Access to this full-text is provided by Wiley.
Content available from Evidence-based Complementary and Alternative Medicine
This content is subject to copyright. Terms and conditions apply.
Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2011, Article ID 531053, 4pages
doi:10.1093/ecam/nen058
Review Article
Spirulina
in Clinical Practice:
Evidence-Based Human Applications
P. D. Karkos,1S. C. Leong,1C. D. Karkos,2N. Sivaji,1andD.A.Assimakopoulos
3
1Department of Otolaryngology, Liverpool University Hospitals, Liverpool, UK
2Department of Surgery, Hippocrateio Hospital, Thessaloniki, Greece
3Department of Otolaryngology, University of Ioannina, Ioannina, Greece
Correspondence should be addressed to P. D. Karkos, pkarkos@aol.com
Received 11 March 2008; Accepted 20 August 2008
Copyright © 2011 P. D. Karkos et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Spirulina or Arthrospira is a blue-green alga that became famous after it was successfully used by NASA as a dietary supplement
for astronauts on space missions. It has the ability to modulate immune functions and exhibits anti-inflammatory properties by
inhibiting the release of histamine by mast cells. Multiple studies investigating the efficacy and the potential clinical applications of
Spirulina in treating several diseases have been performed and a few randomized controlled trials and systematic reviews suggest
that this alga may improve several symptoms and may even have an anticancer, antiviral and antiallergic effects. Current and
potential clinical applications, issues of safety, indications, side-effects and levels of evidence are addressed in this review. Areas of
ongoing and future research are also discussed.
1. Introduction
Spirulina is a microscopic and filamentous cyanobacterium
that derives its name from the spiral or helical nature of
its filaments. It has a long history of use as food and it
has been reported that it has been used during the Aztec
civilization [1]. Spirulina refers to the dried biomass of
Arthrospira platensis, an oxygenic photosynthetic bacterium
found worldwide in fresh and marine waters. This alga
represents an important staple diet in humans and has
been used as a source of protein and vitamin supplement
in humans without any significant side-effects. Apart from
the high (up to 70%) content of protein, it also contains
vitamins, especially B12 andprovitaminA(β-carotenes), and
minerals, especially iron. It is also rich in phenolic acids,
tocopherols and γ-linolenic acid [1]. Spirulina lacks cellulose
cell walls and therefore it can be easily digested [1].
Many toxicological studies have proven Spirulina’ssafety.
Spirulina now belongs to the substances that are listed by
the US Food and Drug Administration under the category
Generally Recognized as Safe (GRAS) [2–6]. Spirulina is
relatively easy to cultivate but flourishes only in alkaline
lakes with an extremely high pH and in large outdoor ponds
under controlled conditions. There are only a few areas
worldwide that have the ideal sunny climate for production
of this alga, including Greece (Nigrita, Serres), Japan, India,
United States and Spain. Currently, Spirulina can be found in
health food stores and is sold mainly as a dietary supplement
in the form of health drinks or tablets. Microalgae have
been used for more than 10 years as dietary supplements
without significant side-effects [7].Theaimsofthisreview
are to summarize the mechanisms of action, highlight the
potential effects of this alga in humans and address current
and possible future clinical applications, based mainly on in
vivo studies and a few well-designed in vitro studies and the
highest levels of evidence available in the literature.
2. Evidence-Based Applications of
Spirulina
2.1. Spirulina and Chronic Fatigue. Spirulina has been
promoted as “the food of the future” with “exceptional
constituents” that contribute to high energy levels. A few of
these constituents such as polysaccharides (Rhamnose and
Glycogen) and essential fat (GLA) are absorbed easily by
human cells and help in energy release. Spirulina increases
healthy lactobacillus in the intestine, enabling the production
of Vitamin B6 that also helps in energy release. Despite
this promotion, the only available placebo-controlled ran-
domized trial showed that the scores of fatigue were not
2 Evidence-Based Complementary and Alternative Medicine
significantly different between spirulina and placebo. Spir-
ulina administered at a dose of 3 g day−1did not ameliorate
fatigue more than the placebo in any of the four subjects and
possibly it has no effect on chronic fatigue [8].
2.2. Allergy, Rhinitis, and Immunomodulation. It has been
well documented that Spirulina exhibits anti-inflammatory
properties by inhibiting the release of histamine from mast
cells [9,10].
In a recent randomized, double-blind placebo-controlled
trial [11], individuals with allergic rhinitis were fed daily,
either with placebo or Spirulina for 12 weeks. Peripheral
blood mononuclear cells were isolated before and after
the Spirulina feeding and levels of cytokines (interleukin-
4 (IL-4), interferon-γ(IFN-γ) and interleukin-2), which
are important in regulating immunoglobulin (Ig)E-mediated
allergy, were measured. The study showed that high dose of
Spirulina significantly reduced IL-4 levels by 32%, demon-
strating the protective effects of this microalga toward allergic
rhinitis.
