Science Round-Up Seconds: Follow-Up on Gum Arabic for Fat Loss. DMAA or Schizandra, Which Caused a Stroke in a Young Soldier? Low Doses of Resveratrol Better Than High Ones? Vitamin E Keeps Diabetic Brains Intact.

When it's served like this, Gum Arabic looks more like a healthy snack than a weight loss adjuvant.

I guess everyone who has already listened to the podcast of yesterday's show or was even able to listen live, will have noticed that the audio quality - yet not my German accent - have improved significantly, now that Carl and I did eventually switch to Skype instead of the landline. I know, you have been telling me that all along... be that as it may, unless my Internet connection hangs up for whatever reasons we will continue to do the SuppVersity Science Round-Ups via Skype from now on. Apropos, there will definitely be another show next Thursday (assuming that the world did not collapse by then ;-)

Follow up on Gum Arabic: Dosing & mechanism

In addition to that, I was actually presently surprised how much ground we were able to cover. Allegedly, we have gone way over the scheduled 60min, and I guess I could have said a couple of additional words on the Gum Arabic study and the astonishing fat loss results what I did mention was that it works astonishingly well, what I did not tell you about - or I have forgotten I did (too little caffeine I guess ;-) - is the dosage and the mechanism of action. At least as far as the former is concerned there is no debating that the fat loss magic (-2.1% from ~20% body fat to ~18% in 6 weeks; cf. Babiker. 2012) happened with just 30g of the substance that's derived  from exudates of Acacia senegal or Acacia seyal trees per day. Oher than the diarrhea and bloating, I did already mention on the show, the on average 19-year old perfectly healthy young women in the active arm of the study complained about nausea (82% in the first week) and an  "unfavourable oral viscous sensation" (100% in the first week). The latter is particularly interesting, because it does actually give us a hint on the underyling mechanism which is "not yet fully elucidated, because of a small number of conducted studies" (on its weight loss effects, but could be related to the increase in plasma leptin (without resistance obviously) as well as the increased fatty acid oxidation in muscle tissue in response to viscous fiber ingestion Islam et al. have reported only recently in Obesity (Silver Spring) earlier this year (Islam. 2012). I guess that we are going to see follow up studies on this one pretty soon and you all know that the Science Round Up and of course the SuppVersity news is where you are going to read about them first ;-)

Now that we lost the working weight loss adjuvants behind us, let's get to one which doesn't have any record of helping with weight and was still in each and every fat burner on earth before it was banned: DMAA (1,3 dimethylamylamine) aka geranium oil or geranium extract.

DMAA induced stroke in young soldier!? Or is it maybe the Schizandra that's to blame?

We all know that the job of a soldier is dangerous. A recently published case-report in Military Medicine does yet show that these dangers may not always be due to standing in the line of fire, but can also arise as a consequence of having too much DMAA supplements in your stash (Young. 2012) :

Is schizandra to blame? While the data is in fact scarce and the overall understanding of it's effects would suggest that the TCM herb would rather protect than harm the brain, it is at least worth noting that (a) schizandra has been found enhance the stimulation of the dompaminergic system (Chang. 1991) and (b) that we know that the abuse of cocaine has very similar effects on neurotransmitters (Prakash. 1993) and is associated with an increased risk of hemorrhagic stroke (Kousik. 2012)

"A 26-year-old male was presented to a military treatment facility in Afghanistan shortly after taking a weight-lifting supplement called Jack3d with a severe headache and was subsequently found to have suffered a Dejerine-Roussy variant right thalamic hemorrhagic stroke. Jack3d active ingredients include geranamine, schizandrol A, caffeine, β-alanine, creatine monohydrate, and L-arginine α-ketoglutarate. A literature search revealed case reports suggesting some of the constituent ingredients may predispose to stroke and hemorrhage and also revealed a substantial paucity of data existed regarding schizandrol A, a herb used in traditional eastern medicine." (Young. 2012)

Now, you always have to take case reports like this with an appropriate amount of skepticism - specifically, when the subject has a personal interest of not disclosing all the "supplements" he may have been taking in order not to lose is job. That being said, you know my take on DMAA from the round-table discussion with Patrick Arnold, Kurtis Frank, and one of the guys from Ergo Log. Bottom line: There really isn't any reason to be pissed of by the ban. Even if it's not to prevent stroke, it will prevent the onset of chronic fatigue syndrome in many aspiring physical culturists.

