Influence of the consumption pattern of magnesium from magnesium-rich mineral water on magnesium bioavailability.

It is generally considered that the absorption of Mg is inversely related to the ingested dose. The objective of the present study was to determine if the mode of administration (bolus v. consumption throughout the day) could influence Mg bioavailability from Mg-rich natural mineral water comparing the same nutritional Mg amount (126 mg). Using a 2 d cross-over design, twelve healthy men were asked to drink 1·5 litres Mg-rich mineral water either as 2 × 750 ml or 7 × 212 ml throughout the day. Two stable isotopes ((25)Mg and (26)Mg) were used to label the water in order to distinguish both regimens. Fractional apparent Mg absorption was determined by faecal monitoring and Mg retention was determined by measuring urinary excretion of Mg isotopes. Higher Mg absorption (50·7 (SD 12·7) v. 32·4 (SD 8·1) %; P = 0·0007) and retention (47·5 (SD 12·9) v. 29·0 (SD 7·5) %; P = 0·0008) from Mg-rich mineral water were observed when it was consumed in seven servings compared with larger servings. Thus, regular water consumption throughout the day is an effective way to increase Mg bioavailability from Mg-rich mineral water.

Pharmacokinetics and metabolism of natural methylxanthines in animal and man.

Caffeine, theophylline, theobromine, and paraxanthine administered to animals and humans distribute in all body fluids and cross all biological membranes. They do not accumulate in organs or tissues and are extensively metabolized by the liver, with less than 2% of caffeine administered excreted unchanged in human urine. Dose-independent and dose-dependent pharmacokinetics of caffeine and other dimethylxanthines may be observed and explained by saturation of metabolic pathways and impaired elimination due to the immaturity of hepatic enzyme and liver diseases. While gender and menstrual cycle have little effect on their elimination, decreased clearance is seen in women using oral contraceptives and during pregnancy. Obesity, physical exercise, diseases, and particularly smoking and the interactions of drugs affect their elimination owing to either stimulation or inhibition of CYP1A2. Their metabolic pathways exhibit important quantitative and qualitative differences in animal species and man. Chronic ingestion or restriction of caffeine intake in man has a small effect on their disposition, but dietary constituents, including broccoli and herbal tea, as well as alcohol were shown to modify their plasma pharmacokinetics. Using molar ratios of metabolites in plasma and/or urine, phenotyping of various enzyme activities, such as cytochrome monooxygenases, N-acetylation, 8-hydroxylation, and xanthine oxidase, has become a valuable tool to identify polymorphisms and to understand individual variations and potential associations with health risks in epidemiological surveys.

Dietary quercetin supplementation is not ergogenic in untrained men.

Quercetin supplementation increases muscle oxidative capacity and endurance in mice, but its ergogenic effect in humans has not been established. Our study investigates the effects of short-duration chronic quercetin supplementation on muscle oxidative capacity; metabolic, perceptual, and neuromuscular determinants of performance in prolonged exercise; and cycling performance in untrained men. Using a double-blind, pretest-posttest control group design, 30 recreationally active, but not endurance-trained, young men were randomly assigned to quercetin and placebo groups. A noninvasive measure of muscle oxidative capacity (phosphocreatine recovery rate using magnetic resonance spectroscopy), peak oxygen uptake (Vo(2peak)), metabolic and perceptual responses to submaximal exercise, work performed on a 10-min maximal-effort cycling test following the submaximal cycling, and voluntary and electrically evoked strength loss following cycling were measured before and after 7-16 days of supplementation with 1 g/day of quercetin in a sports hydration beverage or a placebo beverage. Pretreatment-to-posttreatment changes in phosphocreatine recovery time constant, Vo(2peak,) substrate utilization, and perception of effort during submaximal exercise, total work done during the 10-min maximal effort cycling trial, and voluntary and electrically evoked strength loss were not significantly different (P > 0.05) in the quercetin and placebo groups. Short duration, chronic dietary quercetin supplementation in untrained men does not improve muscle oxidative capacity; metabolic, neuromuscular and perceptual determinants of performance in prolonged exercise; or cycling performance. The null findings indicate that metabolic and physical performance consequences of quercetin supplementation observed in mice should not be generalized to humans.

