Royal Jelly Benefits, Royal Jelly Side Effects
Benefits and side effects - updated on October 02, 2012  zhion@zhion.com
Introduction
Royal Jelly is the milky-white gelatinous substance secreted from the cephalic glands of the worker bees for the growth and of the queen bee.
Without royal jelly, the queen bee would be no different from the worker bees including its life span. Thus, some retails claim the health benefits of
royal jelly on fertility. Chemically, royal jelly is a water-based emulsion of proteins, sugars, lipids and some other ingredients. Some components of
royal jelly have been found to against certain types of bacteria. While the sugar composition of royal jelly is very similar to those found in honey-
fructose and glucose.

Royal jelly is commonly formulated into capsules, chewable tablets, elixir and liquid. [15A] There are two common types of royal jelly preparations –
fresh and freeze-dried. Some manufacturers sell fresh royal jelly directly to the consumers, such that the consumers do not need to worry how long
the products of royal jelly have been sitting on the shelf. Usually, the price for fresh royal jelly is much more expensive than those you can find at
discount stores. Royal jelly is also widely freeze-dried into powder and then packed into capsules. Common brands or products include GNC royal
jelly, bee alive jelly, ginseng royal jelly, fresh royal jelly, royal jelly vitamins, and pure royal jelly.
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Reference:
1. Harwood M et al, Asthma following royal jelly, NZ Med J 1996 Aug 23; 109(1028):325.2. Laporte JR et al, Bronchospasm induced by royal
jelly, Allergy 1996 Jun; 51(6):440.3. Thien FC et al, Asthma and anaphylaxis induced by royal jelly, Clin Exp Allergy. 1996 Feb;26(2):216-22.4.
Peacock S. Respiratory distress and royal jelly, BMJ 1995 Dec. 2;311(7018):1472.5. Leung R et al, Royal jelly-induced asthma and
anaphylaxis: clinical characteristics and immunologic correlations. J. Allergy Clin. Immunol. 1995 Dec;96)6Pt1)1004-7.6. Roger A et al,
Anaphylaxis caused by royal jelly, Allergol Immunopathol (Madr). 1995 May-Jun;23(3):133-5.7. Bullock RJ et al, Fatal royal jelly-induced
asthma, Med J Aust. 1994 Jan 3, 160(1)44.6. Thien FC et al, Royal Jelly induced asthma, Med J Aust. 1993 Nov 1, 159(9)639.7. Takahashi M
et al, Contact dermatitis due to honeybee royal jelly, 1983 Nov9(6):452-5. 8.Murakami K. et al, A case of eosinophilic gastroenteritis induced
by royal jelly, Nippon Shokakibyo Gakkai Zasshi. 1994 Sep;91(9):1447-50. [10] Leung R et al, Royal jelly consumption and hypersensitivity in
the community. Clin Exp Allergy. 1997 Mar;27(3):333-6. [1-9] [1A] Zamami Y, Takatori S, Goda M, Koyama T, Iwatani Y, Jin X, Takai-Doi S,
Kawasaki H. Royal jelly ameliorates insulin resistance in fructose-drinking rats. Biol Pharm Bull. 2008 Nov;31(11):2103-7. [2A] Izuta H,
Chikaraishi Y, Shimazawa M, Mishima S, Hara H. 10-Hydroxy-2-decenoic Acid, a Major Fatty Acid from Royal Jelly, InhibitsVEGF-induced
