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 ⁷⁾.

Royal jelly develops the queen bee gonads. A royal jelly diet induced higher testosterone content and more intensive spermatogenesis in hamster testis ⁸⁾ and increased serum testosterone levels in heat stressed male rabbits ⁹⁾. It may also modulate sex hormones in humans. Dehydroepiandrosterone sulfate (DHEA-S), which declines during normal aging, may serve as a potential longevity marker ¹⁰⁾ and may improve insulin resistance ¹¹⁾. Men with higher serum DHEA-S had a longer life span in a Baltimore longitudinal study of aging male humans ¹²⁾. Estradiol (E2) is more important than testosterone in the pathway to insulin resistance in healthy, young postmenopausal women ¹³⁾.

Royal jelly has been demonstrated (in test tube and animal studies) to possess many pharmacological activities in experimental animals, including antitumor ¹⁴⁾, anti-oxidant ¹⁵⁾, anti-inflammatory ¹⁶⁾, antibacterial ¹⁷⁾, anti-allergic ¹⁸⁾, anti-aging ¹⁹⁾ and antihypertensive properties ²⁰⁾. In humans, its oral ingestion improves lipoprotein metabolism and reduces serum total cholesterol (TC) and low-density lipoprotein (LDL) levels ²¹⁾. Lady 4, a combination of four natural components (evening primrose oil, damiana, ginseng) including royal jelly, promoted health and well-being in postmenopausal women ²²⁾.

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 ²³⁾ and United States Food and Drug Administration ²⁴⁾ 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
Approximates
Energy	kcal	2	160
Protein	g	0	0
Total lipid (fat)	g	0.04	3.2
Carbohydrate, by difference	g	0	0
Sugars, total	g	0.13	10.4
Minerals
Sodium, Na	mg	0	40
Lipids
Fatty acids, total trans	g	0	0

[Source ²⁵⁾]

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 ²⁶⁾. Royal jelly exerts estrogen effects in vitro (test tube) and in vivo (animal) studies, similar to those evoked by 17β-estradiol (Estrogen) ²⁷⁾. 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 ²⁸⁾.

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 ²⁹⁾. Estrogens exert their effects via intracellular receptors, estrogen receptors alpha (ERα) and beta (ERβ) ³⁰⁾. 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 ³¹⁾. 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 ³²⁾.

Figure 2. Royal jelly active compunds

Note: Structures of 17β-estradiol (17β-E2) = Estrogen, 10-hydroxy-2-decenoic acid (10H2DA), 3,10-dihydroxydecanoic acid (3,10DDA) and sebacic acid (SA)

Royal jelly side effects and adverse reactions

In the literature, several cases of hemorrhagic colitis ³³⁾, asthma ³⁴⁾ and anaphylaxis ³⁵⁾ 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 ³⁶⁾.

Royal jelly may cause allergic reactions in humans ranging from hives, asthma, to even fatal anaphylaxis ³⁷⁾, ³⁸⁾, ³⁹⁾. 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 ⁴⁰⁾.