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The Effect of T'ai Chi Exercise on Immunity and Infections: A Systematic Review of Controlled Trials

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  • University of Hong Kong

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Purpose: The aim of this review is to summarize and assess critically clinical trial evidence of the effect of t'ai chi (TC) exercise on immunity and TC efficacy for treating infectious diseases. Methods: Fourteen databases were searched from their respective inceptions through January 2011. No language restrictions were imposed. Quality and validity of the included clinical trials were evaluated using standard scales. Results: Sixteen (16) studies, including 7 randomized controlled trials, 4 controlled clinical trials, and 5 retrospective case-control studies, met the inclusion criteria for this review. One (1) study examined clinical symptoms, 3 studies tested functional measures of immunity (antigen-induced immunity), and the other studies tested enumerative parameters of immunity. such as lymphocytes, immunoglobulins, complements, natural-killer cells, and myeloid dendritic cells. Overall, these studies suggested favorable effects of TC exercise. Conclusions: TC exercise appears to improve both cell-mediated immunity and antibody response in immune system, but it remains debatable whether or not the changes in immune parameters are sufficient to provide protection from infections.
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Review Article
The Effect of T’ai Chi Exercise on Immunity and Infections:
A Systematic Review of Controlled Trials
Rainbow T.H. Ho, PhD,
1,2
Chong-Wen Wang, MD, PhD,
1
Siu-Man Ng, PhD,
2,3
Andy H.Y. Ho, MSocSc,
1
Eric T.C. Ziea, MD, PhD,
4
Vivian Taam Wong, MD, FRCP,
4
and Cecilia L.W. Chan, PhD,
1,2
Abstract
Purpose:The aim of this review is to summarize and assess critically clinical trial evidence of the effect of t’ai chi
(TC) exercise on immunity and TC efficacy for treating infectious diseases.
Methods:Fourteen databases were searched from their respective inceptions through January 2011. No language
restrictions were imposed. Quality and validity of the included clinical trials were evaluated using standard
scales.
Results:Sixteen (16) studies, including 7 randomized controlled trials, 4 controlled clinical trials, and 5 retro-
spective case-control studies, met the inclusion criteria for this review. One (1) study examined clinical symp-
toms, 3 studies tested functional measures of immunity (antigen-induced immunity), and the other studies tested
enumerative parameters of immunity. such as lymphocytes, immunoglobulins, complements, natural-killer cells,
and myeloid dendritic cells. Overall, these studies suggested favorable effects of TC exercise.
Conclusions:TC exercise appears to improve both cell-mediated immunity and antibody response in immune
system, but it remains debatable whether or not the changes in immune parameters are sufficient to provide
protection from infections.
Introduction
Tai Chi (TC), a complementary and alternative
modality of Traditional Chinese Medicine, combines
characteristics of physical exercise and meditative practice.
TC is popularly practiced by a large number of people in
Chinese communities to improve physical fitness and overall
well-being. The gentle movements and postures of the exer-
cise coordinated with breathing patterns and meditation are
designed to achieve a harmonious flow of energy (qi) in the
body. TC exercise is equivalent to moderate-intensity aerobic
exercise. However, TC is not only an exercise but also a mind–
body intervention. Its beneficial effects on health have been
documented in increasing number of studies.
1–3
It is hy-
pothesized that TC as a modality of mind–body intervention
with a moderate intensity of physical exercise may improve
immune functions of human body.
4,5
However, few reviews
have examined the scientific evidence of the effect of TC on
immunity. It is well-known that infections, such as influenza
and herpes zoster, are associated with human body’s immu-
nity, and that individuals who have substantial declines in
immune function are at increased risk for contracting a
number of infectious diseases. Epidemiologic studies have
suggested that moderate exercise training is associated with
reduction in the incidence of upper respiratory–tract infection
(URTI), whereas endurance athletes are at increased risk for
URTIs during periods of heavy training.
5,6
It is still unclear
whether or not TC exercise may reduce the incidence or the
severity of infectious diseases. Thus, this systematic review
aims to summarize and evaluate critically clinical trial evi-
dence of the effectiveness of TC exercise for improving im-
mune functions and its efficacy for treating infectious
diseases.
Methods
Data sources
The following electronic databases were searched from
their respective inceptions through January 2011: PubMed/
MEDLINE; CENTRAL; CINAHL; EMBASE; AMED; Qigong
and Energy Medicine Database; SPORTDiscus Database;
China Journals Full-text Database-Medicine/Hygiene Series,
China Proceedings of Conference Full-text Database, Chinese
Master Theses Full-text Database, China Doctor Dissertations
1
Centre on Behavioral Health,
2
Department of Social Work and Social Administration, and
3
Family Institute, The University of Hong
Kong, Hong Kong SAR, China.
4
Chinese Medicine Department, Hospital Authority of Hong Kong, Hong Kong SAR, China.
THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
Volume 19, Number 2, 2013, pp. 1–8
ªMary Ann Liebert, Inc.
DOI: 10.1089/acm.2011.0593
1
Full-text Database, Electronic Theses and Dissertation Sys-
tem (Taiwan), Taiwan Electronic Periodical Services, and
Index to Taiwan Periodical Literature System. The search
terms used for this review included: tai chi, taichi, tai ji, taiji,
taijichuan, shadowboxing, influenza, infection, infectious,
inflammation, inflammatory, immune, immunity, immuno-
logical, lymphocyte, and antibody. Both traditional and
simplified Chinese translations of these terms were used in
Chinese databases. Reference lists of all included studies,
existing reviews, and other archives of the located publica-
tions were hand-searched for further relevant articles.
Study selection
All controlled clinical trials (CCTs) were included if they
examined the effects of TC exercise on the parameters of im-
munity or for treatment of various infectious diseases. Given
the limited number of prospective clinical trials in the field,
retrospective case-control studies (RCSs) were also included to
provide alternative evidence, but uncontrolled observational
studies were excluded, because of their susceptibility to bias
and lack of significant evidence. Case reports and qualitative
studies were also excluded for lack of significant evidence. To
assess the effect of TC on immunity, studies on any subject
were included, but studies among athletes were excluded
because of their high intensity of physical exercise. To evalu-
ate the effect of TC on infections, any study about TC con-
cerning the incidence or severity of infectious diseases were
included. For all included studies, primary data from the
original sources were reviewed and analyzed.
