The Unbiased Truth About Artificial Sweeteners

Artificial sweeteners continue to be a controversial public health issue, and the research keeps coming. In fact, a new study on artificial sweeteners and weight loss was just published on Monday, and the FDA approved a new artificial sweetener (advantame) last Wednesday.

On one hand, many people are adamantly opposed to the use of artificial sweeteners because of the purported link with increased risk for cancer and other diseases. But on the other hand, artificial sweeteners are becoming increasingly popular as people try to reduce calorie consumption and lose weight.

There’s too much research out there to cover comprehensively in a blog article, but I’ll try to cover the basics: will artificial sweeteners give you cancer or other diseases? Do they actually help with weight loss, or do they hurt? And ultimately, should you be eating them?

Cancer

Artificial sweeteners were first tied to cancer risk in the 1970’s after a study showed that a combination of saccharin and cyclamate (another early artificial sweetener) caused bladder cancer in lab rats. The mechanism behind these effects was later found to be specific to rats and not generalizable to other animals or humans (in these rats, comparable doses of vitamin C can also cause bladder cancer), and further studies demonstrated that neither sweetener is carcinogenic.

However, this study cast a shadow of doubt over artificial sweeteners, and thanks in part to the media’s penchant for blowing things way out of proportion, the reputation of artificial sweeteners has never recovered.

A later study suggested a link between aspartame consumption and brain tumors. The authors based this hypothesis on the fact that both brain cancer and aspartame consumption had increased since 1980 – despite not knowing whether the people getting brain tumors actually consumed artificial sweeteners – and on a rat study where aspartame supplemented diets led to the formation of brain tumors.

This association has been more or less dismissed by the research community because three case-control studies have found no association between brain tumors and aspartame consumption, and subsequent animal studies haven’t been able to replicate the aspartame-induced brain tumors found in the original rat study.

Artificial sweeteners have also been implicated in the development of lymphoma and leukemia, and one observational study found a weak link between artificial sweetener consumption and development of non-Hodgkin lymphoma and multiple myeloma in men, but not in women. The study authors concluded that due to the inconsistency in their results, there isn’t likely a causal link, although it can’t be ruled out.

Artificial sweeteners have also been tested for associations with other cancers, including breast, pancreatic, stomach, colon, and endometrium, with no correlations found. Based on the evidence, I don’t think artificial sweeteners are a huge risk factor for cancer, although the possibility can’t be ruled out and caution is warranted.

Diabetes, Heart Disease, and Metabolic Syndrome

Artificial sweeteners have also been increasingly tied to increased risk for developing metabolic syndrome and related diseases such as diabetes and cardiovascular disease. Numerous observational studies have attempted to parse out a consistent association with disease risk, but for every study that has linked artificial sweetener consumption with metabolic syndrome, heart disease, or diabetes, there’s another that has found no association.

This inconsistency shouldn’t come as a surprise, given the inherent limitations of observational evidence, but because there’s little to no clinical evidence in humans to test these hypotheses, the effect of artificial sweeteners on risk for these diseases remains inconclusive.

Pre-term Delivery

There has been concern in recent years over a potential link between artificial sweetener consumption and pre-term delivery, prompted by two observational studies published in 2010 and 2012. These studies have significant limitations: the associations are small and not linearly dose-dependent; not all artificially-sweetened beverages were accounted for; and women who consume more artificially sweetened drinks also tend to smoke more, have higher BMI, and lower socioeconomic status. All told, the risk seems small, but I would advise pregnant women to avoid artificial sweeteners just to be on the safe side.

Weight Loss

For most people, the primary motivation for consuming artificial sweeteners is a desire to reduce calorie consumption and lose weight. But do artificial sweeteners actually help achieve that goal? Yet again, the evidence is mixed. Many observational studies have found a positive association between artificial sweetener intake and obesity, but in this situation, reverse-causality is particularly likely.

In other words, while it’s possible that artificial sweeteners contributed to weight gain in these studies, it’s also possible that people who are overweight are more likely to choose diet beverages and other artificially sweetened foods in an effort to lose weight. We also have a decent number of clinical trials testing the weight loss effects of artificial sweeteners in humans, although many are too short-term to have much practical significance.

