Anc Sci Life. 2015 Jul-Sep; 35(1): 12–17.

doi: 10.4103/0257-7941.165623: 10.4103/0257-7941.165623
PMCID: PMC4623627
PMID: 26600662

Psycho-neuro-endocrine-immune mechanisms of action of

yoga in type II diabetes
Vijay Pratap Singh, Bidita Khandelwal,1 and Namgyal T. Sherpa2
Address for correspondence: Dr. Vijay Pratap Singh, Department of Physiotherapy, Sikkim
Manipal Institute of Medical Sciences, 5th Mile, Tadong, Gangtok - 737 101, Sikkim, India. E-
mail: moc.liamg@tpmyajivrd
Copyright : © Ancient Science of Life
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INTRODUCTION
Yoga has been found to benefit all the components of health viz. physical, mental, social
and spiritual well being by incorporating wide variety of practices.[1] Yoga techniques
include the practice of prāṇāyāma, which regulates respiration through variety of exercises,
and āsana, which includes various physical exercises and postures in a highly coordinated
manner integrated with systematic breathing.[2] Although yoga is a discipline which is not
just confined to āsana (postural exercises) or prāṇāyāma (breathing exercises), but most
studies are based on exercise effect of yoga. This is so because āsana and prāṇāyāma can
easily be taught and learned and thus incorporated in to life style. These exercises have
been found to bring about positive biochemical and hormonal changes by eliminating stress
and instilling a sense of discipline.[3] Yoga is also easily accepted by the elderly because
yogic exercises consist of slow, rhythmic movements which bring about adequate
stretching of muscles and joints with appropriate strengthening in these structures as well as
it stimulates glands such as pancreas to augment insulin secretion.[4]
Abnormal increase in sympathetic activity and reduction in parasympathetic activity has
been associated with Type II DM. Chronic stress; anxiety and depression have already been
implicated in pathogenesis as well as the aftermath of diabetes. Some studies have shown
positive effects of yoga intervention on stress and anxiety.[5]
Studies and reviews have clearly shown the positive effects of Yoga on glycemic control,
blood pressure, lipid profile, stress, anxiety, and depression but have not identified the
mechanisms of action of Yoga in Type II DM. Previous studies have clearly stated the need
to review mechanisms by which yoga helps in diabetes.[6] This study reviews published
literature to explain psycho-neuro-endocrine and immune mechanisms of action of Yoga in
improving Type II DM.

MATERIALS AND METHODS

Independent search was conducted by two researchers independently using search terms
‘Yoga OR Pranayama AND diabetes OR diabetic IN title or abstract in National Library of
Medicine- MEDLINE (www.pubmed.com) website. The retrieved citations and articles
were appraised and mutual consensus was obtained in presence of the two more
researchers. The included articles were then grouped qualitatively under effect of yoga
explaining psychological, neural, endocrine and immune mechanisms of action.
Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing
psycho-neuro-endocrine or immunologic relations was retrieved from Pubmed and Pubmed
Central and analyzed. Those studies which explained the psycho-neuro-endocrine and
immune mechanisms of action of yoga were included and rest were excluded. Although
primary aim of this study is to explain these mechanisms in Type II DM, studies in non-
diabetic population which had a similar pathway of stress mechanism was included because
they had parallel explanations in line with objective of our study. Aim of this study is not to
quantify the benefits rather it was aimed to explain mechanisms of action (MOA) of yoga
in Type II DM. therefore, studies which have not explained MOA of yoga were excluded.
Further, there seems to be a common pathway of stress mechanisms and immune reactions
especially concerning Hypothalamic- Pituitary- Adrenal (HPA) Axis, therefore some
studies of non-diabetic population have been included to explain immunologic benefits of
yoga extrapolating from cancer studies to postulate possible benefits in diabetic subjects.

RESULTS
Key words used were psychologic, neurologic, endocrine, immune, mechanisms of action,
Yoga and Type II Diabetes Mellitus. Total of 89 studies were retrieved by various
combinations of key words, which was subjected to an expert panel of 4 faculties to include
and exclude studies. Of the 89 articles, we excluded non-English articles (22), editorials
(20) and letters to editor (10). 37 studies were taken in to account for this review.