Ishii et al. [12] studied the influence of Spirulina on IgA
levels in human saliva and demonstrated that it enhances IgA
production, suggesting a pivotal role of microalga in mucosal
immunity.
A Japanese team identified the molecular mechanism of
the human immune capacity of Spirulina by analysing blood
cells of volunteers with pre- and post-oral administration of
hot water extract of Spirulina platensis.IFN-γproduction
and Natural Killer (NK) cell damage were increased after
administration of the microalga extracts to male volunteers
[13].
In a recent double-blind, placebo-controlled study from
Turkey evaluating the effectiveness and tolerability of Spir-
ulina for treating patients with allergic rhinitis, Spirulina
consumption significantly improved the symptoms and
physical findings compared with placebo (P<.001),
including nasal discharge, sneezing, nasal congestion and
itching [14].
It is well understood that deficiency of nutrients is
responsible for changes in immunity, which manifests as
changes in production of T-cells, secretory IgA antibody
response, cytokines and NK-cell activity. The above studies
suggest that Spirulina may modulate the immune system by
its role in covering nutritional deficiencies.
2.3. Antiviral Applications: In Vitro Studies. There are no in
vivo studies providing strong evidence supporting the possi-
ble antiviral properties of Spirulina. The active component
of the water extract of S. platensis is a sulfated polysac-
charide, calcium spirulan (Ca-Sp). According to Hayashi et
al. [15], Ca-Sp inhibits the in vitro replication of several
enveloped viruses including Herpes simplex type I, human
cytomegalovirus, measles and mumps virus, influenza A
virus and human immunodeficiency virus-1 virus (HIV-1).
Another more recent study showed in vitro that an
aqueous extract of S. platensis inhibited HIV-1 replication
in human T-cells, peripheral blood mononuclear cells and
Langerhan cells [16]. The advantage of using herbs and
algal products with proven antiviral properties in fight-
ing certain viruses is that they can be used—through
immunomodulation—even when the infection is estab-
lished.
Of course, the above promising effects need to be studied
further in animal models and humans before any definitive
conclusions are drawn.
2.4. Cholesterol-Lowering Effects and Effects on Diabetes.
Cardiovascular disease remains the number one cause of
death in developed countries, despite increased awareness,
and high cholesterol is one of the most important risk factors
in atherosclerosis.
Nakaya et al. [17], in the first human study, gave 4.2 g
day−1of Spirulina to 15 male volunteers and, although
there was no significant increase in high-density lipoprotein
(HDL) levels, they observed a significant reduction of
high-density lipoprotein (LDL) cholesterol after 8 weeks of
treatment. The atherogenic effect also declined significantly
in the above group [17].
Ramamoorthy and Premakumari [18] in a more recent
study administered Spirulina supplements in ischemic heart
disease patients and found a significant reduction in blood
cholesterol, triglycerides and LDL cholesterol and an increase
in HDL cholesterol. More research is needed before Spirulina
can be recommended to lower cholesterol levels but its role
as a natural food supplement in combating hyperlipidaemia,
in combination with other therapeutic options, should not
be overlooked.
Finally, Mani et al. [19] in a clinical study, found a
significant reduction in LDL : HDL ratio in 15 diabetic
patients who were given Spirulina. However, this study was
small and better studies are needed before Spirulina can be
recommended in diabetes.
2.5. Anticancer Effects. It has been argued that the combined
antioxidant and immune modulation characteristics of Spir-
ulina may have a possible mechanism of tumor destruction
and hence play a role in cancer prevention. Whilst there are
many animal and in vitro studies, there has been only one
trial with human subjects. This study looked specifically at
the effects of Spirulina on oral carcinogenesis, in particular
leukoplakia [20]. It is not surprising that few human studies
exist to date as cancer prevention trials with lower cancer
incidence as an endpoint have logistic problems, rendering
them essentially impossible to conduct for most malignan-
cies. The study conducted by Mathew et al. on a cohort
of 77 patients originates from previous trials on hamsters
that showed tumor regression after topical application or
enteral intake of Spirulina extract [21–23]. They reported
that 45% of their study cohort showed complete regression
of leukoplakia after taking Spirulina supplements for 1 year.
The authors also reported that there was no rise in the serum
concentration of retinal β-carotene despite supplementation
and concluded that other constituents within Spirulina may
have been responsible for the anticancer effects. Whilst
their results appear promising, it was an unblinded, non-
randomized trial and as such cannot be regarded as evidence
of a positive effect.
