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Impact of caffeine and coffee on our health

Elvira Gonzalez de Mejia1 and Marco Vinicio Ramirez-Mares2

1 University of Illinois, Department of Food Science and Human Nutrition, Division of Nutritional Sciences, 228 ERML, 1201W.

Gregory Drive, Urbana, IL 61801, USA2 Institute of Natural Resources, University of the Sea, Puerto Angel, Oaxaca CP 70902, Mexico

Science & Society

Coffee is the most frequently consumed caffeine-con-taining beverage. The caffeine in coffee is a bioactivecompound with stimulatory effects on the central ner-vous system and a positive effect on long-term memory.Although coffee consumption has been historicallylinked to adverse health effects, new research indicatesthat coffee consumption may be beneficial. Here wediscuss the impact of coffee and caffeine on healthand bring attention to the changing caffeine landscapethat includes new caffeine-containing energy drinks andsupplements, often targeting children and adolescents.

Caffeine and coffee consumptionCaffeine is the most routinely ingested bioactive substancethroughout the world. It is a natural alkaloid found in morethan 60 plants including coffee beans, tea leaves, cola nuts,and cocoa pods. Its concentration varies depending on thetype of product, agronomic and environmental factors, andprocessing. Common beverages containing variableamounts of caffeine include coffee (the major dietary con-tributor), tea, soft drinks, energy drinks, chocolate pro-ducts, certain medications (headache treatments andpainkillers), dietary supplements, and over-the-counterstimulants. Americans daily drink more than 400 millioncups of coffee, which is the major source of caffeine in theadult diet, compared with tea and caffeinated soft drinks inchildren and adolescents [1].

Caffeine as part of a blend of compounds in coffeeCoffee is a complex beverage containing, besides caffeine,more than 1000 compounds responsible for its pleasantflavor and aroma. The final sensory properties of a freshlyprepared cup of coffee are the result of a long chain ofchemical transformations that occur from the coffee beanto the coffee cup. Among the many bioactive compoundspresent in coffee are methylxanthines (caffeine, theobro-mine, theophylline) diterpene alcohols (cafestol, kahweol),chlorogenic acids (caffeoylquinic acids, feruloylquinicacids, p-coumaroylquinic acids), flavonoids (catechins,anthocyanins), hydroxycinnamic acids (ferulic acid, caffeicacid, p-coumaric acid), tocopherols, and melanoidins. Caf-feine concentration and the biological activity of coffeedepend on a blend of factors, such as variations in rawmaterials (species, origin, and genetic traits), agricultural

1043-2760/

� 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tem.2014.07.003

Corresponding author: Mejia, E.G.d. (edemejia@illinois.edu).Keywords: caffeine; coffee; energy drinks.

practices (traditional or organic), post-harvest techniques(wet or dry), duration and conditions of storage, roastingdegree (light, medium, or dark), kind of roasting process(standard or torrefacto), type of commercial coffee (roastedground or instant), and grinding and brewing method(boiled, filtered, or espresso). This means that we neverdrink two cups of coffee with the same chemical composi-tion, even when the coffee comes from the same outlet [2].

A snapshot of caffeine concentration in foodsCaffeine concentration varies among different food pro-ducts, with coffee having in general the highest concentra-tion compared with tea, soft drinks, energy drinks, shotdrinks, and solid foods. A significant variation in caffeineconcentration exists within a beverage category; mostenergy drinks contain mainly caffeine, due to its desiredstimulatory effect on the central nervous system, andtaurine because of its physiological function of enhancingendurance performance and to aid in the reduction of lacticacid build-up after exercise [3]. Chocolate and other cocoa-containing foods, sweets, and snacks contribute smallamounts of caffeine to the diet. Table 1 outlines selectedproducts that are available in the market and their caffeineconcentrations. Box 1 summarizes facts related to caffein-ated beverage (CB) consumption and caffeine intake in theUSA.

