Too Much, Too Little Coffee May Boost Seizure Risk in Epilepsy

Too much and too little coffee is tied to an increased risk of a specific seizure type in patients with epilepsy, new research shows.

Investigators found that high and low coffee consumption in patients with epilepsy was associated with up to a twofold increased risk for focal to bilateral tonic-clonic seizure (FBTCS) compared to moderate coffee consumption in this patient population.

In a cross-sectional analysis of more than 600 patients with drug-resistant seizures, the odds ratio (OR) of reporting at least one FBTCS per year was 2.05 in those with high coffee consumption and 1.6 in patients who never drank coffee compared with participants with moderate coffee consumption.

“The main message is that coffee is not contraindicated if you have epilepsy. But maybe the level of coffee consumption is important to discuss because of the potential increase of FBTCS frequency in patients drinking more than four cups per day,” study investigator Julie Bourgeois-Vionnet, MD, a neurologist at Hospices Civils de Lyon, France, told Medscape Medical News.

The findings were published online December 17 in Epilepsy and Behavior.

Role in Seizure Cessation?

Caffeine, the main stimulant in coffee, increases arousal and vigilance by blocking adenosine receptors. Extracellular concentrations of adenosine increase after a seizure, and previous research suggests the chemical may play a role in seizure cessation.

However, the relationship between caffeine intake and seizure frequency is unclear, partly because of a lack of large-scale studies, the researchers note.

To examine the relationship between coffee consumption and seizure frequency, the investigators conducted a cross-sectional analysis. They examined data from the SAVE study, which evaluated the management of antiseizure medication (ASM) withdrawal in patients with drug-resistant seizures.

The study included 619 patients age 18 years or older (mean age, 36.1 years; 54% women) with drug-resistant focal epilepsy for whom data about coffee consumption and seizure frequency were available.

In addition to demographic data, the investigators gathered information about ASMs, monthly frequency of focal seizures, and total number of FBTCS during the previous 12 months. Coffee consumption was determined via patient self-report.

At baseline, patients were using a median of two ASMs. The most frequently used agents were lamotrigine (n = 226), levetiracetam (n = 213), and lacosamide (n = 197).

Rare coffee consumption of less than one to three cups per week was reported by 24.1% (n = 149), moderate consumption of four cups per week to three cups per day was reported by 28.6% (n = 177 patients), and high consumption of at least four cups per day was reported by 16.2% (n = 100). Moderate and high coffee consumption were more common in men and self-reported smokers.

U-Shaped Association

Investigators found no association between coffee consumption and monthly frequency of all seizure types. The number of ASMs and location of the seizure focus were the only factors associated with monthly frequency of all seizure types. Patients with extratemporal epileptogenic zones had greater seizure frequency than those with temporal lobe epilepsy.

In all, 217 participants (35%) reported at least one FBTCS in the previous year. In univariate analyses, number of FBTCS during the past year was significantly associated with usual coffee consumption (P = .029).

“We observed a U-shape association with lower FBCTS frequency in patients who reported moderate coffee consumption than in others,” the investigators report.

Compared with patients with moderate coffee consumption, the OR of at least one FBTCS per year was 1.6 in patients who never drank coffee, 1.62 in patients who drank it rarely, and 2.05 in patients with high coffee consumption.

Number of FBTCS during the past year was also significantly associated with epilepsy duration (P = .03) and current use of carbamazepine (P = .001). The number of FBTCS decreased with epilepsy duration and was lower among those who were taking carbamazepine.

The researchers did not expect to find an association between coffee consumption and FBTCS frequency, Bourgeois-Vionnet noted.

“We know that caffeine acts like an antagonist on the adenosine pathway, but why would it have consequences only on generalized tonic-clonic seizures?” she asked. More studies will be necessary to clarify and explain the association, she added.

Based on the findings, it may be appropriate to advise patients with FBTCS to limit their coffee consumption to moderate levels, said Bourgeois-Vionnet.

“But, of course, we need more studies and prospective studies with more rigorous collection of the exact quantity of coffee to confirm those levels,” she added.

Encourage Moderation

Commenting for Medscape Medical News, Nathalie Jetté, MD, professor of neurology and population health science and policy, Icahn School of Medicine at Mount Sinai, New York, said the study’s limitations include its cross-sectional design and its lack of prospective evaluation of coffee consumption. Jetté was not involved with the research.

It is important to note that the association between coffee consumption and FBTCS frequency was present in univariate analyses but not in the final multiple ordinal logistic regression model, she said.

There is a need for a large, prospective study that accounts for all sources of caffeine consumption, not just coffee, as well as the type and number of ASMs, epilepsy severity, and seizure triggers, Jetté added.

Despite the need for further research, the findings have immediate implications for practice.

“At the very least, as clinicians, we should be discouraging large amount of caffeine consumption, as we know that this could be associated with sleep deprivation, which can lower the seizure threshold,” said Jetté.

Clinicians should always ask patients about all potential seizure triggers, such as alcohol intake, stress, and nonadherence to ASMs, she added.

Moreover, clinicians should talk to patients about health-related behaviors that may help reduce seizure frequency, including physical activity, meditation, dietary patterns, and stress management, Jetté concluded.

The SAVE study was funded by the French Ministry of Health. Bourgeois-Vionnet and Jetté reported no relevant financial relationships.

Epilepsy Behav. Published online December 17, 2021. Abstract

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