Given the great interest in losing weight, preventing weight gain and maintaining weight loss ( 15 ), it is important to understand whether NNS beverages are a benefit or a hindrance to people actively trying to manage their weight. As water has been deemed the “gold standard” beverage recommended for weight management it is important to assess, in a randomized trial, whether NNS beverages and water produce equivalent weight loss among people enrolled in a behavioral weight management program.

The largest and most recent randomized trial ( 14 ) to compare water, diet beverages and an attention control for their effects on weight loss used a superiority trial design. The authors found that the diet beverage treatment, but not water, significantly increased the probability of losing 5% of body weight over the 6‐month study duration compared to a standard weight loss education and monitoring program. Subjects in both treatment groups lost a significant amount of weight but the amount of weight lost compared to the control was not different between treatment groups.

NNS were introduced into the food supply over 50 years ago and are being used in hundreds of different food and beverage products. Despite the long history of usage there continues to be considerable controversy concerning their role in the diet, particularly whether they are a useful tool as an aid in weight loss and weight loss maintenance ( 3 - 6 ). NNS provide sweetness equivalent to NS but contribute essentially zero energy. Since the 1980s a number of short‐term experimental studies have compared NNS to NS and several comprehensive reviews have concluded that the evidence supports either a beneficial effect or no effect of NNS on appetite and energy intake ( 7 - 11 ). Other studies have reported findings of increased hunger with consumption of NNS ( 11 ) but generally without an accompanying increase in caloric intake.

Beverage consumption recommendations ( 1 ) suggest water as the gold‐standard beverage for optimal health. The US Dietary Guidelines ( 2 ) suggest that while beverages with non‐nutritive sweeteners (NNS) are preferable to those with caloric sweeteners, there is still a question about whether they are beneficial for weight management. While numerous clinical trials have examined the effects of nutritive sugar sweetened beverages (NS) compared to NNS beverages on weight loss, few studies have directly compared water and NNS beverages on weight loss using an equivalence trial design.

The primary hypothesis tested in this study was that water and NNS beverage treatments would be equivalent with upper and lower bounds of equivalence set at ±1.7 kg. This body weight difference was chosen as a value that would not be meaningfully different in a clinical setting. To be considered equivalent, the mean and the upper and lower 90% confidence limits for the difference in weight loss between NNS beverage and Water groups would have to be within the pre‐set upper and lower bounds of equivalence, ±1.7 kg. Other weight‐related outcomes included weight change from baseline for participants who completed all 12 weeks of the trial (for whom we had a 12‐week body weight) and percentage of participants who lost at least 5% of their initial weight. Differences between treatment groups for weight loss were assessed using several different methods: a mixed model, ANCOVA and two independent t tests (or chi‐square when appropriate). All methods showed the same results. We report here the t test results [two one‐sided t tests; the standard approach for evaluating equivalence ( 20 )] and 90% confidence intervals. Secondary outcomes (waist circumference, systolic blood pressure, blood measures, urine osmolality, hunger, and physical activity) were analyzed using linear mixed effects model which consisted of classification variables of time (baseline or 12 weeks) and group (NNS or water) as well as their interaction term as fixed effects and an unstructured covariance. Between‐group and within‐group contrasts were tested under this model.

Intent‐to‐treat (baseline observation carried forward) was used as the primary analysis for efficacy of weight loss using the weekly body weights as the dependent variable. As a secondary analysis we also looked at only participants who completed all 12 weeks of the trial. Five participants were randomized but did not begin treatment (Figure 1 ) and were excluded. The primary outcome measure was change in body weight from baseline to 12 weeks. The results were the same using baseline carried forward or a mixed model (accounting for missing data) analytic schemes.

The primary outcome addressed in this report is change in body weight during the 12‐week weight loss phase of this 1 year trial. The study was designed as an equivalence trial with the hypothesis that there would be no clinically meaningful difference in weight change between those consuming NNS beverages or water. Specifically, the bounds of equivalence for between‐group difference in 12‐week weight loss were prespecified to ± 1.7 kg. Assuming the true difference was 0.57 (1/3 of the equivalence margin) and common SD of 3.9 kg, a sample size of 150 per arm was required using two, one‐sided t tests to ensure at least 80% power with an alpha level of P < 0.05 to establish equivalence.

All assessments, except for height, were conducted at baseline and after 12 weeks of treatment. Height without shoes was measured to the nearest 0.1 cm at the screening visit using a wall‐mounted stadiometer. Body weight in light clothing and without shoes was measured to the nearest 0.1 kg on a digital scale. Waist circumference was measured at the top of the iliac crest until two consecutive measures within 0.5 cm were obtained. Resting blood pressure was measured while the subjects were seated after a 5‐min rest; the average of two measures was used. Blood samples were collected using standard venipuncture method after a 10‐ to 12‐h fast for measurement of lipids and glucose. Participants provided a urine sample collected in a sterile container for measurement of urine osmolality. Blood samples from both study sites were analyzed at the University of Colorado Hospital laboratory. Urine samples collected at the Colorado site were measured at the University of Colorado Hospital laboratory; those from Temple University were measured at Quest Diagnostics, Madison, NJ.

