Royal Jelly

Last Updated: September 28, 2022

Royal jelly is a nutritious jelly with a composition similar to pollen, created by worker bees. It is being researched for its effects on testosterone and longevity.

Royal Jelly is most often used for.



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1.

Sources and Composition

1.1

Sources

Royal Jelly is a cream product created by young nurse worker bees for feeding to the queen, queen larvae and other young larvae,[1] and commonly marketed as being the 'Food source of Queen Bees' as Queen Bees ingest royal honey for their entire lives; something not done by other adult bees. The association with the Queen is where the 'Royal' aspect of this jelly comes from.[2] It is produced by the hypopharyngeal and mandibular of insects (salivary glands) and is frequently used to boost growth in larvae.

1.2

Composition

Royal Jelly is a nutritive cocktail designed for bee growth and Queen Bee sustenance, it contains:

  • Lipids, of which the total lipid content is about 80–85% fatty acids, 4–10% phenols, 5–6% waxes, 3–4% steroids and 0.4–0.8% phospholipids[3] with the total lipid fragment being 3-6% in fresh Royal Jelly[4]
  • Dietary Fatty acids, such as 10-hydroxy-2-decanoic acid (10-HDA unique to Royal Jelly at 32% of fatty acids)[5] and others, such as gluconic acid (24%) 10-hydroxydecanoic acid (22%) and 5% other dicarboxylic acids
  • Peptides 2-4 amino acids in length, derived from the proteins, which may be anti-oxidants[6] or insulin-like mimetics[7] and totalling 12-15% of Royal Jelly by weight[4]
  • The 57-kDa protein known as Royalactin that differentiates honey bees into queen bees[8]
  • Carbohydrates, mostly sugars, at 10-16% by weight.[4] These sugars tend to be 90% glucose or fructose with the majority (50-70%) being glucose, although some other monosaccharides and oligosaccharides may be present which varies on the age of the Royal Jelly[9][10]
  • Mineral salts at about 1.5% by weight[3] with their contents being recorded in one study as (all in mg/kg) 215.006 Calcium, 6.39 Copper, 20.054 Iron, 0.501 Gallium, more than 2517 Potassium, 0.139 Lithium, 217.493 Magnesium, 33.203 Zinc, 0.556 Selenium and 0.302 Strontium[11]
  • Acetylcholine[12][13]
  • Adenosine Triphosphate (ATP) and catabolites[14] such as AMP and AMP-N1 oxide[15] with total adenosine content ranging from 5.9 to 2057.4mg/kg over 45 products in one study[16] but another study using Royal Jelly creams finding between 27-50mcg/g (0.0027-0.005%) yet a more variable 2-173mcg/g for oral supplements[17]
  • Testosterone, not a mimetic but the actual hormone[18] at 11.63+/-0.4ng/g in the basic extract and 36.16+/-2.6ng/g in the lysophilized extract

All the above numbers based on weight assume an active water content, and percentages may become relatively higher if using a lyophilised (freeze-dried) product, where water is dropped to less than 5% while protein, fats, and carbohydrates increase to 27–41%, 15–30%, and 22–31% respectively. [3] The composition of royal jelly (percentage-wise) may also vary based on season and cultivar, hence the wide range of possible macronutrient content.[3]

The composition of Royal Jelly, by weight, appears to be similar to a food product in where a good portion of the weight comes from macronutrients. As such, Royal Jelly supplementation confers a protein content and has a caloric value to it and may be treated as a food product similar to a protein-rich honey

In regards to the testosterone content, it has been hypothesized that since Royal Jelly comes from the salivary glands of worker bees, that the testosterone level was sapped from circulating levels in the bees; insects tend to use ecdysteroids for their own biological purposes, but testosterone itself has been found in insects before as well.[18] Testosterone is a component of Pollen,[19] thus it is possible that the testosterone content of pollen just translated into Royal Jelly through production in the worker bee.

1.3

Properties

Royal jelly has a jelly-like consistency with a uniform water content of approximately 60% and a density of 1.1g/mL and a water activity of 0.92, yet demonstrates considerable microbial stability due to its bioactives.[3] The pH of Royal Jelly ranges from 3.4–4.5.

Royal Jelly tends to be white with hints of yellow, growing a bit more yellow pigentation with storage. When not properly stored (not frozen or kept in a refrigerator), Royal jelly may turn from its white-yellowish state into a darker hue while developing a rancid taste.[3] The fatty acid component seems relatively stable, with 0.4-0.6% of total 10-hydroxy-2-decanoic acid degrading over 12 months.[20]

Royal Jelly may need to be stored in a cold environment in order to keep some bioactives preserved

2.

