The analysis showed an association between fast metabolisers and coffee consumption in males, individuals younger than 59 years, and Caucasians, but not in females, individuals older than 59 years, and Asians.
This is the first study to identify a weak association between the fast caffeine metaboliser profile and coffee intake in the Asian population as well as the age and gender related variation. Further research will support our understanding Since individual reactions to caffeine may differ according to genetic variability, individuals tend to only consume the amount of caffeine they feel comfortable with The European Food Safety Authority EFSA advises that daily caffeine intakes of up to mg and single doses of up to mg do not raise concerns when consumed as part of a health balanced diet 4.
EFSA recommends lower levels for pregnant women, who are advised to limit caffeine intake to mg from all sources 4. Further research into caffeine could categorise populations by gene-type consider the impact of caffeine consumption on various functions.
This information is intended for Healthcare professional audiences. Please consider the environment before printing. Caffeine and metabolism Print this page. By contrast, the paraxanthine concentration was higher in the type-2 diabetes participants, consistent with our conclusion that CYP1A2 activity was higher in the patients than in the controls. Furthermore, statistical modelling revealed that high habitual caffeine intake was a significant predictor of faster CYP1A2 enzyme activity in our study sample.
This is because caffeine is a known inducer of CYP1A2 activity [ 4 , 26 , 27 ], and the diabetes patients of the present study consumed larger amounts of caffeine Table 1. Nineteen out of 57 patients administered insulin that has also been described as an inducer of CYP1A2 activity. When only type-2 diabetes patients were assessed, however, there were no significant differences in CYP1A2 activity between insulin users and non-users.
This result suggests that insulin may not be a key driver of CYP1A2 activity in our study participants. Nevertheless, larger samples are needed in future studies to corroborate the existence of higher CYP1A2 activity in the type-2 diabetes patient population, and that this higher activity is due primarily to high caffeine intake.
This finding was in-line with previous research [ 4 ]. Furthermore, there was no significant difference between CYP1A2 enzyme activity of participants who reported taking medication over the long-term, compared to participants that were not taking medications.
This finding may reflect that medication has varying effects on CYP1A2 activity inhibition, induction, or no effect , which are drug-specific [ 2 ]. Because we did not collect information regarding the specific medications of participants, it is impossible to further qualify this result.
In contrast to previous studies [ 4 , 8 ], female gender, contraceptive pill use, smoking, and CYP1A2 genotype also revealed no significant effect on CYP1A2 activity. These low participant numbers may explain why significant effects of these covariates were not seen.
The exact mechanism that links caffeine intake to speed of caffeine clearance is not yet fully understood. Animal studies have shown increased liver microsome CYP1A2 activity and mRNA levels in rats on very high doses of caffeine [ 26 , 27 ]. This observation indicates an auto-induction of caffeine on CYP1A2 [ 4 ]. Support also comes from epidemiological studies, where a 1. Another suggestion is that persons with existing high CYP1A2 activity may consume more coffee because they metabolize it more quickly [ 28 ].
Coffee is a complex blend of organic compounds and therefore, constituent substances, aside from caffeine, may also contribute to its inducing effect [ 4 ]. For example, coffee beans are roasted at high temperatures, and thus may contain compounds similar to those found in tobacco smoke or chargrilled meats - known inducers of CYP1A2 activity [ 29 ]. The limitations of this study include the reliance on self-reports to determine the timing of saliva sampling and the lack of information regarding habitual consumption of some dietary components known to influence CYP1A2 activity, e.
Also habitual caffeine intake was measured by self-report questionnaire. While the validity of this method is established [ 12 , 31 ], variability exists in the amount of caffeine per serving [ 32 ]. Therefore, caffeine use may have been under- or overestimated. However, Fig. This indicates that other, unknown or unmeasured predictor variables were also influencing CYP1A2 activity in our study sample.
Previously, it has been noted that a large proportion of CYP1A2 activity is currently unexplained [ 2 ]. In conclusion, while various factors probably influence CYP1A2 activity, high caffeine intake likely plays an important role. Here, we provide evidence that a positive association between caffeine consumption and CYP1A2 activity is present in our type-2 diabetes patient sample. Future studies are warranted to establish whether higher CYP1A2 enzyme activity is indeed causally related to high caffeine intake.
Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a cohort of healthy Caucasian volunteers.
Eur J Clin Pharmacol. PubMed Google Scholar. Hyperinsulinemia causes a preferential increase in hepatic PA2 activity. Biochem Pharmacol. Breast Cancer Res. Polymorphisms in the cytochrome P CYP1A2 gene CYP1A2 in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism. Br J Clin Pharmacol. Evaluation of caffeine as a test drug for CYP1A2. Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P phenotyping probes.
Fuhr U, Rost KL. Relationships among type 2 diabetes, sleepiness, and habitual caffeine intake: a case—control field study. J Psychopharmacol. In press. The paraxanthine:caffeine ratio in serum or in saliva as a measure of CYP1A2 activity: when should the sample be obtained? Clin Pharmacol Ther.
Article PubMed Google Scholar. Biomed Chromatogr. Pharmacokinetics of caffeine in plasma and saliva, and the influence of caffeine abstinence on CYP1A2 metrics. Kamimori, G. Dose-dependent caffeine pharmacokinetics during severe sleep deprivation in humans.
Kang, A. Effects of furanocoumarins from apiaceous vegetables on the catalytic activity of recombinant human cytochrome P 1A2. Protein J. Ko, F. Inhibition of platelet thromboxane formation and phosphoinositides breakdown by osthole from Angelica pubescens.
