Effects of spirulina on weight loss and blood lipids: a review

Abstract

Spirulina, a cyanobacteria commonly referred to as a blue-green algae, is one of the oldest lifeforms on Earth. Spirulina grows in both fresh and saltwater sources and is known for its high protein and micronutrient content. This review paper will cover the effects of spirulina on weight loss and blood lipids. The currently literature supports the benefits of spirulina for reducing body fat, waist circumference, body mass index and appetite and shows that spirulina has significant benefits for improving blood lipids.

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1
DiNicolantonio JJ, etal. Open Heart 2020;7:e001003. doi:10.1136/openhrt-2018-001003
To cite: DiNicolantonio JJ,
Bhat AG, OKeefe J. Effects of
spirulina on weight loss and
blood lipids: a review. Open
Heart 2020;7:e001003.
doi:10.1136/
openhrt-2018-001003
Accepted 19 February 2020
1Mid America Heart Institute,
Kansas, Kansas, USA
2Department of Internal
Medicine, Baystate
Medical Center, Springeld,
Massachusetts, USA
3Department of Public Heath
Practice, School of Public Health
and Health Sciences, University
of Massachusetts, Amherst,
Massachusetts, United States
4Saint Lukes Mid America Heart
Institute, University of Missouri-
Kansas City, Kansas City,
Missouri, USA
Correspondence to
Dr James J DiNicolantonio;
jjdinicol@ gmail. com
Effects of spirulina on weight loss and
blood lipids: a review
James J DiNicolantonio ,1 Anusha G Bhat,2,3 James OKeefe 4
Editorial
© Author(s) (or their
employer(s)) 2020. Re- use
permitted under CC BY- NC. No
commercial re- use. See rights
and permissions. Published
by BMJ.
AbstrAct
Spirulina, a cyanobacteria commonly referred to as a
blue- green algae, is one of the oldest lifeforms on Earth.
Spirulina grows in both fresh and saltwater sources and is
known for its high protein and micronutrient content. This
review paper will cover the effects of spirulina on weight
loss and blood lipids. The currently literature supports
the benets of spirulina for reducing body fat, waist
circumference, body mass index and appetite and shows
that spirulina has signicant benets for improving blood
lipids.
INTRODUCTION
Spirulina is both a salt and fresh water blue-
green algae, which is being increasingly
studied recently. Spirulina was initially clas-
sified under the plant kingdom due to its
rich plant pigments and its ability to photo-
synthesize, but was later placed into bacterial
kingdom (cyanobacteria) due to its genetic,
physiological and biochemical makeup.1
Spirulina grows naturally in high salt alkaline
water reservoirs in subtropical and tropical
areas of America, Mexico, Asia and Central
Africa.1
Among the many varieties of spirulina,
the most commonly studied species are
Spirulina platensis (Arthrospora platensis),
Spirulina maxima (Arthrospora maxima) and
Spirulina fusiformis (Arthrospora fusiformis).
Spirulina is composed of numerous antioxi-
dants, including beta- carotene, phycocyanin,
tocopherols, micronutrients, polyunsatu-
rated fatty acids, particularly gamma- linolenic
acid and phenolic compounds. The high
nutritive values of spirulina were recognised
by the Intergovernmental Institution for
the use of Microalgae Spirulina Against
Malnutrition in the 1970s, where they
launched Spirulina to fight against starva-
tion and malnutrition.2 Spirulina has also
been recognised and recommended by
National Aeronautics and Space Admin-
istration and the European Space Agency
for food supplementation during long- term
space travels. Since then, there have been
numerous animal and human clinical trials
to determine its beneficial effects as a supple-
ment. Spirulina is a low- cost nutritional
supplement and has not been established to
have any significant side effects. Metabolic
syndrome is currently on rise3 and dyslipi-
daemia and obesity are an integral compo-
nent of its causation. While there are several
other supplements being evaluated for lipid
lowering and weight loss effects, benefits
from supplementation of spirulina are not
limited to the above benefits but also extends
to its antiviral, anticancer, antioxidant, anti-
diabetic, anti- inflammatory, hepatoprotec-
tive, cardioprotective and immunity boosting
properties.4 5 The primary aim of this article
is to review the effects of spirulina on obesity
and dyslipidaemia. Additionally, we also
discuss the potential mechanism of action
for the aforementioned effects.
Anti-inammatory effects of spirulina
The prevalence of obesity has nearly tripled
since 1975.6 According to the 2016 global
health report, more than 1.9 billion adults
were categorised as overweight; 650 million
among them being obese.7 Globally, approxi-
mately 2.8 million adults are estimated to die
every year from it.8 Obesity has been closely
linked to inflammation, hyperlipidaemia and
insulin resistance.9 10 This may be due to the
fact that adipose tissue secretes numerous
biologically active substances like adipokines
and chemokines, which play an important
role in inflammation and the development of
atherosclerosis.11
Although caloric restriction and exercise
are the mainstay treatments for obesity, spir-
ulina has shown significant benefits in aiding
weight loss. The phycocyanin in spirulina
contains a light- harvesting chromophore
called phycocyanobilin, which is capable of
inhibiting nicotinamide adenine dinucleo-
tide phosphate hydrogen (NADPH) oxidase,
a significant source of oxidative stress in
adipocytes playing a key role in inducing
insulin resistance and shifting adipokine
and cytokine production in hypertrophied
adipocytes. Thus, by suppressing adipocyte
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oxidative stress, spirulina may lead to systemic anti-
inflammatory and insulin- sensitising effects.12–20
Weight loss and blood lipids
Several clinical and preclinical trials have been
conducted to test the benefits of spirulina on weight loss.
