(13-12-10) Weight-Loss Maintenance ? Mind over Matter?

David S. Ludwig, M.D., Ph.D., and Cara B. Ebbeling, Ph.D.
Many people can lose weight in the short term
by reducing their intake of calories with the use
of a variety of diets, ranging from low-fat to
very-low-carbohydrate. However, few people successfully
maintain their weight loss.1 One explanation
for the poor efficacy of conventional diets
relates to psychological factors, since the motivation
to adhere to restrictive regimens diminishes
with time, especially in an environment with virtually
instantaneous availability of food. A second,
perhaps more fundamental, explanation is
that weight loss elicits physiological adaptations
? principally an increase in hunger and a decrease
in resting energy expenditure2 ? that
oppose ongoing weight loss.
In the search for more effective strategies,
diets that are low in glycemic index and moderately
high in protein merit special consideration.
The glycemic index describes the way in which
foods affect blood glucose levels in the postprandial
period, controlled for the amount of
carbohydrate.3 The glycemic load, the arithmetic
product of the glycemic index and the amount
of carbohydrate, predicts postprandial glycemic
response among foods with widely varying carbohydrate
contents.4 Most highly processed grain
products have a high glycemic index, whereas
minimally processed grains, whole fruits, legumes,
and nonstarchy vegetables tend to have a
moderate or low glycemic index.
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n engl j med 363;22 nejm.org 2160 november 25, 2010
The mechanisms relating glycemic response
to the regulation of body weight have been examined
in controlled feeding studies.5 Meals with a
low glycemic index or glycemic load elicit acute
hormonal and metabolic changes that may decrease
hunger and energy intake. During weight
loss, a reduction in glycemic load may attenuate
the decline in resting energy expenditure that is
thought to promote weight regain.6 Recently, a
meta-analysis indicated that diets in which there
was a reduction in the glycemic index produced
moderately more weight loss than control diets,7
although the quality of the clinical trials has
been limited by their small size, a failure to
show adherence to treatment, and confounding.
The glycemic response to carbohydrates is
lowered when protein is ingested simultaneously,
since protein delays gastric emptying and stimulates
insulin secretion. Protein also displaces
carbohydrates, as opposed to fat, from the diet
because foods high in protein are also typically
high in fat. Therefore, higher-protein diets tend
to have a reduced glycemic load and might promote
weight loss, at least in part, through the
mechanisms discussed above.
In addition, diets that are based on these
principles may be less psychologically burdensome,
because they do not severely restrict any
macronutrient or major food group. However,
the 2010 U.S. Department of Agriculture Dietary
Guidelines Advisory Committee considers the
effectiveness of reducing the glycemic index to be
unproven. Similarly, there is a lack of consensus
regarding the optimal protein level for achieving
and maintaining weight loss. A study in this
issue of the Journal from the Diet, Obesity, and
Genes (Diogenes) project8 addresses these knowledge
gaps.
Investigators from eight European countries
randomly assigned 773 participants who had
lost at least 8% of their initial body weight to
one of four test diets, using a two-by-two factorial
design (low-glycemic-index vs. high-glycemicindex
diets and low-protein vs. high-protein diets),
or to a fifth, control, diet. Assessment of dietary
intake showed that there was a modest difference
of about 5 glycemic-index units between
the low-glycemic-index and high-glycemic-index
groups and a difference of about 5 percentage
points in protein content between the high-protein
and low-protein groups. After 6 months,
body weight differed by about 2 kg among the
groups, with a direct relationship to glycemic
load ? lowest in the group assigned to the lowglycemic-
index?high-protein diet, intermediate in
the groups assigned to the low-glycemic-index?
low-protein and the high-glycemic-index?highprotein
diets, and highest in the group assigned
to the high-glycemic-index?low-protein diet. Of
note, study completion rates were significantly
better among participants in the low-glycemicindex
and high-protein diet groups.
The study has several notable strengths, including
the large number of participants and a
multicenter, multinational design, providing evidence
of effectiveness and generalizability. The
apparent control for treatment intensity and behavioral
methods across groups (although not
across countries) allows for a fair testing of dietary
hypotheses. Furthermore, the investigative
team appears to have had scientific balance; one
senior member had espoused a skeptical view of
the glycemic index,9 providing confidence that
the study was conducted and interpreted without
unconscious bias. The primary limitation of
the study is the short duration of follow-up. A 2-kg
difference in body weight, by itself, has limited
practical implications. But a diet that could effectively
prevent weight regain over the long term
would have major public health significance. In
this regard, the 12-month and longer follow-up
data will be informative.
