Devil in the Feeding Trough: PGE-Response to "Bad" Red Meat from Grass-Fed Cattle Could Prevent not Cause Cancer, Stroke and a Whole Host of Autoimmune Diseases.

Image 1: You do not need to hunt your red meat like a paleolithic human being, just make sure it comes from grass-fed animals and you will have a "health food" that modulate the your prostaglandin response to inflammatory assaults and thusly reduce your risk of cancer, stroke and autoimmune disesases in a way no fat-free chicken breast will ever do.

I have had this in the news before, in the context of the purported health benefits of CLA, with respect to the modulation of the n3/n6 ratio in your diet and in various other context, you heard me saying, or, I should say, read me writing that rather than popping tons of fish oil caps, you should rather focus on decreasing your overall omega-6 intake by making healthy food choices at the supermarket. In this regard, choosing grass-fed over commercially raised beef (and other meat) products could turn out to be one of the most far-reaching choices you can make. While that alone will help you to concomitantly reduce the n-6 overload, as well as the overall PUFA-burden that is so characteristic of the "Western diet", a recent study shows that eating red meat, even instead of the "healthy" white fat-free chicken breasts, everyone is pounding these days, could actually have profoundly beneficial effects on your (auto-)immune health, protect you from cardivascular disease and (this is important for the ladies) get your menstrual periods and related issues back in order.

How grass-fed beef can help and why it outperforms bison, elk and chicken

In their study, the results of which were published in issue 31 of the journal Nutrition Research, K. Shane Broughton, Daniel C. Rule and Eldon Handrich did what scientists have been doing for decades now. They took mice (your usual carnivorous animal) and put them on one of those grain-based diets that was then enriched with "bad" red meat to make the animals sick. Well, ... while the design was in fact the same, the good news is that the intention was by way of exception not to show "prove" (as if mainstream dietary advice would be interested in "proof", anyway) how bad those nasty red meats are, but to evaluate whether the

[...] consumption of meat from range-fed bison vs range-fed and grain-finished cattle and grain-finished bison would lead to reductions in PGE-2 [prostaglandin E2] release without altering PGI-2 [prostacyclin] release after an infl ammatory stimulus in a mouse model.

Or put simply, the scienists wanted to check whether there was any truth to the superiority of bison compared to the "bad" red meat, when it comes to balancing out the ratio of PGE-2 and PGI-2.

Image 2: Bayer probably won't like it if everyone would start eating grass-fed beef. After all, that would probably reduce the sales of their COX-inhibitor Aspirin protect.

For those of you wondering about a) what those prostaglandins are and / or b) why you would want to modulate their ratio and not eradicate them completely, here is is brief rundown on one of my favorite topics, the Yin&Yang of life and, on a related note, the fallacy of common black-or-white thinking. As with almost everything there are also two sides (in fact there are many more ;-) to the inflammatory coin and PGE-2 and PGI-2, two acronyms that differ by only a single letter, are situated on those opposing sides. If they are expressed at the right ratio, everything is fine. The (relative) over-expression of PGE-2 that is commonly observed in people following the "Western diet", on the other hand, is associated with a host of pathologies, such as elevated risk for color ectal cancer, suppression of ovulation, and increased problems with rheumatoid arthritis and headaches. (Relative) underexperssion of PGI-2, the other hallmark result of the "food" people are poisoning themselves with on a daily basis, in turn, increases the risk of thrombosis and stroke. If any of that does ring a bell, but you do not know which one, you may want to check out the label of your Aspirin tablets - as a cyclooxygenase inhibitor Aspirin also blocks the production of PGE-2... but before you do now pop another of those tabs, I suggest you read on and learn that by paying a few extra bucks for "real meat", you will probably never have to take your daily dose of Aspirin protect.

And while the scientists were right, grass-fed bison is in fact better than grain-fed beef, a closer analysis of their results will show that the often-heard and widely believed statement that "bison is the best form of red meat you can possibly find" is nothing but another of the 1001 dietary fairy-tales of the bloggosphere.

Figure 1: Fatty acid content of the diet (in g per 100g of the whole chow) - saturated, mono- and polyunsaturated fatty acids (n3, n6), left; CLA content, right (data adapted from Broughton. 2011)

But let's first take a look at the experimental diets, the male CD-1 mice were fed for 14 days. What is interesting about these, is that, due to the inclusion of standard rodent chow, the differences in fatty acid composition between the grass-fed vs. corn-fed bison and beef diets and the diets that were based on (wild-type) elk and commercial chicken breast meat were actually not very pronounced (cf. figure 1). And while the inclusion of corn oil in every diet may sound blasphemic in the ears of the hard-core anti-grain croud (I know you are out there ;-), the addition of grass-fed meat to an otherwise standardized (and probably suboptimal) diet is actually a strength of the study. Thusly, the study does reflect pretty well, what could happen, if the average Joe or Jane did nothing else, but replace the corn-fed meat in his/her diet with meat from range-fed animals - and wouldn't you agree that this is a much more realistic scenario than living on nothing but grass-fed beef or bison?

