Caffeine: Is there really a right dose?

Introduction

With its 177 million bags sold worldwide, coffee remains one of the most consumed and appreciated beverages globally in 2024 [1]. Coffee consumption is a widespread phenomenon with deep cultural roots intertwined with the daily habits of millions [2]. While coffee offers benefits, it also exposes consumers to risks associated with caffeine, a mild stimulant that has become a part of everyday life [3]. But what is caffeine, and what are its main effects?

Guess what the caffeine molecule looks like

From a chemical standpoint, caffeine is a xanthine with three methyl groups attached to nitrogen at positions 1, 3, and 7, earning it the name 1, 3, 7 trimethylxanthine. Its unique structure allows it to occupy the space of a crucial neurotransmitter in the bodies of those who consume it. Let’s explore further [4].

The molecular structure of caffeine is similar to adenosine. Caffeine can substitute for adenosine by binding to its receptors in brain cells [4]. However, the two molecules have completely different effects. Adenosine promotes relaxation and depresses the central nervous system, slowing down nerve cell activity. Conversely, caffeine does the opposite, reducing fatigue, creating alertness, and increasing nerve cell activity. The result is a temporary feeling of increased wakefulness and energy [5].

What happens to caffeine in the human body?

Caffeine is typically consumed orally and rapidly spreads through all tissues, crossing the blood-brain barrier and the placenta of pregnant women. To learn more about risks related to caffeine intake during pregnancy, read: The Impact of Caffeine Consumption on Pregnancy and Breastfeeding.

Once in circulation, caffeine reaches its peak plasma concentration within two hours and has a variable half-life ranging from a minimum of 2.5 to a maximum of 4.5 hours [6]. Factors like pregnancy, alcohol consumption, or the use of medications such as contraceptives, cimetidine, disulfiram, and allopurinol further influence the molecule’s half-life [7]. Ingesting 100 mg of caffeine produces plasma concentrations between 1.5 and 1.8 mg/ml [7].

The liver predominantly eliminates caffeine, breaking it down into 1-methyluric acid, 1-methylxanthine, and 7-methylxanthine [8, 9, 10]. About 10% remains unchanged and is excreted through urine. The cytochrome P450 enzyme is directly involved in caffeine metabolism in the liver [11, 12].

According to James Lane, an emeritus professor of psychiatry at the Duke University School of Medicine in Durham, North Carolina, not all caffeine disappears after 8 hours. It might take up to 12 hours to completely eliminate caffeine from a morning cup of coffee. As a result, the drug’s effect often fades when a person is almost ready for bed, making it easier for people to develop caffeine dependence as they desire to continue drinking it the next day [13].

Which plants produce caffeine and why?

Plants that produce caffeine include coffee (Coffea spp.), tea (Camellia sinensis), cocoa (Theobroma cacao), yerba mate (Ilex paraguariensis), and certain guarana plants (Paullinia spp.) [14]. Even mate, often called tea, is a beverage containing caffeine.

Caffeine’s role in plants is intriguing. This alkaloid acts as a natural insecticide, toxic to many insects [15]. Present in varying quantities in fruits, leaves, and other parts of the plant, caffeine interferes with the nervous system of insects, causing their death or discouraging them from attacking the plant again [16]. Besides insects, herbivores are also deterred from feeding on plant parts [17]. Additionally, caffeine serves as an antimicrobial agent, protecting the plant from pathogenic microorganisms [15]. Thus, caffeine is a part of the plant’s natural defense strategy against microorganisms, insects, and other predators [15].

While caffeine is naturally found in the mentioned plants, it can also be present in unexpected places, being added to a wide range of products. Therefore, it is crucial to know the sometimes unsuspected sources of caffeine.

Unexpected Sources of Caffeine

Today, it’s possible to purchase bottled water with added caffeine, caffeinated gummy candies, mints, peanut butter, and chewing gum [18]. There are even caffeinated bath soaps designed to help people wake up in the morning. Caffeine has also been added to hair care products such as shampoos and other beauty items like eye creams, scrub lotions, and shaving creams [22].