Evidence-Based Complementary and Alternative Medicine 3
2.6. Chronic Arsenic Poisoning: A Randomized Trial. Millions
of people in Bangladesh, India, Taiwan and Chile are
consuming high concentration of arsenic through drinking
water and are at risk of chronic arsenic poisoning for which
there is no specific treatment. A placebo-controlled, double-
blind study was conducted to evaluate the effectiveness of
spirulina extract plus zinc in the treatment of chronic arsenic
poisoning [24]. Forty-one patients with chronic arsenic
poisoning were randomly treated by either placebo (17
patients) or spirulina extract (250 mg) plus zinc (2 mg) (24
patients) twice daily for 16 weeks. Each patient was supplied
with arsenic-safe drinking water by installing a locally made
water filter at household level. Effectiveness of spirulina
extract plus zinc was evaluated by comparing changes in skin
manifestations (clinical scores) and arsenic contents in urine
and hair, between the placebo- and spirulina extract plus
zinc-treated groups. Results showed that spirulina extract
plus zinc twice daily for 16 weeks may be useful for the
treatment of chronic arsenic poisoning with melanosis and
keratosis. More randomized trials are required but the results
are promising.
2.7. Antioxidant Effects:NoInVivoStudies. C-phycocyanin
(C-PC) is one of the major biliproteins of Spirulina with
antioxidant and radical scavenging properties. C-PC, a
selective cyclooxygenase-2 inhibitor, induces apoptosis in
lipopolysaccharide-stimulated RAW 264.7 macrophages. It
is also known to exhibit anti-inflammatory and anticancer
properties [25]. To date though, there are no in vivo human
studies on possible antioxidant effects of Spirulina.
3. Conclusions
The positive effects of Spirulina in allergic rhinitis are based
on adequate evidence but larger trials are required. It is
believed that the anticancer effects of Spirulina are perhaps
derived from β-carotene, a known antioxidant; however,
the link between β-carotene level and carcinogenesis cannot
be established as the etiology of carcinoma is frequently
multifactorial [26,27]. There are some positive studies
on the cholesterol-lowering effects of Spirulina but larger
studies are required before any definitive conclusions can be
made. Finally, there are no high-level evidence trials on the
role played by Spirulina in chronic fatigue and in antiviral
applications. At the moment, what the literature suggests is
that Spirulina is a safe food supplement without significant
side-effects but its role as a drug remains to be seen.
References
[1] J. C. Dillon, A. P. Phuc, and J. P. Dubacq, “Nutritional value
of the alga Spirulina,” World Review of Nutrition and Dietetics,
vol. 77, pp. 32–46, 1995.
[2] L. M. Tarantino, “Agency Response Letter GRAS Notice No.
GRN000127,” FDA Home page, October 2003.
[3] M. Salazar, G. Chamorro, S. Salazar, and C. Steele, “Effect of
Spirulina maxima consumption on reproductive and peri- and
postnatal development in rats,” Food and Chemical Toxicology,
pp. 353–359, 1996.
[4] G. Chamorro, S. Salazar, L. Favila-Castillo, C. Steele, and M.
Salazar, “Reproductive and peri-and postnatal evaluation of
Spirulina maxima in mice,” Journal of Applied Phycology, vol.
9, no. 2, pp. 107–112, 1997.
[5] M. Salazar, E. Mart´
ınez, E. Madrigal, L. E. Ruiz, and G. A.
Chamorro, “Subchronic toxicity study in mice fed Spirulina,”
Journal of Ethnopharmacology, vol. 62, no. 3, pp. 235–241,
1998.
[6] A. Belay, “The potential application of Spirulina (Arthrospira)
as a nutritional and therapeutic supplement in Health man-
agement,” Journal of the American Nutraceutical Association,
vol. 5, pp. 27–48, 2002.
[7] R. A. Kay, “Microalgae as food and supplement,” Critical
Reviews in Food Science and Nutrition, vol. 30, no. 6, pp. 555–
573, 1991.
[8] C. Baicus and A. Baicus, “Spirulina did not ameliorate idio-
pathic chronic fatigue in four N-of-1 randomized controlled
trials,” Phytotherapy Research, vol. 21, no. 6, pp. 570–573, 2007.
[9] H.-N. Yang, E.-H. Lee, and H.-M. Kim, “Spirulina platensis
inhibits anaphaylactic reaction,” Life Sciences, vol. 61, no. 13,
pp. 1237–1244, 1997.
[10] H.-M. Kim, E.-H. Lee, H.-H. Cho, and Y.-H. Moon,
“Inhibitory effect of mast cell-mediated immediate-type aller-
gic reactions in rats by Spirulina,” Biochemical Pharmacology,
vol. 55, no. 7, pp. 1071–1076, 1998.
[11] T. K. Mao, J. van de Water, and M. E. Gershwin, “Effects of
a Spirulina-based dietary supplement on cytokine production
from allergic rhinitis patients,” Journal of Medicinal Food, vol.