Longevity and Life Extension

A study in nematodes, a research model for longevity due to their initially short lifespans, noted that Royal Jelly at 10mcg/mL in the diet enhanced overall lifespan by 8%.[21] Treatment with enzymes to degrade the protein constituents failed to abolish the effects, and using isolated fatty acids from Royal Jelly causation for this observation was placed on the fatty acid known as 10-Hydroxy-2-decenoic acid (10-HDA).[21]

3.

Neurology and the Brain

3.1

Cognition

A 6-month study in middle-aged to older persons (42-83) noted that consumption of 3000mg Royal Jelly daily was associated with slight improvements on a SF-36 subscore (survey) of mental health, with no significant influence on other subscores.[22]

4.

Interactions with Glucose Metabolism

4.1

Interventions

One intervention using 3000mg of Royal Jelly for 6 months noted that although fasting blood glucose was lower in the RJ group (preventing an apparent increase seen in placebo) that insulin sensitivity, fasting insulin, and HbA1c were not significantly influenced by Royal Jelly consumption.[22]

4.2

Pertaining to Diabetes

One series of case studies reported using non-blinded application of Royal Jell to diabetic foot ulcers noted that application of a 5% Royal Jelly containing product was able to completely heal 7/8 foot ulcers over a period of 3 months with a mean duration of 41 days, whereas the last ulcer reported to be reduced in length, width, and depth by 40%, 32%, and 28% respectively.[23]

5.

Interactions with Cardiovascular Health

5.1

Atherosclerosis and Plaque

5.2

Interventions

A small human study of 15 persons (7 given Royal Jelly at 6g daily for 4 weeks) in otherwise healthy persons found that Royal Jelly was able reduce circulating triglycerides (194-182.4mg/dL; 6% decrease) reduce low-density lipoprotein (LDL-C) levels (120.3-109.3mg/dL; 11% decrease) with no significant effects on either HDL-C levels or triglycerides.[4] Subject diets were not controlled for, nor was the study blinded. These results on LDL-C were also seen in a larger study in post-menopausal women using Melbrosia (a mixture of Royal Jelly, pollen, and fermented pollen) which was able to increase triglycerides (1.25-1.54mmol/L; 23% increase) decrease LDL-C (3.6-3.07mmol/L; 14% decrease) and increase HDL-C (1.23-1.38mmol/L; 12% increase).[24] Inflammatory markers of C-Reactive protein and VCAM-1 were not significantly affected.

In a letter to an editors here,[25] a trial was outlined in 49 overweight persons with hypercholesterolemia (greater than 200mg/dL) found that 10g of Royal Jelly daily for 14 days found a trend towards reduction of LDL (no statistical significance) and an increase in HDL cholesterol that, although occurring in all patients, was more potent in persons over 60 years of age. HDL at baseline was 67.1+/-22mg/dL and HDL after 2 weeks was 68.8+/-23.2, and although medications were not controlled for there were no side effects reported.[25]

Three human interventions recently suggest positive or inert effects on LDL-C and positive or inert effects on HDL-C, with mixed results on triglycerides; more studies are needed to hammer out inconsistencies and some blinding would be needed as all studies have used unblinded (ex. jelly on toast) methodology

A meta-analysis of human studies conducted in 1995 (24 found, 9 reviewed, 5 meeting meta-analysis criteria) of which the above three studies were not included (published after 1995) found that oral ingestion of 30-150mg of Royal Jelly is associated with a 30-52mg/dL (10-20%) decrease in total cholesterol over a time period ranging from 3-5 weeks, and data on HDL-C and LDL-C were not able to be meta-analyzed.[26] Studies in question do not appear to be indexed online and are subject to an english-language barrier, being published in Eastern European countries, USSR, and Italy in the 60s and 70s.[26]

This study also reported data for serum lipids, or triglycerides, and the 5 studies fitting meta-analysis found unanimous results in decreasing triglycerides with an average weighted effect size of a 52mg/dL decrease in triglycerides with a 95% confidence interval of 37.8mg/dL to 66.19mg/dL decrease.[26] Percentage-wise, these five trials ranged from 6.2% decrease to 15% decrease in total lipids, yet three trials noted an increase the the lipid subset of 'phospholipids'.[26]

Apparently more studies conducted on Royal Jelly that are indexed online currently, and the quality of each study cannot be independently assessed. Still seems to hold a trend for reducing total cholesterol, however

6.