To assess the effects of TC exercise on improvement of
immunity and TC’s effectiveness for treating infectious dis-
eases, such outcome measures as physical symptoms rele-
vant to infections and biomedical indicators of immunity
were considered. Generally, an individual’s immune status
can be assessed using either enumerative or functional
measures.
7
Functional measures assess how well a specific
immune process works (e.g., how effectively natural-killer
[NK] cells destroy laboratory-grown tumor cells or how
much lymphocytes divide following stimulation with a mi-
togen [a substance that induces mitosis or cell division]). In
clinical practice, one of the most valid and commonly used
functional measures of immunity is used to assess people’s
immune responses to antigens that people are highly sensi-
tive to. This technique involves placing a small piece of an-
tigen directly underneath the skin, a procedure that causes a
local inflammatory response consisting of induration (a
swollen round bump) and erythema (redness around the
bump), and measuring the magnitude of this response im-
mediately or 24–48 hours later, depending on the antigen
that is used. Enumerative measures involve counting dif-
ferent immune-system components (or biomarkers), includ-
ing white blood–cell populations (granulocytes, monocytes,
lymphocytes, NK cells, B-lymphocytes, T-lymphocytes,
helper T-lymphocytes, and suppressor/cytotoxic T-lympho-
cytes), antibody populations in the blood (immunoglobulin
[Ig]A, IgG, and IgM) and in saliva (secretory IgA), and an-
tibodies to specific pathogens. The current review focused on
the number and the percentage of white blood cells, mainly
T-lymphocytes, and levels of serum Igs and complements in
peripheral blood, because these biomarkers are commonly
used parameters in clinical practice and in the field of exer-
cise research. Psychosocial outcomes, such as quality of life
and psychologic well-being, were not considered because it
is difficult to attribute effects on such outcomes to the change
of immunity.
Data extraction and assessment
For each included study, data were extracted by 1 main
researcher and then verified by another researcher. All dis-
crepancies were resolved by discussion. The strength of the
evidence was evaluated for all the included studies using the
Oxford Centre for Evidence-based Medicine Levels of Evi-
dence.
8
These criteria are applied to grade the methodolog-
ical rigor of studies from level 1 or grade A (systematic
review of RCTs, 1a; individual RCT with narrow confidence
interval, 1b) to level 5 or grade D (expert opinion). The
quality and validity of the included RCTs were also evalu-
ated using the Jadad scale,
9
which is based on three criteria:
(1) description of randomization and allocation concealment;
(2) double-blinding; and (3) withdrawals or dropouts (the
score ranges from 0 to 5). This is a standard scale used in
systematic reviews of RCTs. Given that it was difficult to
blind patients to TC, only assessor blinding was evaluated.
The risk of bias in the included trials was assessed using the
framework for methodological quality recommended by Juni
et al.
10
According to this framework, biases fall into four
categories: (1) selection bias (biased allocation to comparison
groups); (2) performance bias (unequal provision of care
apart from intervention under evaluation); (3) detection bias
(biased assessment of outcomes); and (4) and attrition bias
(biased occurrence of loss to follow-up).
Results
Study description
The database searches identified 87 potentially relevant
articles (Fig. 1). Of them, 51 articles were excluded because
they were not clinical trials or not related to infection or
immunity. Full reports of 36 studies were acquired, and 20
were also excluded because they were uncontrolled observa-
tional studies (10), studies with unparallel controls (2), du-
plicate publications (3), studies using athletes (2), and studies
with other outcome measures (3). Sixteen studies published
between 1988 and 2010, including 7 RCTs,
11–17
4CCTs,
18–21
and 5 RCSS,
22–26
met this review’s inclusion criteria. These
studies were conducted in the United States,
13,14,16,19
Taiwan,
22
and mainland China.
11,12,15,1 7,18,20,21,23 –26
Seven (7)
studies
13,14,16,19,22,24,25
were published in English, 8 stud-
ies
11,12,15,17,18, 21,23,26
were published in Chinese, and the re-
maining 1 study
20
was a proceeding.
Of the 16 included studies, 4 used samples of young col-
lege students;
11,12,18,20
1 study used a sample of persons with
HIV infection,
16
and the other studies used samples of
middle-age or older healthy adults. Four (4) studies
11,12,17,18
focused solely on females and 2 studies
22,23
focused solely on
males. Sample sizes in the included studies ranged from 16
to 252. A sample shared by 2 studies
11,12
was considered to
be one sample. In total, these studies covered 939 subjects,
including 577 subjects in the TC exercise groups and 362
subjects in the control groups. Characteristics of the included
RCTs and non-RCTs (CCTs and RCSs) are presented in Ta-
bles 1 and 2, respectively.
2 HO ET AL.
Durations of TC intervention ranged from 5 weeks to 6
months for the 11 prospective studies (7 RCTs and 4 CCTs).
The five RCSs
22–26
reported durations of TC practice span-
ning 12 months to 12 years. The majority of the included
studies were conducted with a two-armed parallel-group
design except for 2 studies
18,20
with a 3-armed parallel
group-design and 3 studies
11,12,16
with a 4-armed parallel
group design. One (1) study
20
compared TC with qigong, and
another study
13
used group health education as a control
while the other studies used a wait-list group or a group
with routine activites as a control.
According to outcome measures, these studies could be
divided into 3 categories: (1) 1 study
18
on clinical symptoms
relevant to infections; (2) 3 studies
13,14,19
on functional mea-
sures of immunity (antigen-induced immunity); and (3) other
studies on enumerative parameters of immunity. The most-
often used outcome measure in the included studies was T-
cells
15,16,21,23–26
followed by Igs (IgA, IgE, IgG, and
IgM),
12,15,18,21
complements (C3, C4),
11,20
NK-cells,
17,23
and
myeloid dendritic cells.
