Sugary Drinks as the Culprit in Childhood Obesity? a RCT among Primary School Children

Childhood obesity is a growing health problem. Since 1980, the proportion of overweighted children has almost tripled in the USA:  nowadays approximately 17% of children and adolescents are obese.  (Source: cdc.gov [6])

Common sense tells me that obesity is the result of too high calory intake without sufficient physical activity.” – which is just what the CDC states. I’m not surprised that the CDC also mentions the greater availability of high-energy-dense foods and sugary drinks at home and at school as main reasons for the increased intake of calories among children.

In my teens I already realized that sugar in sodas were just “empty calories” and I replaced tonic and cola by low calory  Rivella (and omitted sugar from tea). When my children were young I urged the day care to restrain from routinely giving lemonade (often in vain).

I was therefore a bit surprised to notice all the fuss in the Dutch newspapers [NRC] [7] about a new Dutch study [1] showing that sugary drinks contributed to obesity. My first reaction was “Duhhh?!…. so what?”.

Also, it bothered me that the researchers had performed a RCT (randomized controlled trial) in kids giving one half of them sugar-sweetened drinks and the other half sugar-free drinks. “Is it ethical to perform such a scientific “experiment” in healthy kids?”, I wondered, “giving more than 300 kids 14 kilo sugar over 18 months, without them knowing it?”

But reading the newspaper and the actual paper[1], I found that the study was very well thought out. Also ethically.

It is true that the association between sodas and weight gain has been shown before. But these studies were either observational studies, where one cannot look at the effect of sodas in isolation (kids who drink a lot of sodas often eat more junk food and watch more television: so these other life style aspects may be the real culprit) or inconclusive RCT’s (i.e. because of low sample size). Weak studies and inconclusive evidence will not convince policy makers, organizations and beverage companies (nor schools) to take action.

As explained previously in The Best Study Design… For Dummies [8] the best way to test whether an intervention has a health effect is to do a  double blind RCT, where the intervention (in this case: sugary drinks) is compared to a control (drinks with artificial sweetener instead of sugar) and where the study participants, and direct researchers do not now who receives the  actual intervention and who the phony one.

The study of Katan and his group[1] was a large, double blinded RCT with a long follow-up (18 months). The researchers recruited 641 normal-weight schoolchildren from 8 primary schools.

Importantly, only children were included in the study that normally drank sugared drinks at school (see announcement in Dutch). Thus participation in the trial only meant that half of the children received less sugar during the study-period. The researchers would have preferred drinking water as a control, but to ensure that the sugar-free and sugar-containing drinks tasted and looked essentially the same they used an artificial sweetener as a control.

The children drank 8 ounces (250 ml) of a 104-calorie sugar-sweetened or no-calorie sugar-free fruit-flavoured drink every day during 18 months.  Compliance was good as children who drank the artificially sweetened beverages had the expected level of urinary sucralose (sweetener).

At the end of the study the kids in the sugar-free group gained a kilo less weight than their peers. They also had a significant lower BMI-increase and gained less body fat.

Thus, according to Katan in the Dutch newspaper NRC[7], “it is time to get rid of the beverage vending machines”. (see NRC [6]).

But does this research really support that conclusion and does it, as some headlines state [9]: “powerfully strengthen the case against soda and other sugary drinks as culprits in the obesity epidemic?”

Rereading the paper I wondered as to the reasons why this study was performed.

If the trial was meant to find out whether putting children on artificially sweetened beverages (instead of sugary drinks) would lead to less fat gain, then why didn’t the researchers do an  intention to treat (ITT) analysis? In an ITT analysis trial participants are compared–in terms of their final results–within the groups to which they were initially randomized. This permits the pragmatic evaluation of the benefit of a treatment policy.
Suppose there were more dropouts in the intervention group, that might indicate that people had a reason not to adhere to the treatment. Indeed there were many dropouts overall: 26% of the children had stopped consuming the drinks, 29% from the sugar-free group, and 22% from the sugar group.
Interestingly, the majority of the children who stopped drinking the cans because they no longer liked the drink (68/94 versus 45/70 dropouts in the sugar-free versus the sugar group).
Ànd children who correctly assumed that the sweetened drinks were “artificially sweetened” was 21% higher than expected by chance (correct identification was 3% lower in the sugar group).
Did some children stop using the non-sugary drinks because they found the taste less nice than usual or artificial? Perhaps.

