The Search for the Ultimate Post-Exercise Anabolic Supplement

The Search for the Ultimate Post-Exercise Anabolic Supplement
by:
Anssi Manninen, M.H.S.
“Performance enhancement is not against the spirit of sport; it is the spirit of sport. To choose to be better is to be human. Athletes should be given this choice.”—J Savulescu et al. British Journal of Sports Medicine, 2004;38:666-670.
Insulin, Amino Acids & Protein Anabolism

Appropriate resistance exercise leads to significant increases in skeletal muscle mass (hypertrophy), which can occur through an increase in muscle protein synthesis, a decrease in muscle protein degradation, or both. While stimulus (i.e., resistance exercise) is important for muscle hypertrophy, nutrient availability plays a critical factor in regulating the degree of hypertrophy. Obviously, the muscle’s hormonal milieu also has a major impact on muscle protein synthesis.

It’s now clear that both increased insulin and increased availability of amino acids are important to maximizing muscle protein anabolism. The importance of availability of amino acids for the stimulatory effects of insulin to be evident was highlighted by Bennet and colleagues, who reported that insulin, given with sufficient amino acids, can significantly stimulate protein anabolism via stimulation of protein synthesis and inhibition of protein breakdown.[2] This is in line with the recent data by Borsheim and co-workers, who showed that protein balance over the muscle remains negative after resistance exercise, when only carbs are ingested.[3] In sharp contrast, amino acid ingestion alone significantly increases muscle protein anabolism after resistance exercise.[60] However, consumption of both amino acids and carbs result in much greater effects on muscle protein anabolism,[57] suggesting an interactive effect between insulin, amino acid availability and resistance exercise. Also, it’s well-established that the stimulatory effect of amino acids after exercise is greater than the effect of amino acids on muscle protein synthesis, when given at rest.[75] Thus, nutrient timing is also an important consideration.[76,77,78,79]

Given the fact that raising the blood insulin level is key to stimulating muscle protein synthesis and limiting protein degradation following exercise,[43] it’s not surprising that some hardcore gym rats abuse insulin to increase muscle mass and strength. According to MD´s own drug guru William Llewellyn, insulin injections can produce “rapid and noticeable [muscle] growth ... almost immediately after starting insulin therapy.”[4]

Most athletes choose to administer insulin immediately after a workout.[4] They apparently realize that it’s the most anabolic time of the day to use this hormone. However, insulin abuse is an extremely risky business— one mistake in dosage and/or diet can be fatal or leave one as a vegetable. Fortunately, recent studies have focused on safe nutritional mixtures containing protein hydrolysates, certain added amino acids (especially leucine) and high-glycemic (fast-acting) carbs.[12,14,15,16,17]

Based on the best available evidence, I would suggest that dietary supplementation-induced post-exercise hyperinsulinemia (a high level of insulin in the blood) supported by protein hydrolysate and leucine ingestion-induced hyperaminoacidemia (high levels of amino acids in blood) increases net protein deposition in muscle, leading to increased skeletal muscle hypertrophy and strength in conjunction with appropriate resistance training. Let’s examine some science behind my hypothesis.
Amino Acid & Insulin Secretion

Insulin is a peptide hormone produced by the beta cells of the pancreas. It was once believed that insulin secretion was controlled almost entirely by blood glucose concentration, i.e., by eating carb-containing foods. However, scientists later realized that amino acids also play a very important role in controlling insulin secretion. Certain amino acids cause insulin release in humans, even under conditions where the blood sugar changes little from its basal level.[5] However, changes in blood sugar levels markedly influence the responsiveness of beta cells to individual amino acids. Studies on isolated perfused rat pancreas and islets have demonstrated that physiological amino acid mixtures and even pharmacological concentrations of individual amino acids require the presence of permissive levels of glucose to be effective beta cell stimulants.5 However, leucine is an exception.[35] Contrary to popular belief, oral arginine isn’t an effective insulin booster.[15]
Leucine & Muscle Protein Synthesis

The key branched-chain amino acid leucine acts as a nutrient signal to stimulate muscle protein anabolism. Leucine affects muscle protein metabolism by decreasing the rate of protein degradation,[8] most likely via increases in circulating insulin. In addition, leucine activates key molecules involved in the regulation of protein synthesis, which has been shown to occur even in the absence of an increase in circulating insulin concentrations.[9] After exercise, recovery of muscle protein synthesis requires dietary protein or branched-chain amino acids to increase tissue levels of leucine.[10] The important bottom line is that insulin and leucine allow skeletal muscle to coordinate protein synthesis with physiological state and dietary intake.[10] If you wish to read a more detailed review, see the recent paper by Norton and Layman in The Journal of Nutrition (136:533S-537S, 2006).
Rapidly Absorbed Protein Hydrolysates

