Controversial - Ghrelin is actually a GOOD thing!

The weight loss community (esp the VSG subset) has been told that the hormone ghrelin is a bad thing. But most of the latest research suggests ghrelin is actually a very beneficial hormone, with substantiated health benefits, as partially summarized below.

I don't want to upset anyone who has already had bariatric surgery (esp VSG), but I do want to make this post for those considering surgery to be provided with all the information in making their decision. (And to those who have already had surgery - remember, nothing is more health promoting that losing all that excess weight, so don't fret.)

Benefical aspects of Ghrelin (research in links):

- increases NPY (antidepressant, antianxiety)
http://endo.endojournals.org/content/147/11/5102.full

- defends against stress-induced depression and anxiety
www.ncbi.nlm.nih.gov/pmc/articles/PMC2765052/

- is reduced 60% by VSG and remains low for as long as has been studied (5 years post-op)
www.weightlosstriumph.com/long-term-effect-of-sleeve-gastrectomy-on-weight-loss-and-ghrelin.html

- fights aging in thymus and thus prevents immune function decline in elderly
www.eurekalert.org/pub_releases/2007-09/joci-hhf083007.php

- protects muscles from atrophy
http://www.news-medical.net/news/20090613/Appetite-stimulating-hormone-may-protect-muscle-from-atrophy.aspx

– caloric restriction (but only with full stomach intact) enhances ghrelin levels during aging, which may help extend lifespan
http://www.ncbi.nlm.nih.gov/pubmed/17875344

- stimulates growth hormone secretion (and blocking GH may explain, at least in part, why VSG reduces blood sugar)
http://www.ncbi.nlm.nih.gov/pubmed/15620414

- enhances learning, cognition, and cognitive adaptation)
http://classic.the-scientist.com/news/display/23132/
http://www.ncbi.nlm.nih.gov/pubmed/19652956

– decreases inflammatory responses, improves organ blood flow, attenuates tissue injury following trauma
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748721

- increases dopamine in substantia nigra and may help slow onset of Parkinson's disease
http://www.ncbi.nlm.nih.gov/pubmed/19906954

- inhibits pro-inflammatory cytokines, reverses age-related thymic involution
http://www.ncbi.nlm.nih.gov/pubmed/17875344

- exerts positive cardiovascular effects and is considered as a direct target for prevention of cardiovascular disease
http://www.hindawi.com/journals/ijpep/2010/248948.html

- exhibits health promoting effects in elderly
http://www.ncbi.nlm.nih.gov/pubmed/18981485

- may be suppressed by either VSG or RNY (though far more consistently by VSG)
http://jcem.endojournals.org/content/88/7/2999.full

this is an informative post, have you posted it on the VSG site?  I think all info is good info (even if it is not what you want to hear).  I dare you to post it LOL!

I did post it on the VSG site, actually, and I tried to make clear I wasn't trying to upset them (and I am actually considering the VSG as well as RNY).  There is almost a religious fervor for some people in the VSG community that ghrelin is bad, but the truth from almost all of the research is just the opposite.

I encourage the RNY people to look on the VSG side at this same post/thread because I added some comments re RNY there, as well, which I hope will be of interest esp to those debating RNY vs VSG.  It explains why RNY patients lose more weight than do VSG patient (not because of malabsorption, which studies have shown is irrelevant to weight loss for proximal RNY despite what most surgeons think), but because of a dramatic increase in energy expenditure (think metabolism) that RNY offers -- but which VSG and the band do not.

Based on the research, here is the ranking between these 3 surgeries:

(1) RNY  
       - drastically increases resting energy expenditure
       - slashes appetite

(2) VSG
       - slashes appetite
       - no increase in resting energy expenditure

(3) Band
       - INCREASE in appetite
       - no increase in resting energy expediture

This is why RNY patient will lose the most weight, VSG the second most, and Band patient very little long term.  Restriction plays, at most, a modest role in weight loss (and arguably very little).  Again, malabsorption of calories plays virtually ZERO role in proximal RNY weight loss (see 2009 Harvard study).

Do you have a full citation for the "2009 Harvard study" so I can look it up?

Everything I have seen in ALL of the medical literature indicates that the temporary caloric malabsorption of RNY is a KEY component of the initial weight loss.  If malabsorption plays no role in the intial weight loss, why would surgeons bother to do the bypass portion?  Why not just create a pouch instead of a sleeve and be done with it?!? 

Can you also explain on what you base the indication that RNY "drastically increases resting energy expenditure" whereas VSG does not?  I am unaware of any way in which RNY increases your metabolism.  The appearance of increased metabolism is a result of the caloric malabsorption (which you are indicating is not a factor). 

Lora

This is great info!

Would you please post it on the Main Board, also?

Thanks!

I am not disputing that there are clearly some positive actions of grehlin (I personally doubt that ANYTHING that naturally occurs in our bodies serves only a negative function), and several of these articles (I did not read all of them, but read some of the abstracts only and some full studies) are quite informative.

