Original Article Obesity

CLINICAL TRIALS AND INVESTIGATIONS

The Effect of Rate of Weight Loss on Long-Term Weight

Regain in Adults with Overweight and Obesity
Roel G. Vink, Nadia J. T. Roumans, Laura A. J. Arkenbosch, Edwin C. M. Mariman, and Marleen A. van Baak

Objective: To investigate the effect of rate of weight loss, with similar total weight loss, on weight regain
in individuals with overweight and obesity.
Methods: Fifty-seven participants (BMI: 28-35 kg/m2) underwent a dietary intervention (DI). They were
randomized to a low-calorie diet (LCD; 1250 kcal/day) for 12 weeks (slow weight loss) or a very-low-
calorie diet (VLCD; 500 kcal/day) for 5 weeks (rapid weight loss) (weight loss (WL) period) followed by a
4-week weight-stable (WS) period and 9 months follow-up. Body weight and body composition (BodPod)
were determined at study start and after each period.
Results: Weight change was similar in both groups after WL (LCD: 28.2 kg and VLCD: 29.0 kg,
P 5 0.24). Weight regain after follow-up was not significantly different between groups (LCD: 4.2 kg and
VLCD: 4.5 kg, P 5 0.73). Percentage fat-free mass loss (%FFML) was higher in the VLCD-group com-
pared to the LCD-group after DI (8.8% and 1.3%, respectively, P 5 0.034) and was associated with
weight regain during follow-up in the whole group (r 5 0.325, P 5 0.018).
Conclusions: The present study showed that, with similar total weight loss, rate of weight loss did not
affect weight regain. However, %FFML after DI was associated with weight regain.
Obesity (2016) 24, 321-327. doi:10.1002/oby.21346

Introduction compared to a more gradual weight loss approach, which increases

the risk of muscle mass loss. Muscle mass is a key contributor to
The number of people with overweight and obesity worldwide has
resting energy expenditure (10,11) and could play a role in long-
risen from 857 million in 1980 to 2.1 billion in 2013 (1). Despite
term weight management. However, the belief that a more gradual
the adverse health problems associated with obesity (2), not a single
weight loss approach is preferred over rapid weight loss in terms
country in the world had a significant decrease in obesity prevalence
of long-term weight control is not supported by scientific evidence
in the past three decades (1). While a dietary intervention (DI) can
(6,7). The discussion is complicated by the fact that most studies
achieve significant weight loss, the greatest challenge is the seem-
on rate of weight loss do not dissociate between the effects of the
ingly inevitable weight regain in the following years. One year after
weight loss, 20% of individuals were able to remain weight stable, rate of weight loss and the total weight loss. At the start of our
when weight stable was defined as an intentional weight loss of study only one other study had investigated the effect of two
10% maintained for at least 1 year (3,4). In a more recent study, different rates of weight loss, with similar total weight loss, on
participants regained on average 70% of their lost weight over 2 weight regain. The results from that study showed that an 8-week
years following diet-induced weight loss (5). Insight in the etiology very-low-calorie diet (VLCD) or a 17-week low-calorie diet
of weight regain and long-term weight management are therefore (LCD) did not result in significant differences in weight regain
strongly needed. after a 1-year weight maintenance diet or after a subsequent 1-year
follow-up period (12). However, it should be noted that both
A widely discussed topic in the prevention of weight regain is the weight loss diets were supplemented with the anorectic compounds
rate of weight loss. The concept that rapid weight loss increases caffeine and ephedrine, and that participants were randomized to
long-term weight regain compared to a more gradual weight loss two different weight maintenance diets. Thus, whether—under con-
approach is a belief held by the general public (6,7), and dietary ditions of similar weight loss—a more gradual weight loss
guidelines in several countries recommend the latter approach in approach is to be preferred over rapid weight loss with respect to
obesity management (8,9). Rapid weight loss diets create a larger successful weight loss maintenance is so far not supported by
energy deficit and contain lower absolute amounts of protein strong scientific evidence.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre1,
Maastricht, The Netherlands. Correspondence: Roel G. Vink ([email protected])

Funding agencies: Netherlands Organisation for Scientific Research TOP, grant number: 200500001.
Disclosure: The authors declare no conflict of interest.
Received: 14 July 2015; Accepted: 28 August 2015; Published online 27 January 2016. doi:10.1002/oby.21346

www.obesityjournal.org Obesity | VOLUME 24 | NUMBER 2 | FEBRUARY 2016 321

Obesity The Effect of Rate of Weight Loss on Weight Regain Vink et al.