In one study, overweight subjects were given supplements of either sucrose or artificial sweeteners for 10 weeks. At the end of the trial period, subjects in the artificial sweetener group on average had experienced a reduction in weight, fat mass, and blood pressure, while subjects in the sucrose group gained weight and had increased blood pressure.

A study just published this week on weight loss and artificial sweeteners was surprisingly positive: over a 12-week period, participants who were instructed to drink 24 ounces of artificially sweetened beverages every day actually lost more weight than participants who were instructed to drink 24 ounces of water daily. (It’s worth noting that this study was fully funded by The American Beverage Association.) Other trials have also shown successful calorie reduction and weight loss in participants who consumed artificial sweeteners (usually in the form of beverages).

Based on this evidence, it seems that artificial sweeteners can be helpful for weight loss in some circumstances, at least over the short term. However, due to the limited nature of these studies and the evidence I’ll present next, I hesitate to draw any conclusions.

Do Artificial Sweeteners ‘Confuse’ The Body?

For most of human history, sweeteners were inextricably tied to caloric density. If our sweet taste receptors evolved primarily to help us identify calorie-rich food sources, how will our bodies respond when our taste receptors are consistently bombarded with sweetness, but with no concomitant calorie surge?

Animal models certainly indicate that artificial sweeteners can impair the innate ability to regulate caloric intake. Rats who are fed with artificial sweeteners consistently gain more weight than rats who are fed with glucose or sucrose. Additionally, the rats don’t tend to lose the excess weight, even after their diets are switched back to glucose or sucrose to re-establish the calorie-predictive nature of sweet taste.

Interestingly, rats who were given stevia solutions gained significantly more weight than the glucose-fed rats, and similar amounts of weight to the saccharin-fed rats. Rats fed with artificial sweeteners also develop an impaired ability to respond to sugar-containing foods. In one study, rats who had been fed artificial sweeteners were unable to compensate for the calorie content of a sugar preload by eating less chow afterwards, while rats who had been fed sugar-containing food compensated almost perfectly for the extra calories in the preload by eating less chow.

Rats that have been conditioned with saccharin also display a reduced thermic effect in response to consumption of a caloric sugar-containing meal, as well as higher blood glucose, compared with rats who had been conditioned with glucose. Additionally, saccharin-fed rats secreted less GLP-1 (which is implicated in satiety and glucose homeostasis) when given a sugar-containing test meal.

Unfortunately, although the animal evidence is fairly robust, evidence in humans is limited. However, two interesting studies that used MRI to measure brain responses to sucrose solutions indicate that artificial sweeteners may alter the brain’s response to sweet tastes in humans. In one study, people who regularly consume artificially sweetened drinks had higher reward responses to both saccharin and sucrose compared with people who don’t consume artificial sweeteners.

Additionally, people who don’t consume artificial sweeteners had different brain responses to the saccharin and sucrose, while those who regularly consume artificial sweeteners responded the same to both sweeteners. Another study found that the amygdala’s response to sucrose consumption was inversely related to artificial sweetener use. (The amygdala is part of the brain that is involved with taste-nutrient conditioning.)

Should You Be Eating Artificial Sweeteners?

My conclusion might seem a little anticlimactic after all that information, but the point I’d like to drive home is that artificial sweeteners are extremely new to the human diet, and for modern, industrial foods, the operating principle should always be “guilty until proven innocent.” We’ve conducted what are essentially population-wide experiments with the introduction of other industrial foods (such as high omega-6 vegetable oils) because the initial evidence seemed promising, and we can see how well that worked out.

Despite some successful short-term weight loss studies, I don’t think the potential therapeutic effects of artificial sweeteners have been demonstrated clearly enough thus far to warrant widespread consumption, especially given the conflicting links with disease risk and the questionable influence on appetite regulation and weight control. Ultimately, while artificial sweeteners are perhaps not as scary as some might believe, I don’t recommend including them in your diet.

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