Can Stevia Help You Ward Off Type II Diabetes? A Review

Can Stevia Help You Ward Off Type II Diabetes? A Review

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Unfortunately, it is not even clear if you need the "white stuff", i.e. pure steviosides, whole leaves of leaf-extracts to maximize the anti-diabetic effects of stevia. What is clear, though, is that there's still a lot of research to be done.

"Can Stevia Help You Ward Off Type II Diabetes?" That's not just the title of today's SuppVersity article, it is also the research question of a recent paper by Esteves A.F. dos Santos from Farmácia Progresso (dos Santos. 2016). An interesting question with an obvious answer: if you replace sugar in your diet with stevia, it will help.

Now, you know that this would not be worth discussing in a SuppVersity article of its own. What is worth discussing, though, is that stevia contains "compounds and other substance obtained from stevioside hydrolyses" (dos Santos. 2016) such as isoteviol of which studies show that they can be used as 'active' diabetes treatments - meaning: they help, even if you take them on top of sugar / your regular diet.

You can learn more about sweeteners at the SuppVersity

Aspartame & Your Microbiome - Not a Problem?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Chronic Sweeten-er Intake Won't Effect Microbiome

Stevia, the Healthy Sweetener?

Sweeteners In- crease Sweet- ness Threshold

To understand how stevia may help you to ward off diabetes, you will first have to understand how the latter actually develops. In the previously references review, dos Santos writes about the consequences of life-style induced weight gain and concomitant increases in body fat and insulin resistance (IR):

Figure 1: Illustration of the etiology of type II diabetes from a secondary source (in dos Santos. 2016)

"After an initial increase of insulin production as a response to IR in peripheral tissue, pancreatic β cells no longer have the ability to control glucose homeostasis, leading to endocrine sys-tem imbalances. Under glucagon influ-ence, the liver contributes significantly in glucose homeostasis because liver makes the balance between capture / storage of glucose, via glycogenesis, and the release of glucose by glycogenolysis and gluconeogenesis. 

Constant, prolonged state of hypergly-cemia enables the formation of Advanced Glycation End-Products (AGEs). AGEs are responsible for the onset of diabetic complications, such as neurological and kidney complications (diabetic nephropathy), aging and cardiovascular complications: dyslipidemia, hyperten-sion, [etc.]" (dos Santos. 2016).

The previously referenced AGEs and the significant increase of reactive oxygen specimen (ROS), which leads to decreased levels of antioxidants enzymes, increase lipid peroxidation, will increase the risk for cardiovascular diseases and exacerbate the state of the disease, which has - at this point - started to self-propel its own progression.

If using stevia could break this vicious cycle, this would obviously be awesome!

Initial evidence that suggests that stevia could do what the subheading suggests, and decrease blood glucose levels comes from ... you guessed it: rodents. In a 4 week supplementation study, rats who were fed Stevia rebaudiana extract - combined with high-carbohydrate and high-fat diets - exhibited a sign. lower increase in glucose and worsening of their glucose tolerance in an oral glucose tolerance test (OGTT) - a result that was soon confirmed in human beings who ingested an infusion of 5 Stevia rebaudiana leaves for 3 days, every 6 hours (see Figure 2):

Figure 2: Effect of stevia leaf extract (5g) blood glucose of 16 healthy subjects on oral glucose tolerance test (Curi. 1986).

Similar results have been observed by Anton et al. (2010) who compared the effect of preloads of stevia with preloads of other sweeteners, such as aspartame or sucrose in obese and normal subjects. As the data in Figure 3 shows, these preloads, which were consumed by study participants 20 minutes before their test lunch and dinner meals, decreased postprandial insulin significantly.

Figure 3: Blood glucose response in man with preloads of either sucrose, aspartame or stevia (Anton. 2010)

Now, the obvious question we have to answer is: how did that work? There are different speculative and proven mechanisms that could contribute to the anti-diabetic effects of stevia:

• one study showed that Stevia rebaudiana will inhibit the pancreatic enzyme alpha-amylase and alpha-glucosidase and thus the breakdown of carbs in the intestine (Adisakwattana. 2010),

• 

  Figure 4: Effects of Stevia extracts on glucose transport activity compared to the effect of insulin. SH-SY5Y (a) and HL-60 (b) cells were treated with steviol glycosides (1 mg/mL), with 100 nM insulin (I), with steviol glycosides and insulin simultaneously, or 1 mM standard compounds (StReb, StStev | Rizzo. 2013).