DISCUSSION
Studies on Yoga provide convincing evidence for its effectiveness over autonomic nervous
system.[7] Bagchi and Wenger reported that yogic meditation induces inner relaxation of
ANS without inducing sleep as well as raising immune levels in the body without
exaggerating physiological manifestation against external stimuli, thereby providing a
balance between body and outside world.[8]
Yoga has a direct effect on optimizing secretion of sympathetic hormones such as cortisol
and catecholamine, thereby improving parasympathetic activity and reducing metabolic
rate.[9] Type II DM has been correlated with stress mechanisms. Stress suppresses body's
immune system and neuro-humoral actions thereby affecting psychological state. It would
not be wrong to state that correlation of diabetes with stress, anxiety and other
psychological factors are bidirectional and make understanding the interrelated mechanisms
difficult.[10,11,12] In such a situation, yoga proves to be promising as it helps the body
come back to balanced state of physical and emotional congruence. A previous study[12]
has reported the influence of stress in disturbing neuro-endocrine and hypothalamus
function that further affects immune modulation and immune homeostasis. Another study
has reported incorporation of stress in Human Information Processing pattern (HIP).[13,14]
Kulkarni and Bera, 2009 reported HIP as a method of neuropsychology to understand role
of cortex and stimulus information processing. HIP has been theorized to constitute five
steps, namely, detection of stimulus, discrimination, decision, memory and reaction time.
These steps succinctly explain processing of cognitive stimuli with meaningful motor
output.[13]
Its conjugation with stress can be understood as stress being the result of withdrawal of
attention and reduced attention sensitivity thereby detrimental towards health. Since the
limbic system is the seat of emotion, any stressful event diverts cortical aspects of attention
process to affective response. This in turn negatively affects the HPA axis. Ultimately the
immune system is also negatively affected.[15] This pathophysiological phenomenon is
represented in a schematic diagram [Figure 1].
Yoga acts via downregulating the HPA axis which gets hyperactivated as a response to
abnormal physical or psychological demand (stressor). Any stressful situation affects
balance between sympathetic and parasympathetic systems by release of increased cortisol
and catecholamines. This response is classic ‘fight or flight’ response which is encountered
by hypermobilization of energy needed to combat the stressor. This constant state of hyper
vigilance resulting from repeated firing of HPA axis leads to dysregulation of normal body
system leading to stress-related diseases such as diabetes, depression, obesity and cardio
vascular diseases. Yoga attenuates the stress cascade by reducing the perception of stress.
Yoga decreases physiological manifestations of stress by reducing heart rate, blood
pressure and respiratory rate.[16,17] A study by Smith et al. showed increased pain
tolerance and lowered pain related brain activity during MRI in yoga practioners.[18]
Tooley et al. found significantly higher plasma melatonin levels in yoga meditators.[19]
Harinath et al. found increased melatonin, improved psychological and cardio respiratory
profiles in yoga practioners after 3 months of practice.[20]
Reduction of cardiovascular risk factors in diabetes is a hallmark of successful diabetes
management.[21,22,23] Yoga seems to be beneficial in doing this. Mechanism of action of
Yoga can be hypothesized under two pathways: Firstly by way of vagal stimulation and
secondly by parasympathetic activation and HPA axis modification.[24] The first
postulated mechanism is through Yoga's action on vagal stimulation by improving
baroreflex sensitivity, reducing inflammatory cytokines, and thereby reducing blood
pressure and resting heart rate.[21,24,25,26,27] Yoga practice also improves endothelial
function and reduces risks of cardiovascular diseases in Type II DM.[24]
Second postulated mechanism of action of yoga is through parasympathetic activation and
associated anti stress mechanisms. It reduces perceived stress and HPA axis activation,
thereby improving overall metabolic and psychological profiles, increasing insulin
sensitivity, and improving glucose tolerance and lipid metabolism.[24] These pathways are
shown in Figure 2.
Stress is a root cause of many diseases.[28] Figure 3 portrays the pathophysiological
cascade of stress and disease. Through constant deregulation of HPA axis and the
sympathetic nervous system, stress keeps the entire mechanism in chaos with dysregulation
of hormones such as cortisol, catecholamines etc. Their increased stimulation over a period
causes diseases such as Type II diabetes. Yoga acts in an opposite manner by bringing
balance to both the autonomic nervous system and the HPA axis. It reduces secretions of
cortisol, catecholamines, inflammatory cytokines, rennin and anti-inflammatory factors.[6]
A previous study has revealed preponderance of alpha waves in yogis recorded through
EEG.[29]
Physiology of neural plasticity is a significant discovery which has provided the basis for
understanding rehabilitation science and the regaining of lost functions after neurologic
insult. The ability of neural structures to repair their functions, reorganize structures
through flexibility in neural structure, is known as neural plasticity. It mainly comprises of
developmental, experience related and regeneration related components. Yoga asanas and
yogic practices involve both motor movements and sensory experiences. Thus, it may be
hypothesized that yogic practices utilize neural plasticity to bring about sustained changes
in structure and function of the brain. Although neural connections and structures are more
dependent on genetics and development, experience related neural plasticity seem to play a
greater role in reshaping neural structures. These theoretical considerations may explain
how pathophysiology of Type II DM and regeneration of beta cells in pancreas may be
positively affected by Yoga.[30]
Yoga practice is directly related to improved insulin sensitivity to glucose signals in Type II
DM. It attenuates the negative relationship between factors causing insulin resistance such
as obesity, increased waist circumference, dyslipidemia etc.[31] Yoga also improves
sensitivity of beta cells of pancreas to glucose signals. Manjunatha et al. have stated that
there is reduction in brisk release of insulin when glucose level tends to fall whereas there
is increased insulin release when glucose tends to rise in blood.[32] This mechanism gets
support from a previous study of Sahay who observed a fall in fasting insulin level when
glucose level is at minimum level. Yoga optimizes insulin secretion as per bodily
requirement through its neuro-endocrinal effects and thereby bringing about normalcy in
the Insulin/Glucose ratio which is suggestive of better peripheral utilization of Insulin and
reduced insulin resistance.[3]