Yousefi et al studied 52 obese participants with a body
mass index (BMI) >25–40 kg/m2 who were randomised
to 2 g spirulina per day with a restricted caloric diet
versus placebo consisting of a restricted calorie diet for
12 weeks. Participants in the spirulina group had signifi-
cantly lower body weight of −3.22+1.97 kg, waist circum-
ference −3.37 ± 2.65 kg, body fat of −2.28+1.74 kg and
BMI of −1.23±0.79 kg/m2 (p<0.001, p=0.049, p=0.049 and
p=0.02, respectively). Additionally, triglycerides (TG)
reduced by −18 mg/dL and high- sensitivity C reactive
protein levels were lower by −1.66±1.9 ng/mL towards
the end of the study period (p=0.03 and p=0.02, respec-
tively).21
Zeinalian et al studied 62 obese subjects after admin-
istering 1 g spirulina for 12 weeks and observed a signif-
icant reduction in appetite by −4.16% (p=0.008), BMI
by −1.9% (p<0.001), body weight by −1.79% (p<0.001)
and a reduction in total cholesterol (TC) by −4.67%
(p=0.002).22 Additionally, high density lipoprotein-
cholesterol (HDL- C) was noted to increase by 1.73%
(p=0.05) with no significant change in TG or low density
lipoprotein (LDL).
Several trials have also used Spirulina maxima to assess
its beneficial effects. In one study, 50 obese subjects with
hypertension under antihypertensive treatment were
given 2 g spirulina per day or placebo for 3 months.
Those given spirulina were found to have significant
improvements in their body mass from 92.96±18.58 kg to
88.97±17.13 kg (p<0.001), BMI from 33.5+6.7 kg/m2 to
31.7±5.8 kg/m2 (p<0.001) and waist circumference from
105.2±15.3 to 103.4+14.1 cm (p<0.002) versus baseline, a
benefit that was not shown with the placebo. Compared
with placebo- treated individuals, those given spirulina
had significantly lowered LDL- cholesterol (LDL- C)
from 3.5+0.9 mmol/L to 3.0±0.6 mmol/L (p<0.001) and
interleukin-6 from 4.3±0.6 mmol/L to 3.9+0.4 mmol/L
(p=0.002) and improved total antioxidant status from
1.8±0.3 to 2.2±1.0 mmol/L (p=0.001) and insulin sensi-
tivity ratio from 3.2±1.8 mg/kg/min to 4.3±2.1 mg/kg/
min (p<0.001).23
Mizcke et al in 2016 demonstrated benefits of spirulina
maxima in 40 hypertensive patients without evidence
of cardiovascular disease when supplemented with 2 g
of spirulina per day versus placebo for 3 months. In
those given spirulina, there was significant reduction
in BMI (26.9±3.1 vs 25.0±2.7 kg/m2, p=0.0032), weight
(75.5±11.8 kg vs 70.5±10.3 kg, p<0.001), systolic blood
pressure (149±7 mm Hg vs 143±9 mm Hg, p=0.0023) and
arterial stiffness index (7.2±0.6 vs 6.9±0.7 m/s, p<0.001),
thus proving beneficial cardiovascular effects with short-
term low- dose spirulina supplementation (table 1).24
BLOOD LIPIDS
Animal studies
Spirulina has been speculated to have lipid lowering
capabilities since 1981.25 Hypocholesterolaemic effect
was initially shown in animal trials.26 Later in 1990, Iwata
et al conducted the first preclinical trial on young and
healthy Wistar rats, which were artificially induced with
hyperlipidaemia by feeding a high- fructose diet. The
groups were either on high fructose diet alone (68%) or
on high- fructose diet with spirulina at 5%, 10% and 15%
concentrations for 4 weeks. Towards the end of the study
period, blood samples were obtained after administra-
tion of intravenous heparin injection at the dose of 200
U per 100 g body weight. The results revealed a signifi-
cant improvement in the lipid profile with concomitant
increased activity of lipoprotein lipase (LPL), although
the difference in lipid levels or LPL was not significantly
different between 5%, 10% or 15% spirulina concentra-
tion groups.27
The hypolipaemic effect of spirulina was also shown in
artificially induced diabetes in mice with administration
of alloxan (250 mg/kg body weight). With administra-
tion of 5% spirulina, hepatic triacylglycerols decreased.
Improvement in serum HDL and lowered serum LDL as
well as VLDL was also noted.28
Li et al found that spirulina given for 8 weeks increased
HDL- C and lowered LDL- C, TG and TC levels when fed
a high fat diet.29 Similar to other previous studies, it was
also shown to normalise hepatic steatosis with improve-
ments in liver function tests, including transaminases,
free fatty acids and overall lipid profile. This action was
thought to be secondary to activation of AMP- activated
protein kinase signalling pathway which subsequently
downregulates the expression of lipid synthesising genes,
namely sterol regulatory element- binding transcription
factor- 1c, 3- hydroxy-3- methyl glutaryl coenzyme A reduc-
tase and acetyl CoA carboxylase which ultimately reduce
TG levels and subsequently inhibit synthesis of fatty acids.
