Estimated Effects of Whole-system Naturopathic Medicine in Select Chronic Disease Conditions: A Systematic Review

Abstract

Background: Naturopathic medicine (NM) is a holistic approach to primary care that almost always employs
multi-modal interventions, i.e. nutrition and lifestyle change recommendations plus dietary supplements. While
evidence supports individual elements of NM, the whole practice is often critiqued for its lack of evidence.

Methods: We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, Cochrane Library and AMED
from inception to April, 2012 as well as conducting hand searches of existing grey literature. For inclusion, studies had to report results from multi-modal treatment delivered by North American naturopathic doctors. The effect size for each study was calculated; no pooled analysis was undertaken. Risk of bias was assessed using the Cochrane risk of bias as well as Downs and Black tools.

Results: Fifteen studies met inclusion criteria, investigating a range of chronic diseases of public health
significance. Studies were of good quality and had low to medium risk of bias including acknowledged limitations of pragmatic trials. Effect sizes (Cohen's d ) for the primary medical outcomes varied and were statistically significant (p<0.05) in 10 out of 13 studies. A quality of life metric was included in all of the randomized controlled trials with medium effect size and statistical significance in some subscales.

Conclusions: Previous reports about the lack of evidence or benefit of NM are inaccurate; a small but compelling body of research exists. Further investigation is warranted into the effectiveness of whole practice NM for across a range of health conditions. [PROSPERO 2012:CRD42012002176]

Full text

Estimated Effects of Whole-system Naturopathic Medicine in Select Chronic
Disease Conditions: A Systematic Review
Erica B. Oberg*, Ryan Bradley, Kieran Cooley, Heidi Fritz, Joshua Z. Goldenberg, Dugald Seely, Jane D. Saxton and Carlo Calabrese
Pacific Pearl La Jolla, San Diego, CA 92037, USA
*Corresponding author: Erica B. Oberg, Professor, Pacific Pearl La Jolla, San Diego, CA 92037, USA, Tel: 8584596919; E-mail: erica.oberg@icloud.com
Received date: March 25, 2015, Accepted date: April 21, 2015, Published date: April 24, 2015
Copyright: © 2015 Oberg EB, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Naturopathic medicine (NM) is a holistic approach to primary care that almost always employs
multi-modal interventions, i.e. nutrition and lifestyle change recommendations plus dietary supplements. While
evidence supports individual elements of NM, the whole practice is often critiqued for its lack of evidence.
Methods: We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, Cochrane Library and AMED
from inception to April, 2012 as well as conducting hand searches of existing grey literature. For inclusion, studies
had to report results from multi-modal treatment delivered by North American naturopathic doctors. The effect size
for each study was calculated; no pooled analysis was undertaken. Risk of bias was assessed using the Cochrane
risk of bias as well as Downs and Black tools.
Results: Fifteen studies met inclusion criteria, investigating a range of chronic diseases of public health
significance. Studies were of good quality and had low to medium risk of bias including acknowledged limitations of
pragmatic trials. Effect sizes (Cohen's d ) for the primary medical outcomes varied and were statistically significant
(p<0.05) in 10 out of 13 studies. A quality of life metric was included in all of the randomized controlled trials with
medium effect size and statistical significance in some subscales.
Conclusions: Previous reports about the lack of evidence or benefit of NM are inaccurate; a small but compelling
body of research exists. Further investigation is warranted into the effectiveness of whole practice NM for across a
range of health conditions. [PROSPERO 2012:CRD42012002176]
Keywords: Cardiovascular disease; Chronic disease; Complementary
and alternative medicine (CAM); Diabetes; Mental health;
Naturopathic medicine; Pain; Pragmatic trial; Quality of life;
Randomized controlled trial; Systematic review; Whole-systems
research
Introduction
The burden of chronic disease on the healthcare system is well
established. Estimates are that 44% of Americans (133 million people)
suffer from at least one chronic disease, while 13% (63 million) suffer
from three or more [1,2]. These numbers are rising, and it is estimated
that by 2020, 157 million Americans will have at least one chronic
disease, while a staggering 81 million are expected to have multiple
chronic conditions, with the most common being hypertension,
hyperlipidemia, diabetes, heart failure, arthritis, and cancer [1,3]. To
take the example of type 2 diabetes, coined as the “the epidemic of the
21st century” [4], approximately 24 million Americans are currently
affected, and this number is expected to double in the next 25 years
[1]. According to the American Diabetes Association, “people
diagnosed with diabetes incur average medical expenditures of about
$13,700 per year, of which $7,900 is attributable to diabetes” [5].
A second disease of epidemic proportions, cardiovascular disease
(CVD) currently affects 83.6 million Americans (greater than one in
three people): 77.9 million have hypertension, and 15.4 million have
coronary heart disease [6]. By 2030, over 40% of the American
population is expected to have some form of CVD [6]. In 2009, 1/6th
of all hospital stays in the US (six million) were attributable to CVD;
the direct cost associated with this was $71.2 billion dollars [6]. Direct
and indirect costs of CVD were $312 billion, and this is expected to
rise to $1.48 trillion dollars by 2030 [6]. When considering the sum of
healthcare expenditure, 75% of all healthcare costs in the US
(equivalent to $1.7 trillion dollars annually) are attributable to chronic
disease [1,3]. It is clear that new solutions are needed, including a
greater emphasis on multidisciplinary, prevention oriented care [2].
Between 2002 and 2005, the Naturopathic Medical Research
Agenda (NMRA) formalized the focus of a research mission for
naturopathic medicine (NM), as practiced in North America. The
NMRA envisioned a pathway for the development of research focused
on evaluating outcomes from naturopathic practice assessed by
applying appropriate “whole practice” methodologies within
pragmatic clinical settings [7]. Parallel to establishing the NMRA, in
By linking the care people get to the outcomes they experience,
clinical outcomes research has become a key to developing better ways
to monitor and improve the quality of care, naturopathic and
otherwise. The limitations of classical medical research designs, such
as the single agent placebo-controlled randomized clinical trial, have
become well-appreciated, especially as they relate to CAM research
[9-12]. Alternative methods, such as patient-centered outcomes
research and the inclusion of metrics that assess quality of life (QOL)
have become increasingly prioritized in research, as exemplified by
Alternative & Integrative
Medicine Oberg, et al., Altern Integ Med 2015, 4:2
http://dx.doi.org/10.4172/2327-5162.1000192
Review Article Open access
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ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

