Actually N-acetyltransferase type 2 is a better marker for caffeine metabolism than CYP1A2 and has been used extensively to characterize caffeine poor metabolizers (PMs) vs extensive metabolizers (EMs) from analysis of urine.
As a retire physician, I cannot fail to be impressed by the superb advancement at the science of individualized medicine, able to recognize who can be helped when and with what, almost a dream come through. And thinking we are still 'wet behind the ears'. A 'shotgun' approach may be coming to an end. And we ought to be mighty happy about it.
6
So now we have some very needed answers regarding young, male, bicyclists. Oh, and let's see, were they all white too?
1
This is a strange comment. This is just how experiments have to work. The researchers have to try as hard as they can to isolate the effect of the gene from other factors that could influence the results. Physiologically, age and sex are both pretty big factors that in any good experiment ought to be controlled. Then follow up work will see if they get the same results in women, older people, other activities, etc. I guess no reason they needed to start with men but (a) they're not extrapolating to other populations (they pretty explicitly disclose the limitations of the study) and (b) you can't test everything all at once, because if you do you're rather testing nothing at all.
8
the point is that young, white men are treated as the baseline, status quo for the entire history of western medicine. there’s no question that this limited regard for variations in genetics, not to mention hormones, is responsible not only for the narrow framework by which we are all treated today, but also the significant flaws and failure of diagnostics & treatments.
@adrian I think that is a sweeping statement, particularly for the later years of western medicine. I hope and trust there was ethnic variation among the "100 willing, young, male athletes".
And yet, almost 20 years into this century we have only data about men. Seriously.
5
This explains some things for me, thanks!
I have lost count of how many times you’ve run fitness stories with universal interest that turn out to have zero relevance to women or anybody over 30.
Please. It’s got to stop. You’ve got to start calling out the biases of these “medical and fitness studies.”
6
I never liked coffee because it always made me jittery and never gave me the caffeine buzz. Then one day I tried a latte. About 1/3 into the cup I got the caffeine buzz. It makes me alert, calm and feels very nice. Nothing like the previous experience. I did not yet work out why the difference. I assumed it was the strength. I have since worked out that it was the quality, age and roast as well as the strength of the beans.
I've noticed it starting to happen again, the jitters, if I happen to buy an opaque bag of beans. Even ordering it online from the place I first had the good coffee the same beans I used to buy in person comes to me much lower quality even looking like a different roast altogether than it used to be. If I had to guess they swept up the spilled and under roasted beans and put them back in with the good beans.
So age of the beans and how they were roasted and how recently they were ground makes a lot of difference. Even if you grind it yourself bad beans will taste bad.
4
Caffeine is also an efficient diuretic so if you're chugging caffeine drinks before or during exercise in high humidity be very careful you can dehydrate.
2
Why, please tell me, are so many of these studies done on young men. Where are the studies on women? On older people? We do exist out here folks.
31
Maybe women mature faster than men. And they're not at dumb as there testosterone driven counterparts. 'Here drink this'. No way says the young woman. I've got better things to do.' While the young man says, 'Sure' and adds, 'I was just chilling anyways.'
1
Doesn't make sense to me. Late coffee can keep me up all night, but also enhances short term performance (short term here being anything from minutes to a few days). Long term (a week, months years) ... I can not tell if there is any overall benefit. What is missing in this study is how it enables neural activity and what hormones are released - and the short term and long term effects of those factors.
1
Thanks, Gretchen. Interesting study.
Anyone have a good recommendation for a reputable CYP1A2 testing source? Do I just ask my primary care provider?
23andme's genetic report shows you the variants of CYP1A2 gene.
3
This information is basically useless without a way for your average individual to determine how quickly (or slowly) he or she metabolizes caffeine.
2
Genetic testing is available for average individuals.
3
Thanks for the column. I am fortunate to be a fast caffeine metabolizer with two copies of CYP1A2. Studies of coffee that fail to take genetics into account are pretty badly flawed. Every thing that the article asserts I have experienced in my exercise and competitive career. There is also little effect on my sleep unless I take a lot of caffeine late in the evening. My sister and mother were the same. Some of the negative comments coming in continue to ignore the genetics.
