CYP1A2 Enzyme: Where Caffeine Meets Genetics

Gene in Focus: Part 4 – CYP1A2 (Caffeine)

CYP1A2 Enzyme: Where Caffeine Meets Genetics

As with all our genes, there are two different CYP1A2 alleles, in this case A and C. The A allele is associated with a higher activity of the CYP1A2 enzyme, and the C allele is associated with lower activity of the enzyme. 

CYP1A2 and your genetic caffeine response

Research on the effects of caffeine on cardiovascular health found that the effect of caffeine differs between genotypes. With regard to caffeine response, AA genotypes tend to metabolise caffeine quicker than AC and CC genotypes. As a result, AA genotypes are called “fast metabolisers” and the AC and CC genotypes are classed as “slow metabolisers”.

A 2006 study found that slow metabolisers who had more than about three cups of coffee per day, increased their risk of suffering from a myocardial infarction (heart attack). Fast metabolisers, however, didn’t see an increase in heart attack risk. The same is true for hypertension.

A 2009 study found that higher amounts of caffeine (around 300mg per day) was associated with an increased risk of hypertension – but only in slow caffeine metabolisers. these studies, and others them, DNAFit recommends that slow metabolisers should limit their intake of caffeine to around 200mg per day.

Fast metabolisers can consume more caffeine should they wish, up to approximately 300mg per day.

200mg of caffeine is equivalent to:

  • approximately two cups of brewed coffee
  • approximately four cups of tea
  • approximately two energy drinks

CYP1A2 and phase-1 detoxification ability

We also look at CYP1A2 from the perspective of phase-1 detoxification ability, which looks at how well your liver can handle two compounds found in cooked meats.

These compounds are HCAs and PAHs which form when meat is cooked at a high temperature, and has become blackened, crispy, or chargrilled.

When we eat this meat, our body starts to break down these HCAs and PAHs creating a toxic by-product.

If you breakdown these HCAs and PAHs quickly, you get a rapid increase in this toxic by-product which overwhelms your body. However, if you break them down slowly, you get a much gentler increase in the toxic by-product – lowering your risk of toxin build up.

CYP1A2 is one of the genes involved in this pathway, and A allele carriers are classed as fast metabolisers, with CC genotypes classed as slow metabolisers.

In the case of fast metabolisers, we recommend that they limit their consumption of grilled or smoked meats, and focus on protecting the meat during the cooking processes. This requires using a lower cooking temperature – so, cooking with a liquid (curries, stews, stir fries, marinades) should help with this.

As you can see, your version of the CYP1A2 gene can have an impact on how well you tolerate caffeine, and how well you process HCAs and PAHs. Both of these things can have a profound impact on your future health. By understanding your body on a genetic this, you can make important dietary changes which can maximise your health both in the short and long term.

Take the DNAFit test to discover your CYP1A2 genotype, to see how much caffeine you can tolerate on a daily basis – without damaging your health.

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CYP1A2 and The Effects of Caffeine on the Body

CYP1A2 Enzyme: Where Caffeine Meets Genetics

Is caffeine bad for you? It may depend on your genes. More specifically, it may depend on one gene—called CYP1A2—that determines how your body metabolizes the caffeine found in fan favorite beverages tea, coffee, and soda. 

What is caffeine—and how does it affect the body? 

Caffeine is a bitter, white substance that’s found naturally in more than 60 different plants, including coffee beans, tea leaves, and kola nuts, which are used to make soda. Caffeine acts as a natural stimulant and for this reason, the FDA has it listed as both a food and a drug. 

To get specific, caffeine targets the central nervous system and makes you feel more awake, energized, and alert. It’s often described as a cognitive and physical performance enhancer.

 Everyone seems to react to caffeine differently; some get jittery and anxious from a few sips of coffee while others can drink cup after cup without blinking an eye.

Recently, researchers discovered these variations in caffeine tolerance can be traced back to genetic differences, which brings us to the CYP1A2 gene. 

What is CYP1A2, aka the caffeine gene? 

The caffeine you ingest passes through the stomach and small intestine, entering the bloodstream in a little as 15 minutes.

