Abstract
This paper provides a literature review of current studies investigating the effects of meditation and mind-body exercise on peripheral concentrations of brain-derived neurotrophic factor (BDNF), an important mediator of the neuroplasticity of the central nervous system and cognitive function. A literature search was conducted to collect currently published randomized controlled, non-randomized controlled and uncontrolled intervention studies. Fifteen studies were identified; and among these studies, seven were randomized controlled studies, three were non-randomized studies, and five were uncontrolled studies. Current limited evidence tends to support that mindfulness meditation and mind-body exercise (e.g. yoga and tai chi) increase circulating BDNF concentrations in healthy and diseased individuals. It is noteworthy that these findings are based on current studies with a relatively small sample size, or without a randomized controlled design. Further studies are needed to identify a definite effect of meditation or mind-body exercise on BDNF and its role in improving/maintaining brain functions in various populations.
Keywords: Meditation, Mind-body exercise, BDNF
Introduction
Brain-derived neurotrophic factor (BDNF) is an important mediator of the neuroplasticity of the central nervous system, and is involved in promoting and maintaining brain functions.1 Peripheral BDNF concentrations decline with several conditions and diseases related to changes in the central nervous system, such as aging, mild cognitive decline, depression, Parkinson's disease and Alzheimer's disease.2, 3, 4, 5 In addition, BDNF appears to be an important biomarker of neuropsychiatric disorders characterized by neurodegenerative changes.5
The effects of physical exercise on BDNF have been well summarized by several published reviews.6, 7, 8, 9, 10, 11 Current evidence supports that physical exercise may alter peripheral BDNF concentrations.6, 7, 8, 9, 10, 11 In general, acute and chronic aerobic exercise increases peripheral BDNF concentrations, while strength exercise does not change BDNF concentrations.6,10 However, recent evidence indicates that both aerobic exercise and resistance exercise seem to increase BDNF concentrations in older adults.8,11
Mindfulness meditation and mind-body exercise (e.g. qigong, yoga, and tai chi) have been reported to benefit brain functions in healthy and diseased individuals.12,13 Considering the important role of BDNF in regulating brain functions, a number of recent studies have focused on the effects of meditation and mind-body exercise on peripheral BDNF concentrations. However, findings from these studies have not been well reviewed. The purpose of this review article is to summarize current evidence on potential effects of meditation and mind-body exercise on BDNF and to provide guidance for future research.
Methods
Electronic searches were conducted using PubMed/Medline, Web of Science, and the Cochrane Library from inception through August 2019. We used the following terms to conduct the searches as follows: “brain-derived neurotrophic factor” OR “BDNF” AND “meditation” OR “mindfulness” OR “qigong” OR “qi gong” OR “yoga” OR “tai chi” OR “tai ji”. Hand searches were also conducted to obtain additional references. Inclusion criteria for the studies were healthy or diseased individuals; meditation, mindfulness, or mind-body exercise protocols; randomized controlled studies, quasi-experimental studies, or uncontrolled studies; written in English; and measurement of peripheral BDNF concentrations. Exclusion criteria were animal studies; no meditation, mindfulness, or mind-body exercise intervention; and acute one-session studies. In the initial search, 115 articles were reviewed from the databases. After removing the duplicates, 35 articles were assessed for eligibility. Among these studies, 15 studies met the inclusion criteria. This is the first review to summarize current evidence regarding the effects of meditation and mind-body exercise on BDNF.
Results
Current randomized controlled studies regarding the effects of meditation and mind-body exercise on peripheral BDNF concentrations are summarized in Table 1.14, 15, 16, 17, 18, 19, 20 To date, 7 randomized controlled studies have been conducted in various populations, including patients with schizophrenia, women with chronic low back pain, older adults with mild cognitive impairment, individuals with major depressive disorder, individuals with primary open-angle glaucoma, and infertile women. The interventions included mindfulness meditation, yoga and tai chi. The term ranged from 3 weeks to 6 months. Overall, the majority of the studies15, 16, 17, 18, 19 reported that mindfulness meditation or mind-body exercise increased or tended to increase peripheral BDNF concentrations in various populations.
Table 1.
