Royal jelly

Royal Jelly: A Comprehensive Reference

1. Identity and Natural Source

Royal jelly is a yellowish-white, acidic substance secreted by the hypopharyngeal and mandibular glands of nursing (young worker) bees, and serves as an exclusive nourishment for developing queen bee larvae throughout the queen's life. It is produced by Apis mellifera (the Western or European honeybee) and closely related Apis species. Royal jelly is the exclusive food for the queen honeybee and larvae, secreted specifically by worker bee hypopharyngeal and mandibular glands. It is sometimes referred to colloquially as "bee milk" due to its creamy white appearance and its nutritive role.

Royal jelly is fed to developing worker larvae during the first three days of life, and for the duration of the queen bee's life. The exclusive and continuous feeding of royal jelly to a larva destined to become a queen is the mechanism by which a genetically identical larva develops into a physically and reproductively distinct queen bee — a phenomenon that has made royal jelly a subject of intense biological and biomedical research.

Common Forms and Preparations

Royal jelly is commercially available in several forms:

• Fresh (raw) royal jelly: Due to its perishable nature, proper processing and cold storage are essential for maintaining its stability. For long-term preservation, fresh royal jelly should be frozen at temperatures below −18°C, which can maintain its potency for up to two years.
• Freeze-dried (lyophilized) powder: Royal jelly, due to its unique bioactive components, has special biological activities, but a great extent of its nutritional value is lost during processing and storage; lyophilization is an effective preservation technique that can feasibly preserve the main bioactive compounds. The moisture content of lyophilized royal jelly powder is less than 1%, compared to approximately 70% in fresh royal jelly. GC-MS analysis has indicated that the concentration of 10-hydroxy-2-decenoic acid (10-HDA) in lyophilized powder is approximately 3.85 times greater than in fresh royal jelly, reflecting concentration of the active constituents.
• Encapsulated supplements: Many commercial capsules contain freeze-dried powder, which is often labeled with an equivalent fresh weight — for example, a 500 mg capsule may be labeled as equivalent to 1,500 mg of fresh jelly.
• Topical preparations: Royal jelly is incorporated into cosmetic creams, serums, and wound-healing formulations.
• Combination products: Royal jelly is also found in dietary supplement combinations, such as Melbrosia, which combines royal jelly with flower pollen and fermented flower pollen.

2. Traditional and Historical Use

Royal jelly has been used since ancient times for care and human health, and is still very important in traditional and folkloristic medicine, especially in Asia within the practice of apitherapy.

Royal jelly has been a prized product in beekeeping for thousands of years, with its history dating back to ancient China and Egypt, where it was considered a rare and precious commodity. In these cultures, royal jelly was believed to possess medicinal and rejuvenating qualities, making it highly sought after by royalty and the wealthy.

Ancient Egypt: In ancient Egypt, royal jelly and other bee products were used in fertility rituals, embalming practices, and skin treatments believed to preserve youth.

Traditional Chinese Medicine (TCM): In traditional Chinese medicine, royal jelly has been used for centuries to enhance energy and boost the immune system, with emperors and nobility hoarding it in the belief that it was a source of vitality.

Traditional European Beekeeping: In traditional European beekeeping, royal jelly was also held in high esteem for its purported health benefits, and was often used as a treatment for various ailments including fever, arthritis, and impotence.

Ayurvedic Medicine: In traditional Ayurvedic medicine, royal jelly is valued for its potential to balance the body's energies and promote longevity.

Imperial Japan and Korea: In imperial Japan and Korea, royal jelly was considered a secret of vitality for emperors and nobles, integrated into teas and restorative tonics.

20th-Century Surge of Interest: Interest in royal jelly surged during the 20th century due to growing interest in natural ingredients, emerging scientific discoveries, and because Pope Pius XII publicly credited it with restoring his health in the 1950s.

3. Chemical Composition and Key Constituents

Royal jelly is a complex bee-derived secretion with a unique composition of proteins, peptides, fatty acids, flavonoids, and phenolic compounds that collectively contribute to its diverse biological effects.

