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Regulatory status of caffeine in the United States
Abstract
This article summarizes the history of the regulation of caffeine, a key component of caffeine-containing energy drinks and other caffeine-containing energy products, in the United States. Caffeine as an ingredient in food has been regulated by the US Food and Drug Administration (FDA) since 1958, when the Food Additives Amendment to the Federal Food, Drug and Cosmetic Act was enacted. It is listed as a substance that is generally recognized as safe by experts for its intended use in cola-type beverages at levels not to exceed 200 parts per million. Here, the history of FDA evaluations of the safe use of, as well as consumer exposure to, caffeine in food in the United States is outlined. Finally, the FDA's current concerns about caffeine and caffeine-containing energy products are reported, along with the current activities to address those concerns.
... The most common sources are coffee beans (Coffea arabica), tea leaves (Camellia sinensis), guarana seeds (Paullinia cupana), cola nuts (Cola nitida/acuminate), yerba mate leaves (Ilex paraguariensis) and cacao beans (Theobroma cacao). [3][4][5][6] Caffeine is one of the most consumed active food ingredients worldwide, mostly in the form of beverages as coffee and tea, but also as soft drinks and energy drinks, in medication, and dietary supplements. Furthermore, caffeine is known for being a central nervous system stimulant which creates highly sought-after effects: increase of mental alertness, decrease of fatigue and improvement of cognition [4,7,8] In general, it has been established that a consumption of 400 mg per day of caffeine would not lead to any adverse effects in a healthy adult. ...
... Furthermore, caffeine is known for being a central nervous system stimulant which creates highly sought-after effects: increase of mental alertness, decrease of fatigue and improvement of cognition [4,7,8] In general, it has been established that a consumption of 400 mg per day of caffeine would not lead to any adverse effects in a healthy adult. [4,6,8] In the European Union (EU), drinks, with the exception of tea and coffee, containing more than 150 mg/mL of caffeine are required to be labeled "high caffeine content" with the exact amount expressed as mg/100 mL. [4,5] In the United States (US), caffeine must be listed as an ingredient but there is no requirement for the quantity of caffeine on the label. ...
... [4] The difficulty of this labeling lies in the variability of the caffeine content in plants, therefore an accurate labeling of the amount of naturally occurring caffeine is complicated. [6] Detection and quantification methods for caffeine have been developed with numerous techniques. Most studies in High Performance Thin Layer Chromatography (HPTLC) aimed at the quantification of caffeine in single herbal powders or extracts such as in green tea leaves, [9] or in mate leaves and mate drinks … [10] In order to avoid numerous methods, the United State Pharmacopeia (USP) is considering harmonization of methods for the identification of botanical origin of caffeine containing herbal drugs. ...
Caffeine is an alkaloid used for long times in food, beverages, medicines, dietary supplements, and in botanicals such as coffee, cacao, cola, guarana, or tea. Today, more and more products are made with caffeine rich extracts from natural sources, or by adding caffeine. In order to prevent confusion about the origin of a caffeine-containing product, a specific method is needed for the determination of the botanical or chemical origin of the caffeine. As caffeine is known to be a central nervous system stimulant that can affect blood pressure and heart rate, all countries in the European Union require drinks (except tea and coffee) with more than 150 mg/L caffeine content to be labeled “high caffeine content”, followed by their caffeine content expressed in mg/100 mL. The United States Department of Agriculture publishes food composition data including levels of caffeine in foods. Until now, there is no regulation for labeling the caffeine content of dietary supplements. This paper describes the development of a harmonized HPTLC method for the determination of the botanical origin of caffeine containing extract, and the detection of added caffeine in cases of adulteration. After identification, the verification of the caffeine content is necessary. In the absence of specific label information, the proposed method can be used to estimate the caffeine content of a product and where specific label information is present, it provides a limit test.
... Caffeine is included in the GRAS (generally recognized as safe) list, as it is used in beverages like cola in accordance with the good manufacturing practices, but the level should not exceed 200 ppm which corresponds to 71 mg of caffeine per 12 ounze serving of cola-type beverages and is considered safe for consumption as per the statement of GRAS (Rosenfeld et al., 2014). Setting up any international standard for caffeine consumption is not easy due to the wide variety of products and varying amounts of caffeine consumed in each country. ...
... To restrict the existing uses and levels of use of caffeine as an added food ingredient, clear information should be declared in the ingredient list on product label. For resolving the issues concerned with the teratogenic and fetotoxic properties of caffeine, FDA further projected to declare caffeine as a food additive on an interim basis pending the completion of safety studies (Rosenfeld et al., 2014). ...
... All ingredients (including caffeine) in a retail food product need to be listed by both their common as well as usual names on the product label. The ingredients present in the packaged food material need to be mentioned in descending order of their proportion by weight (Rosenfeld et al., 2014). ...
Purpose
The purpose of the review paper was to explore the sources of caffeine, its utilization in different food products, along with its impact on human health in terms of benefits and adverse effect.
Design/methodology/approach
The articles reviewed were selected based on the following key descriptors such as caffeine, sources, trends of consumption, utilization, benefits and adverse effects, regulation and labelling.
Findings
There are many physiological effects of caffeine on respiratory, cardiovascular, gastrointestinal, reproductive and central nervous system. It has positive effect in reducing the risk of diabetes, Alzheimer’s disease, Parkinson’s disease, liver injury and at the same time improves mood, psychomotor performance as well as immune response. On the other hand, the negative effects of caffeine include addiction, cancer, heart diseases, insomnia, gastrointestinal disturbances, intoxication etc. Since caffeine when taken in large amount is harmful, therefore as per the regulatory bodies, its concentration should not exceed the set limit and its presence needs to be listed on the label of that particular food product. In nutshell, it can be said that caffeine acts as a boon as well as bane because it possesses both beneficial and adverse effects.
Originality/value
This is a unique and comprehensive review that will provide a brief overview of sources, utilization, healthful as well as harmful effect of caffeine to the readers.
... Relevant to the NP: a. Consumption of up to 400 mg caffeine/d in healthy adults and 300 mg caffeine/d in healthy pregnant women is generally recognized as safe (Hale, 2019;Rosenfeld et al., 2014;Wikoff et al., 2017). b. ...
... The USFDA regulates caffeine levels in foods and dietary supplements; however, there is no requirement to list the amount of caffeine on product labels (Foster, 2017;USFDA & Center for Food Safety and Applied Nutrition, 2018). American Beverage Association (ABA) member companies-representing 95% of energy drinks sold in the United States-comply with the ABA Guidance for Responsible Labeling and Marketing of Energy Drinks and voluntarily include cautionary labels advising against use by children, pregnant/lactating women, and individuals sensitive to caffeine (ABA, 2020; Rosenfeld et al., 2014). Caffeine content varies by product and serving size. ...
... The United States Food and Drug Administration (FDA) has regulated the use of caffeine in food since 1958 (24). Recently, there have been moves to re-evaluate the safety of caffeine in light of the increase in the number of products, and in the popularity of caffeine-containing energy products and their use by children and adolescents (24). ...
... The United States Food and Drug Administration (FDA) has regulated the use of caffeine in food since 1958 (24). Recently, there have been moves to re-evaluate the safety of caffeine in light of the increase in the number of products, and in the popularity of caffeine-containing energy products and their use by children and adolescents (24). Reports also suggest that a significant number of individuals consume more than the commonly cited health reference value of 400 mg/d for healthy adults (25). ...
This study was initiated to examine the effects of caffeine on the DNA damage response (DDR) and homologous recombination (HR). An initial 2 h exposure to 5 mM caffeine slowed a fraction of the cells in G1, but thereafter, continued caffeine exposure permitted this cell fraction to progress through the cycle until they eventually stalled at G2/M and underwent apoptosis. This prolonged caffeine exposure also induced a strong DDR along with subsequent activation of wild-type p53 protein. An unexpected observation was the caffeine-induced depletion of Rad51 (and Brca2) proteins. Consequently, caffeine-treated cells were expected to be inefficient in HR. However, a dichotomy in the HR response of cells to caffeine treatment was revealed. Caffeine treatment rendered cells significantly better at performing the nascent DNA synthesis that accompanies the early strand invasion steps of HR. Conversely, the increase in nascent DNA synthesis did not translate into a higher level of gene targeting events. Levels of Rad51 appear to be irrelevant. Thus, prolonged caffeine exposure stalls the cell cycle, induces a p53-mediated apoptotic response and a down-regulation of critical HR proteins, and stimulates early steps of HR, but not the formation of complete repair products.
... In addition to caffeine, these products may contain other ingredients such as sugars, natural or artificial sweeteners, fruit juice or artificial flavours, food additives, and often other ingredients such as herbal extracts, and vitamins. The amount of caffeine in formulated beverages has especially been a topic of interest (Rosenfeld et al. 2014;Harris and Munsell 2015). While up to 400 mg caffeine per day is considered a safe level of consumption for adults, a lower intake of not more than 2.5 mg kg −1 bodyweight per day has been recommended for children and adolescents to prevent adverse effects (Wikoff et al. 2017). ...
