What’s the one thing the majority of Americans would miss tomorrow if it were suddenly taken away? (Hint: it’s not their cell phone.) Caffeine! About 90 percent of people in the United States ingest caffeine every day, typically in the form of coffee. Not just one cup but multiple cups of coffee are being downed to the tune of 300 milligrams or more of caffeine daily.
For many people, this volume of caffeine doesn’t seem to be a problem. In fact, it’s quite the opposite-more like the proverbial tiger in their tank. Others, however, experience anxiety, diarrhea, headache, insomnia, irregular heart rhythms, headache, muscle tremors, or restlessness. Why? Until now, scientists haven’t been sure.
The difference now comes courtesy of advances in genetics, which is allowing researchers to peer into the wonders of caffeine metabolism. Here’s what they are discovering about the cup of coffee you have every morning and how your parents are responsible for how you metabolize it.
How coffee and caffeine metabolism works Everyone has two copies of a gene-one from each parent–that makes the enzyme responsible for metabolizing caffeine. There are two possible genes you can get: one that makes caffeine metabolize quickly and one that breaks it down slowly. The enzyme is called cytochrome P450 1A2, or CYP1A2.
If you inherit two copies of the fast gene type, you will metabolize coffee rapidly. However, if you get just one copy of the slow gene type, you are destined to be a slow caffeine metabolizer. But we’re not done yet.
Although caffeine can increase metabolism rate, it must have sufficient blood sugar to do so. A conflict can arise, however, because caffeine actually also causes glucose to be withdrawn from the bloodstream as a result of a higher metabolism. If you don’t have enough blood sugar to fuel your cells (hypoglycemia, or low blood sugar), your body reaches a crossroads: it wants to provide your cells with fuel (sugar), yet the caffeine is taking the fuel away. Stress alert!
Your body’s response to this stress is to release glycogen from the liver and to convert fat first (and then protein) into glucose in order to boost blood sugar levels. Scientists have determined that the combination of low blood sugar and the genetics of a slow caffeine metabolizer equals someone who could become hypersensitive or allergic to caffeine. (If you really enjoy the complexities of genetics and caffeine metabolism, check out this new study in Human Molecular Genetics.)
Researchers have uncovered even more about caffeine metabolism. A gene called AHR regulates the CYP1A2 gene, while a recent Harvard School of Public Health study found two new genetic factors associated with how people metabolize caffeine. Yet another study found that the type of adenosine receptors you have in your brain can affect how you respond to the stimulating effects of caffeine.
Levels of caffeine sensitivity According to the Caffeine Informer, there are three levels of caffeine sensitivity based on what we currently know about genetics and caffeine metabolism. Keep in mind that the average 8 ounce cup of coffee contains about 95 mg caffeine.
• Normal sensitivity: The majority of people are in this category. They can usually consume 200 to 400 mg of caffeine per day without experiencing any side effects, such as jitters, insomnia, increased heartbeat, and headache.
• Hypersensitivity. Individuals in this category react to small amounts of caffeine, sometimes less than 100 mg. It typically takes hypersensitive people as much as two times as long to metabolize caffeine as it does those with normal sensitivity. If you are in this group, you should stick to green or black tea or eliminate all caffeine and drink noncaffeinated herbal teas.
• Hyposensitivity. About 10 percent of people metabolize caffeine with super efficiency, even high doses (more than 500 mg). They can fall asleep after drinking coffee while the rest of us toss and turn.
More about coffee and caffeine metabolism
Two other things you should know about coffee and caffeine. Sensitivity to caffeine tends to increase with age, so you may notice you are responding to that morning cup of joe differently than you did in the past. Another factor is that children metabolize caffeine much quicker than do adults since they have a faster metabolism.
Cornelis MC et al. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Molecular Psychiatry 2015 May; 20(5): 647-56
Caffeine informer. Caffeine sensitivity
Cicetti F. Does caffeine sensitivity increase with age?