Fat Loss Principles That Work: 10g+ of EAAs W/ Every Meal. Do Energetic Costs of Protein Synthesis Trigger This Effect?

EAAs beyond whey: It may not necessarily look like this, but this salad (repicecorner) is an EAA power horse with cheddar cheese (25% protein, 0.49 EAA / P ratio), tuna (in oil, 29%,  0.45) and kidney beans (9%, 0.45). You see, it does not always have to be chicken breasts or whey to get beyond the 10g+ EAA threshold, I have repeatedly suggested as one of the fundamental rules of dieting for weight loss, maintenance and muscle gain.

Many people take it for granted that you become fat, when you get old. If you look at the statistics, you could even make a point that obesity has some protective effects with esp. with respect to CVD mortality. Scientists call this the "obesity paradox" (Kastorini. 2013). What's particularly paradox, at least in my humble opinion, is yet not the phenomenon itself, but rather the fact that it gets smart scientists derailed from working on useful dietary and exercise interventions to prevent the development of heart disease, cancer, metabolic syndrome etc. in early years. Instead, they argue ex-post, i.e. when the baby has already been thrown out with the bathtub by comparing sick lean (in parts even cachectic) and sick "obese" people, why their statistical shenanigan that's based on the useless BMI produces paradoxical results. And that, when studies such as the one Jacobs et al. did in 2010 clearly show that 50+ year old men and women with waist circumference >120cm and >110cm, respectively, have 2x higher all-cause mortality risk than their lean peers - irrespective of BMI (Jacobs. 2010)!

To get lean and stay lean, yet not thin and skinny fat is therefore a challenge everyone...

... from the child in the Kindergarten to the obese granny in the nursing home is facing. Against that background a previous study by Loenneke et al. comes to mind. The results of their analysis, which were published in Nutrition and Metabolism in January 2013 clearly show that the amount of times people eat meals with a 10g+ EAA content per day was inversely related to percent central abdominal fat (Loenneke. 2013). In previous studies EAAs have also been shown to improve glucose clearance without increases in insulin and in the absence of effects on the fat burnin and health promoting expresion of AMPK-alpha2 in skeletal muscle tissue (see "EAAs Stimulate Muscle Glucose Uptake by Exponentiating Insulin's Effect on GLUT4 Expression"). With the advanced publication of a study by Coker, Miller, Schutzler, Deutz and Wolfe in the online verison of the Nutrition Journal a couple of days ago, the notion that EAAs have a particularly beneficial effect on fat loss - in this case in obese elderly individuals - gets further support from a well-controlled randomized trial (Cooker. 2013).

EAA-rich protein increases fat loss to a greater extent than low EAA protein

The researchers from the Center for Translational Research in Aging and Longevity and the University of Arkansas for Medical Sciences in Little Rock, AR, USA randomized 12 elderly individuals (mean age 69 years) to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (~850 kcal/day; the exact nutrient composition can be found in figure 1) + ~400kcal from solid foods (total intake: ~1,250kcal/day; the subjects were free to chose their solid meals but were provided with a list of examples the should pick from, if possible).

Figure 1: Macronutrient composition of the meal replacements used in the study (Cooker. 2013)

The diet was designed to induce a 7% weight loss in two months. And while both,  the rate of weight loss (~1.6lbs per week), as well as the relatively high caloric deficit are certainly appropriate for someone with a 30+ BMI and ~40% body fat, leaner people will fare better with a less pronounced kcal deficit or (alternatively) have to add some strategically planned refeeds to the equation in order to minimize the loss of lean mass and, more importantly, avoid the ensuing reduction in energy expenditure (for the obese, the latter is actually less of the problem, because the downsides of being calorically deprived are at least partly counglucose tolerance and leptin sensitivity with every gram of body can actually help the body recognize that there is still plenty of energy that has just not been available (glucose) or "visible" (fat) before).

Figure 2: Changes in lean and fat mass (kg, left) and fractional protein synthesis rates (FSR) in participants receiving iso-caloric meal replacements with identical macronutrient compositions (see figure 1), but different amounts of essential amino acids (EAAs) content (Coker. 2013)

As the data in figure 2 goes to show you even the obese individuals in the study at hand lost a non-negligible amount of lean mass - unfortunately the body composition was measure with a sophisticated, but still body impedance based device, the trends are still accurate, but it is questionable in how much we are actually talking about ~2 and 2.5kg of muscle mass (figure 2, left), because somebody's "lean body mass" does obviously include more than just skeletal muscle.

When it comes to supplements, we are often like children on Christmas eve. About all the new stuff we get we tend to forget our former favorite and often way more fun to play with toys. Don't make this mistake and ditch your PWO whey (personally, I like a ~1.5:1 whey + micellar casein mixture) for EAAs, they don't come close... read more

Be that as it may - since the before and after values were taken with the same device the changes should be correct, so that both the slightly yet not statistically significantly ameliorated loss of lean body mass and, more importantly, the significantly higher degree of body fat loss in the EAA meal replacement (EAAMR) group speak in favor of the 5 servings of a the 170 kcal, 6g EAA per day. Moreover, "the sparing influence of muscle loss might have been demonstrated with a larger sample size", so that you can take it for granted that the preservation of precious muscle mass is an advantage of being choosy with your protein sources and preferring those with higher over those with lower essential amino acid contents.

On a related note: I don't know if you noticed, but with a total energy content of 850kcal and 30g EAA these 5 meal replacements did in fact have exactly those 10g+ of essential amino acids, I have repeatedly recommended to have with each of the 3 meals most people consume in the course of the day.

In all fairness, it should also be mentioned that despite not being significantly different at baseline, the body fat percentage of the subjects in the EAA meal replacement group was ~3% higher to begin with.This may seem irrelevant, since figure 2 compares lean mass and fat mass as absolute changes and not their percentages, but in the end, the amount of fat you you can drop within a given time-frame decreases with lower body fat percentages.

Do the energetic costs of protein synthesis drive fat loss?

Another interesting observation Coker et al. made is the close association between fat loss, on the one hand, and increased protein synthesis (55%), on the other hand. The researchers take this as an incentive to do one of the of the much loved calories in vs. calories out calculation and come up with the following hypothesis:

"Acute administration of EAAMR did promote a significant increase in skeletal muscle protein FSR compared to CMR. Assuming that the energy cost of protein synthesis is 3.6 kJ/g and the baseline GAIA-derived lean tissue mass was 56.4 kg for EAAMR and 54.4 kg for the CMR, we can extrapolate that the overall energy discrepancy between the two groups was roughly equivalent to 27,170 kcal or 3.5 kg of weight loss across the entire caloric restriction-based weight loss paradigm. Based on the amount of total lean mass in each group, this value takes into account a consistent intervention structure of five servings/day across an eight week period. In short, these calculations suggest that differences in the source of intact protein/formulation of EAA may have a significant influence on diet-induced energy expenditure that coincides closely with the greater reduction of adipose tissue in EAAMR compared to CMR." (my emphasis in Coker. 2013)

I usually discard fallacious calculations like this one if they are not highlight the stupidity of trying to eat exactly as much as some funky formula + the figure on your treadmill, pedometer, heart rate monitor or whatever fancy tool you may use to "measure" your energy expenditure suggest you would have burned in the last 24h. In this case, however, I made an exception, because I feel that the notion that protein quality is one of the myriad of parameters that are missing from this foolish calculation is important, for lean and obese people from all age groups who are trying to shed body fat.

