By Josh Beaty
The following interview was conducted by Josh Beaty with Layne Norton, Jamie Hale, Alan Aragon, and Will Brink. Sit back and enjoy a very informative discussion.
J. Beaty: The big focus in hypertrophy research lately has been the mTOR pathway. What impact does this research have on bodybuilders?
L. Norton: The mTOR pathway is a major cellular anabolic pathway that is responsible for much of the anabolic response to nutrient stimulus. In adult subjects, amino acids (specifically leucine) are responsible for triggering mTOR activation. The mTOR pathway essentially acts as a “leucine gage.” If leucine levels increase, mTOR becomes active and activates other components of the protein synthetic pathway because its high leucine levels indicate a “fed” state and ample amino acids are present for protein synthesis to occur. If leucine levels drop, mTOR becomes less active as it senses that there are not enough amino acids and energy to continue protein synthesis. mTOR is also sensitive to total energy intake. If the total energy drops too low, mTOR becomes less activated. This research indicates what many bodybuilders have known for sometime—if your goal is to build muscle mass, make sure that your diet consists of ample calories and amino acids.
W. Brink: I’m not going to have a great response to this question as it’s really not my area of focus or expertise. As far as I know, there is no practical application of the mTOR pathway to athletes at this time. That is to say, I don’t know of any particular change an athlete can make to his or her approach that will profoundly alter this pathway to give any advantages. It may also simply be that the approach we know to be optimal for strength and or low body mass (LBM)—loading, volume, tempos, etc—is already the best we can do as far as influencing mTOR. Like so many areas of research that may have applications to wasting diseases and such (e.g. myostatin), it’s more of an intellectual exercise versus having any real practical application to athletes at this time, non-pharmacologically speaking at least. There is no doubt that the intensive research going on that examines the signaling events that are activated by aerobics or resistance training will explain how muscle adaptations take place, and pharmaceutical interventions are a focus of many researchers. However, I’m unaware of any direct application that an athlete can incorporate in his or her training or diet that will be an improvement on what we already know. The other guests on this roundtable may be more up-to-date on the literature and have a better answer! I’m a bit jaded at this point in that I don’t get particularly excited or interested in the latest holy grail of signaling molecules until some real practical application shows itself.
J. Hale: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a key role in anabolism. mTOR stimulates cell growth by phosphorylating p70 ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding protein 1 (4EBP1). mTOR is stimulated by resistance training, insulin, and leucine (BCAA). When mentioning the mTOR pathway, it’s probably necessary to mention that there are also other kinases that inhibit anabolism when activated. In particular, I’m referring to the Ampk/Akt mTOR switch. Basically, when Ampk is elevated, protein synthesis is inhibited. Ampk (5 Amp-activated protein kinase) is a heterotimeric serine/threonine kinase. Ampk is often referred to as a cellular fuel gauge. It is activated by endurance exercise, elevated levels of cellular AMP, hypoxia, glucose deprivation, and ischemia. When Ampk is elevated, cellular fuel regeneration is a top priority while the pathways that consume energy are inhibited (e.g. protein synthesis). This applies to athletes, as we know that various conditions stimulate these pathways. By optimizing the stimulation of anabolic pathways and minimizing catabolic pathways (intensity and duration of), we obviously optimize performance and physique benefits. Does this really tell us any more than we already knew (proper resistance, protein intake, and sufficient calories maximize growth)? For myself and other practical scientists, I feel like this information is very helpful for enhancing our knowledge of what’s going on at a cellular level. It also helps with program design and recognizing at a molecular level the factors that affect anabolic and catabolic pathways. As far as the typical bodybuilder or trainee is concerned, knowledge of the mTOR pathway may or may not be beneficial. It depends on the bodybuilder and how serious he/she is about furthering his/her knowledge concerning physique and performance.
Although a little off the subject, alcohol intoxication has also been shown to inhibit the mTOR pathway. Studies involving the mTOR pathway also are important in treating muscle wasting disease. 
A. Aragon: First off, I’d like to thank Jamie for inviting me to this roundtable. It’s definitely an honor to be among a carefully chosen few. If I come off too long winded in this, it’s because I made Jamie wait for months for me to participate so I figured I might as well show some gratitude and babble for eons.
