EVIDENCE-BASED INTEGRATIVE MEDICINE UPDATES
ACUPUNCTURE FOR PTSD, NATUROPATHY
FOR CARDIOVASCULAR RISK; YOGA FOR
OSTEOARTHRITIS; CHASTEBERRY FOR PMS;
AND ANTIOXIDANTS FOR
CARDIOVASCULAR EVENTS
| Richard Glickman-Simon, MD, Brian S. Alper, MD, MSPH, FAAFP |
ACUPUNCTURE MAY IMPROVE
SYMPTOMS OF PTSD, AND MAY BE
AS EFFECTIVE AS COGNITIVE
BEHAVIORAL THERAPY AND
SELECTIVE SEROTONIN REUPTAKE
INHIBITORS
Level 2 [mid-level] evidence
Evid Based Complement Altern Med
2013;(2013):615857
Post-traumatic stress disorder (PTSD)
occurs in 25–30% of those who survive a
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Evidence-Based Integrative Medicine Updates
life-threatening or otherwise catastrophic
event.1 It is characterized by three
clusters of symptoms: re-experiencing,
hyper-arousal, and marked avoidance.2
First-line therapy includes a combina-
tion of cognitive behavioral therapy
(CBT) and psycho-pharmaceuticals. In-
adequate response and/or drug intoler-
ance have caused many patients with
PTSD and their advocates to seek
alternative or supplementary treatments.
Acupuncture has emerged as one of the
more actively researched modalities for
this purpose. Two previous reviews (one
of them on acupressure), however, were
unable to draw reliable conclusions
about its benefits.3,4
In the present study, researchers set out
to perform a systemic review of currently
available prospective trials investigating
the effectiveness of classical acupuncture,
electroacupuncture, acupuncture with
moxibustion (needle warming), or auricu-
lar (ear) acupuncture for PTSD.5 (Studies
on acupressure were excluded.) Four ran-
domized controlled trials (N ¼ 543) and
two uncontrolled clinical trials (N ¼ 103)
were included. All but one of the trials
were performed on earthquake victims. In
one trial with 56 patients, acupuncture
significantly improved scores for PTSD
symptoms, depression, anxiety, and func-
tional impairment compared with wait-list
control. The addition of acupuncture to
CBT significantly improved PTSD symp-
tom scores compared to CBT alone in
EXPLORE November/December 2013, Vol. 9, No. 6 385
one trial with 91 patients, and there were
no significant differences in scores for
PTSD symptoms, depression, or anxiety
in another trial with 57 patients comparing
acupuncture vs. CBT. Similarly, no differ-
ences were found in another trial with
256 patients comparing electroacupunc-
ture (alone or in combination with
auricular acupuncture or moxibustion)
vs. selective serotonin reuptake inhibi-
tors (SSRIs). But in a meta-analysis,
combining data from two trials with
115 patients, electroacupuncture plus
moxibustion was associated with signifi-
cantly improved scores for PTSD symp-
toms, depression, and anxiety compared
to SSRIs. Only one RCT had a low risk
of bias. The two uncontrolled trials
reported improvement with acupuncture
in 4 90% of patients.
The results of this review suggest that
acupuncture may be at least as effective
as CBT and SSRIs in the management of
PTSD. Since all of the studies compared
acupuncture with either no treatment or
other forms of therapy, we cannot con-
clude anything about the efficacy of
acupuncture compared to a placebo.
The reliability of these results is further
diminished by the high risk of bias in
the uncontrolled trials and most of
the RCTs. Despite these limitations, a
trial of acupuncture may be worth con-
sidering for patients whose response
to conventional therapy has been disap-
pointing.
ADDITION OF NATUROPATHIC CARE
TO USUAL CARE MIGHT REDUCE
ESTIMATED CARDIOVASCULAR RISK
Level 3 [lacking direct] evidence
CMAJ 2013;185(9):E409–E416.
The practice of naturopathic medicine
is based on the principle of vis medicatrix
naturae, or nature's healing power. A
naturopath views disease largely as a
departure from the natural way of living
and, therefore, believes that the most
sensible way to restore health is to return
to nature. This underlying philosophy
manifests itself in a great variety of treat-
ment strategies, some of which are iden-
tical to current evidence-based recom-
mendations (e.g., eating a well-balanced
diet and exercising regularly). Where natur-
opathic medicine departs from conven-
tional medicine is in its emphasis on
dietary supplements (most notably herbs)
and its use of a variety of other interven-
tions intended, for example, to detoxify the
liver and support the immune and endo-
crine systems.