Figure 1 Study overview of the DI and follow-up. Measurements were performed on clinical investigation
days at the start of the study and at the end of the weight loss period (WL), weight-stable period (WS),
and follow-up. The DI period is the weight loss period and weight-stable period taken together.

We therefore performed a study where weight regain was studied unrestricted amount of low-calorie vegetables. Both groups subse-
after two different rates of diet-induced weight loss with similar quently underwent a 4-week WS-period with a diet based on the
total weight loss in the absence of dietary advice during the follow- energy requirement of the participants. This allowed us to investi-
up period. gate the effect of weight loss, without the interfering effect of a neg-
ative energy balance. The study dietician provided dietary advice
according to the Dutch national guidelines (13) to both groups, to
assist in remaining weight stable throughout the WS-period (four
Methods meetings) and to assist in weight loss during the WL-period in the
Subjects LCD-group (five meetings). Finally, body weight and blood pressure
Sixty-one individuals with overweight and obesity (BMI 28-35 kg/ were measured monthly at the Maastricht University Medical Centre
m2) were recruited by advertisement via local media. Exclusion cri- (MUMC) for 9 months during follow-up. However, dietary advice
teria were smoking, cardiovascular disease, type 2 diabetes mellitus, was no longer given to mimic non-restricted free-living conditions.
liver or kidney disease, use of medication that influences body
weight regulation, pregnancy, marked alcohol consumption (>21 At the start of the study and at the end of each period body compo-
alcoholic units per week for men and >14 alcoholic units per week sition was determined, physical activity (PA) questionnaires were
for women), elevated fasting glucose (>6.1 mmol/L), total choles- completed, and weight, height, and waist and hip circumference
terol (>7.0 mmol/L) or triacylglycerol (>3.0 mmol/L) concentra- were measured. Furthermore, at each visit adverse events were
tions, or blood pressure (>160/100 mmHg). Furthermore, partici- monitored, and body weight and blood pressure were determined.
pants had to remain weight stable (weight change <3.0 kg) 2 The researchers, study participants, and dietician were not blinded to
months prior to the start of the study. Participants were all Cauca- the intervention. This trial is registered with www.clinicaltrials.gov
sians. All subjects gave their written informed consent before partic- as NCT01559415.
ipation in the study. The study was performed according to the Dec-
laration of Helsinki and was approved by the Medical Ethics
Committee of Maastricht University Medical Centre. Diet composition
The VLCD contained: 52 g protein (43 En%), 52 g carbohydrate
(43 En%), and 8 g fat (14 En%). The LCD contained: 90 g protein
Experimental protocol
The participants in our study followed a DI program that was (29 En%), 150 g carbohydrate (48 En%), and 32 g fat (23 En%).
divided in three periods: a 12-week LCD-period or 5-week VLCD- Estimated protein intake was 0.56 g/kg in the VLCD-group and
period (weight loss period, WL), a 4-week weight-stable period 0.97 g/kg in the LCD-group.
(WS), and a 9-month follow-up period. The WL-period and WS-
period taken together was named the DI-period (Figure 1). Partici-
pants were randomly assigned to either the LCD (slow weight loss) Anthropometric measurements
or VLCD (rapid weight loss) group. Both interventions aimed at a Participants were weighed on the same scale (Seca model 861,
weight loss of 10%. In the slow weight loss program, participants Hamburg, Germany) accurate to the nearest 0.1 kg in light clothing
underwent a 12-week LCD providing 1,250 kcal/day designed by after an overnight fast of at least 10 h. Blood pressure was measured
the dietician. The LCD consisted of one meal that was replaced by while participants were seated in a chair with a digital automatic
meal replacements (Modifast; Nutrition et Sante Benelux, Breda, blood pressure monitor (Intellisense, Omron Model M6 comfort).
The Netherlands), two meals that the participants prepared them- We measured waist circumference above the umbilicus and hip cir-
selves based on meal plans designed by our dietician, and three in- cumference at the widest part of the buttocks, both to the nearest
between meal snacks. In the rapid weight loss program, participants 0.5 cm. Body volume was determined with air-displacement plethys-
underwent a 5-week VLCD in which three meals per day were mography (ADP) using the Bod Pod device (Cosmed, Italy, Rome)
replaced by meal replacements, providing 500 kcal/day. During this according to the manufacturer’s instructions and as described by
period participants were advised by our dietician (five meetings) and Dempster and Aitkens (14). The thoracic gas volume was predicted
were allowed to consume two 100 mL instant broth drinks per using the equations incorporated in the Bod Pod software. Body
day containing a high amount of sodium and 7 kcal each and an density, as calculated by the Bod Pod, was used to calculate body

