Caffeine; Dastardly Danger or Benign Booster?
I realize it’s been “a minute” (as is the slang) since my last post. A move 2500 miles across the country and the tribulations there-related will be my poor excuse, but now I’m BACK and ready to tackle a putative baddy: Caffeine.
I’m sure you probably have your own ideas about how caffeine personally affects you, and I’m not here to say they’re wrong; in fact, a lot of the studies I read on this issue talked about the psychosoma as it were related to caffeine intake. Some of the more bunk studies (as usual, opinion-driven surveys; not case-controlled studies) even asked silly questions like “…and how do you feel?” after coffee and all’a that. Well, I’ll just say the ol’ cliche “perception is reality” when it comes to all that; I wanna talk more about scientifically verifiable results so that you might be put at ease (OR LEFT IN FEAR). Either way, I hope this article helps you proceed with confidence in the ixnay or “ORMAY!” of future caffeine FOR-ays in your daily ife-lay.
The Three Amigos
…or, in this case, maybe more like the Three Stooges: I’m talking about caffeine and the two other substances that react with it (or because of it) to cause the effects in the body that we know. The two other substances, adenosine and dopamine can’t really be ignored in any serious discussion about caffeine and its effects in your body (Though I’m not a very serious person, so I’m only going to half-assedly address dopamine).
Adenosine, a biochemical compound found endogenously (inside the body), is responsible for so much regulation and modulation inside the body, it’s really outside the scope of this arti-cool (cop out). I’m just going to go ahead and call it a “protector;” as, with many substances in the body, it mostly attempts to maintain homeostasis. I’m going to lightly touch on more intricate science-y things here to illustrate its role in “dancing with caffeine,” but I’ll try not to make it too yawn-inducing:
Adenosine regulates tissue function by activating four different types of receptors (in this case G-protein coupled receptors) in the body. They are known as A1, A2A, A2B, and A3. For clarity, we’re going to forget about A2B and A3, as they have little to do with and aren’t really affected by caffeine. Still, it should be understood that these receptor sites are responsive to the effects of adenosine and are most notably used in an inflammatory (read: BAD) environment; in other words, adenosine hits these receptor sites in times of inflammation (asthma, ischaemia, arthritis, sepsis) and these sites facilitate healing. Adenosine flooding these areas “reports” tissue injury to surrounding tissue, generating tissue responses which aid the healing process (again, homeostasis!). Exogenous adenosine has even been injected into folks to curb tachycardia (abnormal heart rate), and produced endogenously to assist against auto-immune diseases like HIV. Endogenous adenosine also controls tumor necrosis factor (TNF) production and inhibits superoxide anion (more on these guys in another article) creation by neutrophils (white blood cells) . The “modulation” by adenosine would seem to imply that adenosine doesn’t let the dangerously toxic superoxides get out of control beyond killing what they have to kill.
So yeah, it’s great; now I’m gonna tell you what it has to do with caffeine. I’m pretending I’m Norm Macdonald here and saying “Bet you’re glad you read all that above. Huh? Well, aren’t ya?”
Ines/Eines From A Memory
The caffeine-adenosine interaction within the body is a bit more complex than the “Stooges” metaphor I made, earlier, but a decent illustration; think of caffeine and adenosine as Moe and Curly, respectively (again, as I’m mostly skipping dopamine, that’d make it a good Larry; sorry, Larry): Anyway, adenosine (Curly) might be having a merry time, making pancakes out of rubber cement or whatever, and here comes Moe to get a gander at and finally displace his nonsense with a knock to the nog’.
In the case of adenosine, as implied above, most of its functions aren’t “nonsense;” but caffeine oftentimes comes to lower the same Moe-esque boom, regardless. Caffeine is an adenosine antagonist, as it reduces the efficacy of adenosine in altering systolic blood pressure, heart rate, plasma catecholamines (which prepare the body for physical activity, one of which is ol’ dopamine), plasma renin activity (controlling blood pressure, thirst, and urine output), and aldosterone (increases blood pressure by retaining water in the kidney). In some ways, caffeine is the anti-adenosine: these include its ability to slow adenosine-induced heartrate increases (maybe good), and reverse adenosine-induced vasoconstriction (maybe not-so-good)
Caffeine, in concert with adenosine in “normal amounts of human consumption of the drug,” can induce rapid changes in gene expression, and over time these changes can result in antiepileptic and neuroprotective properties. Caffeine has a half-life of 2.5-4.5 hours when ingested by humans. A single cup of coffee or tea (having about 100mg caffeine) creates peak levels of caffeine in body fluids (from .3 to 3mg/l) in a time period of 15-120 min. after ingestion. As mentioned above: of the four adenosine receptors, A1 and A2A receptors are major targets for activation by caffeine ingestion due to their activation at low basal concentrations of adenosine.