Additionally, spirulina can alter gut microbiota to have
lipid lowering effects. Studies have revealed an increase
in abundance of Prevotella, Porphyromonadaceae, Barnesiella
and Paraprevotella. Prevotella increases bile metabolism to
reduce blood lipid levels. Alloprevotella and Ruminococcus
are short chain fatty acid producers which can be digested
by the intestine. They regulate energy metabolism and
improve insulin sensitivity via specific receptors to ulti-
mately reduce lipid metabolism disorders and prevent
non- alcoholic liver disease. Firmicutes are another group
of bacteria which have been associated with reduction in
body weight and serum LDL- C levels, which improved
with spirulina supplementation.29
Clinical trials
The clinical trials on humans using spirulina include
healthy patients and those with dyslipidaemia, hyperten-
sion, postischaemic heart disease, diabetes, the nephrotic
syndrome and elderly patients. The response to spir-
ulina supplementation has been noted to differ between
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DiNicolantonio JJ, etal. Open Heart 2020;7:e001003. doi:10.1136/openhrt-2018-001003
Editorial
Table 1 Spirulina clinical studies: antiobesity benets
Year Author Participants Spirulina dose Changes in lipids Changes in diabetes
Changes in blood
pressures Changes in body weight
2018 Youse et al21 52 obese participants
what BMI>25 to 40 kg/
m2
2 g spirulina per
day with restricted
caloric diet vs
placebo consisting of
restricted calorie diet
for 12 weeks
Triglycerides reduced
by −18 mg/dL and high-
sensitivity C reactive protein
levels by −1.66±1.9 ng/mL
vs placebo
– – Signicantly lower body weight
of −3.22+1.97 kg, waist
circumference −3.37±2.65 kg, body
fat of −2.28+1.74 kg and BMI of
−1.23±0.79 kg/m2
2017 Zeinalian et al22 62 obese 1 g per day spirulina
for 12 weeks
HDL- C increased by 1.73%
(p=0.05)
– – Appetite reduced by −4.16%
(p=0.008), BMI by −1.9% (p<0.001),
body weight by −1.79% (p<0.001)
2017 Szulinska et al23 50 obese subjects with
hypertension
2 g per day spirulina
or placebo for 3
months
Signicantly lowered LDL- C
from 3.5+0.9 mmol/L to
3.0±0.6 mmol/L (p<0.001)
and interleukin-6 from
4.3±0.6 mmol/L to
3.9+0.4 mmol/L (p=0.002);
improved total antioxidant
status from 1.8±0.3 to
2.2±1.0 mmol/L (p=0.001)
Insulin sensitivity ratio
improved from 3.2±1.8 mg/
kg/min to 4.3±2.1 mg/kg/
min (p<0.001)
– Body mass reduced from
92.96±18.58 kg to 88.97±17.13 kg
(p<0.001), BMI reduced from
33.5+6.7 kg/m2 to 31.7±5.8 kg/m2
(p<0.001) and waist circumference
reduced from 105.2±15.3 to
103.4+14.1 cm (p<0.002) vs baseline
2016 Mizcke et al24 40 hypertensive
patients
2 g of spirulina
vs placebo for 3
months
– – Reduction in SBP
(149±7 mm Hg vs
143±9 mm Hg, p=0.0023)
and arterial stiffness index
(7.2±0.6 vs 6.9±0.7 m/s,
p<0.001) vs placebo
Signicant reduction in BMI (26.9±3.1
vs 25.0±2.7 kg/m2, p=0.0032), weight
(75.5±11.8 kg vs 70.5±10.3 kg,
p<0.001)
BMI, body mass index; HDL- C, high density lipoprotein- cholesterol; LDL- C, low density lipoprotein- cholesterol; SBP, systolic blood pressure.
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Table 2 Hyperlipidaemia- related clinical trials
Year Author Participants Spirulina Blood lipids BG BP Other effects
1988 Nakaya et al30 30 4.2 g per day×8 weeks
in group1; 4.2 g per day
spirulina×4 weeks in
group 2
Signicant reduction in TC; predominately higher among those
with higher serum TC and those with higher dietary content of TC.
– – No change in BW
1996 Ramamoorthy et al31 30 patients with
hypercholesterolaemia (TC>250 mg/
dL) with ischaemic heart disease
2g×3 months in group1;
4g×3 months in group
2 and group three being
control
Signicant lowering in TC, LDL, VLDL, TG and increase in HDL as
compared with the control group.
– – Signicant reduction in BW as
compared with control group.
2000 Mani et al34 15 T2DM 2 g spirulina×2 months Signicant lowering in TC, LDL, VLDL, TG and HDL- C: LDL- C ratio. Signicant reduction in BG. – –
2001 Parikh et al35 25 T2DM 2 g per day×2 months Signicant reduction in TG by 6.4 mg, LDL- C by 7.1 mg, TC by
21.3 mg (p<0.05) and atherogenic indices of TC:HDL- C from
5.4±1.0 to 5.0±1.0 (p<0.05) and LDL- C: HDL- C from 3.5±0.8 to
2.9±0.5 (p<0.05). Apolipoprotein B lowered by 16.1 mg (p<0.05);
apolipoprotein A1 levels increased by 11.4 mg (p<0.05).