22
Effects of TC intervention
One CCT
18
on clinical symptoms suggested a favorable
effect of TC exercise. Three (3) studies, including 2 RCTs
13,14
and 1 CCT,
19
examined the effects of TC on antigen-induced,
virus-specific cell-mediated immunity and antibody re-
sponse in the human immune system. The results of these
studies indicated that TC exercise could augment immune
responses to virus and influenza vaccines.
Six (6) studies, including 2 RCTs,
15,16
1 CCT,
21
and 3
RCSs,
23,25,26
examined number and/or percentage of T-
lymphocytes. One (1) RCT
15
on older adults suggested that
the number of CD4
+
and the ratio of CD4
+
/CD8
+
increased
significantly after 8 weeks of TC practice. Another RCT
16
on
persons with HIV suggested that lymphocyte proliferation
function was augmented significantly at the 6-month follow-
up visit after 10 weeks of TC exercise. One (1) CCT
21
and 3
RCSs
23,25,26
suggested that the number of lymphocytes,
mainly CD4
+
, and the ratio of CD4
+
/CD8
+
were signifi-
cantly higher in TC groups, compared to control groups. One
(1) RCS
24
examined the number and percentage of B-lym-
phocytes and suggested that the number of ZC-rosette-
forming cells (B-lymphocytes) was lower in a TC group at
resting status but increased significantly after 20 minutes of
exercise, compared to controls.
One (1) RCT
17
indicated that number of NK cells increased
significantly after 6 months of TC practice, but 1 RCS
23
suggested that the percentage of NK cells decreased signifi-
cantly in a TC group after 25 minutes of exercise. One RCS
22
examined the effect of TC on circulating myeloid dendritic
cells (the potent antigen-presenting cells linking innate and
adoptive immunity) and indicated a favorable effect of TC
exercise.
Five (5) studies, including 2 RCTs and 3 CCTs, examined
the concentration of Igs in peripheral blood. One (1) RCT
15
and 3 CCTs
18,20,21
suggested favorable effects of TC exercise
on IgG and IgA, while another RCT
12
only suggested a fa-
vorable effect on IgG. One (1) RCT
11
examined concentra-
tions of complements (C3, C4), and the results indicated that
concentrations of C3 and C4 increased significantly after 12
weeks of TC exercise. One (1) CCT
20
also suggested a fa-
vorable effect of TC exercise on C3.
Study quality
Jadad scores for the included RCTs ranged from 1 to 4,
with a value of 3 or above only for 2 studies. Levels of evi-
dence for the included studies were ranked as ‘‘A’’ for 3
studies, ‘‘B’’ for 12 studies, and ‘‘C’’ for 1 study.
Discussion
This review aimed to assess the efficacy and the effec-
tiveness of TC exercise for treating infectious diseases. Fol-
lowing a comprehensive search of existing literature, it was
found that clinical trials of TC in patients with infectious
diseases were very limited. Only one study
18
examined
clinical symptoms relevant to infections among female stu-
dents. The results indicated that the durations of URTIs
shortened significantly after 6 months of TC exercise. In-
stead, many studies in the field examined the effectiveness of
TC exercise on improvement of human immune function.
Overall, this review demonstrated that the available evi-
dence suggested favorable effects of TC exercise both for
increasing effective components of the immune system and
for improving immune function, as indicated by functional
measures of immunity.
The risk of bias for the studies examined in this review
was assessed, based on the descriptions of randomization,
allocation concealment, blinding, and withdrawals.
10
A high
risk of bias might have existed in some of the included trials,
which might have led to false–positive results. Of the 7 in-
cluded RCTs, only 3
13,14,16
described method of randomiza-
tion and allocation concealment; 2 RCTs
13,16
adopted
assessor blinding, and 4 RCTs
13–16
reported details about
dropouts and withdrawals and adopted intention-to-treat
FIG. 1. Selection process for included studies. RCTs, ran-
domized controlled trials; CCTs, clinical controlled trials;
RCSs, retrospective case-control studies.
T’AI CHI EFFECT ON IMMUNITY AND INFECTIONS 3
Table 1. Summary of RCTsofT’ai Chi Exercise on Functional Measures and Enumerative Measures of Immunity
Authors,
years
& references
Subjects
(ages) n
Interventions
(styles) & frequency Control Duration
Outcome
measures Results
Jadad
score
Level
of
evidence
Huang
et al.,
2006
11
Female
students
from a
nursing
school
(NR)
TG 1: 10
TG 2: 10
TG 3: 10
CG: 10
TC exercise (style: NR):
TG 1: 1 time per week
TG 2: 2 time per week
TG 3: 3 time per week
(45 minutes each time)
Wait-list 12 weeks Complement
3, 4 (C3, C4);
activities of
overall
complement
Concentration of serum C3 & C4 as well as
overall supplement activity increased
significantly in TG 3 at 10th & 12th week,
compared to CG & TG1 ( p<0. 05).
1 B (3b)
Huang
et al.,
2006
12
Female
students
from a
nursing
school
(NR)
TG 1: 10
TG 2: 10
TG 3: 10
CG: 10
TC exercise (style: NR):
TG 1: 1 times per week
TG 2: 2 times per week
TG 3: 3 times per week
(45 minutes each time)
Wait-list 12 weeks Serum IgG, IgM,
IgA, IgE
Only IgG increased significantly among
participants in TG 3 at post-intervention ( p
value: NR).
