**Abstract**

Here we review the physiological effects of the calcium salt of alginate (Ca-Alg), focusing on our own work. First, we found that Ca-Alg promotes the excretion and decreases the absorption of various metals, and does so more effectively than sodium alginate (Na-Alg). Ca-Alg also reduced plasma cholesterol (Cho) in rats fed a high-Cho diet for 2 weeks. This was considered to be due to reduced intestinal reabsorption of bile acid, resulting from the binding of Ca-Alg and bile acid; this induces an increase of bile acid synthesis from Cho in the liver, leading to a decrease in Cho in plasma. The increase of blood triglyceride (TG) levels in rats fed a highfat diet for 5 weeks was significantly suppressed by Ca-Alg, leading to decreased fat accumulation in the liver and whole body. Ca-Alg in food was also effective in suppressing the postprandial increase of blood glucose level in rats and humans. An in vitro study suggested that Ca-Alg inhibits the interaction between α-glucosidase and its substrate maltose. In conclusion, Ca-Alg has a number of beneficial effects as a functional food ingredient, and is expected to be a safe and effective food additive for long-term use.

**Keywords:** calcium alginate, toxic metal, cholesterol, bile acid, triglyceride, micelle, fat, blood glucose level, particle size, noodles

## **1. Introduction**

Alginic acid (Alg) is a polysaccharide derived from algae. Sodium alginate (Na-Alg) is commonly used in foodstuffs as a thickening agent and stabilizer, and is also used as a health food to suppress weight gain and lower blood cholesterol (Cho) [1–4]. In addition, Na-Alg has a protective action on the gastric mucosa [5, 6]. Moreover, when Na-Alg is ingested prior to exposure to strontium (Sr), Sr accumulation in the human body is decreased [7]. However, the sodium salt of Alg can potentially cause hypertension, a major risk factor for dyslipidemia and arteriosclerosis [8]. Therefore, if the calcium salt (Ca-Alg) is as effective as, or superior to, Na-Alg, it might prove to be of greater benefit.

In this chapter, focusing on our own work on Ca-Alg, we will firstly describe how Alg enhances excretion and reduces absorption of Sr and cesium (Cs) in rats. Secondly, we discuss the relationship between the physical parameters of various metal ions and their binding affinity to Alg. Thirdly, we describe the

Cho-lowering effect of Ca-Alg, as well as the reducing effect of Ca-Alg on blood triglyceride (TG) levels, which leads to reduced accumulation of fat in the liver and whole body in rats. Finally, we describe how Ca-Alg in food (noodles) moderates the postprandial blood glucose level in rats and humans and we discuss the mechanism of this effect.

## **2. Increased excretion and reduced absorption of strontium and cesium**

Although several years have passed since the nuclear power plant accident following a severe earthquake in Japan in March 2011, public unease over the possible presence of radioactive materials in foods remains. As we anticipated that foods or medicines containing Alg would help to reduce potential harmful effects, we investigated the effect of Alg on the absorption and excretion of Sr and Cs, whose radioactive isotopes have long half-lives (90Sr 28.8 years, 137Cs 30.17 years). Specifically, we examined and compared the effects of Na-Alg and Ca-Alg on the absorption and excretion of Sr and Cs in rats, as well as investigating their safety [9].

Initially, we examined the adsorption of Sr and Cs by water-soluble Na-Alg. We found that Sr alone was adsorbed by Na-Alg in a concentration-dependent manner, as was Cs alone. On the other hand, when a mixture of Sr and Cs was used, adsorption of Cs by Na-Alg was lower than in the case of Cs alone, whereas adsorption of Sr by Na-Alg was the same as with Sr alone. Thus, both Sr and Cs were concentration-dependently adsorbed by Na-Alg, but adsorption of Cs by Na-Alg was partly blocked in the presence of Sr.