A re-appreciation of vitamin E and resveratrol

"Regular" vitamin E, i.e. alpha tocopherol, has gotten somewhat of a bad rep as of late and whenever resvertatrol is found to produce any the myriad astonishing health effects scientists have identified, it's either these effects occur either in the petri dish or in a rodent model with (often injected) mega-doses you imply couldn't afford taking on a regular basis. In this regard, a recently published paper which reports profound reductions in the fatty acid synthase, and fatty acid oxidation in the livers and adipose tissue of mice in response to a 0.005% resveratrol enriched high fat chow (this would be ~36mg/day for a human) is yet more than only an exception to the rule (Cho. 2012).

Figure 1: Metabolic effects of high fat diet (HFD) or HFD with two different doses of resveratrol; data expressed relative to mice on a standard diet (Cho. 2012)

I mean, take a look at the effects this low dose had compared to the 4x higher dosing in a second group of mice who received the human equivalent of ~142mg/day (see figure 1). Is this really another instance where more does not only yield no additional benefits, but actually reduces the effect (incidentally, de la Lastra et al. have discussed the pro-antioxidant effects of high doses of resveratrol in 2007 already; cf. de la Lastra. 2007)? Or is this just because "mice are no little human beings" and the results are therefore meaningless for us?

If you believe the latter is the case, I suggest you simply scroll down to the overview of some recent facebook news instead of reading how the adminstration of vitamin E to alloxan-induced diabetic rodents (standard model for type II diabetes) did ameliorate the shrinkage of Purkinje cells and apoptosis of cells in the granular layer, the mitochondrial defects, the splitting  of the myelin sheaths and widening axonal spaces, as well as the decrease in the number of GFAP-positive astrocytes (those that still produce a protein, namely GFAP that's responsible to keep their structure intact) in the cerebellar cortex (Mohammed. 2012)

 + + + + + + + + + + + + + +

That's it for today: You know the holiday season is coming so having too many Seconds isn't a particular good idea these days. If you still need something I suggest you pick one of the easily digestible Facebook news, for example...

• GI, GL and cancer risk - While there are statistically significant associations, only the ones for the glycemic load, which adds another quality factor namely GI + carbs per 100g to the equation, appear to have real world significance, though (read more)
• Folic acid in pregnancy - It's not all gold that glitters in ads and carries the letters "RDA". Among the profound epigenetic effects that have been observed in rodent studies, some sound as if they were from a list of the most rampant current pathologies (read more)
• Adiposity will shrink your brain - Leptin resistance is associated with reduced brain volume, associations persist even when they are corrected for BMI (read more)

You know there is more and there is even more to come. So in case the world does not explode within the next hours you know where to go if you are bored waiting for the "Zombie Repopulation" to happen.
 
References:

• Babiker R, Merghani TH, Elmusharaf K, Badi RM, Lang F, Saeed AM. Effects of gum Arabic ingestion on body mass index and body fat percentage in healthy adult females: two-arm randomized, placebo controlled, double-blind trial. Nutr J. 2012 Dec 15;11(1):111. 
• Cho SJ, Jung UJ, Choi MS. Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. Br J Nutr. 2012 Dec;108(12):2166-75.
• de la Lastra CA, Villegas I. Resveratrol as an anti-oxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans. 2007;35:1156–1160.
• Islam A, Civitarese AE, Hesslink RL, Gallaher DD:  Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression  of fat oxidation genes in rats. Obesity (Silver Spring)2012, 20(2):349–355.
• Kousik SM, Napier TC, Carvey PM. The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation. Front Pharmacol. 2012;3:121.
• Prakash A, Das G. Cocaine and the nervous system. Int J Clin Pharmacol Ther Toxicol. 1993; 31:575–581.
• Young C, Oladipo O, Frasier S, Putko R, Chronister S, Marovich M. Hemorrhagic Stroke in Young Healthy Male Following Use of Sports Supplement Jack3d. Military Medicine. December 2012; 177(12): 1450-1454(5).
• Zhang L, Niu X. [Effects of schizandrol A on monoamine neurotransmitters in the central nervous system]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1991 Feb;13(1):13-6.

Green, Oolong, Pu'Erh or Black, All Teas May Help Keep Fat in Check. 750ml of Tea Per Day Could Ward Off Some of Your Holiday Weight Gain.

