September 11, 2010
Hormones Predict Sustained Weight Loss

Levels of the hormones ghrelin, leptin, and insulin before weight loss even begins influence whether weight loss can be sustained.

In this study, researchers evaluated a group of 104 obese or overweight men and women during an 8-week low-calorie diet and again 32 weeks after treatment. Researchers measured body weight as well as plasma fasting ghrelin, leptin and insulin concentrations before, during and after dieting. They found that subjects with higher plasma leptin and lower ghrelin levels before dieting were more prone to regain weight lost after dieting and that these hormone levels could be proposed as biomarkers for predicting obesity-treatment outcomes.

"We believe this research is of foremost relevance in clinical terms as it may indicate that the outcome of weight therapy may be pre-conditioned," said Crujeiras. "Furthermore, our findings may provide endocrinology and nutrition professionals a tool to identify individuals in need of specialized weight-loss programs that first target appetite hormone levels before beginning conventional dietary treatment."

Ghrelin increases appetite while leptin reduces it. Correction: So why does a person with lower ghrelin and higher leptin have a weight problem in the first place? See my update below. One possibility: Leptin insensitivity. So once they lose weight and go off their diet their appetites drive them to put on too much weight again. Ghrelin might also cause abdominal fat accumulation.

So any way to adjust your hormone levels in order to keep weight off? Not sure. But Byron J. Richards, author of The Leptin Diet: How Fit Is Your Fat?, argues that snacking is a major cause of low leptin and therefore of weight gain.

No snacks, high protein breakfast, and low carb. A high protein, low carb breakfast is pretty easily doable.

Update: As someone points out in the comments, the study subjects who regained the most weight had higher leptin levels - which one might expect would help them suppress appetite. So what gives? Leptin and ghrelin levels are hard to interpret because some people might have brain insensitivity to leptin (which reminds of type II diabetes which is characterized by insulin insensitivity and higher insulin levels). The result above might really indicate that people gain weight because leptin no longer suppresses their appetite. A high fat diet decreased mouse leptin sensitivity in one study and estrogen deficiency caused leptin sensitivity in rats. A diet that increases leptin sensitivity might be the key to weight loss.

Share |      Randall Parker, 2010 September 11 06:41 PM  Brain Appetite

Daniel in Oregon said at September 12, 2010 12:02 PM:

Your conclusion contradicts the study finding.
If "subjects with higher plasma leptin and lower ghrelin levels before dieting were more prone to regain weight lost after dieting", why would you say "Someone with higher ghrelin and lower leptin before dieting might have a metabolism that pushes them to eat more. So once they lose weight and go off their diet their appetites drive them to put on too much weight again."

Bill Quick said at September 12, 2010 12:34 PM:

What role did insulin play? Some research indicates that insulin influences production of leptin and ghrelin.

Randall Parker said at September 12, 2010 1:04 PM:


You are right. I should have read more carefully. As I say in an update, the study might really be finding overweight people who have leptin insensitivity are the ones who can't keep off weight.

So how to increase leptin sensitivity?


I suspect we have to follow diets that reduce (or avoid) insulin insensitivity and leptin insensitivity.

Tuck said at September 13, 2010 2:48 PM:

There are also a number of foods that reduce leptin sensitivity. Wheat and industrial seed oils both seem to reduce leptin sensitiviy, according to Stephan Guyenet at the Whole Health Source blog (he's a scientist studying leptin). Wheat and industrial seed oils like soybean and canola are a huge part of the American diet... Hmmm.

One of the reasons the paleo or primal diets seems to be effective is because it eliminates wheat and industrial seed oils, and also insulin promoting foods. (Insulin has been shown to lower activity levels, so eating carbs, which raise insulin levels, which reduces activity levels, is like a double-whammy.)

In said at September 13, 2010 7:23 PM:

Matt Stone has written a lot of original thought provoking stuff regarding leptin at his blog. He cites evidence that fructose can lead to leptin resistance:

UF researchers found that rats became resistant to leptin after being fed a diet high in fructose for six months. Although there were no visible signs this change was occurring, the fructose-fed rats gained considerably more weight than rats that never ate fructose when both groups were switched to a high-fat diet.

There are more details on the study at Matt's blog and his analysis is worth reading as well. His position is that starch is not that bad compared to fructose especially high fructose consumption combined with a high fat diet.

In said at September 13, 2010 7:44 PM:

Just watched the vid. I'm skeptical that meal size and frequency are all that important. They could be but usually the mechanisms that control things like the triglycerides burning etc. are more complex than the initial behavior observed. There is usually feedback mechanisms that maintain equilibrium. He could be right if there is a "natural" or evolved eating pattern. However I don't know of any data on the topic.

That said it was interesting that Richards mentions that leptin doesn't work properly with high triglycerides. This is consistent with fructose, especially from refined sources being problematic as fructose consumption raises triglyceride levels.

Randall Parker said at September 14, 2010 8:20 PM:


Fructose causing leptin resistance: Very interesting.

Yes, I have come across pieces of research on fat reducing leptin sensitivity and insulin sensitivity. Fructose -->> triglycerides -->> leptin insensitivity.

richard said at December 11, 2013 1:20 AM:

Could it be that those with high leptin and low ghrelin have been habitual dieters? And if that is the case, could it also be that those with leptin insensitivity actually have ghrelin over-sensitivity in addition? What long-term effects can happen if we habitually ignore ghrelin signals, like in dieting?

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