DebraSY

Ghrelin, the Gremlin: Let’s Study it.

In Weight-Loss Maintenance on October 22, 2010 at 2:24 pm

In my post earlier this week, I promised to talk about endocrine, and how weight-reduced people are different from people who are at the natural, highest weight that their body establishes for them.  Let’s start with my favorite study, Cummings et. al in the New England Journal of Medicine, May 2002.   These are actually MDs mostly, rather than PhDs.  So maybe this mitigates the vitriol of my post last week, and maybe, too, it is a study that MDs feel comfortable taking seriously.

Cummings and crew compared plasma Ghrelin levels in samples of nonsurgically-assisted weight losers to people who underwent gastric bypass surgery. 

Ghrelin is probably the best understood of the hunger hormones.  In the chemical cotillion happening in our body, it dances monogamously with its partner Leptin, who creates satiety (fullness).  When they dance with Leptin moving forward, we are satisfied, when Ghrelin moves forward, we feel hunger.  Simple.

I like to think of Insulin as the party slut.  She dances with all the Ose brothers – Dextr, MonoDextr, Gluc, Sucr, Fruct.  They’re all such sweet boys.  She bounces around inside us, giggling and flirting, and when she and a partner smacks into the monogamists – Leptin and Ghrelin – she pisses them off, so they may start dancing the wrong way.   In real life, you might be minding your own business and perfectly satisfied with regard to food, but Insulin starts doing her Donna Summer thing inside of you, and suddenly your eating impulses set in, and there you are walking into the kitchen again.  Insulin also, from what I understand, messes with other chemicals inside us besides the Ose family.  She isn’t evil, and she’s actually necessary, like the annoying aunt you have to invite to your wedding reception, but she can be exasperating.  There are scientists who devote their lives to studying her moves.  Other chemicals at the cotillion may also affect Ghrelin, which is the featured chemical in the Cummings et. al. study.

Now, the results of this study have their limitations – small sample size, no follow up – but I have to say, the first time I saw this study, I gasped.  It was a chilling “Eureka” moment for me when I printed off Figure 1 and studied it.  “That’s me!” I thought.  “On paper, that’s me.”  I am now always roughly 24% more hungry at any point in the day compared with how I felt before weight-loss.  When I’m hungry, I’m hungrier, and when I’m satisfied, I’m less so.  And what is striking to me is how the graph moves in two almost perfect parallel lines.  No meeting points ever.  Wow.  I have to ask, fellow maintainers, does this chart resonate with you too?  Does this study, weak as it is, affect you as much as it does me?

While we non-surgical losers are dealing with increased ghrelin, the other half of this study shows a 77% suppression of plasma ghrelin among gastric bypass surgery patients.  Surgical maintainers, your chart is labeled Figure 2.  Note that you have nearly none of the peaks and valleys of the matched obese control group, the normal weight controls or the nonsurgical weight-losers over in Figure 1.  

Post-surgical weight-loss maintenance is not my primary area of interest, so I’m not as well versed in the research, but I suspect that this suppressed hunger hormone is only temporary, and possibly caused by the systemic shock of surgery itself or other causes.  While I don’t have the figures (and I’m not confident that the figures out there are accurate) we know that surgery is no guarantee of permanent weight loss and many, maybe most, people regain part or all of their weight after losing from a surgical assist.  So, I would ask you surgical maintainers, how long does it last?  How long is ghrelin tamed?  When would you advise scientists to measure plasma ghrelin, then follow up and measure again?   What features of this study strike you as interesting?

While ghrelin was clearly the star of this study, I took note also of the final sentence of paragraph one in the “Results” section.  I was simultaneously bemused, baffled and yet affirmed.  Talking about the non-surgically assisted weight-losers, the scientists said, “Weight loss was associated with significant reductions in adipose volume, leptin levels, insulin levels, and blood pressure, as well as with increased insulin sensitivity and improved lipid profiles.”  My lay translation:  you take a lot of bad with the good when you intentionally reduce your weight, and the scientists won’t parse which is which, so we may need to help them.  The chemical cotillion is very complex, but increased insulin sensitivity and reduced leptin levels are clearly bad things.  Lower blood pressure and improved lipid profiles are good.  Why would you ever put them in a sentence together?

But I don’t mean to be hard on the study du jour.  Cummings et. al. gave me a thrill with that chart and is rare in how nonjudgmental it is, and so I treasure it.