18
The article and comments demonstrate just how varied the effects of caffeine is on people. Add to the deleterious effects on many: a massive reduction in iron absorption. It is not unusual for suboptimal absorption to result in anemia.
1
I hate to bring bad news to so many stories about coffee helping people. I have Harvard Special Health reports on coffee and alcohol use. They both constrict blood vessels and that can give anyone using that junk a trip to the ER. I don't need either and have been caffein free at least 40 years and never drank alcohol so I hope more will do what I do daily. Eat a proper diet get some exercise at least 3 times a week and rest at night.
But you're bound to die like the rest of us.
7
You are an alien (from space), I assume.
7
Are you any better off? Why preach to the masses? Your message is not science. There are positive effects to both caffeine and alcohol that you are ignoring. Are you in fantastic health? Are you boring? You live in Delaware- not the most exciting or stimulating place in the world. Finally, caffeine is a vasodilator and does not constrict blood vessels.
9
Having just had a complete pharmacogenomics test done on my interaction with my medications, I appreciate this terrific article. I am one of the 10% who are dreadfully slow metabolizers of caffeine, although caffeine was not tested. If I have a cup of coffee after 9 a. m., I cannot get to sleep until 2 or 3 a. m. the next morning. I wonder now how many nights of insomnia I endured until I realized my issue with caffeine, long before genetic testing was available.
11
A 200-mg tablet of caffeine will, about an hour later, give me a boost in speed and endurance. Two 200-mg tablets will impair my performance significantly.
6
I recently read in medical reports I get from Harvard Special health reports that caffein and alcohol constrict blood vessels. In case you are not aware of that you can have a trip to the ER. Try exercising with no dangerous stimulants it will be the better way to go for your heart and your family.
1
I try to avoid coffee if I am swimming and running on a hot summer day. The best food before workout that I have found are bananas, and after workout is a hot chocolate or a big bite of a dark chocolate bar.
Dr. El-Sohemy's study notes that slow metabolizers had a heightened risk of heart attacks if they frequently drank coffee. Well, having too much coffee causes pottasium deficiency (hypokalemia) which in turn are found to cause cardiac arrhythmias. I thought this was well known, which is why potassium intake by having a orange juice (or gatorade etc.) or a banana is important. The key is to avoid potassium deficiency.
Enjoy the chocolate!
5
so-called low sodium salt would work too. it is usually half potassium chloride.i get LoSalt because it has no extra additives
1
As with any drug, if you take more caffeine before you have metabolized or excreted the previous dosage, you will continually increase its concentration within you. This article ignores the likelihood that slow metabolizers simply build up a greater quantity of caffeine in their bodies. Also ignored is the degree to which a person may need a continually greater maintenance dose to get the same effect, as one's body compensates for the effect of the drug. The potential implications of the lack of control for these factors could well be significant, possibly even nullifying the ability to legitimately conclude much of anything from the "study."
A good, science-based, informed article should at least note and, preferably, question gaps and inconsistencies in claims and "studies." Times science articles have become less analytic about "studies" and "claims", more and more and more serving as publicity pieces than as informed, questioning science.
14
Thanks for your interest Steve. Did you get a chance to read the full study that was published? All of your questions and concerns are addressed in the paper. I hope you can appreciate that news articles have a word limit and journalists can’t be expected to cover all of the scientific details in their column. I think Gretchen did a great job at presenting the pertinent information for readers. To address your question, all participants had abstained from caffeine for at least 7 days so there would not have been any “build-up” of caffeine prior to the study. Keep in mind that each subject served as their own control because they each took 0, 2 or 4 mg/kg body weight at different times and in random order. This randomized, cross-over design is the gold standard for this type of research.
28
It still would be cool to access any microbiome effects.
1
Thank you Nanci Guest for responding.
I can certainly understand the knee jerk responses from some comments with regards to the studies summarized in news pieces. However, I still have more faith in science and other professionals, than I do of someone like myself posting in the comments section.
