John Berardi:
To start off with I'd like to throw out a bit of information about caffeine so that everyone is up to speed. Here's a quick crash course.

First of all, caffeine, in our circles, is known as 1,3,7 trimethylxanthine and belongs to a group known as the methylxanthines. Some other methylxanthines with similar effects are theobromine (3,7 dimethylxanthine) and theophylline (1,3 dimethylxanthine). While you can continue to call it caffeine, I want to point out that the tri- and di-methylxanthines are potent chemicals that operate through several distinct physiological mechanisms, as you'll see below.

caffeine, by virtue of inhibiting an enzyme called phosphodiesterase, increases cellular concentrations of a compound known as cyclic AMP. Cyclic AMP is the substrate for phosphodiesterase, so if you inhibit the enzyme, you get more of the substrate. More cyclic AMP means increased neural excitation (cAMP is a second messenger for neurotransmitter receptor systems, meaning that when a neurotransmitter binds its receptor, cAMP increases in the cell. So the more cAMP you have to start with, the less neurotransmitter needed to initiate a cellular event/change). In this regard, caffeine increases the sensitivity of neurons to stimuli. Therefore, when taking caffeine, internal and external stimuli are amplified as is the response to these stimuli.

Caffeine also inhibits chloride channel action. Chloride channels inhibit neuronal transmission. When caffeine comes in, it disinhibits neuronal transmission, making the nerves more likely to fire.

Caffeine antagonizes adenosine receptors. Adenosine itself can act by binding to presynaptic terminals to inhibit neurotransmitter release. In addition, it can bind postsynaptic receptors to prevent neurotransmitters from doing their job. Since caffeine can block these actions of adenosine, it can promote elevated neurotransmitter functionality.

Okay, I hope it's clear that caffeine is a pretty potent pharmacological agent with several mechanisms of action. Just because people drink it every day and nobody's dropping over dead immediately thereafter, it's certainly not acceptable to take its use lightly. At this point, I'd like to get right into the debate. Let's talk caffeine, the good, the bad, and the ugly.

First, the bad and the ugly. In reviewing the correlational or experimental data, do you guys think that there are any negative effects of habitual caffeine or coffee consumption? In other words, are there any grounds (pun intended) for avoiding this stuff?

Doug Kalman:

JB: That was certainly thorough, Doug. I'd agree with your synopsis. I'd like to add in the fact that recent research by Vlachopoulos and colleagues has demonstrated that 250mg of caffeine (two 6oz cups) can acutely induce arterial stiffness and short term hypertension. This work has been duplicated in other studies so it's not just a one-time effect, although it may be only an acute effect. After all, the data correlating caffeine intake and hypertension are mixed. Lonnie, anything to add?

Dr. Lonnie Lowery:

JB: So what I'm hearing is that caffeine use should probably be avoided in cardiac patients, in pregnant women, perhaps in women who are prone to osteoporosis and perhaps in men trying to "free the tadpoles." If that's what you're saying, I'm in full agreement.

However, and you knew it was coming, this roundtable was spawned by my concerns about the effects of caffeine on insulin sensitivity and glucose disposal. How can you ignore the potential negative effects of caffeine in this regard? Are you guys trying to rile up ol' JB or what?

Look, there have been at least eleven human studies conducted using different methodologies demonstrating that caffeine intake has a negative effect on glucose disposal and acute insulin sensitivity. Let me give you a quick review of them ('scuze me while I pull out my notes):

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As you can see, although exercise increased glucose uptake/disposal in both groups, caffeine still blunts this effect. Talking percents, caffeine reduced glucose uptake by 55% in the rested and 51% in the exercised leg. In addition, whole body glucose disposal was 30% lower. Muscle glycogen synthase (the enzyme that promotes the storage of carbs) activity is also reduced.

To corroborate the conjecture that epinephrine release is responsible for the effect of caffeine on insulin sensitivity, several studies have been done:

Therefore, it's clear that it isn't necessarily the adenosine antagonism that's causing the effect but the epinephrine release.

DK (interrupting):

JB: That's rat research. What about the human stuff? Since skeletal muscle tissue is the largest glucose disposal site in the whole body it must be contributing to the resistance. After all, epinephrine, which is released with caffeine use, is well known to reduce glucose disposal (and cause insulin resistance) in human skeletal muscle tissue!