Protein hydrolysates (i.e., pre-digested proteins) are produced from purified protein sources by heating with acid or preferably, the addition of enzymes, followed by purification procedures.[6] Hydrolysis process mimics our own digestive actions; thus, many experts feel it’s an ideal way to process dietary protein, especially when rapid absorption is important (e.g., immediately after exercise). However, extreme bitterness is a negative attribute associated with most protein hydrolysates (“Dude, this stuff taste like donkey ball extract”).

Fortunately, specific debittering methods have produced relatively neutral-tasting protein hydrolysates.[20] Extensively hydrolyzed proteins containing mostly di- and tripeptides (chains of two and three amino acids) are absorbed more rapidly than free-form amino acids, and much more rapidly than intact (non-hydrolyzed) proteins.[6,7,21] The considerably greater absorption rate of amino acids from the di- and tripeptides than from the amino acid mixture appears to be the result of uptake by a system that has a greater transport capacity than the amino acid carrier system, thus minimizing competition among its substrates.[21]

Current evidence indicates that only di- and tripeptides are absorbed intact.48 Larger peptides appear to require hydrolysis before their breakdown products can be absorbed.48 While the starter protein and method of hydrolysis affect absorptive characteristics, the peptide-chain length is the most important variable. Protein hydrolysates produced from various sources showed increased amino acid absorption in humans when the proportion of di- and tripeptides was increased.[48] Thus, in order to maximize the absorption rate, the ideal protein hydrolysate should contain mainly di- and tripeptides. Such a protein hydrolysate seems to produce the most immediate hyperaminoacidemia. In general, it’s the kinetics of the absorption (rather than the net absorption of amino acids) determining the greater nutritional value of the protein hydrolysates.

The use of a protein hydrolysate in post-exercise drinks is preferred because it results in a faster increase in blood amino acid concentrations during a two-hour period than does intact protein.[15] And in turn, the levels of essential amino acids in the blood regulate muscle protein synthesis.[61] A practical advantage is that one can ingest a protein hydrolysate-containing supplement immediately after exercise without getting bloated and not excessively suppressing appetite, so one can eat another meal sooner, possibly optimizing the post-exercise “anabolic window.” In addition, protein hydrolysates strongly stimulate insulin secretion.[14,17] Clearly, hydrolyzed whey protein is the most popular protein hydrolysate among athletes. whey protein has been singled out as the ultimate source of protein based on an excellent amino acid profile.[6,23]

Whey may offer other benefits, too.[6,23,26,27,28,31,32] Casein hydrolysate is also utilized in some protein mixtures, but I prefer whey hydrolysates. By the way, the biological value of hydrolyzed collagen (also known as gelatin) is zero; thus, collagen supplementation as a protein source isn’t recommended, so stay away from those poor-quality protein bars containing collagen. However, it’s been suggested that hydrolyzed collagen may be useful in counteracting degenerative joint diseases (e.g., osteoarthritis).[24,25]

Finally, some commercial products are enriched with wheat gluten hydrolysate (i.e., “glutamine peptides”). Wheat gluten has a unique amino acid profile: glutamyl residues account for about 40 percent of the amino acids.[29] glutamine is an important fuel for some cells of the immune system, and may have specific immunostimulatory effects.[30]
Protein Hydrolysate/Carb/Leucine Drinks, Insulin Secretion & Nitrogen Utilization

A study at the Copenhagen Muscle Research Center was implemented to determine the effects different protein-containing solutions have on insulin response and amino acid availability in healthy humans. Four different 600 mL solutions were used. The glucose solution (control) contained only glucose (25 g/L), and the three additional solutions contained the same quantity of glucose plus protein (0.25 g/kg body mass), but proteins were derived from different sources: whey hydrolysate, pea hydrolysate and a complete cow’s milk solution. This study indicated that:

* Ingestion of glucose and protein hydrolysate results in synergistic and fast increases in blood insulin. In fact, protein hydrolysates stimulated an increase in blood insulin that was two and four times greater than that produced by the intact milk protein solution and glucose solution, respectively.
* Protein hydrolysates are absorbed at a faster rate from the gut than are intact milk proteins, as reflected by the rapid increase in the blood concentration of amino acids in peripheral blood.
* whey protein hydrolysate elicited the greatest availability of amino acids during the three-hour postprandial (occurring after meal) period. The authors attributed this difference to the rapid increase in blood amino acids evoked during the first 40 minutes of the digestive period, during which the increase was about 37 percent greater after the ingestion of whey protein hydrolysate solution than after ingestion of the intact milk protein solution.

