Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial

Article (PDF Available)inBMC Gastroenterology 12(1):32 · April 2012with41 Reads
DOI: 10.1186/1471-230X-12-32 · Source: PubMed
Abstract
Spirulina platensis, a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities. It had been found to activate macrophages, NK cells, T cells, B cells, and to stimulate the production of Interferon gamma (IFN-γ) and other cytokines. Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells. We aimed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation. Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been randomized to either Spirulina or Silymarin treated groups for a period of six months treatment.The two groups were followed up and blindly compared for early (after 3 months) and end of 6 months treatment virological response. The effects of both treatments on each of alanine aminotransferase (ALT), Chronic Liver Disease Questionnaire scores (CLDQ), Arizona Sexual Experience Scale scores (ASEX) and the occurrence of any attributable adverse events were also compared. Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol, 4 patients (13.3%) had a complete end of treatment virological response and 2 patients (6.7%) had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs10. Though the proportion of responders in Spirulina group was greater than in the Silymarin group, the difference was not statistically significant at the end of both 6 months (p = 0.12) and 3 months treatment (p = 0.22) by Exact test. Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group. Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results. WHO Clinical Trial Registration ID: ACTRN12610000958088http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088.
RESEARCH ARTICLE Open Access
Spirulina platensis versus silymarin in the
treatment of chronic hepatitis C virus infection.
A pilot randomized, comparative clinical trial
Mostafa Yakoot
1*
and Amel Salem
2
Abstract
Background: Spirulina platensis, a cynobacterium used frequently as a dietary supplement had been found to
exhibit many immune-stimulating and antiviral activities . It had been found to activate macrophages, NK cells,
T cells, B cells, and to stimulate the production of Interferon gamma (IFN-g) and other cytokines. Natural substances
isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by
blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells.
We aimed to study whether this dietary supplement possesses any therapeutically feasible act ivity worthy of
further larger controlled clinical evaluation.
Methods: Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been randomized
to either Spirulina or Silymarin treated groups for a period of six months treatment.
The two groups were followed up and blindly compared for early (after 3 months) and end of 6 months treatment
virological response. The effects of both treatments on each of alanine aminotransferase (ALT), Chronic Liver
Disease Questionnaire scores (CLDQ), Arizona Sexual Experience Scale scores (ASEX) and the occurrence of any
attributable adverse events were also compared.
Results: Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol, 4
patients (13.3%) had a complete end of treatment virological response and 2 patients (6.7%) had a partial end of
treatment response defined as significant decrease of virus load of at least 2-logs
10
. Though the proportion of
responders in Spirulina group was greater than in the Silymarin group, the difference was not statistically
significant at the end of both 6 months (p = 0.12) and 3 months treatment (p = 0.22) by Exact test. Alanine
aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than
in Silymarin treated group.
Conclusions: Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV
patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging
results.
Trial Registration: WHO Clinical Trial Registration ID: ACTRN12610000958088
http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088
Keywords: Chronic HCV, Spirulina platensis, Cyanobacteria, Silymarin, Safety and Efficacy
* Correspondence: yakoot@yahoo.com
1
Green Clinic and Research Centre, Alexandria 21121, Egypt
Full list of author information is available at the end of the article
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© 2012 Yakoot and Salem; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
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reproduction in any medium, provided the original work is properly cited.
Background
Infection with hepatitis C virus (HCV), an enveloped
virus that belongs to the Flaviviridae family of positive-
strand RNA viruses, is a major cause of chronic li ver
disease. WHO estimated that about 170 million people,
(3% of the worlds populat ion), are i nfected with HCV
and 3-4 million persons are newly infected each year
[1-3].
Prevalence rates vary widely, ranging from 0.15% in
Scandinavia to about 15% in Egypt [4]. The o verall pre-
valence in the United States is 1.8%, corresponding to
an estimated 3.9 million persons with HCV infection [5].
About 80% of newly infected patients progress to
develop chronic infection. Cirrhosis develops in about
10% to 20% of persons with chronic infection. Liver can-
cer develops in 1% to 5% of persons with chronic infec-
tion over a period of 20-30 years [5,6].
