Description, origin and extraction
Royal jelly has a long traditional use as a highly nutritious food suppplment. Its reputation is build on the observation of the effects of royal jelly on the Queen bee’s superior size, strength, stamina and longevity compared with worker bees. Royal jelly is secreted by the hypo-pharyngeal gland (sometimes called the brood food gland of young worker bees, to feed young larvae and the adult queen bee. Royal jelly is always fed directly to the queen or the larvae as it is secreted; it is not stored. Royal jelly can be harvested during queen rearing, when the larvae destined to become queen bees are supplied with an over-abundance of royal jelly. The queen larvae cannot consume the food as fast as it is provided and royal jelly accumulates in the queen cells.
Royal jelly becomes popular in Europe in the 1950s.
Royal jelly is a homogenous substance with the consistency of a fairly fluid paste. It is whitish in colour with yellow or beige tinges, has pungent phenolic odour and characteristic sour flavour. It has a density of approximately 1.1 g/cm3 and is partially soluble in water. Aqueous solutions clarify during basification with soda. Viscosity varies according to water content and age – it slowly becomes more viscous when stored at room temperature or in refrigeration at 5 degrees Celsius. The increased viscosity appears to be related to an increase in water insoluble nitrogenous compounds, together with a reduction in soluble nitrogen and free amino acids.
These changes are apparently due to continued enzymatic activities and interaction between the lipid and protein fractions. If sucrose is added, royal jelly becomes more fluid. Certain debris in royal jelly, is a sign of purity as, for example, the ever present fragments of larval skin. Wax fragments too, are encountered more or less regularly, but their presence is largely dependent on the collection method. Stored royal jelly often develops small granules due to precipitation of components. Much of the world supply of royal is from China. It is further processed in other countries including Italy where it may be mixed with vitamin E, wheat germ oil, honey, bees wax and other ingredients. The mixture is then naturally dried over a period of 4-5 weeks before encapsulation or tableting.
Chemistry
The principle constituents of royal jelly are water, proteins, sugars, lipids and mineral salts. Water accounts for about 60% of fresh royal jelly, but by dry weight, proteins and sugars are by far the largest fractions. Of the nitrogenous substances, proteins average 73.9%, and of the six major proteins four are glycoproteins. All essential amino acids are present and 29 amino acids and derivatives have been identified, the most important being aspartic acid and glutamic acid. The free amino acids are proline and lysine.
A number of enzymes are also present including glucose oxidase, phosphatase and cholinesterase. The sugars consist mostly of fructose and glucose in relatively constant proportions similar to those in honey. Other sugars include maltose, trehalose, melibiose, ribose and erlose. Apalbumin1 (Apa1) is the major royal jelly glycoprotein having various biological properties. The lipid fraction consist of 80-90% by dry weight of free fatty acids. They are mostly short chain (8-10 carbon atoms) hydroxy fatty acids or dicarboxyl acids. These fatty acids are responsible for many of the reported biological properties of royal jelly. The principle acid is 10-hydroxy-2-decanoic acid, followed by its saturated equivalent. In addition to free fatty acids, the lipid fraction contains some neutral lipis, sterols (including cholesterol) and an unsaponifiable fraction of hydroxycarbones similar to beeswax.
The total ash content of royal jelly is about 1% of fresh weight or 2-3% of dry weight. The major mineral salts are, in descending order: K, Ca, Na, Zn, Cu and Mn – with a strong prevalence of potassium. Royal jelly is rich in the B-group vitamins with only traceable levels of vitamin C. Vitamins A, D, E and K are absent. Royal jelly also contains numerous trace elements.
Toxicology
Royal jelly is neither toxic when injected into mice an drats at high dosages of up to 3 g per kg body weight per day nor mutagenic, as tested on DNA of Salmonella typimurium.
Health relationship Antifatigue activity
Royal jelly has been shown to ameliorate the physical fatigue experienced by mice after exercise. The mice were accustomed to swimming in an adjustable-current swimming pool, then subjected to forced swimming five times during a two week period, and the total swimming period until exhaustion was measured. They were separated into three groups with equal swimming capacity, which were administered royal jelly or placebo. All mice were forced to swim for 15 min once; then the maximum swimming time to fatigue was measured after a rest period.
The swimming endurance of the royal jelly group significantly increased compared with those of the other groups. The mice in the royal jelly group showed significantly decreased accumulation of serum lactate and serum ammonia and decreased depletion of muscle glycogen after swimming compared with placebo. These findings suggest that royal jelly can ameliorate the physical fatigue after exercise. An early study also demonstrated that pure powdered lyophilized royal jelly applied directly into a wound improved healing of muscle tissue in an experimental animal model of injury to striped muscle.
