The present study investigated the balance in excretion of silicon versus its intake, using a single dose of typical dietary silicon (28.9 mg) in healthy human volunteers on a standardized diet. Our results show that, within error, all (96 ± 6%) of the ingested dose was excreted in urine and faeces over the 24 h post-dose period. Whether it is, fully, the same Si being excreted that is being absorbed will need to be addressed with a different study design. However, to get within 5% of intake with variance of ~ 6% is better than may have been expected, especially with the complexities of faecal and urine collection and analysis [17, 22]. Typical recovery from such studies, even with radiolabelled compounds, can be 80% or less, much less than from animal studies [23, 24]. The high renal clearance of Si and the lack of interaction with serum proteins probably aids recovery [25, 26].
As mentioned previously, 100% recovery is expected if (a) Si metabolism is regulated but the subjects are in Si balance (i.e. are Si replete) or (b) if Si has no active biological function and thus Si metabolism is not regulated at all. This study cannot prove which is true but we believe that the former is more likely based on previous murine data where urinary Si output was found to be conserved in Si-deprived animals to maintain tissue Si levels . To now show this in humans we will need to repeat the study with subjects who are in negative Si balance (i.e. Si deplete at the start of the supplementation period by prior dietary Si deprivation for a week or so). Supplementation with the Si dose should then result in less Si being excreted, as more is retained to replenish the depleted body Si pool, compared to a Si-replete group.
Secondly, from this current work, we cannot be certain that the Si excreted in urine and faeces all originated from the ingested Si dose and that there was not some exchange with the body Si pool- as for example occurs with dietary phosphate . This can only be answered with an isotope label study, where isotopic Si is used for the dose solution to discriminate it from Si of the body pool and from dietary sources (i.e. the meals ingested). However this is also not straight forward. 31Si and 32Si are both radioactive and would result in exposure to radiation (beta decay) with short (t½ = 157 min) or long (t½ = 153 years) half-lives, respectively. Using a stable isotope such as 29Si would avoid radioactive exposure but it has a high natural abundance (ca. 5% of all endogenous Si(OH)4). Hence, a relatively accurate balance, as now proven is possible in this study, will be key to the success of the follow on stable isotope work. Moreover, with recent developments in inductively coupled plasma – mass spectrometry methods, to measure 28Si and 29Si in biological samples , we are confident that it will now be possible to discriminate the source of excreted Si (i.e. all ‘washed through’ following ingestion or some from the body pool following exchange with absorbed silicon). Both this question and that of Si retention following oral Si challenge to Si-depleted volunteers are big questions in human Si metabolism and this study proves that they may now be answered with carefully designed isotopic balance studies in Si replete and deplete individuals. In the work presented herein subjects were carefully matched to reduce variability between the two groups, however a cross-over design is undoubtedly more robust to really minimise inter-individual variation in silicon handling [29, 30]. Thus, although more burdensome to the subjects, for the future work a cross-over study design will be seriously considered.
Finally, measurement of faecal Si excretion for the first time in a human study, as we report here, allowed the absolute absorption of Si from the orthosilicic acid dose solution to be estimated which, at 61 ± 9% of the ingested dose, is similar to the estimate from total urinary Si output over the 24 h collection period (57 ± 10%). These estimates are comparable with previous data (absorption being stated as ~ 50–60% of the ingested dose) from shorter urine collections, 0–6 or 0–8 h post-dose [20, 25, 29–34]. Hence, we can conclude that (a) urinary silicon does measure silicon absorption following oral Si challenge and (b) in general 0–6 or 0–8 h urinary collections are adequate to estimate absorption/bioavailability of Si from readily absorbed dietary sources, supplements and test solutions (Si materials requiring prolonged digestion prior to absorption may differ in this respect as previously noted .