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!"

artificial sweetener artificial sweeteners diabesity fat gain glucose health insulin leptin lose fat saccharin sweeteners weight gain

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).

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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.

GABA Supplementation Improves Glucose Management - Even in Healthy Subjects | Significant Reduction in Glycated Albumin Levels After Only 7 Days on 3x2g GABA per Day

GABA Supplementation Improves Glucose Management - Even in Healthy Subjects | Significant Reduction in Glycated Albumin Levels After Only 7 Days on 3x2g GABA per Day

anti-diabetes beta cells blood glucose diabetes gaba gamma aminobutyric acid glucagon glucose management health insulin lose fat

No acute changes in blood glucose, but extreme changes in insulin levels. How can this trigger a reduction in glycated albumin - How's that possible? 

You've read about gamma aminobutyric acid (GABA) at the SuppVersity before. While most people think of it mainly as a calming agent, though, SuppVersity readers know that it has the remarkable ability to heal the insulin producing β-cell in rodents by stimulating their replication, protecting them against apoptosis, and attenuating insulitis (Soltani. 2011; Tian. 2013; Prud'homme. 2014; Purwana. 2014). And while these favorable effects were first observed in mice, researchers are quite sure that they are valid in humans, too- that's also because said effects have been confirmed only recently by Tian et al. (2014) and Purwana et al. (2014) in vitro as well as in xenotransplanted human islets.

Learn more about the effects of GABA & co at the SuppVersity

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If you know that, the observations researchers from the Fudan University in Shanghai report in their latest study probably won't come as a surprise. In their investigation into the  pharmacokinetics and pharmacodynamics of GABA in healthy volunteers, the researchers found that the chronic provision of 2g of GABA three times per day triggers a highly significant decrease in glycated albumin (GA) levels, the intermediate measure of blood glucose control (in-between acute blood glucose measurements and HbA1c | Roohk. 2008), within only 7 days.

Figure 1: Acute glucose (top) and insulin (bottom) response after single and repeated administration of 2g of GABA (left). Chronic effects of repeated dose-administration of GABA on glycated albumin (right | Li. 2015).

If you scrutinize the data in Figure 1, though, there are a few questions we still need to find answers to. Obviously, the acute administration of GABA (Figure 1, left) lead to significant increases in insulin - both, under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01).

Glucose, insulin and glucagon: Let's briefly recap how the three are related. To lower your glucose levels, your body produces insulin which will then tell your cells suck the glucose from the bloodstream. If the glucose levels are getting lower and lower, your body produces glucagon which will then trigger a cascade of events to increase your blood glucose levels. This can be done by mobilizing stored glycogen (mostly from the liver) or producing new glucose via gluconeogensis - a process that relies heavily on amino acids, first and foremost alanine and glutamine.

Usually, this 1.4-fold or 1.6-fold increase in insulin should trigger a significant (at least transient) decrease in blood glucose. Since the latter wasn't the case in either the fasted or the fed tests the scientists conducted on the twelve subjects, who participated in the open-labeled, three-period trial, it appears more than counter-intuitive that the chronic administration of GABA which does not accumulate in the body and was found to be almost completely absorbed in 60 minutes and to have a half-life of 5h still lead to an GA decrease of approximately 11-12%.

Now this obviously confirms that GABA, due to its ability to increase islet hormonal secretion, has potential therapeutic benefits for diabetes, what the study does not tell us, though, is whether the lack of immediate effects on blood glucose levels can, as the scientists suspect, "in part be attributed to GABA-induced counter regulatory mechanisms, especially elevated glucagon" (Li. 2015) which rose so that the insulin-to-glucagon ratio remained unchanged. Yet while the latter could explain why the subjects did not become hypoglycemic in the face of increased insulin levels, the lack of certainty with respect to the underlying mechanisms makes the study results difficult to interpret.

As a loyal SuppVersity reader you will know that I talked about the potential need to re-balance glucose levels and its paradoxically agitating effects in a 2013 episode of SHR, already.

