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Critical Reviews in Food Science and Nutrition
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United States Pharmacopeia Safety Evaluation of
Spirulina
Robin J. Marles a , Marilyn L. Barrett a , Joanne Barnes a , Mary L. Chavez a , Paula Gardiner a
, Richard Ko a , Gail B. Mahady a , Tieraona Low Dog a , Nandakumara D. Sarma b , Gabriel I.
Giancaspro b , Maged Sharaf b & James Griffiths b
a United States Pharmacopeia Dietary Supplements Information Expert Committee Members,
Rockville, MD, USA
b United States Pharmacopeia Staff, Rockville, MD, USA
Available online: 27 Jul 2011
To cite this article: Robin J. Marles, Marilyn L. Barrett, Joanne Barnes, Mary L. Chavez, Paula Gardiner, Richard Ko, Gail B.
Mahady, Tieraona Low Dog, Nandakumara D. Sarma, Gabriel I. Giancaspro, Maged Sharaf & James Griffiths (2011): United
States Pharmacopeia Safety Evaluation of Spirulina, Critical Reviews in Food Science and Nutrition, 51:7, 593-604
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Critical Reviews in Food Science and Nutrition, 51:593–604 (2011)
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ISSN: 1040-8398 print / 1549-7852 online
DOI: 10.1080/10408391003721719
United States Pharmacopeia Safety
Evaluation of Spirulina
ROBIN J. MARLES,1MARILYN L. BARRETT,1JOANNE BARNES,1
MARY L. CHAVEZ,1PAULA GARDINER,1RICHARD KO,1
GAIL B. MAHADY,1TIERAONA LOW DOG,1NANDAKUMARA D. SARMA,2
GABRIEL I. GIANCASPRO,2MAGED SHARAF,2and JAMES GRIFFITHS2
1United States Pharmacopeia Dietary Supplements Information Expert Committee Members, Rockville, MD, USA
2United States Pharmacopeia Staff, Rockville, MD, USA
The Dietary Supplements Information Expert Committee (DSI-EC) of the United States Pharmacopeial Convention (USP)
reviews the safety of dietary supplements and dietary supplement ingredients for the purpose of determining whether they
should be admitted as quality monographs into the United States Pharmacopeia and National Formulary (USP–NF).The
United States Food and Drug Administration (FDA) has enforcement authority to pursue a misbranding action in those
instances where a dietary supplement product indicates that it conforms to USP standards but fails to so conform. Recently
DSI-EC undertook a safety evaluation of spirulina, a widely used dietary ingredient. DSI-EC reviewed information from
human clinical trials, animal studies, and regulatory and pharmacopeial sources and analyzed 31 adverse event reports
regarding spirulina to assess potential health concerns. At the conclusion of this review, DSI-EC assigned a Class A safety
rating for Spirulina maxima and S. platensis, thereby permitting the admission of quality monographs for these dietary
supplement ingredients in USP–NF. DSI-EC continually monitors reports concerning the safety of dietary supplements and
dietary supplement ingredients for which USP dietary supplement monographs are developed. The DSI-EC may revisit the
safety classification of spirulina as new information on this dietary ingredient becomes available.
Keywords Spirulina, Arthrospira, blue-green algae, cyanobacteria, USP, dietary supplements
INTRODUCTION
USP was founded by physicians in 1820 as an independent,
science-based, not-for-profit, standards-setting organization for
drugs. It has evolved as an organization setting standards for
modern prescription drugs, biologics, excipients, dietary sup-
plements, and food ingredients. Two of its principal publica-
tions, the United States Pharmacopeia and the National For-
mulary (collectively, USP–NF), are recognized in the federal
Food, Drug, and Cosmetic Act (FDCA) as official compendia
in the United States (US) (Bhattacharya et al., 2004; Schiff
et al., 2006). USP’s documentary standards (monographs and
allied General Chapters) and reference materials, also called
official USP Reference Standards (RS), are used not only in
Address correspondence to N. D. Sarma, Senior Scientific Liaison, Docu-
mentary Standards Division, United States Pharmacopeia, 12601 Twinbrook
Parkway, Rockville, MD 20852-1790, USA. Tel.: +1.301.816.8354, Fax:
+1.301.816.8373. E-mail: dns@usp.org
the US but also in approximately 130 other nations worldwide.
USP’s standards-setting body is the Council of Experts, which
currently has five Expert Committees that create quality stan-
dards for dietary supplements (DS) and dietary ingredients (DI),
as defined in FDCA. These are: the DSI-EC; DS Performance
Standards; DS Botanicals; DS General Chapters; and DS Non-
botanicals Expert Committees. Beyond USP’s documentary
standards and RS, USP has established DS and DI Verification
Programs. These programs involve a current Good Manufactur-
ing Practices (cGMPs) audit, quality system review, and product
testing performed by USP staff scientists to ascertain whether
DS and DI manufacturers participating in the voluntary verifi-
cation program conform to USP–NF quality standards and can
thereby be permitted to use the “USP Verified” mark on the
product label (Atwater, 2003; Atwater et al., 2005).
Unless a product is a new dietary ingredient, the Dietary Sup-
plements Health and Education Act (DSHEA, 1994) amendment
to FDCA does not require FDA approval for dietary supple-
ments before marketing. For new dietary ingredients that were
593
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594 R. J. MARLES ET AL.
not legally marketed in the US before 15 October 1994, DSHEA
requires the manufacturer or distributor to submit a notification
to FDA 75 days before “introducing or delivering for introduc-
tion into interstate commerce a dietary supplement that contains
a new dietary ingredient that has not been present in the food
supply as an article used for food in a form in which the food has
not been chemically altered ...[and] information including any
citation to published articles that is the basis on which the man-
ufacturer or distributor has concluded that a dietary supplement
containing such dietary ingredient will reasonably be expected
to be safe.”1DSHEA also stipulates that if a DS is 1) covered
by the specifications (tests, procedures, and acceptance criteria
of a monograph) of an official compendium, 2) is represented
as conforming to the specifications of an official compendium,
but 3) fails to so conform, then the supplement is considered to
be misbranded under FDCA [§403(s)(2)(D)] (DSHEA, 1994).
However, §403(s)(2)(D) of FDCA makes compliance with USP–
NF specifications strictly voluntary, and DS manufacturers can
decide whether or not to place USP–NF on the product label.
