Slow Release vs Fast Release Protein

Quick Summary Points

In terms of proteins, there are fast release proteins and slow release proteins.
Fast release proteins such as whey isolate and hydrolysates break down quickly and result in a spike of amino acids to the muscles.
Slow release proteins such as casein and vegetarian proteins break down slightly slower, which results in an extended supply of amino acids over a longer period of time.
Most of the research has pointed to a faster releasing whey protein as the ideal type to have.
Newer research though points to the benefits of combining a fast and slow releasing protein to offer the best effects - both for muscle protein synthesis and to prevent muscle protein breakdown.

Slow vs Fast Protein

In recent years there has been a trend for supplement companies to include mixtures of ‘slow-release’ proteins like micellar casein with ‘fast-release’ proteins like whey or soy. The theory being that the inclusion of casein provides a more even release of amino acids in the hours following protein intake than if only whey protein is ingested. The other side to this argument is that slower release proteins help minimise muscle tissue degradation, particularly at night-time during sleep, when there is no residual flow of amino acids into the bloodstream from food intake.

Maximising Muscle Protein Synthesis with Protein Supplements

If you are a competitive or recreational bodybuilder, your primary aim is to gain muscle mass and/or reduce fat mass. It follows that when choosing your protein supplement, you want the one that is going to maximally stimulate muscle protein synthesis in response to your weight training. But what elements are crucial in a protein supplement when it comes to stimulating muscle protein synthesis following an intense workout? Below are some common schools of thought on the issue.

Get as high as possible levels of amino acids/peptides in your blood after your workout.
Maintain a high level of amino acids/peptides in your bloodstream for as long as possible following your workout.
Get amino acids/peptides released into your bloodstream as quickly as possible following your workout?
Get as high as possible levels of certain amino acids/peptides such as leucine into your blood after your workout.

If it all comes down to #1, then whey protein isolate or hydrolysate is all you need worry about as these types of proteins have unequivocally been shown to result in higher blood levels of amino acids versus casein or soy¹. But if it’s all about #2, then casein is your pick, as this type of protein is released more slowly than whey or soy^{2, 3}; leading to a higher average blood level of amino acids in the hours following protein ingestion. As for #3…it’s simple; whey is the way to go. But if it’s about #4, then its whey again because it has higher levels of leucine and BCAAs than casein or soy.

Evolution of Fast & Slow Dietary Proteins

Most supplement companies will tell you it is best to include a mix of a fast protein - to maximise muscle protein synthesis; and a slow protein – to inhibit muscle protein breakdown? The notion of the fast and slow-release proteins came from a series of studies published by a group of researchers led by a gentlemen named Yves Boirie at the Human Nutrition Laboratory at the University of Auvergne, France. In 1997 Boirie and his colleagues showed that casein inhibited whole body protein breakdown by 34%, whereas whey protein had no effect. In contrast, however, whey protein stimulated muscle protein synthesis to a greater extent than casein (i.e. 68% vs 31%), secondary to the higher peak plasma amino acid levels obtained with whey⁴. A few years later in 2001, Boirie showed that ingestion of casein led to a more positive whole-body protein balance (averaged over a 7 h period) when compared with whey or a mixture of free amino acids in healthy, young subjects⁵. As a result of these initial studies, Boirie published a study in 2002 coining the concept of ‘fast’ and ‘slow’ dietary proteins⁶. Since these terms were coined at the turn of the century, there has been a great deal of research on the merits of each type of protein for bodybuilding, which we will go cover in detail below.

The Slow vs Fast Protein Debate

On face value, the theory of combining fast and slow proteins to optimise muscle growth is pretty sound. The fast release of amino acids from whey triggers protein synthesis, whereas the slower-release amino acids from casein inhibit protein breakdown in the hours following protein ingestion. But there are a lot of questions that this model poses, such as:

Can the strength of the muscle protein synthesis trigger provided by whey be modified based on the amount and form (i.e. isolate vs hydrolysate) of whey?
What is the relative importance of muscle protein synthesis vs muscle protein breakdown in accruing muscle mass?
Is whole-body protein breakdown reflective of muscle protein breakdown?

