Carob Mint Spirulina · About This Product

Delicious Instant Energy.
Power Carob-Mint Spirulina tastes delicious and refreshing. It is natural, highly nutritious and safe to take even in megadoses provides the energy boost for people on the go and is an excellent source of natural whole-food nutrition for a healthy lifestyle.

For the physically active - both regular and occasional athletes - Power Carob-Mint Spirulina can make exercise even healthier. It provides easily absorbable nutrition that is needed for sustained physical activity. Furthermore, researchers claim the antioxidants vitamins C and E strengthen your resistance to injury and promote muscle recovery and regeneration.

Power Carob-Mint Spirulina is the natural choice over energy bars and synthetic supplements. Now you can indulge your sweet tooth without inviting tooth decay - and get complete nutrition at the same time!

Pure, Natural And Healthy
We are committed to providing the highest quality spirulina products to support people and their health. We use only the purest ingredients and we do not use chocolate, sugar, animal/dairy products, oils or synthetic additives. Power Carob-Mint Spirulina tastes as good as it is for you.

Indulge yourself, and feel good about it.

 

Carob Mint Spirulina · History

Ancient Sacred Power Plant and Space-Age Food

Ancient cultures were aware of spirulina’s exceptional life-generating energy and held its remarkable energizing and rejuvenating properties in high esteem. The Aztecs considered it a “Sacred Power Plant.” Priests and warriors sustained themselves (at times solely) on dried spirulina wafers. Naturally, NASA has considered spirulina as an ideal food to grow on space stations and has researched the possibility of using it on long-term flights. It would be ideal because it is one of the most efficient and fast-growing oxygen-generating foods.

 

 

Coming Soon...

 

Carob Mint Spirulina · · How to Use

Spirulina is a natural, whole food, so you can take it either with meals or on an empty stomach. The minimum dosage recommended is 6 tablets or 1 tsp powder per day. The powder can be mixed with juice or added to smoothies (see Recipe section).

Some people take as many as 20-40 tablets (2-4 Tbsp powder) per day. It is important to remember that spirulina provides high powered nutrition in a whole food form; it is not synthetic supplementation. We tend to think in terms of taking a certain number of pills per day. This is a fractured approach to nutrition.

Spirulina is offered in tablet form for convenience, but it is a natural whole food.

 

Carob Mint Spirulina · Nutritional Analysis

Spirulina, nature’s richest whole food source of all the essential nutrients, is the main ingredient in Power Carob-Mint Spirulina. Pure Planet Spirulina contains all the nutrients your body needs. The nutrients are highly absorbable because they're contained in bubble-thin cell walls that dissolve upon contact with moisture, which makes spirulina a natural energy food. With spirulina, you get instant energy on demand and the complete nutrition your body needs. For the athlete who burns up energy faster and is more susceptible to tissue injury through physical stress, the nutritional power of spirulina is fortified with Ester-C® and Glycine, both well-known for their beneficial effects on the human body.

Power Carob-Mint Spirulina is the ultimate energizer for the physically active, and these are the reasons:

Spirulina
Spirulina Pacifica is a super strain of Spirulina. The spirulina is grown in a controlled environment and then processed with low-temperature dehydration technology to preserve all the nutrition and freshness. Only the water is removed and nothing is added. Our spirulina powder is the purest, highest quality available today. It is simply the best natural nutrition possible!

Ester-C®
Patented Ester-C® is a complex of vitamin C, essential minerals and vitamin C metabolites that is Body-Ready® and non-acidic. Ester-C® is a readily absorbed and patented form of vitamin C. It helps meet the extra demand for vitamin C that your body might require.

Glycine
Glycine is a simple amino acid that is needed for synthesizing nonessential amino acids. It is required for the central nervous system function and contributes to improved blood circulation, the pituitary function, and a healthy prostate. Glycine helps retard muscle degeneration by supplying additional creatine, which is normally formed in the muscle and is essential for muscle function. It also releases energy for muscle function, stabilizes blood sugar, and mobilizes fat.

Carob
With a flavor similar to chocolate, carob is a nutritionally superior alternative. Unlike chocolate, carob is low in fat and calories and contains no acids, caffeine or other stimulants. It is naturally sweet; it is an excellent source of protein, carbohydrate, phosphorus, potassium, calcium, iron, pectin, and vitamins A, B-1(thiamin) and B-3 (niacin); and it is non-addictive and virtually non-allergenic.

Mint Flavor
The refreshing mint flavor will leave your breath cool and fresh...

Amount Per Serving   5g
Calories   19
Calories from Fat   0g
%Daily Value

Total Fat   0g   0%
Sodium   8mg   0%
Potassium   50mg   1%
Total Carbohydrates   2g   1%
Protein   1g

Vitamin A   10,750 I.U.

Vitamin C   475%
Thiamine   5%
(100% Beta Carotene)   215%
Calcium   5%
Riboflavin   5%
Iron   13%
Vitamin B-12   79%
Niacin   2%

Not a significant source of saturated fat, cholesterol, dietary fiber, and sugars.

· Percent Daily Values are based on 2,000 calorie diet. Your daily values may be higher.

 

Carob Mint Spirulina · Scientific References

The Potential Application of Spirulina (Arthrospira) as a Nutritional and Therapeutic Supplement in Health Management

by - Amha Belay, PHD*
Scientific Director, Earthrise Nutritionals Inc., Calipatria, California

INTRODUCTION

Spirulina, now named Arthrospira, is a microscopic and filamentous cyan bacterium (blue-green alga) that has a long history of use as food. Its name derives from the spiral or helical nature of its filaments (Fig 1). There are reports that it was used as a food in Mexico during the Aztec civilization some 400 years ago. It is still being used as food by the Kanembu tribe in the Lake Chad area of the Republic of Chad where it is sold as dried bread called “dihe”. Spirulina has been produced commercially for the last 20 years for food and specialty feeds. Commercial algae are normally produced in large outdoor ponds under controlled conditions (Fig 2). Some companies also produce directly from lakes. Current production of Spirulina worldwide is estimated to be about 3,000 metric tons. Sold widely in health food stores and mass-market outlets throughout the world. Spirulina's safety as food has been established through centuries of human use and through numerous and rigorous toxicological studies.

Early interest in Spirulina focused mainly on its rich content of protein, vitamins, essential amino acids, minerals, and essential fatty acids. Spirulina is 60-70% protein by weight and contains a rich source of vitamins, especially vitamin B12 and provitamin A ( -carotene), and minerals, especially iron. One of the few sources of dietary -linolenic acid (GLA), it also contains a host of other phytochemicals that have potential health benefits.

The objectives of this paper are 1) to review the available literature on the potential health effects of Spirulina and its extracts, 2) to provide insight into the potential implications of the studies reviewed in the context of possible nutritional and therapeutic applications in health management, and 3) to identify areas of interest for future research.

IMMUNOMODULATION EFFECTS

In a 1993 review of the potential health benefits of Spirulina, Belay et al. 9 presented the limited published information on this alga and called the attention of researchers to the particular areas of immune enhancement and caner. Numerous studies have been published since then. The evidence for immune modulation of Spirulina in various animal models is so striking that structure function claims have already been applied to some Spirulina products.

A summary of the major studies on immunomodulation properties of Spirulina is given on Table 1.

Hayashi et al.10were the first to publish detailed studies on immunomodulatory properties of dietary Spirulina in mice. According to their results. 1) mice fed Spirulina showed increased numbers of splenic antibody-producing cells in the primary immune response to sheep red blood cells. 2) the percentage of phagocytic cells in peritoneal macrophages from mice fed a Spirulina diet was significantly increased. 3) the proliferation of spleen cells by either Concavalin A (Con A) or phytohemagglutinin (PHA) was significantly increased. 4) addition of a hot water extract of Spirulina (SHW) to an in vitro culture of spleen cells significantly increased proliferation of these cells with no effect on thymus cells. 5) the hot water extract also significantly enhanced interluken-1 (IL-1) production from peritoneal macrophages, and 6) addition of the hot water extract to in vitro spleen culture and the supernatant of macrophages resulted in enhancement of antibody production. The authors concluded that Spirulina and its extract enhance immune function through the modulation of macrophage function, phagocytosis, and IL-1 production. These studies confirmed earlier studies of a preliminary nature reported by Liu et al.11

Qureshi et al.12 did similar studies where sephadex-elicited macrophage cultures were exposed to a 10-40 pg/ml (v/v) water-soluble extract of Spirulina for 1-16 hours. They found the following: 1) Spirulina-treated macrophages showed increased spreading and vacuolization with minimal cytotoxicity. 2)the percentage of phagocytic macrophages for unopsonized sheep red blood cells (SRBC) and average number of internalized SRBC was higher in the Spirulina-treated macrophages compared to controls and 3) culture-supernatants from Spirulina-treated macrophages contained a factor with tumoricidal potential similar in reactivity to one produced by macrophages after treatment with liposaccharides.12 Their results support earlier findings by Baojiang et al.13

Qureshi’s group also studied Cutaneous Basophilic Hypersensitivity Response (CBH) and bacterial clearance potential in chicks (B15 B15. Cornell K-strain) fed a Spirulina supplement diet.14CBH was studied by measuring toe web swelling after the injection of PHA-P. Toe web selling is here used as an index of T-cell proliferation. A significant improvement was observed in PHA-P induced peak response in chicks fed Spirulina at levels of 1,000 ppm and beyond. It was concluded that Spirulina supplementation improved T-cell-mediated response in chickens.

Also studied was the effect of Spirulina supplementation on blood clearance profile and splenic bacterial load. Leghorn checks fed a diet containing 1,000 ppm of Spirulina exhibited numerically reduced bacterial load in both circulation and spleen. Spirulina supplementation at 1,000 ppm showed an enhanced E Coli clearance from blood circulation reaching almost negligible levels 30 minutes post injection.14 The effect was ascribed to improvement in the activity of phagocytic cells as reported in their earlier study.12 According to the authors, the reduction of viable bacteria in spleen tissue over time is suggestive of an immunopotentiating effect of a particular dietary compound on mononuclear phagocytic system cells. The antibacterial effect of macrophages activated by Spirulina has also been reported elsewhere.15

In another study involving Cornell K-strain White Leghorn and broiler chicks. Qureshi et al.16 found that K-strain chicks had larger thyme over controls. They also found high anti-red-blood-cell antibody titers in the secondary response, especially at the higher supplementation group (10,000 ppm) compared to the control group (0 ppm). Chicks in the 10,000 ppm Spirulina group also had higher PHA-P-mediated lymphoproliferative response over the controls. Macrophages isolated from both K-strain and broiler chicks had higher phagocytic potential and NK cell activity. The authors concluded that a dietary inclusion of Spirulina at a level of 10,000 ppm might enhance disease resistance potential in chickens16 Qureshi's group did similar studies with cat macrophages exposed to Spirulina extract. They found increased phagocytic potential using red blood cells and E coli.17

In a study involving the effect of Spirulina in channel catfish (lctalurus punctatus). Duncan and Klesius18 found that fish fed Spirulina had a lower percentage of erythrocytes and a higher percentage of lymphocytes than fish fed a control diet. There was no difference in thrombocytes and macrophages in the Spirulina and control diet. However, peritoneally-elicited phagocytes from fish fed Spirulina showed enhanced pahgocylosis to zymosan and increased chemotaxis to Edwardstella ictaluri (5.9 times). Spirulina also enhanced production of antibodies to keyhole limpet hemocyanin (KLH) but not to E ictaluri. Their results are similar to those by Havashi et al.10 who showed in mice that Spirulina increased the antibody response to a thymus-dependent antigen but not a thymus-independent antigen.10 In a similar study by Lee19 the activity granulocytes and hyaline cells was enhanced significantly in tiger prawns (Penaeus monodon) supplied with a feed containing as low as 0.1% (w/w) dry Spirulina. The increase in phagocytic activity of hemocytes was a function of Spirulina content and time. Prawns fed with Spirulina could clear Vibrio parahaemolyticus, a pathogen of prawns, from the hemolymph at half the time taken by control prawns fed with basal diet.

