One of the main reasons why humans become hungry is because of the hormone ghrelin. Ghrelin is primarily secreted by the stomach, which responds to hunger and starvation. Once ghrelin gets into the blood, it circulates the body until it reaches the Vagus nerve, which sends a signal to your brain that tells you “I am hungry!” Actually, for people who have had their Vagus nerve divided (a Vagotomy), ghrelin no longer has a significant impact on hunger. This finding suggests that the Vagus nerve and ghrelin are needed for maximum stimulation of hunger. Also, ghrelin containing neurons are found in the arcuate nucleus, a region of the brain that regulates appetite. In order to stimulate hunger, these neurons send signals to other neurons that contain neuropeptide Y (NPY), which stimulates hunger. However, if the body wants to suppress hunger, it will send signals to neurons containing proopiomelanocortin (POMC). (i)

Now that we know a little about how ghrelin makes us hungry, lets see how the hormone leptin makes us full. Leptin is made in the fat cells (adipose tissue) of our body. The way leptin regulates hunger is by stimulating or not stimulating nerves in the brain. Just like ghrelin, leptin acts on the arcuate nucleus. When leptin is not present, NPY causes us to be hungry. When leptin levels are high, they block NPY and stimulate POMC nerves in the brain that make us full. However, one might ask, if we have more fat cells that produce leptin, why are we still hungry? The answer is that many obese individuals have genetic defects that block the function of leptin. The other is that too much leptin can cause negative feedback to fat cells, which tell the body “hey we have too much leptin, stop making it.” (ii)

Although the exact mechanisms of how ghrelin and leptin work are extremely complex, we see that the three main responses that are contributed to the presence of ghrelin (iii) (iv) are:

1. Stimulation of appetite
2. Reduction of metabolism
3. Reduction of fat catabolism (fat breakdown)

In contrast to ghrelin, leptin’s main responses are:

1. Suppression of appetite
2. Increase in metabolism
3. Increase immune function

The following table summarizes the information on ghrelin and leptin, its relationship with other GI hormones, and its levels after Sleeve Gastrectomy. (v)

By: Chris Tashjian BS – Ara Keshishian MD, FACS, FASMBS

(i) Sato T, Nakamura Y, et al. Structure, regulation, and function of Ghrelin. Journal of Biochemistry. Oct 31, 2011.

(ii) Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998 Oct 22; 395 (6704): 763-70

(iii) Le Roux CW, Aylwin SJ, Batterham RL, et al. Gut Hormone profiles following baraitric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006; 243:108-114.

(iv) Hansen TK, Dall R, Hosoda H. et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin. Endocrinology 2002; 56:203-206

(v) Melissa Gianos, et al. Understanding The Mechanisms of Action of Sleeve Gastrectomy on Obesity. Bariatric Times 8;5: S4-S6 (Supplement)

(vi) Ariyasu H, Takaya K et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endrocrinology Metabolism. 20001;86:4753-4758

(vii) Liu CD, Aloia T, et al. Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders. American Journal of Surgery. 1996 Mar; 62(3) 232-6.

“The LAP-BAND® System is reversible and, if necessary, can be removed — with the stomach usually returning to its original shape.”

This is a direct quotation from the manufacture’s website. It is a statement of its reversible state that is usually used to promote the adjustable gastric banding procedure compared to other surgical alternatives. In my practice I am a very strong advocate of the Duodenal Switch operation and as a distant second, I offer Sleeve Gastrectomy. I do not offer or recommend the Gastric Bypass (RNY, proximal or distal) procedures because of their well known complications of dumping syndrome, weight regain, inadequate weight loss, as well as anatomical complication of stricture or marginal ulcerations that are seen.

I would only assume that the reversibility issue is to be discussed if the procedure is expected to fail frequently . As a surgeon who performs the duodenal switch operation as a primary weight loss surgical procedure, I have rarely had to reverse the procedure. In my opinion, the physiologic reversal of the duodenal switch operation is by far the easiest of all surgical procedures. It involves creation of a side-to-side anastomosis between the alimentary and the biliopancreatic limbs.

The following are images of a Lap-Band® being removed because the patient kept suffering from persistent nausea and vomiting. The operation was performed laparoscopically. The operative finding identified a significant amount of reactive tissue (scar formation) that represented substantial difficulty in the operating room from a technical point of view. The long term damage done to organs by the Lap-Band makes it not easily reversible.

My recommendations for any individual considering a weight loss surgery is not to focus on the ease of reversibility of the procedure, but rather its long-term outcome data as the basis for choosing an operation.

One of the most common and frequent questions asked by patients is the relationship between psychiatric medications and their effect on weight loss after surgery. This is a summary of an article that was published in March 2011 issue of Bariatric Times magazine. The incidence of major depressive disorder is between 2-9% in general population. The World Health Organization reports increasing incidence of depression and other psychiatric illnesses.