Reduced fasting blood
glucose by 19.3 mg (p<0.05),
postprandial blood glucose by
16.1 mg (p<0.05), HbA1c by
1.0% (p<0.05)
– –
2008 Lee et al36 37 T2DM 8 g×12 weeks Signicant reduction in TGs (125.8– 98.5 mg/dL, p<0.05. – Reduced BP Antioxidant effects by lowering
plasma malondialdehyde levels
(p<0.05) and increasing plasma
adiponectin levels (p<0.1)
2002 Samuels et al37 23 paediatric Indian patients with
nephrotic syndrome
Steroid medications
alone or with 1 g/day×2
months
TC decreased signicantly by 116.33 mg/dL vs 69.87 mg/dL
in control); LDL by 94.14 mg/dL vs 61 mg/dL in controls and
triglycerides by 67.72 mg/dL vs 22.6 mg/dL in controls. LDL-
C:HDL- C ratio decreased by 1.66 vs 1.13 (p<0.05) and TC:HDL- C
decreased by 1.96 vs 1.19.
– – –
2003 Kim et al39 12 elderly patients aged 60–75 years 7.5 g/day for 24 weeks Signicant reductions in TG, TC and LDL fraction. – – No anthropometric changes
2005 Kim et al40 51 elderly females with
hypercholesterolaemia (TC >200 mg/
dL) aged 60 years and above
7.5 g/day for 8 weeks Signicant reduction in TC, LDL- C, oxidised LDL and
apolipoprotein B.
– – –
2008 Park et al42 78 individuals aged 60–87 year 8 g/day spirulina vs
placebo for 16 weeks
Signicant reduction in plasma TC and LDL noted.
IL-2 increased and IL-6 reduced.
– – –
2014 Mazokopakis et al32 Cretan Greek newly diagnosed with
dyslipidaemia
1 g per day for 3 months Signicant reduction in TGs by 16.3% (p<0.0001), LDL- C by
10.1% (p<0.0001), TC by 8.9% (p<0.0001), non- HDL- C by
10.8% (p<0.0001) and TC/HDL ratio by 11.5% (p=0.0006).
HDL- C increased by 3.5%.
HellenicSCORE revealing
a reduction in risk from
15.4% to 1.9%.
BG, blood glucose; BP, blood pressure; BW, body weight; HDL- C, high density lipoprotein- cholesterol; IL, interleukin; LDL- C, low density lipoprotein- cholesterol; TC, total cholesterol; TG, triglyceride; VLDL, very low density lipoprotein.
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Editorial
different ages, races, genders, comorbidities and dose/
duration of treatment.
One of the first clinical trials ever done using spirulina
was carried out in 1988 consisting of 30 healthy volun-
teers with mild hypertension or hyperlipidaemia. They
were treated in two groups, one of the groups received
8 weeks of 4.2 g of spirulina versus the other group
which received the same amount of spirulina for 4 weeks
followed by observation for another 4 weeks without any
supplementation. Results were notable for a significant
reduction in TC in the initial 4 weeks of spirulina supple-
mentation, which returned to baseline with its discontin-
uation. These changes in TC were directly proportional
to serum TC and dietary TC concentrations. There were
no changes in HDL, TG or body weight.30
Ramamoorthy et al established the hypolipaemic
effects of spirulina in patients with ischaemic heart
disease and hypercholesterolaemia (serum cholesterol
levels >250 mg/dL), where a total of 30 patients were
spilt into three groups. Groups 1 and 2 were treated
with 2 g or 4 g of spirulina for 3 months, while group 3
was a control arm. Towards the end of the study period,
plasma TC was lowered by 22.4% and 33.5% in group 1
and 2, respectively (p<0.01) and LDL by 31% and 45%
(p<0.01), which were both statistically significant reduc-
tions. Higher reductions in both LDL and TC were noted
among those treated with 4 g spirulina/day. In addition,
HDL- C increased, while TG and VLDL decreased in both
the experimental groups. However, there was no statis-
tical significance between the two experimental groups
while there was significant change when compared with
the control group. Similarly, body weight was reduced in
both the treatment groups while there were no changes
in lipid profiles or body weight in the control arm. The
reduction in body weight in both groups given spirulina
(−2.2 kg) was highly significant compared with control
(0.7 kg; p<0.01).31
Supplementation of 1 g spirulina for 3 months among
Cretan Greek patients with newly diagnosed dyslipi-
daemia also revealed significant improvements in dyslipi-
daemia. Mean levels of TGs reduced by 16.3% (p<0.0001),
LDL- C by 10.1% (p<0.0001), TC by 8.9% (p<0.0001),
non- HDL- C by 10.8% (p<0.0001) and TC/HDL ratio
by 11.5% (p=0.0006). Additionally, HDL- C increased by
3.5%, without any significant changes in weight, BMI or
blood pressures.30 The TG levels reduced by 17.2% on
an average; the reduction was higher (at 21.3%) among
women over 47 years old and those with TG>150 mg/dL
(18.6% reduction). HellenicSCORE is a scoring system
designed to assess risk for development of cardiovascular
disease and associated mortality among the Greek popu-
lation, and the overall cardiovascular risk level on Hellen-
icSCORE in this study projected a reduction in risk from
15.4% to 1.9% during the study period.32 33
In 15 patients with non- insulin dependent diabetes
mellitus, supplementation of 2 g/day of spirulina for 2
months leads to significant reductions in TG, TC, LDL- C,
VLDL- C and LDL- C/ HDL- C ratio.34 Similarly, Parikh et
al enrolled 25 type 2 diabetics and established that 2 g/
day of spirulina for 2 months in this population can lower
fasting blood glucose by 19.3 mg (p<0.05), postpran-
dial blood glucose by 16.1 mg (p<0.05), HbA1c by 1.0%
(p<0.05) in addition to lowering in TG by 6.4 mg, LDL- C