A group of researchers from University of California-Davis 20 reported in 2000 the results of a study that adds evidence for the immunomodulatory effects of Spirulina. Using human peripheral blood mononuclear cells (PBMC), they demonstrated that Spirulina stimulated the secretion of Interlukin (IL)-IL-4, and interferon (IFN)- to nearly 2.0, 3.3, and 13.6 times basal levels, respectively. Induction of (IFN))- by Spirulina was found to be comparable to that seen after phtohemagglotinin (PHA) stimulation while being much less mitogenic than PHA in the induction of IL-4. The preponderance of (IFN)- over IL-4 is believed to show that Spirulina is more effective in stimulating a Th-1-tupe response and hence potentiates cell-mediated immunity. The moderate stimulation of the production of IL-4, that may be due to the antagonistic activity of IFN)- on IL-4, may mean that Spirulina helps balance the production of Th-1 and Th-2 cytokines. Thus Spirulina may provide strong protection against intracellular pathogens and parasites, and may also be effective in fighting in extracellular parasites.20

In a paper presented at the 30th annual meeting of the Japanese Society for Immunology. Saeki et al.21 presented the results of a human study using Spirulina extract. The immune modulation property of the extract in 40-year-old male volunteers was investigated using IL-12IL-18-dependent IFN- secretion induction activity and cell damage activity by NK cell as indices. 50 ml of a commercial Spirulina drink (Dainippon Ink & Chemicals, Inc.) containing 40% Spirulina hot water extract was administrated to over 40-year old male volunteers every day, and the IL-12/IL-18 dependent IFN- secretion induction activity of lymphocyte was chronologically analyzed by ELISA. Natural killer cell damage activity in blood was analyzed simultaneously. The analyses of he above parameters were done before and after administration of the extract. IFN- secretion activity and NK cell damage activities were enhanced significantly after two weeks of Spirulina extract administration. Surprisingly, the IFN- and NK cell activities continued up to 6 months after administration of extract was discontinued.21

In another study reported at the 59th annual meeting of the Japanese Cancer Association, the same group, Saeki et al.,22 reported the results of an investigation on the adjuvant effect of a hot water extract of Spirulina in the regression of tumors in tumor-bearing mice. Co-administration of Spirulina hot water extract with a cell wall component obtained from Tubercle bacillus (BCG-CWS) resulted in a much higher tumor regression in tumor-bearing mice than with BCG-CWS alone or in the untreated control mice. In this study BCG_CWS was administered in the mice, which were then immunized with inactivated b-16 melanoma. Following this, active melanoma cells were implanted subcutaneously. It is believed that microbial cell wall components like BCG-CWS act as inducers of dendritic cells, which play a major role in the induction of tumor-specific cytotoxic T-lymphocytes (CTL). The latter are believed to target high MHC-expressing tumor cells but fail to attack low MHC-expressing cells that are eliminated by natural killer cells. Since Spirulina has been found to be an effective activator of NK cell in previous studies, they suggested tumor cells that escaped attack by CTL cells were probably killed by NK cells. Thus both BCG-CWS and Spirulina extract effectively controlled the tumor. The combined administration of BCG-CWS and Spirulina extract resulted in more than 90% regression.22

The effect of Spirulina or its extracts on allergic reactions caused by food and other factors has been the subject of research recently. According to a Russian patent, the above-normal IgE levels observed in children in highly radioactive areas were normalized by the administration of 5 grams of Spirulina a day for 45 days. The level of IgE in the blood was taken as an index of allergy. The study was conducted with 35 preschool children living constantly in highly radioactive environments. (2-5 kv km2).23

Yang et al.,24 did extensive studies on the effect of orally-administrative Spirulina on anaphylactic reaction. The following is a summary of their findings: 1) Spirulina inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.5 and 1.0 mg/g body weight. 2) Spirulina significantly reduced serum histamine levels induced by compound 48/80 rats, 3) passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE was inhibited to 69%, 4) Spirulina dose-dependently inhibited histamine release from rat peritoneal mast cells by compound 48/80, and 5) Spirulina had a significant effect on the anti-DNP IgE-induced histamine release or tumor necrosis factor or production from RPMC. The authors postulate that the effects observed are possibly due to inhibition of anaphylactic degranulation of mast cells by Spirulina.24

Subsequent studies by Kim et al.25 on the effect of Spirulina on mast-cell-mediated immediate-type allergic reactions in rats also showed similar results. In this study Spirulina dose-dependently inhibited the systemic allergic reaction induced by compound 48/80 in rats. Compound 48/80-induced allergic reaction was inhibited 100% with intraperitoneal doses of 100-1,000 ug/g body weight. In rats treated with intraperitoneal dosages of Spirulina at concentrations ranging from 0.01 to 1,000 ug/g body weight, serum histamine levels were reduced in a dose-dependent manner. Spirulina also does-dependently inhibited histamine release from rat peritoneal cells activated by compound 48/80 or anti-DNP IgE. Spirulina also had a significant inhibitory-effect on anti-DNP IgE-inducted tumor necrosis factor production.25

In a similar study published in 1999. Gonzalez et at,26 reported anti-inflammatory activity of physocynanin extract in-acetic-acid-induced colitis in rats using myeloperoxidase activity and histophathological and ultra structural observations. Physocyanin substantially reduced myeloperoxidase activity and histophathological studies showed inhibition in inflammatory cell infiltration. The protection against inflammation was believed to be due to antioxidative and oxygen scavenging properties of phycocyanin.26

Hayashi et al.27 investigated the influence of dietary Spirulina platens is on different classes of antibodies, including IgA, IgE, and IgG1 in mice as possible evidence of the protective effect of Spirulina toward food allergy and microbial infection. IgE antibody levels increased in mice orally immunized with crude shrimp extract as an antigen (Ag group), Spirulina had no additional effect on the IgE level when administered with the antigen. However, co-administration of Spirulina with the antigen enhanced the level of IgG1 in excess of the level found by antigen administration only. IgA antibody level was significantly enhanced by treatment with Spirulina extract concurrently ingested with shrimp antigen compared with the level of shrimp antigen alone. In mice treated with Spirulina for 4 weeks before antigen stimulation, an enhancement of IgA was observed in lymphoid cells, especially in the spleen and the mesenteric lymph node.27

More recently. Ishii et al.28 studied the influence of Spirulina platens is on IgA levels in the saliva of 127 human subjects. Their results showed that total s-IgA levels were significantly higher when the subjects took Spirulina for over a year compared to those who took Spirulina for less than a year. They also found a significant correlation between the total s-lgA level in the saliva and the total amount of Spirulina consumed.

IMPLICATIONS OF THE RESULTS OF THE STUDIES

Our immune systems are our defense against pathogenic organisms like bacteria, viruses, cancer cells, and parasites, and against a whole series of compounds that are recognized as “foreign” or “non-self”. Any cell or molecule recognized as non-self is attacked by immune system cells and the antibodies they produce. The immune system is a complex system that involves specialized cells that communicate with each other via chemical messengers called cytokines. The immune system is also intricately tied up with nervous and endocrine systems. Hence, impairment of the immune system has far-reaching consequences in the body.

It is now well established that nutrient deficiency is associated with consistent changes in immune responses such as number of T-cells, lymphocyte response to mitogens and antigens, phagocyte function, secretory IgA antibody response, compliment activity, NK cell activity, and production of cytokines.29 Nutrient excesses are also associated with impaired immune function. For example, dietary intake of large quantities of fats impairs immune response. In addition, the immune system can be positively or negatively affected by certain photochemical found in conventional foods and foods derived from other plants like algae, mushrooms, and some herbs.

The findings of the studies summarized above are significant in the context of natural and nutritional therapeutic intervention the prevention of infection by pathogenic organisms. Non-specific cell-mediated immunity of the type found in these studies is the first line of defense against invading organisms. Enhancement of this aspect of the immune system will therefore have far-reaching advantages in body defense. Moreover, Spirulina appears to have a balancing effect on important immune cells and cytokines. Although cytokine-induced responses are generally protective in nature, an excess production and/or activity of cytokines can be harmful. It is known that the body possesses an elaborate system of checks and balances to control the production and activity of individual cytokine and that this process requires proper nutrition. Spirulina may provide such a nutritional role in modulation immune system function favorably.

The role of Spirulina in the activation of INF- and NK cells observed in the human clinical study and the adjuvant effect seen in the regression of implanted mouse tumors are important in relation to the potential nutritional and therapeutic use of Spirulina in cancer immunotherapy. The anti-allergy effects observed in these studies are also significant in relation to natural therapeutic intervention in allergic situations. Spirulina neither induced nor enhanced allergic reactions dependent on IgE. On the contrary, it was found to enhance IgA production when ingested both con-currently with antigen and before antigen and before antigen stimulation, providing protection against allergic reactions. The observation that secretory IgA production was found to correlate with Spirulina consumption may point to the potential role of Spirulina in mucosal immunity. The salivary glands are recognized as part of the common mucosal immune system, and saliva is commonly used to study the effect of various parameters on the human mucosal immune system.30 Recently there is a focus on research in the therapeutic use of antigen feeding for immunization and/or oral tolerance induction.31 It is now well established that oral or intranasal immunization confers protection against a variety of viral and bacterial mucosal pathogens. On mucosal surfaces, secretory IgA antibodies elicit a whole series of biological responses such as agglutination of microorganisms, neutralization of bacterial enzymes, toxins, and viruses, and immune exclusion and inhibition of antigen or allergen absorption.32 Though conjectural , Spirulina may have a role in modulation these beneficial effects that result in the killing or inactivation of pathogens, antigens, and allergens, in addition to protection offered through the stimulation of cell-mediated immunity.

ANTIOXIDANT EFFECTS

A summary of studies related to the antioxidant effects of Spirulina is given in Table 2.

The antioxidant properties of Spirulina and its extracts have attracted the attention of researchers recently. In one of the earliest studies. Manoj et al.33 reported that the alcohol extract of Spirulina inhibited lipid peroxidation more significantly (65% inhibition) than the chemical antioxidants like -tocopherol (35%), BHA (45%), and -carotene (48%). The water extract of Spirulina was also shown to have more antioxidant effect (76%) than gallic acid (54%) and chlorogenic acid (56%). An interesting aspect of their findings is that the water extract had a significant antioxidant effect even after the removal of polyphenols.

In the another study, by Zhi-gang et al.,34 the antioxidant effects of two fractions of a hot water extract of Spirulina were studied using three systems that generate superoxide, lipid, and hydorxyl radicals. Both fractions showed significant capacity to scavenge hydroxyl radicals (the most highly reactive oxygen radical) but no effect on superoxide radicals. One faction had significant activity in scavenging lipid radicals at low concentrations.