I may well be living in a sick fantasy world when I play with the idea that scientists may actually, someday, take us seriously, ask our opinions.  I picture a world in which scientists may stop merely observing our behavior and judging us – concluding, for example, that people regain weight because of a “failure to maintain behavior changes,” which leaves others to assume it’s the regainers’ failure to make good choices or that they just get lazy. We maintainers know there is something much more profound at play here, and we hold on to our losses by tenacity, luck and a little cleverness. 

Next week, let’s look at some more science.  If you want to read ahead, here’s one on leptin and ghrelin after weight loss and here’s one on Peptide YY3-36.   

If you have a study you think we should examine, please send me the citation.  I don’t guarantee I’ll address it, but I like collecting them, and yours may strike my eye.

At some point soon, too, I think we maintainers need to talk about our strategies for getting around our strong hormone impulses, post weight-loss.  (That will be triggering talk for the beyond-dieting size acceptance crowd.)

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  1. Wow. This explains a lot.

    People I know who haven’t gone through a major weight-loss look at me like I’m crazy when, a few hours after a meal, I’m hungry again. They definitely don’t get it when that hunger quickly progresses from minor irritatant to light-headedness, shakiness, and full-on emergency hunger. I’m pretty sure they chalk it up to me exaggerating.

    Thing is, I don’t remember feeling like this in the years before the weight loss. I used to be able to skip a meal, or basically fast until dinner, and not feel as horribly crappy as I do when I get hungry these days.

    Snacking helps, but as you mentioned in an earlier post, 100 calories doesn’t buy you satiety for very long – maybe an hour if you’re lucky. Snacks larger than that mess up my lunch or dinner plans, ’cause I’ve already eaten into my calorie allotment for the day.

    I guess there could be other confounding variables in my case (past pregnancies, medications I’ve taken, and the aging process itself), but this makes a lot of sense. (And the fact that this was published in the NEJM certainly doesn’t hurt its credibility, either.)

  2. I believe you LNJ. Thanks for telling your story.

  3. Umm… did you mean insulin INsensitivity, as occurs with diabetes? I thought increased insulin sensitivity is a good thing.
    Anyway, it appears that the problem of world hunger is almost solved in our lifetime, by simply jeering at people who claim to feel hungry, unless they’re thin. Even the Twilight Zone would have been hard-pressed to come up with something this horrifying.
    Hunger isn’t just an orange fuzzy thing from Weight Watchers commercials, and it deserves more respect than it currently gets.

  4. I went back to the study and it didn’t have the “in” before the word. Nor did they define really what they meant. Perhaps it is a good thing. Does it increase our hunger, though? If it does, then that’s a side effect that’s serious for those of us trying to maintain losses. Or it should be respected for the difficulty it imposes on the process. I know insulin performs several functions, including “flipping switches” in our cells so that we may process sugars, and it also communicates in other ways, and is integral to the hunger/satiety continuum. Perhaps I need to study it more. Join those folks who devote their lives to it.

    I may not know insulin’s precise roll, but I do know the hunger of maintainers is real. Like you said, it’s not a cute orange monster. Not to give away too much, since I’ll deal with it in an actual post (and LNJ picked up on it already, anyway), but I know that, among my “strategies,” I manage hunger much like a friend who has terminal cancer manages her pain. I stay ahead of it. I never let it get a foothold. My friend takes pills before she feels pain or at the slightest hint of on-coming pain. I eat something before I’m hungry or when I get “cues” that I call “pre-hunger.”

  5. RNegade, could you give us a little Insulin 101 please?

  6. Debra,
    Just a point on the ghrelin article: your contention that increased insulin sensitivity and decreased leptin are bad things…it ain’t necessarily so.

    Increased insulin sensitivity means that your body can produce less insulin and have it work better peripherally (in the muscles and liver). Less insulin means better general kinetics, less hunger and smoother food metabolism. Definitely a good thing. Secondly, obese people usually have leptin resistance. They tend to actually have high leptin levels, but their leptin isn’t working normally. Declining levels may indicate a “healing” of the leptin axis.

    • Welcome, Barbara! For you size acceptance folks, Barbara is to maintainers what Marilynn Wann is to size acceptance (A rock star, of sorts). As I was writing this post, I was thinking, “I wish I still had my Barbara Berkeley book, I know she has some grasp of insulin, and I know I read about it in her book, and it was in plain English.” But, as you know, my copy of your book has been passed on to good hands. Must go order another!

