Monday, July 2, 2012

Y3K Fat Burners: Bile Acid Suppositories! Plus: How This Relates to Taurine, Cholesterol, Statins and Diabesity

Image 1: Is the US starving for sulfur amino acids and cholesterol?
You've learned in yesterday's post (cf. "Sodium-Alginate for 30-40% More Weight Loss and Body Fat Reduction on Mild Caloric Deficit") on the surprising fat-loss effects of seaweed extract, or sodium alginate, already that the "fat burner" of the future isn't going to be a stim, ... well, at least not necessarily or exclusively, but rather a compound that acts onto the GBA, the gut-brain axis by modulating your bodies response to food and fasting. Now, as gross as this may seem, a recently published study from the United Arab Emirates University does suggest that this fat burners may not even come in pill, but rather as a suppository!

A fat burning suppository? Wtf....

I see you are shocked, well so was I, but the alternative would be that you take a syringe and... ah, let's just assume they came out with a suppository which could deliver the same 0.66, 2.0, 6.66 and 20.0 mmol (0.36, 1.08, 3.58, 10.75 g) of sodium taurocholate the ten obese type II diabetic volunteers (!) in the study by Adrian et al. received rectally via a silastic cannula in 20 ml of 1% (wt/vol.) carboxymethyl cellulose over a period of 1 min after an overnight fast - a small injection with profound effects:
Figure 1: Response of insulin, blood glucose and GLP-1 to rectal administration of different doses of taurocholate to obese type-2 diabetics (based on Adrian. 2012)
As the data in figure 1 shows the injection of deliquescent yellowish crystalline bile acid, most people know for its involved in the emulsification and absorption of dietary fats and fat-soluble vitamins, exerted profound effects on hormonal peptides we have long believed to be produced mainly in response to the ingestion of specific nutrients or the gastrointestinal production of short-chain fatty acids from the latter (Tolhurst. 2012). In particular, the rectal administratoin of sodium taurocholate (the sodium stabilizes the molecule in water) lead to
  • dose-dependent increases in plasma concentrations of active GLP-1 and total PYY (not shown in figure 1, but increase paralleled GLP-1) both of which were statistically highly significant (p<0.001) with the highest dose of taurocholate leading to a 7.2x increase in active GLP-1 and a 4.2x increase in PYY
  • at the same time plasma insulin increased by 2.6x and the glucose levels decreased progressively over 60 min by up to 3.8 mmol/l
An impressive result which does yet beg the question: Is this good or bad? I mean a 2.6x increase in insulin? That must be bad, right? It certainly would - but if that's a 2.6x increase that does exactly what it's supposed to, i.e. reduce blood glucose levels in obese type II diabetics, it's unquestionably a good thing.
 Figure 2: Food intake 75min after taurocholate administration at different doses; subjects were provided with their favorite meals and advised to eat to satiety (based on Adrian. 2012)
What's yet even better are the downstream effects on subsequent food intake (see figure 2). 75min after the somewhat embarrassing treatment, the subjects had free access to a as much of their favorite food as they wanted. For 2h, their simple task was "eat as much until you are fully satisfied" and the subjects complied. On the occasions where their suppository contained the high dose of taurocholate, the chicken wings, hamburgers, fries and chocolate cakes or whatever these guys indicated were their favorite foods were almost twice as satiating! The 10mol dosage reduced the food intake by roughly 1/4 still and would be in the range of my recommended 'reduce your energy intake by ~20% if you want to maximize fat and minimize lean mass loss' recommendation - yet not as a result of pure willpower, but simply because more was not necessary and much more probably not even possible!
I can control my appetite I don't need these tools

I can see that some of you are now giving a sniff at those gluttonous fatsos who are not able to control their appetite and therefor simply cannot lose weight and I guess for a small minority of dieters that may actually be the case. The emerging research on the far-reaching metabolic effects  of the so-called "satiety hormones" PYY and GLP-1 does yet clearly suggest that gluttony is only part of the reason why the efforts of dieters all around the globe fail time and again. And it is therefore more than reasonable to assume that this satiety induced caloric reduction, contrary to the common will-power based mild to profound starvation,  will actually produce the expected weight loss results as long as it can be sustained over weeks and months.
Figure 3: It's as easy as can be - work against your body, starve yourself, never eat to satiety and lose (top) vs. work with your body, use gut-brain-axis (GBA) modulators and win (bottom)
Direct evidence for this hypothesis comes from yesterday's news, where the reduction in ghrelin, the hunger-inducing counterpart to GLP-1, PYY & co helped the dieters in the high algae fiber group to adhere to their diets, to lose weight and more importantly body fat at a constant rate over the whole 12-week study period (cf. "Sodium-Alginate for 30-40% More Weight Loss and Body Fat Reduction on Mild Caloric Deficit"). 