JB: You want OGTT data? Here you go:

However, when the low GI group got regular coffee with breakfast, their blood profile was worse than that of those who got the high glycemic breakfast and decaf. Therefore coffee/caffeine can turn a low glycemic meal into a high glycemic meal! Finally, the group that drank coffee and had the high glycemic meal ended up looking like diabetics.

I'll admit that most of the studies use relatively high doses of caffeine (3-5mg/kg). But remember, it wouldn't be so hard to accumulate these types of doses with the typical coffee and cola drinking habits of many North Americans (especially the Canadians I see every day). One 8 oz cup of coffee can contain up to 175mg of caffeine. With a five hour half-life, two large morning coffee runs can lead to the types of blood levels of methylxanthines indicated in the studies.


JB: I agree with your comments about the daily variation in glucose measures, but with the consistent findings I've presented above, something has to be going on here. You simply can't deny the statistically significant findings that demonstrate increased glucose and insulin as well as decreased glucose disposal ­ all of this in healthy, young subjects.



JB: First, the effect I'm describing is more of an epinephrine thing than an adenosine thing. Therefore, let's be clear. Research has established that epinephrine causes insulin resistance, some of which occurs in the skeletal muscle. Since caffeine releases epinephrine, there'll be some insulin resistance.

Now, if caffeine also can (and the data are equivocal) block adenosine's effects, it might actually prevent some muscle glucose intolerance and also prevent some glucose uptake in the fat cells. Therefore the epinephrine effects of caffeine aren't so good with respect to insulin sensitivity and glucose disposal. The adenosine antagonism seems to be good. In the end, the balance of the two still leads to less skeletal muscle glucose disposal and higher blood glucose and insulin responses to an OGTT.



JB: Good points, Doug. Before we move on I want everyone to be clear on something. I am in no way suggesting that caffeine use or coffee drinking will cause "clinical diabetes" or clinical insulin resistance. What I'm suggesting is that there are dozens of factors that affect insulin sensitivity (both acute and chronic) including exercise timing and mode, total caloric intake, macronutrient breakdown of the diet, food selection, drugs and medications, and time of day.

While some factors may be more powerful than others, I think it's important to recognize which factors increase insulin sensitivity and which factors decrease it. Once we know these factors we can strive toward making good lifestyle, exercise, and dietary decisions in favor of optimizing insulin sensitivity and glucose disposal in the muscle. Since I think the data are relatively clear on the fact that high dose caffeine decreases insulin sensitivity in healthy young people, we all need to be aware that coffee could present a problem for some individuals, especially those prone to diabetes, those without a regular exercise program, or those with poor dietary habits.

Now, I'll agree with the gist of what you're both driving at, namely that different populations respond differently to various treatments and manipulations. That's what I was referring to before. Indeed, the study subjects I listed in my literature assault above weren't bodybuilders or elite athletes. In fact, some studies included sedentary subjects, others included recreationally active individuals, and others didn't list the exercise habits of the subjects. But all subjects were young and healthy. Since all three of us regularly extrapolate data from "young healthies" and apply it to bodybuilders, I hope you're not getting self-righteous on me now just to support your love of coffee!


JB: Okay, now you're making some sense. Listen, since I'm the moderator and I get ornery if people don't see things my way, if both of you are willing to admit that caffeine does in fact increase glucose and insulin responses to a meal (as evidenced by the studies I've listed above) and may reduce insulin sensitivity, I'm willing to change the focus and discuss whether or not this phenomenon actually matters or if we understand enough about insulin sensitivity to make any definitive statements about it.


JB: Yes, and the studies I mentioned didn't even focus on fasting values. They've looked at post OGTT (i.e. meal) values. This is a very specific situation but the most applicable one. After all, people usually have coffee with meals or with snacks. As I've said, I'm fairly certain that fasted values will remain intact in cases where caffeine is out of the blood by the morning. However, as I said in my last discussion of this, if the first few meals of the day jack blood caffeine levels sky high, then the person will be "diabetic" for some portion of the day while being seemingly "okay" in the morning. Therefore it looks like timing is a huge issue.

The other big issue is dose. Many of the studies I've brought up used pretty high doses, more than might be available in a thermogenic supplement or a daily cup of joe. It may very well be that low dose caffeine intake can offer a nice stimulant effect without the insulin resistance. That remains to be seen. So, there are certainly dose and timing issues to consider.

