An Inventory of Randomized Controlled Trials using Plant-Based Diets - PowerPoint Presentation

An Inventory of Randomized Controlled Trials using Plant-Based Diets Clinical Evidence of Disease Reversal November, 14 2014Micaela Karlsen, MSPH www.PlantBasedResearch.org

PurposeEvidence pointing towards effective clinical recommendationsContext in which to place individual studies Grounding in evidence with which to engage in informed dialogue with colleagues www.PlantBasedResearch.org

Hierarchy of Evidence DE = Disease Endpoints www.PlantBasedResearch.org

Plant-Based Nutrition Research, 1/1/10 - PresentExplosion of studies exploring plant-based / vegetarian diets Only a portion look at chronic disease hard outcomesMany cross-sectional surveysOnly two currently active prospective cohortsSmall 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 studyAnalysis 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

Summary and Strength of EvidenceInventory of Evidence www.PlantBasedResearch.org

LimitationsStudy population belongs to specific religious groupStudy 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 www.PlantBasedResearch.org

LimitationsMay have some selection bias with more health-conscious vegetariansStudy 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…” www.PlantBasedResearch.org

Inclusion Criteria in this InventoryOverall 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 1950 1960 1970 1980 1990 2000 2010 * Single Arm Interventions * Randomized Controlled Trials * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * www.PlantBasedResearch.org

Inventory of RCTs – CVD & Risk Factors Author YearNIntervention 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 www.PlantBasedResearch.org

Inventory of RCTs – CVD & Risk Factors Author YearNIntervention 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 d rug 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 YearNIntervention 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 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 www.PlantBasedResearch.org

Inventory of RCTs – T2D & Risk Factors Author YearNIntervention 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 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? www.PlantBasedResearch.org

Inventory of RCTs – T2D & Risk Factors Author YearNIntervention diet Outcomes Result Limitations 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? www.PlantBasedResearch.org

CVD, T2D & Risk FactorsExample 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 changesDuration of follow-up www.PlantBasedResearch.org

Inventory of RCTs on Cancer AuthorYear NIntervention dietPrimary 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 www.PlantBasedResearch.org

CancerOverall 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 changesPatient adherence Duration of follow-upwww.PlantBasedResearch.org

Inventory of RCTs – Rheumatoid Arthritis & Fibromyalgia Author YearN Intervention diet Outcomes Result Limitations 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, controlled www.PlantBasedResearch.org

Rheumatoid Arthritis & FibromyalgiaOverall Findings (5 studies): Vegan diets produce improvement in symptoms Overall limitations: Small sample sizesWhich factors matter most? (Gluten-free, raw, incorporating fasting) Short duration of follow up www.PlantBasedResearch.org

Inventory of RCTs on Nutrient Intake/Status Author YearNIntervention 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? 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? www.PlantBasedResearch.org

Inventory of RCTs – Nutrient Intake/Status AuthorYear NIntervention dietPrimary 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 & micro nutrient intake Worksite setting, outcome beyond 22 weeks? www.PlantBasedResearch.org

Inventory of RCTs - Weight Loss AuthorYear NIntervention dietPrimary 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 www.PlantBasedResearch.org

Nutrient Intake and Weight LossOverall 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 maintenanceWhich matters most? (Vegan vs. vegetarian vs. improving dietary quality) www.PlantBasedResearch.org

Inventory of RCTs – Acceptability of Plant-Based Diets Author YearN 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

Author Year NIntervention dietOutcomes 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 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 www.PlantBasedResearch.org Inventory of RCTs – Acceptability of Plant-Based Diets

Acceptability of Plant-Based DietsOverall Findings (5 studies): Plant-based diets may be equivalently or better tolerated than meat-containing diets Increase in cost for increased F&V is minimalOverall limitations: Impact of cooking skills, time, economic resources Whole plant foods vs. meat analogues or transition foodsNeed cost analyses of 100% WFPB diets, not just increased plant food diets www.PlantBasedResearch.org

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ConclusionsEvidence base does exist to make clinical dietary recommendations to use plant-based nutritionPlant-based diets are safe, effective, and enjoyablePatients may need substantial training and support for transition www.PlantBasedResearch.org