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Applications of Calcium and its Supplement derived from Marine Organisms

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Applications of Calcium and its Supplement derived


from Marine Organisms
a b c
Se-Kwon Kim , Y. Dominic Ravichandran & Chang-Suk Kong
a
Department of Chemistry, Pukyong National University, Busan, Republic of Korea
b
Organic Chemestry Division, School of Advanced Sciences, VIT University, Vellore, India
c
Department of Food and Nutrition, College of Medical and Life Sciences, Silla University,
Busan, Republic of Korea

Version of record first published: 27 Mar 2012.

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Supplement derived from Marine Organisms, Critical Reviews in Food Science and Nutrition, 52:6, 469-474

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Critical Reviews in Food Science and Nutrition, 52:469–474 (2012)
Copyright C Taylor and Francis Group, LLC
ISSN: 1040-8398 / 1549-7852 online
DOI: 10.1080/10408391003753910

Applications of Calcium and its


Supplement derived from Marine
Organisms
Critical Reviews in Food Science and Nutrition 2012.52:469-474. downloaded from www.tandfonline.com

SE-KWON KIM,1 Y. DOMINIC RAVICHANDRAN,2 and CHANG-SUK KONG3


1
Department of Chemistry, Pukyong National University, Busan, Republic of Korea
2
Organic Chemestry Division, School of Advanced Sciences, VIT University, Vellore, India
3
Department of Food and Nutrition, College of Medical and Life Sciences, Silla University, Busan, Republic of Korea

Calcium, being an essential mineral with many important and diversified functions, plays an important role in the health and
well being of the human. Marine organisms serve as an alternate source for calcium. Calcium has to be solubilized in the
body in order to have the maximum benefits. The increased solubility of calcium from diet contributes to calcium absorption
and bioavailability in the body. In this paper, we report various marine sources of calcium, solubilizing the calcium to
improve the bioavailability and the applications of calcium as an important mineral in controlling different diseases.

Keywords Calcium, marine organisms, bioavailability

INTRODUCTION bioavailability of calcium. The most common and trustable


source of calcium in a typical diet is milk or other dairy prod-
Calcium is an essential mineral required to maintain good ucts (Anderson and Garner, 1996). However, some people have
health with diverse biological functions. The main function of low levels of lactase which can result in symptoms of intoler-
calcium is to strengthen or maintain the bones and teeth, but ance when large loads of lactose are consumed. This makes
it is also required for other functions such as blood coagula- fish a major and important source of calcium (Jung et al.,
tion, nerve function, production of energy, muscle contraction, 2005). Insufficient calcium intake increases bone resorption
heart function (the regulation of the heart’s rhythm), and proper (breakdown of bone), decreases bone mass (Ensrud et al., 2000;
immune function. Furthermore, calcium also plays an impor- Weaver and Liebman, 2002), and increases the risk of osteo-
tant role in preventing the onset of osteoporosis, osteopenia, porosis after menopause (Dawson-Hughes et al., 1990). The
osteomalacia, and rickets (Cashman, 2007). importance of adequate calcium intake for the development
Calcium is readily available from many sources,its major and maintenance of peak bone mass has been well established
source being one’s diet. Even though the green leafy vegeta- (Weaver and Liebman, 2002).
bles, tofu, cereals, and millets are the cheapest dietary sources Adequate or sufficient calcium intake during childhood helps
of calcium, they are not popular because of their taste and prod- people to avoid more serious disease related to calcium defi-
uct formulation issues. Even though low oxalate green vegeta- ciency at a later part of life. Vitamin D is a key ingredient in
bles like kale and bok choy have high calcium bioavailabil- various hormones that enable calcium to pass from the diges-
ity, they are not generally recommended for calcium sources tive system into the blood or bones. The dietary calcium that
because of their low calcium content or low consumption by is absorbed in the small intestine is transferred either into the
many populations. The presence of oxalic acid in green leafy bloodstream or ultimately into the bones. Furthermore, optimal
vegetables like spinach and phytic acid in cereals make the ratios of phosphorus and hormonal secretions of the parathyroid
calcium to precipitate as insoluble compounds like calcium and thyroid glands (parathyroid hormone and calcitonin) also
oxalate and calcium phytate, resulting in the reduction of the help to maintain the calcium equilibrium in the blood. When
the calcium level in the body begins to drop below the optimum
level, the nerves become extremely irritable and the muscles
Address correspondence to Se-Kwon Kim, Marine Bioprocess Research
Center and Department of Chemistry, Pukyong National University, Busan go into spasms, resulting in crampy pains and irregular func-
608-737, Republic of Korea. E-mail: sknkim@pknu.ac.kr tioning of the heart. Recently, marine organisms have emerged

469
470 S-K. KIM ET AL.

