Caffeine is considered a naturally occurring CNS stimulant and is classified as a methylxanthine drug. Over 60 species of plants contain caffeine, most notably: coffee seeds (i.e. “beans”) and tea leaves. It is estimated that 80% (4/5) adults in the United States consume caffeine on a daily basis, and 90% of people throughout the world ingest caffeine (in some format) regularly; the average adult consumes approximately ~200 mg of caffeine per day (equivalent to 2 cups of coffee).
People ingest caffeine for a variety of reasons such as for: cognitive enhancement (learning/memory), increased alertness, heightened energy, and/or to simply “perk up” in the morning. Caffeine elicits these stimulatory effects primarily via antagonism of adenosine receptors; thereby facilitating vigilance and mitigating drowsiness. There are many benefits linked to caffeine consumption including: reduced risk of certain cancers, type 2 diabetes, and neurodegeneration.
However, some people believe there may be deleterious effects associated with regular long-term caffeine consumption including: increased risk of hypertension, circadian rhythm abnormalities (if consumed in the afternoon), and decreased collagen formation. Many people believe the potential risks of caffeine consumption outweigh the benefits. As a result, they’ve decided to cease ingestion of the drug and hope to fully clear caffeine from their systems.
How long does Caffeine stay in your system?
Assuming you’ve abruptly stopped drinking coffee, you’ll likely end up dealing with transient (yet noticeable) caffeine withdrawal symptoms. These discontinuation effects may persist long after caffeine has been fully cleared from your system. Most sources suggest that the average plasma half-life of caffeine in healthy adults is within the range of 3 to 5 hours.
Though 50% of the drug may be cleared from your body within 5 hours, it will take ~1.15 days to fully eliminate caffeine from your system. That said, clearance times of caffeine could be substantially expedited or prolonged based on the individual. Some reports list a greater variation in the half-life of caffeine between 1.5 hours and 9.5 hours.
This would indicate that certain people may clear caffeine from their system within a shorter-term of less than 8.25 hours, whereas others may take up to ~2.18 days for complete clearance. Furthermore, it is necessary to understand that metabolites of caffeine (e.g. theophylline) have longer half-lives than caffeine. As a result, it will take a longer period of time to excrete these metabolites compared to caffeine itself.
- Source: http://www.ncbi.nlm.nih.gov/books/NBK223808/
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/caffeine
Factors that influence how long Caffeine stays in your system
There are a variety of factors that can impact the time caffeine stays in your system prior to clearance. Examples of such influential factors include: individual attributes (age/body mass/genes/health), co-ingestion of other drugs/substances, dosage of caffeine consumed, and how often caffeine is ingested. Understand that certain factors may be slightly more influential than others, but are largely subject to personal variation.
Two people may drink a cup of coffee at the exact same time, with the same caffeine content, yet one may metabolize and excrete the caffeine at a substantially quicker pace than the other. It is understood that variation among individuals could be due to attributes such as: a person’s age, body mass, food intake, liver function, and sex-specific factors (e.g. pregnancy).
Age: The speed and efficiency of caffeine clearance tends to increase with age, reaching a peak in adulthood. Caffeine is known to have a half-life of 5 hours in adults, whereas in neonates, the half-life of caffeine averages 80 hours; a stark contrast. Among elderly individuals (age 65+), ability to metabolize caffeine decreases by 33% compared to adults; from a rate of 1.5 ml/min to 1.0 ml/min. Extremely young children are thought to process caffeine almost as slow as neonates, but their clearance time dramatically decreases in several years.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22924488
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6886969
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/caffeine
Body height/weight/fat: A person’s physical attributes such as height, weight, and body fat could influence how rapidly caffeine is cleared from their system. An individual who is tall/heavy will likely metabolize 100 mg caffeine quicker than a person who is short/light. Usually the greater the amount of caffeine consumed relative to your body size (height/weight), the slower you’ll clear it – and vice-versa. Since having greater body fat is known to expedite metabolism and clearance of various drugs, individuals with more “fat” may process caffeine at a faster rate.
