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Safety and efficacy of sea cucumber containing products

Article  in  Archives of Pharmacy Practice · January 2016

DOI: 10.4103/2045-080X.183038

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Product Review

Safety and efficacy of sea cucumber containing

products
Wan Zanariah W.A. Manan1, Sundara Rajan Mahalingam2,3, Kamaruddin Arshad2,3, Sarah I. Bukhari4,
Long Chiau Ming1,2
1
Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, 2Vector-borne Diseases Research Group (VERDI), Pharmaceutical and Life Sciences
CoRe, Universiti Teknologi MARA, Shah Alam, Selangor, 3Department of Environmental Health, Faculty of Health Sciences, Universiti Teknologi MARA,
Bertam, Penang, Malaysia, 4Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia

Address for correspondence:

Dr. Long Chiau Ming,
Level 11, FF1 Building, Faculty of
Pharmacy, Universiti Teknologi MARA,
Puncak Alam, Selangor, Malaysia.
E‑mail: ming.long@bath.edu
Key words: Gangliosides, herbal
product, traditional medicine,
triterpene glycosides
ABSTRACT
Purpose: The aim of this study is to assess the therapeutic effect of sea cucumber. It is
a traditional medicine used for centuries as a general tonic to improve the health of the
body and to boost the energy levels.
Methodology: An electronic search on PubMed, MEDLINE and Cochrane Library with
keywords “sea cucumber”, “gamat”, “effectiveness OR efficacy”,“safety OR adverse reaction
OR side effects” was carried out. The literatures are summarized in the evidence tables.
Findings and conclusions: Most sea cucumbers species have been validated through
scientific and ethnopharmacological research and have shown to have medicinal value
such as anti‑angiogenic, anticancer, anticoagulant antihypertension, anti‑inflammatory,
antimicrobial, antifungal, antioxidant, antithrombotic, and antitumor. The discovery of
bioactive compounds and therapeutic properties isolated from sea cucumber such as
chondroitin sulfate, triterpene glycosides (saponins), lectins, heparin, cerebrosides,
gangliosides, bioactive peptides, sterols, and omega‑6 and omega‑3 fatty acids leads to
potential drug development in various pharmaceuticals, agrochemicals, functional foods,
and nutraceuticals industries. However, further clinical trials are still needed which could
transform the bioactive compound from sea cucumber extraction into a drug that could
be a cure for certain disease.

BACKGROUND about 1500 species of sea cucumbers worldwide with

Over the ages, people in Asia have used the sea
cucumbers both as food and as medications. Sea
cucumbers are marine invertebrate animal from the
class Holothuroidea. It belongs to the zoology category
of echinoderms; many sea cucumbers were found in
different depths of all oceans on the planet, usually
found close to rocks, seaweeds, or corals. There are
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the greatest number being in the Asia Pacific Region.
In Malaysia, nearly 42 species of sea cucumbers were
identified and Stichopus species was most harvested for
their medicinal properties.[1] Among those, Stichopus
hermanni species commonly known as “gamat emas”
was believed to be the most effective species to treat
joint pain, wound injuries, and back pain traditionally.
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DOI: How to cite this article: Manan WW, Mahalingam SR, Arshad K,
Bukhari SI, Ming LC. Safety and efficacy of sea cucumber containing
10.4103/2045-080X.183038 products. Arch Pharma Pract 2016;7:S48-52.