In a study by Miranda et al.,35 the antioxidant activity of a methanol extract of Spirulina was determined in vitro and in vivo. The in vitro antioxidant assay involved a brain homogenate meubated with and without the extract at 37 C. Peroxidation of rat brain homogenate was inhibited by almost 95% with 0.5 mg of the hethanolic extract. The IC50 of the extract in this system was found to be 180 ug. The in vivo antioxidant capacity was evaluated in plasma and liver of animals receiving a daily does of 5 mg for 2 and 7 weeks. Plasma antioxidant activity in brain homogenate incubated at 47 C showed that the antioxidant capacity of plasma was 97% and 71% for the experimental group and 74% and 54% for the control group after 2 and 7 months. The antioxidant effect was attributed to beta carotene, tocopherol, and phenolic compounds working individually or in synergy.35

In what appears to be the first report on antioxidant and anti-inflammatory properties of c-phycocyanin. Romay et al.36 showed that phycocyanin was able to scavenge hydroxyl (IC50=76 ug/ml) radicals with activity equal to 0.125 mg/ml of dimethyl sulfoxide. (DMSO) and 0.038 ug/ml of trolox, specific scavengers of those radicals respectively. Phycocyanin also inhibited liver microsomal lipid peroxidation (IC50=12 mg/ml). It is interesting to note that the oxygen-scavenging activity of c-phycocyanin was only 3 times lower than that of superoxide dismutase (SOD). The addition of SOD to the phycocyanin did not after the antioxidant activity of the phycocyanin, suggesting a different mechanism of action.36 Further studies by the same group 37 revealed the anti inflammatory activity of phycocyanin in some animal models of inflammatory. Phycocyanin reduced significantly and in a dose-dependent manner the ear edema induced by arachidonic acid and tissue plasminogen activator in mice, as well as carageenan-induced rat paw edema. Phycocyanin also showed anti-inflammatory activity in a sub-chronic cotton pellet granulma test where sterile cotton pellets were implanted in the axillae of rats. Oral administration of phycocyanin resulted in significant anti-inflammatory activity in all models tested. The anti-inflammatory activity observed was attributed to antioxidant and oxygen scavenging activity of phycocyanin and perhaps also due to its inhibitory effect on arachidonic acid metabolism. When compared with indomethacin, a standard anti-inflammatory drug, phycocanin showed a weaker activity (50-300 mg/kg, p.o.) compared to 3-10 mg/kg, p.o., for the former. However, the LD50 Of indomethacin was 12 mg/kg in rats and 50 mg/kg in mice, p.o. and induces many side effects in patients under treatment. The LD50 of phycocyanin in rats and mice was greater than 3g/kg, p.o. in fact, no mortality was observed even at 3g/kg, p.o.37

Vadiraja et al.38 studied the effect of c-phycocyanin from Spirulina platensis on carbon tetrachloride and R-(+)- pulegone-induced hepatotoxicity in rats. In this study a single dose (200 mg/kg) of phycocyanin was administered intraperitoneally to rats one or three hours prior to R- (+) - pulegone (250 mg/kg) or carbon tetrachloride (0.6 ml/kg) challenge. Phycocyanin significantly reduced the hepatoxicity caused by these chemicals. Both chemicals are believed to cause hepatotoxicity due to the formation of free radicals.

The hepatoprotective effect of phycocyanin was therefore attributed to the inhibition of reactions involved in the formation of reactive metabolites and possibly due to its radical scavenging activity. Duran et al. 39 also found a similar hepatoprotective effect in experiments where rats were fed an oil extract of Spirulina or its defatted fraction.39 Recently, Bhat and Madayatha40 reported that c-phycocyanin from Spirulina effectively inhibited CCI4- induced lipid peroxidation in rat liver in vivo. The inhibition by both native and reduced phycocyanin was Table 2.

Type of Study Summary Reference
In Vitro The alcohol extract of Spirulina inhibited lipid peroxidation more significantly than the chemical antioxidants like a-tocopherol, BHA and ß-carotene. Water extract showed more antioxidant activity than gallic acid and chlorogenic acid; antioxidant activity remained high even after removal of polyphenols. 33 In Vitro Two fractions of a hot water extract showed significant capacity of scavenging lipid radicals at low concentrations. 34 In Vitro Peroxidation of rat brain homogenate was inhibited by almost 95% with 0.5 mg of the methanolic extract. The IC50 of the extract in this system was found to be 180µg. 35

Rat Plasma antioxidant activity in brain homogenate incubated at 47°C showed that the antioxidant capacity of plasma was 97% and 71% for the experimental (Spirulina extract) group and 74% and 54% for the control group after 2 months and 7 months, respectively.

35

In Vitro

Phycocyanin was able to scavenge hydroxyl (IC50=0.91 mg/ml) and alkoxyl (IC50= 76 µg/ml) radicals The activity was equal to 0.125 mg/ml of dimethyl sulfoxide (DMSO) and 0.038µg/ml of trolox phycocyanin also inhibited liver microsomal lipid peroxidation (IC50=12mg/ml).

36

Mice, Rats Oral administration of phycocyanin reduced significantly and in a dose-dependent manner the ear oedema induced by Arachidonic Acid (AA) and tissue plasminogen activator (TPA) in mice, as well as carageean-induced rat paw oedema. 37 Rats Phycocyanin also showed anti-inflammatory activity in a sub-chronic cotton pellet granuloma test where sterile cotton pellets were implanted in the axillae of rats. When compared with indomethacin, a standard anti-inflammatory drug, Phycocyanin shows a weaker activity (50-300 mg/kg, p.o.) compared to 3-10 mg/kg,p.o. The LD50 of indomethacin was 12 mg/kg in rats and 50 mg/kg in mice, p.o. The LD50 of phycocyanin in rats and mice was greater than 3g/kg, p.o.

37

Rats

Carbon tetrachloride (0.6 ml/kg) and R-(+)- pulegone (250 mg/kg) - induced hepatotoxicity in rats was reduced significantly when phycocyanin was administered intraperitoneally to rats one or three hours prior to the challenge.

38

Rats A similar hepatoprotective effect as above was seen in actual feeding experiment in rats with an oil extract of Spirulina or its defatted fraction. 39 Rats Oral administration of c-phycocyanin (100 mg/kg) in rats prevented kainic- acid-induced behavioral and glial reactivity in the rat hippocampus, crossing the hemato-encepphalic barrier. The study also shows that phycocyanin reduces experimental status epilepticus. Authors postulate potential use of neurodegenerative diseases such as Alzeimer's and Parkinson’s, diseases induced by oxidative-stress-induced neuronal injury. 40,41 In Vitro Phycocyanin inhibited 2,2’- azobis (2 midinoprapane) dihydroxychloride (AAPH)- induced human erythrocyte haemolysis in the same way as trolox and ascorbic acid, two well known antioxidants. Based on IC50 values phycocyanin was found to be sixteen times more efficient as an antioxidant than trolox and about 20 times more efficient than ascorbic acid. 42 In Vitro The antioxidant activity of phycocyanobilin (a component of phycocyanin) was greater than that of alpha tocopherol, zeaxanthin and caffeic acid on a molar basis. 43 Phycocyanin from spray-dried Spirulina had a similar antioxidant activity as phycocyanin from fresh Spirulina. 43

Rats

In vitro C-phycocyanin from Spirulina effectively inhibited CCI4-induced lipid peroxidation in rat liver in vivo phycocyanin showed a poted peroxyl radical scavenger capacity with a rate constant-ratio of 1.54 compaed to 3.5 for uric acid (a known peroxyl radical scavenger). 40 In vitro Isolated enzyme assays and whole blood assays show that C-phycocyanin from Spirulina platensis is a selective inhibitor of cyclooxygenase-2 (COX-2) with a very low IC50 COX-2/IC50 COX-1 ratio (0.04). 44 In vitro IC50 value obtained for COX-2 inhibition by phycocyanin was much lower (180 nM) as compared to those for celecoxib (255 nM) and rofecoxib (401 nM), the well-known selective COX-2 inhibitors. 44

In vitro
Potential role in hepatoprotection, anti-inflammatory and anti-arthritic action postulated. 44

Concentration-dependent with an IC50 of 11.35 and 12.7µM, respectively. Their studies have shown unequivocally that phycocyanin is a potent peroxyl radical scavenger with a rate-constant ratio of 1.54 compared to 3.5 for uric acid (a known peroxyl radical scavenger). A recent interesting and elaborate study shows that oral administration of c-phycocyanin (100 mg/kg) in rats prevents kainic-acid-induced behavioral and glial reactivity in the rat hippocampus suggesting a corresponding protective effect on neurons. The study showed that phycocyanin reduced experiment status epilepticus, suggesting possible therapeutic intervention in the treatment of some forms of epilepsy. According to the authors,41 kainic acid (KA) triggered excitotoxicities resulted in the production of reactive oxygen species. It is therefore postulated that the protective effect of phycocyanin in neuronal damage may be due to its free-radical scavenging and antioxidant properties. An interesting aspect of this study is the finding that oral administration of phycocyanin exerts its effect in the hippocampus, crossing the hematoencephalic barrier. According to the authors, these findings and the virtual lack of toxicity of phycocyanin suggest that this phytochemical could be used in the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, diseases brought on by oxidative stress-induced neuronal injury.41 Moreover, Romay’s group 42 has recently reported that phycocyanin inhibited 2.2’- azobis (2midinoprapane) dihydroxychloride (AAPH)-induced erythrocyte haemolysis in the same way as trolox and ascorbic acid, well-known antioxidants. Based on IC50 values ( concentration of the additive that gave the 50% inhibition of peroxidative damage), phycocyanin was found to be 16 times more efficient as an antioxidant than trolox and about 20 times more efficient than ascorbic acid.42 These findings were supported by a more recent study 43 that showed that the antioxidant activity of phycocyanobilin ( a component of phycocyanin) was greater than that of alpha tocopherol on a molar basis. The antioxidant effect of phycocyanobilin was evaluated against oxidation of methyl linoleate in a hydrophobic system or with phosphatidylcholine liposomes. The study also showed that phycocyanin from spray-dried Spirulina had a similar antioxidant activity as phycocyanin from fresh Spirulina. The results suggest that the antioxidant activity of phycocyanin is attributable to phycocyanobilin, a prosthetic group in phcocyanin since the apoprotein component may be denatured upon drying.43 The fact that the dried phycocyanin showed the same level of activity as the intact protein makes the preparation and utilization of phycocyanin commercially feasible.

According to Reddy et al.,44 c-phycocyanin from Spirulina platensis is a selective inhibitor of cyclooxygenase-3(COX-2) with a very low IC50 COX-2/IC50 COX-1 ratio (0.04). Interestingly, their study showed that the IC50 value obtained for COX-2 inhibition by phycocyanin was much lower (180 nM) as compared to those for cele-coxib (255 nM) and rofecoxib (401 nM), the well-known selective COX-2 inhibitors. The apoprotein component of phycocyanin was responsible for the inhibition of COX-2 since reduced phycocyanin and phycocyanobilin were found to be ineffective. The authors suggest that the hepatoprotective, anti-inflammatory, and anti-arthritic properties of phcocyanin reported in the literature might be due, in part, to its selective COX-2 inhibitory property, though they did not exclude a similar effect of phycocyanin through its ability to efficiently scavenge free radicals and inhibit lipid peroxidation.

