July 2013: Interview with John Ivy Ph.D

by on July 23, 2013

JMEADOWS: I am very happy to have this month’s expert interview with John Ivy. John is the former Department Chair of Kinesiology and Health Education and Professor Emeritus at the University of Texas. He has had over 170 research papers and review articles published. He also still has his research lab and continues to work with graduate students. John is an expert in nutrient timing, which as you all know is near and dear to my heart. Most importantly, I have a feeling we are all going to learn a thing or two from this discussion!

John can you tell us a bit about more about yourself, and where exactly did your passion for nutrient timing come from?

JIVY: I received my PhD in exercise physiology from the University of Maryland in 1976 and then held a post doctoral research position for several years at Washington University School of Medicine. In 1980 I accepted a faculty position at the University of South Carolina and then moved to the University of Texas in 1982. I have been at UT ever since. I first got interested in Nutrient Timing when I was working on my PhD dissertation. I was trying to determine why muscle glycogen only increased above normal (glycogen supercompensate) when a carbohydrate supplement was consumed post exercise. What I found was that in the absence of insulin the muscle would increase its glycogen levels back to low normal levels when provided a carbohydrate supplement post exercise, but if insulin was present muscle glycogen supercompensation would take place. This lead to a classic experiment in which I tested the effect of timing of carbohydrate supplementation on muscle glycogen synthesis post exercise. What I found was that supplementing with carbohydrate immediately post exercise resulted in twice the rate of glycogen synthesis than if the supplement was delayed by 2 hours. This occurred despite the same insulin response regardless of when the supplement was consumed. Later experiments showed that immediately post exercise as compared to 2 hours post exercise the muscle is highly sensitive to insulin. Because of this increased insulin sensitivity, I later found that insulin is able to increase the number of glucose transporters on the plasma membrane and increase the rate of muscle glucose uptake much more effectively immediately post exercise. This allowed for a faster rate of glycogen storage and an increase in storage. These experiments stimulated my thinking on how providing the right nutrients at the right time would affect exercise performance, recovery and training adaptation.

JMEADOWS: So do you believe that muscles cells selectively soak up glucose after hard training (when sufficient mechanical tension is used)?

JIVY: Yes, muscle will soak up the glucose post exercise if presented with the carbohydrate(glucose). One can accelerate this increased uptake by adding protein to the carbohydrate supplement. This is because the combination of carbohydrate and protein, 1) increases insulin secretion and so insulin levels are higher after a carbohydrate/protein supplement compared to just a carbohydrate supplement, and 2) insulin and the amino acids from the digestion of the protein work together to activate two separate cell signaling pathways that increase glucose uptake and activate glycogen synthase, the enzyme responsible for conversion of glucose to glycogen. In the same way that carbohydrate and protein work synergistically to increase muscle glycogen storage, they also work together to increase muscle development and strength. This is why a carbohydrate/protein supplement immediately post exercise is so important.

JMEADOWS: Everybody, did you hear that, the carbs you eat around training will not make you fat!

JMEADOWS: Something that I have seen a lot is that there seems to be some kind of corrective action taking place with muscle cells after longer periods of high carbohydrate intake (all day). So in other words, here is what I notice. People use nutrient timing and they get fantastic pumps, they grow, feel great, etc. But if that person is jamming carbs all day, it would seem like the constantly high levels of insulin might sort of slow this process down after a while. People will start to lose that “pump” in their muscle, and maybe even some strength. I can’t prove any of this, it’s just what I seem to observe, and why I like occasional periods of lower carbohydrates to restore this function. What is your opinion of this John? Am I off my rocker?

