Glucose Response: Caffeine + Sugar + 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 unique.

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Caffeine, adenosine, alertness, and

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 showed an increase in glucose response when people consumed caffeine prior to a meal, when averaging the response across a large group. However, coffee consumption is associated with a decrease in the risk of type-2 diabetes, overall.

It turns out that the question of whether caffeine increases glucose response for an individual is based on their genes.

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 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 the 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.

Sugar and Caffeine Genotype Report

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

  • C/C: caffeine increases postprandial glucose response
  • C/T: caffeine does not affect postprandial glucose response
  • T/T: caffeine does 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 does not affect glucose response

Members: Your genotype for rs762551 is .



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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.

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