Coffee- Is It a Villain, Superhero, Friend, or Foe?

I was in New York City last week watching the amazing Andrea Bocelli in concert. Words could not express the magnitude that I felt in the presence of such a master of music. This made me think of coffee. You may ask, “how the heck did Andrea (we’re on a first name basis now) make you think of coffee?” It’s from the six degrees of separation theory. In this case, the connection is only 3 degrees:

  1. Andrea Bocelli
  2. New York City
  3. Coffee

When in the streets of New York City, you have to try out the local and organic coffee, right?

Interestingly, on my way back, my aunt and I ran into a man who overheard us discussing the organic coffee shop we had visited in NYC. (Auntie Mo can’t drink coffee because she may exceed her 4 cup/day limit-more on that later). He said, “I love coffee, but it’s bad for you, so I avoid it.” Poor guy! (Alice and the rabbit hole again!)

I started to tout some studies about why this negative connection is probably not true for most people if they aren’t sensitive to caffeine. I also explained to him about the biochemistry of antioxidants and the abundant phenolic compounds in coffee, such as chlorogenic acids (CGAs) and caffeic acids. Finally, I discussed some other potent antioxidant components found in coffee that could be very beneficial. (1) After all, coffee is more than just the caffeine, right? (1-3) As the “essential oils doc,” I’m obsessed with aromatic compounds, so I get excited about these things. For example, did you know caffeic acid is present in rosemary essential oil? (4)  

According to the Royal Society of Chemistry:

Coffee contains a tremendous number of chemicals, with over 1000 aroma compounds. If you are looking for antioxidants, the most abundant phenolic compounds in coffee are chlorogenic acids (CGAs), which account for up to 12 per cent of the dry weight of green unroasted coffee beans. Much of coffee’s bitter taste comes from CGAs, which also cause the acid reflux that is sometimes experienced by coffee drinkers.  

CGAs form in the coffee plant by esterification of trans-cinnamic acids (mainly caffeic, ferulic and p-coumaric acids) with hydroxyl groups on quinic acid. The resulting conjugated CGA structures are known as caffeoylquinic acids, feruloylquinic acids and p-coumaroylquinic acids respectively. 

I had a captive audience, so I started to ask him questions to determine if he was a fast metabolizer of coffee. “Does it keep you awake if you drink it past 3 pm? Do you get shaky if you have too much?” These questions would help me to figure out if he may have a CYP1A2, COMT SNP (single nucleotide polymorphism), or possibly an adenosine or dopamine polymorphism. This could impact his cravings and individualized biochemical responses to coffee. (5-12) To think, the poor man was just trying to be friendly!

Now, in the past I’ve discussed studies on coffee and its benefits. In my recent blog I also review some more recent studies that show correlations between coffee consumption and health outcomes. For example, I discuss the (mostly positive) links to cardiovascular risk, mortality, and blood sugar issues.

However, here I want to take you to a place very few people visit in coffee world—the epigenetic impact. This means that individual differences in how your body breaks down and utilizes components in coffee will make it your friend or foe. So, beyond those studies, let’s look at why some conclusions on coffee may be conflicting.


The Epigenetics of Coffee


The CYP1A2 Effect

This liver detoxifying enzyme powerhouse carries amongst its duties the detoxifying effect of caffeine. (5) Several studies have demonstrated that whether someone has the genetic profile of a “fast” or “slow” metabolizer of caffeine not only affected consumption of the beverage (6-7), but also affected its health outcomes. (7)

One observational study looked at the effect of genetic differences in this enzyme to hypertension outcomes in 553 young Caucasian coffee drinkers:

These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee. (8)

Interestingly, in another study, there was an inverse relationship between coffee consumption independent of this enzyme and diabetes risk. Whereas, this enzyme variance alone wasn’t linked to diabetes, there was an interaction between a certain genetic polymorphism of CYP1A2 with coffee, especially amongst smokers. (9)

Caveat to keep in mind: gender, age, smoking status, medication use, and dietary components are some factors that affect CYP1A2 activity as well.