Your caffeine levels peak about 1-hour after consumption and then start to decrease gradually.

The speed of this decline depends on your CYP1A2 gene, which controls an enzyme (also called CYP1A2) that is in charge of breaking down any caffeine that enters the body.

You have two copies of the CYP1A2 gene—one inherited from each of your parents—and each can be either a “fast” or “slow” version of the gene.

If you have two “fast” versions, you’re considered a fast caffeine metabolizer. According to Dr. Tiffany Lester, M.D.

, physician and medical director at Parsley Health San Francisco, “These are the people that can have an espresso and go right to sleep!”

In contrast, if you have one or two versions of the “slow” version of CYP1A2, you’re labeled a “slow” caffeine metabolizer, meaning you clear caffeine from your system about four times slower than your quick metabolizing counterparts, says Dr. Lester.

How to test for the CYP1A2 gene 

your reaction to caffeinated beverages, you probably already have a hunch as to whether you’re a fast or slow caffeine metabolizer. But how do you test it to know for sure? You can test for the caffeine gene through a simple saliva or blood test that analyzes your DNA. 

“I don’t typically test for CYP1A2 in isolation,” explained Dr. Lester. In other words, it doesn’t influence health in a significant enough way that she would go her way to order the test for every single one of her patients. “It usually comes up if a patient has done a 23andMe or other direct-to-consumer genetic test,” she continued.

If you’re a slow metabolizer, should you avoid caffeine? 

The CYP1A2 gene made headlines a few years ago when a study, published in the Journal of the American Medical Association, showed that slow metabolizers who drink more than four cups of coffee per day have an increased risk for heart disease. 

So if you’re a slow caffeine metabolizer, should you be cutting out caffeine from your routine entirely? “No way!” said Dr. Lester. In fact, Dr. Lester is a slow caffeine metabolizer herself and still enjoys her daily dose of caffeine.

That said, knowing that she has this genetic variant has helped her consume caffeine more strategically. “For someone me who does have that genetic variant, I do not have caffeine after 8 a.m. otherwise it will be difficult for me to fall asleep at night,” she said. 

It’s all about evaluating your relationship with caffeine and figuring out what’s best for your lifestyle and genetics. Parsley Health’s health coaches are experts in helping members determine what works best for them—and how to still enjoy caffeine if they choose.

Are there other reasons to reduce your caffeine intake?

According to Dr. Lester, if you’re dependent on caffeine to function and get through the day—and you’re still tired even after getting plenty of sleep—it could be a sign that you have underlying adrenal fatigue. “In that case, cutting out caffeine entirely for a period may be the best option to discuss with your doctor,” she explained. 

Even if you’re a fast caffeine metabolizer, you can still experience side effects of too much caffeine such as: 

  • Migraine headache
  • Insomnia
  • Restlessness
  • Frequent urination or inability to control urination
  • Stomach upset
  • Nervousness
  • Irritability
  • Fast heartbeat
  • Muscle tremors

According to Mayo Clinic, a healthy caffeine intake can be up to 400 milligrams (mg) a day. If you’re consuming more than that, it might be worth cutting down your caffeine intake, especially if you’re a slow caffeine metabolizer or are experiencing any of the side effects of too much caffeine listed above.

It’s possible to be a fast caffeine metabolizer and still have negative reactions to moderate or even low amounts of caffeine. This could indicate an underlying health concern, such as estrogen dominance. 

Estrogen and caffeine are both broken down in the liver by the CYP1A2 enzyme.

“Women that have estrogen dominance often do not have an abundance of this enzyme and therefore should not consume caffeine as they will also have a hard time detoxing it,” explained Dr. Lester.

The good news is that once you balance your hormones with the help of a doctor, it’s ly you’ll be able to tolerate caffeine again. 

How to reduce caffeine intake and avoid caffeine withdrawal symptoms

If you’ve decided to pull back on your caffeine intake for any reason, the first step is to figure out how much caffeine you’re actually consuming. Not every beverage contains the same amount of caffeine. For example, an 8-ounce cup of coffee has about 95 to 200 mg of caffeine compared to a cup of green tea, which has about 14 to 60 mg in an 8-ounce serving. 