IMPLICATIONS OF THE STUDIES

The relationship between antioxidant intake and incidence of chronic diseases such as cancer, cardiovascular disease, cataracts, and premature aging is now well established through many epidemiological, intervention, and clinical studies. This strong association between diet and cancer led the National Cancer Institute to initiate the 5-A-Day Program in 1991,45 recommending 5 servings of fruits and vegetables daily. The United States Department of Agriculture recommends 5-9. Surveys show that only 23% of adult Americans consume the recommended level, and the median level was about 3 servings a day. People whose lifestyle choices preclude eating properly may want to improve their diets by adding nutritional supplements rich in antioxidants. While the connection between the consumption of fruits and vegetables and the incidence of disease cannot be attributed to the antioxidants play the major role. Fruit and vegetable antioxidants are derived from the carotenoid pigments. Spirulina provides an adequate amount of a spectrum of carotenoid pigments, especially beta carotene (associated with cancer prevention) and zeaxanthin (associated with prevention of age-related macular degeneration (AMD). In this respect Spirulina is a “microvegetable” that can provide some of the antioxidants needed. Many studies have also revealed that antioxidants like the carotenoids in fruits, and vegetables, and Spirulina have a synergistic effect. Thus whole-food supplements are expected to provide more antioxidant protection compared to individual components. Spirulina also contains phycocyanin and polysaccharides, both known to have antioxidant properties. In addition, antioxidants that have a direct effect on reactive oxygen species, Spirulina contains an important enzyme, superoxide dismutase, that acts indirectly by slowing down the rate of oxygen radical generating reactions. The results of the studies summarized above point to the potential use of Spirulina together with other conventional approaches in a nutritional supplementation strategy geared toward the prevention and mitigation of health problems like cancer, heart disease, and premature aging that are associated with free radical damage. In the context of using Spirulina as an antioxidant, it is worth noting that it contains about contains about 7% phycocyanin (dry weight basis) and a relatively high content of superoxide dismutase (1,700 units/g) in addition to a high content of mixed carotenoids. A significant aspect of these studies is that orally-administered phycocyanin is bioavailable and can even pass the blood-brain barrier. The role of phycocyanin in COX-2 inhibition may also result in the potential application of Spirulina in the management of inflammatory conditions and toxicity due to chemicals and drugs.

ANTICANCER EFFECTS

The antioxidant and immune modulation effect of Spirulina and its extracts discussed above are to a certain extent associated with Spirulina’s cancer prevention potential. In this summary we report only those studies targeted directly at cancer research. Table 3 summarizes the studies on anti-cancer effects of Spirulina.

The only human study on the effect of Spirulina on chemoprevention of cancer is that by Mathew et al.,46 who studied the effect of Spirulina on oral leukoplakia (a precancerous lesion) in pan tobacco chewers in Kerala, India. In a study involving 44 subjects in the intervention group and 43 in the placebo group, they found that supplementation with Spirulina at 1 g/day for 1 year resulted in complete regression of lesion in 45% of the intervention group and 7% in the control group. The effect was more pronounced in homogeneous lesions. Since supplementation with Spirulina did not result in increased serum concentrations of retinal beta carotene, the authors concluded that other constituents in Spirulina may be responsible for the regression of lesions observed.46 The results of this study are significant because, even in developed countries, tobacco use is the cause of 30% of the incidence of cancer, with the greatest influence on lung and oral cancer.47 As recommended by the authors, it is worth investigation this potentially useful aspect of Spirulina in more rigorous human trials. If Spirulina proves to have such effect, it can easily be incorporated in the daily diet as a therapeutic agent.

The human oral cancer study corroborates the results found in earlier studies on the effect of Spirulina and Dunaliella extract on experimental cancer in hamster buccal pouches. Schwartz and Shklar48 studied the effect of administration of 250 µg of the extract in 0.1 ml of MEM (minimum essential medium) directly to DMBA (7.12- dimethylben/(a)-anthracine)-induced squamous cell carcinoma of hamster buccal pouches. Other treatments included injection of beta carotene, cantaxanthin, 13 cis-retinoic acid and sham-injected controls. All treatments involved 250µg in 0.1 ml MEM twice weekly for 4 weeks. After four weeks of treatment, total tumor regression was found in 30% of the animals treated with extract, 20% of the beta carotene-treated animals, and 15% of canthaxanthin-treated animals. Partial tumor regression was found in the remaining 70% of the extract-treated animals.48 An interesting observation of this study is that the algae extract appears to be more effective than beta carotene alone, suggesting a synergistic effect between the various components of the algae. In another study Schwartz et al.49 have shown that algae-derived phycocyanin had a cytostatic and cytotoxic activity against squamous cell carcinoma ( human or hamster). Phycocyanin may have played a synergistic effect here as well as in the human study reported above. In subsequent studies, Schwartz et al, 50 were able to demonstrate that an extract of Spirulina and Dunaliella administered orally (140 µg every 3 days for 28 days) prevented tumor development in hamster buccal pouches. Carcinomas that were beginning to develop were destroyed in what appeared to be an immune response. This was surmised from the dense lymphocytic-monocytic infiltrated observed. The monocytes were found to be cytotoxic to tumor target cells in vitro and the lymphocytes were found to be T-cells. Thus the algae extract was believed to prevent cancer development by stimulating an immune response to selectively destroy small initial foci of developing malignant cells.50 It is worth noting that the algae extract was not cytotoxic to normal cells in all experiments performed.

In a murine model, Lisheng et al, 51 found that a polysaccharide extract of Spirulina inhibited the proliferation of ascitic hepatoma cells of mice injected at a dose of 200 mg/kg. In this study 36 healthy female mice were injected with 5x106 of ascitic hepatoma cells, and the controls were injected with distilled water. On the second day after injection of the hepatoma cells, 200mg/kg/day of polysaccharide from Spirulina platensis was injected for 6 days. Another group (prevention group) was injected of the hepatoma cells. Quantification of the ascites was done 6 days after injection of the hepatoma cells. Compared to the control group, those treated with the extract after the transplantation of the tumor showed 54% reduction in tumor progression, while those where the extract was administered five days before tumor transplantation showed a 91% decrease in tumor progression.51 According to Chen et al,52 the number of aberrant crypts formed in the colon of rats by a single or multiple injection of 1,2-dimethyl hydrazine (DMH) was reduced significantly (p<0.01) in rats fed Spirulina particularly during weeks 13 and 16 after injection. Recently, Mishima et al.53 have elegantly demonstrated inhibition of tumor invasion and metastasis by calcium spirulan (Ca-SP), a novel polysaccharide isolated from Spirulina platensis. Seven intermittent i.v. injections of 100µg of Ca-SP in mice caused a marked decrease of lung tumor colonization of B-16-BL6 cells in a spontaneous lung metastasis.

Table 3. Summary of studies on anticancer and antiviral effects of Spirulina or its extracts

Type of Study Summary of Studies Reference
Human In a study involving 44 subjects in the intervention group and 43 in the placebo group supplementation with Spirulina at 1 g/day for 1 year resulted in complete regression of oral leukoplakia in pan tobacco chewers in India. Complete regression was observed in 45% of the intervention group compared to only 7% in the control group. 46 Hamsters Administration of 250 µg of a Spirulina/Dunaliella extract (in 0.1 ml of minimum essential medium, MEM) directly to 7,12 dimethylbenz (a)- anthracine (DMBA)-induced squamous cell carcinoma of hamster buccal pouches resulted in total tumor regression in 30% of the animals treated with extract 20% of the beta-carotene-treated animals and 15% of cnathaxanthin-treated animals showed complete regression. Partial tumor regression was found in the remaining 70% of the extract-treated animals. 48 Human and Hamsters Algae-derived phcocyanin had a cytostatic and cytoxic activity against squamous cell carcinoma (human or hamster).

50

Hamsters

An extract of Spirulina and Dunaliella administered orally (140 µg every 3 days for 28 days) prevented tumor development in hamster buccal pouches. The dense lymphocytic-monocytic infiltrate observed suggested that the anticancer effect could be due to an immune response. The algae extract was not cytotoxic to normal cells in all experiments performed.

49

Mice A polysaccharide extract of Spirulina inhibited the proliferation of ascitic hepatoma cells of mice injected at a dose of 200 mg/kg. The group treated with the extract after the transplantation of the tumor showed a 54% reduction in tumor progression. The group where the extract was administered five days before tumor transplantation showed a 91% decrease in tumor progression. 51 Rats The number of aberrant crypts formed in the colon of rats by a single or multiple injection of 1,2-dimethydrazine (DMH) was reduced significantly (p<0.01) in rats fed Spirulina.

52

Mice Seven intermittent i.v. injections of 100µg of Ca-SP in mice caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. 53

Mice

C-Phycocyanin from Spirulina inhibited the growth of K562 leukemia cells in a dose-dependent manner with statistically significant inhibition observed at 80 &160mgl 1 In XTT dye reduction assay.

54

In vitro

Hamsters Water extract of Spirulina platensis inhibited the replication of Herpes simplex virus type (HSV-1) in HeLa cells within the concentration range of 0.08-50 mg/ml. Extract did not have virucidal effect but interfered with the adsorption and penetration into hose cells. The ID50 for cytotoxicity of the extract to HeLa cells was 26.3 mg/ml, while the ED50 for antiviral activity was found to be 0.173 mg/ml, giving an in vitro therapeutic index of 152. In an experimental study of HSV-1 corneal infection of hamsters, food containing the extract effectively prolonged the survival time of infected hamsters at doses of 100 and 500 mg/kg.

65

In vitro Calcium Spirulan (Ca-SP) from Spirulina platensis found to inhibit the replication of several enveloped viruses including Herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HVMV), measles virus, mumps virus, influenza A virus, and HIV-1 virus. 66 In vitro The anti-HIV-1 activity of Ca-SP was found to be comparable to dextran sulfate, a known potent anti-HIV-1 agent, and its anti-HSV-1 activity was four to five-fold higher than that of dextran sulfate. The anti-HIV-1 activity of Ca-SP or DS was five and four times higher in cultures treated with Ca-SP or DS during infection when compared with that in cultures treated after infection. Ca-SP was considered superior to DS in possible therapeutic application. 67 In vitro An aqueous extract Spirulina ( Arthrospira) platensis inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells. The extract inactivated HIV-1 infectivity directly when pre-incubated with virus before addition to human T-cell lines. 68

Their studies of the invasion of B16-BL6 melanoma, colon 26 M3.1 carcinoma, and HT-1080 fibro sarcoma cells through reconstituted basement membrane (Matrigel) shed light on the mechanism of the inhibition of the invasion. The authors suggest that Ca-SP could reduce lung metastasis of B16-BL6 melanoma cells by inhibiting the tumor invasion of basement membrane, probably through heparanase activity and through the prevention of the adhesion and migration of tumor cells to laminin substrate. Their results showed that Ca-SP strongly inhibited the degradation of heparan sulphate by purified heparanase. According to these workers, this remarkable anti-heparanase activity might provide a promising basis for improved therapeutic approaches to tumor invasion and metastasis.53

In a very recent study54 (2000), c-phycocyanin (C-PC) from Spirulina platensis inhibited the growth of human leukemia K562 cells. The effect of phycocyanin was at first studied following the growth of the K562 cells in semi-solid agar culture at concentrations of 20,40,80, and 160 mg-1 . The results showed that phycocyanin inhibited the growth of the K562 leukemia cells in a dose-dependent manner with statistically significant inhibition observed at 80 and 160mg-1 . The effect of phycocyanin was further studied using cell viability measurement using XTT dye reduction assay. Phycocyanin was again found to inhibit cell viability in a dose-and time-dependent manner. The IC50 value of CPC was found to be 72.5 mg-1. Furthermore, flow cytometric assay based on DNA content analysis revealed that accumulation of K562 cells occurred in the G-1 phase when cells were incubated in C-PC for 6 days. There were higher percentages of cells in the G-1 phase at phycocyanin concentrations of 40 and 80 mg- 1 . DNA fragment analysis did not show the ladder formation typically observed in apoptosis, indicating that a different mechanism may be at play in the inhibition process.54 According to a Japanese patent,55 oral administration of phycocyanin extracted from Spirulina was found to increase the survival rate of mice that had been injected with liver tumor cells. The lymphocyte activity of the treatment group was significantly higher than that of the control group, suggesting some sort of stimulation of the immune system. Another study of interest is that by Qishen et al .56 who reported enhancement of endonuclease activity and repair DNA synthesis by polysaccharides of Spirulina platensis. The effect of the extract was studied by means of endonuclease assay and radio autography. The results showed that the presence of the extract significantly enhanced both the repair activity of radiation-damage DNA excision and the unscheduled DNA synthesis.56 The same group 57 also found that an extract of micronucleus frequencies induced by gamma radiation in mouse bone marrow cells.