This  might indicate that replacing sugar-drinks by artificially sweetened drinks might not be as effective in “practice”.

Indeed most of the effect on the main outcome, the differences in BMI-Z score (the number of standard deviations by which a child differs from the mean in the Netherland for his or her age or sex) was “strongest” after 6 months and faded after 12 months.

Mind you, the researchers did neatly correct for the missing data by multiple imputation. As long as the children participated in the study, their changes in body weight and fat paralleled those of children who finished the study. However, the positive effect of the earlier use of non-sugary drinks faded in children who went back to drinking sugary drinks. This is not unexpected, but it underlines the point I raised above: the effect may be less drastic in the “real world”.

Another (smaller) RCT, published in the same issue of the NEJM [2](editorial in[4]), aimed to test the effect of an intervention to cut the intake of sugary drinks in obese adolescents. The intervention (home deliveries of bottled water and diet drinks for one year) led to a significant reduction in mean BMI (body mass index), but not in percentage body fat, especially in Hispanic adolescents. However at one year follow up (thus one year after the intervention had stopped) the differences between the groups evaporated again.

But perhaps the trial was “just” meant as a biological-fysiological experiment, as Hans van Maanen suggested in his critical response in de Volkskrant[10].

Indeed, the data actually show that sugar in drinks can lead to a greater increase in obesity-related parameters (and vice versa). [avoiding the endless fructose-glucose debate [11].

In the media, Katan stresses the mechanistic aspects too. He claims that children who drank the sweetened drinks, didn’t compensate for the lower intake of sugars by eating more. In the NY-times he is cited as follows[12]: “When you change the intake of liquid calories, you don’t get the effect that you get when you skip breakfast and then compensate with a larger lunch…”

This seems a logic explanation, but I can’t find any substatation in the article.

Still “food intake of the children at lunch time, shortly after the morning break when the children have consumed the study drinks”, was a secondary outcome in the original protocol!! (see the nice comparison of the two most disparate descriptions of the trial design at clinicaltrials.gov [5], partly shown in the figure below).

“Energy intake during lunchtime” was later replaced by a “sensory evaluation” (with questions like: “How satiated do you feel?”). The results, however were not reported in their current paper. That is also true for a questionnaire about dental health.

Looking at the two protocol versions I saw other striking differences. At 2009_05_28, the primary outcomes of the study are the children’s body weight (BMI z-score),waist circumference (replaced by waist to height), skin folds and bioelectrical impedance.
The latter three become secondary outcomes in the final draft. Why?

Click to enlarge (source Clinicaltrials.gov [5])

It is funny that although the main outcome is the BMI z score, the authors mainly discuss the effects on body weight and body fat in the media (but perhaps this is better understood by the audience).

Furthermore, the effect on weight is less then expected: 1 kilo instead of 2,3 kilo. And only a part is accounted for by loss in body fat: -0,55 kilo fat as measured by electrical impedance and -0,35 kilo as measured by changes in skinfold thickness. The standard deviations are enormous.

Look for instance at the primary end point (BMI z score) at 0 and 18 months in both groups. The change in this period is what counts. The difference in change between both groups from baseline is -0,13, with a P value of 0.001.