1 B (3b)
Irwin
et al.,
2007
13
Healthy
older
adults
(59–86)
TG: 59
CG: 53
TCC (a Westernized
Standardized version
of TC)
(40 minutes, 3 times
per week); varicella
vaccine at 16th week
& evaluated 9 weeks
later
Health
education
& group
discussion
25 weeks Levels of VZV-CMI,
indicated by
frequency of
peripheral blood
mononuclear cells
& memory T-cells)
Compared to CG, level of VZV-CMI
increased significantly in TC group at
postintervention ( p<0.05)
4 A (1b)
Irwin
et al.,
2003
14
Healthy
older
adults( 60)
TG: 18
CG: 18
TCC exercise
(45 minutes, 3 times
per week)
Wait-list 15 weeks Levels of VZV-CMI. VZV-specific CMI increased 50% from
baseline to 1-week postintervention in TCC
group ( p<0.05) but unchanged in CG
3 A (1b)
Liu, 2006
15
Older adults
(55–65)
TG: 10
CG: 10
24-style t’ai chi chuan
(1 hour, 4 times
per week)
Routine
activities
8 weeks 1. T-lymphocytes
2. Serum IgG,
IgM, & IgA
1. Significant increase in expression of CD4 +
(p<0.05) & CD4 +/CD8 +ratio ( p<0.01) &
decrease in expression of CD8 +(p<0.05)
in TG at postintervention; no significant
change in T-lymphocytes in CG
2. Concentrations of IgG & IgA increased
significantly ( p<0.05) in TG at
postintervention; no significant change for
these variables in CG
2 B (3b)
McCain
et al.,
2008
16
Persons with
HIV
infection
(NR)
TG 1: 62
TG 2: 65
TG 3: 68
CG: 57
TG 1: Focused TC
exercise
(style: NR)
TG 2: Cognitive–
behavioral
relaxation exercise
TG 3: Spiritual
growth
intervention
Wait-list 10 weeks T-lymphocytes,
NKC cytotoxicity,
Cytokines,
Lymphocyte
proliferation
Compared to CG, all treatment groups had
augmented lymphocyte proliferative
function or increased cellular proliferation
capacity at 6-month follow-up visit
(p<0.01)
4 A (2b)
Wang,
2003
17
Older
female
adults
(55–65)
TG: 10
CG: 6
Group TC exercise
(style: NR
(1 hour/day)
Routine
activities
6 months IL-2
NKC
Number of NK cells & concentration of IL-2
increased significantly in TG at
postintervention, compared to CG ( p
values: NR)
1 B (3b)
RCTs, randomized controlled trials; NR, not reported; TC, t’ai chi; TG, t’ai chi group; CG, control group; Ig, immunoglobulin; TCC, T’ai Chi Chih; VZV, varicella zoster virus; CMI, cell-mediated
immunity; HIV, human immunodeficiency virus; NKC, natural-killer cells, NK, natural killer; IL, interleukin.
4
Table 2. Summary of CCTs and RCSsofT’ai Chi Exercise on Functional and Enumerative Measures of Immunity &Clinical Symptoms
Studies
author, year
& reference Subjects (ages) n
Interventions
(frequency) Controls Duration
Outcome
measures Results
Level
of
evidence
Liu
et al.,
2005
18
Female students
in a college
TG 1: 30
TG 2: 30
CG: 30
24-style t’ai chi chuan
TG 1: 3 times per week
TG 2: 5 times per week
(1 hour each time)
Routine
activities
6 months Symptoms;
serum IgA,
IgM, IgG
1. Duration of URTI became shorter significantly at
postintervention in participants in TG 1 & TG 2,
compared to CG ( p<0.05)
2. Levels of IgA and IgG increased significantly at
postintervention, compared to CG ( p<0.05)
B (2b)
Yang
et al.,
2008
19
Older adults
(TG: 79.5 1.9)
(CG: 74.5 1.6)
TG: 27
CG: 23
Equal parts of TC & qigong
(1 hour, 3 classes
per week), influenza
vaccine during
1st week of
intervention
Routine
activities
20 weeks Anti-influenza
antibody
titer
1. Significant increase ( p<0.05) in magnitude & duration
of antibody response to influenza vaccine in
TG, compared to CG
2. Significant between-group difference at 3 & 20 weeks
after vaccine, & at 20 weeks TG had
significantly higher titers, compared to the prevaccine
timepoint ( p<0.05), whereas CG did not
B (2b)
Yan,
1989
20
College students TC: 40
CG: 30
T’ai chi exercise
(NR)
Qigong
exercise
1 month Serum IgA,
IgG, IgM,
complement
C3 & saliva
lysozyme
Compared with baseline measures, all measures in
TC group increased significantly; in qigong group,
only levels of serum complement C3 & saliva
lysozyme increased significantly
C(4)
Zhang,
2002
21
Older adults
(50)
TG: 12
CG: 12
T’ai chi exercise
(style: NR)
1 hour, 3 times
per week
Wait-list 5 weeks T-lymphocytes;
serum IgG,
IgM, IgA
1. Number of CD4 +and the ratio of CD4 +/CD8 +
increased significantly ( p<0.05; 0.01) & number of CD8 +
decreased significantly ( p<0.05) in TG, whereas number
of CD8 +decreased significantly in CG2.
2. Levels of IgG & IgA increased significantly in TG
(p<0.05); no significant change observed in CG
B (3b)
Chiang
et al.
2010
22
Healthy male adults,
(TG 1: 54.2 8.4
TG 2: 53.8 7.9
CG: 53.1 7.1)
TG 1: 21
TG 2: 22
CG: 20
Yang style t’ai chi
TG 1: Practice
for >5 years
TG 2: Practice
for 2–5 years
Sedentary
lifestyle
Retrospective Myeloid
dendritic
cells in
peripheral
blood
1. Compared to CG,
2. Number of myeloid dendritic cells was significantly
greater in TGs ( p<0.05), whereas the quantity of myeloid
plasmacytoid dendritic cells was similar ( p>0.05).
