Nutrient Timing and the Anabolic Switch

John Ivy is a graduate of Old Dominion College, has a doctorate from the University of Maryland and completed two postdoctoral research positions before coming to the University of Texas 23 years ago. He currently chairs the Department of Kinesiology at the University of Texas, Austin, is the Margie Seay Centennial Professor and also holds an appointment at the College of Pharmacy. Both of his recently published books, Nutrient Timing (2004) and The Performance Zone (2004), are a breath of fresh air for iron-game enthusiasts interested in breaking out of antiquated nutritional models and making real, natural gains.

Ivy is a pioneer in the field of sports science as well. He began his career as a lifelong athlete during his college years and today works out up to six times a week. Looking far younger than his 60 years, he’s living proof of a successful application of the results of his own research.

Ivy’s work in nutrient timing is nothing less than revolutionary. During the 1990s professional athletes and their advisers shifted from relying primarily on testosterone. First human growth hormone, then insulin joined the ‘professional’ supplement list, bringing about bigger, stronger bodies than anyone thought possible. Ivy’s research shows why those supplements work so well. Of far more importance, though, is that he demonstrates how and why just about anyone can optimize muscular development in a natural, drug-free way by using nutrient timing with easy-to-obtain legal supplements.

Ivy and I sat down for a discussion of nutrient timing’its application to aerobic and anaerobic sports, its importance in offsetting type 2 diabetes and its importance to lifelong fitness.

Very little was known about the science of muscular development when we were in college in the ’60s. Almost no laboratories were doing research in that area. How did you get started?

I started out as an engineering major, attending college first on a football scholarship and then later switching to a baseball scholarship. I changed my major to physical education and took a class from a professor with a new Ph.D. who taught exercise physiology at a very high level. I simply fell in love with the course and thought, ‘So this is how the body really works!’

Then in the early ’70s the field [of exercise physiology] just started blossoming. Biological research was being done, and people were trying to answer basic scientific questions about exercise and muscular growth. The field was no longer just a part of physical education; instead, it was becoming a new discipline in its own right. After obtaining my Ph. D., I did post-doctoral work in both human and animal physiology at two different university research centers.

How did your research take off? What questions guided you?

My research began in the early ’80s’research on glycogen loading, which showed that the muscles are much more sensitive to insulin and get a much more rapid rate of glucose uptake after exercise. When you load carbohydrates immediately after exercise, you get an insulin spike and a very rapid rate of glycogen storage’at least with rats. We did some work showing that if you block insulin release, you still get some glycogen storage after exercise, but you can’t supercompensate the glycogen levels without the insulin spike.

We progressed to working with human subjects and showed that when you give them carbohydrates immediately postworkout, you get an immediate rapid rate of glycogen storage but that if you delay giving them carbohydrates for several hours, you do not. In other words, comparing postexercise supplementation to supplementation several hours later, we found blood levels of carbohydrate and insulin to be the same at both times, hence their availability was equal. Delaying taking the supplement for several hours, however, results in glycogen storage being only half as fast as postexercise’it’s used at half the rate. That started my years of research.

What did you look at next?

The regulation of glucose transport across the muscle. When you exercise a muscle, it stimulates the factors in the muscle that produce messenger RNA for certain proteins, and one of those is the glucose transporter protein. So you have the message to produce the transporter, but you really don’t produce a whole lot of transporter until you provide carbohydrate. Then you get a spike in insulin, and you create this protein. As you increase more glucose transporters (which come to the plasma membrane), you increase the transport of glucose into the muscle, and you get more glycogen storage.

If you prevent blood insulin levels from rising, you don’t get the expression (production) of this protein. So my idea was that this isn’t the only protein insulin is affecting; this is probably happening to all proteins. In other words, pretty much all the proteins that are being transcribed occurs when you’re working out. ALL So the way you work out is important.

How you work out determines which proteins are going to be produced when translation is turned on. For example, if you’re doing resistance training, you activate factors to increase the contractile proteins myocin and actin. If you do aerobic-type work, you’re going to produce messenger RNA for mitochondrial biogenesis, cytochrome C and so forth, as well as glucose transporters. But you don’t get a whole lot of protein synthesis unless you make the conditions right. During exercise the body goes from a sort of quiescent state to a catabolic state because it’s trying to mobilize its fuel sources. You get elevations in catecholamines (epinephrine and norepinephrine), cortisol and so forth. You’re supplying energy to the muscles.

