Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
J. Serb. Chem. Soc. 78 (3) 395–405 (2013) UDC *Arthrospira:547.458+66.094.522:641.1/.3
JSCS–4424 Review
395
REVIEW
Health aspects of Spirulina (Arthrospira) microalga food
supplement
THEODORE G. SOTIROUDIS* and GEORGIOS T. SOTIROUDIS
Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research
Foundation, 48 Vassileos Constantinou Avenue, Athens 11635, Greece
(Received 20 October, revised 18 December 2012)
Abstract: Spirulina, now named Arthrospira, is a microscopic and filamentous
cyanobacterium that has a long history of use as a safe food, lacking toxicity. It
is commercially produced in large outdoor ponds under controlled conditions.
The aim of this review article is to summarize the recent available information
concerning the human clinical potential and applications of Spirulina, as well
as clinical data related to the safety and side effects of Spirulina. Potential
health benefits of Spirulina are mainly due to its chemical composition, which
includes proteins (the highest protein content of any natural food, 55–70 %),
carbohydrates, essential amino acids, minerals (especially iron), essential fatty
acids, vitamins and pigments. In this respect, three major bioactive components
of Spirulina, the protein phycocyanin (a biliprotein pigment), sulfated poly-
saccharides and gamma linolenic acid seem to play significant roles in impart-
ing improved human body functions. Furthermore, new experimental evidence
supports the immunomodulation and antiviral effects of Spirulina supplemen-
tation. According to the Dietary Supplements Information Expert Committee of
the United States Pharmacopeial Convention, the available clinical evidence
does not indicate a serious risk to health or other public health concerns due to
Spirulina. However, a few cases of severe side effects have been reported.
Keywords: cyanobacterium; phycocyanin; phycocyanobilin; sulfated polysac-
charides.
CONTENTS
1. INTRODUCTION
2. CHEMICAL COMPOSITION
3. HEALTH ASPECTS
3.1. Immunomodulation
3.2. HIV-infected and undernourished patients
* Corresponding author. E-mail: tsotir@eie.gr
doi: 10.2298/JSC121020152S
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
396 SOTIROUDIS and SOTIROUDIS
3.3. Clinical potential of phycocyanobilin
3.4. Safety aspects
3.5. Side effects
4. CONCLUDING REMARKS
1. INTRODUCTION
Agriculture is faced with multiple challenges in the 21st century: i) increase
in food production for a growing world population, which is expected to increase
by about 2.3 billion people over the next 40 years, mostly in developing coun-
tries, ii) insufficient fresh water supply together with land degradation, which
causes losses in agricultural productivity, iii) increase of the production of feed-
stock for bioenergy, iv) adoption of more efficient and sustainable production
methods and v) adaptation to climate change.1,2. Furthermore, it is presently ac-
cepted that malnutrition is a silent massacre. According to United Nations
sources, millions of children every year die either from malnutrition or are vic-
tims of malnutrition and micronutrient deficiency – the lack of key vitamins and
minerals – with severe consequences on their physical and intellectual develop-
ment.3,4 Moreover, both overweight and underweight people may suffer either
from a deficiency or an excess of the intake of nutrients needed for healthy living.5
Taking into account the above challenges, a future increase of the global
production of food and food protein and a combat of malnutrition could be ad-
dressed through the development of non-traditional farm products by biotechno-
logical intervention. Such a solution seems today economically viable by sup-
porting the mass cultivation of microalgae rich in protein, vitamins and other
functional nutrients known to benefit health. In this respect, Spirulina microalga
seems to offer the perfect solution.
Spirulina, now named Arthrospira, are microscopic photosynthetic and fila-
mentous cyanobacteria (blue–green algae) that have a long history of use as food.
Cyanobacteria are believed to have evolved 3.5 billion years ago and they are the
first group of bacteria that evolved that could fix atmospheric carbon dioxide into
organic carbon compounds using water with the simultaneous evolution of oxy-
gen. Before Columbus, Mexicans (Aztecs) exploited this microorganism as hu-
man food, while presently the African Kanembou tribe in the Lake Chad area
(Republic of Chad) employs it for the same purpose. The name Spirulina derives
from the spiral or helical nature of its filaments. Arthrospira is the scientific
name of a cyanobacteria genus comprising a whole group of edible cyanobacteria
sold under the name Spirulina. Among the various Arthrospira species, A. pla-
tensis and A. maxima are the most important. Arthrospira trichomes (filaments),
which contain cylindrical cells aligned together in spirals or in straight lines.