Genetics: It is well-documented that genes can influence the pharmacodynamics and pharmacokinetics of caffeine. Not only do effects of caffeine differ based on a person’s genetics, but the ability to metabolize and excrete the drug is subject to significant individual variation. Studies have reported that caffeine clearance among people with specific genes may be up to 40-times quicker than individuals with others. Certain polymorphisms may result in rapid metabolism and excretion of the drug (faster-than-average), whereas others may prolong clearance times.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20532872
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242593/
Food intake: Absorption of caffeine can be affected by the presence of food. Someone who consumes caffeine on an empty stomach tend to absorb caffeine at a faster rate than those consuming it on a full stomach. Specifically, individuals who ate a meal high in dietary fiber will not absorb caffeine as quickly. Due to potential delays in absorption times as a result of food intake, it could be speculated that clearance times may also be affected.
Liver/kidney function: Enzymes in the liver are responsible for facilitating the metabolism of caffeine. Individuals with hepatic impairment (i.e. liver abnormalities) tend to clear caffeine at much slower rates that those with healthy liver function. Case studies have shown that the half-life of caffeine had increased between 60 hours and 168 hours among those with liver dysfunction. Furthermore, it is thought that renal impairment (i.e. kidney abnormalities) may also prolong clearance times, but to a lesser extent than hepatic impairment.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7361718
Metabolic rate: It is necessary to understand that a person’s basal metabolic rate (BMR) has an impact on metabolism of exogenous substances. Usually the faster a person’s BMR, the quicker they’ll metabolize caffeine (and other drugs), whereas the slower an individual’s BMR, the longer they’ll take to metabolize caffeine. Though metabolic rate may not play a major role in metabolism and clearance of caffeine (when compared to other factors), it still warrants consideration.
Oral contraceptives: One reason that some women tend to metabolize caffeine at a slower rate than men (and other women) is due to oral contraceptive usage. Women who take oral contraceptives will experience altered distribution of caffeine upon ingestion, and ultimately a delayed clearance. Studies estimate that the half-life of caffeine may be extended by ~3 hours in women using oral contraceptives. Plasma clearance of caffeine decreases by ~0.51 ml/min/kg and free clearance of caffeine decreases by ~0.85 ml/min/kg among those taking oral contraceptives.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7359014
Pregnancy: Another factor that will impact the clearance rates of caffeine among women is pregnancy. Research has suggested that the elimination half-life of caffeine increases by an average of 7.5 hours in the last month of a woman’s pregnancy compared to non-pregnant women. This research considered other potential confounding factors, but concluded that pregnancy significantly slows clearance rates of caffeine. Women in earlier stages of pregnancy do not have as slow of clearance compared to women in later stages.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6954898
Smoker/non-smoker: If you are a smoker, you will clear caffeine at a much quicker rate (155 ml/kg/hr) than non-smokers (94 ml/kg/hr). Some studies have suggested that the half-life of caffeine among smokers is approximately 2.5 hours less than non-smokers. In other words, if it took a non-smoker 5 hours to eliminate 50% of their ingested caffeine, it may take a smoker only 2.5 hours. In part, this is due to the fact that smoking induces activity of AHH (aryl hydrocarbon hydroxylase) in the liver, resulting in faster excretion.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/657717
Co-ingestion of drugs (CYP1A2: Inducers vs. Inhibitors)
If you’re ingesting other drugs (or substances) along with caffeine, these drugs may significantly alter clearance rates. Certain substances are known to expedite the metabolic breakdown of caffeine, ultimately leading to rapid excretion – whereas others are thought to prolong caffeine metabolism, leading to prolonged clearance times. Since caffeine is metabolized in the liver, primarily by CYP1A2 isoenzymes, drugs that affect CYP1A2 tend to influence clearance rates.
A person taking an “inducer” of CYP1A2, will enhance the metabolism of caffeine and expedite the clearance rate. Examples of CYP1A2 inducers include: Tobacco, various foods (broccoli, brussels sprouts, cauliflower, etc.), Insulin, Modafinil, Nafcillin, beta-Naphthoflavone, and Omeprazole. Tobacco is the most commonly ingested CYP1A2 inducer, hence why cigarette smokers excrete caffeine in nearly half the time than non-smokers.