Apart from its numerous contraindications and severe
adverse effects, the current recommended treatment for
chronic hepatitis C is not only too costl y for most per-
sons in developing countries to afford but also weakly
effective [6].
A meta-analysis showed that only about 17% of
patients with chronic hepatitis C obtained a sustaine d
virological response on interferon monotherapy, which
was t he only recommended treatment until the late
1990 [7].
The current gold standard therapy is a combination of
peg-interferon alfa and ribavirin [8,9]. Patien ts with gen-
otype 1 infection have a 42%-51% likelihood of achieving
a sustained virological response (SVR) after 48 wk of
therapy. For patients with genotype 4 (approximately
90% of patients with hepatitis C in Egypt), the sustained
virological response (SVR) rate with 48 weeks of therapy
ranges from 50% to 60%. A significan t proportion of
treated patients thus either fail to respond or relapse fol-
lowing an initial response, and a substantial number of
patients are unable to tolerate treatment [10].
Though around 78%-82% of patients with genotype 2
or 3 infection respond to 24 wk of treatment, those with
high viral load are difficult to treat (< 70% responders)
[11].
Generally, non-responders to prio r standard bitherapy
respond to retreatment in about 13% of the cases and
relapsers in 58.5% of the cases [12].
Therapy requires weekly subcutane ous injection s,
twice-daily oral dosing and frequent visits, with blood
tests. Side effects occur in nearly all patients. As a result,
15%-20% of patients in clinical trials and > 25% in clini-
cal practice discontinue therapy.
Ribavirin does not appear to be effective when used
alone. Furthermore, there is no clear evidence as to
whether treatment reduces the risk of liver related mor-
bidity or mortality [13].
An alternative treatment which is less costly, safer and
more efficacious is bei ng the search of ma ny research
authorities al-over the world.
Many herbal products had been studied and proved to
offer some hepatoprotective activity and showed some
benefit s in the treatment of viral hepatitis, Glycyrrhizin,
Silymarin, Curcumin, Schiszandra are examples [14-18].
Spirulina is a blue-green alga (cyanobacterium) that has
been consumed as food in many countries since ancient
times. It is presently marketed as a food supplement
(nutraceutical) due to its high contents of proteins, g-lino-
lenic acid, vitamins and minerals [19]. Many toxicological
studies have proven Spirulinas safety. Spirulina now is
listed by the US Food and Drug Administration under the
category Generally Recognized as Safe (GRAS) [20-24].
Spirulina and many other Cyanobacteria had been found
to exhibit many immune-stimulating and antiviral activ-
ities not only in-vitro but also in animals and human
volunteers. It had been found to activate macrophages,
NK cells, T cells, B cells, and to stimulate the production
of antibodies and cytokines. It enhances Interferon gamma
(IFN-g) production in an interleukin12, 18 (IL-12/IL- 18)-
dependent fashion [25-29].
Many natural substances derived from blue-green algae
such as Sulfated homopolysaccharides and Sulfoglycolipids
demonstrated monocyte/macrophage activation properties
and found to substantially increase mRNA levels of key
cytokines like interleukin-1beta (IL-1beta) and tumor
necrosis factor-alpha (TNF-alpha) [30].
Calcium spirulan (Ca-SP), a natural sulfated polysac-
chari de, isolated from Spirulina platensis had been found
to be a potent inhibitor agains t several enveloped viruses.
Ca-SP was shown to target not only viral absorption/
penetration stages but also some replicat ion stages of
progeny viruses after penetration into cells [31,32].
Whereas Cyanovirin-N (CV-N)[33-35] an d Microvirin
(MVN)[36,37] are two examples of mannose specific lec-
tins isolated from blue green algae. They had been
found to potently inactivate diverse strains of HIV and
other enveloped viruses in nanomolar concentrations
through preventing essential interactions between the
virus envelope glycoprotein and target cell re ceptors
[33-35].
At low nanomolar concentrations, CV-N was demon-
strated to bind to H CV envelope glycoproteins, t o block
the interaction between the envelope protein E2 and
CD81, a ce ll surface molecul e involved in HCV entry
[38,39].