Participants randomized to the water group were asked to consume at least 24 fluid ounces of water per day, and not drink any NNS beverages. They could, however, eat foods that contained NNS (examples: artificially sweetened yogurt, gum, candies, cookies, ice cream, gelatin, pudding), but could not intentionally add NNS (examples: aspartame—NutraSweet or Equal, sucralose—Splenda, stevia—Truvia; as well as diet creamers) to beverages such as coffee.

Individual energy targets for weight loss were set as equal to each participant's estimated resting metabolic rate (RMR), rounded up to the nearest 100 kcal, determined using a Tanita Model TBF‐300A bioelectrical impedance device that assesses body composition and provides an imputed RMR. Energy targets were adjusted, as needed, by the group leader in an attempt to achieve a weight loss of 1 to 2 pounds per week. Weekly physical activity targets were set based on increasing moderate to vigorous activity by 10 min week −1 above the subject's usual activity level with a target goal to reach 60 min day −1 , 6 days week −1 . Physical activity was assessed by two methods; ( 1 ) participants wore a Body Media armband (Manufacturer: BodyMedia, Model AB155) for 1 week during weeks 1 and 12, and ( 2 ) participants reported daily physical activity minutes on exercise logs turned in weekly. Participants received the same curriculum regardless of which treatment arm they were assigned to with the only difference being discussion of the type of beverages they were instructed to consume during the study.

The study was designed as a 1‐year equivalence randomized trial composed of a 12‐week weight loss phase followed by a 9‐month weight maintenance phase. Participants were randomly assigned to the NNS beverage or water treatment arms by a computer‐generated randomization schedule that ensured an equal distribution of women and men in each behavioral weight loss treatment group. Participants had to be willing to discontinue drinking NNS beverages for the 1‐year study should they be randomized to the water treatment group.

Screening was carried out over the phone or through completion of a secure web based screening form. Eligible participants had to report being weight stable within 10 pounds in the past 6 months, engaging in fewer than 300 min of physical activity per week and consuming at least 3 NNS beverages per week. Applicants were excluded if they were lactating or pregnant within the past 6 months or were planning on becoming pregnant during the time frame of the study. Other exclusions included but were not limited to: diabetes, CVD, uncontrolled hypertension, and use of current medications affecting weight and metabolism. Participants needed physician approval stating they were in good general health and that nutrition and exercise requirements would not be contraindicated.

The mean weight loss difference between Water and NNS was −1.85 kg (90% CI: −1.12 kg, −2.58 kg). Because the lower confidence limit (−2.58 kg) was outside of the equivalence bounds set a priori in our hypotheses, the two treatments were not equivalent and paired comparisons were conducted. This analysis indicated that weight loss in the NNS beverage group [5.95 kg ± 3.94 kg (SD)] was significantly greater than the Water group (4.09 kg ± 3.74 kg (SD), P < 0.0001) using an intent to treat (LOCF) analytic scheme (Table 2 ). Similar findings were observed using observations only from those completing the 12‐week assessment (Table 3 ). In the Water group, 43.0% of participants lost >5% of their body weight, while 64.3% of participants in the NNS beverage group lost > 5% ( P = 0.0002; Figure 2 ).

There were no significant differences between groups in adherence to the study beverages as assessed by the weekly beverage consumption logs. Percent adherence for reported daily consumption of at least 24 ounces of NNS or water was 96.6% vs. 95.7%, respectively ( P = 0.34). Weekly group meeting attendance was also not different between the groups (attendance: 90.8% for NNS; 89.7% for Water, P = 0.24).

A total of 303 participants began the study treatment and 279 participants completed the 12‐week weight loss phase of the study, representing 92% of the starting population (Figure 1 ). Study dropouts were similar across the two study sites (9.27% at Colorado, 9.55% at Temple) as well as between the treatment groups (5.8% for NNS, 10% for water). There were no significant baseline differences in age, gender, race/ethnicity or other study measures between the water and NNS beverage treatment groups (Table 1 ). Almost 80% of the participants were female, 68% white, and 27% African American.

