3x15g/Day E401, Sodium-Alginate, Increase Weight Loss and Reduction in Body Fat % on Mild Caloric Deficit by 30-40%! The GPA (Gut-Brain Axis) Makes it Possible.

Image 1: The small amounts of sodium-alginate, aka E401 many chocolates and commercially produced foods contain is obviously not enough to ward off obesity. Otherwise the obesity rates should have fallen not risen with the increase in crappy foods.

Aside from the ubiquitous stimulant based fatburners there is another class of weight loss supplements emerging as of late. Those of you who have read Adelfo's Thursday post, here at the SuppVersity, may have seen his plug for Myotropics' WM-HDP based "new Fat Burning Carbohydrate" ThermiCarb(TM). Now as hilarious as it may sound, this resistant starch is in fact as much of a "fat burner" as any of the 1001 currently available stims is. After all, none of those products actively burns fat. What still makes them effective, though, is their ability to shift substrate utilization away from glucose and towards fat, to curb appetite and to deliver the energy you need to do what it takes to shed body fat, i.e. to function normally while eating slightly less and working out.

Contrary to the good old (and certainly not obsolete) stims, these new "fat burners" act on the gut-brain axis, instead of HPA (the hypothalamus-pituatary-adrenal axis), by stimulating the release of a whole host of peptides from the gut. Among those, the  incretin hormones GLP-1 & co. (cf. "Eat More, Burn More and Lose Fat Like on Crack with GLP-1!?") are probably the best understood among these mis-understood "satiety hormones" with their profound  downstream effects on overall energy expenditure, glucose and fatty acid metabolism (Mudaliar. 2012). 

Is alginate, a polysaccharide from marine brown algae, a novel "fat burning fiber"?

Next to designer-starches such as WM-HDP there is also an increasing interest in the effects natural fiber / fiber extracts, such as the 15g alginate from brown algae the obese subjects (0–55y; BMI 30-45kg/m²) in a recent study from the University of Copenhagen in Denmark had to consume before each of their three meals in the course of a 12-week double-blind randomized parallel-intervention (Jenson. 2012), exert on the endocrine signals from your gut.

Image 2: Popsticles are not the only products containing sodium alginate (E401) as a thickener and stabilizer. If you take a closer look at the ingredients of the stuff in the supermarkets, you will notice that  many commercially produced low fat dairy products, ready made sauces, gravies, dressings, puddings, pies and pastry fillings contain it, as well.

What is alginate? Alginate is a gelling polysaccharide (gelling = it forms a gel which passes slowly through your digestive tract) that is extracted from marine brown algae. In seaweed the mannuronic and guluronic acid based components are responsible for the mechanical strength and flexibility. During the regular extraction process alginate is bound to sodium. The result, sodium alginate, has been used a E401 in various foodstuffs to stabilize, gel or viscosify it for years now (Brownlee. 2005). The appetite reducing effects of sodium alginate and other marine-derived fiber are widely known, but the underlying mechanism is still not completely elucidated. According to the current paradigm, it is related to the interaction of sodium-alginate and calcium during the digestive process and the subsequent changes in viscosity of the gastric content, which has been associated with slowed gastric emptying and a reduction of postprandial glucose and insulin response. Of these the latter, i.e. the prolonged influx of glucose, the absence of blood glucose spikes and the overall reduction in insulin levels is currently believed to be at the heart of the observed satiety effects (Cani. 2009).

What is interesting about this study is that according to the self-set goals of the scientists, which lay at the ground of their "Intention-To-Treat analysis" (ITT), which evaluated the changes in body weight and overall body composition, as well as the improvements of metabolic risk factors as a whole, yielded no differences between the two study arms.

Figure 1: Changes in body weight and body composition in response to caloric reduction (-300kcal/day) with or without supplemental alginate (15g/day) after 12 weeks (large graph); actual weight development over the whole 12-week study period (small graph; directly from Jenson. 2012)

If you do yet take a closer look at the actual study data (see figure 1), you will see that there were very important differences between those dieters who simply consumed 300kcal/per day less (control group) and those who followed the exact same calorically reduced dietary regimen yet with an additional 15g of fiber from sodium alginate before every meal (alginate group)!

