Saturday, September 12, 2015

Whey vs. Casein - Casein-Exclusive Increase in GLUT-4 Expression Beats Whey's Insulinogenic Effect // Creatine Builds Legs of Young & Old, Rookie & Pro, BB & Cyclist

If you drink "old school" protein shakes with milk and eggs, you don't have to worry if casein or whey is better on hypercaloric diets ;-)
Creatine, whey and - at least optionally - casein are on the list of "must have" supplements for anyone who has been following a solid workout routine a decent high(er) protein diet for a year or longer. And even though this makes any news study on one of the three potentially interesting for a huge part of the SuppVersity readers, the results are often so unsurprising that they are hardly worth an individual SuppVersity article...

I mean, let's be honest: You wouldn't be excited if I wrote about study #1023 showing a practically irrelevant acute increase in protein synthesis, let alone totally meaningless increases in mTOR in response to the ingestion of whey protein, would you?

For today's installment of the short news, I will pick two studies that are at least not as simplistic (and useless) as the previously mentioned 1023rd whey protein study.
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Study #1 sheds some light onto the intricate differences between the way(s) whey and casein may differently affect our energy balance, gut hormones, glucose metabolism, and taste preference (Pezeshki. 2015), while study #2 is actually a meta-analysis that makes a first attempt to actually quantify the average effect of creatine on leg strength (Lanhers. 2015).
  • Whey or casein? The answer to this question probably depends on your goals - That's at least what the complex results of a similarly complex series of experiments from the Snyder Institute for Chronic Diseases at the University of Calgary appears to suggest (Pezeshki. 2015). In the corresponding study, the researchers determined the effects of dietary whey, casein, and a combination of the 2 on energy balance, hormones, glucose metabolism, and taste preference in rats.

    Yes, this does mean that we must not uncritically transfer the results to humans. It does not mean, however, that we cannot use the results of Pezeshki's study, at all. Much of what we know and have later proven in human studies about our metabolism has initially been observed in rodents. Doing the same experiments with humans would not just have been significantly more expensive, it would also have been thwarted by misreported energy intakes and a lack of dietary control. So, if you belong to the "it's a rodent study, so I ignore it, if the results don't fit my world-view" faction, you are free to fast forward to the Lanhers study. If not, here's the elevator pitch on the two experiments the scientists conducted:
    • The hormone / energy expenditure experiment: Obesity Prone CD (OP-CD) rats were fed a high-fat control diet (33% fat energy) for 8 wk, and then randomly assigned to 4 isocaloric dietary treatments (n = 12/group): the control treatment (CO; 14% protein energy from egg white), the whey treatment (WH; 26% whey + 14% egg white), the casein treatment (CA; 26% casein + 14% egg white), or the whey plus casein treatment (WHCA; 13% whey + 13% casein + 14% egg white) for 28 d. Measurements included food intake, energy expenditure, body composition, metabolic hormones, glucose tolerance and key tissue markers of glucose and energy metabolism.
    • The food intake / preference experiment: Naive Obesity Prone CD (OP-CD) rats (not the same rats as in experiment 1) were randomly assigned to 3 groups (n = 8/group). During an 8 d conditioning period, each group received on alternate days either the CO or WH, CO or CA, or CO or WHCA. Subsequently, preferences for the test diets were assessed on 2 consecutive days with food intake measurements at regular intervals.
    If you take a look at my compilation of the most relevant data in Figure 1, you will see significant improvements in glucose management in all groups (Figure 1 | G). You should yet also be able to see that the most significant increase in GLUT-4 expression and thus the muscles ability to take up glucose occurred in the casein and mixed protein groups. In the whey group, on the other hand, where the insulin levels were the highest the increase in GLUT4 receptor expression was negligible and the 60 minutes post value for glucose after the glucose tolerance est was higher, but not significantly higher than in either the mixed protein or casein group.
    Figure 1: 0-60 minute hormone, glucose, cytokine and gene response to glucose tolerance test in diet-induced obese rodents fed diets containing either low amounts of protein or high amounts from whey, casein or a combination of whey + casein (Pezeshki. 2015).
    Since you will usually hear that whey is the #1 glucose repartitioner this may seem odd. In view of the fact that insulin can only drive glucose into the cells if they actually "stretch out their glucose "suckers", i.e. the GLUT-4 receptors, it is yet only logical - and that despite the fact that we cannot (yet) explain the differential GLUT-4 response. 
Whey or casein hydrolysate - or rather no protein - what to use in your intra-workout beverage for endurance? Find out in this SV Classic
What types of casein and whey were used? In spite of the fact that it may be highly relevant to know if we are talking about fast digesting and extremely insulingogenic whey hydrolysate (I assume we are) or regular whey concentrate or isolate (I assume we are not), the scientists don't provide any information on the exact nature of the supplemental whey and casein protein in the diet. And even though this may be less relevant for casein, I would like to point out that most rodent studies use cheap calcium or sodium caseinates which are digested much more rapidly that micellar casein, the casein you may be thinking of when you hear "casein" (I am pretty sure it was not casein hydrolysate, though). If you want to be skeptical about the interpretation of the results, don't focus on the fact that it's a rodent study. A lack of specificity like the one in regard to the exact nature of the protein supplement is at least as good a reason to be careful with the interpretation of the results of this study as the species of the subjects ;-)
  • What remains to be seen, though, is whether this measurable, but not in all details statistically significant difference actually matters. If you look at the food intake and preference data in Figure 3. It would seem as if it didn't. I mean, if we apply "Taubes'ian" logic, here, the high(er insulin levels in the whey group should have made the rats overeat...
    Figure 2: Daily food intake during conditioning trials. Rats were fed, on alternate days, a control diet or whey (A), casein (B), or a combination of whey and casein (C). Mean hourly food intakes on 2 consecutive days of preference testing, with access to both control and one of the high protein diets (D, E, F | Pzeshki. 2015). 
    ... a brief glimpse at the data in Figure 2, however, tells you that this was clearly not the case. It is thus not surprising that the final lean and fat mass percentages in Figure 3 did not differ significantly between the groups, even though some of you will notice a non-significant lean vs. fat mass advantage for the casein group. 
  • Eventually, it would still appear unwarranted to use the study at hand to argue in favor of casein instead of whey protein as your protein supplement of choice. If you are yet already following my suggestion to mix the two (read even more), the results of the study at hand would be another reason to stick to that practice.