Proximate Composition

The chemical composition of royal jelly is highly complex, consisting of water (50–70%), proteins (9–18%), carbohydrates (11–23%), lipids (3–8%), and trace amounts of vitamins, minerals, and other compounds, including several nucleotides as free bases and phosphates such as adenosine 5′-monophosphate (AMP), adenosine 5′-diphosphate (ADP), and adenosine 5′-triphosphate (ATP).

Carbohydrates

Royal jelly contains approximately 7.5–15% sugars, with fructose and glucose comprising the majority, making up around 90% of the sugar content. Additionally, maltose, trehalose, melibiose, ribose, and erlose constitute about 0.8–3.6% of the sugar composition.

Proteins and Peptides

Proteins make up about 50% of royal jelly dry matter, with approximately 80% consisting of nine Major Royal Jelly Proteins (MRJPs), which have molecular weights between 49 and 87 kDa. These proteins are nutritionally valuable and play a crucial role in the development of young female larvae through cell proliferation.

The main proteins are MRJP1 (royalactin) through MRJP9 (representing more than 80% of the protein content, with molecular weights between 49 and 87 kDa), whereas the most often-found peptides in royal jelly are apisimin, royalisin, apidaecin, defensin-1, and jelleines.

MRJP1 is the most abundant type (comprising 31–66% of total royal jelly proteins), followed by MRJP3, MRJP2, and MRJP5. The function of MRJP1 depends on its oligomeric state: in the monomeric form, MRJP1 is a 55 kDa protein also known as royalactin, whereas its oligomeric form, apisin, is a complex of MRJP1 monomers bound to apisimin polypeptides and 24-methylenecholesterol.

Royalactin was found to induce the differentiation of honeybee larvae into queens through an epidermal growth factor receptor (EGFR)-mediated signaling pathway. The glycoprotein royalactin also mimics epidermal growth factor (EGF) effects in rat hepatocytes and regulates developmental processes in bee larvae.

Other royal jelly proteins include jelleines, royalisin, and apisimin, with royalisin and jelleines being antimicrobial peptides that enhance immune responses in bee larvae.

Lipids and Fatty Acids

Lipids, particularly 10-hydroxy-2-decenoic acid (10-HDA), are unique to royal jelly and exhibit antimicrobial and anti-inflammatory properties. 10-HDA is the main fatty acid constituent (approximately 21 mg/g of royal jelly) and is also regarded as a marker of quality and freshness.

Major lipids in royal jelly consist of 10-hydroxy-2-decenoic acid and sebacic acid; 10-HDA is known for its anti-cancerous and anti-angiogenic activity, whereas sebacic acid has anti-aging effects.

Vitamins and Minerals

Royal jelly also contains B-complex vitamins, vitamin C, and minerals such as calcium, potassium, and zinc. Additional bioactive compounds include carbohydrates, lipids, fatty acids, minerals, vitamins, enzymes, hormones, and phenolic compounds, mainly flavonoids.

4. Mechanisms of Action

Biological activities of royal jelly are mainly attributed to the bioactive fatty acids, proteins, and phenolic compounds. Research has identified several specific mechanisms through which royal jelly exerts its effects:

Anti-Inflammatory Mechanisms

10-HDA was proved to inhibit TLR4-induced immune cell activation and inflammatory cytokine expression in LPS-activated macrophages via reducing NF-κB expression. 10-HDA has been shown to inhibit nitric oxide production in a dose-dependent manner, reduce the secretion of TNF-α and IL-1β, and increase the anti-inflammatory cytokine IL-10 in LPS-stimulated macrophages, indicating that 10-HDA is able to attenuate inflammation and the inflammatory polarization of M1 macrophages.

The molecular mechanisms underlying royal jelly's anti-inflammatory effects involve modulation of signalling pathways such as NF-κB, MAPK, and AMPK.

Neuroprotective Mechanisms

In preclinical studies, royal jelly, enzyme-treated royal jelly, 10-HDA, royal jelly peptides, and MRJPs were effective against Alzheimer's disease pathology by interfering with protein misfolding, amyloid synthesis, and amyloid clearance. Furthermore, royal jelly promoted neuronal survival and functioning by targeting inflammation, oxidative stress, mitochondrial dysfunction, disturbed proteostasis, amyloid β (Aβ) toxicity, Ca-mediated excitotoxicity, and bioenergetic failure.