program announcements from the Patient-Centered Outcomes
Research Institute, created under Section 6301 of the Affordable Care
Act of 2010 [13]. Thus, “whole practice” research has emerged as a
strong, valid and relevant methodology to investigate naturopathic
medicine, as well as other multi-modal practices [9].
Standard research methodology designed to test the null hypothesis
often does not specifically examine the magnitude of the effect, nor the
precision around the magnitude of the effect. For clinical questions,
this is critical information since clinicians must be able to evaluate the
relative importance or impact a given therapeutic approach may have
on their patient population, not simply the statistical significance. In
whole systems research, the magnitude of the effect, or the effect size,
of the multi-component intervention may be most appropriate. Meta-
analysis of effect sizes allows for an examination of the clinical
significance of both specific and non-specific effects of a treatment in
comparison to control. Here we report effect size, calculated as a
standard mean difference (Cohen’s d), for all studies in which data
were available (two were missing data required to calculate an effect
size). The standardized mean difference provides a less heterogeneous
metric of the magnitude of the effect of whole-practice naturopathic
medicine and the precision around the range of probable effect size of
the multi-modal naturopathic approach in a given condition or
disease.
The research base describing practice outcomes from NM in health
and disease is typically assumed to be limited [14]. However, in the
domain of patient-centered research, the field of NM has been in the
vanguard, defining its priorities in patient-reported outcomes research
before well-established nomenclature (and avenues for funding) came
into fashion. The purpose of this review was to compile and
consolidate research that has investigated the whole practice of
naturopathic medicine as it is practiced in community settings in
order to better assess the quantity and quality of the research, and
clinical effect, if any.
Methods
Definition of naturopathic medicine
Naturopathic medicine is a distinct primary health care profession,
emphasizing prevention, treatment and optimal health through the use
of therapeutic methods prescribed according to a therapeutic order
which encourage the inherent self-healing process of the body [15].
Clinical practice focuses on the patient as a whole person, and
addresses physical, mental, emotional, spiritual, and environmental
dimensions of health concurrently to promote healing. Naturopathic
doctors (NDs) in Canada and the United States receive training to a
common standard as defined by the Council on Naturopathic Medical
Education (CNME) [15]. Graduates from accredited schools are
eligible for licensing in 17 states, two US territories, the District of
Columbia, and five provinces in Canada. Scope of practice and
training standards differ from practitioners called naturopaths in
Australia, New Zealand, and European and other countries; thus, for
purposes of this review, we limited research to investigations of North
American naturopathic practice.
Identification of eligible studies
In April 2012, a comprehensive search was conducted in the
PubMed/MEDLINE database (1946-2012) to locate studies pertaining
to North American licensed naturopathic medicine with patient-
reported, clinical, and/or cost outcomes. The search included both
controlled vocabulary (MeSH) terms, e.g. Naturopathy and Treatment
Outcome, and natural language words and phrases, e.g. naturopathic
medicine and whole practice. The PubMed/MEDLINE search query
was then “translated” and the following electronic databases were
searched according to their specific conventions: EMBASE
(1966-2012), CINAHL with Full Text (1982-2011), the Cochrane
Library (1966-2012), and AMED (1985-2012). A language filter was
applied limiting citations to English, French and Spanish to reflect the
emphasis on naturopathic medicine as practiced in North America.
No other filters were used, in order to increase search sensitivity.
Additionally, conference proceedings of the American Association of
Naturopathic Physicians (AANP) and Canadian Association of
Naturopathic Doctors (CAND) were scanned for relevant abstracts.
Hand searches of the following journals were conducted: Journal of
Naturopathic Medicine (1990-2000); International Journal of
Naturopathic Medicine (2004-2012; online archive searched); Journal
of Orthomolecular Medicine (1990-2012); Townsend Letter
(1990-2012) as well as grey literature in the form of reference sections
and citations to those studies that met inclusion criteria. The
systematic review, including inclusion criteria, preliminary and final
search strings, were preregistered with PROSPERO [PROSPERO
2012:CRD42012002176] [16].
Study selection
In accordance with PRISMA guidelines [17], two reviewers
independently reviewed the search results to select studies that met
inclusion criteria. To be included, studies had to be longitudinal
clinical studies reporting longitudinal outcomes, in which North
American licensed naturopathic doctors managed clinical conditions
employing their full scope of practice. Observational and randomized
clinical trials (RCTs) were included if they were consistent with whole
practice (i.e. the naturopathic intervention consisted of at least two
different treatment modalities).
Data abstraction
Data abstraction was conducted in duplicate (CC, DS), using
piloted data extraction sheets. The following data items were extracted:
study setting; study population, participant demographics and baseline
characteristics; details of the intervention and control conditions;
study methodology: recruitment and study completion rates;
outcomes and times of measurement; indicators of acceptability to
users; suggested mechanisms of intervention action; information of
assessment of the risk of bias; information on or to calculate effect size.
In the event that data was missing or unclear, a request for
information was sent to the original investigators. Author assessment
took place independently with disagreements being resolved by
consensus.
Methodological assessment and quality rating
Two authors (KC, JG) independently assessed each randomized
controlled trial for risk of bias using the Cochrane risk of bias tool
[18]. The use of the risk of bias tool is explained in detail elsewhere
[19] and includes assessment of the following domains: sequence
generation, allocation concealment, blinding of participants and
personnel, blinding of outcome assessors, incomplete outcome data,
selective outcome reporting, and other sources of bias (e.g.
distribution of baseline characteristics, industry initiation and
funding). The same two authors also used the Downs & Black checklist
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 2 of 10
Altern Integ Med
ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