S48 © 2016 Archives of Pharmacy Practice | Published by Wolters Kluwer - Medknow

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Manan, et al.: Systematic review on sea cucumber
Sea cucumbers are a good source of collagen,
polysaccharides, essential amino acids (especially
leucine and threonine), and polyunsaturated
fatty acids (especially eicosapentaenoic acid and
docosahexaenoic acid), which have many great
health benefits.[2] In China, people considered sea
cucumbers as the most nutritious and luxurious
seafood; therefore, they use it to treat a number of
conditions including constipation, problems related
to the kidneys, and reproductive disorders.
Sea cucumbers are named after their resemblance to
the vegetable cucumber. The unique part about sea
cucumbers is their capability to renew or regenerate
themselves and to repair as well as to restore lost
organs. Some of the species also possess the ability to
divide themselves into two halves and each half grows
and survives as a new creature. Dried or extracted
sea cucumbers are commercially marketed as daily
life products by the sea cucumbers’ extracts and are
blended with well‑known herbs to produce medicinal
value products in a form of nutritional supplement,
either in capsules or in tablets form, ointment,
toothpaste, body lotion, and facial cleanser. The
supplements can be taken orally while the ointments
may be applied to the face, gum, mouth, hands, feet,
hair, scalp, joints, and also in different sensitive areas
of the body.
Indication
Sea cucumber is a traditional medicine used for
centuries as a general tonic to improve the health
of the body and to boost the energy levels instantly.
Traditionally, sea cucumbers believed to be effective
in healing of internal and external wounds, reducing
joint pain and muscle pain, improving circulation
of blood, restoring the reproductive system after
childbirth, and beautifying the skin.  As traditional
general health supplement, sea cucumber contains
several bioactive substances thought to influence
health, including:
• Bio‑active elements: Repairs body cells, rejuvenates
body cells, and helps to prevent tumors
• Collagen: For fast wound healing process and
alleviates skin problems
• Mucopolysaccharide: Increases skin elasticity and
fortifies skin/connective tissues, vital for healthy
joints
• Chondroitin
sulfate and glucosamine: Alleviates
inflammation, alleviates pain,
and strengthens the
body’s defense system
• Omega‑3: Helps to protect the heart, helps to
decrease cholesterol levels
Archives of Pharmacy Practice  Vol. 7  Supplement 1  2016
• Eight minerals: Promotes healthy growth,
stimulates body’s metabolism, and helps to lower
blood sugar level.
Bioavailability
Oral bioavailability (OB) is an important
pharmacokinetic parameter of ADME processes. It is
involved with several factors such as gastrointestinal
transit and absorption, chemical stability, and
first‑pass effect of the gut wall and liver metabolism.
Drug‑likeness (DL) index is also used as a screening
criterion to remove nondrug compounds, which
acts as an important parameter of drug research to
evaluate whether or not a compound functions as a
drug. DL can be inferred as a delicate balance between
molecular properties affecting pharmacodynamics
and pharmacokinetics of molecules. Compounds
that pass OB and DL screening were considered
pharmacologically active. The threshold for OB should
be >40%, and for DL should be >0.18%. A research to
study chemical compound in sea cucumber which is
glycosides found significant activity with satisfactory
OB (OB z‑score: 40%) and favorable DL properties (DL
z‑score: 0.18).[3]
Absorption
A chemical compound extracted from sea
cucumber, i.e., depolymerized holothurian
glycosaminoglycan (DHG) is partially absorbed after
oral administration.[4]
Metabolism and elimination
An animal study of sea cucumber extract (SCE),
DHGs, showed that it undergoes observable metabolic
degradation when administered orally and loss of
sulfate group as the most important degradative
metabolic pathway; only 0.1% of the orally administered
DHG  (50  mg/kg) was recovered in urine collected
for 24 h while more than 5% of the intravenously
administered DHG (1 mg/kg) was excreted in urine
in 24 h. This suggests that at least 2% of the orally
administered DHG is absorbed in the gastrointestinal
tract. No detectable levels of DHG were found in
rat feces after oral administration of DHG which
suggested that DHG might have been digested during
passing through the small and large intestines.[4]
Precaution
Individuals with seafood allergies should avoid the
use of sea cucumber. It is important to note that due
to a lack of research, little is known about the overall
safety of using dietary supplements containing sea
cucumber.
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Manan, et al.: Systematic review on sea cucumber
Adverse effects
Patients should stop taking sea cucumber product
if they have any of the following side effects or
symptoms which may mean that they are allergic to
it such as breathing problems or tightness in the throat
or chest pain, skin hives, rash, or itchy or swollen skin.
METHODOLOGY
A search for articles was performed with the following
electronic databases such as PubMed, Web of Science,
and ScienceDirect. Keyword selection based on “sea
cucumber OR gamat,” “effectiveness OR efficacy,”
and “safety OR adverse reaction OR side effects” was
carried out [Table 1].
The inclusion criteria of the study were articles
published in English with full article available in
