Author(s):
Santosh Kumar Nayak, Saroj Kumar Rout, Akhila Kumar Das, Anil Kumar Patra, Pratap Kumar Sahu
Email(s):
santosh.milu@gmail.com
DOI:
10.52711/0974-360X.2025.00344 
Address:
Santosh Kumar Nayak1*, Saroj Kumar Rout2, Akhila Kumar Das1, Anil Kumar Patra3, Pratap Kumar Sahu1
1Faculty of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha.
2Research and Development, LNK International Inc., New York, USA.
3Research and Development, Medochemie, Limassol3505, Cyprus (Europe).
*Corresponding Author
Published In:
Volume - 18,
Issue - 5,
Year - 2025
ABSTRACT:
Nutraceuticals are the food supplements that play a vital role to maintain healthy body and provide essential supplements required by the body in order to regulate body’s metabolic process as well as to prevent from diseases. Nature provides us a vast diversified flora and fauna which are used tremendously from a long time by different civilizations for their health promoting effects. Unlike modern day synthetic drugs, nutraceuticals have the ability to provide both preventive action as well as nutritive action without exerting any adverse effects. Nutraceuticals have gained interest worldwide due to their nutritional and therapeutic effects without any toxic issues. The substances derived from foods and dietary supplements have shown different metabolic and biological actions on reproductive system in both human as well as animals. The present review discusses the use of nutraceuticals in different reproductive health anomalies. Articles were gathered using search engines such as Scopus, PubMed, Google Scholar, ResearchGate, and ScienceDirect.
Cite this article:
Santosh Kumar Nayak, Saroj Kumar Rout, Akhila Kumar Das, Anil Kumar Patra, Pratap Kumar Sahu. Nutraceuticals in Reproductive and Urinary Disorders: A Brief Review. Research Journal of Pharmacy and Technology. 2025;18(5):2407-5. doi: 10.52711/0974-360X.2025.00344
Cite(Electronic):
Santosh Kumar Nayak, Saroj Kumar Rout, Akhila Kumar Das, Anil Kumar Patra, Pratap Kumar Sahu. Nutraceuticals in Reproductive and Urinary Disorders: A Brief Review. Research Journal of Pharmacy and Technology. 2025;18(5):2407-5. doi: 10.52711/0974-360X.2025.00344 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-5-67
REFERENCES:
1. Kathleen C, Stephen D. Nutraceuticals: what are they and do they work? Kentucky Equine Research, Versailles. 2013; 7 (4):1-50.
2. Yapijakis C. Hippocrates of Kos, the father of clinical medicine, and Asclepiades of Bithynia, the father of molecular medicine. in vivo. 2009; 23(4): 507-14. DOI: 10.21873/invivo.1234
3. Hardy G. Nutraceuticals and functional foods: introduction and meaning. Nutrition (Burbank, Los Angeles County, Calif.). 2000; 16(7-8): 688-9.DOI: 10.1016/S0899-9007(00)00332-4
4. Baradaran A, Madihi Y, Merrikhi A, Rafieian-Kopaei M, Nasri H. Serum lipoprotein (a) in diabetic patients with various renal function not yet on dialysis. Pakistan Journal of Medical Sciences. 2013; 29(S): 354-7. DOI: 10.12669/pjms.291(Suppl).354
5. Setorki M, Rafieian-Kopaei M, Merikhi A, Heidarian E, Shahinfard N, Ansari R, Nasri H, Esmael N, Baradaran A. Suppressive impact of anethum graveolens consumption on biochemical risk factors of atherosclerosis in hypercholesterolemic rabbits. International Journal of Preventive Medicine. 2013; 4(8): 889. DOI: 10.4103/2008-7802.117620
6. Khosravi-Boroujeni H, Mohammadifard N, Sarrafzadegan N, Sajjadi F, Maghroun M, Khosravi A, Alikhasi H, Rafieian M, Azadbakht L. Potato consumption and cardiovascular disease risk factors among Iranian population. International Journal of Food Sciences and Nutrition. 2012; 63(8): 913-20. DOI: 10.3109/09637486.2012.689478
7. Shirzad M, Kordyazdi R, Shahinfard N, Nikokar M. Does Royal jelly affect tumor cells?. Journal of HerbMed Pharmacology. 2013; 2(2).