Adenosine has an inhibitory effect on transmitter release in the nervous system; in effect, this means that excitatory transmitters are inhibited by adenosine. Since adenosine is seen as a homeostatic regulatory factor which serves to match the rate of energy consumption with the amount of regulatory supply, the limiting factors make sense. Adenosine decreases the rate of central neuron firing; when this effect is blocked by caffeine, the result can be epilepsy/seizures (As you’ll see below, though, caffeine has other more positive effects on epilepsy in some amounts). Caffeine also increases the firing of noradrenergic (adrenaline) and dopaminergic (dopamine) neurons, and this is related to its inhibition of adenosine A1 receptors receiving adenosine.
At extremely high doses (50mg caffeine/kg bodyweight), caffeine actually induces gene changes, instigating “immediate early genes” such as c-fos, which has been linked to the creation of cancers. After long-term continued caffeine use, adenosine A1 receptors are increased; this is a factor of caffeine tolerance with serves to dull the effect of caffeine and without its presence strengthens the effect of adenosine (leading to grogginess due to adenosine’s excitement-inhibiting factors).
Caffeine, used in the long term at physiological levels, however, has been shown to decrease susceptibility to ischaemic brain damage (Rudolphi et al, 1989), increase capacity for spatial learning (Von Lubitz et al, 1993a), decrease susceptibility of seizures (Georgiev et al, 1993, Von Lubitz et al, 1993b). Again, all these effects are seen in consistent physiological doses, with acute doses actually showing opposite effects (In other words, high levels of caffeine exacerbate damage from ischaemic brain damage and create an environment in the brain for induction of seizures). However, the author of one of said studies, while acknowledging the beneficial effects, still called caffeine a dirty drug;” I’ll leave you to look up the Wikipedia entry for that one.
GETTING YOUR FIX
So, what about the addictive qualities of caffeine? Should users be worried about withdrawal symptoms? Well, from what I’ve read, not really.
Some effects of caffeine withdrawl are decreases in locomotor activity (not seen when doses are lower than 67mg/kg day), obvious behavior changes, and sleep problems during withdrawl for 30 days after acute levels (20 mg/kg day for 21 days in cats, which would be about 1100 mg/day for a human). Generally, more than 200 mg caffeine is needed to significantly affect sleep.
Withdrawal symptoms and dependence on caffeine has been seen in amounts averaging 357mg/day in normal adults, with dependence being rated in a few categories: 1) use continued despite knowledge of a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by caffeine use (94% of people in said study), persistent desire or unsuccessful efforts to cut down or control use (81%), and upped tolerance (75%). Caffeine withdrawal symptoms were even reported in newborns whose mothers were heavy coffee drinkers during pregnancy. The infants displayed irritability, high emotivity and, eventually, vomiting (sounds like a night out drinking, huh? HURHURHUR). Symptoms begun at birth but spontaneously disappeared after a few days.
Over-time tolerance to the effect of caffeine on blood pressure, heart rate, diuresis (increased urine production), adrenaline levels, and renin activity (enzyme which regulates blood pressure, thirst, and urine output) has been observed in humans, but there is very little evidence to suggest that caffeine’s ability to create alertness is ever changed. Humans who are heavy caffeine users seem to gain tolerance of the ill effects on sleep caffeine creates, while light caffeine users seem to be more sensitive to caffeine’s effects on sleep. Several studies have failed to show behavioral effects of caffeine at doses below 200-300mg.
While caffeine does meet some criteria for drug dependence, it cannot be compared with “classical drugs of abuse,” because it actually leads to a release of dopamine in a different area of the nucleus accumbens (a collection of neurons in the “reward center” of the brain; caffeine gets a dopamine response from the caudate nucleus rather than the shell of the nucleus accumbens, like the other drugs) than as seen with such drugs as cocaine, amphetamines, morphine, nicotine and alcohol. Therefore, dependence on caffeine is much less-pronounced than with such drugs. This means a normal consumption (about 2 cups coffee/day) does not activate the “reward” center in the brain and therefore has low addiction potential.
Dangers related to caffeine, i.e. this case which examined the role of a popular energy drink in the epileptic episode of a previously non-epileptic man, show that caffeine is rarely dangerous in physiological levels taken normally by humans.
Caffeine and Exercise
Much has been made (well, maybe not “much,” but it gets mention) in fitness circles about the beneficial effects of caffeine in use before and during exercise; I’ll explore that a little, here.