Muscle Protein Synthesis Trigger and Whey Proteins

Studies have shown that the form, amino acid-composition and amount of whey protein affect the muscle protein synthesis response following intense resistance exercise^7-12. Studies seem to suggest that the leucine content of whey protein serves as the primary switch/trigger that really turns on muscle protein synthesis^{8, 12}. The next most important factor is blood levels of essential amino acids, which is why whey is favoured again. Lastly, whey protein hydrolysate compared with whey protein isolate lead to a greater increase in insulin; the key anabolic storage hormone responsible for shuttling amino acids into muscle. This unique property of whey protein hydrolysate is thought to be mediated by its di- and tri-peptide content. Based on the combination of these points, hydrolysed whey protein seems to provide the best stimulus for muscle protein synthesis following intense resistance exercise⁸. It generally contains the highest amount of leucine per gram of protein, it’s digested the quickest and it leads to the biggest insulin spike⁸.

Importance of Muscle Protein Synthesis vs Breakdown

But what about the importance of casein for preventing muscle protein breakdown and the notion that it can prevent whole-body protein breakdown better than whey? There are a few great studies worth highlighting in regards to this issue. The first one was published in 2011 and compared the effect of ingesting a single bolus (25g) of whey protein versus ten repeated small “pulse” doses (2.5g) of whey protein every 20 minutes. The pulse dosing was designed to mimic a more slowly digested protein like casein. Interestingly, the larger single dose of 25g resulted in a greater elevation in muscle protein synthesis in both the first 3 hours and the second 3 hours following exercise¹².

The second study simply compared the effects of whey protein hydrolysate versus casein as part of a 10-week resistance training program on changes in lean mass, strength and fat mass. The subjects taking the whey protein hydrolysate had significant improvements in each area compared with subjects taking casein¹⁴.

The third study compared the effect of a casein hydrolysate versus intact casein on the muscle protein synthetic response in elderly men. Casein hydrolysate increased amino acid availability and tended to augment the subsequent muscle protein synthetic response compared to intact casein¹⁵. This study reinforces the importance of the form (i.e. intact vs hydrolysed vs free-form) of the protein in dictating its effects.

Comparing Whole-Body Protein Breakdown with Muscle Protein Breakdown

The other key issue to highlight with casein is that all the published studies on its ability to prevent protein breakdown measured protein turnover at the ‘whole-body’ level as opposed to skeletal muscle protein. As it turns out, skeletal muscle tissue only contributes 25-30% to whole-body protein synthesis¹⁶ and its turnover rate is much lower (in the order of 20x) than, for example, gut proteins^{17, 19}. In fact, a study published by researchers from the Netherlands, which specifically looked at the discrepancy between muscle and whole body protein turnover concluded that whole body measurements cannot be used as a parameter of muscle protein metabolism¹³. So it’s hard to say what meaningful difference, a decrease in whole-body protein breakdown would make at the level of skeletal muscle protein.

Casein: The Ideal Night Time Recovery Protein

With most of the research suggesting that whey protein is the ideal post-workout protein for maximising muscle protein synthesis during the day, the one question left is: which protein is best for maximising muscle protein synthesis overnight. A group of researchers from the Nutrition and Toxicology Research Institute Maastricht, The Netherlands, recently undertook an exciting series of studies which seem to answer this question. In their first study they gave subjects a carbohydrate and casein hydrolysate mix during an evening training session plus two additional doses in the hours following the evening training session before going to bed. While the carbohydrate and casein hydrolysate increased muscle protein synthesis during training, compared to the placebo group who just had water; there was no difference in muscle protein synthesis overnight compared with placebo²⁰. In their next study they had subjects undergo a resistance training session in the evening; immediately consume a whey and carbohydrate recovery drink; then 30 minutes prior to sleep, consume 40g of intact casein or placebo. 40g of intact casein prior to sleep resulted in a rapid rise in circulating amino acid levels which was sustained throughout the remainder of the night; resulting in a muscle protein synthesis rate 22% higher than placebo²¹.

So comparing these two studies it would seem that intact casein versus hydrolysed casein was key in mediating the increase in muscle protein synthesis seen during sleep. Like whey protein hydrolysate, casein hydrolysate is digested quickly, with amino acids peaking in blood within an hour or so. It would appear this pattern of a sharp rise and drop compared to a slower, longer release from intact casein is not ideal for maximising muscle protein synthesis during sleep when there is typically no intake of food for 7-8 hours.