So what's the verdict, then? Whether and for whom GABA can be useful tool to improve his or her blood glucose management is virtually impossible to tell based on the study at hand. In spite of the fact that the scientists observed only minor adverse events such as transient dizziness and a sore throat, a further reduction of glycated albumin levels is not necessary an advantage that's worth having elevated insulin and glucagon levels. The latter would after all promote the use of proteins or rather amino acids as substrate for gluconeogenesis, the process of which the scientists believe that it is responsible for the non-existent instantaneous glucose response in the study at hand, while the former, i.e. the increase in insulin levels, is well-known for its negative effects on fatty acid oxidation.

Overall, "the verdict" is thus that we need additional research in both, healthy and diabetic individuals to be able to tell for whom the benefits of chronic high(er) dose (3x2g per day) GABA supplementation outweigh potential side effects. If you asked me for an educated guess, though, I would say (pre-)diabetics benefit while the average individual sees either no relevant benefits or detrimental effects due to the repeated need to re-stabilize the blood sugar levels... a phenomenon of which I have by the way previously said and written that it may explain the paradoxically agitating effects the ingestion of GABA has on some individuals - most likely those with already low(ish) blood glucose levels | Comment on Facebook!

References:

• Li, Junfeng, et al. "Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics." Frontiers in Pharmacology 6 (2015): 260.
• Prud’homme, Gérald J., et al. "GABA protects human islet cells against the deleterious effects of immunosuppressive drugs and exerts immunoinhibitory effects alone." Transplantation 96.7 (2013): 616-623.
• Prud’homme, Gérald J., et al. "GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity." Biochemical and biophysical research communications 452.3 (2014): 649-654.
• Purwana, Indri, et al. "GABA promotes human β-cell proliferation and modulates glucose homeostasis." Diabetes 63.12 (2014): 4197-4205.
• Roohk, H. Vernon, and Asad R. Zaidi. "A review of glycated albumin as an intermediate glycation index for controlling diabetes." Journal of diabetes science and technology 2.6 (2008): 1114-1121.
• Soltani, Nepton, et al. "GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes." Proceedings of the National Academy of Sciences 108.28 (2011): 11692-11697.
• Tian, Jide, et al. "γ-Aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model." The Journal of Immunology 173.8 (2004): 5298-5304.
• Tian, Jide, et al. "Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis." Autoimmunity 44.6 (2011): 465-470.
• Tian, Jide, et al. "γ-Aminobutyric acid regulates both the survival and replication of human β-cells." diabetes 62.11 (2013): 3760-3765.
• Tian, Jide, et al. "Combined Therapy With GABA and Proinsulin/Alum Acts Synergistically to Restore Long-term Normoglycemia by Modulating T-Cell Autoimmunity and Promoting β-Cell Replication in Newly Diabetic NOD Mice." Diabetes 63.9 (2014): 3128-3134.

World Diabetes Day: Is Bariatric Surgery the Only Tool to Send T2DM into Remission? Adherence to 6 Months of Daily Exercise and Eating 500kcal/day Less Works, Too!

World Diabetes Day: Is Bariatric Surgery the Only Tool to Send T2DM into Remission? Adherence to 6 Months of Daily Exercise and Eating 500kcal/day Less Works, Too!

bariatric surgery diabetes lose fat T2DM weight loss surgery

Diabetes is a disease that is currently often only managed, not treated and that despite the fact that scientists know ways to send T2DM it into remission.

With the 14th of November being the World Diabetes Day, I thought it may be worth taking a look at the available evidence on treating, not just managing diabetes. If you do just that, there is one treatment that sticks out: Bariatric surgery.

There is currently little doubt that weight loss surgery is the most promising tool doctors have to actually "treat" type II diabetes. As Esposito et al. point out in their recent review of the literature,  "more information is [however] needed about the long-term durability of comorbidity control and complications after bariatric procedures" (Esposito. 2015).

