Download Fitness Tools

Should you freak out about a small increase in body weight in a small-scale rodent study that is attributed to the consumption of saccharin in yogurt?

While epidemiological studies show that the consumption of products containing non-nutritive sweeteners (NNS) is associated with increased adiposity (Colditz. 1990; Fowler. 2008), type 2 diabetes mellitus (T2DM), metabolic syndrome and cardiovascular disease (Dhingra. 2007; Lutsey, Steffen. 2008). A mechanistic link between aspartame, sucralose, stevia & co and weight gain as well as its ill metabolic and cardiovascular consequences in humans is non-existent (learn more).

Rather than weight increases controlled human studies show that the consumption of artificially sweetened foods promote, not hinder the loss of body fat (Sørensen. 2014).
In animal models, though, the results have been more conflicting. While many studies show no effect of artificial sweetener consumption, the latest stud by Kelly Carraro Foletto and colleagues is not the first rodent study to suggest that non-nutritive sweeteners may also interfere in the regulation of compensatory appetite promoting weight gain (Davidson. 2011; Polyák. 2010; Rogers. 1988). This does yet not refute the findings of one of the latest meta-analysis of the effects of low-energy sweetener consumption on energy intake and body weight in man - a meta-analysis published in Nature's prestigious International Journal of Obesity that says...

Figure 1: The forest plots of the practically most relevant data of individual and combined effect sizes for sustained intervention studies comparing the effects on body weight of sweeteners versus sugar (upper panel) and versus water (lower panel) shows that not a single long(er) term study found negative effects - the exact opposite is the case. Even compared to water the use of low-energy sweeteners (artificial or not) lead to measurable, yet not always significant decreases in body weight in human trials (Rogers. 2015).

"that the balance of evidence indicates that use of LES [low or no energy sweeteners] in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water" (Rogers. 2015 | my emphasis).

And with respect to the often-cited "evidence" from animal and observational studies, the autors of the meta-analysis submit that...

"[...] the present review of a large and systematically identified body of evidence from human intervention studies, with varying designs, settings and populations (including children and adults, males and females, and lean, overweight and obese groups), provide no support for that view. The question then is whether those hypotheses should be rejected or whether, as seems unlikely, the relevant human intervention studies are consistently flawed in a way that leads, in most cases, to exactly the opposite outcome" (Rogers. 2015)

I do thus want to warn you: Do not overrate the already relatively small amount of extra-weight the rodents in saccharin group of Foletto's recent study gained (see Figure 2, left).

Figure 2: Cumulative weight gain and total cumulative energy intake of (only) 16 male Wistar reds fed diets that were supplemented with either saccharin-sweetened or non-sweetened yogurt added (Foletto. 2015)

In a previous study, Folleto et al. had already observed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. In their latest study they did not try to prove that this effect is independent of the rodents' energy intake and mediated by insulin-resistance and / or modified levels of leptin and PYY in the fasting state.
To this ends, the researchers randomly assigned 16 male Wistar rats to receive ~78kcal per week from either saccharin-sweetened (0.3% saccharin) yogurt or non- sweetened yogurt (0.5 kcal/g) in addition to chow (2.93 kcal/g) and water ad lib. For 14 weeks, Foletto, et al. measured the total food intake (from yogurt and chow) daily and the weight gain on a weekly basis (the results are plotted in Figure 2). Fasting leptin, glucose, insulin, PYY and HOMA-IR levels were measured only at the end of the 14-week study period, though.

Table 1: In view of the fact that any existing negative effects of dietary sweeteners may well be compound-specific. It is certainly worth noting that saccharin is no longer used in modern sweetener formulations of sodas (Wikipedia. 2015)

In spite of the already reported ~5% increase in cumulative weight gain over 14 weeks (p=0.027), the researchers found no differences in HOMA-IR (=insulin resistance), fasting leptin or PYY levels between groups that could mechanistically explain why the rodents who received saccharin sweetened yogurt gained more weight than their peers who received non-sweetened yogurts.
References:

• Foletto, Kelly Carraro, et al. "Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats." Appetite (2015).
• Rogers, P. J., et al. "Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies." International Journal of Obesity (2015).
• Sørensen, Lone B., et al. "Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects." The American journal of clinical nutrition (2014): ajcn-081554.