as one of the important sources for dietary calcium as well blood pressure, as well as for colon cancer and it metastasis
as health supplements. These observations indicate the impor- with a high absorption ratio (Hirota and Sugisaki, 2000).
tance of dietary calcium as an important mineral for the human Coral calx (Praval bhasma) is a natural source of calcium
body. Therefore, in this review, we report marine organisms as widely used in the traditional system of Indian medicine as
rich sources of calcium, the methods to improve the solubi- a supplement in the treatment of a variety of bone metabolic
lization and bioavailability of calcium, and beneficial applica- disorders that include osteoporosis (Reddy et al., 2003). Coral
tions of calcium as an important mineral in controlling different calcium has been marketed in the United States not only as a
diseases. calcium supplement but also as a preventive agent for cancer,
heart disease, diabetes, lupus, multiple sclerosis, and other
Critical Reviews in Food Science and Nutrition 2012.52:469-474. downloaded from www.tandfonline.com

life-threatening diseases (Marcason, 2003). Moreover, coral has


gained increased attention as a potential bone graft substitute
MARINE SOURCES OF CALCIUM material (Laine et al., 2008; Petite et al., 2000; Parikh, 2002).
Hydroxyapatite produced from corals has also been used for
Calcium from Fish implants. In this case, the overall porous structure of the coral
is maintained during conversion to hydroxyapatite (Hu et al.,
Small fish is one of the commonly consumed foods in many 2001; Xu et al., 2001). Resorption in implants appears to be
low-income countries, where milk or dairy products make up a directly related to the coral porosity and therefore it is limited
small part of the diet. The whole small fish with bones is an im- to high porosity corals (Barbotteau et al., 2003). The unique
portant source of calcium in human diets. Even though calcium pore microstructures found in the skeletal calcium carbonate
from fish bone may be considered as unavailable for absorption of certain reef corals can also be replicated or reproduced with
(Hansen et al., 1998), they are easily accessible, inexpensive, high precision by means of the newly developed replamine form
popular, and culturally acceptable. The contribution of calcium processed for hard tissue implant and prosthetic applications
from fish depends on the bones that are eaten. Small fish with (White et al., 2004).
soft bones are likely to be eaten with bones and thus contribute Seaweed species contain minerals such as calcium and phos-
more calcium intake than fish with hard, inedible bones (Roos phorus and some vitamins such as vitamin E in a good amount;
et al., 2003). There is very little information on the bioavailabil- therefore, seaweed is available in a commercial marine minerals
ity of calcium from the bones of small fish in humans (Hansen preparation as well as specific application such as animal and
et al., 1998, Uenishi et al., 1998; Larsen et al., 2000). The in vitro agriculture feeds (IFT Scientific Status Summary). The extract
studies using isotope labelled calcium-47 indicated that calcium of the marine algae (Sargassum horneri) has been found to ex-
absorption from small fish has been comparable with that from hibit the anabolic effect on bone calcinations in animal models
skimmed milk. These fish have proved to be a good source of of osteroporosis (Yamaguchi et al., 2001).
calcium (Hansen et al., 1998). Therefore, efforts should be made
to promote the production of small fish and its consumption, es- Solubilizing and Bioavailability of Calcium
pecially in pregnant or lactating women and young children in
low-income countries (Larsen et al., 2000).
Recently, the structure, distribution, function, and activity of
Shirasuboshi (boiled and semi-dried whitebait) is one of the
organic components in fish bone have been identified (Nishmoto
processed seafoods that is abundant in calcium (Nii et al., 2006).
et al., 2003; Witten and Hall, 2002). Even though fish bone
It is eaten whole and commonly consumed in Japan. The mix-
contains bioactive and nutraceutical molecules, very few efforts
ing of shirasuboshi with citrus fruit juices has been found to
have been made to utilize fish bones as functional materials due
increase the solubilization of calcium. Moreover, it has also
to the low solubility. Moreover, more than 50% of total fishery
been found that the flour from the fish bone of Nile tilapia (Ore-
products (over 120 million tons per year) are discarded annually
ochormis niloticus) and mola (Amblypharyngodon mola) have
as fisheries waste, such as bones, skin, fins, internal organs, and
been reported to be useful sources of calcium (Petenuci et al.,
head. Currently, many studies have been performed to utilize
2008; Larsen et al., 2000).
and to improve the functional properties of large amounts of
protein, oil, mineral, carbohydrate, and nucleic acid originating
Calcium from Marine Coral and Marine Algae from fisheries waste (Kim et al., 2001; 2003; Nagai and Suzuki,
2000; Shahidi and Janak Kamil, 2001). However, studies on
Coral has been used for medical purposes in Okinawa, Japan the utilization of organic components or minerals in the fish
and the Middle Eastern countries. Recently, coral calcium has bone are limited (Kim et al., 2003; Larsen et al., 2000). It is
gained popularity due to the reports that indicate the longest life obvious that calcium must be ionized and soluble to be absorbed.
spans of Okinawans from Japan attributing to the intake of water Even though a calcium salt is precipitated because of alkaline
rich in coral reef substances (Lev, 2003; Ramos et al., 2004). conditions in the ileum, some calcium ions are present in the
Coral calcium constituted by the exoskeleton of marine organ- solution. The total calcium absorption is a complicated function
isms form several colonies of rigid masses and named according of local solubility, the rate of tryansepithelial movement (i.e.,
to their visual shape as fire corals, brain corals, etc. (Laine et al., absorption), and the sojourn time in the particular intestinal
2008). Coral calcium is reported to be excellent for the heart, segment (Duflos et al., 1995).
CALCIUM APPLICATIONS FROM MARINE ORGANISMS 471

