Deanna J. Nelson

To evaluate phosphate‐binding by calcium succinate and combinations of calcium and magnesium salts, ion chromatography (IC) methods were developed and validated for the determination of calcium and magnesium across the pH range in the human gastrointestinal tract (pH 1.2–6.8). Separation was achieved on a Dionex IC system using a Dionex IonPac CS12A column. Cations were eluted using 31 mM methanesulfonic acid and detected by suppressed conductivity. A method for calcium was validated according to USP Category 1 requirements and was applicable from 0.5 to 20 μg/mL calcium in 0.1 N HCl; 0.1 N acetate buffer, pH 4.5; or 0.1 N borate buffer, pH 6.8. A method for magnesium was validated independently and found applicable from 0.5 to 20 μg/mL magnesium in 0.1 N acetate buffer, pH 4.5 or 0.1 N borate buffer, pH 6.8. The validated method was successfully applied for the determination of phosphate‐binding by calcium succinate and calcium acetate over the pH range found in the human gastrointestinal tract, and for monitoring the release of calcium succinate from encapsulated formulations. The validated method for calcium and magnesium was successfully used to determine phosphate‐binding by combinations of calcium and magnesium salts in acetate or borate buffer solutions.

Background/Objectives: Reliable markers of human magnesium (Mg) status are needed. Methods: Current Mg studies report ratios between serum Mg and calcium (Ca) using four interchangeable expressions (i.e., molar or weight calculations of Mg/Ca or Ca/Mg). We propose a scale using ratios of serum Mg and Ca to assess Mg status, unified for all four expressions. We explore its application for case studies and published research. Results: Case Studies (4)—the proposed serum Mg/Ca scale showed better Mg diagnostic value than serum Mg alone. Published Studies—A. The proposed Mg/Ca scale’s “depleted Mg” status predicted mortality among hospitalized COVID-19 patients in ROC/AUC analyses. B. The serum Ca/Mg proposed scale, when applied to “healthy” adults with “normal” serum Mg, exposed a “seriously depleted” to “adequate” range of Mg status. C. In a study of periodontal disease, patients designated “adequate” or “mild” Mg depletion by the proposed scale showed greater 5-year improvement than those with scale’s “moderate to serious” Mg depletion status. D. Finally, the proposed scale demonstrated appropriate diagnostic value of serum Ca/Mg in acute coronary syndrome patients only when “corrected Ca” was NOT used in ratio calculation. Conclusions: The proposed scale needs both total serum Ca and Mg measures in identical units, i.e., mg/dL or mg% (for weight ratios); mmol/L or mEq/L (for molar ratios). Authors/reviewers/editors need to take care when reporting units/methodology of serum Mg and Ca ratios for clear reporting as to weight or molar ratio and use of total or corrected values. Future trials and statistical testing are needed to determine whether ratios between serum Mg and Ca yield more precise measures of physiological Mg status than serum Mg alone. Our findings indicate the proposed scale is worthy of further study as a marker of Mg deficit.

Background/Objectives: Calcium (Ca) and magnesium (Mg) are mutual antagonists that interact in a majority of physiological processes. Thus, maintaining a balance between these two minerals is essential for functional homeostasis. Mg deficiency plays a role in the course and severity of a wide range of chronic health conditions. This knowledge, however, has not translated into active incorporation of serum Mg determination as a reliable diagnostic tool for physiological Mg deficit. Methods: Pioneering work by von Ehrlich and Rosanoff has prompted development of a simple algorithm and scale for using serum Ca and Mg determinations to identify subclinical (i.e., “hidden”) physiological Mg deficiencies. This novel serum Mg/Ca–Ca/Mg scale uses determinations of total serum Ca and Mg and their ratios to alert clinicians to avoidable risks associated with chronic latent Mg deficiency. This review applies this scale to 10 published clinical studies reporting the serum (or plasma) ratio between Mg and Ca. Results: In all 10 studies, application of the serum Mg/Ca–Ca/Mg scale diagnosed deficit Mg status more reliably than serum Mg alone. Conclusions: This review provides both illustrations of the value of the novel scale and support for its consideration in clinical practice and Mg research.