Interactions with Hormones

6.1

Testosterone

Royal Jelly itself does contain a testosterone content, but it is seen as too minute to be practically relevant to muscle building in and of itself.

In rats, low doses (0.1% of feed) are associated with increases in circulating testosterone (from 2.37+/-0.16ng/mL to 4.24ng/mL; 79% increase) and are able to prevent the reduction in testosterone associated with lipid peroxidation.[27] These may be due to increased testosterone synthesis as one study in hamsters using 50 and 500mcg/g diet (0.005-0.05%) which happened to end up being a variable intake of 395-415mcg (50mcg group) and 3,950-4,150mcg (500mcg group) daily noted that free testosterone in the testicles increased to similar degrees in both groups but only statistically significantly in the 500mcg group.[28] This study had an average intake of 2.3-24.2mcg/kg bodyweight in the hamsters, while significantly higher doses of 200-800mg/kg bodyweight are associated with decreased testosterone levels (possibly secondary to damaged testicular function or less LH levels) which is reversible upon cessation for 2 weeks.[2] These higher doses of 200-800mg/kg show increased fertility and testosterone levels, however, if taken once a week in male rabbits.[29]

For human studies, one conducted in infertile men using Royal Jelly at 25, 50, and 100mg daily for 3 months was able to increase testosterone by 22.01%, 19.8%, and 20.4% whereas the control group experienced a non-significant increase of 8.33%; it was concluded that Royal Jelly was significantly more effective than control in increasing testosterone levels in men.[1] Later, a 6-month trial of otherwise healthy persons aged 41-83 consuming 3000mg Royal Jelly found a slight increase in the testosterone/DHEA ratio (+0.12+/-0.04ng/mL) which was though to be from greater conversion from Dehydroepiandrosterone, increases in testosterone did not reach significance per se, just missing with a P-value of 0.0503 in men.[22]

Needs a lot more human studies on it, especially one on optimal dosage. Very promising and at the same time the dose-relation and time-relation are very abnormal for supplements. Promising but inconsistent at this time

6.2

Estrogen

A study in rats, geared for toxicological purposes, found that 800mg/kg bodyweight Royal Jelly was able to significantly increase estrogen levels in the blood while other tested doses (200mg/kg, 400mg/kg) did not significantly influence estrogen.[2] These lack of results were replicated in healthy humans of both genders with 6 months usage of 3000mg Royal Jelly.[22]

Limited evidence suggests that it does not alter circulating estrogen levels

That being said another study noted that Royal Jelly may have weak estrogenic activity, with Royal Jelly binding to and activating the estrogen receptors and inducing MCF-7 cell proliferation (inducing estrogen-like activity)[30] which is blocked by the receptor antagonist tamoxifen.[30][31] Royal Jelly appears to inhibit estradiol binding to receptors in a dose-dependent manner, and at concentration of 1mg/mL can induce more transcription than estrogen at 10nM (when not in the same assay).[31] When tested in vivo, an injection of Royal Jelly to an animal model of menopause noted that it induced estrogenic activity in the uterus but not in the brain; suggesting the bioactives may not cross the blood brain barrier.[31] This study noted that the binding affinity of RJ to inhibit estrogen, when compared to the standard of diethylstilbestrol, was fairly low and nonselective for the ER subtypes.[31] It took upwards of 10,000ng/mL (10mcg/mL) to inhibit estradiol from the estrogen receptors at 20-40% capacity.[31]

A later study suggested that the unique fatty acids in Royal Jelly named 10-H2DA, 10-HDA and Sebacic Acid were contributors.[32] These fatty acids only influenced ERβ (binding to pS2) and appeared to be antagonistic to signalling from estradiol when both are coincubated. These results also do not support direct binding of RJ fatty acids to estrogen receptors, except when 10H2DA is at abnormally high concentrations; the mechanism appears to be from preventing the estrogen receptor from binding to co-activators and thus inducing the nuclear effects.[32] The authors also suggested that the observed ranges tested (10-5 to 10-10M) were within physiological concentrations with 1-3g Royal Jelly.[32]

It is possible that, within physiologically relevant dosages, that the fatty acids in Royal Jelly may be indirect selective estrogen receptor modulators (SERMs) and exert pro-estrogenic effects when there is no or little circulating estrogen (menopause) and anti-estrogenic effects otherwise