Implications for diet coke? None!

While I have deliberately ignored all previous studies discussing potential detrimental effects of saccharin on human health based on super-dose animal models, the one at hand is worth mentioning, because the dosage used is way below the RDA of 0.44mg/kg.

But let's tackle one thing after another. In contrast to the myths about aspartame which are still totally unfounded, the rumors about ill effects of saccharin on kidney and liver metabolism have been concrete enough for all the major players to pull saccharin from their products (see Table 1).
In fact, Tab, a diet cola soft drink introduced in 1963 and was created by Coca-Cola after the successful sales and marketing of Diet Rite cola, owned by The Royal Crown Company has long disappeared from the market... for a reason?

Table 1: Overview of  the amounts of artificial sweeteners in the most popular sodas (Wikipedia. 2015)

If we go by the results of a very recent study from the Universities of Dammam and Cairo, it would seem that the decision makers in the Coca-Cola Company did - whether knowingly or not - the exact right thing when they pulled the Diet Coke precursor from the market.

Figure 1: Changes in markers of liver and kidney health (left) and antioxidant status (right), in the former all changes were statistically significant, for GSH & co only the changes in the high dose group were (Amin. 2015).

You are right, the changes in ALT, AST, ALP usw. (Figure 1, left) Kamal Adel Amin and Hessah Mohammed AlMuzafar observed, would have been a good incentive to pull it now, if they hadn't done that already. Overall, the study is not without flaws, though.

There is more than one reason not to jump to potentially unwarranted conclusions

I will not go into detail on the dozens of spelling and grammar mistakes, as this is nothing that impairs the accuracy of the experimental results, but the fact that the researchers report the diet composition as follows,

"Rats were nourished on the regular basal diet and supplied with tap water and the contents of experimental diets were according to Kim et al., [21], it composed of: lipid 5%, carbohydrates 6%, protein 20.3%, fiber 5%, salts 3.7%, and vitamins 1%" (Amin. 2015),

makes me scratch my head. It's afte all not only that the figures don't add up. If you follow up on the reference, you will find that Kim et al. (2005) used a low and a high fat diet of which none contained only 5% of lipids (instead it's 11.7% and 40%).
Ok, this may still be a typo, but the fact that the scientists administered the 10mg/kg or 500mg/kg body weight saccharin via a stomach tube without having a sham fed control is negligent, because being tube fed is a daily stressor for the rats in the active treatment group that was not present in the rats in the non-supplemented group.

Figure 2: Changes in body weight gain, makers of lipid and glucose metbolism, only full bars are stat. sign. (Amin. 2015).

Yes, you can argue that the group that received methyl-salicylates, the safety of which was assessed in the same study may serve as a control, but come on... what kind of control is that, even if there were no significant changes in any of the measurable variables observed in the third and fourth study groups that received 80 and 250 mg/kg body weight methyl salicylates, a natural or synthetic oil with a characteristic wintergreen odor and taste that is used as a counterirritant in ointments or liniments for muscle pain and also as a flavoring agent.
References:

• Amin, Kamal Adel, and Hessah Mohammed AlMuzafar. "Alterations in lipid profile, oxidative stress and hepatic function in rat fed with saccharin and methyl-salicylates." International Journal of Clinical and Experimental Medicine 8.4 (2015): 6133.
• Kim, Ji Hyun, et al. "Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat." Journal of pharmacological sciences 97.1 (2005): 124-131.
• Udem, Samuel Chukwuneke, and Emmanuel C. Nwobodo. "Investigation into the short-term effect of ingestion of different concentrations of saccharin sodium on some hematological and biochemical profile of rats." Comparative Clinical Pathology 20.5 (2011): 471-474.
• Wikipedia contributors. Tab (soft drink) [Internet]. Wikipedia, The Free Encyclopedia; 2015 Jul 4, 23:49 UTC [cited 2015 Jul 5]. Available from: https://en.wikipedia.org/w/index.php?title=Tab_(soft_drink)&oldid=669980732.