These filaments have variable length (usually 100–200 μm) and a diameter close
to 6–12 μm, but the cell dimensions, degree of coiling and length of filaments
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
HEALTH ASPECTS OF Spirulina 397
vary with species. The cell organization of Spirulina is typical of a prokaryote
gram-negative bacterium with a lack of membrane-bound organelles. The cell
wall constitutes a weak envelope that is composed of a number of layers, mostly
of a peptidoglycan and lipopolysaccharide nature. The Spirulina cells have a
number of inclusions, such as thylacoid membranes with phycobilisomes, carbo-
xysomes, ribosomes, DNA fibrils and gas vacuoles, as well as polyglycan, poly-
phosphate and cyanophycin granules.6–10
Spirulina grows naturally in alkaline lakes but is commercially produced in
large outdoor or greenhouse ponds under controlled conditions. Microalgal culti-
vation is based on a photosynthetic process using sunlight, nutrition elements and
CO2 contained in a fresh water culture medium under a relatively high tempe-
rature (optimum temperature: 35–38 °C). Commercial culture of Spirulina is fol-
lowed by harvesting the biomass, drying and packaging.9,11
World market evolution of Spirulina involves mainly dried Spirulina whole
biomass used as a human health food supplement, assuming that its consumption
may benefit, prevent, help, or cure common diseases and malnutrition. Other
commercial products containing Spirulina biomass or Spirulina extracts or active
ingredients include protein supplements in animal feed, products for the impro-
vement of pet health, natural colors for foods and cosmetics and purified biomo-
lecules for medicine and biotechnology.10 The objectives of this paper are to re-
view recent literature on various health and safety aspects of Spirulina food sup-
plements and their possible side effects.
2. CHEMICAL COMPOSITION
Chemical analysis of Spirulina showed that it is an excellent source of pro-
teins, vitamins, dietary minerals and pigments. The biochemical composition de-
pends upon the specific Arthrospira source, culture conditions and season of pro-
duction.9,10,12–14
The protein content of Spirulina (50–70 % of the dry weight) exceeds that of
meat, dried milk, eggs, soybeans or grains. Spirulina proteins are complete, since
all the essential amino acids are present. The highest values for the essential
amino acids are those for leucine, valine and isoleucine. When compared to
standard alimentary proteins (from meat, eggs or milk), it is somewhat deficient
in methionine, cysteine, and lysine, but is superior to all plant proteins including
proteins from legumes.6,10,13
Spirulina proteins with significant health effects are the phycobiliproteins
phycocyanin C and allophycocyanin at an approximately 10:1 ratio, which are
proteins with linear tetrapyrrole prosthetic groups (phycocyanobilin) that in their
functional state are covalently linked to specific cysteine residues of the proteins
and they form light-harvesting antenna complexes of the cyanobacteria. Spirulina
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
398 SOTIROUDIS and SOTIROUDIS
is the only food containing phycocyanins, which represent about 15–25 % of the
dry biomass of the microalga.15,16
Half of the total Spirulina lipids are fatty acids.12,14 A detailed analysis of
Spirulina fatty acids showed the presence of essential fatty acids (mostly ω-6).