The availability of Spirulina as an over the counter
safe dietary supplement with reasonable costs added to
the abovementioned data supporting both antiviral and
immune-stimulant activities urged us to conduct this
pilot clinical trial to test safety and eff icacy of this sup-
plement in patients with chronic hepatitis C.
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Methods
Study design and setting
The study was c onducted in an o utpatient setting
according to a randomized, double-blind, comparative
study design with mean follow-up of 6 months.
Patients
Sample size
To detect a 0.17 difference in proportion of responders
between both compar ison groups, with 80% po wer and
two tailed 5% level of significance, the minimal sample
size was calculated to be 30 for each group.
Sixty six eligib le patients with documented chronic
hepatitis C, genot ype 4 had been included in the study
according to the following criteria:
Inclusion criteria
Chronic hepatitis C infection genotype 4 with PCR
positive test +/- elevated liver enzymes.
Males or females between 18 and 70 years old.
Interferon naive (not previously treated with inter-
feron alone or combined with ribavirin therapy).
Relapsers (patients with a t ransient virological
response to previous interferon or combined therapy),
or non-responders to interferon or combined therapy
areeligibleiftheystoppedthe antiviral d rugs at least
3 months before recruitment.
Exclusion criteria
Pregnant females.
Patients with other causes of hepatitis, concurrent
HIV virus infection, or active Schistosomiasis.
Critically ill complicated patients with severe hepatic
failure, malignancy or multi-organ failure.
The study protocol was reviewe d and app roved by the
local ethical committee according to the Declaration of
Helsinki. All subjects gave written, informed consent
before any study-related procedures were performed.
Eighty five consecutive patients presenting to the 2
outpatient clinics from October 2008 to March 2010 as
known cases of chronic hepatitis C infection or just
newly diagnosed from history, clinical examination, 3
rd
generation ELISA plus/or minus elevated liver enzymes
were assessed for eligibili ty, by bein g subjected to full
history taking, clinical ex amination and the following
tests:
Detection of HCV-RNA by PCR q uantitative mea-
surements by COBAS Amplicor 2. 0, Roche Molecular
Diagnostics, Pleasanton, CA, USA (lower lim it of detec-
tion of 50 IU/mL).
Screening test for HBsAg, anti-HIV, Shistosoma
antigens.
Upper abdominal and liver ultrasonography,
Liver and kidney functions tests, urine analysis,
stools analysis, complete blood count.
Patients fulfilling the inclusion/exclusion c riteria were
randomly divided into 2 arms:
1. An experi ment al group who st arted treatmen t with
Spirulina 500 mg dry powder ext ract capsules (a product
of Beovita-Safe Pharma, a German - Egyptian Pharmaceu-
tical Company, headquartered in Alexandria, Egypt) in a
dose of one capsule 3 times daily for a period of 6 months.
2. A control group who took Silymarin 140 mg cap-
sules (generic product prepared by the same company)
in a dose of one capsule 3 times daily for the same
period.
Both drugs w ere packed in similar containers of 60
capsules of similar color and shape, packed and coded
by Beovita Safe Company researchers blinded to the
randomization process.
Randomization was done using software generated
block randomization technique and both patients a nd
investigators were blinded for the allocated drug. The
randomization list and the drug codes were locked in
sealed envelopes till the end of follow up period, final
assessment and statistical analysis.
Outcome measures
1. Complete virological response (defined as loss of
detectable hepatitis C virus RNA at the end of 6 months
treatment (c-ETR) and at the end of 3 months treat-
ment (complete early virological response (c-EVR)).
2. Partial virological response (defined as reduction of
virus load by a minimum 2-log
10
)attheendof3
months (p-EVR) and 6 months (p-ETR).
3. Biochemical response (normalization or significant
reduction of elevated alanine tranaminase (ALT) at the
end of treatment.
4. Improvement of health related quality of life scoring
using the Chronic Liver Disease Questionnaire (CLDQ)
developed by Younossi ZM et al. [40,41] The CLDQ
includes 29 items in the following domains: abdominal
symptoms, fatigue, systemic symptoms, activity, emo-
tional function and worry. The response of CLDQ
results in 1 to 7 scales: ranging from 1 = all of the time
(worst) to 7 = none of the time (best). We compared
thechangeofthefinalCLDQoverallscorefrombase-
line. CLDQ overall score is calculated by dividing the
total score by the total number of items (29) resulting
in a 1 to 7 scale [40,41].
