1. The Journal of IHP
1MeditationImpact on gene expression
By Polina Kapoustina, ND (Cand)
December 2014 | www.ihpmagazine.com 52
2. 53 www.ihpmagazine.com | December 2014
Background
There is increasing awareness as well as
research to show the negative impacts of
chronic stress on health. On the other hand,
we are just starting to discover what is
occurring on a molecular level in a relaxed
state. The “relaxation response” (RR) is defined
as a physiological and psychological state
that is opposite to the stress or fight-or-flight
response (Bhasin 2013). The RR can be elicited
through multiple mind-body approaches such
as yoga, mediation, tai chi, qi gong, progressive
muscle relaxation, biofeedback, and breathing
exercises (Bhasin 2013). The common thread
between these techniques is two-fold: (1) the
focus on a word, sound, phrase, repetitive
prayer, or movement and (2) the disregard of
everyday thought. These two steps are critical
in breaking the train of everyday thinking
and influencing physiological changes
including decreased oxygen consumption
and carbon dioxide elimination, changes in
blood pressure, heart and respiratory rate,
norepinephrine responsiveness, increased
heart rate variability, and alterations in cortical
and subcortical brain regions (Bhasin 2013).
Practices such as yoga and meditation
have been in use for over 5000 years in
India (Qu 2013), but there still remain
questions around their biological effects on
our health as well as how yoga compares
to other types of exercise. Recent evidence
shows that meditation practices influence
our biology through epigenetic changes.
Epigenetic changes involve modifications of
gene expression and transcription, with the
potential to affect virtually any cell in the
body through alterations in cell membrane
receptor expression and/ or various signaling
factors. Due to these pervasive and far-
reaching effects, meditation practices have the
potential to modify chronic disease risk and
progression, including heart disease, mood
disorders, and autoimmune disorders, and
cancer. Current studies are looking at how
short and long-term meditation practitioners
may regulate immunity, metabolic rate,
and response to oxidative stress (Ravnik-
Glavac 2012). Such new knowledge helps us
understand the best therapeutic applications of
meditation, and helps reinforce its importance
as an intervention for practitioners and
patients alike. This paper will examine the
current evidence seeking to elucidate the
biological effects of meditation practices.
Clinical Trials
Dusek et al. (2008) provide evidence that a
RR practice results in genomic expression
alterations in healthy subjects. Sustained
genetic expression alterations were found
in both short-term (N2 group) and long-
term meditators (M group) when compared
to novices (N1). These types of changes
are significantly linked to oxidative
phosphorylation, antigen processing and
presentation, and apoptosis (Dusek 2008). The
authors conclude that regular daily practice is
recommended for sustained beneficial effects.
Ravnik et al. (2012) further show that a
higher state of consciousness is associated
with significant changes in gene expression
and brain waves. Table 1 shows a summary
of results from their study that followed two
long-term meditators (20+ years experience)
for one year. Their results showed that a higher
state of consciousness is characterized by both
down-regulation and up-regulation of various
Abstract
There is growing evidence to demonstrate that mind-body practices,
such as yoga and meditation, can influence our gene expression and in
fact counteract cellular damage that may be induced by states of chronic
stress.The changes in genetic expression, as a result of doing these
mind-body exercises to elicit the “relaxation response,” a physiological
and psychological state that is opposite to the fight-or-flight response,
play a significant role in reducing the body's inflammation and states
of anxiety. Clinically, this applies to a variety of treatment approaches
including heart disease, mental health, autoimmune disease and cancer.
These findings highlight the importance of a mind-body "prescription"
in medicine and provide tangible data to reaffirm the benefits of what has
been practiced for centuries in various parts of the globe.
Polina Kapoustina, BA, ND (cand)
Canadian College of
Naturopathic Medicine
Clinic Intern, Robert Schad
Naturopathic Clinic
1255 Sheppard Avenue East,
Toronto, Ontario, M2K 1E2
3. December 2014 | www.ihpmagazine.com 54
The Journal of IHP
1
Reference Method Outcome
Qu 2013 Prospective study
N = 10, male, 18-50 yo, no chronic disease, good psyc
health, in Germany, with previous yoga experience (up
to 5 yrs)
Sudarshan Kriya (SK) yoga program (postures,
breathing, meditation) or control regimen (nature walk
with relaxing music) x 4 consecutive days, 6:30-8:30am
every day
Peripheral blood mononuclear cells (PBMCs) were
isolated from blood sample, taken right before and after
the activities, for gene expression profiling experiments.
Rapid changes (within 2 hours) were found in PBMCs
of yoga group. 97 unique genes were affected in yoga
group vs. 24 in control. Hence a yoga program may have
additional health benefits as compared to exercise plus
simple relaxation. Effects are global and not specific to
molecular pathways.