Next, rats were randomized into control (normal diet), Na-Alg, and Ca-Alg groups, and the changes of native Sr and Cs concentrations in plasma were measured after 2 weeks. In the groups fed Na-Alg and Ca-Alg, the Sr concentrations were significantly decreased to 65 and 63% at 1 week, and 77 and 66% at 2 weeks, respectively, compared with the control group. On the other hand, Cs concentration was significantly reduced (to 60% of the control) only at 2 weeks in the Ca-Alg group. Histopathological observation revealed mineral deposition, due to excessive ingestion of sodium, in the pelvic epithelium of the kidney in the Na-Alg group, and epithelial hyperplasia was observed around the deposits. In contrast, no abnormality at all was detected in the Ca-Alg group. These results indicate that Ca-Alg would be safer than Na-Alg if taken daily for protection against radiation damage.

We also randomized rats into control, Na-Alg, and Ca-Alg groups, and administered SrCl2 or CsCl solution. The maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration curve for 3 hours after administration (AUC0-3 hours) were calculated from the observed data by subtracting the values before administration. When SrCl2 solution was orally administered in the Na-Alg and Ca-Alg groups, absorption of Sr was significantly decreased in comparison with the control group. In the Ca-Alg group, Cmax and AUC0–3 hours were significantly lower than in the control group after oral administration of CsCl solution. No significant difference of Cs plasma concentration profile between the control and Na-Alg groups was observed. Overall, the data suggest that absorption of both Sr and Cs was reduced in the Ca-Alg group, whereas absorption of Cs was not reduced in the Na-Alg group (**Figure 1**).

It should be noted that in these studies we used 10% Na-Alg or Ca-Alg in the diet, whereas 3–4 g/body/day of Alg is typically ingested by humans as a health food [1, 10]. Clinical studies will be required to identify an appropriate level of Ca-Alg for use as a protective agent.

**23**

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

**3. Mechanism of binding of alginate and metals**

that are suitable for long-term administration.

ing affinity were examined.

**Figure 1.**

*means ± S.D. (n = 5).*

metals such as Pb and Cd.

> Mg2+ > Fe2+ > Fe3+ > Co2+ > Al3+ > Ni2+ > Cs+

> Sr2+ > Ca2+ > Mg2+ > Cd2+ >Fe2+**,**Fe3+ >Cs+

In the case of acute oral exposure to toxic metals, health damage can be reduced by immediate treatments such as induction of vomiting and/or the use of a laxative to promote excretion of the metal. However, in the case of chronic exposure, it is essential to use intrinsically safe absorption inhibitors and/or excretion accelerators

*Plasma concentration of Sr (a) or Cs (b) after oral administration of SrCl2 to rats [9]. The data represent* 

Although the effect of Alg on Sr or Cs absorption and excretion has already

) and

been reported, there is little information about its effect on other metals. Therefore, we investigated the relationship between the physical parameters of various metal ions, including toxic metal ions, and the binding affinity of these metal ions for Alg [11]. For this purpose, the binding constants (K, mM<sup>−</sup><sup>1</sup>

the binding amount with Alg were evaluated for Sr, Pb, Tb, Dy, Ca, Cd, Mg, Fe(II), Fe(III), Co, Al, Ni, Cs, Cu, Ag, Li, and K. Aqueous solutions of each metal salt and an equivalent amount of Na-Alg were mixed, and the amount of unbound metal remaining in the filtrate was determined using an atomic absorption photometer. The amount of bound metal was calculated from the amount of remaining unbound metal ion, and K values and the number of binding sites per 1 mg of Alg (n) were analyzed using double-reciprocal plots. The affinity of each metal ion for Alg was calculated by multiplying the n and *K* values. Moreover, the relationships between charge number and radius of these metals and their bind-

The order of K values was as follows: Sr2+ > Pb2+ > Tb3+ > Dy3+ > Ca2+ > Cd2+

metal ions with high K values tended to have ionic radii within the range of about 90–120 pm. On the other hand, the order of affinity for Alg was Pb2+ > Dy3+ > Tb3+

The *K* value and affinity for Alg both tended to be higher for divalent or trivalent metal ions than for monovalent ions. It is well established that Alg forms a cross-linked structure with divalent or trivalent metal ions, resulting in gel formation. These results might indicate that metal ions with an ionic radius of about

Overall, these results indicate that Alg would be effective as an excretion accelerator and/or absorption inhibitor for various toxic metal ions, especially divalent

90–120 pm form more robust and water-insoluble gels (**Figure 2**) [11].