In this trial, researchers investigated the
effect of adjuvant naturopathic care on the
risk of cardiovascular disease in 246 high-
risk Canadian postal workers (total
cholesterol-to-HDL cholesterol ratio 4
1.8).6 Participants were randomized to
usual care (with a primary care physician)
plus seven sessions with a naturopathic
physician vs. usual care alone for one year.
Naturopathic care consisted of indi-
vidualized health promotion with diet
and lifestyle counseling during an initial
one-hour session followed by six 30-
minute sessions at work-site clinics, plus
nutritional medicine and/or dietary sup-
plementation. Differences in the rate of
metabolic syndrome (as defined by the
Adult Treatment Panel III recommenda-
tions7) and 10-year risk of cardiovascular
events (as determined by the Framing-
ham Heart Study algorithm8) were used
as primary outcomes. (An insufficient
number of actual cardiovascular events
precluded the use of this patient-
oriented outcome instead.) Thirty-nine
patients (16%) were lost to follow-up
and not included the analysis. Compar-
ing adjuvant naturopathic care vs. usual
care at one year (adjusted for non-
significant baseline differences), the rate
of metabolic syndrome was 31.6% vs.
48.5% (risk reduction [RR] 16.9% [95%
CI: 29.6% to 4.3%], NNT 6). The
386 EXPLORE November/December 2013, Vol. 9, No. 6
estimated 10-year cardiovascular event
risk was 7.7% vs. 10.8% (RR 3.1%
[95% CI 4.4 to 1.8%]).
This appears to be a seriously flawed
trial with no attention control, no alloca-
tion concealment, and non-standardized
treatments, among other risks of bias. It
should be noted that the researchers did
not set out to investigate what specific
aspects of naturopathic care would benefit
patients at high risk for cardiovascular
disease. Since we do not know what the
naturopathic physicians recommended to
their patients, we do not know whether
the observed benefits are unique to natur-
opathy. It is plausible that the same results
could have been obtained by having the
primary care physicians themselves make a
set of standardized recommendations
(based on naturopathic principles or not)
to one group and not the other. But even
if the results were the same, their real
world applicability would be question-
able. Primary care physicians cannot and
do not spend an additional four hours
with their patients at risk for cardiovascu-
lar disease. Naturopaths, on the other
hand, can and do. An interesting follow-
up study would be to directly compare the
benefits of primary allopathic vs. naturo-
pathic care in this patient population.
Although measuring cardiovascular events
would be far preferable to the surrogate
risk markers used in this trial, the necessary
size and duration of such a study would
be prohibitive.
HATHA YOGA THERAPY MAY BE
MORE EFFECTIVE THAN EXERCISE
THERAPY FOR OSTEOARTHRITIS OF
THE KNEE
Level 2 [mid-level] evidence
J Altern Complement Med 2012;18
(5):463–472.
Hatha yoga, a popular form of the
ancient Indian philosophy and practice,
is based principally on asanas, which are
characterized by the effortless mainte-
nance of postures by internal awareness.9
Like most styles of yoga, it also incor-
porates rhythmic breathing (pranayama),
relaxation techniques, and deep medi-
tation. A key management strategy for
patients with osteoarthritis of the lower
extremities is to improve muscle strength,
flexibility, range of motion, and coordina-
tion. There is evidence that exercise
Evidence-Based Integrative Medicine Updates
therapy can effectively achieve these
goals.10,11 Hatha yoga, which theoretically
can produce many of these effects, may
have the added benefit of promoting
adaptive joint positioning and suppressing
nociceptive pathways through meditation
and stress reduction.
To compare their relative benefits,
researchers randomized 250 Indian patients
between the ages 35 and 80 with knee
osteoarthritis to integrated hatha yoga vs.
exercise therapy.9 During a 15-day super-
vised phase, all patients received conven-
tional physiotherapy daily, consisting of
transcutaneous electrical nerve stimulation
(TENS) and ultrasound treatments fol-
lowed immediately by the yoga or exercise
interventions. Yoga therapy included
40 min of supervised strengthening and
loosening followed by asanas, relaxation
techniques with devotional singing, and
counseling on yoga philosophy. Exercise
therapy included 40 min of supervised
strengthening and loosening of all joints
followed by a brief rest period, specific
knee exercises, and further rest. Hatha
yoga and exercise therapy groups were
taught yoga and non-yoga exercises,
respectively, to do at home every day
for 12 weeks following completion of
the supervised phase. Compared to the
exercise group, the yoga group showed
significantly greater improvements in all
outcomes tested: walking pain, walking
time, knee flexion, clinical examination
(i.e., tenderness, swelling, and crepitus),
and knee disability score (WOMAC) on
days 15 and 90 (P o .001).
