Cutaneous and Ocular Toxicology

ISSN: 1556-9527 (Print) 1556-9535 (Online) Journal homepage: https://www.tandfonline.com/loi/icot20

Acute Effect of Caffeine on Pattern-Reversal Visual

Evoked Potential: A Randomized-Controlled Study

Dilek Top Karti, Omer Karti, Figen Gokcay & Nese Celebisoy

To cite this article: Dilek Top Karti, Omer Karti, Figen Gokcay & Nese Celebisoy (2019): Acute
Effect of Caffeine on Pattern-Reversal Visual Evoked Potential: A Randomized-Controlled Study,
Cutaneous and Ocular Toxicology, DOI: 10.1080/15569527.2019.1583248

To link to this article: https://doi.org/10.1080/15569527.2019.1583248

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Feb 2019.

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ACUTE EFFECT OF CAFFEINE ON PATTERN-REVERSAL VISUAL EVOKED POTENTIAL:

A RANDOMIZED-CONTROLLED STUDY

Dilek Top Karti1, Omer Karti2, Figen Gokcay3, Nese Celebisoy3

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Bozyaka Training and Research Hospital, Department of Neurology, Izmir, Turkey.
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Bozyaka Training and Research Hospital, Department of Ophthalmology, Izmir, Turkey.

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Ege University Medical Faculty, Department of Neurology, Izmir, Turkey.

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Corresponding author: Dilek Top Karti, MD, Department of Neurology, Bozyaka Training and

Research Hospital, Saim Cıkrıkcı cad. No: 59, Bozyaka, Izmir, Turkey, E-mail :
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dilektop2307@hotmail.com, Phone : 0090 505 906 04 61, PBX : 0090 232 261 44 44
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ACUTE EFFECT OF CAFFEINE ON PATTERN-REVERSAL VISUAL EVOKED POTENTIAL:

A RANDOMIZED-CONTROLLED STUDY
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ABSTRACT

Purpose: This study was aimed to investigate the acute effect of caffeine intake on pattern-reversal (PR)

visual evoked potential (VEP).

Methods: This randomized controlled study included 40 participants who were divided into two groups

randomly (group 1 [study group, n=20] and group 2 [control group, n=20]). While the study group

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received coffee beverages made from 6 grams pure coffee beans (36 mg of caffeine per gram) containing

approximately 216 mg caffeine, the control group was given beverages containing 200 mg lactose without

caffeine. PR-VEP test was performed at baseline and 1 hour (h) after the beverage intake. The right eyes

of both groups were used for the statistical analysis.

Results: The median age of group 1 (8 male, 12 female) and group 2 (7 male, 13 female) were 31.0 (range,

21-59) and 36.5 (range, 20-59) years, respectively. No statistically significant difference was found

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between two groups in terms of age (p = 0.398) and gender (p = 0.744). Before the caffeine intake, median

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P100 latency and amplitudes were 109.90 milliseconds (msec) (range: 99.60-120.60) and 12.45 microvolts

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(µV) (range: 5.20-19.30), respectively. 1 h after caffeine intake, corresponding values were 110.70 msec

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(range: 99.00-114.60) and 12.45 µV (range: 5.70-20.0). Baseline P100 latency and amplitude values were

not significantly different from the values recorded 1 h after caffeine intake (p > 0.05).
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Conclusion: This study showed that ingesting moderate amounts of caffeine did not affect PR-VEP
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parameters. Therefore, caffeine restriction does not seem to be required before the PR-VEP test. Further

studies are needed to confirm our findings.