  stevia rebaudiana extracts may also act similar to insulin and are equally effective in increasing glucose uptake,because the co-treatment with insulin and stevia extracts increase glucose uptake significantly higher than the increase due to insulin alone (Rizzo. 2013), , similar results were reported by Akbarzadeh et al. (2015) in STZ-induced diabetic rats
• various studies provide evidence for the anti-oxidant effects of stevia and respective extracts, which will - in view of the inflammatory nature of type II diabetes - obviously contribute to its anti-diabetic effects
• at least one study shows that isostevial, one of the stevia glycosides, appears to work part of its magic via activating the PPAR receptor alpha (Xu. 2012)

Whether there is one specific agent that is responsible for the previously listed effects is still debated. Among the "suspects" are primarily steviol glycosides for which anti-hyperglycemic effect has been observed in doses ranging from 5 mg / kg to 200mg/kg (González. 2014)

Is stevia even safe? You will be surprised to hear that, but the safety of the chronic consumption of stevia, the "natural sweetener", cannot be guaranteed (see possible ill effects on fertility). While studies in adult hypertensive patients show that it is "likely safe" when taken orally (250-500mg stevioside) thrice daily for up to two years, scientists argue that it could be "possibly unsafe, [...w]hen taken [by] children, or pregnant or lactating women or for periods longer than two years, due to insufficient available evidence" (Ulbricht. 2010). The same goes for its use by patients with hypotension, hypocalcemia, hypoglycemia, or impaired kidney function. In view of what we know about the possibility of allergy/hypersensitivity to other members the daisy family (Asteraceae/ Compositae), one may also suspect that allergic reactions, which have not been reported in the literature, yet, are not likely.

More specifically, these compounds have been observed to offset "the glucagon hypersecretion by pancreas α cells that's usually caused by prolonged exposure to fatty acids, and changed genes expression responsible for the metabolism of fatty acids" (dos Santos. 2016). They have also been shown to increase the glucose uptake of pancreatic cells, thus rendering them more sensitive to (small) changes in blood glucose levels; and Gonzalez et al. found them to be capable of increasing proinsulin mRNA concentration and insulin in pancreas INS-1 cells - with the result being a sign. increase the content of insulin in cells.

Figure 5: Glucose (left) and lipid (right) levels in rodents after 14 days on a high fat diet w/ different amounts of isosteviol in the diet - the effects are sign., but the effect size is small (Xu. 2012)

Of the various steviosides, dos Santos highlights isosteviol, a stevioside hydrolyzate, in particular, because it has been shown to have especially pronounced influence on glucose metabolism (Xu. 2012) in a 14-day rodent study in which the animals were fed high-fat chow and the oral administration of  isosteviol orally administrated at doses from 1 to 5 mg/kg/day led to a statistically significant decrease in insulin levels, accelerated glucose clearance and improved insulin sensitivity while simultaneously lowering total and LDL cholesterol and increasing HDL - not bad even if the effect size is relatively small, right?

"The mechanism underlying these effects may be related to the expression of PPARα, since this has changed in the treatment with isosteviol. Furthermore, the pretreatment with isoteviol improves antiapoptosis factor Bcl-2 expression and inhibits the NF-kB expression, and increases SOD and GSH-PX activity. Isosteviol has anti-inflammatory effects, which may possibly be related to hypoglycemic effect and the ability to change lipid profile" (dos Santos. 2016).

Unfortunately, the results Xu et al. presented 4 years ago still await confirmation in human studies. The same goes for the first stevia based anti-diabetes "drugs" which seek to increase the bioavailability (in serum) of steviosides by bioconjugating them on biodegradable Pluronic-F-68 copolymer based PLA nanoparticles by the means of nanoprecipitation (Barwal. 2013). These studies exist, like a recent study by Kassi et al. who introduced low glycemic load snacks based on Stevia to a low calorie diet in patients with metabolic syndrome and found this to be a safe and highly efficient means to "further reduc[e] BP [blood pressure], fasting glucose, ox[idized] LDL and leptin compared to a hypocaloric diet alone, decreasing, thus, further the risk of atherosclerosis and DMT2" (Kassi. 2016) - as part of a regular diet and in place of high sugar foods, stevia is thus the most effective.

Figure 6: One of the few long(er) term studies in (diabetic) humans found no effect of 1g rebaudioside on glycemia (Maki. 2008) - so, don't get too excited about stevia being the new metformin.