If they want to be taken serious about criticizing the news piece, then they need to back up their work.
In the atmosphere and pressure the news media faces as a result of our current screaming and whining political bases. I would like to see those, like yourself who have higher credentials, continue to step out of their professional work-spaces and contribute when they can.
For myself, with regards to the consumption of caffeinated coffee: Like opinions, it mostly causes me to spew urine way more than any of the benefits it appears to offer.
We are finding specific genes that affect the metabolism of caffeine. It seems strange, and most unfortunate, that after all the years of research, we haven't found genes that affect the metabolism of alcohol. We need a test that young people can take to decide whether they are likely to become alcoholics if they drink. If I am wrong and such genes have been identified, I would appreciate it if you could leave a link. It has been proved the genetics is a factor in alcoholism but I don't think a specific gene has been identified.
5
propensity to addiction is much more likely to be shaped by childhood trauma and other psychological factors, rather than genetic (though there is definitely a case for that too)
2
People become alcoholic by drinking too much and it can happen to anyone who practices that problem behavior. It's not preordained like Calvinism.
1
See link below for one (of many) studies that show the link between genes and alcoholism. Per this study, genes are responsible for about half of the risk of AUD (Alcohol Use Disorder).
https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/al...
7
"...the men received a low dose of caffeine (2 milligrams for every kilogram of their body weight, or about the amount found in one large cup of coffee)."
Wait...what? Do they all weigh the same or do they all drink different "large" coffee cups based on their weight?
4
The article ignores the likelihood that slow metabolizers simply build up a greater quantity of caffeine in their bodies. As with any drug, if you take more before you have metabolized or excreted the previous dosage, you will continually increase its concentration within you. Also ignored is the degree to which a person may need a continually greater maintenance dose to get the same effect, as one's body compensates for the effect of the drug.
1
Dr. El-Sohemy, what about me? I'm a healthy, fit, active 65-year-old, and I drink 8-10 (that's eight to ten) Diet Coke cans a day, including right before sleep. Literally. Every day. And I get ZERO effect from it - positive or negative. No energy "jolt", no problem with sleep, no nothing. I just like the taste. Anyone else out there like this?? Cheers.
1
Is there anyone out here with bad taste and foolish eating habits? I do suppose so!
5
While the caffeine may not bother you, the acidity of diet sodas can erode the esophagus... the pH of diet soda is 2.9, the same as stomach acid, according to Dr. Jamie Koufman, layrngologist in NYC.
3
Times science articles have become less analytic about "studies" and "claims", more and more likely to serve as public relations pieces than as informed, questioning science.
This particular article ignores the likelihood that slow metabolizers simply build up a greater quantity of caffeine in their bodies. As with any drug, if you take more before you have metabolized or excreted the previous dosage, you will continually increase its concentration within you. Also ignored is the degree to which a person may need a continually greater maintenance dose to get the same effect, as one's body compensates for the effect of the drug. The potential implications of the lack of control for these factors could well be significant, possibly even nullifying the ability to legitimately conclude much of anything from the "study."
A good, science-based, informed article should at least note and, preferably, question gaps and inconsistencies in claims and "studies."
1
Hi Steve - please see the above response to your similar comment.
6
I've always drunk caffeinated beverages (tea, coffee, soda) all through the day right up until bedtime - and still fall asleep in under 10 minutes. With 23andme now I can verify that I do have this gene variant - and from this I know what it's good for!
5
This study has several glaring problems.
Caffeine doesn't reach peak concentration in blood levels until 1-2 afters consumption, but this study doesn't indicate how long before the workout the coffee was consumed, merely that it's 'before'. Consuming the equivalent of a large cup of coffee and immediately jumping into an intense exercise is not prudent. even if one metabolizes caffeine quickly. A more complete study would measure caffeine's effectiveness after various time intervals, as the speed of metabolization is the real question.
Nor is there any mention of the participant's caffeine tolerance levels. Someone who regularly consumes caffeine will have a far different response to a large cup of coffee than someone who does not, regardless of their metabolic characterization. Were these men questioned on their caffeine habits, or monitored? Self-reporting caffeine consumption is very inconclusive, as most individuals don't actually calculate their daily mg intake.