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Key words: Caffeine, coffee beans, coffee beverages, visual evoked potential test.
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INTRODUCTION
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Caffeine is the most widely used neurostimulant in the world. Large numbers of subjects from all age

groups consume the substance with a wide variety of beverages (coffee, tea, soft drinks, etc.), food

(chocolate, etc.) and drugs (analgesics, antipyretic, etc.). Coffee is the major source of caffeine in the diets

of adults, whereas soft drinks are the primary source for teens. Among adults 18 years and older, the daily

intake ranges between 166 and 336 mg/day [1]. Many physiological effects of caffeine including central

nervous system (CNS) stimulation, a decrease in the heart rate and an increase in blood pressure,

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bronchodilation and promotion of diuresis are well known [2-5]. These effects of caffeine occur by

antagonizing adenosine A1 and A2A receptors [6]. Also, it is well known that caffeine decreases cerebral

and ocular blood flow. Decrease in blood flow of the choroid, optic disc and macula after the

administration of caffeine have already been reported by several studies [7-12]. Pattern-reversal (PR)

visual evoked potentials (VEP) are made up of a series of electric signals recorded from the occipital

cortex that reflect the function beginning from the ganglion cells to visual cortex in response to retinal

stimulation. Previous animal and human studies have demonstrated the linear relationship of cerebral

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blood flow and brain electrical activity [13,14]. In addition, it is known that cerebral circulatory problems

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may lead to ischemia causing differences in VEP parameters between cerebral hemispheres [15].

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A reduction in both cerebral and ocular blood flow has been well defined with caffeine. However, the

effect on PR-VEPs has not yet been fully determined. In this study, therefore, we aimed to investigate the
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acute effect of caffeine on PR-VEPs of normal healthy subjects.
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MATERIALS AND METHODS

Participants: This was a randomized-controlled study approved by the local ethics committee. The study
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protocol adhered to the Declaration of Helsinki. 40 healthy participants were included in the study.
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Participants were divided into two groups randomly (group 1 [study group, n=20] and group 2 [control

group, n=20]).
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Study design: Participants were given either coffee beverages made from 6 grams pure coffee beans
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containing 36 mg of caffeine per gram (approximately 216 mg in total) or beverages containing 200 mg

lactose without caffeine. All participants in both groups were asked not to consume caffeine-containing

food, beverages or drugs within 24 hours prior to basal PR-VEP measurement. All basal PR-VEP

measurements were performed in both groups. This was followed by caffeine or lactose containing

beverages intake. The PR-VEP measurements were repeated 1 h after beverages intake. All participants in

both study and control groups were instructed not to drink, eat, exercise and take any medication until the

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PR-VEP measurements were over. Exclusion criteria for all participants were as follows: subjects with a

history of any neurologic (migraine, epilepsy, etc.), ocular (acquired or hereditary retinal disorders,

glaucoma, optic neuropathies, etc.) or systemic diseases (diabetes mellitus, hypertension, etc.), subjects

with high refractive spherical or cylinder diopter (D) (> ± 3 D), subjects with a history of any chronic

drug usage (phosphodiesterase inhibitors, analgesics, antihistamines, decongestants, etc.), subjects who

consume more than one cup of coffee per day due to a possible tolerance to caffeine.

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PR-VEP measurements: All PR-VEP measurements were performed by the same experienced technician.

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The subjects' refractive errors were corrected with trial lenses before the recordings were made. Medelec

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electrophysiologic device (Medelec Synergy; Oxford Instruments, Oxfordshire, United Kingdom)

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recording unit was used to amplify, average, and store the evoked potential. Potentials were obtained by

using a black-and-white checkerboard displayed on a television screen which reversed each second. Each
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check subtended 378 of visual field. Recordings were performed in a darkroom after monocular full-field

stimulation with the active scalp electrode being Oz, referenced to Cz depending on the International
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Society for Clinical Electrophysiology of Vision (ISCEV) standard for electrode placement and PR-VEP
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recordings [16]. The ground electrode was placed around the forearm. An examiner watched the patients
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and the normal controls during VEP recordings to sustain their fixation on the television screen. The
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frequency limits were set at 2–100 Hz and the analysis time was 500 milliseconds (msec). A total of 256
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responses were averaged. P100, N145 latencies and P100 amplitude were taken into consideration.

Statistical analyses: The statistical analysis was performed with SPSS for Windows 21.0 (SPSS Inc.,
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Chicago, IL). The categorical variables between the group 1 and 2 were analyzed by using x 2 test. Mann

Whitney U test was used for comparing baseline PR-VEP values of group 1 and 2. Wilcoxon test was used

to compare PR-VEP parameters before and after beverage intake. A p-value < 0.05 was considered

statistically significant.

