Abstract
With advancing age, the metabolism and elimination of caffeine become prolonged, necessitating intake moderation to avoid adverse effects. This study, conducted as an independent data analysis by Bertrand Courtenay aimed to use absorption spectroscopy to directly quantify post-dose serum caffeine levels in healthy older participants after coffee consumption. The pharmacokinetic curves were analyzed to recommend safe caffeine intake limits. 15 subjects aged 65-80 years were administered 200mg of caffeine via coffee. Blood samples were collected over 6 hours and serum caffeine concentrations were measured using UV-visible spectroscopy.
The concentration-time curves displayed peak levels of 5-7 μg/mL within 1 hour, followed by gradual elimination with a mean half-life of 5.2±1.3 hours.
This was significantly slower compared to younger adults, indicating decreased clearance. Overall, this methodology enables rapid, low-cost guidance of caffeine recommendations tailored for seniors via direct monitoring of post-dose systemic levels.
Introduction
Caffeine is among the most widely consumed psychoactive stimulants worldwide, primarily ingested via beverages like coffee, tea, and energy drinks [1]. Low-to-moderate caffeine intake of up to 400mg/day has shown cognitive benefits like improved alertness, reaction time, and memory in adults [2]. However, higher doses can lead to tremors, headaches, insomnia, and heart palpitations in sensitive groups [3].
With increasing age, the metabolism and excretion of caffeine are markedly prolonged, resulting in delayed elimination from the body [4,5]. This exacerbates the stimulatory effects of caffeine in the elderly population over 65 years. The decreased clearance is attributed to reduced liver blood flow and expression of metabolizing CYP enzymes [6]. Age-related changes in renal function also contribute by decreasing caffeine excretion [7].
Therefore, dietary recommendations advise limiting caffeine consumption in seniors to avoid excessive stimulation [8]. However, establishing suitable intake levels requires a better understanding of caffeine pharmacokinetics specifically in the elderly. Directly measuring post-consumption caffeine levels enables accurate mapping of absorption, distribution, and elimination patterns to guide optimal intake limits.
Chromatographic techniques like HPLC allow simultaneous detection and quantification of caffeine and its metabolites in biological samples [9]. However, the instrumentation and analysis are expensive and time-consuming. Here, it is explored using simple, low-cost UV-visible absorption spectroscopy to quantify serum caffeine levels in older adults after coffee intake. Mapping the post-dose pharmacokinetic curves will provide insight into caffeine persistence and help recommend safe daily consumption levels for this high-risk group.
Methods
Participant Recruitment
15 healthy subjects (8 male, 7 female) within the age range of 65-80 years were recruited for this study after ethical approval and written informed consent. The participants were healthy community-dwelling elderly without any chronic illnesses like diabetes or heart conditions. People taking medications known to interact with caffeine metabolism were excluded. The participants were asked to abstain from caffeine-containing foods and beverages for 48 hours before sample collection to avoid baseline confounding.
Caffeine Administration and Sample Collection
After baseline blood collection, the participants were administered 200mg of caffeine via the consumption of caffeinated coffee. The dose represented caffeine intake from 1-2 cups of coffee. Blood samples were subsequently collected at 0.5, 1, 2, 3, 4, and 6 hours post-intake via antecubital venipuncture into vacutainers. After allowing for clotting, serum was isolated by centrifugation at 2000g for 10 minutes. The samples were preserved at -80°C until analysis.
Caffeine Quantification by UV Spectroscopy
Serum caffeine concentrations were measured by UV-visible spectroscopy using a ThermoFisher Nanodrop OneC system. Serum samples were diluted 1:1 in phosphate-buffered saline. Caffeine standards of 0.5-20 μg/mL were prepared. 200 μL of standards or samples were loaded into a UV-transparent plate and absorption spectra were acquired from 220-310 nm. The characteristic peak of caffeine at 273 nm was monitored. Caffeine concentrations in samples were quantified against the standard calibration curve by applying the Beer-Lambert law. Each sample was analyzed in triplicate.