322 Obesity | VOLUME 24 | NUMBER 2 | FEBRUARY 2016 www.obesityjournal.org

Original Article Obesity
CLINICAL TRIALS AND INVESTIGATIONS

sample t test. Between-group comparisons were made with the

TABLE 1 Baseline characteristics of the study population
independent-samples t test. Correlations were calculated with
Pearson (normally distributed) and Spearman’s rank (non-normally
Study start
distributed, variable: “weight cycles”) correlation coefficients. Sta-
LCD (n 5 29) VLCD (n 5 28) tistical calculations were performed with SPSS for Macintosh,
Version 21 (Chicago, IL). P < 0.05 was considered statistically
Sex (male/female) 14/15 13/15
significant.
Age (years) 51.8 6 1.9 50.7 6 1.5
Weight (kg) 92.4 6 1.9 92.6 6 1.8 Only 9.8% of our participants were drop-outs and these were
BMI (kg/m2) 31.3 6 0.5 31.0 6 0.4 explained by circumstances deemed unrelated to the intervention
Hip circumference (cm) 110.8 6 1.3 111.1 6 1.1 (cancer development, medication use, and personal circumstances).
Waist circumference (cm) 102.6 6 2.0 101.9 6 1.5 Furthermore, because of the near-complete absence of missing val-
Waist/hip ratio 0.93 6 0.1 0.92 6 0.1 ues the data were considered missing at random.
Body fat (%) 39.9 6 1.8 39.7 6 1.5
Body fat (kg) 36.6 6 1.7 36.2 6 1.2
FFM (kg) 55.4 6 2.2 55.9 6 2.2
Systolic blood pressure 126.8 6 2.4 123.3 6 2.7 Results
(mmHg) Four participants withdrew from the study during the DI, two
Diastolic blood pressure 85.9 6 1.9 84.6 6 1.9 because of cancer (VLCD) and two because of personal circum-
(mmHg) stances (one in each group). Characteristics of the remaining 57
PA-score 9.06 6 0.18 9.05 6 0.21 participants are displayed in Table 1. No significant differences
Weight cycles 2.3 6 0.3 2.0 6 0.4 were observed between diet groups at the start of the study
(Table 1).
Values are mean 6 SEM.
LCD, low-calorie diet; VLCD, very-low-calorie diet; BMI, body mass index; FFM, Two participants started to use prescription medication that could
fat-free mass; PA-score, physical activity score.
influence body weight during follow-up (one in each group) and
were excluded from follow-up analysis.

composition according to the two-compartment model as described

by Siri (15). Diet-induced changes in anthropometry, blood
pressure, and PA-score
The WL-period induced comparable body weight changes in the
Questionnaires on PA and weight cycles slow weight loss group (LCD-group) and rapid weight loss group
Physical activity score (PA-score) was determined with the Baecke ques- (VLCD-group) (28.2 6 0.5 kg vs. 29.0 6 0.4 kg, respectively,
tionnaire for habitual PA (16). The PA-score determines habitual PA in P 5 0.24, Table 2), with an average weight loss of 0.7 kg/week and
the preceding period, whereas the PA-score at study start was a measure 1.8 kg/week, respectively. In the subsequent 4 weeks of the WS-
of the year before study participation. period, body weight did not change significantly in either group
(Table 2). Furthermore, only waist circumference was significantly
Number of weight cycles was determined at study start with a ques-
different between groups over the 4-week WS-period (LCD:
tionnaire that we designed. The questionnaire consisted of one ques-
21.0 6 0.5 cm vs. VLCD: 10.8 6 0.6 cm, P 5 0.037). Systolic
tion: write down the number of weight cycles that you have experi-
blood pressure decreased significantly after rapid weight loss but not
enced in your life, when a weight cycle is defined as losing and
after slow weight loss at the end of both WL and DI (Table 2), but
subsequently regaining at least 5 kg of body weight.
these changes were not significantly different between groups.