Meanwhile, energy drinks can have anywhere from 60 to 250 mg of caffeine per serving. As Dr. Lester explained, “Each of these beverages have different amounts of caffeine with tea being the lowest. So, for example, someone with anxiety may not be able to tolerate an espresso but can happily drink a matcha latte!”

Caffeine can also be hiding in places you might not expect. Kombucha and chocolate are two hidden sources of caffeine that you might not be taking into account. When you’re cutting back on caffeine, Dr.

Lester recommends going slowly or you might experience caffeine withdrawal symptoms headaches, irritability, and fatigue. “A general rule is to go by halves.

Cut down gradually by halving your intake every 3 days until you’re completely off any caffeine source,” she said. 

What are the best healthy caffeine alternatives? 

Cutting back on caffeine isn’t always easy. Caffeine is the most common “drug” in the world and after water, coffee is the most popular beverage on earth. About 1.6 billion cups of coffee are consumed every single day worldwide; in other words, it’s deeply ingrained in our culture and our daily routine. Turning to other caffeine-free drinks can help you ease the transition. 

1. Decaffeinated coffee, tea, and soda 

The most obvious choice is the caffeine-free version of your favorite coffee or tea-based beverage. But proceed with some caution. Many companies use harsh chemicals to remove caffeine that you’ll want to avoid. In this case, opt for organic options or buy from companies that are transparent about the process they use.

2. Caffeine-free herbal tea

Naturally caffeine-free options include herbal teas chamomile, peppermint, rooibos, and hibiscus. You can also find herbal chai—made from rooibos or herbal tea instead of black tea—that tastes your favorite chai without the stimulating effects. 

3. Golden milk 

An ancient Ayurvedic tradition, golden milk is a creamy, lightly sweet beverage that contains turmeric powder and steamed milk—and oftentimes honey and cinnamon, vanilla, and other spices. You can find golden milk or turmeric lattes in many coffee shops and cafes and it is naturally caffeine-free.  

In the end, there’s no cut and dried equation for how much caffeine you should consume. Instead, it’s up to you to be mindful and know how much caffeine is too much for your health and sleep quality. The good news is that even if you’re a slow caffeine metabolizer, you can enjoy your morning coffee as long as you’re wise about your consumption. 


Get to Know an Enzyme: CYP1A2

CYP1A2 Enzyme: Where Caffeine Meets Genetics

Get to Know an Enzyme: CYP1A2

John R. Horn, PharmD, FCCP, and Philip D. Hansten, PharmD

Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy. For an electronic version of this article, including references if any, visit

Table 1
CYP1A2 Substrates Alosetron (Lotronex) Caffeine Clozapine (Clozaril) Flutamide (Eulexin) Frovatriptan (Frova) Melatonin Mexiletine (Mexitil) Mirtazapine (Remeron) Olanzapine (Zyprexa) Ramelteon (Rozerem) Rasagiline (Azilect) Ropinirole (Requip) Tacrine (Cognex) Theophylline Tizanidine (Zanaflex) Triamterene (Dyrenium) Zolmitriptan (Zomig)

The cytochrome P450 enzymes are found primarily in the liver, although some (eg, CYP3A4) are also found in substantial amounts in the intestine.

They are involved in the metabolism of most medications and are the mechanism by which most pharmacokinetic drug interactions occur. Cytochrome P450 3A4 (CYP3A4) is the superstar; it gets attention because a majority of drugs are metabolized by CYP3A4.

Other important CYP450 enzymes include CYP1A2, CYP2C9, CYP2C19, and CYP2D6. Here we will focus on a rising star: CYP1A2.

CYP1A2 Substrates

The importance of CYP1A2 for drug interactions has been increasing over the past decade due to the growing number of drugs metabolized by this enzyme.1 Drugs metabolized by CYP1A2 are called CYP1A2 substrates.