5. The change in The Arizona Sexual Experiences
Scale (ASEX) scores before and aft er 6 months of treat-
ment was compared between groups. ASEX is a 5-item
rating scale that quantifies sex drive, arousal, penile
erection /vaginal lubrication, ability to reach orgasm, and
satisfaction from orgasm. Possible total scores range
from 5 to 30, with lower scores reflecting enhanced sex-
ual function and higher scores reflecting impaired sexual
function [42].
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6. Occurrence of adverse events and toxicity: All sub-
jects were examined and interrogated at each follow up
visit for the occurrence and nature of any adverse
events. All such events were recorded in the patients
case report forms. Adverse e vents were assessed for
causality as probably related, possibly related, unlikely to
be related or not related to study medications.
All patients in both groups had been followed up in
monthly v isits with physical examination, assessment of
CLDQ and ASEX scorings, hematological studies, liver
and kidney function t ests and abdominal ultra-sono-
grams. Quantitative HCV-RNA by PCR test was done
for each patient before treatment and after 3 and
6 months.
Statistical analysis
Data were analyzed using the computer software pack-
age SPSS version 12, SPSS Inc. 233 South Wacker
Drive, 11th Floor, Chicago, IL. Comparisons between
means of paired scale variables before and after treat-
ment were done using paired sample t test. Compari-
sons of means of scal e depe ndent variables between the
independent treatment groups were done using one way
ANOVA or Student t test for independent samples.
Z test for proportions, or Fishers Exact tests were used
for ana lysis of proport ions and catego rical vari ables.
Multivariate analysis of covariance (MANCOVA) using
the treatment group as the fixed independent factor
with the baseline Child-Pugh score and the pre-treat-
ment virus l oad as covariates to adjust for any initial
group differences on the dependent outcome variables
(the difference betw een baseline and post-treatment
CLDQ and ASEX scores and their interaction). Statisti-
cal significance is considered when two sided p < 0.05.
Results
Sixty six eligi ble patients had been randomized to either
Spirulina or Silymarin treatment groups. All patients
hadbeenfollowedupforaperiodof6monthstreat-
ment. Four patients from Silymarin group and three
patients from Spiruli na group did not complete the pro-
tocol (see Flowchart in Figure 1).
The baseline characteristics were almost matched in
both groups (Table 1).
Among the 30 patients who had been treated with Spir-
ulina and completed the 6 months protocol, 4 patients
(13.3%) had a complete end of treatment virological
response. While 2 patients (6.7%) had partial end of treat-
ment response defined as significant decrease of virus
load of at least 2-log
10
at the end of 6 months treatment.
No virological response (non-ETR) (defined as no reduc-
tion of at least 2 logs
10
from the baseline virus load) was
reported in the r emaining 80% of Spirulina treated gro up
(Table 2). While the Silymarin treated group showed
complete end of trea tment virological response in only
one case (3.4%) and no virological response in the
remaining 96.6% of the 29 patients who completed the
full protocol. Though the proportion of responders in
Spirulina g roup was greater than in the Silymarin group;
the difference was not statistically significant at the end
of both 6 months (p = 0.12) and 3 months treatment (p =
0.22) by Exact test (Table 2). The log transformed virus
load levels at baseline, 3 months and 6 months follow up
visits for each treatment gro up were further illustrated in
a Boxplot graph in (Figure 2).
All the 4 Spirulina treated patients who exhibited c-ETR
were from those who had presented with low baseline vir-
emia (virus load 100000 IU/mL). The lower the baseline
viremia the higher was t he response rate, as shown in a
3 × 3 table (Table 3) and verified by FishersExactTest
(value = 8.9, p = 0.028). Whereas out of those patients
with baseline virus load less than 2 millions IU/mL, 6 of
27 (22.2%) in Spirulina group versus 1 of 28 (3.6%) in Sily-
marin group exhibited at least a partial or complete virolo-
gical response at the end of 6 months treatment. The
calculated Z value was 1.67 which was not significant (p =
0.09) at the predetermined two sided 5% level of signifi-
cance, but it reached statistical significance with one
sided Ztestforproportions(p=0.047).