It’s likely that the high levels of blood amino acids and increased insulin explains a superiority of protein hydrolysates over intact proteins in promoting better nitrogen utilization (i.e., protein anabolism). The co-ingestion of carbs appears to affect the absorption kinetics, as Calbet and Holst showed that whey and casein proteins and their respective hydrolysates administered alone produce similar rates of intestinal absorption of amino acids.[22] It should be noted that the degree of hydrolysis (i.e., the peptide-chain length) also affects absorption kinetics. Unfortunately, many scientists don’t provide any information on protein hydrolysates used in their studies.

More recently, Kaastra and colleagues determined the extent to which the combined ingestion of high-glycemic carbs and a casein protein hydrolysate, with or without additional leucine, can increase insulin levels during post-exercise recovery.[14] Fourteen male athletes were subjected to three randomized crossover trials in which they performed two hours of exercise. Thereafter, subjects were studied for three and a half hours during which they ingested carbs only (0.8 g/kg/h), carbs + protein hydrolysate (0.8 and 0.4 g/kg/h, respectively), or carbs + protein hydrolysate + free leucine (0.8, 0.4 and 0.1 g/kg/h, respectively) in a double-blind fashion.

The results revealed that blood insulin responses were 108 percent and 190 percent greater in the carbs + protein hydrolysate and carbs + protein hydrolysate + leucine trial, respectively, compared with the carbs-only trial. This study also indicated that the addition of free phenylalanine, as applied in earlier studies,[15,16] isn’t necessary to obtain such high post-exercise insulin responses.

Similarly, Manders and co-workers examined blood insulin responses after co-ingestion of casein protein hydrolysate, with and without additional free leucine, with a single bolus of high-glycemic carbs.[17] Again, the subjects participated in three trials in which blood insulin responses were determined after the ingestion of beverages of different composition: carbs only (0.7 g/kg), carbs + protein hydrolysate (0.7 and 0.3 g/kg, respectively) or carbs + protein hydrolysate + leucine (0.7, 0.3 and 0.1 g/kg, respectively). The results indicated that blood insulin responses were 66 and 221 percent greater in the healthy subjects in the carbs + protein hydrolysate and carbs + protein hydrolysate + leucine trials, respectively, compared with those in the carbs only trial. In other words, this study also demonstrated that co-ingestion of a protein hydrolysate with additional leucine strongly augments insulin secretion after the consumption of a single bolus of carbs.

The notion that the protein hydrolysates have strong insulin-boosting properties is also supported by the studies examining the effects of intact protein-containing post-exercise drinks. Ivy and co-workers compared effects of carb + intact protein drink (80 g of carbs, 28 g of protein, 6 g of fat), low-carb drink (80 g of carbs, 6 g of fat), or high-carb drink (108 g of carbs, 6 g of fat) and concluded that blood insulin levels didn’t differ at any time among treatments.[46] However, Zawadzki and colleagues observed that blood insulin levels for the carbs + intact protein treatment (112 and 40.7 g, respectively) were somewhat higher than those for the carbs-only treatment (112 g of carbs).[47] A post-exercise drink containing a mixture of free amino acids also has a potent effect on insulin secretion.[57] However, a large dose of amino acids can cause gastrointestinal discomfort.
Protein Hydrolysate/Carb/Leucine Drinks and Post-exercise Muscle Anabolism