Ah, the good ‘ole phosphatidylinositol 3-kinase-mammalian target rapamycin signaling pathway. That should take care of any lack of technical jargon that I contribute to this roundtable right off the bat. mTOR research is not likely to have a significant impact on the furthering of what bodybuilders can physically achieve, but it certainly is giving us some understanding of how these achievements occur. Let’s face it, the majority of the biggest, most ripped guys on the planet haven’t even heard of mTOR.
The first thing most folks think about in relation to mTOR and bodybuilding is leucine, and rightly so. Leucine phosphorylates activate the downstream metabolites of mTOR. But alas, there’s a caveat. Many folks who place an excessive focus on leucine will indiscriminately dose the hell up on it. They’ll tank down isolated leucine, BCAA, and/or whey thinking that they’ve found the ticket to net anabolism. There’s also this false implication that whey, being higher in leucine than casein, is superior. Not true, at least according to the current body of research which indicates that casein, or at the very least a blend of casein and whey, is superior to whey alone for affecting a number of parameters bodybuilders care about.
What people seem to constantly forget is that net gains in muscle are the result of not just protein synthesis but the inhibition of protein breakdown. Casein’s antiproteolytic effect is more profound than whey or leucine’s protein synthetic effect. Hence it’s lead spot in the current body of research. The name of the game seems to revolve back to the old cliché of mixing things up and achieving a variety of sources of
protein from whey to casein to the range of sea and land flesh to Asian women. Just kidding. I wanted to make sure that everyone was awake. In sum, mTOR activation is just a piece of the puzzle. Thus, the beloved leucine is a mere cog in the complex engine of variables that cause net gains in muscle.
J Beaty: What are your thoughts on the reemergence of the macronutrient food combining theory where carbs shouldn’t be mixed with protein/fat meals and fat shouldn’t be mixed with protein/carb meals?
L. Norton: This is a rather simplistic way of looking at nutrition and focuses mainly on insulin rather than looking at the whole picture. While it probably isn’t a good idea to have a really high carb meal with a really high fat meal, there’s nothing wrong with having moderate amounts of both.
W. Brink: Like many theories, it comes around every few years or decades and gets people all worked up over their food. The problem is that it’s no truer today then it was when the book Fit for Life by Harvey and Marilyn Diamond came out. The theory had no scientific support then, and it has none now. Humans have been combining fats, carbs, and proteins quite successfully for eons and as omnivores are perfectly capable of digesting mixed meals.
J. Hale: You are probably referring to the theory that assumes insulin and blood levels of fat should never be raised at the same time. This theory assumes that insulin is the key contributor to obesity. There are a few things wrong with this line of thought. One of the key problems is that it doesn’t recognize something called the acylation stimulating protein (ASP). ASP is a hormone produced by adipocytes and is of importance for the storage of energy as fat. The consumption of dietary fat alone can increase fat storage. Dietary fat affects fat cell metabolism with no increase in insulin. Some studies have indicated that dietary fat loading showed a decrease in hormone sensitive lipase (HSL) and an activation of fat storage despite no increase in insulin. The key reason was the activation of ASP, which is activated by the presence of chylomicrons (basically packaged triglycerides that are found in the bloodstream after the meal). ASP increases glucose uptake into the fat cell, increases insulin release from the pancreas, and has been described as “the most potent stimulator of triglyceride storage” in the fat cells by numerous scientists. Another problem with this line of thought is some proteins cause substantial elevations in insulin. Minimal levels of insulin affect fat cell metabolism. Basal levels can decrease lipolysis by 50 percent. Another consideration is that most bodybuilders are eating every 2–3 hours so nutrients are still being absorbed from previous meals. Therefore, previous meals interact with the blood levels of nutrients of the present meal.
A study conducted by Golay and colleagues compared a diet with equal macronutrient content and substrate percentages that differed only in how the substrates were consumed (mixed diet versus food combining). The results showed no difference in weight loss. Below are the exact results reported by the researchers.