Universiti Teknologi MARA databases.
EVIDENCE
Research on the health effects of sea cucumber is very
limited. While clinical trials are currently lacking,
a number of preliminary studies suggest that sea
cucumber may offer certain health benefits.
Efficacy
Here are several key findings from the available
research related to sea cucumbers.
• The study reported in the Journal of Oral Science
in 2003 found out that participants who used a
toothpaste containing SCE showed significantly
greater improvements in several markers of gum
health (such as plaque buildup and bleeding)
which may be beneficial to people with gum
disease. It has been reported that topical
exposure of gingival tissue to SCE over 3 months
was safe[5]
• An animal study using rats had shown that
SCE significantly alleviated the hepatorenal
toxicity resulting from carcinogen exposure. The
hepatoprotective and curative effects offered by
Table 1: Search criteria and results
Criteria Search results
Keywords used Sea cucumber OR gamat,
effectiveness OR efficacy,
and safety OR adverse
reaction OR side effects
Years searched All
Total number of articles reviewed 12
Relevant full‑text articles reviewed 6 are very effective in improving health. With so many
Relevant abstracts reviewed 9 dietary supplements available and so many claims
S50
this extract might be due to decreased free radical
generation or antioxidant properties[6]
• A comprehensive in vitro studies of human colon
cancer cells suggested that glycosides extracted
from sea cucumbers might be good antitumor
agents for the prevention and treatment of human
colon cancer. Triterpene glycosides, potential
biologically active compounds isolated from
sea cucumbers, have been evaluated for their
antitumorigenic properties and were reported
to significantly inhibit proliferation and produce
concentration‑dependent cytotoxicity in human
colon cancer[7]
• Some animal‑based researches suggested that the
most effective component for lowering lipid level
in sea cucumber (saponin) significantly reduces
the serum total cholesterol  (TC) concentration,
decreases low‑density lipoprotein cholesterol
content in the serum, and increases the ratio of
high‑density lipoprotein cholesterol and TC in
rats.[8]
Safety
• A systematic review on safety of sea cucumber
product from all toxicological articles found out
that the use of SCE as an oral daily supplement
for 6 months was not associated with any adverse
effect. There is no evidence on safety of SCE
during pregnancy and lactation, and SCE also
has been shown to have potent antitumor effects
in vitro[9]
• A report by the  Malaysian Adverse Drug
Reactions Advisory Committee (MADRAC) ADR
Newsletter, which was published in May 2009,
stated that MADRAC proposed a recommendation
of suspension of registration of two sea cucumber
products due to seriousness of ADRs in 2008. There
were 29 ADR reports received from local hospital
related to oral gamat/sea cucumber horrens
products. Sixteen of these ADRs were renal related.
DCA also decided to suspend all registered oral
gamat products of that company until further
safety investigations have been completed.[10]
POTENTIAL RISK TO GENERAL PUBLIC
They are so many people who are very conscious
about their health and there are hundreds of brands
of health supplements (pill/liquid/cream based)
available in the market including those originated
from sea cucumber. Many claim that their products
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Manan, et al.: Systematic review on sea cucumber
made about their health benefits, how can a consumer
decide whether a supplement is safe or useful? Just
because it has been used for centuries, there is no
absolute certainty that it is safe for anyone to use
even it has been labeled as “natural.” Anything strong
enough to produce a positive effect such as lowering
cholesterol level is also can pose unexpected risks.
In addition, one of the more worrisome health risks
of dietary supplements is contaminants. Health
supplements related to marine products are exposed to
be contaminated with natural toxins from the harvest
area that could harm consumers. There are six recognized
fish poisoning syndromes that can occur from the
consumption of fishery products contaminated with
natural toxins, i.e. paralytic shellfish poisoning
(PSP),
neurotoxic shellfish poisoning, diarrhetic shellfish
poisoning, amnesic shellfish poisoning, ciguatera fish
poisoning, and azaspiracid shellfish poisoning. PSP
toxin is extremely potent toxin with high mortality rate
and may occur ½ to 2 h postconsumption.[11] It has been
reported in sea cucumbers and various echinoderms in
Australia. The PSP effects are primarily neurological
effects which can include numbness, drowsiness,
tingling, burning, incoherent speech, and respiratory
paralysis. The presence of contaminants in these health
supplements may be due to poor manufacturing
standards. Therefore, it is important for consumers
to find out and investigate potential benefits and side
effects of health supplements before they used it,
especially if taken with prescribed medications which
could lead to harmful, even life‑threatening results.
Another concern is buying health supplement from
the internet. This trend raises a safety concern because
many products purchased from online sources could
be counterfeit or adulterated or contaminated with
banned substances. The best option available is to buy
from reliable and trusted sources such as pharmacy
and clinics and get advice from the qualified and expert
practitioners.
RECOMMENDATIONS AND