JIVY: There is no need for someone doing strength training to be consuming carbohydrates in large quantities throughout the day. Following an intense workout, muscle glycogen is probably depleted by 50 to 60% in the muscles that were the primary movers. Consuming a good carbohydrate/protein supplement immediately post exercise (about 1.2 gram of carbohydrate per kg of body weight) will start the rapid replenishment of the muscle glycogen stores. Having a normal meal about 2 hours later will keep the glycogen storage process going. Continuing to eat normally until the next workout will have muscle glycogen replenished if the next workout is about 20 hours later. If you are doing two workouts per day, I would recommend having two supplements after working out – one immediately after the first workout and one two hours after. Reduce the carbohydrate in the second supplement to about 0.8 grams per kg body weight. This will have glycogen stores about 85 to 90% filled for the second workout. One can overload on carbohydrate if not doing extreme aerobic type workouts. When muscle glycogen stores are filled, the carbohydrate being consumed has no place to go. This causes insulin levels to remain elevated and promotes suppression of fat burning, an increase in carbohydrate burning and the conversion of excess carbohydrate into fat. I think the drop in strength that you have witnessed may be due to the sluggish feeling one gets from taking in too much carbohydrate. The brain is very aware of carbohydrate intake. Just rinsing the mouth with carbohydrate can improve endurance performance. Overstimulating these sensors in the brain may cause sluggishness. There is a place for carbohydrate and it is very important for supporting training and training adaptation. But too much can have its downsides.

JMEADOWS: Oh wow, rinsing your mouth with carbs can have an effect. Can you talk a little bit more about what is going on physiologically with this?

JIVY: Investigators have found that rinsing the mouth with a glucose or maltodextrin solutions can improve endurance performance as opposed to rinsing with an artificial sweetener. Based on fMRI analysis, the carbohydrate actives senors in the mouth that activate reward-related and motor control brain regions, including the insula/frontal operculum, anterior cingulate cortex and striatum. How activation of these brain regions actually translates into improved performance is not known, but activation may result in reduced sensation of fatigue.

JMEADOWS: Very interesting John. You mentioned artificial sweeteners. Do you have an opinion on their use as an alternative to “sweets”? What affect do they have on brain chemistry and insulin?

JIVY: I try to use artificial sweeteners sparingly. Although they possess little or no calories, they do seem to have an effect on the brain. Some recent research suggests they can increase craving for simple carbohydrates and sweets. They do not have an effect on insulin secretion, but if the craving for sweets results in eating carbohydrates throughout the day this can lead to a sustained elevated blood insulin response. Maintaining an elevated blood insulin level will reduce fat burning, promote fat storage and over time lead to insulin resistance. As previously mentioned, carbohydrates taken at the right time are important, but carbohydrates all the time can have adverse effects. Insulin should be allowed to spike at key times during the day, but not remain continuously elevated.

JMEADOWS: One of the things I see with those running punishing low carb diets is that they seem to get sicker more frequently close to contests (bodybuilders in my world). Those who keep carbs high around periworkout do not. Is there a connection here with your immune system?

JIVY: Starting a low carb diet too early in the process of preparing for competition can reduce the functionality of the immune system. When carbohydrate is severely restricted, blood glucose must be maintained by producing glucose via gluconeogenesis. Gluconeogenesis takes place in the liver and is the conversion of 3 carbon compounds like lactate, glycerol and amino acids to glucose, a 6 carbon compound. Gluconeogenesis is activated by the hormone cortisol. So when blood glucose falls, the blood cortisol level increases. Aside from activating gluconeogenesis, cortisol also activates muscle tissue breakdown in order to provide the amino acids that are used to produce the glucose. It also reduces the functionality of the immune system making the athlete more susceptible to infection and disease. Severely restricting carbohydrates for prolonged periods when training intensely can increase one’s susceptibility to infection and also reduce muscle mass.

JMEADOWS: Highlight for our readers – “Aside from activating gluconeogenesis, cortisol also activates muscle tissue breakdown in order to provide the amino acids that are used to produce the glucose.”

JMEADOWS: How important is the type of carbohydrate eaten in the post meal period John? Do you care about about glycemic load, index, or anything like that?