“Results: There was no significant difference in the amount of weight loss in response to dissociated (6.2 +/- 0.6 kg) or balanced (7.5 +/- 0.4 kg) diets. Furthermore, significant decreases in total body fat and waist-to-hip circumference ratio were seen in both groups, and the magnitude of the changes did not vary as a function of the diet composition. Fasting plasma glucose, insulin, total cholesterol, and triacylglycerol concentrations decreased significantly and similarly in patients receiving both diets. Both systolic and diastolic blood pressure values decreased significantly in patients eating balanced diets. The results of this study show that both diets achieved similar weight loss. Total fat weight loss was higher in balanced diets, although differences did not reach statistical significance. Total lean body mass was identically spared in both groups. Conclusion: In summary, at identical energy intake and similar substrate composition, the dissociated (or “food combining”) diet did not bring any additional loss in weight and body fat.”
Actually looks like a slight increase in fat loss with a mixed diet (balanced diet).
We have tons of anecdotal evidence that denies the need for food combining. But we have evolved on a mixed diet. With all of that said, food combining may be beneficial regarding calorie control. Once you eliminate an entire macronutrient from a meal, this can go a long way in decreasing total caloric intake. If this is what you need to do to control energy intake, feel free to do so.
A. Aragon: I think that the “P+C and P+F = okay, but avoid C+F” principle is idiotic when applied across the board without any contingencies or attention to individual situations. For example, if someone is low-carbing for whatever reason they choose (pathological carbophobia included), they might be done with their carbohydrate intake by early afternoon. Their meal construction for the rest of the day is going to be primarily P+F by sheer default. In the latter scenario, I can see the principle being legit.
However, when issued as a blanket statement, it’s usually based upon the wacky idea that you don’t want fat floating around systemically when your insulin levels are high because this will magically shift your net adipose balance in the positive. That’s false for a number of reasons. First of all, the insulin response generated by CHO + fat generally depends upon the degree of the fat’s saturation. Unsaturated fats tend to either lower insulin response of the coingested carbs or not affect insulin response at all. On the other hand, coingested saturated fat tends to raise insulin response and can do so in a synergistic fashion. But then the question becomes so what? Others have mentioned the more direct role that ASP has in TG synthesis, and indeed, insulin is more of a multitasking anabolic/anticatabolic agent in comparison to ASP, which seems to exist solely to pump up the adipocytes. And of course the kicker is that ASP can do its TG synthesizing magic in the sheer absence of insulin.
And then there’s energy balance. In a negative energy balance, insulinogenesis is a wonderful thing as long as the training stimulus and nutrition are there to work in concert with it to preserve the low body mass. In the condition of a positive energy balance, trainees in general are going to have many more carbs to throw around so this makes the whole separation thing even dicier. Which meals should be carb-free or fat-free in order to pull off this magic separation tactic and why? The logical answers to this question simply don’t exist. If you were to actually adhere to the mechanics of separation, you’d actually be hard-pressed to maintain a stable insulin profile. That’s ironic because the control of insulin is what “separatists” are aiming for. Regardless of all the previous points, the fundamental short sight is that digestion/absorption of meals overlap each other when meal frequency is as high as it should be. Therefore, attempting strict separation of the macros equates to kidding yourself. Not to mention, most foods in nature are a combination of all the macros to begin with.
J. Beaty: Some “experts” claim that coffee should be avoided because of the insulin response that ensues in lieu of the recent studies that have come out on coffee and blood glucose. What is your stance on this?
L. Norton: While acute caffeine ingestion may impair glucose tolerance, studies suggest that long-term caffeine ingestion actually lowers the risk of developing type II diabetes (Battram et al. 2006)). In my opinion, there is probably not enough information at this point to say definitively one way or the other, but I believe caffeine is fine in moderation much like many other compounds. If you don’t abuse it, there is little to worry about.
W. Brink: As far as I’m concerned, there is no sunshine without coffee! Kidding aside, it’s essential to separate an effect seen in the lab and the bigger picture. Insulin is an essential hormone in the pathogenesis of various afflictions. It’s also a hormone we can’t live without. There is not a “direct insulin spike equals terrible things happen” equation, no matter how hard people attempt to paint insulin as the mother of bad guy hormones. Do we see a correlation between coffee and obesity? No. In fact, a study I was just reading found decreased rates of type 2 diabetes in men who drank coffee. If coffee had a negative effect on whole body glucose metabolism, or in other words it elevated insulin for long periods of time or decreased insulin sensitivity to a great degree or what have you, we would not see this reduced risk of type 2 diabetes and coffee consumption. If anything, it appears to have positive effects on glucose metabolism.
