Software: June 2010 Archives


June 10, 2010

Alfred Renyi famously said "A mathematician is a device for turning coffee into theorems." (actually Paul Erdos famously said it, but according to Wikipedia it's actually Renyi). I'd long believed (and thought the evidence showed) that caffeine improved concentration and hence productivity. Now Rogers et al. have come along and spoiled everything:
Caffeine, a widely consumed adenosine A1 and A2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline.

Roughly speaking, this paper says that if you don't use caffeine, taking it won't make you more alert. If you do use it, it will make you more alert but only because you're less alert due to caffeine withdrawal and taking it brings you back up to normal.

What's most surprising here is the result that caffeine doesn't improve alertness in non-users. This contradicts previous work which shows an improvement in alertness from caffeine consumption by non-users. The authors propose one explanation for this might be that people are reporting low/no usage of caffeine when they are actually using it at higher levels (the 40 mg/day level cutoff here between low and moderate is actually quite low; coffee contains something like 100mg/cup.) So, when you force withdrawal and then dose with caffeine you get an improvement in alertness. This is partly borne out by their measurements of caffeine levels in "non-users" which are actually modestly high. However, this seems like it would benefit from more study.

However, it appears that once you are already a regular caffeine user, you do get some benefit from caffeine, in that it restores normal function. So, it's not crazy to take it once you're a user. However, it appears that you could get an equivalent benefit from just abstaining entirely and then (maybe) using caffeine when you needed to be alert (assuming you don't believe the non-user result). Of course if you're a user, you'll have to withdraw, which isn't a lot of fun.

One thing I should note is that the instrument this paper uses is a direct measure of (subjective) perceived alertness. The authors also had subjects do a variety of tasks that presumably required alertness. Those results don't appear in this paper, so it could be that they show improvement in non-users: i.e., they don't feel more alert when taking caffeine but they are more effective, which would make consumption worthwhile. I look forward to the publication of that data.