Our data provide evidence that, following ingestion, MMST [Si(OH)3CH3] is converted to orthosilicic acid [Si(OH)4] and that supplemental use of MMST is safe.
Following four weeks of continuous supplementation with MMST (at the maximum recommended dose of 3.5 mg Si three times per day), fasting serum and urine Si concentrations were, on average, doubled. There appear to be two routes of bio-distribution for dietary silicon following its absorption: namely, rapid urinary excretion for the majority [22–24] and tissue loading and/or cellular metabolism for a minority . As a result, sustained low dose silicon supplementation leads to a marked rise in the body pool of silicon , presumably as the second, minor pathway is increasingly loaded. The biologically important target sites for dietary and supplemental silicon appear to be the connective tissues, such as blood vessels [9, 29], joints, skin [30–32] and, especially, bone [2, 8, 11, 12, 26, 33]. Thus the increase in fasting serum and urine Si concentrations following MMST supplementation must result from silicon that has entered the metabolic pool and not that which is destined for immediate urinary excretion following absorption. We were careful to avoid the latter by using fasting serum and urine samples following a minimum of a 10 h fast and previous data has shown this to be more than adequate [10, 14, 24]. This marked increase in the body pool of silicon supports the argument that MMST is an effective silicon supplement and also explains why this form of silicon has been shown to positively influence bone and blood vessels in mammalian studies [8, 9, 11, 12] in much the same way that dietary silicon does [1, 26, 27, 30–33].
Fasting serum Si levels in this study, before and after supplementation with MMST, were variable, but baseline levels were comparable to what we have previously observed for pre-menopausal women . A few baseline samples were below the LOQ, but this is not unusual for this population and probably reflects either the ethnic diversity of the group with their different dietary Si exposure [2, 35] and/or differences in circulating hormonal levels that could, in theory, impact upon serum and tissue Si levels, although further work is required to confirm this [34, 36]. Even with this variable Si baseline, MMST supplementation significantly increased fasting serum Si level above baseline. Whether this increase in serum Si level is beneficial is not known and was not the aim of this study. This would require a different study design with, probably, a longer period of supplementation. Conversely, the fact that fasting serum Si levels can be increased with Si supplementation could be interpreted to mean that normal dietary Si intake/exposure is sub-optimal but, again, the absence of any known Si deficiency state or symptoms makes this impossible to investigate directly. Nonetheless, as mentioned above, increased dietary Si intake is associated with increased bone mineral density at least in men and pre-menopausal women [26, 27].
Importantly, we provide evidence for the conversion/metabolism of MMST to OSA; namely that organosilicon concentration in urine and serum accounted for only 10% and ca. 50% of the increase in total-Si in the fasting urine and serum samples, respectively. No previous data exist, specifically, for the conversion or metabolism of MMST to OSA. There are, however, data showing that methyl silanes per se (Si-CH3) are broken down/converted to silanols (Si-OH) in both the acid environment of the stomach and systemically [15, 17–19].
In designing the study, we considered how bioconversion of this proposed supplemental silicon [Si(OH)3CH3] to OSA [Si(OH)4] could be demonstrated in humans. Stable isotopic labelling, with 29Si, was discounted due to its relative high natural abundance (ca. 5% of all endogenous Si(OH)4) and the relative insensitivity of 29Si by NMR. Experiments with 32Si would not, these days, allow for administration to humans due to radioactive exposure and long half-life (170 years). Thus, we rationalised that if Si loading (i.e. increased fasting serum levels) is observed following sub-chronic ingestion of MMST in volunteers, as observed for absorbable dietary/supplemental silicon [1, 25], then quantitation for MMST (by 1H-NMR) together with quantitative ICP-OES for the increase in total silicon, would allow for bio-conversion to be proven by ‘balance’. Moreover, 1H-NMR would have detected the conversion of MMST to other organosilicons, although MMST is the smallest organosilicon molecule (building block) and its in vivo anabolism to form larger organosilicon species was neither anticipated nor seen.
Interestingly, and surprisingly, MMST was also detected in baseline urine samples and it is likely that this is due to exposure to other organosilicon compounds that are metabolised through this pathway (i.e. via MMST to OSA). Notably, silicones (e.g. dimethylpolysiloxane, E900) are added to foods such as juice and beer as an anti-foaming agent [7, 37].
Finally, the serum biochemistry and quality of life data over the 4-week periods during which participants received MMST would suggest that this form of silicon is safe upon sustained dosing at supplemental levels (10.5 mg/day or less). This finding is in accordance with reported studies of MMST being administered orally and intravenously in humans [8, 9, 11] and with its long-standing use as a supplement without reported adverse events. Data in rats with the same and higher doses of MMST, over a longer (90 day) supplementation period, have also confirmed the safety of this material (unpublished data).