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Written by
Amy Brownstein
Medically Reviewed by
Dr. Anshul Gupta

Most of us are accustomed to our morning dose of caffeine, whether it is a cup of coffee or tea. Some of us can’t even begin our day without that first cup of coffee — we rely on the initial jolt of caffeine to make us alert and ready for work. But could our reliance on caffeine be contributing to other health problems? Specifically, does caffeine cause inflammation?

This article will discuss the intricacies of establishing whether caffeine consumption causes inflammation. We will review how our health, genetic makeup, and stress response can influence how caffeine affects our bodies. 

Does Caffeine Cause Inflammation?

Caffeine and inflammation have a complex and often contradictory relationship. While studies have shown caffeine is anti-inflammatory, its effects can lead to inflammation.

What Is the Relationship Between Caffeine and Inflammation? 

Researchers think caffeine may decrease inflammation by preventing adenosine (a messenger molecule that influences signaling between neurons) from binding to its receptors. Adenosine is found throughout the body and all cells have adenosine receptors, and the attachment of adenosine to its receptors initiates an inflammatory response. Because caffeine has a structure similar to adenosine, it can attach to adenosine receptors, blocking adenosine and decreasing inflammatory responses. The ubiquitous nature of adenosine explains the widespread effect of caffeine on our bodies. (Source, Source, Source)

Chronic inflammation is associated with autoimmunity and many other conditions, such as cardiovascular disease, cancer, and cognitive decline. Caffeine itself may protect you against chronic inflammation by preventing the production of certain inflammatory molecules associated with the development of these chronic diseases. Moreover, by decreasing inflammation, caffeine intake may contribute to longevity. (Source)

The relationship between caffeine and inflammation is more complex than caffeine just decreasing inflammation. As we’ll see, caffeine can influence inflammation by affecting your response to stress.

Stress Leads to Inflammation 

A stressful event can activate your nervous system and the hypothalamic–pituitary–adrenal (HPA) axis to initiate the “fight or flight” response. The HPA axis is a complex pathway linking the central nervous and endocrine systems. When you perceive a threat, the hypothalamus secretes corticotropin-releasing hormone, which tells the pituitary gland to release adrenocorticotropic hormone, which then stimulates the adrenal glands to secrete cortisol, also known as the stress hormone. Cortisol moves through the bloodstream to initiate the “fight or flight” response. (Source)

The release of cortisol helps mobilize your body in an emergency. However, prolonged elevated levels of cortisol can have a negative effect by creating an inflammatory state. Circulating levels of cortisol can lead to increased pro-inflammatory molecules and create a state of chronic inflammation that may result in stress-related chronic illnesses, such as cardiovascular and metabolic diseases. (Source)

Caffeine Activates Our Response to Stress

Caffeine activates our response to stress, raising cortisol levels. Many of us experience stress in our daily lives. Adding caffeine to an already stressed body creates an additive stress effect and increases cortisol concentrations. Moreover, consuming a caffeinated beverage when cortisol levels are already high may prolong the stress response and prevent cortisol levels from declining, thus contributing to inflammation. (Source, Source)

woman leaning on shoulder

Genetics Affect the Response to Caffeine

How you respond to caffeine is influenced by your genetic makeup. Caffeine is primarily metabolized in the liver by the enzyme CYP1A2. Certain variations of the CYP1A2 gene determine whether we are slow or fast caffeine metabolizers. Other factors, such as heavy caffeine intake and smoking, may also affect our response to caffeine. (Source, Source)

Another gene, ADORA2A (which affects dopamine release), may be responsible for feelings of anxiety after drinking caffeine. Variations in the ADORA2A gene are associated with anxiety in people who are not used to drinking caffeine. However, regular caffeine intake may make us tolerant of its anxiety-provoking effects. (Source

woman sleeping in bed

Caffeine, Stress, Sleep, and Inflammation Are All Connected

Caffeine activates our stress response, which raises cortisol levels. High circulating cortisol can affect our sleep and lead to chronic inflammation. While caffeine itself may not be causing inflammation in this instance, its downstream effect can be persistent low-grade inflammation.

Cortisol Is Released in a Diurnal Pattern

Cortisol is released from the adrenal glands in a diurnal (or daily) manner. Cortisol levels peak in the morning to help wake us up (usually 30–45 minutes after we get up) and steadily decline throughout the day until reaching their lowest levels during the early phases of sleep. Cortisol levels are at their lowest around midnight and begin to rise around 2:00 a.m. or 3:00 a.m. before reaching their peak around 8:30 a.m. Meals can also stimulate the release of cortisol. Levels may peak at noon and 6:00 p.m. following a meal.