Bottom line: The take away message of the study is in the end identical to the previously mentioned study by Loenneke et al.: Make sure you hit the 10g EAA threshold with each and every of your meals, if being lean and muscular not skinny yet fat is your goal.

References:

• Coker RH, Miller S, Schutlzer S, Deutz N, Wolfe RR. Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals. Nutr J. 2013 Dec 11;11(1):105. [Epub ahead of print]
• Jacobs EJ, Newton CC, Wang Y, Patel AV, McCullough ML, Campbell PT, Thun MJ, Gapstur SM. Waist circumference and all-cause mortality in a large US cohort. Arch Intern Med. 2010 Aug 9;170(15):1293-301.
• Kastorini CM, Panagiotakos DB. The obesity paradox: methodological considerations based on epidemiological and clinical evidence--new insights. Maturitas. 2013 Jul;72(3):220-4.
• Loenneke JP, Wilson JM, Manninen AH, Wray ME, Barnes JT, Pujol TJ. Quality protein intake is inversely related with abdominal fat. Nutr Metab (Lond). 2013 Jan 27;9(1):5.

On Short Notice: PWO EAA Supps for Young & Old, Indoor Pools & Low Testosterone, Life-Savingly Low T3/rT3 Ratios, Copper-Zinc-Manganese, Lifting for Prostate Health +More

Image 1: It's neither just as much, nor just as serious, but I would still venture the guess that it will take you more than 30s to digest today's installment of "On Short Notice" - despite the fact that the new format has no lengthy "short news", anymore ;-)

For this installment of "On Short Notice" I have decided to go a somewhat different route than before: Originally, the first post you would have read after this short introduction would have dealt with the potential negative health effects of homogenized milk. What was intended as a "on short notice" item, did however become lengthier and lengthier, until it finally turned into an "almost full-length post" (a slightly extended version of this article is going to be published on Monday). This "incident" made me revisit the last installments of this series only to realize that the majority of the supposedly "short" On Short News items had become "almost full-length posts" and were thus either somewhat overblown or still to short for what the study / topic had to offer...

To cut a long story short, I decided to stick to the very short items, formerly known as "On Very Short Notice" from now on.  If you have any reasonable objections against this practice, feel free to use the comment area of this post to complain. Do not forget, however, that you can still request a longer article on any particularly interesting topic or simply discuss the blurbs with me and others here or on the SuppVersity Facebook wall... Ready? Let's roll!

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  Figure 1: Ratio of muscle intracellular leucine to blood leucine concentration in response to
  resistance exercise and ingestion of 20 g of essential amino acids in young and older men.

  Older physical culturists can't "eat to grow" benefit from EAA ingestion - at least not to the same extend younger lifters do. And while this alone would hardly qualify as "news", the, or I should say one of the underlying reasons Jared M. Dickinson and his colleagues discuss in a paper that's scheduled to be published in the next issue of the Journal of Clinical Nutrition certainly is (Dickinson. 2013).
  One hour after the 7 young (30 ±2yr) and 6 old (70 ±2yr) male "recreationally active" study participants had performed a standardized leg training program consisting of 8 sets of 10 reps on a Cybex leg extension machine at an intensity of 70%RM (3 min rest between sets) Dickinson et al. supplied them with a 500ml of a fluid that contained 20g of leucine enriched essential amino acids (EAA) (exact composition: histidine 8%, isoleucine 8%, leucine 35%, lysine 12%, methionine 3%, phenylalanine 14%, threonine 10%, and valine 10%). In the hours following the leg training the scientists measured the amino acid flux and took muscle biopsies from the vastus lateralis to quantify the amino acid transporter (the "shuttle" that carries the amino acids from the blood stream into the muscle) expression in the trained leg muscles of their subjects.
  Contrary to what happened in the younger subjects, the expression of the transporter proteins was not further augmented (over exercise alone) in response to the ingestion of the EAA supplement in the older study participants. Consequently, the restoration of the intra- to extracellular amino acid ratio which was complete after 5h in the young subjects took more time and was not completed, when the third biopsy was taken at T=5h in the older subjects (see figure 1). A result, which (re-)emphasizes the paramount importance of physical activity in older people not just to become stronger, but also to ward off sarcopenia (=muscle loss) and subsequent frailty!

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  Figure 2: Unadjusted (top, middle) and adjusted (bottom) testosterone levels in adolescent boys depending on their exposure to chlorinated indoor-pool water before the age of 7y (bottom) and 10y (top, middle) respectively.

  Michael Phelps & Co at high risk of low testosterone - That's at least what we'd have to conclude from a 2011 paper that was published in the International Journal of Andrology by Nickmilder et al. who found that there is a clearcut association with early life exposure to chlorinated indoor-pool water and low testosterone levels in adolescence (and probably later in life, although that was not part of the study; cf. Nickmilder. 2011)
  As the data in figure 2 shows, the association with lower testosterone levels is most pronounced (p < 0.01) when the data was adjusting for inhibin B, FSH, age, time of blood sampling and breastfeeding (figure 2, bottom). With p < 0.05 (=5% chance that this is just coincidence) even the unadjusted values for pool water exposures of >250h before the age of 7 years were however statistically significant and as the scientists point out probably a result of the prolonged exposure of the "highly permeable scrotum" (Nickmilder. 2011)  to chlorinated water.
  

  Intriguingly, Bob Weinhold mentions in his otherwise rather critical comment on the study that Shanna Swan, a professor of preventive medicine at the Mt. Sinai School of Medicine, did not just criticize the "paucity of evidence from other studies", but also her hint at "effects from bath water exposures" as potential confounding factors (Weinhold. 2013). Against that background I suggest you go and take a very close look at the label of whatever cosmetic products you pour into your (male) children's bathwater.

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  Image 2: The dreaded low T3/rT3 ratio appears to be life-saving for critical ill patients. And when you come to think about it, it could well be a "natural mini coma" by which your body diverts all available resources to the one thing that's certainly more important than having a six pack: SURVIVAL!

