High Protein Diet Induces Sustained Reduction in Ad Libitum Intake Despite Diurnal Leptin Compensation

I've written several hundred posts on this blog.  There are some, especially from early on in 2010, that I would really like my readers to see, and I sure don't expect folks who are just finding this blog now to go back and read everything to find some that I feel are key.  I refer to this study quite often because I think for those finding themselves gaining a little bit each year and not wanting to hop on some "diet rollercoaster", there is merit to -- especially for us women -- upping the protein as a percentage in the diet.  So when I was compiling graphics for the 24 Hour Leptin Profiles post, this study was the first I knew to go to for a graphic.  So, I'm bumping the original, adding a little emphasis to the text but not changing it, and I'll add some commentary on leptin at the end.  

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Original Publish Date:  4/30/10

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

Background: Ad libitum, low-carbohydrate diets decrease caloric intake and cause weight loss. It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake.

Objective: We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake.

Design: Appetite, caloric intake, body weight, and fat mass were measured in 19 subjects placed sequentially on the following diets: a weight-maintaining diet (15% protein, 35% fat, and 50% carbohydrate) for 2 wk, an isocaloric diet (30% protein, 20% fat, and 50% carbohydrate) for 2 wk, and an ad libitum diet (30% protein, 20% fat, and 50% carbohydrate) for 12 wk. Blood was sampled frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve (AUC) for insulin, leptin, and ghrelin.

Results: Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC. Mean (±SE) spontaneous energy intake decreased by 441 ± 63 kcal/d, body weight decreased by 4.9 ± 0.5 kg, and fat mass decreased by 3.7 ± 0.4 kg with the ad libitum, high-protein diet, despite a significantly decreased leptin AUC and increased ghrelin AUC.

Conclusions: An increase in dietary protein from 15% to 30% of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss. This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets.

My Summary:

Subjects:  19 Adults, mostly Women (16), starting data provides Mean ± Std.Dev

• Weight (kg): 72± 8.9 (56.1–88.3) 
• BMI (kg/m2) : 26.2 ± 2.1  This is moderately overweight 
• Subjects were weight stable for ≥3 mo before the study, and were at their lifetime maximal weight.
• Subjects were healthy and excluded were anyone with a BMI over 30, smokers, regular exercisers, high alcohol consumption, pregnancy, diabetes, and anyone regularly consuming a regular diet of less than 35% or over 55% carb.

The subjects were told this was NOT A WEIGHT LOSS study and they were not to expect to lose weight.  I think this is important, because the weight loss experienced during the ad libitum phase was accomplished without even "trying".

Study phases:  

• 2 Weeks CRC1:  Weight maintaining calorie controlled diet - 15% Protein / 50% Carb / 35% Fat
• 2 Weeks CRC2:  Weight maintaining calorie controlled diet - 30% Protein / 50% Carb / 20% Fat
• 12 Weeks CRC3:  Ad Libitum High Protein  - 30% Protein / 50% Carb / 20% Fat

Essentially this study replaced fat with protein controlling carb content at 50%.  Weight was maintained during the first 4 weeks by maintaining calorie balance.  Simply replacing fat with protein didn't result in any weight loss for constant caloric intake, but greatly improved reported appetite/satiety.

However, when allowed more variety, and provided with about 15% excess food, and counseled not to deliberately change anything just eating to fullness, the study participants spontaneously decreased caloric consumption by ~440 cal/day.  Remember ... these participants didn't think they were even participating in a weight loss study and weren't trying to lose weight.  So even with insulin coursing through their veins, they lost an average of 10.8 lbs in 12 weeks.  

Some Energy Balance Math:  

Caloric Deficit:  440 cal/day * 7 days/week * 12 weeks = 36,960 total average caloric restriction

Caloric Equivalent of Pounds Lost:  10.8 * 3500 cal/pound = 37,800 calories

So as the authors state, the weight loss is in accordance with the spontaneous reduction in calories.  Interestingly enough they did not see demonstrable changes in TEF/RMR from the higher protein content.

*** EDIT:  Not all weight was fat, indeed of 4.9 kg (10.8 lbs) of weight loss, roughly three-fourths was fat mass of 3.7 kg = 8.1 lbs.  So the calc may differ slightly from predicted.  ***

This study demonstrated that when the participants didn't really know the composition of their diets or that they were "on a diet", ate considerably less of a LOW FAT (only 20%) diet when protein content as a percent of intake was doubled.