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Why's that? Well, while the review which comprised three randomized controlled trials and one prospective study that compared the effect of Roux-en-Y gastric bypass (RYGB) procedure against optimal medical therapy, shows that the percentage of diabetic patients in remission (hemoglobin A1C < 6–6.5 % without medications) ranged from 38 to 75 % at the end of follow-up, the large inter-individual differences and the fact that the same review also says that

"[i]ntensive lifestyle intervention is also superior to conventional treatment for inducing remission of type 2 diabetes, with remission rates of type 2 diabetes between 10 and 15 % at 1 year of follow-up" (Esposito. 2015), 

it appears to me as if it was more than worthwhile to highlight that (a) surgery is not the only tool and (b) it is not a reliable method to help people regain control over their health. In fact, it is not the surgery but what happens afterwards that determines ultimate success and here, studies show the same factors to determine between failure and success that would make weight loss surgery obsolete for many non-extremely-obese type II diabetics in the first place. Which factors that would be? Here is a selection that was compiled by Elfhag and Rössner in 2005, already:

Table 1: Factors associated with weight loss maintenance and weight regain after intentional weight loss according to a literature review (Elfhag & Rössner. 2005)

You're seeing patterns you don't observe (left hand) or do observe (right hand side of Table 1) in your type II diabetic uncle or aunt? Well that's certainly no coincidence. The results Elfhag & Rössner published published in 2003 have been repeatedly confirmed.

Figure 1: If you look at the relatively low number of subjects who weren't able to maintain at least 50% of their weight loss, it should become obvious that at least within the first year RYGB surgery is not as black as it is painted by some critics (Cooper. 2015).

Nevertheless, more recent research such as a 2009 study by Odom et al. are useful because they (a) quantify known risk factors and add new ones:

• Food urges is associated with a 5.1x increased risk of weight regain.
• Not feeling that the surgery has improved ones life is linked to a 21.5x increased risk.
• Alcohol or drug use is associated with a 12.74x increased risk.

Against those figures, the 6% reduced risk of significant weight gain  in those with lower scores on a test for depression Odom et al. observed in their analysis of the data appears to be of surprisingly minor practical significance.

After sign. weight loss beta-cells can be "resurrected". Meaning they will undergo a process of apoptosis, death and regeneration (Su. 2015).

But isn't the damage already done? While the damage is done, recent research clearly indicates that once the excess weight and with it the chronic hyperglycaemia, hyperlipidaemia and/or cytokines are gone, the damaged beta-cells "undergo the process of rebirth, which involves apoptosis evasion, regeneration and improved beta-cell function" (Su. 2015). While Su et al. point out that the research is not far enough to copy the effects with a drug, it is yet far enough to say that weight loss surgery works and that's what matters, no?

Self monitoring, on the other hand, doesn't only cut the risk of significant weight gain by 46% and is thus practically relevant, it is also in line with the notion of "being willing and able to do what it takes" that emerges from is the gist of the items on the list Elfhag & Rössner compiled back in 2005.

So what does it take, then?

Self-monitoring is yet only one of the points on the "it takes all this"-list you would have to hand somebody who wants to send his type II diabetes into remission. The be-all and end-all for >90% of the type II diabetics is - even if you are constantly bombarded with opposing messages - the induction of a negative energy balance of which studies Malandrucco et al., who put 14 severely obese type II diabetics on  very low calorie diet (400kcal /day), show improvements in beta cell function after only 7 days! These are experimental results epidemiologists with their "people are not eating too much and moving too little, there must be another reason we are fat"-bogus will have a hard time to debate.

Figure 2: The amount of overweight lost is the only significant predictor of remission of remission of type 2 diabetes mellitus (T2DM) after gastric bypass in a cohort of 177 patients with T2DM who had undergone Roux-en-Y gastric bypass from 1993 to 2003 had 5-year follow-up data available (Chikunguwo. 2010).

I won't negate that there are corollary effects such as changes in satiety hormone production, the new found ability to exercise (let's be honest, with lean and muscular 150lbs it's cheap to say that someone who weighs 500lbs is just too lazy to work out - at that weight he, let alone she, is simply unable to work out!), the motivation that comes with the first visible results and so on and so forth. When all is said and done, though, studies show that "[w]eight regain [is the only] statistically significant, but weak predictor, of T2DM recurrence" after weight loss surgery (Chikunguwo. 2010).