Figure 2: Modulatory effect of 2 weeks on prostaglandin expression of mice after two weeks on diets enriched with range-fed, or feedlot fed meat of different sources (data adapted from adapted from Broughton. 2011)

And, if we focus solely on the PGE-2 to PGI-2 ratio (you can read up on its importance in the red box above), it is obvious that a small dietary change from grain- to grass-fed meets could actually have pretty profound effects on your (auto-)immune health. The data also shows that the "healthy" lean chicken breast your nutritionist has probably told you to eat actually should not be your first choice, when it comes to establishing a healthier prostaglandin milieu - and if you don't believe me, maybe you want to trust Broughton et al.'s judgement:

[...] chicken is promoted for its health benefits, yet in our study, it was no better for possible prevention of PGE 2-associated immune pathophysiology. Furthermore, chicken would not be as beneficial as grain-fed beef and elk consumption in reducing thrombos is and stroke potential.

So, while eating (commercially raised) chicken won't harm you, it will not help you steer your inflammatory response into either the PGE or the PGI direction. Broughton, Rule and Handrich are thusly right, when they conclude that

Based on results of the present study, consumption of any of the range-fed meat sources examined would be better at reducing the possibility of immune-related pathophysiologies than meat from grain-fed cattle. [...] Although range-fed beef and bison consumption would be equivalent for their immune-based role, consumption of range-fed beef would be better for the prevention of thrombosis and stroke.

Now, isn't that surprising? Chicken not the best thing you can eat? The "healthy alternative to beef" that has been pimped in the mass media lately only on par with plain beef and superior as far as reduction in the risk of stroke and thrombosis are concerned? Could it really be possible that the "bad red meat" is not so bad, after all? Is there the remote possibility that it's not red meat per se, but sick meat, or I should say the meat of animals we have been making sick by feeding them the same "healthy whole grains" with which we have been poisoning... ah, I mean nurturing *rofl* ourselves over all these years that is giving us migraines, arthritic joints, cancer, strokes and a whole host of nasty autoimmune diseases? I guess, I will leave it up to you to find and answer to that question ... and I am confident that you are smart to one and one, or rather grain-fed meat and (auto-)immune disease together ;-)

Instant Coffee, Glycemia & Caffeine Powered Post-Workout Glycogen Repletion. Fish Oil, Arachidonic Acid Release & Prostaglandin Modulation. Adipocyte Sizes & Yoyo Dieting

Judged by the way they are looking at each other they don't care about their differential glucose / insulin response too coffee, but if you do, I suggest you scroll down and read the pertaining news item.

7.3% and 21.4%, those are the SuppVersity figures of the week. Figures that stand for the 2011 youth- and 2010 adult obesity rates in Colorado and they represent the nationwide "optimum" - at least according to CDC data from the respective years. Now, it was already hard to find US states with obesity rates below the nationwide average of 13% (youths) and 27.6% (adults). What is yet even harder or rather impossible is to dig up studies which try to elucidate why Colorado is the "leanest" of the 50 US states. Non-exhausting physical activity, for example, would be a candidate, but according to Wyatt et al. the "[e]ven in Colorado, one of the leanest states, very low levels of physical activity are seen in much of the population." (Wyatt. 2005).

Wouldn't it be worth taking some time to try to elucidate what the citizens in Colorado may be doing, their fellow Americans in Mississippi (highest adult obesity rate of 34.5%) or Alabama (highest youth obesity rates of 17%) ain't doing? Are they maybe having more or less fish oil or drinking only half the amount of caffeine? I don't know, but based on today's installment of "On Short Notice", you should be able to answer whether or not it is likely that factors like these could make a difference ;-)

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Coffee, Sex and Your Physique (Gavrieli. 2013) -- The latter two, i.e. sex and your physique are what determines your postprandial glucose and insulin concentrations after escalating dosages of caffeinated coffee. That's at least what Anna Gavrieli from the Harokopio University in Athens and her colleagues from overseas write in a soon-to-be-published paper.

To examine the effects of different amounts of coffee on blood glucose and insulin concentrations in the postprandial phase (after a meal) the scientist recruited thirty-three volunteers [16♀/17♂, 16 normal-weight and 17 overweight/obese, 27.3 ± 7.2 (19–44) y] who came to the lab fasted and obviously without having  had a "wake up coffee" early in the morning. When they arrived, the subjects received a standardized meal, i.e. a slice white bread, 5 g of butter and 10 g of white sugar, providing 142 kcal (6.5% of energy from proteins, 62.5% from carbohydrates and 31.0% from lipids) along with 200 mL of water or instant coffee containing either 3 or 6 mg of caffeine/kg body weight on three different occasions.