The good, the bad, and the ugly of caffeine and coffeeconsumptionDebate persists about whether coffee consumption is ben-eficial or detrimental for human health [4]. Epidemiologi-cal data support the view that habitual coffee consumptionhas several health benefits, including lower risks of Par-kinson’s and Alzheimer’s disease, a favorable effect on liverfunction, a possible role in weight loss (increased metabolicrate, energy expenditure, lipid oxidation, and lipolytic andthermogenic activities), and a decreased risk of developingcertain cancers (endometrial, prostatic, colorectal, liver)[5,6]. Several studies have demonstrated that coffee con-sumption has a significant association with decreased riskof type 2 diabetes (T2D) and that every additional cup ofcoffee is associated with a 7% reduction in disease risk.However, other studies have shown that caffeine alonecauses deterioration of glucose tolerance. Because similarresults are seen for decaffeinated and regular coffee, thismeans that, although caffeinated coffee may induce anincreased glycemic response, other bioactive compoundspresent in coffee, such as chlorogenic acids, other phenoliccompounds, magnesium, and trigonelline, may counteractthis effect by altering glucose absorption, liver glucose

Trends in Endocrinology and Metabolism xx (2014) 1–4 1

Table 1. Caffeine content of selected beverages and foods

Product Serving

size (fl. oz)

Caffeine in one

serving (mg)

Coffee

Regular drip or percolated 8 95–330

Brewed or percolated, decaffeinated 8 3–12

Instant, prepared from powder 8 30–70

Espresso 1 50–150

Tea

Black, regular, brewed or tea bag 8 40–74

Black, decaffeinated 8 2–5

Green, brewed or tea bag 8 25–50

Oolong, brewed or tea bag 8 21–64

White, brewed or tea bag 8 15

Instant, prepared from powder 6 33–64

Yerba mate, brewed or tea bag 8 65–130

Iced tea 12 27–42

Beverages

Carbonated beverages with

caffeine added

12 22–69

Alcoholic beverages with

caffeine added

1 3–9

Energy drinks with caffeine added 8.2–23.5 33–400

Caffeinated waters 16.9–20.0 42–125

Foods

Chocolates 8 oz 0–6

Sweets Various 1–122

Snacks, from US Department of

Agriculture database

1 oz or 1 bar 3–41

Snacks, gums, and mints Various 20–400

Fast foods Various 1–49

Adapted from the 2012 USFDA report on caffeinated food and CBs [Somogyi,

L.P. (2012) Caffeine Intake in the U.S. Population (http://www.fda.gov/downloads/

AboutFDA/CentersOffices/OfficeofFoods/CFSAN/CFSANFOIAElectronicReadin-

gRoom/UCM333191.pdf)].

Box 1. Coffee history and consumption

A taste of history

The name coffee was derived from the Arabic word quahweh and,

in Latin, coffea for the botanical genus [12]. The history of coffee

begins in Ethiopia, where it was discovered in about 850 AD.

Cultivation of coffee bushes was dominated by Yemen and there is

evidence of coffee drinking by the middle of the 15th century. It

disseminated into India, Northern Africa, Turkey, and Balkans.

Coffee was introduced from Mocha (Yemen) to Europe by Venetian

merchants in early 1615. By the end of the 17th century, the use of

coffee in Europe was common and from there it was subsequently

introduced to America [13]. Among the 103 species of coffee

identified, only two, Coffea arabica (arabica) and Coffea canephora

(robusta), produce 99% of the coffee consumed. Coffee is now

grown in 60 tropical and subtropical countries. About 60% of the

coffee produced worldwide comes from the American continent,

where arabica coffee (low bitterness and low caffeine content) is

predominant.

CB consumption and caffeine intake in the USA [11]

� 85% of Americans consume at least one CB per day.

� Among all consumers of CBs, the mean caffeine intake is 165 mg/day.

� The highest caffeine intake occurs in consumers aged 50–64 years

(226 mg/day).

� Coffee is the primary source of caffeine in all age groups.

� Carbonated soft drinks and tea are the major contributors to

caffeine intake in <18-year-olds.

� Consumers of energy drinks represent �10% across all age groups.

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metabolism, incretin release, and insulin sensitivity [5,6].Moreover, the effect of coffee on cardiovascular health is anongoing controversy; coffee consumption was shown tohave adverse effects on serum cholesterol, blood pressure,and plasma homocysteine. However, the effects of coffee onepinephrine concentrations, hyperglycemia, and bloodpressure all appear to be weaker than the effects of thesame amount of caffeine used in isolation. The harmfulcardiovascular effects of caffeine may be offset by thebeneficial effects of other compounds in coffee on thebiological pathways involved in the development of coro-nary heart disease [5,6]. The available evidence on T2Dand cardiovascular effects related to habitual coffee con-sumption is largely reassuring.

In addition, there is no significant relationship betweencoffee consumption and gastric ulcer, duodenal ulcer, re-flux esophagitis, or non-erosive reflux disease. Coffee in-take has been inversely associated with mortality, with thelowest risk among individuals who chronically consumeabout two to four cups per day. Among healthy adults amoderate daily caffeine intake of �400 mg is not associatedwith adverse effects [5–8].