2. Number of myeloid dendritic cells in TG 1 was
significantly more than in TG 2 ( p<0.05)
B (3b)
Liu and
Zhang,
2002
23
Older male adults
(55–67)
TG: 25
CG: 10
TC exercise
(style: NR)
for 6–12 years
Routine
activities
Retrospective T-lymphocytes,
NK cells
Compared to CG, percentage of CD3 +& CD4 +cells
& ratio of CD4 +/CD8 +increased significantly
(p<0.05), whereas percentage of CD16 +(NKC)
decreased significantly in TC group after 25 minutes
exercise ( p<0.05)
B (3b)
Sun
et al.,
1990
24
Healthy aging
subjects
(54–80)
TG: 24
CG: 24
88-style t’ai chi chuan,
Practice for
average of 7 years
Routine
activities
Retrospective Number
& percentage
of ZC-RFL
(B-lymphocytes)
Number & percentage of ZC-RFL in peripheral blood
increased significantly in TG after 20 minutes of exercise,
compared to CG ( p<0.01)
B (3b)
Sun
et al.,
1989
25
Healthy aging
subjects
(NR)
TG: 30
CG: 30
88-style t’ai chi chuan
Practice for
2–10 years
Routine
activities
Retrospective Total & active
T-lymphocytes
(E-RFL)
Total number of T-lymphocytes & number of active
T-lymphocytes increased significantly in TG,
compared to CG controls ( p<0.01)
B (3b)
Zhu
& Sun,
1998
26
Middle-age
& older healthy
adults
(NR)
TG: 24
CG: 24
88-style t’ai chi chuan
Practice for
average of 7 years
Routine
activities
Retrospective WBC; LC, LC%;
E-RFC, E-RFC%;
Y-RFC, Y-RFC%
1. The numbers and the percentages of LC and
E-RFC were higher in TG at resting status, compared
to CG ( p<0.01)
2. After 20 minutes of exercise, number & percentage
of E-RFC & Y-RFC increased significantly in TG,
compared to CG ( p<0.01)
B (3b)
CCTs, controlled clinical trials; RCSs, retrospective case-control studies; TG, t’ai chi group; CG, control group; URTI, upper–respiratory tract infection; Ig, immunoglobulin; TC, t’ai chi; NR, not
reported; ZC-RFL, ZC-rosette-forming lymphocytes; E-RFL, E-rosette-forming lymphocytes; WBC, white blood cells; LC, lymphocytes; E-RFC, E-rosette-forming cells; Y-RFC, Y-rosette-forming cells;
NK, natural killer; NKC, natural-killer cell.
5
(ITT) analyses. The other RCTs did not have descriptions of
their methods of sequence generation or allocation conceal-
ment and the details on dropouts, and were rated as ‘‘un-
clear’’ for these domains, thus, introducing the potential risk
of bias. Details on dropouts and withdrawals were also de-
scribed in 1 CCT,
19
but the ITT analysis was not adopted in
any CCT, which might have led to the exclusion of some
particular patients and might have introduced attrition bia-
ses. The 4 included CCTs and 5 RCSs were subject to a high
risk of selection bias caused by nonrandomized allocation.
Moreover, the 5 included RCSs
21–26
did not adjust the values
of baseline measures; thus, the reliability of the evidence
presented in these studies was clearly limited. One (1)
study
18
was presented at a conference on medical qigong and
had not undergone the process of peer-review, thus, intro-
ducing potential for a number of biases. In the majority of the
included prospective trials, group TC exercise training was
provided preferentially to the intervention groups, whereas
the control groups did not have a matched number of social
contact hours with coparticipants. Thus, these studies might
have been subject to potential risk of performance bias.
Furthermore, the majority of the included studies had small
samples ( <50 subjects) and the results were prone to a type
II error. Therefore, further vigorously designed, large-scale,
placebo-controlled, randomized studies are needed.
Despite methodological flaws, nearly all of the included
studies demonstrated a beneficial effect of TC exercise on one
or more parameters of immunity. Apart from the included
studies, one CCT
27
of TC exercise on mediators (interleukins,
transforming growth factor, and transcription factors) of the
Th1/Th2/T regulatory reaction also suggested a beneficial
effect of TC on improvement of T-cell helper function. All of
the uncontrolled observational studies
28–37
also reported fa-
vorable effects of TC exercise on different parameters of
immunity, but such data were highly susceptible to bias and,
hence, provided little scientific evidence of the specific effects
of TC exercise for improving immune function.
It has been suggested that the mechanisms underlying
exercise-associated immune changes are multifactorial and
include many neuroendocrine factors.
38,39
TC as a form of
moderate-intensity exercise may promote release of neu-
roendocrinologic factors, such as catecholamines (adrenaline,
noradrenaline), growth hormone, and cortisol, through the
sympathetic–adrenal medullary (SAM) axis.
39,40
These fac-
tors induce changes in cellular trafficking, lymphocyte pro-
liferation, and antibody production.
41
As a consequence of
muscular contraction and catecholamine-induced immediate
changes, for instance, cellular components of the immune
system may be mobilized to the blood.
38
Moreover, TC ex-
ercise may lead to an increased oxygen supply and alter-
ations in metabolism and metabolic factors, such as plasma
glutamine and plasma glucose, which also contribute to ex-
ercise-associated changes in immune function.
38,39
An addi-
tional possibility is that immune enhancement is mediated,
in part, by improvements of psychosocial factors that are
promoted by TC as a mind–body intervention.
42
It has been
suggested that psychologic stress can affect immunity
through the hypothalamic–pituitary–adrenal (HPA) axis.
43
Stress-induced activation of the HPA axis results in the re-
lease of neuroendocrine hormones, such as adrenocortico-
tropin, from the anterior pituitary gland. Adrenocotropin
then circulates through the bloodstream to the adrenal
glands, where the hormone induces release of glucocorti-
coids, which can bind receptors at the cell surfaces of lym-
phoid and myeloid cells.
44
TC as a form of mind–body
intervention may buffer the effects of stress on plasma glu-
cocorticoids and, thus, induce alterations in immune func-
tion.
It should be noted that the immune system is a complex
system, and both functional and enumerative measures of
immunity provide rough estimates of specific processes ra-
ther than global indications of the immune system’s capacity
to resist infectious disease.
7
First, the normal functioning
range is very broad for most immune measures, and it is still
unclear whether or not the magnitude of changes induced by
exercise are sufficient to move outside of the normal ranges.
Even if these changes were sufficient, it is not clear whether
or not the alterations would persist for a sufficient duration
of time to alter risk for infectious disease.
7
Second, most of
the included studies were conducted using healthy adults,
and the clinical implications of the changes in these param-
eters in healthy people are unclear. Changes in cell number
may just reflect changes in the dynamics of lymphocyte
migration and recirculation, or shifts in plasma volume, ra-
ther than absolute changes in total cell numbers.
