BEE PRDUCTS AND THE POTENTIAL HEALTH ISSUES ARISING FROM THEIR UNCONTROLLED USE

Öz

In Turkiye, as well as worldwide, traditional and alternative medical practices are employed for the preservation of health and the treatment of various diseases. Among these practices, Apitherapy has gained particular attention, especially in recent years. Since drug use causes serious side effects, especially on human health, people are increasingly turning to alternative medical treatment methods with minimal or no side effects. Apitherapy is a treatment method involving bee products such as honey, pollen, Royal Jel, propolis, and bee venom. It is primarily used for the purpose of promoting a healthier lifestyle. While these products have been traditionally used in various treatments for many years, their systematic use has gained prominence in recent years. Studies have shown that these products strengthen the immune system, provide protection against various types of cancer, and exhibit antimicrobial and antioxidant properties. Furthermore, the high content of protein, vitamins, minerals, and amino acids in these products enhances their therapeutic potential. However, alongside the benefits of these supportive and therapeutic substances, there is a possibility of various toxic effects when used irregularly and without medical supervision. Sometimes, these situations can lead to various organ failures. This review aims to reveal the undesirable effects encountered in the use of bee products and apitherapy applications, and emphasizes that all natural products, especially bee products, should not be used uncontrolled.

Anahtar Kelimeler

• Apitherapy
• honey
• bee polen
• propolis
• apilarnil
• bee venom

Kaynakça

1. Karabagias IK, Badeka AV, Kontakos S, Karabournioti S, Kontominas MG. Botanical discrimination of Greek unifloral honeys with physico-chemical and chemometric analyses. Food Chem. 2014; 165: 181-190.
2. Türk Gıda Kodeksi Bal Tebliği. T.C. Resmi Gazete, Sayı: 31107, 22 Nisan 2020.
3. Karadal F, Yıldırım Y. Balın kalite nitelikleri, beslenme ve sağlık açısından önemi. Erciyes Üniv Vet Fak Derg. 2012; 9(3):197-209.
4. Bogdanov S. Honey composition. The Honey Book. 2009; p. 1-9.
5. Özkök A, D’arcy B, Sorkun K. Total phenolic acid and total flavonoid content of Turkish pine honeydew honey. JAAS. 2010; 2(2): 65-71.
6. Viuda‐Martos M, Ruiz‐Navajas Y, Fernández‐López J, Pérez‐Álvarez JA. Functional properties of honey, propolis, and royal jelly. J Food Sci. 2008; 73(9): R117-R124.
7. Aksoy Z, Dığrak M. Bingöl yöresinde toplanan bal ve propolisin antimikrobiyal etkisi üzerinde in vitro araştırmalar. Fırat Üniv Fen Müh Bilim Derg. 2006; 18(4): 471-8.
8. White JW. Subers MH, Schepartz AI. The identification of inhibine the antibacterial factor in honey, as hydrogen peroxide and its origin in a honey glucose-oxidase system. Biochem Biophys Acta. 1963; 73(1): 57-70.

9. Alvarez-Suarez JM, Giampieri F, Battino M. Honey as a source of dietary antioxidants: Structures, bioavailability, and evidence of protective effects against human chronic diseases. Curr Med Chem. 2013; 20(5): 621-38.
10. Ajibola A, Chamunorwa JP, Erlwanger KH. Nutraceutical values of natural honey and its contribution to human health and wealth. Nutr Metab. 2012; 9(61): 1-13.
11. Koca I, Koca AF. Poisoning by mad honey: a brief review. Food Chem Toxicol. 2007; 45(8): 1315-1318.
12. Aureli P, Franciosa G, Fenicia L. Infant botulism and honey in Europe: a commentary. Pedıatr Infect Dıs J. 2002; 21(9): 866-868
13. Sforcin JM, Bankova V. Propolis: is there a potential for the development of new drugs? J Ethnopharmacol. 2011; 133(2): 253-260.