One belief amongst gurus is that caffeine works to change fat and/or carbohydrate metabolism, but that is apparently not true. Caffeine ingestion during exercise periods increases mobilization of fatty acids into blood plasma at rest periods and increases vascular resistance (due probably to, as mentioned above, adenosine A1 receptor inhibition). Caffeine also increases catecholamines like norephinedrine during exercise. Findings suggest that fat and carbohydrate metabolism in an active muscle is negligible, and most responses to caffeine are seen in resting muscle tissues in the central nervous system and liver.
The majority of studies I read on performance enhancement due to caffeine, such as this one and this ‘un showed that caffeine increases some aspects of performance (namely endurance, focus, and average power), but not others (peak power). One study of interest showed that apparently, caffeine can over-ride the body’s natural Circadian Rhythm (a biological entrainment process like “getting up with the sun.”) and allow early morning athletes to have fully-wakened afternoon-like results. Maybe not surprising given what we all know (and have learned) about the substance, but still. MESSIN’ WITH NATURE.
I will attest to taking caffeine with my BCAAs (branched chain amino acids) before certain workouts (mostly on days I haven’t consumed any blood glucose-raising carbs). From my own personal view point, it has helped in focus (especially on killer exercises like planks). Beyond my personal opinion, I can see results in the “cut” of my muscles and so forth, but again all of that stuff is outta the scope of this article; still, on the subject of caffeine-induced enhancements…
HARDER, BETTER, FASTER, STRONGER
Especially in talking about focus, there has been a lot studied on caffeine’s ability to improve that attribute. In several studies, caffeine has been found to improve performance in tasks dependent on cognition. In one, subjects who had 250mg of black coffee detected more targets on a paper-pencil visual search task than those in placebo conditions. Similar effects were seen in computerized studies with subjects. Since false alarms in these tests between caffeine users and placebos were roughly the same, the overall thought is that caffeine increases attention by assisting subjects in focusing on relevant items as opposed to attempting to eliminate irrelevant items.
At least two studies, however, found the effect of caffeine on the attention system to be negligible, concluding that caffeine’s behavioral effects were a result of improvements in execution of motor responses. Other studies concur that motor response time is decreased with physiological amounts of caffeine. EEG data suggests the prior (attention system modulation) to be true of caffeine; tests conducted using spatial arrangements of dot patterns (Lorist et al 1993a) confirmed this. As well, another study (Kenemans and Lorist
(1995) confirmed the rejection of irrelevant data in a test of spatial frequency and orientation after caffeine ingestion.
Caffeine is also seen to improve mental focus not only in conditions of fatigue, but in well-rested subjects as well; p3b, a subcomponent of an event related potential, seen being affected by caffeine in EEG data shows that even well-rested subjects take a vested interest in the test they’re taking, paying attention even to factors said spatial tests describe as irrelevant in the instructions. Caffeine, especially at about 3.0 mg/kg bodyweight (about 165mg), seems to improve multi-tasking performance.
Caffeine has an effect on the motor system, which results in a reduction of distracting influence of irrelevant information and thus a faster motor response than in the absence of caffeine or the placebo condition. Interestingly, low cortisol (which is caused by lack of dopaminergic response) has been seen to contribute to the onset of diseases like Parkinson’s and fatigue disorders (most people, especially bodybuilders, attribute cortisol to stress and muscle loss, which is accurate, but apparently its absence causes brain dysfunction; just goes to show that everything in the body has a purpose!).
Gender and age considerations and also THIS IS THE PART ABOUT SEX
Caffeine intake after a 10 hour fast has shown increased urinary calcium excretion in men and women of all ages at caffeine intake levels of about 150mg-400mg, and no tolerance has been shown to eventually occur for this problem. Caffeine intakes of 400 mg per person, per day have shown evidence of altered bone remodeling in premenopausal women ages 35-44. Supplementing with 600 mg calcium a day seemed to curb these calcium imbalances/losses, or simply keeping caffeine doses below 400 mg/day made them insignificant. Most studies comparing bone density with caffeine ingestion reflect the same results; that is that with adequate calcium and moderate amounts of caffeine, bone density is not seen to be negatively affected.