... The LDTD-MS/MS results were generally consistent with product labelling (Table 2), with 6 of the 7 drinks having measured caffeine values within 11% of the amount stated on their product labels. While many manufacturers choose to quantitatively label caffeine in their products, it is not required (Rosenfeld et al. 2014;Harris and Munsell 2015). Batch-to-batch variations can occur in products that contain caffeine from plant sources (e.g. ...
A rapid method for quantitative caffeine analysis in carbonated and non-carbonated beverages and liquid dietary supplement products was developed based on the direct sample introduction technique of laser diode thermal desorption atmospheric pressure chemical ionisation with tandem mass spectrometry (LDTD-MS/MS). Product samples were diluted with a mixture of methanol, water, and d3-caffeine internal standard. Sample aliquots were filtered, spotted on a metal-lined LDTD microtitre plate, dried, and thermally desorbed for subsequent ionisation and analysis by MS/MS analysis. Each sample required a 6 s desorption, and sample-to-sample analysis time of less than 30 s per sample. Caffeine yielded a linear calibration curve over the range 0.5–100 μg mL⁻¹ (R² > 0.995). Caffeine recoveries from fortified samples ranged from 97% to 107% with <5% RSD. The caffeine determination was not affected by matrix interferences despite the large range of ingredients, vitamins, sweeteners, extracts, and additives present in the products tested, even though LDTD-MS/MS is a whole-sample desorption technique with no separation of matrix background. The method detection limit was below 0.12 μg mL⁻¹. The method was applied to 33 caffeinated products and LDTD-MS/MS quantitative results closely correlated (R² > 0.998) with the regulatory standard HPLC-UV method (AOAC Official Method 979.08).
... The mean age among the 153 CAERS multiple product cases was 39·5 years (SD = 14·0 years; minimum = 11 years; maximum = 79 years; n 12, 7·8 % were missing age data), (20) . (30) . ‡The χ 2 test indicated statistically significant differences at P < 0·05. ...
... Changes in designation of energy drink products made by the manufacturers themselves, such as with Rockstar ® and Monster ® in 2013 (29) , from dietary supplements to conventional foods/beverages subject to different regulatory requirements (30) , may have contributed somewhat to the capture of fewer CAERS energy drink adverse events in the later years of the study period. However, voluntary reports decreased after 2012, as well. ...
Objective
To describe and compare caffeinated energy drink adverse event (AE) report/exposure call data from the US Food and Drug Administration Center for Food Safety and Applied Nutrition’s Adverse Event Reporting System (CAERS) and the American Association of Poison Control Centers’ National Poison Data System (NPDS).
Design
Cross-sectional.
Setting
Data were evaluated from US-based CAERS reports and NPDS exposure calls, including report/exposure call year, age, sex, location, single v . multiple product consumption, outcome, symptom, intentionality (NPDS only), report type, product name (CAERS only).
Participants
The analysis defined participants (cases) by the number of caffeinated energy drink products indicated in each AE report or exposure call. Single product cases included 357 from CAERS and 12 822 from NPDS; multiple product cases included 153 from CAERS and 931 from NPDS.
Results
CAERS v . NPDS single product cases were older and more frequently indicated serious symptoms. Multiple v . single product consumers were older in both. In CAERS, unlike NPDS, most multiple product consumers were female. CAERS single v . multiple product reports cited higher proportions of life-threatening events, but less often indicated hospitalization and serious events. NPDS multiple v . single product cases involved fewer ≤5-year-olds and were more often intentional.
Conclusions
Despite limitations, both data sources contribute to post-market surveillance and improve understanding of public health concerns.
... For adults, Denmark, U.K., Portugal, Canada, and USA advise to limit caffeine intake to 300 or 400 mg/day. FBDG for Australia, Indonesia, New Zealand, Denmark, Hungary, Malta, Colombia, USA, and Canada state specific concerns for energy drinks, generally defined as any drink with >150 mg of caffeine/liter, but often contain other bioactive ingredients and sugar [16,78]. Some guidelines to avoid or limit caffeine intake were based on human or animal studies of pregnancy outcomes, fetal development, and acute caffeine effects (including diuresis, see below). ...
... While FBDG help individuals optimize their caffeine habits, many countries regulate caffeine intake at the food manufacturing level by setting limits to the amount of caffeine added to foods [78,96]. Several countries have specifically enacted measures to regulate the labeling, distribution, and sale of energy drinks [2,8,97,98]. ...
Coffee, tea, caffeinated soda, and energy drinks are important sources of caffeine in the diet but each present with other unique nutritional properties. We review how our increased knowledge and concern with regard to caffeine in the diet and its impact on human health has been translated into food-based dietary guidelines (FBDG). Using the Food and Agriculture Organization list of 90 countries with FBDG as a starting point, we found reference to caffeine or caffeine-containing beverages (CCB) in 81 FBDG and CCB consumption data (volume sales) for 56 of these countries. Tea and soda are the leading CCB sold in African and Asian/Pacific countries while coffee and soda are preferred in Europe, North America, Latin America, and the Caribbean. Key themes observed across FBDG include (i) caffeine-intake upper limits to avoid risks, (ii) CCB as replacements for plain water, (iii) CCB as added-sugar sources, and (iv) health benefits of CCB consumption. In summary, FBDG provide an unfavorable view of CCB by noting their potential adverse/unknown effects on special populations and their high sugar content, as well as their diuretic, psycho-stimulating, and nutrient inhibitory properties. Few FBDG balanced these messages with recent data supporting potential benefits of specific beverage types.
... [7][8][9][10] The large content of caffeine present in energy drinks is responsible for the advertised stimulatory effects, with many containing well over the amount determined by the Food and Drug Administration (FDA) to be generally recognized as safe (GRAS) for use in cola-type beverages. 7,9,11,12 Caffeine is structurally similar to the compound adenosine and can bind receptors in its place, thus inhibiting the functionality of adenosine. [7][8][9][12][13][14][15] This blocking results in enhanced catecholamine secretion, which stimulates the central nervous system and results in the consumer having the perception of increased energy. ...
... 9 Although energy drinks contain levels well over what is considered GRAS by the FDA for cola-type beverages, they are allowed to be marketed and sold at various locations providing that caffeine is included in the ingredients list on the container. [10][11][12] The Dietary Guidelines for Americans 2015-2020 recommends that adults, who are typical caffeine consumers, do not ingest more than 400 mg caffeine per day. 16 Consumption levels that are safe for children and adolescents have not been determined; however, youth are discouraged from consuming large doses of caffeine and should not exceed 100 mg per day. ...
Energy drinks are beverages marketed to quickly increase alertness and performance of the consumer that typically contain relatively high quantities of caffeine, simple carbohydrates, and a mixture of additional ingredients. The carbohydrate sources, usually glucose and sucrose, found in the beverages supply the substrates needed for physiological energy, while the high caffeine content supplies the perceived energy through enhancing feelings of alertness during fatigued states. Although mean youth caffeine consumption as a whole has decreased over the past 2 decades, adolescent energy drink consumption has significantly increased in the past 10 years. High energy drink consumption of youth is concerning due to the range of reported adverse reactions attributed to excessive caffeine consumption, ranging from mild sleep disturbances to death. Reactions are severe enough to require reporting to the National Poison Data System and may even require emergency medical treatment. Studies have also shown that adolescents who consume energy drinks are likely to also use tobacco, alcohol, and illicit drugs. There is substantial evidence to suggest that the risk energy drinks pose to health are incredibly hazardous and should not be consumed by children and adolescents.
... Las preocupaciones que surgen alrededor de todo esto, se basan principalmente en los siguientes argumentos: a) el uso indiscriminado de las bebidas energizantes va en aumento y cada vez más informes sugieren que las personas están consumiendo más de 400 mg/día de cafeína, valor que comúnmente se ha referenciado como "seguro" (7); b) aunque la cafeína y su concentración sean etiquetadas en las bebidas energizantes, es factible que su cantidad real sea mayor que la referenciada, si las bebidas contienen productos a base de plantas, por ejemplo, café, guaraná o chocolate; c) otros productos diferentes a las bebidas energizantes contienen cafeína, entre ellos gomas de mascar y dulces, que no necesariamente la tienen en la etiqueta, lo que lleva a que la ingesta diaria de cafeína sea mayor que lo calculado; d) la población infantil y adolescente puede ser sujeto de su consumo, y en la actualidad se debaten los riesgos para la salud en estos grupos etarios, relacionados en gran medida con los efectos sobre el sistema nervioso (8); e) hay variación individual en la sensibilidad a la cafeína, aun en consumidores sanos (9). Estas situaciones nos motivaron a revisar los beneficios y riesgos del consumo de estas bebidas. ...
... Dado que la cafeína hace parte fundamental de las bebidas energizantes, sus fabricantes tienden a clasificarlas como alimentos convencionales, o mejor, como bebidas convencionales (8). Desde 1958, la cafeína es una sustancia regulada por la FDA (Food and Drug Administration) de los Estados Unidos como una sustancia generalmente reconocida como segura (GRAS, por la sigla en inglés de Generally Recognized As Safe) para su uso en las bebidas tipo cola en concentraciones que no excedan el 0,02 % (8). ...