The daily release of cortisol helps ensure your body functions at its best. Any changes to this cycle can have a negative effect on your health and wellbeing, affecting immune-system responses and memory, and contributing to depression. (Source, Source, Source)

Caffeine May Affect Your Sleep Schedule

Perhaps you drank coffee or tea at 5:00 p.m., only to realize you could not sleep that night. We each respond to caffeine individually, but taking caffeine late in the day can affect your sleep schedule, delaying your circadian rhythm and keeping you awake longer. In addition to having more trouble falling asleep, the quality of your sleep may also be affected when consuming caffeine later in the day. Drinking caffeine even 6 hours before bed can significantly affect sleep, and experts recommend sipping your last caffeinated beverage before 5:00 p.m. (Source, Source)  

High Cortisol and Poor Sleep Affect Your Health

Sleep and cortisol are closely linked: High cortisol levels can impact our ability to sleep, but lack of sleep also increases cortisol. Elevated cortisol and sleep disruptions can affect our gut microbiota and lead to dysbiosis and an increased risk of inflammatory bowel disease relapse. Additionally, poor sleep quality and stress have been linked to an increased risk of heart disease. Holistic management of autoimmune disease includes adequate and high-quality sleep. (Source, Source)

Despite Tolerance, Caffeine Still Raises Cortisol Levels 

Caffeine tolerance can occur with long-term use, but despite habitual intake you can still feel the effects of caffeine, such as greater alertness, improved mood, and increased blood pressure. It is possible to develop a tolerance to caffeine, where your morning cup of caffeine no longer makes you alert and you now require more caffeine for the same effect. Drinking an additional cup of caffeine in the afternoon will raise cortisol levels even if you have a tolerance to caffeine. (Source

a latte in a glass cup

Caffeine’s Possible Health Benefits

While there are some caveats to caffeine use, it may offer some benefits as well.

Caffeine May Protect Against Chronic Inflammation

As discussed earlier, caffeine may modulate the inflammatory response by attaching to adenosine receptors to prevent the production of inflammatory cytokines. However, the effect of caffeine on the production of inflammatory cytokines may be dose-dependent: lower doses of caffeine decrease cytokine levels whereas higher doses increase cytokine production. (Source, Source)

Research published in the journal Nature Medicine assessed overall caffeine consumption in older participants and found lower levels of inflammatory markers in those who regularly consumed caffeine (coffee or tea). The more caffeine older people drank, the more protected they were against low-grade chronic inflammation. The lower levels of inflammation were associated with increased longevity. (Source)

Caffeine May Have Antioxidant Properties

Caffeine may also provide health benefits through its effect on oxidative stress. Oxidative stress is an imbalance between damaging free radicals and the antioxidants that defend against them, which can lead to inflammation and disease. Caffeine reduces the production of free radicals and affects the amount of glutathione (an important antioxidant in the body’s defense system) present in the body, decreasing levels of oxidative stress. (Source, Source)

coffee pot next to a vase and a stack of books

Coffee May Have Benefits Unrelated to Caffeine

The known benefits of coffee — the most common form of caffeine — may not be related to its caffeine content. A systematic review of meta-analyses published in the British Medical Journal found a decreased risk of all-cause mortality associated with drinking coffee, whether caffeinated or decaffeinated. Chlorogenic acid, a polyphenol in both caffeinated and decaffeinated coffee, offers antioxidant and anti-inflammatory properties, and may inhibit swelling and pain associated with acute inflammation. Researchers concluded that coffee, whether regular or decaf, is associated with more health benefits than harmful health outcomes. (Source, Source)

How Coffee Is Prepared Matters

The type of coffee and method of preparation influences its effect on our health. Bioactive components differ based on the coffee bean. For example, organic coffee contains less caffeine and more antioxidants than regular coffee. The method of preparation — including the degree of roasting, grind setting, and brew type — affects the coffee’s health properties. Roasting the coffee, using a cold-water extraction process, or preparing an espresso reduces the amount of certain toxins that can contaminate coffee during harvest, storage, or transportation. Likewise, unfiltered coffee does not have the same anti-inflammatory properties as filtered coffee. Consider choosing an organic coffee to minimize exposure to pesticides and primary pollutants, which can exacerbate autoimmune symptoms. (Source, Source, Source, Source)

Caffeine and the Autoimmune Protocol

Caffeine itself is not prohibited on the autoimmune protocol (AIP) diet. However, avoiding coffee during the elimination phase is recommended as coffee beans are actually seeds, and seeds are common allergens. Moderate consumption of caffeine — earlier in the day, so it doesn’t interfere with sleep — is acceptable for most people on the AIP diet. 

The Bottom Line on Caffeine and Inflammation

Caffeine can be anti-inflammatory, depending on your genetic makeup, and provided you don’t consume it in excess. Caffeine affects each of us differently, so it is important to consider how caffeine makes you feel when evaluating whether to change your routine. If you choose to continue with your morning cup of caffeine, consider drinking it 30–45 minutes after waking up, when cortisol levels have started to decline. And if you experience anxiety or stress with caffeine, consider decreasing your intake or skipping your daily cup entirely . 

Making evidence-based changes to your lifestyle, including your diet, can greatly improve your quality of life. If you are interested in exploring holistic autoimmune care, learn more about how WellTheory and our Nutritional Therapy Practitioners can support you with tailored guidance and lifestyle changes.

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