Angiogenesis in Human Umbilical Vein Endothelial Cells. Evid Based Complement Alternat Med. 2007 Oct 22. [3A] Kanbur M, Eraslan G,
Beyaz L, Silici S, Liman BC, Altınordulu S, Atasever A. The effects of royal jelly on liver damage induced by paracetamol in mice. Exp
Toxicol Pathol. 2008 Aug 5. [4A] Guo H, Saiga A, Sato M, Miyazawa I, Shibata M, Takahata Y, Morimatsu F. Royal jelly supplementation
improves lipoprotein metabolism in humans. J Nutr Sci Vitaminol (Tokyo). 2007 Aug;53(4):345-8. [5A] Nomura M, Maruo N, Zamami Y,
Takatori S, Doi S, Kawasaki H. Effect of long-term treatment with royal jelly on insulin resistance in Otsuka Yakugaku Zasshi. 2007
Nov;127(11):1877-82. [6A] Kamakura M, Moriyama T, Sakaki T. Changes in hepatic gene expression associated with the
hypocholesterolaemic activity of royal jelly. J Pharm Pharmacol. 2006 Dec;58(12):1683-9. [7A] Nakaya M, Onda H, Sasaki K, Yukiyoshi A,
Tachibana H, Yamada K. Effect of royal jelly on bisphenol A-induced proliferation of human breast cancer cells. Biosci Biotechnol Biochem.
2007 Jan;71(1):253-5. Epub 2007 Jan 7. [8A] Identification of a collagen production-promoting factor from an extract of royal jelly and its
possible mechanism. Koya-Miyata et al, Fujisaki Institute, Japan, BioSci BioTechnol BioChem, 2004 Apr;68(4):767-73. [9A] Antihypertensive
effect of peptides from royal jelly in spontaneously hypertensive rats. tokunaga et al, API Company, Japan. Biol Pharm Bull, 2004
Feb;27(2):189-92. [10A] Royal Jelly inhibits the production of proinflammatory cytokines by activated macrophages. Kohno et al, Fujisaki
Institute, Japan. BioSci BioTechnol BioChem. 2004 Jan;68(1):138-45. [11A] Royal Jelly prolongs the life span of C3H/HeJ mice: correlation
with reduced DNA damage. Inoue et al, Fujisaki Institute, Japan. Exp Gerontol. 2003 Sep;38(9):965-9. [12A] Effects produced by Royal Jelly on
haematopoiesis: relation with host resistance against Ehrlich ascites tumour challenge. Int Immunopharmacol. 2005 Apr; 5(4):679-88. [13A]
Major Royal Jelly Protein 3 modulates immune responses in vitro and in vivo. Okamto et al. Fujisaki Institute, Japan. Life Sci. 2003 Sep
5;73(16):2029-45. [14A] Case report: haemorrhagic colitis associated with royal jelly intake. J Gastroenterol hepatol. 1997 Jul, 12(7):495-9.
[15A] pdr health online publication, December 26, 2005] [16A] Oral administration of Royal Jelly inhibits the development of atopic
dermatitis-like skin lesions in NC/Nga mice. Taniguchi et al, Fujisaki Institute, Japan. Int Immunopharmacol. 2003 Sep;3(9):1313-24. [17A]
Antifatique effect of fresh royal jelly in mice. Kamakura et al, Pola Co., Japan. J Nutr Sci Vitaminol (Tokyo).2001 Dec;47(6):394-401. [18A]
Jelleines; a family of antimicrobial peptides from the royal jelly of honeybees. Peptides. 2004 Jun;25(6):919-28. [19A] A potent antibacterial
protein in royal jelly. Purification and determination of the primary structure of royalisin. Fujiwara et al. Morinaga Milk Industry Company LTD.
Japan. J Biol Chem. 1990 Jul 5;265(19):11333-7. [19A] Katayama M, Aoki M, Kawana S. Case of anaphylaxis caused by ingestion of royal
