The aging process has been shown to reduce the functional capacity of the brain, learning ability, and spatial memory in old age [1]. Many studies have shown an association between low levels of brain-derived neurotrophic factor (BDNF) and depression in the elderly. Exercise can modulate levels of BDNF, but its effect on BDNF at baseline and after exercise is not clear [2]. Studies have shown that ginkgo biloba extract supplementation has neuroprotective effects and improves cognitive function capacity by increasing the concentration of BDNF [3, 4]. This study aims to assess the simultaneous effect of 8 weeks of ginkgo biloba extract supplementation and combined exercise on BDNF level in depressed older men.

In this quasi-experimental study with a pre-test/post-test design, 40 depressed older men with mild severity (score 8 -15 in Beck Depression Inventory) were selected as study samples from an elder care center in Khorramabad, Iran. They were divided into 4 groups of combined exercise (n=10), supplementation (n=10), combined exercise + supplementation (n=10), and control (n=10). After selecting the samples, the working conditions and the study method were fully explained to them and they were assured that taking the supplement or performing exercises would not have any side effects for them. Blood sampling was done In the pre-test phase by a laboratory expert. BDNF levels were measured using a special kit. 24 hours later, in the combined exercise group, the subjects performed the exercise protocol for 8 weeks, 3 sessions per week [5]. In the supplementation group, the subjects consumed 80 mg of ginkgo biloba extract daily for 8 weeks [6]. In the combined exercise + supplementation, subjects received both interventions simultaneously. During this period, the control group performed their daily activities and took a placebo. Blood sampling was again performed 24 hours after the end of intervention.

The results of the present study showed that combined exercise had a significant effect on the level of BDNF in depressed older men (t = -3.204, P=0.011). Their mean BDNF level increased from 68.54 Pg/ml at pre-test phase to 74.37 Pg/ml at post-test phase. Ginkgo biloba extract supplementation also had a significant effect on the level of BDNF in subjects (t = -2.431, P= 0.038). Their mean BDNF level increased from 66.94 Pg/ml at pre-test phase to 72.20 Pg/ml at post-test phase. The simultaneous use of combined exercise and ginkgo biloba extract supplementation also had a significant effect on the level of BDNF in older men (t = -14.578, P= 0.001). Their mean BDNF level increased from 70.55 Pg/ml at pre-test phase to 84.78 Pg/ml at post-test phase. In the control group, no significant difference was reported (t = -0.840, P= 0.423). There was a significant difference between the groups in terms of BDNF (F = 21.825, P=0.001). The results of Bonfrroni post hoc test showed that combined exercises plus ginkgo biloba supplementation increased BDNF by 9.262 Pg/ml compared to combined exercises alone; by 10.508 Pg/ml compared to supplementation alone; and by 19.606 Pg/ml compared to placebo (P<0.05). There was no difference between combined exercise and supplementation groups in BDNF level (P>0.05).

Simultaneous use of combined exercises and ginkgo biloba supplementation for 8 weeks increases the levels of BDNF in depressed older men more than when combined exercises and ginkgo biloba supplementation are used alone. Specialists can use combined exercises along with ginkgo biloba extract supplementation to improve functional capacity of brain in in depressed older men.

All ethical principles are considered in this article. The participants were informed about the purpose of the research and its implementation stages. They were also assured about the confidentiality of their information and were free to leave the study whenever they wished, and if desired, the research results would be available to them.

This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

All authors equally contributed to preparing this article.

The authors declared no conflict of interest.

 

