What is royal jelly
Royal jelly is a honey bee secretion that is used in the nutrition of larvae, as well as adult queens. It is secreted from the mandibular and hypopharyngeal glands of worker bees of the genus Apis mellifera between the sixth and twelfth days of their life 1. Royal jelly is a food essential for the longevity of the queen bee 2 and it is also fed to all larvae in the colony 3. Royal jelly is a complex substance containing a unique combination of proteins (12-15%), sugars (10-12%), lipids (3-7%), amino acids, vitamins, and minerals 4.
The honeybee forms two female castes: the queen and the worker. This dimorphism does not depend on genetic differences but on ingestion of royal jelly 5. When worker bees decide to make a new queen, because the old one is either weakening or dead, they choose several small larvae and feed them with copious amounts of royal jelly in specially constructed queen cells. This type of feeding triggers the development of queen morphology, including the fully developed ovaries needed to lay eggs 6. Compared with the short-lived and infertile worker bees, the queen bee, which is exclusively fed royal jelly, is characterized by her extended lifespan and her well-developed gonads. Therefore, royal jelly has been long- used as a supplement for nutrition, anti-aging or infertility 5.
Royal jelly develops the queen bee gonads. A royal jelly diet induced higher testosterone content and more intensive spermatogenesis in hamster testis 7 and increased serum testosterone levels in heat stressed male rabbits 8. It may also modulate sex hormones in humans. Dehydroepiandrosterone sulfate (DHEA-S), which declines during normal aging, may serve as a potential longevity marker 9 and may improve insulin resistance 10. Men with higher serum DHEA-S had a longer life span in a Baltimore longitudinal study of aging male humans 11. Estradiol (E2) is more important than testosterone in the pathway to insulin resistance in healthy, young postmenopausal women 12.
Royal jelly has been demonstrated (in test tube and animal studies) to possess many pharmacological activities in experimental animals, including antitumor 13, anti-oxidant 14, anti-inflammatory 15, antibacterial 16, anti-allergic 17, anti-aging 18 and antihypertensive properties 19. In humans, its oral ingestion improves lipoprotein metabolism and reduces serum total cholesterol (TC) and low-density lipoprotein (LDL) levels 20. Lady 4, a combination of four natural components (evening primrose oil, damiana, ginseng) including royal jelly, promoted health and well-being in postmenopausal women 21.
Figure 1. Fresh royal jelly surrounding developing queen bee larvae
Royal jelly uses
Royal jelly has long been sold as both a dietary supplement and alternative medicine. Both the European Food Safety Authority 22 and United States Food and Drug Administration 23 have concluded that the current evidence does not support the claim of health benefits, and have actively discouraged the sale and consumption of the jelly. In the United States, the Food and Drug Administration has taken legal action against companies that have used unfounded claims of health benefits to market royal jelly products. There have also been documented cases of allergic reactions, namely hives, asthma, and anaphylaxis, due to consumption of royal jelly.
Table 1. Royal jelly (fresh) nutrition facts
|Nutrient||Unit||tsp 1.25 g||Value per 100 g|
|Total lipid (fat)||g||0.04||3.2|
|Carbohydrate, by difference||g||0||0|
|Fatty acids, total trans||g||0||0|
Royal jelly contains a considerable amount of proteins, free amino acids, sugars, vitamins and sterols, the medium chain fatty acids 10-hydroxy-2-decenoic (10H2DA), 3,10-dihydroxydecanoic (3,10 DDA) and sebacic acids (Figure 2) are major and unique royal jelly components 25. Royal jelly exerts estrogen effects in vitro (test tube) and in vivo (animal) studies, similar to those evoked by 17β-estradiol (Estrogen) 26. Royal jelly competes with 17β-estradiol (estrogen) for binding to the human estrogen receptors (ERs) α and β, though it is much weaker than diethylstilbestrol in terms of binding affinity 26.
Estrogens play pivotal roles in regulating the function of many tissues and organs and estrogen signaling has been associated with a number of diseases, including breast and uterine cancers, disorders of lipid metabolism, cardiovascular diseases, autoimmune inflammatory diseases, osteoporosis, menstrual abnormalities and infertility 27. Estrogens exert their effects via intracellular receptors, estrogen receptors alpha (ERα) and beta (ERβ) 28. In the presence of ligands, both ERα and ERβ are activated and as dimers interact with specific DNA sequences. Activated estrogen receptors (ERs) interact with other nuclear proteins, such as steroid receptor co-regulators, altering the transcription rates of responsive genes. The activated ERα and ERβ can also bind to other transcription factors, such as activator protein 1 (AP-1) and nuclear factor kappa B (NF-kB), affecting their binding to their cognate DNA sequences and their transcriptional effects 29. More recently, the G protein-coupled receptor, GPR30/GPER, has been shown to mediate rapid estrogen effects as well as to regulate transcriptional activation. Possible synergism and antagonism with classical estrogen receptors has been suggested 30.