Image 1: Though color does matter to some extend, the most important thing appears to be that you drink your tea, whether it is green, black, white or well... pu-erh ;-)

Christmas time is approaching and my personal experience tells me that for many of my fellow human beings Santa has more than just iPads, iPhones and iPods in his gunnysack. The two, three or more pounds of body weight, Santa, or rather the festivities in his honor (unfortunately most people have forgotten that we are actually celebrating the birth of Jesus Christ) leave behind on their hips are yet mostly unwanted, so that the results of a recent study which was conducted by scientists from the National Hsinchu University of Education and the National Taiwan University may come pretty handy (Huang. 2011), especially for those of you who plan on having some "healthy" low sugar, but high fructose junk-food over the holidays.

Tea in lieu of hot wine punch could ward off your holiday weight gain 

In their 12-week study, Hsiu-Chen Huang and Jen-Kun Lin fed a group of initially healthy five-weeks-old male wistar rats (body weight: 150-200g) either a standard rat chow (Purina, Ralston Purina, St. Louis, MO) or a chow that consisted of 60% fructose and 40% of the chow.  Now, the latter group was again divided into a fructose control group and 4 experimental groups, where 4% of the standard chow were replaced by ground green, oolong, black or pu-erh tea leaves.

Figure 1: Catechin content of the leaves of green, oolong, black and pu-erh tea.

The scientists' reasoning was that the addition of the catechin-rich tea leaves (cf. figure 1) to the chow would ameliorate the detrimental effects of the high-fructose diets on blood lipids and other measures of metabolic health. Now, the whole rodent vs. human data aside, you are probably not willing to eat tea leaves, are you?

If we do yet assume that the main effect is induced by the "active ingredients" of the leaves and take the catechin content as a measure of how much of that we would have to ingest, eating the whole leaves is probably not even necessary. With their daily food intake of ~27.5g the rodents got roughly 46mg of catechins (calculated for the green tea).

That in turn would equal a dose of 153mg/kg (this calculation takes the weight gain into account) for the rats and 25mg/kg for a human being (cf. my article on human equivalent doses). So, if you weighed 80kg you would have to get 2g of catechins, which is the equivalent of 7.5 mini-cups of 100ml tea each brewed from 1g of tea (the last step in this calculation is based on USDA data from 2007).

Figure 2: Body weight of rats fed either the 40% fructose diet or the same diet enriched with 4% of tea leaves from green, black, oolong or pu-erh tea (data adapted from Huang. 2011)

But let's forget the math and the speculations about whether or not the results are going to translate to human beings for a moment and just have a look at the ameliorative effect the different types of tea had on the weight gain of the high fructose fed rats in the course of the study period. In that, it was not the catechin-laden green tea which had the most profound anti-obesity effect, but the highly oxidized black and the oxidized and fermented pu-erh teas.

Gaining the least weight does not necessarily mean having the "best" blood lipids

Interestingly, a different picture emerges, when we focus exclusively on the blood lipids, where the green tea leaves produce a lipid profile of which current medical "wisdom" tells us that it is the "most beneficial" one ;-)

Figure 3: Relative changes in serum lipid levels due to fructose feeding and fructose + tea leave feeding (data calculated based on Huang. 2011)

As a studious student of the SuppVersity, you will probably already be thinking about possible underlying mechanisms of these anti-obesity and anti-hyperlipidemic effects of the different types of tea leaves. Well, part of those are probably mediated by an old acquaintance: 5' AMP-activated protein kinase or AMPK.

Figure 4: Relative changes in AMPK phosphorylation and fatty acid synthethase in rats in response to feeding with 4% of black, green, oolon or pu-erh tea; my quantification on the left, original blots on the right  (data calculated based on Huang. 2011)

In view of the fact that Huang and Lin were either to lazy or did not consider it necessary to quantify their immunoblots (figure 4, right), I used a standard image processor to come up with the data in figure 4. Since this is obviously not very reliable, I also included the original blots so that you can convince yourselves that both the increase in AMPK phosphorylation, as well as the amelioration of the fructose induced increases in fatty acid synthethase activity correlate with the effects the different types of teas had on lipid metabolism of the rats.

Green, Black, Olong, Pu-Erh? Which tea to chose?

If we take a final look at the "whole picture", it appears that the exotic pu-erh tea would be the tea of choice, when you totally discard taste, price and whatever other factors may influence your choice. After all, it is was exactly as effective in ameliorating the weight gain as the black tea, induced an impressive +244% increase in AMPK phosphorylation and had what I, contrary to the medical establishment, would consider the "optimal" effect on the lipid profile of the rodents (a profound decreases in triglycerides, even below the level of rats fed the normal chow, and a +11% increase in HDL over the control diet despite high fructose feeding). The "classics", black and green tea, on the other hand, share a close and still notable second place, while the fancy oolong tea appears to be the least effective in this quartet of natural health promoters, the potency of which, and this is something I cannot emphasize enough, can hardly be explained based on their catechin content alone (cf. figure 1) and thusly renders the use of respective abstracts for the same purpose more than questionable.