14. Krell R. Value-Added Products from Beekeeping, Fao Agricultural Services Bulletin No. 124, Chapter 3, Pollen;1996.
15. Bankova VS, de Castro SL, Marcucci MC. Propolis: recent advances in chemistry and plant origin. Apidologie. 2000; 31(1): 3-15.
16. Bogdanov S. Propolis: biological properties and medical applications. The propolis book. Chapter 2. 2012; p. 1-42.
17. Marcucci MC. Propolis: Chemical composition, biological properties and therapeutic activity. Apidologie. 1995; 26: 83–99.
18. Yang H, Huang Z, Huang Y, Dong W, Pan Z, Wang L. Characterization of Chinese crude propolis by pyrolysis–gas chromatography/mass spectrometry. JAAP. 2015; 113: 158-164.
19. Piccinelli AL, Mencherini T, Celano R, Mouhoubi Z, Tamendjari A, Aquino RP et al. Chemical composition and antioxidant activity of Algerian propolis. J. Agric. Food Chem 2013; 61(21): 5080-5088.
20. Moura, SALD, Negri G, Salatino A, Lima LDDC, Dourado LPA, Mendes JB, et al. Aqueous extract of Brazilian green propolis: primary components, evaluation of inflammation and wound healing by using subcutaneous implanted sponges. Evidence-Based Complementary and Alternative Medicine. 2011; 8:1-9.
21. Franchin M, Colon DF, Castanheira FV, daCunha MG, Bueno-Silva,B, Alencar SM, Rosalen, PL. Vestitol isolated from Brazilian red propolis inhibits neutrophils migration in the inflammatory process: elucidation of the mechanism of action. J. Nat. Prod. 2016; 79(4): 954-960.
22. Kang LJ, Lee HB, Bae HJ, Lee SG. Antidiabetic effect of propolis: reduction of expression of glucose-6-phosphatase through inhibition of Y279 and Y216 autophosphorylation of GSK-3α/β in HepG2 cells. Phytother Res. 2010; 24(10): 1554-1561.
23. Darendelioglu E, Aykutoglua G, Tartik M, Baydas G. Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis. Acta Histochem. 2016; 118, (4), 369-376,
24. De Castro PA, Savoldi M, Bonatto D, Malavazi I, Goldman MHS, Berretta AA, et al. Transcriptional profiling of Saccharomyces cerevisiae exposed to propolis. BMC Complement Altern Med. 2012; 12: 1-14.
25. Tartik M, Darendelioglu E, Aykutoglu G, Baydas G. Turkish propolis supresses MCF-7 cell death induced by homocysteine. Biomed Pharmacother. 2016; 82: 704-712
26. Basavaiah ND, Suryakanth DB. Propolis and allergic reactions. J Pharm Bioallied Sci. 2012; 4(4): 345.
27. de Groot AC. Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects. Dermatitis, 2013; 24(6): 263-82.
28. Silici S, Okan A, Köklü B, Demiray S, Doğanyiğit Z. Toxicity of Propylene Glycol Extract of Propolis on Central Nervous System and Liver in Pregnant and Neonatal Rats. Z Geburtshilfe Neonatol. 2023; 227(4): 261-268.
29. Wang X, Wang Z, Di S, Xue X, Jin Y, Qi P, et al. Determination of 14 lipophilic pesticide residues in raw propolis by selective sample preparation and gas chromatography–tandem mass spectrometry. Food Anal. Methods. 2020; 13: 1726–1735.
30. Végh R, Csóka M, Mednyánszky Z, Sipos L. Pesticide residues in bee bread, propolis, beeswax and royal jelly- A review of the literature and dietary risk assessment. Food Chem Toxicol. 2023; 176: 113806.