as a second critical appraisal tool for methodological quality of the
studies included in the review [20]. This 28-item checklist is
appropriate for both randomized and non-randomized studies,
quantifying an overall score (out of 28; higher scores indicate greater
methodological rigor) as well as domain-specific scores for reporting
(11), external validity (3), internal validity (bias) (7), internal validity
(confounding) (6) and power (1). Author assessment took place
independently with disagreements being resolved by consensus.
Assessment of clinical outcomes and effect size
Primary outcome measures, as defined by the investigators of the
original research, as well as quality of life metrics, such as the SF-36,
were abstracted from reported results with the intention to compare
and pool effect sizes using forest plots and standard methods for meta-
analyses. When necessary, communication with authors provided
missing data such as standard deviations. The heterogeneity of the
studies we reviewed warranted use of a statistic that could be applied
to summarize results of various study designs. Standardized mean
differences were calculated for each study for the between group
differences in the author-specified primary outcome [19,21]. For
measures of quality of life, standardized mean differences were
calculated for summary scores in physical, mental, and general health
when available.
Using pooled variances for the standard deviations in point
estimates of active and control group outcomes, Cohen’s d effect sizes
were computed. When interpreting Cohen's d values, an effect size of
0.2 to 0.3 is considered a "small" effect, whereas around 0.5 is
considered a "medium" effect and 0.8 or greater is considered a "large"
effect [22].
Though other measures such as Glass’s ∆ or Hedge’s g can be used
to calculate effect size, Cohen’s d was selected based on popular use
and that the calculation accounts for variance in non-specific effects
seen in both the intervention and control group. This calculation
results in a conservative effect size, weighted to maximize the impact
of the control group and minimize the impact of the intervention
group. Study heterogeneity (I2) was calculated and due to significantly
different treatment populations and a large initial I2, the studies were
not pooled for analysis.
Results
The PubMed/MEDLINE search string provided 1,257 total citations
before removing duplicates. After 329 duplicates were removed, 931
citations were reviewed for inclusion. The final selection yielded 12
qualifying clinical studies, one of which had a cost-effectiveness
analysis associated with the primary trial results. Results from hand
searching added two additional studies: a more recently published
randomized controlled trial (RCT) & companion cost-effectiveness
analysis (CEA). In total, 15 studies of whole practice naturopathic
medicine were included [23-37]. Figure 1 shows the literature
flowchart.
Figure 1: Literature flowchart.
Of the five retrospective studies, one included a control group [35].
Two studies were prospective observational cohort studies, of which
one was comparative to an electronically created usual care control
group [24], and one made comparisons to other forms of CAM [34].
Six of the studies were randomized controlled trials (RCTs) with usual
care comparators [23,27-30,32], although one made comparisons to
other forms of CAM as well [30].
Two cost-effectiveness analyses were identified which used data
from two of the included RCTs [31,37]. All studies were in chronic
disease conditions; six evaluated outcomes in diabetes or
cardiovascular disease [23-25,28,33,37], five in musculoskeletal or pain
conditions [26,30-32,34], and four studies were in other conditions
[27,29,35,36]. Summaries of the included studies are in Table 1
[23-37].
Authors Condition N Design (and comparator) Primary Outcome Patient-Reported
outcome
Seely [23] Cardiovascular disease 246 RCT
(enhanced UC)
Framingham risk score,
prevalent metabolic syndrome
SF-36
Bradley [24] Diabetes 40 Prospective observational with
controls
(UC, electronically matched from
EHR)
HbA1c, SDSCA PHQ-8
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 3 of 10
Altern Integ Med
ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