Either way, I agree with both of your comments about how caffeine doesn't chronically impair insulin sensitivity. But caffeine does increase epinephrine and free fatty acids acutely, which causes poor glucose tolerance. Do you agree that if half of your daily meals (the meals after your 16 oz of morning coffee) caused aberrant increases in glucose and insulin, this would be bad for body composition, especially if those meals are higher in carbs?


JB: No, Sir Doug. And I'm glad you bring this up since it relates back to my individual differences and timing comments listed above. Here are some scenarios that we have to recognize.

With sedentary individuals, especially those with a traditional Western diet high in sugar and saturated fats, elevated concentrations of circulating epinephrine and free fatty acids, in my opinion, aren't so good since they'll negatively affect glucose tolerance and drive insulin and glucose concentrations up after meals. And while the epinephrine may cause free fatty acids to be lost from adipose tissue, in the absence of exercise, those free fatty acids will probably just be taken back up and stored again, along with all the glucose that's being driven into the fat cells. No one loses fat using caffeine supplements alone.

With exercising individuals, elevating circulating epinephrine and free fatty acids before exercise are exactly what we're looking for since those fatty acids, which were once part of your love handles, will be escorted into the muscle and burned up. That's why coffee/caffeine before exercise is probably a good thing. Not only does it jack you up for the workout but it also helps you burn up some fat.

However, there may be a negative side to pre-workout caffeine intake if it does reduce glucose disposal. Since exercise powerfully increases insulin sensitivity, the effects of caffeine may not put a dent in the already huge glucose uptake. However, the data above do indicate that high dose caffeine can substantially reduce glucose uptake after exercise. Another few studies are needed before we know what's going on here.

Now, exercising individuals may not suffer from the effects of caffeine induced insulin resistance like their sedentary counterparts; however, I can't imagine that increased post prandial (post meal) insulin and glucose concentrations are desirable if one wants to get leaner or minimize fat gain while trying to gain muscle.

This last comment may be macronutrient specific, though. The effects of caffeine may be negative when on high carbohydrate diets, causing poor glucose disposal, insulin resistance, and fat gain. However, caffeine may be quite positive when on low carbohydrate, high protein and fat diets.



JB: Okay, so I think we've all agreed that timing and dose of caffeine intake are crucial factors in this debate. In addition, it's important to note that we all agree that sedentary individuals and those prone to diabetes are most at risk for caffeine induced insulin resistance. While we can't say conclusively whether or not caffeine intake will present body composition problems for exercising individuals, there's no doubt that metabolism will be altered by caffeine intake in this population.

Okay, we've focused most of this roundtable on the bad and the ugly; what about the good?


JB: Agreed. While we can get metabolic increases from exercise and antioxidant effects from scores of other vitamins and nutrients, it's probably a good idea to use caffeine before exercise or to stay awake if you're the night watchman at Osgood Corporation. Remember, though, the mental alertness benefits of caffeine often fade with habituation so use it only when necessary if you desire its feel good/mental sharpness effects.

To be quite honest, in the past I was quite a coffee "pot head" as Lonnie likes to call it, especially before training. I'd brew up a strong pot of coffee and drink 20 oz of the bitter blend from my Superman mug. After about thirty minutes I'd head off to the gym and I can assure you, my workouts were intense. I gave up this practice because I believe it was causing regular headaches. However, I do miss it. Therefore even the supposed "anti-caffeine" guy believes that there's a time and a place for coffee use (as long as it doesn't cause you to feel like you're getting kicked in the teeth after the effects wear off).


How about some concluding remarks, guys.



While I'm getting sick and tired of agreeing with Lonnie during these roundtables, I'll have to do so again. I am indeed an omniscient stud! Besides that, I tend to take the data a bit more seriously than Doug does. While caffeine may not be the new "silent killer," the knowledge of its effects has to take its rightful place in the planning of any nutritional scheme.

While caffeine intake certainly won't make you fat or diabetic, regardless of who you are, it may increase your glucose and insulin responses to meals and therefore thwart the effects of some of your low glycemic eating. But remember, dose is important. Small doses of caffeine may not be harmful. Timing is important, too. Taken immediately before exercise, caffeine may do some good things. As usual, more data is needed to clarify all the specifics, but in the meantime we'll keep you on the cutting edge of nutritional science.