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How to cite: Strant, M., Yücel, B., Topal E., Puscasu A.M., Margaoan, R., Varadi A., Use of Royal Jelly as Functional Food in Human and
Animal Health, J. Anim. Prod., 2019, 60 (2): 131-144, DOI: 10.29185/ hayuretim.513449
J. Anim. Prod., 2019, 60 (2): 131-144
DOI: 10.29185/ hayuretim.513449
Use of Royal Jelly as Functional Food in
Human and Animal Health
Arı Sütünün İnsan ve Hayvan Sağlığında Fonksiyonel Gıda
Olarak Kullanımı
Alınış (Received): 16.01.2019 Kabul tarihi (Accepted): 08.09.2019
ABSTRACT
Bee products are used as supplements to provide nutrients in prevent or treatment
of some health problems. Royal jelly has a rich nutrient contents in bee hive which
protects and strengthens the health; compared to other bee products, it has a
significant potential and effect. Because of its functional properties, royal jelly is very
effective in accelerating the healing process in many diseases. The use of fresh royal
jelly in our diets nowadays will help us to be healthy.
This review explains the effects of royal jelly on health, animal trials, and clinical
studies for human health. Healthy doses are recommended by apitherapist medical
doctors based on clinical observation and personal experience on the doses of use of
royal jelly on human health. The review also mentions the positive effects of royal
jelly consumption in our daily diet
ÖZ
Arı ürünleri içerdiği besin maddeleri ile sağlık koruyucu ve destekleyici olarak
kullanılmaktadır. Arı sütü; kovanın zengin besin içeriğine sahip, sağlık koruyucu ve
güçlendirici ürünüdür ve diğer arı ürünleriyle karşılaştırıldığında önemli bir
potansiyele ve etkinliğe sahiptir. Arı sütü fonksiyonel özellikleri nedeniyle, pek çok
hastalıkta başarıyla iyileştirici özelliktedir. Günümüzde beslenmemizde taze arı
sütünün kullanımı, vücudumuzun sağlıklı kalmasına yardımcı olmaktadır.
Bu derlemede, arı sütünün hayvan deneylerinde ve insan sağlığında klinik
çalışmalarda sağlık üzerine etkileri anlatılmıştır. İnsan sağlığında arı sütünün kullanımı
ile ilgili doz önerileri özellikle apiterapist tıp hekimleri tarafından klinik gözlemlere ve
kişisel deneyimlere dayalı olarak yapılmıştır. Günlük beslenmemizde arı sütü
tüketiminin olumlu etkilerine de değinilmiştir.
INTRODUCTION
Royal Jelly is a special nutrient used in the feeding
of larvae and queen bee, which is secreted from
hypopharyngeal and mandibular glands of 5 to 15
days old worker bees (Matsuoka et al., 2012; Mărgăoan
et al., 2017). Royal jelly is a bee product with a rather
complex structure. In its composition, substances that
target many different known and unknown biological
functions play an important role on the biomedical
effect of the royal jelly (Stocker et al., 2005).
The composition of RJ is relatively constant at
macro level and varies depending on bee nutrition,
bee species, climate, season, harvesting method, and
the age of the bee larvae (Liu et al., 2008). Royal Jelly
is very rich in protein, fatty acids, sugars, hormones,
vitamins, and minerals required for the development
Article
(
Araştırma Makalesi)
Mirela STRANT
1
0000-0002-1170-3348
Banu YÜCEL
2
0000-0003-4911-7720
Erkan
TOPAL
3
0000-0002-1398-4390
Ana Maria PUSCASU
4
0000-0002-8753-5213
Rodica MARGAOAN
5
0000-0002-9246-1677
Alina VARADI
1
0000-0002-8455-9842
1
Association Health with CasaBIO, Cluj-Napoca,
Romania
2
Ege University, Faculty of Agriculture, Department
of Animal Science, İzmir / Turkey,
3
Aegean Agricultural Research Institute, Apiculture
Section, İzmir / Turkey/
4
Complementary Therapists Association, London,
United Kingdom
5
Advanced Horticultural Research Institute of
Transylvania, Cluj-Napoca, Romania
Corresponding author:
topalerkan@tarimorman.gov.tr
Keywords
:
Royal jelly, apitherapy, apinutrition,
functional food, health.
Anahtar Kelimeler
:
Arı sütü, apiterapi, api
-beslenme,
fonksiyonel gıda, sağlık.
Review
(Derleme)
Strant et al
132
of the larvae. It consists of: 60-70% of water, 18%
protein, 9-18% carbohydrates, 3-6% lipids, 3-8%
minerals, salt and vitamins containing numerous
bioactive substances that have immune regulatory
properties, antibacterial 10-hydroxy-2-decenoic acid
(10-HDA) and peptides (Šimúth et al., 2003; Viuda‐
Martos et al., 2008; Sabatını et al., 2009; Bărnutiu et al.,
2012; Premratanachai and Chanchao, 2014; Kolaylı et
al., 2016; Mărgăoan et al., 2017). The sugars in the
royal jelly are mostly composed of fructose and
glucose, and are stable to the rate of honey. In many
cases, fructose and glucose together constitute 90%
of total sugars. Lipids consist of fatty acids with
unusual structures with acidic, antibacterial, and
fungicidal properties. Royal jelly, also contains neutral
lipids, sterols, and candles. The main minerals are
potassium, calcium, sodium, zinc, iron, copper, and
manganese, with potassium dominance (Menkovska,
2013). It has been reported that the symbiotic effect
of royal jelly and probiotic bacterial species provide
important antioxidant activity (Nabas et al., 2014). The
Royalisin, found in royal jelly is also an antibacterial
peptide and has been reported to have antimicrobial
effect against gram positive and negative bacteria
(Bărnuţiu et al., 2011; Bílikova et al., 2015).
Another compound found in royal jelly, royalactin
is a glycoprotein essential for queen differentiation in
honeybees. Royalactin plays a central role in this
process by switching on the epidermal growth factor
(EGF) receptor signalling pathway, which ultimately
leads to epigenetic changes according to researcher
(Kamakura, 2011).