Bradley [25] Hypertension 85 Retrospective cohort Blood pressure (mm Hg
systolic)
N/A
Szczurko [26] Rotator Cuff Tendinitis 85 RCT
(physical exercise active control)
SPADI SF-36
Bradley [28] Diabetes 37 Retrospective cohort HbA1c, lipids, blood pressure N/A
Cooley [27] Anxiety 75 RCT
(psychotherapy, matched breathing
exercise, and placebo)
Beck Anxiety Inventory SF-36
Shinto [29] Multiple Sclerosis 45 3 arm RCT
(UC and UC+education)
Modified Fatigue Impact Scale SF-36
Ritenbaugh [30] TMJ 160 3 arm RCT
(UC and TCM)
Worst/average score of facial
pain
Effect of pain on ADLs,
social activities
Szczurko [32] Chronic Low Back Pain 75 RCT
(physiotherapy instruction, breathing
exercise, and home exercise
booklet)
Oswestry questionnaire SF-36
Bradley [33] Diabetes 16 Retrospective cohort % HbA1c, % making glycemic
improvement
N/A
Secor [34] Pain 94 3 arm prospective observational
(acupuncture, chiropractic)
Pain VAS SF-12
Cramer [35] Menopausal symptoms 239 Retrospective cohort with controls
(UC, electronically matched in EHR)
% with improvement in 7
symptoms
N/A
Milliman [36] Hepatitis C 41 Consecutive case series ALT N/A
Herman [31] Low back pain (Szczurko) 75 Cost-effectiveness analysis QALYs, societal health costs N/A
Herman [37] Cardiovascular disease
(Seely)
246 Cost-effectiveness analysis QALYs, societal health costs N/A
NOTE:
ADLs: Activities of Daily Living; ALT: Alanine Transaminase; HbA1c: Hemoglobin A1C; PHQ-8: Patient Health Questionnaire; QALYs: Quality Adjusted Life Years;
RCT: Randomized Controlled Trial; SDSCA: Summary of Diabetes Self Care Activities Assessment Scale; SF-36: Short Form-36 and 12; SPADI: Shoulder Pain and
Disability Index; TMJ: Temporomandibular Joint disorders; TCM: Traditional Chinese Medicine; UC: Usual Care (biomedical care by MD/DO/NP); VAS Visual Analog
Scale
Table 1: Characteristics of studies assessing whole system naturopathic medicine.
Study quality and risk of bias
In general, the RCTs included in this review were assessed as having
a low risk of bias on most domains and were clearly reported.
However, none of the included trials were blinded, a recognized
impracticality in whole systems research [10].
Because of this limitation, as well as missing outcome data in some
trials, the assessment of the overall risk of a biased effect estimate was
high in all but one trial. Methodological rigor, as quantified by the
Downs and Black checklist, varied among the studies, with higher
rigor demonstrated by randomized controlled trials and in the more
recent studies; see Figures 2 and 3 and further detail.
Figure 2: Risk of bias of included studies, individually.
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 4 of 10
Altern Integ Med
ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

Figure 3: Risk of bias of included studies, collectively.
Cardiometabolic disease (Cardiovascular disease, diabetes,
hypertension, metabolic syndrome):
Cardiometabolic disease
represents one of the leading public health concerns in the United
States, and the majority of studies of whole practice naturopathic
medicine focused on these conditions. Bradley et al. conducted three
observational studies in diabetes and one in hypertension [24,25,28,33]
and Seely et al. conducted a pragmatic RCT and economic evaluation
[23,37]. In the first retrospective evaluation of diabetes care, glycemic
control and other risk factors improved during receipt of naturopathic
care [33].
Primary clinical outcomes
Studies reported results in comparison to usual care controls or
other CAM modalities, or reported differences between treatment
groups, typically reporting mean changes and p values. To address the
heterogeneity amongst the studies and the need to assess the
magnitude of the observed effects systematically, we calculated effect
sizes for each study, which are presented in Figure 4 for primary
outcomes. No adverse events were reported.
Figure 4: Effect size estimates for primary outcomes.
Rates of health promotion delivery were substantially higher than
national primary care averages. Evidence-based therapeutic lifestyle