Summary

All-in-all, the research overwhelmingly points to whey protein as being the more anabolic protein over casein. Moreover, the stimulus to muscle protein synthesis provided by whey protein and its high leucine content significantly outweighs the anti-catabolic properties of slow-release casein when it comes to post-workout protein. By contrast, current research suggests casein may be ideal as a night time protein (immediately before sleep) to prevent muscle breakdown and increase muscle protein synthesis during sleep.

References

1. Tang JE, Moore DR, Kujbida GW, et al. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol. 2009;107:987–992.
2. Boirie Y, Dangin M, Gachon P, et al. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci USA. 1997;94:14930–14935.
3. Dangin M, Boirie Y, Garcia-Rodenas C, et al. The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab. 2001;280:E340–E348.
4. Boirie Y, Dangin M, Gachon P,et al. Slow and fast dietary proteins differently modulate postprandial protein accretion. Proc Natl Acad Sci U S A. 1997;94(26):14930-14935.
5. Dangin M, Boirie Y, Garcia-Rodenas C et al. The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol Endocrinol Metab. 2001;280:E340–E348.
6. Dangin M, Boirie Y, Guillet C, Beaufrère B. Influence of the protein digestion rate on protein turnover in young and elderly subjects. J Nutr. 2002;132(10):3228S-3233S.
7. Tang JE, Moore DR, Kujbida GW, et al. Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol. 2009;107:987–992.
8. Hulmi JJ, Lockwood CM, Stout JR. Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein. Nutrition & Metabolism.2010; 7:51-62.
9. Yang Y, Breen L, Burd NA, et al. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr. 2012;7:1-9.
10. Pennings B, Boirie Y, Senden JM, et al. Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. Am J Clin Nutr. 2011;93(5):997-1005.
11. Burd NA, Yang Y, Moore DR, et al. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men. Br J Nutr. 2012 Jan 31:1-5. [Epub ahead of print]
12. West DW, Burd NA, Coffey VG, et al. Rapid aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise. Am J Clin Nutr. 2011;94(3):795-803.
13. Koopman R. Dietary protein and exercise training in ageing. Proc Nutr Soc. 2011;70(1):104-113.
14. Cribb PJ, Williams AD, Carey MF, Hayes A. The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab. 2006;16(5):494-509.
15. Koopman R, Crombach N, Gijsen AP et al. Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein. Am J Clin Nutr. 2009; 90:106–115.
16. Nair KS, Halliday D, Griggs RC. Leucine incorporation into mixed skeletal muscle protein in humans. Am J Physiol Endocrinol Metab. 1988;254:E208–E213.
17. Nakshabendi IM, McKee R, Downie S, Russell RI, Rennie MJ. Rates of small intestinal mucosal protein synthesis in human jejunum and ileum. Am J Physiol Endocrinol Metab. 1999;277:E1028–E1031.
18. Nakshabendi IM, Obeidat W, Russell RI, Downie S, Smith K, Rennie MJ. Gut mucosal protein synthesis measured using intravenous and intragastric delivery of stable tracer amino acids. Am J Physiol Endocrinol Metab. 1995;269:E996–E999.
19. Deutz NE, Wagenmakers AJ, Soeters PB. Discrepancy between muscle and whole body protein turnover. Curr Opin Clin Nutr Metab Care. 1999;2(1):29-32.
20. Beelen M, Tieland M, Gijsen AP,et al. Coingestion of carbohydrate and protein hydrolysate stimulates muscle protein synthesis during exercise in young men, with no further increase during subsequent overnight recovery. J Nutr. 2008;138(11):2198-2204.
21. Res PT, Groen B, Pennings B, et al. Protein ingestion prior to sleep improves post-exercise overnight recovery. Med Sci Sports Exerc. 2012 Feb 9. [Epub ahead of print]

On face value, the theory of combining fast and slow proteins to optimise muscle growth is pretty sound. The fast release of amino acids fromOn face value, the theory of combining fast and slow proteins to optimise muscle growth is pretty sound. The fast release of amino acids from