The aquatic environment has an enormous potential for dif- as a protective factor for colorectal cancer and adenomas. Ear-
ferent sources of enzymes. Recovery and characterization of lier research suggests that calcium may help to reduce the risk of
enzymes from fish and aquatic invertebrates have been achieved colon cancer, a killer of older men (Kampman et al., 2000). The
and some interesting and novel applications related to marine study of this nutrient against colorectal cancer was initiated by
enzymes in food processing have emerged (Shahidi ans Janak the mechanisms proposed in the early 1980s (Wargovich et al.,
Kamil, 2001). Among them, digestive enzymes have been ob- 1983; Newmark et al., 1984). Calcium has been found to reduce
served to improve calcium uptake. Taking enzymes with cal- the risk of colorectal cancer by binding to carcinogenic bile
cium containing foods will facilitate breakdown of the food and acids and ionized fatty acids, thereby reducing the proliferative
improve nutrient release to the body (Hunt and Johnson, 1983). activity of these compounds on the colonic mucosa (Lamprecht
Critical Reviews in Food Science and Nutrition 2012.52:469-474. downloaded from www.tandfonline.com

Casein phosphopeptides (CPP) derived from the intestinal di- and Lipkin, 2003; Newmark et al., 1984). It has also been hy-
gestion of casein have been found to enhance bone calcification pothesized to enhance differentiation of colonic cells through
in rats (Tsuchita et al., 1993). CPP like calcium fortifiers also binding to the calcium-sensing receptors, resulting in a wide
have the capacity to chelate calcium ion and to prevent precipi- range of biological actions such as the activation of isozymes
tation of calcium phosphate salts at neutral pH (Berrocal et al., of protein kinase C (Lamprecht and Lipkin, 2003; Chakrabarty
1989). Moreover, the addition of CPP to calcium fortified milk et al., 2003). Alternations in the expression of protein kinase C
could increase calcium absorption by growing rats mainly from isoforms have been observed in human and rodent colon cancer
CaCO3 added to the milk (Tsuchita et al., 2001). Furthermore, cells (Saxon et al., 1994; Frey et al., 2000). The progression
the positive effect of CPPs on passive calcium absorption seems of the disease from normal colonic epithelium to the malignant
to depend on the relative amounts of both species in intestinal phenotype is associated with diverse genetic and epigenetic al-
lumen (Erba et al., 2002). terations (Lamprecht and Lipkin, 2001). In double-blind studies,
Heterogenous enzyme extracted from the intestine of the calcium supplementation has shown to be helpful in protecting
carnivorous fish, bluefin tuna (Thunnus thynnus), and intestinal the cells against precancerous changes in the colon. A few epi-
crude enzyme (TICE) has been found to digest the skeletal demiological studies have also noted an inverse relationship
frames of hoki (Johnius belengerii) that is otherwise discarded between distal colon cancer incidence and calcium intake (Wu
as an industrial process waste. This has improved the utilization et al., 2002; Lin et al., 2005). However, these findings are yet to
of the bone as nutraceutical with the high calcium bioavailability be substantiated.
(Jung et al., 2005). Furthermore, the fish-bone phosphopeptide
(FBP), J. belengerii frame peptide (JFP) from the skeleton
and flesh of hoki (Jung et al., 2006; Jung and Kim, 2007), and Calcium Signaling
Theragra chalcogramm backbone peptide (TBP) from Alaska
Pollack (Jung et al., 2006) have also been found to increase the Cells must signal in order to adapt to changing environments
calcium retention and to decrease the mineral loss of the bone. and signalling requires messengers whose concentration varies
Chitooligosaccharides (COSs) have been found to inhibit with time. Calcium ions (Ca2+) affect every aspect of a cell’s
the formation of insoluble calcium salts efficiently during life and death. These ions bind to thousands of proteins to effect
in vitro and in vivo studies. Chitosan plays a role in wound changes in localization, association, and function. Filling this
healing, drug delivery, excretion of lipids or heavy metals and role, calcium ions (Ca2+) and phosphate ions have come to
irradiation materials throughout the intestinal tract. However, rule cell signalling (Clapham, 2007). Calcium ion (Ca2+) is a
its biological activity was limited to acidic medium because universal messenger with a pivotal role in almost all types of
of its poor solubility at alkaline conditions and low absorba- cells including T cells, B cells, and mast cells (Lewis, 2001;
bility of non-digestible and high molecular polysaccharide. Feske, 2007; Scharenberg et al., 2007). Moreover, Ca2+ signals
Therefore, chitosan has been converted into water soluble can control proliferation, differentiation, and apoptosis of cells
chitooligosaccharides (COSs). It has also been observed that in a variety of transcriptional programs (Hogan et al., 2003;
the water soluble COS supplementation has increased the Lewis, 2007; Hogan and Rao, 2007).
calcium retention and decreased the bone turnover. Moreover,
the COS has increased the levels of femoral total calcium, bone
mineral density, and femoral strength significantly similar to Calcium and Bone Health
those of CPP (Jung et al., 2006).
Osteoporosis is a systemic skeletal disease characterized by
a low bone mass and micro architectural deterioration of bone
BENEFICIAL HEALTH EFFECT OF CALCIUM tissue with a consequent increase in bone fragility and suscep-
tibility to fracture throughout the life span (Anonymous, 1993).
Calcium to Reduce the Colon Cancer It is a universal health problem mainly with postmenopausal
women and particularly elderly people. The two nutrients es-
Colorectal cancer is a predominant cause of mortality in sential for bone health are calcium and vitamin D. Calcium
Western societies. Dietary calcium has been considered for ages intake has an important impact on bone metabolism and bone
472 S-K. KIM ET AL.