jelly. J Dermatol. 2008 Apr;35(4):222-4. [20A] Hattori N, Nomoto H, Fukumitsu H, Mishima S, Furukawa S. Royal jelly and its unique fatty acid,
10-hydroxy-trans-2-decenoic acid, promote neurogenesis by neural stem/progenitor cells in vitro. Biomed Res. 2007 Oct;28(5):261-6. [B1]
Abdelatif M, Yakoot M, Etmaan M. Safety and efficacy of a new honey ointment on diabetic foot ulcers: a prospective pilot study. J Wound Care.
2008 Mar;17(3):108-10. [B2] Sultana A, Nabi AH, Nasir UM, Maruyama H, Suzuki KM, Mishima S, Suzuki F. A dipeptide YY derived from royal
jelly proteins inhibits renin activity. Int J Mol Med. 2008 Jun;21(6):677-81. [S2] Takaki-Doi S, Hashimoto K, Yamamura M, Kamei C.
Antihypertensive activities of royal jelly protein hydrolysate and its fractions in spontaneously hypertensive rats. Acta Med Okayama. 2009
Feb;63(1):57-64. [S3] Hattori N, Ohta S, Sakamoto T, Mishima S, Furukawa S. Royal Jelly Facilitates Restoration of the Cognitive Ability in
Trimethyltin-Intoxicated Mice. Evid Based Complement Alternat Med. 2009 Apr 17 [S4] Sultana A, Nabi AH, Biswas KB, Takemoto M, Suzuki F.
A peptide YY inhibits the human renin activity in a pH dependent manner. Front Biosci. 2009 Jan 1;14:3286-91. [S5] Narita Y, Ohta S, Suzuki
KM, Nemoto T, Abe K, Mishima S. Effects of long-term administration of royal jelly on pituitary weight and gene expression in middle-aged
female rats. Biosci Biotechnol Biochem. 2009 Feb;73(2):431-3. Epub 2009 Feb 7. [S6] Boukraa L. Additive activity of royal jelly and honey
against Pseudomonas aeruginosa. Altern Med Rev. 2008 Dec;13(4):330-3. [S7] Liu JR, Yang YC, Shi LS, Peng CC. Antioxidant properties of
royal jelly associated with larval age and time of harvest. J Agric Food Chem. 2008 Dec 10;56(23):11447-52. [S8] Zamami Y, Takatori S, Goda
M, Koyama T, Iwatani Y, Jin X, Takai-Doi S, Kawasaki H. Royal jelly ameliorates insulin resistance in fructose-drinking rats. Biol Pharm Bull.
2008 Nov;31(11):2103-7. [S9] Suzuki KM, Isohama Y, Maruyama H, Yamada Y, Narita Y, Ohta S, Araki Y, Miyata T, Mishima S. Estrogenic
activities of Fatty acids and a sterol isolated from royal jelly. Evid Based Complement Alternat Med. 2008 Sep;5(3):295-302. [Z1] Harada S, et
al, Two cases of royal jelly allergy provoked the symptoms at the time of their first intakeArerugi. 2011 Jun;60(6):708-13. [Z2] Park HM, Hwang
E, Lee KG, Han SM, Cho Y, Kim SY. Royal Jelly Protects Against Ultraviolet B-Induced Photoaging in Human Skin Fibroblasts via Enhancing
Collagen Production. J Med Food. 2011 Aug 3.
[DD1] Eur J Histochem. 2010 Oct 21;54(4):e35.] [E1] Yakoot M, Salem A, Omar
AM. Effectiveness of a herbal formula in women with menopausal syndrome. Forsch Komplementmed. 2011;18(5):264-8
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Royal Jelly Side Effects
A 26-year-old Japanese woman developed anaphylaxis as a royal jelly side effect after drinking a beverage of crude royal
jelly including honey. She had a history of bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis and
food allergy (abalone). [19A]