IMPLICATIONS OF THE STUDIES

Doll and Peto58 did the landmark study establishing that 35% of all human cancer deaths appear to be associated with diet and nutrition. Since then numerous experimental, epidemiological, and clinical studies have proved this connection.59-60 These studies have demonstrated conclusively that numerous nutrient and non-nutrient constituents in foods in our diet have the potential to confer chemo preventive properties or enhance conventional therapy. For example, there is evidence that vegetable and fruits, rich sources of antioxidants like vitamin C,E, and beta-carotene, might protect against different forms of cancer. There is also a recent body of evidence to suggest that physiological aging of the immune system may affect cell-mediated immunity that in turn results in cancer development, autoimmune disease, and susceptibility to infection.61 Radiation, chemotherapy, and surgery therapies cause side effects often worse than the cancer itself. Preventive and mitigation methods utilizing natural products directly or as adjuvant to conventional cancer treatment are therefore the focus of recent research.62 The studies summarized above suggest such a role for Spirulina. Spirulina may offer some degree of protection against certain forms of cancer through its effect on the immune system, through a direct effect in the repair of DNA, and antioxidant protection form reactive oxygen species generated during normal or abnormal metabolism and from toxic substances in the environment. Further research along these lines is recommended to validate these assumptions.

ANTI-VIRAL EFFECTS

A summary of the studies on the anti-viral effects of Spirulina is given in table 3. Interest in the study of antiviral effects of Spirulina was triggered by a report from researchers at the National Cancer Institute about the discovery of potent antiviral compounds from extracts of blue-green algae. Gustafson et al. 63 found that sulfonic-acid-containing glycolipids isolated from Lyngbya lagerheimmi and phormidium tenue were active against HIV-1 in cultured human lymphoblastoid CEM, MT-2, LDV-7, and C3-44 cell lines. At the time, these sulfolipids were given high priority by the NCI for further preclinical investigators and for evaluation of feasibility as candidates for clinical testing.63 In subsequent studies this group screened about 600 strains of cultured cyanobacteria representing some 300 species. Approximately 10% of the cultures produced substances that caused significant reduction in cytopathic effects normally associated with viral infection.64

According to Hayashi et al.,65 the water extract of Spirulina platensis inhibited the replication in vitro of Herpes simplex virus type (HSV-1) in HeLa cells within the concentration range of 0.08-50 mg/ml. The extract did not have virucidal effect but interfered with the adsorption and penetration of virus into host-cells. Addition of the extract (2 mg/ml) 3 hours before infection resulted in inhibition of virus-specific protein synthesis without affecting host cell protein synthesis. The ID50 for antiviral activity was found to be 0.173 mg/ml, giving an in vitro therapeutic index of 152. In an in vivo study involving experimental HSV-1 corneal infection of hamsters, they found that food containing the extract effectively prolonged the survival time of infected hamsters at doses of 100 and 500 mg/kg. From the data obtained in the in vivo study the authors postulated that Spirulina supplementation might prevent hepetic encephalitis. Hayashi et al.66 isolated from Spirulina platensis a novel sulfated-polysaccharide, calcium spirulan (Ca-SP), that inhibits the replication in vitro of several enveloped viruses including Herpes simplex type 1 (HSV-1), human cytomegalo virus (HVMV), measles virus, mumps virus, influenza A virus, and HIV-1 virus 66 In a later study, Hayashi et al.67 found that the anti-HIV-1 activity of Ca-SP is comparable to that of dextran sulfate (DS; a known potent anti-HIV-1 agent), while its anti-HSV-1 activity was four-to five-fold higher than that of dextran sulfate. The anti-HIV-1 activity of Ca-SP or DS was five and four times higher in cultures treated with these substances after infection. Ca-SP was found to be superior to DS in possible therapeutic application because 1) enhancement of viral replication at low concentrations, a usual phenomenon Is DS, was not observed with Ca-SP was found to have a much lower anticoagulant effect than DS, 3) Ca- SP was found to have a much longer half-life in the blood of mice compared to DS, and 4) Ca-SP was four to five times more effective in inhibiting HSV-1 Compared to DS.67

More recently, Ayehunie et al.68 reported that an aqueous extract of Spirulina (Arhtrospira) platensis inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC). And Langerhans cells. Depending on the cell type used, therapeutic indices (EC50/IC50) ranged between 200 and 6,000. The extract inactivated HIV-1 infectivity directly when pre-incubated with virus before addition to human T-cell lines. These authors found antiviral activity both in the polysaccharide fraction as well as in a fraction depleted of polysaccharides and tannins. The authors believe that the aqueous extract of S platensis might be of potential clinical interest.68

IMPLICATIONS OF THE STUDIES

Abuse and misuse of antibiotics has resulted in the emergence of new antibiotic-resistant bacteria and viruses. The most prominent viral disease, HIV/AIDS has become pandemic. Conventional anti-HIV drugs are beyond the reach of ordinary people. Vaccines are still a long way to come. It is apparent that alternative sources be sought. Therapeutic use of herbs and algae products with known bactericidal and virucidal properties may offer alternative approaches. Whole-plant products and crude extracts often have ingredients that may work synergistically to effect viral or bacterial killing or inactivation. Resistance to these varied substances may not be as easy as to one single antibiotic. It is also known, at least for some natural products, that they exert their protective effect through stimulation or modulation of the immune system. Therefore instead of trying to find the magic chemical bullet to kill viruses or bacteria, the body’s immune system is activated to protect against infection. Such an approach will also be useful even after infection sets in. For example, HIV/AIDS sufferers are usually affected by opportunistic infection once the virus debilitates the immune system. Enhancement of the immune system through therapeutic intervention wit natural products may offer protection against such infection.

As summarized in the studies above, the antiviral activity of the aqueous extract of Spirulina has been demonstrated in various in vitro and animal models. The active component of the extract appears to be Ca-SP. This compound could be a good candidate for therapeutic intervention against HIV-1 and other viruses because of its low anticoagulant activity, long half-life in the blood, and dose dependent bioactivity without stimulation of viral replication at low concentration.69-71 Moreover Ca-SP has been shown to inhibit a host of other viruses that cause opportunistic infection by HIV-1 like cytomgalovirus and Herpes simplex virus. As far as therapeutic use is concerned, the aqueous crude extract has been shown to have similar effects. The crude extract has a potential to be used as a dietary supplement to offer an adjuvant effect to conventional treatment of viral infections. Since the polysaccharide extract is known to boost the immune system, the antiviral effect (inhibition of replication or attachment) may be augmented by the enhancement of the overall immune response of the body. This potential needs to be investigated further in more animal models and humans and under different modes of administration before conclusions are drawn about the effectiveness of such use.

EFFECTS ON HYPERLIPIDEMIA

A summary of studies on the cholesterol-regulatory properties of Spirulina is given in Table 4. One of the earlier studies on the reduction of serum cholesterol by Spirulina was that done on rats by Devi and Venkataraman.72 Since then several workers have confirmed this in studies involving animals and humans.

In an elaborate study involving feeding rats with high cholesterol diets with and without Spirulina supplementation, Kato et al.73 found that the elevation of total cholesterol, LDL+VDL cholesterol, and phospholipids in the serum was reduced significantly when the experimental high cholesterol diet was supplemented with 16% Spirulina. The fall in HDL cholesterol caused by the high cholesterol diet was also reduced in mice fed the high cholesterol diet in the presence of Spirulina. Adipohepatosis induced by a high fat and high cholesterol diet was also reduced rapidly when the mice were shifted from the high fat, high cholesterol diet to a basal medium supplemented with Spirulina. Their findings were supported by more recent studies. De Rivera et al. 74 measured liver levels of triglyccrides and phospholipids in rats fed a diet supplemented with 5% Spirulina, and either 60% glucose or 60% fructose. The control animals were fed either 60% glucose or 60% fructose. Rats fed the Spirulina diet had lower levels of liver triglyccrides and phospholipids compared to control groups.74 Torres-Duran et al 75 Studied the effect of Spirulina on liver and serum lipid levels of rats where fatty liver was induced by a single intraperitoneal injection (1 ml/kg) of carbon tetrachloride. Liver lipid concentrations did not change in rats fed the purified diet with or without Spirulina, However, after carbon tetrachloride treatment, liver triglycerols and cholesterol were significantly lower in rats fed the Spirulina.75

In a study involving rats, Iwata et al.76 found that feeding Spirulina at 5%, 10%, and 15% of the diet resulted in a significant inhibition of total and HDL-cholesterol (p<0.01), triglyccride (p<0.05) and phospholipid (p<0.01) in fructose induced hypolipidemic rats. However, no difference in liver lipids was found between the high fructose diet and Spirulina diet groups. In a subsequent study Iwata et al. 77 attempted to elucidate the mechanism of the hypotrighlyceridemic effect of Spirulina, by studying the activities of two kinds of lipases, lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL). The Spirulina diet group showed a statistically significant (p<0.01) increase in the activity of LPL than the high fructose diet group. There was no significant difference in the activity of H-TGL in the two groups. Since LPL is a key lipolytic enzyme in the metabolism of TG-rich lipoproteins, it was postulated that the hypotriglyceridemic effect of Spirulina might be through its effect on the metabolism of lipoproteins.77