10-HDA has been identified as a novel autophagy inducer, which increases lysosome activity and protein metabolism in neuronal cell lines.

Wound Healing Mechanisms

Royal jelly proteins have been shown to induce wound-repairing activity in keratinocytes. A water-soluble protein fraction mainly consisting of MRJP2, MRJP3, and MRJP7 was found to induce proliferative and migratory effects in human epidermal keratinocytes (HaCaT) without obvious cytotoxicity, implying the potential of MRJPs in the healing of cutaneous wounds.

Estrogenic Mechanisms

Royal jelly has shown estrogenic effects both in vitro and in vivo, with this effect mediated through the interaction with estrogenic receptors (ER).

Antimicrobial Mechanisms

Antimicrobial activities of crude royal jelly, royalisin, 10-hydroxy-2-decenoic acid, jelleines, and major royal jelly proteins against different bacteria have been reported. Royal jelly exhibits broad-spectrum antimicrobial activity due to its complex composition of bioactive molecules, including antimicrobial peptides (AMPs), fatty acids, and MRJPs.

5. Scientific Evidence by Area of Use

Royal jelly shows numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. The following sections summarize the clinical evidence for each major area, characterizing evidence strength honestly.

5.1 Lipid Profile and Cardiovascular Health

Evidence strength: Preliminary to moderate; results mixed across trials.

In a clinical trial involving postmenopausal women, royal jelly treatment resulted in a significant increase in HDL-cholesterol (from 60.2 to 64.7 mg/dL, a 7.7% increase, p = 0.0003), as well as a significant decrease in LDL-cholesterol (from 143.9 to 136.2 mg/dL, a 4.1% decrease, p = 0.011) and total cholesterol (from 224.4 to 216.1 mg/dL, a 3.09% decrease, p = 0.018). The intake of 150 mg of royal jelly for three months was associated with significant improvements in the lipid profile of postmenopausal women.

In a systematic review of 6 randomized controlled trials including a total of 270 patients with type 2 diabetes mellitus, royal jelly treatment at 1–3 g/day for 8 weeks improved serum levels of triglycerides, cholesterol, HDL, LDL, VLDL, and Apo-A1. However, the evidence for cholesterol and lipid profiles is characterized as showing potential benefit but with mixed and inconclusive results overall.

A 2023 systematic review found that royal jelly reduced total cholesterol, especially at doses of ≥3,000 mg/day for ≥8 weeks.

5.2 Glycemic Control and Diabetes

Evidence strength: Preliminary; encouraging signals from small clinical trials, requiring confirmation.

Royal jelly has been shown in one clinical study to significantly improve the levels of triglycerides, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, total cholesterol, and ApoA-1 in diabetic subjects, thereby promoting glycemic balance.

Small randomized trials have reported reductions in fasting blood glucose and HbA1c in people with diabetes after several weeks of royal jelly supplementation. However, many studies on therapeutic effects are preclinical trials, necessitating cautious extrapolation to human applications.

5.3 Menopause and Hormonal Health

Evidence strength: Preliminary to moderate; limited number of human clinical trials, with some positive and some null results.

Royal jelly is used by postmenopausal women for the improvement and treatment of menopause-related complications and aging-related pathologies, due to its similarity with estrogens. The effects of royal jelly during menopause represent an active research subject, though there is only a small amount of human clinical trials, with the majority of investigations performed on ovariectomized animal models.

An uncontrolled, open-label trial treated 55 postmenopausal women with Melbrosia (a dietary supplement combining royal jelly with flower pollen and fermented flower pollen) for 3 months. Melbrosia significantly improved participants' scores on the problem-solving subscale of the Frankfurt Self-concept Scale, relieved depressive and menopausal symptoms, decreased total cholesterol and LDL, and increased HDL and triglycerides, whereas VCAM-1 and C-reactive protein levels were not affected.