CYP1A2 genetic polymorphisms and adenocarcinoma lung cancer risk in the Tunisian population.

AIMS: In this study, the effects of four single nucleotide polymorphisms (SNPs), -3860G>A, -2467delT, -739T>G and -163C>A, of CYP1A2 gene on lung cancer were evaluated in Tunisian population. MAIN METHODS: Four polymorphisms of CYP1A2 gene were analysed in 109 healthy smokers and in 101 lung cancer cases, including 63 with squamous cell carcinoma (SCC) and 41 with adenocarcinoma (AD). The genotyping for the SNPs -3860 G>A, -2467delT, -739T>G and -163C>A was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. KEY FINDINGS: The results showed that smokers with CYP1A2 gene polymorphisms were associated with an increased risk for the development of lung AD. There was however no significant increased risk of developing lung SCC in smokers having CYP1A2 gene polymorphisms. An increased risk of developing AD was observed in smokers who are carriers of at least one copy of -3680A or -739G giving a significant odds ratio (OR) of 6.02 (CI=2.91-12.9) and 3.01 (CI=1.54-5.98), respectively. SIGNIFICANCE: These genotyping data are consistent with the hypothesis that tobacco-specific-N-nitrosamines (TSN) such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are major contributors to the development of lung AD and that CYP1A2 gene product plays an important role in the metabolic activation of NNK. This study suggests that SNPs of CYP1A2 could be considered as promising biomarkers in the aetiology of lung AD in smokers.

Update on the assessment of magnesium status.

Magnesium (Mg) is the fourth most abundant mineral in the body and the most abundant intracellular divalent cation, with essential roles in many physiological functions. Consequently, the assessment of Mg status is important for the study of diseases associated with chronic deficiency. In spite of intense research activities there is still no simple, rapid, and accurate laboratory test to determine total body Mg status in humans. However, serum Mg < 0.75 mmol/l is a useful measurement for severe deficiency, and for values between 0.75 and 0.85 mmol/l a loading test can identify deficient subjects. The loading test seems to be the gold standard for Mg status, but is unsuitable in patients with disturbed kidney and intestinal functions when administered orally. There is also a need to reach a consensus on a standardized protocol in order to compare results obtained in different clinical units. Other cellular Mg measurements, such as total or ionized Mg, frequently disagree and more research and systematic evaluations are needed. Muscle Mg appears to be a good marker, but biopsies limit its usefulness, as is the case with bone Mg, the most important but heterogeneous Mg compartment. The development of new and non invasive techniques such as nuclear magnetic resonance (NMR) may provide valuable tools for routinely analysing ionized Mg in tissues. With the development of molecular genetics techniques, the recent discovery of Transient Receptor Potential Melastatin channels offers new possibilities for the sensitive and rapid evaluation of Mg status in humans.

Cigarette filter and the incidence of lung adenocarcinoma among Tunisian population.

Increasing incidence of lung adenocarcinoma (Ad) is observed for the last two decades in all over the world and may become the most frequent lung cancer subtype in the next years. Its increasing prevalence has been well documented in United States for the last two decades. Geographical differences in the increase of Ad prevalence was also reported in Europe where the Squamous Cell Carcinoma (SCC) still predominates but the increase of Ad incidence was shown in the beginning of 1980s. In Tunisia, the incidence of Ad was relatively low in 1990 when compared to western countries and was shown to continue to increase with a more important rise of Ad incidence over SCC type. In this study the time-dependent increased incidence of Ad is reported between USA, Europe and Tunisia. A lag-time period of 10 years is observed between Tunisia and Europe for this increased incidence in smokers and about 20 years between USA and Tunisia. According to the literature, changes in the types of cigarettes smoked as well as modifications in time and geographical trends seem to explain partly the increased incidence of Ad lung cancer.

Differences in pharmacokinetic and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects.