When you finish exercising, the catabolic condition doesn’t automatically revert to the preexercise state. Instead, protein degradation is actually still elevated. Although some protein synthesis is activated, it’s still a net-protein-loss condition because catabolism is so great then. You don’t have protein synthesis occurring until the bodily environment is right. So the question we faced was, How do you change the bodily environment? If you don’t do anything, it takes a long time to change the bodily environment. By that time the muscle is not in a state where you can rapidly turn on anabolism or protein synthesis.

How did you figure out that it’s possible to rapidly turn on the process?

I thought the best way to convert from a catabolic state to an anabolic state was to increase insulin levels. Most people think testosterone is the most anabolic hormone, but that’s not the case. Insulin turns on protein synthesis, and further down the line it stops protein degradation and promotes amino acid transport across muscles. It’s actually a very strong hormone for anabolism. By just providing carbohydrate, you can rapidly convert from a catabolic state to an anabolic state. Because the insulin level rises, it drives cortisol levels and catecholamines down. Just in thinking about that, we began doing little studies to see what would happen if we were to provide carbohydrates after workouts.

We’d also gotten into the protein aspect of it. I noticed that when we gave carbohydrate immediately postexercise, we got glycogen storage. We started asking how much carbo we could provide and how rapidly we could synthesize muscle glycogen and glucose transporters with the process. We found that when we gave more than 1.5 grams of carbo per kilogram of bodyweight every two hours, we didn’t see any greater rate of glycogen storage than we did with 1.2 grams. We found we could give three grams or double or triple that, and it didn’t make any difference. We conducted studies to find out why.

We thought the rate at which glucose left the stomach’the rate at which carbohydrate entered the intestines and got into the bloodstream’was limiting. So we bypassed that and did a direct infusion into the blood system. We infused the glucose postexercise, finding that, although the blood glucose levels raised to almost twice as high as when we fed, we didn’t see any higher rate of glycogen storage. So we concluded it wasn’t gastric emptying that was slowing the rate of glycogen storage; it was something in the muscle itself. We also noted that when we infused the glucose, we got the same insulin response, although blood glucose levels were higher. So I asked how we could get the insulin response higher.

From rat studies we knew that if we artificially elevated insulin levels we could stimulate greater levels of glycogen storage and protein synthesis. There had once been a medical test in which arginine, an amino acid that stimulates insulin release from the pancreas, was infused into the blood to assess pancreas functionality. So I wondered what would happen if I mixed arginine with carbohydrate’would I get a greater insulin response? We tried that, but the arginine didn’t mix well with the carbohydrate, so we couldn’t use as much as we thought was necessary. Literature we’d reviewed showed that oral administration of arginine doesn’t work as well as infusing it into the blood. What else could we do?

We found that in the 1960s scientists were working with diabetics and studying the effect of different types of meals on insulin response. When carbohydrates and protein were mixed (such as eating meat with potatoes), there was a greater insulin response than with carbohydrates alone (just eating potatoes by themselves). We decided to mix carbohydrate with protein to see what would happen. We found that we got a much greater insulin response. From that we developed the hypothesis that not only should you get greater glycogen storage [when mixing protein with carbohydrate], but you should also get a greater protein synthesis. Literature somewhat evidenced this, and we have shown that with certain proteins’such as glucose transporter and a few others’you can get a much greater level of protein synthesis using protein and carbohydrate combinations. We have also demonstrated that postworkout protein-and-carbohydrate supplementation results in the elevation of protein synthesis while protein degradation is reduced. That means you can switch from a catabolic to an anabolic state very rapidly. One of the great leaders in protein synthesis work is Bob Wolfe at the University of Texas Health Science Center in Galveston.

How did you get from protein-and-carb combinations to nutrient timing?

I knew that muscle became more sensitive to insulin postexercise very early on in my research, when I was looking at glucose transport work, transcription factors and messenger RNA for certain proteins. We saw that postexercise they were all increased, but the case of those for translation of messenger RNA into protein was very slow unless we converted the muscle rapidly to an anabolic state. We also found that if we delayed converting the muscle from a catabolic to an anabolic state by several hours, the effect of the nutrient supplement is much diminished. That’s how I came up with the idea of nutrient timing’by putting the pieces together over time. I didn’t start out looking for nutrient timing; instead, the picture started unfolding through research. The question of how much protein we need daily misses the mark completely. It’s not just how much we take but also when we take it. Protein is not really that effective unless taken postworkout. We’ve shown that if you take it postexercise and continue to take it in small amounts thereafter, you maintain an active anabolic state. Once you’ve started the anabolic process, you can keep it going by continually keeping amino acid and carbohydrate states up in the blood. Your book Nutrient Timing was published in February 2004. Has anything changed about your conclusions since then?