In contrast, a prior randomized controlled trial reported no effect of Melbrosia on biochemical parameters in women with severe menopausal symptoms, although it significantly improved vitality and relieved symptoms of headache, urinary incontinence, and vaginal dryness.

5.4 Neuroprotection and Cognitive Function

Evidence strength: Mostly preclinical; one positive combination-therapy clinical trial in mild cognitive impairment (MCI), but royal jelly was not used in isolation.

In animal models of aging and Alzheimer's disease, royal jelly was able to enhance learning and memory retention, as well as prevent and treat cognitive deficits.

One clinical trial of a combination therapy that included royal jelly improved cognitive functions in mild cognitive impairment. Improvement in the treatment group was significantly greater than in the placebo control group (+2.07 versus +0.13, respectively), and this difference held true after adjusting for age and educational level. However, as royal jelly was part of a multi-ingredient formulation in this study, the contribution of royal jelly alone cannot be isolated.

In the only included clinical study of one systematic review, 66 subjects suffering from mild cognitive impairment were administered a combination of royal jelly, Ginkgo biloba, and Panax ginseng, and a significant improvement (p < 0.01) of cognitive functions compared to control was found after 4 weeks. In other included experiments, performed in animal or cellular models, the neuroprotective activity of royal jelly — capable of hindering the effects of neurotoxic substances and inhibiting beta-amyloid deposition — was demonstrated.

5.5 Anti-Inflammatory and Antioxidant Effects

Evidence strength: Mechanistic evidence is strong at preclinical level; clinical trial data are limited in number and sample size.

A systematic review and meta-analysis examined the impact of royal jelly on inflammation and oxidative stress. This meta-analysis included six articles published between 2014 and 2023 with 356 participants (181 interventions and 175 controls). The intervention duration of all included trials was 8 weeks (except one lasting 4 weeks), with intervention doses ranging from 1,000 to 5,000 mg per day. The participants in the studies were either asymptomatic overweight individuals, patients with addiction, patients with type 2 diabetes mellitus, or healthy adults.

5.6 Antimicrobial Activity

Evidence strength: Robust in vitro data; limited direct clinical trial evidence in humans.

All royal jelly samples tested in one study inhibited multidrug-resistant bacteria, suggesting a potential synergistic effect of crude royal jelly, with inhibition zones ranging from 11.8 mm (against carbapenem-resistant Klebsiella pneumoniae) to 16.8 mm (against methicillin-resistant Staphylococcus aureus). Acinetobacter baumannii was most susceptible (MIC/MBC = 27.2 µg/mL), while Enterococcus faecium was the most resistant (MIC = 96.6 µg/mL, MBC = 126.4 µg/mL).

Royal jelly's antimicrobial effectiveness is particularly pronounced against Gram-positive bacteria.

5.7 Wound Healing

Evidence strength: Preclinical evidence is compelling; early-phase and case-series clinical evidence exists for topical use in diabetic wounds.

In vitro research was the first to report that royal jelly may improve wound closure via MRJP-induced cellular proliferation and migration, and the findings suggest that MRJPs may have potential applications in the treatment of wound healing disorders and diabetic foot ulcers.

Both preclinical and clinical studies have reported that royal jelly improves immune function such as wound healing. Clinical evidence for topical royal jelly in diabetic foot ulcers has been reported in both a case series and a double-blind placebo-controlled clinical trial, though this body of evidence remains limited in scope and scale.

5.8 Oncology Support

Evidence strength: Preliminary; one small RCT for supportive care, not for anti-tumor activity.

The most important biological effects of royal jelly are its anti-inflammatory and antioxidative activities and its ability to exert some control over the immune system. These activities are predicted to be beneficial in the protection against anticancer agent-induced adverse events involving inflammation, oxidative stress, and immune system dysfunction. The protective efficacy of royal jelly against anticancer therapy-associated toxic effects — such as oral mucositis, intestinal damage, and nephro- and hepato-toxicities — has been demonstrated in animal models.

A published randomized, double-blinded, placebo-controlled trial examined oral royal jelly intake for protective effects against tyrosine kinase inhibitor-induced toxicity in patients with renal cell carcinoma, representing one of the few clinical trials in an oncology setting. Women with estrogen-receptor positive breast cancer should be noted as a population for whom caution is warranted, as royal jelly products may stimulate the cancer.