Effects of meditation and mind-body exercise on peripheral BDNF concentrations: Randomized controlled studies.
| Study | Participants | Study Design | Effects on BDNF |
|---|---|---|---|
| Ikai et al. 201414 | 50 patients with schizophrenia or related psychotic disorders | Control group: daycare rehabilitation Experimental group: daycare rehabilitation, plus Hatha yoga 8 weeks |
Compared to the control group, the experimental group: = BDNF |
| Lee et al., 2014 15 |
25 premenopausal women with chronic low back pain | Control group: no intervention Experimental group: Hatha yoga, 1 h each session, 3 sessions each week 12 weeks |
Significant group × time interactions in serum BDNF. Control group: = BDNF Experimental group: ↑BDNF (p < 0.01) |
| Tolahunase et al. 201816 | 58 patients with major depressive disorder | Control group: no intervention Experimental group: yoga and meditation-based lifestyle intervention (YMLI) 12 weeks |
Compared to the control group, YMLI: ↑BDNF (p < 0.001) |
| Dada et al. 201817 |
90 patients with primary open-angle glaucoma | Control group: no intervention Experimental group: mindfulness meditation 3 weeks |
Compared to the waitlist control group, mindfulness meditation: ↑BDNF (p < 0.001) |
| Gagrani et al. 201818 |
60 patients with primary open-angle glaucoma | Control group: standard medical treatment Experimental group: standard medical treatment plus meditation 6 weeks |
Compared to standard medical treatment only, standard medical treatment plus meditation: ↑BDNF (p < 0.01) |
| Sungkarat et al. 201819 | 66 older adults with amnestic mild cognitive impairment | Control group: cognitive education Experimental group: tai chi 6 months |
Compared to education control, tai chi: ↑BDNF (p < 0.05) |
| Nery et al. 201920 | 99 infertile women | Control group: no intervention Experimental group: mindful-based program (MBP) 8 weeks |
Compared to the control group, MBP: = BDNF |
= No change or no difference. ↑ Elevated or higher.
Current quasi-experimental studies and uncontrolled studies regarding the effects of meditation and mind-body exercise on peripheral BDNF concentrations are summarized in Table 2. To date, there are 3 non-randomized controlled studies (belong to the same parent study)21, 22, 23 and 5 uncontrolled studies24, 25, 26, 27, 28 reported in the literature. The subjects were apparently healthy adults, patients with major depressive disorder, and patients with chronic fatigue syndrome. The interventions were mainly yoga and/or meditation lasting 4 days to 3 months. Current non-randomized controlled studies21, 22, 23 and some uncontrolled studies24,26,27 reported significantly increased peripheral BDNF concentrations. Two uncontrolled studies25,28 did not report a significant change; however, it is noteworthy that the intervention term was very short (4 days) in one of the studies.25
Table 2.
Effects of meditation and mind-body exercise on peripheral BDNF concentrations: Quasi-experimental studies and uncontrolled studies.
| Study | Participants | Study Design | Effects on BDNF | |
|---|---|---|---|---|
| Naveen et al. 201321 Naveen et al. 201622 Halappa et al. 201823 |
54-65 patients with depressive disorders | Non-randomized comparison study. Drugs only: antidepressant drug treatment Yoga only: classical and contemporary yoga Drugs plus yoga: combined antidepressant drug treatment and yoga therapy as shown above 3 months |
Compared to drugs only, yoga only and drugs plus yoga: ↑BDNF (p < 0.05) |
|
| Pal et al. 201424 | 60 healthy active males of three age groups (20–29, 30–39, and 40–49 years, n = 20 each) | Uncontrolled study: yogasana, pranayama and meditation 3 months |
All three age groups: ↑BDNF (p < 0.01 to p < 0.001) |
|
| Turakitwanakan et al. 201525 | 30 healthy second-year medical students | Uncontrolled study: mindfulness meditation (breathing and attention training) 4 days |
= BDNF | |
| Cahn et al., 2017 26 |
38 apparently healthy individuals | Uncontrolled study: yoga and meditation 3 months |
↑BDNF (p < 0.05) | |
| Tolahunase et al. 201727 | 96 apparently healthy individuals | Uncontrolled: yoga and meditation based lifestyle intervention 3 months |
↑BDNF (p < 0.05) | |
| Oka et al., 2018 28 |
50 patients with chronic fatigue syndrome | Uncontrolled study: yoga 2 months |
= BDNF | |
= No change or no difference. ↑ Elevated or higher.
Discussion and conclusion
To date, several randomized controlled studies have reported the effects of meditation and/or mind-body exercise on peripheral BDNF concentrations in diseased individuals. Limited findings indicate meditation and mind-body exercise (e.g. yoga and tai chi) tend to increase BDNF concentrations in women with chronic low back pain, older adults with mild cognitive impairment, individuals with major depressive disorder, and individuals with primary open-angle glaucoma. Similar findings have been shown by non-randomized controlled studies and uncontrolled studies. It is noteworthy that current randomized controlled studies have reported a relatively small sample size, or a relatively short intervention term. More studies are needed in the future to confirm these findings and to investigate if BDNF mediates the effects of meditation and mind-body exercise on cognition and other brain functions.