Raspberry Ketones? Why, if Two Grande Caffe Americano Could Suffice To Keep Your Belly & Liver Fat Free and Your Heart Healthy, Even on a +40% Hypercaloric Crap Diet?

Image 1: If I had the choice to have a tasty cup of coffee with the beautiful young lady or a couple of overpriced  raspberry ketone caps with Dr. Oz, I would not even need scientific studies to make my choice ;-)

I am a huge fan of innovation, but when the name of the innovation begins with “raspberry” and ends on “ketones”, is pimped by TV doctors and sold on the 24h shopping channels, I can do well without it and better drink another cup of coffee and eat a couple of lycopene-laden tomatoes, whenever I feel the need to prevent hepatic steatosis on an obesogenic diet. I know this may not be as hip as investing 30-50 bucks in an underdosed “scientifically proven” (by exactly two dubious rodent trials, i.e. Miromoto. 2005, Wang. 2012) raspberry ketone supplement, but, on the other hand, it is also half as stupid and probably at least as efficient (Bahcecioglu. 2010; Vitaglione. 2010; Birerdinc. 2011; Molloy. 2011).

And what's more, picking cafeine over raspberry ketones would not only protect me and my virility from potential anti-androgenic effects of the latest nutraceutical rip-off (Ogawa. 2010), it could, according to a recently published study from the Department of Biological and Physical Sciences at the University of Southern Queensland in Toowoomba, Queensland, Australia, also help me to stay lean by simply blocking fatty acid synthase (FAS) in my adipose tissue (Panchal. 2012).

Caffeine? how boring is that!?

Contrary to the, as of late, often-cited study by Wang et al. on raspberry ketones (Wang. 2012), which is by the way one out of two peer-reviewed in vivo studies (the other one is Morimoto. 2005) to support the claim that raspberry ketones do anything, when they are not administered in unrealistic amounts to cells in a petri dish, Panchal et al. did not just measure a couple of serum markers, but investigated a host of metabolic parameters and structure and function of the heart and the liver of their 6-8 week old male Wistar rats that had been randomly assigned to what you might jokingly call the “pest or cholera” diets for 16 weeks: Corn starch diet (control), corn starch diet plus caffeine (CC), high-carbohydrate, high-fat diet (H), or high-carbohydrate high-fat diet plus caffeine (caffeine supplementation with 0.5g per kg chow took place only in the last 8 weeks of the 16-week study period).

Figure 1: Final body weight and body composition after 8 weeks without and another 8 weeks with caffeine supplementation (based on Panchal. 2012)

If we assume that the cornstarch only diet is pest and the high fat high carbohydrate diet is cholera, the data in figure 1 clearly indicates that 28.1mg/kg body weight caffeine ARE sufficient to reverse the effects of the pest and that 47.9mg/kg body weight caffeine are potent enough to survive any cholera epidemic; or put straight, the rodents on the

• standard cornstarch diet, which consumed 28.1mg caffeine per kg body weight (~360mg for a human being) per day, were leaner than their peers in the “control” group and that despite a 20% increase in energy intake
• high carbohydrate + high fat diet, which consumed 47.9mg caffeine per kg body weight (~612mg for a human) per day, were about as lean as the rodents on the standard diet and that despite a 40% higher energy intake (3% more than their peers in the high carbohydrate high fat diet without caffeine supplementation)

I guess none of you but maybe a few less educated minds could now reply: "Whatever... Dr. Oz said raspberry ketones are healthy; and everyone knows caffeine is not!" So, is this another case where Dr. Oz was at least partially right (cf. "Every Dog Has His Day: Dr. Oz Was Right, Exercise Does Not Just Make You Hungry, But Reduces Energy Intake!")? The increased glucose clearance and the reduction in visceral fat pad weight do speak a different language (cf. figure 2):

Figure 2: Parameters related to glucose and lipid metablism as well as visceral fat depot weight expressed relative to the non-supplemented rodents in the cornstarch control level (based on Panchal. 2012)

The same goes for the cardiovascular and liver parameters who give a damn about the increases in total cholesterol, free fatty acid and triglyceride levels, if those are the result of increased lipolysis (release of fattty acids from aidpose tissue), decreased fatty acid deposition in adipose tissue and an overall increase in metabolic rate, which is a long-established consequence of methylxanthine (=caffeine) intake in rodents and human beings (Bracco. 1995):