Black 2013 RCT
N = 45 familial dementia caregivers
12 mins daily Kirtan Kriya meditation (KKM) or12 mins
daily relaxing music (RM) x 8 weeks
Genome-wide transcriptional profiles were collected at
baseline and 8-week mark.
Reduced activity of pro-inflammatory NF-kB and
increased interferon response factors. The KKM group
showed significantly lower levels of depressive symptoms
and greater improvement in mental health compared with
the RM group following the intervention. In KKM, 65.2%
of the participants showed 50% improvement on the
Hamilton Depression Rating scale, and 52% showed 50%
improvement on the Mental Health Composite Summary
score of the Short Form-36 scale. In RM, 31.2% of the
participants showed 50% improvement on the Hamilton
Depression Rating scale. 19% showed 50% improvement
on the Mental Health Composite Summary score of the
Short Form-36 scale. These proportions were significantly
different across condition (p<0.05).
Bhasin 2013 Prospective (novices) and cross-sectional (long-term
practitioners) study N = 52: 26 healthy subjects (in
Boston, USA) with no RR experience (N1, N2) AND 26
healthy subjects with experience of 4-20 years (M)
20mins CD of Relaxation Response (RR) activity: yoga/
meditation/ qi gong/ tai chi/ progressive /biofeedback/
breathing exercises or 20mins of health education CD
(control) x 8 weeks
Blood was collected immediately prior, immediately after
and 15min after activity, isolating total RNA.
FeNO was measured using a rapid response
chemoluminescent Nitric Oxide Analyzer.
Instant increases in FeNO after 20-minute RR elicitation
among short-term (N2) and long-term (M) practitioners
and the sustained increase 15 minutes later in the
M group. Long-term RR practitioners have more
transcriptional changes as compared to short-term
practitioners at rest. Up-regulated long-term changes
induced by RR are linked to telomerase stability
and maintenance. RR progressively affected energy
metabolism and inflammation pathways. Gene sets for
CYP450 family, steroid hormones, retinol metabolism,
and cell adhesion pathways were up-regulated in M and
N2 with greater enrichment in M. Gene sets linked to
energy metabolism (electron transport chain, integration
of energy metabolism) and insulin secretion pathways
were also up-regulated in M compared to N1 and N2.
Ravnik- Glavac 2012 Preliminary cross-sectional study
N = 2 long-term (20+ years) meditation (using Zen, Kriya
goa, Kundalini yoga, and Pranayama x 25 min; eyes
open or closed) practitioners followed over 1 year.
Age 40-50s, Male, Caucasian
EEG – to measure brain frequencies – during rest and
meditation, every 50 seconds
Blood sample – control samples (non-meditating days)
and test sample (1h and 15 after meditation) – total RNA
isolation performed; analyzed transcription differences b/w
different states of consciousness via micro array analysis
EEG: Increased signal power in theta (4-7Hz) and
alpha (8-12 Hz) brain frequencies during meditation,
mainly in parieto-occipital and frontal regions. Genetic
analysis: Down regulation of metabolic and cell cycle
processes, signaling, protein transport, regulation of
gene expression, DNA repair, epigenetic mechanisms.
Immune system activity, apoptotic processes were both
up and down-regulated, as well as the response to
stress. Up-regulation of genes involved in hemoglobin
synthesis, transport of oxygen and nitric oxide,
significantly enrichment in glutamate transport,
ionotropic glutamate receptor activity, and NADH
dehydrogenase activity.
Dusek 2008 N= 58 healthy subjects (19 long term practitioners (M);
19 control (N1); 20 newly trained (N2))
Listened to 20mins of RR CD daily for 8 weeks
Blood transcriptional profiles assessed.
Significant alterations in cellular metabolism, oxidative
phosphorylation, generation of reactive oxygen species
and response to oxidative stress in long-term and
short-term practitioners of daily RR practice that
may counteract cellular damage related to chronic
psychological stress.
Table 1. Human trials demonstrating the use of yoga practice and its affect on gene expression
4. 55 www.ihpmagazine.com | December 2014
genes, including down-regulation of the stress
response, up-regulation of genes involved in
hemoglobin synthesis, transport of oxygen
and nitric oxide, and enrichment in glutamate
transport, glutamate receptor activity, and
NADH dehydrogenase activity. Brain EEG
showed that there was an increase in theta and
alpha brain frequencies during a meditative
state. This study does have a small sample size
and may not apply to novice meditators, but
the results are statistically significant and it is at
present the only study that has evaluated brain
waves. Long-term meditation practitioners were
chosen in this case, according to the authors,
in order to isolate the expression changes of a
higher state of consciousness, however this does
not mean that benefits would be absent among
novice practitioners.