There are several studies that suggest coffee reduces the rates of metabolic syndrome. This is yet more proof that it’s far too over simplistic to paint coffee as a negative thing due to one outcome, which, in this case, is the effect on insulin. There have also been a bunch of other potential benefits to coffee drinking, so as usual it’s about balance and common sense. A few cups of coffee per day are fine, but ten cups a day is probably not such a good idea. It’s also possible that coffee may be contraindicated for some populations but perfectly fine for the majority of people.
J. Hale: I’m assuming you are referring to caffeinated coffee. Caffeine increases the release of catecholamines (adrenaline, nor-adrenaline, dopamine). Adrenaline hormones increase FFA mobilization from fat cells. Dopamine increases feelings of pleasure and well-being. Increased FFA blood levels due to high concentrations of adrenaline hormones induce insulin resistance. The effect is generally short-term. The severity varies among individuals. We have to ask ourselves is insulin resistance a bad thing? Not always. It just depends.
Fat cell insulin resistance means that insulin can’t inhibit fat breakdown or promote nutrient storage in the fat cells. Muscle cell resistance means the muscle cell can’t uptake glucose. Therefore, it uses an alternative source of fuel—FFAs. The glucose is utilized by the brain, nervous system, and other tissues that need it. During times of dieting and low carbs, insulin resistance is not necessarily a bad thing. When eating excess calories, it generally is a bad thing.
With that being said, athletes have used coffee for years as a performance enhancer. Endurance athletes often ingest coffee because of its benefits on fat metabolism. Some studies suggest coffee may actually reduce the risk of developing type 2 diabetes. Coffee contains other substances which have also shown health benefits. I recommend coffee if your body can handle it. Some people get the shakes and just can’t seem to handle the central nervous system boost. There is also a big difference between drinking two cups of coffee and ten. Moderation is probably the key to enhancing performance and preventing any negative health consequences.
A. Aragon: I’m a coffee lover so I’ll defend it with all my might. Research be damned!! But seriously, all you can do in this instance is take a hard look at the data. The anti-coffee camp says that coffee consumption contributes to insulin resistance. This is a classic case of focusing on acute effects while disregarding what really matters—the chronic effects along with a few critical details. This is also a case of context confusion. Most of the work leading to this conclusion is based on obese folks using isolated alkaloidal caffeine, not coffee. So, to begin with, that pretty much takes most athletes out of the picture who use caffeine for ergogenic purposes. They use it to increase exercise capacity, which inherently improves insulin metabolism. The issue ends right there pretty much.
But we’re unrepentant nerds here, so we can still look at the data. Caffeine acutely raises insulin response when applied to oral glucose tolerance tests. Okay, great. Cocoa raises insulin response when coingested with other foods, but long-term cocoa use also appears to improve insulin sensitivity. Rewind back to coffee. Coffee’s acute insulinogenic nature doesn’t have any negative impact when studies are carried out long-term. For example, several epidemiologic studies found that the ingestion of caffeinated (and decaffeinated) coffee may actually reduce the risk of diabetes compared with those who never drank coffee. In addition, coffee was recently seen to have a beneficial effect on endothelial function, which implies a cardiovascular benefit. For those not impressed by the uncontrolled nature of epidemiology and prospective studies, I challenge anyone to compile the controlled studies on caffeine and dish out the conclusion that moderate coffee consumption has negative effects on health markers.
In addition, there are non-caffeine compounds in coffee currently under investigation such as chlorigenic acid, trigonelline, quinides, antioxidants, and others that have the ability to enhance insulin sensitivity. The moral of the story is that athletes (and regular folks) can use caffeine and/or coffee to their distinct advantage for performance and body composition improvement, and regardless of the population in question, coffee can actually improve insulin sensitivity over the long term. This is likely due to its various beneficial non-caffeine phytonutrients. Check out this recent review. It covers way more than I’d ever care to:
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J. Beaty: What are the most ignorant dietary theories and philosophies out there that are still incorporated by the bodybuilder population?
L. Norton: For starters, don’t eat carbohydrates after “X” o’clock. People believe that since they are closer to sleeping, they should curtail carbohydrate intake. This is simply ludicrous. Carbohydrates at night don’t make you fat. Too many total calories make you fat. Additionally, if you train at night, you NEED those carbohydrates to properly recover.