8. Das L, Bhaumik E, Raychaudhuri U, Chakraborty R. Role of nutraceuticals in human health. Journal of Food Science and Technology. 2012; 49(2): 173-83. Doi:10.1007/s13197-011-0269-4
9. Vannuccini S, Clifton VL, Fraser IS, Taylor HS, Critchley H, Giudice LC, Petraglia F. Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome. Human reproduction update. 2016; 22(1): 104-15. DOI: 10.1093/humupd/dmv044
10. Rotterdam ESHRE/ASRM‐Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Human Reproduction. 2004; 19(1): 41-7. DOI: 10.1093/humrep/deh098
11. Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss III JF, McAllister JM. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. The Journal of Clinical Endocrinology and Metabolism. 2001; 86(12): 5925-33.DOI: 10.1210/jcem.86.12.8072
12. Beemster P, Groenen P, Steegers-Theunissen R. Involvement of inositol in reproduction. Nutrition Reviews. 2002; 60(3): 80-7.DOI: 10.1301/00296640260085800
13. Saptarshi S, Ghosh AK. Pharmacological effects of Sesbania sesban Linn: An overview. PharmaTutor. 2017; 5(7): 16-21.
14. Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med. 1999; 340: 1314–1320. DOI: 10.1056/NEJM199904293401703
15. Gerli S, Papaleo E, Ferrari A, Di Renzo GC. Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci 2007; 11: 347–354.
16. Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013; 95(10): 1811-27. DOI: 10.1016/j.biochi.2013.05.011
17. La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Müllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Human Reproduction Update. 2010; 16(2): 113-30. DOI: 10.1093/humupd/dmp036
18. Ozay AC, EmekciOzay O, Okyay RE, Cagliyan E, Kume T, Gulekli B. Different effects of myoinositol plus folic acid versus combined oral treatment on androgen levels in PCOS women. International Journal of Endocrinology. 2016; 2016. DOI: 10.1155/2016/3206872
19. Genazzani AD, Prati A, Santagni S, et al. Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol Endocrinol. 2012; 28(12): 969-973. DOI: 10.3109/09513590.2012.705382
20. Carlomagno G, De Grazia S, Unfer V, Manna F. Myo-inositol in a new pharmaceutical form: a step forward to a broader clinical use. Expert Opin Drug Deliv. 2012; 9: 267-71. DOI: 10.1517/17425247.2012.654394
21. Fruzzetti F, Benelli E, Fidecicchi T, Tonacchera M. Clinical and Metabolic Effects of Alpha-Lipoic Acid Associated with Two Different Doses of Myo-Inositol in Women with Polycystic Ovary Syndrome. International Journal of Endocrinology. 2020; 2020.DOI: 10.1155/2020/3206135
22. L. Zeng and K. Yang. Effectiveness of myoinositol for polycystic ovary syndrome: a systematic review and meta-analysis. Endocrine. 2018; 59: 30–38.DOI: 10.1007/s12020-017-1479-8
23. Carlomagno G, Unfer V. Inositol safety: Clinical evidences. Eur Rev Med Pharmacol Sci. 2011; 15: 931–6.
24. Scott BC, Aruoma OI, Evans PJ, O'neill C, Van Der Vliet A, Cross CE, Tritschler H, Halliwell B. Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation. Free Radical Research. 1994; 20(2): 119-33. DOI: 10.3109/10715769409145650
25. Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM. Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Current Medicinal Chemistry. 2004; 11(9): 1135-46. DOI: 10.2174/0929867043365323
26. Rago R, Marcucci I, Leto G, Caponecchia L, Salacone P, Bonanni P, Fiori C, Sorrenti G, Sebastianelli A. Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study. J Biol RegulHomeost Agents. 2015; 29(4): 913-23.
