Dietary Fiber - Friend or Foe? Addition of Hydroxpropyl-Methylcellulose, a Non-Fermentable Viscous Fiber, to Standard(!) Rodent Chow Reduces Fat Gain by -22%

Image 1: Just as about everything, these days, you can buy the semisynthetic non-fermentable viscous fiber Hydroxpropyl-Methylcellulose pound-wise from China - this is probably also where the producers of the junk food you hopefully are not eating get their E464 from ;-)

If the health and fitness community on the Internet was a battlefield (personally, I sometimes think it is ;-) one of the ongoing skirmishes would certainly be fought over the question whether the deliberate ingestion of great amounts of dietary fiber was a good or rather a bad thing. I must admit that I have not really made up my mind on the benefits and caveats of increasing or decreasing your fiber intake, partly because the available science appears to be quite inconclusive. This, obviously does not hinder the "ANTI faction" in the fitness and nutrition world to add "fiber" as the 1001 item on their never-ending list of ultimate dietary evils. My gut feeling does yet tells me this has more to do with the fact that mainstream dietary recommendations list dietary fiber as a "healthy food" to eat, than with a thorough research of the available literature, which has, as of lately, been extended by a particularly interesting study from scientists from the Department of Food Science and Nutrition at the University of Minnesota and the Pennington Biomedical Research Center in Baton Rouge, Louisiana (Islam. 2011).

When fiber ain't fiber, natural is not naturally better

Being aware of the partly contradictory results previous studies on the metabolic effect (as measured in the lab and not by the way your poo-poo looks or how often you have to go to the toilette, like the "experts" like to do it ;-), Ajmila Islam and her colleagues fed a group of 6 week-old male Wistar rats a standardized rodent chow (AIN-93G, composition see figure 1 in previous blogpost) with either hydroxypropyl-
methylcellulose (HPMC) or standard cellulose as a source of dietary fiber, which comprised 5% of the animals' otherwise totally identical diets. This obviously sounds nonsensical if you follow the usual black or white approach to nutrition (which btw. is propagated by the mainstream and the ANTIs, as well), after all fiber is fiber and should be good or bad!? Well, it turns out that there are more than subtle differences in

1. the viscosity of the fiber / fiber food mixture, and
2. the fermentability of different types of dietary fiber

Now, cellulose the main component in plant cell walls and "the fiber" most mainstream dietitians (and their ANTI opponents) have in mind, when they are talking about the beneficial / detrimental effects of "dietary fiber", is neither viscous nor readily fermentable. Hydroxypropyl-methylcellulose (HPMC) is also non-fermentable, but contrary to its naturally occurring cousin it has a high viscosity.

Hydroxypropyl-methylcellulose, short HPMC, is a semisynthetic, inert, viscoelastic polymer that is used as an ophthalmic lubricant, as well as an excipient and controlled-delivery component in oral medicaments, and has, under the disguise of the "E-number" E464, already found its way into a lot of commercially produced foodstuff, where it is used as an emulsifier, thickening and suspending agent, and as an alternative to animal gelatin.

While its artificial origin will obviously make the ANTI faction cry out loud, again, I suggest you first read about the effect HPMC had on the animals, before you totally discard it as being "not natural", "non paleo", "the work of Monsatan" or whatever...(btw. it is at least kosher ;-)

Figure 1: Changes in body composition (weights in g) after 6 weeks on standard diet with either non-viscous cellulose or viscous hydroxypropyl-methylcellulose as the primary source (5%) of dietary fiber (data adapted from Islam. 2011).

If you look at the data in figure 1, you will have to assert that the body composition of the lab animals did benefit from 6 weeks on the 5% HPMC diet. With a -29% reduction in the increases in purportedly "dangerous visceral fat", a -22% reduction in total adipose tissue gain and non-significant changes in lean mass accrual HMPC easily outperform the "Allis" and "Orlistats" of the pharmaceutical industry. Moreover, while the latter simply reduce the amount of dietary fat that is actually digested (an idiotic approach to weight loss, if you asked me), the non-fermentable viscous fiber in the Islam study worked its fat burning magic right via increases in AMPK, COX, citrate synthase, PGC-alpha, PPAR-delta and UCP3 expression, or, put simply: The 5% HPMC diet ramped up mitochondrial fatty acid oxidation.

Figure 2: Changes (relative to cellulose group) in gene expression in liver and soleus muscle of HMPC fed rats (data adapted from Islam. 2011).

Nevertheless, the slight, yet statistically significant smaller increases in bone density in the HPMC group (+6.4g vs. +7.4g) do suggest that in addition to these inert metabolic effect, the mere excretion of parts of the diets (with respect to bone density probably minerals like calcium and phosphorus), of which the animals in both groups consumed about identical amounts, could also have contributed to the otherwise beneficial effects of HPMC feeding, which, as the profound decrease (-41%) in liver PEPCK expression suggests, also included reductions in the hepatic rate of gluconeogenesis.