  Low T3/rT3 ratio protects critical ill from death! While 1000s of visitors of various bulletin boards and discussion groups on the Internet are whining about a too low ratio of the "active" to the "inactive" form of triiodothyronine, the observation Marijke Gielen and her colleagues made, when they studied the chance of critically ill patients to be released early and alive from hospital, would suggest that rT3 is way more than a nasty millstone around the neck of (over-)dieters. After all, Gielen et al. found that the patients with the best blood glucose control and lowest T3/rT3 ratios had a +19% increased chance of being released early and alive (Gielen. 2013). An increase in the T3/rT3 ratio, on the other hand, was independently of glucose management, associated with a -14% lower chance of being released early and alive!
  I guess that this should be reason enough to rethink the generally touted "uselessness of rT3", wouldn't you agree? After all, it could well be that it is the rT3 induced metabolic slowdown that allowed for optimal recovery - much similar to the artificial coma physicians will induce in burn victims or other critically patients to have them recover faster / at all. This would yet also imply that having a very low T3/rT3 ratio is - as I've previously mentioned, by the way - a good indicator of other, non-thyroid related pathologies you should better try to spot and take care of before they will eventually show up and turn you into a subject for a follow up study for Gielen et al. (related: "T4+T3 Combination Therapy Instead of T4 Mono-Therapy")

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  Figure 3 (Zhu. 2013): Vitamin D3 is converted to the active metabolite 1,25(OH)2D3 by sequential 25-hydroxylation and 1a-hydroxylation.

  Slow conversion of D3 to 25-OHD in the obese suggests: Low vitamin D is a result of obesity - not vice-versa! Within the past decade(s) many scientists have observed correlations between higher adiposity and lower vitamin D levels (e.g. Arunabh. 2003). Only within the last 5 years or so, however, those results have been interpreted as "scientific evidence" that low vitamin D levels play a causative role in the current obesity epidemic. First evidence for the opposite, i.e. a causative relationship between obesity and the occurrence of chronically low systemic vitamin D levels in obese individuals (90%+ of the obese women in the study had 25OHD level <50 nmol l⁻¹; Wamberg. 2013), does yet come from a study that has been published in the International Journal of Obesity a couple of weeks ago.
  According to the Wamberge et al. present in their paper, the occurence of low 25(OH)D levels in the sera of obese individuals is a direct consequence of the sluggish bioactivation of vitamin D3 in the subcutaneous adipose tissue of obese patients. The latter is due to the -71% and -49% reduced expression of the two of the enzymes from the cytochrome P450 enzyme cascade (25-hydroxylase and 1α-hydroxylase, to be precise, see figure 3), which are responsible for the conversion of dietary or skin-derived (after sun exposure) vitamin D3 to 25(OH)D, which is the form of "vitamin D" your doctor will usually measure, and the "active" form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3) aka calcitriol.

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  Image 3: That's what active prostate cancer prevention can look like - no vaccine necessary!

  Heavy lifting protects against prostate cancer! This is the result of yet another of a whole host of studies which finally acknowledge the value of weight training with respect to all sorts of health benefits that have previously been ascribed to aerobic training only (Teixeira. 2013). Published ahead of print in the online version of the Scandinavian Journal of Medicine & Science in Sports the paper by Teixeira et al. is the first one to report that strength training can reduce the risk of prostate cancer by (re-)establishing a healthy balance between natural cell death and growth.
  In the course of a 91-day period a group of rodents were exposed to a daily "weight lifting regimen" (=jumping, 4x10 jumps with 50–70% of their body weight strapped to the thorax and 60–s rests between sets). This torture lead to an increase in corticosterone (=cortisol), DHT and testosterone levels, and brought about a healthier ratio of cell growth to apoptosis in the prostates of the animals than it was present in the age-matched sedentary control.

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  Figure 4: Building muscle requires more than just pumping existing fibers full of protein (click on the image to read up on the details)

  Scientists confirm Intermittent Thoughts on Building Muscle: Myostatin allows cells to "blow up", but does not facilitate structural changes. What's funny though, is that Lee et al. obviously feel that this is a great thing; and while it may actually be in the context of sarcopenia (pathological muscle dystrophy), where agents that block myostatin could proof very valuable tools, it just confirms that these agents are of little use, if not counterproductive for athletes and physical culturists who would always have to be on the look-out not to outgrow the necessary (re-)construction process, of which I have argued in the Intermittent Thoughts on IGF-1 an Its Splice Variants, already that it is necessary to keep the ever-growing muscles functional.
  So, in case you have a few vials of a real myostatin inhibitor lying around (not the hilarious egg-derived supplement that was sold a couple of years ago by snake oil vendors), you better talk to your medical practitioner about some growth hormone, as well, if you don't want to end up huge, but so weak that you can't make it up the five stairs in front of your gym ;-)

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  Image 4: While some experts say otherwise it appears illogical that the increase in breast tissue density, that's characteristic of women with a non-android body fat distribution would increase breast cancer risk. The majority of studies still ascribes a much higher increase in cancer risk to abdominal obesity (=android fat).

  Silicon boobs? Not necessary if you stay in shape! While the overall size still is a matter of genetics, the density of the female breast shows such a strong negative association with the android : gynoid ratio in young women (one standard deviation up corresponds to a -20% reduction in dense breast tissue; Dorgan. 2013) that it would seem as if simply staying in shape and thus avoiding the accumulation of body fit in the "unfemale" android areas could would (other factors like breastfeeding etc. aside) save one or another woman from a still very much underestimated and by no means just monetarily costly operation (cf. Bolton. 2013). And let's be honest: What are those silicon balls worth anyway, when the blubber starts shortly beneath? What certainly is bad news for the adolescent obesity generation , though is that childhood obesity is an even stronger predictor of low amounts of dense breast tissue. Even after adjustment for adult obesity each BMI z-score, i.e. one standard deviation upwards, was associated with a -27% decrease in tender breast tissue.
  Against that background it appear dubious, whether or not the often touted association between dense breast tissue and breast cancer risk is by any means a causative one... after all Abu-Abid et al. report in their review on the literature that abdominal obesity, i.e. an android body fat pattern is one of the best predictors of increased risk for all cancers (Abu-Abid. 2002).
• Are manboobs a sign of intelligence? Could be if we put any faith into the relation between the size of your hippocampus and your intellectual capacity, the findings Janine Bayer and her mostly female colleagues (this could be important, who knows maybe this is a feminist conspiracy!?) report in their latest paper on the effects a certain genetic polymorphicism (rs700518) in the aromatase enzyme CYP19A1 will have on both systemic as well as hippocampal estrogen levels and had the volume of the posterior hippocampal gray matter (Bayer. 2013). Unfortunately most manboobs today are a simple result of overaromatization due to obesity and whether this is a hallmark feature of superior intelligence appears at least questionable to me (suggested read: "Chest Fat, Bitch Tits, Chesticles and How to Get Rid Off Them")

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  Image 5: 1x 1g of taurine = 1.5% faster 3k-times in trained middle distance runners - another benefit of the underrated sulfur amino acid, taurine

