A new systematic review of artificial sweeteners published in the Canadian Medical Association Journal concludes:

Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk.

Unsurprisingly, this is how the results are being widely reported in the media – that artificial sweeteners “may” increase body weight. I had to take a close look at this review, since a 2015 review of the same question came to a different conclusion. I discussed the 2015 review at the time. Had there been new research that essentially flipped the conclusion?

A brief overview of artificial sweetener research

I gave a summary of the research in my 2015 discussion, which you can read if you are interested in the details. Briefly, there are several types of research looking at the effects of consuming low energy sweeteners (LES), also called non-nutritive sweeteners (NNS). The first is animal research. These studies show some interesting possibilities, that consuming LES may lead to greater calorie consumption overall in some settings. However, these studies tend to be contrived in terms of what the rats eat and the applicability to humans is uncertain.

Human trials are largely divided into cohort studies, in which people are followed over long periods of time, and randomized trials, in which subjects are randomized to consuming water, LES, or sugary drinks. The cohort studies tend to show a small correlation between consuming LES and greater BMI or other measures of obesity. However, these studies show correlation only and are not able to determine causation. It is highly probable that people consume diet drinks because they are overweight, and not the other way around.

The best data is probably randomized controlled trials. These studies vary from short term (as little as one meal) to long term (six months) and have the advantage of randomizing subjects, and therefore we are better able to draw conclusions about causation. In the 2015 review they found a consistent but small benefit to consuming LES over drinks containing sugar, and even over consuming water. While this data is far from definitive, it does suggest a role for consuming LES beverages in weight management.

It is also probably true that effects depend on individual variables, as is true of weight management in general. There are many variables, including psychological ones, that are difficult to pin down. For example, there is a possible unintended consequence that when people do one thing for their health that takes will power, they then feel empowered to indulge in something they know is not good for them. So if they put Splenda in their coffee, they can have that piece of cake.

Further, most attempts at weight loss fail. It is therefore not surprising that attempts at weight loss with LES also have modest benefits. If the research shows any benefit of substituting LES for sugar, it is likely useful.

The new Canadian review

The new review from the CMAJ looked at two different kinds of studies, cohort studies and randomized controlled trials (they did not review animal studies like the 2015 review). In line with the 2015 review, they found that the nonrandomized cohort studies showed a modest correlation with consuming LES and being overweight. They also included several secondary health outcomes, like blood pressure, heart disease, and diabetes. These do not add much to the analysis, in my opinion, because they are all consequences of being overweight, and are therefore just measuring the same thing. There is no reason to conclude or even suspect that LES directly causes any of these secondary outcomes.

So this much of their conclusions is nothing new, and contains the same limitations. We can show correlation only, not causation, and there is a good reason to suspect that the causation is from being overweight to consuming LES. Yet reporting (starting with the study itself) focuses on the less plausible hypothesis that consuming LES causes weight gain.

Further, I think that the results of the randomized trials essentially completely trump the results of the cohort studies, because they are randomized. Here is where the conclusions differ from the 2015 review. The 2015 review concluded:

Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI (energy intake) and BW (body weight), and possibly also when compared with water.

The 2017 Canadian review concluded:

Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management…

The first thing I thought was – were there new studies since the 2015 review that warrants a different conclusion? The CMAJ review reports that there were new studies since the previous review and lists them. I looked through the new studies and found only one that is a relevant randomized controlled trial, this one published in 2016 that concluded:

NNS beverages were superior for weight loss and weight maintenance in a population consisting of regular users of NNS beverages who either maintained or discontinued consumption of these beverages and consumed water during a structured weight loss program. These results suggest that NNS beverages can be an effective tool for weight loss and maintenance within the context of a weight management program.

There was also a late 2015 study comparing LES to water, and found:

Replacement of DBs with water after the main meal may lead to greater weight reduction during a weight-loss program.

The other new studies were either cohort studies or looked at secondary outcomes. Neither of these two studies seem to warrant a reversal of the conclusion that consuming LES has a moderate benefit for weight loss. The first study actually supports a benefit for LES, and the second study is about replacing LES with water, and is not a comparison with sugary drinks.

Where does that leave us?

In the end the conclusions of this review are not dramatically different than the 2015 review – there is only a difference in emphasis which I think reflects the biases of the authors of each review. This is unavoidable because the data is complex, there is no perfect type of data, and the results are mixed and modest. There is therefore a lot of room for interpretation.

The Canadian reviewers acknowledge that the long term randomized trials did show a benefit for consuming LES, but they pointed out that these studies tended to have industry sponsorship. That is a legitimate point, as prior research shows a correlation between industry sponsorship and favorable outcomes, but in itself does not nullify the research findings.

I think the bottom line is that weight loss is difficult and complex. The effects of all interventions are modest and inconsistent. There are many variables, and no study will ever be able to control for all of them. The net effect of consuming LES vs sugary drinks or water is likely dependent on the individual and the situation.

But I do think we can draw a couple of conclusions from all the available research. The first question is this – is there a health or weight disadvantage to consuming sugar? I think the answer here is a clear yes. Sugary drinks contain many calories that add to total calorie consumption and are counterproductive if your goal is calorie control for weight management. Replacing high calorie sugary drinks with low calorie drinks is therefore advantageous.

The second question is this – is there an unintended backfire effect to consuming LES, because it tricks the brain into being more hungry or some other hormonal or metabolic effect? Here I think the answer is probably no, and the new Canadian review does not change this conclusion. Randomized controlled trials in humans supersede cohort studies and animal studies in addressing this question. Those studies find, if anything, a modest benefit to consuming LES. It is obviously possible to disagree about whether or not this benefit is real, given that there are inconsistencies in the data. The randomized trials clearly do not show any disadvantage – no backfire effect.

What I think this means is that, if you are trying to lose weight replacing sugary drinks with low calorie drinks can be a helpful part of your overall strategy. It will not be a panacea, or make weight loss easy. The research shows the most effective strategies involve making permanent changes to your lifestyle regarding food consumption and exercise. Avoiding sugary drinks can be part of those lifestyle changes, and you should not fear drinking LES because of an alleged backfire effect. The research, including this recent review, does not show such an effect in humans.


Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.