5.9 Blood Pressure

Evidence strength: Mostly preclinical; human data are lacking.

In preclinical models, royal jelly and protease-treated royal jelly exhibit antihypertensive effects, including aortic relaxation, improving heart rate variability and baroreceptor sensitivity, and reducing blood pressure. The suggested mechanism of action involves acetylcholine activation of muscarinic receptors, leading to increased nitric oxide.

6. Body Systems and Health Areas Associated with Royal Jelly

Royal jelly and its metabolites have been associated with health benefits for gastrointestinal protection, cardiovascular health, anti-tumor effects, anti-aging, neuroprotection (including Alzheimer's and Parkinson's disease), metabolic disorders (including diabetes, obesity, and hyperlipidaemia), and reproductive disorders.

Royal jelly demonstrates numerous physiological and pharmacological properties, including vasodilatory, hypotensive, antihypercholesterolaemic, antidiabetic, immunomodulatory, anti-inflammatory, antioxidant, anti-aging, neuroprotective, antimicrobial, estrogenic, anti-allergic, anti-osteoporotic, and anti-tumor effects. Moreover, royal jelly may reduce menopause symptoms and improve the health of the reproductive system, liver, and kidneys, and promote wound healing.

7. Dosage Forms and Dosages Reported in Studies

Preparation and formulation of royal jelly dosages vary from individual to individual, as well as from one age group to another. The following dosages are drawn directly from clinical research as reported in the literature:

• In a systematic review of 6 RCTs in type 2 diabetes patients, the dosage used was 1–3 g/day for 8 weeks.
• One clinical trial used 150 mg of royal jelly daily for three months in postmenopausal women, associated with significant improvements in lipid profiles.
• The intervention doses across trials included in one meta-analysis on inflammation ranged from 1,000 to 5,000 mg per day, with most interventions lasting 8 weeks.
• Some clinical studies have utilized doses of up to 4.8 grams daily for short periods.
• Despite these reported ranges, the review literature identifies the need for standardized dosing regimens as a key gap in current knowledge.

Ratanavalachai and Wongchai investigated the stability of royal jelly's antibacterial activity under various storage conditions. They reported that samples stored in the freezer retained their efficacy, whereas prolonged storage at room temperature resulted in diminished antimicrobial effects, attributed to the degradation of active compounds such as 10-HDA and royalisin over time.

8. Safety Considerations and Interactions

Allergic Reactions

Adverse events induced by royal jelly have been reported in recent decades, almost all of which are allergy-associated symptoms. These symptoms range from mild to severe and include rhinitis, eczema, contact dermatitis, urticaria, conjunctivitis, hemorrhagic colitis, acute asthma, bronchospasm, and fatal anaphylaxis. Individuals with asthma or atopic dermatitis are at particular risk of allergic reaction to royal jelly.

It was reported that 52% of allergic patients (n = 75) in Australia had a positive immunoglobulin E (IgE) response to royal jelly; in Hong Kong, 16.8% of 666 adult asthma patient serum samples contained royal jelly-reactive IgE.

The major allergens of royal jelly are MRJP1 and MRJP2, and these are shared with honeybee venom allergens. MRJPs can cause several allergic reactions including asthma, dermatitis, skin rashes, eczema, bronchospasm, anaphylaxis, hemorrhagic colitis, and in some situations anaphylactic shock and death.

Major royal jelly protein 3 (MRJP3) has been identified as the main allergen that can induce anaphylaxis and cross-reactivity with honeycomb.

Drug Interactions

No reports regarding the possible interactions between royal jelly supplements and other drugs concomitantly taken were made in the general literature; however, Lee et al. presented the case of an 87-year-old man on long-term warfarin therapy who was supplemented with royal jelly capsules. In this case report, an elevated INR and subsequent bleeding were observed, with royal jelly identified as the only source of warfarin's enhanced effects.

Laboratory studies suggest royal jelly may increase the cytotoxic effect of the chemotherapy agent temozolomide, though clinical relevance has yet to be determined.