Prior to therapy, elevated serum alanine aminotransfer-
ase (ALT) had been reported in 17 out of the 30 Spirulina
assigned patients and in 15 of the 29 Silymarin group. The
mean (SD) of baseline serum ALT was 74.7 (35) and
78 (33.7) respectively. At t he end of 6 months therapy
there was a statistically significantly greater reduction in
serum ALT in Spirulina treated group than in Silymarin
group by one way ANOVA (F = 8.15, P = 0.006) with
mean (SD) = - 23.7 (22.3) and -6.8 (23.2) respectively.
Both health related quality of life scales as measured
here by the Chronic Liver Disease Questionnaire (CLDQ)
overall scores, and the sexual functions measured by Ari-
zona Sexual Experience Scal e (ASEX) total score s were
statistically significantly improved in both treated group at
the end of 6 months. See (Table 4). The mean differences
in both scale scores from baseline were found to be statis-
tically significantly greater in Spirulina treated group than
the Silymarin treated group (CLDQ, F = 11.45, p = 0.001);
and (ASEX, F = 9.9, p = 0.003). See (Figure 3).
Multivariate analysis of covariance (MANCOVA)
using the treatment group as the fixed independent fac-
tor while adding the baseline Child-Pugh s core and the
pre-treatment virus load as covariates showed that the
treatment group (Hotellings Trace valu e = 0.53 1, p <
0.0001) and the baseline Child-Pugh score (Hotellings
Trace value = 0.153, p = 0.021) exhibited significant
effects on the vector of the two outcome variables (the
improvement in CLDQ and ASEX scores), while the
baseline virus load did not (p = 0.15)
Yakoot and Salem BMC Gastroenterology 2012, 12:32
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It was also clear in the univariate analysis (Table 5)
that the univariate effects of the corrected model and
the treatment groups adjusted for both the baseline
Child-Pugh score and virus load on each o ne of the
outcome variables (CLDQ and ASEX) w ere statistically
significant (Table 5).
No serious adverse effects attributable to th erapy were
reported in both groups, apart from mild transient
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nausea, bloa ting, giddiness and headache in less than
6 patients in both groups.
Discussion
To our knowledge, this study is the first human trial to
address the effect of Spirulina platensis who le unfractio-
nated dried extract on virus load, liver f unction, health
related quality of life and sexual functions in patients
with chronic HCV. There is only so far one article in
Medline by Băicuş C, et al
.
[43] who di d study the effect
of one mon th treatment for chronic HCV patients with
Spirulina on serum aminotransferases and general state
with unfavorable results.
We opted to use the whole herbal extrac t and not any
one of the fractionated bioactive molecules presuming
that the whole natural multi-components as previously
discussed in introduction could offer not only antiviral
activity but als o other immune enhancing activities that
might be summated together to produce ther apeutic
effects on this state of chronic viral infection that evades
the immune system.
Our results showed significantly greater effects of
Spirulina than Silymarin on most studied parameters
Table 1 Baseline characteristics of analyzed patients
Characteristic Spirulina treated Group (n = 30) Silymarin treated group (n = 29)
Age-yr (mean ± SD) 47 ± 12 48 ± 12
Sex - M/F 21/9 18/11
Body mass index 29.8 ± 6.2 29.7 ± 6.8
Baseline HCV RNA (log
10
IU/mL): median (Q1-Q3) 5.35 (4.84-6.07) 5.43 (4.94-6.02)
Baseline ALT: median (Q1-Q3) 76 (44-106) 75 (43-108)
Baseline Child-Pugh score: mean(SD) 7.067 (1.28) 7 (1.25)
Interferon history:
(Naive/Relapser/Non-responder)
23/3/4 20/3/6
Table 2 End of treatment and early virological response in both groups
Treatment group End of Treatment Response (6 months) Total Sig
non-ETR p-ETR c-ETR
Spirulina Count 24 2 4 30 0.12
% within Treatment group 80% 6.7% 13.3% 100%
Silymarin Count 28 0 1 29
% within Treatment group 96.6% 0% 3.4% 100%
Treatment group Early Virological Response (3 months) Total Sig
non-EVR p-EVR c-EVR
Spirulina Count 27 2 1 30 0.22
% within Treatment group 90% 6.7% 3.3% 100%
Silymarin Count 29 0 0 29
% within Treatment group 100% 0% 0% 100%
Figure 2 Box plot graph representation of log tran sformed
virus load (Log PCR) in each treatment group.