So what's the verdict then? Well, I guess you won't be happy if I say that more research is, as usually, necessary. Dos Santos is yet right that "Stevia rebaudiana is a good option to be included in the group of nutraceuticals", in view of its "action and its main compounds (stevioside and rebaudioside A) concerning glycaemia control, diabetes consequences, and early development of IR" (dos Sanots. 2016).

In as much as it can be considered a "medicinal herb," though, its safety of and necessity of higher dosages, as well as the exact mechanism of action require further investigation. Whether it makes sense to develop sustained released, high bioavailability 'stevia drugs' does yet appear questionable to me. - in particularly, because isosteviol "is not subject to intestinal hydrolysis and has shown results as therapeutic agent for type 2 diabetes and its consequences" (dos Santos. 2016), without being chemically / molecularly altered - using "regular" stevia and that to replace sugar does therefore still appear to be the best 'anti-diabetic' use for this sweetener which is up to 150 times sweeter than sugar, heat- and pH-stable, and not fermentable | Comment on Facebook!

References:

• Adisakwattana, Sirichai, et al. "Evaluation of α-glucosidase, α-amylase and protein glycation inhibitory activities of edible plants." International Journal of Food Sciences and Nutrition 61.3 (2010): 295-305.
• Akbarzadeh, Samad, et al. "The Effect of Stevia Rebaudiana on Serum Omentin and Visfatin Level in STZ-Induced Diabetic Rats." Journal of dietary supplements 12.1 (2015): 11-22.
• Anton, Stephen D., et al. "Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels." Appetite 55.1 (2010): 37-43.
• Barwal, Indu, et al. "Development of stevioside Pluronic-F-68 copolymer based PLA-nanoparticles as an antidiabetic nanomedicine." Colloids and Surfaces B: Biointerfaces 101 (2013): 510-516.
• Curi, R., et al. "Effect Of Stev/A Reba Ud/Ana On Glucose Tolerance. In Normal Adult Humans." Braz. j. med. biol. res (1986).
• González, et al. "Stevia rebaudiana Bertoni: a potencial adjuvant in the treatment of diabetes mellitus." CyTa – Journal of Food 12.3 (2014): 218- 226.
• Kassi, Eva, et al. "Long-term effects of Stevia rebaduiana on glucose and lipid profile, adipocytokines, markers of inflammation and oxidation status in patients with metabolic syndrome." (2016).
• Maki, K. C., et al. "Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus." Food and Chemical Toxicology 46.7 (2008): S47-S53.
• Rizzo, Benedetta, et al. "Steviol glycosides modulate glucose transport in different cell types." Oxidative medicine and cellular longevity 2013 (2013).
• Ulbricht, Catherine, et al. "An evidence-based systematic review of stevia by the Natural Standard Research Collaboration." Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Cardiovascular & Hematological Agents) 8.2 (2010): 113-127.

If You Want to Lose Weight and Stave it Off, You'd Better Not Drink Water Instead of Artificially Sweetened Beverages

If You Want to Lose Weight and Stave it Off, You'd Better Not Drink Water Instead of Artificially Sweetened Beverages

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Meanwhile, even many of those who are against the use of sweeteners admit that drinking diet coke is less of an obstacle to weight loss than regular coke. That it could, as the study at hand clearly indicates, even promote weight loss compared to water is controversial, though.

It is one of the die-hard rumors in the fitness industry: Artificial sweeteners will stall your weight / fat loss and have your weight jojo back up, when you stop dieting. As a SuppVersity reader you know that this claim is not supported by science. For the first part, controlled trials like the 2014 study by Sørensen et al. actually show that the exact opposite is the case, i.e. that the consumption of artificially sweetened beverages promotes, not hinders weight loss.

Skeptics, however, will say that "in a caloric deficit, and in comparison to regular beverages", which was the scenario in the Sørensen study,  "everything will work" - a valid argument, I have to admit. After all, the alleged insulinogenic effects said people ascribe to non-nutritive sweeteners would be more harmful during phases of attempted weight maintenance; phases as they've been investigated in a recent follow up to a previous study by Peters et al. (2015).

You can learn more about sweeteners at the SuppVersity

Aspartame & Your Microbiome - Not a Problem?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Chronic Sweeten-er Intake Won't Effect Microbiome

Stevia, the Healthy Sweetener?

Sweeteners In- crease Sweet- ness Threshold

To be more precise, Peters' study was a year-long trial designed to compare the effects of beverages sweetened with non-nutritive sweeteners (NNS) to water as part of a behavioral weight management program consisting of 12 weeks of active weight loss (results previously published in Peters et al. 2014) and 40 weeks of weight maintenance (results now published in Peters, et al. 2016).