Calculations Fat percentage decreased significantly in both diet groups (Table 2)

The primary outcome of this study was absolute body weight change but remained unchanged between groups. FFM loss is often
during follow-up (weight at follow-up minus weight at the end of expressed as the percentage of weight lost as fat-free mass
DI). Percentage weight regain was calculated by dividing the weight (%FFML). %FFML was higher in the VLCD-group compared to the
change during follow-up by the change in weight from study start to LCD-group after WL (17.5% vs. 7.0%, P 5 0.003) and after DI
end of DI (study start minus end of DI), multiplied by 100. Percent- (8.8% vs. 1.3%, P 5 0.034) (Figure 2A). At the end of DI, the
age fat-free mass loss (%FFML) and %FFM gain were calculated by VLCD-group had a 0.6 kg higher FFM loss than the LCD-group.
dividing delta FFM by delta body weight (%FFML: pre 2 post, %FFML was higher after WL compared to after DI within groups
%FFM gain: post 2 pre) over a certain time period, multiplied by (LCD: 7.0% vs. 1.3%, P 5 0.030; VLCD: 17.5% vs. 8.8%,
100. P < 0.001, Figure 2A). The %FFML was not significantly different
between men and women after WL and after DI, both within the
LCD- and VLCD-group (Figure 2B). Furthermore, no significant
Statistics difference was observed in %FFML after DI compared to %FFM
Data are presented as mean 6 SEM. Comparisons of variables gain during follow-up in the whole group (6.52 6 1.95% vs.
between time points within groups were made with the paired- 4.40 6 5.21%, respectively, P 5 0.664).

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Obesity The Effect of Rate of Weight Loss on Weight Regain Vink et al.

TABLE 2 Changes in characteristics at the end of WL and DI compared to study start, and at the end of follow-up compared
to the end of DI

End of WL vs. End of DI vs. End of follow-up vs.

study start study start end of DI
LCD VLCD LCD VLCD LCD VLCD
(n 5 29) (n 5 28) (n 5 29) (n 5 28) (n 5 28) (n 5 27)

Weight (kg) 28.2 6 0.5*** 29.0 6 0.4*** 28.4 6 0.5*** 29.3 6 0.5*** 14.2 6 0.6*** 14.5 6 0.7***
BMI (kg/m2) 22.8 6 0.2*** 23.0 6 0.1*** 22.9 6 0.2*** 23.1 6 0.1*** 11.4 6 0.2*** 11.5 6 0.2***
Hip circumference (cm) 24.9 6 0.6*** 25.9 6 0.6*** 26.2 6 0.7*** 26.3 6 0.6*** 2.0 6 0.7** 1.0 6 0.9
Waist circumference (cm) 27.3 6 0.8*** 27.7 6 0.6*** 28.3 6 1.0*** 26.9 6 0.7*** 13.8 6 0.8*** 13.0 6 0.7***
Waist/hip ratio 20.03 6 0.01** 20.02 6 0.01*** 20.02 6 0.01** 20.01 6 0.01 10.02 6 0.01* 10.02 6 0.01*
Body fat (%) 25.4 6 0.5*** 24.7 6 0.4*** 26.1 6 0.5*** 25.9 6 0.5*** 12.9 6 0.5*** 12.8 6 0.6***
Body fat (kg) 27.6 6 0.5*** 27.4 6 0.4*** 28.3 6 0.6*** 28.6 6 0.5*** 13.9 6 0.6*** 14.0 6 0.7***
FFM (kg) 20.6 6 0.2* 21.6 6 0.2***,‡ 20.2 6 0.2 20.8 6 0.2**,† 10.4 6 0.3 10.5 6 0.2*
Systolic blood pressure (mmHg) 23.1 6 2.1 27.5 6 1.8*** 22.7 6 2.1 26.1 6 1.7*** 13.0 6 2.1 4.7 6 1.6**
Diastolic blood pressure (mmHg) 24.8 6 1.9* 26.8 6 1.2*** 24.9 6 1.5* 26.3 6 1.3*** 12.1 6 1.0* 14.8 6 0.9**
PA-score 10.27 6 0.13 20.11 6 0.15 10.18 6 0.13 20.15 6 0.13 20.3 6 0.1* 20.3 6 0.1*

