# Nutrient Timing of Whey Protein and Creatine Increases Muscle Growth



## Arnold (Oct 13, 2009)

*Nutrient Timing of Whey Protein and Creatine Increases Muscle Growth *
by Robbie Durand  

What's so special about when we eat? To the average person who is not exercising, it does not really matter when you consume nutrients. While nutrient timing isn't critical to the average person, it???s essential to guys who lift weights who are looking to increase muscle mass. Muscle anabolism due to exercise and nutrient intake is influenced by various factors, such as the type of protein. For example, milk protein ingestion following resistance exercise results in greater amino acid uptake by muscle than ingestion of Soy protein.8 Others have documented that a rapidly absorbed protein such as whey is going to lead to a greater insulin and amino acid response than milk casein. Examining the science of nutrient timing in detail, it becomes clear that it's not just the type or the amount of food you eat that counts, but when you consume it in relation to exercise.

For example, researchers investigated the relationship between acute and 24-hour changes in muscle protein metabolism in volunteers over a 24-hour period under two conditions: (1) while resting and (2) when they performed resistance exercise and ingested EAAs (essential Amino Acids). EAA ingestion and exercise increased 24-hour muscle protein synthesis and improved nitrogen balance over 24 hours. More importantly, the difference between rest and exercise was identical whether measured over 3 hours or 24 hours. These results support the contention that acute changes in protein synthesis after resistance exercise represent small changes that occur over longer time periods, resulting in changes in muscle mass.7 Deposition of muscle protein following each bout of exercise is small and the accumulation of these small changes gradually increases muscle mass over a period of training. This gradual accumulation of new proteins may explain why changes in muscle mass with training are generally not measurable until after several weeks of training.


*Windows of Anabolic Muscle Growth*

Many people forget that pre-exercise nutrition is just as important as post-exercise nutrition. Previously, it was reported that ingestion of 6 grams of essential Amino Acids before exercise resulted in greater muscle protein synthesis than when the Amino Acids were given after exercise. The author suggested that the greater rate of protein synthesis was due to increased amino acid delivery to muscle from exercise-induced increases in muscle blood flow.9 Another study reported that when protein supplementation was consumed immediately before exercise over a period of 14 weeks, it resulted in greater hypertrophy of the knee extensors than consuming the same protein after the resistance training session.10

It???s important to emphasize that you don???t need a whole lot of protein either; researchers have noticed measurable changes with as little as 15 grams of protein before exercise. Shortly after resistance exercise, if you have not consumed protein pre-exercise, your body is in a catabolic state in the absence of a good nutritional strategy, and this phase can remain catabolic until Amino Acids are ingested. Many people like to wait till they get home to eat after exercise and some people (after intense exercise) may have a blunted appetite, which causes them to not eat.

New research suggests that having a whey protein shake may be the most anabolic supplement you can take. Interestingly, although the cells are primed for muscle building, a previous study reported that taking a whey protein shake before and immediately after exercise resulted in greater increases in muscle mass compared to a group who consumed whey protein in the morning and right before bed.1 Another study reported that waiting as little as 2 hours to consume a protein shake resulted in blunted muscle hypertrophy and reduced strength gains.2 An anabolic phase occurs immediately after the workout and lasts about an hour or two. New research suggests that taking a small dose of whey protein (15 grams) both before and after exercise may be the optimal anabolic nutrient timing for muscle growth.


*Secrets of Nutrient Timing Revealed*

So how big of a deal is nutrient timing for muscle growth? Researchers randomly assigned subjects to consume a whey protein shake before and immediately after exercise, while another group got a drink that looked and tasted exactly the same as the whey protein shake, but was just a placebo. Neither the subjects nor the researchers knew who was getting the whey protein and who was getting the placebo drink. There was no difference between the daily protein, carbohydrate, fat and total calorie consumption between the two groups; the only difference was a whey protein shake added before and after exercise. So how much of an effect can two little whey protein shakes make?

The men performed resistance exercise for 21 weeks; at the end of the study, the subjects who consumed as little as 15 grams of whey protein before and after exercise had greater increases in muscle hypertrophy than the control group. The group that consumed the whey protein before and after exercise had an increase in muscle quadriceps area of ~10 percent while the control group had an increase of ~7.5 percent. Of the muscle strength variables, whey protein intake had a positive effect only in isometric leg force production in the leg press (the increase was greater than the control group). So here you have two groups doing the exact same exercises and workouts, yet a simple whey protein shake was the only difference for those who got bigger!