Though CYP1A2 inducers will expedite clearance of caffeine from a person’s system, CYP1A2 “inhibitors” will prolong excretion times. CYP1A2 inhibitory agents interfere with the enzymatic breakdown of caffeine in the liver by binding to the same (CYP450) enzyme as caffeine. Examples of CYP1A2 inhibitors include: Ciprofloxacin (and other fluoroquinolones), Fluvoxamine (SSRI), Peppermint, St. John’s wort, and Verapamil.
In addition to inhibitory drugs, ingestion of alcohol has been shown to prolong caffeine clearance. One study showed that 50 g/day of alcohol (equivalent to ~3.5 beers) resulted in a 72% increase in caffeine half-life and decreased overall clearance by 36%. A 72% increase in half-life would prolong total elimination of caffeine to nearly 2 days instead of just over 1 day.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10976659
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3802578
- Source: http://www.ncbi.nlm.nih.gov/books/NBK223808/
Dosage of Caffeine (10 mg to 400 mg)
The dosage of caffeine consumed can impact how long it stays in a person’s system. Someone who ingests low dose (especially relative to their body mass) should clear caffeine from their body quicker than someone who ingests a high dose. Though other factors play a prominent role in clearance, the body can only metabolize and excrete a set amount of caffeine at a time; if this threshold is exceeded – metabolism and clearance is compromised.
An extremely low dose of caffeine would be within the 10 mg to 20 mg range. This range is just enough to feel its effects, and the body shouldn’t have any difficulty efficiently metabolizing such a low dose. Most people consume around 200 mg of caffeine per day, resulting in slower metabolism compared to an individual ingesting a lower dose such as 10 mg.
A heavy caffeine consumer may ingest over 400 mg per day (equivalent to 4 cups of coffee). At this point, enzymes in the liver may be overtaxed and more caffeine (and its metabolites) may accumulate within the body. This accumulation may prevent efficient clearance and result in reabsorption, prolonging excretion times relative to dosage consumed.
Frequency of intake
The more often a person ingests caffeine, the longer it may take for that individual to metabolize and excrete it from their system. A frequent coffee drinker may consume several cups throughout the day, resulting in ~300 mg of ingested caffeine. After the third cup of coffee, the body will not have fully metabolized nor excreted the caffeine content within the first two cups.
As a result, a greater total amount of caffeine metabolites (i.e. paraxanthine) will have accumulated throughout a frequent user’s system. Greater accumulation of caffeine may result in a higher degree of reabsorption prior to elimination, ultimately prolonging clearance times. Furthermore, since the frequent coffee drinker may ingest their final (third) cup of coffee later in the day (e.g. afternoon), it won’t be metabolized nor eliminated as quickly as someone who had just one cup in the morning.
An infrequent caffeine consumer (e.g. someone who drinks just one cup of coffee in the morning) will only need to metabolize a small amount of caffeine, and accumulation / reabsorption are less likely. Additional caffeine will not have been added to the existing dose and metabolism will be more efficient. Also, since the less frequent user ingested caffeine in the morning – it should be eliminated before the frequent (third-cup-in-the-afternoon) user.
Caffeine: Absorption, Metabolism, Excretion (Details)
Upon ingestion of caffeine, it is rapidly absorbed by the gastrointestinal (GI) tract and distributed throughout bodily water. An approximate 99% of the caffeine ingested is absorbed within 45 minutes, and plasma concentrations peak between 15 minutes and 2 hours; peak levels are subject to individual variation based on the aforementioned factors. Following absorption of caffeine, there is no “first-pass effect” within the liver; indicating that none of the ingested caffeine is metabolized before circulating throughout the body.
Caffeine exhibits reversible binding to plasma proteins and is distributed throughout the body at an average volume of ~0.7 liters per kilogram. While caffeine is distributed throughout bodily water (specifically tissues), it is also able to pass through the blood-brain barrier, indicating that it is both hydrophilic and lipophilic. Caffeine is primarily metabolized by enzymes within the liver, predominantly CYP1A2 (cytochrome P4501A2).
CYP1A2 isoenzymes are responsible for 95% of the metabolism of caffeine. An estimated 80% of all ingested caffeine undergoes N-3-demethylation via CYP1A2 to form the metabolite “paraxanthine” (1,7-dimethylxanthine). Around 8% of caffeine undergoes 1-N-demethylation to theobromine, and another 8% undergoes 7-N-demethylation to theophylline.