Figure 3: Changes (relative to cellulose group) in glucose metablism and adipokine expression of HMPC fed rats (data adapted from Islam. 2011).

The overall beneficial effects on glucose and fatty acid metabolism, by the way, are also reflected in the changes in blood glucose and adipokine concentrations I plotted in figure 3. The lower insulin and leptin levels in the presence of reduced body fat stores indicate increased insulin and leptin sensitivity and could be partly mediated by the marked increase in adiponectin expression, as the latter, as Islam et al. point out, has been found to have an "insulin sensitizing effect in both muscle and liver and a thermogenic effect (enhanced lipid metabolism) in skeletal muscle".

"Fiber is good, then! Right?"

Contrary to cellulose and fermentable viscous fiber, such as guar gum, of which a 2010 study by Isken et al. (Isken. 2010) found that it had, fed at 10% of the diet of mice, no effect on body fat levels in the short term (15 weeks) and even increased adiposity in the long-term (from 27 weeks to 43 weeks), short term feeding with 5% hydroxypropyl-methylcellulose (HPMC) exhibited unexpectedly profound beneficial effects on the metabolism of these otherwise healthy and normally fed (this is important, because we usually see fiber supplementation in the context of "high fat" diets) rodents.

Whether it would be advisable to deliberately look for the number E464 on the foods you consume is yet still highly questionable. For one, every food with an "E -number" on its ingredient list should disappear from your grocery list, anyways. I do not care which number it is, but if food has "E"'s in it chances that this is highly processed garbage are 99% and in that case the supposedly insignificant amount of HPMC will not turn junk into health food. And secondly, and certainly more importantly, we are just beginning to understand how the viscosity of the foods we eat and their susceptibility to fermentation interact and which impact(s) these characteristics have on our digestion and metabolism. After all, it could well be possible that, just as in the Isken study, this beneficial short term effects eventually fire back and the formerly lean HMPC rats suddenly start gaining weight (and body fat) like crazy... you see, as usual things are more complicated than the innocent (yet actually invalid) question "Is fiber good or bad?" might suggest.

AICAR & Liraglutide - Exercise & Weight Loss From The Syringe. 50% Body Fat Reduction in 8 Weeks! Is the Pharmacological Obesity Solution Already Out There?

Image 1: "Diabetesity" is prevalent almost every-
where in the USA (CDC data from 2007)

What if I told you that the magic anti-obesity bullet, everybody is looking for these days is already out there? How much would you be inclined to pay for me to tell you this secret? Well, here you have it for free: Exercise & insulin management. Now, before you get mad at me, because you are to lazy to go through the lifestyle changes, which are usually necessary to achieve this aims, I better tell you that articles in the current issues of the Journal of Lipid Research and the Journal of Clinical Therapeutics suggest that a pharmacological short-cut is already out there ...

Coming from scientists from the Universities College of Pharmacy and Health in Atlanta and the School of Pharmacy and Health Performance at the University of Atlanta is a review (Ryan. 2011) of the therapeutic use(-fulness) of Liraglutide, a subcutaneously administered  glucagon-like peptide 1 (GLP-1) agonist that has already been approved for the treatment of diabetes type II in the US and Europe. The drug itself is structurally similar to GLP-1 with artificial modifications that slow absorption and DPP-4 degradation, while increasing aggregation and non-covalend albumin binding. The result, a fine-tuned version of neuroendocrine glucose-increasing hormone GLP-1, which is produced in the enteroendocrine K cells in the duodenum and jejunum and has a much shorter half-life of only 5 to 7 minutes, has been shown to increase glucose-dependend insulin release by 34%-118%, while reducing postprandial glucagon levels by 20% . Furthermore, ...

Liraglutide reduced PPG levels because of its ability to delay gastric emptying and increase satiety, which has been shown to decrease a single-meal intake by 28% (95% CI, 0.73–0.94).

In the 13 randomized human studies the authors reviewed, the synergy of improved beta-cell function, insulin release and glucose uptake along with a satiety-induced reduction in food intake alone facilitated a medial weight loss which ranged from a meager 30g to statistically significant, yet by no means earth-shattering 3.24kg.

Note: In all honesty (and despite all my antipathies against big pharma), some of the more recent data on Metformin seems to indicate that the latter would be the preferred choice for treatment of diabetes, it would, however not work as synergistically with AICAR, because it has lately been found that Metformin appears to share the same working mechanism, i.e. AMPK activation (for a recent review cf. Violett. 2011)

In spite of its negligible effects on weight loss, Ligraglutide, due to its ability to effectively manage blood glucose levels and restore insulin sensitivity, could set the scene for an effective dietary and exercise intervention, which would not only entail weight loss, but could eventually make the use of the GLP-1 analogue obsolete.