The strengths of this trial, compared
to previous yoga studies, include its
relatively large size, attention control,
and integration with physical therapy.
Although the attrition rate was low
(6%), it was not clear how these drop-
outs were handled and if differences
would be significant in a full intention-
to-treat analysis. Also, it is not possible
to determine what aspect of hatha yoga
produced the beneficial effects. Never-
theless, it is interesting and reasonable
to speculate that the added focus on
meditation and postural awareness pro-
moted an enhanced therapeutic effect.
While the favorable outcomes persisted
beyond the active treatment phase, fur-
ther studies are required to determine
long-term outcomes.
CHASTEBERRY MAY IMPROVE
SYMPTOMS IN WOMEN WITH PMS
Level 2 [mid-level] evidence
Phytomedicine 2012;19(14):1325–1331.
Premenstrual syndrome (PMS) regu-
larly affects up to 20% of menstruating
women.12 Symptoms occur during the
luteal phase of the menstrual cycle and
include irritability, mood alteration,
anger, bloating, headache, fatigue, and
breast pain (mastodynia). As the name
implies, fruit of the chasteberry tree
(Vitex agnus castus, VAC) has been used
for centuries to suppress sexual desire.
More recently, its most common use
has been for cyclic mastodynia and
other symptoms of PMS. While its
exact mechanism of action remains un-
known, there is evidence that VAC sup-
presses the release of pituitary prolactin.
However, additional mechanisms are
likely responsible for the full range of
its effects.13 In a previous trial, 178
women with premenstrual syndrome
were randomized to receive either the
VAC fruit extract ZE 440 (standardized
to casticin 20 mg) or placebo orally once
daily for three consecutive cycles.14
ZE 440 was associated with a greater
improvement from baseline (128.5 vs.
78.1 mm, P ¼ .001) using a visual
analog self-assessment score combining
six PMS symptom categories (irritability,
mood alteration, anger, headache, other
menstrual symptoms, including bloat-
ing, and breast fullness).
In the present study, 162 women
between the ages of 18 and 45 with
PMS were randomized into one of
four groups: placebo, 8-mg, 20-mg, or
30-mg extracts of ZE 440 taken orally
daily for three menstrual cycles. Based
on the same six-item visual analog scale,
mean differences from baseline were
32.5, 14.4, 211.1, and 190.3,
respectively.13 Compared to the 20-mg
dose, these differences were statistically
significant for placebo and the 8-mg
dose (P o .0001) but not for the 30-
mg dose (P ¼ .60). Defining response to
treatment as Z 50% reduction in total
symptom score, 11% of the placebo
group and 14% of the 8-mg group
responded (no significant difference).
In the 20-mg group, 81% responded (P
o .001 vs. placebo, P o .05 vs. 8 mg,
NNT 2 for both), and 61% responded in
the 30-mg group (P o .001 vs. placebo,
Evidence-Based Integrative Medicine Updates
NNT 2, not significant vs. 20 mg). These
treatment effects were no different in a
sub-analysis of women (23%) who were
taking oral contraceptives during the
study period. There were no serious
adverse effects in any group.
Although both trials were placebo
controlled, it is unclear if investigators
enrolling patients were blinded to
assignment on trial entry. Nevertheless,
their results suggest that a daily 20-mg
extract of VAC (standardized to casticin)
is effective for the relief of PMS symp-
toms. Increasing the dose to 30 mg adds
no benefit. These results are consistent
with two other trials from China sup-
porting the benefits of chasteberry for
this indication.15,16 Although mastody-
nia would be expected to respond to a
suppression of prolactin release, other,
as yet unidentified, mechanisms are
probably involved in the more global
improvements observed in PMS. Given
its safety and tolerability, it seems rea-
sonable to recommend ZE 440 20 mg
(or similar VCA product standardized to
casticin) to women with PMS who
experience inadequate relief from oral
contraceptives or who do not wish to
take them.
VITAMIN AND ANTIOXIDANT
SUPPLEMENTS DO NOT APPEAR TO
REDUCE RISK FOR CARDIOVASCULAR
DISEASE
Level 2 [mid-level] evidence
BMJ 2013;346:f10.
