Red Meat and Even Pork is Good for You!? Reduced Weight Gain, Improved Insulin Sensitivity and No Adverse Side Effects from "Red Meat Supplementation" Even in Rodents!

Image 1: Must be the red meat between those healthy grain based burger buns that makes this rodent fat, right? What? Yeah... of course epidemiologists count this as a "red meat meal" - it has "red meat" in it... wait, ah yeah: More likely pink slime, with some totally benign ammonia in it, you are right ;-)

Those of you who have been around here at the SuppVersity for some time, may have remembered the "Additional(!) 200g of Pork a Day Build Lean Mass, Improve Blood Lipids & Glucose Levels" from September 2011, when a couple of weeks ago yet another "anti-meat study" hit mainstream media news. You will probably have read enough of the certainly accurate, but in a way pointless criticism of the study, elsewhere in the bloggosphere, so that I decided not to repeat the argumentation, which basically discards the value of all epidemiological data (as long as it is not interpreted in accordance with the respective blogger ;-)... now, not all scientists are epidemiologists, some, like Petzke et al. (see the post I mentioned before) or, more recently Haiyan Chen and his (or her?) Chinese co-workers actually care to conduct experiments on the health effects of red meat consumption and their results are by no means as unequivocal (Chen. 2012), as the introductions and dead-certain conclusions of the epidemiologist would suggest.

If you want to lose weight and ward off diabesity, you "supplement" with red meat!

In their 24 week trial, Chen et al. kept a group of 24 male Wistar rats, who had been pre-fattened on the standard SAD-like "high fat diet" for 14 weeks (an interesting side note: only 24 of the 46 rats who received the HFD diet got actually obese, i.e. they gained +20% more body-fat than their peers - so what does that tell you about the "general" fattening effect of the "high fat diet"?) on either

• regular rodent chow with 67.8% of energy from carbohydrates, 12.8% fat and 19.4% protein, or
• red-meat enriched "high" protein diets with 46.6% of energy from carbohydrates, 16.7% fat and 36.7% protein

The "high protein" (I am putting the term "high" between inverted commas, because I am well aware that for many of you the "medical high protein diet" contains about the least imaginable amount of protein you believe you could get along with; suggested read "20g or 40g of Whey? That is NOT the Question!") contained 780g of lean pork powder per kg. With the other components from the standard chow being added at ratios that would make sure that the rodents from both groups would have an identical caloric intake of 336 kJ/day (=normal caloric intake for adult rats). In the course of the 24-week study period (for rodents with their 2-3 year life expectancy this is like 10-15 human years!), the scientists measured the body weight and fasting  blood glucose levels weekly and every 4 weeks, respectively.

Figure 1: Body weight (in g) during and visceral fat (in g) after 24 weeks on high protein meat or normal protein chow diets (data adapted from Chen. 2012)

As you can see in figure 1 the addition of the "unhealthy red meat" (remember: neither was this "healthy chicken" nor grass-fed beef, but Chinese pork meat - similar to the lean cuts of pork that made the women in the Petzke study lean out and build muscle) reduced the weight gain of the already obese 17-week old rodents by more -57% (!) and left them with 44% less of pro-inflammatory visceral fat mass than their peers on the healthy "meat-less" standard chow. Despite an increase in BUN, the creatinine levels of both groups were identical and there were no signs of kidney damage in any of the rodents kept on the meat-supplemented high protein diet.

Figure 2: Insulin AUC during intravenous glucose tolerance test (IGGT) and fasting GLP-1 levels
(data adapted from Chen. 2012)

The insulin response during an intravenous glucose tolerance test (a measure of insulin resistance), on the other hand, was reduced, just as fasting GLP-1 levels were (P < 0.05; for more information on the intricate relationship between GLP-1, insulin and obesity / fat loss, check out my previous post on WMHDP).

Why the different results? Don't tell me meat is not bad for me!