by 7.1 mg, TC by 21.3 mg (p<0.05) and overall reduction
in atherogenic indices of TC:HDL- C from 5.4±1.0 to
5.0±1.0 (p<0.05) and LDL- C: HDL- C from 3.5±0.8 to
2.9±0.5 (p<0.05). Additionally, apolipoprotein B was
lowered by 16.1 mg (p<0.05) with subsequent increases
in apolipoprotein A1 levels by 11.4 mg (p<0.05), thus a
favourable increase in A1:B ratio. However, the increase
in apo B levels with reduction in apo A1 level was also
significant among the control group. Nevertheless, this
study was able to establish improved short- term control
from spirulina on glucose and lipid profiles among
diabetics.35
Lee et al in 2008 tested 8 g/day of spirulina on 37
Korean subjects with T2DM (Type 2 diabetes mellitus)
for 12 weeks, which resulted in a significant reduc-
tion in TGs (125.8–98.5 mg/dL, p<0.05). Those with
higher plasma TG showed greater reductions in TG
levels. Similarly, the subjects with higher TC and LDL- C
levels showed greater reductions in TC, LDL- C and
improvement in blood pressure. The study also revealed
lowering in plasma malondialdehyde levels (p<0.05) and
increased plasma adiponectin levels (p<0.1), which are
indicative of a reduction in oxidative stress with spirulina
supplementation.36
Dyslipidaemia is a common comorbidity in patients
with nephrotic syndrome. Loss of plasma proteins in
the urine can cause low oncotic pressure, which leads
to hepatic production of albumin and other proteins
including lipoproteins, which can contribute to hyperlip-
idaemia. In this study, 23 paediatric patients with hyper-
cholesterolaemia and nephrotic syndrome, between the
age of 2 and 13 years were treated with steroid medi-
cations alone or in combination with 1 g/day spirulina
for 2 months. At the end of study period, TC decreased
by 116.33 mg/dL vs 69.87 mg/dL in control; LDL by
94.14 mg/dL vs 61 mg/dL in controls and triglycerides by
67.72 mg/dL vs 22.6 mg/dL in controls. LDL- C:HDL- C
ratio decreased significantly by 1.66 vs 1.13 (p<0.05) and
TC:HDL- C decreased by 1.96 vs 1.19. Thus, the overall
findings concluded that spirulina has significant hypolip-
idaemic effects in patients with nephrotic syndrome.37
Hyperlipidaemia and coronary vascular disease (CVD)
are known to increase with advancing age.38 Most of the
clinical trials testing spirulina supplementation on the
elderly population has been in Korea. One study included
12 Korean patients between the age 60 and 75 years old
who were supplemented with 7.5 g/day of spirulina for
24 weeks. The study found significant reductions in TGs,
TC and LDL after 4 weeks of spirulina supplementation.
There was no difference in the reduction among patients
with mild hypercholesterolaemia (TC at or above 200 mg/
dL) vs normocholesterolaemia.39 In 2005, another study
involved 51 elderly females with hypercholesterolaemia
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6DiNicolantonio JJ, etal. Open Heart 2020;7:e001003. doi:10.1136/openhrt-2018-001003
(TC >200 mg/dL) aged 60 years and above, where they
were supplemented with 7.5 mg/day spirulina for 8 weeks
in half of the study population and the other half were
given placebo. Findings were significant for reductions
in TC, LDL- C, oxidised LDL and apolipoprotein B.40 The
most recent randomised controlled trial included 78 indi-
viduals aged 60–87 years, who were randomly assigned to
8 g/day spirulina versus placebo for 16 weeks. The female
were noted to have higher mean TC and LDL- C and also
showed significant reductions in their plasma levels, TC
from 200.5 to 184.8 mg/dL (p=0.03) and LDL from 126.7
to 112.1 mg/dL (p=0.05).41 In addition, interleukin-2
(IL-2) was significantly increased (p<0.0001) and IL-6
was reduced (p<0.05) at the end of the study period. IL-2
has anti- inflammatory properties and is an important
regulator of chronic inflammatory response. IL-2 levels
reduce with increasing age; thus, supplementation with
spirulina may help to boost immunity in the elderly.42
A systematic review published in 2015 encompassing
eight humans studies concluded that spirulina has blood
lipid lowering benefits and antioxidant effects.43 Further-
more, a recent 2018 meta- analysis of 12 clinical studies
in humans showed that spirulina supplementation (1 g
up to 19 g per day) significantly lowered TC (−36.60 mg/
dL; p=0.0001), low- density lipoprotein cholesterol
(−33.16 mg/dL; p=0.0002), triglycerides (−39.2 mg/
dL; p=0.0001), very- low- density lipoprotein choles-
terol (−8.02 mg/dL; p=0.0001), fasting blood glucose
(−5.01 mg/dL; p=0.04) and diastolic blood pressure
(−7.17 mm Hg; p=0.001).41
Overall, the evidence in the literature suggests that spir-
ulina improves several well- established CVD risk factors
including hyperlipidaemia and seems to provide benefits
around weight loss. The variation in response in the clin-
ical trials is likely due to the difference in dose, duration
of treatment and responsiveness among patients based
on their comorbidities. As a whole, supplementing spiru-
lina at 2–8 g/ day may improve lipid profiles, particularly
by reducing TC, TG and LDL- c and improving HDL- c;
improving apolipoprotein A1 and reducing apolipopro-
tein B, aiding weight loss and reducing BMI. Spirulina
also seems to improve insulin resistance, antioxidant/
anti- inflammatory properties, blood glucose and blood
pressure as discussed in this article (table 2).