Although caffeine can be absorbed through the skin, the primary mode of caffeine intake remains oral. Therefore, supplements and medications containing caffeine are the elements to consider if one wishes to monitor their daily caffeine intake [18, 20, 21, 22]. Caffeine can be present in migraine medications, as well as pain relievers and those targeting menstrual pain. It is also sold in the form of caffeine pills, each containing 200 milligrams per tablet [19, 20]. Furthermore, caffeine is found in some weight loss products and dietary supplements [18, 20, 21, 22]. It may be labeled as guaraná, cola nut, yerba mate, green tea extract, or green coffee bean extract, according to the National Institutes of Health [20].

Considering that, according to the European Food Safety Authority (EFSA), single doses of caffeine up to 200 mg (approximately 3 mg/kg of body weight for a 70 kg adult) pose no safety concerns [23], it is prudent to check for the presence of caffeine in medications and supplements to avoid excessive intake.

A healthy daily dose of caffeine can vary significantly from person to person. When doctors talk about moderate caffeine consumption, they refer to an amount ranging between 2 and 300 milligrams. Most coffee consumers tend to fall within this range. Beyond this, 300 milligrams might be perfect for one person but excessive for another. Variability is considerable and depends on factors such as body size, smoking habits, and genetic predisposition to metabolize caffeine slowly [25]. It would be unwise to assert that a specific amount is perfect or excessive.

Women taking contraceptives metabolize caffeine twice as slowly, meaning they get twice the stimulation from the same cup of coffee [24]. Conversely, smokers metabolize it twice as quickly [25]. Some individuals have a genetic predisposition to metabolize caffeine slowly, and they are the ones who will be particularly sensitive to caffeine [25].

Inconsistency in Caffeine Content: A Challenge in Determining the Right Dose

There is no standardized amount of caffeine in each cup of coffee, not even within the same brand.

In a study led by researcher Bruce Goldberger, published in the Journal of Analytical Toxicology [26], it was found that coffees marketed as decaffeinated had caffeine concentrations below 17.7 mg per serving. The caffeine content in caffeinated coffees varied from 58 to 259 mg per serving. The average caffeine content in specialty brewed coffees was 188 mg per 16-ounce cup, just over 470 mL—a substantial amount by European standards but a typical serving size in American-style coffee shops like Starbucks.

Another noteworthy discovery was the wide range of caffeine concentrations (259-564 mg/serving) in the same coffee beverage obtained from the same outlet over six consecutive days. Goldberger found that caffeine levels more than doubled for the same blend within as short a time frame as a week. This implies that we cannot rely on the typical cup of coffee to determine our caffeine intake, as it may vary from day to day, even doubling.

Goldberger is not the only one making such findings. In a study, researchers from the School of Public Health at Griffith University in Australia [27] analyzed ninety-seven samples of espresso. The average caffeine amount was 106 (±38) mg per serving with a concentration of 2473 (± 1092) mg/L. There was a considerable variation in caffeine content, with a per-serving range of 25-214 mg and a concentration range of 580-7000 mg/L. Twenty-four samples (24.7%) contained 120 mg of caffeine or more, and 12 samples (12.3%) exceeded 167 mg per serving.

Therefore, not only American-style coffees but also more European espressos exhibit extremely variable caffeine content.

Conclusions

Caffeine is the protagonist of the mornings for millions worldwide, possessing extraordinary properties. However, determining the right dose for each individual remains challenging. Caffeine may have a much better or worse effect on each of us than clinical studies suggest. In this case, the saying “the dose makes the poison” holds true.

What is the “right” dose?

We all wonder, and there is no one-size-fits-all answer. It depends on our age, body composition, physical activity, existing health conditions, pregnancy status, and the medications we are taking. There is no universal dose for each of us, as every body is different. The EFSA guidelines recommend 200 mg per day, but even this amount could be excessive for caffeine-sensitive individuals or those in specific physical conditions.

Therefore, the crucial thing to know about caffeine is that the right dose needs to be calibrated individually.

 

References

 

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