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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).
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.

I can almost guarantee that the results of this study are not sex-specific. Ladies, pick up the weights fater you hit the treadmill, stairmaster, elliptical or other torture instrument you like to use!

It has been a while since the last study on exercise order (cardio or weights first) has been published. Now, scientists from the University of Kurdistan have conducted another study to investigate the effects of intrasession sequencing of concurrent resistance and endurance training on the serum leptin, testosterone, cortisol responses and body composition in obese men.

And don't worry, we are not talking about useless acute-phase data that shows no correlation with either strength or muscle gains, or fat loss (West. 2012). Sheikholeslami-Vatani and colleagues conducted an eight-week study on thirty obese young male students without continuous exercise history (age: 23.2±1.4 year, BMI: 31.8±1.6 kg/m²).
The subjects were randomly divided into three groups: concurrent resistance-endurance (CRE, n = 10) group, concurrent endurance-resistance (CER, n = 10) group and control (C, n = 10) group (no training program). The concurrent training groups (CER and CRE) trained three times a week on alternate days for 8 weeks. The training itself consisted of which consisted of ...

"running with 70—75% of maximal heart rate (HRmax) for 10 minutes which gradually increased to 80% HRmax for 21.5 minutes [plus] resistance training consisted of 3 sets of 8 repetitions at 80% of 1 repetition maximum (1RM) in 5 resistance exercises (leg extensions, lying leg curl, triceps pushdown, bench press and lateral pull down)" (Sheikholeslami-Vatani. 2015). 

In-between the endurance and resistance (or vice versa) training parts of the workouts, the subjects rested for 5 minutes. Blood sampling and skin-fold measurements to asses the body composition was conducted 48 hours before the start of the course and again 48 hours after the last training session (learn why waiting longer for the body comp test may have been better, but no study does that).

Figure 1: Relative changes in hormone levels (left) and absolute and relative changes in body fat fat free mass and body fat % (right) after 8 weeks of doing nothing (C) or doing cardio (CER) or weights (CRE) first (Sheikholeslami-Vatani. 2015).

I've plotted the most important results in Figure 1a & b. So, let's take a look: The first thing that everyone should see is that both workout regimen had relevant health and physique effects:

• Similar gains w/ weights vs. cardio first in trained men | more.

  normalization of leptin levels (health)
• slight increases in testosterone (health)
• increases in cortisol (which are benign | learn why)
• significant reductions in body fat (health + physique)
• increases in fat free mass (health and physique)

References:

• Sheikholeslami-Vatani, D., et al. "The effect of concurrent training order on hormonal responses and body composition in obese men." Science & Sports (2015).
• West, Daniel WD, and Stuart M. Phillips. "Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training." European journal of applied physiology 112.7 (2012): 2693-2702.

Could BIBA be the active ingredient in a pill that solves your weight problems once and for all? Or is that too good be true?

Beta-aminoisobutyric acid, aka BAIBA, is a natural catabolite of thymine. As with many other purported "next big things in fat loss supplements", early rodent studies suggest that it can significantly reduce body fatness through a mechanism that appears to involve increases in fatty acid oxidation (FAO) and reductions in de novo lipogenesis - in particular in the liver (Maisonneuve. 2003 & 2004; Begriche. 2008).

As Karima Begrich et al. point out in a more recent review of the literature, "experimental evidence [... also] suggested that BAIBA could reduce body adiposity through increased leptin expression and secretion" (Begriche. 2010).
Against that background, it is only logical to ask whether we have overlooked a potent natural fat burner with a mechanism of cation that may be beneficial for both losing fat (increase in fat oxidation and decrease in fat storage) and keeping it off (modulation of leptin expression and secretion).

Unfortunately, it does not take long to find the first evidence that blows a hole into the neat "BAIBA could solve the diabesity epidemic"-theory. It comes right from one of the previously cited studies.
In their 2008 study, Begriche et al. were able to confirm that the provision of 100mg/kg per day (for humans that would be ~8mg/kg per day) of Beta-aminoisobutyric acid triggers significant reductions in body fat gain in lean mice (Figure 1, left).

Figure 1: 100mg/kg/day BAIBA may be an anti-weight gain supplement The data from obese rodents (rights) does yet suggest that it is not a weight loss supplement (Maisonneuve. 2004) | Anti-obesity, but not weight loss effects were also observed in obesity prone rodents in a 2008 study by Begrich et al. at the same dosage of BAIBA.

What the same amount of BAIBA did not do, though, was to prevent the weight gain in already obese mice (Figure 1, right). In view of the fact that the same discrepancies were observed for liver fat and total body weight (not shown in Figure 1), the currently available evidence clearly doesn't support the use of BAIBA as a classic "fat burner".
Overall, it does thus appear as if Begrich's own conclusion that BAIBA supplements "may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity" (Begrich. 2010) is only partly warranted:

• While BAIBA may be useful to ameliorate the body fat gain in lean individuals and would thus in fact be an "attractive pharmacological strategy in order to prevent [...] obesity" (ibid.) in an obesogenic environment,
• it appears to be more than just 'a little too early' to assume that BAIBA supplements could also be used to "treat" (ibid.) obesity in individuals who are already carrying >50% more body fat on their frame than the average lean person.

• Metabolic Damage, Energy Intake & the Human "Energy Thermostat" - An Update Based on Recent Studies | read it!

  the increase in adiponectin that is produced by one's fat cells has been linked to important health markers, like increased insulin sensitivity and improved markers of lipid management.
• the increase in leptin production, however, may be of greater importance, because the diet- or rather fat-loss induced remodelling of the adipose tissue (many small empty fat cells) will reduce the production of the "you're fat enough" signal leptin and thus increase the risk of formerly obese individuals to regain every pound (or even more) of body fat they have painfully lost over months of hard dieting.

References:

• Begriche, Karima, et al. "β‐Aminoisobutyric Acid Prevents Diet‐induced Obesity in Mice With Partial Leptin Deficiency." Obesity 16.9 (2008): 2053-2067.
• Begriche, Karima, Julie Massart, and Bernard Fromenty. "Effects of β‐aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesity." Fundamental & clinical pharmacology 24.3 (2010): 269-282.
• Maisonneuve, Caroline, et al. "Mitochondrial and metabolic effects of nucleoside reverse transcriptase inhibitors (NRTIs) in mice receiving one of five single-and three dual-NRTI treatments." Antimicrobial agents and chemotherapy 47.11 (2003): 3384-3392.
• Maisonneuve, Caroline, et al. "Effects of zidovudine, stavudine and beta-aminoisobutyric acid on lipid homeostasis in mice: possible role in human fat wasting." Antiviral therapy 9.5 (2004): 801-810.