CYP1A2 Inhibitors

Table 2
CYP1A2 Inhibitors Artemisinin Atazanavir (Reyataz) Cimetidine (Tagamet) Ciprofloxacin (Cipro) Enoxacin Ethinyl Estradiol Fluvoxamine Mexiletine Tacrine (Cognex) Thiabendazole Zileuton (Zyflo)

Drugs that inhibit CYP1A2 will predictably increase the plasma concentrations of the medications listed in Table 1, and in some cases adverse outcomes will occur.

Of particular note is fluvoxamine, which is a potent CYP1A2 inhibitor and also inhibits other CYP450 enzymes, such as CYP2C19, CYP3A4, and to some extent CYP2C9. Thus, fluvoxamine may prevent other metabolic pathways from compensating for the CYP1A2 inhibition.

The fluoroquinolone antibiotics, enoxacin and ciprofloxacin, also substantially inhibit CYP1A2.

CYP1A2 Inducers

Table 3
CYP1A2 Inducers Barbiturates Cruciferous vegetables Grilled meat Carbamazepine (eg, Tegretol) Primidone Rifampin (eg, Rifadin) Smoking

Other drugs may stimulate CYP1A2, and they may reduce the efficacy of CYP1A2 substrates. Of particular note is cigarette smoking, which can substantially increase CYP1A2 activity.2 Thus, smoking may reduce the efficacy of any of the CYP1A2 substrates.

For example, it has been known for many years that smoking substantially increases theophylline dosage requirements.

More recently, smoking has been shown to reduce the serum concentrations and efficacy of the atypical antipsychotics, clozapine and olanzapine.

Important Drug Interactions Involving CYP1A2

Some CYP1A2 interactions have limited clinical importance; for example, most patients can withstand an elevated caffeine concentration due to ciprofloxacin without significant adverse consequences. Others, however, can be serious.

Historically, the most important CYP1A2 drug interactions were probably severe theophylline toxicity due to concurrent use of theophylline with CYP1A2 inhibitors such as ciprofloxacin or fluvoxamine. These still occur occasionally, even with reduced use of theophylline, but the many newer CYP1A2 substrates now present drug-interaction problems with CYP1A2 inhibitors.

For example, tizanidine plasma concentrations increased over 30-fold when the potent CYP1A2 inhibitor fluvoxamine was given concurrently.

Assessing CYP1A2 Activity in Patients

For some CYP450 enzymes such as CYP2D6, genetic factors dictate most of the activity of the enzyme, and genotyping of patients may be useful. This is not true for CYP1A2, however, where the activity of the enzyme is dictated largely by environmental, dietary, and other factors in addition to genetics.

1 In this case, phenotyping is more useful, where, instead of genetic testing, a probe compound is given to the patient and the actual enzyme activity is determined. One proposed phenotyping method for CYP1A2 is to obtain a saliva sample following a test dose of caffeine.

One drawback of such testing is that the subject must abstain from coffee, many teas and soft drinks, and chocolate for a day or so before the test.


The enzyme CYP1A2 increasingly is involved in drug interactions as new medications metabolized by this enzyme are released. Some of the substrates that warrant particular attention are theophylline, clozapine, olanzapine, and tizanidine.

Some of the more potent CYP1A2 inhibitors include cimetidine, ciprofloxacin, enoxacin, and fluvoxamine.

Among CYP1A2 inducers, smoking is probably the most important, but the usual enzyme inducers such as rifampin and barbiturates can also substantially increase CYP1A2 activity.


  1. Faber MS, Jetter A, Fuhr U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97:125-134.
  2. Kroon LA. Drug interactions with smoking. Am J Health Syst Pharm. 2007;64:1917-1921.


The Effect of the CYP1A2 −163 C > A Polymorphism on Caffeine Metabolism and Subsequent Cycling Performance

CYP1A2 Enzyme: Where Caffeine Meets Genetics

The effect of caffeine on exercise performance has been thoroughly documented in a variety of activities.1–4 A proposed mechanism for caffeine's ergogenic effect is adenosine receptor blockade.

While adenosine decreases neuronal firing and arousal, caffeine binds to adenosine receptors, thus limiting the aforementioned adenosine responses.

5 It has also been suggested that caffeine metabolites paraxanthine (PX), theobromine (TB), and theophylline (TP) have an even higher affinity for adenosine receptors than caffeine.