This is in contrast to prescription drugs, for which conformance
with USP–NF standards is mandatory, whether products are la-
beled USP–NF or not. Nonetheless, §403(s)(2)(D) of FDCA
provides legal recognition for USP–NF standards for dietary
supplements, creating the possibility of FDA enforcement for
misbranding against those manufacturers who claim compliance
with these standards but fail to so conform.
To select and prioritize candidate dietary ingredients for
monograph development, USP has developed an Admission Cri-
teria and Safety Classification for Dietary Supplements Guide-
line (Guideline) (USP, 2009; Schiff et al., 2006) that evaluates
parameters for admission: 1) apparent efficacy or a presump-
tive belief in some beneficial activity as evidenced by a long
history of use; 2) demand, or the extent of use by the public
sector; 3) public protection, indicating interest by a regulatory
agency; 4) feasibility, suggesting the likelihood that the ingre-
dient could meet compendial criteria; 5) compendial presence,
demonstrated by the existence of monographs in other official
compendia; and 6) safety, as indicated by a long history of use
(or recent data indicating no safety concerns).
As an element of the Guideline, DSI-EC evaluates the DS
safety profile of a dietary supplement ingredient to determine
its admission in USP–NF as a quality monograph. DSI-EC con-
ducts extensive safety reviews of the selected dietary ingredient,
analyzing information from human clinical case reports, adverse
event reports (AERs), animal pharmacological and toxicolog-
ical data, historical use, regulatory status, and global contem-
poraneous extent of use (detailed in USP, 2009; Sarma et al.,
2008; Mahady et al., 2008). Following a thorough review of
this information, DSI-EC assigns one of the following safety
and admission classifications to the DS articles for monograph
development: 1) Class A: Admitted into USP–NF or 2) Class B:
Not admitted into USP–NF. Under Class A, articles for which
the available evidence does not indicate a serious risk to health
1See Title 21 Code of Federal Regulations §190.6(a) (2009).
(defined in USP, 2009; EMEA, 1995) or other public health con-
cern are approved for the development of quality monographs
and are admitted in USP–NF. Following this decision, other
USP DS Expert Committees may consider setting quality stan-
dards, and the DS or DI may be eligible to participate in USP’s
Verification Programs. DSI-EC’s safety review of spirulina was
conducted in accordance with USP’s Guideline.
Several authors have suggested the need for quality standards
for spirulina (Rellan et al., 2009; Eisenbrand et al., 2008). Fol-
lowing a request from a monograph sponsor (i.e., a company
that has volunteered to help develop a monograph by providing
validated data for quality specifications), DSI-EC, working with
USP staff, reviewed the safety of spirulina to determine whether
a spirulina quality monograph could be admitted into USP–NF.
This article summarizes DSI-EC’s safety review of spirulina.
PRODUCT DESCRIPTION
The name Spirulina refers to a large number of eubacterial
species that belong to the phylum Cyanobacteria (Muhling
et al., 2006), family Spirulinaceae or Pseudanabaenaceae
(NCBI, 2009). Spirulina also are known as blue-green algae,
but they are in reality prokaryocytes (they lack the nuclei
and other cellular organization of eukaryotes such as algae).
Thirty-five species of spirulina have been identified (Dillon
et al., 1995). The most commonly used spirulina (also called
Arthrospira) species in dietary supplements are S. maxima
(Setchell and Gardner) Geitler, S. platensis (Nordstedt) Geitler,
and S. fusiformis Voronikhin (McGuffin et al., 2000).
Spirulina use has been widely documented since the 16th
Century (Ciferri, 1983). Spirulina contains several nutrients, in-
cluding about 65% protein, B-complex vitamins, phycocyanin,
chlorophyll, β-carotene, vitamin E, superoxide dismutase, and
numerous minerals (Wang et al., 2008; Dillon et al., 1995; Lums-
den and Hall, 1974). High concentrations of polyunsaturated
fatty acids and γ-linolenic acid also are present (Otles and Pire,
2001). Spirulina is the first prokaryote found to contain stable,
easily extractable ferredoxin (Tanaka et al., 1975). Phycocyanin
is the most abundant protein-bound pigment in Cyanobacteria
and accounts for more than 20% of its dry weight (Romay et al.,
1998). In view of its nutrient content, it is considered suitable
as a functional food (Park et al., 2008).
Several spirulina-based products are available in the US as
food or dietary supplements and in different forms, including
powder or capsules (NBJ, 2009; DSLD, 2009). Although histor-
ical accounts (Ciferri, 1983) indicate consumption of spirulina
(as Dih´
e in Africa) at 10 to 40 g, the contemporary typical intake
of spirulina is 1–5 g daily before meals (Fetrow and Avila, 1999;
NLM, 2009; Gilroy et al., 2000; FDA, 2003). Recent clinical
studies (Yamani et al., 2009) indicate that an intake of about
10 g of spirulina per day for 6 months does not induce adverse
effects.
Other species of Cyanobacteria that are sold for consump-
tion as dietary supplements or foods include Aphanizomenon
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USP SAFETY EVALUATION OF SPIRULINA 595
flos-aquae (L.) Ralfs ex Barnet et Flahault and Nostoc ellip-
sosporum Rabenhorst ex Bornet et Flahault, both in the fam-
ily Nostocaceae (NCBI, 2009). Correct identification of the
cyanobacterial material is an important distinction because of
the well-established presence of toxins in certain genera, in-
cluding Aphanizomenon and Microcystis, (e.g., Schaffer et al.,
1999) and the apparent absence of toxins in other genera, such
as Spirulina. Cyanobacteria either are harvested from natural,
warm, alkaline waters or are grown under controlled conditions.
Richmond (1999) detailed the systems for mass production of
microalgae outdoors. Toxin concentrations in genera other than
Spirulina are affected by environmental factors such as expo-
sure to sun, depth of the water in which the organisms live,
and the types of minerals in the water. Toxin concentrations
fluctuate with environmental changes and are not predictable.
Without scientific testing, users have no reliable way to detect
the presence or concentration of toxins. Several useful reviews
of cyanobacterial toxins are available (Health Canada, 2008a;
Purdue, 2007; Dietrich and Hoeger, 2005; Schaffer et al., 1999).
The proposed standards for the USP quality monograph for spir-
ulina and detailed notes about microcystins are provided in the
section titled “Contaminants” below.