Figure 2. Royal jelly active compunds
Royal jelly side effects and adverse reactions
In the literature, several cases of hemorrhagic colitis 31, asthma 32 and anaphylaxis 33 by ingestion of royal jelly have been reported. Royal jelly should be considered as a causative allergen. Increased consumption of royal jelly in health food supplements may increase incidence of royal jelly-related allergic reactions 33.
Royal jelly may cause allergic reactions in humans ranging from hives, asthma, to even fatal anaphylaxis 34, 35, 36. The incidence of allergic side effects in people who consume royal jelly is unknown. The risk of having an allergy to royal jelly is higher in people who have other allergies 34.References
- Electrophoretic components of the proteins in honeybee larval food. PATEL NG, HAYDAK MH, GOCHNAUER TA. Nature. 1960 May 21; 186():633-4. https://www.ncbi.nlm.nih.gov/pubmed/14430832/
- Moutsatsou P, Papoutsi Z, Kassi E, et al. Fatty Acids Derived from Royal Jelly Are Modulators of Estrogen Receptor Functions. Hansen IA, ed. PLoS ONE. 2010;5(12):e15594. doi:10.1371/journal.pone.0015594. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008742/
- Graham, J. (ed.) (1992) The Hive and the Honey Bee (Revised Edition). Dadant & Sons.
- Takenaka T. Chemical composition of royal jelly. Honeybee Sci. 1982;3:69–74.
- Morita H, Ikeda T, Kajita K, et al. Effect of royal jelly ingestion for six months on healthy volunteers. Nutrition Journal. 2012;11:77. doi:10.1186/1475-2891-11-77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499288/
- Maleszka, R, Epigenetic integration of environmental and genomic signals in honey bees: the critical interplay of nutritional, brain and reproductive networks. Epigenetics. 2008, 3, 188-192.
- Kohguchi M, Inoue S, Ushio S, Iwaki K, Ikeda M, Kurimoto M. Effect of royal jelly diet on the testicular function of hamsters. Food Sci Technol Res. 2004;10(4):420–423. doi: 10.3136/fstr.10.420.
- Royal jelly counteracts bucks’ “summer infertility”. Elnagar SA. Anim Reprod Sci. 2010 Aug; 121(1-2):174-80. https://www.ncbi.nlm.nih.gov/pubmed/20538419/
- Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year follow-up study in a community-based cohort (Tanushimaru study). Enomoto M, Adachi H, Fukami A, Furuki K, Satoh A, Otsuka M, Kumagae S, Nanjo Y, Shigetoh Y, Imaizumi T. J Am Geriatr Soc. 2008 Jun; 56(6):994-8. https://www.ncbi.nlm.nih.gov/pubmed/18422949/
- The effect of dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance. Talaei A, Amini M, Siavash M, Zare M. Hormones (Athens). 2010 Oct-Dec; 9(4):326-31. https://www.ncbi.nlm.nih.gov/pubmed/21112864/
- Biomarkers of caloric restriction may predict longevity in humans. Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D, Metter EJ. Science. 2002 Aug 2; 297(5582):811. https://www.ncbi.nlm.nih.gov/pubmed/12161648/
- Association of endogenous sex hormones and insulin resistance among postmenopausal women: results from the Postmenopausal Estrogen/Progestin Intervention Trial. Kalish GM, Barrett-Connor E, Laughlin GA, Gulanski BI, Postmenopausal Estrogen/Progestin Intervention Trial. J Clin Endocrinol Metab. 2003 Apr; 88(4):1646-52. https://www.ncbi.nlm.nih.gov/pubmed/12679451/
- Studies on the in vitro antitumor activity of fatty acids. I. 10-Hydroxy-2-decenoic acid from royal jelly. TOWNSEND GF, MORGAN JF, TOLNAI S, HAZLETT B, MORTON HJ, SHUEL RW. Cancer Res. 1960 May; 20():503-10. http://cancerres.aacrjournals.org/content/20/4/503.long
- Comparison of bee products based on assays of antioxidant capacities. Nakajima Y, Tsuruma K, Shimazawa M, Mishima S, Hara H. BMC Complement Altern Med. 2009 Feb 26; 9():4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664783/
- Royal jelly inhibits the production of proinflammatory cytokines by activated macrophages. Kohno K, Okamoto I, Sano O, Arai N, Iwaki K, Ikeda M, Kurimoto M. Biosci Biotechnol Biochem. 2004 Jan; 68(1):138-45.