Taurocholate suppositories, taurine, cholesterol, statins and yet another reason we are fat

Image 2: What do panic buying and overeating have in common? In both cases the affected people or their bodies expect that there is going to be a shortage in the future and they got to squirrel goods or nutrients away.
It doesn't take a rocket scientist or SuppVersity student to figure from the name alone that a molecule which goes by the name "taurocholate" could contain taurine and cholesterol, right? Right! So what happens if you don't eat enough sulfur(-amino acids) which are necessary as a precursor for taurine biosynthesis (Brosnan. 2006), because those are mainly found in yummy high cholesterol foods such as eggs and co? Right! You will neither produce enough taurine nor have enough cholesterol to produce those amounts of taurocholate and other bile acids as would be necessary to reach the enteroendocrine cells in the distal colon, which would then release those peptides that will signal your consciousness that you are satiated and your metabolism to keep burning those damn love-handles because there is plenty of energy coming in and no sign of impeding famine.

The result, a mismatch between energy intake and energy sensing / satiety, will not just have you eat, eat and... eat! as if there was no tomorrow (see image 2), it will also have your body squirrel away every calorie it can save right into your evergrowing adipose tissue. You develop diabetes and hyperlipidemia and your doctor who beliefs in "medical standards" throws a bunch of statins at you. The statins reduce your cholesterol further. There is less substrate for bile acid production. The mismatch becomes even greater, your energy metabolism is tumbling and you are hungrier than ever before... the perfect storm, it's raging!

"Where is the evidence?"

Image 3: What happens when you feed rats 375x more cholesterol than usual, from whole eggs of course? Right, their lipid profile improves! How do you know, did you read my previous blogpost on the study by Yang et al. (Yang. 2012)? If you didn't click on the image to get there.
There is no evidence for a hilarious theory like that? Well let's start with what happened, when we stopped eating nutritious foods, began throwing away egg yolks and started replacing regular foods with cholesterol-free junk... we got fatter: Year by year! Let's go ahead and take a look at the host of scientific evidence for the beneficial effects of taurine on glucose and lipid metabolism (e.g. Park. 1998; Hansen. 2001; Mühlfeld. 2011; De la Puerta; 2010; Nardelli. 2011). And let's finally combine that with the still hushed up pro-diabetic effects of statins (cf. "With >50% Increased Risk to Develop New-Onset Diabetes, Statins are "Starter Drugs" for Post-Menopausal Women"). I guess that's not conclusive scientific evidence, yet and as so often only part of "why we get fat", but it is certainly a promising hypothesis that adds another piece to a puzzle where the gut-brain-axis or gut-endocrine-axis is occupying a place that can hardly be underestimated.

References:
  1. Adrian TE, Gariballa S, Parekh KA, Thomas SA, Saadi H, Al Kaabi J, Nagelkerke N, Gedulin B, Young AA. Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers. Diabetologia. 2012 Jun 14.
  2. Brosnan JT, Brosnan ME. The sulfur-containing amino acids: an overview. J Nutr. 2006 Jun;136(6 Suppl):1636S-1640S.
  3. De la Puerta C, Arrieta FJ, Balsa JA, Botella-Carretero JI, Zamarrón I, Vázquez C. Taurine and glucose metabolism: a review. Nutr Hosp. 2010 Nov-Dec;25(6):910-9.
  4. Hansen SH. The role of taurine in diabetes and the development of diabetic complications. Diabetes Metab Res Rev. 2001 Sep-Oct;17(5):330-46.
  5. Mühlfeld A, Kubitz R, Dransfeld O, Häussinger D, Wettstein M. Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis. Arch Biochem Biophys. 2003 May 1;413(1):32-40. 
  6. Nardelli TR, Ribeiro RA, Balbo SL, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats. Amino Acids. 2011 Oct;41(4):901-8.
  7. Park T, Lee K. Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet. Adv Exp Med Biol. 1998;442:319-25.
  8. Stephan ZF, Armstrong MJ, Hayes KC. Bile lipid alterations in taurine-depleted monkeys. Am J Clin Nutr. 1981 Feb;34(2):204-10.
  9. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012 Feb;61(2):364-71.
  10. Yang F, Ma M, Xu J, Yu X, Qiu N. An egg-enriched diet attenuates plasma lipids and mediates cholesterol metabolism of high-cholesterol fed rats. Lipids. 2012 Mar;47(3):269-77. Epub 2012 Jan 11.