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Table 3 Relation of ETR to baseline virus load
Treatment group Baseline viremia ETR Total
non-ETR p-ETR c-ETR
Spirulina Low viremia 100000 Count 51410
% within viremia 50% 10% 40% 100%
Intermediate viremia Count 16 1 0 17
% within viremia 94.1% 5.9% 0% 100%
High viremia > 2 millions Count 3003
% within viremia 100% 0% 0% 100%
Total Count 24 2 4 30
% within viremia 80% 6.7% 13.3% 100%
Table 4 Mean CLDQ and ASEX scores in both groups
Treatment
groups
Compared Pairs Number Variable name Mean SD Paired t Sig.
Spirulina Pair 1 30 CLDQ before Rx 4.730 0.320 6.884 0.0000
30 CLDQ after 6 months 4.301 0.442
Pair 2 30 ASEX before Rx 17.333 4.452 5.323 0.00001
30 ASEX after 6 months 15.167 2.995
Silymarin Pair 1 29 CLDQ before Rx 4.727 0.354 2.416 0.0225
29 CLDQ after 6 months 4.586 0.395
Pair 2 29 ASEX before Rx 17.241 4.265 2.306 0.0287
29 ASEX after 6 months 16.621 3.959
Figure 3 Error-Bar graph depicting the mean ± (CI) difference
from baseline in both CLDQ and ASEX scores after 6 months
in each treatment group.
Table 5 Univariate Analysis of Covariance Tests of
Between-Subjects Effects
Source Dependent Variable F Sig. Partial
Eta
Squared
Corrected Model CLDQ difference from
baseline
5.968 .001 .246
ASEX difference from
baseline
7.523 .000 .291
Baseline Child-Pugh
score
CLDQ difference from
baseline
.033 .856 .001
ASEX difference from
baseline
8.314 .006 .131
Baseline virus load CLDQ difference from
baseline
3.880 .054 .066
ASEX difference from
baseline
.000 .997 .000
Treatment group CLDQ difference from
baseline
13.974 .000 .203
ASEX difference from
baseline
10.152 .002 .156
Yakoot and Salem BMC Gastroenterology 2012, 12:32
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including the significantly greater reduction of serum
ALT and the greater improvement in both disease speci-
fic health related quality of life and sexual functions
scores. Though the virological response rates were not
statistically significantly different between the 2 treat-
ment groups, yet it reached the level of significance with
the one sided Z test for proportions in those who pre-
sented with low or intermediate baseline viremia.
We did not note considerable changes in both virus load
and serum ALT early in the first month as it seems that
the beneficial effects take some times to appear as we
found that improvements in most parameters were even
higher after 6 months treatment than after 3 months.
We hypothesized that there must be a time needed to
establish and solidify the immune mechanisms behind the
activation, release and action of endogenous interferons
and other interplaying cells and mediat ors. Even the par-
enterally administered high dose of interf eron alpha took
some months to manifest its maximal virological response,
that is why we wait at least 3 months t o predict the sus-
tained virological response through the early complete or
even partial virological response.
It is the main limitation of our study that we did not
follow up patients for one year treatment followed by 6
months off-treatment period as the case in the protocols
for the study of interferon alpha based therapy. We
designed this relatively short term pilot study to answer
a simple research question; is there any therapeutically
feasible potential for Spirulina in chronic HCV patients,
worthy to conduct a larger study with longer follow up
period.
The motivation to conduct this study, apart f rom the
theoretically convincing background, was the unintended
data coming from some of our patients who took Spirulina
as nutritional s upplement and reported to us marked
improvement of the general well being and sexual activity.