JIVY: This is a very good question. For endurance athletes, who significantly reduce their muscle glycogen stores during their workouts, rapidly restoring them before their next workout becomes a priority. The type of carbohydrate in a post exercise supplement can effluence the rate of glycogen replenishment. Supplements composed of combinations of simple carbohydrates such as glucose, fructose, sucrose and some simple maltodextrins will enter the circulatory system faster than just a single carbohydrate and increase the rate of muscle glycogen synthesis. Recent research also suggests that supplements composed of a high molecular weight starch with a low osmolarity can also increase the rate of muscle glycogen synthesis. At this point in time, I am not sure if the type of carbohydrate in the post exercise supplement is important for the strength athlete. Relative to replacement of muscle glycogen post exercise, I do not think the carbohydrate used is of importance. Since resistance training does not typically result in muscle glycogen depletion, all carbohydrates when combined with protein will elevate blood insulin levels to promote muscle glycogen storage at a reasonable rate for the strength athlete. However, insulin significantly reduces muscle protein breakdown, and the type of carbohydrate and protein in a post exercise supplement can affect the insulin response. Since protein accretion (muscle development) is the difference between protein synthesis and protein breakdown, blocking protein breakdown can have a significant impact on muscle development. Therefore, maximally elevating the blood insulin response with the right combination of carbohydrate and protein may accelerate the rate of muscle development. However, there has been no research to support this hypothesis, and therefore at this time this has to be considered just a theoretical possibility.

JMEADOWS: I have been using the lowest osmalarity and highest molecular weight carb I can find in client’s intraworkout drinks, branch cyclic dextrin. Research seems to be really thin on it right now, but when combined with high quality hydrolysates I think it is massively tipping the scales in the favor of muscle protein synthesis over muscle protein breakdown. Have you done much work in the way of those two items John (BCD and high grade hydrolysates)?

JIVY: No John, I have not looked at these in combination. Typically, I have used dextrose and protein hydrolysates or whey protein to look at the effects of carbohydrate plus protein on cell signaling, glycogen storage, muscle damage, protein synthesis, etc. As you mentioned, there is little research on high molecular weight carbs. However, I think you are on to something. You know, many times the practitioner figures out the right combination of nutrients to be used in a supplement through trial and error, and the scientist comes along later and figures out how it works.

JMEADOWS: Nutrient timing as you describe also seems to really reduce the amount of DOMS in muscle groups after training. We know we need some inflammation, but it doesn’t seem to be necessary to get yourself crippled sore after weight training (with hypertrophy in mind). Your thoughts?

JIVY: I couldn’t agree more. A good carbohydrate/protein supplement can limit inflammation, reduce soreness and speed recovery. I actually think this facilitates muscle development rather than slows it. While some inflammation can stimulate transcription factors for synthesis of muscle protein mRNA, too much inflammation can be counter-active.

JMEADOWS: Does too much inflammation have an impact on insulin sensitivity too?

JIVY: This is another good question, John. Chronic low grade inflammation such as occurs with obesity is thought to cause insulin resistance and lead to type 2 diabetes. So, yes, too much inflammation can have a significant impact on insulin sensitivity. However, the inflammation caused by intense exercise does not seem to have an adverse effect on insulin sensitivity if the inflammation is not prolonged. The way to limit exercise-induced inflammation is to consume a carbohydrate/protein supplement right after exercise.

JMEADOWS: We are seeing some really cool stuff come out on what we call the “pump” now. Outside of carbs, insulin sensitivity etc, are you aware of any other legitimate ways to increase local bloodflow to a muscle you are training?

JIVY: Boy! You just keep asking one good question right after another. There are a number of products on the market that are designed to increase muscle vasodilation to promote and sustain a great pump. Vasodilation is caused by the production of nitric oxide in the blood vessels. Nitric oxide can be produced by two separate mechanism. The first is by converting the amino acid, L-arginine, to nitric oxide by the enzyme nitric oxide synthase. One will find many products on the market that claim to be nitric oxide boosters because they contain L-arginine and other amino acids. However, the body is not deficient of L-arginine and therefore ingesting large amounts of this amino acid before exercise does not increase nitric oxide production. Furthermore, the enzyme nitric oxide synthase does not work well when oxygen availability and blood pH are low, two conditions that occur during intense resistance exercise. The second mechanism is the conversion of nitrate to nitric oxide. This process actually works best when oxygen availability and blood pH are low and is the primary way nitric oxide is produced during exercise. One can increase his or her nitrate levels and enhance nitric oxide production by consuming vegetables high in nitrate such as beets. In fact, endurance athletes have been using beet juice for several years because it also increases muscle energy efficiency and aerobic endurance. Although drinking beet juice is an effective way to increase nitric oxide levels, it is quite impractical because one has to drink over half a liter 3 hours before working out to elevate the body’s nitrate levels significantly. Also, the taste of beet juice is rather objectionable to many people. There is a new product on the market that I highly recommend. It is called BeetElite and it is made by a company known for it nitric oxide technology, Neogenis Labs. BeetElite is made from dried beet crystals and one 10-gram packet contains the nitrate equivalent of 1 liter of beet juice. What makes BeetElite so special is that one 10-gram packet can be dissolved in 4 to 6 oz of water and taken just 15 minutes before working out. Neogenis has developed a patented technology that allows the nitrate in the BeetElite to be converted to nitric oxide much faster than regular beet juice or other beet products. So for a great pump and increased muscle energy efficiency, I would highly recommend trying BeetElite (NeogenisSports.com). NeogenisSports also has test strips that can be purchased to test one’s nitric oxide levels.