45
In addi-
tion, absolute changes in cell number will not necessarily
result in a significant change in the capacity of the immune
system to make an effective response to antigenic chal-
lenge.
46
Thus, it would be inappropriate to conclude that TC-
induced changes in any specific immune parameter signal a
state of ‘‘immune enhancement’’ or resistance to infections.
7
This review may have had some limitations. Similar to any
systematic review, one major limitation was the potential
incompleteness of the evidence reviewed. The aim was to
identify all controlled trials in this area in a large number of
databases with no restrictions on publication language. The
current authors are confident that the search strategy used
for this review had located all relevant data; however, a
degree of uncertainty remains. Moreover, selective publish-
ing and reporting can be major causes of bias in the included
studies. In addition, it was not possible to perform meta-
analyses because of the heterogeneity of study designs and
outcome measures in the included studies.
Conclusions
The available evidence suggest that TC exercise may im-
prove both cell-mediated immunity and antibody response
in immune system, but it remains debatable whether or not
the exercise-induced alterations in immune function are
sufficient to alter human body defense, disease susceptibility,
and severity.
47
Because of methodological flaws in existing
studies, further vigorously designed large-scale placebo-
controlled, randomized trials are needed. Future studies
should also test the efficacy of TC exercise for reducing the
incidence or the severity of infectious disease.
Acknowledgments
This review was supported by the Hospital Authority of
Hong Kong (HA105/48 PT5).
Disclosure Statement
No competing financial interests exist.
6 HO ET AL.
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Address correspondence to:
Chong-Wen Wang, MD, PhD
Center on Behavioral Health
The University of Hong Kong
5 Sassoon Road
Pokfulam, Hong Kong, SAR
China
E-mail: wangcw@hku.hk
8 HO ET AL.
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Background This overview summarizes the best available systematic review (SR) evidence on the health effects of Tai Chi. Methods Nine databases (PubMed, Cochrane Library, EMBASE, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Sino-Med, and Wanfang Database) were searched for SRs of controlled clinical trials of Tai Chi interventions published between Jan 2010 and Dec 2020 in any language. Effect estimates were extracted from the most recent, comprehensive, highest-quality SR for each population, condition, and outcome. SR quality was appraised with AMSTAR 2 and overall certainty of effect estimates with the GRADE method. Results Of the 210 included SRs, 193 only included randomized controlled trials, one only included non-randomized studies of interventions, and 16 included both. Common conditions were neurological (18.6%), falls/balance (14.7%), cardiovascular (14.7%), musculoskeletal (11.0%), cancer (7.1%), and diabetes mellitus (6.7%). Except for stroke, no evidence for disease prevention was found; however, multiple proxy-outcomes/risks factors were evaluated. One hundred and fourteen effect estimates were extracted from 37 SRs (2 high, 6 moderate, 18 low, and 11 critically low quality), representing 59,306 adults. Compared to active and/or inactive controls, 66 of the 114 effect estimates reported clinically important benefits from Tai Chi, 53 reported an equivalent or marginal benefit, and 6 an equivalent risk of adverse events. Eight of the 114 effect estimates (7.0%) were rated as high, 43 (37.7%) moderate, 36 (31.6%) low, and 27 (23.7%) very low certainty evidence due to concerns with risk of bias (92/114, 80.7%), imprecision (43/114, 37.7%), inconsistency (37/114, 32.5%), and publication bias (3/114, 2.6%). SR quality was often limited by the search strategies, language bias, inadequate consideration of clinical, methodological, and statistical heterogeneity, poor reporting standards, and/or no registered SR protocol. Conclusions The findings suggest Tai Chi has multidimensional effects, including physical, psychological and quality of life benefits for a wide range of conditions, as well as multimorbidity. Clinically important benefits were most consistently reported for Parkinson’s disease, falls risk, knee osteoarthritis, low back pain, cerebrovascular, and cardiovascular diseases including hypertension. For most conditions, higher-quality SRs with rigorous primary studies are required. Systematic review registration PROSPERO CRD42021225708.
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This article reviews evidence for the hypothesis that psychological interventions can modulate the immune response in humans and presents a series of models depicting the psychobiological pathways through which this might occur. Although more than 85 trials have been conducted, meta-analyses reveal only modest evidence that interventions can reliably alter immune parameters. The most consistent evidence emerges from hypnosis and conditioning trials. Disclosure and stress management show scattered evidence of success. Relaxation demonstrates little capacity to elicit immune change. Although these data provide only modest evidence of successful immune modulation, it would be premature to conclude that the immune system is unresponsive to psychological interventions. This literature has important conceptual and methodological issues that need to be resolved before any definitive conclusions can be reached.
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Several studies examining transient stress and immunological functioning were performed. Measurement issues involving method of saliva collection for use in measuring secretory IgA was explored and differences between whole and parotid saliva were detected. Analyses of sIgA antibody to a novel antigen serially measured over several weeks were performed and relationships with psychological coping variables were tentatively observed. IL- 2 and Natural Killer cell assays were developed and tested, and we found that NK assays could not be successfully run from cryopreserved cells. A study replicating and extending previous work with a transient stressor (examinations) was run. Although overall group results did not replicate some previous work, ipsative analyses revealed that subjects who became more anxious in response to the stress had higher levels of lymphocyte proliferation. Keywords: Stress(Psychology), Immunoglobulin A, Interleukin 2, Concanavalin A.