27. Cianci A, Panella M, Fichera M, Falduzzi C, Bartolo M, Caruso S. D-chiro-Inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS. Gynecological Endocrinology. 2015; 31(6): 483-6. DOI: 10.3109/09513590.2015.1006616
28. Shim YY, Gui B, Arnison PG, Wang Y, Reaney MJ. Flaxseed (Linum usitatissimum L.) bioactive compounds and peptide nomenclature: A review. Trends in Food Science and Technology. 2014; 38(1): 5-20. DOI: 10.1016/j.tifs.2014.03.009
29. Goyal A, Sharma V, Upadhyay N, Gill S, Sihag M. Flax and flaxseed oil: an ancient medicine and modern functional food. Journal of Food Science and Technology. 2014; 51(9): 1633-53. DOI: 10.1007/s13197-013-1247-9
30. Adlercreutz H, Höckerstedt K, Bannwart C, Bloigu S, Hämäläinen E, Fotsis T, Ollus A. Effect of dietary components, including lignans and phytoestrogens, on enterohepatic circulation and liver metabolism of estrogens and on sex hormone binding globulin (SHBG). Journal of Steroid Biochemistry. 1987; 27(4-6): 1135-44. DOI: 10.1016/0022-4731(87)90371-4
31. Farzana F, Sulaiman A, Ruckmani A, Vijayalakshmi K, Karunya Lakshmi G, Shri RS. Effects of flax seeds supplementation in polycystic ovarian syndrome. Int J Pharm Sci Rev Res. 2015; 31(1): 113-9.
32. Verma R, Prasad R, Gupta A. Functional properties and health benefits in flaxseed fiber and oil (linum usitatissimum L.). International Journal of Home Science. 2017; 3(1): 368-9.
33. Stanley CA. Carnitine deficiency disorders in children. Annals of the New York Academy of Sciences. 2004; 1033(1): 42-51. DOI: 10.1196/annals.1320.005
34. DiNicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O'Keefe JH. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. InMayo Clinic Proceedings. 2013; 88(6): 544-551. DOI: 10.1016/j.mayocp.2013.02.007
35. Vaz FM, Wanders RJ. Carnitine biosynthesis in mammals. Biochemical Journal. 2002; 361(3): 417-29. DOI: 10.1042/bj3610417
36. Lee BJ, Lin JS, Lin YC, Lin PT. Antiinflammatory effects of L-carnitine supplementation (1000 mg/d) in coronary artery disease patients. Nutrition. 2015; 31(3): 475-9. DOI: 10.1016/j.nut.2014.10.020
37. Zhang Q, Wang SM, Yao PB, Zhang L, Zhang YJ, Chen RX, Fu Y, Zhang JM. Effects of L-carnitine on follicular survival and graft function following auto transplantation of cryopreserved-thawed ovarian tissues. Cryobiology. 2015; 71(1): 135-40. DOI: 10.1016/j.cryobiol.2015.05.001
38. Dunning KR, Robker RL. Promoting lipid utilization with l-carnitine to improve oocyte quality. Animal Reproduction Science. 2012; 134(1-2): 69-75. DOI: 10.1016/j.anireprosci.2012.07.011
39. Ismail AM, Hamed AH, Saso S, Thabet HH. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. European Journal of Obstetrics and Gynecology and Reproductive Biology. 2014; 180: 148-52.DOI: 10.1016/j.ejogrb.2014.06.030
40. Villani RG, Gannon J, Self M, Rich PA. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. International Journal of Sport Nutrition and Exercise Metabolism. 2000; 10(2): 199-207.DOI: 10.1123/ijsnem.10.2.199
41. Anthony MS, Clarkson TB, Hughes Jr CL, Morgan TM, Burke GL. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. The Journal of Nutrition. 1996; 126(1): 43-50. DOI: 10.1093/jn/126.1.43
42. Messina MJ, Loprinzi CL. Soy for breast cancer survivors: a critical review of the literature. The Journal of Nutrition. 2001; 131(11): 3095S-108S. DOI: 10.1093/jn/131.11.3095S
43. Mulvihill EE, Huff MW. Antiatherogenic properties of flavonoids: implications for cardiovascular health. Canadian Journal of Cardiology. 2010; 26: 17A-21A.