The most important, major lipid component of the
royal jelly is 10-hydroxy-2-decenoic acid (10-HDA)
evaluated according to quality (Sesta, 2006; Bărnuţiu
et al., 2011; Honda et al., 2015). A quality royal jelly is
expected to be in the range of 1.4% and 1.8% of 10-
HDA. This value can vary according to the origin of the
flora and fauna of the royal jelly and the technical
procedures applied in the harvest of it. Unlike honey,
the mineral substance composition in the royal jelly is
not affected more than the geographical structure
and vegetation (Kösoğlu et al., 2013). The harvest time
of the royal jelly influences its quality and the content
(Karlıdağ and Genç, 2009; Zheng et al., 2011). In an
analysis made of the local royal jelly produced in
Romania, 10-HDA content was found to be ranging
between 0.75-3.8% (Mărghitaş et al., 2013; Stangaciu
et al., 2015; Mărgăoan et al., 2017). In the chemical
composition of royal jelly produced in Bulgaria and
Romania, low fructose levels were detected with high
protein and sucrose from the Bulgarian royal jelly. It is
reported that climate differences between the two
countries, the different equipment used for the
analysis and even the methods used for the same
purpose, the specific heterogeneity of the royal jelly
can affect the composition of the product (Balkanska
et al., 2013). Besides that, bee races also affect on royal
jelly production (Şahinler and Kaftanoğlu, 2005;
Karlıdağ and Genç, 2009).
Proteins found in the royal jelly play a very
important role in the feeding of larvae, defense of
immunity and task assignment, and have a wide range
of pharmacological and health-promoting functions
for humans (Han et al., 2014). The royal jelly contains
eight of the nine important amino acids, only the
compound lacks tryptophan. The total amount of the
basic amino acids in royal jelly was 247.35 mg/100 g
and the total FAA was 867.39 mg/100 g. The highest
concentration in AA is lysine (LYS) (221.07 mg/100 g),
proline (PRO) 234.10 mg/100 g, glutamine (GLN)
177.59 mg/100 g. Proline is a conditionally necessary
amino acid and it is possible to limit the synthesis
under specific pathophysiological conditions such as
severe catabolic distress (Mărgăoan et al., 2017). The
apicin is found as a heterooligomer consisting of
major royal jelly protein 1 and apismin (Furusawa et
al., 2016), which is composed of a large portion of the
royal jelly’s proteins. According to the study of the
concentration of free amino acids (FAA) and total
amino acids (Taas) in 13 different times to harvest
between 24 and 72 hours of royal jelly. Total free
amino acid concentration in royal jelly was
determined as 4.30 mg/g in 24 hours and 9.48 mg/g in
72 hours as harvest time increased. The highest and
lowest concentrations of total amino acids are 24h
(197.96 mg/g) and 72h (121.32 mg/g) respectively (Jie
et al., 2016).
The number of samples, analysis methods, and
beekeeping techniques that can affect the chemical
composition of the royal jelly are very important to
evaluate its parameters (Kanelis et al., 2015). Because
the proteins in the royal jelly are very sensitive to the
storage temperature, it can therefore be a potential
freshness marker and the best way to preserve the
quality of the royal jelly is under freezing conditions
(Li et al., 2007). The levels of lipids in royal jelly
decrease in time due to lipid oxidation, meanwhile the
protein content increases during storage (Mureşan et
al., 2016).
There is a correlation between the measured
refractive index and water content of the royal jelly.
The presence of a simple linear relationship between
refractive index and water content reveals the
Use of Royal Jelly as Functional Food on Human and Animal Health
133
suitability of the refractometric measurement for
quality control purposes. This relationship provides
similar estimates of water content originating from
the Wedmore equation (R2=0.9999), which is used to
predict the water content in honey. Refractometric
evaluation of water content is fast and simple, which
can provide adequate reliability in the routine quality
control of the royal jelly (Sesta and Lusco, 2008).
The many benefits of the royal jelly are those of
functional foods that have been on the agenda in
recent years. Especially with the health awareness
nowadays, the society is particularly interested in the
quality of the food we consume. The study of royal
jelly used in many health disorders has first started
with animal trials (Topal ve ark., 2015), and
subsequently in human studies too (Tolon, 1997).
The Use of Royal Jelly on Animal Health
Many researches have been conducted to
determining effects of royal jelly on animal health.
According the results of these research, royal jelly
increases the development of cartilage tissue in
animals due to its high collagen content, strengthening
bone and tooth structure because of its calcium and
selenium amount, also protecting blood cells, heart
and liver tissues as well as showing strengthening
effects on the muscles and nervous system due to the
presence of potassium (Stangaciu, 1999). After
injuries, generally there is an inflammatory reaction
and the cells under the dermis begin to increase
collagen production. Then the epithelial tissue is
regenerated. In the study conducted to determine the
effect of different royal jelly ratio on the wound in
mice; the results showed significantly increase in
wound healing activity compared to royal jelly negative
and positive control groups, and no significant
difference was found between 200 mg / kg and 300
mg / kg royal jelly use (p> 0.05). The results of this
study indicate that daily application of royal jelly
possesses better wound healing effects than
Nitrofurazon and every two days usage of royal jelly
(Shirzad et al., 2014).
According to a study performed by Çallı et al.
(2008) it has been investigated the effectiveness of
royal jelly in enhancing healing in tympanic
membrane perforations. The study suggests that royal
jelly is effective in increasing healing of tympanic
membrane perforations in guinea pigs.
