CYP1A2: It’s not just the “caffeine gene”

By: Iman Kassam

After hitting our snooze button one too many times, the first thing that many of us do is grab ourselves a cup of coffee to kick start our day. That magic molecule inside each of our cups that makes us feel more alert is caffeine. For some, one cup does the job, while others find themselves needing another cup to give them that extra boost. The main cause behind these individual differences is a gene called “CYP1A2”.

What is CYP1A2?

When you drink a cup of coffee, it passes through the digestive system before entering the bloodstream. For some people the peak plasma concentration of caffeine may be 15 minutes, but for others, this peak can take up to 2 hours to be reached. After the peak is reached, the effects of caffeine will wear off. The variability between peak times is due to differences in the CYP1A2 gene. This gene is responsible for producing the CYP1A2 enzyme, which is involved in 90% of caffeine metabolism. Like other genes, we inherit 2 copies of the CYP1A2 gene – one from our maternal side, and the other from our paternal side. The gene comes in 2 different forms, a “fast” version, and a “slow” version. Depending on the combination of CYP1A2 versions you inherit, you may be either a fast, medium, or slow metabolizer of caffeine.

Types of Metabolizer

If you inherit 2 copies of the “fast” version of this gene, you are likely someone who can have a cup of coffee before bed, and fall asleep without any issues. The CYP1A2 enzymes in your body are able to metabolize caffeine quickly and get it out of your system. In fact, having one to two 8-oz cups of coffee each day may actually help to reduce your risk of heart disease!

If you inherit one copy of each version of this gene, you are likely a medium metabolizer of caffeine. You’re able to clear coffee from your body, but do not fall on either extreme.

Finally, slow metabolizers inherit two “slow” copies of the CYP1A2 gene from both of their parents. These individuals metabolize caffeine at a slower rate, leading to an increased susceptibility to the negative effects of caffeine such as  jitters, anxiety, nervousness or sleeplessness.

I’m a slow metabolizer. Does this mean I should stop having caffeine?

Though slow metabolizers are more likely to experience some of the negative effects of caffeine, it doesn’t mean you need to halt your caffeine intake. By understanding your metabolizer status, you can consume caffeine strategically. By taking time to understand how your lifestyle can work with your genetics, you can figure out what times might be best for you to have your cup of coffee, all while avoiding some of those negative effects.

Slow metabolizers and heart attacks

Aside from some of the more commonly known side effects, slow metabolizers may also be at an increased risk of heart disease depending on their caffeine consumption. A study published in the Journal of the American Medical Association outlined some of the risks associated with being a slow metabolizer with high caffeine consumption. In this study, it was found that slow metabolizers who had more than 4 cups of coffee a day were at a higher risk of experiencing a nonfatal heart attack (1.63 times more than those who consumed less than one cup a day).

Other substances metabolized by CYP1A2

Aside from caffeine, CYP1A2 also plays a role in the metabolism of a number of other substances. Two of these substances include toxic chemicals, which are produced by smoking and grilling meats. These chemicals are known as heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs), and can cause DNA damage and other health concerns. Your metabolizer status will impact your risk to these issues, but knowing your status can help you make changes in your lifestyle to reduce your risk.

In addition, many commonly prescribed medications are also metabolized by CYP1A2. Knowing your metabolizer status can help you and your healthcare practitioner determine what doses of medications might work best for you. Some of these medications include the following: olanzapine and clozapine (antipsychotics), propranolol (used for anxiety and chronic headaches), zolpidem and melatonin (for sleep), and lidocaine (anesthetic).

Knowledge really is power

By taking the time to learn about your metabolizer status for CYP1A2, you can determine how your body breaks down caffeine as well as toxins, and medications. After all, each one of us is unique, and therefore, understanding our differences is the key to feeling our best. Here at DNALabs, our goal is to help you learn more about your own body to empower you to improve your health and well-being by providing actionable nutrition, exercise and lifestyle recommendations personalized to your unique genetic makeup. For more information on how you can understand your body better, visit us at https://dnalabs.ca/!

References

1. El-Sohemy, A., Cornelis, M.C., Kabagambe, E.K., and Campos, H. (2007). Coffee, CYP1A2 genotype and risk of myocardial infarction. Genes & Nutrition 2, 155–156.
2. Cornelis, M.C., El-Sohemy, A., Kabagambe, E.K., and Campos, H. (2006). Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction. JAMA 295, 1135.
3. Palatini, P., Ceolotto, G., Ragazzo, F., Dorigatti, F., Saladini, F., Papparella, I., Mos, L., Zanata, G., and Santonastaso, M. (2009). CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension: Journal of Hypertension 27, 1594–1601.
4. Rapuri, P.B., Gallagher, J.C., Kinyamu, H.K., and Ryschon, K.L. (2001). Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. The American Journal of Clinical Nutrition 74, 694–700.