Royal jelly appears to be safe to bees and probably human. However, there are piles of reports about
royal jelly side
effects
, and these side effects are related to asthma or anaphylaxis; most happened before 1999. The most recent
incident of royal jelly side effects was reported by Harada Skin Clinic, Japan, in June of 2011. Two young women
experienced severe allergy after the intake of royal jelly at their first time. [Z1] The side effects in most cases include
urticaria, eczema, rhinitis and acute asthma. [1-10] There is a also report of a 53 year old woman with abdominal pain and
bloody diarrhoea (haemorrhagic colitis) associated with royal jelly intake. [14A]

Royal jelly from honeybees (Apis mellifera) was shown to have a weak estrogenic activity mediated by interaction with
estrogen receptors that leads to changes in gene expression and cell proliferation. [S9] Is it good or bad ---- a side effect
or a benefit?

Related Article:
Effect of Royal Jelly on Hair Growth
                                                                           
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Organic Royal Jelly
Organic royal jelly refers to royal jelly obtained in the condition that the bees are kept from any type of spraying. The
market price for organic royal jelly is much higher than regular royal jelly.

Other Information
Royal jelly is popularly combined with bee pollen, bee propolis, eleuthero and ginseng as a food supplement.
Royal Jelly Health Benefits

Antioxidative Activities
The antioxidative activities of royal jelly is a key factor to its health benefits. Research demonstrates that the time of
harvest and the initial larval age affects the antioxidant potencies of royal jelly. Royal jelly collected 24 h after the larval
transfer showed the most substantial antioxidant activities. [S7]

Anti-Inflammatory Activities
Most chronic diseases are related to inflammation, anti-inflammatory action contributes to royal jelly benefits. Royal Jelly's
anti-inflammatory actions have been shown at cytokine level using cultures of mouse peritoneal macrophages. Royal Jelly
exerts its anti-inflammatory actions through inhibiting proinflammatory cytokine production by activated macrophages.
[10A] Let's see how royal jelly benefit condition of colitis, the inflammation of colon. In a study of rats, royal jelly treatment
significantly decreased the number of mast cells and reduced the area of colonic erosion in the colon of royal jelly-treated
rats compared with rats with untreated colitis. [DD1]

Dermatitis is the inflammation of skin. Royal jelly skin benefits are demonstrated in a cell study, it may alleviate atopic
dermatitis. It has been known that royal Jelly promotes collagen production by skin fibroblasts in the presence of ascorbic
acid-2-O-alpha-glucoside. It was further found that purified royal jelly was similar to those of 10-hydroxy-2-decenoic acid,
which can induce the fibroblast cells to produce transforming growth factor-beta 1. Transforming growth factor-beta 1 is
an important factor for collagen production. [8A] It is able to inhibit the production of IL-4, IL-5, IL-10 and antigen-specific
interferon-gamma in spleen cells of ovalbumin(OVA)/Alum-immunized mice. It is also known that both Th1 and Th2
cytokines play pathogenic roles in the development of atopic dermatitis. Royal Jelly suppresses the development of the
lesions, possibly by a combination of down-regulating TNP-specific IFN-gamma production and up-regulating iNOS
expression. [16A]

In another study Park et al, Kyung Hee University, found UVB-irradiated human skin fibroblasts treated with royal jelly and
10-hydroxy-2-decenoic acid had increased procollagen type I and transforming growth factor-β1 productions, but the
level of metalloproteinase-1 was not changed. Thus royal jelly may potentially protect the skin from UVB-induced
photoaging by enhancing collagen production. [17] These studies and some others have demonstrated royal jelly skin
benefits.
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Allergy
Royal Jelly was shown to have potent exhibit anti-allergic properties in a mouse model of immediate hypersensivity. In an another study, a 70 KDa
glycoprotein, ie. the major Royal Jelly Protein 3 (MRJP3), was found suppress IL-4, IL-2 and IFN-gamma production. [13A] Though royal jelly may have
benefits of anti-allergy, royal jelly itself can cause allergy to some people.