References

1. Alipour F, Sajadi H, Forouzan A, Biglarian A, Jalilian A. [Elderly quality of life in Tehran's district two (Persian)]. Salmand: Iranian Journal of Ageing. 2008;3(3-4):75-83. http://salmandj.uswr.ac.ir/article-1-104-en.html
2. Sharifzadeh GR, Moodi M, Akhbari H. [Investigating health status of older people supported by Imam (Persian)]. Salmand: Iranian Journal of Ageing. 2010; 5(3):52-60. http://salmandj.uswr.ac.ir/article-1-279-en.html
3. Hojjati H, Koochaki G, Sanagoo A. [The relationship between loneliness and life satisfaction of the elderly in Gorgan and Gonbad cities (Persian)]. Journal of Research Development in Nursing and Midwifery. 2012; 9(1):61-8. http://nmj.goums.ac.ir/article-1-213-en.html
4. Khodadady N, Sheikholeslami F, Rezamasuoleh S, Yazdani M. [Rate of depression in late-life in superannuated government employed center of ‎Guilan University of Medical Sciences (Persian)]. Journal of Holistic Nursing And Midwifery. 2007; 17(1):16-22. http://hnmj.gums.ac.ir/article-1-247-en.html
5. Sajadi H, Mohaqeqi Kamal H, Vameghi M, Forozan AS, Rafei H, Nosratabadi M. [Systematic review of prevalence and risk factors associated with depression and its treatment in Iranian elderly (Persian)]. Salmand: Iranian Journal of Ageing. 2013; 7(4):7-15. http://salmandj.uswr.ac.ir/article-1-545-en.html
6. Lai DWL. Impact of culture on depressive symptoms of elderly Chinese immigrants. The Canadian Journal of Psychiatry. 2004; 49(12):820-7. [DOI:10.1177/070674370404901205]
7. Cole MG, Dendukuri N. Risk factors for depression among elderly community subjects: A systematic review and meta-analysis. American Journal of Psychiatry. 2003; 160(6):1147-56. [DOI:10.1176/appi.ajp.160.6.1147]
8. Adlard PA, Cotman CW. Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression. Neuroscience. 2004; 124(4):985-92. [DOI:10.1016/j.neuroscience.2003.12.039]
9. Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi JI, et al. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thrombosis and Haemostasis. 2002; 87(04):728-34. [DOI:10.1055/s-0037-1613072]
10. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998; 37(12):1553-61. [DOI:10.1016/S0028-3908(98)00141-5]
11. Ploughman M. Exercise is brain food: The effects of physical activity on cognitive function. Developmental Neurorehabilitation. 2008; 11(3):236-40. [DOI:10.1080/17518420801997007]
12. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nature Neuroscience. 2003; 6(7):736-42. [DOI:10.1038/nn1073]
13. Tsuchida A, Nonomura T, Nakagawa T, Itakura Y, Ono-Kishino M, Yamanaka M, et al. Brain-derived neurotrophic factor ameliorates lipid metabolism in diabetic mice. Diabetes, Obesity and Metabolism. 2002; 4(4):262-9. [DOI:10.1046/j.1463-1326.2002.00206.x]
14. Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor. Sports Medicine. 2010; 40(9):765-801. [DOI:10.2165/11534530-000000000-00000]
15. Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: From animal to human studies. Journal of Physiology and Pharmacology. 2010; 61(5):533-41. [PMID]
16. Nofuji Y, Suwa M, Moriyama Y, Nakano H, Ichimiya A, Nishichi R, et al. Decreased serum brain-derived neurotrophic factor in trained men. Neuroscience Letters. 2008; 437(1):29-32. [DOI:10.1016/j.neulet.2008.03.057]
17. Dubber MJ, Kanfer I. Determination of terpene trilactones in Ginkgo biloba solid oral dosage forms using HPLC with evaporative light scattering detection. Journal of Pharmaceutical and Biomedical Analysis. 2006; 41(1):135-40. [DOI:10.1016/j.jpba.2005.11.010]
18. Gardner CD, Taylor-Piliae RE, Kiazand A, Nicholus J, Rigby AJ, Farquhar JW. Effect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with peripheral artery disease: A randomized clinical trial. Journal of Cardiopulmonary Rehabilitation and Prevention. 2008; 28(4):258-65. [DOI:10.1097/01.HCR.0000327184.51992.b8]