Concentrations of paraxanthine are typically up to 10-fold those of theobromine and theophylline. All remaining caffeine is subject to C-8 hydroxylation, thereby forming 1,3,7-trimethyluric acid. Secondary metabolites of caffeine excreted in urine include: 1-methylxanthine (1X), 1-methyluric acid (1U), 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1,7-dimethyluric acid (17U).
The half-life of caffeine for adults is 5 hours, leading to complete systemic clearance within ~1.15 days. However, just because caffeine has been cleared from a person’s system doesn’t mean its metabolites (paraxanthine, theobromine, theophylline) will have been eliminated. Paraxanthine levels take over 3-fold longer to peak than caffeine and its clearance may be prolonged due to the fact that it can accumulate within the body.
The half-lives of caffeine metabolites theobromine and theophylline are much longer than caffeine itself at ~7.1 hours (theobromine) and ~7.9 hours (theophylline). This means that the metabolites of caffeine will remain in your system for up to 16 hours longer than caffeine itself. The kidneys are responsible for excreting most of the caffeine ingested (and its metabolites), whereas only 1% of caffeine will be excreted unchanged in urine.
- Source: http://www.ncbi.nlm.nih.gov/books/NBK223808/
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/caffeine
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401099/
Types of Caffeine Drug Tests
Due to the fact that caffeine is not regarded as an illicit drug, it is not assessed for on most drug tests. Only high-performance Olympic athletes may be tested for the presence of caffeine. Modalities of caffeine testing include: urine tests, blood tests, saliva tests, and even hair tests.
Urine tests: The easiest way to determine whether someone has ingested caffeine is by testing a fresh urine sample. Though only a small percentage 1-3% of caffeine will be excreted unchanged via the urine, metabolites such as paraxanthine, theobromine, and theophylline can be detected. Furthermore, these metabolites can be detected for a much longer duration than caffeine itself in the urine.
Various caffeine metabolites (theobromine / theophylline) would likely be detectable on a urine test for up to 5 days post-ingestion. Caffeine itself and primary metabolite “paraxanthine” would remain detectable for between 2 and 5 days (depending on the individual). Other secondary metabolites that will appear within urine to detect caffeine ingestion include: 1-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid, 1,7-dimethyluric acid, 1,3,7-trimethyluric acid, and 5-acetylamino-6-amino-3-methyluracil
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25833779
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1368325/
Blood tests: Caffeine intake could be detected via a blood sample within minutes of ingestion. A blood test isn’t commonly used as a means of detecting caffeine, but should detect caffeine for up to 24 hours after ingestion. Detection limits for caffeine and its metabolites in a blood sample are typically set at 5 ng/ml for caffeine and theobromine, and 10 ng/ml for paraxanthine and theophylline.
Only in the event that an individual was hospitalized for a suspected overdose would they likely have their blood drawn and analyzed for caffeine. Should a medical professional detect abnormally high levels of caffeine within the bloodstream, administration of activated charcoal is likely. Additional agents may also be administered to counteract caffeine toxicity.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21265179
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1629311
Hair tests: It is possible to determine whether someone has ingested caffeine by collecting a hair sample. A hair sample typically consists of at least 20 hair follicles (3 cm to 6 cm) from a person’s head. These follicles are then sent to a laboratory and analyzed with GC/MS (gas chromatography/mass spectrometry).
Among healthy individuals, caffeine will show up in the hair at approximately 7.21 ng/mg whereas among those with hepatic impairment, it will appear at an average level of 26.5 ng/ml. Hair tests provide the most benefit in determining how efficiently an individual is metabolizing caffeine within the liver. Someone with liver problems can assess their severity based on how much caffeine appears within hair after ingestion.
Caffeine is detectable in hair for a much longer duration than urine samples. While it may not initially appear in a person’s hair for several days (post-intake), it may remain in a hair follicle for over a month after ingestion. For this reason, hair tests may be preferred to assess caffeine intake over an extended period.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8832505
Saliva tests: Collecting an oral fluid (saliva) sample is the most convenient way to determine whether someone has ingested caffeine. Caffeine is likely to first appear within salivary fluid within 15 minutes of ingestion, and may remain present for up to 24 hours. Furthermore, salivary concentrations tend to correlate well with blood concentrations of caffeine; the greater the levels in saliva, the greater levels within the bloodstream.