JMEADOWS: Very interesting. You know, I was always enamored by all the studies and science that claimed these NO supps were groundbreaking. I always ended up disappointed though. They never worked as good as they sounded on paper. So it is good to know why with your explanation. I wonder how much money I could have saved on that one over the years!

I will definitely give this a try, anything that helps a muscle pump is a friend of mine!

While we are on the topic of supplements, are there any that you can advise my readers and I to avoid so we save a few bucks?

JIVY: First let me say that there are a number of good supplements on the market. However, there are also many that just do not live up to what is stated on the label. The best thing the consumer can do in order to evaluate a supplement intelligently is do a little homework. One cannot rely on the advertisements being truthful. First, the consumer should investigate the product ingredients. Are there scientific data verifying the ingredients will do what they are claimed to do? If the answer is no, I would not purchase the product. If the answer is yes, than the consumer should check to see if the concentrations of the ingredients are sufficient to have the proposed or desired effects. For example, pyruvate was a very hot ingredient serval years back and was added to a lot of products to cut fat. I did a lot of the original research on pyruvate using a fat rat model. Later research on humans revealed that pyruvate could reduce body fat and have a number of other health benefits. However, 10 to 25 grams of pyruvate per day was the effective dose. Because of the expense of pyruvate, all the supplement companies were adding only 2 grams or less to their supplements. Well, these amounts would have no effect at all. This is a typical approach even today. I still see supplements with creatine levels or ß-alinine levels too low to have any beneficial effect. So it would be wise for the consumer to know what an effective dose of an ingredient is, particularly when the supplement contains more than 4 or 5 ingredients. Most supplements that have a large number of claims do not have the concentration of ingredients to actually have the intended effects. The consumer should also take into account where the product is made. Many countries do not have the same safety standards as the USA. Other questions that might be of interest are: 1) is the supplement certified (does it actually contain what is on the label), 2) does the product contain any gentically modified ingredients, 3) are the ingredients all natural, and 4) is the manufacturing facility where the product is being made certified for good production practices. In general, I try and take supplements that keep it simple and have sound scientific rationales for their formulations.

JMEADOWS: What about glutamine? It would seem trashed muscles would benefit from it, your thoughts? Is the peptide form superior?

JIVY: The research data is mixed on glutamine. Personally, I think it can be of benefit when over-reaching with one’s workouts. It can be used to remove nitrogen waste from the muscles, when stored in muscle it facilitates the uptake of leucine which promotes protein synthesis, and it stimulates growth hormone release which can benefit tissue repair. The peptide does enter the circulation faster, but I am not sure that this is crucial. Glutamine is not going to have any rapid acute effect during the workout. Its effects are more chronic in nature. So the time for it to be metabolized is not crucial. However, there is a product on the market that is a dipeptide composed of glutamine and alanine called Sustamine. It does get into the system quite rapidly and has been found to help with recovery from aerobic exercise. Research needs to be done to see if it is the glutamine, alanine or the combination that is having the effect, and if it will enhance recovery from resistance exercise.

JMEADOWS: Great info there. What are your thoughts on BCAA’s and EAA’s. Those would seem like two great candidates to help manage muscle protein breakdown (BCAA) and help augment muscle protein synthesis (EAA)?

