Oral Vitamin D Supplements Increase Serum 25-Hydroxyvitamin D in Postmenopausal Women and Reduce Bone Calcium Flux Measured by 41Ca Skeletal Labeling.

BACKGROUND: Ensuring adequate vitamin D status in older adults may reduce the risk of osteoporosis. The serum 25-hydroxyvitamin D [25(OH)D] concentration is the recommended biomarker of vitamin D status, but the optimal serum 25(OH)D concentration for bone health in postmenopausal women remains unclear. OBJECTIVE: The aim of this study was to apply the highly sensitive (41)Ca skeletal labeling technique and the measurement of urinary (41)Ca:(40)Ca ratios to determine the serum 25(OH)D concentration that has greatest benefit on bone calcium flux in postmenopausal women. METHODS: We administered a mean intravenous (41)Ca dose of 870 pmol to healthy postmenopausal women [n = 24, age (mean ± SD): 64 ± 6.0 y] without osteoporosis. After 6 mo, at the nadir of their wintertime serum 25(OH)D status, each of the women sequentially consumed daily oral cholecalciferol supplements of 10, 25, and 50 µg/d (in this order), each for 3 mo. We assessed serum 25(OH)D concentrations monthly and urinary (41)Ca:(40)Ca ratios biweekly. (41)Ca:(40)Ca ratios were measured with low-energy accelerator mass spectrometry. With the use of pharmacokinetic analysis, we determined the effect of varying serum 25(OH)D concentrations on (41)Ca transfer rates. RESULTS: At baseline, the mean (95% CI) serum 25(OH)D concentration was 16.2 (13.5, 18.8) µg/L. After the first, second, and third intervention periods, mean (95% CI) serum 25(OH)D increased to 29.8 (27.2, 32.4), 36.9 (34.2, 39.7), and 46.6 (41.2, 52.0) µg/L, respectively. Supplementation was associated with a downward shift in the urinary (41)Ca:(40)Ca ratio compared with the predicted (41)Ca:(40)Ca ratio without vitamin D supplementation. In the model, the most likely site of action of the increase in serum 25(OH)D was transfer from the central compartment to a fast exchanging compartment. At this transfer rate, predicted values were a concentration with half-maximal effect of 2.33 µg/L and an estimate of the maximal effect of 31.7%. After the first, second, and third intervention periods, the mean changes in this transfer rate were +18.0%, +25.7%, and +28.5%, respectively. CONCLUSION: In healthy postmenopausal women, increasing serum 25(OH)D primarily affects calcium transfer from the central compartment to a fast exchanging compartment; it is possible that this represents transfer from the extracellular space to the surface of bone. A serum 25(OH)D concentration of ~40 µg/L achieves ~90% of the expected maximal effect on this transfer rate. This trial was registered at clinicaltrials.gov as NCT01053481.

41Ca, 14C and 10Be concentrations in coral sand from the Bikini atoll.

Activation measurements of materials exposed to nuclear bomb explosions are widely used to reconstruct the neutron flux for retrospective dosimetry. In this study the applicability of coral CaCO3 as a biogenic neutron fluence dosimeter is tested. The long-lived radioisotopes (41)Ca, (14)C and (10)Be, which had been produced in nuclear bomb explosions, are measured in several coral sand samples from the Bikini atoll at the 600 kV and 200 kV AMS facilities of ETH Zurich. Elevated concentrations of all studied isotopes are found in a sample from the crater that was initially formed by the high-yield nuclear explosion Castle Bravo in 1954 and that had been used as site for several tests afterward. The observed (14)C concentration is considered too large to originate from neutron irradiation of CaCO3 alone. The relatively low concentration of (10)Be found in the crater sample indicates that production of (10)Be during nuclear bomb testing is generally minor. A simple neutron fluence reconstruction is performed on basis of the (41)Ca/(40)Ca ratio.

Lycopene bioavailability and metabolism in humans: an accelerator mass spectrometry study.

BACKGROUND: To our knowledge, there is no direct information on lycopene metabolism in humans. OBJECTIVE: The objective of this study was to quantify the long-term human bioavailability of lycopene in plasma and skin after a single dose of (14)C-lycopene and to profile the metabolites formed. DESIGN: We preselected 2 male subjects as lycopene absorbers and gave them an oral dose of 10 mg synthetic lycopene combined with ≈6 µg [6,6',7,7'-(14)C]lycopene (≈30,000 Bq; 92% trans lycopene). The appearance of (14)C in plasma, plasma triacylglycerol-rich lipoprotein (TRL) fraction, urine, expired breath carbon dioxide, and skin biopsies was measured over 42 d. The (14)C in lycopene-isomer fractions from plasma and TRL fraction was measured to assess the isomerization of lycopene in vivo. RESULTS: We quantified (14)C from (14)C-lycopene in plasma, the plasma TRL fraction, expired carbon dioxide, urine, and skin. The time to maximum concentration (t(max)) of total (14)C-lycopene in plasma was 6 h, and the elimination half-life (t(1/2)) was 5 d, which were different from the t(max) and t(1/2) of unlabeled lycopene (0.5 and 48 d, respectively). (14)C-Lycopene was extensively isomerized after dosing as a 92% all-trans isomer at dosing but changed to 50% trans, 38% 5 cis, 1% 9 cis, and 11% other cis isomers after 24 h. A similar pattern of isomerization was seen in plasma TRL fractions. CONCLUSIONS: Lycopene was extensively isomerized after dosing and rapidly metabolized into polar metabolites excreted into urine with the rapid peak of (14)CO(2) after dosing, which implies that ß-oxidation was involved in the lycopene metabolism. Lycopene or its metabolites were detected in skin for up to 42 d.

Accelerator mass spectrometry best practices for accuracy and precision in bioanalytical (14)C measurements.

Accelerator mass spectrometers have an energy acceleration and charge exchange between mass definition stages to destroy molecular isobars and allow single ion counting of long-lived isotopes such as (14)C (t½=5370 years.). 'Low' voltage accelerations to 200 kV allow laboratory-sized accelerator mass spectrometers instruments for bioanalytical quantitation of (14)C to 2-3% precision and accuracy in isolated biochemical fractions. After demonstrating this accuracy and precision for our new accelerator mass spectrometer, we discuss the critical aspects of maintaining quantitative accuracy from the defined biological fraction to the accelerator mass spectrometry quantitation. These aspects include sufficient sample mass for routine rapid sample preparation, isotope dilution to assure this mass, isolation of the carbon from other sample combustion gasses and use of high-efficiency biochemical separations. This review seeks to address a bioanalytical audience, who should know that high accuracy data of physiochemical processes within living human subjects are available, as long as a (14)C quantitation can be made indicative of the physiochemistry of interest.