change recommendations (dietary) were made for 100% of patients,
and 94% of patients were prescribed exercise. 69% of patients received
counseling regarding stress reduction techniques. In the second
retrospective evaluation of diabetes care, observations of clinical
outcomes following a mean 27 month duration of care demonstrated
the following significant mean changes in clinical risk factors: -0.65%
for HbA1c (p=0.046), -45 mg/dL for triglyceride (TAG) (p=0.037), -7
mm Hg in Systolic Blood Pressure (SBP) (p=0.02), and -5 mm Hg in
Diastolic Blood Pressure (DBP) (p=0.003) [28]. Mean changes in total
cholesterol did not reach statistical significance. Three unique
dichotomous outcomes were reported for this study: the percentage of
patients who achieved new control (i.e. had not achieved control or
within normal limits after diagnosis but prior to the study), had
clinically significant risk factor improvements, or had any
improvement. For HbA1c, the percent reaching new control was 26%,
42% had clinically significant improvements in risk factors, and 68%
had any improvement. Respectively, percent of patients achieving
these outcomes were LDL,7%, 28%, and 62% for LDL; 0%, 25%, and
39% for HDL; 14%, 38%, and 52% for TAG; 16%, 51%, and 86% for
SBP; and 27%, 54%, and 70% for DBP. In the most recent study, a
prospective observational cohort study conducted within a large health
maintenance organization, a mean HbA1c decrease of -0.90% (P=0.02)
was observed [24]. This was a -0.51% mean difference compared to
usual care (P=0.07), following six-months of care. Significant
improvements were found in most patient-reported measures,
including glucose testing (P=0.001), healthy dietary behaviors
(P=0.001), increased physical activity (P=0.02), improved mood
(P=0.001), increased self-efficacy (P=0.0001) and increased motivation
to change lifestyle (P=0.003).
In the 2011 retrospective evaluation of hypertension (HTN)
outcomes, Bradley et al. found that patients with both stage 1 and stage
2 HTN had blood pressure reductions during receipt of naturopathic
care, with stage 2 patients achieving mean reductions of 26 mmHg
(P<0.0001) and 11 mmHg (P<0.0001) in systolic BP (SBP) and
diastolic BP (DBP), respectively. The proportion of patients with
resolution of hypertension, defined as BP less than <140/90 mmHg,
was 33% (P<0.033) [25].
In 2013, Seely et al. reported results of an RCT comparing the
addition of naturopathic treatment to community based usual care by
a general practice medical doctor (GP) alone [23]. Composite
reduction in cardiovascular disease risk as measured by Framingham
risk scores demonstrated that the group receiving naturopathic care in
addition to usual care experienced a 3.6% favorable difference in risk
compared to usual care alone (NNT=30 for 10 year event risk). This
absolute risk reduction was the equivalent to seeing a risk reduction of
becoming 5.5 years “younger in CV years.” A 27% absolute reduction
in the prevalence of metabolic syndrome was also observed in the
naturopathic care arm. A cost effectiveness analysis also accompanied
this trial [37]. Of the 246 employees who consented to the trial, two-
thirds gave consent to make available their claims and sick leave data.
There were no statistically-significant differences between those who
did and did not give this consent across baseline characteristics,
outcomes, or tendency to miss study visits. The measured risk
reductions came with an average net savings of $1138 in societal costs
and $1187 in employer costs. There was no change in quality-adjusted
life-years across the study year.
Pain
The studies summarizing naturopathic treatment of pain
syndromes cover a wide range of conditions. Pain is among the top
five reasons patients seek medical attention [38]. In the study by Secor
et al., data obtained from an electronic outcome measures data
management system at an integrative pain clinic found significant
improvements in pain scores and quality of life measures [34]. Patients
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 5 of 10
Altern Integ Med
ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

