It was reported that silicon is connected with bone mineralization and osteoporosis , collagen synthesis and ageing of skin , condition of hair and nails , atherosclerosis [33, 34], Alzheimer disease [9, 35, 36], as well as with other biological effects and disorders. Trace minerals are known to generally play a vital role in the human body homeostasis  and the serum levels of silicon are similar to other trace elements, i.e. of iron, copper, and zinc . Silicon is excreted through the urine in similar orders of magnitude as calcium. Some researches claim that silicon does not act as a protein-bounding element in plasma and is believed to exist almost entirely as un-dissociated monomeric ortho-silicic acid . While early analyses showed that serum contains 50–60 μg silicon/dL [38, 39], more recent analyses indicate that human serum contains 11–25 μg silicon/dL, or levels ranging between 24 and 31 μg/dL (8.5 and 11.1 μmol/L), detected by absorption spectrometry in large population groups . Interestingly, pregnant women had very low serum silicon concentrations (3.3-4.3 μg/dL) in comparison with infants that have high concentrations between 34 and 69 μg/dL [27, 41]. Moreover, silicon concentrations in serum showed a statistically significant age and sex dependency, as it seems that silicon concentrations decrease with age, especially in woman .
Biological importance of silicon might be analysed in the context of its bio-distribution in the body. For example, the highest silicon concentration has been measured in connective tissues, especially in the aorta, tracheas, bone, and skin. Low levels of silicon in the form of ortho-silicic acid [42–44] may be found in liver, heart, muscle, and lung . It is therefore plausible to assume that observed decrease of silicon concentration in the ageing population may be linked to several degenerative disorders, including atherosclerosis. Supplementation of the regular diet with bioavailable forms of silicon may therefore have a therapeutic potential including prevention of degenerative processes. Several experiments have already confirmed this hypothesis. For example, in a controlled animal study, spontaneously hypertensive rats had lower blood pressure upon supplementation with soluble silicon , whilst silicon deficiency in animals has been found to be connected with bone defects and impaired synthesis of connective tissue compounds, such as collagen and glycosaminoglycans [46–48]. It is therefore reasonable to assume that silicon deficiency or lower bioavailability may be linked to problems with bone structure and collagen production. Moreover, silicon was shown to be uniquely localized in active growth areas in young bones of animals where a close relationship between silicon concentration and the degree of mineralization has been assessed [46, 49]. Studies confirmed the essential role of silicon in the growth and skeletal development of chicks that during silicon deprivation showed significantly retarded skeletal development . Experimental silicon deprivation in rats [51–53] and chicks [46, 47] demonstrated striking effects on skeletal growth and bone metabolism as well. On the other hand, the controlled animal study of Jugdaohsingh et al.  showed no profound effects of a silicon-deficient diet on the bone growth and skeletal development in rats. Silicon concentrations in the tibia and soft tissues did not differ from those in rats on a silicon-deficient diet where the silicon was supplemented in drinking water. Nevertheless, silicon levels in tibia were much lower compared to the reference group fed by a silicon rich diet. Body and bone lengths were also found to be lower in comparison with the reference group, while reduction in bone growth plate thickness was found in silicon deprived rats .
Moreover, Reffit et al.  found that ortho-silicic acid stimulates collagen type 1 synthesis in human osteoblast-like cells and skin fibroblasts and enhances osteoblastic differentiation in the MG-63 cells in vitro. Ortho-silicic acid did not alter collagen type 1 gene expression, but it modulated the activity of prolyl hydroxylase, an enzyme involved in the production of collagen . Similarly, Schütze et al.  reported that the zeolite A stimulated DNA synthesis in osteoblasts and inhibited osteoclast-mediated bone resorption in vitro. This is probably attributable to the ortho-silicic acid-releasing property of zeolite A.