Most mood effectors, especially negative emotions such as anger, are often only seen after acute doses of caffeine, especially one-off acute doses (400+mg). Children on caffeine have been shown to have better performance in motor tasks, with children tested at high dose even outperforming children on low-dose (at, for example, speech rate and reduction in reaction time in vigilance tests) Many epidemiological studies have been conducted addressing the cancer potential of caffeine ingestion on numerous organs; no association was found in the colon in 13 studies, stomach in 6 studies, prostate in 1, liver in 1, lung in 3, and vulva in 1. Higher caffeine consumption (over 700 mg/day) was not associated with cancer development (specifically breast cancer) in 11 case-controlled studies. Though ill effects have been reported in fetuses of caffeine-consuming pregnant women and there is some evidence that caffeine ingestion can delay conception in women, it has been seen that sperm motility and strength is increased in men after caffeine ingestion; add to this that at least one study has found that women who have been artificially inseminated with their husband’s semen were twice as likely to get pregnant if said semen was treated with caffeine than if not. This sperm-caffeine positive association has been seen to be lost and even reversed in acute doses (+400mg).
Caffeine readily crosses the blood-brain barrier. The liver is the primary site of caffeine metabolism, which could be worrisome given that other more dangerous substances (ethanol, fructose) can only be metabolized in the liver. Infants up to the age of 9 months have a greatly reduced ability to metabolize caffeine, excreting about 85% unchanged in urine (the percentage for most adults is around 3%). The half-life of caffeine within a human body varies between individuals on the basis of age, smoker/non-smoker, pregnancy, et cetera; its half life in females is about 25% shorter than in males, but the half-life in females using contraceptives appears to be twice the amount for normal females. Pregnant females have seen an increase in half-life of about 4 hours to 18 hours in the first and third trimesters, respectively. Fetal growth is inhibited through maternal consumption of caffeine; this inhibition is caused through the reduction of placental corticosteroid 11ß-HSD2 by the metabolite of caffeine, paraxanthine; this substance has been implicated in inhibition of immunity, but also inhibition of tumor necrosis factor and transfer of potassium into skeletal muscles.
Cigarette smoking appears to cut the half-life of caffeine in half in any given person. This study stipulates ingested caffeine amounts of over 500mg/daily (4-7 cups coffee) as a health hazard and even an abuse. It also warns that caffeine use in excess of 400mg daily might cause detrusor instability (unstable bladder) development in women, and cautions against even moderate usage (200-400mg/day) in women with existing bladder problems for this reason.
In rats, pain threshold is lowered when caffeine is administered in doses of caffeine relevant to human intake, and especially that caffeine decreases the efficacy of acetaminophen in pain relief.
WHOO, that’s a lot of info. Let’s boil it down into as simple a brew as we can (A reduction sauce for you fancies, out there).
• As with so many things, in food and otherwise, moderation is key: Caffeine actually has positive effects in moderate amounts. That’s a cup or two of coffee a day (about 100mg caffeine, each). If you’re in Western Europe, it should be noted that the coffee of choice over there (mostly Robusto) has about twice the caffeine of the Arabica we drink almost everywhere else in the world (Yes, this is an indirect jab at the Euro). There are mixed results for perennial intake, so your best bet is probably to use caffeine sparingly and only on tasks where you can truly benefit from the enhanced motor skills and focus it provides.
• WOMEN WHO ARE NURSING OR PREGNANT… Yeah, so you’ll want to stay away from caffeine. Along with staying in your system longer, it has demonstrable detrimental effects on pre and post-born children, even though they can’t even fully metabolize it. Now, when the runts are older maybe give a bit to them on test day as it seems to improve that focus. Just don’t mix it with red dye or anything- brats are hyper enough on caffeine.
• Lunk alarm! Caffeine’s stimulant abilities in the gym may not be as pronounced as once believed, but there seems to be at least some benefit to its use. Again, I’d caution against overuse here, especially in conjunction with sickly-sweetened protein powders and the like (which, as you probably know, I don’t advocate).
• THE JITTERS, MAN. Caffeine also doesn’t seem to have the ability, in physiological doses, to cause addiction and withdrawal. This is due to different dopamine response than is seen in drugs that do create that situation. While it isn’t impossible to become addicted and have withdrawal symptoms, to do so would mean you’re ingesting an awful lot of coffee (or you may have a disposition for caffeine intolerance; rare, but possible). As previously stated, moderation is key. In actuality, all beneficial effects of caffeine seem to oppose themselves completely in plethoric doses of the stuff.
• An added aside: Coffee is actually one of the foods highest in potassium. While I definitely recommend getting it mostly from bananas and things of that nature, you can easily undo a day of “saltin’ out” with a nice cup o’joe.
For now, that’s all. I was pretty surprised by a lot of this stuff. While I’m not going to join the majority of adults in the world in swilling various coffees, teas, and colas, I feel I can utilize caffeine unabashedly when and where I might need a pick-me-up.
Okay, I’m going to sleep.