who received naturopathic care experienced the greatest pain
reductions (60%, p ≤ 0.0001); however, the chiropractic and
acupuncture treatment groups also experienced statistically significant
pain reductions of 34% and 52% respectively.
A three-armed randomized controlled trial of naturopathy (NM),
traditional Chinese medicine (TCM), or standard care (SC) for
temporal mandibular jaw pain was undertaken in a large health
maintenance organization in Portland [30]. TCM and NM both
demonstrated significantly greater in-treatment reductions for worst
facial pain compared to SC; reductions for NM versus SC were greatest
(p=0.019).
In the RCT by Szczurko et al. investigating rotator cuff tendinitis,
pain scores decreased by 54.5% (P<0.0001) in the NM group and by
18% (P=0.0241) in the comparison group which received physical
therapy exercise recommendations [26]. The same team’s 2007 RCT of
naturopathic vs. standard physiotherapy for chronic low back pain
also found significant benefits in the naturopathic treatment group
(-6.89, 95% CI. -9.23 to -3.54, p=<0.0001) as measured by the
Oswestry questionnaire. An additional finding of this trial included a
0.5 kg/m2 reduction in Body Mass Index (BMI) (p=0.01).
Other chronic conditions
The remaining studies investigated other chronic conditions:
multiple sclerosis, hepatitis C, anxiety, and menopausal symptoms.
The 2008 RCT by Shinto et al. investigated outcomes in multiple
sclerosis [29]. Three intervention arms were defined: usual care,
naturopathic medicine plus usual care, and MS education plus usual
care. While there were no significant differences between groups on
any outcome measure, there was a trend favoring the naturopathic
group in the General Health subscale of the SF-36 (p=0.11), Timed
Walk (p=0.11), and neurologic impairment (EDSS) (p=0.07). In 2009,
Cooley et al. randomized people with anxiety to receive naturopathic
care or psychotherapy over a six week period [27]. Beck Anxiety
Inventory scores decreased significantly in the naturopathic group
compared to the psychotherapy group (p=0.003). Significant
differences between groups were also observed in mental health,
concentration, fatigue, social functioning, and vitality. In a
retrospective study of menopausal symptoms, management by both
naturopathic and conventional primary care physicians in a
community health clinic was compared [35]. Multivariate analyses
found that patients treated with NM were approximately seven times
more likely than conventionally treated patients to report
improvements for insomnia (odds ratio [OR], 6.77; 95% confidence
interval [CI], 1.71, 26.63) and decreased energy (OR, 6.55; 95% CI,
0.96, 44.74). NM patients also reported improvements for anxiety (OR,
1.27; 95% CI, 0.63, 2.56), hot flashes (OR, 1.40; 95% CI, 0.68, 2.88),
menstrual changes (OR, 0.98; 95% CI, 0.43, 2.24), and vaginal dryness
(OR, 0.91; 95% CI, 0.21, 3.96) about as frequently as patients who were
treated conventionally. Finally, in 2003, Milliman et al. reported
retrospective outcomes of naturopathic treatment of Hepatitis C [36].
A statistically significant reduction in alanine transaminase (ALT), the
primary liver enzyme, was reported.
Quality of life outcomes
Amongst the RCTs and prospective observational studies evaluated,
all but one included a quality of life outcome measure as well as a
disease-centered metric [23-29,32-36]. The outlier did assess the
impact of the disease state (TMJ) on social function and activities of
daily living [30]. Effect size estimates for quality life outcomes are
summarized in Figure 5.
Figure 5: Effect size estimates for quality of life.
The SF-36 was the most common quality of life measure used (five
RCTs), however the SF-12, PHQ-8 (a depression score), and a rating of
the impact of facial pain on social functioning were also used. All eight
studies using these instruments showed improvements with NM, with
a majority demonstrating a medium effect size and statistical
significance in some scales. In the evaluation of cardiometabolic risk
reduction by Seely et al., improvements between groups were seen in
all domains of the SF-36, but these did not reach statistical significance
and the effect size was relatively small (<0.2) [23]. Bradley et al. found
improved mood (as measured by PHQ-8) in the NM group at 6 and 12
months as compared to usual care (p=0.001, and 0.005, respectively)
[24]. In their study of rotator cuff tendonitis, Szczurko et al. found
statistically significant between-group differences in all SF-36
subscales; the aggregate mental and physical components
demonstrated a 5.73 and 5.71 point difference respectively, favoring
the NM group (p=0.01, p=0.0004 respectively) [26]. Effect size
estimates were medium to small (0.39 to 0.28). In the same team’s low
back pain trial, QOL improved 7.0 (mental) and 8.47 (physical) points
between groups (p-0.004 and <0.0001, respectively) [32]. Effect sizes
were medium (0.33 for the aggregate mental component, 0.56 for the
aggregate physical component). In the study by Ritenbaugh et al.
measuring TMD-related psychosocial interference, NM provided
significantly greater decreases than standard care or TCM (p ≤ 0.02)
with medium effect (0.5) [30]. In the comparison of NM to other CAM
modalities by Secor et al., the effect size of the general health score of
the SF-36 had a large effect (0.77), with the actual differences also
reaching statistical significance (p<0.001). Cooley et al. found
significant differences between groups for mental health,
concentration, fatigue, social functioning, vitality, and overall quality
of life, with the NC group exhibiting greater clinical benefit [27]. Effect
sizes were 0.21 for aggregate physical functioning, 0.44 for aggregate
mental functioning and 0.41 for general health QOL. Finally, in the
study of patients with multiple sclerosis by Shinto et al., while
thresholds for statistical significance were not reached, effect sizes
were large (0.79 for mental health) possibly due to the generally poor
QOL in this patient population [29].
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 6 of 10
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ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

