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