Hormone Suppression May Be Why High-Protein Weight-Loss Diets Work

By Todd Neale, Staff Writer, MedPage Today
Published: January 18, 2008
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of
Medicine, University of California, San Francisco  Earn CME/CE credit
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SEATTLE, Jan. 18 -- Proteins are better at suppressing the appetite-
stimulating hormone ghrelin than carbohydrates and lipids, a finding
that may lead to new, specially designed weight-loss diets,
researchers here suggested.

Consumption of all three macronutrient classes was associated with
significant, but varying, reductions in total ghrelin (P<0.0001) and
acyl ghrelin (P<0.001) levels compared with baseline, Karen E. Foster-
Schubert, M.D., of the University of Washington, and colleagues,
reported online in the Journal of Clinical Endocrinology &
Metabolism.

But ingesting protein had the greatest effect on both total ghrelin
and acyl ghrelin levels over six hours, followed by carbohydrates,
and, lastly, lipids. The researchers measured depth and duration of
suppression by calculating the decremental area-under-the-ghrelin-
curve (D-AUC).

Ghrelin is thought to influence hunger around mealtime, the
researchers said, because levels increase before meals and are
suppressed by food intake. Understanding how different macronutrients
affect ghrelin levels "could facilitate rational design of weight-
reducing diets," they suggested.

So the researchers recruited 16 healthy volunteers (seven men and nine
women, mean age 34) who had a body mass index of less than 30 kg/m2,
had been weight-stable for the preceding six months, and were within
2.5 kg of their lifetime maximum weight.

The study consisted of three six-hour sessions separated by at least
one week. Before each session, the participants refrained from eating
for 12 hours and exercising for 24 hours. All 16 participants
completed the three study visits.

At each session, participants drank a beverage designed to contain
calories equal to 20% of each participant's total daily energy
expenditure. The beverages contained 80% of the type of macronutrient
being evaluated at that particular visit -- proteins, carbohydrates,
or lipids -- and 10% each of the other two.

The researchers took three blood samples at baseline and then one
every 20 minutes for six hours after beverage consumption to measure
acyl and total ghrelin levels.

Using visual analog scales, the participants rated how hungry or full
they felt 20 minutes before the intervention and every 40 minutes
thereafter.

Fasting baseline plasma levels of ghrelin and acyl ghrelin were
equivalent at all three study visits.

Protein ingestion had the most extensive suppressive effect on plasma
acyl ghrelin levels over six hours with a D-AUC of 186 ± 96 hr%,
followed by carbohydrate (140 ± 41 hr%), and, finally, lipid (124 ±
106 hr%).

Protein also had the most pronounced suppressive effect on total
ghrelin levels over six hours with a D-AUC of 72 hr%, followed by
carbohydrate (56 hr%) and, lastly, lipid (38 hr%).

When the researchers looked at just the first three hours after
beverage consumption, they found that carbohydrates had a more
pronounced suppressive effect than did proteins.

In the last three hours after drinking the carbohydrate beverage,
however, both acyl and total ghrelin levels rebounded significantly
above baseline values (P<0.001).

This difference between the first and second halves of the study
period did not occur with protein or lipid, both of which suppressed
acyl and total ghrelin levels until study completion, the researchers
said.

"Our finding of a rebound of total and especially acyl ghrelin above
baseline following high-carbohydrate meals could provide some
physiologic basis for claims made by low-carbohydrate diet advocates
that ingesting carbohydrates prompts an early hunger rebound," the
authors wrote.

However, the type of macronutrient had no significant effect on the
visual analog scale appetite measures, a consequence, perhaps, of
technical difficulties some participants had with the computerized
reporting system, the researchers said.

One possible explanation presented by the authors to explain the spike
in acyl and total ghrelin levels following carbohydrate ingestion is
the faster gastric emptying following carbohydrate consumption
compared with that of protein or lipid.

"The prolonged suppression observed following lipids and proteins
might relate to their prolonged emptying from the stomach, causing
more sustained activation of post-gastric ghrelin-suppressing
mechanisms," they said.

The authors acknowledged several limitations of the study, including
its small size and the fact that the test meals were not typical
foods, being liquid and consisting of very large balanced differences
in macronutrient composition.

They also noted the difficulty some participants had with the hunger
reporting system.

The researchers concluded that, "although the mechanisms by which
specific macronutrients regulate circulating ghrelin are not fully
known, our results could help explain the ability of high-protein
diets to cause weight loss as well as the tendency for high-fat diets
to promote weight gain."

This study was supported by a grant from the National Institute of
Diabetes and Digestive and Kidney Diseases.

Dr. Foster-Schubert received support from the National Center for
Research Resources.

*  *  *
This version published online on January 15, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.
2007-2289

Acyl and Total Ghrelin Are Suppressed Strongly by Ingested Proteins,
Weakly by Lipids, and Biphasically by Carbohydrates

Karen E. Foster-Schubert*, Joost Overduin, Catherine E. Prudom,
Jianhua Liu, Holly S. Callahan, Bruce D. Gaylinn, Michael O. Thorner,
and David E. Cummings
University of Washington School of Medicine (K.E.FS., J.O., H.S.C.,
D.E.C.) Seattle, Washington 98195; Veterans Affairs Puget Sound Health
Care System (K.E.FS., J.O., D.E.C) Seattle, Washington 98108;
University of Virginia Schools of Medicine (J.L., B.D.G., M.O.T.) and
Arts and Sciences (Chemistry) (C.E.P.) Charlottesville, Virginia
22903

* To whom correspondence should be addressed. E-mail:
kfoster@u.washington.edu.

Context Ghrelin is an orexigenic hormone that can increase body
weight. Its circulating levels rise before meals and are suppressed
following food ingestion. Understanding the effects of specific types
of ingested macronutrients on ghrelin regulation could facilitate
design of weight-reducing diets.

Objective We sought to understand how ingestion of carbohydrates,
proteins, or lipids affect acyl (bioactive) and total ghrelin levels
among human subjects, hypothesizing that lipids might suppress ghrelin
levels less effectively than do either carbohydrates or proteins.

Design Randomized, within-subjects cross-over study

Setting University Clinical Research Center

Participants 16 healthy human subjects

Interventions Administration of isocaloric, isovolemic beverages
composed primarily of carbohydrates, proteins, or lipids

Main Outcome Measures Magnitude of postprandial suppression of total
and acyl ghrelin levels (measured with a novel acyl-selective, two-
site ELISA)

Results All beverages suppressed plasma acyl and total ghrelin levels.
A significant effect of macronutrient class on decremental area-under-
the-curve for both acyl and total ghrelin was observed; the rank order
for magnitude of suppression was protein > carbohydrate > lipid. Total
ghrelin nadir levels were significantly lower following both
carbohydrate and protein, compared to lipid beverages. In the first 3
postprandial hours, the rank order for acyl and total ghrelin
suppression was carbohydrate > protein > lipid. In the subsequent 3 h,
there was a marked rebound above preprandial values of acyl and total
ghrelin after carbohydrate ingestion alone.

Conclusions These findings suggest possible mechanisms contributing to
the effects of high-protein/low-carbohydrate diets to promote weight
loss, and high-fat diets to promote weight gain.