Royal jelly also effects the reproductivity in animals. It
has been determined that the use of the royal jelly
increases spermatozoa motility with the intensity of it
reduces the rate of abnormal spermatozoa and
positively affects sperm quality (Temamoğulları et al.,
2006). In another study, the loss of age-related
testosterone function in old hamsters is reported to
be inhibited by the use of royal jelly (Kohguchi et al.,
2007). Other study has noted that with the use of royal
jelly, the negative effect on stress on male rabbit
fertility in hot summer conditions was reduced to a
minimum, total sperm output, sperm motility, live
sperm, and normal sperm showed a significant increase
compared to untreated controls. Concentrations of
plasma total protein, albumin, globulin, glucose, and
HDL were statistically increased significantly when
compared to controls in royal jelly groups, as opposed
to the treatment of royal jelly therapy where plasma
aggregate lipids, triglycerides, cholesterol, and low-
density lipid (LDL) concentrations have been reported
to cause a significant decrease (El-Hanoun et al., 2014).
Cisplatin is one of the most potent and effective
chemotherapeutic agents. Antineoplastic use is
limited due to cumulative nephrotoxic side effects. It
has been reported that the royal jelly can be used as a
preventive tool against subchronic cisplatin-induced
kidney damage in studies conducted to investigate
the nephroprotective potential of nutrition of royal
jelly against subchronic cisplatin toxicity in rats
(İbrahim et al., 2016).
In the case of oxidative stress with serum biochemical
changes in the liver and pancreas of diabetic rats
induced by streptococtosis (Streptozotosin) (STZ),
royal jelly improves the current oxidative damage
(Ghanbari et al., 2016).
Cadmium (Cd) is a highly toxic heavy metal that
causes genotoxic damage to the body. In addition, Cd
changes the system of antioxidant defence enzymes,
causing oxidative damage in various tissues. In the
study, oral administration of two doses (100 and 250
mg / kg body weight) of royal jelly on Cd-induced
genotoxicity and oxidative stress in rats had a
protective role against Cd-induced genotoxicity and
oxidative stress in mice due to the antioxidant effects
(Çavuşoğlu et al., 2009). In another study, aluminum
chloride (AlCl3) was administered to poisoned rats
with follicle stimulating hormone (FSH), luteinizing
hormone (LH), thyroid stimulating hormone (TSH),
thyroxine (T4), triiodothyronine (T3), triiodothyronine/
T4) and testosterone levels, and the use of royal jelly
weakens these effects (Al-Eisa and Al-Nahari, 2017),
while testicular oligospermine leads to the formation
of hypoplasia, occluded blood vessels and exfoliation
tubules, the use of royal weakens these effects. Royal
jelly is a useful treatment for male adult rats receiving
hydrogen peroxide (causing oxidative stress),
especially on the number of spermatozoons, testosterone
Strant et al
134
hormone level, live spermatozoons percentage and
glutathione and malondialdehyde tissue test (Al-
Sanafi et al., 2007; Hassan, 2009). It has also been
reported that royal jelly may be an alternative for
reproductive management which has been found to
increase the rate of ovulation until the start of estrus
(Al-Eisa and Al-Nahari, 2017; Sosa-Pérez et al., 2017).
It has been reported that the performance of
micronutrient components of bee pollen, honey, and
royal jelly added to quail drinking water, propolis
ethanolic extract and diets and the development of
quail immunity system can be improved (Babaei et al.,
2016). In another study, performance parameters and
unsaturated fatty acid ratios in quail tissues were
increased (Seven et al., 2014). Another study
investigates the effect of royal jelly on fat tissue
profiles in quails and it was determined that the ratio
of unsaturated fatty acids in chest, kidney, leg, and
liver tissues was improved (Seven et al., 2013).
The use of royal jelly has been found to increase
hyperglycemia in obese/diabetic K.K.- mice and
partially reduce body weight (Yoshida et al., 2017). It
has been reported that royal jelly is preventing
hyperlipidaemia in rats and improves blood clotting
levels (Premratanachai and Chanchao, 2014). Royal
Jelly supplementation has been again reported to
reduce the development of epidural fibrosis after
laminectomy in rats (Günaldı et al., 2014) and has
been found to significantly reduce serum and hepatic
lipids and cholesterol levels in rats and rabbits, and
also delayed the formation of atheroma of the aorta in
the rabbits fed with hyperlipidaemic diet (Vittek,
1995).
In a study on rats, royal jelly demonstrated
osteoinductive and anti-inflammatory effects in the
treatment of periodontal diseases and prevention
(Yanagita et al., 2011).
The consumption of royal jelly and bee pollen
increased the calcium and phosphorus levels in the
bone tissue and it was determined that osteoporosis-
related bone loss was reduced in the
oophorectomized rats model (Kafadar et al., 2012).
It has been reported that the administration of
royal jelly at a level of 1% may improve premature
mortality in mice through the restoration of immune
system dysfunction caused by low micronutrient
uptake (Kwon et al., 2017).
Feeding royal jelly major proteins (MRJP) to older
rats has been reported to increase spatial memory up
to 48.5% and it has got great potential for inhibiting
cognitive impairment by catabolism of cysteine and
taurine metabolism in elderly rats (Pyrzanowska et al.,
2014; Chen et al., 2017).
For the determination of the immunomodulative
effect of royal jelly in the 4t1 breast cancer model in
rats (0, 5g/kg) in mice bearing 4T1, tumour necrosis
factor-alpha (TNF-a), immunoglobulin G (IgG), and
kidney-upper cells are enlarged. It shows that royal
jelly has an important immune modulator effect
reflected in the serum. Thus, royal jelly has been
reported to be associated with antitumor effects,
which develops immunity in mice with 4T1 (Zhang et
al., 2017a). In another study, using prophylactic-
therapeutic (PTRJ) or therapeutic (trj) method, it has
been shown to nourish the mice carrying 4T1 with
royal jelly. It has been found that royal jelly treatment
in mice reduces the development of breast tumour
and also improves the antioxidant capacity of the
serum, liver, and kidney, especially using prophylactic
treatment method. These results have confirmed the
efficacy of royal jelly supplementation in diets (Zhang
et al., 2017b).