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b>Objective : This systematic review aimed to critically appraise published clinical trials designed to assess the effect of Tai Chi on psychosocial well-being. Data Sources : Databases searched included MEDLINE, CINAHL, EMBASE, HEALT, PsycINFO, CISCOM, the Cochrane Central Register of Controlled Trials of the Cochrane Library, and dissertations and conference proceedings from inception to August 2008. Review Methods : Methodological quality was assessed using a modified Jadad scale. A total of 15 studies met the inclusion criteria (i.e. English publications of randomized controlled trials with Tai Chi as an intervention and psychological well-being as an outcome measure), of which eight were high quality trials. The psychosocial outcomes measured included anxiety (eight studies), depression (eight studies), mood (four studies), stress (two studies), general mental health three studies), anger, positive and negative effect, self-esteem, life satisfaction, social interaction and self-rated health (one study each). Results : Tai Chi intervention was found to have a significant effect in 13 studies, especially in the management of depression and anxiety. Although the results seemed to suggest Tai Chi is effective, they should be interpreted cautiously as the quality of the trials varied substantially. Furthermore, significant findings were shown in only six high quality studies. Moreover, significant between group differences after Tai Chi intervention was demonstrated in only one high quality study (the other three significant results were observed in non-high quality studies). Two high quality studies in fact found no significant Tai Chi effects. Conclusion : It is still premature to make any conclusive remarks on the effect of Tai Chi on psychosocial well-being.<br /
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An ever-growing volume of peer-reviewed publications speaks to the recent and rapid growth in both scope and understanding of exercise immunology. Indeed, more than 95% of all peer-reviewed publications in exercise immunology (currently >2, 200 publications using search terms "exercise" and "immune") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term "physical activity" and the specific category of "exercise", which implies activity for a specific purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes from exercise studies. In this position statement, a panel of world-leading experts provides a consensus of current knowledge, briefly covering the background, explaining what we think we know with some degree of certainty, exploring continued controversies, and pointing to likely directions for future research. Part one of this position statement focuses on 'immune function and exercise' and part two on 'maintaining immune health'. Part one provides a brief introduction and history (Roy Shephard) followed by sections on: respiratory infections and exercise (Maree Gleeson); cellular innate immune function and exercise (Jeffrey Woods); acquired immunity and exercise (Nicolette Bishop); mucosal immunity and exercise (Michael Gleeson and Nicolette Bishop); immunological methods in exercise immunology (Monika Fleshner); anti-inflammatory effects of physical activity (Charlotte Green and Bente Pedersen); exercise and cancer (Laurie Hoffman-Goetz and Connie Rogers) and finally, "omics" in exercise (Hinnak Northoff, Asghar Abbasi and Perikles Simon). The focus on respiratory infections in exercise has been stimulated by the commonly held beliefs that the frequency of upper respiratory tract infections (URTI) is increased in elite endurance athletes after single bouts of ultra-endurance exercise and during periods of intensive training. The evidence to support these concepts is inconclusive, but supports the idea that exercised-induced immune suppression increases susceptibility to symptoms of infection, particularly around the time of competition, and that upper respiratory symptoms are associated with performance decrements. Conclusions from the debate on whether sore throats are actually caused by infections or are a reflection of other inflammatory stimuli associated with exercise remains unclear. It is widely accepted that acute and chronic exercise alter the number and function of circulating cells of the innate immune system (e.g. neutrophils, monocytes and natural killer (NK) cells). A limited number of animal studies has helped us determine the extent to which these changes alter susceptibility to herpes simplex and influenza virus infection. Unfortunately, we have only 'scratched the surface' regarding whether exercise-induced changes in innate immune function alter infectious disease susceptibility or outcome and whether the purported anti-inflammatory effect of regular exercise is mediated through exercise-induced effects on innate immune cells. We need to know whether exercise alters migration of innate cells and whether this alters disease susceptibility. Although studies in humans have shed light on monocytes, these cells are relatively immature and may not reflect the effects of exercise on fully differentiated tissue macrophages. Currently, there is very little information on the effects of exercise on dendritic cells, which is unfortunate given the powerful influence of these cells in the initiation of immune responses. It is agreed that a lymphocytosis is observed during and immediately after exercise, proportional to exercise intensity and duration, with numbers of cells (T cells and to a lesser extent B cells) falling below pre-exercise levels during the early stages of recovery, before returning to resting values normally within 24 h. Mobilization of T and B cell subsets in this way is largely influenced by the actions of catecholamines. Evidence indicates that acute exercise stimulates T cell subset activation in vivo and in response to mitogen- and antigen-stimulation. Although numerous studies report decreased mitogen- and antigen-stimulated T cell proliferation following acute exercise, the interpretation of these findings may be confounded by alterations in the relative proportion of cells (e.g. T, B and NK cells) in the circulation that can respond to stimulation. Longitudinal training studies in previously sedentary people have failed to show marked changes in T and B cell functions provided that blood samples were taken at least 24 h after the last exercise bout. In contrast, T and B cell functions appear to be sensitive to increases in training load in well-trained athletes, with decreases in circulating numbers of Type 1 T cells, reduced T cell proliferative responses and falls in stimulated B cell Ig synthesis. The cause of this apparent depression in acquired immunity appears to be related to elevated circulating stress hormones, and alterations in the pro/anti-inflammatory cytokine balance in response to exercise. The clinical significance of these changes in acquired immunity with acute exercise and training remains unknown. The production of secretory immunoglobulin A (SIgA) is the major effector function of the mucosal immune system providing the 'first line of defence' against pathogens. To date, the majority of exercise studies have assessed saliva SIgA as a marker of mucosal immunity, but more recently the importance of other antimicrobial proteins in saliva (e.g. alpha-amylase, lactoferrin and lysozyme) has gained greater recognition. Acute bouts of moderate exercise have little impact on mucosal immunity but prolonged exercise and intensified training can evoke decreases in saliva secretion of SIgA. Mechanisms underlying the alterations in mucosal immunity with acute exercise are probably largely related to the activation of the sympathetic nervous system and its associated effects on salivary protein exocytosis and IgA transcytosis. Depressed secretion of SIgA into saliva during periods of intensified training and chronic stress are likely