Perhaps most glaring is the focus on young, athletic males. There's considerable evidence that caffeine has differing effects on men and women, and also effects individuals of varying ages differently. How can one reasonably conclude that 50% of the population are 'fast metabolizers", when you've only looked at a very small segment, especially given that segment is perhaps the most inclined towards caffeine consumption?
11
You realize that this is an article about a study and not itself a study?
11
I believe the frequency of the CYP1A2 variants is well known (at least within the CEU, i.e. European population), and it is not affected a person's sex because these genes are on chromosome 15. This is one of our 22 autosomes, not the X or Y chromosome. However, I agree that the study described in the article had the all-too-familiar limit that makes me, a female (who happens to be a fast caffeine metabolizer according to my 23andMe results) roll her eyes. It is certainly possible that there are other variations in the way women's and men's bodies respond to caffeine, i.e. that the magnitude and duration of its effect on our muscles, VO2 Max, etc., varies by sex.
1
Great questions Eric! And I’m happy to say all of these questions/concerns are reported in the published paper of the study! But I’ll address a couple. Peak blood concentrations are reached about 30-90 min after ingestion, which is why we waited 60 minutes before starting the exercise tests. We explain this in the paper. We also reported that habitual intake of caffeine did not differ between the groups. Regardless, all subjects abstained from caffeine for at least one week before the start of the study and all subjects served as their own control since this was a randomized, cross-over design (the gold standard!). News articles about a scientific study can’t possibly include all the pertinent details of a scientific study, so I encourage you to read the full published study if you wish to know more about the details or design (remember that the study was peer-reviewed, which means that other experts, who are not involved with the study, evaluated the design, results and interpretation). The reason we did not include females is because 1) The birth control pill affects the enzyme that breaks down caffeine and finding females between 18-35 not on oral contraception is very difficult! 2) females perform differently throughout the menstrual cycle, so we would have to test them at the exact time every month, over 4 months, instead of over 4 weeks, which makes it much more difficult to retain subjects since they would have to abstain from caffeine for 4 months instead of 4 weeks.
6
Perhaps this genetic variation can explain the custom of offering coffee at the end of a meal, even if it is relatively late into the night. I've always thought it was crazy to offer a stimulant when sleep is supposed to be coming along in the not-too-distant future. If however half of us are rapid metabolizers, it makes sense that the custom endures. If you're not a rapid metabolizer, you'll know soon enough!
3
If genes are dominant or recessive, and if the dominant gene is what is manifest physically for an individual with one of each, how could the combination of one dominant and one recessive gene express in a third, "moderate metabolizer" category?
1
Hi Reader,
Alleles are variants of genes which are inherited from mom and dad - by analogy, if "ice cream" is a gene, then "vanilla" and "chocolate" are like alleles (essentially, flavors). Classically, many genes have a 'dominant' allele, whose expression produces an observed effect (phenotype) in both homozygous-dominant (2 dominant) and heterozygous (1 dominant, 1 recessive) people (with respect to that gene); and a 'recessive' allele, which is only expressed in the absence of the dominant allele (i.e., 2 recessive alleles inherited).
In the case of CYP1A2, which displays "incomplete dominance," both dominant ('fast') and recessive ('slow') alleles are partially expressed. At the molecular level, both enzymes are being produced, and their combined, average ability to metabolize caffeine (and some other drugs) will determine the overall rate of caffeine metabolism, resulting in "Fast", "Moderate", and "Slow" phenotypes.
By analogy, if I were to hire 2 line chefs at my fast-casual restaurant and wanted to monitor the rate of food output, I might observe three combinations of employees:
2 fast employees - High Burger Output
1 fast, 1 slow employee - Moderate Burger Output
2 slow employees - Low Burger Output.
Cheers,
Matthew
20
Not all genes are dominant/recessive.
3
Thanks!
3
How could the funding source not influence the results when the lead investigator is a founder of one of the funding companies?