RESULTS

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Group 1 consisted of 8 males and 12 females with a median age of 31.0 (range: 21-59) years. The median

age of group 2 (7 males, 13 females) was 36.5 (range: 20-59) years. The groups showed no significant

difference regarding age (p=0.398) or gender (p=0.744). Median basal PR-VEP measurements revealed no

significant difference between the two groups (Table 1). In group 1, median basal latencies for P100 and,

N145 and P100 amplitude were 109.90 msec (range: 99.60-120.60), 145.50 msec (range: 128.40-170.00)

and 12.45 µV (range: 5.20-19.30), respectively. 1 h after caffeine intake, corresponding values were

110.70 msec (range: 99.0-114.60), 148.80 msec (range: 130.00-164.00) and 12.45 µV (range: 5.70-20.00).

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Comparison of the PR-VEP parameters taken into consideration before and after caffeine intake revealed

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no significant difference (p > 0.05). Median PR-VEP parameters in both groups at baseline, and 1 h

following caffeine intake are shown in Table 2 and Table 3.

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DISCUSSIONS
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VEPs are measurements of the electrical signal recorded at the scalp over the occipital cortex in response
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to visual stimulus. VEPs provide important data on the functional integrity of the visual pathways [17,18].

It is generally used to investigate optic nerve disorders such as traumatic, ischemic, demyelinating,
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infiltrative, or compressive optic neuropathies. VEPs may be affected by several systemic (diabetes
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mellitus, hypertension, ischemic heart disease, acute pancreatitis, chronic renal failure, etc.), ocular
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(chorioretinitis, macular dystrophies, macular degeneration, glaucoma and other optic neuropathies, etc.),
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and neurological (multiple sclerosis [MS], adrenoleucodystrophy and familial ataxia, etc.) disorders that

may impair conduction within the visual pathways [19]. In addition, toxic agents, nutritional deficiencies
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(B12 deficiency and alcohol-tobacco amblyopia) [20], and various chemical agents such as ethanol [21],

opiates [22], and anti-epileptic drugs [23] can result in abnormal VEPs.

Other than the abovementioned conditions, VEPs may also be affected by many physiological factors

(age, gender, visual acuity, pupil size, etc.) and measurement techniques (luminance, check size, field size,

etc.) [17,24]. Effects of age and gender on VEPs have been examined by many researchers. Results on

gender differences are controversial. Although some studies have reported shorter VEP latency and higher
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VEP amplitude in females compared with males [24,25], other studies have indicated no significant

difference [26,27]. A decrease in amplitude and increase in latency of the VEP components have also been

reported with increasing age [28,29]. These changes were ascribed to axonal swelling, deposit of

lipofuscin or cell death in neurons within the visual system [30].

The effect of some chemical agents on VEPs is well defined. However, the effect of caffeine, which is

widely consumed in the world, on VEPs has not yet been fully elucidated. In this study, we analyzed the

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acute effect of caffeine on the visual responses. The effects of caffeine on the CNS have attracted the

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attention of researchers and a number of studies have been conducted. In particular, the effects of caffeine

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on cognitive performance have been examined [31-33]. Deslandes et al. [31] have reported shortening of

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the P300 latency recorded from the frontal cortex after caffeine intake and showed a positive effect on

cognitive performance. Kozlow et al. [33] reported similar results. Shalini et al. [34], investigated caffeine
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effect on evoked potentials. They recorded PR-VEPs before and 30 min after caffeine intake. A decrease

in the latency of N75, P100 and N145 waveforms and an increase in the amplitude of the P100 waveform
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after caffeine intake was demonstrated. The finding was ascribed to an increase in the speed of
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information processing that was caused by the neuronal stimulating effect of caffeine through the
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blockage of adenosine receptors. However, the study had two important limitations. First, it included only
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six participants and second it was not a randomized-controlled study. We don’t think that the time window
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between caffeine intake and PR-VEP recordings was the cause of the inconsistent results gathered from

the two studies as in both PR-VEP recordings were performed during the peak plasma concentration
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which was demonstrated by pharmacokinetic studies to vary from 15 to 120 min after oral administration

associated with variations in gastric emptying [35]. Since we considered that caffeine reached its peak

plasma concentration at the first hour after oral ingestion, PR-VEP recordings were performed 1 h after

caffeine intake. Shalini et al. [34] used a 30 min time window. Second was that the dose of the caffeine.