The present study investigated pharmacokinetic and electroencephalographic responses to caffeine (140 mg) in two groups of healthy volunteers reporting, or not, caffeine-related sleep disturbances. Significant differences in caffeine consumption and smoking habits were observed between the two groups. Plasma samples were taken from each subject before (T0) and after caffeine intake at 0.5, 1, 2, 4, 6 and 24 h. Three pharmacokinetic parameters: half-life (t1/2), maximum time (Tmax) and maximum plasma concentration (Cmax) were calculated from caffeine plasma concentration measurements determined by reversed phase HPLC analysis. Caffeine-sensitive subjects showed significantly greater half-life values when calculated on 24 h after the administration than tolerant subjects (p<0.05). Since the elimination kinetics were similar on the first 6 h after caffeine administration, the increased caffeine clearance observed overnight, when smoking was resumed in the control group, may indicate a short delay for the induction of hepatic cytochrome, reported here for the first time. Electrophysiological responses to caffeine, including vigilance and cortical activity, were assessed by ambulatory electroencephalographic (EEG) recorded during a period of 6 h before and after caffeine consumption. Following caffeine intake, the caffeine-intolerant subjects presented an increase in vigilance levels with faster peak alpha, beta frequency and lower delta and theta power when compared to tolerant subjects. Pharmacokinetic parameters and EEG data showed significant differences between sleep-sensitive and control subjects. These variations may be, in part, explained by cigarette smoking and the higher caffeine intake observed in the subjects of the control groups while caffeine sleep-sensitive subjects have a significantly lower caffeine intake, as already reported in previous studies on patients with sleep disturbances.

Effect of water deprivation on cognitive-motor performance in healthy men and women.

Whether mental performance is affected by slowly progressive moderate dehydration induced by water deprivation has not been examined previously. Therefore, objective and subjective cognitive-motor function was examined in 16 volunteers (8 females, 8 males, mean age: 26 yr) twice, once after 24 h of water deprivation and once during normal water intake (randomized cross-over design; 7-day interval). Water deprivation resulted in a 2.6% decrease in body weight. Neither cognitive-motor function estimated by a paced auditory serial addition task, an adaptive 5-choice reaction time test, a manual tracking test, and a Stroop word-color conflict test nor neurophysiological function assessed by auditory event-related potentials P300 (oddball paradigm) differed (P > 0.1) between the water deprivation and the control study. However, subjective ratings of mental performance changed significantly toward increased tiredness (+1.0 points) and reduced alertness (-0.9 points on a 5-point scale; both: P < 0.05), and higher levels of perceived effort (+27 mm) and concentration (+28 mm on a 100-mm scale; both: P < 0.05) necessary for test accomplishment during dehydration. Several reaction time-based responses revealed significant interactions between gender and dehydration, with prolonged reaction time in women but shortened in men after water deprivation (Stroop word-color conflict test, reaction time in women: +26 ms, in men: -36 ms, P < 0.01; paced auditory serial addition task, reaction time in women +58 ms, in men -31 ms, P = 0.05). In conclusion, cognitive-motor function is preserved during water deprivation in young humans up to a moderate dehydration level of 2.6% of body weight. Sexual dimorphism for reaction time-based performance is present. Increased subjective task-related effort suggests that healthy volunteers exhibit cognitive compensating mechanisms for increased tiredness and reduced alertness during slowly progressive moderate dehydration.

Mineral water intake reduces blood pressure among subjects with low urinary magnesium and calcium levels.

BACKGROUND: Several previous epidemiological studies have shown a relation between drinking water quality and death in cardiovascular disease whereas others have not found such a relationship. An intervention study was undertaken to evaluate the effect of water with added magnesium and natural mineral water on blood pressure. METHODS: A group of 70 subjects with borderline hypertension was recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or 3) natural mineral water, in a random, double blind fashion during four weeks. RESULTS: Among persons with an initial low excretion of magnesium or calcium in the urine, the urinary excretion of magnesium was increased in the groups consuming the two waters containing magnesium after 4 weeks. A significant decrease in blood pressure was found in the group consuming mineral water at 2 and 4 weeks. CONCLUSION: The results suggest that minerals taken in water are significant for the body burden and that an intake of mineral water among persons with a low urinary excretion of magnesium or calcium may decrease the blood pressure. Further studies should investigate the extent of mineral deficiency in different populations and the efficiency of different vehicles for supplying minerals, particularly magnesium and calcium.

A compartmental model of magnesium metabolism in healthy men based on two stable isotope tracers.

