Effect of Eurycoma longifolia standardised aqueous root extract– Physta® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study
Background: Low testosterone levels cause physiological changes that compromise the quality of life in ageing men. A standardised water extract from the root of Eurycoma longifolia (EL), known as Physta®, is known to increase testosterone levels.
Objective: To evaluate the safety and efficacy of Physta® in improving the testosterone levels and quality of life in ageing male subjects.
Design: This randomised, double-blind, placebo-controlled study enrolled 105 male subjects aged 50–70 years with a testosterone level <300 ng/dL, BMI ≥ 18 and ≤30.0 kg/m2. The subjects were given either Physta® 100 mg, 200 mg or placebo daily for 12 weeks. The primary endpoints were changes in serum total and free testosterone levels. The secondary endpoints included changes in the level of sex hormone-binding globulin (SHBG), dihydroepiandrosterone (DHEA), glycated haemoglobin (HbA1c), insulin-like growth factor-1 (IGF-1), thyroid function tests (T3, T4, TSH and Free T3) and cortisol. Changes in Ageing Male Symptoms (AMS) score, Fatigue Severity Scale (FSS) score and muscle strength are other secondary endpoints. The safety of the intervention products was measured by complete blood count, lipid profile, liver and renal function tests.
Results: There was a significant increase in the total testosterone levels at week 12 (P < 0.05) in the Physta® 100 mg group and at weeks 4 (P < 0.05), 8 (P < 0.01) and 12 (P < 0.001) in the Physta® 200 mg group compared to placebo. No significant between-group differences in free testosterone levels were observed but a significant within-group increase occurred at weeks 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta®100 mg group and at weeks 2 (P < 0.01), 4 (P < 0.01), 8 (P < 0.001) and 12 (P < 0.001) in the Physta® 200 mg group. The AMS and FSS showed significant reduction (P < 0.001) in total scores at all time-points within- and between-group in both Physta® groups. DHEA levels significantly increased (P < 0.05) within-group in both Physta® groups from week 2 onwards. Cortisol levels significantly (P < 0.01) decreased in the Physta® 200 mg group, while muscle strength significantly (P < 0.001) increased in both Physta® groups at week 12 in the within-group comparison. There were no significant changes in SHBG. No safety related clinically relevant changes were observed.
Conclusion: Supplementation of Physta® at 200 mg was able to increase the serum total testosterone, reduce fatigue and improve the quality of life in ageing men within 2 weeks’ time.
Trial registration: This clinical study has been registered in ctri.nic.in (CTRI/2019/03/017959).
- Lanfranco F, Gianotti L, Giordano R, Pellegrino M, Maccario M, Arvat E. Ageing, growth hormone and physical performance. J Endocrinol Invest 2003; 26: 861–72. doi: 10.1007/BF03345237
- Chahal HS, Drake WM. The endocrine system and ageing. J Pathol 2007; 211: 173–80. doi: 10.1002/path.2110
- Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with ageing in men. J Gerontol A Biol Sci Med Sci 2002; 57: 76–99. doi: 10.1093/gerona/57.2.M76
- Batrinos ML. The ageing of the endocrine hypothalamus and its dependent endocrine glands. Hormones 2012; 11: 241–53. doi: 10.14310/horm.2002.1354
- Olarinoye JK, Adebisi SA, Popoola AA. Andropause: an emerging world health problem. West Afr J Med 2006; 25: 84–7. doi: 10.4314/wajm.v25i2.28254
- Kaczmarek MA, Skrzypczak MA. Do ageing male symptoms affect subjective feeling of wellbeing? Var Evol 2002; 10: 39–53.