The researchers wanted to get down to the molecular level to find out what the hell was going on. The researchers also took muscle biopsies to examine changes in gene expression from the legs of the subjects one-half hour before and 1 hour and 48 hours after exercise. So what was the difference between the groups?


*Whey Protein Before and After Exercise Alters Gene Expression*

The researchers found that levels of a protein called cyclin-dependent kinase 2 (cdk2) mRNA increased significantly after the resistance bout, but only in the whey protein group. What???s so special about this protein called cdk2? This protein is a marker of satellite cell activation. Remember, satellite cells are baby muscle stem cells that are sitting around waiting to get activated so they can merge with muscle to increase muscle mass. Interestingly, the increase in cdk2 remained elevated after 21 weeks of resistance training, but again only in the whey protein group. Therefore, it seems evident that protein ingestion close to the resistance exercise bout increases cdk2 mRNA expression and is going to enhance satellite cell activity.

In a separate research study, when scientists altered genes of mice to have reduced muscle gene expression of cdk2 levels, the mice were scrawny compared to the normal group.3 Other studies have shown that cdk2 inhibitors increase myostatin levels and inhibit satellite cells from being activated.4 So taking whey protein before and after exercise can really augment your strength and muscle mass gains, primarily mediated through enhanced satellite cell activations, and it seems that as little as 15 grams of whey is all that is needed. This is the first study that has reported that whey protein shakes before and immediately after exercise enhanced muscle satellite cells. An interesting finding was both groups ate the same amount of protein during the study; the only difference was the timing of the protein.


*Super Stack: Creatine and Protein Enhance More Muscle Mass*

Researchers in Canada at the University of Regina took the research a step further. Previous research has shown that Creatine increases muscle mass and whey/casein protein increases muscle mass, so what happens when you stack both? They took older men and gave them Creatine (.1 g per kg of bodyweight), Creatine plus a whey/casein protein shake, or a placebo. The subjects trained for 10 weeks, three times a week. At the end of the study, the group that consumed the whey/casein protein and Creatine increased muscle mass more than the Creatine group alone.6

The whey/casein protein and Creatine group also had greater increases in bench press compared to the other groups. As I mentioned, this study used older men, but here is the good news for older men: researchers found that a combination of Creatine and whey/casein protein increased muscle mass more in older men than when given to younger men! They also used a really low dose of Creatine (8 grams a day), which was only given on training days. This study is in agreement with a previous study in which Creatine and protein consumed before and after exercise resulted in greater increases in muscle mass than Creatine alone.11

Another interesting aspect of the study is that the researchers alluded to the aspect of nutrient timing of Creatine. The authors suggested that taking Creatine before or after exercise seems to have anabolic effects compared to other times, much like protein ingestion. Based on these findings, it appears that the timing of Creatine is just as important as whey protein before and after resistance training.


*Creatine Increases Muscle IGF-1*

New research shows that Creatine enhances muscle growth by a new mechanism. Researchers found that when muscle fibers were in the process of forming new muscle fibers, Creatine sped up the process. The researchers found that when new muscle fibers are being formed, ATP-dependent reactions are necessary. Creatine selectively enhances ATP in cells, so this process likely sped up the muscle growth process. Multiple studies have demonstrated increasing energy demands during muscle growth. Although energy is supplied through the cooperative interplay of multiple systems, the accumulation of Creatine may facilitate maximal rates of ATP replenishment during muscle growth. Another interesting finding was that the injection of Creatine into injured skeletal muscle increased growth of regenerating muscle fibers. All these results add new insight into the usefulness of Creatine playing a major role in the muscle growth process.

Just when you thought it could not get any better...it does. Researchers in Canada reported that when young men performed eight weeks of resistance training, subjects had a significant increase in muscle IGF-1 expression (55 percent); however subjects consuming Creatine had greater IGF-1 expression in muscle (78 percent)! The Creatine group also had greater increases in type II muscle fibers (28 percent) than the control group (5 percent). Interestingly, the researchers found that the changes in lean muscle mass were correlated to the changes in intramuscular total Creatine levels and the changes in IGF-1 levels in muscle were related to the changes in intramuscular total Creatine levels.5

The supplement market is growing faster and faster, with new products that promise gains in muscle mass but without scientific-based studies to validate these claims...it???s a gamble. The supplements that have been shown to increase muscle mass and satellite cell activity are Creatine, whey protein and leucine; they have been given the stamp of approval for increasing muscle mass when used before and immediately after exercise. It???s the two products that have consistently been research-proven to enhance muscle mass. Guys who pound the iron should be consuming both for consistent gains in muscle mass.


