The Overlooked Link Between Caffeine & Inflammation (+ What This Means For You!)

Caffeine And Inflammation

If you’re a coffee-lover, you may have noticed that scientists can’t seem to make up their minds about whether caffeine is healthy or not. There’s a ton of research on coffee and tea, but many of the studies on the benefits of caffeine directly contradict each other.

Confusing, isn’t it?

So what’s the link between caffeine and inflammation? Does coffee cause inflammation? Or does caffeine cause inflammation? This problem extends to our knowledge of the effects of caffeine on inflammation. One day, it’s on the list of anti-inflammatory ingredients and the next day, one of your favorite wellness experts is telling you to cut it out of your diet.

Is it coffee or caffeine that causes inflammation? Should you cut one or both out of your diet? To answer these questions, we have to dive deep into the relationship between caffeine and inflammation, starting with how caffeine interacts with the body.

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How caffeine works in the body

More than 60 different plants (1) contain caffeine, which comes in the form of a bitter, white substance. Caffeine acts as a natural stimulant and the FDA has it listed as both a food and a drug.

Caffeine affects the body in more ways than one, but it’s probably most famous for interacting with a group of receptors, called adenosine receptors. It’s through the activation of adenosine receptors that caffeine affects brain functions, which include “functions such as sleep, cognition, learning, and memory,” according to a study published in 2010. (2)

Essentially, caffeine attaches itself to adenosine receptors and prevents adenosine—the neurochemical famous for making you sleepy (3)—from doing its job. The result? You feel more awake and alert. Studies, like one (4) published in Nature Medicine, suggest that blocking adenosine may also block pathways that produce inflammatory molecules.

So, does caffeine decrease inflammation then?

Understanding the caffeine and inflammation connection

The short answer is that there is no one right answer to the question of “Does caffeine cause inflammation?” That’s because research shows that caffeine-containing beverages like coffee can have either pro- or anti-inflammatory effects (5), depending on the person drinking the caffeine.

For example, a 2019 systematic review (6) evaluating the effects of caffeine on inflammatory markers showed that interleukin 6, a common inflammatory marker, was increased by caffeine in three out of five studies. Meanwhile, one out of three trials found that caffeine decreased C-reactive protein levels. The authors conclude that “the pro-inflammatory and anti-inflammatory responses to caffeine point to its complex effects on the inflammatory response.”

So why does caffeine seem to affect everyone so differently? There are a few reasons for this—including liver function and gut and mental health status—but a good part of the explanation lies in our DNA; more specifically, with a gene called CYP1A2. Also known as the “caffeine gene,” CYP1A2 determines how quickly (or slowly), we metabolize caffeine.

Your CYP1A2 Gene Determines How You Metabolize Caffeine

We inherit one copy of CYP1A2 from our mom and one from our dad. If you have two of the fast variants of the gene, you - like 40% of the population (7) - are a fast caffeine metabolizer. If you have one fast and one slow copy, you’re a medium caffeine metabolizer (this group makes up about 45 percent of the population). You’re a slow caffeine metabolizer if you have two slow versions of the gene, which applies to about 15 percent of us.

If you’re a slow caffeine metabolizer:

You are much more likely (8) to feel anxious, jittery, and sweaty after consuming caffeine. You may get heart palpitations or even panic attacks. Caffeine withdrawal also commonly causes severe headaches in slow metabolizers, but feeling shaky and on edge aren’t the only health problems associated with caffeine. You also have:

1. Increased risk of high blood pressure (hypertension)

Some fascinating research published in the Journal of Hypertension found that slow metabolizers who drank a lot of coffee were significantly more likely to have high blood pressure. Amazingly, fast metabolizers actually had lower blood pressure after drinking coffee!

2. Increased risk of heart attack

A similar study from the Journal of the American Medical Association (JAMA) found that drinking four or more cups of coffee a day was associated with a 36 percent increased risk of a heart attack, only among slow metabolizers.

3. Higher chance of digestive disorders

Coffee isn’t the only caffeine source, of course. My beloved and oft-recommended green tea, which has only about a third the amount of caffeine as coffee, can trigger diarrhea, gas, and heartburn in some people with sensitive stomachs.

