Ever wonder what the best time is to drink your coffee? You
probably know it is not a good idea to drink part of your daily dose of
caffeine in the afternoon. Especially for those who have problems
sleeping. But, do you ever drink your coffee and feel like it just
didn’t work?
I know I have that feeling sometimes. The
explanation for this has to with a concept that I think is extremely
interesting but rarely discussed: chronopharmacology.
Chronopharmacology
can be defined as the study of the interaction of biological rhythms
and drug action. One of the most important biological rhythms is your
circadian clock. This endogenous 24 hour clock alters your physiology
and behavior in variety of ways but it can also alter many properties of
drugs including drug safety (
pharmacovigilance),
pharmacokinetics,
drug efficacy, and perhaps even
drug tolerance.
But,
what part of the brain produces this 24 hour cycle and what signals
does it receive in order for it to do so properly? It has been known for
a long time that light is a strong
zeitgeber. A zeitgeber is a term used in
chronobiology
for describing an environmental stimulus that influences biological
rhythms. In the case of mammals, light is by far the most powerful.
Following the discovery of connections between the retina and
hypothalamus (the
retinohypothalamic tract), investigations were aimed at the hypothalamus as the putative master clock.
Indeed,
in some of the most elegant brain lesion experiments, Inouye and
Kawamura (1979) provided some of the first evidence demonstrating that
the hypothalamus acts as the master clock in controlling the circadian
rhythm. By creating an "island" in the brain by methodically cutting the
hypothalamus away from any surrounding tissue, the circadian clock was
completely lost (Inouye and Kawamura, 1979).
What does that mean? Well, the output of the hypothalamus nucleus (the
suprachiasmatic nucleus
or SCN) that controls the circadian clock has a variety of functions.
The SCN controls your sleep-wake cycle, feeding and energy consumption,
sugar homeostasis, and in addition to a few other things it controls
your hormones. And, with respect to your alertness, the SCN’s control of
cortisol (often referred to as the "stress" hormone) production is extremely important.
Most
readers here, especially the ones in science enjoy–and desperately
need–their morning coffee. I’ve seen some striking posts (
here and
here
- note the caffeine consumption map with the number of researchers map)
on the internet lately showing the correlation between science and
caffeine. Not surprisingly to me, wherever there are scientists, there
is a lot of caffeine consumed. And, a scientist also happens to be #1
the profession with the greatest caffeine consumption. But, if you are
drinking your morning coffee at 8 AM is that really the best time? The
circadian rhythm of cortisol production would suggest not.
Drug
tolerance is an important subject, especially in the case of caffeine
since most of us overuse this drug. Therefore, if we are drinking
caffeine at a time when your cortisol concentration in the blood is at
its peak, you probably should not be drinking it. This is because
cortisol production is strongly related to your level of alertness and
it just so happens that cortisol peaks for your 24 hour rhythm between 8
and 9 AM on average (Debono et al., 2009). Therefore, you are drinking
caffeine at a time when you are already approaching your maximal level
of alertness naturally.
One of the key principles of
pharmacology is use a drug when it is needed (although I’m sure some
scientists might argue that caffeine is always needed). Otherwise, we
can develop tolerance to a drug administered at the same dose. In other
words, the same cup of morning coffee will become less effective and
this is probably why I need a shot of espresso in mine now. Although
your cortisol levels peak between 8 and 9 AM, there are a few other
times where–on average–blood levels peak again and are between noon to 1
PM, and between 5:30 to 6:30 PM. In the morning then, your coffee will
probably be the most effective if you enjoy it between 9:30 AM and 11:30
AM, when your cortisol levels are dropping before the next spike.
Originally,
when I heard a lecture on this topic, the professor said that since
light is the strongest zeitgeber he suggested driving into work without
sunglasses on. This would allow for stronger signals to be sent along
the retinohypothalamic tract to stimulate the SCN and increase your
morning cortisol production at a faster rate. I still tend to drive with
them on since I feel blinded by the sun in the morning. However, on
mornings when it is partially cloudy out and I did not get a lot of
sleep, I drive with them off because this will help me feel more alert
than if I was shielding what little sunlight was available.
References
Debono
M, Ghobadi C, Rostami-Hodjegan A, Huatan H, Campbell MJ, Newell-Price
J, Darzy K, Merke DP, Arlt W, & Ross RJ (2009). Modified-release
hydrocortisone to provide circadian cortisol profiles. The Journal of
clinical endocrinology and metabolism, 94 (5), 1548-54 PMID: 19223520 Inouye,
S.T., and Kawamura, H. (1979). Persistence of circadian rhythmicity in a
mammalian hypothalamic “island” containing the suprachiasmatic nucleus
Proceedings of the National Academy of Sciences of the United States of
America DOI: 10.1073/pnas.76.11.5962
This post first appeared on Steven Miller's blog. Steven
Miller is a Ph.D. candidate at the Uniformed Services University of the
Health Sciences in Bethesda, Maryland. Steven’s research focuses on
identifying treatments against seizures induced by the chemical weapons
known as nerve agents. He is interested in the electrophysiology of the
brain, seizure disorders, and psychiatric disorders. Twitter:
@NeuroscienceDC.
Image by Peshkova/Shutterstock