*EAA/Carbohydrates During Exercise Also Increases Muscle Mass*

In addition to pre- and post-exercise nutrition, previous research suggests that nutrition during exercise also seems to enhance muscle mass. Previous studies show that essential Amino Acids (EAA) and carbohydrates taken during exercise can reduce protein breakdown for up to 48 hours, suppress exercise-induced cortisol release, as well as stimulate the release of insulin. The increase in insulin and essential Amino Acids creates a hormonal profile more favorable for anabolism. An earlier study examined the effectiveness of intra-workout nutrition; every week for 12 weeks, a group of 32 untrained men performed two total-body workouts lasting 60 minutes (eight exercises, 3 sets of 8-10 repetitions to failure per exercise; 60 seconds of rest between sets). Between sets, the men sipped on a supplement containing 6 grams of EAA and around 40 grams of carbohydrate. The gains in lean muscle were greatest in the group consuming EAA and carbohydrate during exercise. The carbohydrate+EAA group gained 9 pounds of lean mass, compared to just 4 pounds in the placebo group. So, not only is pre- and post-workout nutrition important, but EAA/carbohydrates taken during workouts can produce faster muscle growth in the long term.

Bird SP, Tarpenning KM, Marino FE. Independent and combined effects of liquid carbohydrate/essential amino acid ingestion on hormonal and muscular adaptations following resistance training in untrained men. Eur J Appl Physiol, 2006 May;97(2):225-38.


References:

1.     Cribb PJ, Hayes A. Effects of supplement timing and resistance exercise on skeletal muscle hypertrophy. Med Sci Sports Exerc, 2006 Nov;38(11):1918-25.

2.     Esmarck B, Andersen JL, Olsen S, Richter EA, Mizuno M, Kjaer M (2001) Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans. J Physiol, 535:301-311.

3.     Berthet C, Aleem E, Coppola V, Tessarollo L, Kaldis P (2003) Cdk2 knockout mice are viable. Curr Biol, 13:1775-1785.

4.     McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R. Myostatin negatively regulates satellite cell activation and self-renewal. J Cell Biol, 2003 Sep 15;162(6):1135-47.

5.     Burke DG, Candow DG, Chilibeck PD, MacNeil LG, Roy BD, Tarnopolsky MA, Ziegenfuss T. Effect of Creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults. Int J Sport Nutr Exerc Metab, 2008 Aug;18(4):389-98.

6.     Candow DG, Little JP, Chilibeck PD, Abeysekara S, Zello GA, Kazachkov M, Cornish SM, Yu PH. Low-Dose Creatine Combined with Protein during Resistance Training in Older Men. Med Sci Sports Exerc, 2008 Aug 5.

7.     Tipton, KD, Borsheim, E, Wolf, SE, Sanford, AP & Wolfe, RR. (2003) Acute response of net muscle protein balance refl ects 24-h balance after exercise and amino acid ingestion. Am J Physiol Endocrinol Metab, 284, E76-E89.

8.     Tipton KD, Ferrando AA. Improving muscle mass: response of muscle metabolism to exercise, nutrition and anabolic agents. Essays Biochem, 2008;44:85-98. Review.

9.     Tipton KD, Rasmussen BB, Miller SL, Wolf SE, Owens-Stovall SK, Petrini BE, Wolfe RR. Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Am J Physiol Endocrinol Metab, 2001 Aug;281(2):E197-206.

10.  Candow DG, Chilibeck PD, Facci M, Abeysekara S, Zello GA. Protein supplementation before and after resistance training in older men. Eur J Appl Physiol, 2006 Jul;97(5):548-56.

11.  Candow DG, Chilibeck PD. Timing of Creatine or protein supplementation and resistance training in the elderly. Appl Physiol Nutr Metab, 2008 Feb;33(1):184-90. Review.

  12. O'Connor RS, Steeds CM, Wiseman RW, Pavlath GK. Phosphocreatine as an energy source for actin cytoskeletal rearrangements during myoblast fusion. J Physiol, 2008 Jun 15;586(Pt 12):2841-53.


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