Possible benefits of yoga on immune system-emerging hypotheses

In response to stress, activation of Hypothalamo-Pituitary-adrenal Axis (HPA) results in
secretion of Corticotrophin-Releasing Factor (CRF) from hypothalamus. CRF stimulates
the secretion of ACTH from pituitary, which further activates the adrenal glands to produce
glucocorticoids, which are powerful immune regulators. The effects of glucocorticoids on
cellular and humoral immune responses are quite complex. Although the overall effect of
glucocorticoids on immune responses at the cellular level is immunosuppressive, this effect
may result from suppression of many stimulatory components of immune cascade and
stimulation of some immunosuppressive or anti-inflammatory elements. The relatively
greater sensitivity of components of cellular immunity to glucocorticoid suppression tends
to shift immune response from a cellular to humoral pattern during stress.[33,34]
No well designed experimental study has been reported concerning the effects of yoga on
diabetics’ immune systems. However, studies have reported the efficacy of yoga in
different populations, especially cancer patients.[7] Findings of these studies can be
extrapolated to diabetes and immunology because some of the pathways of its mechanism
of action are similar. A study by Ronson reported allostatic load as a cause of dysregulation
of immune system in cancer patients due to dysfunction of the HPA axis as a result of the
stress of oncologic pathophysiology. Although that study concerned cancer patients,
dysregulation of HPA axis has been reported by many authors as cause of co-morbidities in
Diabetics.[35]
There was decrease in natural killer cells in advanced breast cancer patients following yoga
practice as reported by the present author which is a predictor of survival.[10] Recent
studies reported that Relaxation elicitation, particularly after long-term practice, may evoke
health benefits by improving mitochondrial energy production and utilization and thus
promoting mitochondrial resilience through upregulation of ATPase and insulin function.
Mitochondrial resilience might also be promoted by relaxation induced downregulation of
NF-κB-associated upstream and downstream targets that mitigates stress. NF-κB pathway
genes are known to have a prominent role in inflammation, diabetes, stress, trauma and
cancer – which were suppressed after relaxation response elicitation.[11,36]
In a study by SuQu et al., a yoga program had a rapid and significantly greater effect on
gene expression in peripheral blood mononuclear cells (PBMCs) compared to the control
group who were given only walking exercise with relaxing music. They suggested that gene
expression alteration may be the basis for long term higher level health effects.[14] Another
study reported increase in cortisol level as a stress marker in examinees but this rise was
less in the group of examinees who practiced yoga. Further, the yoga group showed
attenuation of increase in cortisol due to examination stress which was attributed to
relaxing effects of yoga on mind, in turn reducing stimulus to hypothalamus and anterior
pituitary and thereby reducing secretion of cortisol. This study also reported mean plasma
IL-4 rise and serum IFN-y decrease with examination stress. Decrease in serum IFN-y was
significant in control group and non-significant in yoga group. Decrease in serum IFN-y is
a marker of reduced cellular immunity. This study found yoga to exert a buffering effect on
cellular immunity.[37] It was conducted on a group of students with perceived
examination-stress. However pathways of stress have been same as in diabetics and
therefore, the finding is relevant to be discussed here.