5 Cytochrome P450 (CYP1A2) is the enzyme largely responsible for caffeine metabolism in the liver and conversion to its three major metabolites already listed. A single nucleotide polymorphism (CYP1A2 −163 C>A) significantly affects the inducibility of this enzyme such that caffeine metabolism is faster in AA homozygotes and slower in C allele carriers.6,7

Previous studies from our laboratory have observed differences in exercise performance between these genotypes following caffeine supplementation. Womack et al.8 observed that caffeine improved 40 km cycling performance to a greater extent in AA homozygotes than C allele carriers (both A/C heterozygotes and CC homozygotes) in 35 trained male cyclists.

Conversely, Pataky et al.9 found C allele carriers showed a greater ergogenic benefit than AA homozygotes in a 3 km cycling time trial. Algrain et al.10 did not observe any differences in the effect of caffeine gum on a 15 minute performance trial between the genotypes.

However, no main effect of caffeine was observed,10 thus reducing the ability to detect genotype differences.

Clearly, prior findings on the effect of this polymorphism on the ergogenic effect of caffeine are equivocal. Furthermore, none of these prior studies reported the influence of the polymorphism on caffeine metabolism.

If a particular genotype improves performance due to altered metabolism, then assessing metabolism would obviously strengthen conclusions that can be made regarding this hypothesis.

Thus, a mechanistic link between the polymorphism and the ergogenic benefit of caffeine is lacking.

The aim of this study was to determine whether the CYP1A2 −163 C > A polymorphism influenced caffeine metabolism and subsequent 3 km cycling performance in young, healthy, male subjects. We hypothesize that the AA homozygotes will exhibit a greater ergogenic effect from caffeine supplementation and faster caffeine metabolism.

Twenty male subjects between the ages of 18–45 years were recruited from James Madison University (JMU) and the greater Harrisonburg, Virginia area. The descriptive characteristics of this sample are reported in Table 1. There were no statistical differences between groups for any of these descriptive variables.

Subjects reported to JMU's Human Performance Laboratory for all visits, including a graded cycling test to determine peak oxygen uptake (VO2peak), and four 3 km cycling time trials (two familiarization trials, and two experimental trials). Caffeine intake and cycling hours per week were self-reported by the subjects.

The study was approved by the JMU Institutional Review Board and all subjects gave informed consent before the study.

Table 1. Subject Descriptive Characteristics (Mean ± Standard Deviation)

GenotypeAge (years)Height (cm)Caffeine intake (mg/day)Weight (kg)VO2max (ml/kg/min)Cycling hours per week
AA homozygotes (n = 8)23.5 ± 8.4176.0 ± 7.193.0 ± 111.271.8 ± 9.156.6 ± 9.64.3 ± 2.8
C allele carriers (n = 12)25.3 ± 7.4177.2 ± 8.091.6 ± 136.875.1 ± 12.257.7 ± 9.55.3 ± 2.9

All subjects participated in a graded exercise test on a Velotron cycle ergometer (RACERMATE Velotron, Seattle, WA).

Metabolic data were collected using a Moxus Modular VO2 system (AEI Technologies, MOXUS, New Orleans, LA), which utilizes analysis of expired gases channeled into a mixing chamber.

The test was a staged protocol that began at 100–150 W depending on the training status of each subject and increased by 25 W every minute until volitional exhaustion. Heart rate, watts (W), and VO2 were recorded every minute and VO2peak was defined as the highest minute-average.

Familiarization trials consisted of a simulated 3 km time trial on a Velotron cycle ergometer (RACERMATE Velotron). Familiarization trials mimicked the experimental trials, and were conducted to reduce possible learning effects during repeated performance trials.

Performance trials were conducted between the hours of 06:00 am and 10:00 am. Subjects were fasted overnight (≥8 hours) and abstained from caffeine and alcohol for 12 and 24 hours, respectively, before each trial.

Diet and physical activity logs were collected from each subject before each trial so that participants could replicate these logs as closely as possible for subsequent trials. Supplementation consisted of either 6 mg/kg body weight of anhydrous caffeine (CAF) or all-purpose flour (PLA) in two gel capsules.