To investigate the effect of royal jelly on the
growth of WEHI-164 fibrosarcoma cells in syngenic
Balb/C mice, 100, 200, 300 mg / kg royal jelly were
applied to groups 1-4, respectively and the tumour
size in the case group was significantly lower than the
control group (P < 0.05). Metastasis was not observed
in the test and control groups. It appears that royal
jelly has an important role in the control and
regression of fibrosarcoma cells. Since royal jelly has a
delayed effect on fibrosarcoma control, it is
recommended to use it at least 10 days before tumour
inoculation (Shirzad et al., 2013).
It has been reported in rats that royal jelly has a
protective effect on external cardiac muscle ischemia,
increases contraction activity, develops intraventricular
pressures and increases coronary blood flow (Krylov et
al., 2006).
In a study showing the effect of fresh royal jelly on
the mice fatigue: the mice in the group that consume
the royal jelly, serum lactate and serum ammonia
accumulation decreased significantly, while muscle
glycogen has been decreased, therefore the
consumption of royal jelly has been reported that it
can heal physical fatigue (Kamakura et al., 2001). Royal
jelly can modulate behavioural and
histomorphometric disorders caused by Parkinson's
disease in rats (Taherianfard et al., 2017).
According to the study, the effects of RJ on the
change of experimental colitis and mast cell
distribution induced by acetic acid in the rat's colon,
Use of Royal Jelly as Functional Food on Human and Animal Health
135
ensuring that the royal jelly colon mucosa is protected
against the harmful effects of acetic acid. It has also
been reported that rats treated with royal jelly reduce
the number of mast cells MC and the colonic erosion
area in the colon (Karaca et al., 2010). As well, oral
mucosity due to radiotherapy applied to the head and
neck region in rats is effective in decreasing oral
mucositis when administered at appropriate doses
(100 mg/kg) (Cihan and Deniz, 2014).
Restraint and cold stress lead to the release of
corticosterone from the adrenal gland of the
hypothalamic-pituitary-adrenal (HPA) axis, which may
worsen the antioxidant defence system in the central
nervous system. Rats supplemented with RJ have
been found to have reduced corticosterone in the
brain, cerebellum, striatum, and hypocampus, as well
as in the glutathione defence system of the cerebral
cortex and striatum, as well as in hypocampus
glycemia and fractions. This study reveals the anti-
stress and neuroprotective effect of royal jelly in stress
conditions (Teixeira et al., 2017).
It has been determined that royal jelly, propolis,
and bee pollen have the greatest effect on Aeromonas
hydrophila and Vibrio cholerae according to the study
conducted to demonstrate the antibacterial effect
against pathogenic bacterial isolates in the water. The
results of current in vitro studies suggest strong
natural products such as royal jelly, propolis, and
pollen can control pathogenic bacteria (Salimi et al.,
2013).
The Use of Royal Jelly on Human Health
Royal Jelly is effective on the regeneration,
production, and metabolism of cells in the body,
resulting in vitality, health, energy, high immunity,
and vigour in all tissues of the organism. Its structure
is rich in natural hormones, vitamins, essential fatty
acids, amino acids, sterols, phosphorous compounds,
and acetylcholine. Acetylcholine is effective in the
transmission of nerve messages and in the regular
functioning of endocrine glands. Royal jelly, which is
also rich in nucleic acids which are the basic
substances of life, has anti-aging effects because it
also contains gelatinous amino acid which is the basic
component of collagen. Gammaglobulin in its
structure is a factor in the fight against infection and
strengthening of the immune system. 10-HDA content
has strong antibiotic effect against many bacteria and
fungi. It is well known that royal jelly has been
successfully used in oncology, psychiatry and
neurology, geriatrics, bone and cartilage tissue repair,
vascular stiffness, urology, especially infertility
treatment, skin protection, development and growth
due to its anti-tumour and metastatic counteracting
effects (Eshraghi, and Seifollahi, 2003; Doğaroğlu,
2007; Park et al., 2011; Pavel et al., 2011; Ramadan and
Al-Ghamdi, 2012; Filipič and Potokar, 2013; Yang et al.,
2015; Siavash et al., 2015; Ahmadnia et al., 2015). Royal
jelly also contributes to the recovery of damage
caused by 5-fluorouracil (Suemaru et al., 2008). It has
been reported a variety of antitumor, antibiotic,
immunomodulator, estrogenic and neurogenic
pharmacological activities of 10-HDA in royal jelly
(Eshraghi, and Seifollahi, 2003; Sugiyama et al., 2012;
Stratev et al., 2015). Six-month intake of royal jelly has
been noted to improve erythropoiesis, glucose
tolerance, and mental health in humans (Morita et al.,
2012).
It has been recorded that consumption of royal
jelly has a significant impact on sperm count and
motility and positive results are obtained in infertility
treatment (Ahmadnia et al., 2015). Besides that royal
jelly with honey is effective in early menopause
formation and ovarian treatment caused by
Adriamycin (Mahmoud and Anas, 2015). In chronic
diseases such as menopausal osteoporosis and
cardiovascular disorder, the intake of 150 mg royal
jelly for three months has been determined to provide
significant improvements in the lipid profile of
postmenopausal women. It has also been investigated
that royal jelly may be an alternative method for
menopause-related dyslipidaemia control
(Lambrinoudaki et al., 2016). Postmenopausal women
may improve their quality of life in the treatment of
sexual and urinary dysfunctions (Seyyedi et al., 2016).
The oral consumption of 1000 mg capsule of royal
jelly for 2 months is effective in reducing the pre-
menstrual syndrome (PMS) (Taavoni et al., 2014).
Early foetal membrane rupture cases with high
incidence of prematurity and foetal death are very
critical and a study has reported that a mixture of
Indian honey and Indian royal jelly has positive effects
on the foetal membrane (Abdelhafiz et al., 2011).
Trans-10-hydroxy-2-decenoic acid (10-H2DA), 10-
hydroxydecanoic acid (10-HDAA), and sebacic acid
(SEA) are the three major fatty acids in royal jelly (RJ).