METHODS
DSI-EC reviewed the following resources to conduct its
safety review: spontaneous AERs from FDA’s MedWatch pro-
gram, the Canada Vigilance Adverse Reaction Online Database
from the Canadian Department of Health, and the Australian Ad-
verse Drug Reaction Reporting System from Australia’s Ther-
apeutic Goods Administration (search duration mentioned be-
low). In addition, USP staff searched PubMed and TOXNET
(1966 to October 2009) to retrieve clinical case reports and ani-
mal pharmacological or toxicological information. DSI-EC also
collected information concerning the regulatory status and phar-
macopeial standards of spirulina in other countries. The princi-
ples of data collection, evaluation, and integration are detailed
in the Guideline (USP, 2009) and in the Institute of Medicine
Framework for Evaluating Safety of Dietary Supplements (IOM,
2005). Limitations of the dietary supplement AERs (detailed in
Gardiner et al., 2008) are considered in the analysis of the re-
ports. The safety classification for spirulina is based on the
expert opinion of DSI-EC to determine admission to USP–NF
as a quality monograph. The proposed USP standards for spir-
ulina are developed in accordance with principles detailed in
Schiff et al. (2006).
SAFETY REVIEW
DSI-EC found numerous experimental and clinical studies
that investigated the efficacy of spirulina, but the current review
focuses only on reports that concern the safety of spirulina. This
report does not include a review of the efficacy studies from
clinical reports or animal models. The primary objective of this
review is to identify signals of safety concern associated with
the use of spirulina. This section includes analyses of reports
regarding the following aspects of safety:
•Human data—AERs
Clinical case reports
FDA MedWatch reports
Canada Vigilance Program reports
Australian Therapeutic Goods Administration (TGA)
reports
UK Medicines and Healthcare products Regulatory Agency
reports
Uppsala Monitoring Centre
•Animal pharmacological data
•Supplement–drug interactions
•Contaminants such as microcystin, heavy metals, and micro-
bial organisms
•Regulatory status.
Safety information for spirulina-based products follows.
Clinical Case Reports
Although spirulina has a long history of recorded use (Ciferri,
1983), a review of the literature up to and including October,
2009, revealed no systematic clinical safety evaluation in the
public record. This is surprising because historically spirulina
was cultivated from wild open lakes, and contamination with
other blue–green algae that produce microcystins was a matter
of serious concern. In the present review, clinical case reports of
adverse effects of spirulina published in peer-reviewed scientific
journals were identified using the PubMed database (available
at http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed). The
search covered the period from 1966 to October, 2009. The fol-
lowing search terms (number of references in parenthesis) were
used: spirulina (777); arthrospira (78); spirulina AND adverse
effects (72); spirulina AND toxicity (62); spirulina AND clinical
trial (28); spirulina AND toxic effects (17); and spirulina AND
safety (9). Nonduplicate reports were collected from TOXNET
(http://toxnet.nlm.nih.gov/index.html). Most references corre-
sponding to terms “adverse effects,” “toxicity,” “toxic effects,”
and “safety” did not directly correspond to the main topic of the
search. Clinical studies of spirulina were conducted primarily to
evaluate its nutritional or biological activities, and, accordingly,
little safety information was retrievable from these studies. A
review of the reports that directly related to safety concerns in
clinical case reports indicated 3 clinical observations recording
adverse events associated with use of spirulina products.
Mazokopakis et al. (2008) reported a case of acute rhabdomy-
olysis in a 28-year-old man who was taking spirulina tablets as a
dietary supplement (at the manufacturer’s recommended intake
of 3 g/day) during the previous 1-month period. The patient
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596 R. J. MARLES ET AL.
was reportedly not taking other medications and did not use
alcohol or illicit drugs. Hematological tests were indicative of
rhabdomyolysis, showing elevated creatinine kinase concentra-
tions and elevated concentrations of other muscle enzymes such
as myoglobin, ALT, AST, LDH, and aldolase. The patient was
hydrated for 4 days and then discharged. One week later, he re-
mained free of symptoms, and laboratory findings were normal.
The authors hypothesized that under certain conditions blue-
green algae could produce a neurotoxin called BMAA (β-N-
methylamino-L-alanine), which can cause a neurodegenerative
disease (amyotrophic lateral sclerosis–parkinsonism–dementia
complex) but did not provide any evidence for the presence of
BMAA in the product used. Although BMAA is known to be
produced by other cyanobacterial species such as Nostoc (John-
son et al., 2008), its production in spirulina has not been reported
before. Further, a recent study has shown preventive effects of
spirulina on skeletal muscle damage under exercise-induced ox-
idative stress (Lu et al., 2006).
A. flos-aquae and S. platensis were implicated in a patient’s
diagnosis of dermatomyositis (Lee and Werth, 2004). The pa-
tient was a 45-year-old woman with a history of hypertension,
chronic migraines, and fibromyalgia. The patient reportedly de-
veloped redness on her face and over the knuckles of her hands
within 1 to 2 days following use of a supplement composed of
organic cayenne pepper, methylsulfonylmethane (also known
as MSM), A. flos-aquae, and S. platensis. She discontinued the
supplement but a month later resumed it, along with another
multi-ingredient product containing digestive enzymes. Four
days after rechallenge with the supplement, she reported wors-
ening of the rash, including extensive swelling of her face, eyes,
and ears. Subsequent investigations revealed that her antinu-
clear antibody titer was 1:160, and a biopsy supported diagnosis
of dermatomyositis. Later studies showed that the patient was
heterozygous for the –308A tumor necrosis factor-α(TNF-α)
promoter polymorphism, the phenotype of which is increased
TNF-αproduction, which in turn may genetically predispose
an individual to autoimmunity (Lee and Werth, 2004). DSI-EC
views this case report as a classical example of idiosyncratic
reaction. In individuals with a genetic predisposition, a supple-
ment such as spirulina that is claimed to be an immunostimulant
can help precipitate an autoimmune disorder such as dermato-
myositis. Further, the use of more than one product with multiple
ingredients complicates causality assignment.
Iwasa et al. (2002) reported the observation of elevated liver
enzyme concentrations in a 52-year-old Japanese man who used
a spirulina product for 5 weeks. The patient had a history of hy-
pertension, hyperlipidemia, and type 2 diabetes mellitus, and
had taken simvastatin and amlodipine for 7 months. Unfortu-
nately the paper did not discuss the well-documented possibility
that a statin such as simvastatin could cause liver damage. The
report concluded that the adverse reaction possibly was related
to spirulina because the patient’s liver enzyme concentrations
improved after withdrawal of spirulina (positive dechallenge).
However, all the patient’s medications were withdrawn concur-
rently, so alternative explanations for the decline in liver enzyme
concentrations cannot be excluded.