People should, however, read these citations carefully because a few of them are studies related to synthetic or forms of grehlin or grehlin-like substances (des-acyl grehlin, a generic mimetic grehlin called MK-677,   rather than on the natural grehlin in our bodies.  As with many other substances, mimetic forms of grehlin (administered orally or by injection) may not be identical in all asptects to the naturally occurring hormone and may not function identically with the ghrelin receptor.

Lora

Lora,  here is the 2009 Obesity study (forgot to include it in initial set) by Harvard Medical School and Massachusetts General Hospital:

http://www.nature.com/oby/journal/v17/n10/full/oby2009207a.h tml

Please let me know if that addresses your questions.  You will see it shows that the pair-fed subjects lost about 1/2 as much as the RNY ones, and this was solely because of the drastic increase in energy expenditure seen with RNY in the fed state. 

As to your question as to how this could all be possible if restriction is not a dominant player, consider the following.  When an insert is placed into the duodenum EndoBarrier patients lost an avg of 50 lbs (http://www.prweb.com/releases/2010/09/prweb4482324.htm) without any stomach restriction.  This insert also cures diabetes, high blood pressure, high cholesterol, high triglycerides, as with RNY.  The insert moves absorption of calories from duodenum to further downstream in the small intestine.  That does not equate to malabsorption, just further downstream.  The process of absorbing calories further downstream triggers a host of hormonal and metabolic changes also seen in RNY.  Unfortunately, they won't let you keep the insert in permanently, so it is not currently a great lifetime option.  But its efficacy supports the fundamental reasons for RNY success.

Also, consider this -- if restriction were so pivotal, then why do Lap-Band patients not lose very much weight long-term?  It is a purely restrictive procedure.  But the more it restricts, the more hungry they get.  It would be like telling you to breathe 25% less per day, and then to help you restricting your mouth and nose by 25% -- that wouldn't help!  You would just try that much harder because homeostasis is at play.  Likewise, the reason RNY is so successful is because it addresses two key root issues -- (i) it increases energy expenditure in response to eating and this increase does not diminish with weight loss, something lost in morbidly obese people and (ii) it suppresses appetite.  So, RNY fundamentally shifts the homeostasis in our favor.

As to how RNY could increase energy expenditure, again, it has to do with shifting absorption of calories to further down in the small intestine, where proper hormonal signaling can occur.  Many researchers now believe morbid obesity (and likely diabetes and metabolic syndrome) is fundamentally a disorder of the duodenum (first part of small intestine).  Some believe (and my view) that this disorder is characterized by too efficient an absorption by the duodenum, leaving too few calories to be absorbed further downstream in the small intestine.  My own view is that this was an evolutionary adaptation to long term starvation in certain peoples, and this might be supported by some indigenous populations with incredibly sparse food availability who rapidly become incredibly obese (> 500 lbs common) and rapidly become diabetic when entering western society.

I may add some more a little later (have to go) as this is all very interesting to me, but I hope this is a start in addressing some of your questions.

Also, you will see both in the 2009 Harvard study above and also noted in this study (http://jcem.endojournals.org/content/88/7/2999.full) that malabsorption is not a real player for proximal RNY weight loss.  (I have also seen this noted in at least one other study, but don't have the time right now to track it down.) To make sense of how this could be possible, please read my above comments and the Harvard study.

Relevant excepts from the 2009 Harvard study:

 "A growing body of evidence suggests that profound changes in body weight and metabolism resulting from GIWLS, and particularly RYGB, cannot be explained by simple mechanical restriction or malabsorption (12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27)."

"This procedure effects weight loss by altering the physiology of weight regulation and eating behavior rather than by simple mechanical restriction and/or malabsorption as previously thought."

"Although we observed a small decrease in nutrient absorption after RYGB in this model, there was no evidence of clinically significant malabsorption (36)."

Note that the VSG surgery was also performed in this study for comparison, and it did not exhibit the increase in energy expenditures seen in RNY, nor was it seen in pair-fed subjects (given exact same small quantities of food as RNY subjects, just without the surgical modifications of RNY).  So caloric restriction does not remotely account for the drastic increase in energy expenditure seen in this study.
 
Again, hope this addresses your skepticism re malabsorption not being a real player in long term weight loss of proximal RNY (which they call RYGB in Harvard study; also, they refer to Gastrointestinal weight-loss surgery as GIWLS re above quote).

An insert that moved absorption of calories downstream would indeed lead to malabsorption, because part of the small intestine would be unavailable for absorbing calories, just like it is when part of the small intestine is bypassed surgically.

I think the reason so many lap band patients don't lose very much weight is that they have difficulty getting the right amount of restriction.  If there is not enough fluid in the band, then they have no restriction.  But if there is too much fluid in the band, it is too tight and causes vomiting and other problems.  It seems to be difficult to get just the right amount.