19. Bing Y, Zhaobao W. Effects of Ginkgo biloba extract on free radical metabolism of liver in mice during endurance metabolism. African Journal of Traditional, Complementary and Alternative Medicines. 2010; 7(4):291-5. [DOI:10.4314/ajtcam.v7i4.56691]
20. Hajirezaii B, Barari A, Abbassi Daloii A. [Consumption of Ginkgo biloba extract and swimming training on NMDA and BDNF plasma in untrained girls (Persian)]. Journal of Medicinal Plants. 2015; 14(54):183-90. http://jmp.ir/article-1-1020-fa.html
21. Sharifi GR, Bani Hashemi Emam Gheysi M, Rahnama N, Babai Mazrae No AR. [Comparison of the effect of 8 weeks aerobic exercise with resistance exercise on brain-derived neurotrophic factor in elderly men (Persian)]. Salmand: Iranian Journal of Ageing. 2015; 10(3):148-55. http://salmandj.uswr.ac.ir/article-1-814-en.html
22. Ravasi AS, Poornemati P, Kordi MR, Hedayati M. [The effect of two type of resistance and endurance exercise on BDNF and cortisol of young male mice (Persian)]. Journal of Sport Biosciences. 2013; 1(16):49-78. [DOI:10.22059/JSB.2013.30458]
23. Mojtahedi S, Shabkhiz F, Akbarnejad A, Salehian O. [Effect of 8 weeks resistance training on BDNF and TrkB in the hippocampus of adult male rats (Persian)]. Armaghane Danesh. 2014; 19(5):380-9. http://armaghanj.yums.ac.ir/article-1-173-en.html
24. Yarrow JF, White LJ, McCoy SC, Borst SE. Training augments resistance exercise induced elevation of circulating Brain Derived Neurotrophic Factor (BDNF). Neuroscience Letters. 2010; 479(2):161-5. [DOI:10.1016/j.neulet.2010.05.058]
25. Goekint M, De Pauw K, Roelands B, Njemini R, Bautmans I, Mets T, et al. Strength training does not influence serum brain-derived neurotrophic factor. European Journal of Applied Physiology. 2010; 110(2):285-93. [DOI:10.1007/s00421-010-1461-3]
26. Correia PR, Pansani A, Machado F, Andrade M, da Silva AC, Scorza FA, et al. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels. Clinics. 2010; 65(11):1123-6. [DOI:10.1590/S1807-59322010001100012]
27. Parnow A, Karimi I, Hosseini SA. [Effect of resistance training on plasma brain derived neurotrophic factor levels in rats (Persian)]. Journal of Knowledge & Health. 2015; 10(3):9-14. [DOI:10.22100/jkh.v10i3.679]
28. Twiss JL, Chang JH, Schanen NC. Pathophysiological mechanisms for actions of the neurotrophins. Brain Pathology. 2006; 16(4):320-32. [DOI:10.1111/j.1750-3639.2006.00039.x]
29. Erickson KI, Voss MW, Prakash RS, Basak Ch, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences. 2011; 108(7):3017-22. [DOI:10.1073/pnas.1015950108]
30. Lu B, Chang JH. Regulation of neurogenesis by neurotrophins: Implications in hippocampus-dependent memory. Neuron Glia Biology. 2004; 1(4):377-84. [DOI:10.1017/S1740925X05000232]
31. Griffin ÉW, Mullally S, Foley C, Warmington SA, O’Mara SM, Kelly ÁM. Aerobic exercise improves hippocampal function and increases BDNF in the serum of young adult males. Physiology & Behavior. 2011; 104(5):934-41. [DOI:10.1016/j.physbeh.2011.06.005]
32. Savaskan E, Mueller H, Hoerr R, von Gunten A, Gauthier S. Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: Meta-analysis of randomized controlled trials. International Psychogeriatrics. 2018; 30(3):285-93. [DOI:10.1017/S1041610217001892]
33. Weinmann S, Roll S, Schwarzbach Ch, Vauth Ch, Willich SN. Effects of Ginkgo biloba in dementia: Systematic review and meta-analysis. BMC Geriatrics. 2010; 10:14. [DOI:10.1186/1471-2318-10-14]
34. Herrschaft H, Nacu A, Likhachev S, Sholomov I, Hoerr R, Schlaefke S. Ginkgo biloba extract EGb 761^® in dementia with neuropsychiatric features: A randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. Journal of Psychiatric Research. 2012; 46(6):716-23. [DOI:10.1016/j.jpsychires.2012.03.003]