Tab le 1 Clinical trials of spirulina
Study Title Study Details
Vitamin A value of
spirulina carotenoids in
humans
NCT # 00680277 Study design: Phase I and
Phase II; Nonrandomized, Open-label,
Uncontrolled, Single Group Assignment,
Bioequivalence Study 5 g/day of spirulina for
8 weeks (subjects: N =20) Study location /
status: Tufts University/ Recruitment closed
Impact of Spirulina
platensis
supplementation on
general health status of
HIV-infected patients
in Burkina Faso
ISRCTN# 83770226 Study design:
Double-blind randomized controlled trial 5
g/day of spirulina for 12 months (subjects:
N=60) Study location / status: Burkina
Faso/Recruitment closed (Simpore et al.,
2005)
Clinical trials registries (www.clinicaltrials.gov/; http://
www.controlled-trials.com/mrct/search.html; http://hnrim.nih.
gov/; http://crisp.cit.nih.gov/; and www.who.int/ictrp/en)
recorded 2 studies whose primary objective was evaluating the
efficacy of spirulina. Safety and tolerability of spirulina are not
reported in these studies. The Cochrane Library indexed 18
clinical trials (English reports) but no Cochrane Review for the
term spirulina. The trials focused on efficacy investigations and
reported few data relating to safety aspects. Study details for
some clinical trials (Table 1) show that few registered clinical
investigations are documented for spirulina and that no safety
concerns were described in clinical studies.
FDA MedWatch AERs
The authors reviewed FDA MedWatch reports involving spir-
ulina during the period from January, 2001, to July, 2009, and
identified 79 nonduplicate reports. Of these, 38 involved con-
current treatment with ephedra. Because of earlier AERs as-
sociated with ephedra (Woolf et al., 2005), these 38 reports
were excluded from the present analysis. In addition, because
of the well-established presence of toxins in certain genera
of cyanobacteria, including Aphanizomenon and Microcystis,
AERs associated with products that contained these ingredients
were excluded from analysis.
In total, 5 reports of liver damage and 8 reports of other ad-
verse outcomes associated with use of spirulina were identified
(Tables 2 and 3). The most common non-serious adverse events
were nausea, diarrhea, vomiting, fatigue, headache, dizziness,
itching, rash, and abdominal cramps.
As with many spontaneous AERs, several MedWatch reports
lacked information about the quantity of spirulina used, dura-
tion of usage, patient history, and product quality. Further, these
reports do not present a pattern of pathology. These reports were
associated with different dietary supplements containing spir-
ulina, and product information was not available for any of them
so their spirulina content is unknown. If additional information
becomes available, the causality relationship for spirulina in
these reports may change. For example, MedWatch case report
#16471 identifies the product simply as “blue-green algae” that
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USP SAFETY EVALUATION OF SPIRULINA 597
Tab le 2 Details of MedWatch cases reporting liver damage as the outcome
Case Number Received Date Pathology Comments
# 14853 23 April 2001 Elevated liver function test values No other details were recorded
# 15515 28 February 2002 Elevated liver enzymes, resulting in
death
Significant medical history: Hepatitis A, B, C, alcohol usage, jaundice, and
diabetes
# 67512 16 January 2004 Toxic hepatitis The product contains more than 50 ingredients
# 98498 30 November 2007 Elevated liver enzymes Patient was using Depo-Provera and several polyherbal and multivitamin
combinations containing spirulina
# 110611 13 February 2009 Elevated liver enzymes, drug-induced
lupus, hair loss, blot clot
This spontaneous report by a female patient indicated reactions upon use
of a multi-ingredient product containing spirulina
was not analyzed. The neurological manifestations in this re-
port are consistent with the ones produced by the neurotoxins
anatoxin or saxitoxin, which indicates the possibility of contam-
ination with other cyanobacteria such as Anabaena, Oscillatoria,
or Aphanizomenon.
Summary Analysis of Information from Health Canada
Health Canada issued a review of toxins in blue-green algae
(Cyanobacteria) in 2008. The review stated that “consumers
can safely use products made only from Spirulina blue-green
algae as these were found to be free of microcystins.” The re-
view also noted that long-term ingestion of microcystins from
the toxic cyanobacterial species M. aeruginosa can cause liver
damage (Health Canada, 2008a). Children potentially are at
risk of exposure to harmful concentrations of toxins if they in-
gest cyanobacterial products for an extended period of time.
As a precaution, Health Canada recommended that the use of
nonspirulina Cyanobacteria by children be discontinued until
further studies have been conducted (Health Canada, 2008a).
The Canada Vigilance Program (CVP) listed 8 adverse event
reports involving Cyanobacteria and associated with the use of
spirulina-containing products between 1965 and 30 June 2009
(the most recent update). Table 4 provides details of these 8 case
reports. Insufficient details are available regarding the identity
of all the ingredients in the polyherbal products or the quality of
the products, as well as dose and duration of intake. The reports
are confounded by multiple suspect products and concomitant
medications, and in some cases patient history is inadequate
(CVP, 2009 and personal communications). Thus DSI-EC can-
not adequately review these cases for safety.
Australian Adverse Event Reports
In May, 2005, the Australian TGA changed the regulatory
status of S. maxima and S. platensis from “excipient only” to “ac-
tive ingredient” (TGA, 2005). Further, the TGA Herbal Ingre-
dient Names Committee determined that the correct Australian
Approved Names for these two species should be Arthrospira
maxima and A. platensis, respectively, but the committee allows
the use of the more frequently used term spirulina elsewhere
on the label. TGA provided details of 8 case reports related to
spirulina use received up to July 2009. Case #173126 reported
concurrent use of kava (Piper methysticum). Because of earlier
AERs associated with kava, this report was excluded from the
present analysis. Two other reports (#181731 and #215572) de-
scribed headache, dehydration, diarrhea, nausea, dysphasia, re-
nal failure, and oropharyngeal pain, from which the individuals
Tab le 3 Details of MedWatch cases reporting other outcomes
Case Number Report / Received Date Pathology Comments
# 14036 21 March 2003 Severe hypercalcaemia, dehydration, death N/Aa
# 14643 07 February 2001 Transient ischemic attack N/A
# 14926 26 June 2001 Severe diarrhea, vomiting, grand mal
seizures, coma
N/A
# 16471 14 January 2003 Severe parkinsonian syndromebProduct label, manufacturer unknown
# 102994 05 May 2008 Upper body turning red; throat swelling Deemed serious adverse event in view of throat swelling shut. Patient
on Avalide and Coreg.
