Glucose Response: Caffeine and Carbs interact with Your Genes

An interesting study in Nature called Genetic Polymorphisms in ADORA2A and CYP1A2 Influence Caffeine’s Effect on Postprandial Glycaemia (open access!) caught my eye today. The study investigated how the genetic variants for caffeine metabolism interact with carbohydrate consumption.

Spoiler alert: caffeine along with carbs changes glucose response for people with certain genetic variants.

Let me give a little background info:

Adenosine builds up in the brain all day as you use ATP for energy.

As more and more adenosine builds up and binds to the adenosine receptor (ADORA2A), it causes you to get drowsy. This is one reason we feel sleepy and are driven towards sleeping each night.

Caffeine also binds to the adenosine receptor, ADORA2A. It isn’t the same as adenosine, though, so instead, it blocks the action of adenosine at the receptor. This is why caffeine makes you feel more alert — due to the lack of adenosine binding to the receptor.  (Well… more alert until the caffeine wears off and you suddenly feel really sleepy due to the adenosine that is still hanging around and now able to bind to the receptors.)

Adenosine also inhibits norepinephrine and epinephrine release, so caffeine blocking the receptor allows for norepinephrine and epinephrine to be released (surge of energy). Epinephrine, though, also upregulates glucose mobilization…  and thus a link to glucose response for caffeine.

Caffeine is broken down in the body by the CYP1A2 enzyme, and genetic variants there cause people to break down caffeine at different speeds. This is why some people can’t drink caffeine after lunch without it affecting their sleep — and others can drink a cup of coffee at dinner and still sleep well that night.

Previous studies have shown when looking at a general population, there is an increase in glucose response when people consumed caffeine prior to a meal.  Coffee consumption, on the other hand, is linked to a decrease in the risk of type-2 diabetes. The different polyphenols in coffee, though, may come into play here.

Details on the caffeine – carbs – genetics study:

The experiment detailed in Nature used a cross-over design where 18 male participants (in their mid-20s) visited a lab two different times to test their response to caffeine and carbs.

The participants consumed a ‘carbohydrate meal’ initially to see what their glucose response was to carbs.  This carbohydrate meal seems to be just drinking Gatorade. And the carbohydrate plus caffeine meal was Gatorade with caffeine added.

The glucose response was measured for each test condition and the participants were genotyped for their ADORA2A and CYP1A2 variants.

The results showed that those with the CC genotype of ADORA2A variant (listed below) had less of a postprandial glucose response without caffeine than they did with caffeine. For the participants with the CT and TT genotype of ADORA2A, there was no difference in glucose response with caffeine vs without.

Check your genetic data:

Check your genetic data for rs5751876 (23andMe v.4, v.5)

  • C/C: caffeine increased postprandial glucose response
  • C/T: caffeine did not affect postprandial glucose response
  • T/T: caffeine did not affect postprandial glucose response

The CYP1A2 gene codes for the enzyme that metabolizes caffeine.  The study participants with the faster version of this enzyme had a similar glucose profile with and without caffeine. But those with the slower version of the enzyme had their glucose response elevated for a longer time.

Check your genetic data for rs762551 (23andMe v.4, v.5; AncestryDNA):

  • C/C: longer glucose elevation when caffeine added to carbs
  • A/C: longer glucose elevation when caffeine added to carbs
  • A/A: caffeine did not affect glucose response

Again, all of this is based on a study in Nature that I encourage you to read.



You generally don’t want a big spike in your blood glucose levels after you eat. Thus, if you are drinking Gatorade for breakfast, people with the ADORA2A CC genotype should skip the caffeine powder.

More realistically (because who drinks Gatorade with caffeine for breakfast!), this could influence your choice of sweetener in your coffee as well as your carb load at breakfast.

Perhaps a giant chocolate chip muffin along with a grande Starbucks caramel cappuccino isn’t the right idea for some people? (slight sarcasm here)

Read more about caffeine and your genes:


Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.