Clinical Evidence of
Disease Reversal
AN INVENTORY OF RANDOMIZED
CONTROLLED TRIALS
USING PLANT-BASED DIETS
November, 14 2014
Micaela Karlsen, MSPH
www.PlantBasedResearch.org
Purpose
 Evidence pointing towards
effective clinical
recommendations
 Context in which to place
individual studies
 Grounding in evidence with
which to engage in informed
dialogue with colleagues
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Hierarchy of Evidence
Decreasing
bias, more
ability to
identify
causal
relationship
RCTs
of DE
RCTs of Surrogate
Endpoints
Prospective cohort studies
Retrospective cohort studies
Case-control
Cross-sectional
Case reports, anecdotal
www.PlantBasedResearch.org
DE = Disease Endpoints
Plant-Based Nutrition Research, 1/1/10 - Present
 Explosion of studies exploring

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
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plant-based / vegetarian diets
Only a portion look at chronic
disease hard outcomes
Many cross-sectional surveys
Only two currently active
prospective cohorts
Small number of RCTs
Number of studies is increasing!
www.PlantBasedResearch.org
Importance of the Big Picture
 Totality of the evidence is more
important than conclusions from
one individual study
 Analysis of the strength of
evidence is informed by the
methodological rigor of each
study
 Importance of understanding
strengths & limitations of
different study designs
www.PlantBasedResearch.org
Inventory of Evidence
SUMMARY AND STRENGTH OF
EVIDENCE
www.PlantBasedResearch.org
Limitations
Study population
belongs to specific
religious group
Study population
does not also include
those eating high
protein and/or high
fat diets
Diet via FFQ assessed
only once, at
enrollment
7th Day Adventist Health Study II
 Current study is Adventist Health
Study-2 (AHS-2) is a health research
study of 96,000 Seventh-day
Adventists in the U.S. and Canada.
 Primary goal is to study diet and
cancer among a population at
lower risk for all chronic disease
 Follow-up every two years to track
hospitalizations and diagnoses
www.PlantBasedResearch.org
Limitations
May have some
selection bias with
more healthconscious vegetarians
Study population
does not also include
those eating high
protein and/or high
fat diets
EPIC Oxford Cohort
 Begun in 1992, one of two EPIC
cohorts in the UK
 Goal: “…to recruit participants with a
wide range of diets by targeting
vegetarians as well as participants from
the general UK population. As such
EPIC-Oxford is of great scientific value
to the EPIC study as a whole, because
the diets of vegetarians, and especially
vegans, differ substantially from those
of meat-eaters and this range in diets
makes it easier to detect relationships
between nutrition and health…”
www.PlantBasedResearch.org
Inclusion Criteria in this Inventory
 Overall inclusion criteria focus on WFPB dietary
patterns, and studies whose results may be relevant to
the discussion of WFPB diets
 The diet was the main intervention (not single foods or
nutrients)
 The outcomes were markers of disease risk, disease
endpoints, or relevant behavioral outcomes
www.PlantBasedResearch.org
Timeline of Human Intervention
Studies Targeting Plant-Based Nutrition
* Single Arm Interventions
* Randomized Controlled Trials
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1950
1960
1970
www.PlantBasedResearch.org
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1980
1990
2000
2010
Inventory of RCTs – CVD & Risk Factors
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
Ornish
1990
48
Vegetarian,
<10% fat
Coronary atherosclerosis
82% of
experimentalgroup patients
had an average
change towards
regression of
coronary
atherosclerosis
Intervention
includes other
lifestyle changes
Gould
1995
35
Vegetarian,
<10% fat
Myocardial perfusion
abnormalities at baseline
and 5 years after
randomization
Improvement in
perfusion
abnormalities in
intervention
group vs.
worsening in
controls
Intervention
includes other
lifestyle changes
www.PlantBasedResearch.org
Inventory of RCTs – CVD & Risk Factors
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
Ornish
1998
48
(35 )
Vegetarian,
<10% fat
5-year follow up:
Adherence to intensive
lifestyle changes,
changes in coronary
artery percent diameter
stenosis, and cardiac
events.
More regression of
CA occurred after 5
years than after 1
year , CA continued
to progress in
control group
Intervention
included
other lifestyle
changes
Colombo
2005
104
Vegetarian,
low saturated
fat
Decreased: Sat fat,
arachidonic acid, ROMs
Increased: N-3, N-3/N-6
ratio
Improved blood lipid
profile
Diet
contained
animal foods,
outcomes
beyond 18
weeks?
Medkova
2005
84
Vegetarian,
includes milk
Blood lipids from drug
response (athenolol or
hypotiazide), with diet
subgroups for each
drug group
No difference in drug
response, veg diet
for both drugs had
total and LDL
improvement
Intervention
involved drug
treatment
www.PlantBasedResearch.org
Inventory of RCTs – CVD & Risk Factors
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
Barnard
2006
99
Low-fat, vegan
Diabetes medication
use, HbA(1c), body wt,
LDL, urinary albumin
among diabetics
Intervention
diet had sig.
benefits over
Am. Diab. Assoc.
diet
Outcomes
beyond 22
weeks?
