Ghrelin after Gastric Banding vs. Sleeve Gastrectomy

In the last post, we discussed differences in ghrelin production after gastric bypass and sleeve gastrectomy. Today the studies we are going to consider describe the effects of gastric banding and sleeve gastrectomy on ghrelin and weight loss variables.

Langer et al. randomly assigned (love it!) 20 patients to either gastric banding or sleeve gastrectomy. The groups were well-matched on demographics and medical co-morbidities. The researchers measured plasma ghrelin levels at 4 time periods: preoperatively, 1 day after surgery, 1 month after surgery, and 6 months after surgery.

The results are consistent with what we saw in the last post, specifically, that the sleeve gastrectomy produced a significant, immediate and long-term decrease in plasma ghrelin levels. Most ghrelin is produced by the stomach in an area called the gastric fundus, and that part is simply removed by the sleeve gastrectomy. No more fundus, much less ghrelin.

And what about the banding? No change in ghrelin was seen after 1 day, but a significant increase occurred after 1 month and 6 months. Again, this is consistent with other studies we have examined . . . weight loss by dieting or other surgical techniques results in an increase in ghrelin. This is one way to understand yo-yo dieting and what used to be called the setpoint theory of body weight.

Himpens et al. compared other variables in 2 groups of randomly assigned (about to swoon!) patients, namely, weight loss, loss of feeling of hunger, loss of craving for sweets, new diagnoses of gastroesophageal reflux disease (GERD), and surgical complications.

Can you guess the results? Based on what we are learning about ghrelin, you might predict that the only significant differences would be in weight loss and loss of feeling of hunger . . . and you would be right. Specifically, sleeve gastrectomy patients had lost significantly more weight than the gastric banding patients after 1 year and 3 years, and they felt significantly less hunger at the same time points.

And the researchers like this as a working hypothesis . . . that decreased ghrelin production results in appetite suppression and weight loss. However, they also introduce another mechanical factor, the effect of gastric emptying on appetite, and they associate this change with the new anatomy of the stomach after sleeve gastrectomy. I need to read up on this, and maybe consult someone who knows more about this than I do, and get back to you.

The take-away message I want to send to everyone who struggles with their weight is this . . . there are serious and likely redundant biochemical mechanisms that are working to maintain your weight where it is. Sometimes, when it seems like your appetite has a mind of its own, maybe it does. Lighten up on yourself. Keep working to maintain health-promoting behaviors, but don't beat yourself up for being human.


Langer, F., Reza Hoda, M., Bohdjalian, A., Felberbauer, F., Zacherl, J., Wenzl, E., Schindler, K., Luger, A., Ludvik, B., & Prager, G. (2005). Sleeve Gastrectomy and Gastric Banding: Effects on Plasma Ghrelin Levels Obesity Surgery, 15 (7), 1024-1029 DOI: 10.1381/0960892054621125

Himpens, J., Dapri, G., & Cadière, G. (2006). A Prospective Randomized Study Between Laparoscopic Gastric Banding and Laparoscopic Isolated Sleeve Gastrectomy: Results after 1 and 3 Years Obesity Surgery, 16 (11), 1450-1456 DOI: 10.1381/096089206778869933

Comparing Ghrelin Levels Across 2 Bariatric Surgical Techniques

So, what have we learned so far? That ghrelin production is directly related to appetite in normals, but is unpredictable in post-bariatric surgery patients. And that studies of post-surgical patients in the U.S. and Sweden showed contradictory results. So let's throw in another variable - surgical procedure - as well as another location - Greece - and see what we can add to our narrative.

First, a little background from a non-surgeon. Gastric bypass is a procedure in which the stomach is reduced in size from that of a football to that of an egg or even a walnut. The reduction is accomplished by surgically stapling a line through part of the stomach so that a large part of it is just hanging out in the belly, still producing chemicals but not available to hold food. Thus, right off the bat, the amount of food that can be consumed is significantly restricted.

Further, the gastric bypass surgeon attaches this newly created small pouch to the small intestine far enough down the line so that absorption is significantly decreased as well. The new arrangement forms a "Y" and gives the Roux-en-Y its name (Roux was the name of the surgeon who first described the procedure in the 1800's).