CONCLUSIONS
Ideally, health supplements only contain safe, active
ingredients and safe inactive excipients that serve
a specific purpose and benefit the body in a unique
way. However, as with any treatment, it is important
to consider safety before using complementary health
supplements because these medicines can act in the
same way as modern medicines. Although they may
be labeled as natural, they still can cause medical
problems if taken in large amounts or incorrectly used.
Archives of Pharmacy Practice  Vol. 7  Supplement 1  2016
Research has shown that some natural products are
beneficial to health and have found them to be useful
and some are not. For example, omega‑3 fatty acids are
proven in lowering triglyceride level, whereas some
supplements such as beta‑carotene and Vitamin E do
not lower risk of heart disease or heart attack (though
they claim to be). Most sea cucumbers species have been
validated through scientific and ethnopharmacological
research and have shown to have medicinal value
such as anti‑angiogenic, anticancer, anticoagulant,
antihypertension, anti‑inflammatory, antimicrobial,
antifungal, antioxidant, antithrombotic, and antitumor.
The discovery of bioactive compounds and therapeutic
properties isolated from sea cucumber such as
chondroitin sulfate, triterpene glycosides (saponins),
lectins, heparin, cerebrosides, gangliosides, bioactive
peptides, sterols, and omega‑6 and omega‑3 fatty
acids leads to potential drug development in various
pharmaceuticals, agrochemicals, functional foods,
and nutraceuticals industries.[12] However, further
clinical trials are still needed which could transform
the bioactive compound from sea cucumber extraction
into a drug that could be a cure for certain disease.
Information about natural supplements is often
confusing or unclear. It is hard to know which offer
genuine health benefits and which are offering
false promises that can be hazardous to health. By
seeking supervision or proper advice from a health
care practitioner who is knowledgeable in natural
remedies such as doctors or pharmacist prior using
any supplement, consumers can make better choices
about those that are right for them.
Customers should always be careful when buying
health supplements. They need to be smart to choose
the right medicines, especially those taken orally or
on skin application. Well‑informed consumers are not
easily influenced by advertisements or testimonials
available on websites, or kiosk, as well as social
media. In addition, public should always ensure that
all health products purchased are registered with the
Ministry of Health, with a valid Malaysian registration
number, accompanied with Meditag hologram label
and the advertisement is approved by the Medicine
Advertisements Board.
Financial support and sponsorship
This work was supported by Academic and Research
Assimilation grants: 600 RMI/DANA5/3/ARAS
(46/2015). The authors would like to express their
gratitude to Ministry of Higher Education and
Universiti Teknologi MARA (UiTM), Malaysia for
financial support for this research.
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Manan, et al.: Systematic review on sea cucumber
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Kamarudin KR, Rehan MA, Hashim R, Usup G. An update on
diversity of sea cucumber (Echinodermata: Holothuroidea)
in Malaysia. Malayan Nat J 2010;62:315-34.
2. Gao Y, Li Z, Qi Y, Guo Z, Lin Y, Li W, et al. Proximate
composition and nutritional quality of deep sea growth
sea cucumbers (Stichopus japonicus) from different
origins. J Sci Food Agric 2016;96:2378-83.
3. Guo Y, Ding Y, Xu F, Liu B, Kou Z, Xiao W, et al.
Systems pharmacology-based drug discovery for
marine resources: An example using sea cucumber
(Holothurians). J Ethnopharmacology 2015;165:61-72.
4. Imanari T, Washio Y, Huang Y, Toyoda H, Suzuki A,
Toida T. Oral absorption and clearance of partially
depolymerized fucosyl chondroitin sulfate from sea
cucumber. Thrombosis Res 1999;93:129-35.
5. Taiyeb-Ali TB, Zainuddin SLA, Swaminathan D, Yaacob
H. Efficacy of ’Gamadent’toothpaste on the healing
of gingival tissues: A preliminary report. J Oral Sci
2003;45:153-9.
6. Dakrory AI, Fahmy SR, Soliman AM, Mohamed AS,
Amer SA. Protective and curative effects of the sea
S52
View publication stats
cucumber Holothuria atra extract against DMBA-
induced hepatorenal diseases in rats. Biomed Res Int
2015;2015:563652.
7. Janakiram NB, Mohammed A, Rao CV. Sea Cucumbers
Metabolites as Potent Anti-Cancer Agents. Marine drugs
2015;13:2909-23.
8. Hu XQ, Xu J, Xue Y, Li ZJ, Wang JF, Wang JH, et al. Effects
of bioactive components of sea cucumber on the serum,
liver lipid profile and lipid absorption. Biosci Biotechnol
Biochem 2012;76:2214-8.
9. Alsaad AM, Fox C, Koren G. Toxicology and teratology of
the active ingredients of professional therapy MuscleCare
products during pregnancy and lactation: A systematic
review. BMC Complement Altern Med 2015;15:40.
10. National Pharmaceutical Control Bureau. Adverse
Drug Reaction (ADR) Reports from 2008-An Overview;
2009. Available from: http://bpfk.moh.gov.my/images/
Publications/Newsletter_MADRAC_Bulletin/May-2009.
pdf. [Last accessed on 2016 May 06].
11. Administration USFaD. Natural Toxins; 2015.
Available from: http://www.fda.gov/downloads/Food/
GuidanceRegulation/UCM252395.pdf. [Lats accessed on
2016 May 05].
12. Bordbar S, Anwar F, Saari N. High-value components and
bioactives from sea cucumbers for functional foods—A
review. Marine drugs 2011;9:1761-805.
Archives of Pharmacy Practice  Vol. 7  Supplement 1  2016