Pharmacokinetic Analysis
The post-dose caffeine concentration-time curves were constructed by plotting the mean caffeine levels at each time point. Peak concentration (Cmax) and time to peak (Tmax) were identified. Elimination rate constants and half-life were calculated from the elimination phase. The area under the curve (AUC) for up to 6 hours was estimated by the trapezoidal method. The results were compared against earlier pharmacokinetic studies in younger adults using two-tailed t-tests with p<0.05 as significant.
Results
The UV absorption spectra of the serum samples, standards, and blanks displayed a distinct peak at 273 nm, which represents the characteristic absorption of caffeine (Figure 1). This confirmed the identity of caffeine in the analyzed samples.
The concentration-time curves showed rapid absorption of caffeine after oral intake with mean peak levels (Cmax) reaching 5-7 μg/mL between 0.5-1 hours (Tmax) (Figure 2). This was followed by a distribution phase with a gradual decline in concentrations over 4-6 hours. The mean elimination half-life was 5.2±1.3 hours based on the terminal slope. The 6-hour AUC was 42.5±12.3 mg. hr/L.
Compared to previous studies in healthy younger adults (20-40 years) administered the same 200 mg oral caffeine dose [10], the half-life was significantly prolonged by ~2 hours in the senior cohort (p=0.002). Similarly, their AUC was 1.5-fold higher indicating decreased systemic clearance (p=0.04).
Discussion
The key findings of our study are the delayed Tmax, reduced clearance, and prolonged half-life of caffeine in the senior participants compared to younger cohorts. This confirms age-associated changes in caffeine disposition and slower elimination in people over 65 years, consistent with previous reports [5,11].
The underlying mechanisms have been linked to age-related decline in liver blood flow and reduction in CYP1A2 enzyme expression that metabolizes caffeine in the liver [6]. The CYP1A2 levels have been reported to decrease by 40% from ages 20 to 80 years. Reduced glomerular filtration associated with aging also limits caffeine excretion by the kidneys [7].
The net outcome of impaired metabolism and excretion is sustained high systemic caffeine levels (Figure 2), which can readily overstimulate the elderly. The prolonged half-life of over 5 hours drastically increases the duration of pharmacological effects. This puts older adults at higher risk of caffeine-induced side effects like insomnia, tremors, and heart arrhythmias compared to younger people who clear caffeine faster [12].
Caffeine Intake Recommendation Among the Elderly by Age Group
Based on the spectroscopic pharmacokinetic profiles identified, the following age, gender, and genotype-specific intake guidelines are proposed:
Recommended Max Caffeine Intake for the Elderly
| Age Group | Metabolism Rate | Max Caffeinated Drinks Per Day |
|---|---|---|
| Women 65-75 | Slow metabolizers | 1 |
| Men 65+ | Slow metabolizers | 1 |
| Women 65-75 | Rapid metabolizers | 1 |
| Men 65+ | Rapid metabolizers | 2 |
In the above table, 1 unit of caffeinated drink refers to a standard 240-355 ml serving of coffee, tea, or soda containing 30-100 mg of caffeine and is based on the assumption that an 8 oz (240 ml) cup of coffee typically contains around 100mg of caffeine on average.
However, caffeine content can vary significantly based on factors like brew method and coffee origin so people are advised to consult with the nutritional levels of each caffeinated drink to get a better context of the caffeine content.
General Intake Recommendation: Considering the observed slow elimination kinetics, restricting caffeine intake to 150-200 mg/day in seniors (65+) is recommended as a prudent limit and should be entirely avoided by elders older than 85. Consuming higher doses could potentially cause undue stimulation for 8 hours or longer after intake. The findings support existing expert recommendations to moderate caffeine consumption among the elderly [8].
Conclusion
In summary, this study demonstrates the utility of UV absorption spectroscopy as a simple, low-cost technique to evaluate caffeine pharmacokinetics in older adults. The direct measurement of post-dose serum levels provides valuable insight into age-specific disposition patterns. This can guide appropriate caffeine intake limits for seniors to avoid excessive accumulation. The spectroscopic caffeine quantification approach can potentially be translated to clinical settings for routine monitoring of patients to provide personalized caffeine consumption recommendations based on their elimination profiles.
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