31. D'Ercole MC. Prolonged use of propolis can increase liver enzymes. J Gastrointestin Liver Dis. 2020; 29(3): 468-469.
32. Pasupuleti V.R. Sammugam L. Ramesh N. Gan S.H. Honey, Propolis, and Royal Jelly: A Comprehensive Review of Their Biological Actions and Health Benefits. Oxid Med Cell Longev, 2017, 1259510.
33. Silici S. Honeybee Products and Apitherapy. Turk J Food Agric Sci. 2019; 7(9): 1249-1262.
34. Tabatabaei, P. Türkiyenin farklı coğrafi bölgelerinden toplanan arı poleninin fenolik bileşikleri ve antioksidan kapasitelerinin araştırılması. Yüksek Lisans Tezi; Ondukuz Mayıs Üniversitesi Fen Bilimleri Enstitüsü. 2017
35. Thakur M, Nanda V. Assessment of physico-chemical properties, fatty acid, amino acid and mineral profile of bee pollen from India with a multivariate perspective. J. Food Nutr. Res. 2018; 57(4): 328-340.
36. Komosinska-Vassev K, Olczyk P, Kafmierczak J. Mencner L, Olczyk K. Bee pollen: Chemical composition and therapeutic application. Evid Based Complement Altern. 2015; 1(1): 1-6.
37. Kędzia B and Hołderna-Kędzia E. Biological properties and therapeutic action of bee pollen, Postępy Fitoterapii, 2005; 3-4: 103–108
38. Trautmann A, Schmid-Grendelmeier P, Krüger K, Crameri R, Akdis M, Akkaya A, et al. T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma. J Allergy Clin Immunol. 2002; 109(2): 329-337.
39. Geyman JP. Anaphylactic reaction after ingestion of bee pollen. J Am Board Fam Pract, 1994; 7: 250-252.
40. Chivato T, Juan F, Montoro A, Laguna R. Anaphylaxis induced by ingestion of a pollen compound. J Investig Allergol Clin Immunol. 1996; 6: 208–209.
41. Park HJ, Hur GY, Kim HA, Ye YM, Suh CH, Nahm DH, et al. Anaphylactic reaction after the ingestion of bee pollen. Korean J Asthma Allergy Clin Immunol. 2007; 27: 57–60.
42. Cohen SH, Yunginger JW, Rosenberg N, Fink JN. Acute allergic reaction after composite pollen ingestion. J Allergy Clin Immunol. 1979; 64: 270–274.
43. Shahali Y. Allergy after ingestion of bee-gathered pollen: influence of botanical origins. Ann Allergy Asthma Immunol. 2015; 114(3): 250-1
44. Guo J, Wang Z, Chen Y, Cao J, Tian W, Ma B, Dong Y. Active components, and biological functions of royal jelly. J. Funct. Foods. 2021; 82: 104514.
45. Cornara L, Biagi M, Xiao J, Burlando B. Therapeutic Properties of Bioactive Compounds from Different Honeybee Products. Front Pharmacol. 2017; 28(8): 412-433.
46. Melliou E, Chinou I. Chemistry and bioactivity of royal jelly from Greece. J. Agric. Food Chem. 2005; 53(23): 8987–8992.
47. Ramanathan ANKG, Nair AJ, Sugunan VSA. Review on royal jelly proteins and peptides. J. Funct. Foods. 2018; 44: 255–264.
48. Xin X, Chen Y, Chen D, Xiao F, Parnell LD, Zhao J, et al. Supplementation with Major Royal-Jelly Proteins Increases Lifespan, Feeding, and Fecundity in Drosophila. J. Agric. Food Chem. 2016; 64: 5803–5812.
49. Kunugi H, Mohammed Ali A. Royal jelly and its components promote healthy aging and longevity: From Animal Models to Humans. Int J Mol Sci. 2019; 20(19): 4662.
50. Ramadan MF, Al-Ghamdi A. Bioactive compounds and health-promoting properties of royal jelly: a review. J. Funct. Foods. 2012; 4: 39–52.