A baseline venous blood draw was obtained immediately before supplement ingestion and the post-treatment blood draw was taken 1 hour afterward. Immediately after the blood draw, subjects performed a 3 km cycling time trial on the Velotron.

Subjects received information about distance traveled, and distance remaining during the trials but were blinded to time. This study was part of a larger study where subjects also participated in afternoon 3 km time trials on separate days.11

DNA was obtained from whole blood samples using commercially available extraction kits (Illustra blood genomicPrep Mini Spin Kit; GE Healthcare, Pittsburgh, PA). Subjects were genotyped as previously described and grouped as AA homozygotes or C allele carriers.12 Due to the similarities in metabolism in all C allele carriers,7,13 this grouping is consistent with prior research.8,10,13

Serum was collected from the blood samples by centrifuging samples at 2500 rpm (1349 g) for 15 minutes. Serum was stored at × 80° C until thawed and prepared for mass spectrometry (MS) analysis. For MS analysis, 200 μL of serum was extracted by vortexing with 5 mL of ethyl acetate for 5 minutes.

The extract was then centrifuged for 10 minutes at 4000 g to separate the organic and aqueous layers. The top ethyl acetate layer was transferred to a polypropylene tube, extraction repeated, and organic fractions combined.

The extract was then lyophilized in a CentriVap (Labconco, Kansas City, MO) and reconstituted in 200 μL of 96:4 water:methanol for quantitation by liquid chromatography/mass spectrometry (LC/MS).

An Agilent 1290 ultra-high performance liquid chromatograph coupled to a 6224 time of flight mass spectrometer (TOF MS) (Agilent Technologies, Santa Clara, CA) was used to separate caffeine from other metabolites and determine concentrations in the serum extracts. Gradient elution with an Agilent Zorbax Eclipse Plus C18 column (2.1 × 150 mm, 1.

8 μm particles) held at 35°C was performed with mobile phase A (water, 0.1% v/v formic acid) and B (acetonitrile, 0.1% v/v) at 0.45 mL/min as follows: B was held at 4% for 7 minutes and increased to 70% by 12 minutes. At 14.5 minutes the gradient was returned to the initial conditions. Five microliters of serum extract was injected in duplicate.

Analytes were ionized by positive ion electrospray (ESI) as follows: capillary, +3500 V; drying gas, 350°C and 10 L/min; nebulizer 30 psig. Mass spectral data were acquired in profile and centroid mode at 3 specta/s over 100–1700 m/z. TOF ion optics were as follows: fragmentor, 115 V; skimmer, 65 V, and October RF Vp-p, 750 V.

An internal reference mass solution (purine and HP-921; Agilent Technologies) was delivered to the ESI source to ensure high mass accuracy (


Do Coffee Drinkers Really Fall into 3 Groups?

CYP1A2 Enzyme: Where Caffeine Meets Genetics

A new report divides coffee lovers into three groups depending on how their bodies respond to caffeine.

But as fun as it is for caffeine drinkers to figure out which group they fall into, not all experts are on board with the report's clear-cut conclusions.

According to the report, which was published June 6 by the Institute for Scientific Information on Coffee (ISIC), the answer lies in our genes.

Specifically, caffeine sensitivity depends partly on a liver enzyme called CYP1A2, which is coded by the CYP1A2 gene. The enzyme is responsible for “inactivating 95 percent of all ingested caffeine,” the report said.

In other words, this liver enzyme breaks down caffeine in the body. [10 Interesting Facts About Caffeine]

ISIC members include several European coffee companies, including Nestlé.

The versions of the gene vary among people, according to the report, and these genetic variations split the population into two groups: “fast metabolizers” and “slow metabolizers.” The fast group breaks down caffeine more quickly than the slow group, and thus the effects of caffeine don't last as long for this group, the report says.


Langer, a clinical pharmacology lecturer at the University of Copenhagen and the author of the report, claims that these fast metabolizers can drink “multiple cups of coffee a day” because their bodies can quickly clear caffeine from their systems. But for slow metabolizers, caffeine stays in the body longer, so “the physiological effects of caffeine last longer and are more pronounced,” Langer said. Thus, the report recommends lower doses of caffeine for this group.