4. More stress and measurable cortisol spikes

People who are sensitive to caffeine can see a spike in their stress hormone cortisol. This can be an issue especially with adrenal fatigue and other hormone problems. Some people have an initial spike in cortisol from caffeine but gain tolerance over time, while others don’t adapt to caffeine.

If you’re a fast metabolizer:

Remarkably, if you are a fast metabolizer and have a high tolerance for caffeine (for example, you can drink it all day without feeling jittery, or drink it at night and still fall asleep), caffeine is associated with a bunch of awesome health benefits:

1. Longer life

A New England Journal of Medicine study found that people who drank coffee had a much lower risk of dying during the course of the study. Another large Japanese study published in JAMA found that people who drank five or more cups of green tea a day were also significantly less likely to die during the study period. Yet another study from Harvard showed coffee and tea drinkers’ overall risk of premature death is 25 percent lower than those who don’t drink these caffeinated drinks.

2. Faster metabolism

Caffeine can boost your metabolism, increasing fat burning and even improve your exercise and/or athletic performance.

3. Better memory and mood

Caffeine has been shown to improve cognitive function, decrease brain fog, and increase mental acuity. It can also increase the neurotransmitters serotonin and dopamine, improving mood. A study out of Harvard found that people who drank coffee were 20 percent less likely to suffer from depression. Green tea also contains L-theanine, which ramps up GABA production (your calm-down neurotransmitter) for a potent anti-anxiety effect. Put together, caffeine and L-theanine can have a synergistic effect, creating a potent combo for improving brain function. Coffee could even protect from dementia someday – in one study, coffee drinkers were found to have a full 60 percent lower risk of developing Alzheimer’s disease and up to 60 percent lower risk of Parkinson’s disease. Short version: caffeine is great for fast-metabolizer brains!

4. Lower cancer risk

Both coffee and green tea have been associated with a significant decrease in cancer rates, including prostate cancer in men and colon cancer in women.

5. Better blood sugar + insulin balance

Half of U.S. citizens are prediabetic or diabetic. Yikes! So there’s no denying we have a serious blood sugar problem. Caffeine to the rescue! Both coffee and green tea have been shown to decrease diabetes in separate studies.

Knowing this, it will come as no surprise that I advise my slow caffeine metabolizing patients to cut down on caffeine or eliminate it entirely.

So how do you test to see what type of caffeine metabolizer you are? It’s included in most genetic tests, such as 23andMe and FitnessGenes. Once you know what type of caffeine metabolizer you are, you can make smarter choices about your caffeine consumption since the health effects of caffeine - including whether or not it fights inflammation or contributes to it - are dramatically different depending on your metabolizer status.

Can you drink coffee on an inflammatory diet?

The big question is, is coffee inflammatory or anti-inflammatory? If you’re a coffee-lover, there’s good news. Coffee contains polyphenols and other anti-inflammatory compounds that protect our bodies against chronic inflammation.

Cold-Brew vs. Regular Coffee

Cold-brew sales have grown 115 percent (9) in the last year, and all signs point to increased growth. Millennials seem particularly fond of cold brew, with 66 percent of American millennials choosing cold brew concoctions, compared to just 34 percent of generation Xers.

Just what is cold brew? It’s not the same as iced coffee, which is just regular coffee poured over ice. Cold brew is the result of a process in which ground coffee beans are steeped in cold or room-temperature water for 12 to 24 hours. No brewing, no percolating, no French-pressing – just steeping, like tea. The resulting beverage is a concentrate, which can be diluted with water and enjoyed either cold or heated. It is apparently less acidic and many believe it tastes better. Some fans brag that their magical caffeinated elixir is healthier, too.

Are the rumors true? Are the millennials on to something?


Cold brew’s coffee-to-water ratio is around 1:6, compared with the drip-coffee ratio of about 1:20. Dang, that’s a lot of caffeine. But remember, cold brew is a concentrate and you are supposed to dilute it. Also the caffeine level is higher the longer you steep it, and also depends on what beans you use, so all these factors will affect the final caffeine content.