From this probing experience, as well as from the results
of Danoff A, et al. [44] and Soykan A, et al. [45] who
reported an association of chronic HCV with depressed
sexual functions independent of depression, we o pted to
compare the effect of both treatments on sexual functions
beside the other efficacy parameters in such patients. We
ass umed that improvement in sexual appetite; frequency
and perf ormance are logical indicators f or the improve-
ment in the overall wellbeing. Ou r results went in agree-
ment with this assumption. Any how further large sized,
randomized controlled studies with longer follow up peri-
ods are needed to confirm our results.
This study was mainly focusing to help a considerable
percentage of chronic HCV patients who are facing the
situation of contraindication, intolerability or non-
response to the current gold standard therapy. They
usua lly become fe eling hopeless and unsecure with dete-
rioration in t heir overall wellb eing , funct ional status a nd
quality of life. If further studies confirm our results with
reproducibility, this could be an alternative treatment in
such situations if at least it can improve quality of life,
physical activity and performance. We did not focus o n
the luxury of sustained virological response at this explora-
tory stage, but it will be our objective in the coming
planned study.
The raised issues from the already discussed in-vitro and
preclinical data about the potential immune stimulation
and virus entry blocking also urged us to plan to test a
new hypothesis; could the complementary therapy with
Spirulina improve the resp onse to the current gold stan-
dard antiviral therapy?. This will be tried to answer in our
next study; through testing the effect of combining Spiru-
lina with the current gold standard therapy, or the ef fect
of offering a lead-in course for those who have high base-
line virus load.
Conclusions
From our results we can conclude that there is a thera-
peutically feasible potential for Spirulina platensis dried
extract worthy to conduct a larger sized study with a
longer follow up period to confirm these safety and effi-
cacy encoura ging results in the treatment of chronic
hepatitis C infected patients.
Acknowledgements
We acknowledge the sincere help and support of Dr. Medhat Kassem and
Dr. Abdullah Abbass from Beovita, they did a major role in the preparation
and coding of the drug packs.
Author details
1
Green Clinic and Research Centre, Alexandria 21121, Egypt.
2
Mabarrah
Clinics, Alexandria, Egypt.
Authors contributions
MY conceived of the study, formulated the research question, participated in
its design, coordination and conduction. He took active part in all the
process from patient screening to final assessment, statistical analysis and
manuscript writing. AS shared MY in all the steps from screening of patients
to manuscript writing and approval.
Competing interests
Beovita-Safe Pharma, a Joint German Egyptian Company, Katzbachstr. 29, D-
10965 Berlin, had supplied the drugs and partly the costs of the laboratory
tests.
Received: 3 July 2011 Accepted: 12 April 2012 Published: 12 April 2012
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Pre-publication history
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doi:10.1186/1471-230X-12-32
Cite this article as: Yakoot and Salem: Spirulina platensis versus
silymarin in the treatment of chronic hepatitis C virus infection. A pilot
randomized, comparative clinical trial. BMC Gastroenterology 2012 12:32.
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    • "[99] In patients with chronic hepatitis C infection, viral load and ALT levels tended to improve after 6 months of treatment with spirulina in a small, active-controlled trial. [100] Another small, uncontrolled trial reported significant improvements in aspartate aminotransferase, alanin aminotransferase, gamma-glutamyltransferase, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, and the ratio of total cholesterol to high-density lipoprotein cholesterol after 6 months of treatment in patients with NAFLD. According to the authors, spirulina supplementation resulted also in a significant reduction in weight and insulin resistance, and a significant improvement in healthrelated quality of life was observed. "
    [Show abstract] [Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is a common solid malignancy and a leading cause of cancer-related death worldwide. The mechanisms underlying the pathogenesis and development of HCC are complex and heterogeneous. Although mainly related to hepatitis B and C chronic infection; HCC may also arise from diet-associated conditions such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Furthermore, toxins and nutrients such as mycotoxins and alcohol have an established role in the pathogenesis of chronic liver diseases, whereas specific diet patterns or foods have been associated with a reduction in HCC risk. The aim of this review is to provide a thorough overview of the clinically relevant effects-either beneficial or detrimental-of natural products consumed by humans on HCC risk and management.