  Taurine works for 3k-runs as well that's the simple message of a recently published study by Balshaw et al. In the randomized, double-blinded crossover experiment the ingestion of 1,000mg of taurine immediately prior to a 3km run increased the time-trial performance of the eight trained middle-distance runners by statistically significant 1.5%, on average (Balshaw. 2013); this does allegedly not sound like much, but if you take into consideration that this was a single serving effect it is actually quite impressive compared to the the ~1% performance increment in the narrow range of 90-120s activities that has recently reported to come out of weeks of beta alanine supplementation.
  So, if the testosterone boosting, anti-diabetic effects of taurine (see "Up to 180% Increase in Testosterone & More From Taurine") did not already convince you to invest the ~$20 for a 500g batch of this sulfur amino acid, maybe these results and a couple of hours in front of the TV watching track & fields events at the Olympic Games '12 can ;-)

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  Figure 5: Glucose metebalism markers of oxidation and nitric oxide (top) calculated artheorscleortic risk (bottom, left) and body weight gain (bottom right) in the different groups

  Differential and common effects of zinc, copper and manganese supplementation on body weight gain, glucose metabolism and cardiovascular health have recently been reported by scientists from the Usmanu Danfodiyo University in Nigeria. In their paper that has been published in the Journal of Oxidative Medicine and Cellular Longevity Muhammad et al. report that the provision of high copper (4mg/kg), high manganese (10mg/kg) and high zinc (20mg/kg) diets or the addition of all three supplemental minerals to the diets of salt-loaded hypertensive male Wistar rats all offered at least some protection against the oxidative stress, dyslipidemia, and insulin resistance that's associated with hypertension.
  As the data in figure 5 goes to show, the provision of additional copper does yet appear to exert the most benefits. In view of the short duration of the study, it would yet be more than premature to recommend copper only supplementation regimens in the absence of proven and most importantly specific deficiencies. Rather than that those of you who are suffering from the triumvirate of elevated blood pressure, insulin resistance and dislipidemia would probably be better off if they increased their overall intake of these trace minerals.

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  Image 6: Sounds stupid, but if you are concerned about your dopamine receptor count, you better make sure to eat the bun and order an extra large coke (the original with tons of sugar, of course ;-)

  High fat / low carb = reduced striatal dopamine receptor availability this is the quintessence of a short communication that has been published in the International Journal of Obesity three days ago. According to E van de van de Giessen and his co-workers, rats on a high fat high fat diet (this is no typo but the way of the researchers to acknowledge that the "original high fat diet" as it is interpreted by most scientists is almost equally high in carbohydrates (calorie-wise) as it is in fat; not so for the "High Fat High Sugar High Fat" (HFHS hf) diet in the van de Giessen study. Compared to the regular high fat diet, the HFHS-hf diet ameliorated the increase in energy intake, but reduced the availability of D2 & D3 receptors in the nucleus accumbens.
  Overall, the ratio of fat to carbohydrate in the diet and not as it has previously been speculated the degree of adiposity or the total energy intake were the most and only significant correlate of the central dopamine receptor downregulation the researchers observed in their test animals (Giessen. 2013). In view of the fact that Fetissov et al. speculated in 2002, already, that "[l]ow D2 receptor expression may be causal for an exaggerated dopamine release observed in obese rats during food ingestion" (Fettisov. 2002) this is bad news - as it would indicate that the low carb induced reduction of dopamine receptor density could precipitate to reward driven episodes of overeating... an emphasis is on the conditional, here, as the majority of low-carb dieters will probably confirm my gut feeling that during the low carb diet, the exact opposite appears to be the case (at least as long as we are talking about even more fatty foods ;-).

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  Image 8: According to Hwang et al. it does not matter how you cook your broccoli, if you want to keep the glucosinolates intact. The main point is that you do it fast!

  Cooking your veggies without water reduces cholesterol oxidation and improves potassium status that's what a group of Japanese researchers who declare they do not have any affiliation with the producer of multi-ply cookware, Vita Craft Japan Ltd, found in a 2-week intervention study in the course of which both the "just eat your veggies" and the "eat your veggies, but cook them without water in multi-ply cookware(TM)" (the product reference is #5123) increased their beta carotene and vitamin C levels and decreased their LDL and total cholesterol levels, but only the "without water cookers" had significantly reduced oxidized LDL and profoundly improved (=lower) Sodium : Potassium ratios in their urin (Mori. 2013).
  Now, while this sounds as if it would make sense to buy this cooking "gear" things look somewhat different, when you take a look at the absolute differences and outcomes. While the oxidized LDL levels did in fact improve more in the muli-ply group this brought them just back into the exact same range where they were hovering in the other groups, as well. Similarly, the Na:K ratio was better, but it did improve in the "regular cooking" group as well and would thus probably end up in the same range, after another 2-6 weeks of vegetable eating - regardless of whether you cook them with water or not. Things would probably not be much different for the glucosinolate content of broccoli of which Hwang et al. report in the same issue of the International Journal of Food Sciences and Nutrition report that, they decreased significantly and time-dependently during boiling, steaming and microwaving (Hwang. 2013)
• Black tea, lemon and honey: Can you stack it? Yes, you can! Camellia sinensis, Citrus limon and Apis mellifera all have a record of being potent antioxidants, but according to a paper in the August issue of the International Journal of Food Sciences and Nutrition lemon-flavoured black tea becomes an even more potent health drink, when you "spike" it with honey (Pereira. 2013).
  Moreover, Pereira et al. found that the darker species of the different honeys from Lavandula stoechas, Erica sp. pl. and other indigenous floral species from north-east Portugal they tested were more potent than the light amber varieties.

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  Image 9: The powdery Matcha tea is not only already high in catechines, it will also release>130x more of it's EGCG content into the brewing water than most regular green teas! And as if that wasn't enough, it has a 64% higher caffeine concentration (6.4 vs. 3.9mg/g), as well.

  Matcha tea has an uber-potent 137x increased EGCG content! This is one of the "oldie but goldie" studies I hit upon when I did "colleteral research" in response to a Highbrow Paleo member complaining that the over-potent Matcha tea literally blew him away. Actually not very surprising in view of the fact that it contains 137x more EGCG than regular green tea (brand China Green Tips; cf. Weiss. 2003). And while the selection of a specifically catechin rich fraction will figure here, as well, much of the effect is probably simply a result of the increased surface area and thus the greater efflux of the bioactive ingredients into the brew the tea is steeped in.
  In view of the previously reported negative effects very high doses of green tea catechins can have on your testicular health all matcha lovers out there should better limit their daily consumption to one or two cups of the exclusive brew (see "20% Reduction in Testosterone with 5 Cups of Green Tea").
• Oral anti-oxidants restore glutathione in diabetic skin At least in rodents this works pretty damn well. According to Sokmen et al. all it takes to restore the natural antioxidant defense system in the skin of streptozotocin-induced diabetic rats (model of type II diabetes) are 250 mg/kg vitamin C, 250 mg/kg vitamin E and 0.2 mg/kg selenium (Sokmen. 2013). The human equivalent of these orally supplied antioxidants would be 40mg/kg vitamin C, 45 IU/kg vitamin E and 30µg/kg selenium - all much too high to benefit anyone who is not diabetic, by the way.