Hormone-Sensitive Conditions

Women with estrogen-receptor positive breast cancer should avoid products containing royal jelly, as these may stimulate the cancer due to royal jelly's estrogenic properties.

Storage and Degradation

The contents and physiological functions of royal jelly are altered in accordance with storage conditions (ranging from −20°C to 50°C). Proteins and simple sugars in royal jelly change significantly during storage at room temperature, but not at −20°C.

Evidence Gaps and Research Limitations

Further human clinical trials are necessary in order to better observe the beneficial effects, molecular mechanisms of action, and potential side effects of royal jelly as a natural and traditional product. Many studies on therapeutic effects are preclinical trials, necessitating cautious extrapolation to human applications. The overall body of human clinical trial evidence remains limited in terms of sample size, duration, and standardization of preparations.

References

• Royal Jelly in modern biomedicine: A review of its bioactive constituents and health benefits — ScienceDirect (2025)
• Royal jelly: chemical composition, health benefits and food applications: A review — Food Science and Applied Biotechnology (Peykova-Shapkova et al., 2024)
• Chemical Composition of Royal Jelly — ResearchGate / Journal of ApiProduct and ApiMedical Science
• Chemical Composition of Royal Jelly — Springer Nature Link (2025)
• Bioactive compounds and health-promoting properties of royal jelly: A review — Journal of Functional Foods (Ramadan & Al-Ghamdi, 2012)
• Royal jelly a promising therapeutic intervention and functional food supplement: A systematic review — PMC / Heliyon (2024)
• Chemical Characterization and Antibacterial Activity of Royal Jelly Against Multidrug-Resistant Pathogens — PMC (2025)
• Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer's Disease — PMC (2020)
• Royal Jelly—A Traditional and Natural Remedy for Postmenopausal Symptoms and Aging-Related Pathologies — PMC / Molecules (2020)
• Royal Jelly: Biological Action and Health Benefits — PMC / International Journal of Molecular Sciences (2024)
• Royal Jelly — Alzheimer's Drug Discovery Foundation Cognitive Vitality Report
• Greek-origin royal jelly improves the lipid profile of postmenopausal women — PubMed / Gynecological Endocrinology (2016)
• Effects of royal jelly consumption on inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials — PMC / Avicenna Journal of Phytomedicine (2025)
• Royal Jelly: An ancient remedy with remarkable antibacterial properties — ScienceDirect / Pathologie Biologie (2016)
• 10-hydroxy-2-decenoic acid of royal jelly exhibits bactericide and anti-inflammatory activity in human colon cancer cells — PMC / BMC Complementary and Alternative Medicine (2018)
• Integration of Metabolomic and Transcriptomic Provides Insights into Anti-Inflammatory Response to trans-10-Hydroxy-2-decenoic Acid — PMC (2023)
• Royal jelly-derived proteins enhance proliferation and migration of human epidermal keratinocytes in an in vitro scratch wound model — PMC / PLOS ONE (2019)
• Lyophilized royal jelly preparation in nanoscale and evaluation of its physicochemical properties and bactericidal activity — PMC (2023)
• The effects of royal jelly supplementation on anthropometric indices: a GRADE-assessed systematic review and dose-response meta-analysis — PMC / Frontiers in Nutrition (2023)
• Studies of royal jelly and associated cross-reactive allergens in atopic dermatitis patients — PMC / PLOS ONE (2020)
• Determination of royal jelly freshness by ELISA with a highly specific anti-apalbumin 1, major royal jelly protein 1 antibody — PMC (2015)
• Warfarin and Royal Jelly Interaction — Pharmacotherapy (Lee & Fermo, 2006)
• Oral Intake of Royal Jelly Has Protective Effects Against Tyrosine Kinase Inhibitor-Induced Toxicity in Patients with Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Trial — PMC / Medicines (2018)
• Royal Jelly — Memorial Sloan Kettering Cancer Center Integrative Medicine
• Major royal jelly protein — Wikipedia (with underlying cited sources)
• Ectopic expression of structurally similar major royal jelly proteins reveals their distinct functions in Drosophila — PMC (2025)