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Potential Health Benefits of Spirulina platensis

Authors:
  • Teaching Faculty.
  • Shadan Institute of Medical Sciences
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REVIEW ARTICLE
POTENTIAL HEALTH BENEFITS OF SPIRULINA PLATENSIS
D.JALAJA KUMARI1, B. BABITHA1, SK. JAFFAR*2, M.GURU PRASAD2
MD. IBRAHIM3 and MD.SIDDQUE AHMED KHAN3
1 Department of Foods and Nutritional Sciences, Acharya Nagarjuna University.
2 Department of Biochemistry, Acharya Nagarjuna University.
3. Dept of Biochemistry, Shadan Institute of Medical Sciences, Hyderabad, A.P, India.
ABSTRACT:
Spirulina
is free-floating filamentous micro algae growing in alkaline water bodies. With its high
nutritional value,
Spirulina
has been consumed as food for centuries in Central Africa. It is now widely used as
nutraceutical food supplement worldwide. Recently, great attention and extensive studies have been devoted to
evaluate its therapeutic benefits on an array of diseased conditions including hypercholesterolemia,
hyperglycerolemia, cardiovascular diseases, inflammatory diseases, cancer, and viral infections. The cardiovascular
benefits of
Spirulina
are primarily resulted from its hypolipidemic, antioxidant, and anti-inflammatory activities.
Data from preclinical studies with various animal models consistently demonstrate the hypolipidemic activity of
Spirulina
. Although differences in study design, sample size, and patient conditions resulting in minor inconsistency
in response to
Spirulina
supplementation, the findings from human clinical trials are largely consistent with the
hypolipidemic effects of
Spirulina
observed in the preclinical studies. However, most of the human clinical trials are
suffered with limited sample size and some with poor experimental design. The antioxidant and/or anti-
inflammatory activities of
Spirulina
were demonstrated in a large number of preclinical studies. However, a limited
number of clinical trials have been carried out so far to confirm such activities in human. Currently, our
understanding on the underlying mechanisms for
Spirulina
’s activities, especially the hypolipidemic effect, is limited.
Spirulina
is generally considered safe for human consumption supported by its long history of use as food source and
its favorable safety profile in animal studies.
KEYWORDS:
Spirulina platensis, Diabetes, Hypertension, hypolipidemic, and antioxidants
.
INTRODUCTION
Spirulina is classified within the phylum of
Cyanobacteria. Popular food and nutritional
supplements, this Cyanobacterium exists as either
blue-green bacteria or blue-green algae.
Spirulina
is a
specific type of blue-green vegetable micro-algae, and
is unique to only lakes which exhibit a high
alkalinity. Certain African, Asian, and Mexican
civilizations located within the vicinities of such lakes
began to unravel spirulina’s beneficial medicinal
properties thousands of years ago. Today, its
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worldwide popularity continues to grow as many
health conscious consumers recurrently praise its
extraordinary nutritional qualities.
Spirulinas nutritional qualities are truly
one-of-a-kind.‖ With its structure consisting of
nearly 71 percent total protein, spirulina represents
the highest natural source of protein ever discovered.
Its protein is fives times that of meat, and nearly three
times greater than the protein of the ever-popular
soybean. In addition to this astounding amino acid
profile, spirulina also contains a host of other
beneficial nutrients including; carotenoids, essential
fatty acids, B complex vitamins, vitamin E, copper,
manganese, magnesium, iron, selenium, and zinc. [1]
In fact, spirulina’s minerals and growth factor
qualities are only second to milk and evening
primrose oil. Preparations of
Spirulina
are also used
for their therapeutic properties in the treatment of
many diseases, including hypercholesterolemia and
atherosclerosis [2, 3] as well as to reduce body weight
in obese humans [4]. The
Spirulina
components
which are responsible for these therapeutic properties
are thought to be compounds with antioxidant
abilities such as polyunsaturated fatty acids,
phycocyanin and phenolics [6, 5, and 7].