The aim of this study was to build a compartmental model of magnesium (Mg) kinetics by using data collected from six healthy adult men after oral administration of 26Mg and intravenous administration of 25Mg. Blood, urine, and feces were collected for 12 days after administration of the isotopes. Isotopic ratios were determined by inductively coupled plasma-mass spectrometry. Data were analyzed for each subject using SAAMII. We began with a compartmental model previously proposed (Avioli LV and Berman M. J Appl Physiol 21: 1688-1694, 1966) and developed an alternative approach to resolve the discrepancy between model-predicted curves and experimental data. This analysis enables the exploration of 25% of total body Mg that exchanges rapidly from plasma compartment with two extraplasma pools. One of the extraplasma compartments contains 80% of the exchangeable Mg with a transport rate of 48 +/- 13 mg/h. The second exchanges 179 +/- 88 mg of Mg/h. The model permitted estimation of kinetic parameters as well as fractional Mg absorption and fecal endogenous excretion.

Comparison of stable-isotope-tracer methods for the determination of magnesium absorption in humans.

BACKGROUND: The double-labeling (DL) method for determining magnesium absorption is less cumbersome than is the fecal monitoring method, which has been used most often, but it has not been validated. OBJECTIVE: The aim of this study was to compare methods and several sampling protocols for determining magnesium absorption to establish a simple and reliable alternative to the fecal monitoring approach. Fecal monitoring was used as the standard against which the DL methods based on urine data (DLU), plasma data (DLP), and plasma kinetics with the use of a deconvolution analysis (DP) were compared. DESIGN: Six healthy adult men received 70 mg (26)Mg orally and 30 mg (25)Mg intravenously. Multiple blood samples and complete urine and fecal samples were collected over 12 d. Stable-isotope ratios were determined by inductively coupled plasma mass spectrometry. RESULTS: Results from DLU were not significantly different from the fecal monitoring reference value (0.48 +/- 0.05; +/- SD) when based on 3-d urine pools from 72 to 144 h (0.54 +/- 0.04) and when based on the 24-h urine pools from 48 to 72 h (0.49 +/- 0.06), 72 to 96 h (0.51 +/- 0.11), and 96 to 120 h (0.50 +/- 0.06). Results with the DLP method 72 h after isotope administration also compared well with those with the fecal monitoring method (0.54 +/- 0.09). Magnesium absorption was 0.47 +/- 0.06 with the DP method, which also agreed with the fecal monitoring value. CONCLUSIONS: The DL methods are an alternative to fecal monitoring when applied within the appropriate time intervals. Therefore, DLU-the simplest and least invasive approach-is recommended for determining magnesium absorption.

Meal effect on magnesium bioavailability from mineral water in healthy women.

BACKGROUND: Magnesium intakes in many industrialized countries are below recommended daily allowances. Magnesium-rich mineral water may contribute to coverage of magnesium requirements by providing significant amounts of natural, energy-free, bioavailable magnesium. OBJECTIVE: The objectives were to determine magnesium bioavailability from magnesium-rich (110 mg/L) mineral water in healthy subjects when consumed alone and to evaluate the effect of simultaneous meal consumption. DESIGN: Magnesium bioavailability was measured in 10 healthy women with the use of a crossover design. Stable magnesium isotopes ((25)Mg and (26)Mg) were administered orally with mineral water, which was consumed with or without a meal. Apparent magnesium absorption was determined by fecal monitoring, and magnesium retention was determined from urinary excretion of magnesium isotopes. RESULTS: The mean (+/-SD) magnesium absorption from mineral water consumed alone was 45.7 +/- 4.6% (range: 40.2-55.5%) and was significantly greater (P = 0.0001) when it was consumed with a meal (52.3 +/- 3.9%; 46.2-60.2%), a relative difference of 14.4%. Magnesium retention also was significantly greater (P = 0.0004) when mineral water was consumed with a meal (41.5 +/- 4.2%; 35.2-50.6%) than when consumed alone (37.4 +/- 4.0%; 33.1-47.0%), a relative difference of 11.0%. CONCLUSIONS: In healthy young women, approximately 50% of the magnesium from magnesium-rich mineral water was absorbed when consumed alone. Magnesium bioavailability from mineral water is enhanced when the water is consumed with a meal, perhaps because of a slower gastrointestinal transit time, the presence of digestion products from the meal, or both. Regular consumption of magnesium-rich mineral water could make a valuable contribution to magnesium requirements.