There's more than just one study showing that lifestyle changes alone can reverse type II diabetes! Partial or complete remission of diabetes, defined as transition from meeting diabetes criteria to a prediabetes or nondiabetic level of glycemia (fasting plasma glucose <126 mg/dL and hemoglobin A1c <6.5% with no antihyperglycemic medication) can be achieved only, though, if the intervention triggers significant weight loss and improvements in fitness levels. That's what a 2012 review in JAMA shows. With the -7.9% extra weight loss and the +6.4% extra increase in fitness, subjects who participated in intense lifestyle interventions were 6x more likely to achieve remission than those who participated in the typical "you should eat more healthy and do some cardio"-bogus studies. With a remission rate of 11.5% in the first and 7.3% after four years, Gregg's review does yet support the previously highlighted need of determination and consistency.

In the previously cited study by Chikunguwo, for example the subjects who achieved diabetes remission had lost on average 70% of their excess weight. Those who failed to normalize their blood glucose management, still hat ~50% of their overweight on their hips. That long-term success is determined by weight loss, not the often cited changes in satiety hormone production that occur in response to the surgery is also supported by several reviewers. Gumps et al. (2005) for example state that

1. 

   "Metabolic damage" may make it harder, but not impossible for "reduced obese" individuals to stay lean | learn more

   All forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. 
2. Improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake. 
3. In the long-term by decreased fat mass and resulting changes in release of adipocytokines. 

It should and that's the logical and scientifically confirmed conclusion one can draw based on the previously presented facts, thus be possible to see the same beneficial effects that have been observed in many after weight loss surgery in the selected few who manage to lose their weight by "simply" turning their lifestyles' upside down.

Only recently, Philip A. Ades and colleagues from the University of Vermont Medical Center reported in a paper in the Journal of Cardiopulmonary Rehabilitation & Prevention that partial remission of type II diabetes can be achieved within only 6 months if the subjects were willing to participate in a formal lifestyle program that helped them to lose 7.3kg of fat mass (9.7kg total weight loss | see Figure 3 in the bottom-line). The cornerstones of this program, however, won't make every type II diabetic happy. It didn't just involve a 500kcal/day deficit, but also an "almost daily" exercise program consisting of "high-caloric expenditure exercise," with 1 to 3, 45- to 60-minute sessions per week of supervised on-site exercise and home walking on other days for a total of 5 to 6 days per week of exercise.

Figure 3: If a given life-style intervention facilitates high enough rates of fat loss, remission to tolerable HbA1c levels (see dashed line in small graph) occurs in more than half of the subjects (Ades. 2015).

Type II diabetes is treatable! That's the good news. The bad news is that the only treatment that doesn't require the same efforts people were not willing to go through in the years over which they acquired one extra-pound of body fat after the other is bariatric surgery. And even here, only those who are really willing to make a change have a good chance of reversing type II diabetes.

An alternative, in form of an intense diet + exercise lifestyle intervention exists; and while it may take longer to work, remission rates should border zero for all of those who understand that they cannot return to their previous diet and activity levels. Now I will leave it up to you to decide whether that's a good or bad news on "World Diabetes Day" | Let me and others know what you think and comment!

References:

• Ades, Philip A., et al. "Remission of recently diagnosed type 2 diabetes mellitus with weight loss and exercise." Journal of cardiopulmonary rehabilitation and prevention 35.3 (2015): 193-197.
• Chikunguwo, Silas M., et al. "Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass." Surgery for Obesity and Related Diseases 6.3 (2010): 254-259.
• Cooper, Timothy C., et al. "Trends in weight regain following roux-en-Y gastric bypass (RYGB) bariatric surgery." Obesity surgery (2015): 1-8.
• Elfhag, K., and S. Rössner. "Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain." Obesity reviews 6.1 (2005): 67-85.
• Esposito, Katherine, et al. "Remission of type 2 diabetes: is bariatric surgery ready for prime time?." Endocrine 48.2 (2015): 417-421.
• Gregg, Edward W., et al. "Association of an intensive lifestyle intervention with remission of type 2 diabetes." Jama 308.23 (2012): 2489-2496.
• Gumbs, Andrew A., Irvin M. Modlin, and Garth H. Ballantyne. "Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss." Obesity surgery 15.4 (2005): 462-473.
• Malandrucco, Ilaria, et al. "Very-low-calorie diet: a quick therapeutic tool to improve β cell function in morbidly obese patients with type 2 diabetes." The American journal of clinical nutrition 95.3 (2012): 609-613.
• Su, Yinjie, Yanling Zhao, and Chaojun Zhang. "Bariatric surgery: beta cells in type 2 diabetes remission." Diabetes/metabolism research and reviews (2015).