(data are based on the full cohort, with imputed data, taken from Table 2)

Sugar-free group : 0.06±1.00  [0 Mo]  –> 0.08±0.99 [18 Mo] : change = 0.02±0.41  

Sugar-group: 0.01±1.04  [0 Mo]  –> 0.15±1.06 [18 Mo] : change = 0.15±0.42 

Difference in change from baseline: −0.13 (−0.21 to −0.05) P = 0.001

Looking at these data I’m impressed by the standard deviations (replaced by standard errors in the somewhat nicer looking fig 3). What does a value of 0.01 ±1.04 represent? There is a looooot of variation (even though BMI z is corrected for age and sex). Although no statistical differences were found for baseline values between the groups the “eyeball test” tells me the sugar- group has a slight “advantage”. They seem to start with slightly lower baseline values (overall, except for body weight).

Anyway, the changes are significant….. But significance isn’t identical to relevant.

At a second look the data look less impressive than the media reports.

Another important point, raised by van Maanen[10], is that the children’s weight increases more in this study than in the normal Dutch population. 6-7 kilo instead of 3 kilo.

In conclusion, the study by the group of Katan et al is a large, unique, randomized trial, that looked at the effects of replacement of sugar by artificial sweeteners in drinks consumed by healthy school children. An effect was noticed on several “obesity-related parameters”, but the effects were not large and possibly don’t last after discontinuation of the trial.

It is important that a single factor, the sugar component in beverages is tested in isolation. This shows that sugar itself “does matter”. However, the trial does not show that sugary drinks are the main obesity  factor in childhood (as suggested in some media reports).

It is clear that the investigators feel very engaged, they really want to tackle the childhood obesity problem. But they should separate the scientific findings from common sense.

The cans fabricated for this trial were registered under the trade name Blikkie (Dutch for “Little Can”). This was to make sure that the drinks would never be sold by smart business guys using the slogan: “cans which have scientifically been proven to help to keep your child lean and healthy”.[NRC]

Still soft drink stakeholders may well argue that low calory drinks are just fine and that curbing sodas is not the magic bullet.

But it is a good start, I think.

Photo credits Cola & Obesity:  Melliegrunt Flikr [CC]

References

1. de Ruyter JC, Olthof MR, Seidell JC, & Katan MB (2012). A Trial of Sugar-free or Sugar-Sweetened Beverages and Body Weight in Children. The New England journal of medicine PMID: 22998340
2. Ebbeling CB, Feldman HA, Chomitz VR, Antonelli TA, Gortmaker SL, Osganian SK, & Ludwig DS (2012). A Randomized Trial of Sugar-Sweetened Beverages and Adolescent Body Weight. The New England journal of medicine PMID: 22998339
3. Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, & Qi L (2012). Sugar-Sweetened Beverages and Genetic Risk of Obesity. The New England journal of medicine PMID: 22998338
4. Caprio S (2012). Calories from Soft Drinks – Do They Matter? The New England journal of medicine PMID: 22998341
5. Changes to the protocol http://clinicaltrials.gov/archive/NCT00893529/2011_02_24/changes
6. Overweight and Obesity: Childhood obesity facts  and A growing problem (www.cdc.gov)
7. NRC Wim Köhler Eén kilo lichter.NRC | Zaterdag 22-09-2012 (http://archief.nrc.nl/)
8.  The Best Study Design… For Dummies (https://laikaspoetnik.wordpress.com)
9. Studies point to sugary drinks as culprits in childhood obesity – CTV News (ctvnews.ca)
10. Hans van Maanen. Suiker uit fris, De Volkskrant, 29 september 2012 (freely accessible at http://www.vanmaanen.org/)
11. Sugar-Sweetened Beverages, Diet Coke & Health. Part I. (https://laikaspoetnik.wordpress.com)
12. Roni Caryn Rabina. Avoiding Sugared Drinks Limits Weight Gain in Two Studies. New York Times, September 21, 2012

Related articles

• Studies more firmly tie sugary drinks to obesity (news.yahoo.com)
• Teens who cut out sugary drinks slowed weight gain (usatoday.com)
• Evidence against soda is piling up – Philadelphia Inquirer (philly.com)
• Can It! Soda Studies Cite Stronger Link to Obesity (nlm.nih.gov)