SUMMARY OF THE MECHANISMS OF ACTION OF SPIRULINA
►Faecal excretion of cholesterol and bile: In 2005, Nagoaka
et al demonstrated lower micellar solubility of choles-
terol with bile acids and as a result reduced absorp-
tion of fats in the small intestine with higher faecal
excretion of cholesterol and bile acid when fed with
spirulina concentrates. Additionally, phycocyanin
residue diet increased the proportion of cholesterol
excretion, thus indicating the hypolipaemic effects of
spirulina, particularly from phycocyanin.44
►Anti- inflammatory properties: Reactive oxygen species
are frequently associated with tissue inflammation
and damage. Due to Spirulina’s composition of the
blue- green pigments, particularly phycocyanobilin,
a water- soluble photosynthetic pigment possessing
extensive anti- inflammatory and antioxidant prop-
erties. Phycocyanobilin is structurally similar to
bilirubin and can inhibit NADPH oxidase. The anti-
oxidant activity of spirulina has been proven to be
directly proportional to the quantity of phycocyanin
(which contains phycocyanobilin).12–14 45
►Weight loss: The proposed mechanism of action of spir-
ulina is a reduction in macrophage infiltration into
visceral fat, prevention of hepatic fat accumulation,
reduction in oxidative stress, improvement in insulin
sensitivity and satiety.
►Improves satiety: Reduction in appetite may be due to
an improvement in leptin resistance in the arcuate
nucleus.
►Pancreatic lipase inhibition: One of the components of
spirulina is noted to be glycolipid H- b2, which inhibits
pancreatic lipase activity in a dose depended way, thus
reducing postprandial TG levels.46 Similar effects may
be exerted by phycocyanin as well.46
►Prevention of cholesterol accumulation by gamma- linolenic
acid: Spirulina is also composed of gamma- linolenic
acid (GLA). GLA is mostly formed from conversion
of LA in the presence of enzyme delta-6- desaturase,
which may be inhibited with mineral deficiencies,
alcohol/tobacco abuse, infections, ageing and other
severe medical conditions. Moreover, GLA deficien-
cies may worsen arterial thickness, hypertension and
dyslipidaemia.47 48 Additionally, spirulina also contains
vitamin B3, also called niacin, which is also known to
improve dyslipidaemia.49
Overall, spirulina has several benefits for improving
weight loss, dyslipidaemia and obesity. However, further
research including larger clinical trials would be
warranted for confirming these benefits.
Contributors All authors contributed to the nal manuscript.
Funding The authors have not declared a specic grant for this research from any
funding agency in the public, commercial or not- for- prot sectors.
Competing interests JJD is the author of The Salt Fix and Superfuel. JO is owner
of a nutraceutical company but the company does not sell spirulina.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non- commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
is non- commercial. See:http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.
ORCID iDs
James JDiNicolantonio http:// orcid. org/ 0000- 0002- 7888- 1528
JamesOKeefe http:// orcid. org/ 0000- 0002- 3376- 5822
RefeRences
1 Venkataraman LV. Spirulina platensis (Arthrospira): physiology, cell
biology and Biotechnologym edited by Avigad Vonshak 1997.
on March 9, 2020 by guest. Protected by copyright.http://openheart.bmj.com/Open Heart: first published as 10.1136/openhrt-2018-001003 on 8 March 2020. Downloaded from

7
DiNicolantonio JJ, etal. Open Heart 2020;7:e001003. doi:10.1136/openhrt-2018-001003
Editorial
2 Habib MAB. A review on culture, production and use of Spirulina as
food for humans and feeds for domestic animals and sh / M. Ahsan
B. Habib, Tim C. Huntington, Mohammad R. Hasan. Rome, Italy:
Food and Agriculture Organization of the United Nations, 2008.
3 Saklayen MG. The global epidemic of the metabolic syndrome. Curr
Hypertens Rep 2018;20:12.
4 Serban M- C, Sahebkar A, Dragan S, etal. A systematic review and
meta- analysis of the impact of Spirulina supplementation on plasma
lipid concentrations. Clin Nutr 2016;35:842–51.