Health & Weight Loss Start in the Gut: Probiotics Trigger Fat Loss Without Dieting | Casein Improves Lipid Metabolism

Health & Weight Loss Start in the Gut: Probiotics Trigger Fat Loss Without Dieting | Casein Improves Lipid Metabolism

casein gut health health lipid metabolism lose fat probiotics

Gut health is "all the rage", lately. So even if it's true that this may be one of the most culpably neglected areas of research in the past century, we should still be careful not to hype the effect of the gut on your physique and health too much.

Well, probiotics and the human microbiome (the one in the gut and elsewhere) are all the rage, these days. Against that background, it's not really surprising that a probiotic supplement and thus a human microbiome modulator made it into the SuppVersity news (again). What may be surprising, though, is the fact that casein didn't just do the same, but that its appearance here in the news is not due to its muscle building prowess. Rather than that, casein made the cut, because a recent study by Francois Mariotti, et al. shows that - even in comparison to whey protein - casein attenuates the potentially unhealthy postprandial triglyceride response to a mixed high-fat meal in healthy, overweight men.

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• Cheesy! Casein keeps your trigs in check - Due to the interaction between elevated postprandial triglyceride levels, insulin resistance and cardiovascular disease, the results of the previously mentioned study by Mariotti et al. (2015) may be of interest not just for all of us. After all, the proposed mechanism of which the authors, scientists from the AgroParisTech speculate that it is a direct result of the same

  "solubility of casein and its precipitation that forms a gel in the stomach [which have long been] known to influence its rate of absorption and postprandial protein metabolism in the context of regular, low-energy meals" (Mariotti. 2015),

  as the marked effect on the chylomicron kinetics and decrease in postprandial TGs, a risk factor for cardiovascular disease, the French scientists observed in the study at hand.
  

  

  Figure 1: Area under the curve for triglycerides (did respond), amino acids (didn't respond) and glucose (didn't respond) in 10 overweight subjects after consuming isocaloric high-energy meals with 15% of the energy from protein in form of casein (CAS), whey protein (WHE) or alpha-lactalbumin enriched whey (LAC | Mariotti. 2015)

  As you can see in Figure 1, the proteins which made up exactly 15% of the total energy content of the high-fat meal that was fed to 10 healthy overweight men with an elevated waist circumference (>94 cm) did not affect the subjects' postprandial plasma glucose, amino acids, insulin, or nonesterified fatty acid levels (which would, by the way, suggest that ingesting whey or an alpha-lactalbumin enriched whey protein with a meal ruins its amino acid absorption advantage). The study outcome that did differ, though were the postprandial triglycerides (TGs) levels, where the provision of casein lead to a highly significant 22% (+/- 10%) reduction in the 6-h area under the curve.

And I thought casein was bad for the heart? Well, there are in fact concerns that certain forms of casein - more specifically, beta-casein A1 - could be associated with ishaemic heart disease (McLachlan. 2001; Laugesen. 2003). Experimental evidence from humans that would confirm what epidemiologists suggests is yet lacking and the corresponding research happens to be pimped by New Zealand who have the lowest number of A1 cows in their herds | learn more.

• As the authors point out, similar trends were shown for plasma chylomicrons [apolipoprotein (apo)B-48; P < 0.05], yet not for the postprandial oxidative stress (plasma hydroperoxides and malondialdehyde), endothelial dysfunction (salbutamol-induced changes in pulse contour analysis), or low-grade inflammation. This is also why it is as of yet only a logical, but hitherto unsupported hypothesis that consuming casein (micellar casein, not regular sodium or calcium caseinates) would also reduce one's cardiovascular disease risk. Eventually, it does yet appear to be the more reasonable adjunct to a full meal anyway - the purpose of the latter is after all to keep you satiated for a long time; and that's where casein is unquestionably a better choice than whey.
• Probiotics - 0.5% body fat reduction, and a 2.68 cm² reduction in subcutaneous fat area are not much, but they occurred in the absence of diet and exercise - If the trend continued and the 120 nondiabetic and overweight subjects Jung et al. divided into two groups: There was the probiotic group with 60 individuals who consumed 2 g of powder of two probiotic strains, L. curvatus HY7601 and L. plantarum KY1032, each at 2.5 × 109 cfu, twice a day. And there was the and a placebo group, likewise 60 individuals, who consumed the same amount of powder that did not contain any probiotics.
  