# 103049 06 May 2008 Anaphylactic reaction Patient was treated in ER.c
# 103409 20 May 2008 Allergic reaction Skin flushing and throat swelling shut. Visited ER, though not
admitted. Patient and family had no problem with previous 5 bottles.
# 113558 20 May 2009 Heart palpitations A 37-year-old woman reported ER visit because of reactions one week
after using a multi-ingredient product containing spirulina.
Manufacturer reported that the retained sample met all specifications.
aN/A =information not available.
bPatient recovered after 4 months. Doctors suspect a possible neurotoxin, some contaminant in blue-green algae or citrus (grapefruit) supplement, orsome
interaction with the products the patient was taking. Heavy metals were ruled out.
cER =emergency room.
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598 R. J. MARLES ET AL.
Tab le 4 Details of Canada CVP case reports on spirulina-containing products
Case Number Received Date Age/Sex Pathology Comments
# 131254 24 June 1996 30/F Abnormal liver function tests and
malaise
A blue-green algae supplement used
# 131255 12 May 2000 None recorded Hepatic cirrhosis A blue-green algae supplement use for 10 years was reported
# 146563 07 March 2002 36/F Edema, rash Patient reported using a spirulina-based product (Greens Plus)
and concomitant medications (Nexium, Synthroid, Atarax)
# 148360 09 April 2002 37/F Sleep difficulties Patient was using spirulina-containing products for >6 months.
Reportedly recovered without complications.
# 169033 02 April 2004 40/F Insomnia; nausea, vomiting;
hyperalertness
Patient used a product containing 25 mg spirulina for 3 days and
reported adverse reactions; concurrent medication—Celexa.
# 225870 27 November 2007 Age
unknown/F
Nausea; fatigue; numbness Patient used a product containing approximately 1400 mg
spirulina for 4 days and reported adverse reactions;
concurrent medication—Synthroid.
# 316823 21 January 2009 68/M Biopsy of kidney was abnormal,
nephrotoxicity, renal failure
Patient was taking several suspect polyherbal products:
Electrolyte Stamina tablets, Greens +Extra Energy powder,
Recovery powder, and Vigrx Plus tablets, all daily
# 320245 19 March 2009 34/M Hepatic enzyme levels were increased Patient was taking polyherbal Greens +powder and capsules
plus stimulant Xenadrine-EFX daily for 4 months
recovered, associated with the use of multi-ingredient prod-
ucts containing spirulina. Table 5 provides details of the 5 re-
maining case reports. Information about the intake of spirulina
was available for one case (#182013): The patient initially took
2 tablets of spirulina daily for 4 weeks (further details unknown)
without event, but on a separate occasion experienced malaise,
abdominal pain, chest pain, pyrexia, tachycardia, tachypnoea,
and vomiting when she took one tablet. The case report did not
record any treatment for these conditions. This case possibly
could be considered an idiosyncratic reaction.
As with MedWatch reports, the TGA reports involved dif-
ferent products, product information was not available in all the
reports, and the spirulina content in these products was not an-
alyzed. Further, a pattern in the pathology is not apparent from
these reports.
UK MHRA Reports
As of October, 2009, the British Medicines and Healthcare
Products Regulatory Agency (MHRA) did not register any ad-
verse reports involving spirulina (MHRA, 2009).
Uppsala Monitoring Centre Reports
The Uppsala Monitoring Centre (UMC; World Health Orga-
nization Collaborating Centre for International Drug Monitor-
ing) co-ordinates individual case reports of suspected adverse
drug reactions sent by the national pharmacovigilance centers
of 96 participating member countries (as of October 2009). By
November 2009, the UMC had received 8 nonduplicate reports
of suspected adverse reactions associated with spirulina. All
the reports classify the product as “Spirulina spp,” except for 1
Swiss report that specifies S. pratensis. These reports included
two reports from Australia that are cited in Table 5 (#178912
and #222614) and one report from MedWatch cited in Table
2 (#15515). The 5 other reports are summarized in Table 6. A
comparison of the UMC reports and those from other agencies
(such as MedWatch) show that some national reports do not
reach UMC. The UMC caveat statement says: “The information
shown is not homogeneous at least with respect to origin or
likelihood that the pharmaceutical product caused the adverse
reaction. The information does not represent the opinion of the
World Health Organization.”
Animal Pharmacological Data and Reproductive Toxicity
As was the case with the clinical study reports, most publica-
tions using animal models investigated the biological activities
of spirulina and did not directly evaluate safety. Although sev-
eral studies investigated the acute, subchronic, and chronic tox-
icity, reproductive and developmental toxicity, and genotoxicity
of microcystin-LR (of nonspirulina origin) (reviewed in Health
Tab le 5 Details of Australian TGA case reports on spirulina-containing products
Case Number Received Date Age/Sex Pathology Comments
# 178912 28 August 2002 37/F Hemorrhage Intake, duration, identity not recorded
# 182013 23 January 2003 51/F Malaise, abdominal pain, chest pain, pyrexia,
tachycardia, tachypnoea, and vomiting
Positive rechallenge. Patient took spirulina 2 tablets daily for 4
weeks. No treatment.
# 205473 23 February 2005 33/F Breast milk discoloration Product intake, duration, identity not recorded
# 211302 18 July 2005 38/F Photosensitivity reaction; dry mouth, eye pain,
headache
Patient used a multi-ingredient product containing spirulina
# 222614 15 September 2006 50/F Fatigue, muscular weakness Patient suspects that spirulina reduced effectiveness of
venlafaxine (Effexor-XR)
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USP SAFETY EVALUATION OF SPIRULINA 599
Tab le 6 Details of UMC case reports on spirulina-containing productsa
Country of
origin
Patient
(age, sex)
Details of spirulina
use; indication
Date of
onset of
reaction
Reported adverse
reaction(s) Outcome De-/rechallenge information Comment
S Africa 62, F Taken orally 3 daily,
duration of use n/sb;
rheumatoid arthritis
and other inflammatory
polyarthropathies
22
Septem-
ber
2000
Rash Recovered Reaction abated on drug
withdrawal; no rechallenge
No other medicines stated
S Africa 47, F Taken orally 3 daily,
duration of use n/s;
indication n/s
20 August
2003
Diarrhea, cramps Recovered Reaction abated on drug
withdrawal; reaction
recurred on rechallenge
Also taking Eugynon
Switzerland 48, F with
previous
embolism,
thrombosis
Taken orally 12 daily
starting 6 days before
onset of reaction and
continuing; malaise
and fatigue
11 March
2005
Prothrombin time
shortened; drug
(aceno-
coumarol)
ineffective
Recovered Spiruliana: dose reduced,
effect unknown;
rechallenge status
unknown Acenocoumarol:
dose increased, no further
information provided
Also taking acenocoumarol
for thrombosis (daily;
dose n/s) started 11 days
before onset of reaction;
suspected interaction
Switzerland n/s, F S. pratensis taken orally 1
daily, duration of use
n/s; indication n/s
September
2008
Abdominal pain Unknown S. pratensis and chromium
withdrawn, outcome
unknown; rechallenge
status unknown
Also taking chromium
orally 0.16 mg daily for
NIDDMcand MSM 1
daily
Malaysia 15, M Taken orally, 500 mg
daily for 11 days
starting 2 days before
onset of reaction
2 October
2005
Morbiliform rash;
pityriasis rosea
Not recov-
ered
No improvement was
observedondrug
withdrawal; no rechallenge
No other medicines stated
aCaveat statement: “The information shown is not homogeneous at least with respect to origin or likelihood that the pharmaceutical product caused the adverse
reaction. The information does not represent the opinion of the World Health Organization.”