44. Javanbakht MH, Sadria R, Djalali M, Derakhshanian H, Hosseinzadeh P, Zarei M, Azizi G, Sedaghat R, Mirshafiey A. Soy protein and genistein improves renal antioxidant status in experimental nephrotic syndrome. Nefrología (English Edition). 2014; 34(4): 483-90.DOI: 10.3265/Nefrologia.pre2014.Apr.12558
45. Vincent A, Fitzpatrick LA. Soy isoflavones: are they useful in menopause?.InMayo Clinic Proceedings 2000; 75(11): 1174-1184.DOI: 10.4065/75.11.1174
46. Nynca A, Nynca J, Wąsowska B, Kolesarova A, Kołomycka A, Ciereszko RE. Effects of the phytoestrogen, genistein, and protein tyrosine kinase inhibitor–dependent mechanisms on steroidogenesis and estrogen receptor expression in porcine granulosa cells of medium follicles. Domestic Animal Endocrinology. 2013; 44(1): 10-8. DOI: 10.1016/j.domaniend.2012.10.005
47. Jamilian M, Asemi Z. The effects of soy isoflavones on metabolic status of patients with polycystic ovary syndrome. The Journal of Clinical Endocrinology and Metabolism. 2016; 101(9): 3386-94. DOI: 10.1210/jc.2016-1858
48. Rizvi S, Raza ST, Faizal Ahmed AA, Abbas S, Mahdi F. The role of vitamin E in human health and some diseases. Sultan Qaboos University Medical Journal. 2014;14(2): e157
49. Cicek N, Eryilmaz OG, Sarikaya E, Gulerman C, Genc Y. Vitamin E effect on controlled ovarian stimulation of unexplained infertile women. Journal of Assisted Reproduction and Genetics. 2012; 29(4): 325-8. DOI: 10.1007/s10815-011-9701-6
50. Jayakumari S. Can Vitamin E be a Key Supplementation in Polycystic Ovary Syndrome. Indian Journal of Pharmacy Practice. 2019; 12(2).
51. Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ. Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption. Gastroenterology. 1992; 102(6): 2139-42. DOI: 10.1016/0016-5085(92)91747-V
52. Pastori D, Carnevale R, Cangemi R, Saliola M, Nocella C, Bartimoccia S, Vicario T, Farcomeni A, Violi F, Pignatelli P. Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy: a retrospective cohort study. Journal of the American Heart Association. 2013; 2(6): e000364. DOI: 10.1161/JAHA.113.000364
53. Bartow SA, Pathak DR, Black WC, Key CR, Teaf SR. Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study. Cancer. 1987; 60(11): 2751-60. DOI: 10.1002/1097-0142(19871201)60:11<2751::AID-CNCR2820601121>3.0.CO;2-N
54. Schramm L. Going green: the role of the green tea component EGCG in chemoprevention. Journal of Carcinogenesis and Mutagenesis. 2013; 4(142): 1000142. DOI: 10.4172/2157-2518.1000142
55. Gu JW, Makey KL, Tucker KB, Chinchar E, Mao X, Pei I, Thomas EY, Miele L. EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF Expression. Vascular Cell. 2013; 5(1): 9.DOI: 10.1186/2045-824X-5-9
56. Van Aller GS, Carson JD, Tang W, Peng H, Zhao L, Copeland RA, Tummino PJ, Luo L. Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor. Biochemical and Biophysical Research Communications. 2011; 406(2): 194-9. DOI: 10.1016/j.bbrc.2011.02.007
57. Shim JH, Su ZY, Chae JI, Kim DJ, Zhu F, Ma WY, Bode AM, Yang CS, Dong Z. Epigallocatechin gallate suppresses lung cancer cell growth through Ras–GTPase-activating protein SH3 domain-binding protein 1. Cancer Prevention Research. 2010; 3(5): 670-9. DOI: 10.1158/1940-6207.CAPR-09-0243
58. Leone M, Zhai D, Sareth S, Kitada S, Reed JC, Pellecchia M. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Research. 2003; 63(23): 8118-21.