Current randomized contorall studies, non-randomized controlled studies and uncontrolled studies tend to suppot a positive effect of meditaton and mind-body exercise on BDNF concentrations. However, the limited evidence is not sufficient to identify a potential difference between mindfulness meditation and mind-body exercise in their effects on BDNF. It is important to note that exercise itself has shown to increase BDNF concentrations, thus, effect observed from mind-body exercise such as yoga and tai chi may be due to its physical demand rather than the mindfulness of the program. Therefore, it is necessary for future well-designed mind-body exercise studies to consider the influence of physical exercise alone on BDNF and clarify if mind-body exercise has an additional effect in altering peripheral BDNF concentrations in healthy and diseased individuals.
Conflict of interest
The authrs declare no conflicts of interest.
Submission statement
This manuscript has not been published and is not under consideration for publication elsewhere.
Authors' contributions
TJY generated the idea,conducted literature search and drafted the paper. E.F.O., conducted literature search and revised the paper.
References
- 1.Benarroch E.E. Brain-derived neurotrophic factor: regulation, effects, and potential clinical relevance. Neurology. 2015;84:1693–1704. doi: 10.1212/WNL.0000000000001507. [DOI] [PubMed] [Google Scholar]
- 2.Brunoni A.R., Lopes M., Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008;11:1169–1180. doi: 10.1017/S1461145708009309. [DOI] [PubMed] [Google Scholar]
- 3.Diniz B.S., Teixeira A.L. Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and beyond. NeuroMolecular Med. 2011;13:217–222. doi: 10.1007/s12017-011-8154-x. [DOI] [PubMed] [Google Scholar]
- 4.Diniz B.S., Reynolds C.F., 3rd, Begley A., et al. Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study. J Psychiatr Res. 2014;49:96–101. doi: 10.1016/j.jpsychires.2013.11.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Teixeira A.L., Barbosa I.G., Diniz B.S., et al. Circulating levels of brain-derived neurotrophic factor: correlation with mood, cognition and motor function. Biomarkers Med. 2010;4:871–887. doi: 10.2217/bmm.10.111. [DOI] [PubMed] [Google Scholar]
- 6.Knaepen K., Goekint M., Heyman E.M., et al. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med. 2010;40:765–801. doi: 10.2165/11534530-000000000-00000. [DOI] [PubMed] [Google Scholar]
- 7.Mang C.S., Campbell K.L., Ross C.J., et al. Promoting neuroplasticity for motor rehabilitation after stroke: considering the effects of aerobic exercise and genetic variation on brain-derived neurotrophic factor. Phys Ther. 2013;93:1707–1716. doi: 10.2522/ptj.20130053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Coelho F.G., Gobbi S., Andreatto C.A., et al. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr. 2013;56:10–15. doi: 10.1016/j.archger.2012.06.003. [DOI] [PubMed] [Google Scholar]
- 9.Nugraha B., Karst M., Engeli S., et al. Brain-derived neurotrophic factor and exercise in fibromyalgia syndrome patients: a mini review. Rheumatol Int. 2012;32:2593–2599. doi: 10.1007/s00296-011-2348-2. [DOI] [PubMed] [Google Scholar]
- 10.Huang T., Larsen K.T., Ried-Larsen M., et al. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: a review. Scand J Med Sci Sports. 2014;24:1–10. doi: 10.1111/sms.12069. [DOI] [PubMed] [Google Scholar]
- 11.Marinus N., Hansen D., Feys P., et al. The impact of different types of exercise training on peripheral blood brain-derived neurotrophic factor concentrations in older adults: a meta-analysis. Sports Med. 2019;49:1529–1546. doi: 10.1007/s40279-019-01148-z. [DOI] [PubMed] [Google Scholar]
- 12.Simkin D.R., Black N.B. Meditation and mindfulness in clinical practice. Child Adolesc. Psychiatr. Clin. North Am. 2014;23:487–534. doi: 10.1016/j.chc.2014.03.002. [DOI] [PubMed] [Google Scholar]
- 13.Chiesa A., Serretti A. A systematic review of neurobiological and clinical features of mindfulness meditations. Psychol Med. 2010;40:1239–1252. doi: 10.1017/S0033291709991747. [DOI] [PubMed] [Google Scholar]