bn/s =not stated.
cNIDDM: non–insulin-dependent diabetes mellitus; MSM =methylsulfonylmethane.
Canada, 2008b), similar information is not available for spir-
ulina. A review of the literature describing animal experiments
with relevance to safety aspects is presented here.
S. maxima was reported to possess hepatoprotective activity
in a rat model (Torres-Duran et al., 1999; 2006). At 5% con-
centration in feed, spirulina exhibited hepatoprotective activity
against induction of fatty liver by carbon tetrachloride. Simi-
lar protective effects are reported in rat models in cadmium-
induced hepatotoxicity (Karadeniz et al., 2009) and in dibutyl
nitrosamine–induced liver toxicity (Ismail et al., 2009).
Administration of spirulina in rat models did not result in any
reported adverse effects or organ toxicity (Ismail et al., 2009)
and had no effect on pregnancy (Kapoor and Mehta, 1993). The
safety of S. maxima in reproduction was observed in several
studies at 10%–20% feed levels (Chamorro et al., 1996a; 1997;
Salazar et al., 1996; 1998). In animal experiments for acute,
subchronic, and chronic toxicity, reproduction, mutagenicity,
and teratogenicity, spirulina did not cause body or organ toxicity
(Chamorro et al., 1996b). Protective activity of spirulina (up to
800 mg/kg/day; 2 weeks) was reported in cyclophosphamide-
induced mutagenicity in a mouse model (Chamorro-Cevallos
et al., 2008).
Literature is scant with respect to the safety of spirulina
consumption in lactation. Kapoor and Mehta (1998) reported
that feeding rats with spirulina to provide 22% protein during
lactation was without safety concerns. No records were found
for spirulina in the Drugs and Lactation Database (LactMed;
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT).
Supplement–Drug Interactions
Little information is available about the interactions of spir-
ulina and other medications. Small increases in calcium concen-
trations have been associated with spirulina use, although it is
unclear whether this is due to the effects of spirulina alone. Con-
current use of spirulina and calcium supplements may further
increase calcium concentrations (NLM, 2009). Because of the
observed immunomodulatory activity of spirulina (Mao et al.,
2005; Hayashi et al., 1994;1998), its use potentially could in-
terfere with immunosuppressive therapies such as azathioprine,
cyclosporine, corticosteroids, and other medicines that have im-
munological effects. However, at present there is no evidence to
support this hypothesis.
Contaminants—Microcystin, Heavy Metals, and Microbial
Organisms
The primary concern with respect to the quality of spirulina
is the potential for contamination with other blue-green algae,
such as M. aeruginosa, that produce toxic microcystins. Micro-
cystins are known to be hepatotoxic and carcinogenic because
they inhibit protein phosphatases, PP1 and PP2A, leading to hy-
perphosphorylation of cellular proteins (WHO, 1999). Approx-
imately 60 congeners of microcystins (cyclic heptapeptides) are
known, and the predominant one is microcystin-LR. The lethal
dose (LD50) for microcystin-LR following oral administration
is approximately 5 mg/kg body weight in mouse and rat models
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600 R. J. MARLES ET AL.
(WHO, 1999; Fawell et al., 1999). The Health Canada (2008b)
review of cyanobacterial toxins suggested that a maximum ac-
ceptable concentration (MAC) for microcystin-LR in drinking
water is 1.5 ppb (1.5 µg/L).
In a mouse model the no observed adverse effect level
(NOAEL) for microcystin-LR was determined to be 40 µg/kg-
day in a 13-week oral dosing study (Fawell et al., 1999). Apply-
ing a 1000-fold uncertainty factor, the Oregon Health Division
(Gilroy et al., 2000) determined the permitted total daily in-
take (TDI) for microcystins to be 1 µg/g (1 ppm) in spirulina
products, assuming consumption of about 2 g/day spirulina by
adults. Health Canada has published a comparison of the various
methods available (ELISA, protein phosphatase inhibition as-
say, and LC-MS) to determine microcystin concentration levels
(Lawrence et al., 2001).
Because spirulina is either harvested from natural, warm,
alkaline waters or is grown under controlled salinity conditions,
the need to monitor spirulina product quality parameters
was recognized for the following contaminants: microcystins
(Gilroy et al., 2000; Lawrence et al., 2001), heavy metals
such as mercury, cadmium, lead, and arsenic (Johnson and
Shubert, 1986; Sandau et al., 1996), and microbial content (Wu
and Pond, 1981). Neurotoxic anatoxin-a and its metabolites
reportedly were not isolated from samples of food components
containing blue-green algae and spirulina collected in Portugal
and from urban centers across Canada in 2005 (Rawn et al.,
2007). A review of the human health risk assessment for toxins
in cyanobacterial blooms (with an emphasis on microcystins in
A. flos-aquae) concluded that public standards are important for
ensuring the quality of spirulina products (Dietrich et al., 2008).
Following the DSI-EC review, the proposed USP–NF mono-
graph for spirulina (S. platensis and S. maxima) will provide
specifications and methods of testing for the following param-
eters: microscopic description; limit of microcystins (assayed
by ELISA; not more than 1 ppm); heavy metals (according to
USP General Chapter <231>, not more than 10 µg/g); content
of protein (not less than 60%); and microbial enumeration (ac-
cording to USP General Chapter Microbiological Enumeration
Tests—Nutritional and Dietary Supplements <2021>).