By contrast, coffee intake has been associated withbone loss, lower bone density or fractures (heavy coffeeconsumers), and increased blood pressure. Available evi-dence suggests that pregnant women must restrict theircaffeine intake due to an increased risk of poor fetalgrowth and spontaneous abortion with daily ingestionof 300 mg [5,8].

Excessive caffeine intake has been associated withheadaches, nausea, anxiety, hypertension, and restless-ness. The amount of caffeine required to produce adverseeffects varies from person to person depending on weight,sex, age, and differences in susceptibility. Most consumersexperience, and enjoy, increased alertness, improved moodand focus, and the capacity to remain awake. For others,caffeine can have disagreeable symptoms; some peoplemetabolize caffeine more slowly than others due to vari-ability in the enzymatic activity of the metabolizing en-zyme CYP1A2 (Figure 1). Caffeine also has addictiveproperties, with persistent desire to consume caffeine-con-taining foods or drinks and withdrawal symptoms (head-ache, lethargy, and irritability) when caffeine ingestion isabruptly discontinued [6]. Caffeine also enhances memoryconsolidation [9].

Caffeine’s impact on children and adolescentsChildren (2–12 years) and adolescents (13–17 years) me-tabolize caffeine more rapidly than adults. Children ingeneral consume less caffeine (24–37 mg/day) than adults[10,11]. Children and adolescents, including those diag-nosed as hyperactive, are no more sensitive to the effects ofcaffeine than adults. The more caffeine youngsters con-sume, the less sleep they get, which plays a critical role inlearning; this may eventually lead to other health pro-blems [10]. Children ingest caffeine mostly in the form oftea and carbonated soft drinks [11], which should beavoided, particularly because it is unknown how excessivecaffeine intake impacts the developing brain. Among ado-lescents the consumption of sweetened coffee and energydrinks has increased; these are the principal sources of

Caffeine (CA)

General circula�on

CA

CA CA

T1/2 (↑) preterm neonates, pregnancy, oralcontracep�ves, medica�on, or liver diseaseT1/2 (↓) cigare�e smoking or medica�on

T1/2 = 3-7 h

CA + Proteins↔ CA-Proteins

CA

CA

CA CA

CA

CA

CA

Brain

Mouth

Esophagus

Stomach

100% absorp�on

30-45 min

Small intes�ne

Largeintes�ne

Rectum

Anus

Fetus

Amnio�c fluidUrine

excre�on

Kidney

Liver

CYP450 1A2

Theobromine (12%)

Paraxanthine (84%)

Theophylline (4%)relaxes smooth

muscles

95-99%

Placenta

Reabsorp�on

ClR = 0.078 L/h/kg

Acetyla�on andOxida�on systems

Biotransforma�on of CA matabolites

CA metabolites move into the blood stream

Dimethylxanthines, dimethyl andmonomethyl uric acids, trimethyland dimethylallantoin, uracilderiva�ves and 1-5% of CA

Other organsBlood-brain barrier Breast

Milk

↑ Adenosine receptors (A1 and A2A ) blockage (↑ alertness)↑ Dopamine system (↑ s�mulant effect)↑ Adrenaline (↑ alertness and energy)

↑ lipolysis

↑ urine volume

TRENDS in Endocrinology & Metabolism

Figure 1. Overview of the pharmacokinetics of caffeine in humans. After ingestion, caffeine is absorbed into the general circulation within 30–45 min, although

approximately 90% is cleared from the stomach within 20 min; peak plasma concentrations are reached within 1–1.5 h. The half-life (t1/2) varies widely among individuals

according to age (preterm neonates, 50–100 h), sex (20–30% shorter in females), use of oral contraceptives (increases 5–10 h), pregnancy (9–11 h), certain concurrent

medications (decreases with carbamazepine or rifampicin, increases with cimetidine or ciprofloxacin), cigarette smoking (1.5–3.5 h), and liver function (96 h). Caffeine is

promptly reabsorbed by the renal tubules and only 1–5% is excreted unchanged in urine within 48 h. Infants (8–9 months) excrete 85% in urine. The doses typically

contained in coffee, tea, and soft drinks can result in plasma levels of 20–40 mmol/l and caffeine can act as a competitive inhibitor of brain receptors, occupying adenosine

receptor sites and resulting in increased alertness. Caffeine is absorbed completely and is metabolized mainly by the CYP1A2 isozyme of the hepatic microsomal

cytochrome P450 system. Caffeine undergoes demethylation, resulting in paraxanthine, theobromine, and theophylline. Finally, caffeine metabolites are biotransformed by

microsomal enzymes to dimethylxanthines, dimethyl and monomethyl uric acids, trimethyl and dimethylallantoin, and uracil derivatives, which are filtered by the kidneys

and exit the body in the urine [12,14]. Abbreviations: CA, caffeine; ", increase; #, decrease; Prot., protein; ClR, total plasma clearance.