The rare polyunsaturated fatty acid γ-linolenic acid (GLA) with putative medi-
cinal properties represents 10–20 % of the fatty acids in A. maxima, compared to
49 % in A. platensis and can be considered one of the best known source of GLA
after human milk and some little used vegetable oils such as evening primrose,
borage, blackcurrant seed and hemp oil. 10 g of Spirulina provide over 100 mg of
GLA (which corresponds to more than two capsules of evening primrose oil).9
Other major fatty acids present are the unsaturated oleic and linoleic acids as well
as the saturated palmitic acid, which forms more than 60 % of lipids in A. ma-
xima. Monogalactosyl- and sulfoquinovosyl-diacylglycerol as well as phospha-
tidylglycerol are the major Spirulina lipids (20–25 % each).17 It is important that
sulfolipids from cyanobacteria are active against the AIDS virus.10,12
Virtually all the assimilable Spirulina carbohydrates consist of polymers
containing glucose. The major polymeric component in A. platensis is a branched
polysaccharide, structurally similar to glycogen.6 High molecular weight anionic
polysaccharides with antiviral and immunomodulating activities (see below) have
been isolated from Spirulina.18 A sulfated polysaccharide fraction with antiviral
action (calcium spirulan) was extensively purified and shown to be composed of
rhamnose, 3-O-methylrhamnose (acofriose), 2,3-di-O-methylrhamnose, 3-O-me-
thylxylose, uronic acids and sulfates.19,20 Recently, an acidic polysaccharide
fraction has also been isolated from A. platensis, which induces the synthesis of
TNF-α in RAW macrophages.18
Spirulina is claimed to be the richest whole-food source of provitamin A
(β-carotene), with 20 g of Spirulina also fulfilling the significant body require-
ments of vitamins B1 (thiamine), B2 (riboflavin) and B3 (niacin).10,12,13,21 Its
mineral content varies depending on the culture medium. The most interesting
minerals in Spirulina are iron, calcium, phosphorus and potassium.10,12 The ana-
lytical data for the chemical composition of Spirulina are presented in Table I.
Whole-genome sequences of several Spirulina strains have already appeared
in the literature. A. platensis NIES-39 genome structure is estimated to be a
single circular chromosome of 6.8 Mb, yielding 6,630 protein-coding genes, two
sets of rRNA genes and 40 tRNA genes.22 Whole-genome sequencing of the
Arthrospira PCC 8005 strain, which was selected by the European Space Agency
(ESA) as a nutritional product and an oxygen producer of the Micro-Ecological
Life Support System Alternative (MELiSSA) for long-term manned space mis-
sions, showed the presence of 6,279,260 bases with an average G+C content of
44.7 %, 5,856 protein-coding sequences and 176 genes encoding RNA were also
predicted.23 Recently, the draft whole-genome shotgun sequencing of A. maxima
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
HEALTH ASPECTS OF Spirulina 399
was obtained. The draft genome was approximately 6.0 Mb in total, with 5,690
protein-coding sequences.24
TABLE I. Analytical composition of Spirulina (Arthrospira)
Component Relative dry weight, % Reference
Proteins 50–70 12
Carbohydrates 15–25 10,13
Lipids 6–13 14
N
ucleic acids 4.2–6 12
Iron 0.058–0.18 12
Calcium 0.13–1.4 12
Phosphorus 0.67–0.9 12
Potassium 0.64–1.54 12
Carotenoids 0.37–0.59 10,18
Chlorophyll α 0.66–1.2 10,13,18
Ash 3–11 9
Moisture 4–9 9
3. HEALTH ASPECTS
Although historically Spirulina was used as a food component, it has been
thoroughly investigated using in vitro and in vivo experiments, including cell and
tissue culture, animal testing as well as human clinical trials, for its role in human
health management. A huge number of publications in peer reviewed scientific
journals and book chapters covering health aspects of Spirulina have appeared
during the last three decades. These articles described experimental approaches
involving whole cell Spirulina preparations, various cell extracts and purified
biomolecules, aiming at elucidating the potential health benefits of the consump-
tion of this microalga, so far with exciting results. Potential health effects in-
cluded: immunomodulation, antioxidant, anticancer, antiviral and antibacterial
activities, as well as positive effects against malnutrition, hyperlipidemia, diabe-
tes, obesity, inflammatory allergic reactions, heavy metal/chemical-induced toxi-
city, radiation damage and anemias.10,12,25–30 In this respect, the most promising
active Spirulina constituents appeared to be the protein phycocyanin,30 sulfated
polysaccharide fractions,18 GLA31 and certain sulfolipids.32 While these medi-
cinal claims may be based on experimental observations, more research is needed,
especially with larger scale randomized studies in humans, in order to rate the
effectiveness of Spirulina as a nutraceutical and source of potential pharmaceu-
ticals, and to understand the mechanisms of action of specific Spirulina biomole-
cules, their short-term and long-term effects, and the safety of their use in func-
tional foods.
Available new information or data not covered by previous review articles
concerning human clinical potential of Spirulina, and data related to the safety
and side effects of Spirulina are summarized below.