Regulatory Status
FDA has not made a determination regarding the generally
recognized as safe (GRAS) status of spirulina (A. platensis).
However, FDA “had no questions” in response to the submis-
sion of a GRAS Notification package to the agency in which
a manufacturer concluded that spirulina has GRAS status for
use as an ingredient in foods such as specialty bars, powdered
nutritional drink mixes, and popcorn, and as a condiment in sal-
ads and pasta at quantities ranging from 0.5 to 3 g per serving
(FDA, 2003). In November 2008, an Indian company reported
that an independent panel of experts affirmed that the com-
pany’s organic spirulina was “self-affirmed GRAS” when used
at an acceptable daily intake (ADI) of 20 g per day and that it has
received permission to use the “USP Verified” mark from the
USP Dietary Supplements Verification Program (Parry, 2008).
A self-affirmed GRAS substance is one whose safety has been
evaluated in terms of evidence and scientific procedures per-
formed by qualified experts and determined to be safe under the
conditions of intended use (FDA Redbook, 2007). Left unan-
swered is how these GRAS substances differ, if at all, from the
spirulina products that have been associated with adverse events.
Also unknown is the quality standards of the spirulina products
purportedly causing the adverse effects. However, given the cur-
rent status of the DS AERs (Gardiner et al., 2008), it is unfortu-
nate that only a limited amount of information can be obtained
from them.
A search of the Dietary Supplements Labels Database
(DSLD, 2009) reveals that spirulina is found on the labels of
more than 80 dietary supplement products. The majority of
these products contain multiple components, and the content of
spirulina varies from 2 mg to 1000 mg in various formulations
such as powder, tablets, or proprietary blends. The maximum
recommended serving size for the powder was 7 g per day.
Although historically spirulina was used as a food or food
component, no quality monograph is found in the following
resources:
British Pharmacopoeia
European Pharmacopoeia
Health Canada
Pharmacopoeia of the People’s Republic of China
World Health Organization monographs
German Commission E monographs
WHO International Pharmacopoeia
Japanese Pharmacopoeia
Food Chemicals Codex
ESCOP monographs
British Herbal Compendium
Joint Expert Committee on Food Additives (JECFA) Com-
pendium of Food Additives
Codex Alimentarius
Because spirulina is legally marketed as a dietary supplement
in the US and is available in several countries, the current review
shows the need for quality standards.
DISCUSSION
As previously noted, spirulina has a long history of use as
a food and as a food component. Review of the data indicates
that two diverse populations, Aztecs in Mexico and natives of
the Sahara desert in Chad, harvested and utilized the nutritional
properties of spirulina as early as the 16th Century (Ciferri,
1983). Today, several dietary supplement and functional food
products containing spirulina are available in the US market.
Although historically spirulina has been used as a food
component, recent animal experiments led to the exploration
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USP SAFETY EVALUATION OF SPIRULINA 601
of possible immunomodulatory and antioxidant properties of
spirulina products in conventional dosage forms (powder or
capsules) or as functional foods (Mao et al., 2005; NBJ, 2009;
NLM, 2009), often in combination with other ingredients. Thus,
the modern uses of spirulina products as dietary supplements
and their accompanying structure–function claims (immune
system support, anti-oxidant properties, and anti-inflammatory
properties) are not totally in accordance with the historical uses
of spirulina as food. While these structure–function claims may
be based on experimental observations or empirical evidence,
additional insight is needed into the mechanisms of action,
short-term and long-term effects, and potential harms profile
to determine fully the safety of conventional usage of spirulina
products (Man, 2009).
Under US regulations spirulina is a “grandfathered”
dietary ingredient because it was legally marketed before
1994 (DSHEA, 1994). Accordingly, organized clinical dose-
escalation studies to observe safety profile are not required by
US law for spirulina-based supplements and are not available
for review. Another tool to measure the safety of a product
is postmarketing surveillance, which provides valuable infor-
mation about the safety profile of an ingredient in the general
population, in those consumers with chronic conditions, in vul-
nerable populations, and in special populations such as pregnant
or breast-feeding women, older people, children, and prescrip-
tion medication users. DSI-EC’s safety review found very few
such clinical study reports and no organized postmarketing
surveillance studies for products containing spirulina. A recent
review on the evidence-based application of spirulina in clinical
practice calls for fully powered clinical trials to substantiate
the purported positive effects of spirulina (Karkos et al., 2008).
DSI-EC culled 103 AERs for spirulina from several sources (3
clinical case reports, 79 MedWatch reports, 8 Canada CVP re-
ports, 8 Australian TGA reports, and 5 reports from the Uppsala
Monitoring Centre). Of these 103 AERs, DSI-EC reviewed 31
cases that contained minimal information (Tables 2–6). Causal
attribution for the AERs was challenging because of the data
limitations (Gardiner et al., 2008; Mahady et al., 2008). DSI-EC
observed that only a weak causality (possible rating) could be
attributed to most AERs according to the WHO causality scale
(WHO, 2004) or the Naranjo scale (Naranjo et al., 1981). Only
one case report from TGA (#182013) reported rechallenge
information, but even that case is likely to be an idiosyncratic
reaction because the patient initially took only 2 tablets of
spirulina and rechallenge occurred with only 1 tablet (quantity
of spirulina per tablet is unknown). The recent report from the
American Association of Poison Control Centers (Bronstein et
al., 2009) indicates only two cases of “moderate” (and none of
“major”) outcome for blue-green algae products in 2008.
The strengths and limitations of spontaneous AERs are well
documented (Gardiner et al., 2008). They provide important
safety information from a large and diverse exposed population,
compared to premarketing human clinical studies. The impor-
tance of AERs is the ability to detect rare adverse events. For in-
stance, to detect an adverse event with an incidence of 1 in 1000
(with 95% confidence), a clinical trial with 3000 patients is re-
quired (Lewis, 1981; Hanhley and Lippman-Hand, 1983; IOM,
2005). Further, as observed in an FDA-commissioned study,
the agency estimates that it receives less than 1% of all AERs
associated with dietary supplements (Woo, 2007). Thus, the
evaluation of the AERs aids in generation of important safety-
related hypotheses. The core information of an AER consists
of 1) the reporter, 2) the patient, 3) the suspect product, and
4) a narrative report of the adverse event. However, DS AERs
often require additional information, including details of the
DS product (e.g., dose/amount taken and duration of use, brand
name, manufacturer, exact names of ingredients as listed on the
product label, and the time between product administration and
the reaction) and patient characteristics (e.g., age, sex, concomi-
tant use of other medications such as over-the-counter and DS
products, and medical and social history such as smoking and
alcohol use). The DSI-EC review and analysis of the AERs were
affected by the quality of the available AER information. Be-
cause DSI-EC constantly monitors AERs concerning the safety
of supplements for which USP–NF monographs are developed,
the safety classification for spirulina may be reevaluated as new
information becomes available.