> Cu2+ > Ag+

> Li+

>Al3+ >Co2+ >Ni2+ >Cu2+ >Ag+

>K+

. Moreover,

 >K+ >Li+ .

*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*

*Alginates - Recent Uses of This Natural Polymer*

mechanism of this effect.

ing their safety [9].

blocked in the presence of Sr.

against radiation damage.

not reduced in the Na-Alg group (**Figure 1**).

Ca-Alg for use as a protective agent.

Cho-lowering effect of Ca-Alg, as well as the reducing effect of Ca-Alg on blood triglyceride (TG) levels, which leads to reduced accumulation of fat in the liver and whole body in rats. Finally, we describe how Ca-Alg in food (noodles) moderates the postprandial blood glucose level in rats and humans and we discuss the

**2. Increased excretion and reduced absorption of strontium and cesium**

Although several years have passed since the nuclear power plant accident following a severe earthquake in Japan in March 2011, public unease over the possible presence of radioactive materials in foods remains. As we anticipated that foods or medicines containing Alg would help to reduce potential harmful effects, we investigated the effect of Alg on the absorption and excretion of Sr and Cs, whose radioactive isotopes have long half-lives (90Sr 28.8 years, 137Cs 30.17 years). Specifically, we examined and compared the effects of Na-Alg and Ca-Alg on the absorption and excretion of Sr and Cs in rats, as well as investigat-

Initially, we examined the adsorption of Sr and Cs by water-soluble Na-Alg. We found that Sr alone was adsorbed by Na-Alg in a concentration-dependent manner, as was Cs alone. On the other hand, when a mixture of Sr and Cs was used, adsorption of Cs by Na-Alg was lower than in the case of Cs alone, whereas adsorption of Sr by Na-Alg was the same as with Sr alone. Thus, both Sr and Cs were concentration-dependently adsorbed by Na-Alg, but adsorption of Cs by Na-Alg was partly

Next, rats were randomized into control (normal diet), Na-Alg, and Ca-Alg

We also randomized rats into control, Na-Alg, and Ca-Alg groups, and administered SrCl2 or CsCl solution. The maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration curve for 3 hours after administration (AUC0-3 hours) were calculated from the observed data by subtracting the values before administration. When SrCl2 solution was orally administered in the Na-Alg and Ca-Alg groups, absorption of Sr was significantly decreased in comparison with the control group. In the Ca-Alg group, Cmax and AUC0–3 hours were significantly lower than in the control group after oral administration of CsCl solution. No significant difference of Cs plasma concentration profile between the control and Na-Alg groups was observed. Overall, the data suggest that absorption of both Sr and Cs was reduced in the Ca-Alg group, whereas absorption of Cs was

It should be noted that in these studies we used 10% Na-Alg or Ca-Alg in the diet, whereas 3–4 g/body/day of Alg is typically ingested by humans as a health food [1, 10]. Clinical studies will be required to identify an appropriate level of

groups, and the changes of native Sr and Cs concentrations in plasma were measured after 2 weeks. In the groups fed Na-Alg and Ca-Alg, the Sr concentrations were significantly decreased to 65 and 63% at 1 week, and 77 and 66% at 2 weeks, respectively, compared with the control group. On the other hand, Cs concentration was significantly reduced (to 60% of the control) only at 2 weeks in the Ca-Alg group. Histopathological observation revealed mineral deposition, due to excessive ingestion of sodium, in the pelvic epithelium of the kidney in the Na-Alg group, and epithelial hyperplasia was observed around the deposits. In contrast, no abnormality at all was detected in the Ca-Alg group. These results indicate that Ca-Alg would be safer than Na-Alg if taken daily for protection

**22**

**Figure 1.** *Plasma concentration of Sr (a) or Cs (b) after oral administration of SrCl2 to rats [9]. The data represent means ± S.D. (n = 5).*
