in an objective manner. These words are included in scientific publications in order to attract the attention of those (read: everyone in western society, including fat people) who have a strong, unfavorable gut reaction (again, no pun intended) to fat people and obesity.

Last night I came across a blog entry by Matthew Brown (http://www.scientificblogging.com/scientific_notation/self_control_is_to_sudoku_can_you_end_addiction_with_analogies), which discussed data from the laboratory of Dr. Jeremy Gray and others on the inverse correlation of intelligence and self-control. Immediately, I thought wow, if I’m fat because of a lack of self control, does that mean I’m less intelligent than someone who is free of compulsive behaviors?* Despite my initial reaction of shock and horror to this blog entry, I decided to give the scientists a chance to explain themselves. Instead of launching into a rant on my blog, I sent a simple and polite email to the lab requesting a reprint of their latest review article: Green, A. E., Munafo, M. E., DeYoung, C. G., Fossella, J., Fan, J. A., & Gray, J. R. (in press). Using genetic data in cognitive neuroscience: From growing pains to genuine insight. Nature Reviews Neuroscience. I am now reading one of Dr. Gray’s earlier review articles, in an effort to give him the benefit of the doubt. By necessity and probably in order to protect himself, I imagine that this guy has become as skilled as any human being possibly can (without doing any cognitive, psychometric, genetic and fMRI studies on him) at tiptoeing through the proverbial minefield.

My initial reaction to Matthew Brown’s blog entry about the work of Dr. Gray’s lab brought to mind the recent imbroglio that got James Watson booted from his post as the Chancellor of Cold Spring Harbor laboratory in response to comments he made about the genetic basis of intelligence in black people (see the recent New York Times article by Cornelia Dean). Anything that biological scientists, particularly those who are prominent and high profile, say about the biological basis of intelligence is incendiary in the extreme because of the inevitable and very unfortunate consequences for many, many people. The real danger in the scientist’s statements lies in the subjective interpretation of these ideas by idiots (for example, the principal of my high school) who have enough power over people’s lives to determine their future. This, in turn, highlights the essential nature of communicating science to laypersons in a way that is accurate, understandable, and sensitive. The more successfully science journalists are able to do this, the less abuse will result, and the more positive impact they can have on society. This is something that I am striving to work for in addressing the science of obesity.

As with all scientific studies, the key to really taking away the true message conveyed by the data is an understanding of the quality and reproducibility of the data and the experimental designs, the limitations on the conclusions that can be drawn based on the experimental methodology used, and how the new data fit into the existing literature. Unfortunately, only trained scientists, or those who have written about science for many years, can handle the information on this level. This ability is narrowed down even further by their respective specialties. It is very easy for someone with ulterior motives to manipulate the results of a scientific study or series of studies to suit his/her own purposes (in one of the most extreme and vile cases, read Hitler and the Eugenics movement). So how to solve this problem? I believe that the ideal combination of science and journalism would include an explanation of the scientific method with the reporting of any scientific study. Somehow, the public needs to be educated, through engaging and easily readable material, that one study does not make anything fact. They must understand that science progresses only through constantly challenging existing theories based on a growing body of high quality experimental evidence, and therefore, they must always leave room for further questioning.

*Note added in proof, December 20, 2009 – This post was written when I was just starting to learn about the Health at Every Size philosophy and thus contains material that some would find offensive. I am leaving the post in on purpose, to demonstrate how deeply ingrained fat hatred is in the minds of those raised in our society. The association I make here between being fat and lack of self-control is an unfortunate manifestation of these almost instinctive thoughts.

Humans, mice — indeed all mammals — have two types of fat cells in their bodies; white and brown. White fat cells store energy. In contrast, brown fat cells dissipate energy as heat, thus counteracting obesity. Much to the chagrin of humans living in industrialized societies, most fat cells in our (adult) bodies are white fat cells. While this trait served our kind well throughout our evolutionary history, we now face a vast abundance of inexpensive, easily accessible, high energy content foods. This, combined with our body’s tendency to want to store up energy for times when food is scarce, leads to obesity and its accompanying adverse health effects. Wouldn’t it be great if we could have more brown fat cells and less white fat cells?

Scientists like Harvard Medical School’s Bruce Spiegelman would like to figure out a way to help us do just that! Spiegelman, who studies mammalian embryonic fat cell development, is conducting research to understand the adipogenic (i.e. how adipose, or fat cells arise) lineage. One key question that Dr. Spiegelman and his group seek to address is how white and brown fat cell fates are determined.

