Glucose Response: Caffeine and Carbs interact with Your Genes

You may have read that consuming sugar or carbohydrates along with caffeine will bump up your blood glucose levels. It turns out this isn’t true for everyone.

Genetic variants in the adenosine receptor as well as the enzyme that metabolizes caffeine work together to create unique blood glucose responses. We are all different!

A little background info on caffeine:

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 when caffeine blocks the receptor, it allows for norepinephrine and epinephrine to be released (surge of energy). Epinephrine, though, also upregulates glucose mobilization…  and thus a link to glucose response to caffeine.

The CYP1A2 enzyme breaks down the caffeine in the body, and those with the genetic variants break it down 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 show looking at a general population, an increase in glucose response when people consumed caffeine prior to a meal. On the other hand, coffee consumption is associated with a decrease in the risk of type-2 diabetes. The different polyphenols in coffee, though, may come into play here.

Details on the caffeine  and carbohydrates genetics study:

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

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.

Genetic Variants that Impact Glucose Response to Carbs:

Members: Log in to see your data below

Check your genetic data for rs5751876 (23andMe v4, v5)

  • 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

Members: Your genotype for rs5751876 is .

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 v4, v5; 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

Members: Your genotype for rs762551 is .

Again, all of this is based on a study in Nature. Go read it for yourself :-)



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)

Related Genes and Topics:

Caffeine Metabolism and Your Genes
Whether you start your morning with a cup of coffee or a cup of tea, caffeine remains the most popular ‘drug’ of choice for a large percentage of the population. Caffeine wakes us up by blocking the adenosine receptor.  Caffeine also acts as a central nervous system stimulant, increasing reaction time. Genetics determines how quickly your body processes and eliminates the caffeine and whether it is likely to make you jittery or anxious.

Hunter-Gatherer vs. Farmer
Our ancient ancestors lived much differently than we do today. They were hunter-gatherers, living off of fish, meat, and plant foods that they gathered. A huge shift took place when those hunter-gatherers began farming, growing grains, and storing them so that there would be food available all year. Learn if you carry the hunter-gatherer or farmer gene variant.