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
400 SOTIROUDIS and SOTIROUDIS
3.1. Immunomodulation
Forty volunteers of both sexes with an age of 50 years or older took a Spi-
rulina supplement (3 g per day) for 12 weeks. A steady increase in the average
values of the mean corpuscular hemoglobin in subjects of both sexes was re-
corded. An increase of indoleamine 2,3-dioxygenase enzyme activity (a sign of
immune function) and white blood cell count were also observed for the majority
of subjects.33
In a recent clinical trial involving two studies, a pilot study with 11 indi-
viduals and a double-blind placebo controlled study with 12 individuals, healthy
volunteers supplemented their diet with 200 or 400 mg day–1, respectively, for
seven days with Immulina® (a commercial extract of A. platensis, which is
known to activate THP-1 monocytes and CD+ T cells in vitro and enhance
immunological functions in mice). An enhancement of natural killer cell activity
following administration of Immulina® was observed. Evidence was presented
that Braun-type lipoproteins of the Spirulina commercial extract were respon-
sible for the major portion of the in vitro monocyte activation.34
3.2. HIV-infected and undernourished patients
In a randomized study to compare the effect of A. platensis vs. soybean as
food supplements on insulin-resistant HIV-infected patients, 33 patients received
19 g of supplement (Spirulina or soybean) daily for 8 weeks. It was concluded
that the insulin sensitivity in HIV patients improved more when Spirulina rather
than soybean was used as nutritional supplement.35 Furthermore, when HIV-in-
fected or HIV-negative undernourished children and HIV-infected adults were
treated with Spirulina supplementation, clinical improvement was always ob-
served, including weight increase, improvement of hematological parameters and
decrease in the HIV viral load.36–39
3.3. Clinical potential of phycocyanobilin
The chromophore phycocyanobilin (PCB) of Spirulina, was found to strongly
inhibit NADPH oxidase activity, since in mammalian cells it is reduced to phyco-
cyanorubin, a close homolog of bilirubin, which shows a potent inhibitory acti-
vity of this enzyme complex (observed in nanomolar intracellular concentra-
tions). Due to the central roles of NADPH oxidase activation in pathology, PCB
supplementation may induce prevention and therapy of various diseases in part
mediated by NADPH oxidase overactivity in affected tissues. Medical conditions
associated with or linked to NADPH oxidase activity include among others: car-
diovascular diseases, metabolic syndrome, diabetic complications, Parkinson's di-
sease, Alzheimer’s disease, rheumatoid arthritis, allergic reactions and cancer.
Administration of PCB may be achieved by any desirable route including inges-
tion of whole Spirulina, phycocyanin protein or isolated tetrapyrrole chromo-
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
HEALTH ASPECTS OF Spirulina 401
phore. PCB represents about 4.7 % of the mass of phycocyanin. Thus, about
0.66 % of the dry mass of Spirulina is PCB, or about 15 g of Spirulina can be
expected to provide about 100 mg of PCB.40,41
3.4. Safety aspects
Spirulina is regulated as a food and as a dietary supplement.13 The Food and
Drug Administration (FDA) of the USA has categorized several Arthrospira
dried biomass products as “generally recognized as safe” (GRAS) for human
consumption.42 Spirulina has typically been studied in daily doses of 1 to 10 g
and a recommended dosage for adults is usually in the range of 3–10 g
day–1.9,10,12
The amount of iodine contained in 10 g of dried Spirulina biomass is only 3
μg44 or less (not detected).44 Since the upper safe level for total daily intake of
iodine (for a 60 kg bodyweight adult), established by the Scientific Committee on
Food (SCF) and the European Food Safety Authority (EFSA), is 600 μg, while
the corresponding value suggested by the US Institute of Medicine is 1100 μg,45
there is no risk of a consumer taking in excessive iodine by Spirulina consump-
tion.