Aside from the questionnaire based epidemiological studies, where "Pizza Salami" is a "red meat food", I mentioned earlier, there definitely is experimental data (on which the working hypothesis of many of the epidemiological studies are founded, by the way) that would suggest that feeding red meat to rodents is not the best thing to do... now, if we discard species-specific issues for the time being, how can those differences be explained? Chen et al. provide a pretty straight-forward set of potential confounding factors in their discussion, which I am going to summarize for you:

• meat is an energetically denser protein source than dairy - this may explain why, compared to dairy products, meat has been found to be positively associated with weight gain in rats (eg. Belobrajdic. 2003)
• the longer experimental duration - in previous studies there were already "tendencyies toweight loss" at the end of the mostly 10-12 week study periods 
• the age of the animals may have a profound effect on the weight gain; for rats that are younger than the ones in the study at hand, an increased weight could would in fact indicate a healthy effect during the most active growth period of the rodents rats; this would not preclude, though that the same diet would facilitate weight loss in mature rats

Still, aside from the lack of blood lipid profiles, blood calcium and phosphorus levels, which as the scientists concede would have been "important [to judge the] safety of the high-protein diet", there is another factor, I would really insist on, if it had not been for the repeatedly mentioned human trial by the German scientists and that would be that the use clenbuterol, salbutamol and sibutramine - "weight loss adjuvants", or the Chinese would probably say dietary supplements to ensure lean livestock *rofl* - is still daily fare in China, so that - theoretically speaking - we cannot exclude that the rodents received a whopping dose of any, if not all of these drugs in their "meat-supplemented" high protein diets ;-)

TTA + Fish Oil - Fat Burning Superfats or Hepatoxic Pro-Oxidants? Why You Better Avoid Large Amounts of Omega-3 and Tetradecylthioacetic Acid in the Long Run

Image 1: Even if you align them like that, it is at least debatable whether capped fish oil is much more natural than the structurally modified 16 -carbon saturated fatty acid tetradecylthioacetic acid (TTA). As far as their effects on weight loss are concerned, the latter is certainly more potent,... the debate on the side-effects of both is yet still far from being settled. Despite the mainstream hoopla around the former...

At least for those of you who have been around the supplement world for some time, the acronym TTA, which stands for tetradecylthioacetic acid, a structurally modified 16 -carbon saturated fatty acid (SFA), which has been shown to increase fatty acid oxidation and reduce triglyceride levels via interactions with purportedly all PPAR-receptors, should ring a bell. For the rest, it will yet probably be news that, back in the early 2000s, TTA was all the rave as the new star among OTC-fat burners. And in fact, the weight loss people experienced on respective products was non-negligible... yet so were the side-effects which crept up over time (and with ever-increasing dosages): Headaches, cramps, dehydration and water retention specifically in the abdominal area were only the minor complaints. Unbearable fatigue and even palpitations were at the other extreme of the spectrum and probably the actual reason why company after company  altered the formulation of their "effective" and above all commercially successful tetradecylthioacetic acid containing fat burners.

While TTA works well, but has well-known side-effects,...

A recent long-duration rodent study that was conducted by a group of European researchers and which my friend Sean Casey from CasePerformance has brought back up onto my radar (Vigerust. 2012), did now investigate the long term (50 weeks) effects of supplemental tetradecylthioacetic acid and another purportedly saver PPAR-agonist, with similarly beneficial effects on triglycerides yet hardly noticeable effects on weight management - my all-time favorite fish oil! To this extend, the scientist kept their rats on their infamous interpretation of a "high fat" diet, which, as you will probably already have expected, had a moderate fat content of 25% tons of carbs and little protein and had thusly more of the standard American diet than of what people in the bloggosphere usually refer to as a "high fat" diet, i.e. a diet that is really high in fat (>50%) and low in carbohydrates.