linked to altered activity of the hypothalamic-pituitary-adrenal axis, with inhibitory effects on IgA synthesis and/or transcytosis. Consensus exists that reduced levels of saliva SIgA are associated with increased risk of URTI during heavy training. An important question for exercise immunologists remains: how does one measure immune function in a meaningful way? One approach to assessing immune function that extends beyond blood or salivary measures involves challenging study participants with antigenic stimuli and assessing relevant antigen-driven responses including antigen specific cell-mediated delayed type hypersensitivity responses, or circulating antibody responses. Investigators can inject novel antigens such as keyhole limpet haemocyanin (KLH) to assess development of a primary antibody response (albeit only once) or previously seen antigens such as influenza, where the subsequent antibody response reflects a somewhat more variable mixture of primary, secondary and tertiary responses. Using a novel antigen has the advantage that the investigator can identify the effects of exercise stress on the unique cellular events required for a primary response that using a previously seen antigen (e.g. influenza) does not permit. The results of exercise studies using these approaches indicate that an acute bout of intense exercise suppresses antibody production (e.g. anti-KLH Ig) whereas moderate exercise training can restore optimal antibody responses in the face of stressors and ageing. Because immune function is critical to host survival, the system has evolved a large safety net and redundancy such that it is difficult to determine how much immune function must be lost or gained to reveal changes in host disease susceptibility. There are numerous examples where exercise alters measures of immunity by 15-25%. Whether changes of this magnitude are sufficient to alter host defence, disease susceptibility or severity remains debatable. Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Evidence suggests that the prophylactic effect of exercise may, to some extent, be ascribed to the anti-inflammatory effect of regular exercise mediated via a reduction in visceral fat mass and/or by induction of an anti-inflammatory environment with each bout of exercise (e.g. via increases in circulating anti-inflammatory cytokines including interleukin (IL)-1 receptor antagonist and IL-10). To understand the mechanism(s) of the protective, anti-inflammatory effect of exercise fully, we need to focus on the nature of exercise that is most efficient at allieviating the effects of chronic inflammation in disease. The beneficial effects of endurance exercise are well known; however, the antiinflammatory role of strength training exercises are poorly defined. In addition, the independent contribution of an exercise-induced reduction in visceral fat versus other exercise-induced anti-inflammatory mechanisms needs to be understood better. There is consensus that exercise training protects against some types of cancers. Training also enhances aspects of anti-tumour immunity and reduces inflammatory mediators. However, the evidence linking immunological and inflammatory mechanisms, physical activity, and cancer risk reduction remains tentative. (ABSTRACT TRUNCATED)
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Exercise influences natural immunity, T- and B-cell functions, and cytokine responses, through circulatory (hemodynamic) changes and by endocrine hormones secreted in response to physical stress. The magnitude of the effects on the immune system reflects the intensity, duration and chronicity of the exercise. In this review, Laurie Hoffman-Goetz and Bente Klarlund. Pedersen suggest that exercise-immune interactions can be viewed as a subset of stress immunology.
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Aim: To observe the effect of Tai Chi Chuan (TCC) exercise on T lymphocyte and B lymphocyte immune functions in healthy older individuals. Methods: 1 Twenty older inhabitants from Shiguang third country of Shanghai city in October 2004 were selected as subjects. They, aged 55-56 years and including 10 males and 10 females, were randomly divided into two groups: training group (n=10) and control group (n=10). These older individuals have known and consented to the testing scheme and have no disciplinarian exercise recently. 2 Training group: Exercise contents were mostly twenty-four TCC (Commencing form, Part the Wild Horse's Mane on Both Side, White Crane Spreads its Wings, Brush Knee and Twist Step on Both Side and Play Pipa, etc). Exercise loads were sixty minutes every time and four times every week for eight weeks. Every time exercise comprised ten minutes warming-up, forty minutes TCC exercise and ten minutes relaxation at medium intensity (50%-65% maximal heart rate). Control group: The patients had no exercise with individual or collective scheme. 3 At one day before and after 8-week exercise, the percentages of lymphocyte subpopulations were determined by flow cytometry, then the ratio of CD4+/CD8+ was calculated. In addition, the serumal immunoglobulin G (IgG), IgM and IgA were determined by Array 360 system autoanalyzer. Results: Totally 20 older people entered the result analysis. 1The testing results of T lymphocyte subpopulation in two groups had no significant difference before TCC exercise (P > 0.05). After eight-week TCC exercise, the training group showed an increase in the expression of CD4+ and significant increase in CD4+/CD8+ ratio [(41.59±4.32)%, 1.87±0.28; (32.58±3.16)%, 1.07±0.33, t=-4.02, -5.23, P < 0.05,0.01], and decrease in the expression of CD88 [(22.25±5.12)%, (30.41±3.57)%, t=3.05, P < 0.05]. 2There was no significant change in the testing results of T lymphocyte subpopulation in control group before and after TCC exercise (P > 0.05). 2The testing results of immunoglobulin in two groups had no significant difference before TCC exercise (P > 0.05). After eight-week TCC exercise, the training group showed increase in the concentrations of IgG and IgA [(12.78±3.30), (3.18±0.96) g/ L, (11.20±2.32), (2.56±0.42) g/L, t=-3.72, -2.98, P < 0.05], and little increase in concentration of IgM, without significant difference (P > 0.05). The control group showed no significant change in these variables, which were still lower than those before exercise (P > 0.05). Conclusion: TCC exercise is effective for improving T lymphocyte and B lymphocyte immune functions in healthy older individuals.
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To evaluate the effects of a behavioral intervention, Tai Chi, on resting and vaccine-stimulated levels of cell-mediated immunity (CMI) to varicella zoster virus (VZV) and on health functioning in older adults. A prospective, randomized, controlled trial with allocation to two arms (Tai Chi and health education) for 25 weeks. After 16 weeks of intervention, subjects were vaccinated with VARIVAX, the live attenuated Oka/Merck VZV vaccine licensed to prevent varicella. Two urban U.S. communities between 2001 and 2005. A total of 112 healthy older adults aged 59 to 86. The primary endpoint was a quantitative measure of VZV-CMI. Secondary outcomes were scores on the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The Tai Chi group showed higher levels of VZV-CMI than the health education group (P<.05), with a significant rate of increase (P<.001) that was nearly twice that found in the health education group. Tai Chi alone induced an increase in VZV-CMI that was comparable in magnitude with that induced by varicella vaccine, and the two were additive; Tai Chi, together with vaccine, produced a substantially higher level of VZV-CMI than vaccine alone. The Tai Chi group also showed significant improvements in SF-36 scores for physical functioning, bodily pain, vitality, and mental health (P<.05). Tai Chi augments resting levels of VZV-specific CMI and boosts VZV-CMI of the varicella vaccine.