Previous studies have revealed several
pharmacological activities of 10-H2DA and 10-HDAA,
although the anti-inflammatory effects. The results
showed that 10-H2DA, 10-HDAA, and SEA had potent,
dose-dependent inhibitory effects on the release of
the major inflammatory-mediators, nitric oxide, and
interleukin-10, and only SEA decreased TNF-
αproduction. Several key inflammatory genes have
also been modulated by these royal jelly fatty acids,
Strant et al
136
with 10-H2DA showing distinct modulating effects as
compared to the other two FAs. Furthermore, it has
been found that these three FAs regulated several
proteins involved in mitogen-activated protein kinase
(MAPK) and nuclear factor-kappa B (NF-κB) signaling
pathways. Taken together, these findings provide
additional references for using royal jelly against
inflammatory diseases (Chen et al., 2016).
Royal jelly has also a stimulating, activating effects
on the central nervous system, Acetyl-choline like
effects on the intestine and the innervation of the
smooth respiration muscle. These effects result in an
improved muscle tonus and activity. Royal jelly shows
neurotrophic effects on the mature brain via
stimulation of Glial Cell-Derived Neurotrophic Factor,
GDNF production. The enhanced expression of
neurofilament H mRNA is involved in events
subsequently caused GDNF. Royal jelly may play
neurotrophic and/or neuroprotective roles in the
adult brain through GDNF. Recent brain research has
elucidated the mechanism of action for the Royal jelly
effects on the CNS. A unique royal jelly component,
cAMP-N1 oxide, not found in any other materials, acts
directly on neuronal differentiation and stimulates the
formation of different brain cells. Royal jelly facilitates
also the differentiation of all types of brain cells:
neurons, astrocytes, and oligodendrocytes. It also
royal jelly ameliorates neuronal function by
regenerating hippocampal granule cells that function
in the cognition process (Bogdanov, 2015).
There are also studies proving that the royal jelly
has positive effects for diabetes patients
(Pourmoradian et al., 2014; Khoshpey et al., 2016). In
addition, the intake of royal jelly has reported positive
effects on serum total antioxidant capacity and insulin
resistance (Homa-IR) in diabetics (Shidfar et al., 2015).
Other than that, Mobasseri et al, (2015) noted a
significant effect on the glycemic factor in the Type 2
diabetic patients on consumption of royal jelly. It has
been reported that royal jelly intake might be
beneficial in weight management for type-2 diabetes
in women (Pourmoradian et al., 2012).
The use of royal jelly and honey supports the
improvement of the fatigue period in cancer patients
(Mofid et al., 2016). It has also been recorded that
royal jelly improves the symptoms of oral mucosa in
patients undergoing radiotherapy and chemotherapy
and significantly shortens the healing time (Erdem
and Güngörmüş, 2014). Rafat et al, (2016) reported
that royal jelly would have a protective role for 14
days of its consumption versus radiation-induced
apoptosis in human peripheral blood leukocytes. It
has been reported that the use of honey and royal
jelly for the antioxidant effects for the protection of
acute renal damage induced by Cisplatin (the most
potent antineoplastic drug) in cancer patients is
effective in reducing Cisplatin nephrotoxicity and
potentially important for the treatment of Cisplatin
kidney side effects (Osama et al., 2017).
It is reported that the use of royal jelly cannot
prevent the weakening of physical performance in
elderly people, but may slow down muscle strength
(Meng et al., 2017). In the aging process of human
populations, it has been noted that a non-toxic,
natural food product can contribute to the
preservation of memory in the development of a
better quality of life in the elderly (Pyrzanowska et al.,
2014). Royal jelly can protect the skin by increasing
collagen production in the UVB-induced photoaging
(Park et al., 2011).
Pseudomonas aeruginosa is a gram-negative
bacterium that causes respiratory tract infection,
especially in elderly patients. The royal jelly inhibited
P. aeruginosa adhesion and showed that it protects
epithelial cells from extreme inflammatory responses
to P. aeruginosa infection (Susilowati et al., 2017). It
has also been noted that royal jelly plays an
important, protective role against Fumacein toxicity
(El-Nekeety et al., 2007).
Antibiotic resistance of pathogenic bacteria is an
increasing public health problem. Methicillin-resistant
Staphylococcus aureus (MRSA) is an important burden
for healthcare services, as it causes difficulty in
treating people with infections. Honey and royal jelly
have been reported to have the potential as
alternative therapeutic substances against MRSA
infections, in the case of individual or as a
combination, but the clinical trials are needed for
confirmation (Dinkov et al., 2016).
Dry eye; It is a multi-factor disorder characterized
by visual impairment and eye discomfort. The lacrimal
gland function is known to be a strong risk factor for
eye drying and decreases with aging. With the
introduction of technology into our lives, symptoms
such as eye drying and tear deficiency are reported to
occur more frequently. It has been reported that the
use of RJ in this situation is a promising basic
alternative to increase tear secretion within 8 weeks
and to preserve lacrimal gland function (LG), and
topical application of royal jelly is a safe and effective
intervention to increase tear volume in dry-eyed
patients (İmada et al.,2014; Inoue et al., 2017).
The two major bee products, propolis and royal
jelly, have been widely used throughout the world as
Use of Royal Jelly as Functional Food on Human and Animal Health
137
traditional and ethnopharmacological nutrients since
ancient times. Both have a number of factors known
to be effective for various medical conditions. The use
of royal jelly and propolis in upper respiratory tract
infections (Urti) is thought to be given together as a
dietary supplement and can be separately. 10-HDA is
the most prominent active compound in the RJ. The
acid phenethyl Ester is the most effective ingredient in
propolis showing antimicrobial and anti-inflammatory
effects. Compared with propolis, royal jelly is known
to have a rich content for all three main nutrients in
proteins, carbohydrates, and lipids. In addition to
other secondary compounds with health beneficial
effects, more clinical, experimental and fundamental
research is needed to find the best standardized
mixture to cope with URTI, which will be the main
components of royal jelly and propolis. In addition to
classical treatment methods, it is an urgent need to
find the most reliable and standardized best mix
approved for healthy beneficial effects such as
propolis, royal jelly, Echinacea as healing agents for
children to cope with seasonal UTI as an alternative
option (Yüksel and Akyol, 2016).