The mechanism underlying observed biological effects of silicon may probably be ascribed to its interrelationships with other elements present in the body such as molybdenum  aluminium [9, 35, 58, 59], and calcium [46, 49, 50]. For instance, it was proven that silicon levels are strongly affected by molybdenum intake, and vice versa. Furthermore, silicon accelerates the rate of bone mineralization and calcification as shown in controlled animal studies, in a similar manner that was demonstrated for vitamin D [11, 50]. It is well known that vitamin D increases the rate of bone mineralization and bone formation , and that its deficiency leads to less mature bone development. Vitamin D is known to be important in calcium metabolism, but silicon-deficient cockerels’ skulls in a controlled animal study showed lower calcification and collagen levels irrespective of the vitamin D dietary levels suggesting a vitamin D-independent mechanism of action . Jugdaohsingh et al.  found that silicon supplementation in drinking water did not significantly altered silicon concentrations in bones and suggested that some other nutritional co-factor is required for maximal silicon uptake into bone and that this co-factor was absent in rats fed with a low-silicon diet compared to the reference group fed by a silicon-rich diet. They suggested vitamin K as such co-factor, which is important in bone mineralisation through carboxylation of osteocalcin, and whose deficiency might influence incorporation of minerals such as silicon in the bones.
Osteoporosis is among leading causes of morbidity and mortality worldwide . It is defined as a progressive skeletal disorder, characterised by low bone mass (osteopenia) and micro-architectural deterioration . Interestingly, the administration of silicon in a controlled clinical study induced a significant increase in femoral bone mineral density in osteoporotic women . Direct relationship between silicon content and bone formation has been shown by Moukarzel et al. . They found a correlation between decreased silicon concentrations in total parenterally fed infants with a decreased bone mineral content. This was the first observation of a possible dietary deficiency of silicon in humans. A randomized controlled animal study on aged ovariectomized rats revealed that long-term preventive treatment with ch-OSA prevented partial femoral bone loss and had a positive effect on the bone turnover . Dietary silicon is associated with postmenopausal bone turnover and bone mineral density at the women's age when the risk of osteoporosis increases. Moreover, in a cohort study on 3198 middle-aged woman (50–62 years) it was shown that silicon interacts with the oestrogen status on bone mineral density, suggesting that oestrogen status is important for the silicon metabolism in bone health .
Skin and hair
Typical sign of ageing skin is fall off of silicon and hyaluronic acid levels in connective tissues. This results in loss of moisture and elasticity in the skin. Appearance of hair and nails can also be affected by lower silicon levels, since they are basically composed of keratin proteins. As previously discussed, ortho-silicic acid may stimulate collagen production and connective tissue function and repair. For example, Barel et al.  conducted experiments on females, aged between 40–65 years, with clear clinical signs of photo-ageing of facial skin. Their randomized double-blinded placebo-controlled study illustrates positive effects of ch-OSA taken as an oral supplement on skin micro relief and skin anisotropy in woman with photo-aged skin. Skin roughness and the difference in longitudinal and lateral shear propagation time decreased in the ch-OSA group, suggesting improvement in isotropy of the skin. In addition, ch-OSA intake positively affected the brittleness of hair and nails. Oral supplementation with ch-OSA had positive effects on hair morphology and tensile strengths, as shown in a randomized placebo-controlled double blind study by Wickett et al. .
Aluminium (as Al3+ ion) is a well-known neurotoxin. Aluminium salts may accelerate oxidative damage of biomolecules. Importantly, it has been detected in neurons bearing neurofibrillary tangles in Alzheimer's and Parkinson's disease with dementia as shown in controlled studies [69, 70]. Amorphous aluminosilicates have been found at the core of senile plaques in Alzheimer's disease [69, 71], and have consequently been implicated as one of the possible causal factors that contribute to Alzheimer’s disease. Since aluminosilicates are water insoluble compounds, the transport path to the brain is still not well understood. By reducing the bioavailability of aluminium, it may be possible to limit its neurotoxicity. Consumption of moderately high amounts of beer in humans and ortho-silicic acid in animals has shown to reduce aluminium uptake from the digestive tract and slow down the accumulation of this metal in the brain tissue [36, 72]. Silicic acid has also been found to induce down-regulation of endogenous antioxidant enzymes associated with aluminium administration and to normalize tumour necrosis factor alpha (TNFα) mRNA expression . Although the effect of silicic acid on aluminium absorption and excretion from human body produced conflicting results so far as shown in an open-label clinical study , in a controlled clinical study it was shown that silicic acid substantially reduces aluminium bioavailability to humans . In fact, it was already found that silicon reduces the aluminium toxicity and absorption in some plants and animals that belong to different biological systems [74–76]. This is possible as silicon competes with aluminium in biological systems such as fresh water, as suggested by Birchall and Chappell study perfomed on the geochemical ground , and later confirmed by Taylor et al. in randomized double blind study . They found that soft water contains less silicic acid and more aluminium, while hard waters contain more silicic acid and less aluminium.