The next one is the notion that high rep ranges stimulate slow twitch fibers and low reps stimulate fast twitch fibers. The fact of the matter is that while high reps do stimulate slow twitch fibers, so do low reps with heavy weights. You see, your fiber types are recruited in order of need—slow twitch first, then intermediate, and then fast. So as you can see, if you are lifting heavy loads for low reps, you’ve already maximally stimulated your slow twitch fibers.
And finally, the notion that specific rep ranges yield the best results. Some people believe you should only lift high reps because the pump is so important while others believe that you should only do low reps with heavy weights because training this way maximally activates all fiber types. The reality is all rep ranges have benefits, and they should all be utilized to achieve optimal results.
W. Brink: I actually think things in this area have improved greatly. The advent of the internet has probably helped a great deal there. It seems that almost everyone at this point understands and appreciates the basics, which is that you need adequate
protein, fat, and carbs to gain lean body mass. For example, the ultra high carbohydrate low fat diets that were popular back in the day have all but disappeared. Most people know they need some fat in their diet, know they need some
essential fatty acids (EFA), and know the basics between low glycemic index (GI) and high GI carbs, and so on. That’s not to say there isn’t confusion and questions about all of the above, but as a general rule, I think most people have at least a basic understanding more then they did say ten years ago. The area of real ignorance that seems to persist no matter how hard people like me attempt to counter it is in the area of supplementation. Supplements seem an endless source of confusion and scams.
J. Hale: A couple that come to mind immediately are bodybuilders over reliance on supplements and the assumptions that bodybuilders trying to get lean should not eat fruit. The fear of fruit comes from studies suggesting that 50 grams or more of fructose per day can up-regulate de novo lipogenesis (fat synthesis in liver), increase blood triglycerides, and induce insulin resistance. Keep in mind that fruit generally contains 6–7 grams of fructose. That means it would take a bunch of fruit to get 50 grams of fructose. The high consumption of fructose seen in most studies is generally due to the consumption of high levels of high fructose corn syrup (processing where varying portions of glucose are converted to fructose). Another consideration is that fructose causes minimal insulin secretion. Even if fructose consumption was high enough to elevate fat synthesis, the lack of insulin would probably result in increased fat oxidation. Assuming calorie deficit, it probably all evens itself out at the end of the day. Eat fruit. It’s nutritious and generally low in calories.
Bodybuilders have forgotten the meaning of supplementation. It means supplement the training and nutrition regimen. Be sure your training and nutrition are efficient before spending hundreds of dollars on supplements. Some supplements are beneficial and more convenient than fixing food all the time. They (very few) have a role in physique and performance enhancement when used in the appropriate manner.
A. Aragon: The bodybuilding population as a whole is carbophobic. And I’m talking about carbs in all forms. Don’t get me wrong. In the event that calories must be reduced or reduced to a heightened degree such as pre-contest, it is plain stupid to incur a protein deficiency. But in general, bodybuilders are just plain afraid of carbs. Hell, only a small percentage of bodybuilders are up on the science of the matter so the rest are victims of the asinine mass media just like every other layperson. Would it alarm you to know that the majority of “serious” recreational and competitive bodybuilders are literally afraid to have carbs in their final meal? Imagine that. They’re mortally afraid of muscle loss while simultaneously being afraid of a key tactic that can enhance lean mass preservation. True story.
On those same lines, you have the carbophobes who have a mortal fear of insulin, yet megadose on highly insulinogenic branched chain amino acids (BCAA) during training. Oh, no glucose generated there. None at all, ha ha… What many folks don’t realize is that BCAA is approximately twice as insulinogenic as a solution of pure glucose.
On those same lines, you have folks who are stuck on acute substrate utilization during training. I was talking to my friend, Alwyn, the other day, and the following realization dawned on me as a matter of what we discussed: Caring about how much fat is burned during cardio makes as much sense as caring about how much muscle is built during weight training.