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  Image 10: Usually I am really enthusiastic about new technologies, but looking at how careful physicists handle nanomaterials, and how food designers and the cosmetic industry unleash them on the costumers, like the US and UDSSR unleashed the a-bomb radiation on their own soldiers, ignorant of the (un?)known dangers.

  Nano-sizing fish oil doubles absorption - This is the result of a recently conducted rodent trial by Tanmoy kumar Dey the results of which are soon going to be published in Food Research International (kumar Dey. 2013). The more than +50% increased absorption the scientists found for their nano emulsified fish oil in the small intestine of the lab rats is - at least in my humble opinion - somewhat frightening. Firstly, I am really not sure we really need the hilarious amounts of fish oil, where the use of respective products would make sense (it should be said, though, that this new formula has been developed for parenteral nutrition, specifically). We have, secondly, not the slightest idea if those nano-sized fish oil molecules behave anywhere similar to their fluffy large brethren - who tells us that they don't have the exact opposite effect on our health?
  And third and lastly, if nano-sized fish oil is absorbed 100% more efficiently, all other nanomaterials - especially those that are nor increasingly popular in the cosmetic industry - will have a similarly increased "bioavailability" and could thus not only reach places in our body they were never intended to reach, but do just that in very significant amounts!

References

• Abu-Abid S, Szold A, Klausner J. Obesity and cancer. J Med. 2002;33(1-4):73-86. Review.
• Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. 2003 Jan;88(1):157-61.
• Balshaw TG, Bampouras TM, Barry TJ, Sparks SA. The effect of acute taurine ingestion on 3-km running performance in trained middle-distance runners. Amino Acids. 2013 Aug 2.
• Bayer J, Rune G, Kutsche K, Schwarze U, Kalisch R, Büchel C., Sommer T. Estrogen and the male hippocampus: Genetic variation in the aromatase gene predicting serum estrogen is associated with hippocampal gray matter volume in men. Hippocampus. 2013.
• Boulton TN, Malacrida C. Women and cosmetic breast surgery: weighing the medical, social, and lifestyle risks. Qual Health Res. 2013 Apr;22(4):511-23.
• Dickinson JM, Drummond MJ, Coben JR, Volpi E, Rasmussen BB, Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise, Clinical Nutrition. 2013.
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• Fetissov SO, Meguid MM, Sato T, Zhang LH. Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake. Am J Physiol Regul Integr Comp Physiol. 2002 Oct;283(4):R905-10.
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80% Greater Protein Synthesis 3-5h After Workout: 20g+ PWO Protein Threshold Holds. Spiking Lower Amounts With Leucine or EAAs Will Still Yield Sub-Optimal Results

Image 1: Milk (proteins) are not just leucine or EAA - try doing that with half the amount of free-form aminos in water - the results will certainly be "suboptimal", I can vouch for that  ;-)

It has been a while since the last study from Stuart Phillips group at the McMaster University has made it to the SuppVersity news. Their latest publication does yet have the potential to pour oil on troubled waters, because the results appear to confirm that even when every other supplement appears to be failing you, you can always rely on your postworkout whey protein (Churchward-Venne. 2013). And while the study confirms that with some free form amino acid witchcraft, you can actually illicit identical post-exercise increases in protein synthesis, the previously determined threshold dosage of 20g of high quality protein is still the gold standard, for everyone whose interest is to actually build muscle which is, as you as a seasoned SuppVersity veteran know, not happening only in the first hour after a workout but within a 24h+  "window of opportunity" that has the size of barn door (cf. "Opening the 'Anabolic Barn Door' With the Key of Exercise and Nutrition Science!")!

You won't get a-whey without 20g+ of whey!

To elucidate whether the increasingly popular practice of pimping whole proteins with amino acids does make any sense in terms of being able to get away with less total protein, yet identical increases in post-workout protein synthesis Churchward-Venne et al. recruited 24 recreationally active, young adult male volunteers (22±0.6 years; 1.80±0.02m; 76.4±2.0 kg; BMI 24.3kg/m²), who had to perform a standardized 4x4 unilateral leg-workout with 3 min rest between sets consisting of

• 4x 10-12 reps of seated knee-extension and 
• 4x 10-12 reps of leg-press

at ~95% of their individual 10-rep max, which had been determined in a testing session 14 days prior.

Note: The reason Churchward-Venne et al. decided to use a unilateral exercise protocol was that this allowed them to take biopsies from both the exercised and non-exercised leg and thus determine the individual influence of exercise and supplementation.

You better make sure you get your protein, not just EAAs or leucine

Figure 1: Amino acid compositions of the test drinks (Churchward-Venne. 2013)

The study participants, who had consumed a standardized, prepackaged relatively low-protein diet (15% protein,. 55% carbohydrate, 30% fat) the day before the exercise intervention, were randomly assigned to consume one of the following drinks

• whey protein - 25 g whey protein isolate (total leucine: 3g)
• whey + leucine: 6.25 g whey protein isolate supplemented with free-form leucine (total leucine: 3g)
• whey + EAA: 6.25 g whey protein isolate supplemented with free-form EAAs (total leucine: 0.75g)

The 300ml of fluid which contained identical tracers, were consumed immediately post workout, blood and muscle biopsies were taken at regular intervals pre- and post workout and MPS, signaling through mTOR, and amino acid transporter (AAT) mRNA abundance were determined.

Figure 2: Relative expression of p-mTOR (left) and p70S6K (right) compared to baseline (Churchward-Venne. 2013)

Now what is interesting is that the "classic" markers of protein anabolism, p-akt (not shown, but exhibited significant differences between treatment), mTOR and P70S6K (figure 2 & 3) do not show a clear-cut advantage of either of the treatments. Immediately post exercise, the increase in mTOR in the exercised leg, for example, is significantly more pronounced in those subjects who consumed a whey protein shake. The "downstream" activation of p70S6K, which supposedly controls protein synthesis at the ribosome, however, is identical in all groups.

Figure 3: Pseudo (=simply weighed by the timespan) area under the curve (a.u) for mTOR and p70S6K, AUC for leucine (a.u.) and fractional protein synthesis in the exercised leg 3-5h after the workout (based on Churchward-Venne. 2013)

The same is true for the protein synthetic response measured as fractional protein synthesis in the whole post exercise period in the untrained, and up to 3h post exercise in the trained leg. Then, however, we see a markedly higher influx of protein into the trained muscle in the whey protein group, which is - and this is somewhat remarkable - not in accordance with the p70S6K levels, which would suggest that the protein influx should be maximal in the leucine and not in the whey group.