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caffeine intake (83.2 mg/day) but are below current sug-gested maximal levels for adolescents (2.5 mg/kg bodyweight/day or 100–175 mg/day depending on body weight40–70 kg) [11]. The ingestion of energy drinks with alcoholhas become dangerously popular among adolescents. Caf-feine in energy drinks may mask the drowsiness associatedwith alcohol intake, which may increase the potential foralcohol-related injury. People with heart problems shouldbe especially cautious about mixing caffeine and alcohol;both compounds act to increase heart rate and takentogether can result in cardiac arrhythmias. Moreover,some people may have increased sensitivity to the variousingredients (taurine, glucuronolactone, ginseng, ginkgobiloba, green-tea extract) in energy drinks and thus mayhave an acute physiological response, specifically an in-crease in blood pressure and heart rate [10].

A happy endingA daily intake of three to four 8-oz cups of brewed coffee(a total of �400 mg/day of caffeine) or five servings of

caffeinated soft drinks or tea may be considered a moderateamount (110–345 mg/day) for most adults and appears tobe associated with a neutral to potentially beneficial effecton health. Children (6–12 years) can consume 45–85 mg/day and adolescents 100–175 mg/day [11]. People withdyslipidemia may consider brewed or filtered coffee toavoid cafestol and kahweol; these are the main cholester-ol-raising compounds in coffee and are partly retained byfilters, but are conserved on boiling ground beans. Forthose who are at risk of developing osteoporosis, addingtwo tablespoons of milk can offset the amount of calciumlost from consuming one cup of coffee. The recommenda-tion for women trying to become pregnant is to limit theiringestion of caffeine to <300 mg/day. People with highblood pressure or irregular heart rhythms should also limitcaffeine.

In conclusion, a growing body of evidence from epidemi-ological studies suggests that coffee drinking in most peo-ple is beneficial and inversely associated with risk forvarious diseases. However, because association does not

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prove causation, randomized controlled studies are neededto elucidate the relationship between caffeine consumptionand certain diseases and to analyze patterns of consump-tion with respect to health outcomes. The adverse effects ofconsumption of products containing caffeine by childrenand adolescents are largely unknown because most re-search has been on adults. While researchers work to fillthe gaps in our knowledge, especially with respect toenergy drinks, we can take the position of the AmericanAcademy of Pediatrics, which states that ‘there is no placefor the use of energy drinks in the diets of children andadolescents’; this needs to be reiterated by parents, pedia-tricians, politicians, schools, and coaches.

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quantification of bioactive compounds in coffee brews by HPLC–DAD–MSn. J. Food Comp. Anal. 32, 105–115

3 Heckman, M.A. et al. (2010) Energy drinks: an assessment of theirmarket size, consumer demographics, ingredient profile, functionality,and regulations in the United States. Compr. Rev. Food Sci. FoodSafety 9, 303–317

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7 Shimamoto, T. et al. (2013) No association of coffee consumption withgastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive refluxdisease: a cross-sectional study of 8,013 healthy subjects in Japan.PLoS ONE 8, e65996

8 Bhatti, S.K. et al. (2013) Coffee and tea: perks for health and longevity?Curr. Opin. Clin. Nutr. Metab. Care 16, 688–697

9 Borota, D. et al. (2014) Post-study caffeine administration enhancesmemory consolidation in humans. Nat. Neurosci. 17, 201–203

10 Branum, A.M. et al. (2014) Trends in caffeine intake among U.S.children and adolescents. Pediatrics 133, 386–393

11 Mitchell, D.C. et al. (2014) Beverage caffeine intakes in the U.S. FoodChem. Toxicol. 63, 136–142

12 Heckman, M.A. et al. (2010) Caffeine (1,3,7-trimethylxanthine) infoods: a comprehensive review on consumption, functionality, safety,and regulatory matters. J. Food Sci. 75, R77–R87

13 Fredholm, B.B. (2011) Notes on the history of caffeine use. InMethylxanthines, Handbook of Experimental Pharmacology 200(Fredholm, B.B., ed.), pp. 1–9, Springer-Verlag

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