6.3

Luteinizing Hormone

In a study on infertile men, Royal Jelly delivered via 10g honey in doses of either 25,50 or 100mg (with pure honey as control) found increases of 16%, 20.48%, and 20.3% with the Royal Jelly dosages, respectively, and no significant difference between groups.[1] Control group experienced a decline of 5% LH levels during the treatment period.[1]

Higher doses of 200-800mg/kg bodyweight in rats are associated with decreased circulating LH levels, which may be secondary to a reduced pituitary size and are reversible upon cessation of supplementation for 2 weeks.[2]

6.4

Follicle-Stimulating Hormone

The influence of Royal jelly over 3 months in doses of 25-100mg daily was not significantly different than placebo in infertile men.[1]

FSH is decreased during periods of excessive Royal Jelly intake of around 200-800mg/kg bodyweight in rats, but is reversible upon cessation.[2]

6.5

Prolactin

Prolactin mRNA levels in the pituitary were decreased after 7 months of Royal Jelly usage at 5% of the feed in female rats although the changes seen in circulating prolactin (71.3+/-76.5ng/mL in control, Royal Jelly at 65.2+/-43.8ng/mL) were not statistically significant.[33] The authors hypothesized that these effects could minimize the pituitary hypertrophy induced by prolactin that appears with aging, as the Royal Jelly group also had lower pituitary weights at the end of the study.[33]

6.6

Thyroid Hormones

7 months of Royal Jelly usage at 5% of feed in female rats is associated with an increase in TSH mRNA by 1.4-fold (indicative of synthesis of Thyroid Stimulating Hormone in the pituitary) and higher circulating T4 levels (from 1.08+/-20 to 1.16+/-0.15ng/dL), but this increase was not statistically significant.[33]

7.

Interactions with Fertility

7.1

Semen Interactions

After 25, 50, or 100mg Royal Jelly is given to infertile men, Royal jelly appeared to be ineffective at increasing sperm count (increases were similar to control group) but significantly better than control at increasing sperm motility; increasing motility by 25.76-32.6% with no dose-dependence while control experienced an increase of 11.47% that was non-significant.[1]

Royal Jelly, at 0.1% of the diet, has also been demonstrated to protect sperm from oxidative damage induced by hydrogen peroxide.[27]

7.2

Libido

In infertile men, all tested doses of Royal Jelly (25, 50, and 100mg) daily were able to increase sexual desire significantly more than placebo, and no dose-dependence was seen.[1]

7.3

Sex Organs

A histological study in hamsters noted that while degeneration occurred in control during the aging process, that addition of Royal Jelly at low doses (50-500mcg/g food intake) reduced lipid peroxidation in testicular tissues and, thought to be secondary to this, increased the amount of healthy appearing seminiferous tubules capable of spermatogenesis.[28]

8.

Interactions with Organ Systems

8.1

Liver

In an animal model of CCl4 toxicity (oxidative insult resulting in cirrhotic-like lesions) ingesting 50mg/kg, 100mg/kg, or 200mg/kg every other day over a period of 20 days (10 doses) noted that the decrease in Glutathione Peroxidase and SOD (two anti-oxidant enzymes) that occurred during toxicity were still reduced with 50 and 100mg/kg Royal Jelly but to lesser degrees. Catalase appeared to be increased in the Royal Jelly group without toxin, but did not measure the liver tissue itself for damage.[11] A later study did, and using cisplatin-induced toxicity (closely related to oxidation) with Royal Jelly at 300mg/kg noted that RJ was able to attenuate increases in ALT (abolished 70% of the increase) and AST (50%) without influencing these parameters outright.[34] This study, however, saw trends to increase in all anti-oxidant enzymes tested relative to control and significantly increased enzymes relative to cisplatin without RJ; lipid peroxidation was also reduced and histological examinations showed improvements.[34] These protective effects against CCL4 and Cisplatin have also been demonstrated with Paracetemol, suggesting they are general rather than drug specific.[35]

9.