Purpose: Strontium salts may provide support for bone health and treatment for osteoporosis, but the safety and effectiveness of these salts is not completely understood. The aim of this clinical study ( NCT03761979 ) was to obtain safety and pharmacokinetic information following acute oral intakes of three ascending doses of strontium L -lactate by healthy adults. Subjects Methods: Ten healthy men and women, mean age 43 ± 2 years, ingested one of three ascending doses of strontium L -lactate (SrLac) once per week for three weeks in succession. All subjects were administered the Study Product in a sequential manner such that the lowest amount (170 mg Sr) was provided at Visit 2, the next highest amount (340 mg Sr) was provided at Visit 3, and the highest amount (680 mg Sr) was provided at Visit 4. At each visit, fasting blood collections were performed pre-dose and 1, 2, 3, 4, 5, 6, 8 and 12 hours post-dose to determine serum strontium at each interval. Results: The pharmacokinetics related to each of three doses of SrLac that were administered to fasted subjects were similar to the findings for other strontium salts. At a dose of 170 mg strontium, a mean serum C _max of 2.6 ± 0.6 mg Sr/dL was observed about 3.1 h after ingestion. A dose of 340 mg strontium exhibited a mean serum C _max of 6.4 ± 1.8 mg Sr/dL about 3.2 h after ingestion. At a dose of 680 mg strontium, a mean serum C _max of 9.3 ± 2.1 mg Sr/dL was observed about 2.8 h after ingestion. Oral bioavailability was high, reflecting the high solubility of SrLac in water and intestinal fluid. The data suggest that between 27% and 34% of the administered dose was absorbed. At these doses, no strontium-related adverse effects were observed. Conclusions: This clinical study in 10 normal adults (50% females) showed that the strontium ion in SrLac is readily bioavailable after oral administration. The intervention was conducted per study protocol, and no clinically significant protocol deviations occurred. Pharmacokinetic data indicated that doses of 170 and 340 mg strontium provided serum strontium concentrations in ranges known to be beneficial for the treatment of low bone density of osteoporosis and osteopenia. No product-related adverse events were observed.

During pregnancy a mother experiences increased metabolic demands to meet the needs of the fetus. A mismatch between these demands and nutrient intake can result in a host of developmental abnormalities to the fetus and health risks to the mother. Several studies have reported strong correlations between deficiency of the essential mineral, magnesium (Mg2+), and many pregnancy complications, including intrauterine growth restriction, preeclampsia, gestational diabetes, and preterm delivery. Mg2+ also impacts fetal programming and disease presentation in childhood and adulthood, showing that aberrant Mg2+ levels in utero have far reaching consequences. Unfortunately, there is no established clinical range of normal serum Mg2+ levels, which makes it challenging to identify mothers and/or fetuses at risk of adverse effects. In this review, we evaluated recently published data to identify a range of serum Mg2+ concentrations that may reflect chronic Mg2+ insufficiency (0.7- 0.85 mmol/L). We then evaluated independent studies that reported on the relationship between Mg2+ levels and pregnancy outcomes to assess whether this cutoff may help identify patients at risk for adverse events and inform therapeutic strategies. Our literature review showed that chronic Mg2+ insufficiency coupled with a molar ratio of calcium (Ca2+) to Mg2+ greater than 3 may indicate increased risk to mother or fetus. Given the high social and economic burdens of pregnancy complications, nutritional supplementation that includes Mg2+ at all stages of pregnancy may be a safe and cost-effective way to mitigate the risk of adverse outcomes for mother and child.