- Hackney AC, Szczepanowska E, Viru AM. Basal testicular testosterone production in endurance-trained men is suppressed. Eur J Appl Physiol 2003; 89: 198–201. doi: 10.1007/s00421-003-0794-6
- De Ronde W, Van Der Schouw YT, Pols HA, Gooren LJ, Muller M, Grobbee DE, et al. Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem 2006; 52: 1777–84. doi: 10.1373/clinchem.2005.063354
- Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833–76. doi: 10.1210/er.2004-0013
- Khera M. Male hormones and men’s quality of life. Curr Opin Urol 2016; 26: 152–7. doi: 10.1097/MOU.0000000000000256
- Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Baltimore longitudinal study of ageing. Longitudinal effects of ageing on serum total free testosterone levels in healthy men. J Clin Endocrinol Metab 2001; 86: 724–31. doi: 10.1210/jcem.86.2.7219
- Mohr BA, Guay AT, O’Donnell AB, McKinlay JB. Normal, bound and non-bound testosterone levels in normally ageing men: results from the Massachusetts male ageing study. Clin Endocrinol 2005; 62: 64–73. doi: 10.1111/j.1365-2265.2004.02174.x
- Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male ageing study. J Clin Endocrinol Metab 2002; 87: 589–98. doi: 10.1210/jcem.87.2.8201
- Tan RS, Pu SJ. A pilot study on the effects of testosterone in hypogonadal ageing male patients with Alzheimer’s disease. Ageing Male 2003; 6: 13–17. doi: 10.1080/tam.188.8.131.52
- De Ronde W, Van Der Schouw YT, Muller M, Grobbee DE, Gooren LJ, Pols HA, et al. Associations of sex-hormone-binding globulin (SHBG) with non-SHBG-bound levels of testosterone and estradiol in independently living men. J Clin Endocrinol Metab 2005 Jan 1; 90(1): 157–62. doi: 10.1210/jc.2004-0422
- Goglia F, Moreno M, Lanni A. Action of thyroid hormones at the cellular level: the mitochondrial target. FEBS Lett 1999 Jun 11; 452(3): 115–20. doi: 10.1016/S0014-5793(99)00642-0
- Sternbach H. Age-associated testosterone decline in men: clinical issues for psychiatry. Am J Psychiatry 1998 Oct 1; 155(10): 1310–8. doi: 10.1176/ajp.155.10.1310
- Gunnels TA, Bloomer RJ. Increasing circulating testosterone: impact of herbal dietary supplements. Plant Physiol Biochem 2014;2:1–9. doi: 10.4172/2329-9029.1000130
- Jiwajinda S, Santisopasri V, Murakami A, Hirai N, Ohigashi H. Quassinoids from Eurycoma longifolia as plant growth inhibitors. Phytochemistry 2001; 58: 959–62. doi: 10.1016/S0031-9422(01)00333-8
- Ang HH, Hitotsuyanagi Y, Fukuya H, Takeya K. Quassinoids from Eurycoma longifolia. Phytochemistry 2002; 59: 833–7. doi: 10.1016/S0031-9422(01)00480-0
- Bedir E, Abou-Gazar H, Ngwendson JN, Khan IA. Eurycomaoiside: a new quassinoid-type glycoside from the root of Eurycoma longifolia. Chem Pharm Bull 2003; 51: 1301–3. doi: 10.1248/cpb.51.1301
- Rehman SU, Choe K, Yoo HH. Review on a traditional herbal medicine, Eurycoma longifolia Jack (Tongkat Ali): its traditional uses, chemistry, evidence-based pharmacology and toxicology. Molecules 2016; 21: 331. doi: 10.3390/molecules21030331
- Bhat R, Karim AA. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia 2010; 10: 1–11. doi: 10.1016/j.fitote.2010.04.006
- George A, Henkel R. Phytoandrogenic properties of Eurycoma longifolia as a natural alternative to testosterone replacement therapy. Andrologia 2014; 46: 708–21. doi: 10.1111/and.12214
- Talbott SM, Talbott JA, George A, Pugh M. Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects. J Int Soc Sport Nutr 2013; 10: 28. doi: 10.1186/1550-2783-10-28
- Henkel RR, Wang R, Bassett SH, Chen T, Liu N, Zhu Y, et al. Tongkat Ali as a potential herbal supplement for physically active male and female seniors – a pilot study. Phytother Res 2014; 28: 544–50. doi: 10.1002/ptr.5017
- Ang HH, Ngai TH. Aphrodisiac evaluation in non-copulator male rats after chronic administration of Eurycoma longifolia Jack. Fundam Clin Pharm 2001; 15: 265–8. doi: 10.1002/ptr.5017
- Ang HH, Lee KL. Effect of Eurycoma longifolia Jack on orientation activities in middle-aged male rats. Fundam Clin Pharmacol 2002; 16: 479–83. doi: 10.1046/j.1472-8206.2002.00106.x
- Ang HH, Lee KL, Kiyoshi M. Eurycoma longifolia Jack enhances sexual motivation in middle-aged male mice. J Basic Clin Physiol Pharmacol 2003; 14: 301–8. doi: 10.1515/JBCPP.2003.14.3.301
- Udani JK, George AA, Musthapa M, Pakdaman MN, Abas A. Effects of a proprietary freeze-dried water extract of Eurycoma longifolia (Physta) and Polygonum minus on sexual performance and well-being in men: a randomised, double-blind, place-bo-controlled study. Evid Based Complement Alternat Med 2014; 2014:1–11. doi: 10.1155/2014/179529
- Ismail SB, Wan Mohammad WM, George A, Nik Hussain NH, Musthapa Kamal ZM, Liske E. Randomized clinical trial on the use of PHYSTA freeze-dried water extract of Eurycoma longifolia for the improvement of quality of life and sexual well- being in men. Evid Based Complement Alternat Med 2012;2012:1–11. doi: 10.1155/2012/429268
- Choudhary YK, Bommu, P, Ming YK, Zulkawi NB. Acute, sub-acute, and subchronic 90-days toxicity of Eurycoma longi-folia aqueous extract (Physta) in wistar rats. Int J Pharm Pharm Sci 2012; 4(3):232–238.