59. Ermakova S, Choi BY, Choi HS, Kang BS, Bode AM, Dong Z. The intermediate filament protein vimentin is a new target for epigallocatechin gallate. Journal of Biological Chemistry. 2005; 280(17): 16882-90. DOI: 10.1074/jbc.M414490200
60. He Z, Tang F, Ermakova S, Li M, Zhao Q, Cho YY, Ma WY, Choi HS, Bode AM, Yang CS, Dong Z. Fyn is a novel target of (−)‐epigallocatechin gallate in the inhibition of JB6 Cl41 cell transformation. Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center. 2008; 47(3): 172-83. DOI: 10.1002/mc.20370
61. Li M, He Z, Ermakova S, Zheng D, Tang F, Cho YY, Zhu F, Ma WY, Sham Y, Rogozin EA, Bode AM. Direct inhibition of insulin-like growth factor-I receptor kinase activity by (−)− epigallocatechin-3-gallate regulates cell transformation. Cancer Epidemiology and Prevention Biomarkers. 2007; 16(3): 598-605. DOI: 10.1158/1055-9965.EPI-06-0853
62. Liang YC, Lin‐Shiau SY, Chen CF, Lin JK. Inhibition of cyclin‐dependent kinases 2 and 4 activities as well as induction of cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (−)‐epigallocatechin‐3‐gallate. Journal of Cellular Biochemistry. 1999; 75(1): 1-2. DOI: 10.1002/(SICI)1097-4644(19991001)75:1<1::AID-JCB1>3.0.CO;2-H
63. Yu SS, Spicer DV, Hawes D, Tseng CC, Yang CS, Pike MC, Wu AH. Biological effects of green tea capsule supplementation in pre-surgery postmenopausal breast cancer patients. Frontiers in Oncology. 2013; 3: 298. DOI: 10.3389/fonc.2013.00298
64. Jurgens TM, Whelan AM, Killian L, Doucette S, Kirk S, Foy E. Green tea for weight loss and weight maintenance in overweight or obese adults. Cochrane Database of Systematic Reviews. 2012(12). DOI: 10.1002/14651858.CD008650.pub2
65. Nisar T, Iqbal M, Raza A, Safdar M, Iftikhar F, Waheed M. Turmeric: A promising spice for phytochemical and antimicrobial activities. Am Eur J Agric Environ Sci. 2015; 15(7): 1278-88.
66. Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK. Turmeric and curcumin: Biological actions and medicinal applications. Current Science Bangalore. 2004; 87: 44-53. DOI: 10.2307/24107902
67. Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology. 2006; 71(10): 1397-421. DOI: 10.1016/j.bcp.2006.02.009
68. Shukla PK, Khanna VK, Ali MM, Khan MY, Srimal RC. Anti-ischemic effect of curcumin in rat brain. Neurochemical Research. 2008; 33(6): 1036-43. DOI: 10.1007/s11064-007-9535-3
69. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. InThe molecular targets and therapeutic uses of curcumin in Health and Disease 2007 (pp. 453-470). Springer, Boston, MA.DOI: 10.1007/978-0-387-46401-5_20
70. Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Letters. 2008; 269(2): 199-225. DOI: 10.1016/j.canlet.2008.03.009
71. Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Curcumin‐induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IκB kinase and nuclear factor κB activity and are independent of the B‐Raf/mitogen‐activated/extracellular signal‐regulated protein kinase pathway and the Akt pathway. Cancer. 2005; 104(4): 879-90. DOI: 10.1002/cncr.21216
72. Bayet-Robert M, Kwiatowski F, Leheurteur M, Gachon F, Planchat E, Abrial C, Mouret-Reynier MA, Durando X, Barthomeuf C, Chollet P. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biology and Therapy. 2010; 9(1): 8-14. DOI: 10.4161/cbt.9.1.10392
73. Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM, Boggs ME, Crowell J, Rock CL, Brenner DE. Dose escalation of a curcuminoid formulation. BMC Complementary and Alternative Medicine. 2006; 6(1): 1-4. DOI: 10.1186/1472-6882-6-10
74. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature Reviews Microbiology. 2015; 13(5): 269-84. DOI: 10.1038/nrmicro3432