Removal of aluminium from the body and its reduced absorption by simultaneous administration of silicic acid was tested and proven by Exley et al. in controlled clinical study . They showed reduced urinary excretion of aluminium along with unaltered urinary excretion of trace elements such as iron in persons to whom silicic acid-rich mineral water was administered. Moreover, they documented that regular drinking of a silicon-rich mineral water during a period of 3 months significantly reduced the body burden of aluminium. Similar results were obtained by Davenward et al.  who showed that silicon-rich mineral waters can be used as a non-invasive method to reduce the body burden of aluminium in both Alzheimer's patients and control group by facilitating the removal of aluminium via the urine without any concomitant effect. They also showed clinically relevant improvements of cognitive performances in at least 3 out of 15 individuals with Alzheimer disease. This implies a possible use of ortho-silicic acid as long-term non-invasive therapy for reduction of aluminium in Alzheimer's disease patients. The mechanism through which aluminium bioavailability reduction occurs involves interaction between aluminium species and ortho-silicic acid where highly insoluble hydroxyaluminosilicates (HAS) forms are produced [77, 80]. This process makes aluminium unavailable for absorption.
Quartz as a form of crystalline silicon dioxide has been connected with severe negative biological effects. However, in controlled studies on mouse and rats it was shown that sub-chronic and short-term exposure to this compound can actually have beneficial effects on respiratory defence mechanisms by stimulating immune system through the increase of neutrophils, T lymphocytes and NK cells. It also activates phagocytes and consequently additional ROS production [81–83] which can help the pulmonary clearance of infectious agents. In rats, crystalline silica caused proliferation and activation of CD8+ T cells and, to a lesser amount, of CD4+ T cells.
Recently, an “anionic alkali mineral complex” Barodon® has shown immunostimulatory effects in horses , pigs  and other animals. Barodon® is a mixture of sodium silicate (M2SiO3, M= Na,K) and certain metal salts in an alkaline solution (pH= 13.5), where sodium-silicate (sodium water glass) represents 60% of the total content. In a placebo-controlled experiment in pigs, the immunostimulatory effect of Barodon® was assessed by measurement of proliferation and activation of porcine immune cells, especially CD4+ CD8+ double-positive (dpp) T lymphocytes in peripheral blood and in the secondary lymphoid organ . As this type of T lymphocyte cells are characterized by a specific memory cell marker CD29, they may play a role during activation of secondary immune responses as shown in a cross-sectional and longitudinal study on pigs . Moreover, Barodon® acted mainly on the lymphoid organs, implying a role in antigenic stimulation of immune tissues . Barodon® induced increased levels of MHC-II lymphocytes and non-T/non-B (N) cells as well along with increased stimulatory mitogen activity including the activity of PHA, concanavalin A, and pokeweed mitogen [85, 87]. In a placebo-controlled experiment on pigs, it was shown that this mineral complex exerts an adjuvant effect with hog cholera and Actinobacillus pleuropneumoniae vaccines by increasing the antibody titres and immune cell proportions . Moreover, Barodon® showed nonspecific immunostimulating effects in racing horses and higher phagocytic activity against Staphylococcus equi subsp. equi and Staphylococcus aureus as well in a controlled study . Administration of Barodon® in horse herds reduced many clinical complications, including stress-induced respiratory disease, suggesting activation of immune cell populations similarly to the treatment with inactivated Propionibacterium acnes[89, 90]. The exact mechanism of Barodon® immunostimulatory effect is not known, although it has been suggested that sodium silicate, the main mineral ingredient, might be responsible for the observed immune-enhancing properties. Indeed, sodium silicate is known to decompose quantitatively into bioavailable ortho-silicic acid (H4SiO4) in the acidic gastric juice (HCl), and as such being absorbed in the body. In this manner, presumably all observed pharmacological effects of Barodon® are actually originated from the ortho-silicic acid.
Pure sodium metasilicate (Na2SiO3) also bears immunostimulatory effects and acts as a potent mitochondria activator . Dietary silicon in the form of sodium metasilicate activates formation of ammonia by elevating mitochondrial oxygen utilisation as shown in a controlled animal experiment . These findings further corroborate the hypothesis that sodium silicate might be responsible for immunostimulatory effects of Barodon®. Once again, the pharmacologically active species was ortho-silicic acid released upon the action of stomach hydrochlorid acid on sodium metasilicate.