Regeneration processes commenced about two days sooner than in controls. Collagen production-promoting, skin healing and bone stimulating activities Commercially available 10-hydroxy-2-decenoic acid and 10-hydroxydecanoic acid as well as the same fatty acids purified directly from royal jelly have been found to increase the collagen production in a dose-dependent manner. Furthermore, 10-hydroxy-2-decenoic acid induced the fibroblast cell line, NHDF, to produce transforming growth factor-beta 1 (TGF-beta 1) which is an important factor for collagen production. As expected, the collagen production-promoting activity of 10-hydroxy-2-decenoic acid was neutralized by the anti-TGF-beta 1 antibody.
These result suggest that 10-hydroxy-2-decenoic acid promoted the collagen production of fibroblasts by inducing TGF-beta 1 production. Royal jelly has been shown to have some anti-inflammatory activity by decreasing exudation and collagen formation in granulation tissue formation in an experimental study of wound healing in diabetic rats. Royal jelly did not possess insulin-like activity in this study. A study found that royal jelly stimulates bone formation. Royal jelly was found to stimulate collagen production in a bone culture medium and oral administration of royal jelly to normal female mice for 9 weeks increased the ash content of their tibiae.
Quantitative analysis confirmed up-regulation of pro-collagen I alpha1 gene expression. These data suggest that royal jelly as a whole or some of its individual components stimulates production of type I collagen and other activities for bone formation through action on osteoblasts. A study found that royal jelly prevented osteoporosis in a ovariectomy model and in a bone tissue culture model. Royal jelly was found to be almost as effective as 17beta-estradiol in preventing the development of bone loss induced by ovariectomy in rats. However, in a mouse marrow culture model, royal jelly neither inhibited the parathyroid hormone (PTH)-induced calcium loss nor affected the formation of osteoclast-like cells induced by PTH in mouse marrow culture system. Therefore, the results suggest that royal jelly may prevent osteoporosis by enhancing intestinal calcium absorption, but not by directly antagonizing the action of PTH.
Antioxidant, Neuroprotective and Anti-aging Activities
Free radicals can induce oxidative damage to the body and this damage might induce dysfunction of cells, organs and the whole body. The activity of the antioxidant superoxide dismutase has been correlated with life span. Dietary royal jelly has been shown to increase the average life span of mice, possibly by reducing oxidative damage, in a study on tissue DNA oxidative damage and life span in mice (p<0.05). Mice were fed different amounts of a dietary supplement of royal jelly for 16 weeks and the level of 8-hydroxy-2-deoxyguanosis (8-OHdG), a marker of oxidative stress, were significantly reduced in kidney DNA and in the serum. The 8-OHdG levels in kidney DNA were significantly and dose-dependently reduced compared to controls (p<0.05). Serum levels were also significantly lower (p<0.05), whereas no differences were observed in liver and heart tissue. The groups receiving dietary royal jelly did not show any changes in growth, food intake and in appearance, when compared with control groups.
The average survival times were 88 weeks for the control group versus 110 weeks in the groups receiving the highest dose of royal jelly (500 ppm royal jelly powder added to normal powdered diet). Royal jelly did not extend the total life span but improved the 50% survival rates in the mice. This indicates that royal jelly allowed many more mice to reach old age compared to the controls on a normal commercial diet.(Inoue et al. 965-69) A recent study found that once royal jelly is hydrolyzed by enzymes, the hydrolysate possesses much higher antioxidative activity and scavenging activity against active oxygen species. This suggests that royal jelly is well suited as an oral medicinal food to maintain good antioxidant protection against active oxygen species such as superoxide anion and hydroxyl radicals in humans. Recent investigations suggest that neurotrophic factors are involved in the aetiology and/or development of age-related cognitive decline and neuropsychiatric disorders such as Alzheimer’s disease and depression and that synthesis of particular neurotrophic factors may protect against those disorders. Oral administration of royal jelly in mice has been shown to selectively facilitate the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that royal jelly may have neurotrophic and/or neuroprotective roles in the adult brain through GDNF.
Immunemodulatory and anti-allergic activities
Royal jelly has been reported to have such pharmacological characteristics as antitumor, antibacterial, antihypercholesterolemic, antiallergic, antiinflammatory, and immunomodulatory properties. Several animal and in vitro studies suggest that royal jelly has immunostimulatory properties by stimulating antibody production and immunocompetent cell proliferation in mice or depressing humoral immune functions. Apalbumin1, a glycoprotein, has been shown to stimulate macrophages to release tumor necrosis factor alpha (TNFalpha). Other research suggests that royal jelly is a biological response modifier.
Royal jelly has been shown to stimulate antibody production and proliferation of immunmo-competent cells in mice while depressing humoral immune function. It was shown to prevent experimentally induced myelosupression and prolong survival in Ehrlich ascites tumour (EAT)-bearing mice. The increased survival rate ma be related to the decreased Prostaglandin E2 (PGE2) levels observed in EAT-bearing mice after royal jelly treatment. It has furthermore been shown to be effective against the hematopoeitic dysfunction observed in x-ray irradiated mice, promoting macrophage activity and hematopoeitic stem cell proliferation.