51. Khoshpey B, Djazayeri S, Amiri F, Malek M, Hosseini A F, Hosseini S, et al. Effect of royal jelly intake on serum glucose, Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB) and ApoB/ApoA-I ratios in patients with type 2 Diabetes: a randomized, double-blind clinical trial study. Can. J. Diabetes. 2016; 40: 324–328.
52. Silvia C. Remolina & Kimberly A. Hughes. Evolution and mechanisms of long life and high fertility in queen honey bees. AGE. 2008; 30: 177–185
53. Morita H, Ikeda T, Kajita K, Fujioka K, Mori I, Okada H, Uno Y, Ishizuka T. Effect of royal jelly ingestion for six months on healthy volunteers. Nutr. J. 2012; 11(77): 1-7.
54. Yakoot M, Salem A, Helmy S. Effect of Memo, a natural formula combination, on Mini-Mental State Examination scores in patients with mild cognitive impairment. Clin. Interv. Aging. 2013; 8: 975–981.
55. Pan Y, Xu J, Chen C, Chen F, Jin P, Zhu K, et al. Royal jelly reduces cholesterol levels, ameliorates Aβ pathology and enhances neuronal metabolic activities in a rabbit model of Alzheimer’s disease. Front. Aging Neurosci. 2018; 10: 50-65.
56. Botezan S, Baci GM, Bagameri L, Pașca C, Dezmirean DS. Current status of the bioactive properties of royal jelly: A Comprehensive Review with a Focus on Its Anticancer, Anti-Inflammatory, and Antioxidant Effects. Molecules. 2023; 28(3): 1510-1535.
57. Kamakura M. Royalactin induces queen differentiation in honeybees. Nature. 2011; 473: 478–483.
58. Hata T, Furusawa-Horie T, Arai Y, Takahashi T, Seishima M, Ichihara K. Studies of royal jelly and associated cross-reactive allergens in atopic dermatitis patients. PLoS ONE. 2020; 15(6): 1-14.
59. Maghsoudlou A, Mahoonak AS, Mohebodini H, Toldra F. Royal jelly: chemistry, storage and bioactivities. J. Apic. Sci. 2019; 63:17–40.
60. Bogdanov S. Contaminants of bee products. Apidologie. 2006; 37: 1–18.
61. Rosmilah M, Shahnaz M, Patel G, Lock J, Rahman D, Masita A, et al. Characterization of major allergens of royal jelly Apis mellifera. Trop. Biomed. 2008; 25: 243-251.
62. Kolayli S, Keskin M. Natural bee products and their apitherapeutic applications. Stud. Nat. Prod. Chem. 2020; 66: 175–196.
63. Park D, Jung JW, Lee MO, Lee SY, Kim B, Jin HJ, et al. Functional characterization of naturally occurring melittin peptide isoforms in two honeybee species, Apis mellifera and Apis cerana. Peptides. 2014; 53: 185-93.
64. Bogdanov S. Biological and Therapeutic Properties of Bee Venom. In The Bee Venom Book; 2016. Bee Product Science: Bern, Switzerland. p. 1–23
65. Ahmed O, Fahim H, Mahmoud A, Eman Ahmed EA. Bee venom and hesperidin effectively mitigate complete Freund’s adjuvant-induced arthritis via immunomodulation and enhancement of antioxidant defense system. Arch. Rheumatol. 2017; 33:198–212.
66. Oršolić, N. Bee venom in cancer therapy. Cancer Metastasis Rev. 2012; 31: 173–194.
67. Ye M, Chung H-S, Lee C, Yoon MS, Yu AR, Kim JS, et al. Neuroprotective effects of bee venom phospholipase A2 in the 3xTg AD mouse model of Alzheimer’s disease. J Neuroinflammation. 2016; 13(1): 1-12.
68. Wehbe R, Frangieh J, Rima M, El Obeid D, Sabatier JM, Fajloun Z. Bee venom: Overview of main compounds and bioactivities for therapeutic interests. Molecules. 2019; 24(16): 2997.