The observed effects on body weight were
obtained from small mean differences in glycemic
index and protein among the groups. In
principle, more powerful methods for effecting
behavioral change and improved availability of
low-glycemic-index foods may facilitate the longterm
adoption of diets with a substantially lower
glycemic load and result in larger effects on
body weight. Moreover, a low-glycemic-index diet
may reduce the risk of diabetes and heart disease
independently of body weight,5 and data addressing
this possibility will be forthcoming
from the Diogenes trial.
The present study contrasts, but does not
necessarily conflict, with data reported by Sacks
et al.,10 who assigned 811 people to one of four
diets that differed in the percentage of total energy
derived from carbohydrate, protein, and fat.
In contrast to the protocol in the Diogenes trial,
participants in all four groups were counseled
to consume carbohydrates with a low glycemic
index. Similar to the results in the Diogenes trial,
editorials
n engl j med 363;22 nejm.org november 25, 2010 2161
the protein content of the diets at 6 months differed
by only about 5 percentage points. After
2 years, no significant difference in body weight
was found among the groups, although among
subjects who completed the study, those who
consumed higher-protein diets weighed about
1 kg less than those who consumed lower-protein
diets (P = 0.11).10 Together, these two studies
suggest that the ratio of carbohydrate to fat has
relatively little importance for weight control
among persons consuming a low-glycemic-index
diet, and higher protein intake may have additional
benefits.
The Diogenes study provides reassurance regarding
three long-standing concerns about glycemic
index: that measured values apply to individual
foods only and have no relevance to mixed
meals, that effects observed in clinical trials
arise from confounding by macronutrients or
fiber, and that the concepts are confusing and
impractical for the general public. Indeed, the
higher study-completion rate in the low-glycemic-
index groups provides compelling evidence
of the practicality of low-glycemic-index diets.
Several recent clinical trials have shown no
significant difference in weight loss among various
popular diets, leading to the notion that dietary
composition is less important than adherence
to a diet, whatever it might be. However,
this conclusion does not consider the fundamental
relationship between psychology and physiology.
A person?s ability to maintain adherence
over time may be influenced by the way in which
a diet affects hunger and metabolism. Additional
research is needed to clarify the mechanisms by
which dietary composition regulates body weight
and to devise novel strategies to effect behavioral
changes.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
From the Optimal Weight for Life Program, Department of
Medicine, Children?s Hospital; and the Department of Pediatrics,
Harvard Medical School ? both in Boston.
1. Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM.
Meta-analysis: the effect of dietary counseling for weight loss.
Ann Intern Med 2007;147:41-50.
2. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure
resulting from altered body weight. N Engl J Med 1995;
332:621-8. [Erratum, N Engl J Med 1995;333:399.]
3. Jenkins DJ, Wolever TM, Taylor RH, et al. Glycemic index of
foods: a physiological basis for carbohydrate exchange. Am J
Clin Nutr 1981;34:362-6.
4. Brand-Miller JC, Thomas M, Swan V, Ahmed Z, Petocz P,
Colagiuri S. Physiological validation of the concept of glycemic
load in lean young adults. J Nutr 2003;133:2728-32.
5. Ludwig DS. The glycemic index: physiological mechanisms
relating to obesity, diabetes, and cardiovascular disease. JAMA
2002;287:2414-23.
6. Pereira MA, Swain J, Goldfine AB, Rifai N, Ludwig DS. Effects
of a low-glycemic load diet on resting energy expenditure
and heart disease risk factors during weight loss. JAMA 2004;
292:2482-90.
7. Thomas DE, Elliott EJ, Baur L. Low glycaemic index or low
glycaemic load diets for overweight and obesity. Cochrane Database
Syst Rev 2007;3:CD005105.
8. Larsen TM, Dalskov S-M, van Baak M, et al. Diets with high
or low protein content and glycemic index for weight-loss maintenance.
N Engl J Med 2010;363:2102-13.
9. Astrup A. Dietary management of obesity. JPEN J Parenter
Enteral Nutr 2008;32:575-7.
10. Sacks FM, Bray GA, Carey VJ, et al. Comparison of weightloss
diets with different compositions of fat, protein, and carbohydrates.
N Engl J Med 2009;360:859-73.
Copyright ? 2010 Massachusetts Medical Society.

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