For those of you who want to limit the jitters or want more caffeine to boost your workout, could adjust your cold brew accordingly. A 16-ounce coffee contains roughly 200 mg of caffeine, while a hot 16-ounce coffee contains anywhere from 260 to 375 mg, depending on the beans. Clover and blonde roasts tend towards the higher range and dark roasts tend to be on the lower range, relatively speaking. The verdict? OTC cold brew tends to have slightly less caffeine than drip coffee.


Since the process of brewing cold-brew doesn’t involve heat, and heat extracts more bitter compounds and acid, cold brew does tend to be less bitter and less acidic. So yes, granted, cold brew has a relatively smoother, less acidic taste. Because of this, people with more sensitive stomachs or acid reflux tend to tolerate cold brew better than the hot-brewed stuff.


Coffee itself, no matter how you make it, contains some interesting health benefits. There is a lot of exciting research about how coffee can increase insulin sensitivity, fat burning, and even lifespan, as well as how it can decrease the signs of dementia and neurodegeneration. Most of this research focuses on coffee’s inflammation-busting antioxidant content. Coffee compounds like chlorogenic acid are disease-fighting superstars. So how does cold brew measure up? Since it’s a relatively new phenomenon to baristas, and even newer to researchers, there isn’t really any solid evidence comparing cold brew to hot brew when it comes to antioxidant levels. However, logic suggests that because more coffee acid and oils are left behind during the cold brewing process, it may actually contain fewer antioxidants. Either way, you are probably getting good benefits, however, and it’s probably more important, for health reasons, to stick to organic beans, no matter how you brew them, since conventional coffee crops tend to be heavily sprayed with pesticides.

For those who tolerate caffeine and want the longevity and other benefits of coffee, cold brew is your cup of joe if you are looking to minimize stomach symptoms from coffee. If regular coffee doesn’t bother your stomach, then choose the taste you prefer, as people do tend to prefer one or the other.

The best-caffeinated beverages to fight inflammation

Ready for the last piece of the puzzle? Caffeine isn’t typically consumed in isolation, so we also have to consider the health benefits of the specific type of caffeinated beverage you’re drinking.

Studies have shown that different types of tea, including black, green, and oolong teas, have inflammation-fighting properties. Fun fact, green tea is thought to be the healthiest type of tea (10) because of its higher levels of catechins—aka, polyphenols with antioxidant and anti-inflammatory properties (11) - than other types of tea.

But not all caffeinated beverages will have anti-inflammatory health benefits. Energy drinks and sodas are full of sugar, preservatives, chemicals, and artificial colors that can actually trigger inflammation—regardless of whether you’re a slow or fast caffeine metabolizer.

If you’re a fast caffeine metabolizer, some of my favorite healthy caffeinated beverages include organic black coffee blended with MCT oil, Earl grey tea with steamed almond milk (unsweetened, of course!), and an iced matcha with coconut milk and cinnamon. If you’re a slow caffeine metabolizer, try opting for caffeine-free options like herbal teas, rooibos tea, or a golden milk latte.

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  3. Bjorness TE, Greene RW. Adenosine and sleep. Curr Neuropharmacol. 2009;7(3):238‐245. doi:10.2174/157015909789152182
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  7. Anahad O’Conno For Coffee Drinkers, the Buzz May Be in Your Genes The New York Times July 12, 2016
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  9. US Cold Brew Coffee Sales Grow 115% From 2014-2015 Mintel September 18th, 2015
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Dr. Will Cole, DNM, IFMCP, DC is a leading functional medicine expert who consults people around the globe, starting one of the first functional medicine telehealth centers in the world. Named one of the top 50 functional and integrative doctors in the nation, Dr. Will Cole provides a functional medicine approach for thyroid issues, autoimmune conditions, hormonal imbalances, digestive disorders, and brain problems. He is the host of the popular The Art Of Being Well podcast and the New York Times bestselling author of Intuitive Fasting, Ketotarian, The Inflammation Spectrum, and Gut Feelings: Healing the Shame-Fueled Relationship Between What You Eat and How You Feel.

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