A protein pump without protein is useless

Based on the data we have, it is difficult to say whether it is the lack of an individual, a certain combination or the total amount of (non-)essential amino acids that is responsible for this affect. If you take a look at the amino acid composition of the test solutions in figure 1, it does yet appear likely to assume that it is the absence of non-essential amino acids...what? Glutamin? No, I thought so as well, but when you come to think about it, glutamine, of which we have recently seen that it does play a hitherto under-appreciated role in protein synthesis, is unlikely to exert this effect on its own. After all, Chiu et al. based their conclusions with respect to the necessity of glutamine to maximize protein synthesis on increases in mTOR expression (cf. "A New Role for Glutamine in Protein Synthesis?"). 3-5h after the workout the initially increased mTOR levels in the whey protein group had yet returned to baseline and the the leucine, BCAA and EAA levels in the blood of the subjects were identical in all groups (data not shown); and still, the influx of protein into the exercised leg musculature of the whey group was ~80% higher than that in the EAA group.

Image 2 (dormtainment.com): Subjects from the EAA, the leucine and the whey group (from left to right) after ingestion of the respective fluids - just kiddin' *rofl*

But let's be honest, in the end, these results only what common sense should have told us all along: You can push the gas pedal as much as you want (leucine group) and still won't get very far if your protein tank is half empty. Similarly, you can ingest as much leucine as you want and it will still have little effect on total protein synthesis, regardless of whether you train or not. For the practitioner, any further speculations about the minimal amount of leucine, a given persons in a given age-group would need to maximally stimulate protein synthesis, as the authors make them in their discussion of the results are non-significant compared to the following straight forward take home messages:

1. 20-25g of whey protein are still the go to post-workout protein source
2. building a better post workout protein from free form EAAs is not feasible
3. the importance of the non-essential amino acids in "real" protein is probably under-appreciated
4. the importance or I should say potency of leucine is probably much over-estimated
5. muscle protein synthesis and thus skeletal muscle hypertrophy is not a 2h post workout game

In essence, it would suffice to remember just (1) and (5) and to follow the simple yet effective maxime to get 20g+ of quality protein (not 20g leucine ;-) with every meal to get big and muscular and, as all of you who read yesterday's news or one of the many previous posts in which I envoked the findings of Loenneke et al. which show just that: People with a frequent intake of quality protein have the lowest body fat levels (Loenneke. 2013).

References:

1. Chiu M, Tardito S, Barilli A, Bianchi MG, Dall'asta V, Bussolati O. Glutamine stimulates mTORC1 independent of the cell content of essential amino acids. Amino Acids. 2013 May 8. [Epub ahead of print]
2. Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol. 2013 Mar 25.
3. Loenneke JP, Wilson JM, Manninen AH, Wray ME, Barnes JT, Pujol TJ. Quality protein intake is inversely related with abdominal fat. Nutr Metab (Lond). 2013 Jan 27;9(1):5.
4. Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr. 2009 Jan;89(1):161-8.

New Role for Glutamine in Protein Synthesis? Study Suggests Direct Effects on Mammalian Target of Rapamycin (mTOR) - EAAs Alone Won't Produce Optimal Results

Image 1 (Pumping Iron): The guy in the middle, obviously no one else than the Austrian Oak, took glutamine, the rest of the guys forgot about it in all the craze about leucine... no, just kiddin' ;-) Still, someone who trains like Arnold, is probably most likely to benefit from additional l-glutamine

After all those bad news about allegedly effective supplements, I thought it may be about time to present some good news about an allegedly ineffective supplement: Glutamine! Published ahead of print in the online version of the scientific journal Amino Acids, the results from a 2013 study by Martina Chiu and her colleagues from the Unit of General and Clinical Pathology at the Department of Experimental Medicine of the University of Parma in Italy (Chia. 2013), could well explain a recent comment by Macijec who recounts that he saw great improvements in lean-mass retention on a diet from a combined BCAA + glutamine supplement over taking just plain BCAAs. And while I will get to what I believe is a much more likely explanation for this observation in the conclusion of this blogpost, let's initially take a look at what Chiu et al. bring to the table.

Don't take away my glutamine, man!

Previous studies by Evans et al. had already suggested that glutamine, despite its non-essential nature (meaning that your body can produce it from other amino acids by transamination), plays more than just a facilitative role in the phosphorylation of  the mammalian target of rapamycin (mTOR) and skeletal muscle protein synthesis (Evans. 2007 & 2008). To investigate this hypothesis further Chia et al. incubated HepG2 and HeLa cells (the use of these durable and cheap cells instead of myocytes as they were used by Evans, for example, is certainly a downside of the study) and found that

• the presence / abundance of glutamine influences mTORC1 activity 
• this effect is not mediated by glutamine induced increases in cellular leucine content
• the quantitative contribution of leucine and glutamine to the mTORC1 activation is cell-line specific
• even in the absence of glutamine, mTORC1 activity was not completely suppressed 
• in all cells both glutamine and leucine appear necessary for the maximal stimulation of mTORC1 

The cell-line specificity, is unequestionably problematic, still the general finding that glutamine depletion does not lead to a subsequent depletion or lack of uptake of EAAs, which would then in turn reduce the mTOR-induced phosphorylation of the protein uptake regulating enzyme p70S6K (Ribosomal protein S6 kinase beta-1) is probably valid for muscle cells as well. This suggests that" the signals and transduction pathways involved may be also distinct and their sensitivities different." (Chiu. 2013)

So what does that mean? To take or not to take glutamine - this is the question!

If we discard that the exact mechanism behind these observation still remains to be elucidated and invoke that there was a biphasic reaction to glutamine depletion with a minimum from 3h-6h and a subsequent partial rescue pf p70SK activity later, these results would support the value of the ingestion of supplemental glutamine particularly right after intense workouts or in periods of caloric restriction, where the intramuscular glutamine and EAA pools (muscle, liver, intestines) are drawn upon also as a substrate for hepatic glycogenesis (=production of sugar in the liver) and exogenous glutamine may spare "pro-anabolic" BCAAs/EAAs (Holecek. 2002).

Figure 1: Glutamine synthesis
(Self. 2004)

The study at hand, as well as the findings of Candow et al. who report a slight, but eventually negligibly greater increases in lean mass (+0.3%) and strength with 0.9g/kg glutamine supplementation over a 0.9g/kg bw. maltodextrin control in the absence of dietary restrictions do yet suggest that the effects of glutamine cannot be explained solely based on its energy content. And would warrant further investigations into what would be the threshold and optimal EAA and glutamine levels to propel skeletal muscle protein synthesis in vivo and whether or not, a energetically non-restricted high protein diet alone will not eventually provide enough glutamine and respective substrates for it's "on demand" production (cf. figure 1)

Are you training hard to be "glutamine deficient"?