Bacterial Infection
Four peptides in royal jelly were identified to possess anti-microbial properties-Jelleine-I, Jelleine-II, Jelleine-III and Jelleine-IV. [18A] A potent protein
against Gram-positive bacteria was also found in royal jelly. The primary structure of that protein has 51 residues with three intramolecular disulfide
linkages. [19A] Royal jelly intensified honey's activities against Pseudomonas aeruginosa. [S6] A study of 60 patients suffered from limb-threatening
diabetic foot infection suggests that an ointment of royal jelly and panthenol may benefit people with full-thickness skin ulcer or deep tissue infection.
[B1] Thus, royal jelly may benefit people at risk of certain types of infections.

Cancer
Royal jelly may have benefits to people at risk of certain cancers. Royal jelly was able to produce effect on haematopoiesis of Ehrlich ascites
tumor-bearing mice. Royal jelly prevented the myelosupression in mice. [12A] The effect of dietary Royal Jelly on tissue DNA oxidative damage and on
the life span of C3H/HeJ mice was studied. It was found that the levels of 8-hydroxy-2-deoxyguanosine (a marker of oxidative stress) was significantly
reduced if the mice were fed with Royal Jelly for 16 weeks. The dietary Royal Jelly also increased the average life span of C3H/HeJ mice through the
mechanism of reduced oxidative damage. [11A] Vascular endothelial growth factor (VEGF) is reported to be a potent pro-angiogenic factor that plays
a pivotal role in both physiological and pathological angiogenesis. 10-Hydroxy-2-decenoic acid (10HDA), a major fatty acid component of royal jelly,
has been found to have anti-tumor activities.  10HDA actually exerts an inhibitory effect on VEGF-induced angiogenesis, partly by inhibiting both cell
proliferation and migration. The anti-environmental estrogen activity of royal jelly was also demonstrated. Bisphenol A (BPA) is an environmental
estrogen 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. [7A] It make senses that royal jelly may benefit people at risk of certain
cancers.

Diabetes
Royal jelly may benefit people suffered from diabetes. It has been suggested that royal jelly could be an effective functional food to prevent insulin
resistance associated with the development of hypertension in fructose-drinking rats. In the study, male Wistar rats received 15% fructose solution for
eight weeks, they then had high levels of insulin and triglyceride. Royal jelly treatment resulted in a significant reduction in sympathetic
nerve-mediated vasoconstrictor response to periarterial nerve stimulation and tended to increase the calcitonin gene-related peptide nerve-mediated
vasodilator response to periarterial nerve stimulation. [1A] They also reported that treatment of royal jelly could decrease systolic blood pressure in a
type 2 diabetic rats. [5A]
Male Wistar rats (6 weeks old) received 15% fructose solution in drinking water for 8 weeks. Fructose-drinking rats showed significant increases in
plasma levels of insulin and triglyceride. Treatment of royal jelly for 8 weeks significantly decreases the plasma levels of insulin and triglyceride and
systolic blood pressure as well, without affecting blood glucose or total cholesterol levels. Thus, royal jelly may benefit animals at risk of developing
insulin resistance. [S8]

High Blood Pressure
Royal jelly may have benefits of blood pressure lowering effects. There are multiple ingredients of royal jelly contributing to its potential benefits of
blood pressure lowering. Protease N treated royal Jelly and its peptides can inhibit angiotensin I-converting enzyme (ACE) activity and they can lower
the blood pressure in repeated oral doses on spontaneously hypertensive rates. The antihypertensive effect of the peptide mixture could be as high
as 38%. [9A]

A dipeptide YY derived from royal jelly proteins is known to inhibit angiotensin converting enzyme (ACE) activity and the human renin activity at
physiological pH. The renin activity was expressed at a wide pH range with two peaks around at 6.0 and 8.0. The dipeptide YY was found to inhibit the
renin activity only at the acidic pH range lower than
8.0. [S4] Renin is the rate limiting enzyme in the renin-angiotensin system that regulates blood pressure and electrolyte balance. In a study of
spontaneously hypertensive rats, a royal jelly-derived peptide was found to have inhibitory effect on rennin and thus blood pressure lowering
activities. [B2] Angiotensin I-converting enzyme (ACE) inhibitory and blood pressure lowering effect of peptide fractions of royal jelly protein
hydrolysate were also demonstrated in spontaneously hypertensive rats. [S2]