Figure 1: Relative body weight (compared to identical baseline) in rats at different time points during 50 weeks on high fat diet (control) with either TTA, fish oil or both (data calculated based on Vigerust. 2012).

It is thusly not surprising that replacing 10% of the fat by fish oil (~11g EPA + 6g DHA for avg. human) had absolutely no effect on the weight gain of the hyperphagic (overeating) rodents. The miniscule amount of 0.365% TTA, which would be equivalent to a daily intake of ~912.4mg of TTA for someone consuming 2000kcal/day, on the other hand, lead to statistically highly significant reduction in weight gain over the whole 50 week feeding period (cf. figure 1).

Figure 2: Relative expression of uncoupling protein 3 (UCP3, primary axis) and enzymes involved in fatty acid metabolism (secondary axis) at the end of the 50-week dietary intervention; expressed relative to high fat control (data calculated based on Vigerust. 2012).

As evidenced by the elevations in carnitine palmitoyltransferase II (CPT II), which is necessary to shuttle the fat into the cell, HMG-CoA, which is one of the key players in ketogenesis, and peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), which initiates the first enzymatic reaction during beta oxidation, the hepatic fatty acids oxidation in the TTA (and TTA + FO) group was profoundly increased, in conjunction with the exorbitant increase in UCP-3 expression (>1500x in the TTA only, and >1300x in the TTA + FO group) and the subsequent "leakage" of energy in the form of protons, this easily explains the -11% / -19% reduction in total body weight in the TTA and the TTA + FO groups at the end of the 50 week study period.

....fish oil hardly works and has less-known side-effects

In that, it is important to note, that only TTA (respectively its addition to FO), not fish oil, was able to reduce the diet-induced elevations in hepatic triacylglycerol (TAG) levels. This leads to scientists to speculate, that despite similar effects on TAG and cholesterol transport in the liver, ...

[...] animals given the FO diet are less able to metabolize the excess hepatic lipid levels [... so that] FO redistributed lipids without affecting the total lipid level and body weight.

This would also explain the detrimental effects the fish oil supplement had on hepatic cholesterol levels and lipid oxidation, which would suggest that, at least under these dietary conditions (relatively high fat + high carb + high energy = typical western diet), one would be better off taking no fish oil at all, or a combination of fish oil and TTA.

Figure 3: Relative mRNA expression of markers of protein and lipid oxidation in liver and liver mitochondrial fraction of the rodents at the end of the 50-week study period (data calculated based on Vigerust. 2012)

The latter is all the more indicated in view of the fact that the use of the highly oxidizable fish oil alone lead to non-negligible increases in protein oxidative damage (cf. GSA, alpha-AASA, figure 3) and an increase in total hepatic glyco- and lipooxidation, as evidenced by the increase in Ne-Carboxymethyl-lysine (NCL, figure 3) in the whole-liver samples and a corresponding increase in Nɛ-Malondialdehyde-lysine (MDAL), a lipid-specific marker of oxidative damage in whole-liver and the mitichondrial homogenate (liver M-fraction) of the animals in the fish oil (only) group (cf. figure 3).

These detrimental oxidative longterm effects of fish oil supplementation, which "showed a significant positive correlation with DHA content" of the liver (meaning more DHA in tissue = more oxidation), were only ameliorated, yet not totally prevented by co-treatment with tetradecylthioacetic acid (TTA), which reduced the amount of oxidizable PUFA in plasma and tissue and reduced the mitochondrial ROS production via the UCP-3 induced energy leakage and the subsequent relative reduction in oxidative energy production (remember the overall energy expenditure was still increased by TTA, yet not by FO treatment).

Bottom line: Avoid the dietary PUFA burden, eat healthy and exercise...

