Have you been trying to beat fatigue with the help of coffee or cigarettes? While you might get a short-term energy boost, both will have you feeling worse in the long run.

Did you know?

If you’re a heavy coffee drinker, you’re at a higher risk of experiencing side effects from medications such as:

• Antipsychotics
• Pain medications
• Cancer drugs

How can that be?

Recent studies show complex interactions between:

• Caffeine metabolism
• Workload
• Lifestyle
• Genetics
• Age
• Kidney function

Sound familiar? Read on to learn 4 reasons why it’s best to put down your cup of java:

1) Caffeine can aggravate chronic pain.

While the stimulating effect of caffeine prompted drug companies to include it in their pain medications, such as Tylenol #3 (a combination of codeine, acetaminophen and caffeine), the truth is for people suffering from chronic pain, caffeine is counterproductive. A large study of shift-working nurses showed that those who drank coffee in excess had higher shoulder and back pain levels and exercised less. The study assessed multiple risk factors and demonstrated that coffee consumption leads to a vicious cycle of sleep deprivation and fatigue, resulting in lower physical activity and exercise, therefore aggravating chronic pain.

2) Caffeine and DNA can impact cognitive and kidney function.

A large-scale analysis of UK biobank participants noted that high coffee and tea consumption over a long period of time decreases cognitive function. This effect was stronger for women than men. Genetics also plays a significant role in caffeine metabolism and impact.

How does that work?

People with specific genetic variants in the CYP1A2 gene, called “Ultrarapid metabolizers,” have higher levels of this enzyme, especially when exposed to cigarette smoke, air pollution, or eating grilled or smoked foods. Such individuals metabolize caffeine faster, have a lower elevation of blood pressure and feel less jittery. But not so fast; these folks are prone to drink more coffee and thus have a more profound cognitive decline.

Why it matters:

It’s important to understand that coffee stimulates the kidneys, meaning your body lowers blood pressure by increasing its filtration rates. Slow CYP1A2 metabolizers have lower enzyme elevation in response to smoke and higher blood pressure after drinking coffee. Slow metabolizers are more “sensitive” to caffeine and may have a lower risk of cognitive decline. However, if slow metabolizers consume three or more coffee cups daily, it may strain the kidneys, leading to significantly reduced kidney function with age. This suggests that caffeine may play a role in developing kidney disease in susceptible individuals.

3) Interaction between cigarettes and coffee

Smoking tobacco or cannabis stimulates CYP1A2 activity, while caffeine blocks this enzyme. Because of the metabolic effects, smokers require three to four times the amount of caffeine compared to non-smokers to get similar plasma caffeine levels. Therefore, caffeine intake is usually higher in smokers. Both smoking and coffee are bad for your health, especially if you are taking medications for mental health, heart disease or chronic pain.

4) Caffeine and smoking can cause drug-induced side effects.

Caffeine and some medications, including ciprofloxacin, fluvoxamine and vemurafenib, block CYP1A2 and increase the levels of drugs metabolized by this enzyme. Duloxetine (Cymbalta), and to a more significant extent, rasagiline (Azilect, Azipron), imatinib (Gleevec), and nabumetone and are known to require higher doses in smokers to counteract increased drug metabolism, especially for ultrarapid metabolizers.

High coffee consumption is known to gravely increase the risk of severe side effects in people taking antipsychotics, including chlorpromazine (Thorazine), clozapine (Clozaril), loxapine (Loxitane), fluphenazine (Rolixin), olanzapine (Zyprexa)

But how could this impact me?

There have been several reports of emergency hospital admission when people taking antipsychotics began consuming caffeine-containing energy drinks. A young male treated with clozapine ended up in the ER with organ failure because he drank four cans of Red Bull per day over three weeks. Combining energy drinks with alcohol or antipsychotics leads to life-threatening toxicity, resulting in decreased consciousness and acute respiratory and kidney failure. Individuals with underlying heart disease are at an increased risk of potentially fatal caffeine-induced complications.

Genetic testing for drug response can help your doctor assess whether you can still consume caffeine while taking medications and adjust the dose to reduce adverse side effects. If you cannot reduce your consumption, pharmacogenetic test results help you and your healthcare provider assess which medication would be more compatible with your DNA and lifestyle.

Summary

While coffee can give a short-term alertness boost, it can aggravate chronic pain and mental illness and impair cognitive and kidney function in the long term. Your lifestyle and DNA impact your sensitivity to caffeine and drug response. If you are a heavy smoker or coffee lover, a pharmacogenetic test, like Pillcheck, can let you find out about your caffeine metabolism, and more importantly, help your doctor select an alternative medication to manage your condition.

Selected references

Cornelis C et al., Caffeinated Coffee and Tea Consumption, Genetic Variation and Cognitive Function in the UK Biobank J Nutr. 2020 Aug 1;150(8):2164-2174.

Chen YH et al., The Effects of Frequent Coffee Drinking on Female-Dominated Healthcare Workers Experiencing Musculoskeletal Pain and a Lack of Sleep J Pers Med. 2022 Dec 22;13(1):25.

Mahdavi S et al., CYP1A2 Genetic Variation, Coffee Intake, and Kidney Dysfunction. JAMA Netw Open. 2023 Jan 3;6(1):e2247868.

Yartsev A and Peisah C. Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report BMC Psychiatry. 2021 Apr 13;21(1):192.