Spirulina contains substantial amounts of several B12 analogues (corrinoid
forms, pseudovitamin B12) which do not fulfill specific functional roles of vita-
min B12 for humans.46 However, vitamin B12 bioavailability experiments with
animals fed with Spirulina showed that Spirulina intake does not interfere with
mammalian B12 metabolism, thus showing that the B12 analogues do not present
inhibitory actions.47
Spirulina total nucleic acid contents of 4.2-6 % of microalga dry matter have
been reported12 (the RNA content is about 3–4 times higher than that of DNA),6
which are higher than those of animal meat and various plant foods,48 similar to
those of unicellular algae but lower than those of bacteria and yeast.6 Dietary
nucleic acids highly influence serum uric acid levels because of purine metabo-
lism. A maximum safe limit of RNA in the diet of 2 g day–1 has been sug-
gested48 since high levels of uric acid may result in pathological conditions.49
Accordingly, a safety margin of 30 g maximum daily intake of Spirulina was re-
commended.49
3.5. Side effects
The Dietary Supplements Information Expert Committee (DSI-EC) reviewed
recent information from human clinical trials, animal studies, and regulatory and
pharmacopeial sources and analyzed adverse event reports regarding Spirulina to
assess potential health concerns. The DSI-EC concluded that the available evi-
dence does not indicate a serious risk to health or other public health concerns
and assigned a Class A safety rating for A. maxima and A. platensis, thereby
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
402 SOTIROUDIS and SOTIROUDIS
permitting the admission of quality monographs for these dietary supplement in-
gredients in the United States Pharmacopoeia and National Formulary.50 How-
ever, information is limited concerning interactions with pharmaceutical com-
pounds or other dietary supplements. A few side effects have been reported from
the ingestion of Spirulina, including headache, stomach ache, muscle pain, flush-
ing of the face, sweating and concentration difficulties.51 A few cases of severe
side-effects have also been reported, including hepatotoxicity52 and rhabdomyo-
lysis.51 Since Spirulina is an immunomodulatory supplement, it might affect di-
sease severity in patients with autoimmune diseases. These patients have to avoid
the consumption of Spirulina.53,54 A case of anaphylaxis caused by the Spirulina
pigment phycocyanin was also reported. Upon an oral challenge with increasing
Spirulina doses, corresponding to four Spirulina tablets over a 3-h period, a 14-
old year adolescent experienced diarrhea and erythema.55 People with phenyl-
ketonuria should avoid the consumption of Spirulina.51 It has been suggested that
Spirulina when present in the diet exerted a neuroprotective effect in a mouse
model of amyotrophic lateral sclerosis (ALS), by retarding or stopping motor
neuron degeneration.56 Nevertheless, as emphasized by the ALSUntangled
Group,57 at this time there is no evidence that Spirulina is effective for ALS and
there appears to be real and theoretical toxicities that patients with ALS may
encounter with it. Until better efficacy and safety studies are published, the
ALSUntangled Group does not support the use of Spirulina in patients with ALS.57
It must be emphasized that the consumption of Spirulina of unknown origin
or originating from countries that do not guarantee the quality and safety of the
product should be avoided. The major areas of concern for the safe consumption
of Spirulina are microbiological load, heavy metal content, pesticides, extraneous
matter and cyanobacterial toxins.13,50
4. CONCLUDING REMARKS
Spirulina, a microscopic and filamentous cyanobacterium with widespread
usage throughout the world as a dietary supplement and a potential solution for
combating malnutrition, seems to offer significant health advantages to the con-
sumer. The positive effects of Spirulina in relation to its immunomodulation and
antiviral properties are based on clinical evidence but larger trials are required.
The microalga chromophore phycocyanobilin, as a potent inhibitor of NADPH
oxidase, may have versatile potential in the prevention and therapy of various
diseases mediated by overactivity of this enzyme. Spirulina is accepted as a safe
food supplement and the total number of side effects reported in the literature is
relatively small. The iodine and nucleic acid content of Spirulina do not pose
health risks assuming a consumption of Spirulina of up to 30 g per day.