Energy caffeinated beverages are composed mainly of caffeine, carbohydrates and dietary supplements. Although manufacturers claim that these drinks are safe and many consumers perceive that also, there is concern about the possibility that adverse events may occur with their consumption. This led us to review the literature with emphasis on the cardiovascular and neurological risks. It was found that the major health complaints (headache, sleep disorders, irritation and fatigue) were more frequent in consumers than in non-consumers. Emergency room visits motivated by the use of energy drinks were more frequent when there was co-ingestion of ethanol and other drugs. The main cause of cardiovascular emergency consultation was arrhythmia and the neurological one, seizure. The evidence found was of poor quality, which prevented establishing a causal link between the consumption of these drinks and such risks. On the other hand, interpretation of the toxicity of these preparations is complicated because several variables should considered such as dose, individual sensibility, consumption habits, smoking, and co-ingestion of other substances, etc., in order to assess their real risk. Despite this, concomitant consumption of these beverages and ethanol seems to be a risk factor for toxicity.
... Currently, the FDA (2011, 2016b) declares that caffeine is generally recognized as safe up to a level of 0.02% or 200 parts per million, which is approximately 71 mg of caffeine per 12 oz (Reissig et al., 2009). The FDA also adds that overall consumption of caffeine is said to be safe up to 400 mg per day (FDA, 2013;Rosenfeld, Mihalov, Carlson, & Mattia, 2014). Average cups of coffee and soda beverages fit well within these suggested limitations; however, the energy drink marketplace has changed dramatically with excessive caffeine concentrations. ...
... This underrepresentation is true because it is not totaled with other ingredients with stimulating effects, such as guarana (Moustakas et al., 2015). For dietary supplements, the amount of caffeine used as an ingredient must be listed (Rosenfeld et al., 2014), but the quantity does not need to be listed. If the added caffeine is part of a proprietary blend, then the total amount of the blend must be listed, but not necessarily the amount of caffeine itself (Kole & Barnhill, 2013). ...
To date, whether individuals with mental illness use high energy drinks (HED) to offset their symptoms, or whether their use began after diagnosis or psychoac-tive drugs were prescribed is unknown. Their degree of knowledge regarding their symptoms, diagnosis, or what strategies they have used to feel better is also undetermined. A search of the literature yielded no studies about these areas or domains. The current article provides background information on caffeine and HED, with or without alcohol, and the use patterns of consumers of mental health services, as well as their attitudes and knowledge. Participants in the Network for Psychiatric Nursing Researchers, who were consumers, influenced the current study group to expand their thinking about how to address the unknown areas. Their related work and publication are described.
... According to the FDA, a caffeine content of 0.02% (200 parts per million) is generally recognized as safe (GRAS) for use in cola-type beverages (19,20). There are no specific guidelines for caffeine intake in the United States. ...
... Taken together, these findings suggest that caffeine intake has generally remained stable or declined slightly in children overall in most studies; in caffeine consumers 2-11 y of age, significant declining trends were noted. The trends in coffee intake are likely related to a shift in patterns of caffeine sources: declining soda consumption and an increase in caffeine from coffee among children of all ages (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and in energy drinks (among adolescents aged 12-19 y). If these trends of increased coffee and energy drink consumption continue, the decline in caffeine intake via decreased soda consumption would not be offset and would likely be associated with an overall increase in caffeine consumption, particularly among older children over time. ...
There is increasing concern about potential adverse effects of caffeine in children. Our understanding of caffeine intake relies on studies dating to the late 1990s. This article synthesizes information from national studies since then to describe caffeine consumption, its association with sociodemographic factors, key dietary sources including caffeine-containing energy drinks (CCEDs), and trends in caffeine intake and sources among US children. Findings from the Kanter Worldpanel (KWP) Beverage Consumption Panel and the NHANES showed that caffeine consumption prevalence was generally consistent across studies and over time; more than one-half of 2- to 5-y-olds and ∼75% of older children (>5 y) consumed caffeine. The usual intakes of caffeine were 25 and 50 mg/d for children and adolescents aged 2-11 and 12-17 y, respectively (NHANES 2007-2010). Caffeine consumption correlated with age and was higher in non-Hispanic white children. The key sources of caffeine were soda and tea as well as flavored dairy (for children aged <12 y) and coffee (for those aged ≥12 y). The frequency of CCED use varied (2-30%) depending on study setting, methods, and demographic characteristics. A statistically significant but small decline in caffeine intake was noted in children overall during the 10- to 12-y period examined; intakes remained stable among older children (≥12 y). A significant increasing trend in CCED and coffee consumption and a decline in soda intake were noted (1999-2010). In 2009-2010, 10% of 12- to 19-y-olds and 10-25% of caffeine consumers (aged 12-19 y) had intakes exceeding Canadian maximal guidelines. Continued monitoring can help better understand changes in caffeine consumption patterns of youth.
© 2015 American Society for Nutrition.
... Excessive CAF intake may cause adverse effects, including sleep deprivation, increased risk of cardiovascular disease, reduced fertility, and increased incidence of miscarriage [8,9]. According to regulations issued by the US Food and Drug Administration, the concentration of CAF as an ingredient in food and beverages should be limited to 200 parts per million (ppm) (0.02%) [10]. Therefore, an effective, industryoperational preparation method should be developed to obtain enriched EGCG green tea extract with as little CAF content as possible for use in pharmaceuticals, functional foods, and beverages. ...
(–)-Epigallocatechin gallate (EGCG) is a bioactive component of green tea that provides many health benefits. However, excessive intake of green tea may cause adverse effects of caffeine (CAF) since green tea (30–50 mg) has half the CAF content of coffee (80–100 mg). In this work, for enhancing the health benefits of green tea, natural rubber/hexagonal mesoporous silica (NR/HMS) nanocomposites with tunable textural properties were synthesized using different amine template sizes and applied as selective adsorbents to separate EGCG and CAF from green tea. The resulting adsorbents exhibited a wormhole-like silica framework, high specific surface area (528–578 m2 g−1), large pore volume (0.76–1.45 cm3 g−1), and hydrophobicity. The NR/HMS materials adsorbed EGCG more than CAF; the selectivity coefficient of EGCG adsorption was 3.6 times that of CAF adsorption. The EGCG adsorption capacity of the NR/HMS series was correlated with their pore size and surface hydrophobicity. Adsorption behavior was well described by a pseudo-second-order kinetic model, indicating that adsorption involved H-bonding interactions between the silanol groups of the mesoporous silica surfaces and the hydroxyl groups of EGCG and the carbonyl group of CAF. As for desorption, EGCG was more easily removed than CAF from the NR/HMS surface using an aqueous solution of ethanol. Moreover, the NR/HMS materials could be reused for EGCG adsorption at least three times. The results suggest the potential use of NR/HMS nanocomposites as selective adsorbents for the enrichment of EGCG in green tea. In addition, it could be applied as an adsorbent in the filter to reduce the CAF content in green tea by up to 81.92%.
... Caffeine also inhibits adenosine and gamma-aminobutyric acid (GABA) receptors and increases intracellular calcium release. Clinically, it improves and enhances BARCELONA RESPIRATORY NETWORK cognition and memory, while reducing fatigue and drowsiness 16 . Caffeine citrate has been used to treat apnea of prematurity. ...
Phosphodiesterase (PDE) inhibitors act on specific phosphodiesterase enzymes (fundamentally 3, 4 and 5), which are characterized by their expression in different organs. Currently, their use is approved for the treatment of chronic obstructive pulmonary disease (COPD), erectile dysfunction, pulmonary arterial hypertension, psoriasis, psoriatic arthritis and atopic dermatitis. Although the experiences with most have been negative, phosphodiesterase inhibitors (especially type 4) have shown positive results, as they are able to provide additional benefits in patients who are not adequately controlled with bronchodilators, either with or without inhaled corticosteroids. To date, roflumilast is the only drug that has met these expectations in the treatment of a specific COPD phenotype (COPD associated with chronic bronchitis). Work is currently underway to develop more selective inhibitors that, by modulating PDE in specific tissues and cells, can improve the therapeutic effect in a specific organ with fewer side effects.
... Caffeine is a psychoactive drug of the xanthines family with proven health and cognition benefits. Caffeine is the basis of a multibillion industry world wide and belongs to a short list (nicotine, theobromine, theophylline, etc.) of alkaloids that are legal to consume without limitations but whose content in food, beverages, and supplements is regulated by the FDA [1]. Synthetic routes are available [2] to produce the industrial quantities needed for the global demand that caffeine of natural origins cannot satisfy. ...
High level DLPNO–CCSD(T) electronic structure calculations with extended basis sets over B3LYP–D3 optimized geometries indicate that the three methyl groups in caffeine overcome steric hindrance to adopt uncommon conformations, each one placing a C–H bond on the same plane of the aromatic system, leading to the C–H bonds eclipsing one carbonyl group, one heavily delocalized C–N bond constituent of the fused double ring aromatic system, and one C–H bond from the imidazole ring. Deletion of indiscriminate and selective non-Lewis orbitals unequivocally show that hyperconjugation in the form of a bidirectional –CH3 ⇆ aromatic system charge transfer is responsible for these puzzling conformations. The structural preferences in caffeine are exclusively determined by orbital interactions, ruling out electrostatics, induction, bond critical points, and density redistribution because the steric effect, the allylic effect, the Quantum Theory of Atoms in Molecules (QTAIM), and the non-covalent interactions (NCI), all predict wrong energetic orderings. Tiny rotational barriers, not exceeding 1.3 kcal/mol suggest that at room conditions, each methyl group either acts as a free rotor or adopts fluxional behavior, thus preventing accurate determination of their conformations. In this context, our results supersede current experimental ambiguity in the assignation of methyl conformation in caffeine and, more generally, in methylated xanthines and their derivatives.