Figure 1: Weight and waist loss during the initial 12-week weight loss phase of the study (Peters. 2014).

As previously discussed in the SuppVersity News on Facebook, the results from the 12-week weight
loss phase of this trial were in line with those of the previously cited study by Sørensen et al. (2014) - with the important difference, however, that Sørensen et al. compared non-nutritive sweeteners (NNS) to sugar-sweetened beverages, while Peters et al. found that the NNS group experienced greater weight loss during the 12 weeks of active weight loss, as well as more pronounced reductions in waist circumference, blood pressure, cholesterol, LDL, and triglycerides, even if the control group consumed plain water group (Peters. 2014 | see Figure 1 for weight and waist data).

Figure 2: Consuming NNSs decreased the hunger of the subjects during the 12-week weight loss phase (Peters. 2014).

Mechanistically, the observed benefits may be explained by the opposing effects the consumption of NNS sweetened beverages and water had on the subjects' appetite: Unlike the group that kept consuming artificially sweetened beverages and experienced a significant reduction in hunger scores even while dieting, the ones who were allowed to consume only water reported significantly increased levels of hunger on the 0-100 pts hunger scale Peters et al. used (see Figure 2).

Saccharin may be the unhealthy exception to the "inert sweetener" rule.

What about the effects on the microbiome? You may have heard it on BBC's "Trust me I am a doctor": saccharin appears to mess with the gut microbiome in some of us to a degree that affects our blood glucose levels. That's at least what the TV-crews mini-study shows; and in fact, as a SuppVersity reader you know that the grand daddy of artificial sweeteners (that is by the way no longer used in many products) appears to actually exert the negative effects some people ascribe to every form of sweetener. Speaking of other forms. The TV team was also able to show that stevia, which has been shown to affect the microbiome, as well (learn more), does not affect fasting glucose levels.

In the follow up paper, Peters et al. (2015) now report that the 158 male and female subjects in the NNS group did also have an easier time maintaining their weight loss than their 150 peers in the water only group (see Figure 3); a result of which the scientists say that it was neither due to differences in physical activity / sedentary time or caffeine intake, which were (within the usual statistical margins) identical in both groups.

Figure 3: Body weight (in kg) after 52-week (weight maintenance phase | left) and percent body weight regained during the weight maintenance phase (grey = water; black = NNS | right; Peters. 2015).

While Peters et al. (2015) rightly point out that "it is not possible from the present data to explain why the NNS group lost more weight than the water group despite receiving identical weight loss instruction and beverage interventions that both contained zero calories", they are right to conclude that their findings ...

"[...] are important as there continues to be uncertainty about the benefit of NNS for weight management based largely on observational studies showing associations between NNS consumption, obesity and weight gain." (Peters. 2015).

This is particularly true in view of the fact that the data clearly opposes the often voiced claim that NNS promote obesity by interfering with normal mechanisms of energy balance.

Sponsorship? Yes, the study was funded by the American Beverage Association, but (a) the American Beverage Association was not involved in the design, conduct, interpretation, or manuscript preparation of this study and a third-party organization was hired at the PIs’ request to audit data at both clinical sites to check for the accuracy and integrity of the data. Since the latter are furthermore not really open to intepretation, the "sponsorship argument" is a weak one when it comes to defending the initially defined weight loss myth. In addition, it must be said that it is unrealistic to assume that you could do a 1-year study with more than 300 subjects without external funding - especially, if the research question is not on the TOP-list of the government.

This claim, however, is - as far as experimental evidence is concerned - based exclusively on animal studies; studies that conflict with both, the study at hand and the few other published long-term human trials that evaluated NNS for weight loss (Blackburn. 1997; Tate. 2012):

Figure 4: Tate et al. observed that drinking diet beverages (DB) promotes weight loss over water (WA) or paying more attention (attention control | AC) to what you eat (Tate. 2012).

• In a prospective randomized trial, Blackburn et al. found that people with obesity in a weight loss program using NNS food and beverage products lost more weight and maintained a greater weight loss over 2 years compared to subjects not using NNS (Blackburn. 1997). 
• Tate et al. (2012) conducted a 6-month randomized trial in people with obesity and found greater weight loss over 6 months and a greater likelihood of achieving a 5% weight loss in participants drinking beverages with NNS compared with participants in an attention control group. There was no difference in the likelihood of achieving a 5% weight loss between participants in the water group versus the control or between the water group versus the NNS group.