75. Pappas E, Schaich KM. Phytochemicals of cranberries and cranberry products: characterization, potential health effects, and processing stability. Critical Reviews in Food Science and Nutrition. 2009; 49(9): 741-81. DOI: 10.1080/10408390903001719
76. Paquette M, Larqué AS, Weisnagel SJ, Desjardins Y, Marois J, Pilon G, Dudonné S, Marette A, Jacques H. Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: A parallel, double-blind, controlled and randomised clinical trial. British Journal of Nutrition. 2017; 117(4):519-31. DOI: 10.1017/S0007114517000437
77. Novotny JA, Baer DJ, Khoo C, Gebauer SK, Charron CS. Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults. The Journal of Nutrition. 2015; 145(6): 1185-93. DOI: 10.3945/jn.114.205757
78. Hotchkiss Jr AT, Nuñez A, Strahan GD, Chau HK, White AK, Marais JP, Hom K, Vakkalanka MS, Di R, Yam KL, Khoo C. Cranberry xyloglucan structure and inhibition of Escherichia coli adhesion to epithelial cells. Journal of Agricultural and Food Chemistry. 2015; 63(23): 5622-33. DOI: 10.1021/acs.jafc.5b01065
79. Foo LY, Lu Y, Howell AB, Vorsa N. A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-Fimbriated escherichia c oli. Journal of Natural Products. 2000; 63(9): 1225-8. DOI: 10.1021/np000128u
80. Pinzón-Arango PA, Liu Y, Camesano TA. Role of cranberry on bacterial adhesion forces and implications for Escherichia coli–uroepithelial cell attachment. Journal of Medicinal Food. 2009; 12(2): 259-70. DOI: 10.1089/jmf.2008.0196
81. Caljouw MA, van den Hout WB, Putter H, Achterberg WP, Cools HJ, Gussekloo J. Effectiveness of cranberry capsules to prevent urinary tract infections in vulnerable older persons: a double‐blind randomized placebo‐controlled trial in long‐term care facilities. Journal of the American Geriatrics Society. 2014; 62(1): 103-10. DOI: 10.1111/jgs.12609
82. Ross SM. Clinical applications of cranberry in urinary tract infections. Holistic Nursing Practice. 2006; 20(4): 213-4.
83. Valentova K, Stejskal D, Bednář P, Vostálová J, Cihalik C, Vecerova R, Koukalová D, Kolář M, Reichenbach R, Sknouril L, Ulrichová J. Biosafety, antioxidant status, and metabolites in urine after consumption of dried cranberry juice in healthy women: a pilot double-blind placebo-controlled trial. Journal of Agricultural and Food Chemistry. 2007; 55(8): 3217-24. DOI: 10.1021/jf0633322
84. Jain D, Chaudhary HS. Clinical significance of probiotics in human. International Journal of Nutrition, Pharmacology, Neurological Diseases. 2014; 4(1):11.
85. Holzapfel WH, Haberer P, Geisen R, Björkroth J, Schillinger U. Taxonomy and important features of probiotic microorganisms in food and nutrition. The American Journal of Clinical Nutrition. 2001; 73(2): 365s-73s. DOI: 10.1093/ajcn/73.2.365s
86. Rezac S, Kok CR, Heermann M, Hutkins R. Fermented foods as a dietary source of live organisms. Frontiers in Microbiology. 2018; 9: 1785. DOI: 10.3389/fmicb.2018.01785.
87. Goldin BR. Health benefits of probiotics. British Journal of Nutrition. 1998; 80(S2): S203-7. DOI: 10.1017/S0007114500000909.
88. Reid G. Probiotic agents to protect the urogenital tract against infection. The American Journal of Clinical Nutrition. 2001; 73(2): 437s-43s.DOI: 10.1093/ajcn/73.2.437s.
89. Stapleton AE, Au-Yeung M, Hooton TM, Fredricks DN, Roberts PL, Czaja CA, Yarova-Yarovaya Y, Fiedler T, Cox M, Stamm WE. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clinical Infectious Diseases. 2011; 52(10): 1212-7. DOI: 10.1093/cid/cir183.
90. Kiani L. Bugs in our guts–not all bacteria are bad: how probiotics keep us healthy. Ulster, UK: CSA Discovery Guides. 2006:1-21.
91. Vitamin C. Fact Sheet for Health Professionals (2016, February 11).
92. Pauling L. The significance of the evidence about ascorbic acid and the common cold. Proceedings of the National Academy of Sciences. 1971; 68(11): 2678-81.