Rats fed a 20% water-soluble fraction of Spirulina were also found to have a high HDL to LDL ratio and a low fasting serum glucose level compared with rats fed a water insoluble fraction or casein.78 A significant increase in HDL cholesterol was also found in another study.79 Additional evidence for cholesterol-regulating effect comes from Fong et al. 80 who studied the effect of Spirulina on plasma cholesterol and triglyceride levels in mice. Compared to the control group the Spirulina-supplemented mice showed significantly lower levels of total, HDL and LDL cholesterol (31%, 20%, and 54% reduction respectively) after 14 days of feeding The HDL to LDL cholesterol ratio was found to be significantly higher ( 2- to 2.4-fold increase) in mice fed Spirulina. In mice fed Spirulina for 35 days, plasma levels of triglycerides decreased by 44% compared to the control group. Type of study Summary of Studies Reference Mice The elevation of total cholesterol, LDL+VDL cholesterol and phospholipids in the serum was reduced significantly when the high experimental cholesterol diet was supplemented with 16% Spirulina. The reduction in HDL cholesterol caused by the high cholesterol diet was also reduced in the mice fed the high cholesterol diet in the presence of Spirulina. Adipohepatosis induced by a high fat and high cholesterol diet was also reduced rapidly when the mice were shifted from the high fat high cholesterol diet to a basal medium supplemented with Spirulina. 73 Rats Liver levels of trighlycerides and phosphlipids in rats fed a diet supplemented with 5% Spirulina were significantly lower than rats fed either 60% glucose or 60% fructose. 74 Rats Levels of triglcerides and phospholipids in rats fed a diet supplemented with Spirulina compared to those on control diets. Prior to the measurement, fatty liver was induced by a single intraperitoneal injection (1 ml/kg) of carbon tetrachloride to both the control and experimental rats. 75

Rats

Feeding Spirulina at 5%, 10%, and 15% of the diet resulted in a significantly inhibition of total and HDL-cholesterol (p<0.01), triglyceride (p<0.05) and phospholipied (p<0.01) in fructose-induced hypolipidemic rats. The Spirulina diet group showed a statistically significant (p<0.01) increase in the activity of LPL than the high fructose diet group-suggesting role of LPL in lowering triglycerides. 76,77

Rats Rats fed 20% water-soluble fraction of Spirulina were found to have a high HDL to LDL ratio and low fasting serum glucose levels compared to rats fed a water-soluble fraction or casein. 78 Mice Compared to the control group the Spirulina supplemented mice showed significantly lower levels of total HDL and LSL cholesterol (31%, 20%, and 54% reduction, respectively) after 14 days of feeding. Further reduction in cholesterol levels was observed after 35 days of feeding. The HDL to LDL cholesterol ratio was found to be significantly higher (2 to 2.4-fold increase) in mice fed Spirulina. In mice fed Spirulina for 35 days, plasma levels of triglycerides decreased by 44% compared to the control group. 80

Human

In the group (15 baseline value after the In the group (15 male volunteers) taking 4.2 g/day Spirulina continuously for 8 weeks, a statistically significant reduction of LDL-cholesterol (p<0.05) was observed after 8 weeks. In the group taking the same amount for 4 weeks only, a statistically significant reduction in LDL cholesterol was found after 4 weeks (p<0.05), but thereafter increased to its baseline value after the administration of Spirulina was discontinued. The atherogenic effect (a measure of fat deposition in arteries) declined significantly in the former group (p<0.01). No significant difference in the level of HDL.

81

Human In inchemic heart disease patients Spirulina supplementation significantly lowered blood cholesterol, triglycerides, LDL and VLDL cholesterol, and higher HDL cholesterol. Supplementation with 4 g/day Spirulina showed a higher effect in reducing serum total cholesterol and LDL levels than 2 g/day. 82

However, there was no difference in triglyceride levels in the Spirulina and control groups after 14 days of feeding.80

To date, there are three published reports of cholesterol reduction effects of Spirulina in humans. In the first study by Nakaya et al.,81 30 male volunteers with mild hyperlipidemia and mild hypertension were divided into two groups. Group A subjects were given Spirulina at 4.2 g/d-1 and group B subject were given the same amount of Spirulina for 4 weeks and were observed for the next 4 weeks without giving Spirulina. The results showed a statistically significant reduction of LDL-cholesterol (p<0.05) in-group A after 8 weeks. The LDL-cholesterol also fell significantly in group B subjects after 4 weeks (p<0.05), but thereafter increased to its baseline value after the administration of Spirulina was discontinued. No significant difference was observed in the level of HDL cholesterol. On the other hand, the atherogenic index ( a measure of fat deposition in arteries) declined significantly in group A subjects ( p<0.01) after 4 weeks.81 Ramamoorthy and Premakumari82 studied 30 inchemic heart disease patients with blood cholesterol levels above 250 g/dl. Divided into three groups of 10, group A and B subjects were given 2 g and 4 g Spirulina per day, respectively, for 3 months, and group C served as control. The group with Spirulina supplementation had significantly lowers blood cholesterol, triglycerides, LDL and VLDL cholesterol and higher HDL cholesterol. Supplementation with 4 g per day Spirulina showed a higher effect than a 2 g dose in reducing serum total cholesterol and LDL. In a human clinical study involving 15 diabetic patients, Mani et al.83 found a significant reduction in total lipids, free fatty acids, and triglyceride levels. A reduction in LDL/HDL ratio was also observed.

IMPLICATIONS OF THE STUDIES

Collectively the results of the animal and human studies summarized above provide support for the cholesterol lowering activity of Spirulina. A vast amount of experimental and epidemiological evidence shows the connection between diets high in fat and cholesterol and the incidence of cardiovascular disease. There is also an increased awareness among Americans that diets high in cholesterol present a risk of cardiovascular disease. Despite this, cardiovascular disease is the number one killer in the United States claming about one million lives a year and totaling 41% of all deaths. It is often said that a fast lifestyle makes it difficult for many Americans to make proper food choices. Supplementation with natural food supplements like Spirulina may contribute, in part at least, to overall strategy to manage this serious health problem.

OTHER EFFECTS

This section sheds light on less extensively studied potential application of Spirulina.

Probiotic effects
Tsuchilhashi et al.84 found that an intake of Spirulina at 5% of the diet increased the population of Lactobacillus in the caecum of rats by 3 times over a control group of rats not fed Spirulina.84Similar results were obtained by de Mule85 in vitro studies with Lactobacillus lactis and Candida albicans.85 More recently Parada et al.86 have reported a stimulatory effect of intracellular products from algae on lactic acid bacteria including Lactococcus lactis, Streptococcus thermophilus, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus bulgaricus. In humans, Lactobacillus is believed to have three functions: to improve digestion and absorption of foods, to protect from infection, and to stimulate the immune system. In patients with an Acquired Immune Deficiency Syndrome (AIDS), nutrient malabsorption associate with opportunistic infections from microorganisms like Candida albicans can speed expression of disease symptoms. One recommended strategy for halting the progression of AIDS is based on nutrient supplementation as well as supplemental Lactobacillus.87 Spirulina might offer such a nutritional and therapeutic strategy.

Effects against diabetes, obesity, and blood circulation

According to Takai et al.,88 a water-soluble fraction of Spirulina was found effective in lowering the serum glucose level at fasting while the water-insoluble fraction suppressed glucose level at glucose loading.88 Similar results were found in other studies.78-79 In a human clinical study involving 15 diabetics, a significant decrease in the fasting blood sugar level of patients was observed after 21 days of 2 g/day Spirulina supplementation.83 In a double-blind-crossover study versus placebo, Becker et al.,89 have found that a supplementary diet of 2.8 g of Spirulina 3 times d-1 over 4 weeks resulted in a statistically significant reduction of body weight in obese outpatients. Spirulina has also been found to suppress high blood pressure in rats.90 A vasodilatation property of rat aotic rings by Spirulina possibly dependent upon a cyclooxgenase-dependent product of arachidonic acid and nitric oxide has been reported by Paredes-Carajal et al.91

Cheng-Wu Z et al.92 did a preliminary study on the effect of polysaccharides and phycocyanin on peripheral blood and hematopoietic system of bone marrow in mice. Their studies showed that C-phycocyanin and polysaccharides from Spirulina had a high erythropoetin (EPO) activity. Effects against toxicities from heavy metals and other compounds According to Yamane et al.,93 rats with high mercury dosage showed rising blood urea nitrogen (BUN) and serum creatinine, both indicators of acute nephritis. The addition of 30% Spirulina in the diet resulted in a significant decrease in BUN and serum creatinine levels. Rats given 3 pharmaceuticals, para-aminophenol (anodyne), gentamicin (antibiotic), and cis-dichlorodiamino-platinum (anti-cancer), showed similar kidney improvement on a Spirulina diet.93 In a follow-up study, Fukino et al., 94 found similar effects of Spirulina on renal toxicity induced by inorganic mercury and cisplatin. In addition to BUN and serum creatinine, urinary excretion of alkaline phosphatase (ALP) and glutamic oxaloacetate transaminase (GOT) were measured as further indicators of renal function. The activities of both enzymes were significantly reduced in the group fed 30% Spirulina. The effective component was found in the water-soluble fraction of the Spirulina extract, within which the substances with a molecular weight of more than 100,000 were believed to be responsible. From this observation it was suggested that phycocyanin might be responsible in the suppression of renal toxicity.94 Hepatoprotection from toxic compounds has already been discussed above under antioxidant effects of Spirulina. Shastri et al.95 did studies on the protective role of dietary Spirulina on lead toxicity in Swiss albino mice. They observed a significant increase in the survival time in pre and post-treated Spirulina compared with a control group without Spirulina. Lead-induced toxicities were reduced as suggested by the higher testes weight, animal weight, and tubular diameter in the Spirulina treated group.

Radiation protection effects
The radio protective effect of a crude ethanol precipitate (CEP) of Spirulina platensis was studied using the micronucleus test in polychromatic erythrocytes (PCE) of mouse bone marrow. In this system the extract caused a significant reduction of micronucleus frequencies induced by ?-radiation. Gamma-radiation followed by treatment with CEP led to about the same radio protective effect as CEP treatment followed by ?-radiation. From this the authors concluded that the protective compound probably acts as a DNA-stabilizing factor, and they ruled out the possibility of a radical scavenging mechanism.57 The ability of CEP to reduce the incidence of micro nucleated bone marrow cells is believed to reflect its antimutagenic and repair-stimulating capacities much as has been postulated by Schwartz et al.49 Mazo et al.96 subjected rats to gamma irradiation and followed intestinal barrier permeability to polyethylene glycol 4000. Addition of Spirulina to the diet led to near complete normalization of permeability. Feeding phycocyanin extract from Spirulina to rats exposed to x-rays (5Gy) resulted in the normalization of decreases in dehydrogenase activity, energy-rich phosphate level, and efficiency of antioxidant defense observed in rats without phycocyanin supplementation.97

Implications of the Results of the Studies
There are not many studies in the areas mentioned under this section, nor are the studies as rigorous as those done on immune modulation, anti-cancer/anti-viral effect, and cholesterol-reduction effects. Nevertheless they offer insight into the potential of Spirulina to offer diverse health benefits. These areas deserve more research.

CONCLUSION

Despite the few human studies done so far on the health benefits of Spirulina, the evidence for its potential therapeutic application is overwhelming in the areas of immunomodulation, anti-cancer, anti-viral, and cholesterol-reduction effects. Traditional therapies always rely on the use of natural products and have been the source of information for the discovery of many drugs we have today. Currently, increased cost of health care has become a driving force in the shift towards interest in wellness, self-care, and alternative medicine, and a greater recognition between diet and health care. Spirulina is already in use in these new health care approaches. Further clinical research will help solidify the merit of its use.