Lose more weight, more fat and do this at a constant rate beyond week 9!

Despite the fact that onlye the differences between the reduction in total weight and body fat percentage reached statistical significance, this and the absence of the "weight loss plateau" in week 9+ (see figure 1, right) in the alginate group clearly suggest that much contrary to what Jenson et al. had apprehended, the previously demonstrated short-term weight loss benefits of fibrous algae extract and other dietary fiber (Paxman. 2008; Odunsi. 2010; Peters. 2011; Wanders. 2011) did not disappear after an initial adaptation phase. On the contrary! The 40% greater reduction in body weight, as well as the 36% greater reduction in body fat percentage would be of little value if the body weight stagnated after only -6.78kg weight loss in week 9 and left the dieters with an average BMI of 32kg/m² well in the obesity / danger zone.

Figure 2: Changes in glucose metabolism and ghrelin (left) and lipid metabolism (right) in response to caloric reduction (-300kcal/day) with or without supplemental alginate (15g/day) after 12 weeks (large graph); actual weight development over the whole 12-week study period (small graph; directly from Jenson. 2012)

Looking back at the exact weight development in figure 1 (right), we may thus speculate that the observed improvements of the measured markers of blood glucose management and lipid metabolism of which only the HbA1c (not shown in figure 2) showed a statistically significant inter-group difference (+0.01% in control -0.01% in alginate; p < 0.024) would have reached statistical significance after 16-20 weeks. This is particularly true for the insulin levels, for which the difference between control and alginate group is already borderline significant (p < 0.062) after 12 weeks of alginate supported dieting.

Bottom line useful for the obese, safe, well tolerated, but...

Image 3: Duong Nguyen from the first installment of the SuppVersity Student Spotlight at the beginning and end of his amazing 12-week transformation!

As usual we do however have to remember that the subjects in this study were more than just a little chubby, with body fat percentages in the >40% range a reduction of -5.8% (control) and -8.2% (alginate) is easier achieved than a (from a merely mathematical standpoint) equal -12% of the body fat content from 12% to 10%. So, while healthy dieters don't have to care about the minimal, but statistically significantly lower reduction in blood pressure in response to weight loss with sodium-alginate (the scientists ascribe this to the relatively high sodium content of the alginate supplement), the will probably not benefit in the same way as Jenson's obese subjects from the additional 45g of fiber per day. Well, unless, it exerts similar effects effects as they have been observed for hydroxypropyl-distarches (cf. "Waxy Maize Reloaded") on the expression of GIP, GLP-1 and the whole host of the initially mentioned incretin hormones, and adipokines (Sánchez. 2012) and don't just curb appetite and slow digestion.

If it had all those GBA (gut brain axis ;-) effects, seaweed derived sodium-alginate supplements could however make an ideal adjunct to a ~20% reduction in food intake, a reasonable fat loss workout (e.g. "Step By Step Guide to Your Own Workout Routine - Part V: Example Routines - Round 2: Fat Loss Support Routine") and a stimulant-based fat burner of your choice, whenever you strive to cut a few pounds of body weight. I mean, just imagine if Duong (see image 3), who likewise dieted for 12 weeks would have lost 35% more fat mass - yeah you're right, he would probably have been "disgustingly" lean, as Adelfo likes to call it ;-)

References:

1. Brownlee IA, Allen A, Pearson JP, Dettmar PW, Havler ME, Atherton MR, Onsøyen E. Alginate as a source of dietary fiber. Crit Rev Food Sci Nutr 2005;45:497–510.
2. Cani PD, Lecourt E, Dewulf EM, Sohet FM, Pachikian BD, Naslain D, De Backer F, Neyrinck AM, Delzenne NM. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am J Clin Nutr 2009;90:1236–43
3. Jensen GM, Kristensen M, Astrup A. Effect of alginate supplementation on weight loss in obese subjects completing a 12-wk energy-restricted diet: a randomized controlled trial. Am J Clin Nutr. 2012 Jul;96(1):5-13. Epub 2012 May 30.
4. Mudaliar S, Henry RR. The incretin hormones: from scientific discovery to practical therapeutics. Diabetologia. 2012 Jul;55(7):1865-8. Epub 2012 May 4.
5. Odunsi ST, Vazquez-Roque MI, Camilleri M, Papathanasopoulos A, Clark MM, Wodrich L, Lempke M, McKinzie S, Ryks M, Burton D, et al. Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity. Obesity (Silver Spring) 2010;18:1579–84.
6. Paxman JR, Richardson JC, Dettmar PW, Corfe BM. Daily ingestion of alginate reduces energy intake in free-living subjects. Appetite 2008; 51:713–9.
7. Peters HP, Koppert RJ, Boers HM, Stro ¨m A, Melnikov SM, Haddeman E, Schuring EAH, Mela DJ,Wiseman SA. Dose-dependent suppression of hunger by a specific alginate in a low-viscosity drink formulation. Obesity (Silver Spring) 2011;19:1171–6.
8. Sánchez D, Miguel M, Aleixandre A. Dietary fiber, gut peptides, and adipocytokines. J Med Food. 2012 Mar;15(3):223-30. 
9. Wanders AJ, van den Borne JJGC, Graaf EJMF. Effects of three dietary fiber on food in real life setting. Appetite 2011;57:544.

Anti-Creatine β-Guanidinopropionic Acid (GPA) Increases AMPK, Decreases Blood Glucose & Insulin, Induces Weight loss Without Dieting, Increases Oxidative Capacity and Can Even Delay the Development of Mammary Cancer! BUT...

While he may be so fast that he is almost out of the focus, when the photographer finally released the shutter, Usain Bolt, the fasted man on earth actually doesn't look as if his fiber type composition was highly type II dominant, does he? 

While the relation may be distant, you will soon see that today's blogpost is somewhat related to Saturday's news item about the ability of high dose nicotinic acid to shift the muscle fiber type composition from a towards the oxidative side of things. After all, there is hardly anything that is more "glycolytic" (I am using the word here in a very broad sense) than the use of the intramuscular phosphocreatine stores to squeeze out another rep or explode out of the starting block and sprint towards the finish line in less than 10 seconds.

Ah, yes those phosphocreatine stores, they are great and creatine is the staple supplement for anyone looking to improve his glycolytic performance. But hey, wait a minute: Shouldn't that actually mean that taking creatine would be a bad thing for an ironman (not the one from the cinema, but the Hawaiian ;-)?

GPA - Supplemental creatine unloading for edurance athletes!?

Well, the answer to the question "Is creatine bad for endurance athletes" is, as long as you stick to reasonable doses "No! It isn't.". It neither helps nor hinders endurance performance and a "real" Ironman could probably even get away with one of those sugar-laden "cell-volumizers" without doing much harm. His body is would just burn through the carbs without any of them ending up as additional ballast on his hips. That said, previous studies by Vanakoski et al. or Chwalbiñska-Moneta clearly show that performance detriments are not an issue and in the latter of the two studies, the creatine supplement did even improve the "endurance (expressed by the individual lactate threshold) and anaerobic performance, independent of the effect of intensive endurance training" so that the highly trained rowers who participated in the study at hand would in fact have had an edge at the end of the race and may - if they would have otherwise been on par with the competition - probably have won the race (Vanakoski. 1998; Chwalbiñska-Moneta. 2003).

Surprise: Anyone of you who has ever taken NO Xplode 2.0 (new or old formula) has already been supplementing with GPA - both the original and the "advanced strength" formula contain an undisclosed amount of GPA. Apropos, if you are interested in the differences between the two, check out my previous article on the matter - I guess I don't give away too much, when I tell you that they are few and far between.