5 Stepien M, Kujawska- Luczak M, Szulinska M, etal. Benecial
dose- independent inuence of Camellia sinensis supplementation
on lipid prole, glycemia, and insulin resistance in an NaCl- induced
hypertensive rat model. J Physiol Pharmacol 2018;69.
6 Ng M, Fleming T, Robinson M, etal. Global, regional, and national
prevalence of overweight and obesity in children and adults during
1980-2013: a systematic analysis for the global burden of disease
study 2013. Lancet 2014;384:766–81.
7 World Health Organization. Global status report on
noncommunicable diseases 2014, 2014. Available: https://www. who.
int/ nmh/ publications/ ncd- status- report- 2014/ en/
8 World Health Organization. Obesity and overweight, 2018. Available:
https://www. who. int/ news- room/ fact- sheets/ detail/ obesity- and-
overweight [Accessed 16 Feb 2018].
9 Park HS, Park JY, Yu R. Relationship of obesity and visceral
adiposity with serum concentrations of CRP, TNF- alpha and IL-6.
Diabetes Res Clin Pract 2005;69:29–35.
10 Shah A, Mehta N, Reilly MP. Adipose inammation, insulin
resistance, and cardiovascular disease. JPEN J Parenter Enteral Nutr
2008;32:638–44.
11 Skrypnik K, Suliburska J, Skrypnik D, etal. The genetic basis of
obesity complications. Acta Sci Pol Technol Aliment 2017;16:83–91.
12 Terry MJ, Maines MD, Lagarias JC. Inactivation of phytochrome-
and phycobiliprotein- chromophore precursors by rat liver biliverdin
reductase. J Biol Chem 1993;268:26099–106.
13 Zheng J, Inoguchi T, Sasaki S, etal. Phycocyanin and
phycocyanobilin from Spirulina platensis protect against diabetic
nephropathy by inhibiting oxidative stress. Am J Physiol Regul Integr
Comp Physiol 2013;304:R110–20.
14 Strasky Z, Zemankova L, Nemeckova I, etal. Spirulina platensis and
phycocyanobilin activate atheroprotective heme oxygenase-1: a
possible implication for atherogenesis. Food Funct 2013;4:1586–94.
15 Talior I, Tennenbaum T, Kuroki T, etal. PKC- delta- dependent
activation of oxidative stress in adipocytes of obese and insulin-
resistant mice: role for NADPH oxidase. Am J Physiol Endocrinol
Metab 2005;288:E405–11.
16 Furukawa S, Fujita T, Shimabukuro M, etal. Increased oxidative
stress in obesity and its impact on metabolic syndrome. J Clin Invest
2004;114:1752–61.
17 Han CY, Umemoto T, Omer M, etal. NADPH oxidase- derived
reactive oxygen species increases expression of monocyte
chemotactic factor genes in cultured adipocytes. J Biol Chem
2012;287:10379–93.
18 Lin L, Pang W, Chen K, etal. Adipocyte expression of PU.1
transcription factor causes insulin resistance through upregulation of
inammatory cytokine gene expression and ROS production. Am J
Physiol Endocrinol Metab 2012;302:E1550–9.
19 Jankovic A, Korac A, Buzadzic B, etal. Redox implications in
adipose tissue (dys)function- A new look at old acquaintances. Redox
Biol 2015;6:19–32.
20 Prokudina ES, Maslov LN, Ivanov VV, etal. [The Role of Reactive
Oxygen Species in the Pathogenesis of Adipocyte Dysfunction in
Metabolic Syndrome. Prospects of Pharmacological Correction].
Vestn Ross Akad Med Nauk 2017;72:11–16.
21 Youse R, Mottaghi A, Saidpour A. Spirulina platensis effectively
ameliorates anthropometric measurements and obesity- related
metabolic disorders in obese or overweight healthy individuals: a
randomized controlled trial. Complement Ther Med 2018;40:106–12.
22 Zeinalian R, Farhangi MA, Shariat A, etal. The effects of Spirulina
platensis on anthropometric indices, appetite, lipid prole and serum
vascular endothelial growth factor (VEGF) in obese individuals:
a randomized double blinded placebo controlled trial. BMC
Complement Altern Med 2017;17:225.
23 Szulinska M, Gibas- Dorna M, Miller- Kasprzak E, etal. Spirulina
maxima improves insulin sensitivity, lipid prole, and total
antioxidant status in obese patients with well- treated hypertension:
a randomized double- blind placebo- controlled study. Eur Rev Med
Pharmacol Sci 2017;21:2473–81.
24 Miczke A, Szulińska M, Hansdorfer- Korzon R, etal. Effects of
spirulina consumption on body weight, blood pressure, and
endothelial function in overweight hypertensive Caucasians: a
double- blind, placebo- controlled, randomized trial. Eur Rev Med
Pharmacol Sci 2016;20:150–6.
25 Chen LC, Chen JS, Tung TC. [Effects of spirulina on serum
lipoproteins and its hypocholesterolemic activities]. Taiwan Yi Xue
Hui Za Zhi 1981;80:934–42.
26 Kato T, Takemoto K, Katayama H, etal. Effects of Spirulina (Spirulin
a platensis) on dietary hypercholesterolemia in rats. Nippon Eiyo
Shokuryo Gakkaishi 1984;37:323–32.
