Welcome all seeking refuge from low carb dogma!

“To kill an error is as good a service as, and sometimes even better than, the establishing of a new truth or fact”
~ Charles Darwin (it's evolutionary baybeee!)

Sunday, July 4, 2010

Low Carb & Leptin

Lately there's been a lot of buzz around the internet about leptin and leptin resistance.  I've come across a few things over the past several months I wish to share, basically focusing on whether levels of this hormone can be manipulated by varying the macronutrient composition of one's diet.

My general feeling on this is a cautiously stated:  no.  While some studies show differences in postprandrial leptin, fasting leptin, leptin AUC, there doesn't seem to be an overarching trend in this regard one way or the other.  It would appear that leptin has more of a chronic role in energy homeostasis rather than an acute one.  Insulin, OTOH, appears to have a somewhat dual role -- levels respond acutely to nutrient intake, while a basal insulin level generally correlates with one's degree of adiposity.  Indeed in many diet comparison studies, fasting insulin levels go down modestly (usually with weight loss) but to the surprise of low carbers everywhere, I've not seen consistent findings of significant reductions in fasting insulin for LC vs HC diets.

Leptin, however, seems to be less subject to acute responses and is highly correlated with fat mass.  The screenshot I'm posting below has been posted here before.  One of these days I hope to find the study I snagged this from, but I can tell you that it was the differing responses to isocaloric "meals" of each isolated macronutrient.
The timeframe was six hours.  Clearly in the upper right we see the expected insulin response carb>protein>>fat.  But if anything, the postprandr ial response of leptin to food intake is slightly lower levels where protein suppressed the most, fats seeming to have a delayed acute suppression (albeit small) and carbs showing a rebound after an immediate slight reduction.  However those vertical lines tell the whole story, they are the error bars -- IOW, no changes were significant to any statistical measure.

Do LC diets somehow re-set or re-establish normal leptin signaling?  I'm not sure we can conclude this based on this study in T2's I've blogged on previously:  Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes.  In this 2 week study, the low carbers spontaneously reduced caloric consumption by ~1000 cal/day and lost an average of 3.6 lbs and "Mean 24-hour serum insulin and leptin levels profiles were statistically significantly lower at the end of the low-carbohydrate diet than before this diet, while ghrelin profiles increased marginally."

Most acknowledge the appetite suppressive quality of LC diets, and this apparently happened here to the tune of a substantial spontaneous intake reduction.   Clearly this is not due to leptin which is lower (rather than higher) after the LC diet.  It is possible (but a stretch IMO) that along with caloric deficit-induced leptin reduction, leptin resistance was reduced even more.


James Krieger said...

Nice post. My opinion is that the main appetite suppressant effects of low carb diets are mainly acute effects due to the high protein intake combined with dietary ketosis.

CarbSane said...

I agree. I also believe that you see soooooo many examples of LC'ers losing rapidly then plateauing at a higher than normal rate is because we either lose the latter or adapt to it so it no longer suppresses appetite. Severe carb restriction mimics starvation, so having our metabolisms in that "gear" chronically has got to result in adaptation of some sort.

James Krieger said...

Another sign of adaptation is the fact that it is difficult to maintain ketosis even on low carb intakes. This has been shown in research and Lyle McDonald has written about it. Thus, the appetite-suppressant benefits of ketosis probably disappear with time.

Torben Deumert said...

Two things should be pointed out:

1. Leptin levels in the blood are pretting meaningless, because the important question is: Does it work in the brain? LC is said to normalize the functioning of the leptin receptors in the brain and thus less leptin would be needed in the blood. It's similar to insulin, where insulin resistant people push out more insulin, because the receptors to not work appropriately.
Therefore, the lower leptin levels of LC indicates the potential improvement (because with leptin as well, more is not necessarily better).

2. Everybody knows that the adaptation to LC takes some time. In cyclists, the performance was normal after 4 weeks (where before it was impaired), so all those 1-meal, 1-day, 3-day, 1-week and even 2-week study is fundamentally flawed and ultimately useless. Studies on LC need to be at least 4 weeks, and 3 months or 6 months would be a lot better to assess the adaptation processes that LC triggers.

@James Krieger:
The appetite-suppression does not stem from ketosis, but from low carb. Carbs seem to inhibit the leptin receptors in the brain, similar to the insulin receptors in other cells.

LC is the opposite of starvation. That's why people eat less. The brain knows everythings ok. On a too-high-carb-diet, the leptin receptors don't work and because the insulin triggers fat accumulation, which means the energy you just ate gets stored and is not usable. Both contribute to the brain thinking the body is starving; largely because it does not get the leptin. The body is not starving, but the brain thinks it is. This results in more hunger, decreased desire of energy expenditure to save the calories the body is seemingly missing.
Now, during the first few weeks there is a problem, because the body can't get enough energy from FFAs yet, because there are not enough enzymes (and there are other theories for this bump in energy during the first few weeks). But after a few weeks things improve. You don't need to eat so much anymore, because the body can access it's fat depot and knows that it has access to enough energy and therefore you don't feel this constant urge to eat.

Now, after severe fat loss one would expect appetite and food intake to increase, but not because of some further adaptation, but because the adipocytes will no longer product that much leptin, because they are smaller. That might be one of the reasons for the plateaus, although studies which show them or even slight weight gain after ~ 6 months, use the atkins diet, which results in increasing carbs over time. I don't know of any long term study on lc, where people stayed on let's say <= 50g carbs/day. But there are other factors that could explain plateaus and even slight weight gain besides the increased carb content of atkins after some time, like increased water retention and muscle mass because of regular exercise. But I don't know any serious study which looked at that or at aerobic performance for more than 4 weeks, unfortunately.

It would be interesting to see if the improved ability to burn fat will even more than compensate the decrease of energy from the missing carbs (although in LC as well, glucose is created through gluconeogenesis, so glycogen stores might not be necessarily empty) after longer periods of adaptation for specific exercises (like running or cycling).Two things should be pointed out:

Evelyn aka CarbSane said...

Welcome Torben,

WOW, this post is almost 2 years old, and my how much I've learned since.

I have researched IR quite extensively, and in diet induced IR in humans, I've yet to see the defect occur at the insulin receptors. This notion that insulin spikes -> chronic hyperinsulinemia -> loss of receptor sensitivity is simply not supported by any of the evidence.

Leptin seems a far trickier "animal" in this regard. But just recently we were discussing a rat study (it's in comments of The Men Who Made Us Fat) where some rats who were fed a 60% fructose diet for six months exhibited leptin resistance when later transitioned to a high fat diet and gained more weight v. controls. They were not any fatter after 6 mos on 60% fructose however, so it's hard to blame LR for what happened next when it had no effect on them with their extreme habitual diet.

When I compare LC to starvation it is in the sense that the metabolic processes that are upregulated are the same (gluconeogenesis, for example) as in starvation. I'm not so sure the brain thinks all is hunky dory in the long run.

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