Elkan
2008
66
Gluten-free, vegan
Blood lipids & BMI
among rheumatoid
arthritis patients
Lower BMI, LDL
and higher antiPC IgM than
control diet (p <
0.005).
Study
population was
RA patients
Ieromuzo
2012
42
Vegetarian,
includes dairy
Blood lipids response
among CAD patients
on beta-blockers
Decreased
blood pressure,
total and LDL,
increased HDL in
vegetarian
group
Intervention
involved drug
treatment
www.PlantBasedResearch.org
Inventory of RCTs – T2D & Risk Factors
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
Nicholson
1999
11
Low-fat, vegan
Glycemic and lipid
control in patients
with NIDDM
Reductions in fasting
serum glucose
concentration and
body weight
Small sample
size
Barnard
2009
99
Low-fat, vegan
Glycemic response,
weight, and blood
lipids
Vegan diet sig.
lowered total and
LDL cholesterol
compared to Am.
Diab. Assoc. diet,
Outcome after
74 weeks?
Kahleova
2011
74
Calorierestricted
vegetarian diet
with and
without
exercise
Diabetes
medication use,
body wt, insulin
sensitivity,
subcutaneous and
visceral fat
Intervention diet sig.
benefit in all
outcomes compared
to control diet, diff.
greater with exercise
Calorie
restriction
sustainable?
Outcome after
24 weeks?
www.PlantBasedResearch.org
Inventory of RCTs – T2D & Risk Factors
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
TurnerMcGrievy
2011
99
Low-fat, vegan
Glycemic index
load , wt loss, and
HbA1c in T2D
subjects
GI reduced more in
vegan group, GL
reduced more in
conventional group.
GI predicted
changes in wt, wt
loss predicted
changes in HbA1c
Outcome after
22 weeks?
Kahleova
2013
74
Calorie-restricted,
vegetarian
Changes in fatty
acid composition
of serum
phospholipids in
T2D subjects
Linoleic acid
increased in
vegetarian group
but decreased in
control group, neg.
correlated with
visceral fat
Calorierestricted
sustainable?
Exercise in final
12 weeks.
Outcome after
24 weeks?
www.PlantBasedResearch.org
CVD, T2D & Risk Factors
 Example of a strong study design:
 Barnard et al., 74 week intervention with T2D patients
 Overall findings (8 studies): Vegan, low-fat diets
resulted in stronger benefits on cardiometabolic risk
factors and reversal of T2D & CVD
 Overall limitations:
 Interventions including other lifestyle changes
 Duration of follow-up
www.PlantBasedResearch.org
Inventory of RCTs on Cancer
Author
Year
N
Intervention
diet
Primary
Outcome
Result
Limitations
Ornish
2001
93
Low-fat, soysupplemented
vegan diet
PSA among
prostate cancer
patients practicing
surveillance
No adverse events
after 1 year
Intervention
included lifestyle
components
Frattaroli
2008
93
Low-fat, soysupplemented
vegan diet
Clinical events
among prostate
cancer patients
after 2 yrs follow
up
Conventional
treatment in (27%)
control patients
and (5%)
experimental
Intervention
included lifestyle
components
www.PlantBasedResearch.org
Cancer
 Overall outcomes (1 study with follow up): Switching
to a low-fat, vegan diet can help avoid or delay
conventional prostate cancer treatment
 Overall limitations:
 TOO FEW STUDIES (as with all of these topics)
 Interventions including other lifestyle changes
 Patient adherence
 Duration of follow-up
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Inventory of RCTs –
Rheumatoid Arthritis & Fibromyalgia
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
KjeldsenKragh
1999
53
Fasting, gf
vegan,
vegetarian
Symptoms of
rheumatoid arthritis
in RA patients
Intervention group sig.
improved
3 different
treatments
Azad
2000
78
Vegetarian
Pain & morbidity in
fibromyalgia patients
Sig. but small
improvement compared
to drug therapy
Another arm
w/o dairy?
Kaartinen *
2000
33
Vegan
Fibromyalgia
symptoms, total
cholesterol, BMI
Improvement in all
symptoms, wt loss,
lower cholesterol
Nonrandomized,
small sample
size
Agren
2001
29
Raw, vegan
Blood lipids in RA
patients
Vegan diet decreaseed
total and LDL
Small sample
size
Hafstrom
2001
66
Gluten-free,
vegan
Levels of antibodies
to food antigens in
RA patients
Of diet completers, 40%
vegan improvement, 4%
control improvement
Low
completion
rate
www.PlantBasedResearch.org
* Non-randomized, controlled
Rheumatoid Arthritis & Fibromyalgia
 Overall Findings (5 studies): Vegan diets produce
improvement in symptoms
 Overall limitations:
 Small sample sizes
 Which factors matter most? (Gluten-free, raw, incorporating
fasting)
 Short duration of follow up
www.PlantBasedResearch.org
Inventory of RCTs on Nutrient Intake/Status
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
Ruama
1993
43
Raw, vegan
Nutrient intake
among rheumatoid
arthritis patients
Increase energy
and micronutrient
intake, 9% wt loss
vegan group
Outcome
beyond 3
months?