Research suggests that saliva caffeine tests are useful to assess liver functionality. Those with suboptimal liver function (i.e. hepatic impairment) tend to exhibit slower salivary clearance rates of caffeine compared to healthy individuals. Therefore high levels of caffeine in saliva may indicate compromised liver functionality. That said, it would be uncommon to administer a saliva test to determine caffeine levels for purposes other than scientific research.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/3557314
Who may be affected by caffeine testing?
Usually nobody is affected by caffeine testing because it is not tested for – it is a legal drug. Only high-level (Olympic and collegiate) athletes may be subject to caffeine testing to determine whether an individual had ingested extremely high dosages. In both the Olympic and collegiate testing protocols, only an extremely high dosage of caffeine (in far excess of 400 mg would result in penalization).
- Olympic athletes: The International Olympic Committee has set caffeine intake thresholds at 12 micrograms/mL. Some estimate that 12 micrograms per milliliter would be attained after consumption of 8 cups of coffee. Should an individual test positive for caffeine above the threshold of 12 mcg/ml – he/she may be penalized or banned from competition.
- Collegiate athletes: The NCAA (National Collegiate Athletic Association) has set caffeine threshold limits at 15 micrograms/mL. Individuals would likely have ingested over 8 cups of coffee to attain such a high concentration of caffeine. Should an individual test positive for caffeine above the 15 mcg/ml threshold – a temporary suspension may result.
Tips to clear Caffeine from your system
If your goal is to clear caffeine (and its metabolites) from your system as quickly as possible, there may be some tricks you could use to expedite the clearance. Prior to implementing any of these tips, you should always consult a medical professional. Understand that these tricks may not expedite clearance of caffeine for everyone, but may work extremely well for certain individuals.
- Cease caffeine intake: Though ceasing caffeine intake is an obvious tip, many people think they can fully detoxify from caffeine without stopping the drug. If you want to ensure that caffeine is fully eliminated from your system, you’ll need to cease ingestion. Don’t think you can get away with a small cup of coffee now and then if you truly want to excrete all caffeine (as well as paraxanthine, theobromine, and theophylline).
- Enzymatic inducers: There are many substances (some pharmaceutical, others natural) that can aid in the metabolism and excretion of caffeine. Drugs (or supplements) classified as CYP1A2 inducers will significantly decrease total clearance time of caffeine from your system. Examples of such “inducers” include: insulin, modafinil, nafcillin, and tobacco. Understand that these should only be taken with medical approval.
- Eat certain foods: Though drugs are known to affect CYP1A2, so are various foods. Eating foods such as: broccoli, brussels sprouts, and cauliflower can induce activity of CYP1A2, thereby minimizing excretion time of caffeine. It is also known that eating foods high in fiber can significantly slow absorption of caffeine, possibly modifying its clearance rate.
- Stay hydrated: It is known that clearance rates of caffeine can be impacted by urinary flow. The less hydrated an individual, the less total urinary flow – resulting in diminished caffeine clearance. On the other hand, individuals who are adequately hydrated should excrete caffeine at normative, healthy rates.
- Consider activated charcoal: If you recently ingested a considerable amount of caffeine and want to clear it from your body as quickly as possible, you could take activated charcoal. In order for the activated charcoal to be effective, it must be taken quickly after you’ve consumed caffeine. That said, some believe that activated charcoal may still expedite clearance and detoxification from caffeine.
How long has caffeine stayed in your system?
If you stopped drinking caffeine, share a comment below regarding how long you believe it stayed in your system. To help others get a better understanding of your situation, mention whether you have any genetic variants that expedite caffeine metabolism and/or are taking any drugs that may have affected clearance rates. Additionally, mention you age, any health problems (e.g. hepatic impairment), whether you use contraceptives, etc.
Understand that for most healthy adult caffeine users, caffeine should be fully eliminated (100%) from a person’s system within 1.5 days. Its metabolites with longer half-lives (e.g. theobromine, theophylline, etc.) may remain present in the body for nearly 2 days. Most caffeine users will have cleared caffeine and its metabolites from their bodies within 48 hours.