29
Does this mean that for some people, coffee should be considered a performance-enhancing drug? Hard to imagine it being on a list of banned substances but maybe it should be in some circumstances.
I remember Serena asking for a latte during a break and I'm pretty sure I've seen a few tennis players drinking colas during matches. Hmm.
5
Caffeine is included in the World Anti-Doping Authorities's "2018 Monitoring Program" (in competition only). As I understand it, this means it is not banned but WADA are looking for potential misuse.
2
As a weightlifter, I was early on taught about the benefits of drinking coffee before or during workouts. My personal experience is that it has only ever helped my workouts.
3
Well now we know more about you. I wonder if you can explain any use in that.
2
I play 36 holes twice a week walking - made possible with 3 tablespoons of caffeinated peanut butter. Without it I need a cart to do 18 holes.
3
Interestingly, cigarette smoking induces CYP1A2, converting smokers to fast metabolizers for caffeine even if not inherently so. Therefore, even in addition to nicotine, cigarette smoking would enhance the reinforcing effect of another substance, caffeine. Although we typically don’t think of this group as ardent exercisers, it certainly may explain why cigarettes and coffee seem to go hand-in-hand.
35
very interesting! Makes sense, since the CYP's generally play a role in detoxification. I see that eating some foods (cabbage family) also induces CYP1A2, and turmeric, now a popular addition in many coffee shops!, inhibits CYP1A2's activity. So there are many interconnecting factors here. I imagine they used a pretty homogenous group of athletes for their subjects, thus minimizing these effects of diet.
7
I am no longer a smoker but there could well be something to that, as I remember one of life's great simple pleasures being coffee with a cigarette. I cheated and had that combination recently and it was just as good as I remembered.
2
As a male, 73 years of age, I have two large cups of coffee before each workout. By the description in the article, I must be a fast burner, because I do get a jolt of energy from it. Also, coffee in the evening has never disrupted my sleep.
I am lucky with respect coffee consumption and with retaining sufficient health to excercise.
6
Not "lucky" -- you've probably retained your health BECAUSE you exercise. Congratulations!
Editor’s note: This comment has been anonymized in accordance with applicable law(s).
1
Oh gee. Another study that uses only men, then the Times applies the results to all. As opposed to 1/2 of athletic men are fast metabolizers, compared to 1/4 and 1/10 who aren't.
Again, only men. Foolish me. I thought #Me too would have penetrated academia as well.
66
You are expecting to be treated equally? Remember this is in the time of Trump.
1
Sharon...sure...a few months in and every detail has automatically changed.
Fact is, the number of available male athletes for such studies still outnumber females. Just because...
1
I totally appreciate the point and regret, as an older female, that young(ish) males are the "human" benchmark. But I can see why you would select young men for a study involving athletes. Studies want to control as many variables as possible, so unless you had a lot of funds for your project, sample size would probably mean choosing one gender to recruit. I expect there are studies where female subjects are the obvious population to recruit. But as Ms. Kahn points out, medical research needs to take women seriously. It has not.
1
As a former triathlete and ironman, the bigger benefit of caffeine is increased endurance rather than enhanced speed. That because caffeine stimulates your fat-burning capabilities allowing you to draw more energy from stored fat, prolonging your bodies glycogen stores, and thus your endurance. In common terminology, you delay hitting "the wall". Short, intense workouts, like the exercise described in this article, draw exclusively from glycogen. These workouts are done at or beyond your anaerobic threshold. Endurance athletes perform just below that threshold. I'd like to see this study extended to measuring the performance of endurance athletes performing endurance events.
29
Ed Buz - Yes those studies would be interesting. BUT - the trouble with endurance athletes who are well trained, and have low body fat - their fat metabolizing for energy ain't as often in action as you'd like. If a guy is at say 10-15% BF, their ability to metabolize fat is not gonna be what they rely on to prevent bonking. Its training!
And unless you have undergone extreme testing, you - personally - have no idea if your intake of caffeine is boosting your fat metabolizing, at any give moment. One training/event session it might be, the next not at all.