TurnerMcGrievy
2004
59
Low-fat, vegan
Nutrient intake per
1000 kcal in
overweight women
Improved macro &
micronutrient
intake, except for
food sources of D,
B12, Ca, Se, P, Zn
Outcome
beyond 14
weeks?
Dewell
2008
93
Low-fat, vegan
Protective &
pathogenic dietary
factors among
prostate cancer
patients
Increased intake of
protective factors
after 1 year
Outcome
beyond 1 year?
www.PlantBasedResearch.org
Inventory of RCTs – Nutrient Intake/Status
Author
Year
N
Intervention
diet
Primary
Outcome
Result
Limitations
Merrill
2009
119
Increased plant
foods, reduce
animal foods
Nutrient intake
among men and
women
Improved macro &
micronutrient
intake except Ca &
D
More plant
food, doesn’t
eliminate animal
food
Levin
2010
109
Low-fat, vegan
Nutrient intake
among overweight
or T2D employees
Improved macro &
micronutrient
intake
Worksite
setting,
outcome
beyond 22
weeks?
www.PlantBasedResearch.org
Inventory of RCTs - Weight Loss
Author
Year
N
Intervention
diet
Primary
Outcome
Result
Limitations
TurnerMcGrievy
2004
59
Low-fat, vegan
Nutrient
intake per
1000 kcal
Improvements to all
macro and micro intake,
except vitamin D,
vitamin B12, calcium,
selenium, phosphorous,
and zinc
Whole food
sources vs.
fortified or
supplements
TurnerMcGrievy
2007
62
Low-fat, vegan
Wt & diet
adherence at
1 & 2 yrs
Vegan diet and group
support component
predicted more wt loss
Women only
Burke
2008
176
Calorie-restricted,
low-fat lactoovovegetarian
diet
Effect of
preference
and diet
prescribed
Only marginal
improvement in blood
lipids, participants
assigned diet decreased
triglycerides
Diet included
animal food
www.PlantBasedResearch.org
Nutrient Intake and Weight Loss
 Overall outcomes (7 studies):
 Low-fat, vegan diets produce improvements in nutrient intake.
 Low-fat, vegan diet assist in healthy weight loss.
 Attention to micronutrient intake may be required for optimal
dietary quality.
 Overall limitations:
 Duration of follow-up was short for long-term weight
maintenance
 Which matters most? (Vegan vs. vegetarian vs. improving dietary
quality)
www.PlantBasedResearch.org
Inventory of RCTs –
Acceptability of Plant-Based Diets
Author
Year
N
Intervention
diet
Outcomes
Result
Limitations
Barnard
2004
64
Low-fat, vegan
Acceptability, ease of
continuation, dietary
restraint,
disinhibition, hunger
Comparable
acceptability to Nat.
Cholest. Ed. diet
Outcomes after
14 weeks?
Barnard
2009
99
Low-fat, vegan
Disinhibition, hunger,
cravings for fatty
foods, ease of prep
Comparable
acceptability to Am.
Diab. Assoc. diet,
except slightly for
ease of prep
Outcomes after
74 weeks?
Hyder
2009
2254
Increased fruit,
veg, fiber, &
lower fat
More plant-based
diet had increased
cost of $1.22/
person/week
Increased cost was
minimal
Diet still
contained meat
and dairy
www.PlantBasedResearch.org
Inventory of RCTs –
Acceptability of Plant-Based Diets
Author
Year
N
Interventio
n diet
Outcomes
Result
Limitations
Katcher
2010
113
Low-fat,
vegan
Greater mental
health, vitality, lower
food costs, more
difficulty finding food
out
Overall higher diet
satisfaction compared
to control
Worksite
wellness
program –
generalizability?
Lazor
2010
5
schools
15 soyfoods in
place of meat
items in
middle school
lunch
Plate waste and
ratings of new foods
from students
Same amount of soybased and traditional
patties, nuggets, and
pasta, and less soy
than regular chicken
in the salad
Foods tested
were meat
analogues, not
whole plant
foods
www.PlantBasedResearch.org
Acceptability of Plant-Based Diets
 Overall Findings (5 studies):
 Plant-based diets may be equivalently or better tolerated than
meat-containing diets
 Increase in cost for increased F&V is minimal
 Overall limitations:
 Impact of cooking skills, time, economic resources
 Whole plant foods vs. meat analogues or transition foods
 Need cost analyses of 100% WFPB diets, not just increased plant
food diets
www.PlantBasedResearch.org
Download Page for References
http://plantbasedresearch.org/ppod
www.PlantBasedResearch.org
Conclusions
 Evidence base does exist to
make clinical dietary
recommendations to use
plant-based nutrition
 Plant-based diets are safe,
effective, and enjoyable
 Patients may need
substantial training and
support for transition
www.PlantBasedResearch.org