No significant change in any of the anthropometric
parameters such as body weight, waist, and body fat
could be determined by studying the effects of royal
jelly (350 mg / capsule) on mild hypercholesterolemic
participants. Serum total cholesterol and low density
lipoprotein cholesterol levels decreased significantly
(p <0.05) after application of royal jelly, but triglyceride
(TG) and high density lipoprotein cholesterol (HDL-c)
levels did not change significantly. It has also been
reported that the consumption of royal jelly
significantly reduces the risk of cardiovascular disease
and improves the concentration of sex hormones such
as dehydroepiandrosterone sulphate (DHEA-S) and
reduces the risk of cardiovascular disease according to
(KVH) (Chiu et al., 2017).
Another study examined the effects of royal jelly
supplementation on serum lipoprotein metabolism in
humans. Fifteen volunteers were divided into a royal
jelly intake group (n=7) and a control group (n=8). The
royal jelly group took 6 g per day for 4 weeks. Their
serum total cholesterol (TC) and serum low-density
lipoprotein (LDL) decreased significantly compared
with those of the control group (p<0.05). There were
no significant differences in serum high-density
lipoprotein (HDL) or triglyceride concentrations.
Moreover, the relationship between the serum
cholesterol and lipoprotein levels was investigated.
Among the lipoprotein fractions, small very-low-
density lipoprotein was decreased (p<0.05) after RJ
intake. The results suggest that dietary royal jelly
decreases TC and LDL by lowering small VLDL levels
(Guo et al., 2007).
Meta-analysis of royal jelly human studies to
reduce hyperlipidaemia has shown that there is a
significant reduction in total serum lipids and
cholesterol levels and that normalization of HDL and
LDL is determined without decreasing β / α
lipoproteins. The best dose obtained shows that
about 50 to 100 mg of RJ per day reduced total serum
cholesterol levels by about 14% and total serum lipids
by about 10% in the studied group of patients (Vittek,
1995).
Twenty volunteers underwent the standardized
oral glucose tolerance test (OGTT) and afterwards a
second OGTT after ingestion of 20 g of royal jelly.
Serum glucose levels after 2 hours and the area under
the curve for glucose were significantly lower after
royal jelly administration (Münstedt et al., 2009).
It has been determined in children that the clinical
severity score for royal jelly on systemic lupus
erythematosus (SLE) is improved by 3 months of royal
jelly treatment in terms of laboratory markers, and
apoptotic CD4 T lymphocytes that significantly
reduced after royal jelly therapy compared with
baseline values and control group (Zahran et al.,
2016).
Another study evaluates the antibacterial effect of
0.2% of royal jelly and chlorhexidine in dental practice.
As a conclusion of the study, the royal jelly contains
important elements with antibacterial action
compared to the chlorhexidine one (Meto et al., 2017).
Clarification of the components of royal jelly which
possess this effect along with other behavior cell
adhesion, migration, collagen production would lead
to a more complete picture of the effect of royal jelly
on cells. Considering its availability and possibly
positive effect on the periodontium, royal jelly seems
to be an interesting agent in dentistry (Dhanesuan et
al., 2011).
Serum anti-β-IG IgE and IgG have inhibited the
plasma levels of histamine as a result of giving royal
jelly to rats orally and reduced the intestinal
anaphylactic response and histological lesions caused
by β-Lg sensitivity. These results have been reported
that royal jelly can have a beneficial effect by reducing
symptoms in your allergies to cow's milk protein
(Guendouz et al., 2017).
Graves' disease is an organ-specific autoimmune
disease with unknown etiology. It is reported that
royal jelly may be effective as anti-thyroid drug
Strant et al
138
therapy in the treatment of this disease (Erem et al.,
2006).
The validation data showed the potential of 10-
HDA for use in suppressing skin pigmentation. The 10-
HDA has been shown to inhibit melanogenesis, thus it
could be developed as cosmetics skin care products
(Peng et al., 2017).
Long-term overeating or alcohol consumption
causes a viral hepatitis and/or fatty liver intensification
resulting in eventual liver failure. Prolonged intake of
alcohol not only leads to a reduction in immune
function, but also promotes the production of
inflammatory cytokines by Kupffer cells activated by
enterobacterial endotoxins. The use of royal jelly
demonstrates a pro-active effect on alcohol-induced
hepatomegaly and indicates that it may function in
the restoration of transaminase levels caused by
impaired hepatocytes, ie, the ability of the immune
system to function in individuals with alcoholic liver
diseases (Li et al., 2011).
It has been reported that hepatoprotective effects
of royal jelly on paclitaxelin (TXL) -induced toxicity,
which may lead to a clear cross between E2f1 and c-
Myc as two regulators of liver growth (Malekinejad et
al., 2016).
Dietary, freeze-dried royal jelly improves epidermal
hydration with increased ceramide levels in the
epidermis of middle-aged healthy people at a dose of
520 mg / day for 10 weeks. Topical application of royal
jelly has been reported to have beneficial effects on
dry skin protection (reduced epidermal hydration)
according to (Cho et al., 2016).
Foot ulcers and infections in diabetic patients are
the main sources of morbidity. Studies shows that
topical royal jelly application helps in recovering
diabetic foot ulcers and it might be an effective
method for the treatment of diabetic foot ulcers as
well as standard treatment for an average of 41 days
of complete healing over 8% of patients (Siavash et al.,
2011).
Several studies have shown that oxidative stress
occurs in patients with kidney stones. Exposure to Ca
oxalate is caused by oxidative damage with reactive
oxygen species such as superoxide and H2O2. The
produced ROS activate a variety of signal paths. It is
reported that the antioxidants in royal jelly have
positive impact on renal damage caused by
inflammation, inhibits ROS production and supports
the overall antioxidant system (Aslan and Aksoy, 2015).