Plus,there is no known optimal body fat levels for any individual athlete. (other then it being extremely low, and dangerous)
Ever notice that energy supplements, Gu gel ,P-bars,etc - consumed during an event - are all about carbs/sugar and protein and not caffeine...??? And if they do mention caffeine - its a by-product of another ingredient, like tea leaves, and as such is too small to measure.
Ive never seen an endurance event with cups of coffee by the road side. Instead its about water, and some electrolytes, and small amts of protein and more in carbs.
Actually a lot of energy gels / blocks have added caffeine. Clif Blocks black cherry, gels by GU, Hammer Nutrition, Clif shots. And a lot of athletes these days chug energy drinks like Red Bull (more for cool factor than actual physical benefits probably).
This just in, coffee causes cancer.
Er, correct that, this just in, coffee doesn't cause cancer.
Er, this just in the medical community is split on the issue.
Bottom line if coffee agrees with you drink it in moderation, if not don't drink it.
Also it changes with age. When I was younger I could drink 3-5 glasses a day now only one.
12
Actually, a large body of fairly conclusive evidence shows that it protects against cancer, diabetes, and liver injury caused by alcohol consumption. No real corrections, only corroborations, in the past ~20 years......
4
Thank you for your reply Ant'ney. Yes there are some studies that show that. Others are inconclusive. Others show the opposite.
The point being is that moderate drinking of coffee is ok.
If you can get away with a little more fine, if not cut back.
1
When I was young, I was not affected by caffeine, but, starting in my 40s and continuing into now into my 60s, I have become super-sensitive to its effects. How does age factor into this?
30
I can confirm this as i’ve experienced the same thing.
1
The study says it's about "people" but it's really about "young male athletes". So if you don't fit in that category - say, you're in the 50% of the population who is female, you'll have to wait for another study.
75
My sentiments exactly? Why is it always men that seem to get studied? I was so interested in this piece because I am a female who swims laps regularly, drinks coffee, and found that a cup an hour before I enter the pool seems to affect my endurance. But now...who knows?
23
Studies are generally done on young male subjects because they are the most likely population to be consistently healthy (ie. with no other medical conditions that may affect results), not taking any other medications (including birth control) AND most importantly have no possibility of being pregnant or breastfeeding, as these are all things that may affect or confound results.
12
Only part of the answer. The common wisdom is that women's menstrual cycles add "variability" to results (meaning "noise") and thus reduce the sensitivity to find any effects. This has not been investigated to any large degree -and the bigger issue is that if there is variation for women - WE WANT TO KNOW ABOUT IT! Because we aren't men and we want results that pertain to us.
8
i personally think that cofee is good for you
7
Although it may affect one's ability to spell.
11
Impressive ! A randomized, double-blinded, placebo-controlled design. Scientific community seems to change the focus from genes or environmental factors alone to genetic environment interaction, adding something new to the old content topic. Of course we expect more coherent and consistent researches to repeat the results and finally rigorous systematic reviews and meta-analysis. We will be there.
8
Another way in which the world is divided into two types of people.
6
Young and healthy vs the rest of us?
1
Whether coffee revs up your workout may depend on your genes, but also your age, gender, and how many babies you have birthed. The coffee that gets you out on the run is the same one that keeps you ducking into the woods at regular intervals mumbling to yourself about how two cups can equate to four pit-stops.
19
Agreed. The only use for coffee I’ve ever read had to do with a prerun cup to —how do I put this? — get things in optimum working order before heading out.
22
MDB, same use here, except exact timing is sometimes a problem ... sometimes not so optimal ...
1
I wonder if another factor concerning caffeine and athletic performance may be how often one consumes it.
Anecdotally, in the past few months I reduced my coffee intake from five to six cups a day to only one every other day before I run seven miles. I think(!) I have notice much better performance since I started doing this.
13
For what it's worth that very question - does caffeine boost athletic performance even for heavy daily drinkers - was addressed in a May 31 2017 NY Times article.
The gist - yes, a pill equal to 4 cups of coffee revved almost everyone up. Imagine my surprise.
1