Figure 1: Usual and experimental caffeine intake in the subjects (left); effects on glucose metabolism after standardized "breakfast" (=sugar binge) + water or different dosages of instant coffee (Gavrieli. 2013)

As you can see in figure 1, the blood samples the scientists obtained before, immediately after and in regular intervals over the remaining 3 hours after the ingestion of the "breakfast" do support the hypothesis that men and women, light and heavy weights react very differently to the ingestion of 200-500mg.

So what's the verdict then? Is coffee the way to go?

Post workout caffeine supplementation?! Just like dieting, working out is one of the confounding factors which render results like the one at hand valid only in certain scenarios. Against that background it is not surprising that a 2008 study by Pedersen et al., the results of which I have plotted for you in the figure above (Pedderson. 2013), found statistically significant improvements in glycogen resynthesis w/ 8mg/kg caffeine being coingested with 4mg/kg glucose after a workout. Whether this will yield real world benefits is obviously another story ;-)

While coffee delayed the rise of insulin in response to the standardized meal and the fall of glucose concentrations from its maximum levels in the entire study sample, the glucose incremental area under the curve (IAUC) was not just different between the interventions (with both coffee amounts inducing a greater area compared to water, p = 0.009), but also varied according to the sex and body weight of the subjects:

"Secondary, subgroup analysis at the nominal level showed that this might be more evident among females (PIAUC = .05) and overweight/obese participants (PIAUC = .03). Furthermore, coffee, mainly the 6 mg dose, could be lowering insulin concentrations the first 30 min after its consumption compared to water in men and overweight/obese participants." (Gavrieli. 2013)

So what do we make of these results, now? Well, first of all, even if your breakfast does not deserve the name food, having a single regular sized cup of coffee is unlikely to to any harm. Reversing the ratio of breakfast to coffee on the other hand and having a "Sex & The City" breakfast with a croissant and a large cup of breakfast will have you run the risk of having high blood sugar afterwards (esp. if you drink that 400mg+ pot of coffee with tons of sugar).

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The tissue incorporation of regular triglyceride based fish oils is inferior to their phospholipid bound brethren. Want to learn more? Check out my article on that matter from June 2012 (learn more)

3g of fish oil modulate the eicasonoid production from omega-6 fatty acids in young men (Zulyniak. 2013) -- 2g of EPA and 1g of DHA that was the dosage the 10 young healthy males (23.4 ± 1.7 years) had to consume on every day of the 3-months supplementation period in Zulyniak et al.'s experiment which was designed to "better understand the potential health benefits of fish oil supplementation in young healthy males" (Zulyniak. 2013).

What the researchers observed were the expected decreases in serum triglycerides (-38%), a significant increase in the proportion of HDL-c relative to total cholesterol, as well as - and this is the actual news - an increase in eicosanoids production, namely prostaglandin-F2α (P < 0.0001) and thromboxane-B2 (P = 0.0296), after fish oil supplementation.

The latter two are products of omega-6 metabolism and confirm the replacement of arachidonic acid (AA, the long-chain omega-6 fatty acid and the quasi-analogon to DHA) in the cell membranes of the erythrocytes by EPA and DHA. This process must have triggered the increase in PGF2α and TXB2 production of which the scientists state that

On a side note: The results of this study don't change my opinion as far as the usefulness, let alone necessity of fish oil supplementation in healthy, athletic, fish eating SuppVersity readers is concerned. I don't see any.

"[...]previous work by both Boughton-Smith et al. and Scott et al. suggest that PGE2, PGF2α, TXB2, and 6-keto-PGF1α are the primary products of the COX2 pathway when AA is in abundance. Furthermore, Scott and colleagues suggested that with chronic elevation of AA, PGF2α and TXB2 production is more likely to be up-regulated due to their vasoconstrictive qualities, which would prevent the efflux of AA and other more-damaging eicosanoids from cells into circulation." (Zulyniak. 2013)

Whether this is actually a good thing does yet appear at least somewhat questionable to me and even Zulyniak et al. have to admit that future research was necessary to confirm "the production of eicosanoids capable of regulating vasoconstriction" and thus "substantiate this hypothesis" (Zulyniak. 2013). As you can see, we are still learning new stuff about things of which every disciple of Dr Oz believes he already knew everything.

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Study supports hypothesis that regression in adipocyte size during weight loss could be reason for fat loss plateaus and "walls" (Verhoef. 2013) -- As a seasoned SuppVersity veteran, you are probably aware of the possible influence the size of your fat cells could have on weight loss success, failure or stagnation (learn more).