- Facilitative production of an antimicrobial peptide royalisin and its antibody via an artificial oil-body system. Tseng JM, Huang JR, Huang HC, Tzen JT, Chou WM, Peng CC. Biotechnol Prog. 2011 Jan-Feb; 27(1):153-61. https://www.ncbi.nlm.nih.gov/pubmed/21312363/
- Major royal jelly protein 3 modulates immune responses in vitro and in vivo. Okamoto I, Taniguchi Y, Kunikata T, Kohno K, Iwaki K, Ikeda M, Kurimoto M. Life Sci. 2003 Sep 5; 73(16):2029-45. https://www.ncbi.nlm.nih.gov/pubmed/12899927/
- Royal jelly increases collagen production in rat skin after ovariectomy. Park HM, Cho MH, Cho Y, Kim SY. J Med Food. 2012 Jun; 15(6):568-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359633/
- Antihypertensive effect of peptides from royal jelly in spontaneously hypertensive rats. Tokunaga KH, Yoshida C, Suzuki KM, Maruyama H, Futamura Y, Araki Y, Mishima S. Biol Pharm Bull. 2004 Feb; 27(2):189-92. https://www.jstage.jst.go.jp/article/bpb/27/2/27_2_189/_pdf/-char/en
- Royal jelly supplementation improves lipoprotein metabolism in humans. Guo H, Saiga A, Sato M, Miyazawa I, Shibata M, Takahata Y, Morimatsu F. J Nutr Sci Vitaminol (Tokyo). 2007 Aug; 53(4):345-8. https://www.jstage.jst.go.jp/article/jnsv/53/4/53_4_345/_pdf/-char/en
- Effectiveness of a herbal formula in women with menopausal syndrome. Yakoot M, Salem A, Omar AM. Forsch Komplementmed. 2011; 18(5):264-8. https://www.ncbi.nlm.nih.gov/pubmed/22105039/
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to: anthocyanidins and proanthocyanidins (ID 1787, 1788, 1789, 1790, 1791); sodium alginate and ulva (ID 1873); vitamins, minerals, trace elements and standardised ginseng G115 extract (ID 8, 1673, 1674); vitamins, minerals, lysine and/or arginine and/or taurine (ID 6, 1676, 1677); plant-based preparation for use in beverages (ID 4210, 4211); Carica papaya L. (ID 2007); “fish protein” (ID 651); acidic water-based, non-alcoholic flavoured beverages containing calcium in the range of 0.3 to 0.8 mol per mol of acid with a pH not lower than 3.7 (ID 1170); royal jelly (ID 1225, 1226, 1227, 1228, 1230, 1231, 1326, 1328, 1329, 1982, 4696, 4697); foods low in cholesterol (ID 624); and foods low in trans-fatty acids (ID 672, 4333) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA Journal 2011;9(4):2083. [34 pp.]. doi:10.2903/j.efsa.2011.2083. http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2011.2083/pdf
- United States Department of Agriculture Agricultural Research Service. USDA Branded Food Products Database. https://ndb.nal.usda.gov/ndb/search/list
- Chemistry and bioactivity of royal jelly from Greece. Melliou E, Chinou I. J Agric Food Chem. 2005 Nov 16; 53(23):8987-92. https://www.ncbi.nlm.nih.gov/pubmed/16277392/
- Royal jelly stimulates bone formation: physiologic and nutrigenomic studies with mice and cell lines. Narita Y, Nomura J, Ohta S, Inoh Y, Suzuki KM, Araki Y, Okada S, Matsumoto I, Isohama Y, Abe K, Miyata T, Mishima S. Biosci Biotechnol Biochem. 2006 Oct; 70(10):2508-14. https://www.jstage.jst.go.jp/article/bbb/70/10/70_60240/_pdf/-char/en
- Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest. 2006;116:561–570. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373424/
- Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996;93:5925–5930. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC39164/
- Nilsson S, Makela S, Treuter E, Tujague M, Thomsen J, et al. Mechanisms of estrogen action. Physiol Rev. 2001;81:1535–1565.
- Prossnitz ER, Maggiolini M. Mechanisms of estrogen signaling and gene expression via GPR30. Mol Cell Endocrinol. 2009;308:32–38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847286/
- Yonei Y, Shibagaki K, Tsukada N, Nagasu N, Inagaki Y, Miyamoto K, Suzuki O, Kiryu Y. Case report: haemorrhagic colitis associated with royal jelly intake. J Gastroenterol Hepatol. 1997;12(7):495–499. doi: 10.1111/j.1440-1746.1997.tb00472.x. https://www.ncbi.nlm.nih.gov/pubmed/9257239
- Thien FC, Leung R, Baldo BA, Weiner JA, Plomley R, Czarny D. Asthma and anaphylaxis induced by royal jelly. Clin Exp Allergy. 1996;26(2):216–222. doi: 10.1111/j.1365-2222.1996.tb00082.x. https://www.ncbi.nlm.nih.gov/pubmed/8835130
- Katayama M, Aoki M, Kawana S. Case of anaphylaxis caused by ingestion of royal jelly. J Dermatol. 2008;35(4):222–224. doi: 10.1111/j.1346-8138.2008.00448.x. https://www.ncbi.nlm.nih.gov/pubmed/18419679
- Royal jelly consumption and hypersensitivity in the community. Clin Exp Allergy. 1997 Mar;27(3):333-6. https://www.ncbi.nlm.nih.gov/pubmed/9088660
- Food-induced anaphylaxis caused by ingestion of royal jelly. J Dermatol. 2006 Jun;33(6):424-6. https://www.ncbi.nlm.nih.gov/pubmed/16700835
- Lombardi C, Senna GE, Gatti B, Feligioni M, Riva G, Bonadonna P, Dama AR, Canonica GW, Passalacqua G (1998). “Allergic reactions to honey and royal jelly and their relationship with sensitization to compositae”. Allergol. Immunopathol. 26 (6): 288–290.