Values are mean 6 SEM.

b
*P < 0.05, **P < 0.01, ***P < 0.001, paired sample t-test, within-diet change from end of WL vs. study start, end of DI vs. study start, and end of follow-up vs. end of DI.
†
P < 0.05, ‡P < 0.01, change from start of study between diets. No significant differences were observed between the LCD- and VLCD-group at the end of follow-up com-
pared to the end of DI.
c
LCD: low-calorie diet; VLCD, very-low-calorie diet; BMI, body mass index; FFM, fat-free mass; PA-score, physical activity score; WL, weight loss; DI, dietary intervention.

Changes in anthropometry, blood pressure, and Interestingly, %FFML at the end of DI was positively correlated
PA-score during follow-up with weight regain during follow-up in the whole group (r 5 0.325,
Forty-one out of fifty-five participants (75%) regained >2 kg body P 5 0.018, Figure 3A). This correlation remained significant after
weight during the 9-month follow-up period. Mean weight regain adjusting for body fat percentage at study start (r 5 0.384,
was 4.2 kg in the LCD-group and 4.5 kg in the VLCD-group and P 5 0.011). Thus, despite this positive correlation and a significant
was not different between groups (P 5 0.73, Table 2). On average, difference in %FFML between groups after DI, this did not translate
participants on both diets regained more than 50% of their lost into significant differences in weight regain between groups.
weight within 9 months (LCD: 58.6%, VLCD: 54.7%). Variation in
weight loss during the DI-period explained less than 1% of the vari- The PA-score after follow-up, which measures habitual PA during
ation in weight regain after follow-up in the whole group and was follow-up, was negatively correlated with weight regain in the whole
therefore not used in further analyses. Weight regain during follow- group (r 5 20.330, P 5 0.014, Figure 3B) and was mainly explained
up was also not associated with gender, age, or BMI at start of the by a stronger correlation in the slow weight loss group compared to
study (whole group, data not shown). the rapid weight loss group (r 5 20.586, P 5 0.001 vs. r 5 20.094,

Figure 2 (A) Percentage fat-free mass loss (%FFML) in the VLCD-group and LCD-group at the end of weight loss (WL) and dietary intervention
(DI) compared to the study start (n 5 55). (B) Change in %FFML (end of WL and DI compared to study start) was not significantly different
between men and women in the VLCD-group and LCD-group (n 5 55). Data are mean 6 SEM. *P < 0.05, **P < 0.01, ***P < 0.001. LCD, low-
calorie diet; VLCD, very-low-calorie diet.

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Original Article Obesity
CLINICAL TRIALS AND INVESTIGATIONS

more closely, which could improve successful long-term weight

management. Regardless, VLCDs remain a popular strategy for
weight loss in the general population because they are easy to use
and produce quick weight loss results. In accordance with our
results, one study showed that an 8-week VLCD or a 17-week LCD
did not result in significant differences in weight regain after a 1-
year weight maintenance diet or after a subsequent 1-year follow-up
period (12). More recently Purcell et al. (5) compared rapid (12-
week VLCD) with gradual weight loss (36-week LCD) diets, which
resulted in similar total weight loss, on 2-year weight regain in a
large group of individuals with obesity. The results also showed that
the rate of weight loss did not affect the proportion of weight
regained. Additionally, even when the initial weight loss is greater,
as is more common with VLCDs compared to LCDs, studies have
shown that this was correlated with improved weight loss mainte-
nance (17-20). Therefore, the current scientific evidence does not
support a gradual weight loss approach over rapid weight loss in the
prevention of weight regain.