In a previous post on the Yoyo effect, I already discussed some aspects of adipocyte morphology - including the way lower body fat tends to be more stubborn than upper body fat (read more)

A recent study from the Maastricht University does now offer further support for my previously expressed hypothesis that the reduction of adipocyte size that comes with profound weight loss in then formerly obese individuals could be at the heart of the weight loss plateaus and over-pronounced metabolic downregulation formerly obese individuals experience at way higher body fat levels than someone who has never been obese in his / her whole life. Verhoef et al. put a group of twenty-eight overweight (BMI 28-35kg/m²) healthy subjects on a very low energy diet for 2 months. The 500kcal/day period (50g carbs, 52g protein, 7g fat + multi-mineral supplement delivering the RDA of all nutrients) was followed by a 10-month period of weight maintenance.

Over the course of the low energy diet intervention period, the adipocyte size decreased by -16.7%, the body fat level, on the other hand dropped by only 4.7%. Still, the leptin levels plummeted from 20.3 to 13.1 µg/L and did not return to baseline in the course of the "weight maintenance" phase.

Figure 2: Relative changes (compared to baseline) in body composition, adipocyte volume and leptin after the dieting intervention and the miserable weight maintenance phase (Verhoef. 2013)

In how far the suppressed leptin levels were actually responsible for the fact that the "weight maintenance" phase turned out to be a very dirty, fat only bulking phase cannot be said, but we know from previous studies, that the process of shrinking in itself

"has been reported to generate cellular stress and the more [the adipocytes] shrink, the higher will be the resistance against increasing mitochondrial beta-oxidation via HADHsc [hydroxyacyl-Coenzyme A dehydrogenase] during follow-up." (Verhoef. 2013)

And as if that was not enough the slight increase in ATGL (lipolytic protein) and HADHsc in the "weight maintenance" phase are, as the scientists point out, indicative of the appearance of newly differentiated adipocytes that are are metabolically active contribute to an "improved physiological status", but could potentially make future weight loss (esp. the aesthetic one) even more difficult.

"Empty" adipocytes <> lower leptin <> more glucose-to-fat conversion <> rapid fat gain

If CLA worked in humans as it does in rodents, it could solve the "small adipocyte" problem (learn why)

Moreover, the glycolyctic and thus potentially glucose-to-fat conversion promoting enzyme Aldolase-C did not just distinguish the successful weight maintainers (low Aldolase-C) from the yoyo dieters (high Aldolase-C), it also correlated with the leptin production of the fat cells, of which we know from previous studies that it is in turn negatively correlated to their size (Skurk. 2007)... too complicated?

Ok, let's express it the other way around. The "emptier" your adipocytes are (=smaller size), the less leptin they will produce and the more likely they are to convert glucose to fat and stash that away in their empty "tummies".

Suggested read for those who want to dig further into the purported underlying effects of weight regain: Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology's response to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R581-600.

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That's it for an allegedly too lengthy installment of "On Short Notice"... about as much a misnomer as the "weight maintenance" phase in the Verhoef study, I guess. Maybe some of today's Facebook news can make up for that? In the end news like

Want to make HIIT a hit for you? Not a problem, the SuppVersity holds all the information you need. Start out with the respective two post article series and descend into the archives, where you are going to find more about HIIT, how it compares to LISS and which different regimen have shown some promise in peer-reviewed research (learn more)

• High fat dieting reduces the beneficial effects of resistant starch - Reduction in abdominal obesity with 42% fat diet = zero (read more)
• HIIT hits home in 8 young, untrained men - 12 HIIT sessions lead to increased V02 kinetics (read more)
• Ice slurries are the new energy gels - Scientists observe significant increases in cycling performance (read more)
• Physical therapy as effective as surgery for a meniscal tear and osteoarthritis - Unfortunately patients are too lazy and the revenue for the doctors too small to be used more often (read more)
• Evolution is to blame for inflammatory disease - At least that's what the latest "paleo" research would suggest (read more)

are eventually the reason that the saturdaily short news are always so lengthy. The really short stuff is already on Facebook ;-)

References:

• Gavrieli A, et al. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism.2013 [ahead of print]
• Pedersen DJ, Lessard SJ, Coffey VG, Churchley EG, Wootton AM, Ng T, Watt MJ, Hawley JA. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine. J Appl Physiol. 2008 Jul;105(1):7-13.
• Verhoef SP, Camps SG, Bouwman FG, Mariman EC, Westerterp KR. Physiological response of adipocytes to weight loss and maintenance. PLoS One. 2013;8(3):e58011.
• Wyatt HR, Peters JC, Reed GW, Barry M, Hill JO. A Colorado statewide survey of walking and its relation to excessive weight. Med Sci Sports Exerc. 2005 May;37(5):724-30.
• Zulyniak MA, et al. Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men. Metabolism. 2013 [ahead of print]