High levels of methylxanthines in chocolate do not alter theobromine disposition

Shively, Carol A.; Tarka, Stanley M.; Arnaud, Maurice J.; Dvorchik, Barry H.; Passananti, G. Thomas; Vesell, Elliot S.

doi:10.1038/clpt.1985.65

Cited by 35 publications

(18 citation statements)

References 9 publications

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“…This is in line with the fact that paraxanthine is slightly more potent than caffeine in antagonising the effects of adenosine. 29 Although theobromine has also been shown to increase natriuresis and to present similar properties than other methylxanthines, 21 we found no significant association of theobromine with BP. Theobromine has one fifth the stimulant effect of caffeine, and acute theobromine and caffeine intake have previously been shown to exert opposite results on BP among 24 healthy female volunteers.…”

Section: Discussioncontrasting

confidence: 52%

“…Other methylxanthine-related mechanisms possibly involved include sympathomimetic effects, smooth muscle relaxation, and phosphodiesterase inhibition. 20,21 We found no consistent association of 24-hour caffeine and caffeine metabolite excretions with DBP. Although the reason of the differential associations of caffeine and caffeine metabolites on SBP and DBP is not entirely clear, it is compatible with the hypothesis that methylxanthines influence BP via their natriuretic property.…”

Section: Discussioncontrasting

confidence: 41%

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Associations of Ambulatory Blood Pressure With Urinary Caffeine and Caffeine Metabolite Excretions

et al. 2015

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H ypertension is a major risk factor for cardiovascular disease and results from a complex interplay between genetic and environmental factors.1 Intake of caffeinated beverages might be associated with lower cardiovascular mortality.2 Caffeine, >70% of which is provided by coffee consumption, 3 is metabolized by the liver CYP1A2 enzyme into paraxanthine (≈80%), theobromine (≈12%), and theophylline (≈4%). Caffeine and caffeine metabolites are methylxanthines: a family of nonspecific adenosine receptor antagonist with several properties, including diuretic and natriuretic properties. 4,5 The urinary excretion of caffeine and caffeine metabolites is a valid measure of caffeine intake. 6 The relation of blood pressure (BP) with caffeine and caffeine metabolites is of major interest, given their widespread consumption in foods and beverages (eg, coffee, tea, cola drinks, chocolate products) and the public health burden of high BP. Studies on the effect of acute consumption of caffeine at dietary levels on BP produced inconsistent results, 7 with a recent study restricted to nonsmokers showing a decrease in systolic BP (SBP). 8 In a crosssectional study, high reported caffeine intake was associated with a lower prevalence of hypertension only in nonsmokers. 9 To date, studies on the association of caffeine and BP have been limited by the use of reported caffeine intake instead of Abstract-Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and nighttime systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. 14 in Laus...

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Section: Discussioncontrasting

confidence: 52%

Section: Discussioncontrasting

confidence: 41%

Associations of Ambulatory Blood Pressure With Urinary Caffeine and Caffeine Metabolite Excretions

et al. 2015

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“…Clinical investigations with mammals have shown that theobromine exerts diverse pharmacological effects (diuresis, stimulation of the cardiovascular system and glandular secretions) and relaxation of the growth muscles (Shively et al, 1985) while studies with poultry and pigs have recorded pancreatic and liver enlargements (Braude and Foot, 1942;Odunsi and Longe, 1995a) and increased mortality. Theobromine intake was calculated to be 12·8 g/d for chicks fed on the 300 g/kg UCBC diet while the chicks fed on the corresponding WCBC and ACBC diets ingested 5·95 and 4·45 g/d.…”

Section: Growth and Nutrient Retentionmentioning

confidence: 98%

Nutritive value of hot water- or cocoa-pod ash solution-treated cocoa bean cake for broiler chicks

Og²

1998

British Poultry Science

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1. The effectiveness of boiling (90 degrees C for 75 min) in water and alkali (cocoa-pod ash CPA solution) treatments for reducing the antinutritional factor (theobromine) in cocoa bean cake (CBC) and the influence of these treatments on the chemical composition, gross energy and metabolisable energy (ME) of CBC to the broiler chicken were examined. 2. Boiling did not affect crude protein content but resulted in lower ash, crude fibre, ether extract and gross energy values, and a 56% reduction in theobromine, while the use of increasing concentrations of cocoa-pod ash solution decreased crude protein, ether extract, theobromine and gross energy. 3. Mineral elements were significantly affected both by boiling and by cocoa-pod ash solution treatments. 4. There were no significant effects of hot water-treated or 5 g CPA/kg treated CBC on ME or MEn. However, efficiency of energy utilisation was improved. 5. Nutritional evaluation showed that there was a general decrease in performance at high dietary concentrations of CBC (treated or untreated). However, both forms of treatment (hot water-treated and 5 g CPA/kg treated CBC) significantly improved food utilisation and retention of nitrogen and dry matter.

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“…However, there is no information relating to the pharmacokinetics of PX in man although some studies of TB pharmacokinetics and metabolism in humans have been reported Drouillard et al, 1978;Miners et al, 1982Miners et al, , 1985Shively et al, 1985;Simons et al, 1984;Tarka et al, 1983 Protocol Equimolar oral doses of TP, TB, PX (250 mg of each) and CA (270 mg) were separately administered to each subject. Subjects fasted from the evening prior to and until 4 h following methylxanthine administration on each study day.…”

Section: Introductionmentioning

confidence: 99%

Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.

Lelo¹,

Birkett²,

Robson³

et al. 1986

Brit J Clinical Pharma

142

105

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1 The pharmacokinetics of caffeine (CA), paraxanthine (PX), theobromine (TB) and theophylline (TP) were studied in six healthy male volunteers after oral administration of each compound on separate occasions. 2 The total plasma clearances of CA and PX were similar in value (2.07 and 2.20 ml minkg-', respectively) as were those for TP and TB (0.93 and 1.20 ml min-' kg-', respectively).The unbound plasma clearances of CA and PX were also similar in magnitude (3.11 and 4.14 ml min-' kg-', respectively) as were those of TP and TB (1.61 and 1.39 ml min-t kg-', respectively). 3 The half-lives of TP and TB (6.2 and 7.2 h, respectively) were significantly longer than those of CA and PX (4.1 and 3.1 h, respectively).4 The volume of distribution at steady state of TP (0.441 kg-') was lower than that of the other methylxanthines (0.63-0.721 kg-1). The unbound volume of distribution of TP (0.77 1 kg-) was however the same as that of TB (0.791 kg-') whereas the unbound volume of distribution of PX (1.18 1 kg-1) was similar to that of CA (1.06 1 kg-').

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High levels of methylxanthines in chocolate do not alter theobromine disposition

Cited by 35 publications

References 9 publications

Associations of Ambulatory Blood Pressure With Urinary Caffeine and Caffeine Metabolite Excretions

Associations of Ambulatory Blood Pressure With Urinary Caffeine and Caffeine Metabolite Excretions

Nutritive value of hot water- or cocoa-pod ash solution-treated cocoa bean cake for broiler chicks

Comparative pharmacokinetics of caffeine and its primary demethylated metabolites paraxanthine, theobromine and theophylline in man.

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