Skeletal Tissue and Bone

9.1

Mechanisms

Royal Jelly appears to induce its bone-forming abilities in mice lacking estrogen (menopause models) through acting on the estrogen receptor, as estrogen receptor blockers abolish the benefits.[36]

9.2

Dental

Due to its effects on bone metabolism and inflammation, a study has been conducted on the interactions of Royal Jelly and Periodontal Disease.[37] In isolated cells, 0.004-0.5mg/mL RJ failed to induce proliferation of MPDL22 cells (periodontal cell line from mice) although 0.5mg/mL enhanced mRNA expression of several genes and enhanced bone mineralization rates.[37]

9.3

Interventions

One study in female rats subject to oophorectomy (removal of ovaries to create a menopause animal model), found that Royal Jelly at 50mg/kg bodyweight was able to attenuate bone loss in the spine and femur over 12 weeks.[38] Total Bone Mineral Density was not different in any group tested nor control, and lumbar spine density in Royal Jelly was 119% (more dense) that of oophorectic rats and 90% (less dense) than that of control rats. The increase in serum Alkaline Phosphatase seen in the oophorectic animals was not observed with Royal Jelly administration, and Bee Pollen at 50mg/kg was equally effective as Royal Jelly.[38]

10.

Inflammation and Immunology

10.1

Macrophages

Using cultured macrophages, the fatty acid from Royal Jelly (10H2DA) was able to inhibit IFNγ production from NO stimulation between 0.1 and 5mM and attenuate the increase in iNOS secondary to the increase in IFNγ; these effects appear to be secondary to preventing NF-kB activation and the subsequent increase in TNF-α protein and mRNA, with no effect on STAT1 or GAS while inhibiting IRF-8 induction.[39]

10.2

Graves Disease

Graves Disease is an GD is an organ-specific autoimmune disease with unknown etiology, and a common cause for hyperthyroidism. In a study using isolated lymphocytes from healthy controls and patients with Graves disease, Royal Jelly was able to enhance cell viability and proliferation at 4mg/mL and increase secretion of IFN-γ.[40]

11.

Interactions with Aesthetics

Collagen synthesis has been noted to be induced in rat skin after oral intake of 1% Royal Jelly in rat feed over a period of 12 weeks.[41]

Melanin (skin pigmentation) has also been reported to have its production reduced secondary to reduces production of the enzyme tyrosinase, which catalyzes the rate-limiting step in melanin synthesis.[42] This study noted that in B16F1 melanoma cells that incubation with up to 200ug/mL failed to exert cytotoxic effects and reduced melanin content at 25ug/mL (to 67% of control) and more-so at 50ug/mL and 100ug/mL reducing melanin down to 40% of control cells (with no significant difference between these two concentrations).[42] mRNA of tyrosinase was potently reduced to 6.5+/-4.9% of control with 25ug/mL with higher doses being insignificantly better.[42]

12.

Interactions with Oxidation

In rats subject to gamma radiation, ingestion of Royal Jelly was able to attenuate the increase in TBARS and Lipid peroxidation (pro-oxidative measures) seen with radiation[43] and confer protective effects at a rather high dose of 1g/kg lyophilized Royal Jelly bodyweight, a dose exceeding that which has been shown to cause testicular harm in rats.[2] This dose also reported a trend to normalize Nitric Oxide and circulating lipoproteins, which are reduced from radiation via oxidative means.[2]

13.

Safety and Toxicology

13.1

General

When Royal Jelly is administered to pubertal rats at 200,400, and 800mg/kg bodyweight for 4 weeks (where half the group was examined) and then a 2 week cessation period followed (examination of the other half of the group), saw some reductions in the organ weight coefficient (weight of an organ relative to body weight) of the pituitary and the testes, which started to normalize after cessation; no dose-dependence was observed.[2] No influence on body weight overall was observed.

Some adverse histological appearance of the testes occurred in these studies, which reduced sperm count slightly and increasing deformities, but started to normalize after cessation.[2]

In female rats fed 5% of their diet by weight as Royal Jelly (given food intakes of 17.3+/-0.8g/kg in control and 17.9+/-0.6g/kg; this equates to 86-89mg/kg Royal Jelly daily) was not associated with any toxicological signs and did not adversely affect female reproductive organs or menstruation cycles.[33]

13.2

Allergies and Anaphylaxis

Royal Jelly has been associated with anaphylaxis[44] bronchospasms[45] and asthma[46] sometimes leading to death.[47] These appear to be associated with allergins in Royal Jelly, specifically some of the protein compounds that are common to bees and pollen.[48][49][50] It is highly probably that persons with a severe bee or pollen allergy may have allergic reactions to Royal Jelly supplements.

It is definitely possible to be allergic to Royal Jelly, and this allergy appears to be highly similar to general allergies to bee pollen or bees

References
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