There is however a significant difference between not supplementing with creatine and relying on your own body's ability to produce the "meat amino acid" ("creatine" is derived from the greek word for meat) from L-arginine, glycine, and L-methionine and using a "supplement", or rather, another amino acid that does actually hamper its recycling and thus availability by the creatine kinase enzyme. β-guanidinopropionic acid (bGPA, simply GPA or N-(aminoiminomethyl)-beta-alanine), an amino acid with a similar molecular structure as creatine, is such a molecule. GPA reduces the flux through the CK reaction, by reducing cellular creatine uptake and will thus effectively have similar effect as the genetic ablation of the CK enzyme, which does - probably to your surprise - not just hamper the viability of respective mouse mutants, but will also (and here we are getting back to the effects of nicotinic acid) improved their muscular endurance and lead to a shift from type II to type I fiber predominance (Van Deursen 1993; Ventura-Clapier 2004; Vaarmann, 2008).

In short, when you use 5g of creatine as a means to "load" your PCr stores, the administration of GPA will have an "unloading" effect. This effect has in fact been studies in a number of previous studies. The effects and potential side effects of GPA are yet unclear and that despite the notwithstanding that it is freely available on the market and *surprise* you may well have been taking very small quantities of it in the past (maybe even still are), since NO Xplode 2.0 is by no means the only supplement that contains small (and obviously undisclosed) amounts of GPA in its kitchen sink ... ah, I mean "proprietary blend" (see "Ask Dr. Andro: Are There NO Changes in the New N.O.-Xplode 2.0 Advanced Strength Formula?", read full article). Reason enough for Inge Oudman, Joseph F. Clark and Lizzy M. Brewster from the Academic Medical Center in Amsterdam (Netherlands) and the University of Cincinnati to conduct a systematic review to assess the effect of this substance on the mammalian energy metabolism (Oudman. 2013).

So what did the scientists find? Is GPA the "next creatine" we've been waiting for?  ;-)

The primary outcome of the review was the effect of GPA on energy metabolism, function, and morphology of tissues "with high and fluctuating energy demands" (Oudman. 2013) - this includes the obvious,...

• skeletal muscle, where it reduces creatine, phosphocreatine, total creatine, and ATP by 66.1%, 79.7%, 86.7% , and 38.8%, blunted the total creatine kinase activity (-28.6%), but increased the intra-mitochondrial creatine recycling (CK activity) by 200%, reduced the activity of glycolytic enzymes (phosphorylase -38.8%, lactate dehydrogenase -16.2%), increased AMPK expression by 45% and AMPK mRNA by 20%, promoted GLUT-4 expression (+45% in slow-, +33% in fast twitch fibers) and subsequently doubled muscle glycogen content, while decreasing blood glucose (-5%) and insulin levels (-27% in non-diabetic animals), improved endurance during non-/light weight bearing exercises and hampered it during heavier exercise, doubled mitochondrial DNA (evidence for the shift towards an oxidative muscle type), and decreased total and relative muscle weight by 19% and 10% respectively;
• heart muscle, where similar decreases in creatine, phosphocreatine, total creatine, and ATP occurred and GPA decreased the survival rates after myocardial infarction by ~50%

but also the vascular musculature, where no significant effects were observed, in the central nervous system and the brain, where GPA reduced the creatine concentration (brain), doubled the adenylate kinase and succinate dehydrogenase activity (both are involved in energy reallocation), increased the risk of seizures, but showed potentially protective effects against neurodegenerative diseases.  Furthermore the scientists report that GPA reduced creatine uptake in the kidney, reduced the body temperature and increased the amount of BAT (+3.4%, in rodents!). And last, but certainly not least, GPA delayed the development of mammary gland tumors in a rodent model (cf. Chira. 1995; Metzner. 2009)

To summarize...

It looks like a marathon supplement, but it's not even sure that endurance athletes would benefit from taking GPA. In the off.season it could "intensify" the training, but before a race it appears to be rather counter-indicated (photo trainerjosh.com).