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 randomized trial showed
that the scores of fatigue were not significantly
different between
spirulina
and placebo. Spirulina
administered at a dose of 3 g day1 did not
ameliorate fatigue more than the placebo in any of
the four subjects and possibly it has no effect on
chronic fatigue [7].
ALLERGY, RHINITIS, AND IMMUNOMODULATION.
It has been well documented that
Spirulina
exhibits anti-inflammatory properties by inhibiting
the release of histamine from mast cells [8, 9]. In a
recent randomized, double-blind placebo-controlled
trial [10], 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%,
demonstrating the protective effects of this microalga
toward allergic rhinitis. Ishii et al. [11] studied the
influence of
Spirulina
on IgA levels in human saliva
and demonstrated that it enhances IgA production,
suggesting a pivotal role of micro alga in mucosal
immunity. A Japanese team identified the molecular
mechanism of the human immune capacity of
Spirulina
by analyzing blood cells of volunteers with
pre- and post-oral administration of hot water extract
of
Spirulina platensis
. IFN-γ
production and Natural
Killer (NK) cell damage were increased after
administration of the micro alga extracts to male
volunteers [12]. In a recent double-blind, placebo-
controlled study from Turkey evaluating the
effectiveness and tolerability of
Spirulina
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 [13]. It is well understood that deficiency of
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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.
ANTIVIRAL APPLICATIONS: IN VITRO STUDIES.
There are no
in vivo
studies providing strong
evidence supporting the possible antiviral properties
of
Spirulina
. The active component of the water
extract of
S. platensis
is a sulfated polysaccharide,
calcium spirulan (Ca-Sp). According to Hayashi et al.
[14], 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 [15]. The advantage of using herbs and algal
products with proven antiviral properties in fighting
certain viruses is that they can be usedthrough
immunomodulationeven when the infection is
established. Of course, the above promising effects
need to be studied further in animal models and
humans before any definitive conclusions are drawn.
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. [16], in the first human study, gave 4.2
g day1 of
Spirulina
to 15 male volunteers and,
although there was no significant increase in high-
density lipoprotein (HDL) levels, they observed a
significant reduction of Low-density lipoprotein
(LDL) cholesterol after 8 weeks of treatment. The
atherogenic effect also declined significantly in the
above group [16]. Ramamurthy and Premakumari
[17] 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. [18] 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.
ANTICANCER EFFECTS
It has been argued that the combined
antioxidant and immune modulation characteristics
of
Spirulina
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 [19]. 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 malignancies. 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 [20
22]. They reported that 45% of their study cohort
showed complete regression of leukoplakia after
taking
Spirulina
supplements for 1 year. The authors
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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 unblended, non-
randomized trial and as such cannot be regarded as
evidence of a positive effect.
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 [23]. 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.
ANTIOXIDANT EFFECTS: No
Invivo
Studies.
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 [24]. To date
though, there are no
in vivo
human studies on
possible antioxidant effects of
Spirulina
.
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 multifactor [25, 26]. 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.
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ADDRESS FOR CORRESPONDENCE
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... This photosynthetic cyanobacterium have received much attention for its HVM such as α-tocopherol, β-carotene, lutein and γ-linolenic acid 2,3 as well for its bioactive effects (e.g. antifungal, antibacterial, antiviral, antimycotic, cytotoxicity, multi-drug resistance reversers and immunosuppressive actions) [4][5][6] . Also, cyanobacteria consume CO 2 as carbon source, use sunlight for energy and have high productivities 7 . ...
... . The yeast was inoculated in three 250 mL flasks containing 100 mL of YM broth composed of (g/L): glucose(10), peptone(5), malt extract (3), yeast extract(3). The medium was autoclaved at 121 °C, 30 psi during 30 min. ...