Royal jelly used as a supplement is applied as a
criterion of positive change in the phase of adaptation
and exhaustion of young football players' bodies.
Research carried out with 12 years old football players.
It was observed 13 morphological characteristics in
initial and final measuring. It could be concluded that
football players who used royal jelly had statistically
significant increase of body height and muscle
component, and decrease of fat component in final
measurement compared to the initial. Also, the results
show statistically significant increase in circumference
above knee and circumference of lower leg in
experimental group at the end of the treatment. The
results also showed higher average values in body
height, body mass, muscle and bone component, and
lower average value in fat component as well
(Joksimovič et al., 2009).
Another study conducted showed the analgesic
effect of royal jelly on acute pain in a dose of 200
mg/kg was found to be equal to aspirin and lower
than morphine. However, RJ and aspirin have been
found to be more effective on chronic pain. Given its
analgesic, antioxidant, and anti-inflammatory
properties, royal jelly could be recommended for
reduce the pain accordingly (Arzi et al., 2015).
Royal jelly is known as a functional food containing
many useful minerals. This study, shows an anti-
environmental oestrogen activity of royal jelly.
Bisphenol A (BPA) is an environmental oestrogen that
stimulates proliferation of human breast cancer MCF-7
cells. Royal jelly inhibited the growth-promoting effect
of BPA on MCF-7 cells, even though it did not affect
the proliferation of cells in the absence of BPA. In
addition, this inhibiting effect of royal jelly was heat-
stable (Nakaya et al., 2007).
Dosage of Royal Jelly for Human Use
Bee products may trigger an allergic effect for
some people (Paola et al., 2014; Abdullaha and
Abdullahb, 2016). For example, the use of RJ in cases
of asthma and anaphylaxis conditions may cause an
allergic reaction to occur (Thien et al., 1996). People
with allergies should perform allergy tests before
starting to use them, or start using low doses. If they
have allergic symptoms bee products must not be
used. Since each person's immune system is different,
checking a doctor’s advice is an important key to
success.
Recommending royal jelly to the patients is related
very much to their specific needs, their health
conditions, age but also with the results that was
observed in laboratory by the researchers. Sometimes,
very low doses can be very effective, but other times
large doses might be needed. Studies shows that a
dose of 100 mg/kg give the best effect in severe
conditions, higher doses very rarely being needed.
Use of Royal Jelly as Functional Food on Human and Animal Health
139
Infants: Growth and development, strengthen
immunity and nervous system: 0,5 g/day for 2-12
months. For premature babies we found in literature
various dosages to treat the complications of this
condition, starting with 50 mg to 1 gram per day. As a
general observation, in the beginning, practitioners
used very small does of royal jelly, but in time they
increased dosages (sometimes significantly) with
great results and no sides effects. For premature
infants we used a medium doze of 0.25 g/day raw
royal jelly (Gyuzukina and Dimitrieva, 1993; Mahmoud
et al., 1997; Gyuzukina and Dimitrieva, 1998;
Magdalena, 2010; Strant and Grosu, 2016; Strant,
2017a; Strant, 2017b).
Children: low immune system, nervous system
impairment (foetal suffering, delivery complication
when born), weakness, loss of appetite, anorexia,
anaemia, etc. for children aged 1-5 yrs 0.5 g/day and
for children between the age of 5-12 yrs old 0.5-1
g/day royal jelly only or used in combination with
other bee products, it is used in a lower dose due to
synergistic effect. For children aged 1-5 yrs old, 1-3
days 2.5 g/day RJ and 5-12 years for children with
acute infection and colds, 5 g/day royal jelly in the 1-3
daily period (Strant, 2017a; Strant, 2017b).
Adults: Immunity, insomnia, skin disorders,
anaemia, low libido, hormonal imbalance, wounds,
premenstrual syndrome, menopause, osteoporosis,
etc. In such cases, 1 to 2 g / day can be used, diabetes,
depression, Hashimoto's disease, in cases of arthritis
with 3-5 g / day may be used. In cases of recent
depression, different doses are applied to the royal
jelly in our practice. In some cases, larger doses such
as 10g/day are available for a faster, more powerful
response for a shorter period of time (10 days/month
for 3 months). In combinations with other bee
products and plants-1 gr/day royal jelly (immunity,
convalescence, preparation for surgery, autoimmune
diseases, cancer, hormonal imbalances, infertility,
ovarian cyst, uterine fibroma, thyroid problems etc.)
Up to 10 g/day for 1-3 days in the beginning of colds,
10 g/day for 1-3 days in other acute infections, up to 3-
5 days to accelerate post-operative healing, 5-10
g/day. For individuals under heavy working
conditions, 10g/day royal jelly. For early onset of colds
for 1-3 days, 10 g / day cough until it stops, 10 g for 1-
3 days in other acute infectious to accelerate healing
after surgery 5-10 g for 3-5 days. The side effects of
chemotherapy such as paresthesia, pain or burning
sensation of fingers, imbalance during walking, the
sensation of weakness in the legs 3 g/day royal jelly
can be used for 6-8 weeks (Strant, 2014; Strant, 2016;
Strant and Varadi, 2016; Strant and Grosu, 2016;
Strant, 2017a; Strant, 2017b). Neurodegenerative
diseases, multiple sclerosis, long-term 10-15 g/day in
Parkinson's (according to the condition of symptoms.
It is known that royal jelly has good effects for skin
problems (Kohno et al., 2004; Tatsuhiko et al., 2011).
Combination of royal jelly with essential oils can be
used to treat various conditions of skin. One of the
most common condition is the acne, which can be
severe sometimes, affecting not only the good looking
of the patient, but also giving disturbing symptoms
due to the inflamation and also psychological discomfort.
One of the best essential oils is frankincense (Boswellia
spp). Studies showed that frankincense essential oil
applied topically reduce inflammation, determine
significant improvements of fine lines, elasticity of the
skin, reduction of sebum excretion, as well as overall
echographic parameters of skin photoaging
(Calzavara‐Pinton et al., 2010; Hamidpour et al., 2013).