Image 2: "You told me to eat more protein and this burger has both meat and cheese!" - click here for more info on why dietary interventions fail

As far as the amelioration of negative side-effects of the typical Western high carbohydrate, relatively high fat diet are concerned, the results of this study would argue against the longterm use of omega-3 polyunsaturated fatty acids from fish oil (DHA in particular) and for the use of structurally modified 16-carbon saturated fatty acid TTA in order to reduce weight gain, triglyceride and liver cholesterol levels in individuals who are either unwilling or unable to make the necessary life-style-changes that would, instead of just prolonging their suffering, help them finally escape from the maelstrom of the metabolic syndrome (cf. yesterday's blogpost on "High Carb vs. High Fat, When Science Meets Real Life").

Whether the same holds true for athletes, fitness enthusiasts or at least moderately active human beings, who stick to an overall anti-inflammatory low(-er) carb (not "no carb" and not necessarily, but possibly "paleo") diet, would certainly warrant further investigation. It would nevertheless, my previously voiced concerns over the injudicious (over-)use of omega-3 supplements in the futile effort to "balance" the dietary over-indulgence of omega-6s... after all, the most straight-forward explanation for the increase in oxidative damage in the fish oil only group is the increased amount of PUFAs in the liver tissue, which are - across the board, i.e. omega-6 and omega-3 - much more susceptible to oxidative damage due to radical oxygen specimen (ROS). I thusly stick to my previous recommendation to just watch your overall PUFA intake and resort to alternative fat sources, such as coconut oil (which is, by the way, the topic of the first "non-SuppVersity" article of mine in the all-new article-section of the VPX-website; don't worry I won't neglect the SuppVersity and stick to topics without potential "conflicts of interest and objectivity" ;-), butter, dairy and meat products from grass-fed animals, eggs and obviously real fish!

... and you won't need TTA to lose weight or ward off unwanted body fat

Moreover, I strongly caution against a similar injudicious (ab-)use of large amounts of TTA especially over longer periods of time. The latter was probably the underlying reason for the initially mentioned side-effects, due to which most supplement manufacturers either totally removed tetradecylthioacetic acid from their products or reduced the amounts per servings to levels, where the other ingredients would give you palpitations before you would achieve dosages way beyond the 1g range, which, as previous human trials would suggest, appears to be save at least in the short term (<30days, cf. Lovas. 2009). With respect to longer durations and/or higher dosages, you should yet be aware that the very same depletion of plasma and tissue PUFAs which is partly responsible for the overall reduction in oxidative damage in the study at hand, may well backfire and produce exactly those cramps, the water retention, and the profound lethargy reports of which you will find in the archives of various health and fitness boards, all over the web.

SAD - Human Study Shows: Three Days on "High Fat" Standard American Diet Produce Heart Healthier LDL Particle Profile Than NCEP-Approved Low Fat Diet

Image 1: SAD or just mad? It does in fact look like you better stick to Royal TS, French fries & co instead of following a low fat diet according to the guidelines of the National Cholesterol Education Program if you care about your heart health.

In view of the fact that millions of lives depend on it (literally, not just figuratively!) it is actually quite surprising, some would probably say "scandalous" that the experimental evidence (and I am talking about controlled experiments on real, healthy human beings, not about epidemiological and thusly statistical) for the purported beneficial effects of a non-calorically restricted "healthy low fat diet" in the absence of additional exercise interventions is... scarce, to say the least. I was thusly positively surprised, when I hit on a study from a group of researchers from the Institute of Nutraceuticals and Functional Foods at the Laval University and the Lipid Research Center at the CHUL Research Center in Québec, Canada, the title of which suggested that it could provide exactly that - experimental evidence in support of the purportedly healthy low fat diet (Guay. 2012).

Scientists and their interpretation of a "high fat" diet...

I guess, those of you for whom this is not the first visit to the SuppVersity will be aware that I have made a habit of looking at the data first, to make up my mind, before I even take a closer look at the scientists interpretation of the latter (this is what is usually called the "conclusion"). And, geez! The "high-fat diet", the Valérie Guay and her colleagues advertise in the title of their paper turned out to be another case of the standard American diet, the relative fat content of which (32% of total calories) is not exactly, what's on my mind, when I think of a "high fat" diet.