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
HEALTH ASPECTS OF Spirulina 403
ИЗВОД
ЗДРАВСТВЕНИ АСПЕКТИ МИКРОАЛГЕ Spirulina (Arthrospira) КАО ХРАНЉИВОГ
СУПЛЕМЕНТА
THEODORE G. SOTIROUDIS И GEORGIOS T. SOTIROUDIS
Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation,
48 Vassileos Constantinou Avenue, Athens 11635, Greece
Спирулина (Spirulina), позната и као Артроспира (Arthrospira), је микроскопска фи-
ламентозна цијанобактерија која је дуго у употреби у исхрани. Комерцијално се произ-
води у великим отвореним базенима, у контролисаним условима. Циљ овог прегледног
рада је да изнесе нове податке о клиничком потенцијалу и примени спирулине, као и о
резултатима који се односе на безбедност и споредне ефекте. Потенцијалне здравствене
благодети спирулине потичу од њеног хемијског састава, укључујући протеине (највећи
садржај протеина од све природне хране, 55–70 %), угљене хидрате, есенцијане амино-
киселине, минерале (посебно гвожђе), есенцијалне масне киселине, витамине и пиг-
менте. Три најважније компоненте спирулине које имају значајну улогу у побољшавању
телесних функција код људи су протеин фикоцијанин, сулфати полисахарида и
γ
-лино-
ленска киселина. Нови експериментални докази упућују на закључак да спирулина има
имуномодулаторне и антивирусне ефекте. Према подацима америчког комитета
(“Dietary Supplements Information Expert Committee of United States Pharmacopeial Conven-
tion”), досадашње клиничке студије не указују на здравствени ризик услед употребе
спирулине, мада је пријављено неколико случајева са озбиљним пратећим појавама.
(Примљено 20. октобра, ревидирано 18. децембра 2012)
REFERENCES
1. FAO Corporate Document Repository, The Use of Saline Waters for Crop Production,
http://www.fao.org/docrep/T0667E/t0667e04.htm#TopOfPage (accessed on 7/12/2012)
2. FAO, How to Feed the World in 2050, High-Level Expert Forum, Global agriculture
towards 2050, 2009, http://www.fao.org/fileadmin/templates/wsfs/docs/Issues_papers/
/HLEF2050_Global_Agriculture.pdf (accessed on 7/12/2012)
3. D. von der Weid, Malnutrition: a silent massacre, Antenna Technologies, 2000, http://
//www.antenna.ch/en/documents/MonoUK1.pdf (accessed on 7/12/2012)
4. UNICEF, Vitamin and Mineral Deficiency, A global damage assessment report, http://
//www.micronutrient.org/CMFiles/PubLib/Report-67-VMD-A-Global-Damage-Assess-
ment-Report1KSB-3242008-9634.pdf (accessed on 7/12/2012)
5. G. Gardner, B. Halwell, Overfed and Underfed: The Global Epidemic of Malnutrition,
Worldwatch paper 150, 2000, J. A. Petersen, Ed., Worldwatch Institute, http://
//www.worldwatch.org/system/files/EWP150.pdf (accessed on 7/12/2012)
6. O. Ciferri, Microbiol. Rev. 47 (1983) 551
7. O. Ciferri, O. Tiboni, Annu. Rev. Microbiol. 39 (1985) 503
8. A. Vonshak, L. Tomaselli, Arthrospira (Spirulina): Systematics and Ecophysiology, in:
The Ecology of Cyanobacteria, B. A. Whiton, M Potts, Eds., Kluwer Academic Pub-
lishers, Dordrecht, 2001, p. 505
9. M. A. B. Habib, M. Parvin, T. C. Huntington, M. R. Hasan, A Review on Culture, Pro-
duction and Use of Spirulina as Food for Humans and Feeds for Domestic Animals and
Fish, FAO Fisheries and Aquaculture Circular No. 1034, 2008
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
404 SOTIROUDIS and SOTIROUDIS
10. R. Henrikson, Earth Food Spirulina, Ronore Enterprises, Inc., Hana, Maui, Hawaii, 2009,
http://www.Spirulinasource.com/PDF.cfm/EarthFoodSpirulina.pdf (accessed on 7 Dec.,
2012)
11. C. Santillan, Experientia 38 (1982) 40 38
12. J. Falquet, The Nutritional Aspects of Spirulina, Antenna Technologies, http://anten-
na.ch/en/documents/AspectNut_UK.pdf (accessed on 7 Dec., 2012)
13. A. Belay, in Spirulina in Human Nutrition and Health, M. E. Gershwin, A. Belay, Eds.,
CRC Press, Taylor and Francis Group, Boca Raton, London, New York, 2008, p. 1
14. Z. Cohen, The Chemicals of Spirulina in Spirulina platensis (Arthrospira): Physiology,
Cell-biology, and Biotechnology, A. Vonshak, Ed, Taylor and Francis, London, 1996, p.