93. Shukla SP. Level of ascorbic acid and its oxidation in the liver of the scorpion, Palamnaeus bengalensis. Experientia. 1969; 25(6): 602.DOI: 10.1007/BF01898647.
94. Wen Y, Cooke T, Feely J. The effect of pharmacological supplementation with vitamin C on low‐density lipoprotein oxidation. British Journal of Clinical Pharmacology. 1997; 44(1): 94-7.DOI: 10.1046/j.1365-2125.1997.t01-1-00550.x.
95. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proceedings of the National Academy of Sciences. 1976; 73(10): 3685-9. DOI: 10.1073/pnas.73.10.3685.
96. Carr A, Frei B. Does vitamin C act as a pro-oxidant under physiological conditions?. The FASEB Journal. 1999; 13(9): 1007-24. DOI: 10.1096/fasebj.13.9.1007.
97. Institute of Medicine: Food and Nutrition Board. Dietary reference intakes: vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press; 2000.
98. Carlsson S, Govoni M, Wiklund NP, Weitzberg E, Lundberg JO. In vitro evaluation of a new treatment for urinary tract infections caused by nitrate-reducing bacteria. Antimicrobial Agents and Chemotherapy. 2003; 47(12): 3713-8. DOI: 10.1128/AAC.47.12.3713-3718.2003.
99. Institute of Medicine: Food and Nutrition Board. Dietary reference intakes: vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academy Press; 2000.
100. Giunta JL. Dental erosion resulting from chewable vitamin C tablets. Journal of the American Dental Association (1939). 1983; 107(2): 253-6. DOI: 10.14219/jada.archive.1983.0201.
101. Block G. Epidemiologic evidence regarding vitamin C and cancer. The American Journal of Clinical Nutrition. 1991; 54(6): 1310S-4S. DOI: 10.1093/ajcn/54.6.1310s
102. Singh RB, Niaz MA, Rastogi SS, Rastogi S. Usefulness of antioxidant vitamins in suspected acute myocardial infarction (the Indian experiment of infarct survival-3). American Journal of Cardiology. 1996; 77(4): 232-6. DOI: 10.1016/s0002-9149(97)89344-2
103. S Pavlakis P. Prevention of Recurrent Cystitis in Pre-Menopausal Women: From Mechanisms to Therapy. Current Women's Health Reviews. 2012; 8(2): 177-82. DOI: 10.2174/157340412801784627
104. Pitkanen OM, Vanhanen H, Pitkanen E. Metabolic syndrome is associated with changes in D-mannose metabolism. Scandinavian Journal of Clinical and Laboratory Investigation. 1999; 59(8): 607-12. DOI: 10.1080/00365519950185730
105. Vuksan V, Jenkins DJ, Spadafora P, Sievenpiper JL, Owen R, Vidgen E, Brighenti F, Josse R, Leiter LA, Bruce-Thompson C. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes. A randomized controlled metabolic trial. Diabetes Care. 1999; 22(6): 913-9. DOI: 10.2337/diacare.22.6.913
106. Altarac S, Papes D. Use of D-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women. BJU Int. 2014; 113(1): 9-10. DOI: 10.1111/bju.12202
107. Tizard IR, Carpenter RH, McAnalley BH, Kemp MC. The biological activities of mannans and related complex carbohydrates. Molecular Biotherapy. 1989; 1(6): 290-6.
108. DE VL, Cappelli V, Massaro MG, Tosti C, Morgante G. Evaluation of the effects of a natural dietary supplement with cranberry, Noxamicina® and D-mannose in recurrent urinary infections in perimenopausal women. Minerva Ginecologica. 2017; 69(4): 336-41.
109. Casado JS, Galan ML, Mendez-Rubio S, Fuertes ME, Rodríguez AG, Chamorro MV. Efficacy and therapeutic tolerance of 24-hour prolonged-release D-mannose (2 g) (associated with proanthocyanidins), compared to isolated proanthocyanidins in the management of a series of women with recurrent urinary infections. Spanish Archives of Urology. 2018; 71 (2): 169-77.