Using a mask with raw royal jelly combined with
Boswellia essential oil in treatment of severe acne
combined with oral treatment with propolis and
healed the acne completely and reduced the scars.
Royal jelly is an expensive product, so it will be
economically correct to use the dose that will give the
maximum effect.
Royal Jelly and Diet
In general, bee products are a rich source of
intelligent essential nutrients to keep your body
healthy. As a result of environmental pollution and
overuse of chemicals, increasing the load of toxic
environment becomes difficult for us to maintain
health. Both our food supply and diet are often
inadequate in terms of important nutrients. In recent
years we are going to turn this situation off with
functional foods. Royal jelly and other bee products,
have a lot of features of functional products/foods,
that are very important in our diets.
The addition of royal jelly to our diet and using bee
products as food, the composition found works
predominantly in preventive treatment and comes
with valuable nutrients that are found in very little
food. Nutrients such as 10 HDA, B5, B12, folate
(valuable micronutrients), which are found in large
quantities in the royal jelly, provide a high level of
nutrition in the diet of humankind (Lab Reference:
CS20133271, Food Intertek, test report, for the
Romanian royal jelly, 27.02.2017).
Folate is a generic term for a naturally occurring
family of B-group vitamins. It is found naturally in
foods, including royal jelly (folate=40.22 ug/100 g,
Strant et al
140
Intertek Laboratory, United Kingdom test report, for
the Romanian royal jelly, 27.02.2017). Folic acid is a
synthetic form of folate which is widely used in
supplements and for food fortification and
supplementation of folic acid has been associated
with an increased risk for autism during gestation
(Desoto and Hitlan, 2012).
The basic action of royal jelly, which contributes to
our diet more than a meal, is the preventive effect of a
faster recovery by acting on a cell and at the level of
the disease. Two of the most important functions of
royal jelly is balancing and normalizing cell life
functions that are based on detoxification and
renewal (Menkovska, 2013).
Apinutrition refers to the addition of the beehive
products such as honey, fresh bee pollen, royal jelly,
bee bread, queen bee larvae, apilarnil (drone larvae),
propolis to our daily diet to support, nourish and
revitalise our health. These natural foods have
historically played an enormous part in offering an
exceptional quality of nourishment and energy,
immensely supporting all the body functions, to
promote harmony among all the systems due to their
synergistic effect.
The nutritional complexity of the beehive is vast
and bee products are remarkable for their potential to
transform the human body in a number of ways.
Medical trials around the world have shown that bee
products are a great support in keeping and
improving our health, not only through their
nutritional content which is a true fuel for our
wellbeing, but also for their ability to be totally
assimilated by our body without any effort.
Due to the various pharmacological properties,
including antioxidative, anti-inflammatory and
antibiotic properties, RJ is extensively consumed in
daily diets in many countries (Eshraghi and Seifollahi,
2003; Bărnutiu et al., 2012; Stangaciu et al., 2015;
Stratev et al., 2015; Zhang et al., 2017b).
When the results of the scientific studies are
examined, the consumption of RJ eliminates factors of
many diseases and/or helps heal the disease and will
provide support in maintaining our health.
Royal jelly is also used to help reduce allergic
symptoms, to control cholesterol levels, muscle
dystrophy, MS and Parkinson's disease. Especially in
patients receiving radiotherapy and chemotherapy,
the immune system weakens. In such cases, royal jelly
with its high amino acid content can help the immune
system and provide a basic defence against external
elements that normally attack the immunity and
reduce the ability to defend our body. Supporting our
diet with royal jelly helps to reconstruct the good cells
that are destroyed by chemotherapy and help
strengthen the immunity. Royal jelly also contains
amino and gamma globulin, which helps the immune
system to fight viral infections. It also contains sterols,
phosphorous compounds, and acetylcholine, which
are required to transmit nerve messages from cell to
cell. The high concentration of essential amino acids
in royal jelly is very important supporting chronic
fatigue, skin, hair, nails, bones, joints, hormonal
regulator, asthma, sexual vitality, impotence, weight
control, rejuvenation, disease recovery, immune
system stimulation, cardiovascular health/cholesterol
regulator, anti-depressive, anti-anxiety, high blood
pressure, mental condition, memory, depression,
arthritis, liver disorders, eczema, impetigo, skin
disorders, diabetes, wounds (Fujii et al., 1990;
Joksimovič et al., 2009; Sarıtaş et al., 2011; Min et al.,
2013; Menkovska, 2013; Raja, 2016; Meto and Meto,
2017). In addition, RJ is known as an adaptogen
substance, with maximal fertility boosting properties,
providing the maximum life span without diseases
(Menkovska, 2013).
Contraindications and Adverse Reactions of
Royal Jelly
Even of reliable many positive effects of royal jelly,
it can be contraindicated in bronchial asthma in crisis,
possible allergy to any of its components, Addison
disease and cancers in acute phase. Digestive tract
disorders may occur through overdose: stomachaches,
vomiting, diarrhoea, and insomnia (especially in
women). Decreasing the dose, or stopping the royal
jelly administration will eliminate these adverse
reactions. Toxicity may appear in major overdose
cases. Several factors can diminish the effectiveness of
royal jelly. If body is too weak or unable to digest
and/or absorb, or people have major structural or
genetic problems, they can not use the active
compounds from royal jelly properly. In these cases,
more attention pay and many details should be
evaluated before using.
CONCLUSION
In last decades, healthy eating habits for natural
nutrition and non-sickness are increasing demand in
the world. Royal jelly is one of the most important
products in the bee products. Royal jelly, which has
great positive effects on health, will make a big
contribution in the right place at the right time and at
the right dose and doctor's recommendation to use it.
It can be recommended for people without allergy
risk.
Use of Royal Jelly as Functional Food on Human and Animal Health
141
In particular, royal jelly is an excellent food and its
content is very important for the development and
renewal of children and the elderly, and encouraging
consumption by people can be considered as a
measure to meet the substances our bodies need and
as a pre-sickness measure.
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