JIVY: Both BCAA’s and EAA’s will promote muscle protein synthesis. In combination with carbohydrate, they work even better. Their effect on protein breakdown is not very strong, however. The major signal to increase protein synthesis from BCAA’, EAA’s and protein is the amino acid L-leucine. The more L-leucine in the protein or supplement the faster the rate of protein synthesis. Whey protein has one of the highest L-leucine concentrations and this is why it is such a great protein to take to promote muscle development. L-leucine initiates mRNA translation, the first step in protein synthesis, by activating the mTOR signaling pathway. Based on research from my laboratory, L-leucine, the BCAA’s or EAA’s do not appear to strongly inhibit protein breakdown. However, when combined with carbohydrate, protein breakdown can be significantly blunted. This appears to be related to the increase in blood insulin levels that occur with the added carbohydrate. Insulin has a strong inhibitory effect on protein breakdown post-exercise. Now, there is a metabolite, ß-hydroxy ß-methylbutyrate (HMB), which is a by-product of L-leucine metabolism that does inhibit protein breakdown. It does this by inhibiting the enzyme FOXO3A. One might think that consuming L-leucine would increase HMB levels as well, but only about 5% of the L-leucine that is consumed is converted to HMB, and this will not raise the HMB concentration to a functional level. Research from my lab indicates that protein synthesis can be increased and protein breakdown can be inhibited by the combination of protein plus HMB. So bottom line, one can take BCAA’s and EAA’s, but a high quality protein or protein hydrolysate with carbohydrate and HMB works really well. If one wants to juice up the supplement, add about 1 to 2 grams of L-leucine to make sure protein synthesis is maximized.

JMEADOWS: Are you seeing in your lab then that the insulin spike that you get from Leucine is not of significant enough magnitude to have a real effect on reducing protein breakdown? So in other words, people are too quick to assume the Leucine spike is of equal power to one generated by carbs?

JIVY: First, it should be understood that leucine does not inhibit the major cellular pathways controlling protein breakdown, but insulin does. Second, if you only take leucine or a protein supplement post exercise you will only get a small insulin response and therefore protein breakdown will not be inhibited. While leucine is paramount for activating protein synthesis, it has little affect on protein breakdown. Combining leucine or protein with carbohydrates synergistically elevates the post exercise insulin response and this will effectively reduce protein breakdown. Research by Bird, Cribb and others have independently demonstrated that a carbohydrate/protein or carbohydrate/EAA supplement has a much greater effect on training adaptation (increase in muscle mass and strength) than just taking a protein or EAA supplement alone.

JMEADOWS: Ah ok, so what about all this talk about taking BCAA’s before fasted cardio preventing muscle protein breakdown? Fact or fiction?

JIVY: There is certainly research that shows infusion of BCAA’s can reduce muscle protein breakdown under conditions of muscle wasting such as when severely burned or in the later stages of cancer. During exercise, there is release of BCAAs from the liver and muscle to be used as fuel and for conversion to Krebs cycle intermediates, and the rate of their release is inversely proportional to the muscle glycogen stores. There are a couple of research studies that suggest taking large amounts of BCAAs orally before and during aerobic and resistance exercise reduces endogenous BCAA use and lessens muscle tissue breakdown and soreness. The reduced muscle tissue breakdown is based on blood indicators of muscle damage such as creatine kinase and lactate dehydrogenase. However, the use of BCAAs is rather small during exercise, and just blocking their release is not going to eliminate the majority of muscle protein breakdown that occurs during exercise. Therefore, while it may be beneficial to take large amounts of BCAAs before or during exercise, I believe taking BCAAs, EAA or a protein supplement with carbohydrate will result in a much greater reduction in muscle tissue breakdown and faster recovery.

JMEADOWS: And speaking of Leucine, do you think one would get better results from adding a few grams to a meal, or to taking a few grams actually between meals?

JIVY: This is another excellent question. Research on rats would suggest yes, but to my knowledge this has not been tested in humans. However, what I would suggest is that rather than adding leucine to one’s meals, to take it with a light snack between meals on workout days when the training objective is to increase muscle mass.

JMEADOWS: This is a truckload of great and useful information John. Thank you very much for the time you spent teaching us, and let’s please keep in touch!

JIVY: John, this has been a very enjoyable experience. The questions were really cutting edge and caused me to have to think deeply and carefully about my responses. I hope your readers enjoy the interview as much as I enjoyed doing it, and that they find the information provided useful. I would be pleased to have the opportunity to do this again someday. Keep working hard for your cliental.