The movement away from sugar and towards non-caloric artificial sweeteners (NAS), began over a century ago after recognizing that 1) large amounts of calories could lead to obesity and likely a variety of other health problems, and 2) that large amounts of sugar adversely affected hormone levels (in particular insulin), which could also lead to obesity and a variety of other health problems. Thus, consumers looked to NAS as a way to continue to eat sweet foods and beverages while protecting their health. However, research is beginning to indicate that NAS may not be as harmless as we had hoped.
I posted previously about an interesting study in rats, which examined examined the effects of NAS in diet. The results were fascinating as many of the problems we know to arise from over-consumption of sugar, were also found after consuming the artificial sweetener. If you haven’t read my review, it’s worth a read. Recently, another study was published on NAS, this time by Suez and coworkers. Suez et al., 2014 was conducted in both mice and humans.
The Takehome: Glucose intolerance (high levels of blood sugar), often a precursor to Type 2 Diabetes, has been linked to cardiovascular disease, muscle loss, and a variety of other health problems. In this study, the authors found that the commercial non-caloric artificial sweeteners (NAS) saccharine, sucralose, and aspartame all caused mice to develop glucose intolerance. Further examination of saccharine alone (which had the greatest effect of the three), revealed that this intolerance was associated with a change in gut microbiota (bacteria) populations. Fecal matter with these altered microbiota could be transplanted into healthy mice and cause them to become glucose intolerant. In humans, increased consumption of foods with NAS was correlated (a questionnaire-based study) with impaired glucose tolerance and also an alteration of gut microbiota. Finally, ingesting NAS-continaing foods for 1 week was enough time to show reduced glucose tolerance in some, though not all, humans. In these affected humans, microbiota populations were, as expected, altered, though differently than in mice. Nevertheless, when this fecal material from humans was transplanted into healthy mice, the mice developed glucose intolerance. The results of this study indicate that artificial sweeteners don’t give us a free pass to eat without consequence. Although artificial sweeteners do not raise insulin, there appears to be another route by which they can disrupt blood glucose levels, and that is through modification of the bacterial populations that live in our digestive tract. The bacteria in our digestive tract don’t only affect the processing of sugars and artificial sweeteners as highlighted in this study. In fact, they play many other roles in maintaining our health, so it’s quite possible that consumption of artificial sweeteners may negatively impact our health in even more ways than we have yet to realize.
- 10-week (young adult) C57/BL6 mice were given one of three NAS in their drinking water: commercial saccharin, sucralose, or aspartame. Control mice were given either water or water with glucose or sucrose. Note: commercial NAS typically contain large amounts of glucose (~95%) and only small amounts of the artificial sweetener (~5%). The investigators matches these ratios.
- Fecal mibcrobiota composition was assessed in mice through rRNA gene sequencing.
- Fecal matter was removed from mice and cultured in tissue culture dishes to examine direct effects of NAS on microbiota growth.
- The effect of NAS in humans (381 non-diabetic males and females, mean age of 43 years old) was assessed through a food frequency questionnaire.
- 7 humans (5 males, 2 females) who do not normally consume NAS were given NAS-containing foods (at the FDA’s maximal acceptable daily intake levels) for 1 week, after which glucose intolerance and gut microbiota were assessed.
- After 11 weeks, the three groups that drank commercial NAS all had marked glucose intolerance (higher than normal blood sugar levels).
- The greatest intolerance was found in mice who consumed commercial saccharine.
- In mice who were on a high-fat diet (to simulate obesity), glucose intolerance from commercial saccharine ingestion was greater than from glucose ingestion.
- As with commercial saccharine, a lower dose (FDA acceptable daily intake adjusted to mouse) of pure saccharine, also resulted in glucose intolerance in mice on a high fat diet.
- Fasting serum insulin levels and insulin tolerance were similar in all mouse groups, regardless of diet.
- Mice drinking saccharine had a fecal microbiota profile different from their starting profiles and from the profile of all control groups (including a group that drank glucose). Profile differences were present even in mice that were on a high fat diet.
- Gene pathway analysis indicated that the microbiota profile in saccharine-fed mice had gene profiles for enhanced sugar breakdown/fermentation activity. These profiles were previously associated with obesity in mice and humans; overabundance of Bacteroides and under-abundance of Clostridiales.
- Fecal matter isolated from mice and treated with pure saccharine yielded similar shifts in the microbiota profile and transplanting this altered fecal material into normal mice resulted in their developing glucose intolerance.
- In humans, NAS consumption was significantly correlated with higher fasting blood glucose, glycosylated hemoglobin (indicates higher than normal levels of blood glucose), and higher glucose intolerance (as measured by a glucose tolerance test).
- In humans, NAS consumption was significantly correlated with differences in microbiota profiles.
- In 7 humans given NAS-containing food for 1 week, all developed a poorer glucose tolerance as compared to before they started consuming NAS-containing foods.
- Fecal material from humans who consumed NAS-containing food for 1 week and developed impaired glucose tolerance was transplanted into healthy mice and resulted in these mice developing glucose intolerance.
- Although very often a good model for humans, mice are not humans, so differences may exist where the initial mouse data is concerned. However, the pairing of human data with mouse data in this study makes this much less of a limitation.
- After seeing the greatest glucose intolerance effect from saccharine, the authors do not further examine effects/mechanisms in mice using sucralose or aspartame. We therefore do not know if the different sweeteners behave any differently beyond impairing glucose tolerance.
- Insulin levels appear to be unaffected by NAS (as expected), so the exact mechanism of intolerance remains somewhat unclear. We know gut microbiota are involved, but not exactly how.
- Food questionnaires are noted for being inaccurate as participant reporting is often inaccurate despite the participants’ best efforts.
- In humans, the microbiota profile differences resulting from NAS were not identical to those found in mice and were also different human-to-human. This suggests that the effects may vary substantially from person-to-person.
- The human study where NAS-containing foods were consumed had a very low sample size and an unequal distribution of men and women. This would generally be considered “preliminary” data that could be used to support a larger study.
- In the human study where NAS-containing foods were consumed, the types of NAS consumed were variable, so any differences among them could not be examined.