**4. Cholesterol-lowering effect**

Heart disease and cerebrovascular disease are major causes of death in developed countries, accounting for about a quarter of all deaths in Japan [12]. A major factor in their pathogenesis is believed to be dyslipidemia [13–15], which is predominantly a modern lifestyle-related disease [16, 17]. Therefore, there is considerable interest in food additives or health foods that can decrease Cho absorption or promote Cho excretion.

Since Na-Alg reduces the Cho concentration in blood [9], we focused on the Cho-lowering effect of Ca-Alg in rats fed a high-Cho diet [18]. We first examined absorption of the Cho precursor taurocholate by various types of Alg in vitro, using Na-Alg instead of Ca-Alg, since Na-Alg is water-soluble. We found that high-molecular-weight, guluronic acid-rich (HMW-G) Na-Alg showed the greatest adsorption of taurocholate, and so we selected Ca-Alg HMW-G for the following in vivo study.

Rats were fed a high-Cho diet with or without 0.5–2% Ca-Alg for 2 weeks. After 14 days, the plasma concentration of Cho, the portal plasma concentration of bile acid, and the bile acid content in feces were measured. Moreover, in order to monitor safety, blood samples withdrawn after 14 days were used for the measurement of biochemical parameters. In the groups fed the high-Cho diet containing 2% Ca-Alg diet, the plasma concentration of Cho at 2 weeks was significantly lower than that of the group fed high-Cho diet alone. This result was similar to that in the group fed colestimide-containing diet as a positive control. Bile acid excretion in feces tended to increase depending on the concentration of Ca-Alg in the diet. In the group fed the 2% Ca-Alg diet, the portal plasma concentration of bile acid was significantly decreased, compared to that in the high-Cho diet group. Furthermore, the portal

**25**

**Figure 4.**

**Figure 3.**

*Pharmacological Effects and Utility as a Food Additive of Calcium Alginate*

concentration of bile acid was significantly lowered in the 2% Ca-Alg group. There was no significant difference in weight gain or diet intake among the groups during the 2-week experimental period. Microvesicular steatosis was increased in the high-Cho diet and Ca-Alg groups, but remained within the physiological range. While several changes in biochemical parameters and histopathological findings were observed, all values remained within the physiological range (**Figure 3**).

*Cho concentration in plasma at the end of the 2-week period with normal diet, high-Cho diet, or high-Cho diet containing Ca-Alg or colestimide to rats [18]. Rats were fed normal diet, high-cholesterol (Cho) diet, or highcholesterol diet containing Ca-Alg or colestimide. The data represent means ± S.D. (n = 6). The significance of* 

*p < 0.05.*

*differences from the high-Cho diet group was determined by means of Dunnett's test. \**

Overall, these results indicate that Ca-Alg is effective for reducing plasma Cho. A possible mechanism would be enhanced fecal excretion of bile acid due to reduced intestinal reabsorption, which might subsequently stimulate bile acid synthesis

from Cho in the liver, leading to a decrease of Cho in plasma (**Figure 4**).

*A possible mechanism of Cho-lowering effect of Ca-Alg [18].*

*DOI: http://dx.doi.org/10.5772/intechopen.86861*

*Pharmacological Effects and Utility as a Food Additive of Calcium Alginate DOI: http://dx.doi.org/10.5772/intechopen.86861*

#### **Figure 3.**

*Alginates - Recent Uses of This Natural Polymer*

in the presence of Alg.

excretion.

**Figure 2.**

in vivo study.

**4. Cholesterol-lowering effect**

It is noteworthy that the affinity between Alg and Cs is relatively small, even though we had previously shown that Ca-Alg is effective in promoting excretion and decreasing absorption of Cs in rats [9]. Therefore, not only the affinity between Alg and metals, but also other factors arising from the specific combination of Alg and metal ion, may influence excretion and/or absorption of individual metal ions

*Relationships between K value, charge number and ionic radius of metal ions [11].*

Heart disease and cerebrovascular disease are major causes of death in developed countries, accounting for about a quarter of all deaths in Japan [12]. A major factor in their pathogenesis is believed to be dyslipidemia [13–15], which is predominantly a modern lifestyle-related disease [16, 17]. Therefore, there is considerable interest in food additives or health foods that can decrease Cho absorption or promote Cho

Since Na-Alg reduces the Cho concentration in blood [9], we focused on the Cho-lowering effect of Ca-Alg in rats fed a high-Cho diet [18]. We first examined absorption of the Cho precursor taurocholate by various types of Alg in vitro, using Na-Alg instead of Ca-Alg, since Na-Alg is water-soluble. We found that high-molecular-weight, guluronic acid-rich (HMW-G) Na-Alg showed the greatest adsorption of taurocholate, and so we selected Ca-Alg HMW-G for the following

Rats were fed a high-Cho diet with or without 0.5–2% Ca-Alg for 2 weeks. After 14 days, the plasma concentration of Cho, the portal plasma concentration of bile acid, and the bile acid content in feces were measured. Moreover, in order to monitor safety, blood samples withdrawn after 14 days were used for the measurement of biochemical parameters. In the groups fed the high-Cho diet containing 2% Ca-Alg diet, the plasma concentration of Cho at 2 weeks was significantly lower than that of the group fed high-Cho diet alone. This result was similar to that in the group fed colestimide-containing diet as a positive control. Bile acid excretion in feces tended to increase depending on the concentration of Ca-Alg in the diet. In the group fed the 2% Ca-Alg diet, the portal plasma concentration of bile acid was significantly decreased, compared to that in the high-Cho diet group. Furthermore, the portal

**24**

*Cho concentration in plasma at the end of the 2-week period with normal diet, high-Cho diet, or high-Cho diet containing Ca-Alg or colestimide to rats [18]. Rats were fed normal diet, high-cholesterol (Cho) diet, or highcholesterol diet containing Ca-Alg or colestimide. The data represent means ± S.D. (n = 6). The significance of differences from the high-Cho diet group was determined by means of Dunnett's test. \* p < 0.05.*

#### **Figure 4.**

*A possible mechanism of Cho-lowering effect of Ca-Alg [18].*

concentration of bile acid was significantly lowered in the 2% Ca-Alg group. There was no significant difference in weight gain or diet intake among the groups during the 2-week experimental period. Microvesicular steatosis was increased in the high-Cho diet and Ca-Alg groups, but remained within the physiological range. While several changes in biochemical parameters and histopathological findings were observed, all values remained within the physiological range (**Figure 3**).

Overall, these results indicate that Ca-Alg is effective for reducing plasma Cho. A possible mechanism would be enhanced fecal excretion of bile acid due to reduced intestinal reabsorption, which might subsequently stimulate bile acid synthesis from Cho in the liver, leading to a decrease of Cho in plasma (**Figure 4**).