... This may be the cause of different sicknesses such as nausea, vomiting, restlessness, anxiety, depression, tremors, and difficulty sleeping. The acceptable range of caffeine for the average adult is 250 mg per day [8]. Caffeine added as a flavouring agent and to make the drinks acceptable among people and as addictive chemical [5]. ...
Three groups of energy drinks have been examined for sodium benzoate and caffeine using HPLC and spectrophotometer methods. Those brands include original UK brand which coded (RE), another two brands of (RL and B) which are imported from Austria to local companies, and the rest produced locally which are coded (T, FB, S and FE). The results showed that all brands contain sodium benzoate at different concentrations. FB brand comes out on top by containing around 416mg/l which was far above the permitted level by FAO/WHO, on the other hand the RE brand contained the lowest amount of sodium benzoate when analysed using HPLC. Results of caffeine examination showed that all samples contained lower levels of caffeine as it is claimed in their label to contain 300mg/l, in contrary to sodium benzoate the lowest concentration of caffeine found in the FB brand which was 13.78mg/l and the highest level of caffeine was found in FE brand which was 208.95mg/l. From the obtained results it is clear that none of the energy drink brands declared the actual content of both caffeine and sodium benzoate which usually required by food legislation and law. Therefore, it is considered as mislabelling which is recommended that the health authorities in our country to subject the local producers and the importers to present the required information on the labels without misleading consumers. It is also recommended to educate the population and put restriction on the local shops and supermarkets not to sell energy drinks to individuals under 16 years old.
... 37 FDA 2003 yılında aldığı kararla içeceklerdeki maksimum kafein oranının %0.02 olması gerektiğini vurgulamıştır fakat yapılan çalışmalar birçok enerji içeceğinde bu orana uyulmadığını göstermiştir. 38 Ayrıca etiketlemede 12 yaş altı bireylere satılmaması, 12 yaş üstü bireylere ise her 3-4 saatlik aralıklar da 100-200 mg'lık dozların aşılmaması gerektiğinin etiketlenmesi gerektiği bildirilmiştir. 16 Etiketleme yöntemindeki farklılıklar değerlendirildi-ğinde sporcuların enerji içecekleri tüketirken dikkatli olması gerektiğini göstermektedir. ...
... The caffeine content in each cup calculation was done based on estimates reported in several studies and the United States (US) Food and Drug Administration (FDA) database, which has provided the caffeine content in beverages and drugs. These values when multiplied by the average size of one cup (240 ml for regular coffee and 25 ml for Arabic Gahwa) and the number of cups will give an estimate of the caffeine content consumed [17][18]. ...
Introduction
In our clinical practice, we have encountered patients who reported the failure of local anesthesia due to excessive coffee consumption and required higher-than-normal doses of local anesthesia. Therefore, our study aimed to assess the awareness and knowledge of coffee consumption, its effect on local anesthesia, and the available scientific evidence among the public, patients, and clinicians in dental practice.
Material and Methods
A cross-sectional survey with two sets of questionnaires was designed based on the Likert scale. A 5-point scale was used to assess agreement and frequency. Yes/no and open-ended questions were used for the assessment. Questionnaires were distributed among the clinicians, patients, and the public. Data were analyzed with descriptive linear statistics.
Results
Of the 430 responses provided by patients and the general public, more than 40% believed that the local anesthetic failure was caused by excessive coffee consumption. Among the 235 responses provided by the clinicians, 65% of the clinicians reported encountering patients with local anesthesia failure and believed it could be due to excessive coffee consumption. However, only 9% of the clinicians were aware of scientific evidence regarding the effect of coffee consumption on local anesthesia failure.
Conclusion
Surprisingly, the majority of clinicians believed that caffeine had an effect on the reduction of local anesthesia; however, only a few of them had scientific knowledge. The available scientific evidence relates that caffeine can influence cognitive performance by increasing alertness, as well as sleep deprivation causing stress and anxiety, which partially explains the local anesthetic failure among coffee consumers. Therefore, a stress reduction protocol should be a routine daily practice for a dentist to reduce the failure rate of local anesthesia.
... Caffeine levels in brewed beverages can exhibit wide variation depending on the source and the preparation method [22][23][24][25]. Even when purchased from the same vendor, they can vary by as much as 46% from day-to-day [23]. is can present an issue for those wishing to monitor their caffeine consumption for religious [26], sporting [10][11][12], or medical reasons [2,15] and can be a problem for suppliers and manufactures [27]. ...
An extraction-free method requiring microliter (μL) volumes has been developed for the determination of caffeine in beverages. Using a pyrolysis-gas chromatography mass spectrometry system, the conditions required for the direct thermal desorption-gas chromatography mass spectrometry (TD-GC/MS) determination of caffeine were optimised. A 5 μL aliquot was introduced to the thermal desorption unit, dried, and thermally desorbed to the GC/MS. The response was linear over the range 10 to 500 μg/mL (R2 = 0.996). The theoretical limit of detection (3 σ) was 0.456 μg/mL. No interferences were recorded from endogenous beverage components or from commonly occurring drugs, such as nicotine, ibuprofen, and paracetamol. Replicate caffeine determinations on fortified latte style white coffee and Pepsi Max® gave mean recoveries of 93.4% (%CV = 4.1%) and 95.0% (%CV = 0.98%), respectively. Good agreement was also obtained with the stated values of caffeine for an energy drink and for Coca-Cola®. These data suggest that the method holds promise for the determination of caffeine in such samples.
... It is a widely used compound in the pharmaceutical and personal care products industries, food industries and many others sectors, therefore it is present in a wide variety of products consumed daily by the world population. 3 Proving this large presence in many products, for example, so and energy drinks, according to the Food and Drug Administration (FDA), a can of so drink contains around 30-40 mg of caffeine, while just 236 mL of energy drink contain 40-250 mg of caffeine. 4 The FDA recommends the highest level of caffeine in beverages should not exceed 200 mg L À1 . ...
Caffeine is an element that is consumed worldwide. It is present in many products such as beverages, chocolate, coffee, tea, energy drinks and medicines. Portable 3D devices working together with colorimetric and fluorimetric reactions have been able to determine the presence of caffeine in different kinds of samples. Also, digital image-based methods using smartphones have conferred portability and accessibility to miniaturized devices that are innovative and promising options for quick and low cost analyses. This study proposes a miniaturized fluorimetric device to determine caffeine by digital image using a smartphone. The OpenCamera app was used to capture images that were processed using ImageJ software to obtain RGB channels values. The red (R) channel signal intensity was selected as the analytical response. The device developed was applied to determine caffeine in an energy drink and medicines. The method developed presented a linear range from 100 to 600 mg L⁻¹ of caffeine, and quantification (LOQ) and detection (LOD) limits of 100 mg L⁻¹ and 30.0 mg L⁻¹, respectively. The caffeine concentration found in the products analyzed was 328 mg L⁻¹ (±2.5%) for the energy drink, 345 mg L⁻¹ (±15%) for medicine A and 322 mg L−¹ (±7.3%) for medicine B. The proposed device presented important characteristics such as low cost, required small volumes of reagents and samples, quick analysis, portability and suitable to be applied in complex matrices.
... It is worth adding that the overuse of caffeine has been recently defined as 'Caffeine Use Disorder' in the classification of Substance-Related and Addictive Disorders in the fifth edition of the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which is also being considered by other countries [32]. While t current concerns of the US Food and Drug Administration about caffeine and caffeine-containing energy products has been reported recently, along with the current activities to address those concerns, there are no such publications in Poland [33]. ...
Introduction
Recent studies have revealed an increase in the consumption of dietary supplements including frequency
of use of caffeine, which is addictive and potentially harmful in higher doses. Energy drinks include high doses of caffeine
and are particularly targeted at young people.
Objective
The aim of the study was to investigate the frequency of use of caffeine-containing energy products, associated factors and understanding the associated side- effects in university students.
Material and methods
A cross-sectional questionnaire-based survey was conducted among students of the 5 largest
Universities in Krakow. Statistical significance was set at the 0.05 level.
Results
Around 35% of respondents reported the use of different supplements including high doses of caffeine. Frequency
of caffeine-containing products consumption was significantly higher in female students compering to males. Also, those respondents who originated from big cities were more likely to use caffeine-containing products. The study revealed that these substances were also more popular among those participants who study economics. Most students use these substances in order to reduce feeling tired and the duration of sleep, others mainly to increase concentration prior to examinations. Almost one fourth of the group who used these substances admitted to having experienced some sideeffects in the past. They suffered mainly from insomnia, but also from excessive stimulation and muscle trembling. Almost half of the substances users did not know of any potential side-effects.
Conclusions
Attempts should be made to increase public awareness of the side-effects of these substances, particularly
among the student population. These campaigns should be targeted especially at female students who come from bigger
cities. This study is a step towards drawing attention to this issue.
... It acts as a stimulant. Caffeine is included in the GRAS (generally recognized as safe) list as it is used in beverages like cola in accordance with the good manufacturing practices, but the level should not exceed 200 ppm, which corresponds to 71 mg of caffeine per 12-ounce serving of cola-type beverages (29). Caffeine when administered gets readily absorbed in the body and it reaches the brain after 5 minutes of consumption (30) and is also eliminated with an average half-life of 5 hours from the body (31). ...
Background: The purpose of this review paper was to explore the components and their respective health effects and safety aspects regarding the consumption of diet drinks (DDs).
Methods: A wide variety of the relevant publications (published before 2018) were identified through searching electronic databases (ScienceDirect, PubMed, SciELO, Google Scholar, Springer Link, and ResearchGate) on the basis of different keywords such as diet drink, market status, consumption pattern, composition, health effects, and regulations related to DDs. After the search of suitable literature, 139 papers were screened and reviewed.
Results: Numerous brands of DDs have been introduced in the market along with a wide variety of modifications in order to attract the consumers of all age groups along with their respective professions. The major components of DDs are caffeine, taurine, ginseng, guarana, sodium, potassium, and sweeteners that contribute to the good taste, stimulating effect, increased performance and cognitive function, and reduced stress. However, ingestion of DDs over a prolonged course of time can pose multiple deleterious effects, i.e., intoxication, affective disorder, hypertension, reproductive toxicity, and neurological disorders. Consequently, different regulatory bodies of respective countries have formulated and enforced rules and regulations regarding the composition, consumption, labeling, distribution, and sales of DDs.
Conclusions: An awareness regarding the components, consumption, and health effects is greatly required in the present era, and authors have tried to fill this gap.
• Key teaching points
• Rise in socio-economic status, health awareness and change in dietary lifestyle are the major factors that fuel the demand of diet drinks; which has been witnessed by a drastic increase in the consumption pattern of the diet drinks among young to middle-age adults since last decade.
• A wide variety of the ingredients are used in the preparation of diet drinks including caffeine, ginseng (Panax ginseng), guarana (Paullinia cupana), taurine, artificial sweeteners, B Vitamins, sodium, potassium etc.
• Diet drinks are generally served cold and contain high levels of caffeine and other artificial sweeteners; which based on dosage, have been known to be beneficial as well as harmful.
• These ingredients possess numerous health benefits including anti-hypertensive, anti-oxidant, anti-cancer properties, improved metabolic functions, stress reduction and enhanced endurance, exercise and performance and increased cognitive function.
• A wide range of the adverse health effects such as nervousness, sleeplessness, behavioral changes, decreased appetite, heart palpitations, nausea, vomiting, dehydration etc. is being possessed by diet drinks upon the ingestion of these drinks over a prolonged course of time.
• Regulatory bodies should determine the safe limits of all ingredients for different age groups to get maximum health benefits.
... [1,3] Because of undetermined effects from maternal caffeine intake on the fetus and the increased number of caffeine products available for prenatal consumption, health authorities such as the World Health Organization (WHO) and the Food and Drug Administration (FDA) have developed recommendations restricting caffeine intake during pregnancy and declaring caffeine consumption during pregnancy a global healthcare problem. [3][4][5] Over the last decade, organ-on-a-chip technology has grown to become one of the most popular alternatives for drug testing and toxicology in vitro. Its aim is to create a 3D microenvironment reminiscent of specific human organs as a means for replicating their functionality. ...
Due to the particular structure and functionality of the placenta, most current human placenta drug-testing methods have been limited to animal models, conventional cell testing, and cohort/controlled testing. Previous studies have produced inconsistent results due to physiological differences between humans and animals and limited availability of human and/or animal models for controlled testing. To overcome these challenges, we have developed a placenta-on-a-chip system for studying the exchange of substances to and from the placenta. We studied caffeine transport across the placental barrier, because caffeine is a xenobiotic widely consumed on a daily basis. Since a fetus does not carry the enzymes that inactivate caffeine, when it crosses a placental barrier, high caffeine intake may harm the fetus, so it is important to quantify the rate of caffeine transport across the placenta. In this study we performed a quantitative analysis of caffeine transport across the placental barrier when a caffeine concentration of 0.25 mg/ml is introduced into maternal blood flow in vitro, with changes observed over a span of 7.5 hours. A steady caffeine concentration of 0.1513 mg/ml was reached on the maternal side after 6.5 hours, and a 0.0033 mg/ml concentration on the fetal side was achieved after 5 hours.
... Reviews of caffeine intake continue to reinforce its safety from conventional food and beverage sources, including energy drinks. Nevertheless, the U.S. Food and Drug Administration (FDA) has expressed interest in learning about patterns of caffeinated beverage consumption (Rosenfeld et al., 2014). The FDA noted that better characterization of the poorly understood concept of potential clustering of caffeine intake within a particular 'time of day' or 'day of week' may be warranted. ...
Characterization of ‘hour-of-day’ or ‘day-of-week’ caffeine intake for the National Health and Nutrition Examination Survey (NHANES) population is limited. No study has focused on patterns from an individual perspective. The NHANES 2013–2016 survey respondents’ dietary recalls were analyzed to gain a better understanding of caffeine intake patterns for different caffeinated beverage consumer types - defined by beverage type consumed and daily caffeine intake levels. Dominant caffeinated beverage consumers (≥143 mg) were identified by a reported daily caffeine intake level greater than or equal to the 50th percentile among those 1–80 y. Dominant caffeinated beverage consumers - irrespective of age groups investigated - typically reported the greatest caffeine intake early in the day from coffee. Analyses by consumer type, relevant age brackets and ‘hour-of-day’ or ‘day-of-week’ indicated that caffeinated beverage consumers generally do not cluster multiple caffeine intake events over short periods of time (i.e., less than fours). Dominant caffeinated beverage consumers appear to maintain a relatively stable daily caffeine intake by substitution of secondary sources of caffeine. Only a small fraction (4.1%) of individuals within 13–29 y respondents consumed caffeine at levels in excess of 400 mg/day, compared to 14% within the 30–80 y old survey respondent group.
... Some industry organizations now recommend or require that their members disclose caffeine content (mlligrams per serving) when products contain >5 mg caffeine/serving either from caffeine added as a dietary ingredient or present in an herbal ingredient. This will enhance the potential to use the DSLD to assess caffeine intake from dietary supplements (19,20). ...
Objective:
To describe the history, key features, recent enhancements, and common applications of the Dietary Supplement Label Database (DSLD).
Background and history:
Although many Americans use dietary supplements, databases of dietary supplements sold in the United States have not been widely available. The DSLD, an easily accessible public-use database was created in 2008 to provide information on dietary supplement composition for use by researchers and consumers.
Rationale:
Accessing current information easily and quickly is crucial for documenting exposures to dietary supplements because they contain nutrients and other bioactive ingredients that may have beneficial or adverse effects on human health. This manuscript details recent developments with the DSLD to achieve this goal and provides examples of how the DSLD has been used.
Recent developments:
With periodic updates to track changes in product composition and capture new products entering the market, the DSLD currently contains more than 71,000 dietary supplement labels. Following usability testing with consumer and researcher user groups completed in 2016, improvements to the DSLD interface were made. As of 2017, both a desktop and mobile device version are now available. Since its inception in 2008, the use of the DSLD has included research, exposure monitoring, and other purposes by users in the public and private sectors.
Future directions:
Further refinement of the user interface and search features to facilitate ease of use for stakeholders is planned.
Conclusions:
The DSLD can be used to track changes in product composition and capture new products entering the market. With over 71,000 DS labels it is a unique resource that policymakers, researchers, clinicians, and consumers may find valuable for multiple applications.
... The FDA has given caffeine a classification of "Generally Recognized as Safe" (GRAS) for use in cola-type products at concentrations of 0.02% based on industry practice dating back to the 1940s and 1950s. 86 This GRAS designation is given to food additives that are generally accepted by qualified experts to be safe when used as intended; however, it is important to note that the GRAS designation is not given to a substance in general but, rather, the use of a substance under specific circumstances. Energy drinks are classified as supplements and are not considered "foods and beverages," so they are not subject to the same limits on caffeine content and are not included in the GRAS designation from the FDA. ...
Objective
Caffeine use is common in children and adolescents, but the recommendations for safe consumption are based on decades-old data collected exclusively in adults. Increased availability of caffeine-containing products and a concerted marketing effort aimed at children and adolescents, has increased interest in understanding the physiological, behavioral, and psychological effects of caffeine within this population. This manuscript provides a review of the literature concerning trends and safety of ingested caffeine in children and adolescents.
Method
A search of the National Library of Medicine database was conducted using the terms caffeine, children, adolescents, and safety, in addition to tailored searches on specific topics using combinations of search terms such as energy drinks, cardiovascular, mood, cognitive, mental health, sleep, and regulations.
Results
The majority of the literature reviewed here suggests that typical, moderate caffeine consumption in children and adolescents is relatively safe, but that higher doses of caffeine consumption (>400 mg) can cause physiological, psychological, and behavioral harm, in particular in subgroups of children, such as those with psychiatric or cardiac conditions. More attention is being paid to the potential adverse effects of both acute and chronic caffeine use, and additional regulations surrounding the sale and marketing of highly caffeinated beverages are now being considered.
Conclusion
More research is needed to fill in gaps in our knowledge, including understanding the relationship between caffeine use and initiation of other substances, such as cigarettes, alcohol, or marijuana, identifying individuals at risk for caffeine toxicity, and developing harm-reduction strategies.
... The U.S. Food and Drug Administration does not require that energy drink manufacturers label beverage containers with the amount of caffeine in each beverage (U.S. Food and Drug Administration, 2017). While caffeine levels in cola-type beverages are regulated to not exceed 0.02% (approximately 5.9 mg/oz), energy drinks sold in the United States are not strictly regulated, and have a wide range of caffeine contents from 1.5-32.5 mg/oz (Rosenfeld et al., 2014). According to Health Canada regulations, energy drinks cannot contain more than 180 mg of caffeine per 500 mL serving (10.6 mg/oz), and containers must display a warning of high caffeine content and a recommended maximum daily serving (Health Canada: Food Directorate -Health Products and Food Branch, 2013). ...
Alcohol and energy drinks are commonly used substances by youth in Canada, and are often mixed (AmED). While several studies have shown that AmED can have dangerous effects, less well understood is how AmED is associated with driving under the influence of either alcohol or drugs. This study sought to determine whether youth who use AmED were more likely to engage in driving, or being a passenger of a driver, under the influence of alcohol or cannabis compared to youth who use either alcohol or energy drinks alone.
This study used data from grade 10–12 students who took part in the 2014/2015 Canadian Student Tobacco, Alcohol and Drugs Survey (N = 17,450). The association of past-year AmED use with past-30 day: driving under the influence of alcohol or cannabis, and riding with an alcohol- or cannabis-influenced driver, was assessed using logistic regression.
One in four youth had consumed AmED in the previous 12 months. AmED users were more likely to engage in all risk behaviours except riding with a drinking driver, relative to youth who only consumed alcohol. No association was observed for youth who consumed alcohol and energy drinks on separate occasions.
Youth who use AmED demonstrate a higher risk profile for driving under the influence of alcohol or cannabis, than youth who use alcohol alone. Future research should explore the biopsychosocial pathways that may explain why using energy drinks enhances the already heightened risk posed by alcohol on other health-related behaviours such as driving under the influence.
... Numerous papers have reviewed the history of the GRAS process in the United States (Burdock, 2000(Burdock, , 2015 Carabin, 2004; Burdock et al., 2006;Day, 1976;McColl and Janus, 2016;Neltner et al., 2013;Siu et al., 1977). In addition, many specific GRAS substances have been reviewed in the literature, including: sodium (Cobb et al., 2012); inulin and oligofructose (Coussement, 1999); partially hydrogenated oils (Covington & Burling, 2015); long-chain omega-3 fatty acids (Fenton et al., 2013); mono-sodium glutamate (Geha et al., 2000); multilayer films (Hsu et al., 2014); guayusa concentrate (Kapp et al., 2016); probiotics (Mattia and Merker, 2008); nonnutritive sweeteners (Roberts and Wright, 2012); caffeine (Rosenfeld et al., 2014); colicins (Schulz et al., 2015); diacylglycerol (Takase, 2007); and cinnamaldehyde (Upadhyaya et al., 2015). As opposed to focusing on the history of the GRAS process, the mechanism underlying how a substance is determined to be GRAS, or investigating specific substances that have undergone evaluation in the GRAS process, this article conducts a high-level assessment of the first 600 GRAS Notifications submitted to the FDA during the Interim Pilot Program. ...
After publication of the draft Generally Regarded As Safe (GRAS) rule in 1997, the United States (US) Food and Drug Administration (FDA) initiated an Interim Pilot Program encouraging the notification to FDA of GRAS determinations. This paper analyzes GRAS notifications submitted during the Interim Pilot Program along with warning letters issued during the same time period to better understand the evolution of the program and anticipate the future GRAS landscape. The success of the GRAS Notification program is demonstrated by the increasing rate of GRAS Notifications submitted to the FDA during the Interim Pilot Program, as well as the shift from a primarily domestic process to a process featuring an equal to greater contribution of GRAS Notifications from companies outside the US. Analysis of the first 600 GRAS Notifications revealed a number of interesting trends regarding: the inclusion and composition of GRAS Expert Panels; differences in notifications for substances with nutritive, processing aid, or effect; and the duration of GRAS Notifications. The review of FDA warning letters associated with GRAS issues provides additional insight into GRAS, from the perspective of ongoing post-market emphasis on food safety with the implementation of the GRAS Final Rule.
... A recent US Food and Drug Administration (FDA) statement brings to light the additional challenges. According to Rosenfeld et al. (2014), "While patterns of use of caffeine-containing products appear to be changing, the implications of these changes for public health are not well understood." They also note that "While it is commonly stated that different types of caffeinated products are substituted for each other (e.g., caffeine-containing EDs for coffee and vice versa), however, there are few data documenting this assertion." ...
The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled "Caffeine: Friend or Foe?," which was held during the 2015 ILSI Annual Meeting. The panelists' expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session. Expected final online publication date for the Annual Review of Food Science and Technology Volume 7 is February 28, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
Food additives include substances that are directly added to food with the intention of having a particular technical effect on food (known as “direct food additives”), as well as components of materials used in manufacturing, packing, packaging, transporting, or holding food such that their use is not intended to have a technical effect on food but may result in those components migrating to food (known as “indirect food additives” or “food contact substances”). So far, thousands of food additives have been developed to meet the increasing demand for safe, convenient, and nutritious food. With the widespread use of food additives in the food industry, ensuring the safety of food additives is extremely important to protect public health. This chapter provides an overview of both direct and indirect food additives in terms of their definitions, intended uses, regulatory background, and methods for assessing their safety. Additionally, workplace safety considerations related to the production and handling of food additives in occupational settings are briefly discussed. Furthermore, some examples of both types of food additives are given at the end of the chapter, together with related resources available for further information.
Pyrimidines-based drugs are one of the most important drugs for novel and recurring viruses, including the coronavirus. This chapter deals with 41 FDA-approved five-membered ring fused pyrimidine-based drugs, their synthetic strategies, and pharmacological activities.
The potential role of plant-based foods in the promotion of skin health is an emerging area of nutrition research. Plant-based foods are rich in bioactive compounds, including vitamin C, vitamin E, beta-carotene, polyphenols, and phenolic acids, which can contribute to oxidant defense, lower inflammation, and promote structural support of the skin. Epidemiological studies have associated higher intakes of select fruits and vegetables with positive skin health.1,2 Beneficial effects of certain fruits, vegetables, nuts, legumes, and polyphenolic-rich beverages on the skin have been reported, with each of these providing a unique phytochemical composition. While most studies use extracts, this review will focus on data from whole foods and minimally processed products. Collectively, the evidence to date suggests a promising future for plant-based dietary interventions that promote skin barrier health and function. However, additional research is required to address issues such as the optimal quality and duration of intake as well as potential mechanisms. Studies in the above areas will help formulate specific targeted dietary recommendations.
If consumption of unhealthy food is excessive, then a policymaker might respond with a corrective tax. However, she might supplement the tax with a regulatory standard that limits the concentration of an unhealthy ingredient. A tax can restore social efficiency without supplemental regulation if all of four of the following conditions are satisfied: The tax is nutrient specific, the market structure is perfect competition, the magnitude of the distortion is the same across all consumers, and consumers do not react to the tax by substituting to untaxed foods that also have unhealthy ingredients. But if any of these conditions are not met, then there can be benefits to supplementing a corrective tax with a standard.
This study was initiated to examine the effects of caffeine on the DNA damage response (DDR) and homologous recombination (HR) in mammalian cells. A 5 mM caffeine treatment caused the cell cycle to stall at G2/M and cells eventually underwent apoptosis. Caffeine exposure also induced a strong DDR along with subsequent activation of wildtype p53 protein. An unexpected observation was the caffeine-induced depletion of Rad51 (and Brca2) proteins. Consequently, caffeine-treated cells were expected to be inefficient in HR. However, a dichotomy in the HR response of cells to caffeine treatment was revealed. Caffeine treatment rendered cells significantly better at performing the nascent DNA synthesis that accompanies the early strand invasion steps of HR. Additionally, caffeine treatment increased chromatin accessibility and elevated the efficiency of illegitimate recombination. Conversely, the increase in nascent DNA synthesis did not translate into a higher number of gene targeting events. Thus, prolonged caffeine exposure stalls the cell cycle, induces a p53-mediated apoptotic response and a down-regulation of critical HR proteins, and for reasons discussed, stimulates early steps of HR, but not the formation of complete recombination products.
The increasing consumption of energy drinks and caffeine added products, coupled with somewhat inconsistent labeling practices, has generated health concerns from possible excessive caffeine intake. In this paper, we simulate the impacts of potential caffeine content regulatory policies on demand for energy drinks as well as caffeine and sugar consumption. We model demand for energy drinks as a function of price and product characteristics that includes both caffeine levels and the presence of labeled caffeine content. Using our demand estimation results, we simulate the impact of potential policies including mandatory caffeine content labeling, advertising restriction and caffeine content regulations. Results indicate that mandatory labeling and advertising restrictions would reduce the overall sales in the energy drinks sector, but with a limited impact. The effect of caffeine content regulation would vary depending on whether the policy is implemented on a per-ounce basis or a per-can basis. Furthermore, these policies have different impacts on sugar and caffeine consumption, and therefore policymakers should be cautious when implementing caffeine regulations.
Caffeine is a drug substance primarily known in the form of refreshing and energizing drinks such as tea, coffee, hot chocolate etc. Although the origin of using coffee beans ‘toners’ is lost in the mists of time, scientific data on this substance, classified as cortical stimulant, are relatively recent and begin in 1820 when it was isolated from coffee beans. This paper aims to present the main therapeutic effects underlying caffeine use in topical medication, with an initial brief description of the pharmacodynamic actions of caffeine after its absorption into the systemic circulation. The use of caffeine in adjuvant therapy of skin conditions such as cellulitis, alopecia, erythrodermatitises, photoaging and even non-melanoma cancer leads to new scientific data that reinforce the caffeine position as an active substance at the dermal level through complex cellular and molecular mechanisms, some of which are known, others being in research.
Caffeine is one of the most widely consumed psychoactive compounds, and is often marketed for its physical and cognitive performance benefits. The ingestion of potentially toxic amounts of caffeine in the forms of energy drinks, over-the-counter supplements, or anhydrous caffeine products places vulnerable pediatric and adolescent individuals at risk for accidental overdose, resulting in neurologic and cardiac toxicity.
INTRODUCTION: Education frequently dictates students need to study for prolonged periods of time to adequately prepare for examinations. This is especially true with aviation preflight indoctrination (API) candidates who have to assimilate large volumes of information in a limited amount of time during API training. The purpose of this study was to assess caffeine consumption patterns (frequency, type, and volume) among naval aviation candidates attending API to determine the most frequently consumed caffeinated beverage and to examine if the consumption of a nonenergy drink caffeinated beverage was related to energy drink consumption.
METHODS: Data were collected by means of an anonymous 44-item survey administered and completed by 302 students enrolled in API at Naval Air Station Pensacola, FL.
RESULTS: Results indicated the most frequently consumed caffeinated beverage consumed by API students was coffee (86.4%), with daily coffee consumption being approximately 28% and the most frequent pattern of consumption being 2 cups per day (85%). The least frequently consumed caffeinated beverages reported were energy drinks (52%) and energy shots (29.1%). The present study also found that the consumption patterns (weekly and daily) of caffeinated beverages (coffee and cola) were positively correlated to energy drink consumption patterns.
DISCUSSION: Naval aviation candidates’ consumption of caffeinated beverages is comparable to other college and high school cohorts. This study found that coffee and colas were the beverages of choice, with energy drinks and energy shots being the least frequently reported caffeinated beverages used. Additionally, a relationship between the consumption of caffeinated beverages and energy drinks was identified.
Some plants from the tropic belt synthesize caffeine, starting with the purine base xanthosine, and leaves and seeds are particularly effective at caffeine biosynthesis. Communities living alongside these plants have traditionally used them as constituents for beverages or for masticatory consumption. In the modern age, the value of caffeine plants reached the nontropical regions, and caffeine products have become some of the most important commodities worldwide; coffee, tea, and cocoa are discussed in articles within this encyclopedia. The planar structure of caffeine's parent skeleton, purine, with partial charges, allows molecular interactions in aqueous solution, with a preference toward dimerization. In parallel, heteroassociation with molecules of similar geometry but different chemistry in the cellular environment leads to complexes that produce the specific patterns of stimulant behavior that characterize different plant preparations. Due to increasing demand, the natural occurrence of caffeine is complemented by synthetic production. This article describes the discovery, properties, and appearance of caffeine.
Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products.
Energy drinks are relatively new to the United States but are the fastest growing segment of the beverage market. Humans have a long history of consuming caffeine in traditional beverages, such as cocoa, coffee, tea, and yerba maté, but 2 workshops held at the Institute of Medicine (http://www.iom.edu/Activities/Nutrition/PotentialHazardsCaffeineSupplements/2013-AUG-05.aspx) and the NIH (http://ods.od.nih.gov/News/EnergyDrinksWorkshop2013.aspx) in 2013 highlighted many critical gaps in understanding the biologic and behavioral effects of the mixtures of caffeine, vitamins, herbs, sugar or other sweeteners, and other ingredients that typify caffeine-containing energy drinks (CCEDs). For example, different surveys over the same 2010–2012 timeframe report discrepant prevalence of CCED use by teenagers, ranging from 10.3% in 13–17 y olds to >30% of those in grades 10 and 12. Understanding of functional interactions between CCED ingredients, drivers of use, and biologic and behavioral effects is limited. The 4 speakers in the Experimental Biology 2014 symposium titled “Energy Drinks: Current Knowledge and Critical Research Gaps” described recent progress by their groups in extending our understanding of prevalence of CCED use, sources of caffeine in the United States, drivers of CCED use, and behavioral correlations and effects of CCEDs, including effects on attractiveness of both alcoholic and non-alcoholic beverages.
Sales of energy drinks in the United States reached $12.5 billion in 2012. Emergency department visits related to consumption of these products have increased sharply, and while these numbers remain small relative to product sales, they raise important questions regarding biological and behavioral effects. Although some common ingredients of energy drinks have been extensively studied (e.g., caffeine, B vitamins, sugars, inositol), data on other ingredients (e.g., taurine) are limited. Summarized here are data presented elsewhere in this issue on the prevalence and patterns of caffeine-containing energy drink use, the effects of these products on alertness, fatigue, cognitive functions, sleep, mood, homeostasis, as well as on exercise physiology and metabolism, and the biological mechanisms mediating the observed effects. There are substantial data on the effects of some energy drink ingredients, such as caffeine and sugars, on many of these outcomes; however, even for these ingredients many controversies and gaps remain, and data on other ingredients in caffeine-containing energy drinks, and on ingredient interactions, are sparse. This summary concludes with a discussion of critical gaps in the data and potential next steps.
A variety of alkyl substituted phenalenes, including deuterated and 13C labeled compounds, was synthesized via an organometallic reaction. From the respective paramagnetic oxidation products, the phenalenyls, ESR spectra and proton, deuterium and 13C ENDOR resonances could be obtained. From the electron-nuclear-nuclear-TRIPLE resonance experiments the signs of all hyperfine coupling constants could be determined. An interpretation of the spin density distributions on the basis of the hyperconjugation model is given. The results of HMO-McLachlan andINDO calculations are reported.
The fruit of the Amazonian guaraná liana (Paullinia cupana) looks like a human eye, and undoubtedly shows the ‘bird dispersal syndrome’. The seeds were reported to be ingested by large birds such as toucans and guans. We determined the purine alkaloid content of the various fruit and seed parts. The two aspects of defence and dispersal are reflected in the differential seed alkaloid distribution: the seed kernel (embryo with bulky cotyledons) and the seed coat (testa) accumulate much caffeine, i.e. 4.28 and 1.64%, respectively, whereas the ‘white of the eye’, the aril, is virtually alkaloid-free, but contains glucose, fructose and sucrose up to almost 70% of aril dry weight. Furthermore, the aril is strongly hygroscopic and it is suggested that it extends germination power by preventing seed desiccation. Experiments simulating pH and temperature conditions in the avian stomachs showed rapid desintegration of the aril and no caffeine release by the intact seed at pH 4.5 (crop) during the first 30 min of ‘digestion’. Only a tiny fraction (between 0.025 and 0.07%) of total seed caffeine left the intact seed after 60 min at pH 4.5 or during the incubation at pH 2.3 (gizzard), indicating the presence of a very powerful diffusion barrier in the seed coat which at least theoretically should prevent intoxication of the dispersing bird even after an assumed foraging bout of 50 seeds. The cracked seed, however, releases a considerable fraction of its caffeine, considered harmful to destructive birds, if a few seeds were processed in this way. Absence of caffeine in the aril could well be the result of a ‘secondary’ degradation during maturation, analogous to hypoglycin A in the aril of the closely related sapindaceous Blighia sapida.
Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine.
This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson's and cardiovascular diseases in habitual caffeine consumers.
Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of polysubstance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users.
Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.
Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. The possibility that caffeine ingestion adversely affects human health was investigated based on reviews of (primarily) published human studies obtained through a comprehensive literature search. Based on the data reviewed, it is concluded that for the healthy adult population, moderate daily caffeine intake at a dose level up to 400 mg day(-1) (equivalent to 6 mg kg(-1) body weight day(-1) in a 65-kg person) is not associated with adverse effects such as general toxicity, cardiovascular effects, effects on bone status and calcium balance (with consumption of adequate calcium), changes in adult behaviour, increased incidence of cancer and effects on male fertility. The data also show that reproductive-aged women and children are 'at risk' subgroups who may require specific advice on moderating their caffeine intake. Based on available evidence, it is suggested that reproductive-aged women should consume </=300 mg caffeine per day (equivalent to 4.6 mg kg(-1) bw day(-1) for a 65-kg person) while children should consume </=2.5 mg kg(-1) bw day(-1).
Caffeine is the world's most widely consumed drug with its main source found in coffee. We evaluated the caffeine content
of caffeinated and decaffeinated specialty coffee samples obtained from coffee shops. Caffeine was isolated from the coffee
by liquid-liquid extraction and analyzed by gas chromatography with nitrogen-phosphorus detection. In this study, the coffees
sold as decaffeinated were found to have caffeine concentrations less than 17.7 mg/dose. There was a wide range in caffeine
content present in caffeinated coffees ranging from 58 to 259 mg/dose. The mean (SD) caffeine content of the brewed specialty
coffees was 188 (36) mg for a 16-oz cup. Another notable find is the wide range of caffeine concentrations (259–564 mg/dose)
in the same coffee beverage obtained from the same outlet on six consecutive days.
A cross-section of Australian “Espresso/short black” coffee and coffee-flavoured milk samples were purchased and analysed for their caffeine content using micellar electrokinetic capillary chromatography (MEKC). Coffees were collected using convenience cluster sampling across four major cities. Packaged coffee-flavoured milks were collected from national grocery distributors. In all, 131 espresso samples and 20 coffee-flavoured milks were analysed. The mean (±SD) quantity of caffeine from espresso coffee was 107 ± 37 mg/serving with a concentration of 2550 ± 1030 mg/L. The mean (±SD) quantity of caffeine from coffee-flavoured milk was 99 ± 50 mg/carton with a concentration of 193 ± 90 mg/L. There was considerable variation in caffeine content across both categories and within the same espresso brand purchased at different locations. In total, 42 samples (27.5%) contained ≥120 mg per serving of caffeine, and 20 samples (13.1%) exceeded 165 mg per serving.The expanded caffeine data supports our original findings which indicated that the probability of consumer exposure to high caffeine doses from popular coffee beverages in Australia is greater than previously reported.
Context:
Small studies have associated energy drinks-beverages that typically contain high concentrations of caffeine and other stimulants-with serious adverse health events.
Objective:
To assess the incidence and outcomes of toxic exposures to caffeine-containing energy drinks, including caffeinated alcoholic energy drinks, and to evaluate the effect of regulatory actions and educational initiatives on the rates of energy drink exposures.
Methods:
We analyzed all unique cases of energy drink exposures reported to the US National Poison Data System (NPDS) between October 1, 2010 and September 30, 2011. We analyzed only exposures to caffeine-containing energy drinks consumed as a single product ingestion and categorized them as caffeine-containing non-alcoholic, alcoholic, or "unknown" for those with unknown formulations. Non-alcoholic energy drinks were further classified as those containing caffeine from a single source and those containing multiple stimulant additives, such as guarana or yerba mate. The data were analyzed for the demographics and outcomes of exposures (unknown data were not included in the denominator for percentages). The rates of change of energy drink-related calls to poison centers were analyzed before and after major regulatory events.
Results:
Of 2.3 million calls to the NPDS, 4854 (0.2%) were energy drink-related. The 3192 (65.8%) cases involving energy drinks with unknown additives were excluded. Of 1480 non-alcoholic energy drink cases, 50.7% were children < 6 years old; 76.7% were unintentional; and 60.8% were males. The incidence of moderate to major adverse effects of energy drink-related toxicity was 15.2% and 39.3% for non-alcoholic and alcoholic energy drinks, respectively. Major adverse effects consisted of three cases of seizure, two of non-ventricular dysrhythmia, one ventricular dysrhythmia, and one tachypnea. Of the 182 caffeinated alcoholic energy drink cases, 68.2% were < 20 years old; 76.7% were referred to a health care facility. Educational and legislative initiatives to enhance understanding of the health consequences of energy drink consumption were significantly associated with a decreased rate of energy drink-related cases (p = 0.036).
Conclusions:
About half the cases of energy drink-related toxicity involved unintentional exposures by children < 6 years old. Educational campaigns and legal restrictions on the sale of energy drinks were associated with decreasing calls to poison centers for energy drink toxicity and are encouraged.
Kola nut extract is used in the food industry as a flavoring ingredient. Kola nut extract is derived from the seeds of primarily two tropical Cola species (Cola nitida (Vent.) Schott et Endl. or Cola acuminata (Beauv.) Schott et Endl.) of the Family, Sterculiaceae. Present day consumption of kola nut extract is 0.69 mg/kg/day. Caffeine and theobromine are two important constituents of kola nuts. Although limited biological data are available for kola nut extract specifically, the published data of the major constituents of kola nuts suggest the pharmacological/toxicological properties of kola nut extract, parallel to those of a roughly equivalent dose of caffeine. Frank developmental/reproductive effects have not been reported and changes in offspring cannot be extrapolated to humans. A NOEL/NOAEL cannot be defined for repeated oral exposure to kola nut extract from available data. Notwithstanding the foregoing, U.S. consumers have a history of safe consumption of cola-type beverages containing kola nut extract that dates at least to the late 19th Century, with a significant global history of exposure to the intact kola nuts that date centuries longer.
Five surveys, using a previously developed high-performance liquid chromatography procedure to measure caffeine concentrations, indicated great variations in the concentrations of caffeine in tea and coffee. In the study of beverages prepared at home, data on caffeine concentrations in 58 samples of tea and coffee, volumes of cups, and numbers of cups consumed/day, indicated that the range of caffeine intakes for the women participating was 49-1022 mg/day. There were considerable day-to-day variations in caffeine contents in coffee samples from some commercial coffee shops. When 17 samples of five national brands of instant coffee were made into beverages in the laboratory, variations in caffeine concentrations between lots were small but between brands were significant. A considerable range of caffeine concentrations was also found when 12 samples of coffee prepared at work by different individuals using the same jar of instant coffee were analysed. Analysis of tea samples prepared in the laboratory indicated that steeping time had an important influence on resulting caffeine and theobromine concentrations. People preparing their own beverages were found to drink more liquid than the volume offered commerically. The mean caffeine 'contents' of home-made coffee and of coffee prepared by individuals at work were 79.4 and 81.7 mg/cup respectively, indicating a mean intake of approximately 80 mg caffeine/cup. When this amount (80 mg/cup) was used to estimate daily intakes of caffeine from coffee, on the basis of the number of reported cups/day, and the values obtained were compared with the amounts actually consumed by individuals, the potential for misrepresentation of individual consumption became obvious. For example, for subjects consuming three cups of coffee, only 25% would have been correctly categorized in the expected range for the daily intake of caffeine, 39% would have been overestimated and 36% underestimated for the amount of caffeine consumed. These variations in caffeine concentrations and in the volume of coffee consumed have frequently been ignored in examinations of the possible relationship between coffee consumption and various health problems, and this could perhaps partly explain some conflicting results seen in epidemiological studies.
This study provides information on the caffeine intakes of a representative sample of the US population using the US Department of Agriculture 1994 to 1996 and 1998 Continuing Survey of Food Intakes by Individuals. The percentage of caffeine consumers of the total sample (N=18,081) and by age and sex groups and for pregnant women were determined. Among caffeine consumers (n=15,716), the following were determined: mean intakes of caffeine (milligrams per day and milligrams per kilogram per day) for all caffeine consumers, as well as for each age and sex group and pregnant women; mean intakes (milligrams per day) of caffeine by food and beverage sources; and the percent contribution of each food and beverage category to total caffeine intake for all caffeine consumers, as well as each age and sex group and pregnant women. Eight-seven percent of the sample consumed food and beverages containing caffeine. On average, caffeine consumers' intakes were 193 mg caffeine per day and 1.2 mg caffeine per kilogram of body weight per day. As age increased, caffeine consumption increased among people aged 2 to 54 years. Men and women aged 35 to 64 years were among the highest consumers of caffeine. Major sources of caffeine were coffee (71%), soft drinks (16%), and tea (12%). Coffee was the major source of caffeine in the diets of adults, whereas soft drinks were the primary source for children and teens.
Over 60% of soft-drinks sold in the United States contain caffeine, a mildly addictive psycho-active chemical, as a flavor additive. Using sweeteners as controls, we assessed whether caffeine has flavor activity in a cola soft-drink. A forced-choice triangle discrimination methodology was used to determine detection thresholds of caffeine in sweeteners and a cola beverage. The subjects (n=30, 28 female, 23+/-4 years old) were trained tasters and completed over 1600 discrimination tests during the study. The mean detection thresholds for caffeine in the sweet solutions were: 0.333+/-0.1mM sucrose; 0.467+/-0.29 mM aspartame; 0.462+/-0.3mM sucralose, well below the concentration in common cola beverages (0.55-0.67 mM). A fixed concentration of caffeine, corresponding to the concentration of caffeine in a common cola beverage (0.67 mM) was added to the sweeteners and a non-caffeinated cola beverage. Subjects could distinguish between caffeinated and non-caffeinated sweeteners (p<0.001), but all subjects failed to distinguish between caffeinated and non-caffeinated cola beverage (p=1.0). Caffeine has no flavor activity in soft-drinks yet will induce a physiologic and psychologic desire to consume the drink.
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Prepared for FDA under Subcontract Number 70000073494
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CFSAN Adverse Events Reporting System (CAERS) backgrounder for the Institute Of Medicine (IOM) FDA-requested Workshop on Potential Health Hazards of Caffeine in Food and Dietary Supplements
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