Figure 1: Weight of fat pads in g/100g body weight in AICAR (intraperitoneal injections @ 0.7g/kg body weight) treated vs. control male Wistar rats after 4 and 8 weeks of treatment (data adapted from Gaidhu. 2011)

Now, what can you do if - for whatever reason, except laziness - your ability to exercise is compromised? Well, in that case you better try to spell and pronounce 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside correctly and without stuttering, if you do not want to rely on potentially fake or underdosed AICAR (cf. red box below) from the black market, but have your doctor prescribe what could unquestionably be called "exercise from the syringe": AICAR [note this is AICAR, not ALCAR, like in acetyl-L-carnitine]

Attention! In the May issue of Drug Testing and Analysis (Thevis. 2011), Mario Thevis and his colleagues from the Center for Preventive Doping Research - Institute of Biochemistry at the German Sport University in Cologne report that the powdered form of AICAR they had purchased from dubious Internet sources along with GW1516 another AMPK agonist and  PPARδ modulator and a SARM (MK-2866), back in 2010, and which had passed customs mislabeled as containing ‘amino acids’ and ‘green tea extract'  did in fact contain the inosine monophosphate intermediate 5-Aminoimidazole-4-carboxamide ribotide. Yet, of the 100mg of white powder the scientists received, only 45% contained the active ingredient. In this context it is also noteworthy, that a) AICAR is not yet approved as a drug by any federal agency, I know of, so that your doctor could not even prescribe it at the moment and b) it is not even likely that it will ever be approved, because BigPharma won't be interested in a naturally occurring and thus non-patentable peptide that could potentially reduce the sales of blood pressure, diabetes and cholesterol medications to zero. 

The underyling mechanism of AICAR by which AICAR mimmics exercise is an increase in the synthesis of inosine monophosphat, in the synthesis of which 5-Aminoimidazole-4-carboxamide ribotide(AICAR) itself, is an intermediate. The ensuing chronic AMP-kinase activation is similar to what would be seen in one of the cyclists during the Tour de France or other ultra-endurance athletes, as AMPK, which by the way is an m-TOR antagonist is significantly promoted by chronic endurance exercise (cf. Caligari. 2011).

Figure 2: Inguinal mytochondrial density in AICAR (intraperitoneal injections @ 0.7g/kg body weight) treated vs. control male Wistar rats after 4 and 8 weeks of treatment (data adapted from Gaidhu. 2011)

This chronic elevation of the AMP-kinase pathway had profound effects on the AICAR treated (daily intraperitoneal injections @ 0.7g/kg body weight) Wistar rats in a study by Mandeep Pinky Gaidhu et al. (Gaidhu. 2011). After 4 and 8 weeks, the rats in the AICAR group had "reduced adiposity with increased mitochondrial density" in visceral and subcutenous fat pads (cf. figures 1 & 2). And despite the fact that this was "accompanied by reduced circulating leptin", it may be concluded from the observation that "the anorectic effect to exogenous leptin was more pronounced in AICAR-treated animals than controls", that AICAR effectively increased leptin sensitivity.

Did you know? The inhibitory effect of AMP-kinase activity on the m-TOR complex may inhibit muscle growth. On the other hand, AICAR also inhibits the proliferation of cancer cells by the very same mechanism (Rattan. 2005).

Furthermore,  AICAR induced "time-dependent and depot-specific regulation of AMPK phosphorylation and fatty acid oxidation" and increased "[a]mbulatory activity and whole-body energy expenditure (EE)". And although the increase in energy expenditure was significant (+36%) only during the active (dark) cycle of the rats (cf. figure 3), the synergistic effect of the AICAR induced metabolic changes "led to significant reductions in VC and SC adiposity", what is yet really astonishing is that these effects were not accompanied by any "energy-sparing mechanisms that oppose long-term fat loss", which is where the previous analogy of the Tour de France cyclists breaks down: Real chronic endurance exercise - and overtrained dieters will know that - will very well induce energy-sparing mechanisms which will initially stall weight loss and eventually set you up for the dreaded "Yoyo"-effect of cardio-driven (over-)dieting.

Figure 3: Energy expenditure of male Wistar rats in kcal/h in week 8 of treatment with saline (control) or AICAR @ 0.7g/kg body weight (data adapted from Gaidhu. 2011)

A word of caution: Do not fool yourself into believing that the 2 bagels with peanut butter you had along with a cup of "healthy" fructose-corn-syrup sweetened cereals would not matter, now that you have Liraglutide to manage your blood glucose and AICAR to "simulate" exercise. Without getting your lazy ass of the couch and finally banning the all processed nutritional bullshit from your pantry, neither the former nor the latter and not even the combination of both will save you from developing diabetes, heart disease and stroke.