That in fact the intensity of your exercise regimen may be the fundamental determinant of whether you do or don't need supplemental l-glutamine would be supported by the well-established efficiacy of parentally administered glutamine to critically ill patients. As so often inflammation appears to be, once again, the fundamentally important determinant, as it has been shown to increase in the net release of glutamine from peripheral tissues, such as your muscles, to central tissues and complex systems like the immune system  the liver (as mentioned before), the spleen (!) and wounds (Soeters. 2013). Against that background the longstanding practice of ingesting extra amounts of glutamine may well make sense, if the latter would actually make it to the periphery and would not be absorbed by exactly those previously enumerated "central tissues" that do not just need it the most, but that have a relatively comprehensive amount of scientific data to back the usefulness of glutamine as well as glutamine-(di-)peptides such as l-alanylglutamine (brand name Sustamine).

Are those dipeptides so much better? You will probably have heard about the "unbelievable", "unique" and "far superior effects" of glutamine dipeptides compared to the regular, dirt cheap free-form l-glutamine. And despite the fact that I am not aware of studies that would compare one to the other in a relevant, exercise related context, these statements do actually have a rationale basis. After all, the transport of intact peptides by the PEPT transporters in the gastrointestinal tract peptides has the major advantage that the cells of the gut do not avail themselves of as much glutamine as they want before it even reaches systemic circulation (Adibi. 1997). Whatever it's exact effects on protein synthesis may be - on a gram per gram base the dipeptides will therefore be more effective than regular l-glutamine. What you should keep in mind though is that you get both glutamine and alanine from sustamine at a ratio of ~3:2. The 40% of alanine are yet by no means useless. Rather, they could, in and out of themselves, exert (if nothing else) EAA and even glutamine sparing effects, since alanine is, next to lactate and pyruvate, the major gluconeogenic precursor during exercise (Brooks. 1987).

Image 2: I what's on this tummy is all you put in your tummy, l-glutamine alone will probably not prevent the highly undesirable transition from slightly chubby to skinny fat. With a dialed in, but calorically and/or carb restricted diet, l-glutamine supplementation could yet spare help you spare tissue protein, get rid of ammonia and maintain a decent amount of muscle.

The two exercise related studies on the latter by Hoffmann et al., which showed beneficial effects of l-alanylglutamine (AG) supplementation on hydration stress during endurance exercise and overall performance during a basketball match do yet suffer from a non-negligible methodological shortcoming: In both trials the AG solution was compared to plain water instead of an isocaloric carbohydrate solution. Against the background hat glutamine and alanine the individual amino acids the peptide is made of are the main substrates for amino acid driven hepatic gluconeogenesis it is at least very questionable whether the observed effects could not have been achieved by the same amount of plain table sugar, since both the  time to exhaustion during a mild hydration stress (Hoffmann. 2010) and the skill performance and visual reaction time (Hoffnmann. 2013) are unquestionably unrelated to the mTOR effects Chiu et al. observed in their study. 

It would thus warrant a longitudinal study in resistance trained individuals consuming a high protein diet on a high volume strength training regimen (>3 sessions per day, which is the maximum I have come across in hitherto published trials), to see whether your gains would benefit from additional glutamine... if you are dieting, on the other hand, you could argue that you better play safe than be sorry and add another tablespoon of glutamine to your BCAAs ;-)

References:

1. Adibi SA. The oligopeptide transporter (Pept-1) in human intestine: biology and function. Gastroenterology. 1997 Jul;113(1):332-40. 
2. Brooks GA. Amino acid and protein metabolism during exercise and recovery. Med Sci Sports Exerc. 1987 Oct;19(5 Suppl):S150-6.
3. Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T. Effect of glutamine supplementation combined with resistance training in young adults. Eur  J Appl Physiol. 2001 Dec;86(2):142-9.
4. Chiu M, Tardito S, Barilli A, Bianchi MG, Dall'asta V, Bussolati O. Glutamine stimulates mTORC1 independent of the cell content of essential amino acids. Amino Acids. 2013 May 8. [Epub ahead of print]
5. Evans K, Nasim Z, Brown J, Clapp E, Amin A, Yang B, Herbert TP, Bevington A. Inhibition of SNAT2 by metabolic acidosis enhances proteolysis in skeletal muscle. J Am Soc Nephrol. 2008 Nov;19(11):2119-29. Epub 2008 Jul 23. 
6. Evans K, Nasim Z, Brown J, Butler H, Kauser S, Varoqui H, Erickson JD, Herbert TP, Bevington A. Acidosis-sensing glutamine pump SNAT2 determines amino acid levels and mammalian target of rapamycin signalling to protein synthesis in L6 muscle cells. J Am Soc Nephrol. 2007 May;18(5):1426-36. Epub 2007 Apr 11. 
7. Holecek M. Relation between glutamine, branched-chain amino acids, and protein metabolism. Nutrition. 2002 Feb;18(2):130-3. 
8. Self JT, Spencer TE, Johnson GA, Hu J, Bazer FW, Wu G. Glutamine synthesis in  the developing porcine placenta. Biol Reprod. 2004 May;70(5):1444-51. Epub 2004 Jan 21. 
9. Soeters PB, Grecu I. Have we enough glutamine and how does it work? A clinician's view. Ann Nutr Metab. 2013;60(1):17-26. 

Whey More Insulinogenic Than White Bread: Insulin Spike is Mediated by GIP Secretion in the Gut & Effect of EAAs on the Pancreas + Why Whey is Still the Better Choice

Image 1: Peter Czerwinski, aka Furious Pete, certainly did not care about the pro-insulinogenic effects of whey, when he ate 900g of it within 3:30min, click here to watch his record (Furios Pete, 2010)

Among muscle heads and physical culturists, alike, whey protein has become almost synonymous with building slabs of lean muscle.What many of the protein fans - especially the low carbers - tend to overlook or ignore, though, are the pro-insulinogenic effects of whey protein, in general, and purified whey protein isolates and hydrosolates, in particlar, which do not just augment the insulin release in response to carbohydrate ingestion (Morifuji. 2010), but exert a decent increase in pancreatic insulin release in and out of themselves (Claessens. 2009). Further evidence on the hitherto not yet fully understood mechanism behind the whey induced increase in insulin comes from a recently published paper by Albert Salehi and his colleagues from the Lund University in Sweden, the University of Copenhagen in Denmark and the Oxford Center for Diabetes, Endocrinology and Metabolism in the UK (Salehi. 2013).

Whey vs. white bread and human plasma as incubation medium

In the aforementioned paper, the scientists present the results of a combined in-vivo + in-vitro trial on the effects of glucose, amino acids and amino acids mixtures (as they are found in whey) on pancreatic insulin production and its relationship to the incretin response (release of incretin hormones from specialized cells in the small and large intenstine). To this ends, the researchers had their subjects, four men and two women (healthy non-smokers, normal-weight, age 20-30y), consume test meals containing either white bread (3.7g of protein) or whey (16.7g of protein), after an overnight fast, on two different occasions. The meals had to be consumed within 12 minutes and blood samples were taken 7.5,  15, 30 and 45 min after the start of the meal.