- Tambi MI, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat Ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia 2012; 44: 226–30. doi: 10.1111/j.1439-0272.2011.01168.x
- Heinemann LA, Saad F, Zimmermann T, Novak A, Myon E, Badia X, et al. The Aging Males’ Symptoms (AMS) scale: update and compilation of international versions. Health Qual. Life Outcomes 2003 Dec; 1(1): 1–5.
- Chueh KS, Huang SP, Lee YC, Wang CJ, Yeh HC, Li WM, et al. The comparison of the aging male symptoms (AMS) scale and androgen deficiency in the aging male (ADAM) questionnaire to detect androgen deficiency in middle-aged men. J Androl 2012 Sep 10; 33(5): 817–23. doi: 10.2164/jandrol.111.015628
- Valko PO, Bassetti CL, Bloch KE, Held U, Baumann CR. Validation of the fatigue severity scale in a Swiss cohort. Sleep 2008 Nov 1; 31(11): 1601–7. doi: 10.1093/sleep/31.11.1601
- Tambi MI, Kadir AA. Eurycoma longifolia Jack: a potent adaptogen in the form of a water-soluble extract with the effect of maintaining men’s health. Asian J Androl 2006; 8 Suppl 1: 49–50.
- Sambandan TG, Rha CK, Kadir AA, Aminudim N, Saad J, Mohammed M. Bioactive fraction of Eurycoma longifolia. [7132117 B2.]. United States Patent; 2006. https://patents.google.com/patent/US20040087493A1/en.
- Low BS, Das PK, Chan KL. Standardized quassinoid-rich Eurycoma longifolia extract improved spermatogenesis and fertility in male rats via the hypothalamic-pituitary-gonadal axis. J Ethnopharmacol 2013; 145: 706–14. doi: 10.1016/j.jep.2012.11.013
- Low BS, Choi SB, Wahab HA, Das PK, Chan KL. Eurycomanone, the major quassinoid in Eurycoma longifolia root extract increases spermatogenesis by inhibiting the activity of phosphodiesterase and aromatase in steroidogenesis. J Ethnopharmacol 2013; 149: 201–7. doi: 10.1016/j.jep.2013.06.023
- Čeponis J, Swerdloff RS, Wang C. Androgen replacement ther-apy in hypogonadal men. Male hypogonadism: basic, clinical and therapeutic principles. In: Winters SJ, Huhtaniemi IT, eds. Contemporary endocrinology. Cham, Switzerland: Springer; 2017, p. 367.
- Heinemann LA, Moore C, Dinger JC, Stoehr D. Sensitivity as outcome measure of androgen replacement: the AMS scale. Health Qual Life Outcomes 2006; 4: 23. doi: 10.1186/1477-7525-4-23
- Schwid SR, Covington MM, Segal BM, Goodman AD. Fatigue in multiple sclerosis: current understanding and future directions. J Rehabil Res Dev 2002; 39: 211–24.
- Pexman-Fieth C, Behre HM, Morales A, Kan Dobrosky N, Miller MG. A 6-month observational study of energy, sexual desire, and body proportions in hypogonadal men treated with a testosterone 1% gel. Aging Male 2014; 17: 1–11. doi: 10.3109/13685538.2013.858113
- Talbott S, Talbott J, Negrete J, Jones M, Nichols M, Roza J. Effect of Eurycoma longifolia extract on anabolic balance during endurance exercise. J Int Soc Sports Nutr 2006; 3: 1.
- Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006; 154: 899–906. doi: 10.1530/eje.1.02166
- Grossmann M. Low testosterone in men with type 2 diabetes: significance and treatment. J Clin Endocrinol Metab 2011; 96: 2341–53. doi: 10.1210/jc.2011-0118
- Dandona P, Dhindsa S, Chaudhuri A, Bhatia V, Topiwala S, Mohanty P. Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome. Curr Mol Med 2008; 8: 816–28. doi: 10.2174/156652408786733658
- Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with Type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003; 6: 1–7. doi: 10.1080/tam.184.108.40.206
- Heufelder AE, Saad F, Mathijs C, Gooren L. 52-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycaemic control in men with newly diagnosed Type 2 diabetes and subnormal plasma testosterone. J Androl 2009; 30: 726–33. doi: 10.2164/jandrol.108.007005
- Jones H, Howell J, Channer K. Testosterone improves glycaemic control, insulin resistance, body fat and sexual function in men with metabolic syndrome and⁄or type 2 diabetes: a multicentre European clinical trial. The study. Endocrine Abstracts 2010; 21: OC1.6. Societies, Manchester, UK: British Endocrine.
- Groti K, Žuran I, Antonič B, Foršnarič L, Pfeifer M. The impact of testosterone replacement therapy on glycemic control, vascular function, and components of the metabolic syndrome in obese hypogonadal men with type 2 diabetes. Aging Male 2018; 21: 158–69. doi: 10.1080/13685538.2018.1468429
- Umpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, Azevedo MJ, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 2011 May 4; 305(17): 1790–9. doi: 10.1001/jama.2011.576
- Bloise FF, Oliveira TS, Cordeiro A, Ortiga-Carvalho TM. Thyroid hormones play role in sarcopenia and myopathies. Front Physiol 2018; 9: 560. doi: 10.3389/fphys.2018.00560
- Kong SH, Kim JH, Park YJ, Lee JH, Hong AR, Shin CS, et al. Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population. Osteoporos Int 2020; 31: 525–31. doi: 10.1007/s00198-019-05137-w
- Van den Beld AW, Visser TJ, Feelders RA, Grobbee DE, Lamberts SW. Thyroid hormone concentrations, disease, physical function, and mortality in elderly men. J Clin Endocrinol Metab 2005 Dec 1; 90(12): 6403–9. doi: 10.1210/jc.2005-0872
- Meikle AW. The interrelationships between thyroid dysfunction and hypogonadism in men and boys. Thyroid 2004; 14 Suppl 1: S17–25. doi: 10.1089/105072504323024552
- Louwerens M, Appelhof BC, Verloop H, Medici M, Peeters RP, Visser TJ, et al. Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism. Eur J Endocrinol 2012; 167: 809. doi: 10.1530/EJE-12-0501
- Wekking EM, Appelhof BC, Fliers E, Schene AH, Huyser J, Tijssen JG, et al. Cognitive functioning and wellbeing in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur J Endocrinol 2005; 153: 747–53. doi: 10.1530/eje.1.02025
- Collomp K, Baillot A, Forget H, Coquerel A, Rieth N, Vibarel-Rebot N. Altered diurnal pattern of steroid hormones in relation to various behaviours, external factors and pathologies. Physiol Behav 2016; 164: 68–85. doi: 10.1016/j.physbeh.2016.05.039
- Roy TA, Blackman MR, Harman SM, Tobin JD, Schrager M, Metter EJ. Interrelationships of serum testosterone and free testosterone index with FFM and strength in ageing men. Am J Physiol Endocrinol Metab 2002; 283: 284–94. doi: 10.1152/ajpendo.00334.2001
- Lippi G, Lima-Oliveira G, Salvagno GL, Montagnana M, Gelati M, Picheth G, et al. Influence of a light meal on routine haematological tests. Blood Transfus 2010 Apr; 8(2): 94.
- Hajimonfarednejad M, Ostovar M, Raee MJ, Hashempur MH, Mayer JG, Heydari M. Cinnamon: a systematic review of adverse events. Clin Nutr 2019 Apr 1; 38(2): 594–602. doi: 10.1016/j.clnu.2018.03.013
- Sellami M, Slimeni O, Pokrywka A, Kuvačić G, Hayes LD, Milic M, et al. Herbal medicine for sports: a review. J Int Soc Sports Nutr 2018 Dec; 15(1): 1–4. doi: 10.1186/s12970-018-0218-y
- Girish S, Kumar S, Aminudin N. Tongkat Ali (Eurycoma longifolia): a possible therapeutic candidate against Blastocystis sp. Parasit Vectors 2015 Dec; 8(1): 1–7. doi: 10.1186/s13071-015-0942-y
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