A sophisticated study by Koopman and colleagues investigated post-exercise muscle protein anabolism and whole body protein balance following the combined ingestion of high-glycemic carbs, with or without whey protein hydrolysate and/or leucine.[12] Their nutritional protocol was rather rigorous; the subjects received a beverage volume of 3 ml/kg every 30 minutes to ensure a given dose of 0.3 g high-glycemic carbs/kg and 0.2 g/kg of a protein hydrolysate every hour, with or without the addition of 0.1 g/kg/h leucine. Repeated boluses were taken every 30 minutes until t = 330 minutes after exercise. The results revealed that the whole body protein synthesis rates were highest in the carbs + protein hydrolysate + leucine trial. Similarly, muscle anabolism in the vastus lateralis muscle was significantly greater in the carbs + protein hydrolysate + leucine trial compared with the carbs-only trial, with intermediate values observed in the carbs + protein hydrolysate trial. Thus, the authors concluded that, ”The additional ingestion of free leucine in combination with protein and carbohydrate likely represents an effective strategy to increase muscle anabolism following resistance exercise.” This study used rather large doses of added leucine; however, other recent studies have shown that relatively small doses can improve exercise performance[18] and enhance the acquisition of strength.[19]

Although the Koopman study indicates that dietary supplementation-induced, post-exercise hyperinsulinemia plus hyperaminoacidemia can have favorable effects on the acute phase response to resistance training, the effects of repeated supplementation on long-term adaptations to resistance training are currently unclear. To shed some light on this issue, Bird and co-workers examined the effects of chronic, high-glycemic carb and/or essential amino acid supplementation on hormonal and muscular adaptations in untrained young men.[66] All subjects followed the same supervised, resistance-training protocol two times per week for 12 weeks. Following resistance exercise, the subjects consumed either a high-glycemic carb, an essential amino acid (6 g), a combined high-glycemic carb + essential amino acid supplement, or a placebo containing only aspartame and citrus flavoring. The results revealed that carb + essential amino acid supplementation enhances muscular and hormonal adaptations to a greater extent than either carbs or essential amino acids consumed independently. Specifically, carb + essential amino acid ingestion demonstrated the greatest relative increase in type I muscle fiber cross-sectional area. Changes in type II muscle fibers exhibited a similar trend.

While beyond the scope of this article, it’s very likely that chronic reductions in the exercise-induced cortisol response associated with post-exercise carb-amino acid ingestion also positively impact the skeletal muscle hypertrophic adaptation to resistance training via reductions in hormone-mediated protein degradation.
You Can Have Your Protein Shake & Drink It, Too!

Contrary to some beliefs, higher protein intake has no adverse effects on healthy kidneys,[36,37] fluid status,[42] or bone.[36,38,39,41] In fact, proteins appears to have positive effects on bone health, as they increase circulating insulin-like growth factor I (IGF-1), which plays an important role in bone formation.[39] For example, Ballard and co-workers reported that a protein supplement during a strength and conditioning program led to an increase in blood concentrations of IGF-I in those subjects compared with the concentrations in a group of persons who also trained, but consumed an isocaloric carb supplement.[40] Also, serum bone alkaline phosphatase concentrations increased over time and tended to be higher in the protein group than in the carb group, indicating increased bone formation.

In addition, IGF-I plays a critical role in development, growth, repair and maintenance of skeletal muscle.[44] Thus, IGF-I may partially explain why many strength-power athletes (especially bodybuilders) feel that a very high protein intake is beneficial for skeletal muscle hypertrophy. Indeed, studies indicate increased positive nitrogen balance when protein intake is increased;45 however, more research is clearly needed before the mystery of protein requirements in those attempting to increase muscle mass is settled.[45,49,50,54]

Traditionally, the term "protein requirement" has meant the amount of dietary protein that must be consumed to provide the amino acids needed for the synthesis of those proteins irreversibly catabolized in the course of the body's metabolism. It should be noted, however, that strength-power athletes don’t give a crap about the minimum amount of protein necessary to sustain normal body functions. Rather, they are interested in maximal gains in muscle mass and/or strength. Other potential benefits of higher protein intake should be considered, too.[51,52,53,63,80]
Summing Up

The studies reviewed in this article clearly indicate that nutritional mixtures containing protein hydrolysates, added leucine and high-glycemic carbs strongly augment insulin secretion, compared with the high-glycemic carbs-only trial. When post-exercise hyperinsulinemia is supported by protein hydrolysate and leucine ingestion-induced hyperaminoacidemia, net protein deposition in muscle should occur. Thus, I would suggest that post-exercise recovery drinks containing these nutrients (e.g., BioQuest MyoZene) can lead to increased skeletal muscle hypertrophy and strength in conjunction with appropriate resistance training.

PS. Obviously, there are other potentially useful ingredients for post-exercise supplements, but they are discussed in my future MD articles. —AM
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