175
15. C. Romay, R. González, N. Ledón, D. Remirez, V. Rimbau, Curr. Protein Pept. Sci. 4
(2003) 207
16. R. Bernejo, E. M. Talavera, J. M. Alvarez-Pez, J. C. Orte, J. Chromatogr., A 778 (1997)
441
17. G. D. Petkov, S. T. Furnadzieva, C. R. Acad. Sci. 41 (1988) 103
18. M. L. Parages, R. M. Rico, R. T. Abdala-Díaz, M. Chabrillón, T. G. Sotiroudis, C.
Jiménez, J. Appl. Phycol. 24 (2012) 1537
19. T. Hayashi, K. Hayashi, M. Maeda, I. Kojima, J. Nat. Prod. 59 (1996) 83
20. J.-B. Lee, T. Hayashi, K. Hayashi, U. Sankawa, M. Maeda, T. Nemoto, H. Nakanishi, J.
Nat. Prod. 61 (1998) 1101
21. N. K. Sharma, S. P. Tiwari, K. Tripathi, A. K. Rai, J. Appl. Phycol. 23 (2011) 1059
22. T. Fujisawa, R. Narikawa, S. Okamoto, S. Ehira, H. Yoshimura, I Suzuki, T. Masuda, M.
Mochimaru, S. Takaichi, K. Awai, M. Sekine, H. Horikawa, I. Yashiro, S. Omata, H.
Takarada, Y. Katano, H. Kosugi, S. Tanikawa, K. Ohmori, N. Sato, M. Ikeuchi, N. Fujita,
M. Ohmori, DNA Res. 17 (2010) 85
23. P. J. Janssen, N. Morin, M. Mergeay, B. Leroy, R. Wattiez, T. Vallaeys, K. Waleron, M.
Waleron, A. Wilmotte, P. Quillardet, N. Tandeau de Marsac, E. Talla, C.-C. Zhang, N.
Leys, J. Bacteriol. 192 (2010) 2465
24. D. Carrieri, G. Ananyev, O. Lenz, D. A. Bryant, G. C. Dismukes, Appl. Environ.
Microbiol. 77 (2011) 7185
25. A. Belay, J. Am. Nutr. Assoc. 5 (2002) 27
26. Spirulina in Human Nutrition and Health, M. E. Gershwin, A. Belay, Eds., CRC Press,
Taylor and Francis Group, Boca Raton, London, New York, 2008
27. B. Capelli, G. R. Cysewski, Nutrafoods 9 (2010) 19
28. R. Deng, T.-J. Chow, Cardiovasc. Ther. 28 (2010) e33
29. P. D. Karkos, S. C. Leong, C. D. Karkos, N. Sivaji, D. A. Assimakopoulos, Evid.-Based
Compl. Alt. (2011), doi:10.1093/ecam/nen058
30. M. Soheili, K. Khosravi-Darani, Curr. Nutr. Food Sci. 7 (2011) 279
31. J. Vila, C. Gemma, A. Yun Wang, I. Stromberg, P. C. Bickford, in Human Nutrition and
Health, M. E. Gershwin, A. Belay, Eds., CRC Press, Taylor & Francis Group, Boca
Raton, London, New York, 2008, p. 271
32. B. L. Barron, J. M. Torres-Valencia, G. Chamorro-Cevallos, A. Zuniga-Estrada, in
Human Nutrition and Health M.E. Gershwin, A. Belay, Eds., CRC Press, Taylor and
Francis Group, Boca Raton, FL, 2008, p.227
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
HEALTH ASPECTS OF Spirulina 405
33. C. Selmi, P. S. C. Leung, L. Fischer, B. German, C.-Y. Yang, T. P. Kenny, G. R.
Cysewski, M. E. Gershwin, Cell. Mol. Immunol. 8 (2011) 248
34. C. H. Nielsen, P. Balachandran, O. Christensen, N. D. Pugh, H. Tamta, K. J. Sufka, X.
Wu, A. Walsted, M. Schjørring-Thyssen, C. Enevold, D. S. Pasco, Planta Med. 76 (2010)