There is a complex relationship that exists between depression and obesity. This relationship is even more complicated when one considers the sex of the patient. An example is that men with obesity are less likely to suffer from depressive disorders than normal weight men. Underweight men however are more likely to suffer from depressive disorders and suicidal ideation. This data comes from a study that included 40,000 individuals.

There are a number of different classes of psychiatric medications. These include tricyclic antidepressants (TCA), the newer selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI) and dopamine and norepinephrine reuptake inhibitors (DNRI). And then there are a few, such as Wellbutrin, that do not belong to any of those groups noted.

In general weight gain is more common with TCA medications. There are some in which some weight loss is also noted. The table below outlines a summary of weight neutrality, relative weight gain or weight loss for a number medication. The mechanism by which the weight gain or weight loss occurs is not clear for all medications.

The relationship between antidepressants, mood stabilizers, antipsychotic and weight gain is an example of how important it is for all health care providers to be aware off a patient’s medications and it’s possible side effect on weight gain.

By Charles Bankhead, Staff Writer, MedPage Today
Published: June 26, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

DALLAS, June 26 — Patients who undergo gastric bypass surgery often have undiagnosed glucose abnormalities that can lead to bad eating habits and regained weight, a small clinical study suggests.

Almost 80% of the patients had glucose abnormalities, including hyperglycemia, hypoglycemia, or both, Mitchell Roslin, MD, of Lenox Hill Hospital in New York, reported here at the American Society of Metabolic and Bariatric Surgery meeting. Patients were alarmed by the weight regain, but at the same time, they often had a ravenous appetite soon after a meal, accompanied by an almost uncontrollable urge to eat.” Our hypothesis is that . . . patients may have an enhanced insulin response,” said Dr. Roslin. “They have rapid emptying of the pouch that leads to reactive hypoglycemia. The combination of an empty pouch and low blood sugar leads to hunger.” The findings have led him to question whether gastric bypass surgery should remain the gold standard procedure for treating obesity, he added. At the very least, surgeons should consider the possible need to include a valve in gastric bypass.

The study evolved from clinical observations during patients’ periodic postoperative visits. A growing number of patients complained of weight regain and loss of restriction. The complaints often had a common ring.” Patients were saying that one or two hours after eating, they were ravenously hungry,” said Dr. Roslin. “It sounded a lot like hypoglycemia to me.” To investigate the origin of the symptoms, Dr. Roslin and colleagues studied 63 patients who had undergone gastric bypass procedures. All the patients had a 100-g glucose tolerance test, wherein the maximum/minimum glucose ratio was assessed one to two hours after the glucose challenge.The investigators defined reactive hypoglycemia as a glucose value <60 mg/ dL, or a decrease of 100 mg/dL or more within two hours and no glucose value exceeding 200 mg/dL. They defined hyperglycemia as any value >200 mg/dL and no value <80 mg/dL. Follow-up from surgery averaged about four years. The mean age of the group was 48.5, and 81% were women. The patients’ average preoperative weight was 138 kg, with an average body mass index of 49. One-third had preoperative diabetes. The percentage of excess BMI lost averaged 55%, and the patients had regained an average of 12 kg. Glucose tolerance tests showed six patients with hyperglycemia, including five who had normal fasting blood glucose levels. In addition, 35 patients had reactive hypoglycemia, while eight had hyper- and hypoglycemia. “The hyperglycemic cohort was characterized by a rapid rise to high sugar levels,” said Dr. Roslin. “The fact that most of these patients had normal fasting glucose means we need to be very careful of what we call cure or control of diabetes.” Reactive hypoglycemia manifested as a rapid upsurge of glucose levels that correlated with a rise in insulin and then a rapid decline during the second hour after the glucose challenge. Patients with both hyper- and hypoglycemia had even more pronounced swings in glucose and insulin levels, said Dr. Roslin.

The most dramatic rises and falls in blood glucose have been associated with small pouches and wide anastomoses, he added. The findings suggest a need to consider alterations in the standard gastric bypass procedure, such as use of valves, or possibly abandonment of the procedure in favor of another approach. “I believe that vertical-sleeve gastrectomy and duodenal switches that are not severely malabsorptive will be the best options in the future,” said Dr. Roslin.