Participants received higher doses of caffeine (approximately 216 mg caffeine in a fixed dose) in our

study than those in the Shalini et al.'s study [34] (2mg/kg caffeine). Neuronal stimulating effect of lower

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doses of caffeine found by this group needs to be supported by further studies. In another study, dealing

with the effect of caffeine on VEPs during hypoglycemia in 16 healthy subjects, Owen et al. [36] found

that the latency of the P100 component of the PR-VEP increased significantly from rest to hypoglycemia.

In addition, in patients who were more sensitive to a decrease in blood glucose concentration, caffeine

ingestion caused a further increase in P100 latency.

The main limitation of our study is that the sample size is relatively small, though it included more

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participants than the previous studies. However, to the best of our knowledge, this is the first randomized-

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controlled study enabling us to evaluate PR-VEP parameters in both the caffeine and the control groups.

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This study demonstrates the acute effect of ingesting moderate amounts of caffeine on PR-VEPs of normal

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healthy subjects. However, the effects of lower/higher doses or chronic usage are still unknown.

Furthermore, it may be important to know whether the caffeine effects the PR-VEP parameters in
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pathological conditions such as MS-related optic neuritis affecting PR-VEPs. Therefore, we believe that
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our results can guide researchers who are interested in investigating this topic.

In summary, our results indicate that ingesting moderate amounts of caffeine appears to have no
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significant effect on PR-VEPs. Further studies are needed to confirm our findings.
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Acknowledgements; None.
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Financial support and sponsorship; None.

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Declaration of interest; The authors report no conflicts of interest. The authors alone are responsible for

the content and writing of the paper.

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Table 1. The median visual evoked potential measurements of caffeine and control groups at baseline.

VEP parameters Caffeine group Control group p value*

median (min-max) median (min-max)
P100 latans (msec) 109.90 (99.60-120.60) 111.00 (97.80-125.00) 0.398
N145 latans (msec) 145.50 (128.40-170.0) 145.00 (122.00-168.00) 0.841
P100 amplitude (µV) 12.45 (5.20-19.30) 11.00 (6.0-20.30) 0.678

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*Mann-Whitney U test.
Abbreviations: msec, milliseconds; µV, microvolts.

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Table 2. The median visual evoked potential measurements of caffeine group at baseline, and 1 h

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following oral caffeine containing beverages intake.

VEP parameters Baseline 1 h after caffeine containing

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median (min-max) beverages intake median (min-max)
P100 latans (msec) 109.90 (99.60-120.60) 110.70 (99.0-114.60) 0.519
N145 latans (msec) 145.50 (128.40-170.0) 148.80 (130.0-164.0) 0.478
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P100 amplitude (µV) 12.45 (5.20-19.30) 12.45 (5.70-20.0) 0.356
*Wilcoxon test.
Abbreviations: msec, milliseconds; µV, microvolts.
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Table 3. The median visual evoked potential measurements of control group at baseline, and 1 h
following oral lactose containing beverages intake.

VEP parameters Baseline median (min-max) 1 h after lactose containing p

beverages intake median (min-max) value*
P100 latans (msec) 111.00 (97.80-125.00) 110.00 (96.60-126.60) 0.350
N145 latans (msec) 145.00 (122.00-168.00) 146.50 (120.00-163.00) 0.828
P100 amplitude (µV) 11.00 (6.0-20.30) 9.80 (5.50-23.40) 0.906
*Wilcoxon test.
Abbreviations: msec, milliseconds; µV, microvolts.

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