24 Hour Leptin Profiles ... Sleep Off Your Spiked Leptinade?

In Science Krispies ... Spiked Pink Leptinade Anyone?,  I took on Dr. Ron Rosedale's claim  that "glucose spikes leptin".  The study I highlighted looked at 9-hour insulin and leptin profiles holding protein constant and essentially comparing a near-zero carb meal to a near-zero fat meal and fasting.  I've copied that graphic to this post:
A&B = women, C&D = men

OK, so we do see that the HC meal results in slightly elevated leptin, more pronounced in women, delayed about 4-5 hours after the meal vs. HF or fasting.  Over on the Perfect Health Diet blog (thanks for the shout out Paul!) , Paul Jaminet wrote:  
CarbSane partially confirms Dr. Ron Rosedale: eating carbs does raise leptin levels compared to eating fat, but it is a mild rise over an extended period of time, not a “spike.”
I'm not sure that I interpret that study as any sort of confirmation of Rosedale's claims, because the claim is very clearly made that blood sugar spikes are spiking your leptin and that the solution is a VLC diet.   That slight elevations occur in the delayed postprandial period ... one might say that 4-5 hours constitutes the post-absorptive phase ... does not in any way confirm Rosedale's claim, as BG spikes in no way correlate with the leptin response.  But Paul's interpretation got me thinking about leptin a bit more, and although it has not been a major interest of mine, I have read many studies over the past few years that look at leptin as part of the assessment.  I've always gotten the impression that leptin is not a post-prandial hormone but rather a long-acting one.  Indeed leptin levels are low during the day and rise overnight.  I've compiled a half-dozen 24-hour leptin profiles from various studies.  These are shown below with the links to the study they come from in the photo caption.

Nocturnal Rise of Leptin in Lean, Obese, and Non–Insulin-dependent Diabetes Mellitus Subjects

Twenty-Four-Hour Leptin Levels Respond to Cumulative Short-Term Energy Imbalance and Predict Subsequent Intake

Effect of One Morning Meal and a Bolus of Dexamethasone on 24-Hour Variation of Serum Leptin Levels in Humans
Sex Differences in Circulating Human Leptin Pulse Amplitude: Clinical Implications

A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations

Short-Term Fasting Selectively Suppresses Leptin Pulse Mass and 24-Hour Rhythmic Leptin Release in Healthy Midluteal Phase Women without Disturbing Leptin Pulse Frequency or Its Entropy Control (Pattern Orderliness)

OK, notice anything?  Leptin follows a diurnal pattern (defined as any phenomenon that follows a day-night cycle).   In each of the profiles above, subjects ate either one morning meal or three meals, in most cases these meals are "standard", in other words the usual 15-20% protein / 50-60% carb / 20-35% fat.  Whatever the rises in leptin levels during the day in response to dietary intake, they are mostly dwarfed by the leptin levels that rise overnight.   So I guess whatever "spike" your leptinade made will not really be "slept off", but rather "swamped out" by your body's overnight production.

I'm going to go out on a limb here and predict that if I go to look at correlations, one will find that rather than blood glucose levels (spikes or otherwise), or insulin levels (spikes or otherwise), leptin levels will correlate rather significantly with our old friend free fatty acids, NEFA in normal conditions, and that disruptions in this correlation will indicate leptin resistance.  

Pass me some leptinade!  I'm thirsty.  :-)


Anonymous said…
Here's an interesting study.

Stephan Guyenet said…
I don't know why Rosedale thinks spiking leptin is harmful. An acute increase in leptin should be protective against body fat accumulation. If you don't increase leptin, you don't get a homeostatic response... that's what leptin is for.

I think he's confusing basal hyperleptinemia with acute increases in leptin. People do the same thing with insulin all the time, equating the hyperisulinemia of insulin resistance with acute insulin spikes. The two states are, if anything, opposites.
CarbSane said…
Hi Stephan,

This is puzzling to me as well. Hyperleptinemia indicates leptin resistance, but from strictly a fat mass POV wouldn't more even more leptin be desired? Seems to me it would. Are you aware of any way we can "spike" leptin with diet?
Stephan Guyenet said…
Hi Evelyn,

As you said, leptin is a long-term hormone, so it doesn't "spike" on the same timescale as insulin for example. However, it does respond to changes in energy balance that occur over one or two days, even if they don't have much impact on fat mass. That response is superimposed on the longer-term levels that are determined mostly by fat mass.

The most reliable way I know of to increase circulating leptin substantially is to overfeed for 1-2 days. Carbohydrate feeding seems to stimulate it a bit more than fat on that timescale, but I don't know if the difference persists after fat accumulation becomes significant. From what I've seen, carbs seem to provoke a bit more of a homeostatic response in general. It may be due to the effect of insulin on the hypothalamus and/or on leptin secretion by fat tissue.