health. Reduced calcium intake is associated with a reduced benefits (Myer and Champagne, 2007). Calcium supplementa-
bone mass and osteoporosis (Gennari, 2001). Adequate intake tion has proved to reduce systolic and diastolic BP, but people
of calcium and vitamin D can lower the menace of fractures with a relatively low calcium intake (<800 mg per day) have
(Michaelsen et al., 1994). Besides the amount of calcium in the higher BP. Moreover, it is suggested that an adequate calcium
diet, the absorption of dietary calcium in food is also a critical intake should be recommended for the prevention of hyper-
factor in determining the availability of calcium for bone de- tension. Even though there are a number of reports giving the
velopment and maintenance. Thus, there is a need to identify beneficial effects of calcium, more research on BP in people
food components and/or functional food ingredients that may with calcium-deficient diets is warranted (Mierlo et al., 2006).
positively influence calcium absorption (Cashman, 2002).
Critical Reviews in Food Science and Nutrition 2012.52:469-474. downloaded from www.tandfonline.com

A wealth of evidence has shown that supplementation of cal-


cium and vitamin D has a beneficial effect on the bone health CONCLUSION
and fracture risks. Clinical studies have indicated that calcium
and vitamin D supplementation are most effective when targeted Recently, dietary calcium has gained significant importance
to those men who are receiving antiresorptive or anabolic osteo- due to its varied and diversified applications. Even though milk
porosis therapy. These benefits are most apparent when 800 IU and other dairy products are the important sources of calcium,
of vitamin D is complemented with a dose of 1000–1200 mg of they are not very popular as some people do not prefer to take
elemental calcium per day (Boonen et al., 2006). Furthermore, milk due to lactose indigestion and intolerance. This has created
extensive research has shown that increased physical activity a new avenue for the search of calcium supplements. Marine
and calcium intake decrease the rate of bone loss (Nurzenski organisms, particularly fish, serve as a rich source of calcium.
et al., 2007). However, very few efforts have been made to utilize them as
functional materials due to their low solubility. The peptides in
the fish solubilize the bone and increase the bioavailability of
calcium. Moreover, the fish bones are considered as industrial
Calcium and Hypertension
wastes and their conversion into useful functional food would
not only be challenging but also profitable.
High levels of calcium in the body have been associated
with a lower risk of cardiovascular disease in postmenopausal
women. It also lowers cholesterol levels and decreases the symp- ACKNOWLEDGEMENTS
toms of premenstrual syndrome. It has also been observed that
regular fish consumption is associated with a low risk of cardio- This research was supported by a grant from the Marine
vascular mortality (Kromhout, 2001). Bioprocess Research Center of the Marine Biotechnology Pro-
Hypertension is an important public health challenge. Recent gram funded by the Ministry of Land, Transport, and Maritime,
efforts to reduce the prevalence of hypertension have focused Republic of Korea.
specifically on diet (Houston and Harper, 2008). Calcium plays
an important role in blood pressure (BP) regulation, but the
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