To answer this question, Dr. Spiegelman’s group performed a screen for molecular regulators including transcription factors that may be unique to either brown or white fat cells. The researchers identified a transcriptional co-regulator called PRDM16, which is expressed exclusively in brown fat cells. When the investigators studied the effect of increasing PRDM16 expression in white fat cell precursors in culture, they observed that the overall gene expression profile was distinctly that of brown fat cells. Then, they made transgenic mice that selectively overexpressed PRDM16 in white fat cells, and found that pockets of brown fat cells grew in the white fat cell depots. Similar results are obtained when mice are exposed to low temperatures for extended periods of time, or by prolonged exposure to b-adrenergic stimulation. Together, these results suggest that PRDM16 is an excellent candidate for a master molecular switch that can convert white fat cells into brown fat cells. However, since “suggestion” is not proof, the researchers performed additional experiments to investigate this.

To their surprise, the scientists found that when PRDM16 expression is inhibited in primary brown fat cells in culture, they differentiated not into white fat cells, but into myotubes, or skeletal muscle cells! This result suggested that brown and white fat cells did not come from one common progenitor cell type. Instead, they may in fact be two entirely separate lineages. Additional experiments provided strong evidence for this.

So where do these results leave Bruce Spiegelman and his group? The data showing that white fat cells can become brown fat cells by overexpression of PRDM16 still hold promise for therapy. Spiegelman aspires to make this type of therapy a reality, by employing a transplant model. White fat cells, which are easily obtained by liposuction, can be engineered to express PRDM16, and transplanted back into the original fat cell donor. These experiments are currently being performed in mice.

Important questions remain. For example, how many cells would be needed for the procedure to succeed, and how the body would respond to the engineered cells? Could these engineered “brown” fat cells lead to positive results by reducing obesity and restoring energy balance, or could there be negative effects? Bruce Spiegelman as well as many people suffering from obesity are sincerely hoping for the former.

This entry is based on a talk given by Dr. Spiegelman on Thursday, May 15, 2008 at the New York Academy of Sciences. Dr. Spiegelman was a featured speaker at the NYAS Conference on Integrative Physiology. I originally posted this entry on another of my blogs, Parallelaphors (http://parallelaphors.wordpress.com/), on July 30, 2008.

Today I had an appointment with Judith Townsend, the Physician’s Assistant who works with Dr. Louis Arrone, in New York City. Dr. Arrone is an expert in medications to treat obesity. I go there with the intention of trying medications to help me reduce my weight, which is an approach I haven’t yet tried. When I last had my blood tested (about 2 months ago), my glucose was a little high (114), and while my primary care physician felt that was fine as long as I continued to be vigilant about exercise and nutrition, Judith was alarmed. In response, she prescribed metformin for me, which makes the  liver more efficient at processing glucose and helps it to lower blood glucose. I have been taking it for about a month, and am in the process of getting used to it. I think Judith was hoping that it would decrease my cravings for sugary foods and reduce my appetite and therefore my weight. Although I have just begun to notice a decrease in my appetite and my cravings for sugar (YAY!), my weight was basically the same as it was a month ago.

Today, I got a lecture from Judith about my poor pancreas, which really cares that my blood glucose levels are too high, and therefore futilely keeps pumping out insulin to try and reduce it (high blood glucose levels are toxic to the body’s cells). Alas, due to insulin resistance, the cells in my body (primarily in my liver, skeletal and cardiac muscle and adipose tissue) that routinely take up glucose in response to insulin are not responding to the insulin because THEY JUST CAN’T TAKE IT ANYMORE. They are saying to the increased levels of insulin that keep trying to bind to the receptors on my body’s cells, “get lost, we’re sick of you already!” (by decreasing or “downregulating” the number of insulin receptors on their surfaces). They’ve shut the door in the insulin’s face. But my poor pancreas just can’t hear what the liver and muscle cells are saying, and can’t tell that they’ve rejected the insulin that it works so hard to make. So it keeps churning out insulin. Eventually, if I continue to ingest too much sugar, the cells in my pancreas that manufacture the insulin (called beta cells) will just get tired and wear out, like a treadmill that has been left on constantly for months. Then my pancreas will never make its own insulin again (I think – I have to look into this), and my blood glucose will shoot up to levels that will eventually kill my organs and me, unless I inject synthetic insulin (as do most people being treated for type 2 diabetes). According to my blood work, my insulin levels have always been in the normal range. However, this is not conclusive evidence that I am not insulin resistant.