In contrast, the sleeve gastrectomy is a purely restrictive procedure. And you may be tipped off by the -ectomy suffix . . . a large portion of the stomach is removed. And that's it. No reversibility, no band that needs to be filled with fluid, no port infections, just a long thin stomach where a football used to be.

Researchers in Greece performed a double-blind prospective study (a reader's favorite terms) with 32 patients, 16 in each surgical group. Measurements of dependent variables were taken at 5 times: preoperatively, and then postoperatively at 1, 3, 6, and 12 months. Of course, both groups lost a significant amount of weight and enjoyed improvements in medical outcomes during that first year.

More interestingly, the patients in the gastric bypass group did not show a significant change in fasting plasma ghrelin levels in the same period. And the patients in the sleeve gastrectomy group did.

A subset of patients were also tested 2 hours after a meal, and ghrelin levels from before and after eating were compared. The patients in the sleeve gastrectomy group showed a decrease of 21.3%, a statistically significant change, and those in the Roux-en-Y group showed a 14% decrease, which was not statistically significant.

So, this study seems to suggest that there is a specific spot or area in the stomach responsible for production of ghrelin, and that sometimes that spot is removed or neutralized with surgery. Again, in bariatric surgery as in real estate, some value may be attributed to location, location, location.



Karamanakos, S., Vagenas, K., Kalfarentzos, F., & Alexandrides, T. (2008). Weight Loss, Appetite Suppression, and Changes in Fasting and Postprandial Ghrelin and Peptide-YY Levels After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy Annals of Surgery, 247 (3), 401-407 DOI: 10.1097/SLA.0b013e318156f012

Is Ghrelin Simply Related to Weight Loss?

In direct contradiction to the results discussed in the last post, Holdstock, et al. found that ghrelin levels do not fall precipitously after gastric bypass. In fact, they concluded that ghrelin responds to weight loss in a predicted manner . . . by increasing.

Holdstock, et al. measured four substances involved in metabolism that we will collectively call gut hormones: ghrelin, adinopectin, insulin and leptin. They compared the levels of these hormones in the blood of their research participants before gastric bypass, 6 months after, and 12 months after. In contrast to Cummings' results, Holdstock found that ghrelin increased only as participants lost weight, which is what we would expect under normal circumstances.

In another part of the study, Holdstock compared ghrelin levels in obese women who had had gastric bypass and those who had not. Perhaps you can anticipate the finding . . . there was no significant difference between the two groups.

As Holdstock concludes: "Apparently, further detailed studies are needed to fully elucidate the effect of gastrointestinal surgery on circulating ghrelin levels" (p. 3180). I know, I know. Just like a scientist to say we need more research. And more research we shall find.

I wonder, could the surgical techniques used in Uppsala, Sweden (Holdstock) differ enough from those used in Seattle, Washington (Cummings) to explain such disparate conclusions? I mean, is there a sweet spot in the stomach where ghrelin is produced, and sometimes it is surgically bypassed and sometimes it is not?


Holdstock, C. (2003). Ghrelin and Adipose Tissue Regulatory Peptides: Effect of Gastric Bypass Surgery in Obese Humans Journal of Clinical Endocrinology & Metabolism, 88 (7), 3177-3183 DOI: 10.1210/jc.2002-021734

Ghrelin and Gastric Bypass

Ghrelin (pronounced GRELL-in) is a peptide, a type of chemical compound. It was first discovered and named by Japanese researchers led by Masayasu Kojima in 1999. Ghrelin is produced in the stomach and has been shown to stimulate the release of growth hormone in humans and rats. It also increases appetite and, thus, food intake.

Research by Cummings, et al has also shown that ghrelin levels fluctuate throughout the day, increasing before meal time and decreasing after eating. In addition, when one is restricting food intake, ghrelin production increases. It may thus be implicated in the battle we have to keep weight off. As soon as we lose some weight, ghrelin is working overtime to make us gain it back. Ghrelin appears to participate in a homeostatic process described by "set point" theory.

Cummings and his associates also compared ghrelin levels in the blood of dieters, gastric bypass patients, and normal controls. As they expected, the fluctuation of ghrelin in the dieters and the normal controls followed a similar pattern, peaking before meals and dropping afterward. Also as expected, the dieters produced more ghrelin after a 6-month weight loss program than they did before the program.