    Full-text · Article · Mar 2016
    • "It had been found to activate macrophages, NK cells, T-cells, B-cells, and to stimulate the production of interferon gamma and other cytokines. Natural substances isolated from S. platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption penetration and some replication stages of progeny viruses after penetration into cells [13]. Spirulina has been shown to have important antiviral activity, when administered at a low concentration it results in reduced viral replication whereas, at higher concentrations it blocks replication. "
    [Show abstract] [Hide abstract] ABSTRACT: Aim: To compare the seminal attributes of neat, pre-freeze (at equilibration), and post-freeze (24 h after freezing) semen in pure and crossbred Jersey bulls. Materials and Methods: Total 36 ejaculates (3 ejaculates from each bull) were collected from 6 pure Jersey and 6 crossbred Jersey bulls and evaluated for various seminal attributes during neat, pre-freeze, and post-freeze semen. Results: The mean (±standard error [SE]) values of neat semen characteristics in pure and crossbred Jersey bulls were recorded such as volume (ml), color, consistency, mass activity (scale: 0-5), and sperm concentration (millions/ml). The extended semen was further investigated at pre-freeze and post-freeze stages and the mean (±SE) values recorded at neat, pre-freeze, and post-freeze semen were compared between pure and crossbred Jersey bulls; sperm motility (80.55±1.70%, 62.77±1.35%, 46.11±1.43% vs. 80.00±1.80%, 65.00±1.66%, 47.22±1.08%), live sperm count (83.63±1.08%, 71.72±1.09%, 58.67±1.02% vs. 80.00±1.08%, 67.91±1.20%, 51.63±0.97%), total abnormal sperm count (8.38±0.32%, 12.30±0.39%, 16.75±0.42% vs. 9.00±0.45%, 12.19±0.48%, 18.11±0.64%), hypo-osmotic swelling (HOS) reacted spermatozoa (71.88±0.77%, 62.05±0.80%, 47.27±1.05% vs. 72.77±1.02%, 62.11±0.89%, 45.94±1.33%), acrosome integrity (89.05±0.83%, 81.33±0.71%, 71.94±0.86% vs. 86.55±0.57%, 78.66±0.42%, 69.38±0.53%), and DNA integrity (99.88±0.07%, 100, 99.66±0.11% vs. 99.94±0.05%, 100, 99.44±0.18%,). The volume, color, consistency, sperm concentration, and initial motility in pure and crossbred Jersey bulls did not differ significantly (p>0.05). The mass activity was significantly (p
    Full-text · Article · Oct 2015
    • "A total of 1,035 abstracts were reviewed; among these articles, 55 were retrieved, including 12 RCTs [8–12, 22–28] that are closely related to the current subject. However, two [22, 23] were excluded because these articles were basic research, two [24, 25] were excluded because these articles did not use placebo as a control, two [26, 27] were excluded because of duplication, and one [28] was excluded because of unavailable inclusion outcomes; hence, five RCTs89101112 were selected on the basis of our inclusion criteria (Table 1). A total of 222 and 167 patients were randomly treated with silymarin (or intravenous silibinin) and placebo, respectively. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: This study aimed to evaluate the efficacy and safety of silymarin on chronic hepatitis C virus- (HCV-) infected patients. Methods: Randomized controlled trials (RCTs) of silymarin in chronic HCV-infected patients up to April 1, 2014 were systematically identified in PubMed, Ovid, Web of Science, and Cochrane Library databases. Results: A total of 222 and 167 patients in five RCTs were randomly treated with silymarin (or intravenous silibinin) and placebo, respectively. Serum HCV RNA relatively decreased in patients treated with silymarin compared with those administered with placebo, but no significance was found (P = 0.09). Meta-analysis of patients orally treated with silymarin indicated that the changes of HCV RNA are similar in the two groups (P = 0.19). The effect on alanine aminotransferase (ALT) of oral silymarin is not different from that of placebo (P = 0.45). Improvements in quality-of-life (Short Form-36) in both silymarin and placebo recipients were impressive but relatively identical (P = 0.09). Conclusion: Silymarin is well tolerated in chronic HCV-infected patients. However, no evidence of salutary effects of oral silymarin has yet been reported based on intermediate endpoints (ALT and HCV RNA) in this population. Moreover, intravenous administration of silymarin should be further studied.
    Full-text · Article · Aug 2014
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