Recommended intake from several manufacturers of spir-
ulina products and other literature sources indicate that spirulina
consumption ranges from approximately 1 to 10 g per day, and
consumption of up to about 40 g a day is also not uncommon. For
this review, members of the DSI-EC critically read the AERs
to evaluate the relationship between the dose and duration of
use of spirulina at which AERs were observed and the typical
consumption of spirulina (1–10 g per day). Reflecting the lim-
itations of the current DS AER system (OIG, 2001), DSI-EC
could not establish this relationship from the available informa-
tion. Further, only limited relevant information is available from
animal studies in this regard. In a mouse model, oral adminis-
tration of 800 mg/kg bodyweight of spirulina for 2 weeks did
not lead to any toxic effects (Chamorro-Cevallos et al., 2008).
The total number of spontaneous AERs received is relatively
small, although the impact of the introduction of mandatory re-
porting of serious adverse events in the US remains to be seen. A
total of 16 AERs was filed with FDA’s MedWatch since January
2008, the period when serious adverse event reporting for di-
etary supplements became mandatory (Dietary Supplement and
Nonprescription Drug Consumer Protection Act, Public Law
109–462, 120 Stat. 3469). Further, researchers need to assess
the impact that current cGMP requirements for dietary supple-
ments have on product quality and reporting of adverse events.
This review also finds a need for further research on the safe
use of spirulina in special populations. For example, studies
are needed to ascertain the safety in usage of spirulina as a
dietary (protein) supplement by nursing women. The current
review found no information concerning appropriate use rec-
ommendations during lactation (Briggs et al., 2008; Blumenthal
et al., 2000; Bradley, 1992; Brinker, 2001; McGuffin et al.,
1997; Mills and Bone, 2005). DSI-EC encourages nursing
mothers to discuss the use of spirulina with their healthcare
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602 R. J. MARLES ET AL.
professionals. In accordance with USP–NF General Notices
relating to the labeling of botanical-containing products, the
proposed quality monograph for spirulina intended for use as
a dietary supplement will contain the following statement: “If
you are pregnant or nursing a baby, seek the advice of a health
professional before using this product.”
Contamination of spirulina with other Cyanobacteria (such
as M. aeruginosa) is a matter of serious concern because the
contaminating culture may produce hepatotoxic microcystins.
Eight cases of hepatotoxicity were associated with use of spir-
ulina products, including 1 case report by Iwasa et al. (1982)
(with concurrent simvastatin use), 5 MedWatch case reports (in-
cluding case #15515 involving significant prior medical history,
and case #67512 involving a multi-ingredient product), and 2
case reports from CVP (with a product of unknown identity
or quality and no data about intake or patient history). These
reports do not make clear if the hepatotoxic microcystins were
present as a result of contamination with other Cyanobacteria
such as M. aeruginosa. While some AERs indicated a rare pos-
sibility of liver damage from spirulina, data from some exper-
imental studies in animal models and clinical studies indicated
no hepatotoxicity from spirulina (B˘
aius¸ and T˘
an˘
asescu, 2002;
Torres-Duran et al., 1999; 2006).
Review of the toxicology of cyanobacteria suggests that
microcystins are not produced by spirulina, in contrast to some
other blue-green algal species (Health Canada, 2008a). The use
of other non-Spirulina species of Cyanobacteria as blue-green
algae, including A. flos-aquae and M. aeruginosa, which also
grow in natural, warm, alkaline waters is a safety concern.
Gilroy et al. (2000) and Lawrence et al. (2001) showed that
a significant portion of the commercially available spirulina
products exceed the limit of microcystins beyond 1 µg/g (1
ppm). The recent opinion from the Senate Commission on
Food Safety of the German Research Foundation (Eisenbrand
et al., 2008) expressed concerns about the concentrations of
microcystins in algal products used as food supplements. Cox
et al. (2005) reported isolation of neurotoxic β-N-methylamino-
L-alanine (BMAA) from 77% of the Cyanobacteria tested, but
the study did not include spirulina. A leading manufacturer
reported that its spirulina supplements did not contain BMAA
(NTP, 2008). Considering the risk of cyanobacterial toxins from
nonspirulina species in blue-green algae, conforming to quality
controls is very important to ensure the safety of spirulina.
DSI-EC DELIBERATIONS AND CONCLUSIONS
DSI-EC reviewed literature relating to the safety and tox-
icology of spirulina to determine whether spirulina could be
admitted into USP–NF as a quality monograph. After reviewing
the information reported here, DSI-EC unanimously decided
that the available evidence does not indicate a serious risk to
health or other public health concern that precludes admission
of a spirulina quality monograph into the compendium. Accord-
ingly, assignment of Class B (prohibiting monograph develop-
ment) is considered inappropriate for spirulina. DSI-EC based
this decision on the lack of a pattern in pathology, lack of in-
formation about the products and product quality, confounding
variables involving multi-ingredient formulations, and likeli-
hood that the reported adverse reactions may be due to toxic
microcystin contamination. The Committee determined that the
proposed monograph would need to include a method to test
for the presence of microcystins and that the microcystin con-
tent should be limited to NMT 1 ppm based on a review of the
available safety literature.
Considering the range of the data reviewed and because of the
limited information available in the AERs, DSI-EC unanimously
voted for a Class A safety assignment for S. maxima and S.
platensis, indicating that the available evidence does not indi-
cate a serious risk to health or other public health concern that
precludes admission of quality monographs into US–NF when
these dietary ingredients are properly identified, formulated, and
used. Based on this determination, USP is developing a qual-
ity monograph for spirulina and has verified a spirulina dietary
ingredient under its Dietary Ingredient Verification Program.
In accordance with USP’s continuous revision approach (USP,
2009), DSI-EC also reviews new information as it becomes
available in periodic safety revisions.
ACKNOWLEDGMENTS
DSI-EC thanks Stefan Schuber, PhD, ELS, director of sci-
entific reports, at USP for his editorial assistance. We thank
Australian TGA for providing us information about case
reports.
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