But where did the third group come from?

“You have the genes for the liver enzymes, but you also have to consider how coffee affects the brain,” Langer told Live Science.

That’s where adenosine, a neurotransmitter, comes in. Adenosine binds to adenosine receptors, leading to the sensation of being tired. But caffeine can also bind to these receptors, blocking the adenosine from binding and, in turn, preventing tiredness and boosting alertness.

As with the liver enzyme responsible for breaking down caffeine, there are also genetic variations in the genes that produce the adenosine receptor, according to the report.

These variations, along with variations in the enzymes, “combine to factor into the three caffeine sensitivity groups: high, regular and low,” Langer said.

(The low-sensitivity group includes the “fast metabolizers” while the high-sensitivity group includes the “slow metabolizers.”)

The report says that, because individuals tend to consume “the amount of caffeine they feel comfortable with,” their levels of consumption are “self-regulating mechanisms rooted in the individual's genetic make-up.

” In turn, the report advises those with high sensitivity to consume caffeine in small amounts and says those with regular sensitivity will be “safe and without problems” with a “moderate caffeine consumption of 5 cups a day.

” (It's unclear, however, if the report was referring specifically to 8 ounces of coffee as a cup, or a more colloquial definition; in Europe, coffee is typically served in smaller cups than it is in the U.S.)

Caffeine concerns remain

But the new report has not been fully accepted by the scientific community. Nanci Guest, a dietitian and researcher at the University of Toronto who was not involved with the new report, said it's largely misleading. [10 Things You Need to Know About Coffee]

“The gist of this report is that you drink as much coffee as you feel comfortable with, and you'll be OK,” Guest told Live Science. “That take-home message is not based in any real evidence, and this report freely promotes coffee intake without considering any of the risks.”

According to Guest, the term “sensitivity” is not an accurate description because it assumes that individuals can “feel the effects of caffeine intake,” including the possibility of “increased heart attack risk, high blood pressure and decreased endurance performance.”

Langer, however, said that he defines sensitivity as “what you feel when you drink coffee,” and hopes that this report will help people recognize that “everyone is a unique coffee drinker.”

He also cautioned against drinking excessive amounts of coffee to achieve the effects of caffeine, stating that although “low sensitivity” individuals may need more caffeine to feel the effects, there are potential negative effects.

These negative effects include mainly “anxiety and panic attacks,” particularly if you’re sensitive to caffeine, Langer said, but these sensitive individuals are in “the minority.”

Guest emphasized that “the jitters” are just the tip of the iceberg when it comes to the negative effects of caffeine.

She also noted that there are inaccuracies in the report and that the advice given should be taken with a grain of salt. For example, while the report states that pregnant women should limit their caffeine intake to 200 milligrams (mg), Guest said zero caffeine intake is the safest. (The American College of Obstetricians and Gynecologists, however, supports the 200-mg. limit.)

Guest also refuted the “moderate” five cups of coffee a day, stating that such levels of intake should be considered carefully.

Moreover, while the report states that coffee consumption has possible preventive effects against Parkinson's disease, these reports have been disputed recently, Guest said.

Originally published on Live Science.


Cytochrome P450 1A2

CYP1A2 Enzyme: Where Caffeine Meets Genetics

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576).

Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH–hemoprotein reductase) (PubMed:9435160, PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576).

Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317).

Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver.

Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376).

Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160).

May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase- reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable).

Manually curated information which has been inferred by a curator his/her scientific knowledge or on the scientific content of an article.


Manual assertion inferred by curator fromi

Manually curated information for which there is published experimental evidence.


Manual assertion experiment ini

  • an organic molecule + O2 + reduced [NADPH—hemoprotein reductase] = an alcohol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]

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    Manual assertion inferred by curator fromi



  • 17β-estradiol + O2 + reduced [NADPH—hemoprotein reductase] = 2-hydroxy-17β-estradiol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]

    Manual assertion experiment ini

    This reaction proceeds in the forward

    Manual assertion inferred by curator fromi


  • Source: