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Temple JL (January 2019). "Review: Trends, Safety, and Recommendations for Caffeine Use in Children and Adolescents". Journal of the American Academy of Child and Adolescent Psychiatry. 58 (1): 36–45. doi: 10.1016/j.jaac.2018.06.030. PMID 30577937. S2CID 58539710. Muriel P, Arauz J (July 2010). "Coffee and liver diseases". Fitoterapia. 81 (5): 297–305. doi: 10.1016/j.fitote.2009.10.003. PMID 19825397. a b American College of Obstetricians and Gynecologists (August 2010). "ACOG CommitteeOpinion No. 462: Moderate caffeine consumption during pregnancy". Obstetrics and Gynecology. 116 (2 Pt 1): 467–8. doi: 10.1097/AOG.0b013e3181eeb2a1. PMID 20664420. Until recently, the Seventh-day Adventist Church asked for its members to "abstain from caffeinated drinks", but has removed this from baptismal vows (while still recommending abstention as policy). [282] Some from these religions believe that one is not supposed to consume a non-medical, psychoactive substance, or believe that one is not supposed to consume a substance that is addictive. The Church of Jesus Christ of Latter-day Saints has said the following with regard to caffeinated beverages: "... the Church revelation spelling out health practices (Doctrine and Covenants 89) does not mention the use of caffeine. The Church's health guidelines prohibit alcoholic drinks, smoking or chewing of tobacco, and 'hot drinks' – taught by Church leaders to refer specifically to tea and coffee." [283] For the general population of healthy adults, Health Canada advises a daily intake of no more than 400mg. [72] This limit was found to be safe by a 2017 systematic review on caffeine toxicology. [73] Children

Some analog substances have been created which mimic caffeine's properties with either function or structure or both. Of the latter group are the xanthines DMPX [210] and 8-chlorotheophylline, which is an ingredient in dramamine. Members of a class of nitrogen substituted xanthines are often proposed as potential alternatives to caffeine. [211] [ unreliable source?] Many other xanthine analogues constituting the adenosine receptor antagonist class have also been elucidated. [212] Commercially prepared coffee- flavoured milk beverages are popular in Australia. [236] Examples include Oak's Ice Coffee and Farmers Union Iced Coffee. The amount of caffeine in these beverages can vary widely. Caffeine concentrations can differ significantly from the manufacturer's claims. [226] Caffeine, like other xanthines, also acts as a phosphodiesterase inhibitor. [173] As a competitive nonselective phosphodiesterase inhibitor, [174] caffeine raises intracellular cyclic AMP, activates protein kinase A, inhibits TNF-alpha [175] [176] and leukotriene [177] synthesis, and reduces inflammation and innate immunity. [177] Caffeine also affects the cholinergic system where it is a moderate inhibitor of the enzyme acetylcholinesterase. [178] [179] Pharmacokinetics Caffeine is metabolized in the liver via a single demethylation, resulting in three primary metabolites, paraxanthine (84%), theobromine (12%), and theophylline (4%), depending on which methyl group is removed. Urinary metabolites of caffeine in humans at 48 hours post-dose [180] O'Connor A (4 March 2008). "Really? The claim: caffeine causes dehydration". New York Times. Archived from the original on 3 September 2011 . Retrieved 3 August 2009.

The command line is now interpreted and shows in the tooltip. This means you can see what Caffine has recognised. Global coffee consumption, 2020/21". Statista. Archived from the original on 3 March 2021 . Retrieved 10 March 2021. Simulated keypress changed from right context menu key to F15 as this is likely to be even less intrusive. Coffee and the Liver". British Liver Trust. Archived from the original on 12 May 2023 . Retrieved 12 May 2023. Caffeine Drug Monographs". UpToDate. Archived from the original on 25 April 2013 . Retrieved 28 November 2018.Cano-Marquina A, Tarín JJ, Cano A (May 2013). "The impact of coffee on health". Maturitas. 75 (1): 7–21. doi: 10.1016/j.maturitas.2013.02.002. PMID 23465359. a b Downs J, Giust J, Dunn DW (September 2017). "Considerations for ADHD in the child with epilepsy and the child with migraine". Expert Review of Neurotherapeutics. 17 (9): 861–869. doi: 10.1080/14737175.2017.1360136. PMID 28749241. S2CID 29659192. According to the International Classification of Diseases (ICD-11), cases of very high caffeine intake (e.g. > 5 g) may result in caffeine intoxication with symptoms including mania, depression, lapses in judgment, disorientation, disinhibition, delusions, hallucinations or psychosis, and rhabdomyolysis. [140] Energy drinks Doherty M, Smith PM (April 2005). "Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis". Scandinavian Journal of Medicine & Science in Sports. 15 (2): 69–78. doi: 10.1111/j.1600-0838.2005.00445.x. PMID 15773860. S2CID 19331370.

Caffeine in coffee and other caffeinated drinks can affect gastrointestinal motility and gastric acid secretion. [86] [87] [88] In postmenopausal women, high caffeine consumption can accelerate bone loss. [89] [90] a b "Caffeine (Systemic)". MedlinePlus. 25 May 2000. Archived from the original on 23 February 2007 . Retrieved 3 August 2009.a b c d e f g h i j k l m n o p "Caffeine". DrugBank. University of Alberta. 16 September 2013. Archived from the original on 4 May 2015 . Retrieved 8 August 2014. Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N (2010). "Caffeine intake and dementia: systematic review and meta-analysis". Journal of Alzheimer's Disease. 20 (Suppl 1): S187-204. doi: 10.3233/JAD-2010-091387. PMID 20182026. Mathew OP (May 2011). "Apnea of prematurity: pathogenesis and management strategies". Journal of Perinatology. 31 (5): 302–10. doi: 10.1038/jp.2010.126. PMID 21127467.

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