Caffeine, the world’s most widely used psychoactive substance, attracts a lot of research. PubMed contains 23,000+ citations for caffeine, for instance.

Caffeine also attracts controversy.

Some scientists argue that caffeine is a benign and useful drug whose side effects are only of concern in regard to a small number of “sensitives”, including those with pre-existing anxiety or similar symptoms. They note that caffeine improves attention, reaction time, numeric and verbal memory, and work output and endurance in long-term exercise.

Other researchers claim that caffeine has multiple damaging effects ranging from boosting blood pressure to disrupting sleep, and that these affect hundreds of millions.

Much of the debate swirls around the kind of stimulation that caffeine conveys. Does caffeine enhance attention, psychomotor performance, and some cognitive capabilities above normal physiological functioning, or can its stimulative effects be attributed merely to overcoming a withdrawal syndrome? There is evidence for both views, but two major confounders have kept scientists from ascertaining the truth in detail and with certainty.

The first confounder is that food companies have funded researchers who, not surprisingly, tend toward a favorable view of caffeine. The new insistence of some scientific journals on divulging conflicts of interest is perhaps curbing excesses (various articles from the older literature read like lawyers’ briefs). But corporate funding has skewed the discussion and the data available. Of course, just because a researcher defends caffeine doesn’t mean he/she is in the pay of the food companies, and just because a study is funded by them doesn’t mean its findings lack validity.

The second confounder is that, to the extent that withdrawal reversal explains caffeine’s effects, experimental designs have not provided proper control groups. Irish researcher Jack James notes that withdrawal symptoms (including sleepiness) are noticed within 12-16 hours, peak at 24-48 hours, and abate within 3-5 days (James and Keane in Human Psychopharmacology: Clinical and Experimental, 2007). So long-term studies are needed in which subjects are abstinent for at least one week.

James and other researchers have assembled formidable evidence to support the withdrawal reversal theory. James doesn’t deny that, in abstinent people, caffeine can elicit certain improvements above normal in physical and mental performance. But he notes that the overwhelming majority of caffeine consumption occurs in habitual users. They do not achieve above-normal performance from caffeine but merely reverse the effects of withdrawal.

Caffeine may also bring functioning of individuals not in caffeine withdrawal up to full performance. For instance, those with orthostatic hypoxia (hypotension) may find that caffeine overcomes the drowsiness they feel in a stuffy room or after some time spent reading. Caffeine might furnish similar restorative effects to people with anemia or alcohol hangovers. So aside from the above-normal effects that abstinent people may feel until they become habituated after 3-5 days of ingesting caffeine, caffeine may prove useful in specific circumstances. A broad characterization of caffeine, therefore, would be primarily as an Overcomer of Deficits.

Certainly, the intriguing finding that nurses who drank coffee were less liable to commit suicide than those who did not suggests a role for caffeine in a specific situation (Paton and Beer, International Journal of Psychiatry in Clinical Practice, 2001). However, one trait connected with caffeine withdrawal is depressed mood, and the use of caffeine by psychiatric patients is seven times higher than average (Broderick and Benjamin, Journal of the Oklahoma State Medical Association, 2007), which has led researchers to ask to what degree intake of caffeine exacerbates psychiatric syndromes.

James also points out that, because sleepiness is a prime characteristic of withdrawal, there is a danger that caffeine intake can lead to accidents from drowsiness as withdrawal sets in. Thus the benefits of caffeine for drivers and military personnel come at a risk.

A Stealth Bomber?

A 1995 study by Landolt et al. in Brain Research found that dosing with 200 mg of caffeine (equivalent to 1 1/2 cups of coffee) at 7:10 a.m. led to detectable amounts of caffeine in the blood at 10:55 p.m., to increased sleep latency (i.e., it took subjects longer to fall asleep), and to increased electroencephalogram activity compared to data for the same subjects when abstinent.

This raises the disturbing question of whether caffeine is responsible for a much larger portion of insomnia than the obvious cases where people ingest caffeine just a few hours before going to bed. Either the small amounts of caffeine could be having this effect or there is a hitherto unrecognized cumulative loss of sleep drive during waking hours under the influence of caffeine, Landolt et al. suggest. Or, one might add, it is possible that agitation from withdrawal could disturb normal sleep patterns.

From this perspective, caffeine could act, at least in some individuals, as a kind of Stealth Bomber. After drinking coffee at 10 a.m., they could even manage to take a nap in the afternoon. Yet they might not be able to get to sleep at night until 1 a.m., when withdrawal would release enough adenosine receptors (caffeine works via adenosine receptor blockade) to achieve normal sleep. Indeed, they might feel most agitated at the very end of the effects of caffeine–in this case, at 1 a.m. Given the remoteness of their morning intake and the misleading afternoon nap, neither they nor their physicians might spot the true source of the insomnia.

The flip side of insomnia is, of course, daytime sleepiness. Here the data from a 2006 study of caffeine in adolescents (Orbeta et al. in Journal of Adolescent Health) are telling. For children and adolescents, the primary source of caffeine is soft drinks, 70% of which contain caffeine in the United States. More than two out of three adolescents in the study consumed at least one soda per day, and a minority drank coffee as well. Of 4,243 American students, those in the top quartile of caffeine intake were 1.9 times more likely to have difficulty sleeping and 1.8 times more likely to be tired in the morning than subjects in the bottom quartile.

How many people fit this pattern? Is being a “sensitive” a question of genetics or of psychological category? Or is it, in many people, a function of how abstinent they have previously been? In this sense everyone would have the potential to be a sensitive, given a sufficiently long washout period. And those who can drink several cups of coffee in the evening before dropping off to sleep like babies might in fact confront a powerful withdrawal syndrome in the morning. Meanwhile, people who religiously avoid caffeine may be making themselves a good deal more sensitive to its effects when they unwittingly ingest caffeine hidden in many foods, drinks, and medicines.

So there is a palpable need for more statistical evidence in caffeine studies. We need to know what percentage of the general population are sensitives, what portion of the effects of caffeine can be ascribed to genetic predisposition, and–in view of the above considerations–what percentage of sleep disorders are caused by caffeine. We do know, however, roughly what percentage of the adult population are habitual users: 80%. That alone justifies the most meticulous research about the effects of this psychoactive substance.

Take-home Lessons

Five conclusions suggest themselves:

1. In habitual users, caffeine acts via withdrawal reversal, not by boosting performance above normal level.

2. In abstinent people and during the first several days of intake, caffeine can convey improvements above normal level in physical and mental performance.

3. In those with orthostatic hypoxia or anemia, heavy ingesters of alcohol, contemplators of suicide, and perhaps other specific categories, caffeine may prove useful.

4. In certain individuals, caffeine can disrupt sleep even 15 hours after intake.

5. Caffeine may play a much more pervasive role than is generally recognized in sleep disorders and other conditions.

Kenneth J. Dillon

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