Other studies have found that royal jelly has anti-inflammatory and anti-allergic activity. Royal jelly has been shown to inhibit the production of pro-inflammatory cytokines by lipopolysaccharide activated macrophages. In vitro research has shown it to dose-dependently inhibit the release of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-1 without having cytotoxic effects on macrophages, since the growth of peritoneal macrophages was not inhibited but rather augmented by the addition of royal jelly. Further investigations suggest that royal jelly act directly on the activated macrophages to inhibit pro-inflammatory cytokine production, especially of TNF-alpha. It is suggested that the activity is due to the royal jelly proteins.
In vitro study using lymphocytes from newly diagnosed and untreated patients with Grave’s disease found that royal jelly shifted the Th1/Th2 cytokine ratio to the side of Th1 cytokine which suggests that royal jelly has a immunomodulatory effect. Oral administration of royal jelly has been shown to inhibit the development of atopic dermatitis-like skin lesions in mice. Interperitoneal administration of royal jelly has been shown to significantly both ovalbumin specific IgG and IgE production, and IL-4, IL-5 and IL-10 production by spleen cells stimulated with ovalbumin. Royal jelly also inhibited IFN-gamma production by ovalbumin-stimulated spleen cells and tended to down-regulate ovalbumin-specific IgG2a production. In a similar experiment, royal jelly did not produce significant changes to the cytokine production by spleen cells in response to concanavalin A.
Furthermore, oral administration of royal jelly also resulted in a significant inhibition of both ovalbumin-specific IgE and total IgE production. These results suggest that royal jelly exhibits anti-allergic functions.(Kataoka et al. 174-80) It has also been shown that royal jelly may suppress allergic reactions in association with the restoration of macrophage function and the improvement of Th1/Th2 cell response in mice. Oral administration of royal jelly (1 g/kg) significantly decrease the serum levels of antigen-specific IgE and significantly inhibited histamine release from mast cells in an experimental model of hypersensitivity, resulting in the suppression of immediate hypersensitivity reactions of the skin. Further investigation suggest that the suppression of antigen-specific IgE production and histamine release from mast cells was associated with the restoration of macrophage function and improvement of the Th1/Th2 cell responses. Royal jelly, however, did not reduce the incidence or severity of allergic rhinitis in children in a double-blind, randomised study of 64 children aged 5-16 years.
Neuroprotective activity
Recent investigations suggest that neurotrophic factors are involved in the aetiology and/or development of age-related cognitive decline and neuropsychiatric disorders such as Alzheimer’s disease and depression and that synthesis of particular neurotrophic factors may protect against those disorders. Oral administration of royal jelly in mice has been shown to selectively facilitate the mRNA expression of glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and neurofilament H, a specific marker predominantly found in neuronal axons, in the adult mouse hippocampus. These observations suggest that royal jelly may have neurotrophic and/or neuroprotective roles in the adult brain through GDNF.
Effect on cholesterol and total lipids
A placebo-controlled study with 37 patients suffering advanced atherosclerosis has found that royal jelly, 50 mg daily for 40 days, clear but not significant improvements in serum levels of cholesterol and total lipids as well as fibrinolytic activity. Placebo treatment resulted in a non-significant increase in the averages of the observed parameters. A significant decrease was observed in 30-44.4% of the patients treated with royal jelly, whereas the administering of placebo did not produce any significant, favourable result. The fatty acid 10-HDA has been found to be the functional factor of preventive and therapeutic effects of royal jelly on hyperlipoidemia.
The preventive and therapeutic effects of 10-HDA were tested on hyperlioidemic rat model induced by high fat food. The study found that 10-HDA could reduced the content of total cholesterol, triglycerides and beta-lioprotein and raised the content of HDL. The 57-kDa protein has furthermore been found to stimulate hepatocyte DNA synthesis suggesting that the protein is likely to promote liver regeneration and may have a cytoprotective action on hepatocytes. Pooled and statistically evaluated animal data suggest that royal jelly significantly decrease serum and liver total lipids and cholesterol cholesterol levels in rats and rabbits and also retarded the formation of atheromas in the aorta of rabbits fed a hyperlipemic diet. Meta-analysis of the controlled human trials of RJ to reduce hyperlipidemia showed a significant reduction in total serum lipids and cholesterol levels and normalization of HDL and LDL as determined from decrease in beta/alpha lipoproteins. The best available evidence suggests that royal jelly at approximately 50 to 100 mg per day, decreased total serum cholesterol levels by about 14%, and total serum lipids by about 10% in the group of patients studied.