  

  Figure 2: Changes in body composition according to waist measurement and CT scans - All values are relative changes in waist and fat area measure from week 0 to week 12 (Jung. 2015).

  Both groups were advised to take their supplements immediately after breakfast and dinner, but only the probiotic group saw relevant improvements in body fat at slow) pace - albeit a pace at which it would take them "only" 5 years to finally make it into healthy body fat zones.

Probiotics under urgently needed scrutiny: Many Probiotics Contain Antibiotic Resistant Bacteria. Plus: Number of Live Bacteria is up to 95% Below Label Claims | Learn more.

Prebiotic supplements are not created equal! You may remember my recent article on (a) antibiotic resistances in supplemental probiotics and (b) the lack of viable bacteria in the different supplements the researchers analyzed. It should be obvious that these results mean that even though the study at hand appears to suggest that everyone should take probiotics, further research is needed before we can say which of the many pills on the market this should be... ah, and by the way. It is still not clear whether the same bacteria that are benefical for the obese are anywhere close to beneficial for lean athletic individuals. Rather than general recommendations, I expect the future of probiotic supple-ments to be individual (based on diet and metabolic data).

• Ok, that's painfully slow, but given the fact that the food intake of both groups didn't differ significantly, it is still noteworthy that the 2 g of probiotic powder which contained contained 0.1 g of L. curvatus HY7601, 0.1 g of L. plantarum KY1032, 1.24 g of crystalline cellulose, 0.5 g of lactose, and 0.06 g of blueberry-flavouring agent made the subjects lose significant amounts of body fat, while their peers who received 2 g of a placebo powder that contained 1.34 g of crystalline cellulose, 0.6 g of lactose, and 0.06 g of blueberry-flavouring agent kept gaining.
  

  

  Figure 3: The provision of the probiotic supplement did also trigger significant improvements in the above markers of cardiovascular disease risk - if it's not the small fat loss, it would thus be the potential CVD risk reduction that makes the use of probiotic supplements attractive especially for overweight individuals (Jung. 2015).

  In conjunction with the likewise statistically significant beneficial effects on health markers like LDL oxidation and LDL particle size which indicate significant improvements in cardiovascular disease risk, this is still the first non-sponsored study (the study was financed by Korean Ministry of Science) that shows that supplementing with commercially available probiotics in man may actually produce health-relevant beneficial effects.

Probiotics aren't for the overweight and obese, only. A recently discussed study, for example, showed that a patented multi-strain probiotic will reduce the fat gain on a 4-week "bulk" by more than 50% - and that's in twenty young men who consumed an extra 1,000kcal per day | more.

You are kidding me, right? No, I am not. I know that neither casein nor probiotics appear to be game-changers, but eventually you will have to understand that the one trick, supplement or modification of your lifestyle cannot correct the 10,000 mistakes you have or even are still making. Losing fat and getting healthy is about taking one baby step at a time; and the studies by Mariotti et al. and Jung et al. describe two promising ways of taking another of these steps.

In that it would be great if we knew for sure how both of them work on a mechanistic (molecular) level. As of now, the only thing that appears to be certain, though, is that they act at the level of the gut. One by affecting the digestive process, the other by modifying the make-up of the intestinal microbiome of which more and more studies appear to suggest that it may not be triggering, but at least perpetuating the ill health effects of obesity | Comment!