I recently had a rather public debate and by all counts absolutely destroyed my opponent’s argument that “fasted” cardio was across the board better for fat loss than “fed” cardio. He was focused on the acute effects (during and shortly after exercise), not the long-term effects or anything close to the research blatantly refuting his stance. More reading on the subject of “fat burning” cardio can be found here:
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This brings me to another rant. Folks with any intention to use being published in peer-reviewed journals as some sort of credibility crutch have another thing coming. People of sound mind don’t give half a rat’s ass where someone’s been published. We don’t care what degrees you have, and we don’t care how many hours you’ve spent in a classroom listening to the drone of professors who have never driven near the gym. I can tell within five sentences whether someone is worth listening to or not. Paper credentials are fine and dandy, but they mean nothing compared to the ability to reason, comprehend, and synthesize ideas and information. In the realm of bodybuilding, academic degrees also must take yield to experience using these abilities firsthand either on your self and/or in working with clients. That’s the most relevant “lab” as far as I’m concerned.
This brings me to the duality of scientific research. We as “thinking” bodybuilders rely on research to mold our beliefs, support our stance on controversial issues, and ultimately dictate our protocols. Science indeed is infinitely more reliable than random opinions of buff dudes with huge biceps and ripped abs. But unfortunately, even science is puppeteered by money and politics. For example, whoever pays for the study is going to get the results they want. That’s brutal but true. The best we can do in any given debate is see whether controlled research over time is able to produce counter results from the opposition (which hasn’t yet occurred in the case of the anti-milk camp, HAH!) or whether relatively non-vested replication and further validation ensues. It goes without saying that all research must be scrutinized for strengths and weaknesses.
Which brings me to another rant…I can’t stand it when anyone picks a stance and makes a bulletproof commitment to it, turning a blind eye to any opposing data regardless of its legitimacy. Many guys in this industry seriously handicap themselves by assuming a singular position that they feel defines them. This is something we’re all guilty of from time to time, and it definitely impedes the growth of wisdom.
There’s more so perhaps we could cover them in another segment.
J. Beaty: Who are the brightest minds in the world of nutrition?
L. Norton: I’m biased since he is my graduate adviser, but I would say Dr. Donald Layman really has a tight grasp on most facets of nutrition. He understands the biochemical details but never loses sight of the big picture and is always asking the question, “How does this (insert topic) relate to the real world and how can we apply it effectively?” Dr. Peter Garlick’s work on protein metabolism is outstanding, as is Dr. Leonard Jefferson’s. I comment on these individuals as they are some of the best in the field of protein synthesis/metabolism, which is the field I specialize in. I’m sure there are many other great minds that I have left out, but I don’t feel qualified to comment on experts in other areas of nutrition.
W. Brink: Too many to list. Also, no matter how many people I list, someone will be left out and take it personally.
J. Hale: I like numerous people in the field including Lyle McDonald, my fellow panelists for this roundtable, M.J. Rennie, Kevin Tipton, and Dan Moore to name a few.
A. Aragon: As far as authors go, my earliest influences were Michael Colgan and Dan Duchaine. I don’t know anyone in his right mind who lived during Dan’s rise in print media who wouldn’t name him on their list either at or near the very top. More recently, Lyle McDonald has impressed me in terms of both his books and his ongoing science and logic-based contributions to the fitness community at large. That’s the thing. Many guys attempt to be scientific, but they miss the boat on being logically consistent. That list isn’t very voluminous, but I’m open to suggestions. I just happen to spend way too much time on Medline, and I’m sure much of the current crop of worthwhile book authors has escaped my radar.
As far as research scientists go, it would give me a headache to rattle off even a fraction of the ones whose work I’ve admired and benefited from. Peter Lemon, Kevin Tipton, David Costill, Mark Tarnopolsky, Susan Holt, Robert Demling, Xavier Pi-Sunyer, Robert Wolfe, William Kraemer, Edward Melanson, and Mark Febbraio really stand out. I’m sure that on any given moment I can think of others I missed who have really made an impact on my personal methods and perspectives.
Bobo of anabolicminds.com isn’t a book author or researcher in the formal sense, but he’s a bodybuilder who influenced how I view the current dogma. Almost any intelligent person who you have a lengthy heated debate with inevitably imparts some sort of wisdom upon you, and Bobo stands out in that arena.
Oh yeah, Jamie, go ahead and add yourself to the list. Readers, let me tell you that Jamie is one of the most obsessively voracious students