27 Iwata K, Inayama T, Kato T. Effects of Spirulina platensis on plasma
lipoprotein lipase activity in fructose- induced hyperlipidemic rats. J
Nutr Sci Vitaminol 1990;36:165–71.
28 Rodríguez- Hernández A, Blé-Castillo JL, Juárez- Oropeza MA, etal.
Spirulina maxima prevents fatty liver formation in CD-1 male and
female mice with experimental diabetes. Life Sci 2001;69:1029–37.
29 Li T- T, Liu Y- Y, Wan X- Z, etal. Regulatory Efcacy of the
Polyunsaturated Fatty Acids from Microalgae Spirulina platensis on
Lipid Metabolism and Gut Microbiota in High- Fat Diet Rats. Int J Mol
Sci 2018;19. doi:10.3390/ijms19103075. [Epub ahead of print: 09
Oct 2018].
30 Nakaya N, Homma Y, Goto Y. Cholesterol lowering effect of spirulina.
Nutrition reports international 1988;37:1329–37.
31 Ramamoorthy A, Premakumari S. Effect of supplementation of
Spirulina on hypercholesterolemic patients 1996.
32 Mazokopakis EE, Starakis IK, Papadomanolaki MG, etal.
The hypolipidaemic effects of Spirulina (Arthrospira platensis)
supplementation in a Cretan population: a prospective study. J Sci
Food Agric 2014;94:432–7.
33 Panagiotakos DB, Fitzgerald AP, Pitsavos C, etal. Statistical
modelling of 10- year fatal cardiovascular disease risk in Greece: the
HellenicSCORE (a calibration of the ESC score project). Hellenic J
Cardiol 2007;48:55–63.
34 Mani UV, Desai S, Iyer U. Studies on the long- term effect of Spirulina
supplementation on serum lipid prole and glycated proteins in
NIDDM patients. J Diet Suppl 2000;2:25–32.
35 Parikh P, Mani U, Iyer U. Role of Spirulina in the control of glycemia
and Lipidemia in type 2 diabetes mellitus. J Med Food 2001;4:193–9.
36 Lee EH, Park J- E, Choi Y- J, etal. A randomized study to establish
the effects of spirulina in type 2 diabetes mellitus patients. Nutr Res
Pract 2008;2:295–300.
37 Samuels R, Mani UV, Iyer UM, etal. Hypocholesterolemic effect of
spirulina in patients with hyperlipidemic nephrotic syndrome. J Med
Food 2002;5:91–6.
38 Castelli WP, Wilson PW, Levy D, etal. Cardiovascular risk factors in
the elderly. Am J Cardiol 1989;63:12–19.
39 Kim WY, Park JY. The effects of Spirulina on lipid metabolism,
antioxidant capacity and immune function in Korean Elderlies.
Korean J Nutr 2003;36:287–97.
40 Kim WY, Kim MH. The change of lipid metabolism and
immune function caused by antioxidant material in the
hypercholesterolemic elderly women in Korea. Korean J Nutr
2005;38:67–75.
41 Huang H, Liao D, Pu R, etal. Quantifying the effects of spirulina
supplementation on plasma lipid and glucose concentrations,
body weight, and blood pressure. Diabetes Metab Syndr Obes
2018;11:729–42.
42 Park HJ, Lee YJ, Ryu HK, etal. A randomized double- blind, placebo-
controlled study to establish the effects of spirulina in elderly
Koreans. Ann Nutr Metab 2008;52:322–8.
43 Hernández Lepe MA, Wall- Medrano A, Juárez- Oropeza MA, etal.
Spirulina and its hypolipidemic and antioxidant effects in humans: a
systematic review]. Nutr Hosp 2015;32:494–500.
44 Nagaoka S, Shimizu K, Kaneko H, etal. A novel protein C-
phycocyanin plays a crucial role in the hypocholesterolemic action of
Spirulina platensis concentrate in rats. J Nutr 2005;135:2425–30.
45 Piñero Estrada JE, Bermejo Bescós P, Villar del Fresno AM.
Antioxidant activity of different fractions of Spirulina platensis
protean extract. Farmaco 2001;56:497–500.
46 Han L- K, Li D- X, Xiang L, etal. [Isolation of pancreatic lipase
activity- inhibitory component of spirulina platensis and it reduce
postprandial triacylglycerolemia]. Yakugaku Zasshi 2006;126:43–9.
47 Hornych A, Oravec S, Girault F, etal. The effect of gamma- linolenic
acid on plasma and membrane lipids and renal prostaglandin
synthesis in older subjects. Bratisl Lek Listy 2002;103:101–7.
48 Horrobin DF. Nutritional and medical importance of gamma- linolenic
acid. Prog Lipid Res 1992;31:163–94.
49 Zeb Shah T, Ali AB, Ahmad Jafri S, etal. Effect of Nicotinic Acid
(Vitamin B3 or Niacin) on the lipid prole of diabetic and non -
diabetic rats. Pak J Med Sci 2013;29:1259–64.
on March 9, 2020 by guest. Protected by copyright.http://openheart.bmj.com/Open Heart: first published as 10.1136/openhrt-2018-001003 on 8 March 2020. Downloaded from