Figure 1: Relative macronutrient composition of the baseline and the isocaloric test (high and low fat) diets (left); total fiber, cholesterol and phytosterol content, as well as polyunsaturated to saturated fatty acid (PUFA/SFA) ratio and total fat in % of total calories (right; data calculated based on Guay. 2012)

The fact that this paper still made into the news, although the researchers' interpretation of a "high fat" diet was designed to "reflected as closely as possible current North American men averages", does yet already tell you that the results were not that the "healthy low fat diet bet the crap out of the standard American one".

SAD! Standard American Diet beats the nasty small LDL particles out of a healthy low fat diet

In fact, a closer look at the somewhat cryptically presented study results revealed that, at least as far as the measured outcome variables of this particular study are concerned, the exact opposite was the case: It was not the purportedly healthy low-fat diet which was designed according to the recommendations of the National Cholesterol Education Program Adult Treatment Panel III (cf. JAMA. 2001) which induced favorable changes in the lipid profile of the twelve initially healthy normal-weight male volunteers (~27.1y; BMI 25.2kg/m²) who took part in this 3-day randomized, double-blind, crossover study, but the calorie-, fiber- and vegetable- and animal-protein-wise identical "high fat" diet, which had been designed in the image of the infamous "standard American diet" (SAD).

Figure 2: Lipid profile (left) and its relative changes (compared to baseline, right) in response to the 3-day dietary intervention (data calculated based on Guay. 2012)

If you look at the data in figure 2 through Pfizer-ish-blue glasses you will probably say: "Wait a minute! The cholesterol level did decrease in the low fat group! So this must be the better diet." And yes, this may actually be the case, if you define better according to the same fundamentally "cholesterol is bad for you"-paradigm which has been flushing billions of dollars (and of course Euros ;-) into the coffers of Pfizer & Co over the last decades. If you have yet been following the by no means "latest" scientific research on the correlation of cholesterol and heart disease, you will be aware that neither total cholesterol, nor total LDL levels, but rather the amount of highly oxidizable small LDL particles is a relatively reliable marker of the risk of heart disease (Lamarche. 1997)- and, fortunately, Guay et al. are aware of that, as well, and measured the characteristics of LDL particles by the means of electrophoresis.

Figure 3: Relative distribution of LDL particle sizes (left), cholesterol content (mmol/L) of LDL fractions (middle), and mean LDL particle size and LDL peak particle diameter (LDL-PPD; right); * indicates p < 0.05; ** indicates p < 0.001 (data adapted from Guay. 2012)

The results of the LDL-particle analysis shown in figure 3, show quite neatly, that the unquestionably unhealthy standard American diet (Attention: Do not misinterpret these study results as a carte blanche to stick to eating your regular crappy diet!) did not only result in more favorable triglyceride (1.48 vs 1.01mmol/L, p = 0.0003) and HDL levels (1.29 vs 1.41 mg/L, p = 0.05; cf. figure 2), than its allegedly "healthy" low fat counterpart, it was ...

[...] also associated with a significant increase in LDL particle size (255.0 vs 255.9Å; p = 0.01) and a significant decrease in the proportion of small LDL particle (<255.0 Å) (50.7% vs 44.6%, p = 0.01).

And although Guay et al. are quick to point out that "because the present study was only conducted in men, the results cannot be generalized to the whole population", I would say that these results should at least.make you reconsider if following a "healthy low fat diet" in accordance with the dietary guidelines of the National Cholesterol Education Program will help you lower your risk of heart disease... unless, of course, you have already popped so much Lipitor & co that the chronic lack of cholesterol is already hampering your cognitive abilities -.what? Ah, yes... of course, the favorable results occur only if you take you daily dose of statins with your low fat meals... right, how could I forget that ;-)