And if we take a look at the totality of research, it becomes obvious that even observational data, some of which is often used to support the claim that artificial / non-nutritive sweeteners were among the driving motors of the obesity pandemic, indicate that artificially sweetened beverages and foods are valuable weight loss tools (Phelan. 2009). Among those of the subjects listed in the National Weight Control Registry who maintained a weight loss of at least 30 pounds for at least 1 year, for example, the vast majority of 78% says that artificially sweetened products has helped them tremendously to achieve and maintain their weight loss (Catenacci. 2014).

Artificial Sweetened Foods Promote, Not Hinder Fat(!) Loss. 1.2kg Body Fat in 70 Days By Eating Artificially Sweetened Products. Lower Hunger, Higher Fat Oxidation | more

So what's the verdict? Reliable experimental evidence for the alleged obesogenic effects of artificially or, more generally, non-nutritively sweetened beverages in humans does not exist. The number of studies showing that it supports short- and long-term weight loss and weight maintenance, on the other hand, is ever increasing.

This does not mean, though, that individual differences may make you more susceptible to overeat when you consume artificially sweetened beverages while dieting. For the average dieter, however, the 2014 study by Peters et al.  and its follow-up show that the opposite is the case. It is thus only logical that the majority of 78% of the successful weight maintainers in Catenacci's observational study from 2014 say "that they helped them control or reduce their total food or calorie intake" | Comment on Facebook!

References:

• Blackburn, George L., et al. "The effect of aspartame as part of a multidisciplinary weight-control program on short-and long-term control of body weight." The American journal of clinical nutrition 65.2 (1997): 409-418.
• Catenacci, Victoria A., et al. "Low/No calorie sweetened beverage consumption in the National Weight Control Registry." Obesity 22.10 (2014): 2244-2251.
• Peters, John C., et al. "The effects of water and non‐nutritive sweetened beverages on weight loss during a 12‐week weight loss treatment program." Obesity 22.6 (2014): 1415-1421.
• Phelan, Suzanne, et al. "Use of artificial sweeteners and fat-modified foods in weight loss maintainers and always-normal weight individuals." International Journal of Obesity 33.10 (2009): 1183-1190.
• 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.
• Tate, Deborah F., et al. "Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial." The American journal of clinical nutrition 95.3 (2012): 555-563.

Artificial Sweetener Saccharin Increases Weight Gain in Rodent Study Without Increasing Food Intake | Plus: Meta-Analysis of Human Studies Says: "No Reason to Worry!"

Artificial Sweetener Saccharin Increases Weight Gain in Rodent Study Without Increasing Food Intake | Plus: Meta-Analysis of Human Studies Says: "No Reason to Worry!"

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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).

You can learn more about sweeteners at the SuppVersity

Aspartame & Your Microbiome - Not a Problem?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Chronic Sweeten-er Intake Won't Effect Microbiome

Stevia, the Healthy Sweetener?

Sweeteners In- crease Sweet- ness Threshold

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.

Was it fat they gained or lean tissue mass? Well, I would like to answer these important questions, but Foletto did not disclose (or not even measure?) this important parameter. The practical relevance and reliability of their results is further reduced due to the small cages (44x34x16 cm individual cages) into which the rodents were confined to reduce their voluntary physical activity during the 14 weeks of the experiment, as well as the exclusion of rats who didn't consume the aspired 70% of the planned 75 kcal in form of yogurt per week (the number of rats who fell into this category is also not disclosed).

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.

Measurable weight increases are a common pattern in rodent studies particularly for the (today rarely used) artificial sweetener saccharin. It is thus well possible that any existing negative effects are compound-specific. For aspartame, for example, similar evidence is rare to non-existent.

Bottom line: In the absence of a proven theory about the mechanism that may trigger the increased weight gain and in view of the lack of health-relevant data (no information about the body composition of the rodents) and health-relevant side-effects you would usually see in response to pathologic weight gain (changes in insulin resistance, leptin or PYY), I can only refer you back to the quote from the latest meta-analysis of the effects of low- to no-energy-sweetener intake on food intake and weight gain in humans, which say 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).

Furthermore, more relevant evidence from human clinical trials supports the use of artificially sweetened foods as dieting aids (Sørensen. 2014 | learn more).

Whether that's enough to convince you that the unproven negative effects of saccharin on caloric expenditure or increases in the glucose transport mediated by gut sweet-receptors, of which Foletto et al. speculate that they may explain the results of their study, are relevant enough to avoid non-nutritive sweeteners altogether is now up to you. For me it's not enough... | Comment on Facebook!

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.