Editorial: The about article was sent to me by Vicki Blackburn- Thank you Vicki. This was one of the many presentations that was made at the ASMBS meeting held in Dallas. I will be sharing other presentation in the future newsletters. This article describes what those if us that have been preforming duodenal switch operation have knows for years. This explains why the size of the pouch does not matter, that dumping does not protect against weight gain and why duodenal switch operation is far better option that the alternatives. As with other procedures the science will eventually shed light on all the facts. Dr. Roslin indicates the time is now to consider what should be the benchmark standard for weight loss.
Ara Keshishian MD, FACS

The term “probiotic” is getting much attention in professional circles as well as in the advertising media but is still poorly understood by many. The term describes beneficial bacteria that are added to our diet to help populate our digestive system with a healthy population of good bacteria. It is becoming ever clearer that a healthy population of bacteria is very important for our overall health. Our gut is the most intimate contact between the interior of our body and the outside world much as our skin is. The gut must remain permeable to nutrients which we absorb from foods yet impermeable to invading bacteria and viruses. The bacterial population of our gut plays important roles in both of those functions. It is also very important in the function of our overall immune function. I will leave that for another time. The purpose today is to discus the use and function of probiotic products.

The human gut is populated by tens of billions of bacteria of a yet to be discovered number of species. In excess of six hundred have already been isolated and identified. Some of these species are beneficial, some are harmful and some are a bit of both. Unfortunately modern society tends to have a negative impact on the health and balance of the members of the probiotic population. Chlorinated water, antibiotics both as medications and in our food and even our food choices can cause an imbalance in this population. When this balance is severely disrupted it is termed “Disbiosis”. A disbiotic gut is not a happy thing. We perceive this disbiosis as digestive symptoms of some sort. We may have gas and bloating, constipation or diarrhea, or even both or all of the above. One of the unfortunate aftereffects of having bariatric (weight loss) surgery is it can allow the gut to become disbiotic more easily.

In the DS gut food reaches the large intestine far more nutrient rich than in the “normal” gut. This provides the population of bacteria living there much more food. Given more food the population can flourish. If this population is out of balance it is even more sensitive to poor food choices thereby making the symptoms of this imbalance even worse. This is why the DS patient needs to make prudent food choices and may well enjoy great benefit from proper doses of high quality probiotic products containing the correct species.

The problem is that not all probiotic products are what they say they are and not all probiotic products have the same species. Add to that the fact that each gut is individual. We may need to do some experimentation to find the right combination of dose and product.

Some people have what I term a McDonald’s mentality. A Big Mac in one town is exactly the same as one from a different town or, as another example, a gallon of Shell unleaded gasoline is essentially the same as a gallon of gas from the Chevron station. This is not the case with probiotic products. Some products contain only one species and some contain thirteen or more. These various species, with one exception fall, into two large groups these are Lactobacillus species which predominate in the small intestine and Bifidobacterium species which predominate in the large intestine. The one exception is actually not a bacterium at all but rather a specific yeast. This yeast is very important and beneficial. It is called Saccharomyces boulardii. Some patients have reported good results with single species products such as Align (B. infantus), Culturelle (L. rhamnosus) or Floristor (S. boulardii). My feeling is that these products are overly expensive as they are heavily advertised and that cost is built into the price. They also tend to be rather low dose.

We also need to address the correct dosage. It is important to read the label. Minimum “therapeutic” dosage is thought to be 20 billion colony forming units (CFU’s). I personally am using 50 billion CFU’s per day as maintenance. I have taken as much as 200b CFU’s per day. I am also aware of research going on that also is looking at similarly high dosage.

I think a good product to start with is “Primal Defense Ultra”. Make sure it is the “Ultra” as it is the stronger blend. It is reasonably priced and contains a total of 13 species including the very important S. boulardii. For DS patients experiencing a disbiosis creating very foul flatus and stool. This species as an ingredient is very important. The S. boulardii has very specific activity against some of the nastiest bad guys in our gut such as Clostridium difficile, Candida albicans and even Entameba histolytica and Giardia lamblia which have been shown to enhance the effectiveness of conventional therapy for these conditions. In less severe cases the probiotics alone may be sufficient to correct the disbiosis but more severe cases antibiotic therapy may be indicated.

As stated previously the dosage needs to be sufficient. Three caps per day of Primal Defense Ultra (PDU) is a commonly used dose. This provides a total of 45b CFU’s with 12b of that total as S. boulardii. This was the dose used in a recent case study looking at DS patients with recurring frank C.diff treated with antibiotic and S. boulardii. Statistically very significant benefit was shown.

Also as stated previously every gut is different. Some may do well on small doses and some may need more. Every patient needs to find the dose that works for them. We need to start slowly and work up. Some increase in gas and bloating may occur. Once the disbiosis is improved patients can experiment with different blends. It is suggested that there be several species of both the lacto and bifido groups. The only allergic reaction I have heard of is one patient who developed a slight rash which subsided after lowering the dose. You can find this is most health food stores but it is a much better deal on line. Typically about 90 caps for $37 vs. 218 caps for about $50. General rule of thumb is that the refrigerated brands are superior to the less expensive freeze dried ones. But, many do well with the less expensive brands. Again, you need to experiment.

Also as stated prudent food choices are extremely important. Things like lean protein, complex carbohydrates and whole grains. Avoidance artificial sweeteners and simple sugars and white flour are all prudent decisions.

By: David Caya, DC