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With the aim to reach the maximum recovery of bulk and specialty bioproducts while minimizing waste generation, a multi-product biorefinery for ethanol and lactic acid production from the biomass of cyanobacterium Arthrospira platensis was investigated. Therefore, the residual biomass resulting from different pretreatments consisting of supercritical fluid extraction (SF) and microwave assisted extraction with non-polar (MN) and polar solvents (MP), previously applied on A. platensis to extract bioactive metabolites, was further valorized. In particular, it was used as a substrate for fermentation with Saccharomyces cerevisiae LPB-287 and Lactobacillus acidophilus ATCC 43121 to produce bioethanol (BE) and lactic acid (LA), respectively. The maximum concentrations achieved were 3.02 ± 0.07 g/L of BE by the MN process at 120 rpm 30 °C, and 9.67 ± 0.05 g/L of LA by the SF process at 120 rpm 37 °C. An economic analysis of BE and LA production was carried out to elucidate the impact of fermentation scale, fermenter costs, production titer, fermentation time and cyanobacterial biomass production cost. The results indicated that the critical variables are fermenter scale, equipment cost, and product titer; time process was analyzed but was not critical. As scale increased, costs tended to stabilize, but also more product was generated, which causes production costs per unit of product to sharply decrease. The median value of production cost was US$ 1.27 and US$ 0.39, for BE and LA, respectively, supporting the concept of cyanobacterium biomass being used for fermentation and subsequent extraction to obtain ethanol and lactic acid as end products from A. platensis.
... Spirulina has antioxidant properties which attributed mainly to the polyunsaturated fatty acids, phycocyanin and phenolic contents [9] also it has radioprotective properties [10] . ...
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Introduction: The widespread use of several electrical and telecommunication applications that produce electromagnetic fields is increasing rapidly. One of the most important organs which affected by numerous types of electromagnetic waves is the thyroid gland. Aim of the Study: This study targets to explore the effects of electromagnetic fields exposure on the thyroid and the protective influence of Spirulina platensis and vit E. Material and Methods: Fifty healthy rats of adult male albino type were separated into five equal groups. Control group, EMW-exposed at which, rats were subjected to the effect of electric magnetic field individually 4 hours daily for a period of one month. EMW exposed+ Spirulina treated group at which rats received Spirulina at a dosage of 300 mg/kg b.wt. just previous to EMW exposure daily for one month. EMW exposed + Vit E treated group at which , rats were subjected to EMF like that of group II and given Vit E orally at a dosage of 200 mg/kg. b.wt and a recovery group at which the rats kept for one month after one month of exposure to low frequency electro magnetic field then the thyroid tissues were examined for histopathological and immunohistochemical changes. Results: The group subjected to EMW showed thyroid follicles with degeneration and disorganization. Also numerous collagen fibers were present within the CT septa in the masson stained thyroid sections .The amount of PAS positive central colloid showed obvious decrease, with Strong Ki-67 immunoreactivity and TGFᵦ1 immuno expression. Spirulina platensis and vit E reduces the effect of EMW on thyroid gland , but vit E revealed obvious increase in the PAS positive central colloid amount, a significant decrease in collagen fibers, Ki-67 immunoreactivity and TGFᵦ1 immuno expression compared with that in spirulina group. Conclusion: The use of spirulina platensis during the period of EMW exposure considered to has a protecting influence. Meanwhile the utilization of vit E has a more protection than spirulina
... 1 Spirulina is almost a complete functional food and dietary supplement, it contains almost all vital nutrients that are required for the healthy functioning of the body. 2 It has a high content of polyphenols, phytosterols, carotenoids, polysaccharides, lectins, mycosporine-like amino acids, halogenated compounds, polyketides, protein, polyunsaturated fatty acids, minerals, vitamins, and various other bioactive compounds. [3][4][5][6] Spirulinacan be considered as one of the few sources of dietary polyunsaturated fatty acid γ-linolenic acid (GLA) after human milk; the unsaturated fatty acids, oleic and linoleic acids as wellas the saturated fatty acids palmitic acids are other major fatty acids that Spirulina can offer to the human diet. 4 Due to its suitable nutrient composition, Spirulina is recently drawing attention to nutraceuticals, pharmaceuticals, food, and feed productions. ...
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... Spirulina has antioxidant properties which attributed mainly to the polyunsaturated fatty acids, phycocyanin and phenolic contents [9] also it has radioprotective properties [10] . ...