References:

• Jung, Saem, et al. "Supplementation with two probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, reduced body adiposity and Lp-PLA 2 activity in overweight subjects." Journal of Functional Foods 19 (2015): 744-752.
• Laugesen, Murray, and R. B. Elliott. "Ischaemic heart disease, Type 1 diabetes, and cow milk A1 β-casein." (2003).
• Mariotti, François, et al. "Casein Compared with Whey Proteins Affects the Organization of Dietary Fat during Digestion and Attenuates the Postprandial Triglyceride Response to a Mixed High-Fat Meal in Healthy, Overweight Men." The Journal of nutrition (2015): jn216812.
• McLachlan, C. N. S. "β-Casein A 1, ischaemic heart disease mortality, and other illnesses." Medical Hypotheses 56.2 (2001): 262-272.

Nine Short Workouts (AM+PM) p. Week Yield Extra Strength, Size and Performance Gains Compared to Volume Matched 3-Day Split, All Differences are Non-Significant, Though

Nine Short Workouts (AM+PM) p. Week Yield Extra Strength, Size and Performance Gains Compared to Volume Matched 3-Day Split, All Differences are Non-Significant, Though

AM/PM bodybuilding build muscle exercise science fitness fitness model frequency high volume lose fat performance training science training volume workout frequency workout routines

15 min in the AM, 15 in the PM = Win? For many of you that may sound laughable, but according to a recent study from the University of Copenhagen it is at least as effective as three "mammoth" workouts-sessions per week.

What kind of trainee are you? Do you hit the gym thrice a week, spend two hours there and crawl out of the gymdoors totally exhausted? Yeah... Well that means you're not the fitness model guy, who trains twice a day for 15-20 minutes only and swears that this is the only way to do it?

After all these questions you're probably asking yourself if the answers you gave in your mind were good or bad for ya? Right? Well, eventually, both forms of training can be equally effective. If we take a closer look at the non-significant study outcomes in a recent paper by scientists from the University of Copenhagen (Kilen. 2015), though body composition and strength may in fact benefit more if you train more frequently - even if the total workout volume is the same.

No single workout routine works forever. Periodize to make continuous progress!

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Workout volume? Yes, that's the number of sets and reps. So, let's say you do three 45-minute training sessions weekly, including 1 strength on Monday, 1 high intensity cardiovascular (HIIT) session on Wednesday, and 1 muscle endurance session on Thursday, then those 3x45 minutes + warm-up exercise are your total workout volume.

In case that's what you're doing on a regular basis, you're training just like those of the 21 study subjects (10 men, 11 women; 25 +/- 3 years) with some previous training experience who were randomly assigned to the "classical" training program in the previously mentioned study by Kilen, et al. (2015). If you're rather the fitness model type, you may recognize your own training in what the other subjects did, i.e. a "micro training" program with a total of nine 15-minute training sessions weekly that were divided equally between strength training, high-intensity cardiovascular training, and muscle endurance training and performed in the AM and PM from Monday to Friday (there was no PM training on Friday, though, and cardio and strength were rotated | see caption of Table 1).

Table 1: Description of the two different training regimen (Kilen. 2015) | *To minimize the potential negative effect of concurrent cardio + strength training, MI performed 2 days of strength (Mon and + Tue) and 1 day of cardio training (Wed) in odd weeks, and 1 day of strength (Mon) and 2 days of cardio training (Tue + Wed) in even weeks.

Unlike the training frequency and rest between workouts, the strength training, HIIT and muscular endurance training sessions, themselves, were identical in both groups:

• Strength training consisted of leg exercises (deadlifts, lunges, step-ups, and 1 leg squats), with 1–2 warm-up sets and 2–3 target sets of 8RM, and upper-body exercises (pullups, dips, weighted push-ups, and 1 arm rows), with 1–2 warm-up sets and 2–3 target sets of 5RM. For progression, the exercises were adjusted using extra loading (sandbags in 1-kg steps) if the subjects were able to accomplish more repetitions than prescribed. If the subjects were not able to perform the number of repetitions prescribed, they performed as many as they could in proper form and finished the set conducting only the eccentric phase of the exercise. 
• High-intensity cardiovascular training (HIIT) consisted of running for 2 and 4 minutes at an average speed of 15.1 and 14.5 km/h, respectively, which elicited ;90% maximal heart rate during exercise. Micro training performed two 4-minute run intervals in the morning with 3 minutes of rest in between and four 2-minute run intervals in the afternoon with 1 minute of rest in between. Classical training performed three 4-minute and six 2-minute run intervals in the same training session with the same rest as MI in between. The training volume was evaluated and the only significant difference was running distance during 2-minute and 4-minute intervals, where MI ran significantly further than CL in each interval. 
• Muscle endurance training consisted of three 5-minute exercise sessions involving 5 different exercises performed continuously for 30 seconds with 30-second rest periods. Micro training conducted 3 sessions; the first was “easy,” the second “hard,” and the third “very hard.” Classical training conducted 9 sessions in the same order, starting over with “easy” on the fourth and seventh sessions. The exercises were weighted lunges (with a 20-kg sandbag); push-ups; shuttle runs; abdominal exercises ([a] regular sit-ups from a supine position with knees bent at 908, fists in contact with the ears and the lumbar arch supported by a folded towel, and [b] diagonal sit-ups from a horizontal supine position, outstretched hand to opposite raised foot, alternating); and back exercises ([a] back extensions on an incline bench and [b] kettlebell swings in a standing position). 