1802
35. A.-K. Marcel, L. G. Ekali, S. Eugene, O. E. Arnold, E. D. Sandrine, D. von der Weid, E.
Gbaguidi, J. Ngogang, J. C. Mbanya, Nutrients 3 (2011) 712
36. J. Simpore, F. Zongo, F. Kabore, D. Dansou, A. Bere, J.-B. Nikiema S. Pignatelli, D. M.
Biondi, G. Ruberto, S. Musumeci, Ann. Nutr. Metab. 49 (2005) 373
37. J. Simpore, F. Zongo, Y. Ouattara, F. Kabore, D. Dansou, A. Bere, J.-B. Nikiema S.
Pignatelli, S. Musumeci, Pak. J. Biol. Sci. 8 (2005) 589
38. J. Simpore, F. Kabore, F. Zongo, D. Dansou, A. Bere, S. Pignatelli, D. M. Biondi, G.
Ruberto, S. Musumeci, Nutr. J. 5 (2006) 1
39. J. Teas, M. R. Irhimeh, J. Appl. Phycol. 24 (2012) 575
40. M. F. McCarty, J. Med. Food 10 (2007) 566
41. M. F. McCarty, S. S. Hendler, D. M. Rorvik, T. Inoguchi, US 2010/0172971 A1
42. FDA, Agency Response Letter GRAS Notice No. GRN 000127, 2003, http://
//www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRA
SListings/ucm153944.htm (accessed on 7 Dec., 2012)
43. I. M. Mosulishvili, E. I. Kirkesali, A. I. Belokobylsky, A. I. Khizanishvili, M. V. Fron-
tasyeva, S. S. Pavlov, S. F. Gundorina, J. Pharm. Biomed. Anal. 30 (2002) 87
44. V. Romaris-Hortas, C. Garcia-Sartal, M. del Carmen Barciela-Alonso, R. Dominguez-
Gonzalez, A. Moreda-Pineiro, P. Bermejo-Barrera, Food Chem. 124 (2011) 1747
45. D. P. Ridsardson, Food Sci. Tech. Bull. Funct. Foods 4 (2007) 51
46. F. Watanabe, E. Miyamoto, J. Liq. Chromatogr. Related Technol. 25 (2002) 1561
47. H. Van den Berg, L. Bradsen, B. J. Sinkeldam, J. Nutr. Biochem. 2 (1991) 314
48. D. A. Jonas, I. Elmadfa, K.-H. Engel, K. J. Heller, G. Kozianowski, A. König, D. Müller,
J. F. Narbonne, W. Wackernagel, J. Kleiner, Ann. Nutr. Metab. 45 (2001) 235
49. G. Chamorro-Cevallos, B. L. Barrón, J. Váasquez-Sánchez, in Spirulina in Human
Nutrition and Health, M. E. Gershwin, A. Belay, Eds., CRC Press, Taylor and Francis
Group, Boca Raton, FL, 2008, p. 27
50. R. J. Marles, M. L. Barrett, J. Barnes, M. L. Chavez, P. Gardiner, R. Ko, G. B. Mahady,
T. Low Dog, N. D. Sarma, G. I. Giancaspro, M. Sharaf, J. Griffiths, Crit. Rev. Food Sci.
Nutr. 51 (2011) 593
51. E. E. Mazokopakis, C. M. Karefilakis, A. N. Tsartsalis, A. N. Milkas, E. S. Ganotakis,
Phytomedicine 15 (2008) 525
52. M. Iwasa, M. Yamamoto, Y. Tanaka, M. Kaito, Y. Adachi, Am. J. Gastroenterol. 97
(2002) 3212
53. A. N. Lee, V. P. Werth, Arch. Dermatol. 140 (2004) 723
54. O. Kraigher, Y. Wohl, A. Gat, S. Brenner, Int. J. Dermatol. 47 (2008) 61
55. M. Petrus, R. Culerrier, M. Campistron, A. Barre, P. Rouge, Allergy 65 (2010) 924
56. S. Garbuzova-Davis, P. Bickford, Open Tissue Eng. Regen. Med. J. 3 (2010) 36
57. The ALSUntangled Group, Amyotroph. Lateral Scler. 12 (2011) 153.
__________________________________________________________________________________________________________________________
2013 Copyright (CC) SCS
Available online at shd.org.rs/JSCS/