No. People are more accepting of the conclusions now. Some still want to perpetuate stuff debated back in the ’50s, but there’s so much data coming out to support our work’and not just from our labs but from other labs as well. The important thing we’ve shown is that if you can get protein/carbohydrate immediately after exercise, you’re so much more recovered four hours later. If you have a second competition, say as a powerlifter, for example, you’re in better shape. We documented how tremendous the improvement is. From the point of view of a 24-hour improvement, you’re able to come back and work out harder too.

Here’s something people forget. When you’re working out and trying to develop a training adaptation (whether it be an increase in endurance through mitochondrial biogenesis or added strength and increased muscle mass), all you’re doing in the workout is setting the platform for that development’training adaptation. The adaptation occurs postexercise. Now, how effectively that’s going to be is determined by what nutrients you eat and when you eat them. That’s what controls the environment in which you put the tissue to recover and adapt. It’s really important, not just from the standpoint of recovery so you can work out harder but also from the standpoint of putting the body in a situation where it can most effectively adapt to training.

Training adaptation is protein synthesis. It doesn’t matter if it’s mitochondrial, contractile, liver or immune-tissue protein. It just doesn’t matter. The adaptation is protein synthesis. That’s what you want to stimulate.

You’re not presupposing any specific level or kind of training?

[Nutrient timing] works with all kinds of training.

What about frequency?

We haven’t addressed that yet. I do think the nutrient-timing approach allows for a greater frequency of training because it allows for a quicker recovery. As for the training aspect of it, there are a lot of good programs’periodization and so forth. We’re not dealing with training itself but rather with creating the environment in which the adaptation to that training can best be achieved. Some people recover more quickly than others. People have to recognize the limits they have for recovery: Maybe it has to be daily, or every other day, or every third day. Following nutrient timing for me means 1) I’m less sore, even when I do really hard workouts, and 2) I recover better so the next time I train I can work out harder. For me, nutrient timing definitely helps.

I’ve always been a slow recoverer. I remember in high school by the end of the football season I’d really be dragging. The coach had me doing what he had everybody else doing. Everybody had to do the same thing. And I think that kind of training is a mistake. Some kids need to be treated differently because they respond differently

What about carbs?

Carbs get a bad rap. If you look at the general population, they take in carbs in the form of simple sugars. But getting the right carbs at the right time is beneficial. Protein synthesis is an energy-requiring process. If you can turn on protein synthesis postexercise with carbohydrate and protein supplementation, you’ll use your fat as energy to support the protein synthesis because the carbohydrate you’ve consumed is rapidly converted into glycogen for storage. So you use fat, and that helps with body composition and recovery.

Some people hold to the idea that workouts shouldn’t exceed 45 minutes due to onset of the catabolic state. How does nutritional timing address that?

Nutrient timing offsets it. You do get more of a catabolic response, but the longer you train, the more level it tends to get as far as hormone levels are concerned. At a point, for example, catecholamines and cortisol will normally level off. But that can be actively reversed with nutrient supplementation during the workout and with the postexercise supplement.

When you take the postexercise protein-and-carbohydrate supplement, very rapid hormone changes occur. Once that happens, the muscle changes in response. The catabolic state is set up in the first place by the hormonal changes that occur with exercise, and once you reverse the catabolic effect, the anabolic condition occurs pretty rapidly. You just mentioned supplementation during the workout. What do you recommend taking as you train?

You can get a good response mixing about 25 grams of high-glycemic carbs, such as glucose, sucrose and/or maltodextrin, with five grams of whey protein in 12 ounces of water. Drink that during your workout instead of straight water. Other good additives are leucine, one gram; vitamin C, 30 to 120 milligrams; vitamin E, 20 to 60 I.U.; sodium 100 to 250 milligrams; potassium, 60 to 120 milligrams; and magnesium, 60 to 120 milligrams.

Syndrome X onset, up to development of type 2 diabetes, occurs in many people as they age. How important is nutrient timing for them, and what are the benefits of using it along with training?

Really important. You can probably take most type 2 diabetics who haven’t progressed to the point where they’re taking insulin injections and have them work out, change their diets appropriately, incorporate certain principles of nutrient timing as well as a few other food changes, and completely reverse the diabetes. It all has to do with weight loss to some extent, which nutrient timing and certain other dietary changes can effect.