Koenigs, L. Mechanism-based inactivation of human liver cytochrome P 2A6 by 8-methoxypsoralen. Drug Metab. Dispos 25 12 , — Kolis, S. The metabolism of 14C-methoxsalen by the dog. Dispos 7 4 , — Kot, M. Caffeine as a marker substrate for testing cytochrome P activity in human and rat. Law, F. Irreversible binding of14C-diphenyl ether-derived radioactivity to liver microsomesin vitroand tissoe proteinsin vivo.
Drug Chem. Food Additives and Contaminants 13 2 , — Physiologically based pharmacokinetic modeling of tea catechin mixture in rats and humans.
Letteron, P. Inactivation and induction of cytochrome P by various psoralen derivatives in rats. Li, J. Simultaneous determination of osthole, bergapten and isopimpinellin in rat plasma and tissues by liquid chromatography-tandem mass spectrometry. B , 77— Lim, H. Lipton, R. Caffeine in the management of patients with headache. Headache Pain 18, Liu, Z.
B , — Mays, D. Bioactivation of 8-methoxypsoralen and irreversible inactivation of cytochrome P in mouse liver microsomes: modification by monoclonal antibodies, inhibition of drug metabolism and distribution of covalent adducts. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Meyer, H. Bioavailability of apigenin from apiin-rich parsley in humans. Nawrot, P. Effects of caffeine on human health. Food Additives and Contaminants 20, 1— Perera, V.
Peterson, S. Food Chem. Sahali-Sahly, Y. In VitroStudies on the metabolic activation of the furanopyridine L,, a highly potent and selective mechanism-based inhibitor of cytochrome P 3A4.
Shephard, S. Measurement of 5-methoxypsoralen and 8-methoxypsoralen in saliva of PUVA patients as a noninvasive, clinically relevant alternative to monitoring in blood. Sheriffdeen, M. Therapies Med. Shimada, T. Siddiqui, A. Comparison of serum levels and clinical results of PUVA therapy with three different dosage forms of 8-methoxypsoralen. Stolk, L.
Serum and urine concentrations of 5-methoxypsoralen after oral administration. Tang-Liu, D. Disposition of caffeine and its metabolites in man.
Tian, D. Effects of common CYP1A2 genotypes and other key factors on intraindividual variation in the caffeine metabolic ratio: an exploratory analysis. Tinel, M. Inactivation of human liver cytochrome P by the drug methoxsalen and other psoralen derivatives.
Villeneuve, D. Derivation and application of relative potency estimates based on in vitro bioassay results. Walther, T. Variability of serum levels for three oral 8-methoxypsoralen brands. Photoimmunol Photomed. Wikoff, D. Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children.
Yang, L. Computational andin vitrostudies on the inhibitory effects of herbal compounds on human cytochrome P 1A2. Xenobiotica 42, — Zhang, Y. PKSolver: an add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Methods Programs Biomed. Zhuang, X. Compared with the quercetin nontreatment phase, the MRs were decreased by Quercetin is widespread in human diet and globally recognised as an alternative or complementary medicine.
Just like its application, the HDI may be the major concern for people [ 14 , 15 ]. Quercetin could affect the activities of certain CYPs, for which some researches have provided evidences: the bioavailability of oral doxorubicin, diltiazem, moxidectin, etoposide, and pioglitazone has been significantly increased after coadministration with quercetin, and the underlying mechanism might be through the inhibition of CYP3A [ 4 — 6 , 16 , 17 ].
CYP1A2 is one of the important enzymes in the oxidative metabolism of exogenous substances. The and of the main metabolite paraxanthine were decreased by quercetin treatment, which indicated that day quercetin treatment has significantly inhibited the CYP1A2 activity in vivo , and consequently suppressed the transformation of caffeine into paraxanthine.
Although the MRs were decreased by quercetin treatment in the two genotype groups, we failed to find any significant difference in the inhibition degree on MR between the two genotype groups, neither on the and reduction degrees of paraxanthine, indicating that CYP1A2 genotype had similar or no effect on quercetin treatment.
The possible mechanism might be that quercetin inhibits the CYP1A2 activity at the enzyme level, with no effect on the expression at mRNA level. The hypothesis needs to be elucidated by further experiments. Since the CYP1A2 primarily is involved in the metabolism of various drugs such as caffeine, theophylline, phenacetin, clozapine, arachidonic acid, and R-warfarin [ 18 ], the potential HDI associated with quercetin should be taken into consideration in clinical practice.
The authors declare that there is no conflict of interests regarding the publication of this paper. This work was supported by the National Scientific Foundation of China nos.
This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Academic Editor: Daniela Parolaro. Received 17 Mar Revised 14 May Accepted 28 May Published 15 Jun Abstract Background.
Introduction Quercetin, a member of the flavonoids family, is one of the most prominent dietary antioxidants. Methods 2. Study Protocol The study had a randomized design with 2 treatment phases separated by a 2-week washout period.
HPLC Method for Caffeine and Paraxanthine Plasma samples were processed and analyzed with the same method, and the concentration of caffeine and paraxanthine was determined by HPLC based on the reported analytical method with some modifications [ 12 , 13 ].
Sample Preparation Plasma samples were prepared according to the literatures [ 12 , 13 ]. Table 1. Pharmacokinetic parameters of caffeine and its metabolite paraxanthine 17X and the relationship with CYP1A2 genotype in 12 healthy subjects before and after the day quercetin treatment. Figure 1. Figure 2. Figure 3.
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