8, no. 1, pp. 27–30, 2005.
[12] K. Ishii, T. Katoch, Y. Okuwaki, and O. Hayashi, “Influence
of dietary Spirulina platensis on IgA level in human saliva,”
Journal of Kagawa Nutrition University, vol. 30, pp. 27–33,
1999.
[13] T. Hirahashi, M. Matsumoto, K. Hazeki, Y. Saeki, M. Ui, and
T. Seya, “Activation of the human innate immune system by
Spirulina: augmentation of interferon production and NK
cytotoxicity by oral administration of hot water extract of
Spirulina platensis,” International Immunopharmacology, vol.
2, no. 4, pp. 423–434, 2002.
[14] C. Cingi, M. Conk-Dalay, H. Cakli, and C. Bal, “The effects of
spirulina on allergic rhinitis,” European Archives of Oto-Rhino-
Laryngology. In press.
[15] K. Hayashi, T. Hayashi, M. Maedaa, and I. Kojima, “Calcium
spirulan, an inhibitor of envelope virus replication, from
ablue-greenalgaSpirulina platensis,” Journal of Natural
Products, vol. 59, pp. 83–7, 1996.
[16] S. Ayehunie, A. Belay, T. W. Baba, and R. M. Ruprecht,
“Inhibition of HIV-1 replication by an aqueous extract of
Spirulina platensis (Arthrospira platensis),” Journal of Acquired
Immune Deficiency Syndromes and Human Retrovirology, vol.
18, no. 1, pp. 7–12, 1998.
[17] N. Nakaya, Y. Homa, and Y. Goto, “Cholesterol lowering effect
of Spirulina,” Atherosclerosis, vol. 37, pp. 1329–1337, 1988.
[18] A. Ramamoorthy and S. Premakumari, “Effect of supplemen-
tation of Spirulina on hypercholesterolemic patients,” Journal
of Food Science and Technology, vol. 33, no. 2, pp. 124–128,
1996.
[19] U. V. Mani, S. Desai, and U. Iyer, “Studies on the long-
term effect of Spirulina supplementation on serum lipid
profile and glycated proteins in NIDDM patients,” Journal of
Nutraceuticals, Functional and Medical Foods,vol.2,no.3,pp.
25–32, 2000.
4 Evidence-Based Complementary and Alternative Medicine
[20] B. Mathew, R. Sankaranarayanan, P. P. Nair et al., “Evaluation
of chemoprevention of oral cancer with Spirulina fusiformis,”
Nutrition and Cancer, vol. 24, no. 2, pp. 197–202, 1995.
[21] G. Shklar and J. Schwartz, “Tumor necrosis factor in experi-
mental cancer regression with alphatocopherol, beta-carotene,
canthaxanthin and algae extract,” European Journal of Cancer
and Clinical Oncology, vol. 24, no. 5, pp. 839–850, 1988.
[22] J. Schwartz, G. Shklar, S. Reid, and D. Trickler, “Prevention of
experimental oral cancer by extracts of Spirulina-Dunaliella
algae,” Nutrition and Cancer, vol. 11, no. 2, pp. 127–134, 1988.
[23] J. Schwartz and G. Shklar, “Regression of experimental
hamster cancer by beta carotene and algae extracts,” Journal
of Oral and Maxillofacial Surgery, vol. 45, no. 6, pp. 510–515,
1987.
[24] M. Misbahuddin, A. Z. Islam, S. Khandker, I. Al-Mahmud,
N. Islam, and Anjumanara, “Efficacy of spirulina extract plus
zinc in patients of chronic arsenic poisoning: a randomized
placebo-controlled study,” Clinical Toxicology, vol. 44, no. 2,
pp. 135–141, 2006.
[25] M. C. Reddy, J. Subhashini, S. V. K. Mahipal et al., “C-
Phycocyanin, a selective cyclooxygenase-2 inhibitor,
induces apoptosis in lipopolysaccharide-stimulated RAW
264.7 macrophages,” Biochemical and Biophysical Research
Communications, vol. 304, no. 2, pp. 385–392, 2003.
[26] N. Malila, J. Virtamo, M. Virtanen, P. Pietinen, D. Albanes, and
L. Teppo, “Dietary and serum alpha-tocopherol, beta-carotene
and retinol, and risk for colorectal cancer in male smokers,”
European Journal of Clinical Nutrition, vol. 56, pp. 615–21,
2002.
[27] K. Liede, J. Hietanen, L. Saxen, J. Haukka, T. Timonen, R.
H¨
ayrinen-Immonen et al., “Long-term supplementation with
alpha-tocopherol and beta-carotene and prevalence of oral
mucosal lesions in smokers,” Oral Diseases, vol. 4, pp. 78–83,
1998.