As Kilen et al. point out, "[a]ll training sessions were supervised by scientific staff, and subject attendance" as well as "[h]eart rate [...] during high-intensity cardiovascular training and muscle endurance training for the last 5 weeks of the training intervention" (Kilen. 2015) were recorded.

Figure 1: Relative pre- vs. post changes in all measures performance markers (calculated based on Kilen. 2015).

After the 8-weeks on the respective training regiment, a comparison of the pre- vs. post-training data yielded the following results:

• Increases in shuttle run performance were observed in both group, albeit with a higher significance as far as the pre- vs. post-difference is concerned in the classical training (CL) vs. micro training (MI) group (MI: 1,373 +/- 133 m vs. 1,498 +/- 126 m, p < 0.05; CL: 1,074 6 213 m vs. 1,451 6 202 m, p , 0.001).
• Significant improvements in peak oxygen uptake (3,744 6 +/- 615 mL/min vs. 3,963 +/- 753 mL/min | p < 0.05), maximal voluntary isometric (MVC) force of the knee extensors (646 +/- 135 N vs. 659 +/- 209 N | p < 0.001), MVC of the finger flexors (408 +/- 109 N vs. 441 +/- 131 N, p < 0.05), and the maximal number of lunges performed in 2 minutes (65 +/- 3 vs. 73 +/- 2, p , 0.001), however, were seen only in the micro = high frequency training group.

The question you may be asking yourselves now is: Why does the headline say that there were no significant differences? Well, the lack of statistical significance of the improvements in the classical training group does not suffice for a statistically significant between difference to the micro training group. Statistical significant inter-group differences did not exist either before or after the study. The scientists conclusion that

"similar training adaptations can be obtained with short, frequent exercise sessions or longer, less frequent sessions where the total volume of weekly training performed is the same" (Kilen. 2015)

is thus absolutely correct. The fact that statistical significance for the aforementioned study outcomes was achieved in the micro, yet not in the classical training group does still suggest that the high(er) frequency training regimen may have an adaptive edge... albeit in terms of study outcomes not everyone will deem practically relevant.

Figure 2: Neither the in-group nor the inter-group changes in body composition did reach statistical significance (calculated base on Kilen. 2015). At least in my humble opinion, though, they are still interesting.

Speaking of what people will deem relevant: We haven't addressed the changes in body composition yet. Why's that? Well, if we go by statistical significance, there were none. If we go by %-ages, though, the increase in lean and decrease in fat mass in the micro training, as well as the opposite trends in the classical training group add to the non-significant evidence that it may make sense to train more frequent and that - when all is said and done - total volume may eventually not be the only thing that matters... I mean, if you look at the data in Figure 2 it would - in defiance of the statistical insignificance of the changes - still seem as if the previously mentioned fitness model was right: For him or her, for whom improves body composition are the primary goal, his / her frequent AM/PM training regimen does in fact appear to be the training model of choice | Comment!

References:

• Kilen, Anders, et al. "Adaptations to Short, Frequent Sessions of Endurance and Strength Training Are Similar to Longer, Less Frequent Exercise Sessions When the Total Volume Is the Same." The Journal of Strength & Conditioning Research 29 (2015): S46-S51.