Bhasin et al. (2013) studied the acute
changes in gene expression that took place
within a single session of a RR-eliciting practice.
Over an 8-week period, healthy novice subjects
were exposed to 20 minutes of any of the
following mind-body interventions: yoga/
meditation/ qi gong/ tai chi/ progressive /
biofeedback/ breathing exercises. Fractional
exhaled nitric oxide (FeNO) samples were
collected at three time points during each
session to explain the physiological effects of RR
including reduction in blood pressure. FeNO
is known to play a prominent role in vascular
dilatation (Bashin 2013). This study showed that
a relaxed state influences various pathways via
mitochondrial signaling. Subjects experienced
down-regulation of the NF-kB pathway,
mitigating oxidative stress, inflammation, and
chronic disease vulnerability. Qu (2013) also
looked at the immediate changes that occur
within two hours of yoga for four consecutive
days. This study showed that yogic practices
have rapid effects at the molecular level in
circulating immune cells.
5. December 2014 | www.ihpmagazine.com 56
The Journal of IHP
1
Practices such as yoga and meditation have been
in use for over 5000 years in India, but there still
remain questions around their biological effects
on our health as well as how yoga compares to
other types of exercise.
References
Bhasin MK, Dusek JA, Chang BH, Joseph MG, Denninger JW, Fricchione
GL, Benson H, Libermann TA. Relaxation response induces temporal tran-
scriptome changes in energy metabolism, insulin secretion and inflammatory
pathways. PLoS One. 2013 May 1;8(5):e62817.
Black DS, Cole SW, Irwin MR, Breen E, St Cyr NM, Nazarian N, Khalsa DS,
Lavretsky H. Yogic meditation reverses NF-κB and IRF-related transcrip-
tome dynamics in leukocytes of family dementia caregivers in a randomized
controlled trial. Psychoneuroendocrinology. 2013 Mar;38(3):348-55.
Dusek JA, Otu HH, Wohlhueter AL, Bhasin M, Zerbini LF, Joseph MG,
Benson H, Libermann TA. Genomic counter-stress changes induced by the
relaxation response. PLoS One. 2008 Jul 2;3(7):e2576.
Qu S, Olafsrud SM, Meza-Zepeda LA, Saatcioglu F. Rapid gene expression
changes in peripheral blood lymphocytes upon practice of a comprehensive
yoga program. PLoS One. 2013 Apr 17;8(4):e61910.
Ravnik-Glavač M, Hrašovec S, Bon J, Dreo J, Glavač D. Genome-wide
expression changes in a higher state of consciousness. Conscious Cogn. 2012
Sep;21(3):1322-44.
All the studies described thus far have been prospective or
cross-sectional. However, a randomized control trial (RCT)
conducted in 2013 investigated a unique population group
experiencing chronic stress: caregivers of elderly family
members with dementia. This was defined as caring for the
family member for at least three days per week. Caregivers
often report lower levels of satisfaction with life than healthy
controls, showing higher markers of inflammation such as
C-reactive protein and IL-1 receptor antagonist, and reduced
levels of cellular immunity such as interferon (IFN) (Black
2013). This RCT tested whether a daily yogic meditation
intervention could reverse a pattern of pro-inflammatory and
anti-antiviral leukocyte transcriptional alterations induced
by stress. Results showed a reduction in the activity of pro-
inflammatory NF-kB and increased interferon response factors
(IRF) (Black 2013). The authors concluded that eight weeks
of structured daily yogic meditation reversed the pattern of
increased NF-κB-associated pro-inflammatory gene expression
and decreased expression of IRF1-associated genes.
Future Directions
In summary, there is a growing body of evidence to show that
mind-body practices such as yoga and meditation indeed
influence our gene expression and counteract cellular damage
induced by chronic stress. More questions still remain: are
there certain populations or individuals this kind of practice
can make a bigger impact? How do we measure one’s progress
in clinical practice based on this information (how much,
how often, what type of activity and technique, alone or in a
group, how advanced)? Could individual genetic backgrounds
influence the ability to achieve higher state of consciousness?
Nonetheless, we now know that the changes in genetic
expression as a result of doing mind-body exercises to elicit
the relaxation response, both over short and long-term, can
play a role in general health but also in specific diseases by
reducing inflammation, hypertension (via FeNO vasodilation),
and influence states of anxiety. The potential to alter gene
expression profiles of circulating immune cells toward a less
pro-inflammatory profile is impressive. Clinically this could
also have significant implications in treatment approaches of
autoimmune disease, cancer and chronic infections. These
findings highlight the importance of not underestimating a
mind-body prescription: the importance of taking time to de-
stress and bring one’s awareness to the present moment.