Systematic screening for therapeutic substances from algae, particularly cyanobacteria (blue-green algae), has received greater attention recently.64,98 should therapeutic application be established for it, Spirulina would offer the following unique advantages and possibilities: (1) the technology for mass cultivation and harvest of Spirulina is well established. (2) Spirulina has undergone two decades of toxicity testing in addition to its known centuries of human use. (3) Microbiological and other safety standards have been established for Spirulina products. (4) The two most commonly grown species Spirulina (Arthrospira) platensis and Spirulina (Arthrospira) maxima are free from cyanobacteria toxins and can be grown (under controlled conditions) free of contaminant cyanobacteria by virtue of their adaptation to a highly alkaline environment. Indeed, it is this same property that makes it possible to grow Spirulina in land unsuitable for conventional agriculture, and (5) Spirulina has already been popularized through two decades of commercialization as a food and dietary supplement. In a similar review article published in the Journal of Applied Phycology in 1993, we called the attention of researchers to further research in the areas of immunomodulation and anti-cancer effects of Spirulina. A comparison of the number of papers reviewed then and now clearly shows the great attention that is being given to research of the potential health benefits of Spirulina. The future holds great promise for more socially and professionally beneficial research. It is hoped that a careful evaluation of the results of the studies summarized above will provide a guide to future research and a basis for current therapeutic use of Spirulina.

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SPIRULINA SAFETY & QUALITY STANDARDS
Thirty years of Food Quality and safety Research

Food Safety Research

Spirulina has a history of use in Chad where locals traditionally consume 9-13 grams per meal, and these meals are from 10 to 60% of the meals.1 “The attention of the U.N. FAO was attracted by the fact that algae was being consumed by humans. The FAO organized an educational campaign in Chad to encourage consumption of spirulina harvested from natural sources. More than 6000 meals were distributed under the supervision of the FAO and the campaign was crowned as a success. The program was suspended due to the outbreak of war. ”2

Another report stated “dih* (spirulina sauce) was served at the school canteen. One must admit the introduction of this product in the young people's food gave no problem in this region where the majority were kanembou. But equally at Fort Lamy (now Ndjemena) we noted the product was accepted by other people. ”3

Spirulina was given to malnourished children and adults in clinical studies beginning in the early 1970s. Since the late 1970s, millions of people in the developed countries have used it as a health food supplement, taking 3 to 20 grams a day. Rarely are there any reports of allergies or sensitivities.

In the 1970s, spirulina underwent extensive safety studies with animals and fish. Independent feeding tests in France, Mexico and Japan showed no undesirable results and no toxic side effects on humans, rats, pigs, chickens, fish and oysters. Many independent rat feeding trials were conducted in Japan and no negative effects at all were found for acute or chronic toxicity or reproduction. 4,5

In 1980, one of the most important and comprehensive animal studies was sponsored by the U.N. industrial Development Organization (UNIDO) on rats and mice. Spirulina comprised 10% to 35% of the total diet. No second or third generation reproduction, fertility, lactation or birth defect problems were found. No cancer causing properties were found. No problems with heavy metals, nucleic acids, pesticides or bacteria were found. The study concluded any further research would demonstrate its complete safety as a human food. 6

Toxicology research has continued through the 1980s and 1990s, showing spirulina has no peri- and postnatal toxicity in rats, no adverse effects on gestation, and no increase in number of abnormal offspring. 7,8,9

Nucleic Acid Safety Research

Spirulina has about 4% nucleic acids (DNA and RNA), lower than chlorella and other microalgae, yeast and fungi (6-11%). Although there was once some concern that eating microalgae might increase uric acid levels because of the nucleic acids, there is little evidence to support this. In fact, one study found that uric acid levels did not increase in humans taking up to 30 grams a day of chlorella protein (50 grams of chlorella). 10 since spirulina is lower in nucleic acid content, eating up to 50 grams a day is safe as well, and means it can be safely used as major protein source.11

Published studies from independent laboratories around the world confirm the absence of any toxic effects even when it provides a significant amount of dietary protein.12,13,14 since its introduction as a human food in 1979, its success has confirmed the work of the earlier animal studies. Spirulina has been safely consumed by millions of people in North and South America, Asia,

Europe and Africa.
Heavy Metal Safety Research

Mercury, lead, cadmium and arsenic are widespread in our environment form industrial pollution. Heavy metals are toxic to humans in small amounts. Prolonged eating of foods contaminated with heavy metals can lead to long term health problems. Few companies or organizations disclose levels of these heavy metals in foods.

Earthrise Farms, has published strict standards for heavy metals in spirulina.15 A five year testing program in California showed heavy metals were either not detectable or extremely low. Based on 120 independent lab tests, Earthrise set some of the toughest standards for heavy metals.

Mercury was not detectable in 40 tests, and the standard for mercury was set at less than 0.05 parts per million (pip). In comparison, the US FDA standard in 'aquatic animals' is 1.0 ppm, permitting over 20 times more mercury. Standards were set for cadmium (less than 0.05ppm), lead (less than 1.0 ppm) , and arsenic (less than 1.0 ppm). By comparison, the UN Protein Advisory Group standard for single cell protein permits higher heavy metals: 1.0 ppm for mercury; 1.0 ppm for cadmium, 5.0 ppm for lead; and 2.0 ppm for arsenic.

Algal Toxin Safety Research

An important quality control issue surrounding production of blue-green algae ( cyanobacteria) is the possibility of inadvertently harvesting other blue-green algae containing cyanotoxins. This is a risk when harvesting algae from natural bodies of water with mixed cultures of microscopic algae. Algal toxins are capable of causing widespread poisoning of animals and humans.16

In 1995-96, a group of leading microalgae producers sponsored research conducted by algal toxicologists. The result was a Technical Booklet for the Microalgae Biomass Industry as a guide to the use of a very sensitive enzyme linked immunosorbant assay (ELISA) and a protein phosphate inhibition assay (PPIA) for the detection of toxic microcystins and nodularins. These methods can detect, monitor and control cyanotoxins, so producers can assure a safe, nutritious product for human and animal food supplements. 17

Reprinted with permission from the book Earth Food Spirulina (4th Edition 1997), by Robert Henrikson. (c) 1997 Ronore Enterprises.

References:

1. Delpeuch, F. et. Al. Consumption as food and nutritional composition of blue-green algae among populations in the Kanem region of Chad. Ann. Nutr. Alinment. 29, 497-516. 1976

2. Institut Francais du Petrol. Rapport ou Comite Consultatif des Proteines OAA/OMS/FISE-Etat d’Avancement du Procede IFP de Production d’algues Dec 1970, p.11.

3. Fadoul, L. Les algues bleues du Kanem. Rapport de mission par L. Fadoul, A. Avrem et G. Le Guedes ( experts de la division de la nutrition, FAO) Juin 1971.

4. Takemoto, K. Subacute toxicity study with rats. Saitama Medical College, Japan, 1982.

5. Atatsuka, K. Acute toxicity and general pharmaclolgical studies. Meiji College of Pharmacy, Japan, 1979.

6. Chamorro-Cevallos, G. Toxicological research on the alga spirulina. UNIDO, 24 Oct. 1980, UF/ MEX/78/048. (French)

7. Becker, W.E., Vanattaraman, L.V. et al. Production and utilization of the blue-green algae spirulina in India. Biomass, 4, 105-125, 1984.

8. Chamorro, G. et al. Subchronic toxicity study in rats fed spirulina. J. de Pharmacie de Belgique 43,29-36,1988.

9. Slazar, M., Chamorro, G. et al. Effect of spirulina consumption on reproduction and peri- and postanl development in rats. Food and chemical Toxicity 34, 353-359. 1996.

10. Waslein, C. et al. Uric acid levels in men fed algae and yeast as protein sources. J. Food. Sci. 1970, 35, 294-8.

11. Jassby, Alan. Spirulina: a model for microalgae as human food. Algae and Human Affairs, Cambridge Univ Press, 1988, P.159

12. Boudene, C. et al. Evaluation of long term toxicity on rats with spirulina. Ann Nutr. Alinment., 1976, 30: 577-588.

13. Til, H.p, and Williams, M. Sub-chronic toxicity study with dried algae in rats. Cent. Inst. For Nutrition and Food Research, Zeist, Ned., 1971.

14. Fevrier, C. and Seve, B. Incorporation of spirlina into pig diets. Ann Nur. Aliment., 1976,29: 625-30 (French)

15. Earthrise Farms. Five year testing of heavy metals in spirulina, 1983-1987. 1988.

16. Carmichael, W.W. The toxins of Cyanobacteria. Sci. American, Jan. 1994, P. 78-86

17. An, J., and Carmichael, W.W Technical Booklet for the Microalgae Biomass Industry: Detection of microcystims and nodularins usining an enzyme linked immunosobant assay (ELISA) and a protein phosphate inhibition assay (PPIA). Dept. Bio. Sci. Wayne State Univ, Dayton OH. July 1996.

SPIRULINA SAFETY AND QUALITY STANDARDS

[ Spirulina Safety Assurance] [ Comparing Spirulina and ’Wild’ Blue-Green Algae] [ World Spirulina Production 1975 to 1999] [ Available in Over 70 Countries] [ 30 Years of Research ] [Food Safety] [ Heavy Metal Safety] [Algal Toxin Safety ] [ International Safety Guidelines] [ USA Natural Food Industry] [ Earthrise Farms Standards]

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Science Update

MSM Shown to Help
Reduce Inflammation

GREENVILLE, PA -- According to Carolwood Corp., a recent study on animal articular cartilage showed that Lignisul brand MSM produced a significant reduction in the production of inflammatory mediators (notably prostaglaindin E2), which produce the characteristic pain, heat and swelling associated with joint disease. “In addition, cartilage was protected from the pro-inflammatory effect or interleukin, a chemical used to stimulate inflammation, and there was a mild chondroprotective effect with respect to matrix proteoglycans (a fundamental building block of articular cartilage) depletion, ” added researcher Mark Hurtig, DVM, Comparative Orthopaedic Research Laboratory, University of Guelph, Guelph, ON. “These results corroborate previous human and animal studies which show that MSM provides significant anti-inflammatory and analgesic effects, ” said Hurtig. “However, now we have definitive prood that MSM works at the cellular level and understand more how it works. ”

CLA Shown to Enhance Immunity
CHANNAHON, IL-- In a 13-week human trial, conjugated linoleic acid (CLA) supplementation significantly increased the presence of virus specific antibodies, according to research conducted by Loders Crklaan, manufacturer of Clarinol brand CLA. “Considerable evidence exists that CLA enhances immune function in vitro and in animal studies, ” said Marianne O’ Shea, PhD, manager of nutrition and technical services at Loders Croklaan, during a presentation of the results at an NIH workshop. “Our study clearly demonstrates stimulation of the humoral immune response by CLA supplementation as reflected by an increase in antibody level. ” Using the hepatitis B vaccination as infection model, 75 human subjects were divided into three treatment groups who were supplemented for 13-week period: a control group and two CLA groups who received two different ratios of the naturally occurring isomers c9, t11, t10 and c12; one group at the ratio of 50:50 and the other group at the ratio of 80:20.

Those who received CLA supplementation with equal (50:50) concentration of the active isomers performed significantly better than those in the control group. In fact, at the conclusion of the study, the antibody level in those who received CLA in a 50:50 ratio was twice as high as those who received CLA with those isomers in an 80:20 ratio or those who received no CLA at all.

“The results of this study are very encouraging, ” said O'Shea. “The influence of CLA on the immune system might be of clinical importance in the prevention and treatment of infections or allergic reactions. ” Additional research is now under way at Loders Croklaan to further investigate the findings of this initial study.