69. Lewin M, Samuel S, Merkel J, Bickler P. Varespladib (LY315920) appears to be a potent, broad-spectrum, inhibitor of snake venom phospholipase A2 and a possible pre-referral treatment for envenomation. Toxins. 2016; 8(9): 248.
70. Bogdanov S. Bee venom: composition, health, medicine: a review. Peptides. 2015; 1:1-20.
71. Zhang S, Liu Y, Ye Y, Wang XR, Lin LT, Xiao LY, et al. Bee venom therapy: Potential mechanisms and therapeutic applications. Toxicon. 2018; 148: 64–73.
72. Liu S, Yu M, He Y, Xiao L, Wang F, Song C, et al. Melittin prevents liver cancer cell metastasis through inhibition of the Rac1-dependent pathway. Hepatology. 2008; 47: 1964–1973
73. McDonald J, Li F, Mehta C. Cancer mortality among beekeepers. Journal of Occupational Medicine. 1980; 21(12): 811–813.
74. Simons FER, Frew AJ, Ansotegui IJ, Bochner BS, Golden DBK, Finkelman FD, et al. Practical allergy (PRACTALL) report: risk assessment in anaphylaxis. Allergy. 2008; 63(1): 35-37.
75. Harfmann D, Florea A. Experimental envenomation with honeybee venom melittin and phospholipase A2 induced multiple ultrastructural changes in adrenocortical mitochondria. Toxicon. 2023; 229: 1-15.
76. Sturm GJ, Varga EM, Roberts G, Mosbech H, Bilò MB, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy. 2018; 73:744–764.
77. Han SM, Lee GG, Park KK. Acute dermal toxicity study of bee venom (Apis mellifera L.) in rats, Tox Research. 2012; 28:99-102.
78. Ramirez L, Shekhtman A, Pande, J. Nuclear magnetic resonance-based structural characterization and backbone dynamics of recombinant bee venom melittin. Biochemistry. 2018; 57(19): 2775-2785.
79. Kim CMH. Apitherapy—Bee Venom Therapy. In Biotherapy-History, Principles and Practice. A Practical Guide to the Diagnosis and Treatment of Disease using Living Organisms; Springer: Heidelberg, Germany. 2013. p. 77–112.
80. Park JH, Yim BK, Lee JH, Lee S, Kim TH. Risk associated with bee venom therapy: a systematic review and meta-analysis. PloS one. 2015; 10(5): 01-26
81. Colomar AApilarnil Therapy: The Healing Power of Bee Larvae. J Apitherapy. 2023; 10 (09): 1-2
82. Ram SKM, Jayapal N, Nanaiah P, Aswal GS, Ramnarayan B, Taher SM. The therapeutic benefits of bee venom. Int J Curr Microbiol App Sci. 2014; 3: 377-381.
83. İnci H, Ilkaya M. And İzol E. Apilarnil (Drone Larvae) Chemical Content, Bioactive Properties and Supporting Potential in Medical Treatment of Some Diseases in Terms of Human Health. Ulus Gıda Tar Hayv Derg, 2021; 1 (1): 1-7
84. Tunca RI, Taşkin A. ve Karadavut U. Determination of bee products consumption habits andawareness level in some provinces in Turkey. Turk J Food Agric Sci. 2015; 3(7): 556-561.
85. Aoşan C. Apitherapy in the daily practice clinical applications. In Apimedica and Apiquality Forum, Rome, 2016. p. 22-24.
86. Lee BW, Shek LPC, Gerez IFA, Soh SE, Van Bever HP. Food Allergy--Lessons from Asia. World Allergy Organ J, 2008; 1(7): 129-133.