My question is, is Judith an alarmist? If one is clinically defined as obese, does it necessarily mean that one is insulin resistant? If I maintain my weight (my BMI is roughly 36, I am not morbidly obese), do regular moderate exercise, watch what I eat and monitor my glucose levels by getting my blood tested every 6 months or so, will I necessarily become diabetic? I eat a lot of healthy foods – lean protein, fruits and vegetables, whole grains, but I also need my chocolate. Is this an attempt to scare me straight? How much is Judith’s concern motivated by actual scientific evidence and how much is it motivated by cultural bias against obesity, which all of us carry around with us, just like unwanted extra pounds? Time will tell. I guess the clock is ticking for me.

In the 1995 film “The Basketball Diaries”, Leonardo DiCaprio brilliantly portrays Jim Caroll’s descent into heroin addiction. When I attempt to explain to people who do not suffer from obesity what complete, sudden withdrawal from refined carbohydrates is like, based on my own experience, I get a mental picture of what DiCaprio’s Jim Carroll goes through as he suffers the torture of withdrawal from heroin. Although this is an extreme example, withdrawal resulting from completely eliminating refined carbohydrates or other binge foods from one’s diet is more than a matter of putting up with a migraine, insomnia, or general feelings of malaise, although all of these symptoms may result. Kay Sheppard, the author of “Food Addiction – The Body Knows”, explains that the food addict is compelled, as if by knife point, to acquire and devour binge food, and that only complete abstinence from refined flour, sugar and wheat can arrest the addiction. It is Kay Sheppard’s food plan that helped me, twice, to lose 60 lbs. and keep most of it off for 5 years. I was able to do this only with the help of Overeaters Anonymous and the most wonderful sponsor I could ever have hoped for. Unfortunately, she became too ill to continue as my sponsor. I have since fallen off the wagon again, and have regained those 60 lbs. for a third time.

Long considered a joke in contemporary western society, the idea of biologically based addiction to refined carbohydrates and other “addictive” foods is finally gaining a foothold in high quality scientific data. Bartley Hoebel’s group at the Princeton University Department of Psychology has published a series of papers detailing their experiments on sugar addiction using an animal model originally established for studying opiate addiction. Nicole M. Avena is the lead author on several studies that provide some of the most compelling evidence yet of the biological mechanisms of addiction to sweets, and their similarity to the biological basis of opiate addiction.

In a recent review article, Nicole Avena, Pedro Rada, and Bartley Hoebel (Avena NM, Rada P, Hoebel BG. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32(1):20-39. Epub 2007 May 18.) explain why addiction to sugar shares the same basic neurochemical mechanisms that underlie opiate addiction. The first aspect of the theory is based on evolutionary mechanisms that motivated survival in an environment where food was scarce. Feelings of comfort in response to feeding were necessary to insure survival. The same brain mechanisms that are responsible for this feeling of comfort have been shown by many laboratories to underlie opiate addiction. They also cite circumstantial evidence from the testimony of many people that they are compelled to eat sugary foods in a way that is comparable to alcoholics who have overwhelming urges to drink. Also, with approximately 25-30% of United States citizens characterized as overweight or obese, along with the multi-million dollar diet and fitness industry, it is clear that many people put considerable effort into weight loss and yet fail to maintain the loss. Therefore, clearly, it is worth investigating the neurochemical mechanisms that are the basis of this seemingly addictive behavior.

Throughout this review article, terms that define addiction, including bingeing, withdrawal, craving and sensitization, are interwoven with scientific data from experiments with rats which have intermittent access to sugar solutions. When ingested, addictive drugs cause an increase in dopamine levels in an area of the brain called the nucleus accumbens. Hoebel’s group has found that same phenomenon in rats. Other changes in the nucleus accumbens, including decreased enkephalin gene expression are also seen both with opioids and sugar. And, as with other opiates and psychostimulants, withdrawal symptoms are observed when the rats are deprived of sugar. Another important series of observations show that as with addictive drugs, after becoming accustomed to having regular intermittent access to sugar each day and then being deprived of the sugar solution, the rats exhibit classic signs of withdrawal, including anxiety, depression, craving, and even “cross-sensitization” to other substances of abuse (substituting another addictive substance in the absence of the drug of choice).

After presenting and analyzing all the available data, Dr. Hoebel’s group concludes that in a rat model which has proven relevance to human addiction, intermittent access to a sugar solution followed by periodic deprivation results in most of the same molecular and behavioral changes associated with rats that become addicted to other drugs of abuse. What this group is proving on a neurochemical and behavioral level would not surprise many of us who have instinctively known “food addiction” for years.