The impact on bone mineral density (BMD) has also been studied regarding coffee intake and CYP1A2 activity. According to a 2010 association study of 359 men and 358 women, the impact of the activity of this enzyme had an effect on bone mineral density in men only who drank 4 or more cups of coffee a day:

Results: Men consuming 4 cups of coffee or more per day had 4% lower BMD at the proximal femur (p = 0.04) compared with low or non-consumers of coffee. This difference was not observed in women. In high consumers of coffee, those with rapid metabolism of caffeine (C/C genotype) had lower BMD at the femoral neck (p = 0.01) and at the trochanter (p = 0.03) than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coffee and BMD.

Conclusion: High consumption of coffee seems to contribute to a reduction in BMD of the proximal femur in elderly men, but not in women. BMD was lower in high consumers of coffee with rapid metabolism of caffeine, suggesting that rapid metabolizers of caffeine may constitute a risk group for bone loss induced by coffee. (10)


Asian college students







The “More than CYP1A2” Effect

Other studies indicate that variances in other enzymes amongst individuals (SNPs or single nucleotide polymorphisms) along with different components in coffee may also have an impact on coffee’s health effects. (7, 11-12) For example, a rat study looked at the metabolism of coffee vs. the isolated diterpenes kahweol and cafestol. The effect of these isolated diterpenes on various hepatic cytochrome P450 (CYP450) enzymes and sulfotransferase (SULT) differed than that of coffee. This suggests that coffee and its components may have a multitude of effects beyond one or more isolated constituent. (11)

In a review paper of the literature on the genetics of caffeine, variations in adenosine and dopamine receptors in the body also had an impact on how one responds to coffee:

Objective: This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers.

Results: Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of polysubstance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users.

Conclusion: Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.(7)


So, What’s the Take Home Message?

You probably already have an idea if you are fast metabolizer of coffee and feel “wonky on coffee.” If you feel better off coffee, it may be because you aren’t an efficient metabolizer of caffeine or you have another SNP that impacts the benefits you could receive from a cup of joe.  If you feel good on coffee, you may really reap rewards if you imbibe it! Just remember the power of dosing. Specifically, stick with less than four cups a day (which in my opinion is quite high). You also want to make sure the quality of your coffee is optimal, as coffee can contain toxins and mold.

Learn more about SNPs here.

Happy Holidays Everyone!
girl with sled








(1) RSC. Chemistry in Every Cup. May 2011. Royal Society of Chemistry 2012.

(3) Cao C, Wang L, Lin X, Mamcarz M, Zhang C, Bai G, Nong J, Sussman S, Arendash G. Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice. J Alzheimers Dis. 2011;25(2):323-35.

(4) Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials. Indian J Exp Biol. 1999 Feb;37(2):124-30.

(5) Role of cytochrome P450 in drug interactions. Nutrition & Metabolism. 2008, 5:27. doi:10.1186/1743-7075-5-27.

(6) CYP1A2 and coffee intake and the modifying effect of sex, age, and smoking. Am J Clin Nutr. July 2012. 96(1):182-187. doi: 10.3945/ajcn.111.027102

(7) Genetics of caffeine consumption and responses to caffeine. Psychopharmacology (Berl). 2010 Aug;211(3):245-57. doi: 10.1007/s00213-010-1900-1. Epub 2010 Jun 9.

(8) CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens. 2009 Aug;27(8):1594-601. doi: 10.1097/HJH.0b013e32832ba850.

(9) Kohno M, Tajima O, Uezono K, Tabata S, Abe H, et al. (2013) Cytochrome P450 1A2 Polymorphisms, Coffee Consumption and Impaired Glucose Metabolism in Japanese Men. Endocrinol Metab Synd. 2:119. doi: 10.4172/2161-1017.1000119

(10) Coffee Consumption and CYP1A2 Genotype in Relation to Bone Mineral Density of the Proximal Femur in Elderly Men and Women: A Cohort Study. Nutr Metab. 2010;7(1):12.

(11) Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver. Food Chem Toxicol. 2008 Apr;46(4):1230-8. Epub 2007 Sep 25. PMID:17983700

(12) Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson’s disease. Neurology. 2003 Dec 9;61(11 Suppl 6):S55-61. PMID: 14663012

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