About 90 percent of Americans consume caffeine daily. More than half of all American adults consume 300 milligrams or more caffeine every day, making it America's most popular drug, according to Live Science. The world’s too, by the way.
Numerous scientific studies and common experience tells us that for most of us, 200 to 300 milligrams a day are mostly invigorating, not harmful. That’s most of us - how about the ones who exhibit or are in the process of developing sensitivity to caffeine?
We all know that caffeine can cause restlessness, anxiety, irritability, muscle tremors, sleeplessness, headaches, nausea, diarrhea and abnormal heart rhythms. Unfortunately, these symptoms are not specific only to caffeine but to a host of other conditions and ailments. So it has been very hard till now to connect them. No longer, thanks to rapid advances in genetics.
The metabolism of caffeine in our body
Let us look at a more scientific side of what happens to caffeine inside our body. We will also use this as a means to compare the metabolism of children to adults.
Caffeine is metabolized in the body by the enzyme Cytochrome P450 1A2 (CYP1A2) in the liver. Every person has two copies of the gene which makes the enzyme CYP1A2 (one copy from each parent). There are 2 variations of this gene which affect how quickly a person metabolizes caffeine. The CYP1A2*1A variety (“allele”) makes an enzyme that metabolizes caffeine very rapidly. However, the CYP1A2*1F allele metabolizes caffeine slowly. The difference between these two alleles is one single nucleotide, an A to C substitution at position 734 of the CYP1A2 gene.
Individuals who have two copies of the fast CYP1A2*1A allele are fast caffeine metabolizers; whereas people who have at least one copy of the slow CYP1A2*1F allele are slow caffeine metabolizers.
As caffeine is metabolized, it is broken down into theophylline, paraxanthine, and theobromine. These travel all over our body and influence many body organs and functions. These also sway moods and prevent the calming effect of dopamine. Theophylline causes smooth muscles to relax and that is why we usually feel like going to the comfort room after ingesting caffeine. On the other hand, theobromine adds to the oxygen and nutrient levels in our body which are used by muscles and the brain.
Stimulation by caffeine increases the rate of metabolism
Although stimulation from caffeine increases the rate of metabolism, it can only achieve this effect when the metabolic support for it is there. The most important element of this support is sufficient blood glucose - blood sugar - in our body. Feeling anxious or shaky is, in most cases, a result of low blood sugar (hypoglycemia).
Add to this that once caffeine is in your system, even more glucose is removed from the bloodstream, since caffeine further stimulates the body’s metabolism. Problems begin when our body cannot provide enough fuel for cells, given the level of stimulation. If too much stimulation occurs, a stress alarm goes off, that mobilizes resources to provide energy to cells. Your body says, “We’ve got lots of stimulation going on here; we need to mobilize resources right now.”
The stress alarm’s basic function is to raise the blood sugar level. This involves the release of glycogen from the liver under the direction of adrenaline and glucagon, and the conversion of body fat first, and protein after that, into glucose using the liver’s help, as it is intimately involved in blood sugar regulation.
Combining low blood sugar (hypoglycemia) and being a slow caffeine metabolizer may give us the explanation as to how people could become sensitive or allergic to caffeine.
Measuring caffeine sensitivity
Caffeine sensitivity is the inversely proportional with the amount of caffeine that will affect a person. The more caffeine needed to produce an impact on someone, the less sensitive he or she is to caffeine. It is common to say that the smaller or older the person, the less caffeine required to make an effect.
Unfortunately for many of us, sensitivity to caffeine does tend to increase together with increase in age. Children metabolize caffeine quicker than adults. Since children have faster metabolism, they also process the caffeine faster while older people with slower metabolism become somewhat thin-skinned to caffeine and store it for a while.
Other helpful information
Caffeine metabolism DNA testing
The CaffeineGEN™ test by Consumer Genetics is a simple, accurate genetic test that will tell you if you have the fast or slow caffeine metabolizing gene. All you need to do is collect a simple cheek swab sample in the comfort of your home and just days later you will be ready to make positive changes in your life based on your personal genetics.
By knowing your genetic makeup, you can adjust your daily caffeine intake accordingly and manage your overall well-being.
Genetic links to caffeine sensitivity
Ted Kallmyer of CaffeinInformer.com is one of the foremost experts in all things having to do with caffeine. As he describes in his Caffeine Sensitivity article (see link below):
"Caffeine is metabolized in the liver using the enzyme CYP1A2. The ability to produce this enzyme is regulated by the CYP1A2 gene. Slight changes in the DNA sequence of this gene determine how efficiently a person can metabolize caffeine and thus eliminate it from the body."
The Cornelis study
According Cornelis et al. a person who is a fast metabolizer of caffeine can drink up to 6 cups of coffee a day and have no effects. However, bear in mind that the lethal dose is 2 grams of caffeine per day.*
Additionally, the Cornelis et al. study finds that people who have the slow caffeine metabolizing gene can still enjoy caffeinated food and beverages so long as their caffeine consumption doesn’t exceed more than 200 mg per day or more than 2-3 cups of coffee per day.
* Other sources give different values. Some even go up to 14 grams a day!
http://www.livescience.com/6252-caffeine-sensitivity-increase-age.html - Fred Cicetti
http://www.functionalps.com/blog/2014/06/04/coffee-done-right-tips-to-help-avoid-coffee-intolerance/ - Team FPS
Cornelis MC, El-Sohemy A, Kabagambe EK, and Campos H. “Coffee, CYP1A2 genotype, and risk of myocardial infarction.” JAMA 2006, 295:1135-1141