Spirulina May Help Repair Brain Tissue
PETALUMA, CA -- According to Earthrise, its product, Earthrise spirulina reversed degenerative effects of aging on the brain in a rat study. The study, published in the July 15 issue of the Journal of Neuroscience, described the application of standard electrophysiological techniques to compare neuronal function in young and old rats fed either a control diet or a diet supplemented with spirulina, apple, or cucumber (5 mg daily for 14 days). Young rats fed the control diet had a significantly higher neuronal activity than aged rats fed the control diet. When old rats were fed a diet supplemented with spirulina, the activity of their neurons reverted to the higher-level observed in young rats, according to the company. Apples showed an intermediate effect while cucumbers had no effect at all.

The study adds “to the mounting evidence on the role of antioxidants in fruits and vegetables in reducing age related declines in central nervous system function, ” said Dr. Amha Belay, scientific director, Earthrise Nutritionals. “The present study points to the potential application of spirulina in the prevention and mitigation of neurodegenerative effects of damage by oxygen radicals. ”

Vitamin C Can Help Reduce Cataract Risk
PARSIPPANY, NJ- According to Roche Vitamins, a self-sponsored study published in the March issue of the American Journal of Clinical Nutrition, supports a role for vitamin C in reducing the risk for developing cortical cataracts in women under the age of 60, and for carotenoids in diminishing the risk of posterior subcapsular cataracts (PSC) in women who have never smoked.

The study was the second analysis from the Nurses Health Study (NHS) that measured the occurrence of cataracts in women. The study, led by Allen Taylor, PhD, director of the laboratory for Nutrition and Vision Research at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, found no associations between usual intakes of nutrients from food and/or supplements overall for either cortical or PSC lens opacities, but significant associations were seen in selected subgroups. A 57 percent lower risk for cortical lens opacities was observed in women younger than 60 with a vitamin C intake of greater than 362 mg daily compared to those with an intake of less than 140 mg daily. Also, women who took vitamin C supplements for more than 10 years had a 60 percent lower risk than those who didn't take a vitamin C supplement. The prevalence of PSC lens opacities was reduced in women who never smoked with higher intakes of carotenoids.

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The Potential Application of Spirulina (Arthrospira) as a Nutritional and Therapeutic Supplement in Health Management

by - Amha Belay, PHD*
Scientific Director, Earthrise Nutritionals Inc., Calipatria, California

Continued...

Latest Scientific Research On Spirulina:
Effects on the Aids Virus, Cancer And The Immune System
By Richard Kozlenko DPM Ph.D. M.P.H. and Ronald H. Henson.

Spirulina is gaining more attention form medical scientists as a nutraceutical and source of potential pharmaceuticals. There are several new peer reviewed scientific studies about Spirulina’s ability to inhibit viral replication, strengthen both the cellular and humoral arms of the immune system and cause regression and inhibition of cancer. While these studies are preliminary and more research is needed, the results so far are exciting.

Potent Anti-Viral Activity

In April 1996, Scientists from the Laboratory of Viral pathogenesis, Dana-Farber cancer institute and Harvard Medical School, Boston, Massachusetts, and Earthrise Farms, Calipatria. California, announced on-going research. Saying “Water extract of spirulina platensis inhibits HIV-1 replication in human derived T-cell lines and in human peripheral blood mononuclear cells. A concentration of 5-10 ug/ml was found to reduce viral production. ” HIV-1 is the AIDS virus. Small amounts of spirulina extract reduced viral replication while higher concentrations totally stopped its reproduction. Importantly, with a therapeutic index of >100, Spirulina extract was non-toxic to the human cells at concentrations stopping viral replication.

Another group of medical scientists has published new studies regarding a purified water extract unique to spirulina named Calcium-Spirulan. It inhibits replication of HIV-1, Herpes Simplex, Human Cytomegalovirus, Influenza A virus, Mumps virus and Measles virus in-vitro yet is very safe for human cells. It protects human and monkey cells from viral infection in cell culture. According to peer reviewed scientific journal reports this extract, “...holds great promise for treatment of ...HIV-1, HSV-1, and HCM infections, which is particularly advantageous for AIDS patients who are prone to these life-threatening infections. ” Calcium-Spirulina is a polymerized sugar molecule unique to spirulina containing both Sulfur and Calcium. Hamsters treated with this water-soluble extract had better recovery rates when infected with an otherwise lethal Herpes virus. How does it work? When attacking a cell, a virus first attaches itself to the cell membrane. However, because of spirulina extract, the virus cannot penetrate the cell membrane to infect the cell. The virus is stuck, unable to replicate. It is eventually eliminated by the body’s natural defenses. Spirulina extracts may become useful therapeutics that could help AIDS patients lead longer more normal lives.

What Is Spirulina?

Spirulina, (rhymes with “ballerina”), is a traditional food of some Mexican and African peoples. It is a plank tonic blue-green algae found in warm water alkaline volcanic lakes. Wild Spirulina sustains huge flocks of flamingos in the alkalin East Africa Rift Valley Lakes. It possesses an amazing ability to thrive in conditions much too harsh for other algae. As might be expected, it has highly unusual nutritional profile. Spirulina has a % amino acid content, is the world's richest natural source of Vitamin B-12 and contains a whole spectrum of natural mixed carotene and xanthophylls phytopigments. Spirulina has a soft cell was made of complex sugars and protein, and is different form most other algae in that it is easily digested. Millions of people worldwide eat Spirulina cultivated in scientifically designed algae farms. Current world production of Spirulina for human consumption is more than one thousand metric tons annually. The United States leads world production followed by Thailand, India and China. More countries are planning production as they realize it is a valuable strategic resource.

Spirulina is not Chlorella, or the blue-green algae harvested from Klamath Lake, Oregon. Chlorella, green micro-algae, is a nutritious food but does not have the same anti-viral, anti-cancer and immune stimulating properties of Spirulina. The Chlorella cell was is made of indigestible cellulose, just like green grass, while the cell wall of Spirulina is made of complexed proteins and sugars.

The Klamath Lake blue-green algae has the scientific name Aphanizomenon flos-aquae,5 because it can sometimes contain potent nerve toxins. While the scientific literature is full of information concerning the toxicity of Aphanizomenon flos-aquae and its dangers to humans and animals, there are few, if any, peer review scholarly scientific papers regarding therapeutic benefit. In contrast, the scientific literature is full of information concerning the benefits and safety of humans and animals eating Chlorella and Spirulina.4

ANTI-CANCER EFFECTS
Several studies show Spirulina or its extracts can prevent or inhibit cancers in humans and animals. Some common forms of cancer are thought to be a result of damaged cell DNA running amok, causing uncontrolled cell growth. Cellular biologists have defined a system of special enzymes called Endonuclease which repair damaged DNA to keep cells alive and healthy. When these enzymes are deactivated by radiation or toxins, errors in DNA go unrepaired and, cancer may develop. In vitro studies suggest the unique polysaccharides of Spirulina enhance cell nucleus enzyme activity and DNA repair synthesis. This may be why several scientific studies, Observing human tobacco users and experimental cancers in animals, report high levels of suppression of several important types of cancer. The subjects were fed either whole Spirulina or treated with its water extracts.3,12,13

STRENGTHENS IMMUNE SYSTEM
Spirulina is a powerful tonic for the immune system. In scientific studies of mice, hamsters, chickens, turkeys, cats and fish, Spirulina consistently improves immune system function. Medical scientists find Spirulina not only stimulates the immune system, it actually enhances the body’s ability to generate new blood cells. Important parts of the immune system, the Bone marrow Stem Cells, Macrophages, T-cells and Natural Killer Cells, exhibit enhance activity. The Spleen and Thymus glands show enhanced function. Scientists also observe Spirulina causing macrophages to increase in number, become “activated” and, more effective at killing germs. Feeding studies show that even small amounts of Spirulina build up both the humoral and cellular arms of the immune system.16 Spirulina accelerates production of the humoral system, (antibodies and cytokines), allowing it to better protect against invading germs. The cellular immune system includes T-cells, Macrophages, B-cells and the anti-cancer Natural Killer cells. These cells circulate in the blood and are especially rich in body organs like the liver, spleen, thymus, lymph nodes, adenoids, tonsils and bone marrow. Spirulina up-regulates these key cells and organs, improving their ability to function in spite of stresses from environmental toxins and infectious agents.2,10.12,14,15,16

SPIRULINA PHYCOCYANIN BUILDS BLOOD
Spirulina has a dark blue-green color, because it is rich in a brilliant blue polypeptide called phycocyanin. Studies show that pycocyanin affects the stem cells found in bone marrow. Stem cells are "Grandmother" to both the white blood cells that make up the cellular immune system and red blood cells that oxygenate the body. Chinese scientists document phycocyanin stimulating hematopoiesis, (the creation of blood), emulating the affect of the hormone erythropoetin, (EPO). EPO is produced by healthy kidneys and regulates bone marrow stem cell production of red blood cells. Chinese scientists claim Phycocyanin also regulates production of white blood cells, even when bone marrow stem cells are damaged by toxic chemicals or radiation.17

Based on this effect, Spirulina is approved in Russia as a “medicine food” for treating radiation sickness. The children of Chernobyl suffer radiation-poisoning form eating food grown on radioactive soil. Their bone marrow is damaged, rendering them immunodeficient. Radiation damaged bone marrow cannot produce normal red or white blood cells. The children are anemic and suffer from terrible allergic reactions. Children fed just five grams of Spirulina in tablets each day make dramatic recoveries within six weeks. Children not given Spirulina remain ill.6

OTHER POTENTIAL HEALTH BENEFITS

Spirulina is one of the most concentrated natural sources of nutrition known, It contains all the essential amino acids, rich in chlorophyll, beta-carotene and its con-factors, and other natural photochemical. Spirulina is the only green food rich in GLA essential fatty acid. GLA stimulates growth in some animals and makes skin and hair shiny and soft yet more durable. GLA also acts as an anti-inflammatory, sometimes alleviating symptoms of arthritic conditions. Spirulina acts as a functional food, feeding beneficial intestinal flora, especially Lactobacillus and Bifidus. Maintaining a healthy population of these bacteria in the intestine reduces potential problems from opportunistic pathogens like E.coli and Candida albicans. Studies show when Spirulina is added to the diet, beneficial intestinal flora increase.

CONCLUSION
Based on this preliminary research, scientists hope the use of Spirulina and its extracts may reduce or prevent cancers and viral disease. Bacterial or parasitic infections may be prevented or respond better to treatment and wound healing may improve. Symptoms of anemia, poisoning and immunodeficiency may be alleviated. Scientists in the USA, Japan, China, Russia, India and other countries are studying this remarkable food to unlock its potential. More research is needed to determine its usefulness against AIDS and other killer diseases. However, it is already clear this safe and natural food provides concentrated nutritional support for optimum health and wellness

 

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Carob Mint Spirulina · Recipes

Power Carob-Mint Shake. TM

Ingredients:

8 oz. Chilled, Vanilla Rice Milk
1 Tbs. Carob-Mint Powder
Vanilla Ice Cream (optional)

Directions:
Place ingredients in a blender or jar with lid tight and blend or shake until well mixed. Enjoy refreshing, instant energy, and whole food nutrition when taking Pure Planet Power Carob-Mint Spirulina.

 

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