When Genes, Fitness, and Coffee Collide: Influences on Blood Pressure
It’s Not Just Coffee
I recently wrote a blog post about how the endurance-enhancing effects of caffeine might be influenced by your DNA — specifically, which variant of the CYP1A2 gene you carry. For those who recall (and those who don’t), the CYP1A2 (cytochrome p450 1A2, for short) is primarily responsible for the metabolism of caffeine.
In non-technical terms, the three different isoforms, namely AA (fast metabolizers), AC (intermediate/slow metabolizers), and CC (slow metabolizers) are all proposed to mediate different effects on an individual in response to caffeine. In the literature, it is the “slow metabolizers” who seem to be most susceptible to the short and long-term negative cardiovascular (i.e. blood pressure) benefits of caffeine, while the “fast metabolizers” have recently been shown to receive performance benefits, as well as not really respond much to acute caffeine ingestion.
A new study published in Vascular Pharmacology wanted to take the current hypothesis about genotype effects even further. Researchers investigated whether the gene variant had any effect on the blood-pressure effects of caffeine ingestion, and also whether or not this effect was influenced by the physical activity levels of the participants, or their caffeine consumption habits.
The reasoning behind this? As it is “well known” — long-term use of caffeine can result in caffeine tolerance, and thus, the blood pressure raising effect of caffeine may be attenuated or completely abolished in habitual caffeine users (in this study, that meant >300 mg/day, or about 2 cups of joe, it’s only 7 a.m and I’ve already had twice that…) As such, researchers stratified the study population into “habitual heavy caffeine consumers” and “non-habitual caffeine consumers.”
What about physical activity? It has been suggested that certain adaptations to exercise might influence how one responds to caffeine ingestion. Long term physical activity is associated with overall lower blood pressure. This, along with other physiological adaptations (baroreflexes, etc) might “protect” against the caffeine-induced increase in blood pressure.
Below, is a simple explanation of how the participants were categorized.
In a simple study design, participants had their resting blood pressure (systolic and diastolic; SBP/DBP from now on) measured, and then consumed a capsule containing 6mg/kg of caffeine. This is a pretty decent dose (i.e. a typical 70kg man would be consuming around 420 mg of caffeine, about 3 cups of coffee). After 1 hour of rest, participants blood pressure measurements were taken again.
In addition to having a higher resting DBP, the “slow metabolizers” in this study also experienced an increase in SBP from 121 to 126 mmHg after the ingestion of caffeine, and this was statistically significant. The “fast metabolizers” experienced no such increase in SBP. Both groups showed an increase in diastolic blood pressure after consuming caffeine. From this, it seems as if the “fast metabolizers” were in fact “protected” from the blood-pressure raising effects of caffeine. This may be due, per the researchers, to the fact that the presence of the “fast” enzyme is thought to protect against harmful, cell-damaging reactive oxygen species in the body.
Fitness: Also Protective Against Blood Pressure Increases
In general, those who were categorized as “physically active” (engaging in >150 min/week of activity) had lower baseline DBP interestingly, only if they possessed the “fast” gene variant.
How fit you were seemed to influence the response to caffeine ingestion. Those categorized as “sedentary” who were also “slow metabolizers” showed an increase in SBP after caffeine consumption — making these the most “at risk” individuals in this study. However, the same “slow metabolizers” who were physically active experienced no such increase, once again providing evidence of exercise having a protective effect on the cardiovascular system. In the “fast metabolizer” group — physical activity didn’t seem to have an effect.
Don’t Make it a Habit
Participants in this study who reported consumption of “heavy” caffeine (again, >300mg/day) and having the “slow” isoform presented with a 12mmHg higher baseline DBP than the fast metabolizers who also reported heavy caffeine use. After caffeine ingestion, the only group to experience an increase in SBP (from 119 to 125mmHg) was the non-habitual/ “slow” genotype group. Those who habitually consumed caffeine but had the “slow” genotype seemed to be immune to the increase in blood pressure — possibly a result of caffeine tolerance. Interestingly, regardless of gene variant (slow or fast), both habitual and non-habitual caffeine consumers experienced an increase in DBP 1 hour after caffeine ingestion.
So — more evidence accumulating in what is becoming a hot topic in exercise and nutrition research. Namely, that genes influence more than we previously thought. This has implications for design of future research studies. We have long known about those evil “confounding variables” such as environment, diet, external stress, etc. Not, we may need to take into consideration such variables as the subjects CYP1A2 variant. Not only that, but other individual factors such as exercise status and caffeine tolerance level can have profound influences on study outcomes. This small, but insightful study moves us a little further into better understanding humans — for we are all so very, very complicated.
Soares et al. The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.Vascul Pharmacol. 2018 Mar 6. pii: S1537–1891(17)30135–0