A new finding was that gastric bypass patients (9 to 31 months after surgery) had ghrelin levels scarcely above the detectable limit, with barely any peaks and valleys. In other words, their ghrelin production was at a consistently low level throughout the day and overnight. Could this account for the descriptions these patients gave of the abrupt change in appetite and food choices they experienced immediately after surgery? Could a sudden decrease in ghrelin production explain the "honeymoon" period after gastric bypass?

A word about the "honeymoon" period . . . Clinicians and researchers have been fascinated, and surgical candidates have been lured, by descriptions of the post-surgical state known as the "honeymoon" period. Of course, patients eat less because their stomachs are a fraction of their former size. But, as if by magic, patients also report a new willingness to eat fruits, vegetables, low-fat dairy products and whole grains. They seem to naturally avoid high-fat foods like red meat and chocolate cake. Many report a phenomenon they never dreamed possible . . . feeling satisfied with a single taste of a craved food (say, cheesecake) and then throwing the rest away.

Alas, the explanation of the "honeymoon" period is not so simple as we might wish. Further studies have showed different results regarding the amount of ghrelin produced before and after gastric bypass. And there is also a likelihood that, even if gastric bypass does decrease ghrelin levels, this result is not permanent. Honeymoons don't last forever, in marriage, politics or gastric bypass. Alas.

More on ghrelin and other "gut hormones" in the next post.


Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, & Kangawa K (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402 (6762), 656-60 PMID: 10604470

Cummings, D. (2002). Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery New England Journal of Medicine, 346 (21), 1623-1630 DOI: 10.1056/NEJMoa012908

Health Care Policy Debate

Our discussion of food takes place during a heated health care policy debate. I highly recommend this op-ed piece by Michael Pollan published in the New York Times. Pollan foresees a battle between the health insurance industry and the food industry, a clash of the titans if ever there were one! Here's the link:

http://www.nytimes.com/2009/09/10/opinion/10pollan.html?scp=1&sq=michael%20pollan%20op%20ed&st=cse

Also, here is an email I wrote to President Obama, with copies to Senator John Kerry and Congressman Michael Capuano:

Dear Mr. President,

I am a loyal Democrat who voted for you and supports universal health care. I am a psychologist in the private practice of psychotherapy and almost all of my patients use health insurance.

So you can imagine how disappointed I am when I hear you criticize doctors for making health care decisions for patients based on how much they will be reimbursed by insurance companies. I know that you are commenting on the fee-for-service strategy but you end up insulting doctors.

And when you say these things you sound uncharacteristically ignorant because, first, most doctors are honorable and make decisions based on what their patients require, and second, when you talk about a doctor deciding between prescribing medication or performing surgery, you ignore the obvious fact that the same doctor would not be providing these different services and thus decision making based on reimbursement does not make sense.

One more thing . . . you have spoken a lot about lifestyle changes that would make Americans healthier and cut health care costs, such as quitting smoking, losing weight, and exercising more. However, I have not heard you speak about how these changes are to be accomplished. Clearly, if admonitions by primary care doctors to quit smoking were effective, millions of Americans would have quit years ago. Behavioral changes like these are supported by behavioral health clinicians, mental health providers such as psychologists. Please acknowledge us in the future.

Thank you for your attention and good luck with your efforts to make health care universal.

Sincerely,
Maureen McCormick, Ph.D.

Why Aren't We Addicted to Broccoli?

This question about being addicted to food comes up over and over again in my practice, and I hear it in the media very often too. Here's a question that has intrigued me for a long time: why don't we become addicted to broccoli? Why cocaine, tobacco and chocolate?

Let me recommend a book that lays excellent groundwork for a discussion of our relationship to food: The End of Overeating: Taking Control of the Insatiable American Appetite by David A. Kessler, M.D. A former FDA commissioner, Kessler explains how the food industry has figured out how to make the foods they sell as luscious and appealing as possible. Not surprising at all. But food consultants take this a step further - or many steps further - and literally engineer the taste, texture and other sensory properties of food with chemicals. So there are very good reasons why, for example, "you can't eat just one" of just about anything that comes in a package.

