AN INVENTORY OF RANDOMIZED CONTROLLED TRIALS USING PLANT-BASED DIETS Clinical Evidence of Disease Reversal November, 14 2014 Micaela Karlsen, MSPH

AN INVENTORY OF RANDOMIZED CONTROLLED TRIALS

USING PLANT-BASED DIETS

Clinical Evidence of Disease Reversal

November, 14 2014Micaela 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


Hierarchy of Evidence

RCTs of DE

RCTs of Surrogate Endpoints

Prospective cohort studies

Retrospective cohort studies

Case-control

Cross-sectional

Case reports, anecdotal

DE = Disease Endpoints


Decreasing bias, more ability to identify causal relationship

Plant-Based Nutrition Research, 1/1/10 - Present

Explosion of studies exploring plant-based / vegetarian diets

Only a portion look at chronic disease hard outcomes

Many cross-sectional surveysOnly two currently active

prospective cohortsSmall number of RCTsNumber of studies is

increasing!


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


SUMMARY AND STRENGTH OF EVIDENCE

Inventory of Evidence


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 IICurrent 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


http://www.llu.edu/public-health/health/faq.page?

http://www.llu.edu/public-health/health/faq.page?

http://www.llu.edu/public-health/health/progress/index.page?

Limitations

May have some selection bias with more health-conscious vegetarians

Study population does not also include those eating high protein and/or high fat diets

EPIC Oxford CohortBegun in 1992, one of two EPIC

cohorts in the UKGoal: “…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…”


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


Timeline of Human Intervention Studies Targeting Plant-Based Nutrition

1950 1960 1970 1980 1990 2000 2010

* Single Arm Interventions

* Randomized Controlled Trials

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Inventory of RCTs – CVD & Risk Factors

Author Year

N Intervention diet

Outcomes Result Limitations

Ornish 1990 48 Vegetarian, <10% fat

Coronary atherosclerosis

82% of experimental-group 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



Author Year

N Intervention diet


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, ROMsIncreased: 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 treatmentwww.PlantBasedResearch.org


Author Year

N Intervention diet


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 anti-PC 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


Inventory of RCTs – T2D & Risk Factors

Author Year

N Intervention diet


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 Calorie-restricted 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?


Inventory of RCTs – T2D & Risk Factors

Author Year

N Intervention diet


Turner-McGrievy

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

Calorie-restricted sustainable? Exercise in final 12 weeks. Outcome after 24 weeks?


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


Inventory of RCTs on Cancer

Author Year

N Intervention diet

Primary Outcome

Result Limitations

Ornish 2001 93 Low-fat, soy-supplemented vegan diet

PSA among prostate cancer patients practicing surveillance

No adverse events after 1 year

Intervention included lifestyle components

Frattaroli 2008 93 Low-fat, soy-supplemented 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


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


Inventory of RCTs – Rheumatoid Arthritis & Fibromyalgia

Author Year

N Intervention diet


Kjeldsen-Kragh

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

Non-randomized, 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* Non-randomized,

controlledwww.PlantBasedResearch.org

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


Inventory of RCTs on Nutrient Intake/Status

Author Year

N Intervention diet


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?

Turner-McGrievy

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?


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?


Inventory of RCTs - Weight Loss

Author Year

N Intervention diet

Primary Outcome

Result Limitations

Turner-McGrievy

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

Turner-McGrievy

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 lacto-ovovegetarian diet

Effect of preference and diet prescribed

Only marginal improvement in blood lipids, participants assigned diet decreased triglycerides

Diet included animal food


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)


Inventory of RCTs – Acceptability of Plant-Based Diets

Author

Year N Intervention diet



Acceptability, ease of continuation, dietary restraint, disinhibition, hunger

Comparable acceptability to Nat. Cholest. Ed. diet

Outcomes after 14 weeks?


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


Author

Year N Intervention diet


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 soy-based and traditional patties, nuggets, and pasta, and less soy than regular chicken in the salad

Foods tested were meat analogues, not whole plant foods


Inventory of RCTs – Acceptability of Plant-Based Diets

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


Download Page for References


http://plantbasedresearch.org/ppod

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


Documents

AN INVENTORY OF RANDOMIZED CONTROLLED TRIALS USING PLANT-BASED DIETS Clinical Evidence of Disease Reversal November, 14 2014 Micaela Karlsen, MSPH