Figure 1: GIP and GLP-1 response to whey and white bread (left, top & bottom); insulin release (%) per islet relative to glucose after incubation with different amino acids, amino acid mixtures and mixture + GIP (Salehi. 2013)

As you can see in figure 1 (left), the ingestion of  ~20g of whey protein (containing 16.7g of protein + lacose + minimal amounts of fat) produced a significantly more pronounced in increase in glucose-dependent insolinotropic peptide (GIP, see previous post "Waxy Maize Reloaded" for more information) than the white bread meal. GIP is a hormone-like substance that is produced by the enteroendocrine cells of the gut lining, amplifies the glucose-induced production of insulin in the pancreas, slows down digestion, increases glucose absorption, ramps down fatty acid oxidation and sets you into energy "storage mode" - unfortunately in both forms, skeletal and liver glycogen and fat!

Figure 2: Simplified schematic illustration of mechanism behind the EAA induced GLUT-4 increase in skeletal muscle (click here to learn more)

GLUT-4 activation - another reason, why whey is way better than sugar: If you remember Monday's blogpost on the isolated effects of essential amino acids (EAAs) on the GLUT-4 (glucose transporter = the shuttle that carries glucose from the blood stream into the cell) expression on skeletal muscle cells, it is evident that contrary to sugar or most forms of carbohydrates, whey protein, or rather the essential amino acids in whey, cod, soy, beef, pea, egg and other high EAA protein sources exert nutrient-repartitioning effects due to selectively increasing insulin induced glucose uptake in skeletal muscle and constant glucose uptake in adipose tissue (Lavigne. 2001).

Against that background it is not surprising that the combined effects of GIP (figure 1, top-left) and the amino acid induced increase in insulin production (figure 1, right, orange) lead to a more than 7-fold increase (compared to glucose control) in pancreatic insulin production after incubation of mouse Langerhans cellls (the cells of the pnacreas that are responsible for insulin mediated glucose control) with sera containing a mixture of EAAs and GIP that was matched to the respective EAA and GIP concentrations in the preceding whey vs. white bread human experiment.

Don't worry there are also benefits that can compensate for the insulin spike

Now these results certainly seem odd, after all "the experts" say that insulin is the root cause of all evil! Now whey spikes insulin and GIP and still we see study after study popping up, reporting "beneficial effects" of whey protein on glucose metabolism and overall health - how can that be? The reasons are manifold and actually quite straight forward:

1. Insulin is not the devil - Contrary to common believe the problem is not insulin, but insulin resistance and overspilling glucose stores. If your insulin spikes and you are not insulin resistant, the cells will suck up glucose, your blood sugar will drop and your insulin will drop as well; so, in terms of negative side effects, the most obvious one would be postprandial hypoglycemia in response to large boluses of whey protein (and even that is usually compensated for by increases in glucagon and consequently gluconeogensis)  - that the latter can have long-term detrimental effects on insulin sensitivity is a whole other issue, though...
2. Many studies use (pre-)diabetic subjects - In a pre-diabetics an increase in insulin release due to whey will improve postprandial glycemia and must thus be considered beneficial - it's "nature's insulin supplement", if you will, and particular helpful for non-insulin-dependent type-II-diabetics.
3. Effects on skeletal muscle are neglected - Anything that can potentially help build and maintain muscle tissue (and we all know whey can do that) will help with glycemia, obesity and lipid metabolism, because the increase or (esp. in the elderly) maintenance of skeletal muscle mass ("Metabolic Currency" - Carl Lanore) will allow for greater intra-muscular glucose stores and fatty acid oxidation (assuming you are still insulin sensitive, cf. 1)
4. The "satiety hormones" are overlooked - Similar to the muscle building effects, the increase in GLP-1, a hormone which is by no means just responsible for inducing satiety (read all about GLP-1 in my previous post "Eat More, Burn More and Lose Fat Like on Crack With GLP-1") have been hitherto largely ignored. And that despite the fact that increases in GLP-1 could be among the main reasons that whey and other EAA-rich protein sources have repeatedly been shown to help weight- and, more importantly,  fat loss and increase metabolic health (Ranganath. 1996; Baggio. 2007; Akhavan. 2011; Gerspach . 2011). 

Image 2: Real foods are better protein choices for the last weeks of a contest prep (image directly from Adelfo Cerame's kitchen)

In other words, while some of the "beneficial effects" in obese and insulin resistant individuals could actually turn against lean, active individuals, the muscle-building and "satiety hormone" induced metabolic effects make up for the potential fat storage in scenarios of energy overconsumption (remember: there is a certain margin of carloric surplus, where the laws of thermodynamics do apply, cf. "A Tale of Macro- and Micronutrient Modifications")

Whey is probably not your best choice for the final weeks of a contest prep, though

Still, if you are in the final phase of prepping for a contest and want that "paper-thin" skin conditioning, like our common friend Adelfo Cerame does, real-food protein sources like chicken, fish, lean meat etc. should be your main sources and protein shakes, an exclusive post-workout thing (in the last days, maybe not even that).

References:

1. Akhavan T, Luhovyy BL, Anderson GH. Effect of drinking compared with eating sugars or whey protein on short-term appetite and food intake. Int J Obes (Lond). 2011 Apr;35(4):562-9. Epub 2010 Aug 24.
2. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007 May;132(6):2131-57.
3. Claessens M, Calame W, Siemensma AD, van Baak MA, Saris WH. The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects. Eur J Clin Nutr. 2009 Jan;63(1):48-56. Epub 2007 Sep 12
4. Gerspach AC, Steinert RE, Schönenberger L, Graber-Maier A, Beglinger C. The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E317-25. 
5. Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A. 2001. Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats. Am. J. Physiol. Endocrinol. Metab. 281:E62–71
6. Morifuji M, Ishizaka M, Baba S, Fukuda K, Matsumoto H, Koga J, Kanegae M, Higuchi M. Comparison of different sources and degrees of hydrolysis of dietary protein: effect on plasma amino acids, dipeptides, and insulin responses in human subjects. J Agric Food Chem. 2010 Aug 11;58(15):8788-97.
7. Ranganath LR, Beety JM, Morgan LM, Wright JW, Howland R, Marks V. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut. 1996 Jun;38(6):916-9. 
8. Salehi A, Gunnerud U, Muhammed SJ, Ostman E, Holst JJ, Björck I, Rorsman P. The insulinogenic effect of whey protein is partially mediated by a direct effect of amino acids and GIP on beta-cells. Nutr Metab (Lond). 2013 May 30;9(1):48.