Cost outcomes
Two cost-effectiveness analyses (CEAs) were performed in
conjunction with two of the clinical trials [31,37]. Both trials recruited
from a population of Canadian postal workers and had access to the
same employment data. Both CEAs revealed societal and employer
savings associated with use of NM. In one study, naturopathic
treatment of LBP showed participant savings and significant benefit in
quality-adjusted life years [31]. The cost-effectiveness analysis found
that patients randomized to the naturopathic group improved their
health status by the equivalent to 9.4 "perfect health" days over the
three-month study period. In addition, naturopathic care significantly
reduced societal costs by $1212 per participant. From the perspective
of the employer, the intervention cost $154 per absentee day avoided.
This compares favorably to employer cost of lost productivity of $172
per day, translating into a return on investment of 7.9% under the
healthcare coverage limits set by this employer, assuming the employer
paid the full cost of naturopathic care. Participants experienced
savings related to lower expenditures on additional care of $1096 per
participant [31].
Discussion
While the sample sizes of many of the studies are small, the results
of this meta-analysis indicate that receiving whole-system
naturopathic medicine as practiced in North America is associated
with improved health outcomes, as well as improved quality of life, in
patients with or at risk for chronic conditions, including
cardiovascular disease, diabetes, chronic pain, anxiety, multiple
sclerosis, hepatitis C, as well as menopausal symptoms. Although cost-
effectiveness data are limited on naturopathic medicine in the context
of chronic disease, the data thus far suggest the use of NM results in
cost savings to employers as well as reductions in societal costs. This is
especially relevant in the current era when healthcare resources are
increasingly consumed by the management of chronic diseases and
associated complications. Additional demonstrations and evaluations
of licensed North American naturopathic doctors are warranted to
enhance current strategies and improve health outcomes and should
focus on diverse healthcare environments in generalizable
populations.
Primary outcomes, patient-centered outcomes
The primary outcomes that were assessed and that showed
improvement with the short-term use of NM were: reduced prevalence
of metabolic syndrome by 16.9% compared to usual care [23];
improvements in glycemic control (reduced HbA1c), reductions in
blood pressure (systolic and diastolic blood pressure reductions up to
26 and 11 mmHg respectively) [24,25,28]; improvement in anxiety
(>50% reduction compared to active psychotherapy controls) [27];
reduced pain severity (>50% reductions in chronic low back pain and
rotator cuff tendonitis compared to active physiotherapy controls)
[26,32], and improvement in the pain of temporomandibular
syndrome (TMJ) and other body pain compared to controls receiving
other complementary modalities [30,34]. Although not statistically
significant, point estimates of effect also suggest improvement in
fatigue, neurologic, and cognitive impairment associated with multiple
sclerosis compared to enhanced usual care [29], menopausal
symptoms when compared to usual care [35], as well as ALT levels in
hepatitis C patients [36]. For quality of life, patients treated with multi-
modal interventions by naturopathic doctors showed small to
moderate improvements in overall QOL scores as well as for physical
function and mental function [26,32], and specific symptoms such as
psychosocial interference [30], mental health, concentration, fatigue,
social functioning, and vitality [27]. No adverse effects were reported
in any of the studies. When considered collectively, the results of our
study suggest that the care delivered by naturopathic doctors improves
the health outcomes of patients affected by chronic disease, as
measured by both clinical and patient-reported outcomes, as well as
reduces direct and indirect costs.
Characterizing the NM intervention
Naturopathic doctors employ a diverse toolkit of treatment
modalities which are selected based on the therapeutic order and
emphasize healthy lifestyle choices and minimally invasive treatments.
Details of the specific modalities used in each intervention can be
found in the original studies and summarized in Table 1. In summary,
the naturopathic interventions included diet counseling and
nutritional recommendations, specific home exercises and physical
activity recommendations, deep breathing techniques or other stress
reduction strategies, dietary supplements including vitamins,
hydrotherapy, soft-tissue manual techniques, electrical muscle
stimulation, and botanical medicines. None of the studies included
pharmaceutical agents even though these are sometimes part of
naturopathic practice.
As a multi-modal system emphasizing diet and lifestyle
interventions, outcomes of naturopathic medicine can be compared to
other behavioral change research. For instance, a Scandinavian study
with a very similar inclusion criteria had outcomes of similar effect on
cardiovascular disease risk factors such as adiposity and blood
pressure [39-41]. In studies based on the Diabetes Prevention Program
protocol, intensive lifestyle modification reduced waist circumference
-1.9 cm (-2.80 to -0.90), and diastolic blood pressure -2.3 mmHg (-4.04
to -0.51) compared to the control group [39,40]. In Seely 2013, the NM
intervention reduced systolic (mean -6.55 mmHg, 95% CI -9.70 to
-3.42) and diastolic (-3.33 mmHg, -5.92 to -0.75) blood pressure [23],
improved lipids; LDL (-0.01 mmol/L, -0.28 to 0.25) and the ratio of
total cholesterol to HDL (-0.79 points, 95% CI -1.24 to -0.35) [23].
For diabetes management, the Look AHEAD trial provides a
relevant lifestyle change comparator. In the Look AHEAD trial, the
intensive lifestyle intervention achieved improvements in HbA1c level
(-0.36%), systolic (-5.33 mmHg) and diastolic (-2.92 mm Hg) blood
pressure, HDL (3.67) and triglycerides (-25.56) compared to baseline
values [42]. Similarly naturopathic care (Bradley 2009) improved
HbA1c by -0.65%, triglycerides by -45 mg/dL, as well as systolic (-7
mmHg), and diastolic (-5 mmHg) blood pressure compared to
baseline [28]. And in Bradley 2012, mean HbA1c was reduced by
-0.90% (p=0.02) with naturopathic care, a -0.51% HbA1c difference
compared to usual care [24].
Impact of comparators
As a multi-modal system, naturopathic medicine is inherently
difficult to evaluate using the single-agent placebo-controlled model.
In the real world of clinical practice (independent of discipline),
interventions are typically utilized in combination and patients are not
blinded, are unlikely to be representative of a narrowly defined disease
group, often present with co-morbidities, and typically receive other
forms of care. No randomized, placebo-controlled trial is able to
recruit these heterogeneous participant samples, nor mimic real world
clinical settings. Therefore, objective evaluations of “whole practice”
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 7 of 10
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ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