Limitations and scope for future

This study has examined mechanisms for the action of yoga in Type II Diabetes, especially
the integrative mechanisms of psycho-neuro-endocrine and immune relationships. These
are interrelated and complex to be understood and therefore there is no definite verdict on
these mechanisms. Many experimental studies which have reported these probable
mechanisms were limited by several issues such as unclear methodology, interventions and
program structure, quasi experimental, lack of control group, confounding variables and
smaller sample sizes. Some studies have even presented few data or too many confounders
which make them difficult to generalize. However, we have tried to discuss the
mechanisms of action of yoga in terms of psycho-neuro-endocrine and immune
mechanisms in Type II diabetes with scope for future research. We recommend well
designed blinded randomized studies to evaluate effect of yoga on immune markers in
diabetics to obtain valid results. We also recommend experimental studies which can
evaluate effect of yoga on psycho-neuro-endocrine mechanisms to prove the theories laid
down by various studies discussed here.

CONCLUSION
It is difficult to identify any single pathophysiologic mechanism of action of yoga in Type
II DM as the risk factors and etiologies of Type II DM are multifactorial. Similarly it is
difficult to postulate any single unidirectional pathway of Yoga action in Type II DM.
Yoga's mechanisms of action in Type II DM are integrated and their effect is
multisystemic. The psycho-neuro-endocrine and immune mechanisms of action of yoga in
Type II DM represent a possible approach to understanding its holistic effects on disease
modulation of Type II DM. This review suggests psycho-neuro-endocrine and immune
mechanisms that may be important to understanding yoga's actions on Type II DM.
Summing up, the words Samatvam yoga ucyate (2:48; Bhagvad Gita): Equanimity is yoga.
Samatvam is being able to maintain one's balance of mind in success and failure, gain and
loss, pleasure and pain, and that is the aptitude of a perfect Yoga master who remains
equipoised in all circumstances. Samatvam of the mind can contribute in preventing many
illnesses. Yoga of equanimity has the potential to control negativity of brain and behavior
by modulating its activity through psycho-neuro-endocrine and immune mechanisms to
restore and maintain health in the true sense.

Financial support and sponsorship

Indian Council of Medical Research, ICMR.

Conflicts of interest
There are no conflicts of interest.

Acknowledgements
Dean, SMIMS, Gangtok and ICMR.

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Figures and Tables

Figure 1

Schematic diagram showing pathophysiology of Stress and Stress related disorders due to abnormal
HIP-PNE model. HIP-PNE: Human Information Processing - PsychoNeuroEndocrine information, HPA:
Hypothalamo-Pituitary-Adrenal axis
Figure 2
 Open in a separate window
Postulated pathways of Yoga benefits in reducing Cardiovascular risk factors in pathogenesis of Type II
DM through autonomic nervous system
Figure 3
Pathophysiologic mechanisms of stress and its impact on Hypothalamic-Pituitary-Adrenal axis(HPA).[6]
*Yoga seems to be promising in its anti stress mechanism and positive modulation of HPA axis

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