87. Cifuentes, L. Allergy to honeybee… not only stings. Curr Opin Allergy Clin Immunol. 2015; 15(4): 364-368.
88. Eshraghi S and Seifollahi F. Antibacterial Effects of Royal Jelly on Different Strains of Bacteria. Iranian J Publ Health, 2003: 32 (1):25-30
89. Stangaciu S. Bee products and their medicinal uses. Honeybee Science. 2002; 23(3): 97–104.
90. Jayaraj R, Megha P, Sreedev P. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment. Interdiscip toxicol. 2016; 9(3-4): 90–100.
91. Johnson RM, Dahlgren L, Siegfried BD, Ellis MD. Acaricide, Fungicide and Drug Interactions in Honeybees (Apis mellifera). PLoS ONE. 2013; 8(1): 1-11.
92. Hepburn HR, Pirk CWW, Duangphakdee O. Synthesis of Beeswax. Honeybee Nests. 2014, pp 341–365
93. Crane E. Bee Products. Encyclopedia of Insects. 2009. p. 71–75.
94. Fratini F, Cilia G, Turchi B, Felicioli A. Beeswax: A minireview of its antimicrobial activity and its application in medicine. Asian Pac J Trop Med. 2016; 9(9): 839-843.
95. Apan MA, Zorba M, Kayaboynu Ü. Honey bee and honey bee products. Sinop Uni J Nat Sci. 2021; 6(2): 202-223.
96. Sorucu A. Bee products and apitherapy. Bulletin of Veterinary Pharmacology and Toxicology Association. 2019; 10(1): 1-15.
97. Topal E, Ceylan Ö, Kösoğlu M, Mărgăoan R, Cipcigan Mc. Bal Mumunun Yapisi, Kullanim Alanlari ve Bazi Temel Sorunlari. U Arı D. 2020; 20(2): 209-220.
98. Kačániová M, Vukovic N, Chlebo R, Hascik P, Rovna K, Cubon J, et al. The antimicrobial activity of honey, bee pollen loads and beeswax from Slovakia. Arch Biol Sci. 2012; 64(3): 927-934.
99. Illnait J, Rodríguez I, Mendoza S, Fernández Y, Mas R, Miranda M, et al. Effects of D-002, a mixture of high molecular weight beeswax alcohols, on patients with nonalcoholic fatty liver disease. Korean J Intern Med. 2013; 28(4): 439-448.
100. Puente R, Illnait J, Mas R, Carbajal D, Mendoza S, Fernández JC, et al. Evaluation of the effect of D-002, a mixture of beeswax alcohols, on osteoarthritis symptoms. Korean J Intern Med. 2014; 29(2): 191-202.
101. Perugini M, Tulini SMR, Zezza D, Fenucci S, Conte A, Amorena M. Occurrence of agrochemical residues in beeswax samples collected in Italy during 2013–2015. Sci Total Environ. 2018; 625: 470-476.
102. Bommuraj V, Chen Y, Klein H, Sperling R, Barel S, Shimshoni JA. Pesticide and trace element residues in honey and beeswax combs from Israel in association with human risk assessment and honey adulteration. Food Chem. 2019; 299:1-10.
103. Gokulakrishnaa RK, Thirunavukkarasu S. Apitherapy: A valuable gift from honey bee. J Entomol Zool Stud. 2020; 8(5): 2317–2323.
104. Alvarez-Suarez JM. Bee products-chemical and biological properties. Springer. 2017.
105. Abd El-Wahed AA, Farag MA, Eraqi WA, Mersal GA, Zhao C, Khalifa SA, et al. Unravelling the beehive air volatiles profile as analysed via solid-phase microextraction (SPME) and chemometrics. J King Saud Univ Sci. 2021; 33(5): 1-8.
106. Kekeçoğlu M, Bellici AE, Yıldırım İ, Kınalıkaya A, Çaprazlı T, Yüksel B. The Use of Bee Products and Undesirable Effects Related to Apitherapy Applications: A Systematic Review. Journal Of Traditional Medical Complementary Therapies. 2023; 6(2): 169-183