- 14.Ikai S., Suzuki T., Uchida H., et al. Effects of weekly one-hour Hatha yoga therapy on resilience and stress levels in patients with schizophrenia-spectrum disorders: an eight-week randomized controlled trial. J Alternative Compl Med. 2014;20:823–830. doi: 10.1089/acm.2014.0205. [DOI] [PubMed] [Google Scholar]
- 15.Lee M., Moon W., Kim J. Effect of yoga on pain, brain-derived neurotrophic factor, and serotonin in premenopausal women with chronic low back pain. Evid. base Compl. Alternat Med. 2014;2014 doi: 10.1155/2014/203173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Tolahunase M.R., Sagar R., Faiq M., et al. Yoga- and meditation-based lifestyle intervention increases neuroplasticity and reduces severity of major depressive disorder: a randomized controlled trial. Restor Neurol Neurosci. 2018;36:423–442. doi: 10.3233/RNN-170810. [DOI] [PubMed] [Google Scholar]
- 17.Dada T., Mittal D., Mohanty K., et al. Mindfulness meditation reduces intraocular pressure, lowers stress biomarkers and modulates gene expression in glaucoma: a randomized controlled trial. J Glaucoma. 2018;27:1061–1067. doi: 10.1097/IJG.0000000000001088. [DOI] [PubMed] [Google Scholar]
- 18.Gagrani M., Faiq M.A., Sidhu T., et al. Meditation enhances brain oxygenation, upregulates BDNF and improves quality of life in patients with primary open angle glaucoma: a randomized controlled trial. Restor Neurol Neurosci. 2018;36:741–753. doi: 10.3233/RNN-180857. [DOI] [PubMed] [Google Scholar]
- 19.Sungkarat S., Boripuntakul S., Kumfu S., et al. Tai chi improves cognition and plasma BDNF in older adults with mild cognitive impairment: a randomized controlled trial. Neurorehabil Neural Repair. 2018;32:142–149. doi: 10.1177/1545968317753682. [DOI] [PubMed] [Google Scholar]
- 20.Nery S.F., Paiva S.P.C., Vieira E.L., et al. Mindfulness-based program for stress reduction in infertile women: randomized controlled trial. Stress Health. 2019;35:49–58. doi: 10.1002/smi.2839. [DOI] [PubMed] [Google Scholar]
- 21.Naveen G.H., Thirthalli J., Rao M.G., et al. Positive therapeutic and neurotropic effects of yoga in depression: a comparative study. Indian J Psychiatr. 2013;55:S400–S404. doi: 10.4103/0019-5545.116313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Naveen G.H., Varambally S., Thirthalli J., et al. Serum cortisol and BDNF in patients with major depression-effect of yoga. Int Rev Psychiatr. 2016;28:273–278. doi: 10.1080/09540261.2016.1175419. [DOI] [PubMed] [Google Scholar]
- 23.Halappa N.G., Thirthalli J., Varambally S., et al. Improvement in neurocognitive functions and serum brain-derived neurotrophic factor levels in patients with depression treated with antidepressants and yoga. Indian J Psychiatr. 2018;60:32–37. doi: 10.4103/psychiatry.IndianJPsychiatry_154_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Pal R., Singh S.N., Chatterjee A., et al. Age-related changes in cardiovascular system, autonomic functions, and levels of BDNF of healthy active males: role of yogic practice. Age. 2014;36:9683. doi: 10.1007/s11357-014-9683-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Turakitwanakan W., Mekseepralard C., Busarakumtragul P. The pilot study of the effect of meditation to the serum brain-derived neurotrophic factor (BDNF) of medical students, srinakharinvirot university. J Med Assoc Thai. 2015;98(10):S107–S111. [PubMed] [Google Scholar]
- 26.Cahn B.R., Goodman M.S., Peterson C.T., et al. Yoga, meditation and mind-body health: increased BDNF, cortisol awakening response, and altered inflammatory marker expression after a 3-month yoga and meditation retreat. Front Hum Neurosci. 2017;11:315. doi: 10.3389/fnhum.2017.00315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Tolahunase M., Sagar R., Dada R. Impact of yoga and meditation on cellular aging in apparently healthy individuals: a prospective, open-label single-arm exploratory study. Oxid Med Cell Longev. 2017;2017 doi: 10.1155/2017/7928981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Oka T., Tanahashi T., Sudo N., et al. Changes in fatigue, autonomic functions, and blood biomarkers due to sitting isometric yoga in patients with chronic fatigue syndrome. Biopsychosoc Med. 2018;12:3. doi: 10.1186/s13030-018-0123-2. [DOI] [PMC free article] [PubMed] [Google Scholar]