outcomes and the conduct of pragmatic trials provides the best true
estimates of “real world” expectations for the effects of any new
clinical service, including assessments of naturopathic medicine.
However, even in pragmatic research, appropriate comparators
remain necessary to assess the incremental value of an experimental
health service. For evaluations of naturopathic medicine, rather than
comparison to placebo or overly contrived time-attention control
groups mimicking services that do not exist, the appropriate
comparator is the usual care practices within the same clinical setting,
i.e., the status quo.
Three of the included RCTs employed usual care/enhanced usual
care comparators [23,29,30]. but one included an active control arm as
well [30]. The other RCTs used active comparators [26,27,32]. Of the
five retrospective studies, one included an electronically created usual
care control group matched from medical records [35]. Two studies
were prospective observational cohort studies, of which one was
compared to an electronically created usual care control group [24].
The other made comparisons to other forms of CAM [34]. Use of
enhanced usual care and active controls (acupuncture, chiropractic,
education, psychotherapy) provides a useful picture of real-world
effect. When most patients seek care from a naturopathic doctor, they
are motivated to engage in something more and might be looking for
other additions to their usual care. While heterogenous, the different
comparators provide a real-world perspective about what can be
expected at the population level, especially in our era of increasing
valuation of patient-preferences and autonomy.
Similarly, for evaluations of non-pharmacological therapies,
appropriate comparators were chosen based on customary usual care
practices, such as standardized physical exercises for rotator cuff
tendonitis and standardized psychotherapy for anxiety [26,27,32]. The
studies analyzed here are all examples of evaluations of actual practice
outcomes, i.e., pragmatic research, which most accurately estimates
the effectiveness in a real world setting, and thus the results have
greater external validity than could be achieved from any placebo-
controlled clinical trial [43-45].
Impact of study design
Evidence now shows that unblinded studies are not inherently
inferior to double blinded, placebo controlled trials with respect to
internal validity, bias, and methodological rigor. In fact, contrary to
common perception, evidence favors non-blinded studies utilizing
objective measures [46]. Wood et al., have shown that unlike trials
with subjective outcomes (which may exaggerate treatment effects
when there is inadequate allocation concealment or lack of blinding)
unblended trials with objective outcomes do not exaggerate treatment
effects [46]. Savovic et al. conducted an analysis of 234 meta-analyses
containing 1973 trials and reported similar findings, with little
evidence of bias in non-randomized or non-blinded trials utilizing
objective and mortality outcomes [47]. Therefore despite the lack of
comparator for several of the observational studies, the emphasis on
objective outcome measures of clinical risk and health status
strengthens the results, and limits the bias inherent in observational
studies.
The observational studies of whole practice naturopathic medicine
themselves are of methodologic interest. Observational studies have
been recognized as an important method for the evaluation of
healthcare delivery, in part due to their generally larger size and longer
duration, as well as including a more representative patient population
than RCTs [48]. Research has also confirmed that well- designed
observational studies can capture outcomes data that is comparable in
accuracy to that reported by RCTs, without systematic overestimation
of the magnitude of treatment effects [49,50]. Large analyses published
in the New England Journal of Medicine have found that observational
and randomized studies conducted in the same conditions and using
similar outcome measures report similar estimations of treatment
effects [49,50]. Yet, observational studies remain limited in their ability
to control for confounders that may influence outcomes, e.g., other
concurrent care services, and thus interpretation should remain
conservative regarding attribution of cause and effect. Despite these
limitations, the outcomes reported demonstrate no evidence of harm
or worsening clinical status secondary to exposure to naturopathic
medicine, and in fact suggest clinical benefit in all occasions.
Limitations
Despite finding beneficial effects on recognized predictors of
cardiovascular events, the studies included in our review were not able
to assess the effect of naturopathic medicine on the incidence of
cardiovascular events or mortality from cardiometabolic disease.
Second, due to heterogeneity among studies, we were not able to pool
primary outcomes or quality of life data. It is hoped that with the
growth of evidence in this area, a more rigorous synthesis of data may
be possible in future. It should be noted that although the studies
included here were pragmatic in nature, the delivery of care within the
context of a research study may not always reflect that in the clinical
field. The studies included here examined the practice of North
American naturopathic medicine only, so these findings are not
necessarily generalizable to the European or Australian practice of NM
and also may not reflect the entirety of evidence relating to whole
practice naturopathic medicine, or therapies used by naturopathic
doctors in the treatment of chronic conditions. Finally, a considerable
amount of time has elapsed from the date of the earliest published
studies, during which naturopathic medicine has evolved to its current
form.
Future Directions
Despite the results presented here in select conditions, research on
the practice and outcomes of naturopathic medicine is in its infancy,
and more research is required to further assess its contributions to
health care. Because of the difficulties inherent in evaluating the multi-
modal, non-pharmaceutical-dependent, interventions used by
emerging disciplines, we recommend all future evaluations of whole
practice naturopathic medicine include objective outcomes, provided
they are clinically relevant and important to the patient. Additionally,
extreme care should be taken to avoid (or quantify and carefully
describe) participant withdrawals, losses to follow-up, and other
causes of missing outcome data. Trials with large amounts of missing
outcome data may benefit from sensitivity analyses especially extreme
plausible analyses [51,52]. In addition to design considerations, future
research on naturopathic medicine should assess its potential on
additional high morbidity, high mortality chronic diseases for which
usual practices results in disappointing clinical outcomes (e.g.,
depression, chronic kidney disease, advanced cardiovascular disease,
asthma, irritable bowel syndrome, inflammatory bowel disease,
fibromyalgia, chronic fatigue syndrome) as well as include larger
replication studies for diabetes, CVD prevention, pain conditions and
mental health.
Citation: Oberg EB, Bradley R, Cooley K, Fritz H, Goldenberg JZ, et al. (2015) Estimated Effects of Whole-system Naturopathic Medicine in
Select Chronic Disease Conditions: A Systematic Review. Altern Integ Med 4: 192. doi:10.4172/2327-5162.1000192
Page 8 of 10
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ISSN:2327-5162 AIM, an open access journal Volume 4 • Issue 2 • 1000192

Conclusion
When examined as a body of literature, the universally positive
trends in favor of naturopathic medicine warrant increased funding to
continue and expand research efforts. The quality of research assessing
clinically relevant disease-oriented and patient-centered outcomes of
whole practice naturopathic medicine is generally good. Naturopathic
medicine appears to be a system of medicine with potentially positive
public health implications for a wide variety of chronic health
conditions.
Acknowledgements
With appreciation to the Naturopathic Physicians Research
Institute (501(c)3) for supporting this work. The authors have no
conflicts of interest to declare.
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