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Spirulina platensis (SP) has a high impact on multidiscipline usage worldwide. Vitamins are considered as growth promoters due to their metabolic bio-regulating roles. This study was conducted to investigate the effect of vitamins: riboflavin (B2), thiamine (B1), and ascorbic acid (C) on SP growth and contents of pigments, phenols, and phytochemicals besides its antioxidant activities. Vitamins were added in different concentrations to Zarrouk’s medium and tested for their effects weekly for three weeks of spirulina cultivation. The results revealed that 25 mg·L−1 thiamine or riboflavin promoted the most significant contents of chlorophyll and carotenoids, respectively, after 14 days of cultivation. However, adding 10 mg·L−1 thiamine achieved the most significant increase in algal biomass yield and contents of chlorophyll, carotenoids phycocyanin, allophycocyanin, phycoerythrin, and phycobiliprotein after 21 days of cultivation. Qualitative analysis showed that both SP and SP supplemented with 10 mg·L−1 thiamine (SPt) for 21 days contain tannins and flavonoids but quantitative analysis approved that SPt recorded significant increase in phenolic and tannin contents. Moreover, SPt induced a significant increase of total antioxidant activity in vitro 1,1-diphenyl-1,2-picrylhydrazyl assay in comparison with SP. Vitamins especially thiamine added during SP culture could improve SP biomasses, pigments, and phytochemical contents and hence increased antioxidant capacity.
... Spirulina has antioxidant properties which attributed mainly to the polyunsaturated fatty acids, phycocyanin and phenolic contents [9] also it has radioprotective properties [10] . ...
... 1 Spirulina is almost a complete functional food and dietary supplement, it contains almost all vital nutrients that are required for the healthy functioning of the body. 2 It has a high content of polyphenols, phytosterols, carotenoids, polysaccharides, lectins, mycosporine-like amino acids, halogenated compounds, polyketides, protein, polyunsaturated fatty acids, minerals, vitamins, and various other bioactive compounds. [3][4][5][6] Spirulinacan be considered as one of the few sources of dietary polyunsaturated fatty acid γ-linolenic acid (GLA) after human milk; the unsaturated fatty acids, oleic and linoleic acids as wellas the saturated fatty acids palmitic acids are other major fatty acids that Spirulina can offer to the human diet. 4 Due to its suitable nutrient composition, Spirulina is recently drawing attention to nutraceuticals, pharmaceuticals, food, and feed productions. ...
Chapter
In the current century, people worldwide are facing hunger due to limitations in the food supply; to combat the scarcity of food, we are looking for an alternate source of food that contains all the necessary nutrients which are present in our normal diet which boost the immune system and provide energy to our body. Spirulina belonging to Cyanophyta has emerged as food for the future or super nutrition of the future as it contains all the necessary nutrients required in our diet. Spirulina is regarded as one of the most studied and commercialized alga having a higher concentration of proteins content. Furthermore, easily digestible nature and various health benefits, the leading world organization such as WHO and FAO consider spirulina as a superfood or future food. In the existing literature, we would focus on the biochemical composition of the alga, properties that make it future food, and prospective related to the algal food and market scenario of the present and future.Keywords Spirulina NutraceuticalsMarket trendToxicological aspectNutrition etc.
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Bioactivity-directed fractionation of a hot H2O extract from a blue-green alga Spirulina platensis led to the isolation of a novel sulfated polysaccharide named calcium spirulan (Ca-SP) as an antiviral principle. This polysaccharide was composed of rhamnose, ribose, mannose, fructose, galactose, xylose, glucose, glucuronic acid, galacturonic acid, sulfate, and calcium. Ca-SP was found to inhibit the replication of several enveloped viruses, including Herpes simplex virus type 1, human cytomegalovirus, measles virus, mumps virus, influenza A virus, and HIV-1. It was revealed that Ca-SP selectively inhibited the penetration of virus into host cells. Retention of molecular conformation by chelation of calcium ion with sulfate groups was suggested to be indispensable to its antiviral effect.