Diet-induced weight loss is often accompanied by loss of FFM, which

varies based on the type of weight loss intervention. Chaston et al.
(21) previously stated that a comparison of LCDs and VLCDs gave
clear evidence that the degree of caloric restriction affects %FFML.
However, this systematic review used studies that differed in total
weight loss and did not include studies in which participants were
randomly assigned to a LCD or VLCD. Our study is, to our knowl-
edge, the first to directly confirm with a randomized approach with
similar weight loss that a VLCD induced greater loss of FFM com-
pared to a LCD. Nevertheless, the clinical relevance of this finding
remains to be established since the difference in FFM loss between
groups was relatively small (0.6 kg) and did not result in a difference
in weight regain between groups. Interestingly, Purcell et al. (5) did
not observe a difference in FFM loss between rapid and gradual
Figure 3 (A) Correlation between percentage fat-free mass loss (%FFML) during the weight loss groups in participants that lost 12.5% of body weight.
dietary intervention (DI) and weight regain (n 5 53), r 5 0.325, P 5 0.018. (B) Corre- Bioelectrical impedance was used to assess FFM in the latter study
lation between physical activity score (PA-score) during follow-up and weight regain
(n 5 55), r 5 20.330, P 5 0.014. LCD, low-calorie diet; VLCD, very-low-calorie diet. while the present study used ADP (Bod Pod), and the difference in
techniques might explain this discrepancy. Furthermore, %FFML was
not significantly different between men and women in this study, in
P 5 0.642, respectively). Furthermore, the PA-score after follow-up contrast to a recent study that showed that FFM loss was greater in
was significantly lower compared to after DI (Table 2) and the other men with overweight and obesity compared to women (22).
two time points (data not shown).
A remarkable finding was that the %FFML after DI was lower than
after the WL-period. Heymsfield et al. already stated that %FFML
Effects of weight cycling can vary with the amount of energy intake and the different phases
Number of weight cycles was significantly higher in women com- of a diet (23). These phases can induce changes not only in the mus-
pared to men (2.7 6 0.3 vs. 1.4 6 0.2, respectively, P 5 0.001). cle mass, but also in the hydration of FFM. Indeed, within 4 days
Number of weight cycles did not correlate with weight regain after after starting a VLCD it was shown that the average glycogen loss
follow-up (whole group: Spearman’s rho 5 0.026, P 5 0.859). was 0.4 kg (24), which can account for 1.6-2.0 kg of FFM because
glycogen is stored with three to four parts of water (25). Additional
water losses may have occurred during weight loss because increased
ketone-body excretion will lead to extra sodium and potassium losses
together with water (26,27). Unfortunately we are unable to distin-
Discussion guish between the water and muscle content of FFM with the current
The present study showed that, with similar total weight loss, the technique used, ADP. However, we believe that the loss of glycogen
rate of weight loss did not affect weight regain. Participants and water at the end of weight loss is restored with the initiation of
regained on average more than 50% of their lost weight within the a normal diet in the following weeks. Therefore, the FFM measured
9-month follow-up period in both groups. This finding directly con- at the end of DI reflects, in our view, the actual muscle mass
tradicts the current dietary guidelines of several countries, which changes more accurately than at the end of the WL-period.
recommend a more gradual weight loss approach for prevention of
weight regain (8,9). While VLCDs are often seen as a temporary Although the rate of weight loss and weight cycling were not corre-
means to lose weight, LCDs are thought to mimic a healthy lifestyle lated with weight regain, the PA-score after follow-up and the

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Obesity The Effect of Rate of Weight Loss on Weight Regain Vink et al.

%FFML during DI were correlated with weight regain. The reduced role of rate of weight loss in dietary recommendations and in the
level of PA during follow-up could have increased weight regain via etiology of weight regain should be critically reviewed.O
a lowered energy expenditure. In accordance, the level of PA was
previously shown to be related to long-term weight maintenance
(3,28). However, the drop in PA level during follow-up was surpris- Acknowledgments
ing and difficult to explain. It might have occurred due to reduced
motivation in some participants in response to the regained weight. Authors thank Imco Janssen, Helena Schaap, and Christianne Pijls
Muscle mass is a key contributor to resting energy expenditure for their assistance on test days. Also, authors thank the study par-
(10,11), and loss of muscle mass, and possibly organ mass, can ticipants for their contribution to the trial.
reduce total energy expenditure and potentially increase weight C 2016 The Obesity Society
V
regain. Alternatively, a compensatory increase in food intake during
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