The biggest problem with diabetics is they’re so very out of shape that it takes time for exercise to become beneficial. At first exercise is very difficult for them, and they can do very little of it. Otherwise they’re just like anyone else. So when they use nutrient timing, they rapidly store glycogen and they’re going to improve their insulin sensitivity.

With exercise’which is the problem in the first place’they’re going to promote protein synthesis, and in doing that they’re going to burn fat and lose weight. So it can be quite beneficial for a type 2 diabetic to apply exercise and the principles of nutrient timing.

Taking postexercise carbohydrates is actually not bad for diabetics. What people don’t understand is that type 2 diabetics actually use up more carbohydrates during exercise than the average person because their bodies don’t use fat efficiently. So they need to replace that carbohydrate, and as they get into better shape, they start burning fat more effectively.

With individuals in their 70s protein synthesis becomes very difficult. For the average person muscle mass begins to decline at about age 50. If you work out, you can maintain it, but putting on muscle mass becomes very difficult, especially after the age of 65 or 70. A study done in Germany recently took two groups of individuals, giving them a carbohydrate-and-protein supplement either immediately or two hours postexercise. The age of the subjects averaged 74 years, and all subjects were older than 70. The postexercise supplementing group increased both muscle mass and strength, whereas the two-hour postexercise supplementation group didn’t. Here we’re defying the aging process by putting on muscle with nutrient-timing principles.

Are there systemic outcomes with increases in testosterone, HGH, etc., from nutrient timing?

Nutrient timing does change and optimize hormone levels. Immediate postexercise carbohydrate-and-protein supplementation results in cortisol going down and insulin going up. You see a decline in testosterone, which is elevated during exercise. When we saw that testosterone was declining, we asked what happened to luteinizing hormone, since it controls testosterone secretion. We saw that the luteinizing hormone wasn’t changing. We then hypothesized that the fall in testosterone was due to a greater rate of testosterone uptake by the tissue at that time’which would also turn on protein synthesis. Actually, William Kraemer at the University of Connecticut has now shown that’s what is going on. We also found that when you take a carb-and-protein postexercise supplement, HGH is elevated above normal five hours postexercise.

Nutrient timing dictates that 30 percent of the diet be fat’pretty high for bodybuilders. Why not cut it to 15 to 20 percent? By the same token, 25 percent protein seems too low for bodybuilders.

There’s evidence that if you cut fat too much, you lose out on two essential fatty acids. If you do reduce fat intake, it’s important to supplement with EFAs to offset the deficiency. We developed nutrient timing in a way to keep it realistic for the average diet. If someone really wants to cut fat, then that person should use more protein and reduce the fat content.

In general, 25 percent protein seems like plenty. How much protein is consumed is not as important as when you consume it to optimize usage. Immediate postworkout carbohydrate-and-protein supplementation is a must. Then use additional supplementation every two hours for at least four hours to maintain the anabolic condition. Here the percentage of protein to carb increases. We also recommend using slower-digesting casein prior to sleep to have a sustained-release effect to maintain anabolism while sleeping.

How long does the anabolic process last? Can it be sustained for hours or days?

You can continue to supplement beyond four hours and still affect the anabolic processes. We propose that you should consider supplementing in a 24-hour cycle (light breakfast, high-protein snack, light lunch, workout, postworkout supplement, post-two-hour supplement, dinner, prebedtime high-protein supplement). Of course, your workouts wouldn’t be the same each day. Maybe upper body one day, lower body the next and an aerobic workout the third day. Repeat for the next three days, and then on the seventh day have a light workout or take the day off. That’s close to what I do. We know that you can keep the anabolic process going for more than 12 hours. I haven’t tested it, but I have read several studies suggesting that protein synthesis can be enhanced postworkout for up to 48 hours. I think that’s possible if you work out hard and continue to keep amino acid levels elevated in the blood.

Editor’s note: Ivy’s decades of research have revealed what really happens in our bodies as we work out, recover and adapt with increased muscle size and strength. His approach works for athletes of all ages, and his research continues paving the way for those seeking health and fitness. Ivy’s research and the practical, easy-to-follow system for applying nutrient timing are all included in his book Nutrient Timing.

Ken O’Neill is a fitness author and personal trainer. His Web site is www.longlifefitness.net, and he can be reached for consultation at [email protected]. IM

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