Discussion

In this 12‐week weight loss study, consuming water and NNS beverages were not equivalent for weight loss, with the NNS group losing significantly more weight than the water group. The results provide support for the use of NNS beverages in the context of a behavioral weight management program and should be reassuring for people who choose to consume NNS beverages. It demonstrates that they can drink a NNS beverage without the caloric contribution of nutritive sweeteners and without concern that their weight loss efforts will be undermined and, in fact, may be slightly enhanced. It should be noted that because eligible subjects were already NNS drinkers assignment to the NNS treatment did not require as great a behavior change as the Water group who had to abstain from NNS beverages for the trial. We chose this design rather than admitting all comers in order to ensure that subjects assigned to NNS would adhere to the treatment giving us the ability to see if NNS adversely affected weight loss. Despite this, subject completion was high and did not differ between groups and adherence to the treatment was >95% based on beverage logs.

These findings build on the only other published study similar to the present trial. Tate et al. (14) compared water, diet beverages and an attention control over 6 months of intentional weight loss using a superiority trial design in 318 participants. Those authors found no significant differences in mean weight loss between the water and diet beverage groups when compared to the attention control group. However, the probability of losing 5% of body weight was significantly better in the NNS group compared to the attention control group (P = 0.04). The likelihood of achieving a 5% loss was not different between the group assigned to water compared to the attention control (P = 0.13). A significant difference between that study and the present trial is the intensity of the intervention. Tate et al. asked participants to make a single substitution in their diet, changing beverage options, while in our study participants in both the water and NNS groups received a comprehensive behavioral treatment program. Participants in the Tate trial lost <2% of body weight on average over the first 12 weeks while participants in the present trial lost between 4 and 7% of body weight. Taken together, results from both studies suggest that NNS beverages can be an effective strategy for weight management both in low intensity and high intensity behavioral interventions. Furthermore, in the present study NNS beverages performed better than water in supporting weight loss during the 12‐week weight loss phase.

The purpose of this trial was to compare directly the “gold standard” beverage for supporting good health, water, with NNS beverages in the context of weight loss. This is an important question as many people choose to consume NNS beverages as part of a weight management strategy, and others may be more likely to do so if they had confidence that it would not hinder their success. The popular media continues to raise questions about the value of NNS beverages in weight loss (21, 22) citing concerns from some experts that NNS beverage usage is associated with obesity and weight gain in observational studies (21-23). The current results, along with results of Tate et al. (14), provide strong evidence from large randomized controlled trials that NNS beverages do not hinder and can help with weight loss when compared to water. In addition, Phelan and Wing examined the use of NNS beverages by those in the National Weight Control Registry and found that successful weight losers drank three times the NNS beverages compared to those who had never lost weight (24).

We chose 12 weeks as the weight loss phase because most studies show that weight loss slows considerably after 6 months of treatment with more than half of the weight loss occurring in the first 12 weeks (25, 26), probably owing to difficulty with longer term adherence to a hypocaloric regimen. Furthermore, it is now recognized that weight loss is a different process from weight maintenance, both behaviorally and physiologically, so it is important to study treatment effects on these two processes separately (27). The benefit of the current 1 year trial is that we will be able to compare both weight loss and weight loss maintenance within the same group of participants. The trial was designed to allow preplanned analysis of the treatment effects after just the 12‐week weight loss phase as well as after 9 months of weight maintenance (still underway) which will be reported separately.

While most secondary outcomes were not different between the groups, the NNS group showed greater reductions in total‐ and LDL‐cholesterol. This may be due to the greater weight loss in the NSS group. There was also no significant difference between the groups in urine osmolality although osmolality decreased slightly in the water and increased slightly in the NNS group. It is unlikely that changes in hydration status were responsible for the significant differences in body weight between treatments. The small changes observed were well within the normal range for urine osmolality (500‐800 mOsmol kg−1) suggesting no adverse effect on fluid intake regulation. Physical activity increased significantly in both groups as a function of the behavioral treatment but was not significantly different between groups. Sedentary behavior actually decreased significantly in the Water group over time but not the NNS group. The changes over time were not significant between groups. Taken together, changes in physical activity and sedentary behaviors cannot account for the difference in weight loss observed.

Based on the design of this study we are unable to say, what is the mechanism for the greater weight loss in the NNS group compared to the water group. Weekly hunger scores were significantly lower among the NNS group than the water group although the absolute changes were small. While it is plausible that the NNS participants were more likely to adhere to the dietary recommendations due to less hunger than the Water group we cannot conclude this based on this study. Some authors (3, 5, 6) have suggested that use of NNS may increase appetite for sweet foods and disrupt regulation of energy balance. Weight loss results for the present study suggest that NNS consumption did not increase energy intake from other foods compared to water. This is consistent with other studies that have not found increased consumption of sweet or high energy foods while using NNS (28, 29). Further studies will be needed to ascertain the mechanism(s) that may be responsible for the weight loss results.

These results strongly suggest that NNS beverages can be part of an effective weight loss strategy and individuals who desire to consume them should not be discouraged from doing so because of concerns that they will undermine short‐term weight loss efforts. A longer term follow‐up of this randomized cohort, now underway, will clarify the utility of NNS beverages in weight loss maintenance.