During pregnancy a mother experiences increased metabolic demands to meet the needs of the fetus. A mismatch between these demands and nutrient intake can result in a host of developmental abnormalities to the fetus and health risks to the mother. Several studies have reported strong correlations between deficiency of the essential mineral, magnesium (Mg2+), and many pregnancy complications, including intrauterine growth restriction, preeclampsia, gestational diabetes, and preterm delivery. Mg2+ also impacts fetal programming and disease presentation in childhood and adulthood, showing that aberrant Mg2+ levels in utero have far reaching consequences. Unfortunately, there is no established clinical range of normal serum Mg2+ levels, which makes it challenging to identify mothers and/or fetuses at risk of adverse effects. In this review, we evaluated recently published data to establish a range of serum Mg2+ concentrations that may reflect chronic Mg2+ insufficiency (0.7- 0.85 mmol/L). We then evaluated independent studies that reported on the relationship between Mg2+ levels and pregnancy outcomes to assess whether this cutoff may help identify patients at risk for adverse events and inform therapeutic strategies. Our literature review showed that chronic Mg2+ insufficiency coupled with a molar ratio of calcium (Ca2+) to Mg2+ greater than 3 may indicate increased risk to mother or fetus. Given the high social and economic burdens of pregnancy complications, nutritional supplementation that includes Mg2+ at all stages of pregnancy may be a safe and cost-effective way to mitigate the risk of adverse outcomes for mother and child.

Management of calcium and phosphate in biofluids is key to maintaining physiological mineral homeostasis (i.e., appropriate mineralization of hard tissues and an absence of mineral deposition in soft tissues). This review describes and contrasts the ways vertebrates manage calcium phosphate in two biological fluids (breast milk and serum) and illustrates the benefits of mineral sequestration by proteins. In milk, phosphoprotein-sequestered calcium magnesium phosphates provide nutritional support, whereas in serum, protein-sequestered calcium phosphates control transport and delivery of calcium and phosphate to tissues for biological function or excretion. In addition, subsets of sequestered phosphates in serum have been identified as culprits underlying ectopic deposition of calcium phosphates and toxicity.

: In COVID-19 pneumonia, there is massive increase in fatty acid levels and lipid mediators with a predominance of cyclooxygenase metabolites, notably TxB2 ≫ PGE2 > PGD2 in the lungs, and 11-dehydr...

Ion chromatography (IC) has evolved into one of the most widely used separation techniques of analytical chemistry. Consequently, the number of users of this method is continuously growing. Analysts often assume that widely used guidelines for HPLC method validation in regulated environments routinely apply to IC. This manuscript provides an analysis of the potential shortcomings of traditional approaches to development and validation of IC methods using suppressed conductivity detection and a risk-based alternative approach to these activities. The goal of the alternative approach is a reduction in the risk of erroneous determinations of analytes when IC methods using suppressed conductivity detection are employed.

Iron bioavailability from supplements and fortificants varies depending upon the form of the iron and the presence or absence of iron absorption enhancers and inhibitors. Our objectives were to compare the effects of pH and selected enhancers and inhibitors and food matrices on the bioavailability of iron in soluble ferric pyrophosphate (SFP) to other iron fortificants using a Caco-2 cell culture model with or without the combination of in vitro digestion. Ferritin formation was the highest in cells treated with SFP compared to those treated with other iron compounds or chelates. Exposure to pH 2 followed by adjustment to pH 7 markedly decreased FeSO₄ bioavailability but had a smaller effect on bioavailabilities from SFP and sodium iron(III) ethylenediaminetetraacetate (NaFeEDTA), suggesting that chelating agents minimize the effects of pH on iron bioavailabilty. Adding ascorbic acid (AA) and cysteine to SFP in a 20:1 molar ratio increased ferritin formation by 3- and 2-fold, respectively, whereas adding citrate had no significant effect on the bioavailability of SFP. Adding phytic acid (10:1) and tannic acid (1:1) to iron decreased iron bioavailability from SFP by 91 and 99%, respectively. The addition of zinc had a marked inhibitory effect on iron bioavailability. Calcium and magnesium also inhibited iron bioavailability but to a lesser extent. Incorporating SFP in rice greatly reduced iron bioavailability from SFP, but this effect can be partially reversed with the addition of AA. SFP and FeSO₄ were taken up similarly when added to nonfat dry milk. Our results suggest that dietary factors known to enhance and inhibit iron bioavailability from various iron sources affect iron bioavailability from SFP in similar directions. However, the magnitude of the effects of iron absorption inhibitors on SFP iron appears to be smaller than on iron salts, such as FeSO₄ and FeCl₃. This supports the hypothesis that SFP is a promising iron source for food fortification and dietary supplements.