110. Muneer A, Kalsi J, Nazareth I, Arya M. Erectile dysfunction. BMJ. 2014; 348: g129. DOI: 10.1136/bmj.g129
111. Jia L, Zhao Y. Current evaluation of the millennium phytomedicine-ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations. Current Medicinal Chemistry. 2009; 16(19): 2475-84. DOI: 10.2174/092986709788682119
112. Chen X, Lee TJ. Ginsenosides‐induced nitric oxide‐mediated relaxation of the rabbit corpus cavernosum. British Journal of Pharmacology. 1995; 115(1): 15-8. DOI: 10.1111/j.1476-5381.1995.tb16325.x
113. Yang WM, Park SY, Kim HM, Park EH, Park SK, Chang MS. Effects of Panax ginseng on glial cell‐derived neurotrophic factor (GDNF) expression and spermatogenesis in rats. Phytotherapy Research. 2011; 25(2): 308-11. DOI: 10.1002/ptr.3260
114. Park WS, Shin DY, Yang WM, Chang MS, Park SK. Korean ginseng induces spermatogenesis in rats through the activation of cAMP-responsive element modulator (CREM). Fertility and Sterility. 2007; 88(4): 1000-2. DOI: 10.1016/j.fertnstert.2006.12.081
115. Hong B, Ji YH, Hong JH, Nam KY, Ahn TY. A double-blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. The Journal of Urology. 2002; 168(5): 2070-3. DOI: 10.1097/01.ju.0000035437.34593.97
116. Kiefer DS, Pantuso T. Panax ginseng. American Family Physician. 2003; 68(8): 1539-42.
117. Palop V, Catalán C, Rubio E, Martínez-Mir I. Gynecomastia in a male and ginseng. Medicina Clinica. 1999; 112(19): 758.
118. Bilgi N, Bell K, Ananthakrishnan AN, Atallah E. Imatinib and Panax ginseng: a potential interaction resulting in liver toxicity. Annals of Pharmacotherapy. 2010; 44(5): 926-8. DOI: 10.1345/aph.1m634
119. Wani SA, Kumar P. Fenugreek: A review on its nutraceutical properties and utilization in various food products. Journal of the Saudi Society of Agricultural Sciences. 2018; 17(2): 97-106 DOI: 10.1016/j.jssas.2016.01.007
120. Wilborn C, Taylor L, Poole C, Foster C, Willoughby D, Kreider R. Effects of a purported aromatase and 5 α-reductase inhibitor on hormone profiles in college-age men. International Journal of Sport Nutrition and Exercise Metabolism. 2010; 20(6): 457-65. DOI: 10.1123/ijsnem.20.6.457
121. Park HJ, Lee KS, Lee EK, Park NC. Efficacy and safety of a mixed extract of trigonellafoenum-graecum seed and lespedeza cuneata in the treatment of testosterone deficiency syndrome: a randomized, double-blind, placebo-controlled clinical trial. The World Journal of Men's Health. 2018; 36(3): 230-8. DOI: 10.5534/wjmh.180017
122. Sharma RD, Sarkar A, Hazra DK, Misra B, Singh JB, Maheshwari BB. Toxicological evaluation of fenugreek seeds: a long term feeding experiment in diabetic patients. Phytotherapy Research. 1996; 10(6): 519-20.DOI: 10.1002/(SICI)1099-1573(199612)10:6<519::AID-PTR267>3.0.CO;2-0
123. Jurenka J. Therapeutic applications of pomegranate (Punica granatum L.): a review. Alternative Medicine Review. 2008; 13(2).DOI: 10.1016/j.jpsychores.2014.01.001
124. Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. Journal of Ethnopharmacology. 2007; 109(2): 177-206. DOI: 10.1016/j.jep.2006.09.006
125. Ignarro LJ, Byrns RE, Sumi D, de Nigris F, Napoli C. Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide. Nitric Oxide. 2006; 15(2): 93-102.DOI: 10.1016/j.niox.2006.03.001
126. Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. International Journal of Impotence Research. 2007; 19(6): 564-7. DOI: 10.1038/sj.ijir.3901531
127. Andrade C. Potentially significant versus clinically significant drug interactions: pomegranate juice as a case in point. The Journal of Clinical Psychiatry. 2014; 75(4): 292-3. DOI: 10.4088/JCP.13f08847