      With regard to leptin, do you have some recent studies you may send my way to cogitate? When I last read up on leptin, it was my impression that it’s discovery held out such hope, and people were soooo excited and thinking that all we’d need to do is come up with some kind of leptin drug to cut hunger, BUT it then proved much more complicated than first thought, and we’re still in left field. Is my metaphor of a confusing chemical cotillion in our bodies somewhat on target?

  7. Wonderful metaphors, as always!

    Like Mulberry, I interpret the study (and I read the original paper, too) as saying that insulin sensitivity increased. Which means that a given amount of insulin will process more glucose than it did previously (per the formula used in this paper, which was drawn from this 1979 paper: http://ajpendo.physiology.org/cgi/content/abstract/236/6/E667). This is the opposite of insulin resistance (where a given amount of insulin processes less glucose), which is what occurs with diabetes (see, e.g., http://en.wikipedia.org/wiki/Insulin_resistance). But this is drawn from a few minutes of internet-based research; I’m no expert on this topic.

  8. Hmmmmm. But what does this means with regard to persistent hunger/eating impulses?

    Thanks for the studies, I’ll go take a peek.

  9. I concur with Dr. Berkeley’s interpretation of insulin sensitivity.

    Moreover, as a human being who has lost 100+ lbs previously, 3 times to be accurate, who regained all of the weight each of those times (plus extra), and who has lost 80 lbs so far this year, I am grateful when anyone (MD or PhD or average Jill) takes the problem of hunger seriously. On one of those previous forays into weight loss/regain, I kept the weight off for almost three years before the regain began…right on the tail of a return to a state of near-constant hunger that went on month after month after month. If becoming bulimic was a choice, rather than a mental illness, I would have chosen bulimia over the regain(s)–so extreme was the pain, both emotional and physical.

    I believe stress hormones play a major role in contributing to increased hunger (which, in my experience, can return long after the excess weight is gone and *goal* weight seems to be stable) but I am not aware of any studies that can support my belief. There simply is not much published research that addresses the issue of living with hunger.

  10. I’m no expert but I’m enjoying a little bit of respite from the constant hunger by not eating flour, sugar, beans, peanuts, potatoes, pasta. I do eat nuts, meat (a little bit), vegetables and fruit. And I’ve added in about 70 oz. of water a day in addition to all the other things I drink. (Barbara Berkeley’s plan) I hope.

  11. I know I am late to the party, but I was re-reading this article and looking at the charts and I have an observation/question.

    The actual ghrelin levels in the after diet-induced weight loss chart are actually at about the same level as the normal weight group. While the ghrelin levels prior to diet induced weight loss and the obese control group also match up pretty well. It appears that ghrelin levels in the obese subjects were about 24% lower than in the normal weight controls.

    Do you think that the problem with hunger might be more with a sensitivity to ghrelin in the diet induced weight loss group, rather than the amount of ghreliin? It seems that normal levels are ghrelin are more triggering than in normal weight folks.

    I am interested in your opinion…

    • Thanks for joining the conversation, Nancy. Better late than never. I am about to be “too distracted and occupied to blog” for about a week, so I’m not in a position to review the piece. I’ll make a note to look at it when I get back.

  12. Nancy, first of all, I am so sorry to have put this off for so long. I have known this is here waiting for me, and I wanted to give it some good attention. What you say is intriguing. It would be nice to have Figure one and Figure two color coded and on tranparency cells so we could lay them one on top of the other. There are places where they appear to track together, and places they seem to differ significantly, and it may be related to time of day. Hmmm.

    What you suggest about “sensitivity” may also be at play here. We measure insulin sensitivity and leptin sensitivity, why not ghrelin sensitivity? Would make sense to me.

    Since you got me back in the study, I looked more closely at Table 2. Here I’m really out of my depth as a nonscientist, but the changes in Leptin and Insulin seem worth looking at too. Hmmmm, again.

    As I write this, a small Australian study has recently come out looking more dimensionally at hunger and the hormones involved. While it’s not a great study from a design perspective, it’s getting a lot of play in the media, and it’s on the right track, in my humble opinion. We’ve been discussing it in the final post, if you’re interested.

    Also, if you didn’t see them when they were posted, do a search on the Katarina Borer studies we discussed here. Borer wrote the premier text on Endocrine and Exercise and has recently done some experiments that looked, in part, at Ghrelin. Her take is that Ghrelin is not the mirror opposite of Leptin, as we’ve kind of assumed it to be — one goes up, the other goes down and they both affect hunger directly. Her take is that Ghrelin actually does it’s work in the reward centers of our brain. All very heady stuff.

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