The weight loss observed over 12 Weeks is comparable to that seen with LC diets.  Aside from those deliberately choosing high fat proteins and adding lots of fat on top of that, I think the 30% protein content of this diet is probably comparable to what most consume doing Atkins or similar plans "by the book".  What this study demonstrated was that an unstructured low fat high carb diet can lead to weight loss comparable to that of an unstructured low carb high fat diet.  

I do think this sort of diet might be harder to achieve w/o some sort of planning (study participants were provided with foods) than your basic LC diet.  Counting carbs will naturally increase protein content of the diet because whole meats and eggs contain relatively high percentages.  It is easier to keep carbs under some threshold (20g or 50g) which would amount to 5-10% of calories in average reducing diets and the protein has to be considerable.  However if one is shooting for 1500 calories, then 30% would be 450 calories = 112.5g protein.  If one is eating 3 meals and 2 snacks, a loosely structured plan could be accomplished by eating 30g protein at each meal and 10g protein for each snack, choosing leaner proteins and limiting added fats and eating lots of veggies and fruit, and reasonable portions of whole carbs (potatoes, brown rice, legumes, wholegrain bread).

Yet another study demonstrating that reduced caloric intake and not macronutrient composition of the diet is what results in weight loss.  No Metabolic Advantage either way was even demonstrated in this study replacing fat with protein.

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New Content:  Below left are the 24 hour leptin profiles, leptin levels (top) and change in leptin levels (bottom) for CRC1 (□), CRC2 (•), and CRC3 (▵).  Below right is the table of various 24 hour leptin assessments (taken the last 24 hours of each study phase)

It's interesting that the "peak-to-nadir" (max-to-min) swing was lower on the high protein diet in both the isocaloric phase and the ad lib (spontaneous calorie reduced) phase vs. the standard diet, but the 24 hour AUC of leptin was relatively unchanged between the isocaloric diets but significantly reduced in the ad libitum phase.  The ad libitum phase lasted 3 months during which subjects lost an average of almost 11 lbs.  It is possible that this reflects an improvement in leptin sensitivity with weight loss.  However this raises more questions on how macro composition of a diet impacts leptin.  It does not appear to be have much if any impact during the postprandial phase -- I hope we can put Rosedale's notions of anything "spiking" leptin to sleep sometime soon!  But it is rather interesting to note that swapping 15% fat for 15% protein on a rather high carb diet (50%) lowers the overnight (diurnal) rise in leptin in similar fashion, independent of caloric intake.  The two leptin curves for high protein phases are almost identical, just translated vertically down after weight/intake reduction.

It does not appear that leptin has anything to do with the satiety/appetite reduction unless it is somehow impacting leptin sensitivity.  In the words of the study authors:  "The anorexic effect of dietary protein, which may be due in part to increased CNS leptin sensitivity, is apparently stronger than any orexigenic effect of increased ghrelin concentrations accompanying weight loss with a high-protein diet."Grehlin -- often associated with increased appetite, was greater in this study with increased protein!  At right is the plot of change in fat mass vs. leptin concentration for all 19 subjects (note CRC2 is end of isocaloric phase, CRC3 is end of 12 weeks weight loss of avg. ~ 1 lb/week).  

These authors had previously done this experiment replacing 15% fat with carbohydrate.  The result?  A spontaneous reduction in caloric intake roughly half that seen in this current experiment.  I'll have to blog on that study sometime.  As to any sort of leptin "spike" ... or rather "pulse", from the discussion:

Havel et al (32) reported that substitution of carbohydrate for dietary fat increased the diurnal circulating leptin pulse amplitude (peak minus nadir plasma leptin concentration). These authors speculated that, as for other endocrine systems (33,34), the CNS might interpret an increase in leptin pulse amplitude as a signal calling for a decrease in appetite independently from any change in the integrated circulating leptin concentration (32). Our data directly address this hypothesis because we observed a decrease in leptin pulse amplitude between visit CRC1 and visit CRC2 (decreased peak minus nadir plasma leptin concentration and decreased AUC of the change in leptin) without a significant change in integrated circulating leptin concentration (leptin AUC). The subjects reported a marked increase in satiety despite this isolated reduction in leptin pulse amplitude. These data suggest that if diurnal leptin pulse amplitude is a signal regulating energy balance, it is less important than the putative change in CNS leptin sensitivity observed in the present study.

I would note, insulin AUC was increased for the high protein phases, and yet the participants lost significant weight they were not to expect to lose when allowed to "eat as much as they wanted".   More TWICHOO* busting stuff!  But according to Gary, we've been duped into thinking protein is satiating ... it's fat that is!  This study says otherwise.

*Taubes Wrong Insulin Carbohydrate Hypothesis Of Obesity