Overall the review confirms the notion that the administration of GPA leads to marked reductions in creatine, phosphocreatine, and ATP concentrations and reduces cytosolic, while increasing mitochondrial CK activity in skeletal muscle. These observations stand in line with a shift from a glycolitic to a mitochondrial oxidative metabolism that is facilitated / goes hand in hand with

• a shift from type II to type I fiber predominance,
• increased glucose tolerance, and
• reduced skeletal muscle and body weight

which do not incidentally remind us of the adaptive responses to endurance exercise. It goes without saying that mainstream science is psyched about the "reduced body weight with unchanged food intake" of which the Oudman et al. argue that it "may be related to the fiber type shift, as an association between type II fiber predominance and body weight was previously reported".

Other, per se unquestionably more favorable confounding factors are the increased cellular fatty acid transporter protein concentration, fatty acid oxidative capacity and the compensatory increase in AMPK expression that is actually a response to the perceived energy (ATP) deficiency that develops in response to the administration of GPA (click here to learn more about AMPK's role in fatty acid oxidation and glucose metabolism). So, as paradox as it may sound: Despite its negative effects on the use of glucose as a substrate GPA could actually improve, not deteriorate glucose metabolism via an AMPK mediated "metformin-esque" effect on GLUT-4 expression.

---

Way too many trainees tend to forget the true meaning of "supplement". Supplements are something that "supplement" something else. In the case of creatine supplementation the latter supplements your efforts in the gym and won't (and this has recently been confirmed) build muscle on its own.

So what's the verdict then? Now, all that does certainly sound pretty cool, well - at least for a cut - so would it be better to avoid creatine for leaner muscle gains and use GPA, whenever you are cutting? The first of these bottom-line questions is easy to answer: No! Studies have repeatedly shown that creatine supplementation does not only increase the mass gains, it also improves the ratio of lean to fat mass more than resistance training alone (as long as you the baseline diets are identical).

What about GPA as a diet tool, then? While it certainly would appear that taking (hitherto by the way unknown) amounts of GPA could help you lose weight, it is unlikely that this weight loss will make you look the way, you want to look. I mean if you have to lose weight at all costs, because your health depends on it, GPA could provide a viable AMPK promoter that may help you achieve just that.

Especially strength athletes, sprinters and the like, as well as anyone wanting to look / perform like one of these athletes should yet resort to the tried and proven dietary tweaks to get rid of the extra weight. And there is actually no reason not to continue taking a regular maintenance dose of 3g of creatine during the cut,also in view of the fact that the "beneficial" effects of GPA supplementation are actually brought about by blocking one out of two energy sources - much like keto dieting, by the way, but that's a topic for another blogpost ;-)

Related read: "Ask Dr. Andro: The Pharmacokinetics of Creatine"- Part I & Part II

References:

• Chwalbiñska-Moneta J. Effect of creatine supplementation on aerobic performance and anaerobic capacity in elite rowers in the course of endurance training. Int J Sport Nutr Exerc Metab. 2003 Jun;13(2):173-83.
• Metzner L, Dorn M, Markwardt F, Brandsch M. The orally active antihyperglycemic drug beta-guanidinopropionic acid is transported by the human proton-coupled amino acid transporter hPAT1. Mol Pharm. 2009; 6: 1006– 1011.
• Ohira Y, Inoue N. Effects of creatine and beta-guanidinopropionic acid on the growth of Ehrlich ascites tumor cells: i.p. injection and culture study. Biochim Biophys Acta. 1995; 1243:367–372.
• Oudman I, Clark JF, Brewster LM. The Effect of the Creatine Analogue Beta-guanidinopropionic Acid on Energy Metabolism: A Systematic Review. PLoS One. 2013;8(1):e52879.
• Vaarmann A, Fortin D, Veksler V, Momken I, Ventura-Clapier R. Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice. Biochim Biophys Acta. 2008; 1777: 39–47.
• Vanakoski J, Kosunen V, Meririnne E, Seppälä T. Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations. Int J Clin Pharmacol Ther. 1998 May;36(5):258-62.
• Van Deursen J, Heerschap A, Oerlemans F, Ruitenbeek W, Jap P. Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity. Cell. 1993; 74: 621–631
• Ventura-Clapier R, Kaasik A, Veksler V. Structural and functional adaptations of striated muscles to CK deficiency. Mol Cell Biochem 2004; 256–257: 29–41.