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We investigated the effects of the powders of Spirulina platensis (SPP) on anaphylactic reactions. SPP inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.5, and 1.0 mg/g body weight (BW). SPP significantly inhibited serum histamine levels induced by compound 48/80 in rats. SPP (0.5 mg/g BW) inhibited to 68.7% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. SPP dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80. Moreover, SPP had a significant effect on anti-DNP IgE-induced histamine release or tumor necrosis factor-alpha production from RPMC. These results suggest that SPP may contain compounds with actions that inhibit mast cell degranulation in the rat.
An aqueous extract of the blue-green filamentous algae Arthrospira platensis (previously called Spirulina platensis) inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC). Extract concentrations ranging between 0.3 and 1.2 microg/ml reduced viral production by approximately 50% (50% effective concentration [EC50]) in PBMCs. The 50% inhibitory concentration (IC50) of extract for PBMC growth ranged between 0.8 and 3.1 mg/ml. Depending on the cell type used, therapeutic indices ranged between 200 and 6000. The extract inactivated HIV-1 infectivity directly when preincubated with virus before addition to human T-cell lines. Fractionation of the extract revealed antiviral activity in the polysaccharide fraction and also in a fraction depleted of polysaccharides and tannins. We conclude that aqueous A platensis extracts contain antiretroviral activity that may be of potential clinical interest.
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We investigated the effect of spirulina on mast cell-mediated immediate-type allergic reactions. Spirulina dose-dependently inhibited the systemic allergic reaction induced by compound 48/80 in rats. Spirulina inhibited compound 48/80-induced allergic reaction 100% with doses of 100-1000 microg/g body weight, i.p. Spirulina (10-1000 microg/g body weight, i.p.) also significantly inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. When rats were pretreated with spirulina at a concentration ranging from 0.01 to 1000 microg/g body weight, i.p., the serum histamine levels were reduced in a dose-dependent manner. Spirulina (0.001 to 10 microg/mL) dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, when spirulina (10 microg/mL) was added, transiently and significantly increased about 70-fold at 10 sec compared with that of control cells. Moreover, spirulina (10 microg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results indicate that spirulina inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.
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To assess the effect of alpha-tocopherol and beta-carotene supplementation on the prevalence of oral mucosal lesions in smokers. An end-point examination of a random sample of participants in a controlled trial for 5-7 years (Alpha-Tocopherol Beta-Carotene Cancer Prevention Study) in Helsinki, Finland. A total of 409 white male cigarette smokers, aged 55-74 years who received either alpha-tocopherol (50 mg per day) or beta-carotene (20 mg per day) supplementation, both of these or placebo capsules. Clinical examination of oral mucosae, histological examination of lesions showing leukoplakia and cytological examination of buccal epithelium. Statistical analysis using Fisher's exact test. No statistically significant differences were found between the study groups either in the prevalence of oral mucosal lesions or in the cells of unkeratinized epithelium. Leukoplakia was present in 24 (5.9%) of the subjects. Seven lesions showed dysplasia. The present study on oral health does not support the hypothesis that alpha-tocopherol or beta-carotene supplementation plays an essential role in preventing oral mucosal changes in smokers.
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Spirulina platensis is a cyanobacterial species that is surmised to potentiate the immune system leading to suppression of cancer development and viral infection. Here, we identified the molecular mechanism of the human immune potentiating capacity of Spirulina by analyzing blood cells of volunteers with pre and post oral administration of hot water extract of Spirulina. NK functions represented by IFN gamma production and cytolysis were enhanced after administration of Spirulina in >50% subjects. IFN gamma was produced in an IL-12/IL-18-dependent fashion. In vitro stimulation of blood cells with BCG cell wall skeleton (CWS) allowed more potent IL-12 p40 production in cells from volunteers given Spirulina than in cells without pre-exposure to Spirulina. As BCG-CWS serves as a ligand for Toll-like receptor (TLR) 2 and 4 to raise the maturation stage of monocytes/macrophages, Spirulina may be involved in the signaling responses through Toll in blood cells even when orally administered. These observations indicated that in humans Spirulina acts directly on myeloid lineages and either directly or indirectly on NK cells. The presence of co-operative IL-12 and IL-18 is critically important for NK-mediated IFN gamma production.