Preclinical studies have long supported
the theory that supplementation with vita-
mins and antioxidants inhibit the develop-
ment of atherosclerosis.17,18 According to
the oxidative modification model of athe-
rogenesis, the complete oxidation of accu-
mulated subendothelial low-density lipo-
protein (LDL) causes macrophages to
aggressively devour cholesterol, stimulates
the endothelial binding of monocytes, and
promotes lipid and liposomal enzyme
release.17 Increasing the endothelial con-
centration of antioxidants by dietary
supplementation theoretically decelerates
atherogenesis. Observational studies over
the past few decades have given credence
to this theory by consistently demon-
strating an association between higher
intake of antioxidant-rich fresh fruits
and vegetables and lower incidence
EXPLORE November/December 2013, Vol. 9, No. 6 387
of cardiovascular events.19 However, the
findings from numerous randomized con-
trolled trials investigating the clinical effi-
cacy of the antioxidant constituents of
these foods have been inconsistent.20
In the present meta-analysis, research-
ers set out to compile a single, compre-
hensive report on the efficacy of dietary
vitamin and antioxidant supplementa-
tion for preventing major cardiovascular
events.21 After evaluating all pertinent
randomized controlled trials from the
past 24 years, they ultimately included
50 studies with 294,478 patients
between the ages of 49 and 82.
Supplementation and follow-up periods
ranged from 6 months to 12 years. Of
the studies included, 30 were primary
prevention trials and 20 were secondary
prevention trials. Supplements included
vitamins A, B6, B12, C, D, E, β-carotene,
folic acid, and selenium. Methodologic
quality of the trails averaged 4.3 on the
Jadad scale (range 2–5). Outcomes
included cardiovascular death, fatal or
non-fatal myocardial infarction, angina,
sudden cardiac death, fatal or non-fatal
stroke, and transient ischemic attack.
In the overall analysis there was no
association between vitamin and antiox-
idant supplementation and risk of any
major cardiovascular event. The same
was true for subset analyses by type
of prevention (primary vs. secondary),
type of supplement (vitamin only,
antioxidant only, and singly or in com-
bination), methodologic quality (Jadad
r 4 vs. 5), duration of treatment
(o 5 vs. Z 5 years), funding source
(pharmaceutical industry vs. independ-
ent organization), supplement supplier
(pharmaceutical vs. non-pharmaceutical
industry), control (placebo vs. no pla-
cebo), and number of trial participants
(o 10,000 vs. Z 10,000). Low-dose
vitamin B6 (3–25 mg/day) slightly
decreased the risk of major cardiovascu-
lar events (relative risk [RR] 0.92, 95%
CI 0.85–0.99) in eight trials, but the
effect disappeared when the analysis was
restricted to five high-quality trials. Vita-
min B6 and vitamin E (any dose) were
associated with lower risk of cardiovas-
cular death (eight trials, RR 0.91, 95%
CI 0.83–0.99) and myocardial infarction
(12 trials, RR 0.77, 95% CI 0.65–0.91),
respectively. Both of these effects dis-
appeared, however, when the analysis
was restricted to non-industry-support-
ed trials. High-dose vitamin A (25,000 IU
daily) increased the risk of major cardio-
vascular events in one trial (RR 1.41, 95%
CI 1.15–1.73).
It is clear, based on the results of this
meta-analysis, that vitamin and antiox-
idant supplementation has no effect on
major cardiovascular outcomes in men
and women who are 49 to 82 years old
and should not be recommended for
this purpose. The discrepancy between
the findings from clinical trials vs. pre-
clinical and observational studies has at
least two possible explanations.21 First,
the cardiovascular effects of these
substances depend on their interaction
with numerous other nutrients in fresh
fruits and vegetables and lose their
beneficial effects when administered in
isolation. Second, for these supplements
to be helpful they must be administered
at the earliest stages of atherogenesis
(say, prior to the age of 40 years).
Importantly, vitamin and antioxidant
supplementation may not be without
risk. Although this systematic review did
not find an increase risk in mortality,
other studies have. In a Cochrane review
of 78 randomized trials (N ¼ 296,707), an
increase in mortality was found in
subgroup analyses of high-quality trials
for vitamin E and β-carotene.22 The
authors theorized that enhanced anti-
oxidation may interfere with critical
defense mechanisms, such as apoptosis,
phagocytosis, and detoxification.
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Richard Glickman-Simon, MD, is a
family physician, Integrative Medicine
Editor of DynaMed, and Assistant Pro-
fessor of Public Health and Community
Medicine at Tufts University School of
Medicine in Boston, MA, and a con-
tributor to DynaMed in Ipswich, MA.
Brian S. Alper, MD, MPSH, FAAFP,
is a family physician, Editor-in-Chief of
DynaMed and Medical Director for
EBSCO Publishing, Inc.