"[...] there was removal of fat from the abdominal area, and this fat was not transported to the
other fat-storing areas, including subcutaneous fat [...] The increase in plasma lipid components, especially NEFA, reflects the removal of fat from the abdomen [...with] the excess plasma
lipids are being metabolized rather than stored in the organs [...]" (Panchal. 2012)

The fact that the fat is simply "burned off" also explains that the increased non-esterified fatty acid concentrations, scientists usually associate with cardiovascular dysfunction and hepatic steatosis (fatty liver) did not lead to any of these complications in the study at hand. On the contrary, ...

[...] despite much higher plasma concentrations of NEFA in the caffeine-supplemented rats [..t]hese rats showed decreased infiltration of inflammatory cells, decreased collagen deposition, and decreased diastolic stiffness in the left ventricle, attenuation of non-alcoholic steatohepatitis [...]

Now, the question still remains: Why, are not all Starbucks customers lean then? The answer is pretty simple and "visualized" in image 2, it carries names such as "Peppermint White Chocolate Mocha" contains the sugar equivalent of 8½ scoops Edy’s Slow Churned Rich and Creamy Coffee Ice Cream and is "America's Worst Espresso Drink" - at least according to foodfacts.com. And while you can easily make it worse by adding some caramel syrup or junk, the average normal weight woman (if those still exist today) would almost get the +40% caloric intake the rodents in the high fat high carbohydrate diet consumed from that one "coffee" alone!

2-3 cups of black coffee would suffice!

Image 2: Starbucks Peppermint White Chocolate Mocha with Whipped Cream, 660kcal, sugar equivalent: 8½ scoops Edy’s Slow Churned Rich and Creamy Coffee Ice Cream (foodfacts.com)

If you pass those diabolic sugar bombs and pick up one Grande Caffe Americano (225mg caffeine per serving) in the AM and another one in the afternoon or before your workout (cf. "Pre-Workout Caffeine: Fat Liberator, Substrate Modulator, Trans-Fatty Acid Eliminator & Performance Upregulator!"), make sure to get your 20g+ of protein with every meal and refrain from drinking 100 bottle of Pinot Noir every day, to make sure to  get your share of fat-burning, strength building and endurance enhancing resveratrol (cf. "Resveratrol from 100l of 1994 Pinot Noir Could Increase Fat Oxidation by 71%, Strength by 18-58% and Endurance by 20%"), your liver, heart and metabolic health will thank you for that. Your belly and the raspberry ketone producers and snake oil vendors, on the other hand, will probably be offended - but I guess, you can live with that, right?

References:

1. Bahcecioglu IH, Kuzu N, Metin K, Ozercan IH, Ustündag B, Sahin K, Kucuk O. Lycopene prevents development of steatohepatitis in experimental nonalcoholic steatohepatitis model induced by high-fat diet. Vet Med Int. 2010
2. Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2012 Jan;35(1):76-82. doi: 10.1111/j.1365-2036.2011.04916.x. Epub 2011 Nov 7.
3. Bracco D, Ferrarra JM, Arnaud MJ, Jéquier E, Schutz Y. Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women. Am J Physiol. 1995 Oct;269(4 Pt 1):E671-8.
4. Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology. 2012 Feb;55(2):429-36. doi: 10.1002/hep.24731. Epub 2011 Dec 22.
5. Morimoto C, Satoh Y, Hara M, Inoue S, Tsujita T, Okuda H. Anti-obese action of raspberry ketone. Life Sci. 2005 May 27;77(2):194-204. Epub 2005 Feb 25.
6. Ogawa Y, Akamatsu M, Hotta Y, Hosoda A, Tamura H. Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4. Epub 2010 Feb 21.
7. Panchal SK, Wong WY, Kauter K, Ward LC, Brown L. Caffeine attenuates metabolic syndrome in diet-induced obese rats. Nutrition. 2012 Jun 19. [Epub ahead of print]
8. Vitaglione P, Morisco F, Mazzone G, Amoruso DC, Ribecco MT, Romano A, Fogliano V, Caporaso N, D'Argenio G. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology. 2010 Nov;52(5):1652-61.
9. Wang L, Meng X, Zhang F. Raspberry ketone protects rats fed high-fat diets against nonalcoholic steatohepatitis. J Med Food. 2012 May;15(5):495-503.