Predicting and Testing Bioavailability of Magnesium Supplements

Abstract

Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.

Keywords: Magnesium; bioaccessibility; bioavailability; supplements.

Figure 1

Relative (%) Mg²⁺ release during the stomach incubation upon simulated ingestion of 15 Mg-containing formulations under fasted and fed conditions. Data are shown as average (n = 3) ± standard deviation (STDEV).

Figure 2

Relative (%) Mg²⁺ absorption during the small intestinal incubation upon simulated ingestion of 15 Mg-containing formulations under fasted and fed conditions. Data are shown as average (n = 3) ± STDEV.

Figure 3

(A) Significant correlation between percentage Mg released in pH 6.8 (dissolution testing) and Mg bioaccessible in fed conditions (Simulator of the Human Intestinal Microbial Ecosystem (SHIME) testing). (B) Significant correlation between percentage Mg released in pH 6.8 (dissolution testing) and Mg bioavailable in fed conditions (SHIME testing). White dots represent the magnesium formulations that were further used for in vivo testing (Ultractive (A) and B-Magnum (O)), black dots are all other tested magnesium formulations.

Figure 4

Serum magnesium levels following ingestion of two tablets of Supplement A or placebo. Concentrations were measured 60’ before and immediately before (0’) ingesting the supplements and 30’, 60’, 90’, 120’, 150’, 180’, 4 and 6 h after ingestion.

Figure 5

(A) The difference in serum magnesium concentration between the peak value and the concentration before ingestion of two tablets of either the placebo or Supplement A (* p = 0.05). (B) The incremental area under the curve (iAUC) of the serum magnesium concentration starting from 60’ before ingestion of the supplement or placebo (fasted sample) up to six hours after ingestion (* p = 0.02).

Figure 6

(A) Serum magnesium levels following ingestion of one tablet of Supplement A vs. one tablet of Supplement O, * p ≤ 0.005 (B) serum magnesium levels following ingestion of two tablets of Supplement A vs. one tablet of Supplement O. Concentrations were measured 60’ before and immediately before (0’) ingesting the supplement and 30’, 60’, 90’, 120’, 150’, 180’, 4 and 6 h after ingestion, * p ≤ 0.005.

Figure 7

(A) The difference in serum magnesium concentration between the peak value and the concentration before ingestion of one or two tablets of Supplement A vs. one tablet of Supplement O (* p = 0.048 for one tablet of Supplement A vs. Supplement O and p = 0.001 for two tablets of Supplement A vs. Supplement O). (B) The incremental area under the curve (iAUC) of the serum magnesium concentration starting from ingestion of the supplement up to six hours after ingestion (* p = 0.009 for one tablet of Supplement A vs. Supplement O and p = 0.011 for two tablets of Supplement A vs. Supplement O). * p ≤ 0.05.