Changes

There is some research indicating that there are genetic differences that change how caffeine effects people, but the research is a little unclear. However, it seems that having your genome tested could provide valuable information into how to use caffeine. The enzyme CYP1A2 metabolizes many drugs, and it's been shown to be responsible for over 95% of the metabolism of caffeine<ref name="BegasKouvaras2007"/>. The CYP1A2 enzyme is produced by the CYP1A2 gene, and a genetic change at rs762551 impacts how the enzyme is produced, with AA having greater activity than the AC or CC genotypes<ref name="snpe_rs76"/>. Sometimes the subjects with the AA variant are called "fast metabolizers". (I had my genome tested using 23andme.com which showed I have the AA variant of CYP1A2/rs762551.)

I had my genome tested using 23andmeIt seems rather counterintuitive to me that the faster you metabolize caffeine, the greater the benefit.com which showed I have It suggests that maybe it's a metabolite of caffeine that improves performance rather than the AA variant of CYP1A2/rs762551caffeine itself, but that's pure supposition on my part.

Caffeine is rapidly absorbed, and its clearance varies with multiple variables, including exercise. It seems that exercise might increase clearance, which in turn might increase the needed dosage for ultra-endurance events. * About 99% of consumed caffeine is absorbed within 45 minutes, with peak concentrations after about 30 minutes<ref name="NehligAlexander2018"/>.* Caffeine half-life is generally 2.5-5 hours with some dose dependency and individual variability<ref name="CamandolaPlick2018"/>.* A study found that lean subjects cleared caffeine faster than the obese, with the half life of 2.6 hours rather than 4.4 hours<ref name="Kamimori-1987"/>.* An hour's light exercise (30% [[VO2max|V̇O₂max]]) reduced the half life from 4 hours to 2.3 hours in healthy subjects<ref name="Collomp-1991"/>.* A study of 14 active ([[VO2max|V̇O2max]] of 50) subjects (8 women) found no change in caffeine clearance with exercise<ref name="McLeanGraham2002"/>. Subjects exercised for 1.5 hours at 60-65% of [[VO2max|V̇O₂max]], starting 1 hour after ingesting 6 mg/Kg of caffeine. Half life was ~6 hours. * The half-life of caffeine seems dose dependent<ref name="ChengMurphy1990"/>. In healthy subjects, the half-life at 70mg was 4.5 hours, at 200mg was 60 hours, and at 300mg was 6.4 hours. (Impaired liver function can dramatically increase the half-life to 25-30 hours.)* Caffeine is metabolized by the liver enzyme CYP1A2<ref name="KalowTang1993"/>, and the activity of this enzyme can be effected affected by drugs and diet, with tobacco and chargrilled meat increasing levels<ref name="Flockhart-2007"/>. Things may not be so simple, as about 85% of caffeine is metabolized to Paraxanthine <ref name="GuerreiroToulorge2008"/> and Paraxanthine in mice is a stronger stimulant than caffeine<ref name="Okuro-2010"/>, while similar in humans<ref name="BenowitzJacob1995"/>. Paraxanthine has a half-life of 3.1-4.1 hours<ref name="CamandolaPlick2018"/>, and levels become higher than caffeine after 8-10 hours<ref name="NehligAlexander2018"/> (There is a common genetic mutation in dogs that prevents the formation of CYP1A2, making these dogs unable to metabolize caffeine and some other substances<ref name="AretzGeyer2011"/>.)

We get a resulting caffeine concentration in the milk of 4ug/ml to 8ug/ml<ref name="Stavchansky-"/>, which is a total caffeine intake of between 2mg to 13mg, or 0.6 to 4 mg/Kg body weight. The upper end of that level is quite high. However, the baby's half-life for caffeine is 31-132 hours (average 82 hours)<ref name="Parsons-1981"/>, compared with an adult's 2-10 hour half-life, so the caffeine will build up over time. A 24 hour half live (which is easier to calculate) would result in about a 3mg to 26mg, which is 1 to 8 mg/Kg. I'm guessing that would result in the baby not sleeping well! Conversely, a baby whose mother takes caffeine during pregnancy and is then given formula milk may undergo caffeine withdrawal after birth<ref name="McGowan-1988"/>. Even if the mother breast feeds, the varying levels of caffeine may cause withdrawal symptoms<ref name="Martín-2007"/>. Also, caffeine has been shown to increase fetal [[Heart Rate]]<ref name="Buscicchio-2012"/>. There is research indicating that Caffeine may not reduce to subtherapeutic levels until around 11-12 days<ref name="Doyle-2016"/>.