High Lipid Profiles
It is very likely royal jelly may benefit people at risk of high cholesterol levels. The cholesterol-lowering effect of royal jelly is likely related to the
regulation of squalene epoxidase and low-density lipoprotein receptor. Kamakura M and co-workers from Toyama Prefectural University, Japan,
reported royal jelly was able to hinder the gene expression of squalene epoxidase (SQLE). SQLE is a key enzyme in cholesterolbiosynthesis, and
sterol regulatory element-binding protein (SREB)-1, which may be a transcriptional factor of SQLE. In addition, royal jelly tends to increase gene
expression of low-density lipoprotein receptor (LDLR), which is involved in cholesterol incorporation in liver. [6A] In Japan, Guo H and co-workers at
Nippon Meat Packers, Inc demonstrated that intake of 6 gram of royal jelly supplement for 4 weeks decreased the total cholesterol and low-density
lipoprotein significantly in seven human volunteers. [4A]

Fatigue
Mice was found to swim in an adjustable-current swimming pool in a study. It was found that mice fed with a 5 7-kDa protein extracted from Royal Jelly
showed significantly decreased accumulation of serum lactate and serum ammonia. This suggests that Royal Jelly can ameliorate the physical fatigue
after exercise. [17A] Thus, royal jelly may have benefit of anti-fatigue.

Fertility
As royal jelly is a nutrient dense substance, some marketers promote royal jelly as a king of superfoods at helping with fertility. Those marketers even
claim that royal jelly can increase libido and support egg health. Totally, there are five scientific reports about these topics, but only one shows limited
support to these claims, the content of these reports are not really related to human fertility. (as of August 20, 2011) Royal jelly may benefit certain
people, but clinical studies are needed to prove this health claim.
This website discusses the benefits and side effects of various supplements, herbs and drug products. Different side
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www.fda.gov., or report the adverse side effects to the manufacturer, you should be able to
find the contact information on the label.

There are always new information. Please, send me an email (
zhion@zhion.com) to correct my mistake(s). Reasonable
care has been taken in preparing this document and the information provided herein is believed to be accurate. The
information is not intended to be a substitute for professional medical advice. It is important to seek the advice of a
physician about any medical condition or symptom or the benefits and side effects of a supplement or a drug product.
Finally, please, do not transfer the article to other website. Thank you. ALL RIGHTS RESERVED.
Liver Damage
In a study of 90 female Swiss Albino mice, paracetamol altered the levels of liver enzymes while administration of royal jelly
restored the levels to normal values. [3A] Thus, royal jelly may benefit animals suffered from liver damage, but more
scientific evidence is needed to support this health claim.

Menopausal Syndrome
A research group in Egypt combined evening primrose oil, damiana, ginseng and royal jelly together and they fed 120
women with menopausal symptoms daily for 2 and 4 weeks. They found improvement in the outcome of Menopause
Rating Scale II compared to placebo treatment. [E1]

Neural Degradation
Royal jelly may benefit people at risk of certain neural issues. Royal jelly and its10-hydroxy-trans-2-decenoic acid were
found to be able to increase the generation of neurons and decrease that of astrocytes from neural stem/progenitor cells
(NSCs). [20A] Orally administered royal jelly was found to increase the number of hippocampal dentate gyrus granule
cells and simultaneously improve the cognitive impairment in trimethyltin-intoxicated mice. Trimethyltin is a toxic organotin
compound that induces acute neuronal death selectively in the hippocampal dentate gyrus. [S3] In a study of middle-aged
female rats, several animals showed age-related increases in pituitary weight, while intake of royal jelly compensated the
increase. Royal jelly down-regulated prolactin mRNA and up-regulated thyroid-stimulating hormone beta mRNA in the
pituitary. [S5]