    Overall, we do yet have to remember that significant treatment effects in response to the increase in protein were observed in all groups. In that, it may be true that the casein group had the highest reduction in food intake (30-43% reduction) and appears to have ended up with a slightly better body composition, but hey, we are talking about non-significant differences in a study that was not just done on rodents, but on obese rodents ... and you know that the weight status obese vs. lean / athletic can make more of a difference in the way people / lab animals react to supplements than the difference between man and mouse.
  • Creatine and lower limb strength - what to expect? You are probably asking yourself now: "Why on earth is Adel so interested in this meta-analysis?" Well, the answer is as simple as it is personal: The only body part of mine that appears to to have ever really benefited from creatine supplementation, strength-wise, are my legs. Accordingly, I was attracted to the Lanhers' meta-analysis, because I hoped to find some clues on why this may be the case.

    Now, I guess I don't give away too much, when I say that the paper didn't provide me with new insights in this respect. What the scientists' compilation and meta-analysis of the data did do, however, was to confirmation that I am not the only one whose "wheels" respond extremely favorably to creatine supplementation: One of the main results of Lanhers' meta-analysis of 60 (!) studies is after all that the effect of creatine supplementation on leg strength is not just statistically significant in almost every study they reviewed, it is also and maybe even more importantly and astonishingly independent of population characteristics, training protocols, and supplementary doses and duration (reread this - you don't have to superdose it!).

    In that, I find it particularly striking that even training for mostly aerobic team sports, like handball, for example, can trigger significant increases in squat performance if the players are consuming 3-5g of creatine before or after their training sessions (Note: In the corresponding study by Izquierdo, the handball players also saw significant increases in bench press performance - It's thus by no means as if creatine was a "leg strength booster", only!).
    Figure 4: Meta-analysis on maximal weight lifted (kg) in squat. CI confidence interval, M male, SD standard deviation, T0 baseline, T1 following supplementation (Lanhers. 2015).
    For the total workout volume (not shown in Figure 4), Lanhers et al. report almost identical effect sizes as the researchers determined them based on the absolute increase in squat performance in kg (see Figure 4); and just like the relative strength gains, the relative volume increases did not depend on the training status or age (subjects were 21-69 years old) of the subjects.

    In view of these results, there's really no good reason to doubt the scientists' conclusions that (a) "[c]reatine supplementation is effective in lower limb strength performance" and (b) works "for exercise with a duration of less than 3 min". If you also take into account that the average effect size for weight and volume are in the range of ~30% irrespective of the population characteristic, training protocols, and supplementary doses and duration, I hope that you can agree that there's also no reason to doubt my repeatedly voiced recommendation to "take your creatine bros" ... ah, and take it with sodium bicarbonate, obviously ;-)
Bottom line: In view of the fact that both items of today's short news already have their own bottom lines, I am not sure if you even need an extra summary, but here you go: With the Pezeshki study we have initial evidence to question the longstanding, but hardly researched assumption that whey is the protein of choice for weight loss and glucose management. In spite of the fact that the results show only trends towards better body composition and improved glycemia with casein vs. whey and need confirmation in non-obese, even better athletic human beings, I will keep an eye on potential follow-up or related studies.

Suggested SuppVersity Classic: "10+ Things You Probably Didn't Know Whey & Peptides That Form During its Digestion Can Do" - When you've read this article, I promise you will (re-)appreciate the benefits of whey and forget the Pezeshki study until a follow-up / related study is published | more
In that, I don't believe we will see an earth-shattering difference between the two protein sources in any potential follow-up, but what I really would like to know is the reason and mechanism behind the unexpected and unexplaind casein-induced increase in GLUT-4 receptor expression on the cell surface Pezeshki et al. observed in the study at hand (other studies often measure only total GLUT4!).

In contrast to the Whey vs. Casein study, Lanhers' meta-analysis of the effects of creatine on leg muscle strength and maximal training volume is so simple to interpret that you can summarize its implications in one sentence: "If you know that creatine will make you stronger, irrespective of how old you are, how you train and whether you take only 3g of much more, you either want to be weak or must be an idiot if you don't take it" | Comment on Facebook!
  • Izquierdo, M. I. K. E. L., et al. "Effects of creatine supplementation on muscle power, endurance, and sprint performance." Medicine and Science in Sports and Exercise 34.2 (2002): 332-343.
  • Lanhers, Charlotte, et al. "Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses." Sports Medicine (2015): 1-10.
  • Pezeshki, et al. "Dietary Whey and Casein Differentially Affect Energy Balance, Gut Hormones, Glucose Metabolism, and Taste Preference in Diet-Induced Obese Rats." The Journal of Nutrition. First published ahead of print August 26, 2015.