So what are those food consultants doing? Are they addicting us to food? Can our brains become addicted to food? Well, yes and no. I've heard dozens of patients swear to me that they feel addicted to food. And we've surely all had the experience of eating something - chips, nuts, cookies - and not being able to put the brakes on. Even when we tell ourselves we have to stop, this is out of control, and we know we are going to feel sick when we finish, we can keep on going to the bottom of the box, wipe out the remaining sugar and salt with our finger, enjoy that last lick, and even wish for more.

It certainly feels like addiction. There are a couple of issues with this stance, however. First, we are clearly not addicted to all food. As much as you might like carrots or apples or tuna, have they ever evoked the same "I just can't stop" feeling you get from a bag of chips? I doubt it, unless you were beyond hungry.

And second, addiction has such a negative connotation that I have always advised my patients to avoid making food the enemy. We have to come to a peaceful coexistence with food. Unlike cigarettes and cocaine, food nurtures us and is necessary for our survival. Further, we cannot expect to eliminate even the least nutritious foods from our diet forever. Even the most health conscious person will have birthday cake, Halloween candy or holiday treats at some point. Unlike illicit drugs, sugary salty fatty food is all around us and is part of mainstream culture. We don't have a Dunkin' Cocaine on every corner or an eager grandma urging us to smoke her special Thanksgiving blend of tobacco!

And yet, we cannot deny the pull of certain foods. Kessler explains that we are not addicted to food, but we can become addicted to sugar, fat and salt. Our brains respond with more pleasure to sugar, fat and salt than to other nutrients. Experiments have demonstrated that animals will work harder to get them and will eat more of them. (Ditto cocaine.) Daily overeating of sugar, fat and salt condition us to eat more and more and more to get the same amount of pleasure.

Now, it may sound that we are doomed to overeating, ill health, obesity and feelings of failure. That's the "half-empty" reading of this piece. The "half-full" conclusion is that we are not overeaters because we lack willpower; rather, we have trained our brains to behave in a certain way. And what can be trained can be untrained.

Read Kessler's book. You won't be disappointed. As we go on, I will explore what we can learn from gastric bypass patients about the brain-food relationship.

Introduction

Welcome to my blog. The name GourMind is meant to suggest the intimate relationship between our emotional love of food, our biological need for food, and our attempts to negotiate between the two. GourMind allows me to report on what I read and keep it organized, while also inviting comments from readers.

I spent my first few years of graduate school observing, railing against, hearing criticism for, worrying about, and finally accepting my writing process. It’s primarily a thinking process. I read and think and read some more and fit things together and read and read and read and think and fit and read. Then some internal equivalent of an oven timer goes off – usually shortly before a due date – and I write and write and write and write.

So, without the constraint of a deadline, you may correctly conclude that I have been thinking about writing this blog for quite some time. Here’s what I have been thinking about:

Why is it so difficult to eat well and maintain a proper weight in a prosperous nation?

Why does “I should” so often lose the battle against “I want”?

What can we learn from those who do lose weight and keep it off?

Are we battling our own bodies and brains (because that is certainly what it feels like sometimes)?

What is a craving?

How can we understand the so-called French Paradox? And why are French women starting to get fat? Mon Dieu !

How can we take advantage of the concept of taste satiety to eat a more varied and more healthful diet without overeating?

What can we apply to eating problems from the research on addiction to alcohol and drugs?

What can we learn from those who have had bariatric surgery, especially from the 12- to 24-month “honeymoon period” after gastric bypass?

I’ll approach these questions with the curiosity of a journalist and the tools of a Ph.D. in psychology. I’ll include anecdotes and describe trends from my clinical practice. And I’ll contact researchers for their input as well. Some of the rock stars in my psycho-neuro-cuisine iPod are Nora Volkow, Kelly Brownell, Wolf Singer, Antonio Damasio, Julia Child, Thomas Keller and Ana Sortun.

Using a multidisciplinary approach, I intend to use the GourMind blog:

to summarize and clarify the state of the art research in the neuroscience of appetite, the experience of taste satiety, the portability of the French Paradox, the workings of the diffuse enteric nervous system, and the neuropsychological effects of bariatric surgery

to raise questions for research that will fill the gaps in our current knowledge

to translate these findings into useful tools for the daily life of the omnivore in a toxic environment

I anticipate an interesting and delicious journey.