This large clinical trial showed that moderately high protein low GI diet may improve changes to keep weight off after initial weight loss.

1. www.pronutritionist.net
Diets with High or Low Protein Content
and Glycemic Index for Weight-Loss
Maintenance
Larsen T et al.
N Engl J Med 2010; 363: 2102-2113
Page 1 Larsen T et al. N Eng J Med 2010; 363: 2102-2113

2. Page 2
Pronutritionist’s background
• There is a constant dispute if macronutrient content of diet is
a major determinant of success in weight loss, or not
• Diet low in carbohydrates and high in fat and protein have
proved to be effective in weight loss.
• It is speculated that protein rich diet enhances satiety and
thermogenesis and may prevent wasting of muscles during
weight loss (Halton & Hu 2004)
• However, a long term trial could not confirm the assumed
benefits of high protein diet in weight loss (Sacks et al 2009)
• Low glycemic index diet may produce gastrointestinal
anorectic hormones via receptors that bind short chain fatty
acids, the end products of fermentable carbohydrates, and
possibly improve satiety (Hord & Frost 2010)
Larsen T et al. N Eng J Med 2010; 363: 2102-2113 www.pronutritionist.net

3. Methods (1/2)
• a randomized dietary-intervention study
• n = 773 (entered the weight-maintenance phase)
– BMI 27 – 47
• Phase 1: 8-week low-calorie-diet period
– 800 kcal per day (Modifast products)
– 400 g vegetables/d was allowed
– total energy intake with vegetables and Modifast
800-1000 kcal
• Phase 2: weight-maintenance
– randomization to one of five maintenance diets
– duration 26 weeks
Page 3 Larsen T et al. N Eng J Med 2010; 363: 2102-2113 www.pronutritionist.net

4. Methods (2/2)
• Five maintenance diets were:
– a diet low in protein (13 E%) with a low glycemic index
– a diet low in protein (13 E%) with a high glycemic index
– a diet high in protein (25 E%) with a low glycemic index
– a diet high in protein (25 E%) with a high glycemic index
– a control diet (followed dietary guidelines in each participating
country)
• All diets were designed to have a fat content of 25-30 E
%
• There was no restrictions on energy intake
– in order to test the ability of the diets to regulate appetite and
body weight
• Dietary intake was followed by 3 day food diaries
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 4

5. Results (1/6)
• The mean initial weight loss with the low-calorie
diet was 11 kg
• Mean weight regain during the maintenance period
was 560 g. Only the participants assigned to the
diet that was low in protein with a high glycemic
index had significant weight regain (1.67 kg)
• In high protein low GI diet participants lost -0,4 kg
during the follow up
• The weight increase during the maintenance
period was
– 930 g higher in the low-protein groups than in the high-
protein groups (p = 0.003)
– 950 g higher in the high-glycemic-index groups than in the
low-glycemic-index groups (p = 0.003)
• No differences in satiety were observed
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 5

6. Results (2/6): changes in body weight
and waist circumference
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 6
Kg/
cm

7. Results (3/6): drop-out rates at 26
weeks
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 7
*) More drop outs in low
protein high GI diet than
in either all low GI or all
high protein diets (P =
0.02 and P = 0.01)

8. Results (4/6)
• Achieved difference in protein content was 5.4
percentage points between the high-protein and
the low-protein groups
– targeted difference was 12 E% (13 E% vs. 25 E%)
• Achieved difference in glycemic index was 4.7
glycemic-index units between the low-glycemic-
index and the high-glycemic-index groups
– targeted difference was 15 glycemic-index units
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 8

9. Results (5/6): Dietary intake at week 26
Low protein
Low GI
Low protein
High GI
High protein
Low GI
High protein
High GI
Control diet
Energy (kcal/d) 1673 1826 1753 1673 1716
Carbohydrates (E
%)
50.8 50.9 44.6 44.7 46.4
Total fat (E%) 29.8 30.9 32 31.2 33.7
Protein (E%) 18.2 16.7 21.7 22.6 18.7
Fiber (g/d) 21 20.3 21.4 19 19.6
Glycemic index 56.2 61.6 56.5 61.4 59.4
Glycemic load
(g/d)
121 137.9 108.9 113.1 117.6
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 9
Low protein
Low GI
Low protein High
GI
High protein
Low GI
High protein
High GI
Control diet
Protein (in grams) 76 76 95 95 80

10. Results (6/6): Changes in fat and fat
free mass from 0 to week 26
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 10
Low protein
Low GI
Low protein
High GI
High protein
Low GI
High protein
High GI
Control diet
Protein (in grams) 76 76 95 95 80
Changes in body
composition are not
statistically significant
kg

11. Pronutritionist’s discussion 1/4
• In this trial, the achieved dietary changes were again far
from targeted
• In protein intake, the targeted difference at 1800 kcal
level was 54 grams but the achieved difference was
circa 20 grams ( 76 vs. 95 grams)
• However, the achieved level of protein intake may be
more feasible in real life and therefore the results may
have clinical high relevance
• Protein-low GI diet did not improve self-reported satiety
which is a bit against expectations. This may be a
function of less than expected differences in diets
• High protein diet in the trial contained same amount of
protein as typical Western diet at level of circa 2 200
kcal/day
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 11

12. Pronutritionist’s discussion 2/4
• Authors conclude “ … a diet that was moderately high in
protein content and slightly reduced in glycemic index…
appears to be ideal for preventing weight gain” . Why do
the authors not refer to a longer term trial which did not
show significantly improved weight loss results on a diet
rich protein (Sacks et al 2009) ?
• As a diet for weight maintenance is expected to be life
long, the effects of high protein diet on vascular health
require attention. Interestingly, the authors do not point
out this either. This argument has been one key
argument against low carbohydrate diets
• Given the above, the effects of protein rich diet need to
confirmed in long term trials (several years) to clarify the
effects of high (animal) protein intake on vascular health
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 12

13. Pronutritionist’s discussion 3/4
• Achieved results were reached by the exclusive
interplay of protein and carbohydrate changes while fat
intake was kept constant. According to the authors, this
further underlines the importance of lowering glycemic
load
• Authors do not ponder the mechanisms how low-GI-
diets may induce weigh loss or maintenance. Hord &
Frost 2010 have suggested that indigestible
carbohydrates may trigger release of anorectic
gastrointestinal compounds via specific short chain fatty
acid receptors
• In a sub study of shop centers (Danish and Dutch
centers) where foods were provided for free, high
protein diet resulted in 3,7 kg greater weight loss
compared to low protein diet. This further strengthens
the observed effects
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 13

14. Pronutritionist’s discussion 4/4
• There were no differences in body compositions
between the groups. Muscle mass seemed to be
preserved similarly. This is a bit contrary to what is
commonly believed. In the initial weight loss period, all
groups lost comparable shares of fat and fat free mass
• In this rather short term trial (26 weeks), moderately high
protein and low GI diet improved maintenance of the
diet. High protein diets (both of them) resulted in 1 kilo
smaller weight gain, and so did both low GI diets. Low
protein high GI diet was the only diet that induced
significant weight gain (1,7 kg)
• This study further underlines the importance of protein in
maintaining healthy weight but leaves many questions
open
www.pronutritionist.netLarsen T et al. N Eng J Med 2010; 363: 2102-2113Page 14